bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Simple and One-pot Synthesis of Tetrahydrobenzo[b]pyrans and Spirooxindoles Catalyzed by H-Fe3O4@DA-SO3H as an Efficient, Light and Reusable Nanocatalyst
Authors: Mirhosseyni Marzie Sadat , Nemati Firouzeh , Elhampour Ali 
Published: August 2018

Aim and Objective:
One of the principles of green chemistry is using inexpensive
reagents and catalysts to design green route for synthesis of organic compounds. Recently magnetic
nanoparticles have provided a considerable merits. In this study, hollow Fe3O4@Dopamine-SO3H
has been successfully applied for the green synthesis of tetrahydrobenzo[b]pyrans and
spirooxindoles via one-pot multi-component reaction.

Materials and Methods:
Chemical reagents were purchased from Merck and Aldrich. Melting points
were determined using an Electrothermal 9100. Fourier transform infrared and NMR spectra were
recorded with a Shimadzu 8400 spectrometer and Bruker spectrometer, respectively.

Results:
The reaction between benzaldehyde, malononitrile and dimedone was selected as the model
for synthesis of tetrahydrobenzo[b]pyran. The obtained results showed that the best amount of
catalyst is 0.01 g and the reaction has occurred in solvent free condition at 70°C. The results showed
that both electron-withdrawing and electron-donating substituents have an acceptable yield in the
reaction. After that the scope of this method was evaluated in one-pot synthesis of spirooxindole
derivatives through three-component reaction of isatin derivatives, malononitrile or ethyl
cyanoacetate and 1,3-cycllic diketone. The optimum condition was 0.01 g catalyst using H2O under
reflux condition. Then other derivatives produced in excellent yields during short reaction times.

Conclusion:
Tetrahydrobenzo[b]pyran and spirooxindole derivatives in the presence of this catalyst
were synthesized. The ease of preparation and handling of the catalyst and operational simplicity are
some of the main advantages of this work. In addition, the catalyst could be recycled and reused at
least six times without notable reduction in its catalytic activity.
Probiotic Supplementation in Patients with Alzheimer’s Dementia - An Explorative Intervention Study
Authors: Leblhuber Friedrich , Steiner Kostja , Schuetz Burkhard , Fuchs Dietmar , Gostner Johanna M. 
Published: August 2018

Background:
Dysbiosis of intestinal microbiota in the elderly can cause a leaky gut, which
may result in silent systemic inflammation and promote neuroinflammation - a relevant pathomechanism
in the early course of Alzheimer’s disease.

Objective:
The rebalancing of the microbiome could benefically impact on gut inflammation and immune
activation.

Methods:
In this study, routine laboratory tests in twenty outpatients (9 females, 11 males, aged 76.7 ±
9.6 years) with Alzheimer’s disease were investigated. The mean Mini Mental State Examination score
was 18.5 ± 7.7. Biomarkers of immune activation – serum neopterin and tryptophan breakdown - as
well as gut inflammation markers and microbiota composition in fecal specimens were analyzed in 18
patients before and after probiotic supplementation for 4 weeks.

Results:
After treatment a decline of fecal zonulin concentrations and an increase in Faecalibacterium
prausnitzii compared to baseline were observed. At the same time, serum kynurenine concentrations
increased (p <0.05). Delta values (before - after) of neopterin and the kynurenine to tryptophan ratios
(Kyn/Trp) correlated significantly (p <0.05).

Conclusion:
Results show that the supplementation of Alzheimer’s disease patients with a multispecies
probiotic influences gut bacteria composition as well as tryptophan metabolism in serum. The correlation
between Kyn/Trp and neopterin concentrations points to the activation of macrophages and/or dendritic
cells. Further studies are warranted to dissect the potential consequences of Probiotic supplementation
in the course of Alzheimer’s disease.
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors, Reality or Dream in Managing Patients with Cardiovascular Disease
Authors: Alkhalil Mohammad 
Published: August 2018

Background:
Statins have been a major keystone in the management of patients with atherosclerotic cardiovascular
disease. The benefits of inhibiting HMG CoA reductase, via statins, were translated into reduction in
LDL-c with proportionate decrease in cardiovascular events in response to the magnitude of LDL-c reduction. Despite
major advances in pharmacological treatments, including the use of high-dose statins, there are urgent need to
further reduce future cardiovascular risk. This is in particularly important since 1 out of 5 high-risk atherosclerotic
patients who achieve low LDL-c return with a second cardiovascular event within five years. Although this residual
risk post-statin is largely heterogeneous, lowering LDL-c beyond ‘normal’ or guidelines-recommended level using
novel therapies has resulted in further reduction in cardiovascular events.
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Objective: The current review will discuss the use of PCSK9 inhibitors in patients with atherosclerotic disease.
PCSK9 inhibitors are a new class of lipid-lowering drugs that are either fully human monoclonal antibodies (evolocumab
and alirocumab) or humanised monoclonal antibodies (bococizumab) that effectively reduce LDL-c to unprecedented
level. By blocking circulating PCSK9, these drugs would preserve LDL receptors and prevent them
from cellular degradation. This process promotes recycling of LDL receptors back to hepatocytes surface, leading
into further reduction of LDL-c. Combining PCSK9 inhibitors with statin have led into lower LDL-c, reduction in
plaque volume and more importantly reduction in future cardiovascular events.

Conclusion:
These drugs are very promising, nonetheless, the unselective approach of applying these monoclonal
antibodies may not prove to be cost-effective and potentially exposing some patients to unnecessary side effects.
Survey of Machine Learning Techniques in Drug Discovery
Authors: Stephenson Natalie , Shane Emily , Chase Jessica , Rowland Jason , Ries David , Justice Nicola , Zhang Jie , Chan Leong , Cao Renzhi 
Published: August 2018

Background:Drug discovery, which is the process of discovering new candidate medications, is very important for pharmaceutical industries. At its current stage, discovering new drugs is still a very expensive and time-consuming process, requiring Phases I, II and III for clinical trials. Recently, machine learning techniques in Artificial Intelligence (AI), especially the deep learning techniques which allow a computational model to generate multiple layers, have been widely applied and achieved state-of-the-art performance in different fields, such as speech recognition, image classification, bioinformatics, etc. One very important application of these AI techniques is in the field of drug discovery.Methods:We did a large-scale literature search on existing scientific websites (e.g, ScienceDirect, Arxiv) and startup companies to understand current status of machine learning techniques in drug discovery.Results:Our experiments demonstrated that there are different patterns in machine learning fields and drug discovery fields. For example, keywords like prediction, brain, discovery, and treatment are usually in drug discovery fields. Also, the total number of papers published in drug discovery fields with machine learning techniques is increasing every year.Conclusion:The main focus of this survey is to understand the current status of machine learning techniques in the drug discovery field within both academic and industrial settings, and discuss its potential future applications. Several interesting patterns for machine learning techniques in drug discovery fields are discussed in this survey.
Oral and Written Naming in Alzheimer’s Disease: A Longitudinal Study
Authors: Gonzalez-Nosti Maria , Cuetos Fernando , Martinez Carmen 
Published: August 2018

Background:
The expressive difficulties in patients with Alzheimer’s dementia have been
extensively studied, mainly in oral language. However, the deterioration of their writing processes has
received much less attention.

Objective:
The present study aims to examine the decline of the performance of patients with Alzheimer’s
disease in both oral and written picture-naming tasks.

Method:
Sixty-four participants (half with Alzheimer’s disease and half healthy elderly) were compared
in the oral and written versions of a picture-naming task. Follow-up lasted two and a half years and patients
were evaluated every six months.

Results:
Cross-sectional data indicate that the controls performed better than the patients, and both
groups showed a different pattern of errors. In terms of longitudinal data, the results show a similar pattern
of deterioration in both tasks. In terms of errors, lexical-semantics were the most numerous at the
beginning and their number remained constant throughout all evaluations. In the case of non-responses,
there was a significant increase in the last session, both in oral and written naming.

Conclusion:
These results replicate those found in previous studies and highlight the utility of the naming
task to detect minimal changes in the evolution of patients with Alzheimer’s disease.
Deformation-based Statistical Shape Analysis of the Corpus Callosum in Mild Cognitive Impairment and Alzheimer’s Disease
Authors: Jiang Zihan , Yang Huilin , Tang Xiaoying 
Published: August 2018

Objective: In this study, we investigated the influence that the pathology of Alzheimer’s disease
(AD) exerts upon the corpus callosum (CC) using a total of 325 mild cognitive impairment (MCI)
subjects, 155 AD subjects, and 185 healthy control (HC) subjects.

Method:
Regionally-specific morphological CC abnormalities, as induced by AD, were quantified using
a large deformation diffeomorphic metric curve mapping based statistical shape analysis pipeline.
We also quantified the association between the CC shape phenotype and two cognitive measures; the
Mini Mental State Examination (MMSE) and the Alzheimer’s Disease Assessment Scale-Cognitive
Behavior Section (ADAS-cog). To identify AD-relevant areas, CC was sub-divided into three subregions;
the genu, body, and splenium (gCC, bCC, and sCC).

Results:
We observed significant shape compressions in AD relative to that in HC, mainly concentrated
on the superior part of CC, across all three sub-regions. The HC-vs-MCI shape abnormalities were also
concentrated on the superior part, but mainly occurred on bCC and sCC. The significant MCI-vs-AD
shape differences, however, were only detected in part of sCC. In the shape-cognition association, significant
negative correlations to ADAS-cog were detected for shape deformations at regions belonging
to gCC and sCC and significant positive correlations to MMSE at regions mainly belonging to sCC.

Conclusion:
Our results suggest that the callosal shape deformation patterns, especially those of sCC,
linked tightly to the cognitive decline in AD, and are potentially a powerful biomarker for monitoring
the progression of AD.
Ezrin Expression is Increased During Disease Progression in a Tauopathy Mouse Model and Alzheimer’s Disease
Authors: Vega Irving E. , Umstead Andrew , Wygant Cassandra M. , Beck John S. , Counts Scott E. 
Published: August 2018

Background:
The lack of diagnostic tools and disease-modifying treatments against Alzheimer’s
disease (AD) and related disorders, collectively known as tauopathies, has led to a socioeconomic
burden of epidemic proportion. Proteomics approaches can be used to identify novel proteome
changes that could help us understand the pathogenesis of tau-related pathological hallmarks and/or cellular
stress responses associated with tauopathy. These studies, however, need to be conducted taking
into consideration brain region specificity and stage of neurodegeneration in order to provide insights
about the pathological role of the identified proteins.

Methods:
We used a tauopathy mouse model (JNPL3) that expresses human tau bearing a P301L mutation
and develops motor impairment, the severity of which correlates with the increased accumulation of
pathological tau. Tissue was dissected from asymptomatic and severely motor impaired JNPL3 mice as
well as non-transgenic littermate controls and subjected to two-dimensional gel electrophoresis. Differentially
abundant protein spots were identified by tandem mass spectrometry. Postmortem mild cognitive
impairment (MCI), AD and normal aging controls were used to validate the pathological significance
of the identified protein.

Results:
Ezrin was identified as a protein that is upregulated in tau-mediated neurodegeneration. We
demonstrate that Ezrin protein abundance increased in JNPL3 mice preceded motor impairment and was
sustained in severely motor impaired mice. Ezrin expression was also increased in the temporal cortex of
MCI and AD patients.

Conclusion:
The results demonstrate that increased Ezrin protein abundance changes are associated with
the early stages of neurodegeneration in tauopathy models and human disease. Understanding the role of
Ezrin in tauopathies such as AD may provide new insights for targeting tau-mediated neurodegeneration.
The Evaluation of Animal Models in the Development of Anticancer Agents: From Preclinical to Clinical Tests
Authors: Wang Jie , Dong Haiyan , Liu Jian , Zheng Ning , Xie Xiaodong , Jia Lee 
Published: August 2018

Background:
One of the main reasons for most of the anticancer drugs to fail in the late
preclinical testing and early clinical trials is the differences in drug effects observed from animals
and patients, and the challenge has been to find a balance to reduce the inherent differences from
species.

Objective:
Predicting safe starting doses and dosing schedules for human clinical trials is the main
purpose of toxicological studies of anticancer drugs.

Methods:
Relevant information and data were assimilated from manuscripts, congress publications,
and online sources.

Results:
We systematically overview the cons and pros of animal models and briefed the ways to
determine human clinical starting doses derived from animal toxicological studies for anticancer
drugs.

Conclusion:
This information helps smart select the suitable predictive model for anti-cancer drugs
with the different mechanisms and emphasized the pharmaceutical challenges behind and ahead.
Hydrops Fetalis and THE Parvovirus B-19
Authors: Kontomanolis Emmanuel N. , Fasoulakis Z. 
Published: August 2018

Definition:
Hydrops Fetalis (HF) or fetal hydrops is identified as an abnormal interstitial
collection of fluid in at least 2 or more compartments of the fetal torso (peritoneal cavity, pleura,
and pericardium). An alternative definition discusses about liquor accumulation in two fetal anatomical
areas or an effusion in one site and anasarca.

Background:
Parvovirus B-19 is a common childhood illness; the virus can cause fetal anemia,
non-immune fetal hydrops, and spontaneous abortion and might lead to fetal demise.

HF is the pathological distribution of body fluids between the interstitial and the intravascular areas
of the fetus. Normally, in the fetal organism there is a continuous circular movement of the lymph
from the interstitial space into the vascular system and vice versa. The detection of a solely effusion
represents the initial stage of a systemic disorder that will lead to a fully developed hydrops or remain
just a local disorder.

Objective:
The connection between parvovirus B-19 and fetal hydrops.

Conclusion:
The view is unbeatable, severely swollen babies; immune hydrops is surfaced because
of the maternal antibodies targeted against red blood cells with Rh positive antibody of the fetus,
while the non-immune is due to a variety of pathological conditions in pregnancy.
Post Chikungunya Chronic Arthritis: Systemic Inflammatory Status Triggering Acute Coronary Syndrome
Authors: Patel Dhruvkumar M. , Patel Mukundkumar V. , Sharma Kamal H. , Patel Greshaben R. , Patel Manish B. , Shah Vipul V. 
Published: August 2018

Background:
Atherosclerosis, inflammation and coronary plaque destabilization are
linked to each other. Infections due to various microbes may trigger Acute Coronary Syndrome
(ACS) by systemic inflammation cascade.

Methods:
We have evaluated the prevalence of Post Chikungunya Chronic Arthritis (PCCA)
among 400 consecutive ACS patients (Case group) and compared with control group subjected to
elective surgery by the prospective case-control observational study. Cases were excluded if standard
criteria of ACS were not satisfied and in the control group if the patient suffered a Myocardial
Infarction (MI) within 28 days of elective surgery. PCCA duration more than two years or serum
IgM anti-CCP positive patients were also excluded from the case as well as a control group.

Results:
The case and control groups were similar except, less number of heart failure (O.R.7.3,
95% C.I. 3.3-15.9) and chronic kidney injury patients (O.R. 0.5, 95% C.I. 0.3-0.9) in the elective
surgery (control) group. PCCA was present in 24 out of 400 ACS cases and 8 out of 400 control
group. Among ACS case-patients, those suffering from PCCA tended to be younger and more often
women, with more diabetes, hypertension, chronic kidney injury and high mean CRP. In unadjusted
analysis PCCA was three times more common in the case versus control (O.R. 3.0, 95% C.I. 1.4-
6.4); results were indistinguishable after multidiscipline adjustment (O.R. 3.0, 95% C.I. 1.3-6.8).

Conclusion:
PCCA is common among patients with ACS and post-infective systemic inflammation
of PCCA may trigger plaque destabilization.
Potential Utility of Self-Report Measures of Affect to Optimise Exercise Adherence in People with Type 2 Diabetes
Authors: Cox Emily R. , Keating Shelley Elizabeth , Coombes Jeff S. , Burton Nicola W. 
Published: August 2018

:
Exercise is essential for managing type 2 diabetes, however approximately only 40% of people
with the condition meet guidelines. The aim of this review is to examine the evidence regarding the
use self-report measures of affect to understand and predict exercise adherence. Self-reported affect has
been successfully used to regulate exercise intensity, monitor training load, prevent injury, and predict
future physical activity participation in otherwise healthy and some clinical populations.

:
Specific recommendations are provided for research to explore the utility of self-report measures of affect
to promote exercise adherence in people with type 2 diabetes.
Hypertension, Diabetes and Neurodegenerative Diseases: Is there a Clinical Link through the Ca2+/cAMP Signalling Interaction?
Authors: Bergantin Leandro Bueno 
Published: August 2018

Background:Hypertension, diabetes and neurodegenerative diseases are among the most prevalent medical problems around the world, costing millions of dollars to the medical health systems. Indeed, hypertension has been associated with higher risk for decline of cognition, as evidenced in patients with Alzheimer´s disease (AD). Furthermore, there is a clear relationship between hypertension and diabetes, reflecting substantial overlap in their etiology. Calcium (Ca2+) channel blockers (CCBs) have been classically prescribed for treating hypertension because of their mechanism of action due to reducing the influx of Ca2+ into the smooth muscles cells. In addition, many clinical and experimental studies have been demonstrating pleiotropic effects for CCBs. For instance, in hypertensive patients treated with CCBs, it can be observed lower incidence of neurodegenerative diseases such as AD. The virtual mechanism of action could be attributed to a restoration and maintenance of Ca2+ homeostasis, which is dysregulated in the neurodegenerative diseases, including also a reduction of neuronal apoptosis as part of these CCBs pleiotropic effects. Similarly, in hypertensive patients treated with CCBs, it can be observed an improvement of diabetes status such as glycemic control. A possible mechanism of action under debate could be attributed to a restoration of insulin secretion, then achieving glycemic control, and reduction of pancreatic β-cell apoptosis.Conclusion:Considering the discovery of our group entitled “calcium paradox” due to Ca2+/cAMP signalling interaction, in this review I discussed the virtual involvement of this interaction in the pleiotropic effects of CCBs, including the possible role of the Ca2+/cAMP signalling interaction in the association between hypertension and higher risk for the decline of cognition, and diabetes.
Modulation of Mitochondrial and Epigenetic Targets by Polyphenols-rich Extract from Araucaria angustifolia in Larynx Carcinoma
Authors: Branco Catia S. , Duong Angela , Machado Alencar K. , Scola Gustavo , Andreazza Ana C. , Salvador Mirian 
Published: August 2018

Background:
Araucaria angustifolia extract (AAE) is a polyphenol-rich extract that has gained interest
as a natural anticancer agent. Recent work suggests that AAE induces oxidative damage and apoptosis through its
action on decreasing complex I activity of the mitochondrial Electron Transport Chain (ETC).

Aims and Methods:
In the present study, we aimed to further examine the specific targets by which AAE exerts proapoptotic
effects in HEp-2 cancer cells. Specifically, the effect of AAE on the: 1) levels of pyruvate dehydrogenase
was assessed by ELISA assay; 2) levels of mitochondrial ETC complexes, focusing on complex I at the gene transcript
and protein level relevant to ROS generation was evaluated by multiplex ELISA followed by qRT-PCR and
immunoblotting; 3) mitochondrial network distribution analysis was assessed by MitoTracker Red CMXRos; and 4)
chemical variations on DNA was evaluated by dot-blotting in HEp-2 cells.

Results:
Results demonstrated that AAE increased protein levels of PDH, switching energy metabolism to oxidative
metabolism. Protein expression levels of complex I and III were found decreased in AAE-treated HEp-2 cells.
Analyzing the subunits of complex I, changes in protein and gene transcript levels of NDUFS7 and NDUFV2 were
found. Mitochondria staining after AAE incubation revealed changes in the mitochondrial network distribution. AAE
was able to induce DNA hypomethylation and decreased DNA (cytosine-5)-methyltransferase 1 activity.

Conclusion:
Our data demonstrate for the first time that AAE alters expression of NDUFS7 and NDUFV2
mitochondrial subunits and induce epigenetic changes in HEp-2 cancer cells leading to a possible suppression of
oncogenes.
Sofosbuvir: Really Meets the Unmet Needs for Hepatitis C Treatment?
Authors: Chopra Deepti , Bhandari Bharti 
Published: August 2018

:
Chronic hepatitis C remains a major public health concern with a prevalence of more than
1% worldwide. Of late, with the discovery of newer drugs, chronic HCV treatment has touched new
dimensions. The treatment has progressed from Interferons to Pegylated interferon (Peg IFN) based
therapy, with or without ribavirin to treatment with orally active Direct Acting Antivirals (DAA)
with Peg IFN and ribavirin and eventually to various combinations of DAA, without IFN.

:
Introduction of newer DAAs has transfigured the treatment of chronic HCV. Chronic HCV patients
with advanced liver disease, psychiatric condition, anemia or autoimmune diseases, not eligible for
Peg IFN based therapy have a ray of hope now. Amongst all DAAs, nucleoside inhibitors have been
the most promising agent.

:
Thus the present review focuses on Sofosbuvir, one of the most effective nucleoside inhibitors; in
terms of potency, resistance profile, activity against all genotypes of HCV and adverse effects. FDA
approved Sofobuvir for clinical use in 2013. Chemically, it is 2'-deoxy-2'-α-fluoro-β-Cmethyluridine-
5'-triphosphate; a phosphoramidate prodrug that is activated by enzyme present in
human liver. It is a highly potent inhibitor of HCV NS5B polymerase.

:
Efficacy of the Sofosbuvir has been established in various phase 2 and phase 3 clinical trials like
PROTON, ELECTRON, FUSION, POSITRON etc. Sofosbuvir has a good safety profile with few
mild to moderate adverse effects. Evidence reveals that sofosbuvir has substantial impact on the
treatment of HCV.