bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adherence to the OARSI recommendations for designing, conducting, and reporting of clinical trials in knee osteoarthritis: a targeted literature review
Authors: Hummer Charles D. , Huang Yili , Sheehan Brendan 
Published: February 2022

Abstract
Background
The Osteoarthritis Research Society International (OARSI) updated their guideline for clinical trials on knee osteoarthritis (KOA) in 2015, which contains recommendations for the conduct, design, and reporting of clinical trials. The purpose of this study was to assess the quality of clinical trials published between 2010 and 2020 investigating intra-articular interventions in patients with KOA using the OARSI recommendations.

Methods
A targeted literature review was conducted to identify randomized controlled trials in patients with KOA receiving intra-articular interventions, published between 2010 and 2020. Included studies were assessed using the OARSI recommendations. For a comparison between the time periods before and after the introduction of the new OARSI recommendations, the year 2016 was selected as the cut-off.

Results
One hundred forty-eight publications, representing 139 unique trials, were included in this review. Included studies adhered to between 9 and 24 recommendations (median: 19). The highest increase in adherence from studies published in 2016 or earlier compared to after 2016 was seen in the reporting and registration of trials and the use of structural outcome measures. Overall, adherence to the recommendations related to the collection of biochemical biomarkers and the use of structural outcome measures remained low.

Conclusion
An improvement can be made in the conduct, design, and reporting of clinical trials for intra-articular therapies in KOA. Despite proper guidelines, quality of clinical trials varies, and the methodological deficiencies found are preventable and can be corrected. The quality of research should be considered when making treatment decisions for patients with KOA in clinical practice.
Predictors of adverse events after percutaneous pedicle screws fixation in patients with single-segment thoracolumbar burst fractures
Authors: Dong Shengtao , Li Zongyuan , Tang Zhi-ri , Zheng Yuanyuan , Yang Hua , Zeng Qiuming 
Published: February 2022

Abstract
Background
Percutaneous pedicle screw fixation (PPSF) is the primary approach for single-segment thoracolumbar burst fractures (TLBF). The healing angle at the thoracolumbar junction is one of the most significant criteria for evaluating the efficacy of PPSF. Therefore, the purpose of this study was to analyze the predictors associated with the poor postoperative alignment of the thoracolumbar region from routine variables using a support vector machine (SVM) model.

Methods
We retrospectively analyzed patients with TLBF operated at our academic institute between March 1, 2014 and December 31, 2019. Stepwise logistic regression analysis was performed to assess potential statistical differences between all clinical and radiological variables and the adverse events. Based on multivariate logistic results, a series of independent risk factors were fed into the SVM model. Meanwhile, the feature importance of radiologic outcome for each parameter was explored. The predictive performance of the SVM classifier was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy (ACC) and confusion matrices with 10-fold cross-validation, respectively.

Results
In the recruited 150 TLBFs, unfavorable radiological outcomes were observed in 53 patients (35.33%). The relationship between osteoporosis (p = 0.036), preoperative Cobb angle (p = 0.001), immediate postoperative Cobb angle (p = 0.029), surgically corrected Cobb angle (p = 0.001), intervertebral disc injury (Score 2 p = 0.001, Score 3 p = 0.001), interpedicular distance (IPD) (p = 0.001), vertebral body compression rate (VBCR) (p = 0.010) and adverse events was confirmed by univariate regression. Thereafter, independent risk factors including preoperative Cobb angle, the disc status and IPD and independent protective factors surgical correction angle were identified by multivariable logistic regression. The established SVM classifier demonstrated favorable predictive performance with the best AUC = 0.93, average AUC = 0.88, and average ACC = 0.87. The variables associated with radiological outcomes, in order of correlation strength, were intervertebral disc injury (42%), surgically corrected Cobb angle (25%), preoperative Cobb angle (18%), and IPD (15%). The confusion matrix reveals the classification results of the discriminant analysis.

Conclusions
Critical radiographic indicators and surgical purposes were confirmed to be associated with an unfavorable radiographic outcome of TLBF. This SVM model demonstrated good predictive ability for endpoints in terms of adverse events in patients after PPSF surgery.
To debate or not to debate? Examining the contribution of debating when studying medical ethics in small groups
Authors: Amar-Gavrilman Nehora , Bentwich Miriam Ethel 
Published: February 2022

AbstractBackgroundMedical ethics is a significant learning topic for medical students, and often studied through small group learning (SGL) to encourage critical thinking (CT) and tolerance for ambiguity, both considered particularly important when coping with medical ethics dilemmas. However, a previous study about CT and tolerance for ambiguity in medical ethics SGL produced mixed results. Debating is a pedagogical tool known to enhance CT but never used before in medical ethics learning. This paper examines whether the use of debate may enhance medical ethics SGL by contributing to the CT of students and their tolerance of ambiguity.MethodsIntervention study using the qualitative microanalysis research method, based on videotaped observations that were analyzed through Kamin’s model of CT and non-CT. The study was conducted at Bar-Ilan University’s Faculty of Medicine in the years 2017–2019. Forty-four students and 4 facilitators participated, equally split between 4 small groups. Twenty-four medical ethics SGL sessions at the beginning and end of the year were videotaped, 2 groups – with no intervention, 1 group included partial debate intervention and 1 group fully used debates. Results were compared for changes in CT and ambiguity before and during the intervention period.ResultsThe full intervention (debating) group had the highest increase in utterances reflecting CT, thus actually doubling the median number of CT utterances at the end of the year in comparison to the median number at the beginning of the year. In a similar manner, the debate group exhibited the only group in which there was an increase in the median utterances of tolerance to ambiguity. Nevertheless, the debate group also exhibited the largest increase in the median non-CT utterances and the lowest decrease of intolerance to ambiguity, when comparing the end of the year to the beginning of the year sessions.ConclusionsDebating is an important enhancement to SGL in medical ethics; however, it does not guarantee a complete absence of non-CT.
Associations between cervical intraepithelial neoplasia during pregnancy, previous excisional treatment, cone-length and preterm delivery: a register-based study from western Sweden
Authors: Wiik Johanna , Kärrberg Cecilia , Nilsson Staffan , Strander Björn , Jacobsson Bo , Sengpiel Verena 
Published: February 2022

Abstract
Background
Excisional treatment of cervical intraepithelial neoplasia (CIN) has been associated with increased risk of preterm delivery (PTD), although the underlying mechanism is as yet unclear. Studies on formalin-fixed excised tissue indicate that the risk increases with cone-length, but the magnitude of increase is uncertain, especially in case of minor excisions (≤10 mm), as well compared to women with untreated CIN during pregnancy. This study assesses the impact of cone-length at previous treatment for CIN as well as diagnosis of CIN during pregnancy on the risk of PTD.

Methods
A register-based cohort study in western Sweden linking cervical cytology, histology, and treatment data from the Swedish National Cervical Screening Registry to data on obstetric outcomes in singleton pregnancies 2008–2016 from the Swedish Medical Birth Registry. These groups were compared for PTD and other obstetric outcomes: (1) women with one excisional treatment (n=3250, including a subgroup (n=2408) with cone-length measured before fixation; (2) women with untreated CIN diagnosed during pregnancy (n=1380); and (3) women with normal cytology (n=42,398). Logistic regression analyses were adjusted for socioeconomic and health-related confounders.

Results
Treated women had increased risk of PTD (adjusted odds ratio (aOR) 1.60, 95% confidence interval (CI) 1.21–2.12), spontaneous PTD (aOR 1.95, 95% CI 1.40–2.72) and preterm prelabor rupture of membranes (pPROM) (aOR 2.74, 95% CI 1.66–4.51) compared to the CIN during pregnancy group. ORs were similar when compared to the normal cytology group. Risks of these outcomes increased with cone-length. Mean cone-length was 9.1 mm. Cone-length ≤10 mm was associated with increased risk of PTD (aOR 1.41, 95% CI 1.02–1.94), spontaneous PTD (aOR 1.73, 95% CI 1.18–2.54), and pPROM (aOR 2.44, 95% CI 1.40–4.28), compared to the CIN during pregnancy group. The PTD risk was similar for cone-lengths 3–10 mm, thereafter increasing by 15% with each additional millimeter.

Conclusions
This study suggests that all excisional treatment, including small cones, are associated with increased risk of PTD and pPROM. Risks increase further with cone-length. In women of reproductive age, clinicians should aim to remove all CIN but minimal healthy cervical tissue.
Cone-length should be recorded at treatment, for future prenatal risk estimation.
Determinants of pre-vaccination antibody responses to SARS-CoV-2: a population-based longitudinal study (COVIDENCE UK)
Authors: Talaei Mohammad , Faustini Sian , Holt Hayley , Jolliffe David A. , Vivaldi Giulia , Greenig Matthew , Perdek Natalia , Maltby Sheena , Bigogno Carola M. , Symons Jane , Davies Gwyneth A. , Lyons Ronan A. , Griffiths Christopher J. , Kee Frank , Sheikh Aziz , Richter Alex G. , Shaheen Seif O. , Martineau Adrian R. 
Published: February 2022

Abstract
Background
Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking.

Methods
We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults recruited between May 1 and November 2, 2020, without a positive swab test result for SARS-CoV-2 prior to enrolment. Information on 88 potential sociodemographic, behavioural, nutritional, clinical and pharmacological risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots obtained between November 6, 2020, and April 18, 2021. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively.

Results
Of 11,130 participants, 1696 (15.2%) were seropositive. Factors independently associated with higher risk of SARS-CoV-2 seropositivity included frontline health/care occupation (aOR 1.86, 95% CI 1.48–2.33), international travel (1.20, 1.07–1.35), number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.29, 1.06–1.57, P-trend = 0.01), body mass index (BMI) ≥ 25 vs. < 25 kg/m2 (1.24, 1.11–1.39), South Asian vs. White ethnicity (1.65, 1.10–2.49) and alcohol consumption ≥15 vs. 0 units/week (1.23, 1.04–1.46). Light physical exercise associated with lower risk (0.80, 0.70–0.93, for ≥ 10 vs. 0–4 h/week). Among seropositive participants, higher titres of anti-Spike antibodies associated with factors including BMI ≥ 30 vs. < 25 kg/m2 (aGMR 1.10, 1.02–1.19), South Asian vs. White ethnicity (1.22, 1.04–1.44), frontline health/care occupation (1.24, 95% CI 1.11–1.39), international travel (1.11, 1.05–1.16) and number of visits to shops and other indoor public places (≥ 5 vs. 0/week: 1.12, 1.02–1.23, P-trend = 0.01); these associations were not substantially attenuated by adjustment for COVID-19 disease severity.

Conclusions
Higher alcohol consumption and lower light physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between South Asian ethnic origin and obesity and higher risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, behavioural, nutritional, clinical, and pharmacological factors investigated. Among seropositive participants, higher titres of anti-Spike antibodies in people of South Asian ancestry and in obese people were not explained by greater COVID-19 disease severity in these groups.
Machine learning and bioinformatics analysis revealed classification and potential treatment strategy in stage 3–4 NSCLC patients
Authors: Li Chang , Tian Chen , Zeng Yulan , Liang Jinyan , Yang Qifan , Gu Feifei , Hu Yue , Liu Li 
Published: February 2022

Abstract
Background
Precision medicine has increased the accuracy of cancer diagnosis and treatment, especially in the era of cancer immunotherapy. Despite recent advances in cancer immunotherapy, the overall survival rate of advanced NSCLC patients remains low. A better classification in advanced NSCLC is important for developing more effective treatments.

Method
The calculation of abundances of tumor-infiltrating immune cells (TIICs) was conducted using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT), xCell (xCELL), Tumor IMmune Estimation Resource (TIMER), Estimate the Proportion of Immune and Cancer cells (EPIC), and Microenvironment Cell Populations-counter (MCP-counter). K-means clustering was used to classify patients, and four machine learning methods (SVM, Randomforest, Adaboost, Xgboost) were used to build the classifiers. Multi-omics datasets (including transcriptomics, DNA methylation, copy number alterations, miRNA profile) and ICI immunotherapy treatment cohorts were obtained from various databases. The drug sensitivity data were derived from PRISM and CTRP databases.

Results
In this study, patients with stage 3–4 NSCLC were divided into three clusters according to the abundance of TIICs, and we established classifiers to distinguish these clusters based on different machine learning algorithms (including SVM, RF, Xgboost, and Adaboost). Patients in cluster-2 were found to have a survival advantage and might have a favorable response to immunotherapy. We then constructed an immune-related Poor Prognosis Signature which could successfully predict the advanced NSCLC patient survival, and through epigenetic analysis, we found 3 key molecules (HSPA8, CREB1, RAP1A) which might serve as potential therapeutic targets in cluster-1. In the end, after screening of drug sensitivity data derived from CTRP and PRISM databases, we identified several compounds which might serve as medication for different clusters.

Conclusions
Our study has not only depicted the landscape of different clusters of stage 3–4 NSCLC but presented a treatment strategy for patients with advanced NSCLC.
The adverse impact of coronary artery disease on left ventricle systolic and diastolic function in patients with type 2 diabetes mellitus: a 3.0T CMR study
Authors: Wang Jin , Li Yuan , Guo Ying-Kun , Huang Shan , Shi Rui , Yan Wei-Feng , Qian Wen-Lei , He Guang-Xi , Yang Zhi-Gang 
Published: February 2022

Abstract
Background
Coronary artery disease (CAD) confers considerable morbidity and mortality in diabetes. However, the role of CAD in additive effect of left ventricular (LV) function has rarely been explored in type 2 diabetes mellitus (T2DM) patients. This study aimed to investigate how CAD affect LV systolic and diastolic function in T2DM patients.

Materials and methods
A total of 282 T2DM patients {104 patients with CAD [T2DM (CAD +)] and 178 without [T2DM (CAD −)]} and 83 sex- and age- matched healthy controls underwent cardiac magnetic resonance scanning. LV structure, function, global strains [including systolic peak strain (PS), peak systolic (PSSR) and diastolic strain rate (PDSR) in radial, circumferential and longitudinal directions] and late gadolinium enhancement (LGE) parameters were measured. T2DM (CAD +) patients were divided into two subgroups based on the median of Gensini score (60) which was calculated to assess the severity of CAD. Multivariable linear regression analyses were constructed to investigate the determinants of reduced LV function.

Results
Compared with normal controls, T2DM (CAD −) patients exhibited increased LV end-diastolic and end-systolic volume index and decreased LV global strains, while T2DM(CAD +) patients showed more marked increase and decrease than T2DM(CAD-) and healthy controls, except for longitudinal PDSR (PDSR-L) (all P < 0.017). All of LV global strains demonstrated a progressive decrease from normal controls, through Gensini score ≤ 60, to Gensini score > 60 group, except for PDSR-L (all P < 0.017). CAD was an independent predictor of reduced LV global circumferential PS (GCPS, β = 0.22, p < 0.001), PSSR (PSSR-C, β = 0.17, p = 0.005), PDSR (PDSR-C, β = 0.22, p < 0.001), global radial PS (GRPS, β = 0.19, p = 0.001), and global longitudinal PS (GLPS, β = 0.18, p = 0.003) in T2DM. The Gensini score was associated with decreased GCPS, PSSR-C, PDSR-C, GRPS, and GLPS in T2DM (CAD +) (all p < 0.05).

Conclusion
CAD has an additive deleterious effect on LV systolic and diastolic function in T2DM patients. Among T2DM (CAD +) patients, the Gensini score is associated with reduced LV contractile and diastolic function.
Trial registration Retrospectively registered
RNA helicase DHX15 decreases cell apoptosis by NF-κB signaling pathway in Burkitt lymphoma
Authors: Chen Yuan , Chen Xianglei , Pan Lili , Huang Yuanmao , Cai Yuanhua , Li Jinggang , Li Yang , Wang Shaoyuan 
Published: February 2022

Abstract
Background
DHX15 is one of the RNA helicase family members involving in several biological processes. Studies have reported that overexpression of DHX15 is related to cancer progression. However, the role of DHX15 in Burkitt lymphoma (BL) and latent Epstein-Barr virus (EBV) infection remains to be elucidated.

Methods
Expression of DHX15 was measured in BL patient by immunohistochemical staining. In vitro study, a CCK-8 assay was used to analyze cell proliferation and flow cytometry was performed to assess cell cycle, apoptosis and mitochondria membrane potential. Members of NF-κB signaling pathway and apoptotic-related proteins expression were measured by western-blot. EBV latent infection products and RNA polymerase III transcripts expression were determined by quantitative real-time PCR and western-blot. In vivo study, HE, IHC, TUNEL and ISH assays were used to analyze the effect of DHX15 on subcutaneous tumor nodes formation.

Results
DHX15 was overexpressed in Burkitt lymphoma patients and tends to be associated with poor progression-free survival and poor overall survival. Knockdown of DHX15 significantly inhibited BL tumor growth, reduced cell proliferation, induced cell cycle arrest and increased cell apoptosis. Further analysis showed that canonical NF-κB signaling and its downstream targets, mitochondria and Caspase were involved in the increased cell apoptosis after DHX15 gene knockdown. Furthermore, knockdown of DHX15 reduced EBV latent infection products expression and inhibited RNA polymerase III activity.

Conclusion
DHX15 may be an oncogene in the development of BL and a potential therapeutic target for the treatment of BL and latent EBV infection.
Appropriateness of referrals from primary care for lumbar MRI
Authors: Krogh Susanne Brogaard , Jensen Tue Secher , Rolving Nanna , Thomsen Janus Nikolaj Laust , Hansen Casper Brink , Werenberg Christoffer Høj , Rasmussen Erik , Carlson Rune , Jensen Rikke Krüger 
Published: February 2022

Abstract
Background
International guidelines do not recommend routine imaging, including magnetic resonance imaging (MRI), and seek to guide clinicians only to refer for imaging based on specific indications. Despite this, several studies show an increase in the use of MRI among patients with low back pain (LBP) and an imbalance between appropriate versus inappropriate use of MRI for LBP. This study aimed to investigate to what extent referrals from general practice for lumbar MRI complied with clinical guideline recommendations in a Danish setting, contributing to the understanding and approaches to lumbar MRI for all clinicians managing LBP in the primary sector.

Materials and methods
From 2014 to 2018, all referrals for lumbar MRI were included from general practitioners in the Central Denmark Region for diagnostic imaging at a public regional hospital. A modified version of the American College of Radiology Imaging Appropriateness Criteria for LBP was used to classify referrals as appropriate or inappropriate, based on the unstructured text in the GPs’ referrals. Appropriate referrals included fractures, cancer, symptoms persisting for more than 6 weeks of non-surgical treatment, previous surgery, candidate for surgery or suspicion of cauda equina. Inappropriate referrals were sub-classified as lacking information about previous non-surgical treatment and duration.

Results
Of the 3772 retrieved referrals for MRI of the lumbar spine, 55% were selected and a total of 2051 referrals were categorised. Approximately one quarter (24.5%) were categorised as appropriate, and 75.5% were deemed inappropriate. 51% of the inappropriate referrals lacked information about previous non-surgical treatment, and 49% had no information about the duration of non-surgical treatment. Apart from minor yearly fluctuations, there was no change in the distribution of appropriate and inappropriate MRI referrals from 2014 to 2018.

Conclusion
The majority of lumbar MRI referrals (75.5%) from general practitioners for lumbar MRI did not fulfil the ACR Imaging Appropriateness Criteria for LBP based on the unstructured text of their referrals. There is a need for referrers to include all guideline-relevant information in referrals for imaging. More research is needed to determine whether this is due to patients not fulfilling guideline recommendations or simply the content of the referrals.