bluuebunny/crossref_metadata_2025 huggingface dataset:
Making Data and Workflows Findable for Machines
Authors: Weigel Tobias , Schwardmann Ulrich , Klump Jens , Bendoukha Sofiane , Quick Robert
Published: November 2019

Research data currently face a huge increase of data objects with an increasing variety of types (data types, formats) and variety of workflows by which objects need to be managed across their lifecycle by data infrastructures. Researchers desire to shorten the workflows from data generation to analysis and publication, and the full workflow needs to become transparent to multiple stakeholders, including research administrators and funders. This poses challenges for research infrastructures and user-oriented data services in terms of not only making data and workflows findable, accessible, interoperable and reusable, but also doing so in a way that leverages machine support for better efficiency. One primary need to be addressed is that of findability, and achieving better findability has benefits for other aspects of data and workflow management. In this article, we describe how machine capabilities can be extended to make workflows more findable, in particular by leveraging the Digital Object Architecture, common object operations and machine learning techniques.
Ontology-based Access Control for FAIR Data
Authors: Brewster Christopher , Nouwt Barry , Raaijmakers Stephan , Verhoosel Jack
Published: November 2019

This paper focuses on fine-grained, secure access to FAIR data, for which we propose ontology-based data access policies. These policies take into account both the FAIR aspects of the data relevant to access (such as provenance and licence), expressed as metadata, and additional metadata describing users. With this tripartite approach (data, associated metadata expressing FAIR information, and additional metadata about users), secure and controlled access to object data can be obtained. This yields a security dimension to the “A” (accessible) in FAIR, which is clearly needed in domains like security and intelligence. These domains need data to be shared under tight controls, with widely varying individual access rights. In this paper, we propose an approach called Ontology-Based Access Control (OBAC), which utilizes concepts and relations from a data set's domain ontology. We argue that ontology-based access policies contribute to data reusability and can be reconciled with privacy-aware data access policies. We illustrate our OBAC approach through a proof-of-concept and propose that OBAC to be adopted as a best practice for access management of FAIR data.
FAIR Convergence Matrix: Optimizing the Reuse of Existing FAIR-Related Resources
Authors: Sustkova Hana Pergl , Hettne Kristina Maria , Wittenburg Peter , Jacobsen Annika , Kuhn Tobias , Pergl Robert , Slifka Jan , McQuilton Peter , Magagna Barbara , Sansone Susanna-Assunta , Stocker Markus , Imming Melanie , Lannom Larry , Musen Mark , Schultes Erik
Published: November 2019

The FAIR principles articulate the behaviors expected from digital artifacts that are Findable, Accessible, Interoperable and Reusable by machines and by people. Although by now widely accepted, the FAIR Principles by design do not explicitly consider actual implementation choices enabling FAIR behaviors. As different communities have their own, often well-established implementation preferences and priorities for data reuse, coordinating a broadly accepted, widely used FAIR implementation approach remains a global challenge. In an effort to accelerate broad community convergence on FAIR implementation options, the GO FAIR community has launched the development of the FAIR Convergence Matrix. The Matrix is a platform that compiles for any community of practice, an inventory of their self-declared FAIR implementation choices and challenges. The Convergence Matrix is itself a FAIR resource, openly available, and encourages voluntary participation by any self-identified community of practice (not only the GO FAIR Implementation Networks). Based on patterns of use and reuse of existing resources, the Convergence Matrix supports the transparent derivation of strategies that optimally coordinate convergence on standards and technologies in the emerging Internet of FAIR Data and Services.
Social Data: CESSDA Best Practices
Authors: Dekker Ron
Published: November 2019

The European Commission report “Turning FAIR into reality” provides an index of 27 FAIR Action Plan recommendations. This index is used for a self-assessment on CESSDA, the Consortium of European Social Science Data Archives. CESSDA is performing well on “Concepts for FAIR implementation”, “Skills for FAIR”, and “Investment in FAIR”; there is work in progress on “FAIR culture”, and work to start up on “FAIR ecosystem” and especially on “Incentives and metrics for FAIR data and services”. Next, an analysis on the FAIR components, reveals that CESSDA has accomplished the “F”, is working on the “A” – considering the sensitivity and security requirements of social data, just started on “I”, and that there is lack of clarity on what should be in “R”. On Findability, the CESSDA Data Catalogue is explained, showing the building blocks that need to be in place before one can produce a catalogue. The article ends with a forward look on CESSDA's deployment on the FAIR principles.
State of FAIRness in ESFRI Projects
Authors: Wittenburg Peter , de Jong Franciska , van Uytvanck Dieter , Cocco Massimo , Jeffery Keith , Lautenschlager Michael , Thiemann Hannes , Hellström Margareta , Asmi Ari , Holub Petr
Published: November 2019

Since 2009 initiatives that were selected for the roadmap of the European Strategy Forum on Research Infrastructures started working to build research infrastructures for a wide range of research disciplines. An important result of the strategic discussions was that distributed infrastructure scenarios were now seen as “complex research facilities” in addition to, for example traditional centralised infrastructures such as CERN. In this paper we look at five typical examples of such distributed infrastructures where many researchers working in different centres are contributing data, tools/services and knowledge and where the major task of the research infrastructure initiative is to create a virtually integrated suite of resources allowing researchers to carry out state-of-the-art research. Careful analysis shows that most of these research infrastructures worked on the Findability, Accessibility, Interoperability and Reusability dimensions before the term “FAIR” was actually coined. The definition of the FAIR principles and their wide acceptance can be seen as a confirmation of what these initiatives were doing and it gives new impulse to close still existing gaps. These initiatives also seem to be ready to take up the next steps which will emerge from the definition of FAIR maturity indicators. Experts from these infrastructures should bring in their 10-years' experience in this definition process.
The Need of Industry to Go FAIR
Authors: van Vlijmen Herman , Mons Albert , Waalkens Arne , Franke Wouter , Baak Arie , Ruiter Gerbrand , Kirkpatrick Christine , da Silva Santos Luiz Olavo Bonino , Meerman Bert , Jellema Renger , Arts Derk , Kersloot Martijn , Knijnenburg Sebastiaan , Lusher Scott , Verbeeck Rudi , Neefs Jean-Marc
Published: November 2019

The industry sector is a very large producer and consumer of data, and many companies traditionally focused on production or manufacturing are now relying on the analysis of large amounts of data to develop new products and services. As many of the data sources needed are distributed and outside the company, FAIR data will have a major impact, both by reducing the existing internal data silos and by enabling the efficient integration with external (public and commercial) data. Many companies are still in the early phases of internal data “FAIRification”, providing opportunities for SMEs and academics to apply and develop their expertise on FAIR data in collaborations and public-private partnerships. For a global Internet of FAIR Data & Services to thrive, also involving industry, professional tools and services are essential. FAIR metrics and certifications on individuals, data, organizations, and software, must ensure that data producers and consumers have independent quality metrics on their data. In this opinion article we reflect on some industry specific challenges of FAIR implementation to be dealt with when choices are made regarding “Industry GOing FAIR”.
Considerations for the Conduction and Interpretation of FAIRness Evaluations
Authors: de Miranda Azevedo Ricardo , Dumontier Michel
Published: November 2019

The FAIR principles were received with broad acceptance in several scientific communities. However, there is still some degree of uncertainty on how they should be implemented. Several self-report questionnaires have been proposed to assess the implementation of the FAIR principles. Moreover, the FAIRmetrics group released 14, general-purpose maturity for representing FAIRness. Initially, these metrics were conducted as open-answer questionnaires. Recently, these metrics have been implemented into a software that can automatically harvest metadata from metadata providers and generate a principle-specific FAIRness evaluation. With so many different approaches for FAIRness evaluations, we believe that further clarification on their limitations and advantages, as well as on their interpretation and interplay should be considered.
Toward Training and Assessing Reproducible Data Analysis in Data Science Education
Authors: Yu Bei , Hu Xiao
Published: November 2019

Reproducibility is a cornerstone of scientific research. Data science is not an exception. In recent years scientists were concerned about a large number of irreproducible studies. Such reproducibility crisis in science could severely undermine public trust in science and science-based public policy. Recent efforts to promote reproducible research mainly focused on matured scientists and much less on student training. In this study, we conducted action research on students in data science to evaluate to what extent students are ready for communicating reproducible data analysis. The results show that although two-thirds of the students claimed they were able to reproduce results in peer reports, only one-third of reports provided all necessary information for replication. The actual replication results also include conflicting claims; some lacked comparisons of original and replication results, indicating that some students did not share a consistent understanding of what reproducibility means and how to report replication results. The findings suggest that more training is needed to help data science students communicating reproducible data analysis.
Perception and Comprehension of the Extended Forecast Graphic: A Survey of Broadcast Meteorologists and the Public
Authors: Reed Jacob R. , Senkbeil Jason C.
Published: November 2019

There have been multiple efforts in recent years to simplify visual weather forecast products, with the goal of more efficient risk communication for the general public. Many meteorological forecast products, such as the cone of uncertainty, storm surge graphics, warning polygons, and Storm Prediction Center (SPC) convective outlooks, have created varying levels of public confusion resulting in revisions, modifications, and improvements. However, the perception and comprehension of private weather graphics produced by television stations has been largely overlooked in peer-reviewed research. The goal of this study is to explore how the extended forecast graphic, more commonly known as the 7, 10 day, etc., is utilized by broadcasters and understood by the public. Data were gathered from surveys with the general public and also from broadcast meteorologists. Results suggest this graphic is a source of confusion and highlights a disconnect between the meteorologists producing the graphic and the content prioritized by their audiences. Specifically, timing and intensity of any precipitation or adverse weather events are the two most important variables to consider from the viewpoint of the public. These variables are generally absent from the extended forecast graphic, thus forcing the public to draw their own conclusions, which may differ from what the meteorologist intends to convey. Other results suggest the placement of forecast high and low temperatures, use of probability of precipitation, icon inconsistency, and length of time the graphic is shown also contribute to public confusion and misunderstanding.
Inverse Modeling of Global and Regional Energy and Water Cycle Fluxes using Earth Observation Data
Authors: Thomas Christopher M. , Dong Bo , Haines Keith
Published: November 2019

The NASA Energy and Water Cycle Study (NEWS) climatology is a self-consistent coupled annual and seasonal cycle solution for radiative, turbulent, and water fluxes over Earth’s surface using Earth observation data covering 2000–09. Here we seek to improve the NEWS solution, particularly over the ocean basins, by considering spatial covariances in the observation errors (some evidence for which is found by comparing five turbulent flux products over the oceans) and by introducing additional horizontal transports from ocean reanalyses as weak constraints. By explicitly representing large error covariances between surface heat flux components over the major ocean basins we retain the flux contrasts present in the original data and infer additional heat losses over the North Atlantic Ocean, more consistent with a strong Atlantic overturning. This change does not alter the global flux balance but if only the errors in evaporation and precipitation are correlated then those fluxes experience larger adjustments (e.g., the surface latent heat flux increases to 85 ± 2 W m−2). Replacing SeaFlux v1 with J-OFURO v3 (Japanese Ocean Flux Data Sets with Use of Remote Sensing Observations) ocean fluxes also leads to a considerable increase in the global latent heat loss as well as a larger North Atlantic heat loss. Furthermore, including a weak constraint on the horizontal transports of heat and freshwater from high-resolution ocean reanalyses improves the net fluxes over the North Atlantic, Caribbean Sea, and Arctic Ocean, without any impact on the global flux balances. These results suggest that better characterized flux uncertainties can greatly improve the quality of the optimized flux solution.
Modal Analysis of Internal Wave Propagation and Scattering over Large-Amplitude Topography
Authors: Lahaye Noé , Llewellyn Smith Stefan G.
Published: November 2019

Coupled-mode equations describing the propagation and scattering of internal waves over large-amplitude arbitrary topography in a two-dimensional stratified fluid are derived. They consist of a simple set of ordinary differential equations describing the evolution of modal amplitudes, based on an orthogonality condition that allows one to distinguish leftward- and rightward-propagating modes. The coupling terms expressing exchange of energy between modes are given in an analytical form using perturbation theory. This allows the derivation of a weak-topography approximate solution, generalizing previous linear solutions for a barotropic forcing that were described in 2002 by Llewellyn Smith and Young . In addition, the orthogonality condition derived is valid for a different set of eigenmodes defined on a sloping bottom, which shows a better convergence rate when compared with the standard set of modes. The work presented here provides a useful and simple framework for the investigation of internal wave propagation in an inhomogeneous ocean, along with theoretical insight.
Screening for Orthostatic Intolerance in Symptomatic Children Presenting for Concussion Care
Authors: Kokorelis Christina , Slomine Beth , Rowe Peter C. , Suskauer Stacy
Published: November 2019

Following concussion, children often experience nonspecific symptoms that overlap with those of other common pediatric conditions, including orthostatic intolerance (OI). The primary goal of this study was to evaluate OI in youth presenting for clinical care for concussion and reporting symptoms frequently observed in OI. Eighty-two of 114 patients aged 10 to 22 years endorsed symptoms based on 8 screening questions, and 24 of those 82 patients met criteria for OI based on an active standing test. No screening question generated clinically useful likelihood ratios for predicting OI. The prevalence of OI in this cohort is considerably higher than estimates in the general pediatric population, suggesting a link between concussion and OI. Future work is needed to evaluate the best method of testing for OI, the natural history of OI symptoms in youth with concussion, and the response to intervention in children with both concussion and OI.
Evaluating Universities’ Readiness in Qualifying Graduates to Achieve Saudi Vision 2030: A Constructive Analysis of Baldrige Scale
Authors: ALSharari Mufadhi Ratyan Mufadhi
Published: November 2019

The study sought to measure the Saudi universities’ capabilities and readiness for qualifying graduates to achieve the Saudi Vision 2030 to overcome the gap between the readiness of the university and the national goal if exist to help decision makers to explore actual achievements against the national goals. To assess the performance, this study adopted the Baldrige Scale for excellence in education as a measurement tool which was modified by adding the scientific research requirements and collaboration among universities and university investments as a modern domain of the scale’s entities based on Saudi Vision demands 2030. A Baldrige-based survey has been conducted on a study group of ( n = 540) academics from the Northern Border University. Following a statistical test of Relative Importance Index (RII) and the Contractual Pathway Analysis, the study revealed that the university’s readiness to outcome a qualified graduate is relatively moderate, with a clear decline in the university investment and research publication consultants. Furthermore, there is a strong correlation between the measurement entities used in the readiness test.
What Do Surveys of Program Completers Tell Us About Teacher Preparation Quality?
Authors: Bastian Kevin C. , Sun Min , Lynn Heather
Published: November 2019

Surveys of teacher preparation program (TPP) completers have become one widely used measure for program accountability and improvement, yet there is little evidence as to whether perceptions of preparation experiences predict the workforce outcomes of teachers. In the present study, we use statewide completer survey data from North Carolina to assess whether perceptions of preparation quality and opportunities to learn during teacher preparation predict completers’ value-added estimates, evaluation ratings, and retention. We perform multiple analyses to address validity concerns—that is, selection into TPPs, sorting into K-12 schools, simultaneity in survey and outcome measures, and differential survey response rates across TPPs. Results are not always consistent across these analyses; however, evidence suggests that completer perceptions are modestly associated with teacher effectiveness and retention. Continued research can further address validity concerns and build a body of evidence on completer perceptions and teacher outcomes.
Professional status and well-being in healthcare organizations
Authors: Tomo Andrea , De Simone Stefania
Published: November 2019

This paper aims to explore what aspects of work-life affect healthcare professionals’ well-being and if these aspects may explain a possible categorization considering different professional status. We administered a slightly altered version of the Copenhagen Psychosocial Questionnaire to assess the well-being of patient care workers in a government-funded healthcare organization in Southern Italy. Then, we run an analysis of variance test to explore the aspects affecting the well-being of patient care workers, and to understand if these aspects vary per different professional status (physicians, nurses, and health technicians). Results show important differences among the various professional categories of patient care workers, thus providing the basis for reflections and interventions to improve employee well-being, relevant from a theoretical, practical, and above all policy-making perspectives.
Epidemiological differences and risk factors for hospitalization in people living with HIV in Istanbul, Turkey
Authors: Şenoğlu Sevtap , Yeşilbağ Zuhal , Karaosmanoğlu Hayat K , Aydın Özlem A
Published: November 2019

We aimed to determine the risk factors for hospitalization in treatment-naïve people living with HIV (PLHIV) and also the frequency of HIV-related comorbidities in hospitalized patients. Sociodemographic, clinical, and laboratory findings of treatment-naïve PLHIV followed up in our department between January 2015 and July 2018 were retrospectively evaluated and risk factors for hospitalization at initial presentation were analyzed. A total of 629 patients were included. In all, 558 patients (88.7%) were male and 326 (51.8%) were men who have sex with men (MSM), and 8.6% of all patients were hospitalized at initial presentation. When comparing outpatient and inpatient groups, the mean age (p < 0.001), rates of having heterosexual (HS) intercourse (p < 0.001), low education level (p < 0.001), late presenters (p < 0.001), and CD4 cell count < 50 cells/mm3 (p < 0.001) were significantly higher in the inpatient group. In logistic regression analysis, older age and CD4 T lymphocyte count < 50 cells/mm3 were found to be independent risk factors for hospitalization. Among hospitalized patients, 55.5% had oropharyngeal/esophageal candidiasis, 38.9% had tuberculosis, corresponding to a HIV-related comorbidity in 118 patients, among whom a mortality rate of 9.2% was detected. The rate of hospitalization was high among our patients. The majority of the hospitalized patients were HS individuals with a relatively older age who had low educational level. A lower rate of hospitalizations in a higher risk group such as MSM suggests that educational and preventive activities are required to increase awareness and to encourage HIV testing, not only in high-risk groups, but also in the general population.
The Sign Effect in Past and Future Discounting
Authors: Molouki Sarah , Hardisty David J. , Caruso Eugene M.
Published: November 2019

We compared the extent to which people discounted positive and negative events in the future and in the past. We found that the tendency to discount gains more than losses (i.e., the sign effect) emerged more strongly for future than for past outcomes. We present evidence from six studies (total N = 1,077) that the effect of tense on discounting is tied to differences in the contemplation emotion of these events, which we assessed by measuring participants’ emotions while they either anticipated or remembered the event. We ruled out loss aversion, uncertainty, utility curvature, thought frequency, and connection to the future and past self as explanations for this phenomenon, and we discuss why people experience a distinct mixture of emotions when contemplating upcoming events.
Position and attitude tracking of uncertain quadrotor unmanned aerial vehicles based on non-singular terminal super-twisting algorithm
Authors: Alqaisi Walid , Kali Yassine , Ghommam Jawhar , Saad Maarouf , Nerguizian Vahé
Published: November 2019

This paper proposes an improved non-singular terminal super-twisting control for the problem of position and attitude tracking of quadrotor systems suffering from uncertainties and disturbances. The super-twisting algorithm is a second-order sliding mode known to be a very effective control used to provide high precision and less chattering for uncertain nonlinear electromechanical systems. The proposed method is based on a non-singular terminal sliding surface with new exponent that solves the problem of singularity. The design procedure and the stability analysis of the closed-loop system using Lyapunov theory are detailed for the considered system. Finally, the proposed control scheme is tested in simulations and by experiments on the parrot-rolling spider quadrotor. Moreover, a comparison is made with the standard super-twisting algorithm in the simulation part. The results obtained show adequate performance in trajectory tracking and chattering reduction.
Deglutition in Patients With Hypernasality Associated With Unilateral Cleft Lip and Palate Evaluated With High-Resolution Manometry
Authors: Kallusky Johanna , Zimmerer Rüdiger , Tavassol Frank , Gellrich Nils-Claudius , Ptok Martin , Jungheim Michael
Published: November 2019

Objective:

To evaluate pharyngeal pressure profiles during swallowing in patients with unilateral cleft lip and palate (UCLP) and identify compensation mechanisms.

Design:

Prospective experimental study.

Setting:

University Hospital and Medical School.

Participants:

Ten volunteers and 10 patients with nonsyndromic repaired UCLP with hypernasality (age: 19-27 years, 5 females and 5 males per group) were included.

Interventions:

All participants swallowed 2 and 10 mL of water and underwent high-resolution manometry (HRM).

Main Outcome Measures:

Pharyngeal and upper esophageal sphincter (UES) parameters were measured using HRM. Student t test was used for statistical intergroup comparisons. Additionally, the Sydney Swallowing Questionnaire (SSQ) was used as a subjective measure.

Results:

Patients exhibited reduced velopharyngeal closing pressure and velopharyngeal and tongue base (TB) region contraction times, compared to volunteers ( P < .05). The UES opening and closing functions did not change. The SSQ revealed nasal regurgitation in some patients.

Conclusions:

In patients with UCLP, velopharyngeal region alterations are caused by impaired muscle force and function. The reduced TB contraction time may be a compensation mechanism allowing bolus transportation without nasal regurgitation. However, deglutition is not completely altered since UES function remains normal. Future studies will need to reveal at which point a decrease in velopharyngeal closing pressure will result in velopharyngeal insufficiency.
An Analysis of Mobility Patterns in Sexual Homicide
Authors: Chopin Julien , Caneppele Stefano , Beauregard Eric
Published: November 2019

This article—based on a national data set ( N = 173)—focuses on extrafamilial sexual homicides and their spatial mobility. The study combines the location of the crime scene and the offenders and victims’ residences in mobility crime triangles. The findings reveal that most of the homicides fall within the categories of offender mobility and total mobility. Our results show the validity of the distance decay function, with over 70% of homicides occurring within 10 km of the offender’s residence. It appears that under certain circumstances, sexual murderers perceive their surroundings as a safe place to commit a homicide. Finally, the study proposes a four-category spatial typology of sexual homicide.
Human models of NUP98-KDM5A megakaryocytic leukemia in mice contribute to uncovering new biomarkers and therapeutic vulnerabilities
Authors: Cardin Sophie , Bilodeau Mélanie , Roussy Mathieu , Aubert Léo , Milan Thomas , Jouan Loubna , Rouette Alexandre , Laramée Louise , Gendron Patrick , Duchaine Jean , Decaluwe Hélène , Spinella Jean-François , Mourad Stéphanie , Couture Françoise , Sinnett Daniel , Haddad Élie , Landry Josette-Renée , Ma Jing , Humphries R. Keith , Roux Philippe P. , Hébert Josée , Gruber Tanja A. , Wilhelm Brian T. , Cellot Sonia
Published: November 2019

Key Points

Engineered human models of high-fatality pediatric leukemia are relevant to uncover disease biomarkers and therapeutic vulnerabilities. NUP98-KDM5A–associated AMKL expresses SELP, MPIG6B, and NEO1 biomarkers and is sensitive to pharmacologic inhibition with ruxolitinib.
Variation in the initial assessment and investigation for ovarian cancer in symptomatic women: a systematic review of international guidelines
Authors: Funston Garth , Van Melle Marije , Baun Marie-Louise Ladegaard , Jensen Henry , Helsper Charles , Emery Jon , Crosbie Emma J. , Thompson Matthew , Hamilton Willie , Walter Fiona M.
Published: November 2019

Background

Women with ovarian cancer can present with a variety of symptoms and signs, and an increasing range of tests are available for their investigation. A number of international guidelines provide advice for the initial assessment of possible ovarian cancer in symptomatic women. We systematically identified and reviewed the consistency and quality of these documents.

Methods

MEDLINE, Embase, guideline-specific databases and professional organisation websites were searched in March 2018 for relevant clinical guidelines, consensus statements and clinical pathways, produced by professional or governmental bodies. Two reviewers independently extracted data and appraised documents using the Appraisal for Guidelines and Research Evaluation 2 (AGREEII) tool.

Results

Eighteen documents from 11 countries in six languages met selection criteria. Methodological quality varied with two guidance documents achieving an AGREEII score ≥ 50% in all six domains and 10 documents scoring ≥50% for “Rigour of development” (range: 7–96%). All guidance documents provided advice on possible symptoms of ovarian cancer, although the number of symptoms included in documents ranged from four to 14 with only one symptom (bloating/abdominal distension/increased abdominal size) appearing in all documents. Fourteen documents provided advice on physical examinations but varied in both the examinations they recommended and the physical signs they included. Fifteen documents provided recommendations on initial investigations. Transabdominal/transvaginal ultrasound and the serum biomarker CA125 were the most widely advocated initial tests. Five distinct testing strategies were identified based on the number of tests and the order of testing advocated: ‘single test’, ‘dual testing’, ‘sequential testing’, ‘multiple testing options’ and ‘no testing’.

Conclusions

Recommendations on the initial assessment and investigation for ovarian cancer in symptomatic women vary considerably between international guidance documents. This variation could contribute to differences in the way symptomatic women are assessed and investigated between countries. Greater research is needed to evaluate the assessment and testing approaches advocated by different guidelines and their impact on ovarian cancer detection.
Suppression of nicotinamide phosphoribosyltransferase expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin
Authors: Bolandghamat Pour Zahra , Nourbakhsh Mitra , Mousavizadeh Kazem , Madjd Zahra , Ghorbanhosseini Seyedeh Sara , Abdolvahabi Zohreh , Hesari Zahra , Ezzati Mobasser Samira
Published: November 2019

Background

Nicotinamide phosphoribosyltransferase (NAMPT) enzyme acts as the major enzyme in the nicotinamide adenine dinucleotide (NAD) synthesis salvage pathway. Deregulation of NAD could be associated with progression of several cancers such as breast cancer. Here, the consequence of NAMPT inhibition by miR-154 was investigated on breast cancer cells.

Methods

MDA-MB-231 and MCF-7 cancer cell lines were transfected with the mimic and inhibitors of miR-154-5p and their corresponding negative controls. Consequently, levels of NAMPT and NAD were assayed employing qRT-PCR, Western blotting and enzymatic method, respectively. Subsequently, flow cytometry and colorimetric methods were performed to evaluate apoptosis and cell viability. Bioinformatics analyses as well as luciferase assay were done to investigate whether the 3′-UTR of NAMPT is directly targeted by miR-154.

Results

According to the obtained results, NAMPT was recognized as a target for binding of miR-154 and the levels of this miRNA was inversely associated with both mRNA and protein levels of NAMPT in breast cancer cell lines. Functionally, miR-154 inhibited the NAD salvage pathway leading to a remarkable decrease in cell viability and increased rate of cell death. When breast cancer cells were simultaneously treated with doxorubicin and miR-154 mimic, cell viability was considerably reduced compared to treatment with doxorubicin alone in both cell lines.

Conclusions

It was concluded that the inhibition of NAD production by miR-154 might be introduced as an appropriate therapeutic approach in order to improve breast cancer outcome either alone or in combination with other conventional chemotherapeutic agents.
Systemic high-dose intravenous methotrexate in patients with central nervous system metastatic breast cancer
Authors: Bazan F. , Dobi E. , Royer B. , Curtit E. , Mansi L. , Menneveau N. , Paillard M. J. , Meynard G. , Villanueva C. , Pivot X. , Chaigneau L.
Published: November 2019

Background

Infusion of high-dose intravenous methotrexate (MTX) has been demonstrating to penetrate the blood-brain barrier. The aim of this present study was to assess the efficacy and safety of high dose MTX in patients with central nervous system (CNS) metastases of breast cancer.

Methods

Twenty-two patients with CNS metastases treated by MTX (3 g/m2) between April 2004 and October 2009 were enrolled. Clinical response rate, time to progression (TTP), overall survival (OS), and safety were assessed.

Results

In terms of brain metastases, 2 patients (9%) achieved a partial response, 10 patients (45%) had disease stabilization, and 10 patients (45%) had disease progression. In others metastatic sites, 7 patients (39%) achieved a disease stabilization, and 11 patients (61%) had disease progression. TTP and OS were 2.1 (95%CI 1.4–2.9) and 6.3 (95%CI 1.8–10) months, respectively.

Conclusion

High-dose MTX demonstrated a moderate activity at 3 g/m2. Nonetheless, the favorable toxicity profile should suggest the possibility to increase the dosage and further study are planned.
A clinical trial of enteral Levetiracetam for acute seizures in pediatric cerebral malaria
Authors: Birbeck Gretchen L. , Herman Susan T. , Capparelli Edmund V. , Dzinjalamala Fraction K. , Abdel Baki Samah G. , Mallewa Macpherson , Toto Neema M. , Postels Douglas G. , Gardiner Joseph C. , Taylor Terrie E. , Seydel Karl B.
Published: November 2019

Background

Acute seizures are common in pediatric cerebral malaria (CM), but usual care with phenobarbital risks respiratory suppression. We undertook studies of enteral levetiracetam (eLVT) to evaluate pharmacokinetics (PK), safety and efficacy including an open-label, randomized controlled trial (RCT) comparing eLVT to phenobarbital.

Methods

Children 24–83 months old with CM were enrolled in an eLVT dose-finding study starting with standard dose (40 mg/kg load, then 30 mg/kg Q12 hours) titrated upward until seizure freedom was attained in 75% of subjects.

The RCT that followed randomized children to eLVT vs. phenobarbital for acute seizures and compared the groups on minutes with seizures based upon continuous electroencephalogram. Due to safety concerns, midway through the study children allocated to phenobarbital received the drug only if they continued to have seizures (either clinically or electrographically) after benzodiazepine treatment. Secondary outcomes were treatment failure requiring cross over, coma duration and neurologic sequelae at discharge. PK and safety assessments were also undertaken.

Results

Among 30 comatose CM children, eLVT was rapidly absorbed and well-tolerated. eLVT clearance was lower in patients with higher admission serum creatinine (SCr), but overall PK parameters were similar to prior pediatric PK studies. Within 4 h of the first dose, 90% reached therapeutic levels (> 20 μg/mL) and all were above 6 μg/mL. 7/7 children achieved seizure freedom on the initial eLVT dose.

Comparing 23 eLVT to 21 phenobarbital patients among whom 15/21 received phenobarbital, no differences were seen for minutes with seizure, seizure freedom, coma duration, neurologic sequelae or death, but eLVT was safer (p = 0.019). Phenobarbital was discontinued in 3/15 due to respiratory side effects.

Conclusion

Enteral LVT offers an affordable option for seizure control in pediatric CM and is safer than phenobarbital.

Trial registration

NCT01660672.

NCT01982812.
Bacterial profile and antibacterial susceptibility of otitis media among pediatric patients in Hawassa, Southern Ethiopia: cross-sectional study
Authors: Tadesse Bereket , Shimelis Techalew , Worku Mesfin
Published: November 2019

Background

Otitis Media (OM) is the most common disease of childhood. Twenty thousand people die each year from otitis media. It is an important cause of preventable hearing loss, affects children's intellectual performance and language development. There are very small numbers of studies done in Ethiopia concerning this topic. This study aimed to identify bacterial pathogens related to ear infection and to assess antibacterial susceptibility of isolated organisms.

Method

A cross-sectional study was conducted on 152 children from April 2018 to July 2018 at selected health facilities in Hawassa city, SNNPR, Ethiopia. All pediatric patients having ear discharge were included. Convenient sampling technique was used to collect clinical and demographic data using standard questionnaires after child care-takers signed the consent. Ear discharge specimens were collected using a sterile swab, and transported using Amies transport media to Hawassa University Comprehensive Specialized Hospital laboratory. Bacterial isolates were characterized based on colony appearance, Gram reaction, culture characteristics, and biochemical tests after inoculating on appropriate culture media. Antibacterial susceptibility testing was performed using the disc diffusion method according to the criteria of the Clinical and Laboratory Standards Institute (CLSI).

Results

Among 152 children included, 115(75.6%) of them demonstrated pathogenic bacterial growth. Staphylococcus aureus 41(27%) was the most frequently isolated pathogen, followed by Proteus mirabilis 19 (12.5%). Of the total isolates, 11.2 and 7.3% were resistant to gentamicin and ciprofloxacin respectively. Over three-fourth (85.2%) of the isolates were resistant to ampicillin. More than two-third of the isolates were resistant to both penicillin (71.4%) and trimethoprim-sulphamethoxazole (72.0%).

Conclusions

S. aureus is the most commonly isolated bacterial pathogen from ear discharge among children. Even though gentamicin is a parenteral drug and ciprofloxacin is rarely used in children due to concerns of bone/joint effects, these two drugs were highly effective antibiotics and thus should be considered in treating children with otitis media since most organisms were resistance or poor response to first line drugsHigh level of antibiotic resistance was observed so antimicrobial susceptibility test is needed before prescribing drugs for treatment of OM.
Characterization of mental health in cannabis dispensary users, using structured clinical interviews and standardized assessment instruments
Authors: Yau Jade C. , Yu Shu Min , Panenka William J. , Pearce Hadley , Gicas Kristina M. , Procyshyn Ric M. , MacCallum Caroline , Honer William G. , Barr Alasdair M.
Published: November 2019

Background

Cannabis is commonly used for its medical properties. In particular, cannabis is purported to have beneficial effects on a wide range of neuropsychiatric conditions. Studies assessing mental health in cannabis dispensary users typically evaluate symptoms using self-report check lists, which provide limited information about symptom severity, and whether subjects meet criteria for a psychiatric diagnosis. There is, therefore, a need for studies which assess mental health in dispensary users with standardized and well validated scientific instruments, such as those used in clinical drug trials.

Methods

One hundred medical cannabis users were recruited from a community dispensary. All subjects completed a structured clinical interview with the Mini-International Neuropsychiatric Interview (MINI). Subjects also completed the Perceived Stress Scale-10, PROMIS Fatigue Scale, PROMIS Sleep Disturbance Scale, Beck Depression Inventory, the Patient Health Questionnaire-15 and the Brief Pain Inventory. Details about cannabis use were also recorded.

Results

Lifetime prevalence of mental illness in this cohort was high, and a large proportion of subjects endorsed psychological symptoms. The proportion of subjects who met criteria for classification of a current psychiatric disorder was low for mood disorders, but high for anxiety disorders and substance abuse/dependence. Cannabis use differed between the main psychiatric conditions.

Conclusions

The present results indicate that rates of mental illness may be high in medical cannabis dispensary users. Use of structured clinical assessments combined with standardized symptom severity questionnaires provide a feasible way to provide a more rigorous and detailed evaluation of conditions and symptoms in this population.
Effect and cost of two successive home visits to increase HIV testing coverage: a prospective study in Lesotho, Southern Africa
Authors: Labhardt Niklaus Daniel , Ringera Isaac , Lejone Thabo Ishmael , Amstutz Alain , Klimkait Thomas , Muhairwe Josephine , Glass Tracy Renee
Published: November 2019

Background

Home-based HIV testing and counselling (HB-HTC) is frequently used to increase awareness of HIV status in sub-Saharan Africa. Whereas acceptance of HB-HTC is usually high, testing coverage may remain low due to household members being absent during the home visits. This study assessed whether two consecutive visits, one during the week, one on the weekend, increase coverage.

Methods

The study was a predefined nested-study of the CASCADE-trial protocol and conducted in 62 randomly selected villages and 17 urban areas in Butha-Buthe district, Lesotho. HB-HTC teams visited each village/urban area twice: first during a weekday, followed by a weekend visit to catch-up for household members absent during the week. Primary outcome was HTC coverage after first and second visit. Coverage was defined as all individuals who knew their HIV status out of all household members (present and absent).

Results

HB-HTC teams visited 6665 households with 18,286 household members. At first visit, 69.2 and 75.4% of household members were encountered in rural and urban households respectively (p < 0.001) and acceptance for testing was 88.5% in rural and 79.5% in urban areas (p < 0.001), resulting in a coverage of 61.8 and 61.5%, respectively. After catch-up visit, the HTC coverage increased to 71.9% in rural and 69.4% in urban areas. The number of first time testers was higher at the second visit (47% versus 35%, p < 0.001). Direct cost per person tested and per person tested HIV positive were lower during weekdays (10.50 and 335 USD) than during weekends (20 and 1056 USD).

Conclusions

A catch-up visit on weekends increased the proportion of persons knowing their HIV status from 62 to 71% and reached more first-time testers. However, cost per person tested during catch-up visits was nearly twice the cost during first visit.

Trial registration

NCT02692027 (prospectively registered on February 21, 2016).
Assessment of factors affecting vaccine cold chain management practice in public health institutions in east Gojam zone of Amhara region
Authors: Bogale Hewan Adam , Amhare Abebe Feyissa , Bogale Alemtsehay Adam
Published: November 2019

Background

Maintaining quality of vaccines is one of the main challenges of immunization programs in Ethiopia. The objectiveof this study is to assess the factor affecting vaccine cold chain management practice in immunization health institutions in East Gojam zone of Amhara region, Ethiopia.

Method

An institutional based cross-sectional study was conducted from March to April 2017 in ten districts of East Gojam zone of Amhara Region. Descriptive statistics and Logistic regression analysis were carried out to identify factors related to the practice of cold chain management.

Result

Among 60 health institutions, only 46(76.7%) had functional refrigerators. Twenty-one (35%) had a functional generator for backup service and 28(46.6%) had a car/motorbike for transportation of vaccines in case of refrigerator/power failure. Twenty-nine (48.3%) had known the correct vaccine storage temperature (2 °C – 8 °C) in the refrigerator and the results of this study revealed that only 23(38.3%) of respondents had sufficient knowledge about vaccine cold chain management. The finding of this study also revealed that 35(58.3%) had appropriate vaccine cold chain management practice and the rest 25(41.7%) had inappropriate practice. Logistic regression showed us the knowledge gap and profession were significantly associated with vaccine cold chain management practice atP < 0.05.

Conclusion

This study indicates that there was a knowledge gap of health workers who are working on cold chain management. There is an urgent need to improve knowledge and practice on cold chain management through improved supervision and training at a different level of health care system.
Prognosis of pulmonary fibrosis presenting with a usual interstitial pneumonia pattern on computed tomography in patients with myeloperoxidase anti-neutrophil cytoplasmic antibody-related nephritis: a retrospective single-center study
Authors: Watanabe Toshikazu , Minezawa Tomoyuki , Hasegawa Midori , Goto Yasuhiro , Okamura Takuya , Sakakibara Yosuke , Niwa Yoshikazu , Kato Atsushi , Hayashi Masamichi , Isogai Sumito , Kondo Masashi , Yamamoto Naoki , Hashimoto Naozumi , Imaizumi Kazuyoshi
Published: November 2019

Background

Myeloperoxidase anti-neutrophil cytoplasmic antibody-related nephritis (MPO-ANCA nephritis) is occasionally accompanied by lung abnormalities such as pulmonary fibrosis. However, the clinical features of pulmonary fibrosis in patients with MPO-ANCA nephritis have not been well documented. This study was performed to compare the prognosis of a usual interstitial pneumonia (UIP) pattern of lung fibrosis in patients with MPO-ANCA nephritis with the prognosis of idiopathic pulmonary fibrosis (IPF).

Methods

We retrospectively reviewed the medical records of 126 patients with MPO-ANCA nephritis and identified 31 with a UIP pattern of lung fibrosis on high-resolution or thin-slice computed tomography (CT). We compared the characteristics and prognosis of these patients with those of 32 patients with IPF. In 18 patients from both groups, we assessed and compared the decline in lung volume over time using three-dimensional (3D) CT images reconstructed from thin-section CT data.

Results

The numbers of male and female patients were nearly equal among patients with MPO-ANCA nephritis exhibiting a UIP pattern; in contrast, significant male dominancy was observed among patients with IPF (p = 0.0021). Significantly fewer smokers were present among the patients with MPO-ANCA nephritis with a UIP pattern than among those with IPF (p = 0.0062). There was no significant difference in the median survival time between patients with MPO-ANCA nephritis with a UIP pattern (50.8 months) and IPF (55.8 months; p = 0.65). All patients with IPF in this cohort received antifibrotic therapy (pirfenidone or nintedanib). Almost half of the deaths that occurred in patients with MPO-ANCA nephritis with a UIP pattern were caused by non-respiratory-related events, whereas most deaths in patients with IPF were caused by respiratory failure such as acute exacerbation. In the 3D CT lung volume analyses, the rate of decline in lung volume was equivalent in both groups.

Conclusions

MPO-ANCA nephritis with a UIP pattern on CT may have an unfavorable prognosis equivalent to that of IPF with a UIP pattern treated with antifibrotic agents.