bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteochondral Lesions of the Distal Tibial Plafond: A Systematic Review of Lesion Locations and Treatment Outcomes
Authors: Allahabadi Sachin , Allahabadi Sameer , Allala Ruthvik , Garg Kartik , Pandya Nirav K. , Lau Brian C. 
Published: April 2021

Background: Osteochondral lesions of the tibial plafond (OLTPs) remain less common than osteochondral lesions of the talus (OLTs), but recognition of the condition has increased. Purpose: To systematically evaluate the literature on lesion locations and treatment outcomes of OLTPs, whether in isolation or in combination with OLTs. Study Design: Systematic review; Level of evidence, 4. Methods: A search was performed using the PubMed, Embase, and CINAHL databases for studies on lesion locations or with imaging or treatment outcomes of OLTPs. Case reports and reports based on expert opinion were excluded. Lesion locations as well as outcome measure results were aggregated. The Methodological Index for Non-randomized Studies score was used to assess methodological quality when applicable. Results: Included in this review were 10 articles, all published in 2000 or later. Most studies were evidence level 4, and the mean Methodological Index for Non-randomized Studies score was 8.6 (range, 8-10). Overall, 174 confirmed OLTP cases were identified, and the mean patient age was 38.8 years. Of the 157 lesions with confirmed locations, the most common was central-medial (32/157; 20.4%). Of 6 studies on treatment outcomes, all but 1 evaluated bone marrow stimulation techniques. Microfracture of small lesions (<150 mm2) was the most common treatment utilized. Imaging and functional outcomes appeared favorable after treatment. The data did not support differences in outcomes between isolated OLTPs and OLTPs with coexisting OLTs. Conclusion: Osteochondral lesions of the distal tibia most commonly occurred at the central-medial tibial plafond. Microfracture of small lesions was the most common treatment utilized, and clinical and magnetic resonance imaging results were favorable, although data were heterogeneous. Areas for future research include the following: the effect of patient factors and additional pathologies on outcomes; larger or deeper lesion treatment; more direct comparisons of outcomes between kissing or coexisting lesions and isolated lesions; and head-to-head comparison of treatments, such as microfracture, bone marrow–derived cell transplantation, and osteochondral autografts/allografts.
Improving Patient\Population Health: Using ‘Why’ to Develop a Transformative Research Center
Authors: Aebersold Michelle , McCullagh Marjorie , Titler Marita , Jiang Yun , Zhang Xingyu , Tschannen Dana , Friese Christopher 
Published: April 2021

Introduction Novel approaches to address the most vexing problems facing patients and vulnerable populations are needed. The purpose of this project was to establish an innovative research Center based on the principles of transformational organizations. Methods A new Center formed included faculty members with expertise in cancer, serious illness, and population health. Applying Sinek’s “why, how, and what” framework, members developed and refined a purpose statement and strategic objectives. The Center now includes members representing diverse disciplines. Year 1 accomplishments included a refined mission and vision statement, two funded research proposals, one submitted training grant, one administrative hire, and active recruitment of two-research faculty to support Center activities. Conclusions The newly-formed Center for Improving Patient and Population Health has enabled scholars within a research-intensive school of nursing to forge new partnerships to compete successfully for larger, complicated grant proposals on shorter deadlines. Opportunities exist to integrate students and research staff more fully into Center operations.
Geographic Distribution of Foot and Ankle Orthopedic Surgeons Throughout the United States
Authors: Fanelli Matthew , Cush Coleman , Zhang Hui , Wagner Benjamin , Young Amanda J. , Grandizio Louis Christopher , Cush Gerard 
Published: April 2021

Background: At present, the geographic distribution of orthopedic foot and ankle (OFA) surgeons in the United States is poorly defined. The purpose of this investigation is to determine the geographic distribution of OFA surgeons in the United States. We hypothesize that there will be differences in OFA surgeon density throughout the United States and that economic factors may play a role in access to subspecialty OFA care. Methods: A current membership list was obtained from the American Orthopaedic Foot & Ankle Society (AOFAS). Active members were categorized relative to states and US congressional districts, using publicly available census data. The relationship between income and surgeon density was determined using a Pearson correlation. Results: We identified a list of 1103 active AOFAS members. There was an average of 0.38 and 0.40 OFA surgeons per 100 000 people in each state and congressional district, respectively. We found a weak negative relationship demonstrating that regions with higher levels of poverty had fewer OFA surgeons, with a Pearson correlation coefficient of –0.14 (95% CI: –0.24, –0.04), P = .008. Conclusion: There is wide geographic variation of OFA surgeon density throughout the United States. Regions with higher levels of poverty were weakly associated with decreased population density of OFA surgeons compared to regions with lower poverty levels. Understanding these trends may aid in developing both recruitment and referral strategies for complex foot and ankle care in underserved regions. Level of Evidence: Level V.
Diagnostic Performance of Ultrasonography in Patients With Pneumonia: An Updated Comparative Systematic Review and Meta-analysis
Authors: Sistani Sharareh Sanei , Parooie Fateme 
Published: April 2021

Objectives: A chest radiograph (CXR) is still the preferred diagnostic method when pneumonia is suspected, although the sensitivity is relatively low. The aim of this study was to compare the diagnostic sensitivity, specificity, and accuracy of ultrasonography (US) for the diagnosis of community-acquired pneumonia (CAP), compared with CXR. Materials and Methods: A principled search was conducted to identify original English articles using PubMed, EMBASE, Web of Science, Scopus, and the Cochrane library, with the end date of October 2020. A combination of keywords, such as “ultrasound” or “ultrasonography,” “pneumonia,” “sensitivity,” and “specificity,” was used. Methodologic quality was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 criteria. Statistical analysis was completed on the resulting study data. Results: The search produced 16 eligible articles that reported on 2040 patients. The overall pooled sensitivity for US and CXR, to diagnose pneumonia, was 0.96 and 0.65, respectively. The overall pooled specificity for US and CXR was 0.85 and 0.81, respectively. The overall pooled positive likelihood ratio for US and CXR was 9.74 and 3.67, respectively. The negative likelihood ratio for US and CXR was 0.05 and 0.42, respectively. In addition, summary receiver operative characteristics areas under the curve were 0.98 for US and 0.77 for CXR. Conclusion: This review demonstrated that lung US is a useful technique for the diagnosis of pneumonia. This diagnostic method can be used by emergency physicians with high accuracy, sensitivity, and specificity. Among an elderly population, this diagnostic method may be a better choice than CXR. The rapid performance of lung US may facilitate a quick, cost-effective, and safe diagnosis of this potentially fatal disease.
Type 2 diabetes risk in sarcoidosis patients untreated and treated with corticosteroids
Authors: Entrop Joshua P. , Kullberg Susanna , Grunewald Johan , Eklund Anders , Brismar Kerstin , Arkema Elizabeth V. 
Published: April 2021

BackgroundThe rate of type 2 diabetes mellitus (T2D) is increased in sarcoidosis patients but it is unknown if corticosteroid treatment plays a role. We investigated whether the T2D risk is higher in untreated and corticosteroid-treated sarcoidosis patients compared with the general population.MethodsIn this cohort study, individuals with two or more International Statistical Classification of Diseases and Related Health Problems (ICD) codes for sarcoidosis were identified from the Swedish National Patient Register (NPR) (n=5754). Corticosteroid dispensations within 3 months before or after the first sarcoidosis diagnosis were identified from the Swedish Prescribed Drug Register (PDR). General population comparators without sarcoidosis were matched to cases 10:1 on age, sex and region of residence (n=61 297). Incident T2D was identified using ICD codes (NPR) and antidiabetic drug dispensations (PDR). Follow-up was from the second sarcoidosis diagnosis/matching date until T2D, emigration, death or study end (December 2013). Cox regression models adjusted for age, sex, education, country of birth, healthcare regions and family history of diabetes were used to estimate hazard ratios (HRs). We used flexible parametric models to examine the T2D risk over time.Results40% of sarcoidosis patients were treated with corticosteroid at diagnosis. The T2D rate was 7.7 per 1000 person-years in untreated sarcoidosis, 12.7 per 1000 person-years in corticosteroid-treated sarcoidosis and 5.5 per 1000 person-years in comparators. The HR for T2D was 1.4 (95% CI 1.2–1.8) associated with untreated sarcoidosis and 2.3 (95% CI 2.0–3.0) associated with corticosteroid-treated sarcoidosis. The T2D risk was highest for corticosteroid-treated sarcoidosis in the first 2 years after diagnosis.ConclusionsSarcoidosis is associated with an increased risk of T2D especially in older, male, corticosteroid-treated patients at diagnosis. Screening for T2D for these patients is advisable.
High serum granulocyte-colony stimulating factor characterises neutrophilic COPD exacerbations associated with dysbiosis
Authors: Chakrabarti Arindam , Mar Jordan S. , Choy David F. , Cao Yi , Rathore Nisha , Yang Xiaoying , Tew Gaik W. , Li Olga , Woodruff Prescott G. , Brightling Christopher E. , Grimbaldeston Michele , Christenson Stephanie A. , Bafadhel Mona , Rosenberger Carrie M. 
Published: April 2021

IntroductionCOPD exacerbations are heterogeneous and can be triggered by bacterial, viral, or noninfectious insults. Exacerbations are also heterogeneous in neutrophilic or eosinophilic inflammatory responses. A noninvasive peripheral biomarker of COPD exacerbations characterised by bacterial/neutrophilic inflammation is lacking. Granulocyte-colony stimulating factor (G-CSF) is a key cytokine elevated during bacterial infection and mediates survival, proliferation, differentiation and function of neutrophils.ObjectiveWe hypothesised that high peripheral G-CSF would be indicative of COPD exacerbations with a neutrophilic and bacterial phenotype associated with microbial dysbiosis.MethodsSerum G-CSF was measured during hospitalised exacerbation (day 0 or D0) and after 30 days of recovery (Day30 or D30) in 37 subjects. In a second cohort, serum and sputum cytokines were measured in 59 COPD patients during stable disease, at exacerbation, and at 2-weeks and 6-weeks following exacerbation.ResultsSerum G-CSF was increased during exacerbation in a subset of patients. These exacerbations were enriched for bacterial but not viral or type-2 biologies. The median serum G-CSF level was 1.6-fold higher in bacterial exacerbation compared to nonbacterial exacerbation (22 pg·mL−1versus13 pg·mL−1, p=0.0007). Serum G-CSF classified bacterial exacerbations with an area under the curve (AUC) for the receiver operating characteristic (ROC) curve equal to 0.76. Exacerbations with a two-fold or greater increase in serum G-CSF were characterised by neutrophilic inflammation, with increased sputum and blood neutrophils, and high sputum interleukin (IL)-1β, IL-6 and serum amyloid A1 (SAA1) levels. These exacerbations were preceded by dysbiosis, with decreased microbiome diversity and enrichment of respiratory pathogens such asHaemophilusandMoraxella. Furthermore, serum G-CSF at exacerbation classified neutrophilic-dysbiotic exacerbations (AUC for the ROC curve equal to 0.75).ConclusionsHigh serum G-CSF enriches for COPD exacerbations characterised by neutrophilic inflammation with underlying bacterial dysbiosis.
Endothelial dysfunction in COPD: a systematic review and meta-analysis of studies using different functional assessment methods
Authors: Theodorakopoulou Marieta P. , Alexandrou Maria Eleni , Bakaloudi Dimitra Rafailia , Pitsiou Georgia , Stanopoulos Ioannis , Kontakiotis Theodoros , Boutou Afroditi K. 
Published: April 2021

BackgroundCardiovascular disease is a major cause of morbidity and mortality in COPD. Endothelial dysfunction is suggested to be one of the pathogenetic mechanisms involved. This is a systematic review and meta-analysis of studies using any available functional method to examine differences in endothelial function between patients with COPD and individuals without COPD (controls).MethodsLiterature search involved PubMed and Scopus databases. Eligible studies included adult patients and evaluated endothelial damageviafunctional methods. The Newcastle–Ottawa scale was applied to evaluate the quality of retrieved studies. Subgroup analyses were performed to explore heterogeneity across the studies. Funnel plots were constructed to evaluate publication bias.ResultsOf the 21 reports initially identified, 19 studies with a total of 968 participants were included in the final meta-analysis. A significantly impaired response in endothelium-dependent (weighted mean between-group difference (WMD) −2.59, 95% CI −3.75 to −1.42) and -independent vasodilation (WMD −3.13, 95% CI −5.18 to −1.09) was observed in patients with COPD compared to controls. When pooling all studies together, regardless of the technique used for assessment of vascular reactivity, pronounced endothelial dysfunction was observed in COPD compared to controls (standardised mean difference (SMD) −1.19, 95% CI −1.69 to −0.68). Subgroup analysis showed that the difference was larger when patients with COPD were compared with nonsmoking controls (SMD −1.75, 95% CI −2.58 to −0.92). Sensitivity analyses confirmed the results.ConclusionsPatients with COPD have significantly impaired endothelial function compared to controls without COPD. Future studies should delineate the importance of endothelial dysfunction towards development of cardiovascular disease in COPD.
LncRNA XIST upregulates TRIM25 via negatively regulating miR-192 in hepatitis B virus-related hepatocellular carcinoma
Authors: Wang Jiancheng , Yin Gang , Bian Hu , Yang Jiangli , Zhou Pengcheng , Yan Kai , Liu Cheng , Chen Pei , Zhu Jun , Li Zhi , Xue Tongqing 
Published: April 2021

Abstract
Background
Long non-coding RNA (lncRNA) XIST has been implicated in the progression of a variety of tumor diseases. The purpose of this study was to explore the molecular role of lncRNA XIST in human hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

Methods
The expression levels of lncRNA XIST, miR-192 and TRIM25 in HBV-related HCC tissues and HepG2.2.15 cells were detected by qRT-PCR. Biological information and luciferin gene reporter assay were performed to detect the interaction among lncRNA XIST, miR-192 and TRIM25. CCk-8 assay, wound healing assay and colony formation assay were conducted to detect the proliferation and migration ability of HepG2.2.15 cells.

Results
qRT-PCR results showed that the expression levels of lncRNA XIST were remarkably increased in HBV-related HCC tissues and HepG2.2.15 cells. In addition, miR-192 was a direct target gene of lncRNA XIST, and the expression of miR-192 and lncRNA XIST were negatively correlated. Moreover, overexpression of miR-192 observably inhibited the proliferation and migration of HCC cells, while overexpression of lncRNA XIST showed an opposite effect. Furthermore, TRIM25 was a direct target of miR-192, and lncRNA XIST could up-regulate the expression of TRIM25 by targeting miR-192.

Conclusion
LncRNA XIST could up-regulate the expression of TRIM25 by targeting and binding to miR-192, thus accelerating the occurrence and development of HCC.
Localized environmental heterogeneity drives the population differentiation of two endangered and endemic Opisthopappus Shih species
Authors: Ye Hang , Wang Zhi , Hou Huimin , Wu Jiahui , Gao Yue , Han Wei , Ru Wenming , Sun Genlou , Wang Yiling 
Published: April 2021

Abstract
Background
Climate heterogeneity not only indirectly shapes the genetic structures of plant populations, but also drives adaptive divergence by impacting demographic dynamics. The variable localized climates and topographic complexity of the Taihang Mountains make them a major natural boundary in Northern China that influences the divergence of organisms distributed across this region. Opisthopappus is an endemic genus of the Taihang Mountains that includes only two spatially partitioned species Opisthopappus longilobus and Opisthopappus taihangensis. For this study, the mechanisms behind the genetic variations in Opisthopappus populations were investigated.

Results
Using SNP and InDel data coupled with geographic and climatic information, significant genetic differentiation was found to exist either between Opisthopappus populations or two species. All studied populations were divided into two genetic groups with the differentiation of haplotypes between the groups. At approximately 17.44 Ma of the early Miocene, O. taihangensis differentiated from O. longilobus under differing precipitation regimes due to the intensification of the Asian monsoon. Subsequently, intraspecific divergence might be induced by the dramatic climatic transformation from the mid- to late Miocene. During the Pleistocene period, the rapid uplift of the Taihang Mountains coupled with violent climatic oscillations would further promote the diversity of the two species. Following the development of the Taihang Mountains, its complex topography created geographical and ecological heterogeneity, which could lead to spatiotemporal isolation between the Opisthopappus populations. Thus the adaptive divergence might occur within these intraspecific populations in the localized heterogeneous environment of the Taihang Mountains.

Conclusions
The localized environmental events through the integration of small-scale spatial effects impacted the demographic history and differentiation mechanism of Opisthopappus species in the Taihang Mountains. The results provide useful information for us to understand the ecology and evolution of organisms in the mountainous environment from population and species perspective.
Temporal transcriptome profiling of developing seeds reveals candidate genes involved in oil accumulation in safflower (Carthamus tinctorius L.)
Authors: Li Dandan , Wang Qing , Xu Xin , Yu Jingsheng , Chen Zhiyu , Wei Bo , Wu Wei 
Published: April 2021

Abstract
Background
The investigation of molecular mechanisms involved in lipid metabolism plays a critical role for the genetic engineering of safflower (Carthamus tinctorius L.) to increase the oil accumulation level or to change the oil composition. Although transcript sequences are currently available for the leaves and flowers of safflower, a wide range scan of temporal transcripts at different stages of seed development has not been conducted for safflower.

Results
In this study, temporal transcriptome sequencing was executed at 10, 14, 18, and 22 days after flowering (DAF) to uncover the molecular networks concerned in the biosynthesis of unsaturated fatty acids (USFAs). The results revealed that the biosynthesis of fatty acids is a dominant cellular process from 10 to 14 DAF, while degradation mainly happens after 18 DAF. Significant expression changes of two genes, stearoyl-[acyl-carrier-protein] 9-desaturase gene (SAD) from 10 to 14 DAF and oleate desaturase (FAD2–1) from 14 to 18 DAF, were detected at the transcriptomic levels, and the temporal expression patterns revealed by the transcriptomic analysis were confirmed using quantitative real-time PCR experiments. In addition, 13 candidate transcription factors (TFs) involved in regulating the expression level of the FAD2–1 gene were identified.

Conclusions
These results create a link between fatty acid biosynthesis and gene expression at different developmental stages of the seeds, provide insight into the underlying lipid metabolism, and meanwhile lay an important foundation for the genetic engineering of safflower varieties. We have identified novel candidate genes, including TFs, that are worthy of further exploration.
Differentiation of brain metastases from small and non-small lung cancers using apparent diffusion coefficient (ADC) maps
Authors: Müller Sebastian Johannes , Khadhraoui Eya , Neef Nicole E. , Riedel Christian Heiner , Ernst Marielle 
Published: April 2021

Abstract
Background
Brain metastases are particularly common in patients with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC showing a less aggressive clinical course and lower chemo- and radio sensitivity compared to SCLC. Early adequate therapy is highly desirable and depends on a reliable classification of tumor type. The apparent diffusion coefficient is a noninvasive neuroimaging marker with the potential to differentiate between major histological subtypes. Here we determine the sensitivity and specificity of the apparent diffusion coefficient to distinguish between NSCLC and SCLC.

Methods
We enrolled all NSCLC and SCLC patients diagnosed between 2008 and 2019 at the University Medical Center Göttingen. Cranial MR scans were visually inspected for brain metastases and the ratio of the apparent diffusion coefficient (ADC) was calculated by dividing the ADC measured within the solid part of a metastasis by a reference ADC extracted from an equivalent region in unaffected tissue on the contralateral hemisphere.

Results
Out of 411 enrolled patients, we detected 129 patients (83 NSCLC, 46 SCLC) with sufficiently large brain metastases with histologically classified lung cancer and no hemorrhage. We analyzed 185 brain metastases, 84 of SCLC and 101 of NSCLC. SCLC brain metastases showed an ADC ratio of 0.68 ± 0.12 SD, and NSCLC brain metastases showed an ADC ratio of 1.47 ± 0.31 SD. Receiver operating curve statistics differentiated brain metastases of NSCLC from SCLC with an area under the curve of 0.99 and a 95% CI of 0.98 to 1, p < 0.001. Youden's J cut-point is 0.97 at a sensitivity of 0.989 and a specificity of 0.988.

Conclusions
In patients with lung cancer and brain metastases with solid tumor parts, ADC ratio enables an ad hoc differentiation of SCLC and NSCLC, easily achieved during routine neuroradiological examination. Non-invasive MR imaging enables an early-individualized management of brain metastases from lung cancer.
Trial registration: The study was registered in the German Clinical Trials Register (DRKS00023016).