bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical coherence tomography angiography of flat irregular pigment epithelial detachments in central serous chorioretinopathy
Authors: Liu Tingting , Lin Wei , Zhou Shuping , Meng Xiangjuan
Published: April 2020

Background

To identify and analyse the character and relationship between flat irregular pigment epithelial detachment feature (FIPED), choroidal thickness and choroidal neovascularisation (CNV) network seen on optical coherence tomography angiography (OCTA) in eyes with central serous chorioretinopathy (CSCR) in Chinese patients.

Method

In the present study, 152 eyes of 144 Chinese patients, who were previously diagnosed with CSCR, were retrospectively studied. Patients’ baseline characteristics, the course of CSCR, best-corrected visual acuity, the pattern of CNV on OCTA, FIPED and choroidal thickness detected by enhanced depth imaging-OCT (EDI-OCT) were analysed.

Results

It was disclosed that 7.23% of CSCR patients had CNV. Age and the course of CSCR were found to be correlated with the occurrence of CNV. Among the eyes with CNV network (11 eyes), 100% of them had FIPED, whereas, among the eyes without CNV (141 eyes), 18.04% had FIPED. The maximum width and en-face area of PED were greater in the CNV group compared with that in the non-CNV group (p<0.001). It also was revealed that female gender and a poor vision were risk factors for CNV in eyes with CSCR. The choroidal thickness detected by EDI-OCT was also statistically significant between eyes with CNV and eyes without CNV. The patients who have CNV complicated with FIPED are susceptible to have low vision.

Conclusion

The present research demonstrated that the majority of CNV cases were linked to FIPED, and the thinner thickness of choroid. The greater width and en-face area of PED may point towards the presence of an underlying CNV network.
Systematic review of gender differences in the epidemiology and risk factors of exertional heat illness and heat tolerance in the armed forces
Authors: Alele Faith , Malau-Aduli Bunmi , Malau-Aduli Aduli , Crowe Melissa
Published: April 2020

Objectives

This review aimed to describe the epidemiology of all heat-related illnesses in women compared with men in the armed forces and to identify gender-specific risk factors and differences in heat tolerance.

Design

A systematic review of multiple databases (MEDLINE, Emcare, CINAHL, PsycINFO, Informit and Scopus) was conducted from the inception of the databases to 1 April 2019 using the preferred reporting items for systematic review and meta-analysis guidelines.

Eligibility criteria

All relevant studies investigating and comparing heat illness and heat tolerance in women and men in the armed forces were included in the review.

Results

Twenty-four studies were included in the systematic review. The incidence of heat stroke in women ranged from 0.10 to 0.26 per 1000 person-years, while the incidence of heat stroke ranged from 0.22 to 0.48 per 1000 person-years in men. The incidence of other heat illnesses in women compared with men ranged from 1.30 to 2.89 per 1000 person-years versus 0.98 to 1.98 per 1000 person-years. The limited evidence suggests that women had a greater risk of exertional heat illness compared with men. Other gender-specific risk factors were slower run times and body mass index. Although there was a higher proportion of women who were heat intolerant compared with men, this finding needs to be interpreted with caution due to the limited evidence.

Conclusion

The findings of this review suggest that men experienced a slightly higher incidence of heat stroke than women in the armed forces. In addition, the limited available evidence suggests that a higher proportion of women were heat intolerant and being a female was associated with a greater risk of exertional heat illnesses. Given the limited evidence available, further research is required to investigate the influence of gender differences on heat intolerance and heat illness.
Trend analysis of tuberculosis case notifications with scale-up of antiretroviral therapy and roll-out of isoniazid preventive therapy in Zimbabwe, 2000–2018
Authors: Takarinda Kudakwashe C , Harries Anthony D , Mutasa-Apollo Tsitsi , Sandy Charles , Choto Regis C , Mabaya Simbarashe , Mbito Cephas , Timire Collins
Published: April 2020

Objectives

Antiretroviral therapy (ART) and isoniazid preventive therapy (IPT) are known to have a tuberculosis (TB) protective effect at the individual level among people living with HIV (PLHIV). In Zimbabwe where TB is driven by HIV infection, we have assessed whether there is a population-level association between IPT and ART scale-up and annual TB case notification rates (CNRs) from 2000 to 2018.

Design

Ecological study using aggregate national data.

Setting

Annual aggregate national data on TB case notification rates (stratified by TB category and type of disease), numbers (and proportions) of PLHIV in ART care and of these, numbers (and proportions) ever commenced on IPT.

Results

ART coverage in the public sector increased from <1% (8400 PLHIV) in 2004 to ~88% (>1.1 million PLHIV patients) by December 2018, while IPT coverage among PLHIV in ART care increased from <1% (98 PLHIV) in 2012 to ~33% (373 917 PLHIV) by December 2018. These HIV-related interventions were associated with significant declines in TB CNRs: between the highest CNR prior to national roll-out of ART (in 2004) to the lowest recorded CNR after national IPT roll-out from 2012, these were (1) for all TB case (510 to 173 cases/100 000 population; 66% decline, p<0.001); (2) for those with new TB (501 to 159 cases/100 000 population; 68% decline, p<0.001) and (3) for those with new clinically diagnosed PTB (284 to 63 cases/100 000 population; 77.8% decline, p<0.001).

Conclusions

This study shows the population-level impact of the continued scale-up of ART among PLHIV and the national roll-out of IPT among those in ART care in reducing TB, particularly clinically diagnosed TB which is largely associated with HIV. There are further opportunities for continued mitigation of TB with increasing coverage of ART and in particular IPT which still has a low coverage.
Novel health systems service design checklist to improve healthcare access for marginalised, underserved communities in Europe
Authors: Lazarus Jeffrey V , Baker Lee , Cascio Mario , Onyango Denis , Schatz Eberhard , Smith Alyna C , Spinnewijn Freek
Published: April 2020

Background

Marginalised communities such as homeless people, people who use drugs (PWUD), lesbian, gay, bisexual, transgender and intersex people (LGBTI), prisoners, sex workers and undocumented migrants are at high risk of poor health and yet face substantial barriers in accessing health and support services. The Nobody Left Outside (NLO) Service Design Checklist aims to promote a collaborative, evidence-based approach to service design and monitoring based on equity, non-discrimination and community engagement.

Methods

The Checklist was a collaborative project involving nine community advocacy organisations, with a focus on homeless people, PWUD, LGBTI people, prisoners, sex workers, and undocumented migrants. The Checklist was devised via a literature review; two NLO platform meetings; a multistakeholder policy workshop and an associated published concept paper; two conference presentations; and stakeholder consultation via a European Commission-led Thematic Network (including webinar).

Results

The NLO Checklist has six sections in line with the WHO Health Systems Framework. These are: (1) service delivery, comprising design stage (6 items), services provided (2 items), accessibility and adaptation (16 items), peer support (2 items); (2) health workforce (12 items); (3) health information systems (7 items); (4) medical products and technologies (1 item); (5) financing (3 items); and (6) leadership and governance (7 items). It promotes the implementation of integrated (colocated or linked) healthcare services that are community based and people centred. These should provide a continuum of needs-based health promotion, disease prevention, diagnosis, treatment and management, together with housing, legal and social support services, in alignment with the goals of universal health coverage and the WHO frameworks on integrated, people-centred healthcare.

Conclusions

The Checklist is offered as a practical tool to help overcome inequalities in access to health and support services. Policymakers, public health bodies, healthcare authorities, practitioner bodies, peer support workers and non-governmental organisations can use it when developing, updating or monitoring services for target groups. It may also assist civil society in wider advocacy efforts to improve access for underserved communities.
Community engagement with immigrant communities involving health and wellness research: a systematic review protocol towards developing a taxonomy of community engagement definitions, frameworks, and methods
Authors: Turin Tanvir C , Abedin Tasnima , Chowdhury Nashit , Ferdous Mahzabin , Vaska Marcus , Rumana Nahid , Urrutia Rossana , Chowdhury Mohammad Ziaul Islam
Published: April 2020

Introduction

The importance of community engagement has been established globally in health and wellness research. A certain degree of ambiguity remains, however, regarding the meaning of community engagement, which term has been used for various purposes and implemented in various forms. In this study, we aimed to explore the different definitions of community engagement, discuss the various objectives that have been proposed and uncover the diverse ways this concept has been implemented among researchers working for the betterment of the health and wellness of immigrant communities in host countries.

Methods and analysis

Taxonomy is a process for classifying complex and multifaceted matters using logical conceptual domains and dimensions for clearer way of contextualising. We will develop a taxonomy to organise the available literature on community engagement in immigrant health and wellness research in a way that captures user knowledge and understanding of its various meanings and processes. Specific methodological and analytical frameworks for systematic review and taxonomy development will guide each step. We will conduct a comprehensive systematic search in relevant databases, from inception to December 2019, using appropriate keywords followed by snowball search (single-citation tracking, reference lists). Papers will be included if they fall within predefined inclusion criteria (seen as most likely informative on elements pertaining to community engagement) and are written in English, regardless of design (conceptual, qualitative and quantitative). Two reviewers will independently employ two-stage screening (title–abstract screening followed by screening of the full text to determine inclusion). Finally, information that helps to develop taxonomy of the concept and practice of community engagement will be abstracted and used towards taxonomy development, where different levels of stakeholder research team members will be involved.

Ethics and dissemination

Ethical approval is not required for this systematic review. We have opted for an integrated knowledge translation or a community-engaged knowledge mobilisation approach where we are engaged with community-based citizen researchers from the inception of our programme. We plan to disseminate the results of our review through meetings with key stakeholders, followed by journal publications and presentations at applicable platforms.
Association between functional social support and cognitive function in middle-aged and older adults: a protocol for a systematic review
Authors: Rutter Emily C , Tyas Suzanne L , Maxwell Colleen J , Law Jane , O'Connell Megan E , Konnert Candace A , Oremus Mark
Published: April 2020

Introduction

Maintenance of cognitive function into old age is important for ageing populations. Researchers seek to identify modifiable risk and protective factors for cognitive function. One such modifiable factor is functional social support, that is, one’s perception of whether their social network can provide resources such as material help, companionship, information and emotional contact, if needed. While the literature generally reports positive associations between functional social support and cognitive function, results vary according to study methods such as the tool used to measure functional social support or the specific cognitive domain under investigation. Our review will summarise the association between functional social support and cognitive function in middle-aged and older-aged adults who reside in any setting (eg, community dwelling, long-term care facilities). We will also identify sources of discrepant findings between studies.

Methods and analysis

This protocol was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guideline. PubMed, PsycINFO, Sociological Abstracts, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Scopus will be searched from inception to the present using a search strategy developed with a medical librarian’s help. We will supplement the database searches with a grey literature search. English-language or French-language studies with a comparison group will be subject to inclusion, regardless of the measures used to assess functional social support or cognitive function. We will assess risk of bias with the Cochrane Risk of Bias Tool-Version 2 or the Newcastle-Ottawa Scale, narratively synthesise the extracted data and conduct a meta-analysis of studies with similar characteristics (eg, sample age and sex, cognitive function outcomes). Two independent raters will screen articles and assess risk of bias.

Ethics and dissemination

This review is timely given the push toward early diagnosis and treatment of dementia/major neurocognitive disorder and other types of cognitive impairment. This protocol does not require a formal ethics review. We will publish our findings in a peer-reviewed journal.
Prognosis and causes of death of patients with acute exacerbation of fibrosing interstitial lung diseases
Authors: Salonen Johanna , Purokivi Minna , Bloigu Risto , Kaarteenaho Riitta
Published: April 2020

Background

The aim of this study was to compare the clinical characteristics, causes of death and factors impacting on the prognosis of patients with idiopathic pulmonary fibrosis (IPF) and other fibrosing interstitial lung disease (FILD) with a history of acute exacerbation (AE) of IPF or FILD.

Methods

Retrospective data of hospital treatment periods caused by AE-IPF and AE-FILD were collected from medical records. Clinical features and survival data of IPF and non-IPF cases were evaluated and compared. The underlying and immediate causes of death were gathered from death certificates.

Results

A total of 128 patients fulfilled the criteria for inclusion. IPF (n=79/62%), rheumatoid arthritis-associated interstitial lung disease (RA-ILD; n=17/14%) and asbestosis (n=11/8.6%) were the most common FILD subgroups in the study. The median survival after hospitalisation in AE-IPF was 2.6 months compared with 21 months in other AE-FILDs (p<0.001). The survival difference was not explained by age, gender or pulmonary function test results at the time of hospitalisation. Patients with non-specific interstitial pneumonia and RA-ILD had the most favourable prognosis. ILD was the most common underlying cause of death in both patients with IPF and with other FILD accounting for 87% and 78% of deaths, respectively.

Conclusions

We detected a significantly longer survival in AE of patients with non-IPF compared with that of AE-IPFs. The prognosis of patients was affected by the underlying lung disease since pulmonary fibrosis was the underlying cause of death in the majority of all patients with FILD having experienced an AE.
Predictive value of non-specific bronchial challenge testing for respiratory symptoms and lung function in aluminium smelter workers
Authors: Abramson Michael J , Gwini Stella May , de Klerk Nicholas H , Del Monaco Anthony , Dennekamp Martine , Fritschi Lin , Dimitriadis Christina , Mohebbi Mohammadreza , Musk Arthur William (Bill) , Sim Malcolm Ross
Published: April 2020

Objective

To assess the predictive value of bronchial hyper-responsiveness (BHR) for the subsequent development of respiratory symptoms, airflow limitation and decline in lung function among aluminium smelter workers.

Methods

An inception cohort study of new employees at two Australian aluminium smelters was conducted. Participants completed a modified British Medical Research Council respiratory questionnaire, spirometry and a methacholine bronchial challenge test at baseline and at annual follow-up reviews. BHR was defined as PD20 ≤4000 µg. Poisson and mixed effects models were fitted to respiratory symptoms and lung function (forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC)).

Results

Baseline interview and lung function testing were completed by 278 workers, who were followed for a median of 4 years. BHR at baseline, present in 82 workers, was not associated with incident wheeze risk ratio (RR)=1.07 (95% CI 0.74 to 1.55) and cough RR=0.78 (95% CI 0.45, 1.35), but there was some increased risk of chest tightness RR=1.40 (95% CI 0.99, 1.98) after adjustment for age, sex, smoking and atopy. BHR at baseline was associated with lower FEV1 and FVC, although the rate of annual decline in FEV1 or FVC was similar between those with or without BHR. The specificity of BHR was 77% for wheeze, 70% for cough and 77% for chest tightness, but the sensitivity was poor, at 33%, 24% and 39%, respectively.

Conclusion

Methacholine challenge testing at entry to employment was not sufficiently predictive of later adverse respiratory outcomes, and notwithstanding the study limitations is unlikely to be a useful pre-employment or preplacement screening test in the aluminium smelting industry.
Increased extracellular vesicles mediate inflammatory signalling in cystic fibrosis
Authors: Useckaite Zivile , Ward Mark P , Trappe Anne , Reilly Rebecca , Lennon Jenny , Davage Holly , Matallanas David , Cassidy Hilary , Dillon Eugene T , Brennan Kiva , Doyle Sarah L , Carter Suzanne , Donnelly Seamas , Linnane Barry , McKone Edward F , McNally Paul , Coppinger Judith A
Published: April 2020

Rationale

Mutations in the cystic fibrosis transmembrane regulator (CFTR) gene form the basis of cystic fibrosis (CF). There remains an important knowledge gap in CF as to how diminished CFTR activity leads to the dominant inflammatory response within CF airways.

Objectives

To investigate if extracellular vesicles (EVs) contribute to inflammatory signalling in CF.

Methods

EVs released from CFBE41o-, CuFi-5, 16HBE14o- and NuLi-1 cells were characterised by nanoparticle tracking analysis (NTA). EVs isolated from bronchoalveolar lavage fluid (BALF) from 30 people with CF (PWCF) were analysed by NTA and mass spectrometry and compared with controls. Neutrophils were isolated from the blood of 8 PWCF to examine neutrophil migration in the presence of CFBE41o- EVs.

Results

A significantly higher level of EVs were released from CFBE41o- (p<0.0001) and CuFi-5 (p=0.0209) relative to control cell lines. A significantly higher level of EVs were detected in BALF of PWCF, in three different age groups relative to controls (p=0.01, 0.001, 0.002). A significantly lower level of EVs were released from CFBE41o- (p<0.001) and CuFi-5 (p=0.0002) cell lines treated with CFTR modulators. Significant changes in the protein expression of 126 unique proteins was determined in EVs obtained from the BALF of PWCF of different age groups (p<0.001–0.05). A significant increase in chemotaxis of neutrophils derived from PWCF was observed in the presence of CFBE41o EVs (p=0.0024) compared with controls.

Conclusion

This study demonstrates that EVs are produced in CF airway cells, have differential protein expression at different ages and drive neutrophil recruitment in CF.
Neural ODEs as the deep limit of ResNets with constant weights
Authors: Avelin Benny , Nyström Kaj
Published: April 2020

In this paper, we prove that, in the deep limit, the stochastic gradient descent on a ResNet type deep neural network, where each layer shares the same weight matrix, converges to the stochastic gradient descent for a Neural ODE and that the corresponding value/loss functions converge. Our result gives, in the context of minimization by stochastic gradient descent, a theoretical foundation for considering Neural ODEs as the deep limit of ResNets. Our proof is based on certain decay estimates for associated Fokker–Planck equations.
Hyperbranched lutecium phthalocyanines grafted ethylenediamine@graphene oxide with enhanced nonlinear optical properties
Authors: Cui Zengduo , Wang Xin , Ding Jiale , Zhang Yunhe , Jiang Zhenhua , Li Xuefeng
Published: April 2020

To enhance the nonlinear optical properties of graphene oxide in organic solvent and polymeric matrix, lutecium phthalocyanines (LuPc) and hyperbranched lutecium phthalocyanines (HBLuPc) have been grafted on the surface of graphene oxide, respectively. After the surficial modification, the electron transfer process between phthalocyanines and graphene oxide has been also facilitated, resulting in significant fluorescence quenching. Given the combination of nonlinear scattering, two-photon absorption with reverse saturable absorption and the photo-induced electron or energy transfer from the electron donor (phthalocyanine moiety) to the acceptor (graphene oxide), stronger nonlinear optical properties can be realized based on graphene oxide hybrids compared with graphene oxide and phthalocyanines. Furthermore, graphene oxide hybrid modified by hyperbranched lutecium phthalocyanines exhibits the best optical limiting response and the highest nonlinear extinction coefficient at 532 nm in both organic solvent and polymeric matrix. Interestingly, we also find that it could exhibit better optical limiting properties than those possessed by pure phthalocyanine at 1064 nm.
Towards Integrated Classification Lexicon for Handling Unknown Words in Chinese-Vietnamese Neural Machine Translation
Authors: Che Wanjin , Yu Zhengtao , Yu Zhiqiang , Wen Yonghua , Guo Junjun
Published: April 2020

In Neural Machine Translation (NMT), due to the limitations of the vocabulary, unknown words cannot be translated properly, which brings suboptimal performance of the translation system. For resource-scarce NMT that have small-scale training corpus, the effect is amplified. The traditional approach of amplifying the scale of the corpus is not applicable, because the parallel corpus is difficult to obtain in a resource-scarce setting; however, it is easy to obtain and utilize external knowledge, bilingual lexicon, and other resources. Therefore, we propose classification lexicon approach for processing unknown words in the Chinese-Vietnamese NMT task. Specifically, three types of unknown Chinese-Vietnamese words are classified and their corresponding classification lexicon are constructed by word alignment, Wikipedia extraction, and rule-based methods, respectively. After translation, the unknown words are restored by lexicon for post-processing. Experiment results on Chinese-Vietnamese, English-Vietnamese, and Mongolian-Chinese translations show that our approach significantly improves the accuracy and the performance of NMT especially in a resource-scarce setting.
The behavior of gradual types: a user study
Authors: Tunnell Wilson Preston , Greenman Ben , Pombrio Justin , Krishnamurthi Shriram
Published: April 2020

There are several different gradual typing semantics, reflecting different trade-offs between performance and type soundness guarantees. Notably absent, however, are any data on which of these semantics developers actually prefer.

We begin to rectify this shortcoming by surveying professional developers, computer science students, and Mechanical Turk workers on their preferences between three gradual typing semantics. These semantics reflect important points in the design space, corresponding to the behaviors of Typed Racket, TypeScript, and Reticulated Python. Our most important finding is that our respondents prefer a runtime semantics that fully enforces statically declared types.
Model-based security analysis of feature-oriented software product lines
Authors: Peldszus Sven , Strüber Daniel , Jürjens Jan
Published: April 2020

Today's software systems are too complex to ensure security after the fact – security has to be built into systems by design. To this end, model-based techniques such as UMLsec support the design-time specification and analysis of security requirements by providing custom model annotations and checks. Yet, a particularly challenging type of complexity arises from the variability of software product lines. Analyzing the security of all products separately is generally infeasible. In this work, we propose SecPL, a methodology for ensuring security in a software product line. SecPL allows developers to annotate the system design model with product-line variability and security requirements. To keep the exponentially large configuration space tractable during security checks, SecPL provides a family-based security analysis. In our experiments, this analysis outperforms the naive strategy of checking all products individually. Finally, we present the results of a user study that indicates the usability of our overall methodology.
Exploring feature interactions without specifications: a controlled experiment
Authors: Soares Larissa Rocha , Meinicke Jens , Nadi Sarah , Kästner Christian , de Almeida Eduardo Santana
Published: April 2020

In highly configurable systems, features may interact unexpectedly and produce faulty behavior. Those faults are not easily identified from the analysis of each feature separately, especially when feature specifications are missing. We propose VarXplorer, a dynamic and iterative approach to detect suspicious interactions. It provides information on how features impact the control and data flow of the program. VarXplorer supports developers with a graph that visualizes this information, mainly showing suppress and require relations between features. To evaluate whether VarXplorer helps improve the performance of identifying suspicious interactions, we perform a controlled study with 24 subjects. We find that with our proposed feature-interaction graphs, participants are able to identify suspicious interactions more than 3 times faster compared to the state-of-the-art tool.
Inferring ownership domains from refinements
Authors: Khalaj Ebrahim , Abi-Antoun Marwan
Published: April 2020

Ownership type qualifiers clarify aliasing invariants that cannot be directly expressed in mainstream programming languages. Adding qualifiers to code, however, often involves significant overhead and difficult interaction.

We propose an analysis to infer qualifiers in the code based on developer refinements that express strict encapsulation, logical containment and architectural tiers. Refinements include: makeOwnedBy, to make an object strictly encapsulated by another; makePartOf, to make an object logically contained in another; makePeer, to make two objects peers; makeParam, to make an object more accessible than the above choices; or makeShared, to allow an object to be globally aliased. If the code as-written matches the requested refinements, the analysis generates qualifiers that type-check; otherwise, it reports that the refinements do not match the code, so developers must investigate unexpected aliasing, change their understanding of the code and pick different refinements, or change the code and re-run the analysis.

We implement the analysis and confirm that refinements generate precise qualifiers that express strict encapsulation, logical containment and architectural tiers.
Rash: from reckless interactions to reliable programs
Authors: Hatch William Gallard , Flatt Matthew
Published: April 2020

Command languages like the Bourne Shell provide a terse syntax for exploratory programming and system interaction. Shell users can begin to write programs that automate their tasks by simply copying their interactions verbatim into a script file. However, command languages usually scale poorly beyond small scripts, and they can be difficult to integrate into larger programs. General-purpose languages scale well, but are verbose and unwieldy for common interactive actions such as process composition.

We present Rash, a domain-specific command language embedded in Racket. Rash provides a terse and extensible syntax for interactive system administration and scripting, as well as easy composition of both Racket functions and operating system processes. Rash and normal Racket code can be nested together at the expression level, providing the benefits of a shell language and a general-purpose language together. Thus, Rash provides a gradual scale between shell-style interactions and general-purpose programming.
Measuring effectiveness of sample-based product-line testing
Authors: Ruland Sebastian , Luthmann Lars , Bürdek Johannes , Lity Sascha , Thüm Thomas , Lochau Malte , Ribeiro Márcio
Published: April 2020

Recent research on quality assurance (QA) of configurable software systems (e.g., software product lines) proposes different analysis strategies to cope with the inherent complexity caused by the well-known combinatorial-explosion problem. Those strategies aim at improving efficiency of QA techniques like software testing as compared to brute-force configuration-by-configuration analysis. Sampling constitutes one of the most established strategies, defining criteria for selecting a drastically reduced, yet sufficiently diverse subset of software configurations considered during QA. However, finding generally accepted measures for assessing the impact of sample-based analysis on the effectiveness of QA techniques is still an open issue. We address this problem by lifting concepts from single-software mutation testing to configurable software. Our framework incorporates a rich collection of mutation operators for product lines implemented in C to measure mutation scores of samples, including a novel family-based technique for product-line mutation detection. Our experimental results gained from applying our tool implementation to a collection of subject systems confirms the widely-accepted assumption that pairwise sampling constitutes the most reasonable efficiency/effectiveness trade-off for sample-based product-line testing.
RT-trust: automated refactoring for trusted execution under real-time constraints
Authors: Liu Yin , An Kijin , Tilevich Eli
Published: April 2020

Real-time systems must meet strict timeliness requirements. These systems also often need to protect their critical program information (CPI) from adversarial interference and intellectual property theft. Trusted execution environments (TEE) execute CPI tasks on a special-purpose processor, thus providing hardware protection. However, adapting a system written to execute in environments without TEE requires partitioning the code into the regular and trusted parts. This process involves complex manual program transformations that are not only laborious and intellectually tiresome, but also hard to validate and verify for the adherence to real-time constraints. To address these problems, this paper presents novel program analyses and transformation techniques, accessible to the developer via a declarative meta-programming model. The developer declaratively specifies the CPI portion of the system. A custom static analysis checks CPI specifications for validity, while probe-based profiling helps identify whether the transformed system would continue to meet the original real-time constraints, with a feedback loop suggesting how to modify the code, so its CPI can be isolated. Finally, an automated refactoring isolates the CPI portion for TEE-based execution, communicated with through generated calls to the TEE API. We have evaluated our approach by successfully enabling the trusted execution of the CPI portions of several microbenchmarks and a drone autopilot. Our approach shows the promise of declarative meta-programming in reducing the programmer effort required to adapt systems for trusted execution under real-time constraints.
Engineering Approaches for Addressing Opioid Use Disorder in the Community
Authors: Griffin Paul M.
Published: April 2020

Many communities in the United States are struggling to deal with the negative consequences of illicit opioid use. Effectively addressing this epidemic requires the coordination and support of community stakeholders in a change process with common goals and objectives, continuous engagement with individuals with opioid use disorder (OUD) through their treatment and recovery journeys, application of systems engineering principles to drive process change and sustain it, and use of a formal evaluation process to support a learning community that continuously adapts. This review presents strategies to improve OUD treatment and recovery with a focus on engineering approaches grounded in systems thinking.
The inducible β5i proteasome subunit contributes to proinsulin degradation in GRP94-deficient β-cells and is overexpressed in type 2 diabetes pancreatic islets
Authors: Khilji Muhammad Saad , Bresson Sophie Emilie , Verstappen Danielle , Pihl Celina , Andersen Phillip Alexander Keller , Agergaard Jette Bach , Dahlby Tina , Bryde Tenna Holgersen , Klindt Kristian , Nielsen Christian Kronborg , Walentinsson Anna , Zivkovic Dusan , Bousquet Marie-Pierre , Tyrberg Björn , Richardson Sarah J. , Morgan Noel G. , Mandrup-Poulsen Thomas , Marzec Michal Tomasz
Published: April 2020

Proinsulin is a misfolding-prone protein, and its efficient breakdown is critical when β-cells are confronted with high-insulin biosynthetic demands, to prevent endoplasmic reticulum stress, a key trigger of secretory dysfunction and, if uncompensated, apoptosis. Proinsulin degradation is thought to be performed by the constitutively expressed standard proteasome, while the roles of other proteasomes are unknown. We recently demonstrated that deficiency of the proinsulin chaperone glucose-regulated protein 94 (GRP94) causes impaired proinsulin handling and defective insulin secretion associated with a compensated endoplasmic reticulum stress response. Taking advantage of this model of restricted folding capacity, we investigated the role of different proteasomes in proinsulin degradation, reasoning that insulin secretory dynamics require an inducible protein degradation system. We show that the expression of only one enzymatically active proteasome subunit, namely, the inducible β5i-subunit, was increased in GRP94 CRISPR/Cas9 knockout (KO) cells. Additionally, the level of β5i-containing intermediate proteasomes was significantly increased in these cells, as was β5i-related chymotrypsin-like activity. Moreover, proinsulin levels were restored in GRP94 KO upon β5i small interfering RNA-mediated knockdown. Finally, the fraction of β-cells expressing the β5i-subunit is increased in human islets from type 2 diabetes patients. We conclude that β5i is an inducible proteasome subunit dedicated to the degradation of mishandled proinsulin.
Multilabel Classification Using Low-Rank Decomposition
Authors: Yang Bo , Tong Kunkun , Zhao Xueqing , Pang Shanmin , Chen Jinguang
Published: April 2020

In the multilabel learning framework, each instance is no longer associated with a single semantic, but rather with concept ambiguity. Specifically, the ambiguity of an instance in the input space means that there are multiple corresponding labels in the output space. In most of the existing multilabel classification methods, a binary annotation vector is used to denote the multiple semantic concepts. That is, +1 denotes that the instance has a relevant label, while −1 means the opposite. However, the label representation contains too little semantic information to truly express the differences among multiple different labels. Therefore, we propose a new approach to transform binary label into a real-valued label. We adopt the low-rank decomposition to get latent label information and then incorporate the information and original features to generate new features. Then, using the sparse representation to reconstruct the new instance, the reconstruction error can also be applied in the label space. In this way, we finally achieve the purpose of label conversion. Extensive experiments validate that the proposed method can achieve comparable to or even better results than other state-of-the-art algorithms.
Improved Clonal Selection Algorithm Based on Biological Forgetting Mechanism
Authors: Yang Chao , Chen Bing-qiu , Jia Lin , Wen Hai-yang
Published: April 2020

The antibody candidate set generated by the clonal selection algorithm has only a small number of antibodies with high antigen affinity to obtain high-frequency mutations. Among other antibodies, some low-affinity antibodies are replaced by new antibodies to participate in the next clonal selection. A large number of antibodies with high affinity make it difficult to participate in clonal selection and exist in antibody concentration for a long time. This part of inactive antibody forms a “black hole” of the antibody set, which is difficult to remove and update in a timely manner, thus affecting the speed at which the algorithm approximates the optimal solution. Inspired by the mechanism of biological forgetting, an improved clonal selection algorithm is proposed to solve this problem. It aims to use the abstract mechanism of biological forgetting to eliminate antibodies that cannot actively participate in high-frequency mutations in the antibody candidate set and to improve the problem of insufficient diversity of antibodies in the clonal selection algorithm, which is prone to fall into the local optimal. Compared with the existing clonal selection and genetic algorithms, the experiment and time complexity analysis show that the algorithm has good optimization efficiency and stability.
Segmentation of Overlapped Cervical Cells Using Asymmetric Mixture Model and Shape Constraint Level Set Method
Authors: Huang Yiming , Zhu Hongqing
Published: April 2020

Accuracy segmentation of the nuclei and cytoplasm in Pap smear images is challenging in cervix cytological analysis. In this paper, a new fusion algorithm combining the asymmetric generalized Gaussian and Cauchy mixture model (GGCMM) with a shape constraint level set method to segment overlapping cervical smear cells is put forward. The proposed approach starts by separating nuclei and cytoplasm cluster through asymmetric GGCMM, where each component is a mixture of generalized Gaussian distribution and Cauchy distribution. The proposed asymmetric GGCMM takes into account the asymmetry of generalized Gaussian distribution and the heavier tail of Cauchy distribution. New probability distribution fits different shapes of observed data more flexibly. Then, we apply the morphological operation to remove fake nuclei which is usually much smaller than real nuclei. After that, the improved level set energy function with a distance map and a new shape prior term are applied to extract the contours of overlapping cervical cells. Due to this new level set energy function, the segmentation of every individual cell worked well, especially in overlapping areas. We evaluate the proposed method by using the ISBI 2014 Challenge Dataset. The results demonstrate that our approach outperforms existing methods in extracting overlapping cervical cells and obtains accurate cell contours.
Uniqueness of Iterative Positive Solution to Nonlinear Fractional Differential Equations with Negatively Perturbed Term
Authors: Tan Jingjing , Li Meixia , Pan Aixia
Published: April 2020

We prove that there are unique positive solutions for a new kind of fractional differential equation with a negatively perturbed term boundary value problem. Our methods rely on an iterative algorithm which requires constructing an iterative scheme to approximate the solution. This allows us to calculate the estimation of the convergence rate and the approximation error.
Assessment of the Role of Ginsenoside RB1 Active Substance in Alginate/Chitosan/Lovastatin Composite Films
Authors: Thach Thi-Loc , Nguyen Thuy-Chinh , Vo An-Quan , Do Minh-Thanh , Nguyen Quang-Tung , Nguyen Tuan-Anh , Bach Long-Giang , Thai Hoang
Published: April 2020

This article reports the effect of ginsenoside Rb1 on some properties, morphology, and the drug release process of the chitosan (CS)/alginate (AG)/lovastatin (LOV) composite films prepared by a solution method using different contents of ginsenoside Rb1. The ratio of AG/CS was fixed at 4/1 (wt.%/wt.%), the content of LOV was 10 wt.%, and the content of ginsenoside Rb1 was changed from 1 to 5 wt.%. The results of scanning electron microscopy and Fourier transform infrared spectroscopy analysis showed that the composite films have a heterogeneous structure and the ginsenoside Rb1 content influenced on the structure of composite films. The presence of ginsenoside Rb1 did not influence on the melting temperature of these films but caused a significant difference in the melting enthalpy of the films. The ginsenoside Rb1 was also contributed positively on the LOV release from these films in different pH buffer solutions. The LOV release process from these films included two stages (fast/burst release and slow/control release). It was increased remarkably by the synergic effect of LOV and ginsenoside Rb1 in the drug release process. From the obtained results, we suggested that ginsenoside Rb1 plays an important role not only in the enhancement of health and immunity as general but also as an efficient agent in control of the LOV size as well as LOV drug release from the composite films.
Differentiating Grade in Breast Invasive Ductal Carcinoma Using Texture Analysis of MRI
Authors: Yuan Gaoteng , Liu Yihui , Huang Wei , Hu Bing
Published: April 2020

Purpose. The objective of this study is to investigate the use of texture analysis (TA) of magnetic resonance image (MRI) enhanced scan and machine learning methods for distinguishing different grades in breast invasive ductal carcinoma (IDC). Preoperative prediction of the grade of IDC can provide reference for different clinical treatments, so it has important practice values in clinic. Methods. Firstly, a breast cancer segmentation model based on discrete wavelet transform (DWT) and K-means algorithm is proposed. Secondly, TA was performed and the Gabor wavelet analysis is used to extract the texture feature of an MRI tumor. Then, according to the distance relationship between the features, key features are sorted and feature subsets are selected. Finally, the feature subset is classified by using a support vector machine and adjusted parameters to achieve the best classification effect. Results. By selecting key features for classification prediction, the classification accuracy of the classification model can reach 81.33%. 3-, 4-, and 5-fold cross-validation of the prediction accuracy of the support vector machine model is 77.79%~81.94%. Conclusion. The pathological grading of IDC can be predicted and evaluated by texture analysis and feature extraction of breast tumors. This method can provide much valuable information for doctors’ clinical diagnosis. With further development, the model demonstrates high potential for practical clinical use.
Two-Year Outcomes after Left Main Coronary Artery Percutaneous Coronary Intervention in Patients Presenting with Acute Coronary Syndrome
Authors: Jia Si-Da , Yao Yi , Song Ying , Tang Xiao-Fang , Zhao Xue-Yan , Gao Run-Lin , Yang Yue-Jin , Xu Bo , Gao Zhan , Yuan Jin-Qing
Published: April 2020

Objectives. We aim to evaluate long-term outcomes after left main coronary artery (LMCA) percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS). Background. PCI of the LMCA has been an acceptable revascularization strategy in stable coronary artery disease. However, limited studies on long-term clinical outcomes of LMCA PCI in ACS patients are available. Methods. A total of 6429 consecutive patients with ACS undergoing PCI in Fuwai Hospital in 2013 were enrolled. Patients are divided into LMCA group and Non-LMCA group according to whether the target lesion was located in LMCA. Prognosis impact on 2-year major adverse cardiovascular and cerebrovascular events (MACCE) is analyzed. Results. 155 (2.4%) patients had target lesion in LMCA, while 6274 (97.6%) patients belong to the non-LMCA group. Compared with non-LMCA patients, LMCA patients have generally more comorbidities and worse baseline conditions. Two-year follow-up reveals that LMCA patients have significantly higher rate of cardiac death (2.6% vs. 0.7%, p=0.034), myocardial infarction (7.1% vs. 1.8%, p<0.001), in-stent thrombosis (4.5% vs. 0.8%, p<0.001), and stroke (7.1% vs. 6.4%, p=0.025). After adjusting for confounding factors, LMCA remains independently associated with higher 2-year myocardial infarction rate (HR = 2.585, 95% CI = 1.243–5.347, p=0.011). Conclusion. LMCA-targeted PCI is an independent risk factor for 2-year myocardial infarction in ACS patients.
The Supernatant of Tonsil-Derived Mesenchymal Stem Cell Has Antiallergic Effects in Allergic Rhinitis Mouse Model
Authors: Park In-Su , Kim Ji Hye , Bae Jun-Sang , Kim Dong-Kyu , Mo Ji-Hun
Published: April 2020

Background and Purpose. Recently, tonsil-derived mesenchymal stem cells (T-MSCs) have attracted great attention in various medical fields due to easier harvest of T-MSCs and more immunomodulatory effects than adipose-derived MSCs. However, there was still little evidence of the effect of conditioned media from T-MSCs (T-MSCs-CM) on allergic rhinitis (AR). Therefore, we investigated the impact of T-MSCs-CM on an AR mouse model. Methods. We isolated T-MSCs from human palatine tonsil and evaluated the ingredients of T-MSCs-CM. The effect of T-MSCs-CM was evaluated in the AR mouse model that was randomly divided into five groups (negative control, positive control, and T-MSCs-CM treated (0.1 mg, 1 mg, and 10 mg)). To investigate the therapeutic effect, we analyzed rhinitis symptoms, serum immunoglobulin (Ig), inflammatory cells, and cytokine expression. We also assessed T cell receptor signal, including MAP kinase (ERK/JNK), p65, and NFAT1. Results. We identified the increment of TGF-β1, PGE2, and HGF in the T-MSCs-CM. In an animal study, the T-MSCs-CM-treated group showed significantly reduced allergic symptoms and infiltration of eosinophils and neutrophils in the nasal mucosa, whereas there was no significant difference in total IgE and the OVA-specific IgE level. Additionally, we found that the 10 mg T-MSCs-CM-treated group showed a significantly decreased IL-4 mRNA expression, compared to the (+) Con group. In the analysis of T cell receptor signal, the phosphorylation of MAP kinases, translocation of p65, and activation of NFAT1 were inhibited after T-MSCs-CM. Conclusions. Our findings suggest that T-MSCs-CM showed a partial immunomodulatory effect on the AR mouse model by the inhibition of T cell activation via MAP kinase, p65, and NFAT1.