bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated Transcriptomics and Reverse Pharmacophore Mapping-based
Network Pharmacology to Explore the Mechanisms of Natural Compounds
against Doxorubicin-induced Cardiotoxicity
Authors: Fang Luo , Zhu Junfeng , Yi Xiaojiao , Ding Haiying , Zhong Like 
Published: August 2021

Background:
Doxorubicin-Induced Cardiotoxicity (DIC) has greatly limited the clinical
benefits of this frontline drug in oncotherapy. Drug combination with Natural Compounds (NCs)
that possess potency against DIC is considered as a promising intervention strategy. However, the
Mechanisms of Action (MoAs) underlying such drug interactions remain poorly understood. The
aim of this study was to systematically pursuit of the molecular mechanisms of NCs against DIC.

Methods:
First, the gene expression signatures of DIC were characterized from transcriptomics
datasets with doxorubicin-treated and untreated cardiomyocytes using differentially expressed gene
identification, functional enrichment analysis, and protein-protein interaction network analysis.
Secondly, reverse pharmacophore mapping-based network pharmacology was employed to
illustrate the MoAs of 82 publicly reported NCs with anti-DIC potency. Cluster analysis based on
their enriched pathways was performed to gain systematic insights into the anti-DIC mechanisms
of the NCs. Finally, the typical compounds were validated using Gene Set Enrichment Analysis
(GSEA) of the relevant gene expression profiles from a public gene expression database.

Results:
Based on their anti-DIC MoAs, the 82 NCs could be divided into four groups, which
corresponded to ten MoA clusters. GSEA and literature evidence on these compounds were
provided to validate the MoAs identified through this bioinformatics analysis. The results
suggested that NCs exerted potency against DIC through both common and different MoAs.

Conclusion:
This strategy integrating different types of bioinformatics approaches is expected to
create new insights for elucidating the MoAs of NCs against DIC.
Diabetic Neuropathy: Review on Molecular Mechanisms
Authors: Sanaye Mrinal M. , Kavishwar Samruddhi A. 
Published: August 2021

:
Diabetic mellitus is a worldwide endocrine and metabolic disorder with insulin
insensitivity or deficiency or both whose prevalence could rise up to 592 million by 2035.
Consistent hyperglycemia leads to one of the most common comorbidities like Diabetic
Peripheral Neuropathy (DPN). DPN is underlined with unpleasant sensory experience,
such as tingling and burning sensation, hyperalgesia, numbness, etc. Globally, 50-60%
of the diabetic population is suffering from such symptoms as microvascular
complications. Consistent hyperglycemia during DM causes activation/inhibition of
various pathways playing important role in the homeostasis of neurons and other cells.
Disruption of these pathways results into apoptosis and mitochondrial dysfunctions,
causing neuropathy. Among these, pathways like Polyol and PARP are some of the
most intensively studied ones whereas those like Wnt pathway, Mitogen activated
protein kinase (MAPK), mTOR pathway are comparatively newly discovered.
Understanding of these pathways and their role in pathophysiology of DN underlines a
few molecules of immense therapeutic value. The inhibitors or activators of these
molecules can be of therapeutic importance in the management of DPN. This review,
hence, focuses on these underlying molecular mechanisms intending to provide
therapeutically effective molecular targets for the treatment of DPN.
Low pH and Temperature of Airway Surface Liquid are Key
Determinants that Potentiate SARS-CoV-2 Infectivity
Authors: Sharma Nilesh Kumar , Sarode Sachin C. 
Published: August 2021

:
Overwhelming responses are seen at preclinical and clinical levels to
understand and combat coronavirus disease 2019 [COVID-19] pandemic that is caused
by severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]. Encouraging
successes are achieved in view of diagnostic, therapeutic and preventive measures,
including vaccines development. In fact, structural information of SARS-CoV-2 and
molecular steps that help this virus target AECs are appreciably studied. Furthermore,
the heterogeneous and complex nature of COVID-19 is extensively revealed at
molecular, genetic, and epigenetic and microenvironment levels. In spite of these
developments in COVID-19 pathogenesis, the reasons behind the targeted infection by
SARS-CoV-2 to AECs are poorly understood. In this mini-review, we highlight the roles
of pH and temperature of airway surface liquid [ASL] as a key determining factor that
may contribute towards enhanced targeted infection by SARS-CoV-2 leading to COVID-
19.
Chemical Composition, Acetylcholine Esterase and Anti-bacterial Activities of Essential Oils of Elaeosilenum thapsioides (Desf.) Maire from Algeria
Authors: Barbeche Zakaria , Laouer Hocine , Erenler Ramazan , Hajji Mohamed , Flamini Guido , Pieracci Ylenia , Khattabi Latifa , Bensouici Chawki , Akkal Salah 
Published: August 2021

Background:
Traditionally, the Algerian medicinal plant Elaeosilenum thapsioides
(Desf.) Maire has been used for many diseases. The present research work aims to explore the
chemical and biological characterization of its essential oil.

Methods :
The essential oils were obtained by hydrodistillation of different Elaeosilenum thapsioides
(Apiaceae) aerial parts samples collected from two different regions (Mahouane and Megres)
from Setif, Eastern Algeria. The chemical characterization of the obtained essential oils is reported
here for the first time. Besides, they were evaluated for their in vitro Acetylcholinesterase
(AChE) inhibitory activity involved in Alzheimer’s disease using Ellman’s spectrophotometric
method.

Results:
Additionally, their in vitro antimicrobial activity was assessed by the disc diffusion
method. Both activities were performed at various oil concentrations. The GC/MS analysis of the
essential oils from aerial parts (leaves, stems, flowers, and seeds) of E. thapsioides identified 47
constituents. Monoterpene hydrocarbons were the main components, ranging from 72.78 to
99.13%. Oxygenated monoterpenes and oxygenated sesquiterpenes ranged between 1.37 and
17.25% and 0.12 and 3.53% in essential oils from leaves and stems. Sesquiterpene hydrocarbons
were present in small to large quantities in the essential oils of both populations, ranging from 0.69
to 13.44%. The presence of m-Methoxybenzyl isothiocyanate was recorded in stems essential oils
from Mahouane and leaves essential oils from Merges, which was 9.73% and 3.72%, respectively.

Conclusion:
The stems essential oils obtained from plants collected in Mahouane showed the highest
AChE inhibitory activity. The highest anti-bacterial activity was shown by the essential oil obtained
from Megres leaves against Bacillus cereus ATCC 11778. The oils exhibited a moderate inhibitory
activity in both tests.
Phenanthrene Dimers: Promising Source of Biologically Active Molecules
Authors: De Natale Antonino , Pollio Antonino , De Marco Anna , Luongo Giovanni , Di Fabio Giovanni , Zarrelli Armando 
Published: August 2021

:
To date, just over a hundred phenanthrenoid dimers have been isolated. Of these, forty-two
are completely phenanthrenic in nature. They are isolated from fourteen genera of different plants
belonging to only five families, of which Orchidaceae is the most abundant source. Other nine completely
acetylated and five methylated dimers were also defined, which were effective in establishing
the position of the free hydroxyls of the corresponding natural products, from which they were obtained
by semi-synthesis. Structurally, they could be useful chemotaxonomic markers considering that
some substituents are typical of a single-family, such as the vinyl group for Juncaceae. From a biogenetic
point of view, it is thought that these compounds derive from the radical coupling of the corresponding
phenanthrenes or by dehydrogenation of the dihydrophenanthrenoid analogs. Phenanthrenes
or dihydroderivatives possess different biological activities, e.g., antiproliferative, antimicrobial, antiinflammatory,
antioxidant, spasmolytic, anxiolytic, and antialgal effects. The aim of this review is to
summarize the occurrence of phenanthrene dimers in the different natural sources and give a comprehensive
overview of their structural characteristics and biological activities.
CT Imaging Research Progress in COVID-19
Authors: Shen Zhi Yong , Yan Xun Cheng , You Xiao Dong , Zhang Xue Wen 
Published: August 2021

:
The highly contagious novel coronavirus disease 2019 (COVID-19) broke out at the end
of 2019 and has lasted for nearly one year, and the pandemic is still rampant around the world. The
diagnosis of COVID-19 is on the basis of the combination of epidemiological history, clinical
symptoms, and laboratory and imaging examinations. Among them, imaging examination is of importance
in the diagnosis of patients with suspected clinical cases, the investigation of asymptomatic
infections and family clustering, the judgment of patient recovery, rediagnosis after disease recurrence,
and prognosis prediction. This article reviews the research progress of CT imaging examination
in the COVID-19 pandemic.
Pleiotropic Beneficial Effects of Dietary L-Ascorbic Acid Fortification in
Middle-Aged Mice
Authors: Olofinnade Anthony , Onaolapo Adejoke , Onaolapo Olakunle , Olowe Olugbenga 
Published: August 2021

Background:
An enhanced knowledge of the multiple effects of ascorbic acid (AA) in
health can broaden our understanding of the impacts of its deficiency.

Method:
Mice (10-12 month old) were either fed standard rodent feed or AA-fortified diet at 100,
200 and 300 mg/kg of feed, respectively for 8 weeks. On completion of the study, animals were sacrificed,
following which haematological, inflammatory/apoptotic marker, oxidative stress markers,
and markers of hepatic/renal integrity were assessed.

Results:
Across the groups, AA fortified diet was associated with an increase in food consumption;
however, body weight reduction occurred at the lowest concentration, while weight gain was observed
at the higher concentrations. Haematological indices (white cell count, granulocytes, lymphocytes,
and red cell count) increased at the highest concentration; while some other red cell parameters
decreased. A concentration-dependent improvement in antioxidant status, with the greatest
benefit at the highest concentration, was observed. Also, a concentration-dependent modulation
of inflammatory markers, lipid peroxidation, lipid profile, and biochemical markers of liver and kidney
function was observed.

Conclusion:
Dietary fortification with AA in middle-aged mice impacted several measurable parameters
in a concentration dependent manner. In addition to its antioxidant effects, it was also associated
with anti-inflammatory and anti-apoptotic effects.
Design, Synthesis and Pharmacological Evaluation of Novel Benzimidazole Derivatives as Anticancer Agents
Authors: R.S. Remya 
Published: August 2021

Background:
Cancer is undoubtedly a major challenge of modern era and is the second
leading cause of death in the world. Lung cancer is the second most common cancer and the leading
cause of cancer death among men and women. Non-Small Cell Lung Cancer (NSCLC) accounts
for 84% of all lung cancer diagnosed. Benzimidazoles are important heterocyclic compounds
possessing a variety of biological activities such as anticancer, antioxidant, anti-inflammatory,
and analgesic, anti-viral, anti-bacterial, anti-fungal and hypoglycemic activities. Pyrazolines reported
antitumor, immunosuppressive, antibacterial and anti tubercular agents. Biological activities
of the benzimidazole derivatives depend on the functional group attached to the benzimidazole moiety.

Objective:
The present research focused on incorporating pyrazoline nucleus into benzimidazole
nucleus to form a potent anticancer agent targeting lung cancer therapy.

Method:
The in silico novel pyrazoline substituted benzimidazole derivatives were designed.
Docking was performed to know the binding interactions of the newer agents with the enzymes.
The compounds were found to be active in docking studies synthesized and tested for anticancer activity.
In vitro screening of the selected derivatives for anticancer activity by MTT assay method
showed very good results. Cytotoxicity of compounds BZ1, BZ2, BZ10 and BZ16 studied against
fibrosarcoma and lung cancer cell line.

Results:
The compound BZ1 showed highest activity against fibrosarcoma and lung cancer cell
line.

Conclusion:
Further studies on these compounds to prove it as a lead compound in cancer therapy
should be conducted.
The Hepatoprotective Role of Warburgia salutaris and Iso-Mukaadial Acetate
on Carbon Tetrachloride Intoxicated Rats Model
Authors: Ayeni Gideon , Simelane Mthokozisi Blessing Cedric , Islam Md. Shahidul , Pooe Ofentse Jacob 
Published: August 2021

Background:
Medicinal plants, together with their isolated bioactive compounds, are
known for their antioxidant properties, which constitute therapeutic agents that are routinely employed
in the treatment of liver diseases.

Aims of the Study:
The current study sought to explore the protective role of Warburgia salutaris
and its isolated compound, iso-mukaadial acetate, against carbon tetrachloride (CCl4)-induced hepatic
injury.

Methods:
Thirty-five male Sprague Dawley rats were divided into seven groups of five animals
each and injected with CCl4 to induce hepatic injury.

Results:
Treatment with the crude extract of W. salutaris and iso-mukaadial acetate significantly reduced
the levels of alkaline phosphatase, alanine and aspartate amino transaminases, and total
bilirubin and malondialdehyde in a dose-dependent manner compared to untreated groups. Liver
histology revealed a reduction in hepatic necrosis and inflammation.

Conclusion:
The current investigation has demonstrated that W. salutaris extract and iso-mukaadial
acetate could mitigate the acute liver injury inflicted by a hepatotoxic inducer in rats.
Investigating Potential Drug-Drug Interactions from Greek e-Prescription Data
Authors: Lalagkas Panagiotis-Nikolaos , Poulentzas Georgios , Tsiolis Lampros , Berberoglou Eleftherios , Hadjipavlou-Litina Dimitra , Douros Antonios , Kontogiorgis Christos , Constantinides Theodoros 
Published: August 2021

Background:
The prevalence of potential drug-drug interactions (pDDIs) is indicative
of the prevalence of actual drug-drug interactions and prescription quality. However, they are significantly
understudied in Greece.

Objective:
The objective of the study was to determine the prevalence of pDDIs among outpatients
and identify factors associated with their occurrence.

Methods:
Anonymous e-prescription data between 2012 and 2017 were obtained from community
pharmacies in Thessaloniki, Greece. Patients taking more than one medication for at least three
months were included. pDDIs were identified and categorized depending on their clinical significance
using Drug Interactions Checker. Crude and adjusted odds ratios (ORs) with accompanying
95% confidence intervals (CIs) of risk factors of pDDIs occurrence were identified using multivariable
logistic regression.

Results:
During the study period, 6,000 anonymous e-prescriptions (1,000 per year) satisfying the
inclusion criteria were collected. The overall prevalence of major pDDIs was 17.4% (63.0% for
moderate pDDIs). The most common major pDDIs were between amlodipine and simvastatin
(22.8% of major interactions), followed by clopidogrel and omeprazole (6.4% of major interactions).
Polypharmacy (≥5 concomitantly received medications) was associated with an increased risk
of major pDDIs (adjusted OR, 5.72; 95% CI, 4.87-6.72); no associations were observed regarding
age, sex, and number of prescribing physicians.

Conclusion:
The prevalence of pDDIs in this study was higher than previously reported in other
European countries, with polypharmacy being a potential risk factor. Those results argue for a need
for improvement in the area of prescribing in Greece.
Novel Methods in the Surveillance of Influenza-Like Illness in Germany Using Data From a Symptom Assessment App (Ada): Observational Case Study
Authors: Cawley Caoimhe , Bergey François , Mehl Alicia , Finckh Ashlee , Gilsdorf Andreas 
Published: August 2021

Background
Participatory epidemiology is an emerging field harnessing consumer data entries of symptoms. The free app Ada allows users to enter the symptoms they are experiencing and applies a probabilistic reasoning model to provide a list of possible causes for these symptoms.

Objective
The objective of our study is to explore the potential contribution of Ada data to syndromic surveillance by comparing symptoms of influenza-like illness (ILI) entered by Ada users in Germany with data from a national population-based reporting system called GrippeWeb.

Methods
We extracted data for all assessments performed by Ada users in Germany over 3 seasons (2017/18, 2018/19, and 2019/20) and identified those with ILI (report of fever with cough or sore throat). The weekly proportion of assessments in which ILI was reported was calculated (overall and stratified by age group), standardized for the German population, and compared with trends in ILI rates reported by GrippeWeb using time series graphs, scatterplots, and Pearson correlation coefficient.

Results
In total, 2.1 million Ada assessments (for any symptoms) were included. Within seasons and across age groups, the Ada data broadly replicated trends in estimated weekly ILI rates when compared with GrippeWeb data (Pearson correlation—2017-18: r=0.86, 95% CI 0.76-0.92; P<.001; 2018-19: r=0.90, 95% CI 0.84-0.94; P<.001; 2019-20: r=0.64, 95% CI 0.44-0.78; P<.001). However, there were differences in the exact timing and nature of the epidemic curves between years.

Conclusions
With careful interpretation, Ada data could contribute to identifying broad ILI trends in countries without existing population-based monitoring systems or to the syndromic surveillance of symptoms not covered by existing systems.
Effect of Preconception Care Intervention on Maternal Nutritional Status and Birth Outcome in a Low-Resource Setting: Proposal for a Nonrandomized Controlled Trial
Authors: Swain Dharitri , Begum Jasmina , Parida Swayam Prangnan 
Published: August 2021

Background
The provision of preconception care approaches such as maternal assessments and education on healthy lifestyle (including physical activity, nutrition, and dietary supplements such as folic acid), general and sexual health, avoidance of high-risk behavior, and immunizations has been shown to identify and reduce the risk of adverse birth outcomes through appropriate management and preventive measures.

Objective
The goal of the study is to determine the effect of an integrated preconception care intervention on delivery outcomes, which is a novel challenge for lowering unfavorable birth outcomes in India’s low-resource setting. The main objectives are to investigate the relationship of birth outcomes to both maternal and paternal preconception health and determine the effect of preconception care intervention on improvement of maternal nutritional status and reduction of the risk of adverse birth outcomes such as prematurity, low birth weight, and maternal and neonatal complications.

Methods
A nonrandomized controlled trial design will be used for comparing 2 groups: preconception care with a standard maternal health care (MHC) program and an integrated MHC program (without preconception care). Two rural field areas of Khordha district, Odisha, will be selected for conducting the study. The study will enroll 782 married women between the ages of 18 and 35 years with their spouses, with 391 women in each group. The couples will receive preconception care based on their health circumstances, and they will be followed up at 3-month intervals before pregnancy. Following pregnancy, they will be followed up for 8 prenatal monitoring and care visits as well as 6 weeks after delivery as part of the standard MCH program. The preconception care intervention package includes couples counseling, contraceptive education and distribution, sex education, lifestyle modification, and nutritional supplementation of iron and folic acid, along with multivitamins if needed.

Results
The proposal was approved by the institutional ethical committee for conducting the study in June 2020 (Ref No: T/EMF/Nursing/20/6). Participants were enrolled in phase 1 in April 2021, phase 2 of offering preconception services will begin in August 2021, and study outcomes will be measured from 2023 to 2024.

Conclusions
Through preconception care and counseling, the eligible couples will recognize, embrace, and implement the actions to improve their preconception health. Finally, it is expected that maternal and paternal health will have a significant impact on enhancing maternal nutritional status and birth outcomes.

Trial Registration
Clinical Trials Registry–India CTRI/2021/04/032836; http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=48239&EncHid=&userName=CTRI/2021/04/032836

International Registered Report Identifier (IRRID)
PRR1-10.2196/28148
Team Dynamics in Hospital Workflows: An Exploratory Study of a Smartphone Task Manager
Authors: Hettiachchi Danula , Hayes Lachie , Goncalves Jorge , Kostakos Vassilis 
Published: August 2021

Background
Although convenient and reliable modern messaging apps like WhatsApp enable efficient communication among hospital staff, hospitals are now pivoting toward purpose-built structured communication apps for various reasons, including security and privacy concerns. However, there is limited understanding of how we can examine and improve hospital workflows using the data collected through such apps as an alternative to costly and challenging research methods like ethnography and patient record analysis.

Objective
We seek to identify whether the structure of the collected communication data provides insights into hospitals’ workflows. Our analysis also aims to identify ways in which task management platforms can be improved and designed to better support clinical workflows.

Methods
We present an exploratory analysis of clinical task records collected over 22 months through a smartphone app that enables structured communication between staff to manage and execute clinical workflows. We collected over 300,000 task records between July 2018 and May 2020 completed by staff members including doctors, nurses, and pharmacists across all wards in an Australian hospital.

Results
We show that important insights into how teams function in a clinical setting can be readily drawn from task assignment data. Our analysis indicates that predefined labels such as urgency and task type are important and impact how tasks are accepted and completed. Our results show that both task sent-to-accepted (P<.001) and sent-to-completed (P<.001) times are significantly higher for routine tasks when compared to urgent tasks. We also show how task acceptance varies across teams and roles and that internal tasks are more efficiently managed than external tasks, possibly due to increased trust among team members. For example, task sent-to-accepted time (minutes) is significantly higher (P<.001) for external assignments (mean 22.10, SD 91.45) when compared to internal assignments (mean 19.03, SD 82.66).

Conclusions
Smartphone-based task assignment apps can provide unique insights into team dynamics in clinical settings. These insights can be used to further improve how well these systems support clinical work and staff.