bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Efficacy of Intra-articular Mesenchymal Stromal Cells for the Treatment of Knee Osteoarthritis: A Double-Blinded Prospective Randomized Controlled Clinical Trial
Authors: Garza Jaime R. , Campbell Richard E. , Tjoumakaris Fotios P. , Freedman Kevin B. , Miller Lawrence S. , Santa Maria Daniel , Tucker Bradford S. 
Published: February 2020

Background: Currently, there are limited nonoperative treatment options available for knee osteoarthritis (OA). Cell-based therapies have emerged as promising treatments for knee OA. Autologous stromal vascular fraction (SVF) has been identified as an efficient medium for intra-articular administration of progenitor cells and mesenchymal stem cells derived from adipose tissue. Hypothesis: Patients receiving intra-articular SVF would show significantly greater improvement than patients receiving placebo injections, and this improvement would be dose dependent. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This was a multisite prospective double-blinded randomized placebo-controlled clinical trial. Adult patients with symptomatic knee OA were eligible. Thirty-nine patients were randomized to high-dose SVF, low-dose SVF, or placebo (1:1:1). SVF was obtained via liposuction, processed to create the cellular implant, and injected during the same clinical visit. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and magnetic resonance images were obtained preoperatively and at 6 and 12 months after injection. The Wilcoxon rank sum nonparametric test was utilized to assess statistical significance, and the Hodges-Lehmann location shift was used to assess superiority. Results: The median percentage change in WOMAC score at 6 months after injection for the high-dose, low-dose, and placebo groups was 83.9%, 51.5%, and 25.0%, respectively. The high- and low-dose groups had statistically significant changes in WOMAC scores when compared with the placebo group (high dose, P = .04; low dose, P = .02). The improvements were dose dependent. The median percentage change in WOMAC score from baseline to 1 year after injection for the high-dose, low-dose, and placebo groups was 89.5%, 68.2%, and 0%, respectively. The high- and low-dose groups displayed a greater percentage change at 12 months when compared with the placebo group (high dose, P = .006; low dose, P = .009). Magnetic resonance image review revealed no changes in cartilage thickness after treatment. No serious adverse events were reported. Conclusion: Intra-articular SVF injections can significantly decrease knee OA symptoms and pain for at least 12 months. The efficacy and safety demonstrated in this placebo-controlled trial support its implementation as a treatment option for symptomatic knee OA. Registration: NCT02726945 (ClinicalTrials.gov identifier)
Relationship of the Medial Patellofemoral Ligament Origin on the Distal Femur to the Distal Femoral Physis: A Systematic Review
Authors: Sochacki Kyle R. , Shea Kevin G. , Varshneya Kunal , Safran Marc R. , Abrams Geoffrey D. , Donahue Joseph , Sherman Seth L. 
Published: February 2020

Background: The relationship between the medial patellofemoral ligament (MPFL) and the distal femoral physis has been reported in multiple studies. Purpose: To determine the distance from the MPFL central origin on the distal femur to the medial distal femoral physis in skeletally immature participants. Study Design: Systematic review. Methods: A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Multiple databases were searched for studies investigating the anatomic origin of the MPFL on the distal femur and its relationship to the medial distal femoral physis in skeletally immature participants. Study methodological quality was analyzed with the Anatomical Quality Assessment tool, with studies categorized as low risk, high risk, or unclear risk of bias. Continuous variable data were reported as mean ± SD. Categorical variable data were reported as frequency with percentage. Results: Seven articles were analyzed (298 femurs, 53.7% male patients; mean age, 11.7 ± 3.4 years). There was low risk of bias based on the Anatomical Quality Assessment tool. The distance from the MPFL origin to the distal femoral physis ranged from 3.7 mm proximal to the physis to 10.0 mm distal to the physis in individual studies. Six of 7 studies reported that the MPFL origin on the distal femur lies distal to the medial distal femoral physis in the majority of specimens. The MPFL originated distal to the medial distal femoral physis in 92.8% of participants at a mean distance of 6.9 ± 2.4 mm. Conclusion: The medial patellofemoral ligament originates distal to the medial distal femoral physis in the majority of cases at a mean proximal-to-distal distance of 7 mm distal to the physis. However, this is variable in the literature owing to study design and patient age and sex.
Value of CT Imaging in the Differentiation of Gastric Leiomyoma From Gastric Stromal Tumor
Authors: Wang Jian , Zhou Xiaoxuan , Xu Fangyi , Ao Weiqun , Hu Hongjie 
Published: February 2020

Purpose: To discuss significant computed tomography (CT) findings that differentiate gastric leiomyomas (GLs) from small gastric stromal tumors (GSTs). Methods: One hundred sixty cases with pathologically proven GLs (n = 50) and GSTs (n = 110) with comprehensive CT images were enrolled in this retrospective study. Computed tomography findings (ie, size, location, contour, growth pattern, enhancement degree, necrosis, ulceration, calcification, and lymph nodes) were analyzed through the χ2 or Fisher exact test, independent T test, and multivariate (logistic regression) analysis. Sensitivity and specificity were also calculated. Results: Features of cardia location, endophytic growth, homogeneous gradual enhancement, absent of necrosis, long diameter less than 24 mm, short diameter less than 20 mm, unenhanced CT value larger than 35.2 Hounsfield units (HU), portal venous phase CT value larger than 67.4 HU, and enhancement degree of arterial and venous phase less than 16.2 HU and 32.4 HU were found to be statistically significant between GLs and small GSTs ( P < .05). On multivariate analysis, cardia location, endophytic growth, and homogeneous gradual enhancement were independent predictive factors for GLs and small GSTs. Conclusion: These 10 CT criteria are very helpful to differentiate GLs from small GSTs. Especially cardia location, endophytic growth, and homogeneous gradual enhancement are of high value in differential diagnosis.
Evolving phenotype of systemic lupus erythematosus in Caucasians: low incidence of lupus nephritis, high burden of neuropsychiatric disease and increased rates of late-onset lupus in the ‘Attikon’ cohort
Authors: Nikolopoulos D , Kostopoulou M , Pieta A , Karageorgas T , Tseronis D , Chavatza K , Flouda S , Rapsomaniki P , Banos A , Kremasmenou E , Tzavara V , Katsimbri P , Fanouriakis A , Boumpas D T 
Published: February 2020

Objective This study aimed to analyse the phenotype of systemic lupus erythematosus (SLE) at first presentation and during follow-up in a newly established SLE cohort based at ‘Attikon’ University Hospital. The hospital combines primary, secondary and tertiary care for the region of Western Attica, Greece. Methods This study comprised a mixed prevalent and incident cohort of 555 Caucasian patients diagnosed with SLE according to American College of Rheumatology 1997 criteria and/or the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 criteria. Demographic and clinical characteristics, patterns of severity, treatments and SLICC damage index were recorded for each patient at the time of diagnosis and at last evaluation. Results The mean age at lupus diagnosis was 38.3 years (standard deviation = 15.6 years), with a median disease duration at last follow-up of two years (interquartile range 1-11). At initial presentation, the most common ‘classification’ manifestations were arthritis (73.3%), acute cutaneous lupus (65%) and unexplained fever (25%), while among symptoms not included in any criteria set, Raynaud’s phenomenon (33%) was the most common. Kidney and neuropsychiatric involvement as presenting manifestations were present in 10.3% and 11.5% cases, respectively. Irreversible damage accrual was present in 17.8% within six months of disease diagnosis, attributed mainly to thrombotic and neuropsychiatric disease. At last evaluation, 202 (36.4%) patients had developed severe disease, of whom more than half were treated with pulse cyclophosphamide. Conclusion In this cohort of Caucasian patients, lupus nephritis is not as common as in older cohorts, while neuropsychiatric disease is emerging as a major frontier in lupus prevention and care. These data may help to document changes in the natural history and treatment of SLE over time and may have implications for its early recognition and management.
Sutureless Closure of Arterial Cannulation Sites
Authors: Pasrija Chetan , Bernstein Daniel A. , Rice Maryjoe , Tran Douglas , Morales David , Grintz Todd , Deatrick Kristopher B. , Gammie James S. , Madathil Ronson , Kaczorowski David J. 
Published: February 2020

Objective Percutaneous femoral cannulation for venoarterial extracorporeal membrane oxygenation (ECMO) is commonly performed but percutaneous removal of arterial cannulas has not been broadly accepted. We hypothesized that a system that allows endovascular access to ECMO circuits along with the MANTA® large-bore vascular closure device could be used to successfully close arterial ECMO cannulation sites in a large animal model. Methods Yorkshire swine (40 to 60 kg, n = 2) were used for this study. In the first swine, the infrarenal abdominal aorta was exposed. The aorta was cannulated once using a 15 Fr cannula and twice with a 19 Fr arterial cannula. A novel adaptor system that facilitates endovascular access to ECMO circuits was connected, and a 0.035″ Benston wire was placed through the adaptor and guided into the aorta. The cannula was removed over the wire and manual pressure was applied. The MANTA® sheath was inserted over the wire followed by the closure unit and was deployed. The process was repeated at 2 separate sites. A similar experiment was performed in a second swine, but through a median sternotomy to cannulate the ascending aorta. Results Good hemostasis was achieved at all cannulation sites. Angiography demonstrated unobstructed flow across all closure sites with no evidence of extravasation. Conclusions The data presented here support the use of the MANTA® vascular closure device for the closure of arterial cannulation sites following ECMO decannulation and demonstrates utility of a novel adaptor system for establishing endovascular access in this context.
Efficacy and safety of revefenacin for nebulization in patients with chronic obstructive pulmonary disease taking concomitant ICS/LABA or LABA: subgroup analysis from phase III trials
Authors: Sethi Sanjay , Donohue James F. , Ferguson Gary T. , Barnes Chris N. , Crater Glenn D. 
Published: February 2020

Background: Combinations of a long-acting muscarinic receptor antagonist (LAMA), long-acting β-agonist (LABA), and inhaled corticosteroid (ICS) are used for patients with persistent chronic obstructive pulmonary disease (COPD) exacerbations on bronchodilator monotherapy. In this prespecified subgroup analysis, we assessed the efficacy and safety of the LAMA revefenacin in patients with COPD taking concomitant LABA, including ICS/LABA (LABA subgroup). Methods: Efficacy data were obtained from two 12-week, replicate, placebo-controlled trials and safety data were pooled from the 12-week and a 52-week tiotropium-controlled trial. Patients received revefenacin 175 µg or placebo in the 12-week or tiotropium 18 µg in the 52-week studies. The efficacy endpoint was least squares (LS) mean change from baseline in trough forced expiratory volume in 1 second (FEV1). Clinical health outcomes were assessed using the St. George’s Respiratory Questionnaire (SGRQ). Results: Revefenacin produced similar improvements from baseline in trough FEV1 in the non-LABA and LABA subgroups [placebo-adjusted LS mean change (95% confidence interval) in day 85 trough FEV1, 150.9 (110.3−191.6) ml and 139.2 (82.9−195.5) ml; p < 0.0001 versus placebo]. Similar improvements were observed in SGRQ scores in the non-LABA and LABA subgroups [−3.3 (−5.4 to −1.2) and −3.4 (−6.3 to −0.6)]. Improvements in lung function and health outcomes were observed regardless of airflow obstruction severity. Revefenacin was well tolerated with more adverse events reported in the LABA than the non-LABA subgroup. Conclusions: Once daily revefenacin for nebulization can be an effective and well-tolerated treatment for patients who require concomitant use of LABA with or without ICS. ClinicalTrials.gov identifiers: NCT02512510, NCT02459080, NCT02518139 The reviews of this paper are available via the supplemental material section.
Comparison of pathway and gene-level models for cancer prognosis prediction
Authors: Zheng Xingyu , Amos Christopher I. , Frost H. Robert 
Published: February 2020

AbstractBackgroundCancer prognosis prediction is valuable for patients and clinicians because it allows them to appropriately manage care. A promising direction for improving the performance and interpretation of expression-based predictive models involves the aggregation of gene-level data into biological pathways. While many studies have used pathway-level predictors for cancer survival analysis, a comprehensive comparison of pathway-level and gene-level prognostic models has not been performed. To address this gap, we characterized the performance of penalized Cox proportional hazard models built using either pathway- or gene-level predictors for the cancers profiled in The Cancer Genome Atlas (TCGA) and pathways from the Molecular Signatures Database (MSigDB).ResultsWhen analyzing TCGA data, we found that pathway-level models are more parsimonious, more robust, more computationally efficient and easier to interpret than gene-level models with similar predictive performance. For example, both pathway-level and gene-level models have an average Cox concordance index of ~ 0.85 for the TCGA glioma cohort, however, the gene-level model has twice as many predictors on average, the predictor composition is less stable across cross-validation folds and estimation takes 40 times as long as compared to the pathway-level model. When the complex correlation structure of the data is broken by permutation, the pathway-level model has greater predictive performance while still retaining superior interpretative power, robustness, parsimony and computational efficiency relative to the gene-level models. For example, the average concordance index of the pathway-level model increases to 0.88 while the gene-level model falls to 0.56 for the TCGA glioma cohort using survival times simulated from uncorrelated gene expression data.ConclusionThe results of this study show that when the correlations among gene expression values are low, pathway-level analyses can yield better predictive performance, greater interpretative power, more robust models and less computational cost relative to a gene-level model. When correlations among genes are high, a pathway-level analysis provides equivalent predictive power compared to a gene-level analysis while retaining the advantages of interpretability, robustness and computational efficiency.
The canine oral microbiome: variation in bacterial populations across different niches
Authors: Ruparell Avika , Inui Taichi , Staunton Ruth , Wallis Corrin , Deusch Oliver , Holcombe Lucy J. 
Published: February 2020

AbstractBackgroundMicrobiota from different niches within the canine oral cavity were profiled and compared. Supragingival plaque and stimulated saliva, were collected alongside samples from the buccal and tongue dorsum mucosa, from 14 Labrador retrievers at three timepoints within a 1 month timeframe. The V3-V4 region of the 16S rRNA gene was sequenced via Illumina MiSeq.ResultsSupragingival plaque microbiota had the highest bacterial diversity and the largest number of significant differences in individual taxa when compared to the other oral niches. Stimulated saliva exhibited the highest variability in microbial composition between dogs, yet the lowest bacterial diversity amongst all the niches. Overall, the bacteria of the buccal and tongue dorsum mucosa were most similar.ConclusionsThe bacterial community profiles indicated three discrete oral niches: soft tissue surfaces (buccal and tongue dorsum mucosa), hard tissue surface (supragingival plaque) and saliva. The ability to distinguish the niches by their microbiota signature offers the potential for microbial biomarkers to be identified in each unique niche for diagnostic use.
Pre-treatment with IL2 gene therapy alleviates Staphylococcus aureus arthritis in mice
Authors: Bergmann Berglind , Fei Ying , Jirholt Pernilla , Hu Zhicheng , Bergquist Maria , Ali Abukar , Lindholm Catharina , Ekwall Olov , Churlaud Guillaume , Klatzmann David , Jin Tao , Gjertsson Inger 
Published: February 2020

Abstract
Background
Staphylococcus aureus (S. aureus) arthritis is one of the most detrimental joint diseases known and leads to severe joint destruction within days. We hypothesized that the provision of auxiliary immunoregulation via an expanded compartment of T regulatory cells (Tregs) could dampen detrimental aspects of the host immune response whilst preserving its protective nature. Administration of low-dose interleukin 2 (IL2) preferentially expands Tregs, and is being studied as a treatment choice in several autoimmune conditions. We aimed to evaluate the role of IL2 and Tregs in septic arthritis using a well-established mouse model of haematogenously spred S. aureus arthritis.

Methods
C57BL/6 or NMRI mice we intravenously (iv) injected with a defined dose of S. aureus LS-1 or Newman and the role of IL2 and Tregs were assessed by the following approaches: IL2 was endogenously delivered by intraperitoneal injection of a recombinant adeno-associated virus vector (rAAV) before iv S. aureus inoculation; Tregs were depleted before and during S. aureus arthritis using antiCD25 antibodies; Tregs were adoptively transferred before induction of S. aureus arthritis and finally, recombinant IL2 was used as a treatment starting day 3 after S. aureus injection. Studied outcomes included survival, weight change, bacterial clearance, and joint damage.

Results
Expansion of Tregs induced by IL2 gene therapy prior to disease onset does not compromise host resistance to S. aureus infection, as the increased proportions of Tregs reduced the arthritis severity as well as the systemic inflammatory response, while simultaneously preserving the host’s ability to clear the infection.

Conclusions
Pre-treatment with IL2 gene therapy dampens detrimental immune responses but preserves appropriate host defense, which alleviates S. aureus septic arthritis in a mouse model.
Exclusion of pregnancy in dialysis patients: diagnostic performance of human chorionic gonadotropin
Authors: Haninger-Vacariu Natalja , Herkner Harald , Lorenz Matthias , Säemann Marcus , Vychytil Andreas , Jansen Martin , Marculescu Rodrig , Kramar Reinhard , Sunder-Plassmann Gere , Schmidt Alice 
Published: February 2020

Abstract
Background
A positive pregnancy test in acute or chronically ill patients has implications for the use of potentially mutagenic or teratogenic products in urgent medical therapies such as the use of chemotherapies or therapies with immunosuppressants, for anesthesia, and for time-sensitive indications like urgent surgery or organ Transplantation.
Despite a lack of evidence, it is currently believed that human chorionic gonadotropin serum concentrations are always elevated in female dialysis patients even without pregnancy. It is also believed that human chorionic gonadotropin cannot be used to confirm or exclude pregnancy.

Methods
Human chorionic gonadotropin was examined in female dialysis patients (18–50 years of age), and was classified as positive above 5 mlU/ml. In addition, fertility status was determined. For an enhanced index test, the cut-off of 5 mIU/ml was used for potentially fertile patients and 14 mIU/ml for infertile patients to calculate diagnostic test accuracy. The ideal cut-off for human chorionic gonadotropin was estimated using Liu’s method with bootstrapped 95% confidence intervals. Predictors of human chorionic gonadotropin increase were analyzed using multivariable linear regression.

Results
Among 71 women, two (2.8%) were pregnant, 46 (64.8%) potentially fertile, and 23 (32.4%) infertile. We observed human chorionic gonadotropin concentrations > 5 mIU/ml in 10 patients, which had a sensitivity of 100% (95% confidence interval: 100 to 100), a specificity of 86% (95% confidence interval: 77 to 94), a positive predictive value of 17% (95% confidence interval: 8 to 25) and a negative predictive value of 100% (95% confidence interval: 100 to 100) for the diagnosis of pregnancy. Using a cut-off > 14 mIU/ml for infertile patients or the exclusion of infertile patients increased specificity to 93% or 98%, respectively. The ideal cut-off was 25 mIU/ml (95% confidence interval: 17 to 33). Pregnancy and potential fertility, but not age, were independent predictors of human chorionic gonadotropin.

Conclusion
Human chorionic gonadotropin is elevated > 5mIU/ml in 14.5% of non-pregnant dialysis patients of child-bearing age. In potentially fertile women, this cut-off can be used to exclude pregnancy. In case of an unknown fertility status, the ideal human chorionic gonadotropin cut-off was 25 mIU/ml.
Karyomegalic interstitial nephritis with a novel FAN1 gene mutation and concurrent ALECT2 amyloidosis
Authors: Law Steven , Gillmore Julian , Gilbertson Janet A. , Bass Paul , Salama Alan D. 
Published: February 2020

Abstract
Background
Karyomegalic interstitial nephritis (KIN) is a rare hereditary cause of chronic kidney disease. It typically causes progressive renal impairment with haemoproteinuria requiring renal replacement therapy before 50 years of age. It has been associated with mutations in the Fanconi anaemia-associated nuclease 1 (FAN1) gene and has an autosomal recessive pattern of inheritance. Leukocyte chemotactic factor 2 amyloidosis (ALECT2) is the third most common cause of amyloid nephropathy presenting with chronic kidney disease and variable proteinuria. We report a novel mutation in the FAN1 gene causing KIN and to our knowledge, the first case of concurrent KIN and ALECT.

Case presentation
We describe the case of 44 year old Pakistani woman, presenting with stage four non-proteinuric chronic kidney disease, and a brother on dialysis. Renal biopsy demonstrated KIN and concurrent ALECT2. Genetic sequencing identified a novel FAN1 mutation as the cause of her KIN and she is being managed conservatively for chronic kidney disease. Her brother also had KIN with no evidence of amyloidosis and is being worked up for kidney transplantation.

Conclusion
This case highlights two rare causes of chronic kidney disease considered underdiagnosed in the wider population due to their lack of proteinuria, and may contribute to the cohort of patients reaching end stage renal disease without a renal biopsy. We report a novel mutation of the FAN1 gene causing KIN, and report the first case of concurrent KIN and ALECT2. This case highlights the importance of renal biopsy in chronic kidney disease of unclear aetiology which has resulted in a diagnosis with implications for kidney transplantation and family planning.