bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cross-sectional study of Foot-Ground Clearance in Healthy Community Dwelling Japanese Cohorts Aged 50, 60 and 70 Years
Authors: Nagano Hanatsu , Sparrow William Anthony , Mizukami Katsuyoshi , Sarashina Eri , Begg Rezaul 
Published: January 2021

Abstract
Background Falls-related injuries are particularly serious for older people, causing pain, reduced community engagement and associated medical costs. Tripping is the leading cause of falls and the current study examined whether minimum ground clearance (MFC) of the swing foot, indicating high tripping risk, would be differentiated across cohorts of healthy 50-, 60- and 70-years old community residents in Japan.Methods A cross-sectional population comprising the three groups (50s, 60s and 70s) of 123 Konosu City residents consented to be recorded when walking on an unobstructed surface at preferred speed. Gait biomechanics was measured using high speed (100 Hz) motion capture (OptiTrack – Natural Point Inc.), including step length and width, double support, foot contact angle and MFC (swing toe height above the ground). Multivariate Analysis of Variance (MANOVA) was used to confirm ageing effects on MFC and fundamental gait parameters. Pearson's correlations were performed to identify the relationships between mean MFC and other MFC characteristics (SD and SI), step length, step width, double support time and foot contact angle. Results Compared to 50s, lower step length was seen (2.69cm and 6.15cm) for 60s and 70s, respectively. No other statistical effects were identified for spatio-temporal parameters between the three groups. The 50s cohort MFC was also significantly higher than 60s and 70s, while step-to-step MFC variability was greater in the 70s than 50s and 60s. Pearson’s correlations demonstrated that more symmetrical gait patterns were associated with greater MFC height, as reflected in greater symmetry in step width (50s), MFC (60s) and foot contact angle (70s).. In the 70s increased MFC height correlated with higher MFC variability and reduced foot contact angle. Conclusion MFC height reduces from 60 years but more variable MFC appears later, from 70 years. While symmetrical gait was accompanied by increased MFC height, in the 70s group attempts to increase MFC height may have caused more MFC variability and lower foot contact angles, compromising foot-ground clearance. Assessments of swing foot mechanics may be a useful component of community falls prevention.
Cross-sectional study on Traditional pig rearing practices and cysticercosis in the southern region of Côte d’Ivoire
Authors: Eugène Koffi Kouassi , Man-Koumba Soumahoro , Marcel Boka O. , Jihen Melki , Borel Ndri , NOWAKOWSKI Mireille , André Touré O. , Joseph Djaman A. , Elieser N’goran K. , Jambou Ronan 
Published: January 2021

Abstract
BackgroundIn West Africa, pig meat, known as pork, is often supplied by traditional farms in rural districts. This practice causes significant sanitary risk because of the lack of veterinary control of farms and slaughterhouses in rural districts. This study aims to describe pig breeding practices used in southern Côte d'Ivoire to establish a surveillance system for cysticercosis disease. This survey was conducted among traditional pig producers living in villages surrounding Dabou, Aboisso, and Agboville. The data collected focused on the profile of producers and the characteristics of the farms.ResultsA total of 321 pig producers were identified (Dabou 72 (22.4%), Aboisso 26 (8.1%), and Agboville 223 (69.5%)). Most of the herders were male (87.8%). The total count of animals was 3,663 heads of pigs, with mostly youngpiglets (60.2%) and sow (29.3%). The local race was predominant (80.6 %) for only 15.5% of half-caste races. Most of the farms used permanent divagation rearing (53.3%). Following examination, random samples of pigs were tracked in all the selected villages using the quota methods. Animals' blood samples and serums were analyzed using Ac-ELISA and Western Blot. Out of the selected 639 animals, 13.2 % had antibodies against cysticercosis with considerable variations from one village to another.ConclusionsThe study highlighted that, in these regions, pig farming remains essentially traditional, with free grazing of animals, which constitutes a significant sanitary risk, especially for Taenia solium.
Manufacturing and Banking Canine Adipose-Derived Mesenchymal Stem Cells for Veterinary Clinical Application
Authors: Luo Huina , Li Dongsheng , Chen Zhisheng , Wang Bingyun , Chen Shengfeng 
Published: January 2021

Abstract
BACKGROUND: Mesenchymal stem cells (MSCs) have generated a great amount of interest in recent years as a novel therapeutic application for improving the quality of pet life and helping them free from painful conditions and diseases. It has now become critical to address the challenges related to the safety and efficacy of MSCs expanded in vitro. In this study, we establish a standardized process for manufacture of canine adipose-derived MSCs (AD-MSCs), including tissue sourcing, cell isolation and culture, cryopreservation, thawing and expansion, quality control and testing, and evaluate the safety and efficacy of those cells for clinical applications. RESULTS: After expansion, the viability of AD-MSCs manufactured under our standardized process was above 90 %. Expression of surface markers and differentiation potential was consistent with ISCT standards. Sterility, mycoplasma, and endotoxin tests were consistently negative. AD-MSCs presented normal karyotype, and did not form in vivo tumors. No adverse events were noted in two cases treated with intravenously AD-MSCs. CONCLUSION: Herein we demonstrated the establishment of a feasible bioprocess for manufacturing and banking canine AD-MSCs for veterinary clinical use.
CKD and CKDu in Northern Peru: a cross-sectional analysis under the DEGREE protocol
Authors: Ruiz-Alejos Andrea O. , Caplin Ben , Miranda J. Jaime , Pearce Neil , Bernabé-Ortiz Antonio 
Published: January 2021

Abstract
Background: This study estimated the prevalence and risk factors for decreased estimated glomerular filtration rate (eGFR) in those without known hypertension, type 2 diabetes mellitus, or heavy proteinuria as a surrogate marker for chronic kidney disease of unknown cause (CKDu) among adults in the North of Peru.Methods:A cross-sectional study was conducted following the Disadvantaged Populations eGFR Epidemiology (DEGREE) Study protocol. Low eGFR was defined based on a single eGFR ≤60 mL/min/1.7m2 estimated using the CKD-EPI equation. Environmental conditions related to CKDu (i.e., work in agriculture or sugarcane, water source, heat intolerance, and pesticide exposure) were evaluated, in addition to traditional risk factors for CKD (i.e., smoking, heavy drinking, physical activity, hypertension, type 2 diabetes mellitus, urolithiasis, among others).Results:A total of 1514 subjects were included in the study, mean age 45.1 (SD: 16.4), and 55.2% were females. Overall, only 26 cases (1.7%; 95%CI: 1.1% - 2.5%) had an eGFR <60mL/min/1.7m2 compatible with CKD definition; when those with hypertension and type-2 diabetes or heavy proteinuria were excluded, according to the DEGREE protocol, the estimate fell to 0.9% (95%CI: 0.4% - 1.5%). Low physical activity levels (OR = 1.99; 95%CI: 1.18 – 3.34), hypertension (OR = 2.07; 1.26 – 3.41), and urolithiasis (OR = 1.97; 95%CI: 1.18 – 3.27) were factors associated with low eGFR.Conclusions: A low population-based prevalence of low eGFR (as a surrogate for CKDu), both in rural and urban settings areas, in the Northern Peru, was found. Low physical activity levels, hypertension and urolithiasis were factors associated with low eGFR. Interventions to prevent CKD cases may be focused on well-known CV risk factors and urolithiasis.
Design of Stirred Tank Reactor for Cellulase Enzyme Rumen Liquid Based Bioethanol Production from Banana Rod
Authors: Nisa Qurrotun Ayuni Khoirun , Paramita Vita 
Published: January 2021

Abstract
Due to pandemic, supply of alcohol as desinfectant really needed for nowadays. This research aims to determine the levels of bioethanol produced from banana rods by the hydrolysis process. The target to be achieved with the reactor design is to achieve high ethanol purity using a first order reaction kinetics approach. The study was carried out on various variables including fermentation time (6 - 30 hours), hydrolysis temperature (80 - 90 oC), and substrate enzyme ratio (1: 1 - 1: 3). While the parameters to be tested are glucose levels and bioethanol levels. The optimal effect of the variable on alcohol content is obtained when the alcohol content value is more than 17.2% with an enzyme ratio of 3 - 3.5 at a temperature of 94 - 96 oC for 35 - 40 hours. From the research, it was found that it is possible to enlarge the reactor up to 200 times by using a ratio to obtain the ideal stirred tank reactor dimensions with a conversion of 97.15%.
Teacher Talk in Scientific Approach in EFL Classroom: A Speech Acts Perspective
Authors: Faturrochman Rihza Galih , Darmawan Achmad Anang , Hadi Faishol 
Published: January 2021

This paper reviews teacher’s utterances in the EFL Classroom using Speech Acts’ perspective. Specifically when the teacher applying scientific appraoch in the learning process. Teacher’s utterance has a lot of influence in the language learning process, such as: students’ input and practice (Xiao-yan, 2006) and (Cullen, 1998). Even though the restiction on using scientific approach in all subject has been revoked, some schools still applying scientific approach in EFL Classroom which is relatively unfamiliar. Theoretically, since Indonesia use English as foreign learning, teacher’s utterance has a prominent role in the process of learning in the classroom. In the classroom context, teacher talk can be found in the form of questions and feedback (Cullen, 1998)And (Xiao-yan, 2006). The research had been done using qualitative method, which means the data of the research are analysed using qualitative methods and the result is presented in paragraph. In order to gather the data, observation and interview had been done in the early of 2020. As result, a teacher in MA Bilingual Muslimat NU Sidoarjo uses the directive sentence mostly in the classroom, since she believes that encourage students to speak in English is very necessary for English as foreign language learner.
El Estado democrático de Derecho y la paradoja del acceso a la información pública por inexistencia de la información solicitada. Un análisis del razonamiento del Tribunal de Transparencia y Acceso a la Información Pública del Perú
Authors: Alarcón Requejo Gílmer 
Published: January 2021

El presente artículo examina la labor interpretativa del Tribunal de Transparencia y Acceso a la Información Pública en relación a la denegatoria del acceso a la información pública por inexistencia de la misma, a propósito del caso Angulo vs. Jurado Nacional de Elecciones (Expediente 00010-2017-JUS/TTAIP). A partir de la metodología del estudio de caso, se articulan exigencias epistémicas del derecho de acceso a la información pública y criterios argumentativos tanto de disposiciones autoritativas legislativas y reglamentarias como de lineamientos jurisprudenciales del Tribunal Constitucional. Además, desde la facticidad y validez normativa, se reflexiona sobre una paradójica complejidad y complementariedad entre transparencia activa y pasiva, considerando el ideal regulativo del gobierno abierto y el Estado democrático de Derecho en Perú.
Preparation and Formulation Optimization of Methotrexate-loaded Human Serum Albumin Nanoparticles Modified by Mannose
Authors: Chen Zhenyu , Luo Zhongling , Lyu Jiayao , Wang Jianxin , Liu Zhongbing , Wei Jun , Lin Yan , Zhong Zhirong 
Published: January 2021

Background:
Methotrexate (MTX) is the representative drug among the disease-
modifying anti-rheumatic drugs. However, the conventional treatment with MTX
showed many limitations and side effects.

Objective:
To strengthen the targeting ability and circulation time of MTX in the treatment
of rheumatoid arthritis, the present study focused on developing a novel drug delivery
system of methotrexate-loaded human serum albumin nanoparticles (MTX-NPs) modified
by mannose, which are referred to as MTX-M-NPs.

Methods:
Firstly, mannose-derived carboxylic acid was synthesized and further modified
on the surface of MTX-NPs to prepare MTX-M-NPs. The formulation of nanoparticles
was optimized by the method of central composite design (CCD), with the drug lipid ratio,
oil-aqueous ratio, and cholesterol or lecithin weight as the independent variables. The
average particle size and encapsulation efficiency were the response variables. The response
of different formulations was calculated, and the response surface diagram, contour
diagram, and mathematical equation were used to relate the dependent and independent
variables to predict the optimal formula ratio. The uptake of MTX-M-NPs by neutrophils
was studied through confocal laser detection. Further, MTX-M-NPs were subjected
to assessment of the pharmacokinetics profile after intravenous injection with
Sprague-Dawley rats.

Results:
This targeting drug delivery system was successfully developed. Results from
Nuclear Magnetic Resonance and Fourier Transform Infrared Spectroscopy analysis can
verify the successful preparation of this drug delivery system. Based on the optimized formula,
MTX-M-NPs were prepared with a particle size of 188.17 ± 1.71 nm and an encapsulation
rate of 95.55 ± 0.33%. MTX-M-NPs displayed significantly higher cellular uptake
than MTX-NPs. The pharmacokinetic results showed that MTX-M-NPs could prolong
the in vivo circulation time of MTX.

Conclusion:
This targeting drug delivery system laid a promising foundation for the treatment
of RA.
Murburn Precepts for Cytochrome P450 Mediated Drug/Xenobiotic Metabolism and Homeostasis
Authors: Parashar Abhinav , Manoj Kelath M. 
Published: January 2021

Aims:
We aim to demonstrate why deeming diffusible reactive oxygen species (DROS) as toxic
wastes do not afford a comprehensive understanding of cytochrome P450 mediated microsomal xenobiotic
metabolism (mXM).

Background:
Current pharmacokinetic investigations consider reactive oxygen species formed in microsomal
reactions as toxic waste products, whereas our works (Manoj et al., 2016) showed that DROS are the reaction
mainstay in cytochrome P450 mediated metabolism and that they play significant roles in explaining several unexplained
physiologies.

Objective:
Herein, we strive to detail the thermodynamic and kinetic foundations of murburn precepts of cytochrome
P450 mediated drug metabolism.

Methodology:
Primarily, in silico approaches (using pdb crystal structure files), murburn reaction chemistry logic
and thermodynamic calculations to elucidate the new model of CYP-mediated drug metabolism. The theoretical
foundations are used to explain experimental observations.

Results:
We visually elucidate how murburn model better explains- (i) promiscuity of the unique P450-reductase;
(ii) prolific activity and inhibitions of CYP3A4; (iii) structure-function correlations of important key
CYP2 family isozymes- 2C9, 2D6 and 2E1; and (iv) mutation studies and mechanism-based inactivation of
CYPs. Several other miscellaneous aspects of CYP reaction chemistry are also addressed.

Conclusion:
In the light of our findings that DROS are crucial for explaining reaction outcomes in mXM, approaches
for understanding drug-drug interactions and methodologies for lead drug candidates' optimizations
should be revisited.
Antibiotics as Inhibitor of Glutathione S-transferase: Biological Evaluation and Molecular Structure Studies
Authors: Ayna Adnan , Khosnaw Luqman , Temel Yusuf , Ciftci Mehmet 
Published: January 2021

Background:
The glutathione S-transferases (GSTs) are family of enzymes that are notable for their
role in phase II detoxification reactions. Antibiotics have been reported to have several adverse effects on the
activity of the enzymes in mammals.

Aim:
The aim of this study was the structural and biochemical characterization of rat erythrocyte GST and understanding
the effects of gentamicin, clindamycin, cefazolin, ampicillin and scopolamine butylbromide on the
activity of human erythrocyte GST using rat as a model.

Methods:
The enzyme was purified by GSH-agarose affinity chromatography. In vitro GST enzyme activity
was measured at 25°C using CDNB as a model substrate. IC50 of drugs was measured by activity % vs compound
concentration graphs. Lineweaver Burk graphs were drawn to determine the inhibition type and Ki constants
for the drugs. The structure of the enzyme was predicted via Protein Homology/analogy Recognition Engine.

Results:
In this study, GST was purified from rat erythrocyte with a specific activity of 6.3 EU/mg protein, 44
% yield and 115 fold. Gentamicin and clindamycin inhibited the enzymatic activity with IC50 of 1.69 and 6.9
mM and Ki of 1.70 and 2.36 mM, respectively. Ampicillin and scopolamine butylbromide were activators of
the enzyme, while the activity of the enzyme was insensitive to cefazolin. The enzyme was further characterized
by homology modeling and sequence alignment revealing similarities with human GST.

Conclusion:
Collectively, it could be concluded that gentamicin and clindamycin are the inhibitors of erythrocyte
GST.
Popularizing Recombinant Baculovirus-derived OneBac System for Laboratory Production of all Recombinant Adeno-associated Virus Vector Serotypes
Authors: Wu Yang , Han Zengpeng , Duan Mingzhu , Jiang Liangyu , Tian Tiantian , Jin Dingyu , Wang Qitian , Xu Fuqiang 
Published: January 2021

Background:
On the basis of our previously established single recombinant baculovirus expression vector
(BEV)-derived OneBac system, we have optimized the process and expanded the rAAV production
range to the full range of serotypes rAAV1-13.

Objective:
Recombinant adeno-associated virus (rAAV) has been widely used as an efficient
transgenic vector in biomedical research, as well as gene therapy. Serotype-associated transduction
efficiency, tissue- or cell-type tropism and immunological profile are major considerations in
the various applications of rAAVs. There are increasing needs for different serotypes of rAAV, either
naturally isolated or artificially engineered. However, affordable and scalable production of a desired
serotype of rAAV remains very difficult, especially for researchers lacking relevant experience.

Methods:
Firstly, the AAV Cap gene was optimized to translate by ribosome leaky scanning and the
gene of interest (GOI) was cloned into the pFD/Cap-(ITR-GOI)-Rep2 shuttle plasmid. Following the
classical Bac-to-Bac method, sufficient BEV stock containing all rAAV packaging elements can be
quickly obtained. Finally, we can repeatedly scale up the production of rAAVs in one week by using a
single BEV to infect suspension-cultured Sf9 cells. The rAAV1-13 shows relatively high yields ranging
from 5×104 to 4×105 VG/cell. More than 1×1015 VG purified rAAVs can be easily obtained from 5
L suspension-cultured Sf9 cells.

Results:
As expected, rAAV serotypes 1-13 show different potencies for in vitro transduction and
cell-type tropisms.

Conclusion:
In summary, the single BEV-derived OneBac system should prove popular for laboratory
scaling-up production of any serotype of rAAV.
A Multi-target Drug Designing for BTK, MMP9, Proteasome and TAK1 for the Clinical Treatment of Mantle Cell Lymphoma
Authors: Qureshi Shahrukh , Khandelwal Ravina , Madhavi Maddala , Khurana Naveesha , Gupta Neha , Choudhary Saurav K. , Suresh Revathy A. , Hazarika Lima , Srija Chillamcherla D. , Sharma Khushboo , Hindala Mali R. , Hussain Tajamul , Nayarisseri Anuraj , Singh Sanjeev K. 
Published: January 2021

Background:
Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma characterized
by the mutation and overexpression of the cyclin D1 protein by the reciprocal chromosomal
translocation t(11;14)(q13:q32).

Aim:
The present study aims to identify potential inhibition of MMP9, Proteasome, BTK, and TAK1
and determine the most suitable and effective protein target for the MCL.

Methodology:
Nine known inhibitors for MMP9, 24 for proteasome, 15 for BTK and 14 for TAK1
were screened. SB-3CT (PubChem ID: 9883002), oprozomib (PubChem ID: 25067547), zanubrutinib
(PubChem ID: 135565884) and TAK1 inhibitor (PubChem ID: 66760355) were recognized as drugs
with high binding capacity with their respective protein receptors. 41, 72, 102 and 3 virtual screened
compounds were obtained after the similarity search with compound (PubChem ID:102173753),
PubChem compound SCHEMBL15569297 (PubChem ID:72374403), PubChem compound
SCHEMBL17075298 (PubChem ID:136970120) and compound CID: 71814473 with best virtual
screened compounds.

Results :
MMP9 inhibitors show commendable affinity and good interaction profile of compound holding
PubChem ID:102173753 over the most effective established inhibitor SB-3CT. The pharmacophore
study of the best virtual screened compound reveals its high efficacy based on various interactions.
The virtual screened compound's better affinity with the target MMP9 protein was deduced
using toxicity and integration profile studies.

Conclusion:
Based on the ADMET profile, the compound (PubChem ID: 102173753) could be a
potent drug for MCL treatment. Similar to the established SB-3CT, the compound was non-toxic with
LD50 values for both the compounds lying in the same range.
Multi-target Drug Discovery via PTML Modeling: Applications to the Design of Virtual Dual Inhibitors of CDK4 and HER2
Authors: Kleandrova Valeria V. , Scotti Marcus T. , Scotti Luciana , Speck-Planche Alejandro 
Published: January 2021

Background:
Cyclin-dependent kinase 4 (CDK4) and the human epidermal growth factor
receptor 2 (HER2) are two of the most promising targets in oncology research. Thus, a series of computational
approaches have been applied to the search for more potent inhibitors of these cancerrelated
proteins. However, current approaches have focused on chemical analogs while predicting the
inhibitory activity against only one of these targets, but never against both.

Aims:
We report the first perturbation model combined with machine learning (PTML) to enable the
design and prediction of dual inhibitors of CDK4 and HER2.

Methods:
Inhibition data for CDK4 and HER2 were extracted from ChEMBL. The PTML model
relied on artificial neural networks to allow the classification/prediction of molecules as active or
inactive against CDK4 and/or HER2.

Results:
The PTML model displayed sensitivity and specificity higher than 80% in the training set.
The same statistical metrics had values above 75% in the test set. We extracted several molecular
fragments and estimated their quantitative contributions to the inhibitory activity against CDK4 and
HER2. Guided by the physicochemical and structural interpretations of the molecular descriptors in
the PTML model, we designed six molecules by assembling several fragments with positive contributions.
Three of these molecules were predicted as potent dual inhibitors of CDK4 and HER2, while
the other three were predicted as inhibitors of at least one of these proteins. All the molecules complied
with Lipinski’s rule of five and its variants.

Conclusion:
The present work represents an encouraging alternative for future anticancer chemotherapies.
5-Methoxy-1-methyl-2-{[4-(2-hydroxyphenyl)piperazin-1-yl]methyl}-1Hindole (KAD22) with Antioxidant Activity
Authors: Kaczor Agnieszka A. , Wojtunik-Kulesza Karolina , Wróbel Tomasz M. , Matosiuk Dariusz , Pitucha Monika 
Published: January 2021

:
Compound KAD22 (5-methoxy-1-methyl-2-[4-(2-hydroxyphenyl)piperazin-1-yl]methyl-1H-indole) was designed as a potential dopamine D2 receptor agonist with antioxidant activity for possible treatment of Parkinson’s disease.
The compound was obtained from 5-methoxy-1-methyl-1H-indole-2-carbaldehyde and 2-(piperazin-1-yl)phenol. KAD22
showed no affinity to dopamine D2 receptor but it is a potent antioxidant. Experimental and computational structural studies
(conformational analysis, HOMO and LUMO orbitals, electrostatic potential map, non-covalent interaction plot, spectral
properties, ligand-receptor interactions) of KAD22 were performed to address its biological activity.