bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of active cervical therapeutic exercise on dynamic intervertebral foramen changes in neck pain patients with disc herniation
Authors: Wu Shyi-Kuen , Chen Han-Yu , You Jia-Yuan , Bau Jian-Guo , Lin Yu-Chen , Kuo Li-Chieh 
Published: July 2022

Abstract
Background
To better understand biomechanical factors that affect intervertebral alignment throughout active therapeutic exercise, it is necessary to determine spinal kinematics when subjects perform spinal exercises. This study aims to investigate the outcomes of active cervical therapeutic exercise on intervertebral foramen changes in neck pain patients with disc herniation.

Methods
Thirty diagnosed C4/5 and/or C5/6 disc-herniated patients receiving an 8-week cervical therapeutic exercise program were followed up with videofluoroscopic images. The dynamic changes in the foramen were computed at different timepoints, including the neutral position, end-range positions in cervical flexion-extension, protrusion-retraction, and lateral flexion movements.

Results
The results showed that the active cervical flexion, retraction, and lateral flexion away from the affected side movements increased the area of the patients’ intervertebral foramen; while the active extension, protrusion, and lateral flexion toward the affected side reduced the areas of intervertebral foramen before treatment. After the treatment, the active cervical flexion significantly increased the C2/3, C3/4, and C6/7 foramen area by 5.02–8.67% (p = 0.001 ~ 0.029), and the extension exercise significantly reduced the C2/3 and C4/5 area by 5.12–9.18% (p = 0.001 ~ 0.006) compared to the baseline. Active retraction movement significantly increased the foramen area from C2/3 to C6/7 by 3.82–8.66% (p = 0.002 ~ 0.036 with exception of C5/6). Active lateral flexion away from the affected side significantly increased the foramen by 3.71–6.78% (p = 0.007 ~ 0.046 with exception of C6/7).

Conclusions
The 8-week therapeutic exercises including repeated cervical retraction, extension, and lateral flexion movements to the lesion led to significant changes and improvements in intervertebral foramen areas of the patients with disc herniation.

Trial registration
ISRCTN61539024
Informational content of two-dimensional panoramic radiographs and lateral cephalometric radiographs with respect to the bone volume of intraoral donor regions considering CBCT imaging
Authors: Brockmeyer Phillipp , Wiechens Bernhard , Sevinc Tayhan , Schliephake Henning , Hahn Wolfram 
Published: July 2022

AbstractBackgroundTo test the hypothesis that cephalometric parameters in two-dimensional routine dental radiographs correlate with the bone volume of intraoral bone donor sites.MethodsOne-hundred and eight radiographs [36 panoramic radiographs (PRs), 36 lateral cephalometric radiographs (LCRs), and 36 cone-beam computed tomography scans (CBCT)] of 36 patients (all three imaging techniques applied according to the needs of treatment planning), were analyzed individually. Cephalometric parameters (PR and LCR) were correlated with the bone volume measurement in three-dimensional CBCT scans in three intraoral donor sites (chin, mandibular retromolar region, and zygomatic alveolar crest).ResultsThe mean bone volumes measured for the chin were (3.10 ± 1.11 cm³ SD), the mandibular retromolar region (1.66 ± 0.54 cm³ SD), and the zygomatic alveolar crest (0.17 ± 0.04 cm³ SD). Cephalometric parameters were significantly correlated (allp-values < 0.05) with the bone volume in the chin and the mandibular retromolar region. The bone volume of the zygomatic alveolar crest exhibited no correlations (p > 0.05) with cephalometric parameters. However, it was significantly correlated (p < 0.01) with the mandibular retromolar bone volume. No gender-specific differences (p > 0.05) were observed concerning bone volumes in all bone harvesting regions. Nevertheless, the male population’s interforaminal distance in the chin region was significantly higher (p = 0.001).ConclusionsPRs and LCRs can be used at the initial stage of peri-implant augmentation planning to deduce conclusions about the bone volume in different intraoral bone donor sites. It can help describe indications and justify additional diagnostic options, such as three-dimensional radiologic techniques.
Visual-spatial dimension integration in digital pathology education enhances anatomical pathology learning
Authors: Wan Ken Lee , Sen Arkendu , Selvaratnam Lakshmi , Naing Mohd Imran Mohd , Khoo Joon Joon , Rajadurai Pathmanathan 
Published: July 2022

AbstractLiterature review demonstrated a surprising lack of publications on digital e-learning pathology resources for senior medical undergraduates and interns. An interactive Digital Pathology Repository (iDPR) integrating two- and three-dimensional (2D, 3D) high-resolution anatomical pathology images with correlated digital histopathology was developed. The novel iDPR was rigorously evaluated using mixed methods to assess pathology knowledge gains (pre- and post-tests), quality impact analysis (questionnaire), user feedback (focus group discussions) and user visual behaviour (eye gaze tracking analysis of 2D/ 3D images).Exposure to iDPR appeared to improve user pathology knowledge, as observed by significantly increased test scores on topic-related quizzes (n = 69,p < 0.001). In addition, most users were highly satisfied with the key design elements of the iDPR tool. Focus group discussion revealed the iDPR was regarded as a relevant online learning resource, although some minor technical issues were also noted. Interestingly, visual behaviour trends indicated that specific diagnostic pathological lesions could be correctly identified faster in 3D images, when compared to 2D images.The iDPR offers promise and potential in pathology education for senior clinical students and interns, gauging from both qualitative and quantitative positive user feedback. With incorporation of image annotations and interactive functionality, and with further technology development, this would prove a useful tool for diagnostic pathology and telepathology. As images with added visual-spatial dimension can provide enhanced detail and aid more rapid diagnosis, future applications of the iDPR could include virtual reality or holographic images of anatomical pathology specimens.
Hospitals during economic crisis: a systematic review based on resilience system capacities framework
Authors: Foroughi Zeynab , Ebrahimi Parvin , Aryankhesal Aidin , Maleki Mohammadreza , Yazdani Shahram 
Published: July 2022

Abstract
Background
Hospitals are the biggest users of the health system budgets. Policymakers are interested in improving hospital efficiency while maintaining their performance during the economic crisis. This study aims at analysing the hospitals’ policy solutions during the economic crisis using the resilience system capacities framework.

Method
This study is a systematic review. The search strategy was implemented on the Web of Science, PubMed, Embase, Scopus databases, and Econbiz search portal. Data were extracted and analysed through the comparative table of resilience system capacities framework and the World Health Organization (WHO) health system’s six building blocks (i.e., leadership and governance, service delivery, health workforce, health systems financing, health information systems, and medicines and equipment).

Findings
After the screening, 78 studies across 36 countries were reviewed. The economic crisis and adopted policies had a destructive effect on hospital contribution in achieving Universal Health Coverage (UHC). The short-term absorptive capacity policies were the most frequent policies against the economic crisis. Moreover, the least frequent and most effective policies were adaptive policies. Transformative policies mainly focused on moving from hospital-based to integrated and community-based services. The strength of primary care and community-based services, types and combination of hospital financing systems, hospital performance before the crisis, hospital managers’ competencies, and regional, specialties, and ownership differences between hospitals can affect the nature and success of adopted policies.

Conclusion
The focus of countries on short-term policies and undermining necessary contextual factors, prioritizing efficiency over quality, and ignoring the interrelation of policies compromised hospital contribution in UHC.
PO2RDF: representation of real-world data for precision oncology using resource description framework
Authors: Zhao Yiqing , Dimou Anastasios , Shen Feichen , Zong Nansu , Davila Jaime I. , Liu Hongfang , Wang Chen 
Published: July 2022

AbstractBackgroundNext-generation sequencing provides comprehensive information about individuals’ genetic makeup and is commonplace in precision oncology practice. Due to the heterogeneity of individual patient’s disease conditions and treatment journeys, not all targeted therapies were initiated despite actionable mutations. To better understand and support the clinical decision-making process in precision oncology, there is a need to examine real-world associations between patients’ genetic information and treatment choices.MethodsTo fill the gap of insufficient use of real-world data (RWD) in electronic health records (EHRs), we generated a single Resource Description Framework (RDF) resource, called PO2RDF (precision oncology to RDF), by integrating information regarding genes, variants, diseases, and drugs from genetic reports and EHRs.ResultsThere are a total 2,309,014 triples contained in the PO2RDF. Among them, 32,815 triples are related to Gene, 34,695 triples are related to Variant, 8,787 triples are related to Disease, 26,154 triples are related to Drug. We performed two use case analyses to demonstrate the usability of the PO2RDF: (1) we examined real-world associations between EGFR mutations and targeted therapies to confirm existing knowledge and detect off-label use. (2) We examined differences in prognosis for lung cancer patients with/without TP53 mutations.ConclusionsIn conclusion, our work proposed to use RDF to organize and distribute clinical RWD that is otherwise inaccessible externally. Our work serves as a pilot study that will lead to new clinical applications and could ultimately stimulate progress in the field of precision oncology.
Differences in the characteristics and pulmonary toxicity of nano- and micron-sized respirable coal dust
Authors: Zhang Yinci , Li Amin , Gao Jiafeng , Liang Jiaojiao , Cao Niandie , Zhou Shuping , Tang Xiaolong 
Published: July 2022

Abstract
Background
The characteristics of coal dust (CD) particles affect the inhalation of CD, which causes coal worker’s pneumoconiosis (CWP). CD nanoparticles (CD-NPs, < 500 nm) and micron particles (CD-MPs, < 5 μm) are components of the respirable CD. However, the differences in physicochemical properties and pulmonary toxicity between CD-NPs and CD-MPs remain unclear.

Methods
CD was analyzed by scanning electron microscopy, Malvern nanoparticle size potentiometer, energy dispersive spectroscopy, infrared spectroscopy, and electron paramagnetic resonance spectroscopy. CCK-8 assay, ELISA, transmission electron microscope, JC-1 staining, reactive oxygen species activity probe, calcium ion fluorescent probe, AO/EB staining, flow cytometry, and western blot were used to determine the differences between CD-NPs and CD-MPs on acute pulmonary toxicity. CCK-8, scratch healing and Transwell assay, hematoxylin–eosin and Masson staining, immunohistochemistry, immunofluorescence, and western blot were applied to examine the effects of CD-NPs and CD-MPs on pneumoconiosis.

Results
Analysis of the size distribution of CD revealed that the samples had been size segregated. The carbon content of CD-NPs was greater than that of CD-MPs, and the oxygen, aluminum, and silicon contents were less. In in vitro experiments with A549 and BEAS-2B cells, CD-NPs, compared with CD-MPs, had more inflammatory vacuoles, release of pro-inflammatory cytokines (IL-6, IL-1β, TNFα) and profibrotic cytokines (CXCL2, TGFβ1), mitochondrial damage (reactive oxygen species and Ca2+ levels and decreased mitochondrial membrane potential), and cell death (apoptosis, pyroptosis, and necrosis). CD-NPs-induced fibrosis model cells had stronger proliferation, migration, and invasion than did CD-MPs. In in vivo experiments, lung coefficient, alveolar inflammation score, and lung tissue fibrosis score (mean: 1.1%, 1.33, 1.33) of CD-NPs were higher than those of CD-MPs (mean: 1.3%, 2.67, 2.67). CD-NPs accelerated the progression of pulmonary fibrosis by upregulating the expression of pro-fibrotic proteins and promoting epithelial–mesenchymal transition. The regulatory molecules involved were E-cadherin, N-cadherin, COL-1, COL-3, ZO-1, ZEB1, Slug, α-SMA, TGFβ1, and Vimentin.

Conclusions
Stimulation with CD-NPs resulted in more pronounced acute and chronic lung toxicity than did stimulation with CD-MPs. These effects included acute inflammatory response, mitochondrial damage, pyroptosis, and necrosis, and more pulmonary fibrosis induced by epithelial–mesenchymal transition.
Mechanism research and treatment progress of NAD pathway related molecules in tumor immune microenvironment
Authors: Xu QinChen , Liu Xiaoyan , Mohseni Ghazal , Hao Xiaodong , Ren Yidan , Xu Yiwei , Gao Huiru , Wang Qin , Wang Yunshan 
Published: July 2022

AbstractNicotinamide adenine dinucleotide (NAD) is the core of cellular energy metabolism. NAMPT, Sirtuins, PARP, CD38, and other molecules in this classic metabolic pathway affect many key cellular functions and are closely related to the occurrence and development of many diseases. In recent years, several studies have found that these molecules can regulate cell energy metabolism, promote the release of related cytokines, induce the expression of neoantigens, change the tumor immune microenvironment (TIME), and then play an anticancer role. Drugs targeting these molecules are under development or approved for clinical use. Although there are some side effects and drug resistance, the discovery of novel drugs, the development of combination therapies, and the application of new technologies provide solutions to these challenges and improve efficacy. This review presents the mechanisms of action of NAD  pathway-related molecules in tumor immunity, advances in drug research, combination therapies, and some new technology-related therapies.
The relationship between animal flesh foods consumption and rheumatoid arthritis: a case-control study
Authors: Hatami Elahe , Aghajani Mobina , Pourmasoumi Makan , Haeri Farahnaz , Boozari Behnoosh , Nezamoleslami Saeed , Clark Cain C. T. , Nezamoleslami Shokufeh , Ghiasvand Reza 
Published: July 2022

AbstractBackgroundRheumatoid arthritis (RA) is a chronic, systemic inflammatory, and debilitating autoimmune illness. The objective of the present study was to evaluate the relationship between animal flesh foods consumption and rheumatoid arthritis.MethodsMeat consumption was assessed by using a semi-quantitative Food Frequency Questionnaire (168 items) in a case-control study of 297 subjects (100 newly diagnosed cases and 197 healthy controls). An expert rheumatologist diagnosed patients based on the American College of Rheumatology definitions, 2010. Multivariate logistic regression, adjusted for lifestyle and nutritional confounders, was used to evaluate the relationship between dairy consumption and rheumatoid arthritis.ResultsParticipants with greater consumption of fish and seafood were less likely to have RA (OR 0.52; 95% CI 0.27–0.98). Conversely, a higher processed meat intake was associated with increased odds of RA (OR 3.45; 95% CI 1.78–6.68). However, no significant association was found between red meats and poultry consumption and the risk of RA in the fully adjusted model.ConclusionsThe present study suggests an inverse association between fish and seafood consumption and the risk of RA. On the contrary, a higher amount of processed meat intake was associated with increased odds of RA. However, further studies are warranted to confirm the veracity of our findings.
Effect of soy isoflavones supplementation on migraine characteristics, mental status and calcitonin gene-related peptide (CGRP) levels in women with migraine: results of randomised controlled trial
Authors: Babapour Maedeh , Khorvash Fariborz , Rouhani Mohammad Hossein , Ghavami Abed , Ghasemi‐Tehrani Hatav , Heidari Zahra , Karbasi Mojtaba , Moradi Fatemeh , Askari Gholamreza 
Published: July 2022

Abstract
Background
Literature suggests a relationship between estrogen levels and migraine headache pathogenesis. However, the effect of soy isoflavones on migraine characteristic remains unclear. This study aimed to investigate the effect of soy isoflavones on migraine characteristics and calcitonin gene-related peptide (CGRP) levels in women with migraine.

Methods
Eighty-three participants completed a randomized double-blind controlled trial, receiving 50 mg per day soy isoflavones or placebo supplementation for 8 weeks. Migraine severity, migraine days per month, frequency and duration of attacks, mental status, quality of life and serum CGRP levels were measured at baseline and the end of the intervention. Bivariate comparison and intention-to-treat (ITT) were used for analysis.

Results
Soy isoflavones intake resulted in a significant decrease in mean frequency (-2.36 vs -0.43, P < 0.001), duration (-2.50 vs -0.02, P < 0.001) of migraine attacks and CGRP level (-12.18 ng/l vs -8.62, P = 0.002) in compared to placebo group. Also, a significant improvement was found in quality of life (16.76 vs 2.52, P < 0.001). Although, reduction in the migraine severity and mental status did not reach a statistically significant level (P > 0.05).

Conclusion
soy isoflavones supplementation may be considered as a complementary treatment for women with migraine to improve migraine characteristics and reduce the burden of disease.
Reducing VEGFB accelerates NAFLD and insulin resistance in mice via inhibiting AMPK signaling pathway
Authors: Li Rongrong , Li Yuqi , Yang Xueling , Hu Yaorui , Yu Haining , Li Yana 
Published: July 2022

Abstract
Objective
Vascular endothelial growth factor B (VEGFB) was regarded to improve lipid metabolism and reduce obesity-related hyperlipidemia. Whether VEGFB participates in lipid metabolism in nonalcoholic fatty liver disease (NAFLD) has not been clear yet. This study investigated the involvement of VEGFB in lipid metabolism and insulin resistance via the AMPK signaling pathway in NAFLD.

Methods
We constructed the animal and cell model of NAFLD after VEGFB gene knockout to detect liver damage and metabolism in NAFLD. Bioinformatics analysis of VEGFB and the AMPK signaling pathway relative genes to verify the differential proteins. And mRNA levels of NAFLD fatty acid metabolism-related genes were detected.

Results
After the systemic VEGFB knockout mice were fed with high fat, the body fat, serum lipoprotein, NAFLD score, and insulin resistance were increased. Animal and cell experiments showed that the expression levels of phosphorylated proteins of CaMKK2 and AMPK decreased, the expression of proteins related to AMPK/ACC/CPT1 signaling pathway decreased, and the target genes CPT1α and Lcad decreased accordingly, reducing fatty acid oxidation in hepatocyte mitochondria; The expression of AMPK/SREBP1/Scd1 signaling pathway relative proteins increased, ACC1 and FAS increased correspondingly, which increased lipid synthesis in the endoplasmic reticulum.

Conclusion
VEGFB can participate in lipid metabolism and insulin resistance of NAFLD through the AMPK signaling pathway.
Modulation of hepatic stellate cells by Mutaflor® probiotic in non-alcoholic fatty liver disease management
Authors: Hany Noha M. , Eissa Sanaa , Basyouni Manal , Hasanin Amany H. , Aboul-Ela Yasmin M. , Elmagd Nagwa M. Abo , Montasser Iman F. , Ali Mahmoud A. , Skipp Paul J. , Matboli Marwa 
Published: July 2022

Abstract
Background
NAFLD and NASH are emerging as primary causes of chronic liver disease, indicating a need for an effective treatment. Mutaflor® probiotic, a microbial treatment of interest, was effective in sustaining remission in ulcerative colitis patients.

Objective
To construct a genetic-epigenetic network linked to HSC signaling as a modulator of NAFLD/NASH pathogenesis, then assess the effects of Mutaflor® on this network.

Methods
First, in silico analysis was used to construct a genetic-epigenetic network linked to HSC signaling. Second, an investigation using rats, including HFHSD induced NASH and Mutaflor® treated animals, was designed. Experimental procedures included biochemical and histopathologic analysis of rat blood and liver samples. At the molecular level, the expression of genetic (FOXA2, TEAD2, and LATS2 mRNAs) and epigenetic (miR-650, RPARP AS-1 LncRNA) network was measured by real-time PCR. PCR results were validated with immunohistochemistry (α-SMA and LATS2). Target effector proteins, IL-6 and TGF-β, were estimated by ELISA.

Results
Mutaflor® administration minimized biochemical and histopathologic alterations caused by NAFLD/NASH. HSC activation and expression of profibrogenic IL-6 and TGF-β effector proteins were reduced via inhibition of hedgehog and hippo pathways. Pathways may have been inhibited through upregulation of RPARP AS-1 LncRNA which in turn downregulated the expression of miR-650, FOXA2 mRNA and TEAD2 mRNA and upregulated LATS2 mRNA expression.

Conclusion
Mutaflor® may slow the progression of NAFLD/NASH by modulating a genetic-epigenetic network linked to HSC signaling. The probiotic may be a useful modality for the prevention and treatment of NAFLD/NASH.
Latent classes of early response trajectories to biologics initiation in juvenile idiopathic arthritis: an analysis of four trials
Authors: Lim Lily Siok Hoon , Shobhan Shamsia , Lokku Armend , Ringold Sarah , Pullenayegum Eleanor 
Published: July 2022

Abstract
Aims
1) To delineate latent classes of treatment response to biologics in juvenile idiopathic arthritis (JIA) patients in the first 16 weeks after initiation. 2) To identify predictors of early disease response.

Methods
The study population was drawn from four biologics trials in polyarticular course JIA: Etanercept 2000, Abatacept 2008, TRial of Early Aggressive Therapy (TREAT) 2012 and Tocilizumab 2014. The outcome was active joint counts (AJC). Semiparametric latent class trajectory analysis was applied to identify latent classes of response to treatment; AJC was transformed for this modelling. We tested baseline disease and treatment characteristics for their abilities to predict class membership of response.

Results
There were 480 participants, 74% females. At baseline, 26% were rheumatoid factor positive. 67% were on methotrexate at enrollment. Three latent class solution provided the best fit. Baseline AJC was the sole best predictor of class membership. Participants classified by their highest membership probabilities into high baseline AJC (> 30) and slow response (26.5%), low baseline AJC (< 10), early and sustained response (29.7%), and moderate baseline AJC progressive response (43.8%). Participants were classified into the latent classes with a mean class membership posterior probability of 0.97. Those on methotrexate at baseline were less likely to belong to high baseline AJC class.

Conclusions
Three latent classes of responses were detectable in the first 16 weeks of biologics therapy. Those with the highest baseline AJC demonstrated very slow response in this window and were less likely to be on concomitant methotrexate.

Trials registration
TREAT 2012 (NCT NCT00443430) (Wallace et. al, Arthritis Rheum 64:2012–21, 2012), tocilizumab trial 2014 (NCT00988221), abatacept trial 2008 (NCT00095173). Etanercept 2000 from Amgen does not have a trial registration number.