bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical treatment of neuromuscular Early Onset Scoliosis with a bilateral posterior one-way rod compared to the Spring Distraction System: study protocol for a limited-efficacy Randomized Controlled Trial (BiPOWR)
Authors: Lemans Justin V.C. , Tabeling Casper S. , Scholten E. Pauline , Stempels Hilde W. , Miladi Lotfi , Castelein René M. , Kruyt Moyo C. 
Published: January 2023

Abstract
Background
Early Onset Scoliosis (EOS) is a progressive spinal deformity in children, and a potentially life-threatening disease. “Growth-friendly” surgical techniques aim to control the deformity, while allowing the spine and trunk to maintain growth. Current “growth-friendly” systems such as the traditional growing rod (TGR) and magnetically controlled growing rod (MCGR) have limitations that reduce their efficacy and cost-effectiveness. Recently, two “growth-friendly” systems have been developed that mitigate many of these limitations, the Spring Distraction System (SDS) and the One Way Self-Expanding Rod (OWSER). The purpose of the multicenter BiPOWR trial is to investigate, describe and compare the 1-year limited-efficacy and -safety of both strategies in the treatment of neuromuscular EOS.

Methods
After informed consent, 28 neuromuscular EOS patients will be randomized to receive either the SDS or the OWSER. Patients and caregivers will be blinded to allocation until after surgery. Primary outcomes will be maintenance of coronal curve correction and the occurrence of serious adverse events. In addition, spinal growth, implant lengthening, and perioperative findings are recorded systematically. At each follow-up moment, the Early Onset Scoliosis Questionnaire (EOSQ-24) will be used to assess health-related quality of life. All outcomes will be compared between groups.

Discussion
The BiPOWR trial is the first randomized controlled trial that compares two specific “growth-friendly” implants in a specified EOS population. It will determine the 1-year limited-efficacy and safety of the SDS and OWSER implants.

Trial registration
Clinicaltrials.gov: NCT04021784 (13–06-2019). CCMO registry: NL64018.041.17 (06–05-2019).
Low-level laser therapy prevents medication-related osteonecrosis of the jaw-like lesions via IL-1RA-mediated primary gingival wound healing
Authors: Zheng Yi , Dong Xian , Chen Shuo , He Yang , An Jingang , Liu Meng , He Linhai , Zhang Yi 
Published: January 2023

Abstract
Background
Medication-related osteonecrosis of the jaw (MRONJ) is a serious debilitating disease caused by anti-resorption and anti-angiogenesis drugs, significantly affecting patients' quality of life. Recent studies suggested that primary gingival wound healing may effectively prevent the development of MRONJ. This study aimed to evaluate the effects of low-level light therapy (LLLT) on promoting gingival wound healing in extraction sockets of MRONJ-like mice and preventing the occurrence of MRONJ. Furthermore, we explored underlying mechanisms.

Methods
Mice were randomly divided into the Ctrl, Zol, and Zol + LLLT groups. Administration of zoledronate and tooth extraction of bilateral maxillary second molars were used to build the MRONJ model, and LLLT was locally administered into the tooth sockets to examine the effect of LLLT. Next, to explore the function of IL-1RA, we performed LLLT with interleukin-1 receptor antagonist (IL-1RA) neutralizing antibody (named Zol + LLLT + IL-1RA NAb group) or negative control antibodies for tooth extraction in subsequent rescue animal experiments. Stereoscope observations, micro-computed tomography, and histological examination were conducted to evaluate gingival wound healing and bone regeneration in tooth sockets. The effects of LLLT on the migration capacities of zoledronate-treated epithelial cells were assessed in vitro.

Results
LLLT promoted primary gingival wound healing without exposed necrotic bone. Micro-computed tomography results showed higher bone volume and mineral density of the tooth sockets after LLLT. Histology analysis showed complete gingival coverage, obvious bone regeneration, and reduced soft tissue inflammation, with down-regulated pro-inflammation cytokines, like interleukin-1 beta (IL-1β) and tumor necrosis factor-α (TNF-α), and up-regulated IL-1RA expression in the gingival tissue in the LLLT group. The rescue assay further showed that the effects of LLLT promoting gingival wound healing and preventing MRONJ might be partially abolished by IL-1RA neutralizing antibodies. In vitro studies demonstrated that LLLT accelerated zoledronate-treated epithelial cell migration.

Conclusions
LLLT might promote primary gingival wound healing and contribute to subsequent bone regeneration of the tooth extractions in MRONJ-like lesions via IL-1RA-mediated pro-inflammation signaling suppression.
Cone beam computed tomography in the assessment of TMJ deformity in children with JIA: repeatability of a novel scoring system
Authors: Augdal Thomas A. , Angenete Oskar W. , Shi Xie-Qi , Säll Mats , Fischer Johannes M. , Nordal Ellen , Rosendahl Karen 
Published: January 2023

Abstract
Background
The temporomandibular joint (TMJ) is frequently involved in juvenile idiopathic arthritis (JIA). Diagnostic imaging is necessary to correctly diagnose and evaluate TMJ involvement, however, hitherto little has been published on the accuracy of the applied scoring systems and measurements. The present study aims to investigate the precision of 20 imaging features and five measurements based on cone beam computed tomography (CBCT).

Methods
Imaging and clinical data from 84 participants in the Norwegian study on juvenile idiopathic arthritis, the NorJIA study, were collected. Altogether 20 imaging features and five measurements were evaluated independently by three experienced radiologists for intra- and interobserver agreement. Agreement of categorical variables was assessed by Fleiss’, Cohen’s simple or weighted Kappa as appropriate. Agreement of continuous variables was assessed with 95% limits of agreement as advised by Bland and Altman.

Results
“Overall impression of TMJ deformity” showed almost perfect intraobserver agreement with a kappa coefficient of 0.81 (95% CI 0.69–0.92), and substantial interobserver agreement (Fleiss’ kappa 0.70 (0.61–0.78)). Moreover, both “flattening” and “irregularities” of the eminence/fossa and condyle performed well, with intra- and interobserver agreements of 0.66–0.82 and 0.55–0.76, respectively. “Reduced condylar volume” and “continuity” of the fossa/eminence had moderate intra- and interobserver Kappa values, whereas continuity of the condyle had Kappa values above 0.55. Measurements of distances and angles had limits of agreement of more than 15% of the sample mean.

Conclusions
We propose a CBCT-based scoring system of nine precise imaging features suggestive of TMJ deformity in JIA. Their clinical validity must be tested.
Systemic inhibition of 5-lipoxygenase by MK-886 exacerbates apical periodontitis bone loss in a mouse model
Authors: Petean Igor Bassi Ferreira , Silva-Sousa Alice Corrêa , da Silva Raquel Assed Bezerra , Lucisano Marília Pacífico , da Silva Léa Assed Bezerra , de Castro Guilherme Piedade Assed , Sousa-Neto Manoel Damião , Faccioli Lúcia Helena , Paula-Silva Francisco Wanderley Garcia 
Published: January 2023

Abstract
Background
To investigate if 5-LO selective inhibitor (MK-886) could be used for systemic treatment of experimentally induced apical periodontitis in a mouse model.

Methods
Twenty-four C57BL/6 mice were used. After coronal opening, a solution containing Escherichiacoli LPS (1.0 µg/µL) was inoculated into the root canals of the lower and upper right first molars (n = 72 teeth). After 30 days apical periodontitis was established, and the animals were treated with MK-886 (5 mg/kg), a 5-LO inhibitor, for 7 and 14 days. The tissues were removed for histopathological and histometric analyses, evaluation of osteoclast number and gene expression for receptor activator of nuclear factor kappa-B (Tnfrsf11a), receptor activator of nuclear factor kappa-B ligand (Tnfsf11), osteoprotegerin (Tnfrsf11b), tartrate-resistant acid phosphatase (Acp5), matrix metalloproteinase-9 (Mmp9), cathepsin K (Ctsk) and calcitonin receptor (Calcr). Statistical data analysis was performed using Kruskal Wallis followed by Dunn’s tests (α = 0.05).

Results
Administration of MK-886 for 7 days exerted no effect on apical periodontitis progression compared to LPS inoculation without treatment (p = 0.3549), while treatment for 14 days exacerbated bone loss (p < 0.0001). Administration of MK-886 enhanced osteoclastogenesis signaling and osteoclast formation within 7 days (p = 0.0005), but exerted no effect at 14 days (p > 0.9999). After 7 days of treatment, MK-886 induced mRNA expression for Acp5 (p = 0.0001), Calcr (p = 0.0003), Mmp9 (p = 0.0005) and Ctsk (p = 0.0008), however no effect in those gene expression was observed after 14 days (p > 0.05).

Conclusion
Systemic treatment with MK-886 exacerbated LPS-induced apical periodontitis in a mouse model.
Voices of women in homelessness during the outbreak of the COVID-19 pandemic: a co-created qualitative study
Authors: Mattsson Elisabet , Lindblad Marléne , Kneck Åsa , Salzmann-Eriksson Martin , Klarare Anna ,   Women Advisory Board for Inclusion Health
Published: January 2023

Abstract
Background
Women in homelessness face extreme health- and social inequities. It could be postulated that during societal crises, they become even more vulnerable. Thus, the aim was to explore experiences related to the COVID-19 pandemic among women in homelessness.

Methods
Ten interviews were conducted with women in homelessness, in Stockholm, Sweden, using researcher-driven photo elicitation. The data analysis was guided by the DEPICT model for collaborative data analysis and a qualitative content analysis was performed. A collaborative reference group of women with lived experience of homelessness contributed to the research process through designing the data collection, performing the data analysis, and providing feedback during report writing.

Results
For women in homelessness, the COVID-19 pandemic was adding insult to injury, as it significantly affected everyday life and permeated most aspects of existence, leading to diminished interactions with others and reduced societal support. Thus, in an already dire situation, the virus amplified health- and social issues to another level. The women strived to find their balance on the shifting sands of guidelines and restrictions due to the pandemic. Adhering to the new social distancing rules and guidelines in line with the rest of society, was simply impossible when experiencing homelessness. However, for some women the pandemic was nothing but a storm in a teacup. The harsh reality continued irrespectively, living one day at a time and prioritizing provision for basic human needs.

Conclusions
The COVID-19 pandemic and homelessness can be viewed as two intersecting crises. However, the women’s aggregated experiences were greater than the sum of experiencing homelessness and meeting the threat of the virus. Gender, exposure to violence, poverty, social isolation, and substance use were additional factors that further marginalized the women during the pandemic. To rebuild a better and more sustainable post-pandemic future for all, global commitment to ending homelessness is crucial. In addition, addressing social determinants of health must be the number one health intervention.
Impact of dyadic practice on the clinical self-efficacy and empathy of nursing students
Authors: Kamali Maryam , Hasanvand Shirin , Kordestani-Moghadam Parastou , Ebrahimzadeh Farzad , Amini Mitra 
Published: January 2023

Abstract
Background
Dyadic practice of learners creates supportive learning. So far, few studies have investigated the impact of this approach on students’ empathy and self-efficacy. This study aimed to investigate the effect of dyadic practice on nursing students’ clinical self-efficacy and empathy.

Methods
This study was based on a pretest-posttest randomized group from September to December 2018. All the junior nursing students (n = 44) were divided into intervention (n = 22) and control groups (n = 22) using stratified random sampling. The intervention group was trained for 6 days as student dyads, while the control group was under the supervision of an instructor and worked individually. The students’ levels of empathy and self-efficacy were evaluated on the first day (pretest) and the last day (post-test) by The Self-Efficacy in Clinical Performance Scale and Mehrabian and Epstein empathy scale. The data were analyzed using the SPSS software by Fisher’s exact test, Mann-Whitney test, independent t-test paired t-test, Wilcoxon signed-rank, and Analysis of covariance.

Results
Dyadic practice increased empathy in the intervention group compared to the control group (P < 0.001). The adjusted mean of total empathy in the intervention group was 21.1 degrees higher than the adjusted mean of total empathy in the control group. However, no significant differences were found between the two groups in clinical self-efficacy (P = 0.762).

Conclusions
The employment of this approach seems helpful in creating an empathic atmosphere. However, further studies are required to prove the effectiveness of this method on self-efficacy.
Outlier identification and monitoring of institutional or clinician performance: an overview of statistical methods and application to national audit data
Authors: Pavlou Menelaos , Ambler Gareth , Omar Rumana Z. , Goodwin Andrew T. , Trivedi Uday , Ludman Peter , de Belder Mark 
Published: January 2023

AbstractBackgroundInstitutions or clinicians (units) are often compared according to a performance indicator such as in-hospital mortality. Several approaches have been proposed for the detection of outlying units, whose performance deviates from the overall performance.MethodsWe provide an overview of three approaches commonly used to monitor institutional performances for outlier detection. These are the common-mean model, the ‘Normal-Poisson’ random effects model and the ‘Logistic’ random effects model. For the latter we also propose a visualisation technique. The common-mean model assumes that the underlying true performance of all units is equal and that any observed variation between units is due to chance. Even after applying case-mix adjustment, this assumption is often violated due to overdispersion and a post-hoc correction may need to be applied. The random effects models relax this assumption and explicitly allow the true performance to differ between units, thus offering a more flexible approach. We discuss the strengths and weaknesses of each approach and illustrate their application using audit data from England and Wales on Adult Cardiac Surgery (ACS) and Percutaneous Coronary Intervention (PCI).ResultsIn general, the overdispersion-corrected common-mean model and the random effects approaches produced similarp-values for the detection of outliers. For the ACS dataset (41 hospitals) three outliers were identified in total but only one was identified by all methods above. For the PCI dataset (88 hospitals), seven outliers were identified in total but only two were identified by all methods. The common-mean model uncorrected for overdispersion produced several more outliers. The reason for observing similarp-values for all three approaches could be attributed to the fact that the between-hospital variance was relatively small in both datasets, resulting only in a mild violation of the common-mean assumption; in this situation, the overdispersion correction worked well.ConclusionIf the common-mean assumption is likely to hold, all three methods are appropriate to use for outlier detection and their results should be similar. Random effect methods may be the preferred approach when the common-mean assumption is likely to be violated.
The main e-cigarette component vegetable glycerin enhances neutrophil migration and fibrosis in endotoxin-induced lung injury via p38 MAPK activation
Authors: Su Vincent Yi-Fong , Chen Wei-Chih , Yu Wen-Kuang , Wu Huai-Hsuan , Chen Hao , Yang Kuang-Yao 
Published: January 2023

AbstractWe investigated the effects of vegetable glycerin (VG), a main e-cigarette constituent, on endotoxin-induced acute lung injury (ALI). Mice received intratracheal administration of 30% VG in phosphate buffered saline (PBS) vehicle or only PBS (control) for 4 days. On Day 5, mice received an intratracheal instillation of lipopolysaccharide (LPS) (LPS group and VG + LPS group) or PBS (VG group and control group). Lung histopathology, expression of chemokine receptors, and regulatory signaling were analyzed 24 h after the Day 5 treatment. VG significantly increased ALI-associated histopathological and fibrotic changes in both the VG group and LPS-induced ALI mice (VG + LPS group). Immunohistochemistry (IHC) and western blot analyses revealed that VG administration resulted in upregulation of neutrophil markers [lymphocyte antigen 6 complex locus G6D (Ly6G) and myeloperoxidase (MPO)] as well as upregulation of the expression of transforming growth factor-β (TGF-β), a central mediator of fibrogenesis, in the lungs of both VG and VG + LPS groups. VG enhanced the expression of adhesion molecules [very late antigen 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1)] and increased activation of p38 mitogen-activated protein kinase (p38 MAPK) to prompt neutrophil recruitment in the lungs of mice with ALI. Intraperitoneal administration of a p38 inhibitor attenuated these histopathological changes significantly as well as VG-induced upregulation in expression of Ly6G, MPO, VLA-4, VCAM-1, TGF-β, and collagen-1 in mice with ALI. In conclusion, VG enhances neutrophil chemotaxis and fibrosis and it amplifies the inflammatory response associated with LPS-induced ALI in the lungs via enhancement of p38 MAPK activity.
Crosstalk between 5-methylcytosine and N6-methyladenosine machinery defines disease progression, therapeutic response and pharmacogenomic landscape in hepatocellular carcinoma
Authors: Tian Yu , Xiao Haijuan , Yang Yanhui , Zhang Pingping , Yuan Jiahui , Zhang Wei , Chen Lijie , Fan Yibao , Zhang Jinze , Cheng Huan , Deng Tingwei , Yang Lin , Wang Weiwei , Chen Guoyong , Wang Peiqin , Gong Peng , Niu Xing , Zhang Xianbin 
Published: January 2023

Abstract
Background
Accumulated evidence highlights the significance of the crosstalk between epigenetic and epitranscriptomic mechanisms, notably 5-methylcytosine (5mC) and N6-methyladenosine (m6A). Herein, we conducted a widespread analysis regarding the crosstalk between 5mC and m6A regulators in hepatocellular carcinoma (HCC).

Methods
Pan-cancer genomic analysis of the crosstalk between 5mC and m6A regulators was presented at transcriptomic, genomic, epigenetic, and other multi-omics levels. Hub 5mC and m6A regulators were summarized to define an epigenetic and epitranscriptomic module eigengene (EME), which reflected both the pre- and post-transcriptional modifications.

Results
5mC and m6A regulators interacted with one another at the multi-omic levels across pan-cancer, including HCC. The EME scoring system enabled to greatly optimize risk stratification and accurately predict HCC patients’ clinical outcomes and progression. Additionally, the EME accurately predicted the responses to mainstream therapies (TACE and sorafenib) and immunotherapy as well as hyper-progression. In vitro, 5mC and m6A regulators cooperatively weakened apoptosis and facilitated proliferation, DNA damage repair, G2/M arrest, migration, invasion and epithelial-to-mesenchymal transition (EMT) in HCC cells. The EME scoring system was remarkably linked to potential extrinsic and intrinsic immune escape mechanisms, and the high EME might contribute to a reduced copy number gain/loss frequency. Finally, we determined potential therapeutic compounds and druggable targets (TUBB1 and P2RY4) for HCC patients with high EME.

Conclusions
Our findings suggest that HCC may result from a unique synergistic combination of 5mC-epigenetic mechanism mixed with m6A-epitranscriptomic mechanism, and their crosstalk defines therapeutic response and pharmacogenomic landscape.
Quantities of CD3+, CD8+ and CD56+ lymphocytes decline in breast cancer recurrences while CD4+ remain similar
Authors: Mutka Minna , Joensuu Kristiina , Eray Mine , Heikkilä Päivi 
Published: January 2023

Abstract
Background
Much is known about tumor infiltrating lymphocytes (Tils) in primary breast cancer, as this has been the focus of much research in recent years, but regarding recurrent breast cancer, only few studies have been done. Our aim was to compare the quantities of Tils in primary breast carcinomas and their corresponding recurrences and to analyze the differences in the tumor Tils compositions in correlations with recurrence-free times and the clinicopathology of the tumor.

Methods
One hundred thirty-seven breast cancer patients self-paired for primary- tumor-recurrence were divided into three groups based on the length of the recurrence-free interval. H&E-staining and immunohistochemical staining with antiCD3, antiCD4, antiCD8 and antiCD56 were performed. Differences in Tils between primaries and recurrences, between the recurrence-free interval groups, and between different clinicopathologic parameters were statistically analyzed.

Results
Fewer stromal CD3+, CD8+ and CD56+ lymphocytes were found at recurrences compared to the primaries. No significant change in the percentage of CD4+ stromal lymphocytes. ER-negative primaries, PR-negative or HER2-positive tumors had more Tils in some subgroups. Ductal primaries had more Tils than lobular primaries and G3 tumors had more Tils than lower-grade tumors. The corresponding differences at recurrences could either not be detected or they were reversed. The fastest recurring group had generally more Tils than the slower groups.

Conclusions
CD4+ cell numbers did not decline from primary to recurrence in contrast to all other subclasses of lymphocytes. The proportion of CD4+ cells was higher in recurrences than in primaries. Tumors with a higher grade and proliferation rate had higher percentages of Tils. HER2+ and hormone receptor negative tumors tended to have higher Tils scores. In recurrences these differences were not seen or they were reversed.