bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to improve participant compliance and retention in clinical trials：A Scoping Review
Authors: Yu Mingkun , Lin Ziyi , Liang Changhao , Li Chengze , Zhang Zhijia , Liu Kexin , Li Xun , Liu Jianping , Fei Yutong 
Published: November 2020

Abstract
Background: The reliability of results can be compromised when subsets of participants who remain on a study differ from those who drop out. Although recent studies have investigated strategies for improving compliance and retention , there has been very little investigation of process factors, regardless of the type of literature and the publication date. factors that may influence how and why compliance and retention may be successful (or not).Aim: To identify process factors that may influence participant compliance and retention in clinical trials, and potential strategies to improve the compliance and retention, from published studies, grey literature, and the reference lists of included articles to facilitate future design and implementation of trials.Methods : Six databases and two clinical trial registries were searched on November 29, 2019. Surveys, interviews, retrospective data analyses, theoretical research, reviews and clinical studies aiming at investigating factors and potential strategies were included. Data synthesis followed an iterative process to develop a list of process factors and potential retention strategies.Results were presented mainly as texts, including visualization using word cloud, and descriptive data.Results: 182 publications were included in this review, composed of 58 retrospective reflection of RCTs based on 1,132 clinical trials with 177804 participants, 27 implementation researches, 22 theoretical researches, 20 interviews, 18 surveys, 17 randomized controlled trials, 8 literature reviews, 5 systematic review and meta analysis, 3 mixed methods researches, 2 case report, 1 meta-ethnographic synthesis and 1 cohort study. We identified 70 process factors that may affect the compliance and retention . The most commonly addressed factors were age, education, economy, trust in clinical trials, supporting from surrounding people, safety concerns and effectiveness. We found 42 potential strategies to improve compliance and retention. Strategies reported most frequently were that researchers should pay attention to the changes on participants' psychological condition, try their best to build good relationships, provide some compensation and educate the participants about compliance and retention . Conclusion：These factors that may affect the compliance and retention can help researchers predict participants who are less likely to adhere and develop screening tools to find efficiently their suitable participants. These potential strategies that may improve the compliance and retention.
WITHDRAWN: Management of canine insulinomas with toceranib phosphate: 30 cases (2009-2019).
Authors: Sheppard-Olivares Sabina , Bello Nora , Johannes Chad M , Hocker Samuel , Billler Barbara , McKee Talon , McMillan Mattison , Husbands Brian , Wood Elizabeth , Wouda Raelene M 
Published: November 2020

Abstract
BACKGROUND: Insulinomas are the most common tumour of the endocrine pancreas in dogs. These are malignant tumours with a high metastatic rate and limited efficacious chemotherapeutic options available. Recent literature supports the use of the multi-receptor tyrosine kinase inhibitor sunitinib malate for treatment of metastatic insulinoma in people. Toceranib phosphate is a veterinary targeted therapy that may provide benefit in treatment of canine insulinomas. The primary objectives of this study were to describe the duration of clinical benefit, defined as absence of clinical signs associated with hypoglycemia and/or measurable response according to the response evaluation criteria for solid tumours in dogs (cRECIST), and measures of outcome, namely progression free interval (PFI) and overall survival time (OST) in dogs diagnosed with insulinoma treated with toceranib. A secondary objective was to describe the adverse effects of toceranib in dogs with insulinoma.RESULTS: A medical record search identified 30 dogs diagnosed with insulinoma and treated with toceranib at five university hospitals and eight veterinary specialty referral hospitals. A majority (66.7%) of dogs with measurable disease experienced either complete response (CR), partial response (PR), or stable disease (SD) with toceranib therapy. The overall median progression free interval (PFI) was 561 days (95% confidence interval: [246, 727 days]). The overall median survival time (OST) was 656 days [310, 1045 days]. Larger dogs were at increased risk for disease progression (P = 0.0310) and death (P = 0.0064), with every 1 kg increase in body weight resulting in hazard ratios (HRs) of 1.045 [1.003, 1.084] and 1.05 [1.012, 1.090], respectively. In addition, time to disease progression was associated with use of therapies prior to toceranib (P = 0.0050) and type of veterinary practice (P = 0.0025). The most common adverse events with toceranib therapy were grade 1 or 2 gastrointestinal toxicities.CONCLUSIONS: Clinical benefit was reported in the majority of dogs diagnosed with insulinoma treated with toceranib, but randomized, prospective studies are needed to assess and quantify the effect of this therapy. The most commonly observed adverse events (AEs) were gastrointestinal AEs.
Upregulated CDKN2A expression may be an independent protective factor in Luminal-like breast cancer
Authors: Qiu Yier , Lu Guowen , Wu Yingjie 
Published: November 2020

Abstract
Background: Previous studies revealed that CDKN2A (cyclin-dependent kinase inhibitor 2A) functioned as a tumour suppressor in various types of malignant tumours. The aim of the study was to clarify the value of CDKN2A expression in the prognosis of breast cancer.Method: Using the Cancer Genome Atlas (TCGA) database, we compared CDKN2A mRNA levels between breast cancer tissues and normal tissues and analyzed the relationship between clinical features and CDKN2A expression with the Wilcox test and the Kruskal-Wallis test. Kaplan-Meier and Cox analyses were performed to determine the correlation between CDKN2A expression and breast cancer prognosis. Gene set enrichment analysis (GSEA) was performed using the TCGA data set.Results: We first found that CDKN2A expression was markedly higher in breast cancer tissues than in normal tissues using the TCGA database (P=0.000). In addition, CDKN2A mRNA expression in breast cancer was positively correlated with age (P=0.018), histological types (P=0.028), ER status (P=0.000), PR status (P=0.000) and molecular subtypes (P=0.000). Kaplan-Meier analysis showed that increased CDKN2A expression was associated with increased survival time in breast cancer patients (P=0.000), especially in Luminal-like subtype. Univariate and multivariate Cox analyses indicated that CDKN2A expression was an independent prognostic biomarker for breast cancer (P=0.037). GSEA suggested that pathways involving cell adhesion molecules (CAMs), cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity were differentially enriched in the CDKN2A-high expression group.Conclusion: Our research demonstrated that high CDKN2A mRNA expression may be an independent protective factor for improved prognosis in Luminal-like breast cancer. Additionally, the signaling pathways related to CAMs, cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity regulated by CDKN2A mRNA expression should be further studied.
Moderately Reduced Estimated Glomerular Filtration Rate (eGFR) among Community - Dwelling Older People Associated with Increased Long Term Mortality: A Study from Low to Middle Income Country in Asia.
Authors: Skulratanasak Peenida , Chalermsri Chalobol , Aekplakorn Wichai , Srinonpras Varalak 
Published: November 2020

Abstract
Background: Reduced glomerular filtration rate (GFR) is regarded as a component of renal senescence; however, the full impact of chronic kidney disease (CKD) among older people is still not fully understood. This study aimed to investigate the effect of reduced GFR on all-cause mortality, and the combined effect of socioeconomic status and CKD on mortality among older Thai population. Methods: A retrospective cohort of Thai population aged >60 years was enrolled from the Fourth National Health Examination Survey, and estimated GFR (eGFR) and comorbid disease data were collected. Mortality information was gathered from the National Civil Registration and Vital Statistics System. Factors associated with all-cause mortality were determined using Cox proportional hazards model. Results: A total of 9,080 participants (mean age: 69.5 years) were included. Prevalence of CKD stage 3-5 was 53.3%. During the 2008-2015 period, the overall mortality rate among CKD was 28.9 per 1,000 person-years. The stages of CKD significantly associated with increased mortality were stages 3b, 4, and 5, as follows: HR: 1.4 (95% CI: 1.2-1.63), 2.2 (95% CI: 1.78-2.71), and HR: 5.9 (95% CI: 4.26-8.15), respectively. People with higher socioeconomic status and moderate-stage CKD had lower mortality than lower socioeconomic status moderate-stage CKD. Conclusion: Moderate decline in eGFR was found to be independently associated with all-cause mortality in Thai elderly population. Socioeconomic disparities were also observed among older CKD. Implementation of a mass screening program to identify asymptomatic individuals would accelerate diagnosis and treatment, and this would reduce the costs of care associated with advanced-stage disease.
Changing Rainfall Patterns in India: A Spatiotemporal Analysis of Trends &amp; Impacts
Authors: Patel Praharsh , Khan Adeel 
Published: November 2020

Abstract
The hydrological cycle that starts with rainfall has been under major threat from the global temperature rise and climatic changes. In India, rainfall changes not only jeopardize water security but also have a major set-back for socio-economic stability. There have been attempts to decode the changing rainfall patterns in India but most of them conducted at wider spatial resolution (such as national, state, or sub-divisional level) fail to capture the essence of spatial variation in rainfall characteristics. To get a clearer understanding of change in key rainfall parameters, this paper analyses more than 197 million 0.25˚ x 0.25˚ gridded rainfall data points. The fine resolution 117 years (1901-2017) of daily rainfall data is utilized to test significant spatiotemporal trends in the quantum of rainfall and other key rainfall parameters such as rainy days, monsoon onset and withdrawal dates, occurrences of extreme rainfall events, and frequency of drought and high rainfall years. With an emphasis on changing climatic patterns since perceived climate change onset in the 1970s, the study identifies the regions with significant changes in rainfall patterns by comparing key parameters pre- & post- 1970s. The paper also highlights the major repercussions and challenges for the identified regions with significant changing rainfall patterns.
Eco-Friendly Synthesis of Peptides Using Fmoc-Amino Acid Chlorides as Coupling Agent Under Biphasic Condition
Authors: Khatavi Santosh Y. , Kantharaju Kamanna 
Published: November 2020

Background:
Agro-waste derived solvent media act as a greener process for the peptide
bond formation using Nα-Fmoc-amino acid chloride and amino acid ester salt with in situ neutralization
and coupling under biphasic condition. The Fmoc-amino acid chlorides are prepared by the
reported procedure of freshly distilled SOCl2 with dry CH2Cl2. The protocol found many added advantages
such as neutralization of amino acid ester salt and not required additional base for the neutralization,
and directly coupling take place with Fmoc-amino acid chloride gave final product
dipeptide ester in good to excellent yields. The protocol occurs with complete stereo chemical integrity
of the configuration of substrates. Here, we revisited Schotten-Baumann condition, instead
of using inorganic base.

Objective:
To develop green protocol for the synthesis of peptide bond using Fmoc-amino acid
chloride with amino acid esters salt.

Methods:
The final product isolated is analyzed in several spectroscopic and analytical techniques
such as FT-IR, 1H-, 13C-NMR, Mass spectrometry and RP-HPLC to check stereo integrity and purity
of the product.

Conclusion:
The present method developed greener using natural agro-waste (lemon fruit shell
ash) derived solvent medium for the reaction and not required chemical entity.
Natural Compounds as Inhibitors of SARS-CoV-2 Main Protease (3CLpro): A Molecular Docking and Simulation Approach to Combat COVID-19
Authors: Rehman Md. Tabish , AlAjmi Mohamed F. , Hussain Afzal 
Published: November 2020

Background:
The emergence and dissemination of SARS-CoV-2 has caused high mortality and
enormous economic loss. Rapid development of new drug molecules is the need of hour to fight COVID-19.
However, the conventional approaches of drug development are time consuming and expensive. Here, we have
adopted a computational approach to identify lead molecules from nature. Ligands from natural compounds library
available at Selleck Inc (L1400) have been screened for their ability to bind and inhibit the main protease
(3CLpro) of SARS-CoV-2.

Methods:
The natural compounds library of Selleck Inc. (Catalog No. L1400) were retrieved from
www.selleckchem.com. It contains 2230 compounds in sdf format, curated from natural sources. Prior to molecular
docking, all the ligands were prepared by adding hydrogen atoms and merging them with non-polar hydrogen
atoms. Gasteiger partial charges were added, rotatable bonds were defined, and the energies were minimized
using MMFF94 forcefield (11,12). The three-dimensional coordinates of the main protease (Mpro), also
known as 3C-like protein (3CLpro), was downloaded from the protein databank available at
https://www.rcsb.org/structure/6LU7. The structure was solved to a resolution of 2.16 Å and is bound with a
peptide-like inhibitor (N3)(8). The structure of target was prepared for molecular docking by adding hydrogen
atoms, Kollman united atom type charges and solvation parameters using AutoDock Tool (ADT) (13).

Results:
We found that Kaempferol, Quercetin, and Rutin were bound at the substrate binding pocket of
3CLpro with high affinity (105-106 M-1) and interact with the active site residues such as His41 and Cys145
through hydrogen bonding and hydrophobic interactions. In fact, the binding affinity of Rutin (~106 M-1) was
much higher than Chloroquine (~103 M-1) and Hydroxychloroquine (~104 M-1), and the reference drug
Remdesivir (~105 M-1).

Conclusion:
The results suggest that natural compounds such as flavonoids have the potential to be developed
as novel inhibitors of SARS-CoV-2 with a comparable/higher potency as that of Remdesivir. However, their
clinical usage on COVID-19 patients is a subject of further investigations and clinical trials.
Applications and Functions of γ-Poly-Glutamic Acid and its Derivatives in Medicine
Authors: Wang Guoliang , Liu Qing , Yang Young M. , Lee Soo-Ung , Han Jee-Soo , Jang Kyoung-Jin , Kang Dong Y. , Sp Nipin , Li Zhandong , Tong Tao 
Published: November 2020

Background:
γ-Poly-Glutamic Acid (γ-PGA) is a naturally occurring homo-polyamide produced
by various strains of Bacillus. It is made from repeating units of L-glutamic acid, D-glutamic acid,
or both connected through amide linkages between α-amino and γ-carboxylic acid groups. As a biopolymer
substance, the attractive properties of γ-PGA are that it is water-soluble, biodegradable, biocompatible,
non-toxic, non-immunogenic, and edible. Therefore, it can be used as a green and environmentally
friendly biological material.

Methods:
The review concentrates on the reports revealing the functions and potential use of γ-PGA
and its derivatives in medicine.

Results & Discussion:
γ-PGA is described to possess several properties that may be exploited in medicine.
The biopolymer reportedly has been successfully applied not only as a metal chelator, drug carrier/
deliverer, and gene vector, but also used safely as a vaccine adjuvant, tissue engineering material, and
contrast agent.

Conclusion:
γ-PGA could be potentially considered as a potential biomedical material in the field of
medicine.
An Overview of Computer-aided Drug Design Tools and Recent Applications in Designing of Anti-diabetic Agents
Authors: Kaur Paranjeet , Khatik Gopal 
Published: November 2020

Background:In this fast-growing era, high throughput data is now being easily accessed by getting transformed into datasets which store the information. Such information is valuable to optimize the hypothesis and drug design via computer-aided drug design (CADD). Nowadays, we can explore the role of CADD in various disciplines like Nanotechnology, Biochemistry, Medical Sciences, Molecular Biology, etc.Methods:We searched the valuable literature using a pertinent database with given keywords like computer-aided drug design, anti-diabetic, drug design, etc. We retrieved all valuable articles which are recent and discussing the role of computation in the designing of anti-diabetic agents.Results:To facilitate the drug discovery process, the computational approach has set landmarks in the whole pipeline for drug discovery from target identification and mechanism of action to the identification of leads and drug candidates. Along with this, there is a determined endeavor to describe the significance of in-silico studies in predicting the absorption, distribution, metabolism, excretion, and toxicity profile. Thus, globally, CADD is accepted with a variety of tools for studying QSAR, virtual screening, protein structure prediction, quantum chemistry, material design, physical and biological property prediction.Conclusion:Computer-assisted tools are used as the drug discovery tool in the area of different diseases, and here we reviewed the collaborative aspects of information technologies and chemoinformatic tools in the discovery of anti-diabetic agents, keeping in view the growing importance for treating diabetes.
Application of Ultrasound Elastography for Assessing Intestinal Fibrosis in Inflammatory Bowel Disease: Fiction or Reality?
Authors: Gabbiadini Roberto , Zacharopoulou Eirini , Furfaro Federica , Craviotto Vincenzo , Zilli Alessandra , Gilardi Daniela , Roda Giulia , Loy Laura , Fiorino Gionata , Peyrin-Biroulet Laurent , Danese Silvio , Allocca Mariangela 
Published: November 2020

Background:
Intestinal fibrosis and subsequent strictures represent an important burden
in inflammatory bowel disease (IBD). Both the detection and evaluation of the degree of fibrosis in
stricturing Crohn’s disease (CD) are important when deciding the best therapeutic strategy (medical
anti-inflammatory therapy, endoscopic dilation, surgery). Ultrasound elastography (USE) is a
non-invasive technique that has been proposed in the field of IBD for evaluating intestinal stiffness
as a biomarker of intestinal fibrosis.

Objective:
The aim of this review is to discuss the ability and
current role of ultrasound elastography in the assessment of intestinal fibrosis. Results and Conclusion:
Data on USE in IBD are provided by pilot and proof-of-concept studies with small sample
size. The first type of USE investigated was strain elastography, while shear wave elastography has
been introduced recently. Despite the heterogeneity of the methods of the studies, USE has been
proven to be able to assess intestinal fibrosis in patients with stricturing CD. However, before introducing
this technique in current practice, further studies with larger sample sizes are needed. In addition,
the use of homogeneous parameters, the assessment of reproducibility, and the identification
of validated cut-off values are essential.
Comparative Evaluation of the Transdermal Permeation Effectiveness of Fu’s Cupping Therapy on Eight Different Types of Model Drugs
Authors: Miao Yanyan , Xu Jian , Liu Yao , Yang Fangfang , Zheng Xiaoxia , Xie Weijie , Zhang Yongping 
Published: November 2020

Background::
Overcoming the skin barrier to achieve the transdermal penetration of
drugs across the Stratum Corneum (SC) remains a significant challenge. Our previous study
showed that Fu’s Cupping Therapy (FCT) contributes to the transdermal enhancement and percutaneous
absorption rate of representative drugs and improves their clinical effects. This work evaluated
the transdermal enhancement effect of FCT on drugs with different Molecular Weights (MW).

Methods::
We investigated the enhancements in the transdermal penetration of eight types of model
drugs through the skin of BALB/c-nu mice and Sprague Dawley rats using Franz diffusion devices.
In addition, 3% azone, 5% azone, 3% peppermint oil, and 5% peppermint oil were used as penetration
enhancers to study the transdermal behaviour of these drugs.

Results::
Our results showed that the BALB/c-nu mouse skin was the best transdermal media, and
the optimal time for FCT was 10 min. Compared with other penetration enhancers, FCT exerted a
significantly improved effect on enhancing the percutaneous penetration of the selected log(P)-
model drugs in addition to the two large MW drugs (ginsenoside Rg1 and notoginsenoside R1). Statistical
analysis revealed that the relationship between the log(P) of various model drugs and the
permeability coefficient [log(Pcm)] of the FCT group was log(Pcm)=0.080(log(P))2-0.136
(log(P))-0.282.

Conclusion::
FCT may be used as a novel method for enhancing physical penetration and thus effectively
promoting the transdermal absorption of drugs and might lay a foundation for future research
on drug transdermal technology.
Cutaneous Autoimmune Phenomena of the Anti-TNFa Biosimilars. Casebased Review
Authors: Pelechas Eleftherios , Papoudou-Bai Alexandra , Voulgari Paraskevi V. , Drosos Alexandros A. 
Published: November 2020

Background:
Psoriasis (Pso) is a common chronic inflammatory disease affecting the
skin, both sexes, and all ages. It can be associated with other chronic inflammatory musculoskeletal
disorders and certain drugs, including tumor necrosis factor α (TNFα) antagonists.

Case Presentation:
A 64-year-old man with seronegative rheumatoid arthritis (RA) refractory to leflunomide
and prednisone was treated with SB-4 (Benepali), an etanercept biosimilar 50mg/week
subcutaneously. He responded well to the treatment, but a year later, he developed erythematous
skin eruptions affecting mainly in the palms of both hands. Skin biopsy showed a picture compatible
with Pso. SB-4 was discontinued, and the skin lesions disappeared with the addition of topical
steroid therapy. This is the only case of psoriatic skin lesions associated with SB-4 treatment.

Conclusion:
Thus, we review and discuss the relevant literature of Pso cases related to SB-4 and
other anti-TNFα biosimilars. Rheumatologists dealing with patients on anti-TNFα biosimilars
should be aware of and recognize these complications.