bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D microenvironment attenuates simulated microgravity-mediated changes in T cell transcriptome
Authors: ElGindi Mei , Sapudom Jiranuwat , Laws Praveen , Garcia-Sabate Anna , Daqaq Mohammed , Teo Jeremy 
Published: May 2022

Abstract

Human space travel and exploration are of interest to both the industrial and scientific community. However, there are many adverse effects of spaceflight on human physiology. In particular, there is a lack of understanding to the extent by which microgravity affects the immune system. T cells, key players of the adaptive immune system and long term immunity, are present not only in blood circulation, but also reside within tissue. As of yet, studies investigating the effects of microgravity on T cells are limited to peripheral blood or traditional 2D cell culture that recapitulates circulating blood. To better mimic interstitial tissue, 3D cell culture has been well established for physiologically and pathologically relevant models. In this work, we utilize 2D and 3D cell culture to gain an understanding of how simulated microgravity affects both circulating and tissue resident T cells. T cells were studied in both resting and activated stages. We found that 3D cell culture attenuates the effects of simulated microgravity on the T cells transcriptome and nuclear irregularities compared to 2D cell culture. Interestingly, simulated microgravity appears to have less effect on activated T cells compared to those in the resting stage. Overall, our work provides novel insights into the effects of simulated microgravity on circulating and tissue resident T cells which could provide benefits for the health of space travelers.
Association of mesothelioma deaths with cumulated neighborhood exposures due to a large-scale asbestos cement plant in Amagasaki City, Japan: A nested case-control study
Authors: Kitamura Yuri , Zha Ling , Liu Rong , Shima Masayuki , Nakaya Tomoki , Kurumatani Norio , Kumagai Shinji , Goji Junko , Sobue Tomotaka 
Published: May 2022

Abstract
Background: Although a causal relationship between mesothelioma and asbestos exposure is well known, few studies have shown a relationship to non-occupational exposure, including neighborhood exposure, most likely because of the large effect size of occupational exposure. The aim of this study was to quantify the risk of malignant mesothelioma death associated with neighborhood asbestos exposure due to a large-scale asbestos-cement (AC) plant in Amagasaki, Japan, by properly adjusting for occupational exposure. Methods: We conducted a nested case-control study in which a fixed population of 143,929 residents who had been living in Amagasaki City between 1975 and 2002 were followed from 2002 to 2015. All 133 cases and 403 matched controls were interviewed about their occupational, domestic, household, and neighborhood asbestos exposures. Odds ratios (ORs) for mesothelioma death associated with neighborhood exposure were estimated by a conditional logistic-regression model that adjusted for other asbestos exposures. We adopted cumulative indices that considered residence-specific asbestos (crocidolite) concentrations and durations during the potential exposure period of 1957-1975 to evaluate individual neighborhood exposures.Results: There was an increasing, dose-dependent risk of mesothelioma death associated with neighborhood exposure, demonstrated by ORs in the highest quintile category that were 21.4 (95% CI: 5.8 - 79.2) for all, 23.7 (95% CI: 3.8 -147.2) for males, and 26.0 (95% CI: 2.8 - 237.5) for females, compared to the lowest quintile, respectively. These results clearly demonstrated no substantial differences between males and females in relation to the magnitude of risk from neighborhood exposure.Conclusions: By adjusting for occupational and other asbestos exposures, a dose-dependent relationship was demonstrated between mesothelioma death and neighborhood asbestos exposure from a large-scale AC plant. Our findings suggest that the risk of mesothelioma death associated with neighborhood exposure persists and will not be diminished for many years, even though it has been decades since the AC plant closed.
The influence of inlet to outlet width ratio on The hydraulic performance of piano key weir (PKW-type A)
Authors: Mero Shimal Khalid , Haleem Dilshad Abdul Jabbar , Yousif Ali Abduljabbar 
Published: May 2022

Abstract
A piano key weir (PKW) is a modified version of non-linear weirs and it can be obtained via amending the centerline length of the weir by a small footprint. It is developed to increase the hydraulic performance of the linear weirs via increasing the pass discharge and the energy dissipation. A laboratory investigation is conducted on five physical PKW (Type A) models to investigate the effect of inlet to outlet width ratio (Wi/Wo) on the hydraulic performance of PKWs. The results showed that the (Wi/Wo) ratio has a predominant influence on the hydraulic performance of PKW. It was found out that the best hydraulic performance was obtained with Wi/Wo ratio equal to 1.25 among other investigated Wi/Wo ratios because the discharge coefficient was the highest for the given discharge and head. Further, the results revealed that the variation of Wi/Wo ratio from 1.25 had a negative impact on both discharge coefficient and efficiency. It was found out that the percentages of reduction in discharge coefficient when Wi/Wo=0.8, 1, 1.5% and 2 were 11%, 6%, 2% and 8%, respectively in comparison with the Wi/Wo=1.25. Similarly, for these Wi/Wo ratios, the percentages of reduction in discharge decrease by 11%, 6.5%, 2.35% and 9%, respectively, relatively to Wi/Wo=1.25. The linear regression equations' coefficients for the PKW models varied from 0.983 to 0.994, which means the performance of the models are good for the given Wi/Wo ratios.
The impact of yield uncertainty on planting and water-saving decisions for high water consumption crops
Authors: Ding Jianpeng , Chen Liuxin , Deng Menghua 
Published: May 2022

AbstractIn this study, we propose an optimization-simulation approach to investigate the impact of yield uncertainty on the farmer's decisions for planting high water consumption crops. In addition, the influence of the subsidy programs provided by the government has also been investigated. We consider two different subsidy programs: one is the planting acreage subsidy (PAS) program; the other is the water-saving effort subsidy (WES) program. For each program, we have derived the optimal decisions for the farmer and the government. Furthermore, we investigated the impact of yield uncertainty on the farmer's profit, consumer surplus and social welfare, by numerical experiments. We show that the PAS program can bring greater improvements to the farmer's profit, consumer surplus and social welfare than the WES program, but it leads to higher government expenditure.
Integration of Network Pharmacology and Molecular Docking Technology Reveals the Mechanism of the Therapeutic Effect of Xixin Decoction on Alzheimer's Disease
Authors: Zhang Zhuo , Shi Jing , Xu Jianglin , Ma Suya , Lin Nan , Hou Minzhe , Wei Mingqing , Li Ting 
Published: May 2022

Background:So far, only a few researchers have systematically analyzed the constituents of the traditional Chinese medicine prescription Xixin Decoction (XXD) and its potential mechanism of action in treating Alzheimer’s disease (AD). This study aimed to explore the potential mechanism of XXD in the treatment of AD using network pharmacology and molecular docking.Methods:The compounds of XXD were searched within the Traditional Chinese Medicine System Pharmacology Database (TCMSP) and the Traditional Chinese Medicine Integrated Database (TCMID) databases. Overlapping AD-related targets obtained from the two databases and the predicted targets of XXD obtained from SwissTargetPrediction platform were imported into the STRING database to build PPI networks including hub targets; Cytoscape software was used to construct the herb-compound-target network while its plug-in CytoNCA was used to screen the main active compounds of XXD. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses explored the core biological mechanism and pathways via the Metascape platform. In addition, we used AutoDock Vina and PyMOL software to investigate the molecular docking of main compounds to hub targets.Results:We determined 114 active compounds, 973 drug targets, and 973 disease targets. However, intersection analysis screened out 208 shared targets.Protein-protein interaction (PPI) network identified 9 hub targets. The hub targets were found to be majorly enriched in several biological processes (positive regulation of kinase activity, positive regulation of cell death, regulation of MAPK cascade, trans-synaptic signaling, synaptic signaling, etc.) and the relevant pathways of Alzheimer's disease, including neuroactive ligand-receptor interaction, dopaminergic synapse, serotonergic synapse, and the MAPK signaling pathway, etc. The pathway-target-compound network of XXD for treating AD was then constructed. 8 hub targets exhibited good binding activity with 9 main active compounds of XXD in molecular docking.Conclusion:In this study, we found multi-compound-multi-target-multi-pathway regulation to reveal the mechanism of XXD for treating AD based on network pharmacology and molecular docking. XXD may play a therapeutic role through regulating the Alzheimer's disease pathway, its downstream PI3K/Akt signaling pathway or the MAPK signaling pathway, thereby treating AD. This provides new insights for further experiments on the pharmacological effects of XXD.
Serum Biomarker Panel for Rapid Early Diagnosis of Lung Cancer
Authors: Wu Shucai , Zhang Jiawen , Wei Hongyan , Liu Ying , Dai Xianli , Xue Jinyu , Shen Ting , Liu Xinyan 
Published: May 2022

Background:
Lung cancer is the leading cause of cancer death in most countries. Although
early diagnosis and treatment critically influence prognosis, lung cancers are generally only discovered
in the late stages of the disease.

Objective:
Widely-used screening and diagnostic methods are not suitable for preventive screening,
and high-throughput technologies based on serum biomarkers are needed.

Methods:
We screened 501 serum samples, including 224 lung cancer (LC), 126 disease control (DC),
and 151 healthy donor (HC) samples for new serum autoantibodies as biomarkers in the early diagnosis
of lung cancer. In phase I, we used HuProtTM microarrays to perform preliminary serum antibody
screening on 24 LC and 24 HC samples. In phase II, we screened 60 LC, 60 DC, and 60 HC serum
samples using focused arrays constructed with 22 of the candidate autoantibody biomarkers screened
out in phase I.

Results:
After data modeling and validation, we selected four potential early LC protein biomarker
candidates, IL2RB, CENPB, TP53, and XAGE1A, with individual specificities >90% and sensitivities
ranging from 21.2% to 32.2%. These four biomarkers had a specificity of >90% and a sensitivity
of >65.5% for early LC when they combined in a panel. Further evaluation of these four biomarker
candidates using ELISA assays and 273 serum samples (140 LC, 66 DC, and 67 HC) gave similar results
(specificity of >91.7%, sensitivity >61.43%).

Conclusion:
IL2RB, CENPB, TP53, and XAGE1A combined biomarker panel holds potential for rapid
screening and improving the diagnosis of early-stage LC, thus potentially also improving its prognosis.
In-silico Studies, Synthesis, and Evaluation of Anti-inflammatory Activity
of Novel Pyrimidine Scaffold
Authors: Munde Ganesh , Menghani Sunil , Rarokar Nilesh , Kerzare Deweshri , Chittur Md. Asif Iqbal , Khedekar Pramod 
Published: May 2022

Background:
The heterocyclic nucleus pyrimidine is present in several natural and synthetic
chemical analogues and has proved its broad medicinal applications. Further, pyrimidine in the form of
parent structure or basic skeleton of RNA and DNA is involved in controlling the immune functioning,
and in turn, inflammatory reactions.

Objective:
The objective of the present study is to evaluate some novel pyrimidine analogues for antiinflammatory
action.

Methods:
Molecular docking studies of Indomethacin and selected analogues were carried out with the
COX-2 enzyme (PDB: 4ZOL). The synthesis of derivatives of 4-Phenyl-6-(phenylamino)pyrimidine-2-ol
derivatives was begun by following Perkin condensation between substituted acetanilides and substituted
aromatic aldehydes to yield an intermediate, which in turn produces the required nucleus for treatment
with urea. All synthesized compounds were evaluated for in vivo and in vitro anti-inflammatory activity.

Results:
The docking interaction reflects a good dock score when compared with indomethacin, a potent
Anti-inflammatory drug. In the majority of the compounds, pyrimidine was able to form hydrogen bonding
while the rest of the part was involved in hydrophobic bonding. All compounds were synthesized in
good yield and confirmed by physical and spectral studies. In vitro studies showed that compounds 5a and
5e were better at controlling inflammation than the conventional treatment Antipyrine, while in vivo data
showed that compounds 5a, 5c, 5e, and 5h were better at controlling inflammation than the standard drug
Antipyrine.

Conclusion:
The compound with more than one electron releasing group on the aniline moiety of pyrimidine
yields a decent result in the synthetic and experimental studies, but the absence of an electron withdrawing
group favours stronger anti-inflammatory activity on the target.
Virtual Screening, Molecular Docking, and Physiochemical Analysis of
Novel 1,3-diphenyl-2-propene-1-one as Dual COX-2/5-LOX Inhibitors
Authors: Mittal Roopal , Sharma Shailesh , Mittal Amit , Kumar Shubham , Kushwah Ajay Singh 
Published: May 2022

Background:
Chronic inflammation is usually combated with non-steroidal anti-inflammatory
drugs (NSAIDs). However, long-term use of NSAIDs causes side effects comprising gastric ulceration,
abdominal discomfort, lack of anti-thrombolytic activity, and myocardial infarction. Emerging reports
indicate alteration of arachidonic acid metabolism, via cyclooxygenase and lipoxygenase pathways, being
investigated as potential anti-inflammatory agents. There is a dynamic balance shift toward lipoxygenase
on cyclooxygenase inhibition, therefore there is a need to identify naïve dual COX-2/5-LOX inhibitory
agents with better therapeutic and minimal side effects.

Objective:
The current research focused on identifying a prospective natural candidate molecule (1,3-
diphenyl-2-propene-1-one derivative) as a dual COX-2/5-LOX inhibitor by using structure-based
database screening, molecular modelling, and in-silico ADMET analysis.

Methods:
Virtual screening using the ZINC database, molecular docking of potential compounds, and
ADME analysis of hit compounds were performed.

Results:
A virtual library of 116 chalcone-based molecules was screened out. The molecules were docked
for COX-2 (PDB ID-3LN1) and 5-LOX (PDB ID-3V99) enzymatic active pockets and resulted in
compounds C96, C8, C83, C45, C20 better than zileuton. The potent compounds and zileuton showed
good binding affinity in the range of -8.0 to -8.7Kcal/mol in the COX-2 and -7.0 to -8.7Kcal/mol in the 5-
LOX active site respectively. These compounds were further subjected to ADME analysis giving two
plausible lead compounds C45 and C64 following ideal pharmacokinetic properties.

Conclusion:
The research work provides abundant opportunities to explore computational and medicinal
research areas which will facilitate the development of novel dual COX-2/5-LOX inhibitors in future
experimental studies.
Assessment of Binding Site and Development of Small Molecule Inhibitors Targeting Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer (NSCLC)
Authors: Wakte Pravin S. , Karnik Kshipra S. , Sarkate Aniket P. , Rajhans Aishwarya P. 
Published: May 2022

Background:Mutations occurring in the epidermal growth factor receptor of the tyrosine kinase family concerned with non-small cell lung cancer have been specifically targeted.Objectives:The library design and R-group enhancement technique have been carried out on the preexisting marketed drugs to increase the binding affinity of the designed novel compounds. The screening of compounds was done using a flexible docking protocol.Methods:Molecular docking studies provided information about binding pockets and interactions of molecules with the mutant (PDB: 4I1Z) as well as wild-type (PDB: 4I23) EGFR enzymes. The flexible docking was well supported by ADMET and molecular dynamic simulation studies.Results:On the basis of docking score and protein-ligand interactions, the highest-scoring molecule was selected for molecular dynamics simulation, providing a complete insight into the ligand interaction and saturationConclusion:The screened molecules can act as potential EGFR inhibitors in the management of drug resistance.
Assessment of Alternative Medicine Use, Costs, and Predictors of
Medication Adherence among Diabetes Mellitus Patients in Palestine
Authors: Mosleh Rami , U’wais Ala’ , Hamdan Anas , Ghanim Mustafa , Jarrar Yazun 
Published: May 2022

Background:
Diabetes Mellitus (DM) is considered the fourth leading cause of death in
Palestine, with a prevalence of 9.1% in patients aged 20-79 years, and has increased to 20.6% in 2020.

Aims:
This study aims to estimate DM costs, compare DM total health care cost among patient
characteristics and DM management (e.g. anti-diabetic medications and alternative medicine), as
well as assess MA and its predictors including patient characteristics, DM management, alternative
medicine use, and DM costs.

Methods:
A cross-sectional study was conducted for the past one year among 479 diabetic patients,
selected by convenience sampling and snowball sampling methods via electronic post of an online
questionnaire, including a web link to the questionnaire page in a Google Form via email or public
social media pages and applications. Data on patients’ socio-demographic and clinical characteristics,
medication profile, use of medicinal plants as alternative medicine, costs, and Medication Adherence
(MA) were collected. The Statistical Package for Social Sciences (SPSS v. 25) was used to
perform a descriptive, Kolmogorov-Smirnov test, univariate analysis, Mann-Whitney or Kruskal-
Wallis test, multiple linear regression, binary logistic regression, and multiple logistic regression
analysis. A p-value < 0.05 was considered statistically significant.

Results:
More than half of the participants were male and living in villages (50.7%, 59.1%, respectively).
Approximately 51.4% received Oral Hypoglycemic Drugs (OHDs) and only 16.1% received
insulin. The participants receiving ≤3 medications daily acquired the highest percentage
(55.7%), and less than half received medicinal plants as an alternative medicine for the management
of DM. The estimated total DM health care cost per year incurred by patients and family
members was Israeli Shekel 988,276 (US Dollar 307,590). More than half of the participants were
considered adherent with the Eight–Item Morisky Medication Adherence Scale (MMAS–8) score
≥6. It is noteworthy that the use of alternative medicine was significantly associated with total
health care cost and MA. Furthermore, DM duration was significantly associated with MA. These
results are worth taking into consideration.

Conclusion:
This study reflects the need for strengthening the patient-health care professionals’ relationship,
and to enhance the role of preventive education, and the importance of awareness about MA,
DSCMBs, and the use of alternative medicine based on evidence-based strategies to improve MA,
glycemic control, meanwhile reducing the costs incurred by patients and family members.
Electronic Method (Pro-Kin) for Improving and Speeding Up the
Recovery After Ankle Sprain
Authors: Marvulli Riccardo , Ianieri Giancarlo , Pignatelli Giovanni , Santagati Dario , Ranieri Maurizio , Megna Marisa 
Published: May 2022

Background and Objective:
Ankle sprains, very common injuries occurred especially
during sports activities, are mainly caused by indirect trauma, which influences exaggerated stress
exceeding the strength of stabilization mechanisms. Up to 85% of such injuries result from a sudden
flexion and inversion of the foot. In this study, we analyzed the effectiveness of the platform
Pro-kin, an innovative system that has given us the possibility to combine the functionality of the
older proprioceptive boards with very accurate software in order to improve and accelerate the recovery
after ankle injuries.

Methods:
30 patients with moderate ankle sprain outcomes in two groups (A and B) were included
in this study. Group A was only treated with proprioceptive exercises for 3 weeks, while the group
B was trained with the innovative Pro-kin. In both groups, we evaluated VAS scale, the ratio between
the number of circumductions performed by the injured foot and the time spent on doing
them and the percentage of load among the injured and the healthy foot in statics and dynamics
with electronic baropodometry. Our data has been collected at t0 (beginning of study), t1 (one
week later), t2 (two weeks later), t3 (one month later), t4 (two months later), and then analyzed by
the two-way analysis of variance (2-way ANOVA) test.

Results:
At t0 no statistical differences of pain in the 2 groups (3.3 and 3.4); the values were similar,
as well as at time t1, t2, t3 and t4. Therefore we deduce that Pro-kin treatment is not painful.
The number of circumductions performed was definitely better in B group since the first week; for
the A group the values considerably increased only at t3 (one month later). Comparing the load percentages
on two feet detected by the electronic baropodometer in statics and in dynamics, we deduced
that the patients of A group tend to lean mostly on the healthy foot than B group.

Conclusions:
This study demonstrates that new technological resources (such as Pro-kin) may be
helpful to improve and speed up the recovery of ankle sprain in athletes.
Tomato as a Natural Source of Dyes in the Food Industry: A Patent Data
Analysis
Authors: de Lima Silva Vanessa , Leite Bruna Santos , do Espírito Santo de Jesus Fabiane , Martins Lissa Daltro , Assunção Larissa Santos , Leal Ingrid Lessa , Colauto Nelson Barros , Colauto Giani Andrea Linde , Souza Machado Bruna Aparecida , Ferreira Ribeiro Camila Duarte 
Published: May 2022

Background:
Foods that promote health benefits are being increasingly used. Innovative
techniques, such as nanotechnology, have been used to improve functional properties, sensory characteristics,
or the conservation of foods.

Objective:
The objective of this study was to identify the technological domain of patents for tomato
products with or without nanotechnology and elucidate the technological advances associated with the
recent use of tomatoes as a natural food dye in the food industry by exploring patent documents.

Methods and Results:
The search was conducted using the Espacenet and INPI databases. There was
an increase in patent document applications employing nanotechnology in 2013, with a peak between
2017 and 2018. China is the lead country in the number of patent applications. In Brazil, the patent applications
are variable, and the food industry is most involved in studies on tomatoes as a natural food
dye. Most patent deposits using nanotechnology were from companies, and the main sources of the patent
application were the food and pharmaceutical industries.

Conclusion:
There is an increasing trend for the use of tomatoes as natural food dyes, produced with or
without nanotechnology, and number of patents filed yearly. New technologies are being developed in
several application areas.