bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agents
Authors: Gholaminejad Alieh , Gheisari Yousof , Jalali Sedigheh , Roointan Amir 
Published: April 2021

Abstract
Background
IgA nephropathy (IgAN) is a kidney disease recognized by the presence of IgA antibody depositions in kidneys. The underlying mechanisms of this complicated disease are remained to be explored and still, there is an urgent need for the discovery of noninvasive biomarkers for its diagnosis. In this investigation, an integrative approach was applied to mRNA and miRNA expression profiles in PBMCs to discover a gene signature and novel potential targets/biomarkers in IgAN.

Methods
Datasets were selected from gene expression omnibus database. After quality control checking, two datasets were analyzed by Limma to identify differentially expressed genes/miRNAs (DEGs and DEmiRs). Following identification of DEmiR-target genes and data integration, intersecting mRNAs were subjected to different bioinformatic analyses. The intersecting mRNAs, DEmiRs, related transcription factors (from TRRUST database), and long-non coding RNAs (from LncTarD database) were used for the construction of a multilayer regulatory network via Cytoscape.

Result
“GSE25590” (miRNA) and “GSE73953” (mRNA) datasets were analyzed and after integration, 628 intersecting mRNAs were identified. The mRNAs were mainly associated with “Innate immune system”, “Apoptosis”, as well as “NGF signaling” pathways. A multilayer regulatory network was constructed and several hub-DEGs (Tp53, STAT3, Jun, etc.), DEmiRs (miR-124, let-7b, etc.), TFs (NF-kB, etc.), and lncRNAs (HOTAIR, etc.) were introduced as potential factors in the pathogenesis of IgAN.

Conclusion
Integration of two different expression datasets and construction of a multilayer regulatory network not only provided a deeper insight into the pathogenesis of IgAN, but also introduced several key molecules as potential therapeutic target/non-invasive biomarkers.
Changes in public knowledge and perceptions about antibiotic use and resistance in Jordan: a cross-sectional eight-year comparative study
Authors: Abdelmalek Suzanne , AlEjielat Rowan , Rayyan Walid Abu , Qinna Nidal , Darwish Dana 
Published: April 2021

Abstract
Background
Resistance to antibiotics is a growing problem, worldwide and particularly in developing countries like Jordan. Raising public awareness on appropriate antibiotic use is crucial to combat this problem. The current study describes the change in public Knowledge and attitudes towards the use of antibiotics over a period of 8 years.

Methods
Two cross-sectional studies were performed 8 years apart on Jordanians of different age groups, and social settings, residing in Amman, Jordan. Convenience non-probability sampling techniques were used. In 2010, a questionnaire was distributed in paper form, whereas in 2018 snowball sampling was used to disseminate an identical electronic questionnaire. Chi-square test and post hoc analysis were done using the z-test to compare column proportions, adjustment for multiple testing using the Bonferroni method. Multiple logistic regression was used to adjust for case mix for each survey. Comparisons were made across the two studies and within each study.

Results
A total of 711 participants in 2010 and 436 participants in 2018 were surveyed. Over the 8-year period, there was a significant improvement in the beliefs regarding the use of antibiotics such as disagreeing to keeping left over antibiotics for later use from 57 to 70% (p < 0.05) and disagreeing to buying antibiotics without physicians’ consent increased from 80 to 89% (P value < 0.001). There was no significant change in the beliefs that support self-medication such as: using antibiotics from a friend (72 to 77%) buying antibiotics without a prescription (42 to 45%), and getting information about medication use from leaflet without referring to a health care professional (60 to 63%). There were some areas of confusion regarding antibiotic range of effectiveness, and origin of resistance. Agreement about antibiotic resistance being a problem in Jordan increased significantly from 44 to 60% (p < 0.001). In addition, there was a significant increase in the percentage of participants who said that they don’t request antibiotics from physicians (56 to 75% (P ≤ 0.001) and who said they would trust physicians’ decisions about the necessity of antibiotics (70 to 83% P < 0.05).

Conclusion
Findings indicate the need for better suited, and more inclusive, public educational campaigns.
Construction of an index system for evaluating the effectiveness of transitional care in kidney transplant recipients
Authors: Zhou Xinyi , Ding Ping , Yang Qiaolan , Wang Ping , Zhou Haimei , Fu Jing , Miao Dongrui 
Published: April 2021

Abstract
Background
Previous studies showed that transitional care reduces the complication rate and readmission rate and improves the quality of life in kidney transplant receipts, nevertheless, in fact there are no standard evaluation indexes and debatable scientific of existing indexes in kidney transplant recipients. Therefore, the aim of this study was to construct an evaluation index system to assess the effects of transitional care in kidney transplant recipients.

Methods
Based on Omaha system, an initial evaluation index system about the effects of transitional care in kidney transplant recipients was drafted by the literature review and semi-structured interview. Two rounds of correspondence were conducted in 19 experts and the analytic hierarchy process (AHP) was used to calculate the weights of all indexes.

Results
Five first-level indexes, sixteen second-level indexes, and forty-eight third-level indexes were selected in the initial evaluation index system. The authority coefficient of two-round expert consultations was 0.90 and coordination coefficients of indexes ranged from 0.24 to 0.34.

Conclusion
The established evaluation index system for the effectiveness of transitional care for kidney transplant recipients was scientific and reliable. Furthermore, it would be a potential method to evaluate effects of transitional care in kidney transplant recipients after further examination.
A review of statistical methods for dietary pattern analysis
Authors: Zhao Junkang , Li Zhiyao , Gao Qian , Zhao Haifeng , Chen Shuting , Huang Lun , Wang Wenjie , Wang Tong 
Published: April 2021

AbstractBackgroundDietary pattern analysis is a promising approach to understanding the complex relationship between diet and health. While many statistical methods exist, the literature predominantly focuses on classical methods such as dietary quality scores, principal component analysis, factor analysis, clustering analysis, and reduced rank regression. There are some emerging methods that have rarely or never been reviewed or discussed adequately.MethodsThis paper presents a landscape review of the existing statistical methods used to derive dietary patterns, especially the finite mixture model, treelet transform, data mining, least absolute shrinkage and selection operator and compositional data analysis, in terms of their underlying concepts, advantages and disadvantages, and available software and packages for implementation.ResultsWhile all statistical methods for dietary pattern analysis have unique features and serve distinct purposes, emerging methods warrant more attention. However, future research is needed to evaluate these emerging methods’ performance in terms of reproducibility, validity, and ability to predict different outcomes.ConclusionSelection of the most appropriate method mainly depends on the research questions. As an evolving subject, there is always scope for deriving dietary patterns through new analytic methodologies.
Facile fabrication of multi-pocket nanoparticles with stepwise size transition for promoting deep penetration and tumor targeting
Authors: Hou Xingyu , Zhong Dan , Li Yunkun , Mao Hongli , Yang Jun , Zhang Hu , Luo Kui , Gong Qiyong , Gu Zhongwei 
Published: April 2021

Abstract
Background
Nanocarriers-derived antitumor therapeutics are often associated with issues of limited tumor penetration and dissatisfactory antitumor efficacies. Some multistage delivery systems have been constructed to address these issues, but they are often accompanied with complicated manufacture processes and undesirable biocompatibility, which hinder their further application in clinical practices. Herein, a novel dual-responsive multi-pocket nanoparticle was conveniently constructed through self-assembly and cross-linking of amphiphilic methoxypolyethylene glycol-lipoic acid (mPEG-LA) conjugates to enhance tumor penetration and antitumor efficacy.

Results
The multi-pocket nanoparticles (MPNs) had a relatively large size of ~ 170 nm at physiological pH which results in prolonged blood circulation and enhanced accumulation at the tumor site. But once extravasated into acidic tumor interstices, the increased solubility of PEG led to breakage of the supramolecular nanostructure and dissolution of MPNs to small-sized (< 20 nm) nanoparticles, promoting deep penetration and distribution in tumor tissues. Furthermore, MPNs exhibited not only an excellent stable nanostructure for antitumor doxorubicin (DOX) loading, but rapid dissociation of the nanostructure under an intracellular reductive environment. With the capacity of long blood circulation, deep tumor penetration and fast intracellular drug release, the DOX-loaded multi-pocket nanoparticles demonstrated superior antitumor activities against large 4T1 tumor (~ 250 mm3) bearing mice with reduced side effect.

Conclusions
Our facile fabrication of multi-pocket nanoparticles provided a promising way in improving solid tumor penetration and achieving a great therapeutic efficacy.

Graphic Abstract
Effect of sidedness on survival among patients with early-stage colon cancer: a SEER-based propensity score matching analysis
Authors: Huang Zhuang-Sheng , Wu Jun-Wei , Li Ying , Lin Yu-Hai , Li Xu-Yuan 
Published: April 2021

Abstract
Background
Most previous studies compared survival between left-sided and right-sided colon cancer without adjustment for clinicopathological parameters. We investigated the effect of sidedness on survival among patients with early-stage colon cancer, using a propensity score matching method.

Methods
The 18 registry custom data within the SEER database were used to identify patients who were diagnosed with colon cancer between 2010 and 2014. A propensity score matching analysis was performed using the nearest neighbor method. Survival was estimated using the Kaplan–Meier method. A Cox proportional hazards model was applied to determine the prognostic factors.

Results
In the unmatched cohort, 25,094 (35.72%) patients were diagnosed with left-sided colon cancer and 45,156 (64.28%) with right-sided colon cancer. After propensity score matching, each cohort included 5118 patients, and the clinicopathological characteristics were well balanced. In the unmatched cohort, left-sided colon cancer had superior all-cause (χ2=315, P<0.01) and cancer-specific (χ2=43, P<0.01) survival than right-sided tumors. However, in the matched cohort, no difference was observed for all-cause (χ2=0.7, P=0.4) and cancer-specific (χ2=0, P=0.96) survival between left and right colon cancer. The Cox model did not indicate sidedness as a prognostic factor. In the subgroup analysis, stage II right-sided colon cancer had a better survival outcome, while stage III left-sided tumors had a better survival outcome.

Conclusions
After adjusting for clinicopathological characteristics in this study, sidedness showed no impact on survival in early-stage colon cancer. However, sidedness was associated with prognostic differences in stages II and III early-stage colon cancer.
External application of liver compresses to reduce fatigue in patients with metastatic cancer undergoing radiation therapy, a randomized clinical trial
Authors: Ghadjar Pirus , Stritter Wiebke , von Mackensen Irina , Mehrhof Felix , Foucré Clara , Ehrhardt Vincent H. , Beck Marcus , Gebert Pimrapat , Kalinauskaite Goda , Luchte Jacqueline S. , Stromberger Carmen , Budach Volker , Eggert Angelika , Seifert Georg 
Published: April 2021

Abstract
Background
Liver compresses are frequently used in integrative medicine as supportive therapy during cancer treatment in order to reduce fatigue. We performed a pilot study to test whether the external application of yarrow liver compresses impacts fatigue in patients with metastatic cancer undergoing radiation therapy.

Methods
A randomized prospective pilot trial was performed including patients with brain metastasis or bone metastasis of solid tumors. Patients underwent either palliative radiation therapy (RT) of the metastatic lesions (control group) over two weeks or the same RT with additional external application of yarrow liver compresses once daily during RT. The primary objective was improvement on the general fatigue subscale of the multidimensional fatigue inventory (MFI-20) at the end of treatment, where a mean difference of two points is considered clinically relevant. Secondary objectives included psychological distress, quality of life and qualitative analysis with self-established visual analogue scales (VAS). Mean differences in general fatigue at the end of treatment compared to baseline were analyzed using the ANCOVA test.

Results
From 09/2017 to 08/2019 a total of 39 patients were randomized. Due to drop outs 24 patients (12 per group) were available for analysis. Patients in the intervention group received a mean number of 10.5 (range, 7–14) applications of yarrow liver compresses. The mean improvement at the end of therapy on the general fatigue subscale of the MFI-20 was 2 points in favor of the intervention group (p = 0.13), and all other MFI-20 subscales showed at least a trend towards improvement in favor of the intervention group. Likewise, psychological distress and VAS data was improved, the latter reaching statistical significance for the symptoms fatigue, tension and lack of drive. Major toxicities were not observed.

Conclusions
External application of liver compresses appears to reduce fatigue within a clinical relevant range in patients with metastatic cancer undergoing radiation therapy.
Trial registration: ISRCTN, ICTRP DRKS00012999
Pharmacological inhibition of nSMase2 reduces brain exosome release and α-synuclein pathology in a Parkinson’s disease model
Authors: Zhu Chunni , Bilousova Tina , Focht Samantha , Jun Michael , Elias Chris Jean , Melnik Mikhail , Chandra Sujyoti , Campagna Jesus , Cohn Whitaker , Hatami Asa , Spilman Patricia , Gylys Karen Hoppens , John Varghese 
Published: April 2021

Abstract
Aim
We have previously reported that cambinol (DDL-112), a known inhibitor of neutral sphingomyelinase-2 (nSMase2), suppressed extracellular vesicle (EV)/exosome production in vitro in a cell model and reduced tau seed propagation. The enzyme nSMase2 is involved in the production of exosomes carrying proteopathic seeds and could contribute to cell-to-cell transmission of pathological protein aggregates implicated in neurodegenerative diseases such as Parkinson’s disease (PD). Here, we performed in vivo studies to determine if DDL-112 can reduce brain EV/exosome production and proteopathic alpha synuclein (αSyn) spread in a PD mouse model.

Methods
The acute effects of single-dose treatment with DDL-112 on interleukin-1β-induced extracellular vesicle (EV) release in brain tissue of Thy1-αSyn PD model mice and chronic effects of 5 week DDL-112 treatment on behavioral/motor function and proteinase K-resistant αSyn aggregates in the PD model were determined.

Results/discussion
In the acute study, pre-treatment with DDL-112 reduced EV/exosome biogenesis and in the chronic study, treatment with DDL-112 was associated with a reduction in αSyn aggregates in the substantia nigra and improvement in motor function. Inhibition of nSMase2 thus offers a new approach to therapeutic development for neurodegenerative diseases with the potential to reduce the spread of disease-specific proteopathic proteins.
Genomic insights into the origin, domestication and genetic basis of agronomic traits of castor bean
Authors: Xu Wei , Wu Di , Yang Tianquan , Sun Chao , Wang Zaiqing , Han Bing , Wu Shibo , Yu Anmin , Chapman Mark A. , Muraguri Sammy , Tan Qing , Wang Wenbo , Bao Zhigui , Liu Aizhong , Li De-Zhu 
Published: April 2021

AbstractBackgroundCastor bean (Ricinus communisL.) is an important oil crop, which belongs to the Euphorbiaceae family. The seed oil of castor bean is currently the only commercial source of ricinoleic acid that can be used for producing about 2000 industrial products. However, it remains largely unknown regarding the origin, domestication, and the genetic basis of key traits of castor bean.ResultsHere we perform a de novo chromosome-level genome assembly of the wild progenitor of castor bean. By resequencing and analyzing 505 worldwide accessions, we reveal that the accessions from East Africa are the extant wild progenitors of castor bean, and the domestication occurs ~ 3200 years ago. We demonstrate that significant genetic differentiation between wild populations in Kenya and Ethiopia is associated with past climate fluctuation in the Turkana depression ~ 7000 years ago. This dramatic change in climate may have caused the genetic bottleneck in wild castor bean populations. By a genome-wide association study, combined with quantitative trait locus analysis, we identify important candidate genes associated with plant architecture and seed size.ConclusionsThis study provides novel insights of domestication and genome evolution of castor bean, which facilitates genomics-based breeding of this important oilseed crop and potentially other tree-like crops in future.
Roles of three putative salmon louse (Lepeophtheirus salmonis) prostaglandin E2 synthases in physiology and host–parasite interactions
Authors: Dalvin Sussie , Eichner Christiane , Dondrup Michael , Øvergård Aina-Cathrine 
Published: April 2021

Abstract
Background
The salmon louse (Lepeophtheirus salmonis) is a parasite of salmonid fish. Atlantic salmon (Salmo salar) exhibit only a limited and ineffective immune response when infested with this parasite. Prostaglandins (PGs) have many biological functions in both invertebrates and vertebrates, one of which is the regulation of immune responses. This has led to the suggestion that prostaglandin E2 (PGE2) is important in the salmon louse host–parasite interaction, although studies of a salmon louse prostaglandin E2 synthase (PGES) 2 gene have not enabled conformation of this hypothesis. The aim of the present study was, therefore, to characterize two additional PGES-like genes.

Methods
Lepeophtheirus salmonis microsomal glutathione S-transferase 1 like (LsMGST1L) and LsPGES3L were investigated by sequencing, phylogenetics, transcript localization and expression studies. Moreover, the function of these putative PGES genes in addition to the previously identified LsPGES2 gene was analyzed in double stranded (ds) RNA-mediated knockdown (KD) salmon louse.

Results
Analysis of the three putative LsPGES genes showed a rather constitutive transcript level throughout development from nauplius to the adult stages, and in a range of tissues, with the highest levels in the ovaries or gut. DsRNA-mediated KD of these transcripts did not produce any characteristic changes in phenotype, and KD animals displayed a normal reproductive output. The ability of the parasite to infect or modulate the immune response of the host fish was also not affected by KD.

Conclusions
Salmon louse prostaglandins may play endogenous roles in the management of reproduction and oxidative stress and may be a product of salmon louse blood digestions.

Graphical Abstract
Associations of healthy lifestyles with cerebrospinal fluid biomarkers of Alzheimer’s disease pathology in cognitively intact older adults: the CABLE study
Authors: Hou Xiao-He , Xu Wei , Bi Yan-Lin , Shen Xue-Ning , Ma Ya-Hui , Dong Qiang , Tan Lan , Yu Jin-Tai 
Published: April 2021

Abstract
Objective
We aimed to investigate the associations between healthy lifestyles and Alzheimer’s disease (AD) biomarkers in cerebrospinal fluid (CSF).

Methods
A total of 1108 cognitively intact individuals from Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study were examined to evaluate the associations of AD biomarkers with healthy lifestyle factors, including no current smoking, no harmful drinking, absence of social isolation, and regular physical activity. The participants were categorized into groups of favorable, intermediate, and unfavorable lifestyles according to the lifestyle factors. The associations between overall lifestyle and CSF biomarkers were also analyzed.

Results
Among cognitively intact older adults, those having more social engagement had lower CSF tau (p = 0.009) and p-tau (p < 0.001) than those who had social isolation. Regular physical activity was associated with higher CSF Aβ42 (p = 0.013) and lower levels of CSF tau (p = 0.036) and p-tau (p = 0.007). However, no significant associations were found of smoking status or alcohol intake with CSF biomarkers. When the overall lifestyle of the participants was evaluated by all the four lifestyle factors, favorable lifestyle profiles were related to lower levels of CSF tau (p < 0.001) and p-tau (p < 0.001).

Conclusions
These findings suggest that healthy lifestyles had a beneficial effect on AD pathology among cognitively intact elders.
Establishing a comprehensive search strategy for Indigenous health literature reviews
Authors: Harding Louise , Marra Caterina J. , Illes Judy 
Published: April 2021

Abstract
Background
Appropriate search strategies are essential to ensure the integrity and reproducibility of systematic and scoping reviews, as researchers seek to capture as many relevant resources as possible. In the case of Indigenous health reviews, researchers are met with the special challenge of creating a search strategy that can encompass this large, diverse population group with no universally agreed upon identification criteria.

Main body
With an aim to promote improved review methodologies that uphold standards of justice, autonomy, and equity for Indigenous peoples and other heterogeneous populations, we describe critical gaps and approaches to close them. We report organizational and transparency issues around how Indigenous populations are indexed in several major databases, and draw on examples of published reviews and protocols to demonstrate the challenges inherent to creating a comprehensive search strategy.

Conclusions
The conduct and communication of results from health literature research on global Indigenous populations are compromised by challenges of methodology that are rooted in the complexities inherent to defining Indigenous peoples. These challenges must be urgently addressed to improve this important field of inquiry moving forward.