bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Crystallographic Data for the Development of Machine Learning Models to Predict Protein-Ligand Binding Affinity
Authors: Veit-Acosta Martina , de Azevedo Junior Walter Filgueira 
Published: February 2021

Background:
One of the main challenges in the early stages of drug discovery
is the computational assessment of protein-ligand binding affinity. Machine learning techniques
can contribute to predicting this type of interaction. We may apply these techniques
following two approaches. Firstly, using the experimental structures for which
affinity data is available. Secondly, using protein-ligand docking simulations.

Objective:
In this review, we describe recently published machine learning models based
on crystal structures, for which binding affinity and thermodynamic data are available.

Method:
We used experimental structures available at the protein data bank and binding
affinity and thermodynamic data was accessed through BindingDB, Binding MOAD, and
PDBbind databases. We reviewed machine learning models to predict binding created using
open source programs, such as SAnDReS and Taba.

Results:
Analysis of machine learning models trained against datasets, composed of crystal
structure complexes indicated the high predictive performance of these models when
compared with classical scoring functions.

Conclusion:
The rapid increase in the number of crystal structures of protein-ligand complexes
created a favorable scenario for developing machine learning models to predict
binding affinity. These models rely on experimental data from two sources, the structural
and the affinity data. The combination of experimental data generates computational models
that outperform the classical scoring functions.
Therapeutic Properties of PDMS Nanoparticles: A Promising New Drug
Delivery Vehicle against Inflammatory Conditions
Authors: Biju Prabath Gopalakrishnan , Ajitha Aiswarya Anilkumar , Kumar Sri Siva , Viswanathan Gayathri , Baby Sabulal 
Published: February 2021

Background:
Over the last few decades, there has been a stupendous change in the area of drug delivery using particulate delivery systems, with increasing focus on nanoparticles in recent times. Nanoparticles helps to improve and alter the pharmacodynamic properties and pharmacokinetics of various types of drug molecules. These features help to protect the drug entity in the systemic circulation, access of the drug to the chosen sites, and to deliver the drug in a controlled and sustained rate at the site of action.

Objective:
Nanoparticle based targeted delivery of anti-inflammatory drugs/signal modulatory agents to the cytoplasm or nuclei of the targeted cell can significantly enhance the precision and efficacy of intended therapeutic activity. To this end, we report ligand free, enhanced intra-nuclear delivery model of anti-inflammatory therapeutics via PDMS nanoparticles.

Method:
PDMS nanoparticles were prepared by sacrificial silica template-based approach and details of their characterization for suitability as a nanoparticle-based delivery material is detailed herein.

Results:
Biological evaluation for compatibility was carried out and the results showed that the PDMS nanoparticle has no toxicity on RAW 264.7 cells in the concentration range of 10, 20, 40, 60, 80, 100 and 120 μg/mL in culture. Biocompatibility and absence of toxicity was determined by morphological examination and cell viability assays. Drug loading and release kinetics were carried out with the anti-inflammatory drug Diclofenac.

Conclusion:
In this paper we clearly demonstrate the various aspects of nanoparticle articulation, characterization, effect of their characteristics and their applications as a non-toxic drug delivery molecule for its potential applications in therapeutic delivery of drugs for sustained release.
Comparison of the Inhibitory Effects of Clotrimazole and Ketoconazole against Human Carboxylesterase 2
Authors: Zhao Tingting , Wang Dalong , Zhao Shan , Chen Jing , Dou Tongyi , Ge Guangbo , Wang Changyuan , Meng Qiang , Sun Huijun , Liu Kexin , Wu Jingjing 
Published: February 2021

Background:
Both clotrimazole and ketoconazole have been verified to have an inhibitory effect on
CYP3A4. hCE2 is an enzyme closely related to the side effects of several anti-cancer drugs. However, the interactions
between hCE2, clotrimazole, and ketoconazole remain unclear.

Objective:
The objective of this study was to investigate and compare the inhibition behaviors of the two antifungal
agents, ketoconazole and clotrimazole, on the human liver microsome hCE2 and to explore their underlying
mechanism.

Methods:
The inhibitory effects were investigated in human liver microsomes (HLMs) using fluorescein diacetate
(FD), N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN) and irinotecan (CPT-
11) as substrates of hCE2.

Results:
Clotrimazole significantly inhibited the hCE2 activity, which was manifested by attenuated fluorescence
when the substrates were FD and NCEN. The inhibitory effect of clotrimazole towards hCE2 was much
stronger than that of ketoconazole, and the inhibitory behaviors displayed substrate-dependent inhibition. The
IC50 value of clotrimazole, with CPT-11 as the substate, increased by 5 and 37 times more than that with FD
and NCEN, respectively. Furthermore, the inhibitions of clotrimazole towards hCE2-mediated hydrolysis of
FD, NCEN, and CPT-11 were all in competitive mode with the Ki values of 0.483 μM, 8.63 μM, and 29.0 μM,
respectively. Molecular docking result of clotrimazole binding to hCE2 illustrated that clotrimazole could efficiently
orient itself in the Z site cavity of hCE2.

Conclusion:
Clotrimazole displayed a strong inhibitory effect against hCE2, which might be used as a potential
combined agent co-administrated with CPT-11 to alleviate the hCE2-mediated severe side effects.
Collagen Peptides, in Association with Vitamin C, Sodium Hyaluronate,
Manganese and Copper, as Part of the Rehabilitation Project in the Treatment
of Chronic Low Back Pain
Authors: Farì Giacomo , Santagati Dario , Pignatelli Giovanni , Scacco Venera , Renna Domenico , Cascarano Giuseppe , Vendola Francesco , Bianchi Francesco Paolo , Fiore Pietro , Ranieri Maurizio , Megna Marisa 
Published: February 2021

Background and Objective:
Low back pain (LBP) is a frequent symptom. Among the
causes that can determine it, lumbar osteoarthritis plays an important role. Therapeutic exercise, according
to McKenzie method, has been shown to be effective in the treatment of LBP. Oral supplementation
with collagen peptides represents a new therapeutic possibility in osteoarthritis. The aim
of this study is to evaluate the combined efficacy of therapeutic exercise and oral administered viscosupplements
in the treatment of osteoarthritis-related chronic LBP.

Methods:
Sixty patients were recruited and randomly divided into two groups (Group A and B).
Group A performed only kinesitherapy, Group B carried out the same kinesitherapy combined with
the daily administration of food supplements such as Fortigel®, Vitamin C, sodium hyaluronate,
manganese and copper, during the whole treatment period. Patients were evaluated at the time of recruitment
(T0), at the end of the treatment (T1 - 3 weeks after T0) and 6 weeks after T1 (T2). The
outcome measures used were: Visual Analogue Scale (VAS), Oswestry Disability Index (ODI),
and Short Form-12 (SF-12).

Results:
All the outcomes improved significantly at T1 in both groups, but more markedly in
group B. Furthermore, in group A at T2, there was a statistically significant worsening in the
scores of VAS, ODI and physical component of the SF-12, while in group B, this variation has not
been detected.

Conclusions:
The combination of rehabilitation based on McKenzie back exercises and oral viscosupplementation
with Fortigel®, Vitamin C, sodium hyaluronate, manganese and copper represents
a valid option in patients with chronic LBP, as it ensures pain relief and improvement in the
quality of life and in lumbar spine functionality. These therapeutic benefits are more evident and
long-lasting compared to those obtained with rehabilitation alone.
Minocycline and Doxycycline: More Than Antibiotics
Authors: Singh Sher , Khanna Deepa , Kalra Sanjeev 
Published: February 2021

:
Minocycline and doxycycline both are second-generation tetracycline antibiotic with similar chemical structures and comparable antibacterial spectrum. Minocycline has also emerged as the tetracycline of choice for multidrug-resistant Acinetobacter baumannii infections, although doxycycline has also shown the activity. Minocycline showed promising results in experimental neurology, which was due to its highly lipophilic nature. It is clinically safe and effective adjunct to antipsychotic medications.The objective of the current review is to provide clinical and preclinical, non-antibiotic uses of minocycline as well as doxycycline.Relevant literature covers antibiotic actions but is more specifically concerned with the non-antibiotic biological aspect of the tetracyclines. Non-antibiotic biological effects for both the antibiotics were identified through searching relevant databases including: PubMed, Scopus, and Web of Science up to 2020, using the keywords ‘minocycline and doxycycline’. Anti-inflammatory, anti-oxidant, anti-apoptotic neuroprotective, immunomodulatory and number of other non-antibiotic effects were compiled for minocycline and doxycycline.
Aryltetralin-type Lignan of Podophyllum: A Comprehensive Review
Authors: Kumar Dharmendra , Rajagopal Mogana , Akowuah Gabriel Akyirem , Lee Yong-Xin , Chong Chua Wei , Gan Pei Wen , Liew Jeou Chyi 
Published: February 2021

:
Podophyllotoxin is a nonalkaloid toxin aryltetralin lactone lignan, occurring naturally
and extracted from the rhizomes and roots of Podophyllum species. Podophyllotoxin and its derivatives
have been shown to possess a broad spectrum of pharmacological activities, mainly antineoplastic
and antiviral properties. Podophyllotoxin serves as a potential anticancer agent and also the
precursor for the chemical synthesis of some clinically important anticancer agents. The chemical
modification and pharmacological investigation of podophyllotoxin derivatives have become a concern
nowadays. Research interest has been stimulated towards the innovation of podophyllotoxin
derivatives as the semi-synthetic anticancer agents, especially etoposide and teniposide. Podophyllotoxin
and its derivatives are available in several formulations and also found to be effective in
combination therapy. This review article aims to provide an overview of the role of podophyllotoxin,
its mechanism of action, pharmacological activities, pharmacokinetics, available formulations,
and its effects in combination therapy. This article also reviews the biosynthesis, structure
and modifications of podophyllotoxin and its derivatives as an anticancer agent.
Curcumin Loaded Ethosomal Gel for Improved Topical Delivery: Formulation,
Characterization and Ex-vivo Studies
Authors: Kumar Bhumika , Sahoo P.K. , Manchanda Satish 
Published: February 2021

Background:
Curcumin is a curcuminoid which is an active constituent of turmeric and is obtained from the rhizomes of Curcuma longa, family Zingiberaceae. Curcumin modulates the activity of various transcription factors and regulates the expression of inflammatory enzymes, cell survival proteins, adhesion molecules and cytokines by binding to a variety of proteins and inhibiting the activity of various kinases. Curcumin falls in the BCS class IV drug, with poor solubility and poor permeability which makes it very challenging in utilizing the maximum therapeutic potential of this moiety.

Objective:
The major aim of the study was to enhance transdermal penetration of curcumin via ethosomal gel and to overcome the barriers of poor permeability of transdermal drug delivery.

Methods:
Curcumin loaded ethosomes were prepared with varying quantities of ethanol and soya lecithin by cold method and were optimised based on entrapment efficiency, vesicular size and Ex-vivo studies. Optimised ethosomal formulation was further incorporated into a gel and was evaluated. Ex-vivo studies were performed with the ethosomal gel of curcumin and was compared with simple drug solution.

Result:
Prepared ethosomal system showed a vesicle size ranging from 211 to 320 nm with spherical, smooth surface and entrapment efficiency of 87 to 91%. Optimised ethosomal system (ET3) was incorporated into gel and was further evaluated.

Conclusion:
The findings of the research work suggested that the ethosomal gel holds an excellent potential for transdermal delivery of curcumin.
An Apparatus Designed for Coating and Coloration of Filaments Used in Fused Filament Fabrication (FFF) 3D Printing
Authors: Chohan Piyush , Yadav Aniket , Kumar Ranvijay , Kumar Raman , Chohan Jasgurpreet Singh 
Published: February 2021

Background:
Three dimensional (3D) printing is emerging technology, capable of manufacturing a solid layer by layer. With the advancements of materials for 3D printing, this technology is applicable in almost every sector. But in accordance with the product requirements we need to modify the mechanical properties of material. To achieve good surface finish we require coating of filament. For this purpose an apparatus is designed for coating of material over a filament, which is capable of coating filaments uniformly and with automated process.

Objective:
The objective of present invention is directed to a filament feeding device for applying uniform coating on a filament in order to make 3D solid objects with good quality finishing, thereby eliminating the chances of strains and imperfect coating on the filament.

Methods:
The present invention relates to a filament feeding device, comprising a container equipped within the device for storing a chemical solution in a liquefied form, an inlet port fabricated on the container for inserting a filament inside the container, plurality of relief valves placed at a bottom portion of the container for controlling the leakage of the filaments during insertion of the filaments. A stepper motor in association with a blade equipped within the container to rotate the main extruder of a 3D printer, and an outlet port designed opposite to the inlet port for discharging the filament from the container for 3D printing of the filament in order to manufacture the solid object.

Results:
The apparatus makes it easy for coating and coloration of materials to make the reinforced composite filaments. As this apparatus provides uniform coating of material on the filaments, the product printed by filaments have good surface finish.

Conclusion:
The proposed method can reduce coating time and printing time. This work provides meaningful implication to researchers who are doing research in the domain of additive manufacturing.
Identifying Myocardial Infarction Using Hierarchical Template Matching–Based Myocardial Strain: Algorithm Development and Usability Study
Authors: Bhalodiya Jayendra Maganbhai , Palit Arnab , Giblin Gerard , Tiwari Manoj Kumar , Prasad Sanjay K , Bhudia Sunil K , Arvanitis Theodoros N , Williams Mark A 
Published: February 2021

Background
Myocardial infarction (MI; location and extent of infarction) can be determined by late enhancement cardiac magnetic resonance (CMR) imaging, which requires the injection of a potentially harmful gadolinium-based contrast agent (GBCA). Alternatively, emerging research in the area of myocardial strain has shown potential to identify MI using strain values.

Objective
This study aims to identify the location of MI by developing an applied algorithmic method of circumferential strain (CS) values, which are derived through a novel hierarchical template matching (HTM) method.

Methods
HTM-based CS H-spread from end-diastole to end-systole was used to develop an applied method. Grid-tagging magnetic resonance imaging was used to calculate strain values in the left ventricular (LV) myocardium, followed by the 16-segment American Heart Association model. The data set was used with k-fold cross-validation to estimate the percentage reduction of H-spread among infarcted and noninfarcted LV segments. A total of 43 participants (38 MI and 5 healthy) who underwent CMR imaging were retrospectively selected. Infarcted segments detected by using this method were validated by comparison with late enhancement CMR, and the diagnostic performance of the applied algorithmic method was evaluated with a receiver operating characteristic curve test.

Results
The H-spread of the CS was reduced in infarcted segments compared with noninfarcted segments of the LV. The reductions were 30% in basal segments, 30% in midventricular segments, and 20% in apical LV segments. The diagnostic accuracy of detection, using the reported method, was represented by area under the curve values, which were 0.85, 0.82, and 0.87 for basal, midventricular, and apical slices, respectively, demonstrating good agreement with the late-gadolinium enhancement–based detections.

Conclusions
The proposed applied algorithmic method has the potential to accurately identify the location of infarcted LV segments without the administration of late-gadolinium enhancement. Such an approach adds the potential to safely identify MI, potentially reduce patient scanning time, and extend the utility of CMR in patients who are contraindicated for the use of GBCA.
The Impact of Enhanced Recovery After Surgery on Total Joint Arthroplasty: Protocol for a Systematic Review and Meta-analysis
Authors: Rele Siddharth , Shadbolt Cade , Schilling Chris , Taylor Nicholas F , Dowsey Michelle M , Choong Peter F M 
Published: February 2021

Background
The number of total joint arthroplasties (TJAs) being performed is increasing worldwide. To match this increasing demand, there has been focus on hastening patients’ recovery of function. This effort has culminated in the formulation of enhanced recovery after surgery (ERAS) strategies. However, with evolving ERAS programs and new recommendations, a review of current evidence is required to provide clinicians with up-to-date information about its effect on outcomes for TJA.

Objective
The objective of this study is to assess the utility of ERAS programs on patient, health service, and economic outcomes for primary, elective total hip arthroplasty (THA) and total knee arthroplasty (TKA).

Methods
A systematic search will be conducted in Medline (Ovid), EMCARE (Ovid), EMBASE (Ovid), Web of Science, CINAHL, National Health Service Economic Evaluations Database, and the Cochrane Library. Analytical, observational, and experimental designs will be included in this systematic review. Only studies including patients undergoing primary TKA and THA comparing ERAS programs with conventional surgery and postoperative care will be included. Data related to patient outcomes, health service outcomes, safety, and economic evaluation will be extracted.

Results
The search terms and primary database searches have been finalized. Findings will be reported in narrative and tabular form. Where appropriate, random effects meta-analyses will be conducted for each outcome, and heterogeneity quantified with Cochran Q test and I2 statistic. Measures of effect or mean differences will be reported with 95% confidence intervals. The results of this systematic review will be disseminated in a peer-reviewed journal.

Conclusions
This protocol will guide a systematic review assessing outcomes associated with ERAS surgery in primary THA and TKA.

Trial Registration
Open Science Framework osf.io/y4bhs; https://osf.io/y4bhs

International Registered Report Identifier (IRRID)
PRR1-10.2196/25581
Health Care Students’ Knowledge of and Attitudes, Beliefs, and Practices Toward the French COVID-19 App: Cross-sectional Questionnaire Study
Authors: Montagni Ilaria , Roussel Nicolas , Thiébaut Rodolphe , Tzourio Christophe 
Published: February 2021

Background
Many countries worldwide have developed mobile phone apps capable of supporting instantaneous contact tracing to control the COVID-19 pandemic. In France, a few people have downloaded and are using the StopCovid contact tracing app. Students in the health domain are of particular concern in terms of app uptake. Exploring their use and opinions about the app can inform improvements and diffusion of StopCovid among young people.

Objective
The aim of this study is to investigate health care students’ knowledge of and attitudes, beliefs, and practices (KABP) toward the StopCovid app.

Methods
A field survey was conducted among 318 students at the health sciences campus of the University of Bordeaux, France, between September 25 and October 16, 2020. A quota sampling method was used, and descriptive statistics and univariate analyses were performed.

Results
Of the 318 respondents, 77.3% (n=246) had heard about the app, but only 11.3% (n=36) had downloaded it, and 4.7% (n=15) were still using it at the time of the survey. Among the 210 participants who had heard about the app but did not download it, the main reasons for not using the app were a belief that it was not effective given its limited diffusion (n=37, 17.6%), a lack of interest (n=37, 17.6%), and distrust in the data security and fear of being geolocated (n=33, 15.7%). Among the 72 students who had not heard of the app and were given a brief description of its functioning and confidentiality policy, 52.7% (n=38) said they would use it. Participants reported that the main solution for increasing the use of the app would be better communication about it (227/318, 71.4%).

Conclusions
Even among health students, the contact tracing app was poorly used. The findings suggest that improved communication about its advantages and simplicity of use as well as clarifying false beliefs about it could help improve uptake.
Thresholds of Glycemia and the Outcomes of COVID-19 Complicated With Diabetes: A Retrospective Exploratory Study Using Continuous Glucose Monitoring
Authors: Shen Yun , Fan Xiaohong , Zhang Lei , Wang Yaxin , Li Cheng , Lu Jingyi , Zha Bingbing , Wu Yueyue , Chen Xiaohua , Zhou Jian , Jia Weiping 
Published: February 2021

OBJECTIVE
Although elevated glucose levels are reported to be associated with adverse outcomes of coronavirus disease 2019 (COVID-19), the optimal range of glucose in patients with COVID-19 and diabetes remains unknown. This study aimed to investigate the threshold of glycemia and its association with the outcomes of COVID-19.

RESEARCH DESIGN AND METHODS
Glucose levels were assessed through intermittently scanned continuous glucose monitoring in 35 patients for an average period of 10.2 days. The percentages of time above range (TAR), time below range (TBR), time in range (TIR), and coefficient of variation (CV) were calculated. Composite adverse outcomes were defined as either the need for admission to the intensive care unit, need for mechanical ventilation, or morbidity with critical illness.

RESULTS
TARs using thresholds from 160 to 200 mg/dL were significantly associated with composite adverse outcomes after adjustment of covariates. Both TBR (&lt;70 mg/dL) and TIR (70–160 mg/dL), but not mean sensor glucose level, were significantly associated with composite adverse outcomes and prolonged hospitalization. The multivariate-adjusted odds ratios of the CV of sensor glucose across tertiles for composite adverse outcomes of COVID-19 were 1.00, 1.18, and 25.2, respectively.

CONCLUSIONS
Patients with diabetes and COVID-19 have an increased risk of adverse outcomes with glucose levels &gt;160 mg/dL and &lt;70 mg/dL and a high CV. Therapies that improve these metrics of glycemic control may result in better prognoses for these patients.