bluuebunny/crossref_metadata_2025_split huggingface dataset:
A simple sensitivity analysis of the turbulence-induced flocculation model of cohesive sediment
Authors: Zhu Zhongfan 
Published: March 2019

Abstract
In this study, the local and global sensitivity analyses of the Winterwerp model to the input parameters have been carried out using the Garson algorithm and the PaD2 method by virtue of an artificial neural network. The main results of the sensitivity analyses are that the model is most sensitive to the breakup parameter and that only two parameters (the floc aggregation and breakup parameters) are significant. The result that the model output is less sensitive to the choice of fractal dimension seems to imply that the modification work on the fractal dimension might be unnecessary.
Antenatal Corticosteroids for Fetal Lung Maturity - Too Much of a Good Thing?
Authors: Hrabalkova Lenka , Takahashi Tsukasa , Kemp Matthew W. , Stock Sarah J. 
Published: March 2019

Background:Between 5-15% of babies are born prematurely worldwide, with preterm birth defined as delivery before 37 completed weeks of pregnancy (term is at 40 weeks of gestation). Women at risk of preterm birth receive antenatal corticosteroids as part of standard care to accelerate fetal lung maturation and thus improve neonatal outcomes in the event of delivery. As a consequence of this treatment, the entire fetal organ system is exposed to the administered corticosteroids. The implications of this exposure, particularly the long-term impacts on offspring health, are poorly understood.Aims:This review will consider the origins of antenatal corticosteroid treatment and variations in current clinical practices surrounding the treatment. The limitations in the evidence base supporting the use of antenatal corticosteroids and the evidence of potential harm to offspring are also summarised.Results:Little has been done to optimise the dose and formulation of antenatal corticosteroid treatment since the first clinical trial in 1972. International guidelines for the use of the treatment lack clarity regarding the recommended type of corticosteroid and the gestational window of treatment administration. Furthermore, clinical trials cited in the most recent Cochrane Review have limitations which should be taken into account when considering the use of antenatal corticosteroids in clinical practice. Lastly, there is limited evidence regarding the long-term effects on the different fetal organ systems exposed in utero, particularly when the timing of corticosteroid administration is sub-optimal.Conclusion:Further investigations are urgently needed to determine the most safe and effective treatment regimen for antenatal corticosteroids, particularly regarding the type of corticosteroid and optimal gestational window of administration. A clear consensus on the use of this common treatment could maximise the benefits and minimise potential harms to offspring.
Can IL-33 and Endocan be New Markers for Retinopathy of Prematurity?
Authors: Cakir Ufuk , Tayman Cuneyt , Yucel Cigdem , Ozdemir Ozdemir 
Published: March 2019

Background:
Retinopathy of Prematurity (ROP) is a pathophysiologic condition of the
retina due to abnormal proliferation of retinal vessels.

Objective:
The study aimed too ascertain the importance of vascular endothelial growth factor
(VEGF), insulin-like growth factor-1 (IGF-1), interleukin-33 (IL-33) and endocan in the diagnosis
and follow-up of ROP.

Methods:
This prospective cohort study was conducted in the neonatal intensive care unit (NICU)
of Health Science University, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey,
between February 2017 and August 2018. Preterm infants (gestational age (GA) of ≤32 weeks and
birth weight of ≤1500 gr), diagnosed ROP were included in the study. VEGF, IGF-1, IL-33 and
endocan levels were evaluated in the cord blood and in the serum before and after treatment of
infants in the ROP and control groups.

Results:
A final number of 146 infants were included in the study. During the study period, 73
infants were identified as the ROP group, and 73 infants were allocated as the control group. In the
ROP group, the cord blood VEGF value was higher than the control group (p <0.05). However,
IGF-1 levels in the cord blood were lower in the ROP group than control (P<0.05). IL-33 and
endocan values in the cord blood were similar in both control and ROP groups (p>0.05). Although
serum levels of IL-33, VEGF and endocan were higher before laser treatment, these biomarkers
decreased significantly after laser treatment (p <0.05).

Conclusion:
We determined that serum IL-33 and endocan levels might be suggested as sensitive
novel markers for the prediction of severe ROP.
Identifying the Potential Substrates of the Depalmitoylation Enzyme Acyl-protein Thioesterase 1
Authors: Liu Huicong , Yan Peipei , Ren Junyan , Wu Can , Yuan Wei , Rao Muding , Zhang Zhongjian , Kong Eryan 
Published: March 2019

Background:The homeostasis of palmitoylation and depalmitoylation is involved in various cellular processes, the disruption of which induces severe physiological consequences. Acyl-protein thioesterase (APT) and palmitoyl-protein thioesterases (PPT) catalyze the depalmitoylation process. The natural mutation in human PPT1 caused neurodegenerative disease, yet the understanding of APT1 remains to be elucidated. While the deletion of APT1 in mice turned out to be potentially embryonically lethal, the decoding of its function strictly relied on the identification of its substrates.Objective:To determine the potential substrates of APT1 by using the generated human APT1 knockout cell line.Methods :The combined techniques of palmitoyl-protein enrichment and massspectrometry were used to analyze the different proteins. Palmitoyl-proteins both in HEK293T and APT1-KO cells were extracted by resin-assisted capture (RAC) and data independent acquisition (DIA) quantitative method of proteomics for data collection.Results:In total, 382 proteins were identified. The gene ontology classification segregated these proteins into diverse biological pathways e.g. endoplasmic reticulum process and ubiquitin-mediated proteolysis. A few potential substrates were selected for verification; indeed, major proteins were palmitoylated. Importantly, their levels of palmitoylation were clearly changed in APT1-KO cells. Interestingly, the proliferation of APT1-KO cells escalated dramatically as compared to that of the WT cells, which could be rescued by APT1 overexpression.Conclusion:Our study provides a large scale of potential substrates of APT1, thus facilitating the understanding of its intervened molecular functions.
Polyisoprenylated Cysteinyl Amide Inhibitors Deplete K-Ras and Induce Caspase-dependent Apoptosis in Lung Cancer Cells
Authors: Nkembo Augustine T. , Amissah Felix , Ntantie Elizabeth , Poku Rosemary A. , Salako Olufisayo O. , Ikpatt Offiong Francis , Lamango Nazarius S. 
Published: March 2019

Background:
Non-small cell lung cancers (NSCLC) harboring mutation-induced dysregulation
of Ras signaling present some of the most difficult-to-manage cases, since directly targeting
the constitutively active mutant Ras proteins has not resulted in clinically useful drugs. Therefore,
modulating Ras activity for targeted treatment of cancer remains an urgent healthcare need.

Objective:
In the current study, we investigated a novel class of compounds, the polyisoprenylated
cysteinyl amide inhibitors (PCAIs), for their anticancer molecular mechanisms using the NSCLC
cell panel with K-Ras and/or other mutant genes.

Methods:
The effect of the PCAIs on intracellular K-Ras levels, cell viability, apoptosis, spheroid
and colony formation were determined.

Results:
Treatment of the lung cancer cells with the PCAIs, NSL-RD-035, NSL-BA-036, NSL-BA-
040 and NSL-BA-055 resulted in concentration-dependent cell death in both K-Ras mutant (A549,
NCI-H460, and NCI-H1573), N-Ras mutant (NCI-H1299) and other (NCI-H661, NCI-H1975, NCIH1563)
NSCLC cells. The PCAIs at 1.0 -10 μM induced the degeneration of 3D spheroid cultures,
inhibited clonogenic cell growth and induced marked apoptosis via the extrinsic pathway. The most
potent of the PCAIs, NSL-BA-055, at 5 μM induced a seven-fold increase in the activity of caspase-
3/7 and a 75% selective depletion of K-Ras protein levels relative to GAPDH in A549 cells that correlated
with PCAIs-induced apoptosis. NSL-BA-040 and NSL-BA-055 also induced the phosphorylation
of MAP kinase (ERK 1/2).

Conclusion:
Taken together, PCAIs may be potentially useful as targeted therapies that suppress
NSCLC progression through disruption of Ras-mediated growth signaling.
Inhibition of PI3K/mTOR Pathways with GDC-0980 in Pediatric Leukemia: Impact on Abnormal FLT-3 Activity and Cooperation with Intracellular Signaling Targets
Authors: Al-Ghabkari Abdulhameed , Perinpanayagam Maneka A. , Narendran Aru 
Published: March 2019

Background:GDC-0980 is a selective small molecule inhibitor of class I PI3K and mTOR pathway with a potent anti-proliferative activity.Objective:We set out to evaluate the efficacy of GDC-0980, in pre-clinical studies, against pediatric leukemia cells.Methods:The anti-neoplastic activity of GDC-0980 was evaluated in vitro using five different pediatric leukemia cells.Results:Our data show that GDC-0980 significantly inhibited the proliferation of leukemia cell lines, KOPN8 (IC50, 532 nM), SEM (IC50,720 nM), MOLM-13 (IC50,346 nM), MV4;11 (IC50,199 nM), and TIB-202 (IC50, 848 nM), compared to normal control cells (1.23 µM). This antiproliferative activity was associated with activation of cellular apoptotic mechanism characterized by a decrease in Bcl-2 protein phosphorylation and enhanced PARP cleavage. Western blot analyses of GDC-0980 treated cells also showed decreased phosphorylation levels of mTOR, Akt and S6, but not ERK1/2. Notably, FLT3 phosphorylation was decreased in Molm-13 and MV4;11 cells following the application of GDC-0980. We further examined cellular viability of GDC-0980-treated primary leukemia cells isolated from pediatric leukemia patients. This study revealed a potential therapeutic effect of GDC-0980 on two ALL patients (IC50’s, 1.23 and 0.625 µM, respectively). Drug combination analyses of GDC-0980 demonstrated a synergistic activity with the MEK inhibitor Cobimetinib (MV4-11; 11, CI, 0.25, SEM, CI, 0.32, and TIB-202, CI, 0.55) and the targeted FLT3 inhibitor, Crenolanib (MV4-11; 11, CI, 0.25, SEM, CI, 0.7, and TIB-202, CI, 0.42).Conclusion:These findings provide initial proof-of-concept data and rationale for further investigation of GDC-0980 in selected subgroups of pediatric leukemia patients.
Foeniculum Vulgare and Pelargonium Graveolens Essential Oil Mixture Triggers the Cell Cycle Arrest and Apoptosis in MCF-7 Cells
Authors: El-Garawani Islam , El Nabi Sobhy Hassab , Nafie Ebtesam , Almeldin Samar 
Published: March 2019

Background:Fennel (Foeniculum vulgare) and rose geranium (Pelargonium graveolens) oils are known for their various biological effects including anticancer properties.Objective:This study aimed to evaluate the anticancer mechanism of fennel and geranium oils combined treatment on MCF-7 cells.Methods:The GC-MS method for essential oil characterization as well as the in vitro cytotoxicity, morphological changes, real-time PCR and immunocytochemical investigation for apoptosis-related markers, in addition, to flow cytometric cell cycle distribution analysis were done.Results:The major constituents of both essential oils were anethole (55.33 %) and estragole (11.57 %) for fennel essential oil. However, cintronellol (34.40 %) and geraniol (8.67 %) were identified in geranium oil. The results revealed an IC50 of 220±5.7 and 60±2.1µg/ml for fennel and geranium oils, respectively. The mechanistic anticancer properties were investigated throughout the 70, 50, and 25µg/ml of oils mixture. The marked apoptotic morphology and the flow cytometric cell cycle distribution analysis in addition to the levels of apoptosisrelated makers such as p53, caspase-3, mir-21, mir-92a, Bcl-2, and ki-67 confirmed that fennel and geranium oils combination induced cell cycle arrest and apoptosis in MCF-7 cells. Moreover, the oils mixture did not exert any significant (P<0.01) toxicity on normal human peripheral blood lymphocytes in vitro.Conclusion:The findings showed that the mixture of oils exerted selective cytotoxicity towards MCF-7 cells through induction of cell cycle arrest and apoptosis which may be triggered by the synergistic effect between the active ingredients of fennel and geranium oils.
Computational Drug Designing and Prediction Of Important Parameters Using in silico Methods- A Review
Authors: Khan Tahmeena , Lawrence Alfred J. , Azad Iqbal , Raza Saman , Joshi Seema , Khan Abdul Rahman 
Published: March 2019

Background::Computational or in silico studies are undertaken to assess the drug like properties of lead compounds. These studies help in fast prediction of relevant properties.Objective: :Through this review, an effort is made to encapsulate some of the important parameters which should be met by a compound for it to be considered as a potential drug candidate along with an overview of automated softwares which can be used for making various predictions.Methods::Drug uptake, its absorption, evacuation and associated hazardous effects are important factors for consideration in drug designing and should be known in early stages of drug development. Several important physicochemical properties like molecular weight, polar surface area (PSA), molecular flexibility etc. have to be taken into consideration in drug designing. Toxicological assessment is another important aspect of drug discovery which predicts the safety and adverse effects of a drug.Results: :Additionally, bioactivity scores of probable drug leads against various human receptors can also be predicted to evaluate the probability of them to act as a potential drug candidate. The in vivo biological targets of a molecule can also be efficiently predicted by molecular docking studies.Conclusion::Some important software like iGEMDOCK, AutoDock, OSIRIS property explorer, Molinspiration, MetaPrint2D, admetSAR and their working methodology and principle of working have been summarized in this review.
Sex-Related Differences in Plasma Oxytocin Levels in Humans
Authors: Marazziti Donatella , Baroni Stefano , Mucci Federico , Piccinni Armando , Moroni Ilenia , Giannaccini Gino , Carmassi Claudia , Massimetti Enrico , Dell’Osso Liliana 
Published: March 2019

Background:Increasing evidence supports a key role of Oxytocin (OT) as a modulator of social relationships in mammals.Objective:The aim of the present study was to investigate possible sex-related differences in plasma OT levels in human beings.Methods:Forty-five healthy men and 45 women (mean age: 34.9 ± 6.2 years), were included in the study. Plasma preparation, peptide extraction and OT radioimmunoassay were carried out according to standardized methods.Results:The results showed that OT plasma levels (pg ̸ ml, mean ± SD) were significantly higher in women than in men (4.53 ± 1.18 vs 1.53 ± 1.19, p ˂ 0.001).Conclusions:The present finding demonstrates sex-related differences in plasma OT levels in humans. It is tempting to hypothesize that such differences might be related to behaviours, attitudes, as well as susceptibility to stress response, resilience and social emotions specific of women and men.
A Brief History of Modern Endocrinology and Definitions of a True Hormone
Authors: Bahadoran Zahra , Mirmiran Parvin , Azizi Fereidoun , Ghasemi Asghar 
Published: March 2019

Background and Objective:
An overview of the history of endocrinology indicates that
definitions of some initially developed concepts, including the term ‘hormone’ have been changed over
time. This review provides a historical overview of current definitions of ‘hormone’ and the criteria of
a true hormone. In addition, a brief history of hormone-related concepts and their transformation over
time are discussed.

Results:
Classically, a hormone is a chemical substance secreted into the bloodstream and acts on distant
tissues, usually in a regulatory fashion. Several newly discovered bioregulators and chemical signaling
molecules are far from the classical definition of a true hormone and could not fulfill many relevant
criteria. Major developments in the field of endocrinology accompanied by the complex terminology,
currently used to describe hormonal actions of chemical messengers, underscore the need of the
revision of such classical concepts.

Conclusion:
Complex terminology currently used to describe different hormonal actions of chemical
messengers, suggests that it is time to conceptualize the term hormone and revise its classical definition.
Impaired Myocardial MIF/AMPK Activation Aggravates Myocardial Ischemia Reperfusion Injury in High-Fat Diet-Induced Obesity
Authors: Meng Fanqing , Li Dongliang , Song Bingfeng , Li Liang 
Published: March 2019

Background:
Obese patients are more sensitive to myocardial ischemia, which has been
linked with high mortality rates. The following study investigates the effects of impaired macrophage
Migration Inhibitory Factor (MIF)/AMP-Activated Protein Kinase (AMPK) activation on increased
susceptibility to myocardial ischemia/reperfusion (I/R) in high-fat diet-induced obesity.

Methods:
Male C57BL/6J mice were fed with a normal diet (10% kcal as fat, lean group) or a high-fat
diet (60kcal as fat, obese group) for 12 consecutive weeks. To detect the MIF expression and AMPK
activation in response to I/R in isolated hearts from lean and obese mice, myocardial samples were
collected from left ventricular areas at different time points. To determine whether MIF supplementation
is protective against I/R injury, recombined MIF (10 ng/mL) was applied before ischemia. Myocardial
infarct size was estimated by triphenyltetrazolium staining. Western blot was used to detect
myocardial MIF expression, AMPK activation and membrane glucose transporter 4 (Glut4) expression.

Results:
The expression of MIF was remarkably higher in obese group compared to lean group.
Ischemia increased myocardial MIF expression and phosphorylation of AMPK in lean mice, whereas it
had no significant effect on obese mice. Furthermore, administration of recombinant MIF increased
ischemic AMPK activation and membrane Glut4 expression in both lean and obese mice, while it reduced
the infarct size in lean mice only.

Conclusion:
An impaired MIF/AMPK activation response and consequent reduced membrane Glut4
expression may play an important role in increasing myocardial susceptibility to I/R in obesity.
Long-term Outcomes in Peripartum Cardiomyopathy
Authors: Mahowald Madeline K , Basu Nivedita , Subramaniam Latha , Scott Ryan , Davis Melinda B. 
Published: March 2019

Background:
Prior studies of Peripartum Cardiomyopathy (PPCM) are limited by short-term follow-up. Contemporary long-term outcomes and change in myocardial function over time are poorly characterized.

Methods and Results:
This retrospective cohort study included women with PPCM at the University of Michigan (2000-2011), with follow-up on March 31, 2017. Subsequent pregnancies were excluded. Recovery was sustained left ventricular Ejection Fraction (EF) ≥55%. Major Adverse Events (MAE) included death, cardiac transplantation, left ventricular assist device, or inotrope-dependence. A total of 59 women were included (mean [SD] age at diagnosis, 29.5 [6.8]; 28.8% Black), with a mean follow-up of 6.3 years. Recovery occurred in 22 women (37%); of these, 8 women (36%) had delayed recovery (>12 months). All cause mortality was 20% (12/59) with median survival 4.2 years; of these, 9 women (75%) died after the first year (range 2 - 10 years). MAE occurred in 19 women (32%); of these, 11 women (42%) had MAE >12 months from time of diagnosis (range 2-20 years). Deterioration in EF by >10% from the time of diagnosis occurred in 16 women (27%). This group had worse long-term outcomes, including lower final EF (mean 25 vs 42%, p=0.010), less recovery (12 vs 46%, p=0.016), and higher rates of death (38 vs 14%, p=0.046) and MAE (56 vs 23%, p=0.016).

Conclusion:
Women with PPCM have long-term risks of mortality, MAE, and subsequent decline in EF, even in the absence of a subsequent pregnancy. Deterioration in EF is associated with adverse events; thus, long-term management is important.
Detection of OXA Beta Lactamases Among Clinical Isolates of Acinetobacter baumannii Isolated from Tehran Hospitals, Iran
Authors: Ranjbar Reza , Zayeri Shahin , Afshar Davoud , Farshad Shohreh 
Published: March 2019

Background and Objective:Acinetobacter baumanniiis a non-motile Gram-negative bacterial pathogen with the history of vast resistant to antibiotics. The aim of this study was to determine the possibility of existence of OXAs genes among clinical isolates ofA. baumanniiobtained from Tehran hospitals.Materials and Methods:A total of 101 isolates were identified asA. baumanniiby common biochemical and molecular tests. The susceptibility to different antibiotics was assessed with Kirby-Bauer disk diffusion method. Phenotypic Detection of MBLs was performed with CDT test and PCR assay was also performed for detection ofblaOXA-23-like,blaOXA-24-like,blaOXA-40-like,blaOXA-51-like,blaOXA-58-likeandblaOXA-143-likegenesResults:All isolates ofA. baumanniishowed high-level of resistance to all antibiotics except for Polymyxin B. TheblaOXA-51 likegenes was found in all of the isolates and the prevalence ofblaOXA-143like,blaOXA-23like,blaOXA-40likeandblaOXA-24likewere 56%, 45.45%, 33% and 11.8%, respectively.Conclusion:TheblaOXA-51-likewas the predominant mechanism of resistance to imipenem inA. baumanniiand therefore, early recognition of carbapenem-resistantA. baumanniiisolates is a useful tools to prevent their spreading within the hospital environment.
Isolation Detection and Characterization of Syringolin A produced from the Probiotic Strain Bacillus Cereus Isolated from Donkey Milk
Authors: D Rashmi , T Sharmila , Patil Sushama , Apine Onkar , Sistla Srinivas , Jadhav Jyoti 
Published: March 2019

Syringolin A is a non-ribosomal virulence factor secreted by few Pseudomonas strains. Syringolin A is an well known irreversible proteasome inhibitor and antitumor compound. The present study is focused on the extraction of Syringolin A through a non-tedious and economical process. Syringolin A is extracted from culture supernatants by the immiscible organic layer by mixing of dichloromethane or chloroform (trichloromethane). Syringolin A was identified by the characteristic peak at 350 nm by UV spectra. The compound was further characterized by Thin Layer Chromatography (TLC) with the retention value, Rf was found to be in the range of 0.78-0.83 run using a combination of solvent systems water and methanol. The molecular weight of the compound was found to be 492.2614 g mol-1 identified and analyzed by UHPLC–QTOF-MS analysis. Due to its significant pharmacological importance in proliferative diseases, further studies on production and optimization of these compounds are necessary.