bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Aceclofenac-L-Cystine and Aceclofenac-Urea Cocrystals with Enhanced Oral Bioavailability
Authors: Kumar Saroj , Gupta Amresh , Mishra Chanchal Kumar , Singh Satyawan 
Published: February 2021

Aim:
Present research work focuses on the improvement of biopharmaceutical properties
of aceclofenac (ACF) by the cocrystal approach.

Background:
ACF is one of the frequently used Nonsteroidal Anti-Inflammatory Drugs (NSAID).
ACF is a BCS Class - II drug (low solubility and high permeability) with poor solubility and low
oral bioavailability. Hence, the improvement in solubility and bioavailability of ACF is very crucial
for successful product development. Nowadays, pharmaceutical cocrystals are considered a
novel solid form of drugs. These cocrystals may have different physicochemical as well as biopharmaceutical
properties as compared to the parent drug. In a previous study, the cocrystal of ACF
(ACF-l-CYS NG and ACF-UREA NG) was successfully prepared and characterized. These cocrystals
have shown superior solubility and dissolution rate than pure ACF in HCl buffer (pH 1.2). The
synthesized cocrystals were also found non-hygroscopic and stable for 6 months under standard
test settings. However, pharmacokinetic evaluation of these cocrystals has not been explored yet.

Objective:
The specific objective of this research work was the measurement of bioavailability and other pharmacokinetic parameters of ACF cocrystals prepared by the mechanochemical grinding method.

Methods:
Cocrystals of ACF with l-cystine and urea were prepared by neat grinding (NG) method
and in-vivo oral bioavailability of prepared cocrystals was measured in Wistar rats. The plasma
drug concentration was measured by high-performance liquid chromatography (HPLC), and the
pharmacokinetic data was analyzed by “PK solver” software.

Results :
Percent relative bioavailability of ACF-l-CYS NG and ACF-UREA NG cocrystals in Wistar
rats was found to be 242.05 ± 65.27and 178.93 ± 45.21 respectively, which were significantly
higher (ANOVA, P < 0.05) than that of pure ACF.

Conclusion:
The present study indicates that the enhanced aqueous solubility of the prepared cocrystals leads to enhanced oral bioavailability of ACF. Thus, the cocrystals may be an alternative crystalline form of the drug that can enhance the solubility, dissolution rate, and oral bioavailability of many poorly soluble drugs.
Effect of Different Carriers on In Vitro and In Vivo Drug Release Behavior of Aceclofenac Proniosomes
Authors: Sammour Rana M.F. , Chatterjee Bappaditya , Taher Muhammad , Saleh Mohammed S.M. , Shahiwala Aliasgar 
Published: February 2021

Background:
Improved bioavailability of Aceclofenac (ACE) may be achieved through
proniosomes, which are considered as one of the most effective drug delivery systems and are expected
to represent a valuable approach for the development of better oral dosage form as compared
to the existing product. However, the carrier in this system plays a vital role in controlling
the drug release and modulating drug dissolution. Accordingly, a comparative study on different
carriers can give a clear idea about the selection of carriers to prepare ACE proniosomes.

Objective:
This study aims to evaluate the role of maltodextrin, glucose, and mannitol as carriers
for in vitro and in vivo performance of Aceclofenac (ACE) proniosomes.

Methods:
Three formulations of proniosomes were prepared by the slurry method using the 100
mg ACE, 500 mg span 60, 250 mg cholesterol with 1300mg of different carriers, i.e., glucose
(FN1), maltodextrin (FN2), and mannitol (FN3). In vitro drug release studies were conducted by
the USP paddle method, while in vivo studies were performed in albino rats. Pure ACE was used as
a reference in all the tests. Lastly, the results were analyzed using the High-Pressure Liquid Chromatography
(HPLC) method, and data were evaluated using further kinetic and statistical tools.

Results:
No significant differences (p > 0.05) in entrapment efficiency (%EE) of FN1, FN2, and
FN3 (82 ± 0.5%, 84 ± 0.66%, and 84 ± 0.34% respectively) were observed and formulations were
used for further in vitro and in vivo evaluations. During in vitro drug release studies, the dissolved
drug was found to be 42% for the pure drug, while 70%, 17%, and 30% for FN1, FN2, and FN3, respectively,
at 15 min. After 24 hrs, the pure drug showed a maximum of 50% release while 94%,
80%, and 79% drug release were observed after 24 hr for FN1, FN2, and FN3, respectively. The in
vivo study conducted on albino rats showed a higher Cmax and AUC of FN1 and FN2 in comparison
with the pure ACE. Moreover, the relative oral bioavailability of proniosomes with maltodextrin
and glucose as carriers compared to the pure drug was 183% and 112%, respectively. Mannitol-
based formulation exhibited low bioavailability (53.7%) that may be attributed to its osmotic behavior.

Conclusion:
These findings confirm that a carrier plays a significant role in determining in vitro
and in vivo performance of proniosomes and careful selection of carrier is an important aspect of
proniosomes optimization.
Association of Red Blood Cell Indices with Mild Cognitive Impairment in Chinese Elderly Individuals: A Matched Case-control Study
Authors: Du Yue , Jin Mengdi , Liu Qian , Zhao Jiangang , Song Aili , Li Wen , Chang Hong , Ma Fei , Huang Guowei 
Published: February 2021

Background:
Mild cognitive impairment (MCI) represents an intermediate and modifiable
stage between normal aging and dementia. There is an urgent need for simple, non-invasive testing of
MCI by blood biomarkers.

Objective:
This study aimed to retrospectively evaluate the association of red blood cell (RBC) indices
with MCI, and select the best hematologic characteristic for detection of MCI in elderly Chinese.

Methods:
Matched case-control study was carried out with 85 pairs of MCI subjects and healthy controls.
The matching criteria was age, gender and education attainment. All samples were analyzed for
RBC indices, including hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV),
mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width-standard deviation
(RDW-SD). A conditional logistic regression model was used to evaluate the association between
RBC indices and MCI. The diagnostic efficacy of the biomarkers was evaluated by receiver operating
characteristics (ROC).

Results:
Among all RBC indices, there were significant differences in HGB (124.82 ± 7.89 vs. 133.93
± 4.52, P < 0.001) and RDW-SD (45.29 ± 2.03 vs. 41.34 ± 4.41, P < 0.001) between two groups. In the
logistic regression model, after adjustment for lifestyle factors and comorbidities, significant statistically
associations have been found between higher HGB and lower risk of MCI (adjusted OR: 0.831;
95% CI: 0.773-0.893), higher RDW-SD and a higher risk of MCI (adjusted OR: 1.575; 95% CI: 1.326-
1.872). ROC analysis suggested that the largest area under the ROC curve (AUC) was found with the
combination of HGB and RDW-SD (AUC = 0.842), followed by HGB(AUC = 0.795), and finally by
modest RDW-SD (AUC = 0.777). Combination of HGB <131 g/L and RDW-SD >43.4 fL yielded a
sensitivity of 92% and a specificity of 89%, overall diagnosis efficiency of which were better than
HBG and RDW-SD alone.

Conclusion:
Lower HGB and higher RDW-SD alone were significantly found to be associated with
increased risk of MCI, and offered modest sensitivity and specificity as a diagnostic marker. The combination
of HGB and RDW-SD was more sensitive and had higher classification accuracy for differentiating
MCI from healthy controls. Further prospective research is needed to clarify whether HGB in
combination with RDW-SD may be a potential diagnostic tool for early diagnosis of AD.
Ecofriendly Synthesis of Formamidine Derivatives Catalyzed by Al-MCM-
41 Mesoporous Materials
Authors: Yazid Datoussaid , Tewfik Ali-Dahmane , Nawel Mehiaoui , Brahmi Lamia , Zahira Kibou , Rachida Hamacha , Noureddine Choukchou-Braham 
Published: February 2021

Abstract:
Formamidine derivatives have been synthesized in excellent yields at room temperature from
primary amine and N,N-dimethylformamide dimethylacetal (DMF-DMA) in the presence of a catalytic
amount of Al-MCM-41 synthesized from natural bentonite as silica and aluminum source. The advantages
of this method are the use of a cheap, stable, non-toxic, and readily available catalyst, easy
work-up, improved yields, and solvent-free conditions.
Liver Cancer: New Insights into Surgical and Nonsurgical Treatments
Authors: Sharifian Masoud , Baharvand Parastoo , Moayyedkazemi Alireza 
Published: February 2021

Introduction:
Hepatocellular carcinoma (HCC) is the most common type of liver cancer
that has increased in recent years worldwide. Primary liver cancer or HCC is considered the 5th and
7th most common cancer among men and women, respectively. It is also the second leading cause
of cancer death worldwide. Unfortunately, HCC is frequently diagnosed at an advanced stage when
the majority of the patients do not have access to remedial therapies. Furthermore, current systemic
chemotherapy shows low efficacy and minimum survival benefits. Liver cancer therapy is a multidisciplinary,
multiple-choice treatment based on the complex interaction of the tumour stage, the
degree of liver disease, and the patient's general state of health.

Methods:
In this paper, we reviewed new insights into nonsurgical and surgical treatment of liver
cancer in five English databases, including Scopus, PubMed, Web of Science, EMBASE, and Google
Scholar up to December 2019.

Results:
The results demonstrated, in addition to current therapies such as chemotherapy and surgical
resection, new approaches, including immunotherapy, viral therapy, gene therapy, new ablation
therapies, and adjuvant therapy, are widely used for the treatment of HCC. In recent years, biomaterials
such as nanoparticles, liposomes, microspheres, and nanofibers are also regarded as reliable
and innovative patents for the treatment and study of liver cancers.

Conclusion:
Multidisciplinary and multi-choice treatments and therapies are available for this liver
cancer, while there are differences in liver cancer management recommendations among specialties
and geographic areas. Current results have shown that treatment strategies have been combined
with the advancement of novel treatment modalities. In addition, the use of new approaches with
greater efficacy, such as combination therapy, biomaterials, ablation therapy, etc. can be considered
the preferred treatment for patients.
Shedding Light on the Pathophysiology of Preeclampsia-Syndrome in the
Era of Cardio-Obstetrics: Role of Inflammation and Endothelial Dysfunction
Authors: Pereira María M. , Torrado Juan , Sosa Claudio , Zócalo Yanina , Bia Daniel 
Published: February 2021

Background:
Preeclampsia (PE) is a pregnancy complication with serious maternal and
neonatal consequences worldwide. Our understanding of PE pathophysiology has significantly
evolved over the last decades by recognizing that endothelial dysfunction and systemic inflammation,
with an associated angiogenic imbalance, are key pieces of this incomplete puzzle. In the present
era, where no single treatment to cure or treat this obstetric condition has been developed so
far, PE prevention and early prediction are the most useful clinical approach to reduce the PE burden.

Introduction:
Although most PE episodes occur in healthy nulliparous women, the identification
of specific clinical conditions that increase the risk of PE dramatically provides a critical opportunity
to improve outcomes by acting on potentially reversible factors, and also contributes to better understand
this pathophysiologic enigma.

Methods:
Pertinent studies were searched in PubMed/Medline and Google Scholar (updated August
2020) using common keywords applied in the field of preeclampsia, inflammation and endothelial
dysfunction. Given the design of this work as a narrative review, no formal criteria for
study selection or appraisal were utilized.

Conclusion:
In this review, we highlight major clinical contributors of PE and shed light on their
potential link with endothelial dysfunction and inflammation.
A Simplified Framework for the Detection of Intracranial Hemorrhage in CT Brain Images Using Deep Learning
Authors: Kumaravel Praveen , Mohan Sasikala , Arivudaiyanambi Janani , Shajil Nijisha , Venkatakrishnan Hari Nishanthi 
Published: February 2021

Background:
The need for accurate and timely detection of Intracranial hemorrhage
(ICH) is of utmost importance to avoid untoward incidents that may even lead to death. Hence, this
presented work leverages the ability of a pretrained deep convolutional neural network (CNN) for
the detection of ICH in computed tomography (CT) brain images.

Methods:
Different frameworks have been analyzed for their effectiveness for the classification of
CT brain images into hemorrhage or non-hemorrhage conditions. All these frameworks were investigated
on the CQ500 dataset. Furthermore, an exclusive preprocessing pipeline was designed
for both normal and ICH CT images. Firstly, a framework involving the pretrained deep CNN,
AlexNet, has been exploited for both feature extraction and classification using the transfer learning
method. Secondly, a modified AlexNet-Support vector machine (SVM) classifier is explored,
and finally, a feature selection method, Principal Component Analysis (PCA), has been introduced
in the AlexNet-SVM classifier model, and its efficacy is also explored. These models were trained
and tested on two different sets of CT images, one containing the original images without preprocessing
and another set consisting of preprocessed images.

Results:
The modified AlexNet-SVM classifier has shown an improved performance in comparison
to the other investigated frameworks and has achieved a classification accuracy of 99.86% and
sensitivity and specificity of 0.9986 for the detection of ICH in the brain CT images.

Conclusion:
This research has given an overview of a simple and efficient framework for the classification
of hemorrhage and non-hemorrhage images. The proposed simplified deep learning
framework also manifests its ability as a screening tool to assist the radiological trainees in the accurate
detection of ICH.
Construction and Comprehensive Analysis of a Special Competitive Endogenous RNAs Network to Reveal Potential Prognostic Biomarkers for Endometrial Carcinoma
Authors: Qiao Feng , Zhang Xu 
Published: February 2021

Background:
Endometrial carcinoma (EC) is one of the most common malignancies in
women worldwide. For EC patients discovered at an early stage, the prognosis is good. However,
the advanced EC patients (stage III-IV) have very poor prognoses. The competitive endogenous
RNAs (ceRNA) regulatory network in EC remains unclear, and the relationship between hub
RNAs and important clinical characters (clinical stage) has not been strictly studied yet.

Objective:
In order to study the development of endometrial carcinoma and the identification of
early diagnostic markers, the relationship between hub RNAs and important clinical traits (clinical
stage) was strictly studied.

Methods:
The co-expression networks of mRNA, lncRNA, and miRNA were constructed by
weighted gene co-expression network analysis. Gene ontology (GO) biological process terms and
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried
out for DEmRNA. AceRNA regulated network was constructed based on miRcode, miRDB, TargetScan,
and miRTarBase. Furthermore, survival analysis, regression analysis of mRNA-lncRNA
pairs, and gene set enrichment analysis were carried out.

Results:
A ceRNA network containing 11 mRNAs, 4 miRNAs, and 18 lncRNAs was constructed
based on aberrantly expressed RNAs in the co-expression modules. In this network, 7 mRNAs, 4
lncRNAs, and 1 miRNA were found closely related to the overall survival of EC. The positive
correlations of 35 pairs of mRNA and lncRNA in the ceRNA network were obtained. Notably, 5
mRNAs, 3 lncRNAs, and 1 miRNA were identified as potential prognostic biomarkers for EC.
Single gene GSEA analysis revealed that the signal pathways related to cell cycle and cancer were
highly enriched.

Conclusion:
Identification of five mRNAs (CBX6, PIM1, RIMS3, SOX11, and XKR7), three
lncRNA (WT1-AS, LINC00494, and LINC00501), and one miRNA (miR-195) as potential prognostic
biomarkers for EC was helpful for the early diagnosis, prognosis, and development of new
treatment strategies of EC patients.
Molecular and Cellular Biomarkers of COVID-19 Prognosis: Protocol for the Prospective Cohort TARGET Study
Authors: Kurizky Patricia , Nóbrega Otávio T , Soares Alexandre Anderson De Sousa Munhoz , Aires Rodrigo Barbosa , Albuquerque Cleandro Pires De , Nicola André Moraes , Albuquerque Patrícia , Teixeira-Carvalho Andréa , Naves Luciana Ansaneli , Fontes Wagner , Luz Isabelle Souza , Felicori Liza , Gomides Ana Paulo Monteiro , Mendonça-Silva Dayde Lane , Espindola Laila Salmen , Martins-Filho Olindo Assis , de Lima Sheila Maria Barbosa , Mota Licia Maria Henrique , Gomes Ciro Martins 
Published: February 2021

Background
Since the beginning of the COVID-19 pandemic, the world’s attention has been focused on better understanding the relation between the human host and the SARS-CoV-2 virus, as its action has led to hundreds of thousands of deaths.

Objective
In this context, we decided to study certain consequences of the abundant cytokine release over the innate and adaptive immune systems, inflammation, and hemostasis, comparing mild and severe forms of COVID-19.

Methods
To accomplish these aims, we will analyze demographic characteristics, biochemical tests, immune biomarkers, leukocyte phenotyping, immunoglobulin profile, hormonal release (cortisol and prolactin), gene expression, thromboelastometry, neutralizing antibodies, metabolic profile, and neutrophil function (reactive oxygen species production, neutrophil extracellular trap production, phagocytosis, migration, gene expression, and proteomics). A total of 200 reverse transcription polymerase chain reaction–confirmed patients will be enrolled and divided into two groups: mild/moderate or severe/critical forms of COVID-19. Blood samples will be collected at different times: at inclusion and after 9 and 18 days, with an additional 3-day sample for severe patients. We believe that this information will provide more knowledge for future studies that will provide more robust and useful clinical information that may allow for better decisions at the front lines of health care.

Results
The recruitment began in June 2020 and is still in progress. It is expected to continue until February 2021. Data analysis is scheduled to start after all data have been collected. The coagulation study branch is complete and is already in the analysis phase.

Conclusions
This study is original in terms of the different parameters analyzed in the same sample of patients with COVID-19. The project, which is currently in the data collection phase, was approved by the Brazilian Committee of Ethics in Human Research (CAAE 30846920.7.0000.0008).

Trial Registration
Brazilian Registry of Clinical Trials RBR-62zdkk; https://ensaiosclinicos.gov.br/rg/RBR-62zdkk

International Registered Report Identifier (IRRID)
DERR1-10.2196/24211
Technology-Based Fall Risk Assessments for Older Adults in Low-Income Settings: Protocol for a Cross-sectional Study
Authors: Thiamwong Ladda , Stout Jeffrey R , Park Joon-Hyuk , Yan Xin 
Published: February 2021

Background
One-third of older adults have maladaptive fall risk appraisal (FRA), a condition in which there is a discrepancy between the level of fear of falling (FOF) and physiological fall risk (balance performance). Older adults who overestimate their physiological fall risk and report a high FOF are less likely to participate in physical activity. Limited data suggest that the association among FOF, body composition, and physical activity intensity differs by fear severity.

Objective
This study aims to examine the associations among FRA, body composition, and physical activity using assistive health technology, including the BTrackS balance system, bioelectrical impedance analysis, and activity monitoring devices. This study also aims to examine the feasibility of recruitment and acceptability of technologies and procedures for use among older adults in low-income settings.

Methods
This cross-sectional study will be conducted in older adults’ homes or apartments in low-income settings in Central Florida, United States. Following consent, participants will be contacted, and our team will visit them twice. The first visit includes questionnaire completion (eg, sociodemographic or FOF) and balance performance test using the BTrackS balance system. The participants will be stratified by the FRA matrix. In addition, they will perform hand grip strength and dynamic balance performance tests. Participants will then be asked to wear the ActiGraph GT9X Link wireless activity monitor on the nondominant wrist for 7 consecutive days. The second visit includes body composition testing and a structured interview about the acceptability of the technologies and procedures.

Results
Ethical approval was obtained from the institutional review board of the University of Central Florida (protocol number 2189; September 10, 2020). As of December 2020, participation enrollment is ongoing and the results are expected to be published in Summer 2022.

Conclusions
Accurate FRA is essential for implementing physical activity programs, especially in older adults with low income. This study will provide data for developing technology-based fall risk assessments to improve participation in physical activity, thus enhancing healthy longevity among older adults in low-income settings.

International Registered Report Identifier (IRRID)
PRR1-10.2196/27381
Faktor dominan kejadian konstipasi fungsional pada remaja di Jakarta
Authors: Thea Felicia , Sudiarti Trini , Djokosujono Kusharisupeni 
Published: February 2021

Dominant factors of functional constipation among adolescent in JakartaBackground: The impact of functional constipation, including the quality of life decreases, increase the additional health costs that must be incurred, and reduce productivity. Previous research in various places in Indonesia shows that functional constipation is experienced among adolescents, percentages between 24.6-68.5%.Objective: Determine the relationship and dominant factor between gender, fiber intake, fluids intake, consumption of probiotic drinks, physical activity, nutritional status, stress, and nutritional knowledge on the incidence of functional constipation.Methods: The study design was cross-sectional. The number of respondents studied was 150 high-school students from class X and XI. The sample selected by using a total sampling system. Data collected using the Roma III questionnaire of functional constipation, physical activity using the Physical Activity Questionnaire for Adolescent, and stress level using the Holmes and Rahe Stress Scale for students. Nutritional knowledge was obtained by filling out a questionnaire. Food recall 2x24 hours to assess fiber intake, fluid, and probiotic drinks. Measure body weight and height of students to determine nutritional status. Data analyzed using univariate, Chi-Square test for bivariate, and multiple logistic regression tests for multivariate.Results: 75.3% of students had functional constipation, 64.0% less fiber intake,54.0% less fluid intake, 91.3% less physical activity, 62.0% did not consume probiotic drinks, 38.7% were obese and 30.0% lacking in nutrition knowledge. Dominant factor of functional constipation was physical activity (p-value 0.035; OR 3.57; CI 1.09-11.66).Conclusions: Low physical activity can increase the incidence of functional constipation in adolescents at Jakarta.