bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone Modifier Differentially Regulates Gene Expression and Unravels Survival Role of MicroRNA-494 in Jurkat Leukemia
Authors: Jayaraman Arathi , Zhou Tong , Jayaraman Sundararajan 
Published: April 2021

Background:
Although the protein-coding genes are subject to histone hyperacetylation-
mediated regulation, it is unclear whether microRNAs are similarly regulated in the T cell
leukemia Jurkat.

Objective:
To determine whether treatment with the histone modifier Trichostatin A could concurrently
alter the expression profiles of microRNAs and protein-coding genes.

Methods:
Changes in histone hyperacetylation and viability in response to drug treatment were analyzed,
respectively, using western blotting and flow cytometry. Paired global expression profiling
of microRNAs and coding genes was performed and highly regulated genes have been validated by
qRT-PCR. The interrelationships between the drug-induced miR-494 upregulation, the expression
of putative target genes, and T cell receptor-mediated apoptosis were evaluated using qRT-PCR,
flow cytometry, and western blotting following lipid-mediated transfection with specific anti-microRNA
inhibitors.

Results:
Treatment of Jurkat cells with Trichostatin A resulted in histone hyperacetylation and
apoptosis. Global expression profiling indicated prominent upregulation of miR-494 in contrast to
differential regulation of many protein-coding and non-coding genes validated by qRT-PCR. Although
transfection with synthetic anti-miR-494 inhibitors failed to block drug-induced apoptosis
or miR-494 upregulation, it induced the transcriptional repression of the PVRIG gene. Surprisingly,
miR-494 inhibition in conjunction with low doses of Trichostatin A enhanced the weak T cell receptor-
mediated apoptosis, indicating a subtle pro-survival role of miR-494. Interestingly, this prosurvival
effect was overwhelmed by mitogen-mediated T cell activation and higher drug doses,
which mediated caspase-dependent apoptosis.

Conclusion:
Our results unravel a pro-survival function of miR-494 and its putative interaction
with the PVRIG gene and the apoptotic machinery in Jurkat cells.
Design and Analysis of Hybrid Fused Filament Fabrication Apparatus for Fabrication of Composites
Authors: Yadav Aniket , Chohan Piyush , Kumar Ranvijay , Chohan Jasgurpreet Singh , Kumar Raman 
Published: April 2021

Background:
Additive manufacturing is the most recognized technology which uses
metals, polymer, ceramics, and composites for fabrication with a layer-by-layer deposition
strategy. Due to its lower cost, higher accuracy, and less material wastage, this technology is
used for engineering and domestic applications. But in many applications, there is a need to alter
the properties of the product in a specific direction with the help of some reinforcements. With
reinforcements, composite layers can be fabricated using additive manufacturing techniques,
which will enhance the directional properties. A novel apparatus is designed to spray the
reinforcement material into the printed structures quickly and precisely. This spray nozzle is
fully automated, which works according to toolpaths generated by slicing software. The
alternate deposition of layers of reinforcement and build materials helped to fabricate
customized composite products.

Objective:
This study aims to design and analyze the working principle of a novel composite
manufacturing technique that has been developed to fabricate composite materials using
additive manufacturing. The apparatus is numerically controlled by computer according to CAD
data, which facilitates the deposition of alternate reinforcement and matrix material layers. The
major challenges during the design process and the functioning of each component have been
explored.

Methods:
The design process is initiated after a comprehensive literature review is performed to
study previous composite manufacturing processes. The recent patents published by different
patent offices of the world are studied in detail, and analysis has been used to design a low-cost
composite fabrication apparatus. A liquid dispensing device comprises a storage tank attached
with a pump and microprocessor. The microprocessor receives the signal from the computer as
per tool paths generated by slicing software which decides the spray of reinforcements on
polymer layers. The spraying apparatus moves in coordination with the primary nozzle of the
Fused Filament Fabrication process.

Results:
The hybridization of the Fused Filament Fabrication process with the metal spray
process has been successfully performed. The apparatus facilitates the fabrication of low-cost
composite materials and the flexibility of complete customization of the composite
manufacturing process.

Conclusion:
The anisotropic behavior of products can be easily controlled and managed during
fabrication which can be used for different applications.
Utilizing Lean Software Methods To Improve Acceptance of Global eHealth Initiatives: Results From the Implementation of the Basic Emergency Care App
Authors: Rose Christian , Nichols Taylor , Hackner Daniel , Chang Julia , Straube Steven , Jooste Willem , Sawe Hendry , Tenner Andrea 
Published: April 2021

Background
Health systems in low- and middle-income countries face considerable challenges in providing high-quality accessible care. eHealth has had mounting interest as a possible solution given the unprecedented growth in mobile phone and internet technologies in these locations; however, few apps or software programs have, as of yet, gone beyond the testing phase, most downloads are never opened, and consistent use is extremely rare. This is believed to be due to a failure to engage and meet local stakeholder needs and the high costs of software development.

Objective
World Health Organization Basic Emergency Care course participants requested a mobile point-of-care adjunct to the primary course material. Our team undertook the task of developing this solution through a community-based participatory model in an effort to meet trainees’ reported needs and avoid some of the abovementioned failings. We aimed to use the well-described Lean software development strategy—given our familiarity with its elements and its ubiquitous use in medicine, global health, and software development—to complete this task efficiently and with maximal stakeholder involvement.

Methods
From September 2016 through January 2017, the Basic Emergency Care app was designed and developed at the University of California San Francisco. When a prototype was complete, it was piloted in Cape Town, South Africa and Dar es Salaam, Tanzania—World Health Organization Basic Emergency Care partner sites. Feedback from this pilot shaped continuous amendments to the app before subsequent user testing and study of the effect of use of the app on trainee retention of Basic Emergency Care course material.

Results
Our user-centered mobile app was developed with an iterative participatory approach with its first version available within 6 months and with high acceptance—95% of Basic Emergency Care Course participants felt that it was useful. Our solution had minimal direct costs and resulted in a robust infrastructure for subsequent assessment and maintenance and allows for efficient feedback and expansion.

Conclusions
We believe that utilizing Lean software development strategies may help global health advocates and researchers build eHealth solutions with a process that is familiar and with buy-in across stakeholders that is responsive, rapid to deploy, and sustainable.
Bispectral Index Alterations and Associations With Autonomic Changes During Hypnosis in Trauma Center Researchers: Formative Evaluation Study
Authors: Dunham C Michael , Burger Amanda J , Hileman Barbara M , Chance Elisha A , Hutchinson Amy E 
Published: April 2021

BackgroundPrevious work performed by our group demonstrated that intermittent reductions in bispectral index (BIS) values were found during neurofeedback following mindfulness instructions. Hypnosis was induced to enhance reductions in BIS values.ObjectiveThis study aims to assess physiologic relaxation and explore its associations with BIS values using autonomic monitoring.MethodsEach session consisted of reading a 4-minute baseline neutral script and playing an 18-minute hypnosis tape to 3 researchers involved in the BIS neurofeedback study. In addition to BIS monitoring, autonomic monitoring was performed, and this included measures of electromyography (EMG), skin temperature, skin conductance, respiratory rate, expired carbon dioxide, and heart rate variability. The resulting data were analyzed using two-tailed t tests, correlation analyses, and multivariate linear regression analyses.ResultsWe found that hypnosis was associated with reductions in BIS (P<.001), EMG (P<.001), respiratory rate (P<.001), skin conductance (P=.006), and very low frequency power (P=.04); it was also associated with increases in expired carbon dioxide (P<.001), skin temperature (P=.04), high frequency power (P<.001), and successive heart interbeat interval difference (P=.04) values. Decreased BIS values were associated with reduced EMG measures (R=0.76; P<.001), respiratory rate (R=0.35; P=.004), skin conductance (R=0.57; P<.001), and low frequency power (R=0.32; P=.01) and with increased high frequency power (R=−0.53; P<.001), successive heart interbeat interval difference (R=−0.32; P=.009), and heart interbeat interval SD (R=−0.26; P=.04) values.ConclusionsHypnosis appeared to induce mental and physical relaxation, enhance parasympathetic neural activation, and attenuate sympathetic nervous system activity, changes that were associated with BIS values. Findings from this preliminary formative evaluation suggest that the current hypnosis model may be useful for assessing autonomic physiological associations with changes in BIS values, thus motivating us to proceed with a larger investigation in trauma center nurses and physicians.
Presence of Urinary Exosomes for Liquid Biopsy of Clear Cell Renal Cell Carcinoma: Protocol for a Pilot Feasibility Study
Authors: Li Guorong , Mallouk Nora , Flandrin Pascale , Garcin Arnauld , Lambert Claude , Berremila Sid Ali , Habchi Hocine , Mottet Nicolas 
Published: April 2021

Background
Approximately 70%-80% of kidney cancers are clear cell renal cell carcinomas (CCRCCs). Patient management is based on imaging (abdominal ultrasound and computerized tomography), surgical excision of the tumor, and pathological analysis. A tissue biopsy is therefore necessary to confirm the diagnosis and avoid unnecessary nephrectomy. For metastatic cancers, a tissue biopsy is essential for establishing the targeted therapy. This biopsy of tumor material is invasive and painful. Other techniques such as liquid biopsy would help reduce the need for tissue biopsy. The development of a simple biological test for diagnosis is essential. CA9 is a powerful marker for the diagnosis of CCRCC. Exosomes have become a major source of liquid biopsy because they carry tumor proteins, RNA, and lipids. Urine is the most convenient biological liquid for exosome sampling.

Objective
The aim of this study (PEP-C study) is mainly to determine whether it is possible to detect urinary exosomal CA9 for the molecular diagnosis of CCRCC.

Methods
This study will include 60 patients with CCRCC and 40 noncancer patients. Exosomes will be isolated from urine samples and exosomal CA9 will be detected by transmission electron microscopy, flow cytometry, and reverse transcription-quantitative polymerase chain reaction.

Results
This study is currently underway with funding support from the CHU Saint-Etienne of France.

Conclusions
We expect to demonstrate that urinary tumor exosomes could be a novel liquid biopsy to diagnose CCRCC and to guide clinicians in treatment decision-making.

Trial Registration
ClinicalTrials.gov NCT04053855; https://clinicaltrials.gov/ct2/show/NCT04053855

International Registered Report Identifier (IRRID)
DERR1-10.2196/24423
The United States Chronic Thromboembolic Pulmonary Hypertension Registry: Protocol for a Prospective, Longitudinal Study
Authors: Kerr Kim M , Elliott C Greg , Benza Raymond L , Channick Richard N , Chin Kelly M , Davis R Duane , Jain Sonia , LaCroix Andrea Z , Madani Michael M , McLaughlin Vallerie V , Park Myung H , Tapson Victor F , Auger William R 
Published: April 2021

Background
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare sequela of acute pulmonary embolism that is treatable when recognized. Awareness of this disease has increased with recent advancements in therapeutic options, but delays in diagnosis remain common, and diagnostic and treatment guidelines are often not followed. Data gathered from international registries have improved our understanding of CTEPH, but these data may not be applicable to the US population owing to differences in demographics and medical practice patterns.

Objective
The US CTEPH Registry (US-CTEPH-R) was developed to provide essential information to better understand the demographics, risk factors, evaluation, and treatment of CTEPH in the United States, as well as the short- and long-term outcomes of surgical and nonsurgical therapies in the modern treatment era.

Methods
Thirty sites throughout the United States enrolled 750 subjects in this prospective, longitudinal, observational registry of patients newly diagnosed with CTEPH. Enrollment criteria included a mean pulmonary artery pressure ≥25 mmHg by right heart catheterization and radiologic confirmation of CTEPH by a multidisciplinary adjudication committee. Following enrollment, subjects were followed biannually until the conclusion of the study. Quality of life surveys were administered at enrollment and biannually, and all other testing was at the discretion of the treating clinician. Details regarding surgical therapy, balloon pulmonary angioplasty, and medical therapy were collected at enrollment and at follow-up, as well as information related to health care utilization and survival.

Results
Data from this registry will improve understanding of the demographics, risk factors, and treatment patterns of patients with CTEPH, and the longitudinal impact of therapies on quality of life, health care utilization, and survival.

Conclusions
This manuscript details the methodology and design of the first large, prospective, longitudinal registry of patients with CTEPH in the United States.

Trial Registration
ClinicalTrials.gov NCT02429284; https://www.clinicaltrials.gov/ct2/show/NCT02429284

International Registered Report Identifier (IRRID)
DERR1-10.2196/25397
The Presence of Fungal and Parasitic Infections in Substances of Human Origin and Their Transmission via Transfusions and Transplantations: Protocol for Two Systematic Reviews
Authors: Dinas Petros C , Domanovic Dragoslav , Koutedakis Yiannis , Hadjichristodoulou Christos , Stefanidis Ioannis , Papadopoulou Kalliope , Dimas Konstantinos , Perivoliotis Konstantinos , Tepetes Konstantinos , Flouris Andreas D 
Published: April 2021

Background
The European Union Directives stipulate mandatory tests for the presence of any infections in donors and donations of substances of human origin (SoHO). In some circumstances, other pathogens, including fungi and parasites, may also pose a threat to the microbial safety of SoHO.

Objective
The aim of the two systematic reviews is to identify, collect, and evaluate scientific evidence for the presence of fungal and parasitic infections in donors and donations of SoHO, and their transmission via transfusion and transplantation.

Methods
An algorithmic search, one each for fungal and parasitic disease, was applied to 6 scientific databases (PubMed, EMBASE, Web of Science, Scopus, Cochrane Library [trials], and CINAHL). Additionally, manual and algorithmic searches were employed in 15 gray literature databases and 22 scientific organization websites. The criteria for eligibility included peer-reviewed publications and peer-reviewed abstract publications from conference proceedings examining the prevalence, incidence, odds ratios, risk ratios, and risk differences for the presence of fungi and parasites in donors and SoHO donations, and their transmission to recipients. Only studies that scrutinized the donors and donations of human blood, blood components, tissues, cells, and organs were considered eligible. Data extraction from eligible publications will be performed independently by two reviewers. Data synthesis will include a qualitative description of the studies lacking evidence suitable for a meta-analysis and a random or fixed-effect meta-analysis model for quantitative data synthesis.

Results
This is an ongoing study. The systematic reviews are funded by the European Centre for Disease Prevention and Control, and the results are expected to be presented by the end of 2021.

Conclusions
The systematic reviews will provide the basis for developing a risk assessment for fungal and parasitic disease transmission via SoHO.

Trial Registration
PROSPERO International Prospective Register of Systematic Reviews CRD42020160090; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020160090 ; PROSPERO International Prospective Register of Systematic Reviews CRD42020160110; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020160110

International Registered Report Identifier (IRRID)
DERR1-10.2196/25674
Implementation of Wearable Sensors and Digital Alerting Systems in Secondary Care: Protocol for a Real-World Prospective Study Evaluating Clinical Outcomes
Authors: Iqbal Fahad Mujtaba , Joshi Meera , Khan Sadia , Ashrafian Hutan , Darzi Ara 
Published: April 2021

Background
Advancements in wearable sensors have caused a resurgence in their use, particularly because their miniaturization offers ambulatory advantages while performing continuous vital sign monitoring. Digital alerts can be generated following early recognition of clinical deterioration through breaches of set parameter thresholds, permitting earlier intervention. However, a systematic real-world evaluation of these alerting systems has yet to be conducted, and their efficacy remains unknown.

Objective
The aim of this study is to implement wearable sensors and digital alerting systems in acute general wards to evaluate the resultant clinical outcomes.

Methods
Participants on acute general wards will be screened and recruited into a trial with a pre-post implementation design. In the preimplementation phase, the SensiumVitals monitoring system, which continuously measures temperature, heart, and respiratory rates, will be used for monitoring alongside usual care. In the postimplementation phase, alerts will be generated from the SensiumVitals system when pre-established thresholds for vital parameters have been crossed, requiring acknowledgement from health care staff; subsequent clinical outcomes will be analyzed.

Results
Enrolment is currently underway, having started in September 2017, and is anticipated to end shortly. Data analysis is expected to be completed in 2021.

Conclusions
This study will offer insight into the implementation of digital health technologies within a health care trust and aims to describe the effectiveness of wearable sensors for ambulatory continuous monitoring and digital alerts on clinical outcomes in acute general ward settings.

Trial Registration
ClinicalTrials.gov NCT04638738; https://clinicaltrials.gov/ct2/show/NCT04638738.

International Registered Report Identifier (IRRID)
DERR1-10.2196/26240
Presenteeism Among Nurses in Switzerland and Portugal and Its Impact on Patient Safety and Quality of Care: Protocol for a Qualitative Study
Authors: Pereira Filipa , Querido Ana Isabel , Bieri Marion , Verloo Henk , Laranjeira Carlos António 
Published: April 2021

Background
Nurses dispense direct care in a wide variety of settings and are considered the backbone of the health care system. They often work long hours, face emotional stress, and are at a high risk of psychosocial and somatic illnesses. Nurses sometimes fall sick but work regardless, leading to presenteeism and subsequent risks to quality of care and patient safety due to the increased likelihood of patients falling, medication errors, and staff-to-patient disease transmission.

Objective
This study aims to understand presenteeism among frontline nurses and nurse managers in acute, primary, and long-term health care settings and to contribute to the development of future interventional studies and recommendations.

Methods
A qualitative study based on online focus group discussions will explore the perceptions of, attitudes to, and experiences with presenteeism among frontline nurses and nurse managers. Using a pilot-tested interview guide, 8 focus group discussions will involve nurses working in acute care hospitals, primary care settings, and long-term residential care facilities in Switzerland’s French-speaking region and Portugal’s Center region. The data collected will be examined using a content analysis approach via NVivo 12 QSR International software.

Results
The University of Applied Sciences and Arts Western Switzerland’s School of Health Sciences and the Polytechnic of Leiria’s School of Health Sciences in Portugal have both approved funding for the study. The research protocol has been approved by ethics committees in both countries. Study recruitment commenced in February 2021. The results of the data analysis are expected by September 2021.

Conclusions
This present study aims to gain more insight into the dilemmas facing nurses as a result of all causes of presenteeism among frontline nurses and nurse managers in different health care settings. The researchers will prepare manuscripts on the study’s findings, publish them in relevant peer-reviewed journals, exhibit them in poster presentations, and give oral presentations at appropriate academic and nonscientific conferences. Regarding further knowledge transfer, researchers will engage with stakeholders to craft messages focused on the needs of nurses and nurse managers and on disseminating our research findings to deal with the issue of nursing presenteeism.

International Registered Report Identifier (IRRID)
PRR1-10.2196/27963
POTRET MUSHAF KONTEMPORER DI INDONESIA
Authors: Purnawan Imam Arif 
Published: April 2021

Mushaf Al-Qur'an Standar Indonesia (MSI) adalah mushaf rujukan bagi para penerbit mushaf di Indonesia. Sejak penetapan MSI pada 1984, model dan penyajian mushaf di Indonesia mengalami transformasi dari masa ke masa. Berbagai model desain sampul terus disajikan dari tahun ke tahun dengan memunculkan berbagai inovasi baru. Para penerbit Al-Qur'an terus berinovasi melakukan modifikasi sampul dan model penyajian mushaf Al-Qur'an dengan menyesuaikan trend yang sedang disukai oleh masyarakat. Tulisan ini mencoba mengurai sejauh mana perubahan itu terjadi dan faktor apa saja yang mempengaruhi perubahan model penyajian mushaf tersebut. Hasil dari penelitian ini adalah bahwa perubahan terjadi secara signifikan pada awal tahun 2000-an, perubahan dapat dilihat dari model tulisan (khat), desain sampul, dan isi teks tambahan (sumplemen). Beberapa faktor yang mendorong perubahan tersebut adalah perkembangan teknologi percetakan, dan trend membaca Al-Qur'an yang meningkat di kalangan menengah Muslim. Di sisi lain, dalam hal penyajian model desain mushaf, budaya lokal ternyata mempunyai pengaruh cukup kuat.