bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Alterations in Pediatric Fibroblastic/Myofibroblastic Tumors: An Appraisal of a Next Generation Sequencing Assay in a Retrospective Single Centre Study
Authors: Slack Jonathan C , Bründler Marie-Anne , Nohr Erik , McIntyre John B , Kurek Kyle C 
Published: May 2021

Background Pediatric fibroblastic/myofibroblastic tumors (PFMTs) can be challenging to definitively classify. Large case series or diagnostic updates have not been recently published despite identification of molecular alterations that could improve diagnostic accuracy. Our review of the literature found that over two-thirds of the more than 30 types of PFMTs harbor recurrent molecular alterations. We performed an institutional review of PFMTs to highlight limitations of a predominantly morphological classification, and evaluated the utility of a next-generation sequencing assay to aid diagnosis. Methods PFMTs identified over a period of 12 years were reviewed, categorized per the new WHO classification, and tested using the Oncomine Childhood Cancer Research Assay. Results Eighty-seven specimens from 58 patients were reviewed; 50 were chosen for molecular analysis, 16 (32%) lacking definitive classification. We identified alterations, some novel, in 33% of assayed cases. Expected alterations were identified for most known diagnoses and mutations were identified in 6 of 16 tumors (38%) that were initially unclassified. Conclusion We confirmed a significant subset of PFMTs remain difficult to classify using current criteria, and that a combined DNA/RNA assay can identify alterations in many of these cases, improving diagnostic certainty and suggesting a clinical utility for challenging cases.
Application of OSNA Nomogram in Patients With Macrometastatic Sentinel Lymph Node: A Retrospective Assessment of Accuracy
Authors: Combi Francesca , Andreotti Alessia , Gambini Anna , Palma Enza , Papi Simona , Biroli Alice , Zaccarelli Stefania , Ficarra Guido , Tazzioli Giovanni 
Published: May 2021

Introduction: Almost 50% to 70% of patients who undergo axillary lymph node dissection (ALND) because of a single metastatic sentinel lymph node (SLN) have no further metastatic nodes at the axillary histology. On these grounds, the one-step nucleic acid amplification (OSNA) nomogram was designed and validated. As a mathematical model, calculated through tumor size (expressed in millimeters) and CK19 mRNA copy number, it is thought to predict nonsentinel lymph node (NSLN) status. The aim of the study is to verify the diagnostic accuracy of the OSNA nomogram in a group of patients with macrometastatic SLN, with a retrospective analysis. Methods: The OSNA nomogram was retrospectively applied to a group of 66 patients with macrometastatic SLN who underwent ALND. The result of the final histology of the axillary cavity was compared to the nomogram prediction. We calculated the prevalence of NSLN metastasis in patients who underwent ALND, sensitivity and specificity, negative and positive predictive value of the nomogram. Results: In patients with macrometastasis in SLN, the prevalence of patients with metastatic NSLN was 45%. The sensitivity of the nomogram was excellent (90%). The specificity was low (36%). Positive predictive value amounted to 54%, while negative predictive value was good (81%). Conclusions: These results suggest that the OSNA nomogram is a valid instrument that can help choose the best surgical strategy for the treatment of axillary cavity. The mathematical model is useful to avoid surgery in a selected group of patients because it accurately predicts NSLN status.
Shoulder Arthroscopy Simulator Training Improves Surgical Procedure Performance: A Controlled Laboratory Study
Authors: Hauschild Jordan , Rivera Jessica C. , Johnson Anthony E. , Burns Travis C. , Roach Christopher J. 
Published: May 2021

Background: Previous simulation studies evaluated either dry lab (DL) or virtual reality (VR) simulation, correlating simulator training with the performance of arthroscopic tasks. However, these studies did not compare simulation training with specific surgical procedures. Purpose/Hypothesis: To determine the effectiveness of a shoulder arthroscopy simulator program in improving performance during arthroscopic anterior labral repair. It was hypothesized that both DL and VR simulation methods would improve procedure performance; however, VR simulation would be more effective based on the validated Arthroscopic Surgery Skill Evaluation Tool (ASSET) Global Rating Scale. Study Design: Controlled laboratory study. Methods: Enrolled in the study were 38 orthopaedic residents at a single institution, postgraduate years (PGYs) 1 to 5. Each resident completed a pretest shoulder stabilization procedure on a cadaveric model and was then randomized into 1 of 2 groups: VR or DL simulation. Participants then underwent a 4-week arthroscopy simulation program and completed a posttest. Sports medicine–trained orthopaedic surgeons graded the participants on completeness of the surgical repair at the time of the procedure, and a single, blinded orthopaedic surgeon, using the ASSET Global Rating Scale, graded participants’ arthroscopy skills. The procedure step and ASSET grades were compared between simulator groups and between PGYs using paired t tests. Results: There was no significant difference between the groups in pretest performance in either the procedural steps or ASSET scores. Overall procedural step scores improved after combining both types of simulator training ( P = .0424) but not in the individual simulation groups. The ASSET scores improved across both DL ( P = .0045) and VR ( P = .0003), with no significant difference between the groups. Conclusion: A 4-week simulation program can improve arthroscopic skills and performance during a specific surgical procedure. This study provides additional evidence regarding the benefits of simulator training in orthopaedic surgery for both novice and experienced arthroscopic surgeons. There was no statistically significant difference between the VR and DL models, which disproved the authors’ hypothesis that the VR simulator would be the more effective simulation tool. Clinical Relevance: There may be a role for simulator training in the teaching of arthroscopic skills and learning of specific surgical procedures.
Episodes of fissure formation in the Alps: connecting quartz fluid inclusion, fissure monazite age, and fissure orientation data
Authors: Gnos Edwin , Mullis Josef , Ricchi Emmanuelle , Bergemann Christian A. , Janots Emilie , Berger Alfons 
Published: May 2021

AbstractFluid assisted Alpine fissure-vein and cleft formation starts at prograde, peak or retrograde metamorphic conditions of 450–550 °C and 0.3–0.6 GPa and below, commonly at conditions of ductile to brittle rock deformation. Early-formed fissures become overprinted by subsequent deformation, locally leading to a reorientation. Deformation that follows fissure formation initiates a cycle of dissolution, dissolution/reprecipitation or new growth of fissure minerals enclosing fluid inclusions. Although fissures in upper greenschist and amphibolite facies rocks predominantly form under retrograde metamorphic conditions, this work confirms that the carbon dioxide fluid zone correlates with regions of highest grade Alpine metamorphism, suggesting carbon dioxide production by prograde devolatilization reactions and rock-buffering of the fissure-filling fluid. For this reason, fluid composition zones systematically change in metamorphosed and exhumed nappe stacks from diagenetic to amphibolite facies metamorphic rocks from saline fluids dominated by higher hydrocarbons, methane, water and carbon dioxide. Open fissures are in most cases oriented roughly perpendicular to the foliation and lineation of the host rock. The type of fluid constrains the habit of the very frequently crystallizing quartz crystals. Open fissures also form in association with more localized strike-slip faults and are oriented perpendicular to the faults. The combination of fissure orientation, fissure quartz fluid inclusion and fissure monazite-(Ce) (hereafter monazite) Th–Pb ages shows that fissure formation occurred episodically (1) during the Cretaceous (eo-Alpine) deformation cycle in association with exhumation of the Austroalpine Koralpe-Saualpe region (~ 90 Ma) and subsequent extensional movements in association with the formation of the Gosau basins (~ 90–70 Ma), (2) during rapid exhumation of high-pressure overprinted Briançonnais and Piemontais units (36–30 Ma), (3) during unroofing of the Tauern and Lepontine metamorphic domes, during emplacement and reverse faulting of the external Massifs (25–12 Ma; except Argentera) and due to local dextral strike-slip faulting in association with the opening of the Ligurian sea, and (4) during the development of a young, widespread network of ductile to brittle strike-slip faults (12–5 Ma).
Association between suicidal risks and medication-overuse headache in chronic migraine: a cross-sectional study
Authors: Wang Yen-Feng , Yu Chia-Chun , Kuan Ai Seon , Chen Shih-Pin , Wang Shuu-Jiun 
Published: May 2021

Abstract
Background
Behaviors of substance dependence are common among patients with medication-overuse headache (MOH). Whether MOH, like other substance use disorders, is associated with an increased risk for suicide is unknown.

Methods
In this cross-sectional study, newly diagnosed chronic migraine (CM) patients with or without coexisting MOH were enrolled prospectively. Headache diagnoses were made through face-to-face interviews by headache specialists, and a specifically designed questionnaire was used to collect demographics, headache profiles, Migraine Disability Assessment, Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, etc. Suicidal ideation and prior suicide attempt were specifically questioned.

Results
In total, 603 CM patients (485F/118M, mean age 42.03 ± 12.18 years) were recruited, including 320 with MOH (257F/63M, mean age 42.8 ± 11.7 years) (53.1%), and 214 (35.5%) and 81 (13.4%) had suicidal ideation and prior suicide attempt, respectively. Among CM patients, the presence of MOH increased the risks of suicidal ideation (odds ratio [OR] = 1.75 [95% CI = 1.20–2.56], p = 0.004) and prior suicide attempt (OR = 1.88 [1.09–3.24], p = 0.024), after controlling for demographics, headache profile, disabilities, symptoms of anxiety and depression, and sleep quality.

Conclusions
In CM patients, MOH is associated with an increased risk for suicidal ideation and prior suicide attempt, which deserves attention for clinicians taking care of headache patients. However, further studies are needed to determine the causal relationship, as well as the underlying pathophysiology.
DR2S: an integrated algorithm providing reference-grade haplotype sequences from heterozygous samples
Authors: Klasberg Steffen , Schmidt Alexander H. , Lange Vinzenz , Schöfl Gerhard 
Published: May 2021

Abstract
Background
High resolution HLA genotyping of donors and recipients is a crucially important prerequisite for haematopoetic stem-cell transplantation and relies heavily on the quality and completeness of immunogenetic reference sequence databases of allelic variation.

Results
Here, we report on , an R package that leverages the strengths of two sequencing technologies—the accuracy of next-generation sequencing with the read length of third-generation sequencing technologies like PacBio’s SMRT sequencing or ONT’s nanopore sequencing—to reconstruct fully-phased high-quality full-length haplotype sequences. Although optimised for HLA and KIR genes, is applicable to all loci with known reference sequences provided that full-length sequencing data is available for analysis. In addition, integrates supporting tools for easy visualisation and quality control of the reconstructed haplotype to ensure suitability for submission to public allele databases.

Conclusions
is a largely automated workflow designed to create high-quality fully-phased reference allele sequences for highly polymorphic gene regions such as HLA or KIR. It has been used by biologists to successfully characterise and submit more than 500 HLA alleles and more than 500 KIR alleles to the IPD-IMGT/HLA and IPD-KIR databases.
Identification of the conserved long non-coding RNAs in myogenesis
Authors: Bhattacharya Anupam , Champramary Simang , Tripathi Tanya , Thakur Debajit , Ioshikhes Ilya , Singh Satyendra Kumar , Nandi Soumyadeep 
Published: May 2021

Abstract
Background
Our understanding of genome regulation is ever-evolving with the continuous discovery of new modes of gene regulation, and transcriptomic studies of mammalian genomes have revealed the presence of a considerable population of non-coding RNA molecules among the transcripts expressed. One such non-coding RNA molecule is long non-coding RNA (lncRNA). However, the function of lncRNAs in gene regulation is not well understood; moreover, finding conserved lncRNA across species is a challenging task. Therefore, we propose a novel approach to identify conserved lncRNAs and functionally annotate these molecules.

Results
In this study, we exploited existing myogenic transcriptome data and identified conserved lncRNAs in mice and humans. We identified the lncRNAs expressing differentially between the early and later stages of muscle development. Differential expression of these lncRNAs was confirmed experimentally in cultured mouse muscle C2C12 cells. We utilized the three-dimensional architecture of the genome and identified topologically associated domains for these lncRNAs. Additionally, we correlated the expression of genes in domains for functional annotation of these trans-lncRNAs in myogenesis. Using this approach, we identified conserved lncRNAs in myogenesis and functionally annotated them.

Conclusions
With this novel approach, we identified the conserved lncRNAs in myogenesis in humans and mice and functionally annotated them. The method identified a large number of lncRNAs are involved in myogenesis. Further studies are required to investigate the reason for the conservation of the lncRNAs in human and mouse while their sequences are dissimilar. Our approach can be used to identify novel lncRNAs conserved in different species and functionally annotated them.
Variations in volume of emergency surgeries and emergency department access at a third level hospital in Milan, Lombardy, during the COVID-19 outbreak
Authors: Castoldi Laura , Solbiati Monica , Costantino Giorgio , Casiraghi Elena 
Published: May 2021

Abstract
Background
During the recent outbreak of COVID-19 (coronavirus disease 2019), Lombardy was the most affected region in Italy, with 87,000 patients and 15,876 deaths up to May 26, 2020. Since February 22, 2020, well before the Government declared a state of emergency, there was a huge reduction in the number of emergency surgeries performed at hospitals in Lombardy. A general decrease in attendance at emergency departments (EDs) was also observed. The aim of our study is to report the experience of the ED of a third-level hospital in downtown Milan, Lombardy, and provide possible explanations for the observed phenomena.

Methods
This retrospective, observational study assessed the volume of emergency surgeries and attendance at an ED during the course of the pandemic, i.e. immediately before, during and after a progressive community lockdown in response to the COVID-19 pandemic. These data were compared with data from the same time periods in 2019. The results are presented as means, standard error (SE), and 95% studentized confidence intervals (CI). The Wilcoxon rank signed test at a 0.05 significance level was used to assess differences in per-day ED access distributions.

Results
Compared to 2019, a significant overall drop in emergency surgeries (60%, p < 0.002) and in ED admittance (66%, p ≅ 0) was observed in 2020. In particular, there were significant decreases in medical (40%), surgical (74%), specialist (ophthalmology, otolaryngology, traumatology, and urology) (92%), and psychiatric (60%) cases. ED admittance due to domestic violence (59%) and individuals who left the ED without being seen (76%) also decreased. Conversely, the number of deaths increased by 196%.

Conclusions
During the COVID-19 outbreak the volume of urgent surgeries and patients accessing our ED dropped. Currently, it is not known if mortality of people who did not seek care increased during the pandemic. Further studies are needed to understand if such reductions during the COVID-19 pandemic will result in a rebound of patients left untreated or in unwanted consequences for population health.
Measurement of fasting breath hydrogen concentration as a simple diagnostic method for pancreatic exocrine insufficiency
Authors: Uetsuki Kota , Kawashima Hiroki , Ohno Eizaburo , Ishikawa Takuya , Iida Tadashi , Yamamoto Kenta , Furukawa Kazuhiro , Nakamura Masanao , Honda Takashi , Ishigami Masatoshi , Hirooka Yoshiki , Fujishiro Mitsuhiro 
Published: May 2021

Abstract
Background
Pancreatic exocrine insufficiency (PEI) is associated with the outcome of pancreatic disease. However, there is no method for assessing PEI that can be used noninvasively and easily for outpatient. It has been reported that changes in intestinal bacteria caused by PEI may increase breath hydrogen concentration (BHC) levels during glucose or lactose loading. We have evaluated the usefulness of fasting breath hydrogen concentration (FBHC) measurement without glucose loading for the evaluation of PEI.

Methods
Sixty patients underwent FBHC measurement, BT-PABA testing, and microbiome analysis. They were classified into PEI group (PABA excretion rate < 73.4%, n = 30) and non-PEI group (n = 30). The FBHC of the two groups were compared, and the diagnostic ability of PEI by them was evaluated. The 16 s rRNA (V3–V4) from fecal samples was analyzed by MiSeq.

Results
FBHC levels was higher in the PEI group 15.70 (1.4 to 77.0) ppm than in the non-PEI group 2.80 (0.7 to 28.2) ppm (P < 0.0001). FBHC was negatively correlated with PABA excretion rate (r =  − 0.523, P < 0.001). The cutoff value of FBHC of 10.7 ppm (95% CI: 0.678–0.913, P < 0.001) showed a sensitivity of 73.3% and specificity of 83.3% for PEI diagnosis. In the PEI group, there was a significant increase of relative abundance of phylum Firmicutes (P < 0.05) and the genus Clostridium (P < 0.05).

Conclusion
FBHC shows good potential as a simple and repeatable test for the diagnosis of PEI. The elevated FBHC levels may be caused by hydrogen-producing bacteria such as Clostridium.
Prevalence of and risk factors for metabolic associated fatty liver disease in an urban population in China: a cross-sectional comparative study
Authors: Chen Yu-ling , Li Hao , Li Shu , Xu Zhou , Tian Shen , Wu Juan , Liang Xin-yu , Li Xin , Liu Zi-li , Xiao Jun , Wei Jia-ying , Ma Chen-yu , Wu Kai-nan , Ran Liang , Kong Ling-quan 
Published: May 2021

Abstract
Background
Metabolic associated fatty liver disease (MAFLD) is a new definition for liver disease associated with known metabolic dysfunction. Based on new diagnostic criteria, we aimed to investigate its prevalence and risk factors in Chinese population.

Methods
We conducted this study in a health examination population who underwent abdominal ultrasonography in China. The diagnosis of MAFLD was based on the new diagnostic criteria. The characteristics of the MAFLD population, as well as the associations between MAFLD and metabolic abnormalities, were explored. Mann–Whitney U test and chi-square test were performed to compare different variables. Binary logistic regression was used to determine the risk factors for MAFLD.

Results
Among 139,170 subjects, the prevalence of MAFLD was 26.1% (males: 35.4%; females: 14.1%). The prevalence based on female menopausal status, that is, premenopausal, perimenopausal, and postmenopausal, was 6.1%, 16.8%, and 30.2%, respectively. In different BMI groups (underweight, normal, overweight and obese), the prevalence was 0.1%, 4.0%, 27.4% and 59.8%, respectively. The proportions of abnormal metabolic features in the MAFLD group were significantly higher than those in the non-MAFLD group, as was the proportion of elevated alanine aminotransferase (ALT) (42.5% vs. 11%, P < 0.001). In nonobese individuals with MAFLD, the proportions of abnormal metabolic features were also all significantly higher than those in nonobese individuals without MAFLD. The prevalence of metabolic syndrome (MS), dyslipidaemia, and hyperuricaemia, respectively, in the MAFLD group (53.2%, 80.0%, and 45.0%) was significantly higher than that in the non-MAFLD group (10.1%, 41.7%, and 16.8%). Logistic regression revealed that age, BMI, waist circumference, ALT, triglycerides, fasting glucose, uric acid and platelet count were associated with MAFLD.

Conclusions
MAFLD is prevalent in China and varies considerably among different age, sex, BMI, and female menopausal status groups. MAFLD is related to metabolic disorders, especially obesity, while metabolic disorders also play important roles in the occurrence of MAFLD in nonobese individuals. MAFLD patients exhibit a high prevalence of MS, dyslipidaemia, hyperuricaemia, and elevated liver enzymes. MAFLD tends to coexist with systemic metabolic disorders, and a deep inner relationship may exist between MAFLD and MS. Metabolic disorders should be considered to improve the management of MAFLD.
Normalization of γ-glutamyl transferase levels is associated with better metabolic control in individuals with nonalcoholic fatty liver disease
Authors: Ma Qianqian , Liao Xianhua , Shao Congxiang , Lin Yansong , Wu Tingfeng , Sun Yanhong , Feng Shi-Ting , Ye Junzhao , Zhong Bihui 
Published: May 2021

Abstract
Background
The normalization of liver biochemical parameters usually reflects the histological response to treatment for nonalcoholic fatty liver disease (NAFLD). Researchers have not clearly determined whether different liver enzymes exhibit various metabolic changes during the follow-up period in patients with NAFLD.

Methods
We performed a retrospective analysis of patients with NAFLD who were receiving therapy from January 2011 to December 2019. Metabolism indexes, including glucose levels, lipid profiles, uric acid levels and liver biochemical parameters, were measured. Magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) and liver ultrasound were used to evaluate steatosis. All patients received recommendations for lifestyle modifications and guideline-recommended pharmacological treatments with indications for drug therapy for metabolic abnormalities.

Results
Overall, 1048 patients with NAFLD were included and received lifestyle modification recommendations and pharmaceutical interventions, including 637 (60.7%) patients with abnormal GGT levels and 767 (73.2%) patients with abnormal ALT levels. Patients with concurrent ALT and GGT abnormalities presented higher levels of metabolism indexes and higher liver fat content than those in patients with single or no abnormalities. After 12 months of follow-up, the cumulative normalization rate of GGT was considerably lower than that of ALT (38% vs. 62%, P < 0.001). Greater weight loss resulted in higher cumulative normalization rates of GGT and ALT. Weight loss (OR = 1.21, 95% CI 1.11–1.32, P < 0.001), ALT normalization (OR = 2.75, 95% CI 1.41–5.36, P = 0.01) and lower TG and HOMA-IR values (OR = 2.03, 95% CI 1.11–3.71, P = 0.02; OR = 2.04, 95% CI 1.07–3.89, P = 0.03) were independent protective factors for GGT normalization. Elevated baseline GGT (OR = 0.99, 95% CI 0.98–0.99, P = 0.01) was a risk factor.

Conclusions
For NAFLD patients with concurrently increased ALT and GGT levels, a lower normalization rate of GGT was observed, rather than ALT. Good control of weight and insulin resistance was a reliable predictor of GGT normalization.