bluuebunny/crossref_metadata_2025_split huggingface dataset:
Navigating Research Toward the Re-emerging Nipah Virus- A New Piece to the Puzzle
Authors: Ramharack Pritika , Devnarain Nikita , Shunmugam Letitia , Soliman Mahmoud E.S. 
Published: July 2019

Background:The recent Nipah virus (NiV) outbreak in India has caused a state of chaos, with potential to become the next international pandemic. There is still a great deal to learn about NiV for the development of a potent treatment against it. The NiV non-structural proteins play important roles in the lifecycle of the virus, with the RNA-dependent RNA-polymerase (RdRp) being a vital component in viral replication. In this study, we not only provide a comprehensive overview of all the literature concerning NiV, we also propose a model of the NiV RdRp and screen for potential inhibitors of the viral enzyme.Objectives:In this study, computational tools were utilized in the design of a NiV RdRp homology model. The active site of RdRp was then identified and potential inhibitors of the protein were discovered with the use of pharmacophore-based screening.Methods:In this study, computational tools were utilized in the design of a NiV RdRp homology model. The active site of RdRp was then identified and potential inhibitors of the protein were discovered with the use of pharmacophore-based screening.Results:Ramachandran plot analysis revealed a favourable model. Upon binding of nucleoside analog, 4’- Azidocytidine, active site residues Trp1714 and Ser1713 took part in stabilizing hydrogen bonds, while Thr1716, Ser1478, Ser1476 and Glu1465 contributed to hydrophobic interactions. Pharmacophore based screening yielded 18 hits, of which ZINC00085930 demonstrated the most optimal binding energy (-8.1 kcal/mol), validating its use for further analysis as an inhibitor of NiV.Conclusion:In this study we provide a critical guide, elucidating on the in silico requirements of the drug design and discovery process against NiV. This material lays a foundation for future research into the design and development of drugs that inhibit NiV.
NINJ2 Gene Polymorphisms and Susceptibility to Ischemic Stroke: An Updated Meta-Analysis
Authors: Nie Fangfang , Yu Mingli , Liu Mengwei , Shang Mengke , Zeng Fanxin , Liu Wanyang 
Published: July 2019

Background:
Ischemic stroke (IS) is a significant disease which threatens human health
condition. Genome-wide association studies (GWAS) have demonstrated that two intergenic single-
nucleotide polymorphisms (SNPs) rs11833579 and rs12425791 G>A on chromosome 12p13
are associated with IS susceptibility. However, later studies came to contradictory outcomes. Thus,
we carried out a meta-analysis to identify the association between nerve injury-induced protein 2
(NINJ2) gene polymorphisms (rs11833579 and rs12425791) and the risk of IS.

Methods:
PubMed, Embase, Web of Science, CBM, Wanfang, VIP, and CNKI databases were
searched until March 2019. Data was analyzed by RevMan 5.3 and STATA 12.0 software. The
pooled odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the strength of the
association.

Results:
Eighteen qualified articles were selected in total. For rs12425791 and rs11833579, a total
of 14055 cases with 13148 controls and 10635 cases with 10462 controls, respectively, were identified
for the present study. Our meta-analysis found that rs12425791 was associated with IS for
three genetic models (allele model: OR=1.04, 95% CI: 1.00-1.08, P=0.04; dominant model:
OR=1.06, 95% CI: 1.01-1.12, P=0.01 and heterozygous model: OR=1.07, 95% CI: 1.01-1.12,
P=0.02). Whereas rs11833579 polymorphism was not associated with IS among different genetic
models.

Conclusion:
NINJ2 gene rs12425791 confers a susceptible factor for IS, while there is no association
between NINJ2 gene rs11833579 and IS. Larger sample size studies should be performed to
find the association between NINJ2 gene and IS.
Constipation Increases Disability and Decreases Dopamine Levels in the Nigrostriatal System through Gastric Inflammatory Factors in Parkinson’s Disease
Authors: Zhou Yongtao , Su Yusheng , Xu Weihua , Wang Wei , Yao Shukun 
Published: July 2019

Objective:
Recent studies suggest that not only is constipation a clinical marker of premotor
phase in Parkinson’s Disease (PD), but is also correlated with the duration and severity.
Some reports indicated that inflammatory from gut dysbiosis might be involved in the pathogenesis
of PD, but the correlation between them remains poorly understood. This study aims to investigate
how the presence of constipation affects the dopamine level of nigrostriatal system and
whether gastrointestinal (GI) inflammation is involved in the brain-gut axis.

Methods:
Clinical materials, serum inflammatory factors, and datum of dopamine level including
84 cases and 83 controls, were collected consecutively and randomly from November 1, 2017 to
October 31, 2018. Dopamine levels of nigrostriatal system were detected by [18F]-DTBZ radiotracer
(18F-AV-133). Data analysis was conducted by variance, covariance analysis, bicorrelation,
partial correlation, chi-square analysis and logistic regression.

Results:
The mean age of cases was older than that of controls, and male predominance was also
observed (P<0.05). The mean scores of Hoehn-Yahr and unified Parkinson’s disease rating scale
Ⅲ (UPDRS-Ⅲ) were of significantly different duration between two groups (P<0.05). The total
dose of levodopa was not different between two groups (P>0.05). The dopamine levels of putamen
and caudate nucleus, especially in the dorsal part of putamen, were significantly decreased in cases
than that in controls (P<0.05). There were significant differences of complement 3 (C3) and complement
4 (C4) between cases and controls (P<0.05). Dopamine levels in putamen and caudate nucleus
were negatively correlated with serum concentrations of immunoglobulin A (IgA), immunoglobulin
G (IgG) and C3 in cases (P<0.05). But we did not observe similar negative correlations in
controls (P>0.05).

Conclusion:
The presence of constipation may increase the severity of motor symptoms and decrease
dopamine levels of nigrostriatal system in PD. Inflammatory factors may be involved in the
brain-gut axis of PD.
Uses of Cyclohexan-1,3-dione for the Synthesis of Thiazole, Pyrazole, Thiophene, Isoxazole and Pyran Derivatives with Antitumor Activities
Authors: Mohareb Rafat Milad , Megally Abdo Nadia Youssef , Al-darkazali Waleed Nabeel 
Published: July 2019

Background:
A wide range of thiazole, pyrazole and pyran derivatives gained special
attention due to pharmacological activities especially therapeutic activities. Many pharmacological
drugs containing the thiazole and pyrazole nuclei are known in the market.

Methods:
The 2-arylidencyclohexan-1,3-dione 3a-c were the key starting compounds for many
heterocyclic reactions to produce substituted heterocyclic derivatives.

Results:
Antiproliferative activities of the produced compounds against six cancer cell lines A549,
HT-29, MKN-45, U87MG, SMMC-7721 and H460 were measured in which the compounds showed
high inhibition. The most promising compounds were tested against tyrosine kinases (c-Kit, Flt-3,
VEGFR-2, EGFR, and PDGFR). Structure-Activity Relationship (SAR) was rationalized by
assessing the varying structural features of the molecules. In addition, the most active compounds
were selected for Pim-1 inhibition.

Conclusion:
Thirty compounds were synthesized. Ten of them (3a, 3c, 5a, 5c, 7a, 10f, 11a, 13c, 16a
and 16c) were the most active compounds for selected cancer cell lines. Compounds 3c, 5c, 7a, 10f,
13c and 16c showed high inhibition toward the tyrosine kinases while compounds 3c, 5c and 10f
were the most potent to inhibit Pim-1.
Prevalence and Risk Factors for Diabetes Mellitus in A State in South East Nigeria: Results of a Population Based House to House Survey
Authors: Ezeani Ignatius U. , Chukwuonye Innocent I. , Onyeonoro Ugochukwu U. , Chuku Abali , Ogah Okechukwu S. 
Published: July 2019

Background:
Population based studies on diabetes mellitus (DM) are scarce in Nigeria.

Introduction:
This was a population-based house to house survey aimed at determining the prevalence
of DM and assessing the risk factors associated with DM in a state in Southeast Nigeria.

Methods:
This was a cross-sectional observational study in which 1680 adults were recruited using a
multistage sampling method to randomly select not more than two suitable participants of both sex in
each household from four enumeration areas (EAs) in each local government area (LGA) and the three
senatorial zones in the state. A modified World Health Organization (WHO) Stepwise Approach to
Surveillance questionnaire was used for data collection and random blood glucose (RBG) was measured
after anthropometric assessment. Test statistics used were chi-square, t-test, and logistic regression.

Results:
The overall prevalence of DM in this study was 3.3%. A positive family history of DM was
significantly higher in patients with diabetes: 18.2% vs. 9.6% (p=0.036). The mean (SD) of weight,
body mass index (BMI), hip circumference (HC) and waist circumference (WC) were significantly
higher in patients with DM(p=0.001,<0.001,<0.001,<0.001, respectively).The odd ratio (95% CI) of a
person>35years developing DM was 3.89(1.11-13.60). The OR (95% CI) for waist-hip ratio (WHR)
was 3.04 (1.02-9.03) and family history of DM had an OR of 2.62(0.88-6.50). The odd of developing
DM is positively associated with age>35years, increased WHR, WC, family history of DM,
BMI>25Kg/m2, and HC. The odd of developing DM was negatively associated with smoking.

Conclusion:
The prevalence of DM in this study was 3.3%. A BMI>25 kg/m2, WHR >0.85, family history
of DM, HC, and older age were associated with significantly higher prevalence.
The Perplexity of Synergistic Duality: Inter-molecular Mechanisms of Communication in BCR-ABL1
Authors: Elrashedy Ahmed A. , Ramharack Pritika , Soliman Mahmoud E.S. 
Published: July 2019

Background:Aberrant and proliferative expression of the oncogene BCR-ABL in bone marrow cells is one of the prime causes of Chronic Myeloid Leukemia (CML). It has been established that the tyrosine kinase domain of the BCR-ABL protein is a potential therapeutic target for the treatment of CML. Although the first and second line inhibitors against the enzyme are available, recent studies have indicated that monotherapeutic resistance has become a great challenge.Objective:In recent studies, the dual inhibition of BCR-ABL by Nilotinib and Asciminib has been shown to overcome drug resistance. This prompted us to investigate the dynamics behind this novel drug combination.Methods:By the utilization of a wide range of computational tools, we defined and compared BCR-ABL’s structural and dynamic characteristics when bound as a dual inhibitor system.Results:Conformational ensemble analysis presented a sustained inactive protein, as the activation loop, inclusive of the characteristic Tyr257, remained in an open position due to the unassailable binding of Asciminib at the allosteric site. Nilotinib also indicated stronger binding at the catalytic site in the presence of Asciminib, thus exposing new avenues in treating Nilotinib-resistance. This was in accordance with intermolecular hydrogen bond interactions with key binding site residues GLU399, Asn259 and Thr252.Conclusion:The investigations carried out in this study gave rise to new possibilities in the treatment of resistance in CML, as well as assisting in the design of novel and selective inhibitors as dual anti-cancer drugs.
Telomerase Biology Associations Offer Keys to Cancer and Aging Therapeutics
Authors: Smith-Sonneborn Joan 
Published: July 2019

Background:
Although telomerase has potential for age-related disease intervention, the
overexpression of telomerase in about 90% of cancers, and in HIV virus reservoirs, cautions against
se in anti-aging telomerase therapeutics. While multiple reviews document the canonical function
of telomerase for maintenance of telomeres, as well as an increasing numbers of reviews that reveal
new non-canonical functions of telomerase, there was no systematic review that focuses on the array
of associates of the subunit of Telomerase Reverse transcriptase protein (TERT) as pieces of
the puzzle to assemble a picture of the how specific TERT complexes uniquely impact aging and
age-related diseases and more can be expected.

Methods:
A structured search of bibliographic data on TERT complexes was undertaken using databases
from the National Center for Biotechnology Information Pubmed with extensive access to
biomedical and genomic information in order to obtain a unique documented and cited overview of
TERT complexes that may uniquely impact aging and age-related diseases.

Results:
The TERT associations include proper folding, intracellular TERT transport, metabolism,
mitochondrial ROS (Reactive Oxygen Species) regulation, inflammation, cell division, cell death,
and gene expression, in addition to the well-known telomere maintenance. While increase of cell
cycle inhibitors promote aging, in cancer, the cell cycle check-point regulators are ambushed in favor
of cell proliferation, while cytoplasmic TERT protects a cell cycle inhibitor in oxidative stress.
The oncogene cMyc regulates gene expression for overexpression of TERT, and reduction of cell
cycle inhibitors-the perfect storm for cancer promotion. TERT binds with the oncogene RMRP
RNA, and TERT-RMRP function can regulate levels of that oncogene RNA, and TERT in a TBN
complex can regulate heterochromatin. Telomerase benefit and novel function in neurology and
cardiology studies open new anti- aging hope. GV1001, a 16 amino acid peptide of TERT that associates
with Heat Shock Proteins (HSP’s), bypasses the cell membrane with remarkable anti disease
potential.

Conclusions:
TERT “associates” are anti-cancer targets for downregulation, but upregulation in
antiaging therapy. The overview revealed that unique TERT associations that impact all seven pillars
of aging identified by the Trans-NIH Geroscience Initiative that influence aging and urge research
for appropriate targeted telomerase supplements/ stimulation, and inclusion in National Institute
on Aging Intervention Testing Program. The preference for use of available “smart drugs”,
targeted to only cancer, not off-target anti- aging telomerase is implied by the multiplicity of TERT
associates functions.
Kadar Hormon Kortisol dan Rasio Neutrofil/Limfosit (N/L) Satwa Lutung Jawa pada Saat di Kandang Perawatan dan Kandang Karantina di Hutan Coban Talun, Batu
Authors: Titisari Nurina , Asri Khairiza , Fauzi Ahmad , Masnur Ida , Kurniawan Iwan 
Published: July 2019

Program rehabilitasi lutung Jawa di Javan Langur Center menggunakan tiga kandang adaptasi yaitu kandang perawatan, karantina dan sosialisasi. Lutung yang baru datang sering mengalami stress akibat perbedaan perlakuan selama dipelihara oleh masyarakat. Hal ini bisa menimbulkan tidak terbentuknya interaksi kawanan satwa pada saat pengelompokan sebelum dilepasliarkan. Perubahan tingkah laku satwa sifatnya individual sehingga terkadang tidak dapat menunjukkan kondisi stres. Untuk itu perlu dilakukan pengukuran tingkat stres yang lain seperti hormon kortisol dan rasio neutrophil per limfosit. Tujuannya adalah untuk mengetahui kesiapan satwa tersebut sebelum dimasukkan ke kandang sosialisasi. Hewan coba berasal dari hutan Coban Talun, Javan Langur Center (JLC), Batu yang sedang menjalani program rehabilitasi.Â Sebanyak lima ekor lutung Jawa berumur 2 hingga 8 tahun, berjenis kelamin betina dan jantan diambil sampel serum dan darah. Pengujian kadar hormon kortisol dengan metode enzyme-linked immunosorbent assay (ELISA) dan uji diferensiasi leukosit.dilakukan untuk menghitung rasio neutrofil: limfosit. Hasil penelitian menunjukkan bahwa rerata kadar kortisol dan rasio N/L pada sampel lutung Jawa pada kandang karantina mengalami penurunan dibandingkan pada saat berada di kandang perawatan. Namun secara individual juga terdapat satwa yang mengalami peningkatan. Terdapatnya variasi tingkat stress pada lutung Jawa ini tergantung kepada kemampuan individu satwa dalam menganggapi cekaman.
Perbandingan Kadar Kortisol dan Rasio N/L (Neutrofil/Limfosit) Antara Lutung Jawa Jantan dan Betina di Kandang Sosialisasi
Authors: Titisari Nurina , Anindia Niko , Fauzi Ahmad , Masnur Ida , Kuniawan Iwan 
Published: July 2019

Status sosial lutung Jawa pada satu kelompok dapat menyebabkan peningkatan stress. Primata dominan cenderung menunjukkan tingkat stress yang lebih rendah dibandingkan primata subordinat. Di tempat penangkaran kejadian ini sering muncul pada lutung Jawa di kandang pengelompokan. Dalam penelitian ini kandang tersebut adalah kandang sosialisasi yang merupakan kandang terakhir sebelum dilepaskan ke alam. Kelompok primata tersebut harus terbebas dari penyakit dan memiliki tingkat stres yang rendah agar mampu bertahan hidup. Tujuan penelitian ini adalah untuk melihat tingkat stres sebagai salah satu indikator kesiapan pelepasan lutung jawa yang diukur berdasarkan kadar kortisol serum dan rasio Neutrofil per limfosit darah. Lutung Jawa yang digunakan berasal dari pusat rehabilitasi satwa yang terletak di kota Batu. Rentang umur satwa yang digunakan adalah 2-10 tahun dengan jenis kelamin jantan dan betina. Kadar kortisol diukur menggunakan metode ELISA indirect gelombang 450 nm dan kadar neutrofil per limfosit diukur menggunakan hematology analyzer. Data yang didapatkan dianalisa secara deskriptif. Hasil penelitian didapatkan kadar kortisol rata-rata pada lutung betina sebesar 118.01 ng/mL sedangkan pada lutung Jawa jantan sebesar 117.04 ng/mL.Â Nilai rasio neutrofil per limfosit lutung jantan sebesar 5.43 dan betina sebesar 7.88. Kesimpulannya nilai kadar kortisol dan rasio neutrophil/limpfosit dikandang sosialisasi pada lutung jantan lebih rendah daripada lutung betina.
Identifikasi Sifat-Sifat Produksi Persilangan Babi Duroc ean Yokshire
Authors: Tribudi Yuli Arif , Andri Andri , Lestari Retno Budi 
Published: July 2019

Penelitian dilakukan di peternakan babi PT Fajar Semesta Indah di Singkawang Kalimantan Barat. Penelitian bertujuan untuk mengetahui performans produksi pada babi Duroc, Yorkshire serta persilangannya. Materi yang digunakan dalam penelitian ini bangsa babi Yorkshire, Duroc, persilangan Yorkshire-Duroc serta persilangan Duroc- Yorkshire dengan jumlah masing-masing 197 ekor; 264 ekor; 168 ekor dan 275 ekor. Metode yang digunakan dalam penelitian ini adalah pengamatan dan pengukuran langsung pada ternak babi dengan menggunakan data primer. Penentuan sample menggunakan purposive sampling. Variabel yang diamati adalah litter size, berat lahir, berat sapih dan mortalitas anak babi prasapih. Untuk mengetahui pengaruh bangsa terhadap sifat produksi digunakan analisis ragam Rancangan Acak Lengkap. Hasil penelitian menunjukkan rataan litter size, berat lahir dan berat sapih anak babi masing-masing pada bangsa babi Yorkshire (9,38Â±2,87 ekor; 1,24Â±0,25 kg dan 6,73Â±0,71 kg), DurocÂ (8,41Â±3,26 ekor; 1,23Â±0,26 kg dan 6,54Â±1,07 kg); babi persilangan Yorkshire-Duroc (9,88Â±3,04 ekor; 1,26Â±0,36 kg dan 6,84Â±0,78 kg) serta persilangan Duroc-Yorkshire (9,48Â±2,63 ekor; 1,28Â±0,26 kg dan 6,91Â±0,86 kg). Laju kematian anak prasapihÂ secara berturut turut yaitu pada babi persilangan Yorkshire-Duroc sebesar 17,85 persen; Yorkshire sebesar 15,74 persen; Duroc 13,64Â persen serta persilangan Duroc-Yorkshire sebesar 11,64 persen. Disimpulkan sistem perkawinan antar bangsa babi tidak berpengaruh terhadap litter size dan berat lahir tetapi berpengaruh sangat nyata (P<0,01) terhadap berat sapih anak babi. Disarankan untuk meningkatkan produktivitas babi di PT Fajar Indah Semesta sebaiknya melakukan perkawinan silang.
Morphometric Characteristics and Features of Metachronous Breast Cancer
Authors: Dyakiv Iryna , Kryzhanivska Anna 
Published: July 2019

An important morphological criterion for the development of the degree of malignancy of breast cancer is the change in the structure of cell nuclei. At the same time, both the morphometric parameters of metachronous breast cancer and their connection with the molecular biological characteristics of these tumors are currently unknown.
The objective of the research was to identify metachronous malignant disease in the patients with breast cancer.
Materials and methods. The study is based on a retrospective analysis of tumors in 63 patients with breast cancer, who developed uterine cancer or ovarian cancer within 5 years after diagnosis of breast cancer. All the patients received treatment at the Ivano-Frankivsk Regional Clinical Oncology Center. The criterion for selecting patients in the study was the presence of gynecologic cancer after the treatment of breast cancer. The age of patients with breast cancer involved in the study ranged from 24 to 83 years, averaging 56.8±1.5 years.
Results and discussion. The maximum values ​​of the perimeter, radius, and area of ​​cell nuclei (19.21±0.7, 3.05±0.4 and 36.3±0.9, respectively) were observed in tumors of the patients with metachronous breast cancer. The improvement of the perimeter, radius, and area of ​​tumor cell nuclei in the patients with metachronous breast cancer was associated with an increase in the size of the tumors and the presence of metastases in regional lymph nodes.
Conclusions. The morphometric sign of the high risk of developing metachronous breast cancer is the increase in the perimeter, radius, and cell nucleus area on the background of increased proliferative activity of low-grade cancer in the presence of large tumors and metastases in regional lymph nodes.
Negosiasi Pemuda dalam Fleksibilitas Pasar Kerja: Studi Netnografi terhadap Mikro-Selebriti di Daerah Istimewa Yogyakarta
Authors: Darmawan Arif Budi , Azis Faishal Abdul , Aini Mei Nurul 
Published: July 2019

Today the labor market flexibility to be a trend among young people. This emergence of flexibility becomes an ambivalence. On the one hand, it is a form of adaptation with increasingly mobile work. However, according to Guy Standing flexibility actually produces new dangerous class. The vulnerability arises in the form of no guarantee of protection for workers and the security of the labor market. Through netnographic studies the author seeks to examine the employment choices of youth as micro-celebrities, the benefits gained, obstacles faced and negotiations carried out to answer the uncertainty that leads to his work. The researcher observed through the internet and conducted in-depth interviews. The selection of research informants was purposively conducted, namely, micro-Sebritic workers living in the Special Region of Yogyakarta in ages 16-30 years. From the results of the study found that: First, working as a micro-celebrity is the need for leisure. For young people working as micro-celebrities is a hobby as well as a profession. Second, many micro-celebrities are faced with dilemmas and uncertainty situations, both coming from themselves and parents. Finally, negotiations are carried out by youth to deal with uncertainty over their work and the dilemma they face.