bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Decade’s Review of miRNA: A Center of Transcriptional Regulation of Drugmetabolizing Enzymes and Transporters under Hypoxia
Authors: Duan Yabin , Zhu Junbo , Yang Jianxin , Gu Wenqi , Bai Xue , Liu Guiqin , Xiangyang Li 
Published: May 2021

Background:
Hypoxia has a negative effect on the cardiovascular system, nervous system, and metabolism,
which contributes to potential changes in drug absorption, distribution, metabolism, and excretion (ADME).
However, hypoxia can also alter the expression of microRNA (miRNA), thereby regulating drug-metabolizing enzymes,
transporters, and ADME genes, such as hypoxia-inducible factor, inflammatory cytokine, nuclear receptor,
etc. Therefore, it is crucial to study the role of miRNA in the regulation of drug-metabolizing enzymes and transporters
under hypoxia.

Methods:
A systematic review of published studies was carried out to investigate the role of miRNA in the regulation
of drug-metabolizing enzymes and transporters under hypoxia. Data and information on expression changes in
miRNA, drug-metabolizing enzymes, and transporters under hypoxia were analyzed and summarized.

Results:
Hypoxia can up or down-regulate the expression of miRNA. The effect of hypoxia on Cytochrome P450
(CYP450) is still a subject of debate. The widespread belief is that hypoxia decreased the activity and expression of
CYP1A1, CYP1A2, CYP2E1, and CYP3A1 and increased those of CYP3A6 and CYP2D1 in rats. Hypoxia increased
the expression of a multidrug resistance-associated protein, breast cancer resistance protein, peptide transporter,
organic cation transporter, and organic anion transporter. miRNA negatively regulated the expression of drugmetabolizing
enzymes and transporters.

Conclusion:
The findings of this review indicated that miRNA plays a key role in the expression changes of drugmetabolizing
enzymes and transporters under hypoxia.
Effect of Rat Bone Marrow Derived-Mesenchymal Stem Cells on Granulocyte Differentiation of Mononuclear Cells as Preclinical Agent in Cellbased Therapy
Authors: Fathi Ezzatollah , Azarbad Sheyda , Farahzadi Raheleh , Javanmardi Sara , Vietor Ilja 
Published: May 2021

Background:
Bone marrow mononuclear cells (BM-MNCs), as a collection of hematopoietic
and mesenchymal stem cells (MSCs), are capable of producing all blood cell lineages. The use of
cytokines, growth factors or cells capable of secreting these factors will help in stimulating the proliferation
and differentiation of these cells into mature cell lines. On the other hand, MSCs are multipotent
stromal cells that can be differentiated into various cell lineages. Moreover, these cells can control
the process of hematopoiesis by secreting cytokines and growth factors. The present study aimed to
investigate the effect of BM-derived MSCs on the differentiation of MNCs based on the assessment of
cell surface markers by flow cytometry analysis.

Methods:
For this purpose, the MNCs were purified from rat BM using density gradient centrifugation.
Thereafter, they were cultured, expanded, and characterized. Next, BM-derived-MSCs were cocultured
with MNCs, and then were either cultured MNCs alone (control group) or co-cultured MNCs
with BM-derived-MSCs (experimental group). Finally, they were collected on day 7 and subjected to
flow cytometry analysis for granulocyte markers and ERK protein investigation.

Results:
It was found that the expression levels of CD34, CD16, CD11b, and CD18 granulocyte
markers as well as protein expression of ERK have significantly increased in the experimental group
compared to the control group.

Conclusion:
Therefore, it can be concluded that MSCs could affect the granulocyte differentiation of
MNCs via ERK protein expression, which is a key component of the ERK signaling pathway.
Novel Self-micro Emulsifying Drug Delivery System for Safe Intramuscular Delivery with Improved Pharmacodynamics and Pharmacokinetics
Authors: Jain Subheet Kumar , Panchal Neha , Singh Amrinder , Thakur Shubham , Shahtaghi Navid Reza , Sharma Surbhi , Guleria Akshay 
Published: May 2021

Background:
Diclofenac Sodium (DS) injection is widely used in the management of
acute or chronic pain and inflammatory diseases. It incorporates 20% w/v Transcutol-P as a solubilizer
to make the stable injectable formulation. However, the use of Transcutol-P in high concentration
leads to adverse effects such as severe nephrotoxicity, etc. Some advancements have resulted
in the formulation of an aqueous-based injectable but that too used benzyl alcohol which is reported
to be toxic for human use.

Objective:
This study aimed to develop an injectable Self-Micro Emulsifying Drug Delivery System
(SMEDDS) as a novel carrier of DS for prompt release with better safety and efficacy.

Methods:
A solubility study was performed with different surfactants and co-surfactants. The conventional
stirring method was employed for the formulation of SMEDDS. Detailed in vitro characterization
was done for different quality control parameters. In vivo studies were performed using
Wistar rats for pharmacokinetic evaluation, toxicological analysis, and analgesic activity.

Results:
The optimized formulation exhibited good physical stability, ideal globule size (156±0.4
nm), quick release, better therapeutics, and safety, increase in LD50 (221.9 mg/kg) to that of the
commercial counterpart (109.9 mg/kg). Furthermore, pre-treatment with optimized formulation reduced
the carrageenan-induced rat paw oedema by 88±1.2% after 4 h, compared to 77±1.6% inhibition
with commercial DS formulation. Moreover, optimized formulation significantly (p<0.05) inhibited
the pain sensation in the acetic-acid induced writhing test in mice compared to its commercial
equivalent with a better pharmacokinetic profile.

Conclusion:
The above findings confirmed that liquid SMEDDS can be a successful carrier for the
safe and effective delivery of DS.
Inebilizumab-cdon: USFDA Approved for the Treatment of NMOSD (Neuromyelitis
Optica Spectrum Disorder)
Authors: Ali Faraat , Sharma Kamna , Anjum Varisha , Ali Asad 
Published: May 2021

:
Inebilizumab-cdon (Uplizna™) was currently approved by the United States Food and
Drug Administration (USFDA) for the treatment of NMOSD (neuromyelitis optica spectrum disorder).
It was developed by Viela Bio (Nasdaq: VIE) USA. Inebilizumab-cdon (formerly MEDI-551)
is a humanized antibody, which induces CD19 + B cell depletion by increasing antibody-dependent
cell cytotoxicity (ADCC) and cell phagocytosis (ADCP) of effector cells. Various clinical
trials exhibit its safe and effective pharmacokinetic and pharmacodynamic profile. In June 2019,
Viela Bio submitted Biologics License Application (BLA) to the FDA based on the findings obtained
from the N-Momentum trial. This article summarizes the milestones in the development of
Inebilizumab-cdon leading to this approval for the treatment of advanced NMOSD.
Bisphenol A as a Factor in the Mosaic of Autoimmunity
Authors: Lazurova Zora , Lazurova Ivica , Shoenfeld Yehuda 
Published: May 2021

:
The population worldwide is largely exposed to bisphenol A (BPA), a commonly used
plasticizer, that has a similar molecular structure to endogenous estrogens. Therefore, it is able to
influence physiological processes in the human body, taking part in pathophysiology of various endocrinopathies,
as well as, cardiovascular, neurological and oncological diseases. BPA has been
found to affect the immune system, leading to the development of autoimmunity and allergies, too.
In the last few decades, the prevalence of autoimmune diseases has significantly increased that
could be explained by a rising exposure of the population to environmental factors, such as BPA.
BPA has been found to play a role in the pathogenesis of systemic autoimmune diseases and also
organ-specific autoimmunity (thyroid autoimmunity, diabetes mellitus type 1, myocarditis, inflammatory
bowel disease, multiple sclerosis, encephalomyelitis etc), but the results of some studies
still remain controversial, so further research is needed.
Mobile Game Design Guide to Improve Gaming Experience for the Middle-Aged and Older Adult Population: User-Centered Design Approach
Authors: Lee Seyeon , Oh Hyunyoung , Shi Chung-Kon , Doh Young Yim 
Published: May 2021

Background
The number of older adult gamers who play mobile games is growing worldwide. Earlier studies have reported that digital games provide cognitive, physical, and socioemotional benefits for older adults. However, current mobile games that understand older adults’ gameplay experience and reflect their needs are very scarce. Furthermore, studies that have analyzed older adults’ game experience in a holistic manner are rare.

Objective
The purpose of this study was to suggest mobile game design guidelines for adults older than 50 years from a holistic gaming experience perspective. Adopting a human-centric approach, this study analyzes middle-aged and older adults’ gameplay experience and suggests practical design guides to increase accessibility and satisfaction.

Methods
We organized a living laboratory project called the “Intergenerational Play Workshop.” In this workshop, 40 middle-aged and older adults (mean age 66.75 years, age range 50-85 years) played commercial mobile games of various genres with young adult partners for 1 month (8 sessions). Using a convergent parallel mixed-method design, we conducted a qualitative analysis of dialogue, game diaries, and behavioral observations during the workshop and a quantitative analysis of the satisfaction level of the game elements for the mobile games that they played.

Results
This project was active from April 2019 to December 2021, and the data were collected at the workshops from July 1 to August 28, 2019. Based on the identified themes of positive and negative experiences from the qualitative data, we proposed 45 design guides under 3 categories: (1) cognitive and physical elements, (2) psychological and socioemotional elements, and (3) consumption contextual elements. Our empirical research could reaffirm the proposals from previous studies and provide new guidelines for improving the game design. In addition, we demonstrate how existing commercial games can be evaluated quantitatively by using the satisfaction level of each game’s elements and overall satisfaction level.

Conclusions
The final guidelines were presented to game designers to easily find related information and enhance the overall understanding of the game experience of middle-aged and older adults.
Performance of the Severe Acute Respiratory Illness Sentinel Surveillance System in Yemen: Mixed Methods Evaluation Study
Authors: Alkholidy Ghamdan Gamal , Anam Labiba Saeed , Almahaqri Ali Hamoud , Khader Yousef 
Published: May 2021

Background
The national severe acute respiratory illness (SARI) surveillance system in Yemen was established in 2010 to monitor SARI occurrence in humans and provide a foundation for detecting SARI outbreaks.

Objective
To ensure that the objectives of national surveillance are being met, this study aimed to examine the level of usefulness and the performance of the SARI surveillance system in Yemen.

Methods
The updated Centers for Disease Control and Prevention guidelines were used for the purposes of our evaluation. Related documents and reports were reviewed. Data were collected from 4 central-level managers and stakeholders and from 10 focal points at 4 sentinel sites by using a semistructured questionnaire. For each attribute, percent scores were calculated and ranked as follows: very poor (≤20%), poor (20%-40%), average (40%-60%), good (60%-80%), and excellent (>80%).

Results
As rated by the evaluators, the SARI surveillance system achieved its objectives. The system’s flexibility (percent score: 86%) and acceptability (percent score: 82%) were rated as “excellent,” and simplicity (percent score: 74%) and stability (percent score: 75%) were rated as “good.” The percent score for timeliness was 23% in 2018, which indicated poor timeliness. The overall data quality percent score of the SARI system was 98.5%. Despite its many strengths, the SARI system has some weaknesses. For example, it depends on irregular external financial support.

Conclusions
The SARI surveillance system was useful in estimating morbidity and mortality, monitoring the trends of the disease, and promoting research for informing prevention and control measures. The overall performance of the SARI surveillance system was good. We recommend expanding the system by promoting private health facilities’ (eg, private hospitals and private health centers) engagement in SARI surveillance, establishing an electronic database at central and peripheral sites, and providing the National Central Public Health Laboratory with the reagents needed for disease confirmation.
New Evidence in the Booming Field of Online Mindfulness: An Updated Meta-analysis of Randomized Controlled Trials
Authors: Sommers-Spijkerman Marion , Austin Judith , Bohlmeijer Ernst , Pots Wendy 
Published: May 2021

Background
There is a need to regularly update the evidence base on the effectiveness of online mindfulness-based interventions (MBIs), especially considering how fast this field is growing and developing.

Objective
This study presents an updated meta-analysis of randomized controlled trials assessing the effects of online MBIs on mental health and the potential moderators of these effects.

Methods
We conducted a systematic literature search in PsycINFO, PubMed, and Web of Science up to December 4, 2020, and included 97 trials, totaling 125 comparisons. Pre-to-post and pre-to-follow-up between-group effect sizes (Hedges g) were calculated for depression, anxiety, stress, well-being, and mindfulness using a random effects model.

Results
The findings revealed statistically significant moderate pre-to-post effects on depression (g=0.34, 95% CI 0.18-0.50; P<.001), stress (g=0.44, 95% CI 0.32-0.55; P<.001), and mindfulness (g=0.40, 95% CI 0.30-0.50; P<.001) and small effects on anxiety (g=0.26, 95% CI 0.18-0.33; P<.001). For well-being, a significant small effect was found only when omitting outliers (g=0.22, 95% CI 0.15-0.29; P<.001) or low-quality studies (g=0.26, 95% CI 0.12-0.41; P<.001). Significant but small follow-up effects were found for depression (g=0.25, 95% CI 0.12-0.38) and anxiety (g=0.23, 95% CI 0.13-0.32). Subgroup analyses revealed that online MBIs resulted in higher effect sizes for stress when offered with guidance. In terms of stress and mindfulness, studies that used inactive control conditions yielded larger effects. For anxiety, populations with psychological symptoms had higher effect sizes. Adherence rates for the interventions ranged from 35% to 92%, but most studies lacked clear definitions or cut-offs.

Conclusions
Our findings not only demonstrate that online MBIs are booming but also corroborate previous findings that online MBIs are beneficial for improving mental health outcomes in a broad range of populations. To advance the field of online MBIs, future trials should pay specific attention to methodological quality, adherence, and long-term follow-up measurements.
A Machine Learning Approach for Mortality Prediction in COVID-19 Pneumonia: Development and Evaluation of the Piacenza Score
Authors: Halasz Geza , Sperti Michela , Villani Matteo , Michelucci Umberto , Agostoni Piergiuseppe , Biagi Andrea , Rossi Luca , Botti Andrea , Mari Chiara , Maccarini Marco , Pura Filippo , Roveda Loris , Nardecchia Alessia , Mottola Emanuele , Nolli Massimo , Salvioni Elisabetta , Mapelli Massimo , Deriu Marco Agostino , Piga Dario , Piepoli Massimo 
Published: May 2021

Background
Several models have been developed to predict mortality in patients with COVID-19 pneumonia, but only a few have demonstrated enough discriminatory capacity. Machine learning algorithms represent a novel approach for the data-driven prediction of clinical outcomes with advantages over statistical modeling.

Objective
We aimed to develop a machine learning–based score—the Piacenza score—for 30-day mortality prediction in patients with COVID-19 pneumonia.

Methods
The study comprised 852 patients with COVID-19 pneumonia, admitted to the Guglielmo da Saliceto Hospital in Italy from February to November 2020. Patients’ medical history, demographics, and clinical data were collected using an electronic health record. The overall patient data set was randomly split into derivation and test cohorts. The score was obtained through the naïve Bayes classifier and externally validated on 86 patients admitted to Centro Cardiologico Monzino (Italy) in February 2020. Using a forward-search algorithm, 6 features were identified: age, mean corpuscular hemoglobin concentration, PaO2/FiO2 ratio, temperature, previous stroke, and gender. The Brier index was used to evaluate the ability of the machine learning model to stratify and predict the observed outcomes. A user-friendly website was designed and developed to enable fast and easy use of the tool by physicians. Regarding the customization properties of the Piacenza score, we added a tailored version of the algorithm to the website, which enables an optimized computation of the mortality risk score for a patient when some of the variables used by the Piacenza score are not available. In this case, the naïve Bayes classifier is retrained over the same derivation cohort but using a different set of patient characteristics. We also compared the Piacenza score with the 4C score and with a naïve Bayes algorithm with 14 features chosen a priori.

Results
The Piacenza score exhibited an area under the receiver operating characteristic curve (AUC) of 0.78 (95% CI 0.74-0.84, Brier score=0.19) in the internal validation cohort and 0.79 (95% CI 0.68-0.89, Brier score=0.16) in the external validation cohort, showing a comparable accuracy with respect to the 4C score and to the naïve Bayes model with a priori chosen features; this achieved an AUC of 0.78 (95% CI 0.73-0.83, Brier score=0.26) and 0.80 (95% CI 0.75-0.86, Brier score=0.17), respectively.

Conclusions
Our findings demonstrated that a customizable machine learning–based score with a purely data-driven selection of features is feasible and effective for the prediction of mortality among patients with COVID-19 pneumonia.
Hubungan Karakteristik, Kepatuhan, dan Outcome Klinis Pasien Tuberkulosis Paru Di Puskesmas Kabupaten Bantul
Authors: Bakhtiar Muh Irham , Wiedyaningsih Chairun , Yasin Nananng Munif , Kristina Susi Ari 
Published: May 2021

Tuberkulosis (TB) merupakan penyakit menular yang disebabkan oleh Mycobacterium tuberculosis. Berdasarkan Hasil Profil Kesehatan Kabupaten Bantul Provinsi Daerah Istimewa Yogyakarta (DIY) tahun 2017, keberhasilan terapi tuberkulosis sebesar 65% dalam hal ini berada dalam posisi terendah dan dibawah target minimal 85% (secara nasional). Angka keberhasilan pengobatan penyakit TB erat kaitannya dengan kepatuhan pengobatan. Berdasarkan laporan WHO 2019 Angka putus berobat pada pasien TB dindonesia 26%. Angka putus berobat ini sangat berbahaya karena jika pengobatan tidak dilakukan secara teratur akan memberikan outcome klinis yang buruk bahkan target nasional adalah tidak boleh melebih >10 %. Tujuan penelitian ini yaitu melihat gambaran pengetahuan pasien TB Paru, mengetahui gambaran kepatuhan pengobatan dan melihat hubungan antara kepatuhan pengobatan terhadap outcome klinis. Penelitian ini merupakan penelitian observasional analitik dengan rancangan studi cross sectional yang dilakukan di wilayah Kabupaten Bantul tersebar di 15 Puskesmas pada periode Maret-Juni 2020. Alat ukur kepatuhan pengobatan menggunakan kuesioner Morisky Green Levine Test (MGLT). Total subyek dalam penelitian ini adalah 57 responden dari populasi yang memenuhi kriteria inklusi dan ekslusi penelitian. Semua responden mimiliki pengetahuan yang tinggi (>5) baik pada pasien patuh maupun tidak patuh. Gambaran kepatuhan pengobatan TB paru bahwa terdapat 51 (89,5%) responden patuh dalam pengobatan dengan menjawab “ Tidak” pada 4 pertanyaan dalam Kuesioner MGLT dan terdapat 6 (10,5%) responden yang tidak patuh dalam pengobatan TB paru dengan jawaban yang beragam mulai dari bahwa responden merasa tidak membaik sebanyak 60%, beralasan lupa sebanyak 33%, karena lalai dalam pengobatan 16% responden dan karena merasa dirinya membaik 16%. Hubungan antara kepatuhan pengobatan dengan outcome klinis pasien tuberkulosis paru tidak ada perbedaan signifikan secara statistik dikarenakan outcome klinis membaik pada kelompok patuh maupun tidak patuh.Kata Kunci : Kepatuhan Pengobatan, Outcome Klinis, TB-Paru, MGLT
A Comparative Study on Efficacy of Ballistic Stretching Versus Modified Hold Relax Technique in Increasing Hamstring Flexibility
Authors: Dr. Abhijit Dutta  
Published: May 2021

In the literature, the terms “flexibility” and “muscle length” are often used synonymously when referring to the ability of muscles to be lengthened to their end range. The flexibility of the hamstring muscle is important in the prevention of injury, muscular and postural imbalance and maintenance of a full range of joint movement optimal musculoskeletal function and enhanced performance in day-to-day activities. To evaluate the comparative effectiveness of modified hold-relax technique and ballistic stretching for increasing hamstring flexibility in football players. To evaluate the comparative effectiveness of modified hold-relax technique and ballistic stretching for increasing hamstring flexibility in football players. This study includes (N=50) subjects with hamstring tightness within the age group of 18-28 years. They were randomly assigned into 2 groups (Group A and B). Group A had 25 (N=25) subjects who are treated with Modified hold- relax stretching, Group B had 25 (N=25) who are treated with ballistic stretching. The subjects were given intervention 3 sessions per week for 4 weeks. ANOVA one way classification was used to compare between and within the groups. Test within the subject of effect is highly significant for both the groups. Each group has p=0.000. Test between the subjects were used to compare between the groups, it showed highly significant p=0.000. But clinically modified hold- relax is superior to ballistic stretching. The findings suggest that modified hold- relax and ballistic stretching both was statistically significant in improving hamstring flexibility. But modified hold- relax technique showed better results compared to ballistic stretching.