bluuebunny/crossref_metadata_2025_split huggingface dataset:
Syngonanthus nitens (Bong.) Ruhland Derivatives Loaded into a Lipid Nanoemulsion for Enhanced Antifungal Activity Against Candida parapsilosis
Authors: C. de Lima Laura , A.S. Ramos Matheus , Toledo Luciani G. de , Rodero Camila F. , Hilário Felipe , dos Santos Lourdes C. , Chorilli Marlus , Bauab Taís M. 
Published: March 2020

Background:
Vaginal infections caused by non-albicans species have become common in women of
all age groups. The resistance of species such as Candida parapsilosis to the various antifungal agents is a risk
factor attributed to these types of infections, which instigates the search for new sources of active compounds in
vulvovaginal candidiasis (VCC) therapy.

Objective:
This study evaluated the antifungal activity of Syngonanthus nitens Bong. (Ruhland) derivatives and
employed a lipid nanoemulsion as a delivery system.

Methods:
In this study, a lipid nanoemulsion was employed as a delivery system composed of Cholesterol (10%),
soybean phosphatidylcholine: Brij 58 (1: 2) and PBS (pH 7.4) with the addition of 0.5% of a chitosan dispersion
(80%), and evaluated the antifungal activity of S. nitens Bong. (Ruhland) derivatives against planktonic cells and
biofilms of Candida parapsilosis. By a biomonitoring fractionation, the crude extract (EXT) and one fraction (F2)
were selected and incorporated into a lipid nanoemulsion (NL) composed of cholesterol (10%), a 1:2 mixture of
soybean phosphatidylcholine:polyoxyethylene -20- cetyl ether (10%), and phosphate buffer solution (pH 7.4)
with a 0.5% chitosan dispersion (80%). The NL presented a diameter size between 50-200 nm, pseudoplastic
behavior, and positive charge. The EXT and five fractions were active against planktonic cells.

Results and Discussion:
The incorporation of EXT and F2 into the NL increased antifungal activity and enhanced
the anti-biofilm potential. This study classified the use of an NL as an important tool for the administration
of S. nitens derivatives in cases of infections caused by this C. parapsisilosis.

Conclusion:
This work concluded that S. nitens derivatives were important sources of active molecules against C.
parapsilosis and the use of a lipid nanoemulsion was an important tool to promote more effective F2 release and
to improve the antifungal activity aiming the control of C. parapsilosis infections.
Vaccinium myrtillus L. Fruits as a Novel Source of Phenolic Compounds with Health Benefits and Industrial Applications - A Review
Authors: Pires Tânia C. S. P. , Caleja Cristina , Santos-Buelga Celestino , Barros Lillian , Ferreira Isabel C.F.R. 
Published: March 2020

:
Consumers’ demand for healthier foods with functional properties has had a clear influence on the food
industry and in this sense, they have been attaching natural sources of bioactive ingredients into food products.
Vaccinium myrtillus L. (bilberry) is known to be a functional food, presenting its fruits in the form of a small dark
blueberry. This coloration is due to its high content in anthocyanin, being also associated with bilberries’ beneficial
health effects. In the bilberry industry, there is a very high annual loss of this fruit due to the less aesthetic
shape or appearance, in which they cannot be considered suitable for sale and are therefore disposed of as biological
waste. Therefore, it is of great importance to valorize this fruit and this review aimed to completely characterize
the fruits of V. myrtillus in order to comprehend the relationship between their consumption and the beneficial
effects regarding consumer’s health. Thus, this review provides a description of the nutritional and bioactive
compounds present in bilberry fruits, followed by their beneficial health effects. An overview of the natural pigments
present in these fruits was also explored, focusing particularly in the anthocyanins composition, which
represents the most widely studied class of bioactive compounds of V. myrtillus fruits. Finally, industrial applications
of these fruits and by-products, as an efficient approach to the production of value-added products with
economical and environmental impact, were also discussed.

:
In general, V. myrtillus is a rich source of micronutrients and phytochemical compounds, such as organic acids,
sugars, vitamins, fibers and phenolic compounds (anthocyanin and non-anthocyanin compounds), with nutritional
and functional properties, that justify the growing interest in these berries, not only for food applications, but also
in the pharmaceutical industry.
Therapeutic Nanoemulsion: Concept to Delivery
Authors: Barkat Md. A. , Harshita  , Rizwanullah Md. , Pottoo Faheem H. , Beg Sarwar , Akhter Sohail , Ahmad Farhan J. 
Published: March 2020

:Nanoemulsions (NEs) or nanometric-scaled emulsions are transparent or translucent, optically isotropic and kinetically stable heterogeneous system of two different immiscible liquids namely, water and oil stabilized with an amphiphilic surfactant having droplet size ranges up to 100 nm. They offer a variety of potential interests for certain applications: improved deep-rooted stability; excellent optical clarity; and, enhanced bioavailability due to its nanoscale of particles. Though there is still comparatively narrow insight apropos design, development, and optimization of NEs, which mainly stems from the fact that conventional characteristics of emulsion development and stabilization only partly apply to NEs. The contemporary article focuses on the nanoemulsion dosage form journey from concept to key application in drug delivery. In addition, industrial scalability of the nanoemulsion, as well as its presence in commercial and clinical practice, are also addressed.
Formulation of Extended-Release Beads of Lamotrigine Based on Alginate and Cassia fistula Seed Gum by QbD Approach
Authors: Jain Dixita , Sodani Akshay , Ray Swapnanil , Ghosh Pranab , Nandi Gouranga 
Published: March 2020

Aim:
This study was focused on the formulation of the multi-unit extended-release peroral
delivery device of lamotrigine for better management of epilepsy.

Background:
The single-unit extended-release peroral preparations often suffer from all-or-none effect.
A significant number of multi-unit delivery systems have been reported as a solution to this problem.
But most of them are found to be composed of synthetic, semi-synthetic or their combination having
physiological toxicity as well as negative environmental impact. Therefore, fabrication and formulation
of multi-unit extended-release peroral preparations with natural, non-toxic, biodegradable polymers employing
green manufacturing processes are being appreciated worldwide.

Objective:
Lamotrigine-loaded extended-release multi-unit beads have been fabricated with the incorporation
of a natural polysaccharide Cassia fistula seed gum in calcium-cross-linked alginate matrix employing
a simple green process and 23 full factorial design.

Methods:
The total polymer concentration, polymer ratio and [CaCl2] were considered as independent
formulation variables with two different levels of each for the experiment-design. The extended-release
beads were then prepared by the ionotropic gelation method using calcium chloride as the crosslinkerions
provider. The beads were then evaluated for drug encapsulation efficiency and drug release. ANOVA
of all the dependent variables such as DEE, cumulative % drug release at 2h, 5h, 12h, rate constant
and dissolution similarity factor (f2) was done by 23 full factorial design using Design-Expert software
along with numerical optimization of the independent variables in order to meet USP-reference release
profile.

Results:
The optimized batch showed excellent outcomes with DEE of 84.7 ± 2.7 (%), CPR2h of 8.41±
2.96 (%), CPR5h of 36.8± 4.7 (%), CPR12h of 87.3 ± 3.64 (%) and f2 of 65.9.

Conclusion:
This approach of the development of multi-unit oral devices utilizing natural polysaccharides
might be inspiring towards the world-wide effort for green manufacturing of sustained-release drug
products by the QbD route.
Dehydroepiandrosterone (DHEA) and its Sulphate (DHEAS) in Alzheimer’s Disease
Authors: Strac Dubravka S. , Konjevod Marcela , Perkovic Matea N. , Tudor Lucija , Erjavec Gordana N. , Pivac Nela 
Published: March 2020

Background:Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease.Objective:The aim of the article was to provide a comprehensive overview of the literature on the involvement of DHEA and DHEAS in Alzheimer’s disease.Method:PubMed and MEDLINE databases were searched for relevant literature. The articles were selected considering their titles and abstracts. In the selected full texts, lists of references were searched manually for additional articles.Results:We performed a systematic review of the studies investigating the role of DHEA and DHEAS in various in vitro and animal models, as well as in patients with Alzheimer’s disease, and provided a comprehensive discussion on their potential preventive and therapeutic applications.Conclusion:Despite mixed results, the findings of various preclinical studies are generally supportive of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer’s disease, showing some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms of action, prior to their applications in clinical practice.
Joint Effect of ABCA7 rs4147929 and Body Mass Index on Progression from Mild Cognitive Impairment to Alzheimer’s Disease: The Shanghai Aging Study
Authors: Xi Jianxiong , Ding Ding , Zhao Qianhua , Liang Xiaoniu , Zheng Li , Guo Qihao , Hong Zhen , Fu Hua , Xu Jianfeng , Xiao Qianyi 
Published: March 2020

Background:
Approximately 40 independent Single Nucleotide Polymorphisms (SNPs) have
been associated with Alzheimer’s Disease (AD) or cognitive decline in genome-wide association studies.

Methods:
We aimed to evaluate the joint effect of genetic polymorphisms and environmental factors on
the progression from Mild Cognitive Impairment (MCI) to AD (MCI-AD progression) in a Chinese
community cohort.

Conclusion:
Demographic, DNA and incident AD diagnosis data were derived from the follow-up of 316
participants with MCI at baseline of the Shanghai Aging Study. The associations of 40 SNPs and environmental
predictors with MCI-AD progression were assessed using the Kaplan-Meier method with the
log-rank test and Cox regression model.

Results:
Rs4147929 at ATP-binding cassette family A member 7 (ABCA7) (AG/AA vs. GG, hazard ratio
[HR] = 2.43, 95% confidence interval [CI] 1.24-4.76) and body mass index (BMI) (overweight vs.
non-overweight, HR = 0.41, 95% CI 0.22-0.78) were independent predictors of MCI-AD progression. In
the combined analyses, MCI participants with the copresence of non-overweight BMI and the ABCA7
rs4147929 (AG/AA) risk genotype had an approximately 6-fold higher risk of MCI-AD progression
than those with an overweight BMI and a non-risk genotype (HR = 6.77, 95% CI 2.60-17.63). However,
a nonsignificant result was found when participants carried only one of these two risk factors (nonoverweight
BMI and AG/AA of ABCA7 rs4147929).

Conclusion:
ABCA7 rs4147929 and BMI jointly affect MCI-AD progression. MCI participants with the
rs4147929 risk genotype may benefit from maintaining an overweight BMI level with regard to their
risk for incident AD.
Detection of Mild Cognitive Impairment Based on Virtual Reality: A Scoping Review
Authors: Wang Shuo , Yin Huiru , Li Guichen , Jia Yong , Leng Minmin , Meng Qiuyan , Wang Chunyan , Chen Li 
Published: March 2020

Background:
To delay the decline in cognition and reduce the incidence of dementia, the
precise detection of Mild Cognitive Impairment (MCI) is necessary. The application of Virtual Reality
(VR) technology in this detection can overcome the shortage of traditional paper-and-pencil tests.

Objective:
This review aimed to summarize the research progress of the detection of MCI using VR.

Methods:
Eight databases from their inception to November 19, 2019, were systematically searched for
studies applying VR in the detection of MCI. A thematic analysis was conducted according to the specific
detection purpose and the main corresponding cognitive domains assessed were summarized; characteristics
of the VR applications were also summarized.

Results:
Twenty-eight studies were finally included. The detection purposes included discrimination
between healthy controls and those with MCI, discrimination between aMCI subtypes, detection of MCI
patients at risk of Alzheimer’s Disease (AD), and discrimination between MCI and AD. VR tasks assessing
spatial memory were applicable for all detection purposes, and the assessment of combinations
of memory and executive function seemed more sensitive. Executive function and intentional episodic
memory could be assessed to discriminate among healthy controls, individuals with MCI and those with
AD. Incidental episodic memory was effective in detecting MCI with hippocampal atrophy. The most
common characteristics of the VR applications were the use of semi-immersion, joysticks or gamepad
interactions and simple, one-time behavioral assessments.

Conclusion:
VR applications are promising in the detection of MCI, but further research is needed for
clinical use.
Association Between Anemia and Dementia: A Nationwide, Populationbased Cohort Study in Taiwan
Authors: Hong Chien-Tai , Hsieh Yi-Chen , Liu Hung-Yi , Chiou Hung-Yi , Chien Li-Nien 
Published: March 2020

Background:
In addition to the traditional risk predictors, whether anemia is an early biomarker
of dementia, needs to be confirmed.

Objective:
This population-based cohort study aimed to investigate the dementia risk in patients with
newly diagnosed anemia using data from the Taiwan National Health Insurance Research Database.

Methods:
All newly diagnosed anemia patients (n = 26,343) with no history of stroke hospitalization,
central nervous disease other than dementia, psychiatric disorders, traumatic brain injury, major operations,
or blood loss diseases, were enrolled. A group of non-anemic controls, 1:4 matched with anemic
patients on the basis of demographics and comorbidities, was also included. A competing risk analysis
was used to evaluate the dementia risk in anemic patients compared to that of their matched controls.

Results:
The adjusted subdistribution hazard ratio (SHR) of dementia risk in anemic patients was 1.14
(95% confidence interval [CI]: 1.08~1.21, p<0.001). Patients with iron supplements tended to exhibit a
lower dementia risk (adjusted SHR: 0.84; 95% CI: 0.75~0.94, p=0.002) compared to patients without
iron supplement. A subgroup analysis showed that a positive association between dementia and anemia
existed in females, those aged 70 years and older, and patients without hypertension, diabetes, or hyperlipidemia.

Conclusion:
The present population-based cohort study identified that newly diagnosed anemia is a risk
factor for dementia and also that iron supplementation was able to reduce the risk of dementia in people
with iron deficiency anemia.
Association between ALDH2 Gene Polymorphism and Late-onset Alzheimer Disease: An Up-to-date Meta-analysis
Authors: Liu Haitao , Ge Wei , Chen Wei , Kong Xue , Jian Weiming , Wang Anhui 
Published: March 2020

Objectives:
Previous case-control studies have focused on the relationship between ALDH2
gene polymorphism and late-onset Alzheimer's Disease (LOAD), but no definite unified conclusion has
been reached. Therefore, the correlation between ALDH2 Glu504Lys polymorphism and LOAD remains
controversial. To analyze the correlation between ALDH2 polymorphism and the risk of LOAD, we implemented
this up-to-date meta-analysis to assess the probable association.

Methods:
Studies were searched through China National Knowledge Infrastructure (CNKI), VIP Database
for Chinese Technical Periodicals, China Biology Medicine, PubMed, Cochrane Library, Clinical-
Trials.gov, Embase, and MEDLINE from January 1, 1994 to December 31, 2018, without any restrictions
on language and ethnicity.

Results:
Five studies of 1057 LOAD patients and 1136 healthy controls met our criteria for the analysis.
Statistically, the ALDH2 GA/AA genotype was not linked with raising LOAD risk (odds ratio (OR) =
1.48, 95% confidence interval (CI) = 0.96-2.28, p = 0.07). In subgroup analysis, the phenomenon that
men with ALDH2*2 had higher risk for LOAD (OR = 1.72, 95%CI = 1.10-2.67, p = 0.02) was observed.

Conclusions:
This study comprehends only five existing case-control studies and the result is negative.
The positive trend might appear when the sample size is enlarged. In the future, more large-scale casecontrol
or cohort studies should be done to enhance the association between ALDH2 polymorphism and
AD or other neurodegenerative diseases.
Prognostic Significance of Relative Hyperglycemia after Percutaneous Coronary Intervention in Patients with and without Recognized Diabetes
Authors: Zhao Qi , Zhang Ting-Yu , Cheng Yu-Jing , Ma Yue , Xu Ying-Kai , Yang Jia-Qi , Zhou Yu-Jie 
Published: March 2020

Background:
The research on the association between the relative glycemic level postpercutaneous
coronary intervention (PCI) and adverse prognosis in non-ST-segment elevation acute
coronary syndrome (NSTE-ACS) patients is relatively inadequate.

Objective:
The study aimed to identify whether the glycemic level post-PCI predicts adverse prognosis
in NSTE-ACS patients.

Methods:
Patients (n=2465) admitted with NSTE-ACS who underwent PCI were enrolled. The relative
glycemic level post-procedure was calculated as blood glucose level post-PCI divided by HbA1c level,
which was named post-procedural glycemic index (PGI). The primary observational outcome of this
study was major adverse cardiovascular events (MACE) [defined as a composite of all-cause death,
non-fatal myocardial infarction (MI) and any revascularization].

Results:
The association between PGI and MACE rate is presented as a U-shape curve. Higher PGIs
[hazard ratio (HR): 1.669 (95% confidence interval (CI): 1.244-2.238) for the third quartile (Q3) and
2.076 (1.566-2.753) for the fourth quartile (Q4), p<0.001], adjusted for confounding factors, were considered
to be one of the independent predictors of MACE. The association between the PGI and the risk
of MACE was more prominent in the non-diabetic population [HR (95%CI) of 2.356 (1.456-3.812) for
Q3 and 3.628 (2.265-5.812) for Q4, p<0.001]. There were no significant differences in MACE risk between
PGI groups in the diabetic population.

Conclusion:
Higher PGI was a significant and independent predictor of MACE in NSTE-ACS patients
treated with PCI. The prognostic effect of the PGI is more remarkable in subsets without pre-existing
diabetes than in the overall population. The predictive value of PGI was not identified in the subgroup
with diabetes.
Biomarker Identification for Liver Hepatocellular Carcinoma and Cholangiocarcinoma Based on Gene Regulatory Network Analysis
Authors: Huo Qiuyan , Ma Yuying , Yin Yu , Qin Guimin 
Published: March 2020

Background:
Liver hepatocellular carcinoma (LIHC) and cholangiocarcinoma (CHOL)
are two main histological subtypes of primary liver cancer with a unified molecular landscape, and
feed-forward loops (FFLs) have been shown to be relevant in these complex diseases.

Objective:
To date, there has been no comparative analysis of the pathogenesis of LIHC and CHOL
based on regulatory relationships. Therefore, we investigated the common and distinct regulatory
properties of LIHC and CHOL in terms of gene regulatory networks.

Method:
Based on identified FFLs and an analysis of pathway enrichment, we constructed pathway-specific co-expression networks and further predicted biomarkers for these cancers by network clustering.

Resul:
We identified 20 and 36 candidate genes for LIHC and CHOL, respectively. The literature
from PubMed supports the reliability of our results.

Conclusion:
Our results indicated that the hsa01522-Endocrine resistance pathway was associated
with both LIHC and CHOL. Additionally, six genes (SPARC, CTHRC1, COL4A1, EDIL3, LAMA4
and OLFML2B) were predicted to be highly associated with both cancers, and COL4A2, CSPG4,
GJC1 and ADAMTS7 were predicted to be potential biomarkers of LIHC, and COL6A3, COL1A2,
FAP and COL8A1 were predicted to be potential biomarkers of CHOL. In addition, we inferred that
the Collagen gene family, which appeared more frequently in our overall prediction results, might be
closely related to cancer development.
Cytotoxic Dehydroabietylamine Derived Compounds
Authors: Wiemann Jana , Al-Harrasi Ahmed , Csuk René 
Published: March 2020

Background and Methods:
Chemotherapy remains one of the most important methods for the treatment of
cancer. More recently in this context, some products derived from natural products have raised scientific interest which
especially include many terpenes. Thereby, diterpenoids represent a special class, and within this class of important
secondary natural products, especially compounds derived from Dehydroabietylamine (DA), are of particular interest.

Results:
This review not only gives a summary of the most important findings on the cytotoxic behavior of DAderived
compounds but also shows some drawbacks of these compounds, such low bioavailability and/or poor solubility
of several derivatives of DA. It focusses on the chemical aspects and summarizes the DA related biological
effects without deep discussion of underlying biochemical pathways.

Conclusion:
Dehydroabietylamine-derived cytotoxic compounds hold a high potential to be developed into efficient
antitumor active drugs.
Community Psychiatry in a Latin American Context: Perú as a Case Example
Authors: Alarcón Renato D. , Vargas-Murga Horacio , Caballero-Peralta July , Cutipé-Cárdenas Yuri 
Published: March 2020

Background:
Historical and conceptual issues related to community psychiatry as
an innovative approach to clinical assistance across the world, precede a more or less detailed
examination of its presence, role and current accomplishments in Latin America, particularly
related to child and adolescent subpopulations. Information about transition processes
from the traditional hospital-centered model to the community-based approach, applicable
mental health policies, levels of implementation and quality of the available reports in
different countries, are duly evaluated.

Objective:
Within an understanding of the broader Latin American context, the paper describes
the situation in Perú, a country considered representative of the Low and Middle Income
(LMIC) group in the subcontinent.

Methods:
The situation in Perú is presented with particular emphasis on a recently established
community-based mental health centers program across its territory.

Results:
This description includes consideration of variables such as personal, family and
identity empowerment, a focus on integrated care, and clinical outcomes and community relations.
The development of community mental health centers across Perú is described.

Conclusion:
Adolescents represent the unique future of socio-culturally diverse Latin
American countries, and must be the target population of well-conceived, cohesive community
mental health policies and programs. The importance of political will to promote community
health centers that provide adolescents access to services is critical.