bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of rheumatoid arthritis on higher reoperation rate over time following lumbar spinal fusion -A nationwide cohort study-
Authors: Hong Jae-Young , Park Jin-Sung , Park Se-Jun , Park Jiwon , Shin Gijun 
Published: February 2022

Abstract
This study aimed to compare the rates of reoperation over time following first lumbar fusion between rheumatoid arthritis (RA) patients and non-RA patients. This study was conducted using Korean Health Insurance Review and Assessment (HIRA) data. We identified the RA group as 2,239 patients who underwent first lumbar fusion with RA and the control group as 11,195 patients without RA. This reflects a ratio of 1:5, and participants were matched by sex, age, and index surgery date. Index dates were between 2012 and 2013. When comparing the rate of patients undergoing reoperation, the adjusted HR was 1.31(95%CI: 1.10-1.6) in the RA group (p=0.002). In terms of the three-time intervals, the values in the time frames <3 months and 3months-1year were not statistically significant. However, after 1year post-surgery, there was a higher risk of reoperation in the RA group, as demonstrated by the Kaplan-Meier cumulative event analysis. This higher risk of reoperation continued to increase through 5years of follow-up, after which it was stable until the last follow-up at 7years. This population-based cohort study showed that the RA patients had a 1.31times higher risk of reoperation following lumbar fusion than did the controls. This difference was more pronounced after 1year post-surgery.
Comparative Study of Zf-BED Encoding Genes in Land Plants and Their Roles in Cotton
Authors: Hussain Athar , Liu Jinbao , Mohan Binoop , Burhan Akif , Naseem Zunaira , Bano Raveena , Ameen Ayesha , Zaynab Madiha , Mukhtar M. Shahid , Pajerowska-Mukhtar Karolina M. 
Published: February 2022

Abstract
Zinc-finger (Zf)-BED proteins are a novel superfamily of transcription factors that controls numerous activities in plants including growth, development, and cellular responses to biotic and abiotic stresses. Despite their important roles in gene regulation, little is known about the specific functions of Zf-BEDs in land plants. The current study identified a total of 750 Zf-BED-encoding genes in 35 land plant species including mosses, bryophytes, lycophytes, gymnosperms, and angiosperms. The gene family size was somewhat proportional to genome size. All identified genes were categorized into 22 classes based on their specific domain architectures. Of these, class I (Zf-BED_DUF-domain_Dimer_Tnp_hAT) was the most common in the majority of the land plants. However, some classes were family-specific, while the others were species-specific, demonstrating diversity at different classification levels. In addition, several novel functional domains were also predicated including WRKY and nucleotide-binding site (NBS). Comparative genomics, transcriptomics, and proteomics provided insights into the evolutionary history, duplication, divergence, gene gain and loss, species relationship, expression profiling, and structural diversity of Zf-BEDs in land plants. The comprehensive study of Zf-BEDs in Gossypium sp., (cotton) also demonstrated a clear footprint of polyploidization. Overall, this comprehensive evolutionary study of Zf-BEDs in land plants highlighted significant diversity among plant species.
Paeoniflorin Promotes Apoptosis of Fibroblast-Like Synoviocytes by Upregulating lncRNA MALAT1 to Inhibit Activation of the Wnt1/β-Catenin Pathway in Collagen-Induced Arthritis Rats
Authors: Yang Fan , Wang Dongyi , Shen Junyi , Han Jun , Zhou Kailun , Zhao Zhiming , Cai Hui , Shang Wei 
Published: February 2022

Abstract
This study explored the effect of paeoniflorin(PAE) on apoptosis of fibroblast-like synoviocytes(FLS) mediated by the Wnt1/β -catenin pathway in collagen-induced arthritis(CIA) rats based on the expression of lncRNA MALAT1. Sprague-dawley(SD) rats were randomly divided into control group, CIA model group, PAE low-dose group, PAE medium-dose group and PAE high-dose group. Quantitative polymerase chain reaction (qPCR) was then performed to determine the expression of MALAT1 in rat FLS. Next, the apoptosis rate of FLS was detected by terminal-deoxynucleotidyl transferase-mediated nick end labeling(TUNEL), whereas cell morphology was observed by electron microscopy. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of TNF –α, IL-6, and IL-2 cytokines. The mRNA expressions of Wnt1, β-catenin, Caspase-3, Caspase-9, Bcl-2 and Bax were determined by qPCR, whereas the protein expressions of Wnt1, β-catenin, Caspase-3, Caspase-9, Bcl-2 and Bax were measured by western blot analysis. PAE alleviated arthritis in CIA rats in a dose-dependent manner. In CIA rats, PAE reduced arthritis scores and decreased joint histopathological changes. The expression level of MALAT1 was lower in the CIA group compared with the control group, but the expression was reversed after PAE treatment. The expression levels of Wnt1 and β-catenin in the CIA group were increased compared with the control group, and the levels of cytokine TNF –α, IL-6, and IL-2 were raised compared to the control group. However, treatment with PAE decreased the levels of all these cytokines. Besides, PAE could improve the cell apoptosis rate, and increase the expression levels of Caspase-3, Caspase-9 and Bax, reducing the expression level of Bcl-2. PAE may promote the apoptosis of RA-FLS by up-regulating MALAT1 to inhibit activation of the Wnt1/β -catenin pathway, thereby alleviating arthritis in CIA rats.
Impact of Myocardial Fibrosis on Cardiovascular Structure, Function and Functional Status in Heart Failure With Preserved Ejection Fraction
Authors: Lewis Gavin , Rosala-Hallas Anna , Dodd Susanna , Schelbert Erik B. , Williams Simon G. , Cunnington Colin , McDonagh Theresa , Miller Christopher A. 
Published: February 2022

Abstract
Purpose: Myocardial fibrosis, measured using cardiovascular magnetic resonance extracellular volume (ECV), is associated with adverse outcome in heart failure with preserved ejection fraction (HFpEF), but the mechanisms by which myocardial fibrosis exerts this deleterious effect are unclear. We aimed to determine whether myocardial fibrosis causes changes in cardiovascular structure and function, circulating biomarkers and functional status.Methods: Mediation analyses of data from the PIROUETTE (The Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction) trial were conducted using the Baron and Kenny approach under a structural equation modelling framework to estimate average causal mediation effects, in order to determine whether changes in myocardial ECV, absolute myocardial extracellular matrix volume, and myocardial cellular volume (the mediator variables) following antifibrotic therapy, caused changes in cardiovascular structure and function, circulating biomarkers and functional status (the outcome variables).Results: Regression of myocardial fibrosis correlated with improvements in functional status (6-minute walk test distance [r=-0.28, p=0.021] and KCCQ clinical summary score [r=-0.23, P=0.045]). Pirfenidone had significant effects on the mediator variables, but the only outcome variable that demonstrated a treatment effect was left ventricular ejection fraction (LVEF) (p=0.011). The estimated average causal mediation effects of myocardial ECV, absolute myocardial extracellular matrix volume and absolute myocardial cellular volume on LVEF were 6.1%, 21.5%, and 13.7% respectively, none of which were significant (p=0.608, p=0.123 and p=0.186 respectively).Conclusion: Regression of myocardial fibrosis was associated with improvements in functional status. The small improvement in LVEF associated with pirfenidone was not mediated by myocardial fibrosis regression.(PIROUETTE; NCT02932566).
Effects of continuous positive airway pressure therapy on nocturnal blood pressure fluctuation patterns in patients with obstructive sleep apnea
Authors: Kumagai Hajime , Sawatari Hiroyuki , Hoshino Tetsuro , Konishi Noriyuki , Kiyohara Yuka , Kawaguchi Kengo , Haseda Yoko , Arita Aki , Sasanabe Ryujiro , Shomi Toshiaki 
Published: February 2022

Abstract
Purpose: Continuous positive airway pressure (CPAP) therapy is a well-established treatment for obstructive sleep apnea (OSA). In this study, we aimed to assess the effects of CPAP therapy on nocturnal blood pressure (NBP) fluctuations (NBPFs) during rapid eye movement (REM) and non-REM sleep, and the NBPF patterns in patients with OSA. Methods: This retrospective study included 34 patients with moderate-to-severe OSA who underwent polysomnography using pulse transit time pre-CPAP therapy and 3–6 months post-CPAP therapy. We investigated NBP and the frequency of NBPFs in REM and non-REM sleep, as well as changes in NBPFpatterns post-CPAP therapy. Results: The apnea-hypopnea index (AHI), arousal index, systolic NBP, diastolic NBP, diurnal systolic BP (SBP), diastolic BP (DBP), and frequency of NBPFs in REM and non-REM sleep were significantly reduced post-CPAP therapy (all p < 0.01). A higher pre-CPAP AHI was associated with a reduction in diurnal SBP, systolic NBP, and NBPFs post-CPAP (r = 0.32, p = 0.028; r = 0.40, p = 0.019; and r = 0.51, p = 0.002; respectively). However, 58.8% of the patients showed no NBPF pattern change with CPAP therapy. Conclusion: In REM and non-REM sleep, almost all sleep-related parameters, NBP, and frequency of NBPFs significantly improved post-CPAP therapy, whereas NBPF patterns showed varying changes 3–6 months post-CPAP therapy. These results suggest that factors other than OSA influence NBPF pattern changes.
Cadmium bioaccumulation and oxidative-stress-induced DNA alterations in the freshwater cladoceran Moina macrocopa (Straus 1820) following consecutive short-term exposure assessments
Authors: Samarakoon Thilomi , Fujino Takeshi , Hagimori Masayori , Saito Rie 
Published: February 2022

Abstract
Moina macrocopa is a toxicologically less explored, yet widely distributed freshwater cladoceran found throughout the world. The present study is aimed at determining the cadmium (Cd) bioaccumulation and Cd-induced molecular and biochemical biomarkers, including DNA damage and antioxidant enzyme responses (i.e., catalase (CAT) and glutathione S-transferase (GST) activities), in M. macrocopa neonates. Cd bioaccumulation was determined using a Cd-sensitive fluorescence probe after acute exposure to Cd. The results indicated a concentration-dependent Cd bioaccumulation, especially in the gut region, where it was statistically significant in neonates exposed to ≥5 Cd μg/L. DNA damage was determined by the randomly amplified polymorphic DNA (RAPD) technique after a short-term exposure to sublethal Cd concentrations. Significant DNA alterations were observed in individuals exposed to ≥10 Cd μg/L. Short-term exposure to sublethal Cd concentrations did not change CAT levels. However, low Cd concentrations (10 μg/L) significantly induced GST levels, and higher concentrations (50 μg/L) significantly inhibited the GST levels. Taken together, the results of the present study indicated that bioaccumulation of Cd in M. macrocopa causes oxidative stress even at sublethal concentrations, which may be one of the underlying causes of the observed DNA damage. Furthermore, the findings of the present study highlight the importance of utilizing molecular and biochemical biomarkers for toxicity assessment in cladocerans owing to their high sensitivity and rapid responses even under short-term exposure conditions with low concentrations.
Social Accountability in Medical Education Defined: A Multi-perspective Qualitative Interview Study
Authors: Oudbier Janique , Boerboom Tobias , Peerdeman Saskia , Suurmond Jeanine 
Published: February 2022

Abstract
Background. Nowadays, medical education is mainly bio-medical oriented and societal themes are not systematically integrated. However, medical education has an obligation to align education, research, and healthcare with societal needs. Education in social accountability equips students with the knowledge and skills to be a socially accountable health professional. This study aims to investigate the way educational staff and students in a medical school define social accountability.Methods. A qualitative study was conducted in which 28 educational staff members and 16 students at a medical school in the Netherlands were individually interviewed using a semi-structured interview script. The interviews were qualitatively analyzed according to the grounded theory method.Results. Social accountability is seen as a reciprocal, institutional, context-dependent, and multifactorial construct. The following aspects are distinguished: sustainability, interprofessional collaboration, person-centeredness, diversity, moral issues, and community-based learning.Discussion. We conclude that social accountability in the context of medical education can be defined as follows: A reciprocal relationship between the institution of medical schools and society. This relationship involves the obligation of medical schools to direct their education, research and service activities towards current and significant societal factors such as diversity, sustainability, and moral issues. The community and the patient are central. The formulated definition can be used to guide the implementation of social accountability in medical schools.
Pathways for securing government commitment for activities of collaborative approaches
Authors: Pugel Kimberly , Javernick-Will Amy , Mussa Muhammed , Mekonta Lemessa , Dimtse Desta , Watsisi Martin , Huston Angela , Linden Karl 
Published: February 2022

Abstract
Decentralization in many African countries makes local governments responsible for water, sanitation, and hygiene (WASH) service provision. Yet service provision is complex and requires concerted inputs from many actors, thus local governments are increasingly collaborating with internal and external stakeholders. These ‘collaborative approaches’, which bring together diverse stakeholders to solve complex problems facing service delivery, have been found to strengthen service provision when they obtain support and commitment from local government decision makers. However, the ways to obtain this commitment remain understudied. This cross-case comparative study investigated how collaborative approaches in Ethiopia and Uganda obtained government commitment for their activities. Results draw upon experiences of 13 cases where sufficient commitment either was or was not gained. Deep case knowledge of the research team, aided by Qualitative Comparative Analysis, revealed that the collaborative must (a) be seen as legitimate and credible, (b) align activities within government mandates, and (c) demonstrate the value of the activities to decision-makers. Together this strategy provides a reliable way for collaborative approaches to secure government commitment for their activities. Notably, the results also show that commitment can be obtained even amidst turnover and political dynamics.
Analyte Interactions with Oxoporphyrinogen Derivatives: Computational Aspects
Authors: Hill Jonathan P. , Karr Paul A. , Zuñiga Uy Roxanne A. , Subbaiyan Navaneetha K. , Futera Zdeněk , Ariga Katsuhiko , Ishihara Shinsuke , Labuta Jan , D’Souza Francis 
Published: February 2022

Abstract:
The binding of anions by highly-coloured chromophore compounds is of interest
from the point-of-view of the development of optical sensors for analyte species. In this review,
we have summarised our work on the interactions between oxoporphyrinogen type host
compounds and different analyte species using computational methods. The origin of our
interest in sensing using oxoporphyrinogens stems from an initial finding involving anionhost
interactions involving a conjugated oxoporphyrinogen molecule. This review starts from
that point, introducing some additional exemplary anion binding data, which is then elaborated
to include descriptions of our synthesis work towards multitopic and ion pair interactions.
In all the projects, we have consulted computational data on host structure and hostguest
complexes in order to obtain information about the interactions occurring during complexation.
Density functional theory and molecular dynamics simulations have been extensively used for these purposes.
Mechanism of Action of Ermiao San on Rheumatoid Arthritis Based on
Bioinformatics and Molecular Dynamics
Authors: Ye Zhizhong , Xiao Jianwei , Wang Rongsheng , Cai Xu , Huang Xinmin 
Published: February 2022

Background:
Ermiao San, one of the Chinese medicine formulas, has been widely used
to treat rheumatoid arthritis (RA). Our previous study has demonstrated that Ermiao San is effective
in treating RA. However, its pharmacological mechanisms remain unclear. Therefore, the purpose
of this study was to decipher the potential mechanism of action of Ermiao San in rheumatoid
arthritis (RA) by bioinformatics, network pharmacology, molecular docking, and molecular
dynamics.

Methods:
Gene expression data (GSE77298) were obtained from the GEO database. Differentially
expressed genes (DEGs) were analyzed by R. The active ingredients of Huangbai (Phellodendron)
and Cangshu (Atractylodes), two main constituents of Ermiao San, and their predicted target genes
were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform.
Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes
(KEGG) pathway enrichment analyses were performed using the overlapping genes between DEGs
of the RA dataset and the predicted target genes of Ermiao San. The gene-gene interaction network
was analyzed and visualized by Cytoscape. Molecular docking and dynamics simulations were performed
to study the interaction between selected target genes (Chemokine ligand 2 (CCL2) and
matrix metalloproteinase 1 (MMP1)) and active ingredients (quercetin and wogonin) of Ermiao
San.

Results:
A total of 16 potential targets for Ermiao San were identified, with significantly enriched
GO terms, such as cytokine-mediated signaling pathways, oxidoreductase activity, cell space, etc.,
and IL-17 signaling pathway, rheumatoid arthritis pathway, and NF-κB signaling pathway were
identified as enriched pathways through KEGG analysis. CCL2 and MMP1 were identified and
verified to be the targets of both quercetin and wogonin, the two active ingredients of Ermiao San,
by molecular docking and molecular dynamics.

Conclusion:
Ermiao San may target CCL2 and MMP1 via its active ingredients by exerting therapeutic
effects on RA.
CPP-Based Bioactive Drug Delivery to Penetrate the Blood-Brain Barrier:
A Potential Therapy for Glioblastoma Multiforme
Authors: Mehdipour Golnaz , Wintrasiri Milint Neleptchenko , Ghasemi Sorayya 
Published: February 2022

Background:
A large number of studies have been conducted on the treatment of glio-blastoma multiforme (GBM). Chemotherapeutic drugs cannot penetrate deeply into the brain paren-chyma due to the presence of the blood-brain barrier (BBB). Hence, crossing BBB is a significant obstacle in developing new therapeutic methods for GBM.

Objective:
Cell-penetrating peptides (CPPs) have emerged as new tools that can efficiently deliver various substances across BBB. CPPs beneficial properties, such as BBB penetration capacity, low toxicity, and the ability to achieve active targeting and controllable drug release, have made them worthy candidates for GBM treatment. However, their application is limited by several drawbacks, including lack of selectivity, insufficient transport efficacy, and low stability. In order to overcome the selectivity issue, tumor targeting peptides and sequences that can be activated at the target site have been embedded into the structure of CPPs. To overcome their insufficient transport efficacy into the cells, which is mostly due to endosomal entrapment, various endosomolytic moieties have been incorporated into CPPs. Finally, their instability in blood circulation can be solved through dif-ferent modifications to their structures. As this field is moving beyond preclinical studies, the dis-covery of new and more efficient CPPs for GBM treatment has become crucial. Thus, by using dis-play techniques, such as phage display, this encouraging treatment strategy can be developed fur-ther.

Conclusion:
Consequently, despite several challenges in CPPs application, recent progress in stud-ies has shown their potential for the development of the next generation GBM therapeutics.
Anti-cancer Effects of 5-Aminoimidazole-4-Carboxamide-1-β-D-Ribofuranoside
(AICAR) on Triple-negative Breast Cancer (TNBC) Cells: Mitochondrial
Modulation as an Underlying Mechanism
Authors: Tripathi Versha , Jaiswal Pooja , Assaiya Anshul , Kumar Janesh , Parmar Hamendra Singh 
Published: February 2022

Background:
Triple-negative breast cancer (TNBC) is known for Warburg effect and defects
in the mitochondria. AMP-dependent kinase (AMPK) activates the downstream transcription
factors PGC-1α, PGC-1β, or FOXO1, which participate in mitochondrial biogenesis. 5-
aminoimidazole-4-carboxamide riboside (AICAR) is an analog of adenosine monophosphate and is a
direct activator of AMPK.

Objectives:
In the present study, we have made an attempt to understand the influence of AICAR on
TNBC cells, MDA-MB-231, and the underlying changes in mitochondrial biogenesis, if any.

Methods:
We investigated AICAR induced changes in cell viability, apoptosis, migratory potential,
and changes in the sensitivity of doxorubicin.

Results:
In response to the treatment of MDA-MB-231 breast cancer cells with 750 μM of AICAR
for 72 hours, followed by 48 hours in fresh media without AICAR, we observed a decrease in viability
via MTT assay, reduction in cell numbers along with the apoptotic appearance, increased cell
death by ELISA, decreased lactate in conditioned medium and decrease in migration by scratch and
transwell migration assays. These changes in the cancer phenotype were accompanied by an increase
in mitochondrial biogenesis, as observed by increased mitochondrial DNA to nuclear DNA ratio, a
decrease in lactic acid concentration, an increase in MitoTracker green and red staining, and increased
expression of transcription factors PGC-1α, NRF-1, NRF-2, and TFAM, contributing to mitochondrial
biogenesis. Pre-treatment of cells with AICAR for 72 hours followed by 48 hours treatment
with 1 μM doxorubicin showed an increased sensitivity to doxorubicin as assessed by the MTT
assay.

Conclusion:
Our results show that AICAR exerts beneficial effects on TNBC cells, possibly via
switching off the Warburg effect and switching on the anti-Warburg effect through mitochondrial
modulation.
La quinceañera, un fenómeno de transculturación e interculturalidad
Authors: Saborío Carranza Mayavel 
Published: February 2022

La festividad tradicional familiar de "los quince años" migra de la mano de nuestros paisanos y se transforma al mezclarse con tradiciones semejantes de migrantes de otros países latinoamericanos, y se convierte en un símbolo cultural hispano en Estados Unidos.
En el presente ensayo se analizan las causas económicas, culturales, religiosas, por las que esta celebración se ha convertido en algo tan significante para los "latinos" en Estados Unidos, tan característica, que es de las manifestaciones culturales que los diferencia de otras etnias y les da cohesión como hispanos.