bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Musculoskeletal and Pulmonary Bacterial Infections With [124I]FIAU PET/CT
Authors: Cho Steve Y. , Rowe Steven P. , Jain Sanjay K. , Schon Lew C. , Yung Rex C. , Nayfeh Tariq A. , Bingham Clifton O. , Foss Catherine A. , Nimmagadda Sridhar , Pomper Martin G. 
Published: June 2020

Purpose: Imaging is limited in the evaluation of bacterial infection. Direct imaging of in situ bacteria holds promise for noninvasive diagnosis. We investigated the ability of a bacterial thymidine kinase inhibitor ([124I]FIAU) to image pulmonary and musculoskeletal infections. Methods: Thirty-three patients were prospectively accrued: 16 with suspected musculoskeletal infection, 14 with suspected pulmonary infection, and 3 with known rheumatoid arthritis without infection. Thirty-one patients were imaged with [124I]FIAU PET/CT and 28 with [18F]FDG PET/CT. Patient histories were reviewed by an experienced clinician with subspecialty training in infectious diseases and were determined to be positive, equivocal, or negative for infection. Results: Sensitivity, specificity, positive-predictive value, negative-predictive value, and accuracy of [124I]FIAU PET/CT for diagnosing infection were estimated as 7.7% to 25.0%, 0.0%, 50%, 0.0%, and 20.0% to 71.4% for musculoskeletal infections and incalculable-100.0%, 51.7% to 72.7%, 0.0% to 50.0%, 100.0%, and 57.1% to 78.6% for pulmonary infections, respectively. The parameters for [18F]FDG PET/CT were 75.0% to 92.3%, 0.0%, 23.1% to 92.3%, 0.0%, and 21.4% to 85.7%, respectively, for musculoskeletal infections and incalculable to 100.0%, 0.0%, 0.0% to 18.2%, incalculable, and 0.0% to 18.2% for pulmonary infections, respectively. Conclusions: The high number of patients with equivocal clinical findings prevented definitive conclusions from being made regarding the diagnostic efficacy of [124I]FIAU. Future studies using microbiology to rigorously define infection in patients and PET radiotracers optimized for image quality are needed.
Performance of the European Society of Cardiology 0/1-hour algorithm in the diagnosis of myocardial infarction with high-sensitivity cardiac troponin: Systematic review and meta-analysis
Authors: Burgos Lucrecia M , Trivi Marcelo , Costabel Juan P 
Published: June 2020

Abstract

Introduction
A rapid rule-out or rule-in protocol based on the 0-hour/1-hour algorithm using high-sensitivity cardiac troponin (hs-cTn) is recommended by the European Society of Cardiology (ESC); recently multiple studies have validated it in their settings. We aimed to assess the diagnostic accuracy of the 2015 ESC guidelines for management of acute coronary syndrome in patients without ST-segment elevation 0-hour/1-hour algorithm using hs-cTn for the early rule-out and rule-in of acute myocardial infarction (AMI) on presentation.

Methods
Systematic searches were conducted using PubMed, the Cochrane Library and the International Clinical Trials Registry Platform to identify prospective studies from 2015 to October 2019 involving adults presenting to the emergency department with possible acute coronary syndrome in which hs-cTn measurements were obtained according to the ESC algorithm and AMI outcomes were adjudicated during the initial hospitalization.

Results
Eleven studies, involving 19,213 patients, were identified. Pooled prevalence of AMI during the index hospitalization was 11.3% (95% confidence interval (CI) 3.9–18.8%). Summary sensitivity and specificity in diagnosing AMI were 99% (95% CI 98–99%; I2 63%) and 91% (95% CI 91–92%; I2 96%) respectively. The summary positive likelihood ratio was 11.6 (95% CI 8.5–15.8; I2 97%) and the pooled likelihood ratio negative 0.02 (0.01–0.03; I2 52%). Cumulative all-cause mortality at 30 days in the rule-out group was 0.11%, and 2.8% in the rule-in group, and 30 days AMI in the rule-out group was 0.08%.

Conclusion
The ESC 0-hour/1-hour algorithm using high-sensitivity cardiac troponin has high diagnostic accuracy; it allows safe rule-out as well as accurate rule-in of AMI, with low cumulative 30-day mortality and AMI in patients assigned the rule-out zone.
Arthroscopic Modified Bosworth Procedure for Refractory Lateral Elbow Pain With Radiocapitellar Joint Snapping
Authors: Jeon In-Ho , Kwak Jae-Man , Zhu Bin , Sun Yucheng , Kim Hyojune , Koh Kyoung-Hwan , Kholinne Erica 
Published: June 2020

Background: Radiocapitellar joint snapping due to the presence of synovial plica has been described as a contributory intra-articular pathology of lateral epicondylitis (LE). Hypothesis: The arthroscopic modified Bosworth technique can provide a safe and favorable outcome for refractory LE with radiocapitellar snapping. Study Design: Case series; Level of evidence, 4. Methods: Patients treated with the arthroscopic modified Bosworth procedure for refractory LE with radiocapitellar joint snapping were included in this study. The sequential surgical procedures included excision of the upper portion of the anterolateral annular ligament, removal of the synovial plicae, and release of the extensor carpi radialis brevis for all patients. Clinical outcomes were measured at a minimum 1-year follow-up. Results: A total of 22 patients with a mean ± SD age of 51.2 ± 10.4 years were included in this study. The mean follow-up was 29.4 ± 7.7 months (range, 21-42 months). The overall visual analog scale score (from preoperative to final follow-up) was 7.5 ± 1.2 vs 2.5 ± 1.8 ( P < .001); flexion-extension motion arc was 133.8° ± 11.2° vs 146.4° ± 7.1° ( P = .001); pronation-supination motion arc was 101.8° ± 9.2° vs 141.7° ± 10.2° ( P = .001); Disabilities of the Arm, Shoulder and Hand score was 54.5 ± 13.2 vs 3.6 ± 4.1 ( P < .001); and Mayo Elbow Performance Score was 51.9 ± 12.2 vs 84.3 ± 10.3 ( P < .001). Conclusion: Radiocapitellar joint snapping may coexist with LE as a disease spectrum. The arthroscopic modified Bosworth technique provides safe and favorable outcomes for patients with refractory LE associated with radiocapitellar joint snapping.
Key diagnostic markers for autoimmune lymphoproliferative syndrome with molecular genetic diagnosis
Authors: Molnár Emese , Radwan Nesrine , Kovács Gábor , Andrikovics Hajnalka , Henriquez Frances , Zarafov Anton , Hayman Matthew , Linzner Daniela , Thrasher Adrian J. , Buckland Matthew , Burns Siobhan O. , Gilmour Kimberly C. 
Published: June 2020

Abstract
Autoimmune lymphoproliferative syndrome (ALPS) is a rare immunodeficiency caused by mutations in genes affecting the extrinsic apoptotic pathway (FAS, FASL, CASP10). This study evaluated the clinical manifestations, laboratory findings, and molecular genetic results of 215 patients referred as possibly having ALPS. Double-negative T-cell (DNT) percentage and in vitro apoptosis functional tests were evaluated by fluorescence-activated cell sorting; interleukin 10 (IL-10) and IL-18 and soluble FAS ligand (sFASL) were measured by enzyme-linked immunosorbent assay. Genetic analysis was performed by next-generation sequencing. Clinical background data were collected from patients’ records. Patients were categorized into definite, suspected, or unlikely ALPS groups, and laboratory parameters were compared among these groups. Of 215 patients, 38 met the criteria for definite ALPS and 17 for suspected ALPS. The definite and suspected ALPS patient populations showed higher DNT percentages than unlikely ALPS and had higher rates of lymphoproliferation. Definite ALPS patients had a significantly more abnormal in vitro apoptosis function, with lower annexin, than patients with suspected ALPS (P = .002) and patients not meeting ALPS criteria (P &lt; .001). The combination of elevated DNTs and an abnormal in vitro apoptosis functional test was the most useful in identifying all types of ALPS patients; the combination of an abnormal in vitro apoptosis functional test and elevated sFASLs was a predictive marker for ALPS-FAS group identification. Lymphoproliferation, apoptosis functional test, and DNTs are the most sensitive markers; elevated IL-10 and IL-18 are additional indicators for ALPS. The combination of elevated sFASLs and abnormal apoptosis function was the most valuable prognosticator for patients with FAS mutations.
Genetic mutations and features of mantle cell lymphoma: a systematic review and meta-analysis
Authors: Hill Holly A. , Qi Xinyue , Jain Preetesh , Nomie Krystle , Wang Yucai , Zhou Shouhao , Wang Michael L. 
Published: June 2020

AbstractMantle cell lymphoma (MCL) is an incurable rare subtype of non-Hodgkin lymphoma and is subject to relapse and therapeutic resistance. Molecular aberrations in MCL affect pathogenesis, prognosis, and therapeutic response. In this systematic review, we searched 3 databases and selected 32 articles that described mutations in MCL patients. We then conducted a meta-analysis using a Bayesian multiregression model to analyze patient-level data in 2127 MCL patients, including prevalence of mutations. In tumor or bone marrow samples taken at diagnosis or baseline, ATM was the most frequently mutated gene (43.5%) followed by TP53 (26.8%), CDKN2A (23.9%), and CCND1 (20.2%). Aberrations were also detected in IGH (38.4%) and MYC (20.8%), primarily through cytogenetic methods. Other common baseline mutations were NSD2 (15.0%), KMT2A (8.9%), S1PR1 (8.6%), and CARD11 (8.5%). Our data also show a change in mutational status from baseline samples to samples at disease progression and present mutations of interest in MCL that should be considered for future analysis. The genes with the highest mutational frequency difference (&gt;5%) are TP53, ATM, KMT2A, MAP3K14, BTK, TRAF2, CHD2, TLR2, ARID2, RIMS2, NOTCH2, TET2, SPEN, NSD2, CARD11, CCND1, SP140, CDKN2A, and S1PR1. These findings provide a summary of the mutational landscape of MCL. The genes with the highest change in mutation frequency should be included in targeted next-generation sequencing panels for future studies. These findings also highlight the need for analysis of serial samples in MCL. Patient-level data of prevalent mutations in MCL provide additional evidence emphasizing molecular variability in advancing precision medicine initiatives in MCL.
Nationwide survey of systemic chronic active EBV infection in Japan in accordance with the new WHO classification
Authors: Yonese Ichiro , Sakashita Chizuko , Imadome Ken-Ichi , Kobayashi Tohru , Yamamoto Masahide , Sawada Akihisa , Ito Yoshinori , Fukuhara Noriko , Hirose Asao , Takeda Yusuke , Makita Masanori , Endo Tomoyuki , Kimura Shun-ichi , Ishimura Masataka , Miura Osamu , Ohga Shouichi , Kimura Hiroshi , Fujiwara Shigeyoshi , Arai Ayako 
Published: June 2020

Abstract
Systemic chronic active Epstein-Barr virus infection (sCAEBV) was defined as a T- or NK-cell neoplasm in the 2017 World Health Organization (WHO) classification. To clarify the clinical features of sCAEBV under this classification and review the effects of chemotherapy, we performed a nationwide survey in Japan from 2016 through 2018 of patients with sCAEBV newly diagnosed from January 2003 through March 2016. One hundred cases were evaluated. The patients were aged 1 to 78 years (median, 21) and included 53 males and 47 females. Spontaneous regression was not observed in patients with active disease. In the childhood-onset group (age, &lt;9 years), 78% of the patients were male. In contrast, 85% of the patients in the elderly-onset group (age, &gt;45 years) were female. The prognosis of the childhood-onset group was better than those of the adolescent/adult- and elderly-onset groups. The main chemotherapies used were a combination of cyclosporine A, steroids, and etoposide (cooling therapy) in 52 cases and cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) in 45 cases. The rate of complete response (CR), defined as complete resolution of disease activity, was 17% for cooling therapy and 13% for CHOP. Virological CR was not observed. The 3-year overall survival rates in patients treated with chemotherapy only (n = 20), chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT; n = 47), and allo-HSCT only (n = 12) were 0%, 65%, and 82%, respectively. Distinct characteristics were observed between childhood- and elderly-onset sCAEBV, and they appeared to be different disorders. Chemotherapy is currently insufficient to resolve disease activity and eradicate infected cells. The development of an effective treatment is urgently needed.
Methylation data imputation performances under different representations and missingness patterns
Authors: Lena Pietro Di , Sala Claudia , Prodi Andrea , Nardini Christine 
Published: June 2020

Abstract
Background
High-throughput technologies enable the cost-effective collection and analysis of DNA methylation data throughout the human genome. This naturally entails missing values management that can complicate the analysis of the data. Several general and specific imputation methods are suitable for DNA methylation data. However, there are no detailed studies of their performances under different missing data mechanisms –(completely) at random or not- and different representations of DNA methylation levels (β and M-value).

Results
We make an extensive analysis of the imputation performances of seven imputation methods on simulated missing completely at random (MCAR), missing at random (MAR) and missing not at random (MNAR) methylation data. We further consider imputation performances on the popular β- and M-value representations of methylation levels. Overall, β-values enable better imputation performances than M-values. Imputation accuracy is lower for mid-range β-values, while it is generally more accurate for values at the extremes of the β-value range. The MAR values distribution is on the average more dense in the mid-range in comparison to the expected β-value distribution. As a consequence, MAR values are on average harder to impute.

Conclusions
The results of the analysis provide guidelines for the most suitable imputation approaches for DNA methylation data under different representations of DNA methylation levels and different missing data mechanisms.
Wingless and Archipelago, a fly E3 ubiquitin ligase and a homolog of human tumor suppressor FBW7, show an antagonistic relationship in wing development
Authors: Nam Sujin , Cho Kyung-Ok 
Published: June 2020

Abstract
Background
Archipelago (Ago) is a Drosophila homolog of mammalian F-box and WD repeat domain-containing 7 (FBW7, also known as FBXW7). In previous studies, FBW7 has been addressed as a tumor suppressor mediating ubiquitin-dependent proteolysis of several oncogenic proteins. Ubiquitination is a type of protein modification that directs protein for degradation as well as sorting. The level of beta-catenin (β-cat), an intracellular signal transducer in Wnt signaling pathway, is reduced upon overexpression of FBW7 in human cancer cell lines. Loss of function mutations in FBW7 and overactive Wnt signaling have been reported to be responsible for human cancers.

Results
We found that Ago is important for the formation of shafts in chemosensory bristles at wing margin. This loss of shaft phenotype by knockdown of ago was rescued by knockdown of wingless (wg) whereas wing notching phenotype by knockdown of wg was rescued by knockdown of ago, establishing an antagonistic relationship between ago and wg. In line with this finding, knockdown of ago increased the level of Armadillo (Arm), a homolog of β-cat, in Drosophila tissue. Furthermore, knockdown of ago increased the level of Distal-less (Dll) and extracellular Wg in wing discs. In S2 cells, the amount of secreted Wg was increased by knockdown of Ago but decreased by Ago overexpression. Therefore, Ago plays a previously unidentified role in the inhibition of Wg secretion. Ago-overexpressing clones in wing discs exhibited accumulation of Wg in endoplasmic reticulum (ER), suggesting that Ago prevents Wg protein from moving to Golgi from ER.

Conclusions
We concluded that Ago plays dual roles in inhibiting Wg signaling. First, Ago decreases the level of Arm, by which Wg signaling is downregulated in Wg-responding cells. Second, Ago decreases the level of extracellular Wg by inhibiting movement of Wg from ER to Golgi in Wg-producing cells.
Counterbalancing the time-dependent effect on the human mitochondrial DNA molecular clock
Authors: Cabrera Vicente M. 
Published: June 2020

Abstract
Background
The molecular clock is an important genetic tool for estimating evolutionary timescales. However, the detection of a time-dependent effect on substitution rate estimates complicates its application. It has been suggested that demographic processes could be the main cause of this confounding effect. In the present study, I propose a new algorithm for estimating the coalescent age of phylogenetically related sequences, taking into account the observed time-dependent effect on the molecular rate detected by others.

Results
By applying this method to real human mitochondrial DNA trees with shallow and deep topologies, I obtained significantly older molecular ages for the main events of human evolution than were previously estimated. These ages are in close agreement with the most recent archaeological and paleontological records favoring the emergence of early anatomically modern humans in Africa 315 ± 34 thousand years ago (kya) and the presence of recent modern humans outside of Africa as early as 174 ± 48 thousand years ago. Furthermore, during the implementation process, I demonstrated that in a population with fluctuating sizes, the probability of fixation of a new neutral mutant depends on the effective population size, which is in better accordance with the fact that under the neutral theory of molecular evolution, the fate of a molecular mutation is mainly determined by random drift.

Conclusions
I suggest that the demographic history of populations has a more decisive effect than purifying selection and/or mutational saturation on the time-dependent effect observed for the substitution rate, and I propose a new method that corrects for this effect.
Contribution to understanding the evolution of holometaboly: transformation of internal head structures during the metamorphosis in the green lacewing Chrysopa pallens (Neuroptera: Chrysopidae)
Authors: Zhao Chenjing , Ang Yuchen , Wang Mengqing , Gao Caixia , Zhang Kuiyan , Tang Chufei , Liu Xingyue , Li Min , Yang Ding , Meier Rudolf 
Published: June 2020

AbstractBackgroundMetamorphosis remains one of the most complicated and poorly understood processes in insects. This is particularly so for the very dynamic transformations that take place within the pupal sheath of holometabolous insects. Only few studies address these transformations especially with regard to cranial structures of those holometabolous species where the larval and adult forms have a similar diet. It thus remains unclear to what extent the internal structures undergo histolysis and rebuilding. Here, the development of the brain and skeleto-muscular system of the head ofChrysopa pallens(Rambur, 1838) is studied. This species is a predator of aphids in the larval and adult stage.ResultsWe used micro-computed-tomography (μ-CT) to study the transformations of the larval, prepupal and pupal head within the cocoon. We first assessed the morphological differences and similarities between the stages. We then determined the point in time when the compound eyes appear and describe the re-orientation of the head capsule which transforms the prognathous larva into a hypognathous adult. The internal head muscles are distinctly more slender in larvae than adults. In addition, the adults have a significantly larger brain which is likely needed for the processing of the signals obtained by the adults vastly expanded sensory organs that are presumably needed for dispersal and mating. Our study shows that the histolysis and modification of the inner muscles and skeletal elements take place within the prepupa. The central nervous system persists throughout metamorphosis but its morphology changes significantly.ConclusionOur study reveals that not only the inner structures, but also the outer morphology continues to change after the final larval moult. The adult cuticle and internal structures form gradually within the cocoon. The histolysis and rebuilding begin with the skeletal elements and is followed by changes in the central nervous system before it concludes with modifications of the musculature. This order of events is likely ancestral for Holometabola because it is also known from Hymenoptera, Diptera, Mecoptera, and Coleoptera.
Genome-wide identification and characterization of multiple C2 domains and transmembrane region proteins in Gossypium hirsutum
Authors: Hao Pengbo , Wang Hantao , Ma Liang , Wu Aimin , Chen Pengyun , Cheng Shuaishuai , Wei Hengling , Yu Shuxun 
Published: June 2020

Abstract
Background
Multiple C2 domains and transmembrane region proteins (MCTPs) may act as transport mediators of other regulators. Although increased number of MCTPs in higher plants implies their diverse and specific functions in plant growth and development, only a few plant MCTPs have been studied and no study on the MCTPs in cotton has been reported.

Results
In this study, we identified 31 MCTPs in G. hirsutum, which were classified into five subfamilies according to the phylogenetic analysis. GhMCTPs from subfamily V exhibited isoelectric points (pIs) less than 7, whereas GhMCTPs from subfamily I, II, III and IV exhibited pIs more than 7.5, implying their distinct biological functions. In addition, GhMCTPs within subfamily III, IV and V exhibited more diverse physicochemical properties, domain architectures and expression patterns than GhMCTPs within subfamily I and II, suggesting that GhMCTPs within subfamily III, IV and V diverged to perform more diverse and specific functions. Analyses of conserved motifs and pIs indicated that the N-terminus was more divergent than the C-terminus and GhMCTPs’ functional divergence might be mainly contributed by the N-terminus. Furthermore, yeast two-hybrid assay indicated that the N-terminus was responsible to interact with target proteins. Phylogenetic analysis classified multiple N-terminal C2 domains into four subclades, suggesting that these C2 domains performed different molecular functions in mediating the transport of target proteins.

Conclusions
Our systematic characterization of MCTPs in G. hirsutum will provide helpful information to further research GhMCTPs’ molecular roles in mediating other regulators’ transport to coordinate growth and development of various cotton tissues.