bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation Profiling of BCR-ABL Kinase Domain in Chronic Myeloid Leukaemia Patients with Imatinib Resistance
Authors: Yusoff Yuslina Mat , Anoar Sharifah Zahra , Seman Zahidah Abu , Said Siti Shahrum Mohamed , Kamaluddin Nor Rizan , Abdullah Julia , Yaacob Aliza Mohd , Esa Ezalia , Zakaria Zubaidah 
Published: January 2020

Abstract
Objective: Emergence of mutation in the BCR-ABL kinase domain (KD) impairs imatinib mesylate (IM) binding capacity, thus contribute to IM resistance. Identification of these mutations is important for treatment decision and precision medicine in CML patients. Our study aims to determine the genomic landscape of BCR ABL KD mutations in CML patients with IM resistance. Result: BCR-ABL KD mutations were observed in 23 patients (26.7%). Fifteen different types of mutations have been identified; Y253H, E255K, T267A, K285I, A287T, M290R, F311I, T315I, F317L, F359V, F359I, F359C, K357T, A399T and E459K. We also discovered three novel mutations; M290R, K285I and K357T and two silent mutations at codon 389 and 401. Mutational analysis is recommended to identify patients at risk of disease progression. Therefore, early detection of such mutations may allow timely treatment intervention to prevent or overcome resistance. Keywords: Chronic Myeloid Leukaemia; BCR-ABL kinase domain; imatinib resistance mutation.
Characteristics and outcomes of Stanford type A aortic dissection patients with post-operation severe hyperbilirubinemia: a retrospective cohort study
Authors: Chen Xiaolan , Bai Ming , Zhao Lijuan , Li Yangping , Yu Yan , Zhang Wei , Ma Feng , Zhou Meilan , Li Li , He Juan , Wang Yan , Wei Lei , Sun Shiren , Chen Xiangmei 
Published: January 2020

Abstract
Objective Hyperbilirubinemia is one of the common complications after cardiac surgery and is associated with increased mortality. However, to the best of our knowledge, the report on clinical significance of postoperative severe hyperbilirubinemia in Stanford type A aortic dissection (AAD) patients is limited. Therefore, the purpose of our present study is to assess the characteristics and outcomes of AAD patients with post-operation severe hyperbilirubinemia.Methods Patients who underwent surgical treatment for AAD in our center between January 2015 and December 2018 were retrospectively screened. In-hospital mortality, long-term mortality, acute kidney injury (AKI), and the requirement of continuous renal replacement therapy (CRRT) were assessed as endpoints. Univariate and multivariate regression models were employed to identify the risk factors of these endpoints.Results Of the 2210 screened patients, 271 (12.3%) were included. Of the included patients, 222 (81.9%) experienced postoperative AKI, and 50 (18.5%) received CRRT. In-hospital mortality was 30.3%. The 1-year, 2-year, and 3-year cumulative mortality were 32.9%, 33.9%, and 35.3%, respectively. Multivariate Logistic regression analysis indicated that age ( P < 0.033), AKI stage 3 ( P < 0.001), the total amount of blood transfusion after surgery ( P = 0.019), mean arterial pressure (MAP) in the first postoperative day ( P = 0.012), the use of extracorporeal membrane oxygenation (ECMO) after surgery ( P = 0.02), and the peak total bilirubin (TB) concentration ( P = 0.023) were independent risk factors of in-hospital mortality. The optimal cut-off value of peak TB on predicting in-hospital mortality was 121.2 μmol/l. Older age, high preoperative serum creatinine (SCr) concentration, and prolonged cardiopulmonary bypass (CPB) time were identified as the independent risk factors of AKI. High preoperative SCr concentration was identified as the only independent risk factor of the requirement of CRRT.Conclusions Post-operation severe hyperbilirubinemia is a common clinical presentation in AAD surgery patients. Post-operation severe hyperbilirubinemia AAD patients with older age, lower MAP, increased blood transfusion, stage 3 AKI, the use of ECMO, and the increased peak TB had higher risk of in-hospital mortality.
Rural communities' perception of and willingness to pay for wastewater and stormwater management infrastructure in Bihar, India
Authors: Rashid Mohammad , Pandit Debapratim 
Published: January 2020

Abstract
Management of wastewater and stormwater is required for achieving total sanitation and conservation of fresh water resources. The wastewater and stormwater management (WSM) infrastructure suitable to rural areas is usually determined based on technical, environmental, and economic considerations and local communities' perception of infrastructure is ignored. This study analyses the rural communities' choice and perception of WSM infrastructure and their willingness to pay (WTP) for their improvement and maintenance. The households' choice and perception of different aspects of rural WSM infrastructure are determined using the RIDIT (relative to an identified distribution and transformation) analysis, service quality gap analysis, through establishing the relationship between households' satisfaction with individual aspects and overall quality of WSM, and WTP for the service improvement and maintenance. The study finds that rural people like to dispose of wastewater offsite as a good network of drains is found in the villages. However, several aspects of WSM are perceived as poor and require the attention of the policymakers. The rural households want improvement in several attributes and are willing to pay for the maintenance of improved service. The service quality of individual attributes of WSM infrastructure and socioeconomic characteristics of the households are essential determinants of their WTP.
Polymer-Lipid Hybrid Nanoparticles: A Next-Generation Nanocarrier for Targeted Treatment of Solid Tumors
Authors: Rizwanullah Md. , Alam Meraj , Harshita  , Mir Showkat R. , Rizvi Mohd. M.A. , Amin Saima 
Published: January 2020

:
At present, cancer is the most deadly disease and one of the most common causes of death worldwide
providing different obstacles to chemotherapy including non-specific biodistribution of chemotherapeutic drugs,
dose-related adverse effects, development of metastasis and chemoresistance. Nanoparticle-based targeted delivery
of chemotherapeutics gained enormous attention in the treatment of solid tumors as they provide many significant
advantages including prolonged drug release, enhanced systemic half-life, decreased toxicity and targeted
drug delivery. Polymer–lipid hybrid nanoparticles (PLHNPs) are the most effective nanoplatform that develop
from building blocks of polymers and lipids. PLHNPs combine the unique advantages of both lipid-based
nanoparticles as well as polymeric nanoparticles. PLHNPs integrate biocompatible polymers and biomimetic
lipids in their architecture, which imparts PLHNPs with wide versatility for delivering chemotherapeutic drugs of
different physicochemical characteristics to their target site of action. The hybrid architecture of PLHNPs provides
many exceptional advantages such as small particle size, encapsulation of more than one anticancer drugs,
high drug loading capacity and modified drug release profile. Furthermore, the surface decoration of PLHNPs
improves the therapeutic potential of the chemotherapeutic drug by selective targeting of tumor tissue and reduces
the side effects by decreasing non-specific biodistribution. This review highlights the challenges in the treatment
of solid tumors by using nanoparticles system, rationale and targeting strategies of PLHNPs in the targeted treatment
of solid tumors, and current progress of PLHNPs in the management of different types of solid tumors.
Recent Nano-based Therapeutic Intervention of Bioactive Sesquiterpenes: Prospects in Cancer Therapeutics
Authors: Ansari Mohammad A. , Badrealam Khan F. , Alam Asrar , Tufail Saba , Khalique Gulshan , Equbal Mohammad J. , Alzohairy Mohammad A. , Almatroudi Ahmad , Alomary Mohammad N. , Pottoo Faheem H. 
Published: January 2020

:
In the recent scenario, nanotechnology-based therapeutics intervention has gained tremendous impetus
all across the globe. Nano-based pharmacological intervention of various bioactive compounds has been explored
on an increasing scale. Sesquiterpenes are major constituents of essential oils (EOs) present in various plant species
which possess intriguing therapeutic potentials. However, owing to their poor physicochemical properties;
they have pharmacological limitations. Recent advances in nano-based therapeutic interventions offer various
avenues to improve their therapeutic applicability. Reckoning with these, the present review collates various
nano-based therapeutic intervention of sesquiterpenes with prospective potential against various debilitating diseases
especially cancer. In our viewpoint, considering the burgeoning advancement in the field of nanomedicine;
in the near future, the clinical applicability of these nano-formulated sesquiterpenes can be foreseen with great
enthusiasm.
The Potential Targets and Mechanisms of a Carbazole and Pyrazole Containing Anticancer Compound
Authors: Xie Jingping , Gore John C. 
Published: January 2020

Aims:
Characterization of a small anticancer compound.

Background:
The development of small molecules as new anti-cancer therapeutics is necessary to
improve anti-tumor efficacy and reduce toxicities, especially for the treatment of brain tumors,
where only small molecules can effectively cross the brain-blood barrier. Several novel hits were
previously selected by concurrently screening colon and glioma cancer cell lines with a sensorconjugated
reporter system. Here, we focused on one of them.

Objective:
Elucidating the potential target(s) of a novel anticancer compound.

Methods:
Computer-assisted structural and motif analysis (least absolute shrinkage and selection
operator or LASSO score) was used to assess compound’s targets, then direct kinase activity assays
were used for the confirmation; Western blot of phosphorylated kinases, as well as FACS and
caspase 3/7 activity assays, were used to decipher the action mechanisms. Finally, the expression
profiling of proteins involved in various G-protein pathways by real-time PCR was performed.

Result:
The small chemical, (4E)-4-[2-(9-ethyl-9H-carbazol-3-yl)hydrazin-1-ylidene]-3-methyl-
4,5-dihydro-1H-pyrazol-5-one, with a formula C18H17N5O and MW of 319.36, designated as
VUGX01, was predicted to be a ligand/inhibitor to receptor tyrosine kinases (RTKs) by computer
analysis (least absolute shrinkage and selection operator or LASSO score). However, direct analysis
with recombinant kinases showed that it is not an effective inhibitor to the popular receptor kinases
at 1μM concentration. This compound can activate caspases in some tumor cell lines but has minimal
effects on the cell cycle. Drug treatments lead to the changes in phosphorylation of AKT and c-
RAF, as well as the expression level of MAP2K, suggesting this compound may interact with Gprotein
coupled receptors (GPCRs). The expression profiling of 82 proteins involved in various Gprotein
pathways by real-time PCR showed that the treatment up-regulates the expression of several
proteins, including angiotensinogen, angiotensin II receptor, and IP3-kinase catalytic subunit
gamma.

Conclusion:
VUGX01 can effectively block proliferation and induce apoptosis of certain types of
cancer cells, even it is predicted by high LASSO score, but it is not an effective RTKs inhibitor, it
may inhibit cell growth through acting as a novel ligand to one or several GPCRs.
Abnormalities of Cortical Thickness in Pediatric Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis
Authors: Deng Kan , Zou Rushi , Huang Bingsheng , Zeng Ping , Liang Dong , Huang Lifei , Bin Guo , Zou Dongfang , Zeng Hongwu , Zhang Jian 
Published: January 2020

Objective:
Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is
the most common intractable seizure type of pediatric epilepsy, with alterations in the cortex
across the whole brain. The aim of this study is to investigate the abnormalities of cortical thickness
in pediatric MTLE-HS.

Methods:
Subjects were recruited from Shenzhen Children’s Hospital between September 2015
and December 2016. MTLE was confirmed by the experienced neurological physician based on
International League Against Epilepsy (ILAE) diagnosis criteria, and structural magnetic resonance
imaging (MRI) was performed at 3T for quantitative assessment of cortical thickness. A
general linear model with age and gender as covariates was used to examine the vertex-wise differences
in cortical thickness between 1) left MTLE-HS (LMTLE-HS) and healthy controls (HC),
and 2) right MTLE-HS (RMTLE-HS) and HC. The family-wise error corrected significance
threshold was set at P < 0.05. Through a combination of probability and cluster-size thresholding,
cluster-wise P values were obtained for the resulting clusters.

Results:
13 LMTLE-HS, 6 RMTLE-HS, and 20 age-matched HC were finally enrolled in the
study. No significant difference in the mean age (LMTLE-HS vs. HC, p=0.57; RMTLE-HS vs.
HC, p=0.39) and gender ratio (LMTLE-HS vs. HC, p=0.24; RMTLE-HS vs. HC, p=0.72) was
found between MTLE-HS and HC. In LMTLE-HS, cortical thickness was found significantly decreased
in the ipsilateral caudal middle frontal gyrus (p=0.012) and increased in the contralateral
inferior temporal gyrus (p=0.020). In RMTLE-HS, cortical thickness significantly decreased in the
ipsilateral posterior parietal lobe (superior, p<0.001 and inferior parietal gyrus, p=0.03), the anterior
parietal lobe (postcentral gyrus, p=0.006), the posterior frontal lobe (precentral gyrus, p=0.04
and the lateral occipital gyrus, p<0.001), and the contralateral lateral occipital gyrus, middle frontal
(p<0.0001) and superior frontal gyrus (p<0.001), and pericalcarine cortex (p=0.020).

Conclusion:
We detected significant cortical abnormalities in pediatric MTLE-HS patients compared
with HC. These cortical abnormalities could be explained by specific pathogenesis in
MTLE-HS, and may finally contribute to understanding the intrinsic mechanism of MTLE-HS.
A Comprehension into Target Binding and Spatial Fingerprints of Noscapinoid Analogues as Inhibitors of Tubulin
Authors: Mandavi Seema , Verma Sant Kumar , Banjare Laxmi , Dubey Amit , Bhatt Renu , Thareja Suresh , Jain Akhlesh Kumar 
Published: January 2020

Background:
Owing to its potential to interfere in microtubule dynamics in the mitotic
phase of cell cycle and selectively induce apoptosis in cancer cells without affecting normal cells,
noscapine and its synthetic analogues have been investigated by other research groups in different
cell lines for their capability to be used as anti-cancer agents.

Objective:
The present study is focused on the investigation of the mode of binding of noscapinoids
with tubulin, prediction of target binding affinities and mapping of their spatial fingerprints
(shape and electrostatic).

Methods:
Molecular docking assisted alignment based 3D-QSAR was used on a dataset (43 molecules)
having an inhibitory activity (IC50 = 1.2-250 μM) against human lymphoblast (CEM) cell
line.

Results:
Key amino acid residues of target tubulin were mapped for the binding
of most potent noscapine analogue (Compound 11) and were compared with noscapine. Spatial
fingerprints of noscapinoids for favorable tubulin inhibitory activity were generated and are proposed
herewith for further pharmacophoric amendments of noscapine analogues to design and develop
novel potent noscapine based anti-cancer agents that may enter into drug development pipeline.
Lead Adsorption in Manganese Oxides as Powders and Coatings Supported on Silica Gel Beads and Tin Inverse Opal-Like Structures
Authors: Martínez Maria Guadalupe Almanza , de Jesús Pérez Bueno José , Reza Elizabeth Manríquez , López Maria Luisa Mendoza 
Published: January 2020

Background:
Pollution in water is of concern because of its negative influence on human
health and impact on ecosystems. Three-dimensional (3D) structures in the form of inverse opals and
opals-like structures were constructed on a scale of millimeters for their use in the adsorption of
heavy metals adsorption on manganese oxide-covered surfaces.

Objective:
Manganese oxides both, as commercial powders and as synthesized coatings by the chemical
bath method, have a high capacity of lead ions adsorption. The inverse opals and opals-like
structures increase the contact area and regulate the flux.

Methods:
The chemical bath method was used to coating surfaces of inverse opals and opals-like
structures. The size of structures was proposed in millimeters to guarantee an easier flow of water.

Results:
The manganese oxide deposits were predominantly constituted by an amorphous phase. The
present crystalline forms were identified as γ − MnO2, ε − MnO2, Birnessite, and pyrolusite. The best
adsorption was obtained with Mn(II, III) and Mn(II), with 91.4% and 80.6%, respectively.

Conclusion:
Mn(II, III) and Mn(II) had approximately three times better performance than oxides of
Mn(III), Mn(IV), and chemical bath deposited MnO2 in powder form in the lead adsorption.
Medication Non-adherence in Patients with Osteoporosis: Implications for Clinical Pharmacists and Osteoporosis Care Providers
Authors: Jarab Anan S. , Mukattash Tareq L. , Hilan Hayat 
Published: January 2020

Background:
Poor adherence to the prescribed therapy leads to low bone mineral density
and enhance the development of osteoporosis complications and unnecessary hospitalization.

Objective:
To explore factors associated with medication non-adherence in patients with osteoporosis.
Findings would help guide the development of future pharmaceutical care interventions aim at
improving health outcomes for patients with osteoporosis.

Methods:
The study was conducted at an outpatient osteoporosis clinic at the Royal Medical Services
Hospital. Variables including socio-demographics and medical factors were collected using
medical records and custom-designed questionnaire. Medication adherence was assessed using the
validated 4-item Morisky Medication Adherence Scale. Logistic regression was performed to develop
a model with variables that best predicted medication non-adherence in patients with osteoporosis
in Jordan.

Results:
A total of 296 patients participated in the study. Most of the study participants (72.3%)
were found non-adherent. Patients were found less likely to adhere to the prescribed medications
with each unit increase in the number of prescribed medications (OR = 2.503, CI = 1.103-5.680)
and if they did not have a trust in the efficacy of the medications (OR = 5.544, CI = 0.990-31.058).

Conclusion:
Medication adherence for patients with osteoporosis has considered scope for improvement
in Jordan. Simplifying dosage regimen in addition to taking patients’ preferences when
selecting the medications should be taken into account in future interventions designed to improve
health outcomes for patients with osteoporosis.
Agile Approach as a Universal Remedy for the Usual Failure in the Development of Software Projects
Authors: Srivastava Sonam , Kumar Ashwani 
Published: January 2020

Background:
Agile is not a methodology neither can it be considered as a peculiar way
of developing any software also it is neither a framework nor a process. Agile is a mindset or a collection
of beliefs that can be used by the teams for taking the decisions while working on any software
development. Agile mindset adopted for the development of software has gained attention of
the researchers and industries across the world because otherwise the software project would turn
out to be uncertain and very turbid. The universal remedy for the usual failure of the software project
development is the agility. Actually saying agile is nothing novice instead it is a meta model
based on best practices from the preceding models like waterfall, iterative, incremental and rapid
application development method.

Objective:
The objective of this paper is to highlight various points of comparison between them
and conclude that failing fast is failing cheap in case of agile for software development.

Methods:
So, we can say that an agile always existed but not in a structured and a formal manner.
The two main methodologies of agile as an umbrella term are XP and scrum.

Results:
Thus in this paper we have discussed about scrum as a major methodology and also how
various scrum roles contribute towards making teams self-organized to reduce the usual rate of failure
of development projects.

Conclusion:
The success rate of the software applications developed through the agile concept is
three times than that of the traditional waterfall method and also the percentage of cost and time
overruns is much lower.
Exposure of Hepatocellular Carcinoma Cells to Ankaferd Blood Stopper® Alters Cell Death Signaling Networks Confirmed by Oncoproteomic and Genomic Profiling Studies
Authors: Nenni Merve , Öncül Selin , Ercan Ayşe , Çelebier Mustafa , Süslü İncilay , Haznedaroğlu İbrahim Celalettin 
Published: January 2020

Background:
Ankaferd Blood Stopper® is a commercially available herbal extract with potent blood-stopping property and is clinically used to treat immediate dental, dermal, external and internal bleeding. Its possible anti-neoplastic effect or whether it ingenerates drug resistance in cells has not been previously scrutinized.

Objective:
In the present study HEPG2 hepatocellular carcinoma cell line was exposed to clinically used dose (8 μL/mL) of the blood stopper for 24 h and the behavioral changes were investigated on both proteomic and genomic levels.

Method:
Cell culture experiments were performed by using Ankaferd® application in HepG2 cell line. Cytotoxic activity experiments with MTT, oncoproteomic studies with 2d gel electrophoresis, genomic studies were performed with RT-PCR.

Results:
It was seen that the agent did not significantly inhibit cell viability subsequent to 24 h of the treatment meanwhile, it clearly deducted cell viability after 72 h. Although reduction of HEPG2 cell proliferation was not witnessed as a response to 24 h of treatment with Ankaferd®, genomic and oncoproteomic analysis demonstrated diversification.

Conclusion:
It was established that protein processing networks in endoplasmic reticulum
which regulate protein folding, relocation and degradation were effected. Additionally, it
was proved that along with the elongation of the exposure period, mitochondrial apoptotic
pathway may be activated due to hnRNP F-p53 interaction. Given to the fact that the agent
did not cause P-glycoprotein-dependent drug resistance unlike many clinically used chemotherapeutic
agents, it can also be considered for combination treatment. Overall, these findings
suggest that Ankaferd® offers a novel promising approach against hepatocellular carcinoma
which needs further investigation.