bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence of salivary IgA anti-citrullinated protein antibodies associate with higher disease activity in patients with rheumatoid arthritis
Authors: Roos Ljungberg Karin , Börjesson Emil , Martinsson Klara , Wetterö Jonas , Kastbom Alf , Svärd Anna 
Published: November 2020

AbstractBackgroundCirculating IgA anti-citrullinated protein antibodies (ACPA) associate with more active disease, but a previous study implied that salivary IgA ACPA is related to a less severe disease. Therefore, we aimed to characterize the IgA ACPA response in the saliva and serum in relation to clinical picture and risk factors among patients with rheumatoid arthritis (RA).MethodsRA patients (n = 196) and healthy blood donors (n = 101), included in the cross-sectional study “Secretory ACPA in Rheumatoid Arthritis” (SARA), were analyzed for ACPA of IgA isotype, and for subclasses IgA1 and IgA2 ACPA in paired saliva and serum samples using modified enzyme-linked immunosorbent assays (ELISA) targeting reactivity to a cyclic citrullinated peptide (anti-CCP). Cutoff levels for positive tests were set at the 99th percentile for blood donors. Antibody levels were related to clinical characteristics, radiographic damage, smoking habits, and carriage of HLA-DRB1/shared epitope (SE).ResultsIgA ACPA in the saliva was found in 12% of RA patients, IgA1 occurred in 10%, and IgA2 in 9%. In serum, IgA ACPA was found in 45% of the patients, IgA1 in 44%, and IgA2 in 39%. Levels of IgA ACPA in the saliva correlated significantly with serum levels of IgA (r = 0.455). The presence of salivary IgA ACPA was associated with a higher erythrocyte sedimentation rate (ESR), 28-joint disease activity score, tender joint count, and patient global assessment at the time of sampling. None of the antibodies was associated with smoking, SE, or radiographic damage.ConclusionSalivary IgA ACPAs were detected in a subset of RA patients in association with higher disease activity. This suggests that mucosal ACPA responses in the oral cavity may contribute to disease-promoting processes in RA.
The miRNA 196a2 rs11614913 variant has prognostic impact on Turkish patients with multiple myeloma
Authors: Kirik Melya Pelin , Pehlivan Mustafa , Nursal Ayse Feyda , Oyaci Yasemin , Pehlivan Sacide , SERIN Istemi 
Published: November 2020

AbstractObjectiveMultiple myeloma (MM) arises from malignant plasma cells as a single clone in the bone marrow. Accumulating evidences have reported that there is an association betweenmiR-196a2(rs11614913) variant and various cancers while there were unverified and inconsistent results in MM. The goal of this study is to investigate the impact of themiR-196a2 variant on clinical findings and susceptibility in MM. Two hundred MM patients (156 patients under transplantation of autologous stem cell) and 200 healthy controls included in this study.ResultsThe statistical analysis showed no significant relationship for allele and frequencies ofmiR-196a2genotype between patients and controls (p > 0.05). Log-rank test showed that gender has highly significant impact on both OS and PFS (p = 0.027, p = 0.045).In the univariate analysis, TT genotype (p = 0.022), and CT/TT (p = 0.008) had better OS. In the multivariate analysis, CC/CT-TT were associated with positively OS (p = 0.041). Currently, the most valuable prognostic markers in MM that has clinical implication are genetic abnormalities. It can be concluded from the results thatmiR-1962avariant is effective in prognosis of the MM. It is believed that these findings will help us understand the molecular basis of disease.
Mitochondrial metabolism and DNA methylation: a review of the interaction between two genomes
Authors: F. C. Lopes Amanda 
Published: November 2020

AbstractMitochondria are controlled by the coordination of two genomes: the mitochondrial and the nuclear DNA. As such, variations in nuclear gene expression as a consequence of mutations and epigenetic modifications can affect mitochondrial functionality. Conversely, the opposite could also be true. However, the relationship between mitochondrial dysfunction and epigenetics, such as nuclear DNA methylation, remains largely unexplored.
Mitochondria function as central metabolic hubs controlling some of the main substrates involved in nuclear DNA methylation, via the one carbon metabolism, the tricarboxylic acid cycle and the methionine pathway. Here, we review key findings and highlight new areas of focus, with the ultimate goal of getting one step closer to understanding the genomic effects of mitochondrial dysfunction on nuclear epigenetic landscapes.
Meconium androgens are correlated with ASD-related phenotypic traits in early childhood in a familial enriched risk cohort
Authors: Terloyeva Dina , Frey Alexander J. , Park Bo Y. , Kauffman Elizabeth M. , Mathew Leny , Bostwick Anna , Varner Erika L. , Lee Brian K. , Croen Lisa A. , Fallin Margaret D. , Hertz-Picciotto Irva , Newschaffer Craig J. , Lyall Kristen , Snyder Nathaniel W. 
Published: November 2020

Abstract
Background
Prenatal exposure to increased androgens has been suggested as a risk factor for autism spectrum disorder (ASD). This hypothesis has been examined by measurement of steroids in amniotic fluid, cord blood, saliva, and blood with mixed results.

Methods
To provide an orthogonal measure of fetal exposure, this study used meconium, the first stool of a newborn, to measure prenatal androgen exposure from infants in the Early Autism Risk Longitudinal Investigation (EARLI). EARLI is a familial-enriched risk cohort that enrolled pregnant mothers who already had a child with an ASD diagnosis. In the younger child, we investigated the association between meconium unconjugated (u) and total (t) concentrations of major androgens testosterone (T), dehydroepiandrosterone (DHEA), and androstenedione (A4), and ASD-related traits at 12 and 36 months of age. Traits were measured at 12 months with Autism Observation Scale for Infants (AOSI) and at 36 months with total score on the Social Responsiveness Scale (SRS). One hundred and seventy children had meconium and AOSI, 140 had meconium and SRS, and 137 had meconium and both AOSI and SRS.

Results
Separate robust linear regressions between each of the log-transformed androgens and log-transformed SRS scores revealed three-way interaction between sex of the child, sex of the proband, and testosterone concentration. In the adjusted analyses, t-T, u-A4, and u-DHEA (P ≤ 0.01) were positively associated with AOSI scores, while u-T (P = 0.004) and u-DHEA (P = 0.007) were positively associated with SRS total score among females with female probands (n = 10). Additionally, higher concentrations of u-T (P = 0.01) and t-T (P = 0.01) predicted higher SRS total score in males with male probands (n = 63).

Limitations
Since we explored three-way interactions, this resulted in a limited sample size for some analyses. This study was from an enriched-risk cohort which may limit generalizability, and this study used ASD-assessment scales as outcomes instead of diagnostic categories. Additionally, the novel use of meconium in this study limits the ability to compare the results in this cohort to others due to the paucity of research on meconium.

Conclusions
This study supports the utility of meconium for studies of endogenous fetal metabolism and suggests the sex of older siblings with autism should be considered as a biological variable in relevant studies.
Computed tomography-derived myocardial extracellular volume: an early biomarker of cardiotoxicity in esophageal cancer patients undergoing radiation therapy
Authors: Capra Davide , Monti Caterina Beatrice , Luporini Alberto Gianluigi , Lombardi Fabrizio , Gumina Calogero , Sironi Andrea , Asti Emanuele Luigi Giuseppe , Bonavina Luigi , Secchi Francesco , Sardanelli Francesco 
Published: November 2020

Abstract
Objectives
We aimed to assess extracellular volume (ECV) through non-gated, contrast-enhanced computed tomography (CT) before and after radiation therapy (RT) in patients with esophageal cancer (EC).

Materials and methods
EC patients who had undergone CT before and after RT were retrospectively assessed. Patients with preexisting cardiovascular disease or with heavily artifacted CT were excluded. ECV was calculated using density values for the myocardial septum and blood pool. Data were reported as mean and standard deviation or median and interquartile range according to their distribution; t test or Wilcoxon and Pearson r or Spearman ρ were subsequently used.

Results
Twenty-one patients with stage ≥ IB EC, aged 64 ± 18 years, were included. Mean and maximum RT doses were 21.2 Gy (16.9–24.1) and 42.5 Gy (41.8–49.2), respectively. At baseline (n = 21), hematocrit was 39% ± 4%, ECV 27.9% ± 3.5%; 35 days (30–38) after RT (n = 20), hematocrit was 36% ± 4%, lower than at baseline (p = 0.002), ECV 30.3% ± 8.3%, higher than at baseline (p = 0.081); at follow-up 420 days (244–624) after RT (n = 13), hematocrit was 36% ± 5%, lower than at baseline (p = 0.030), ECV 31.4% ± 4.5%, higher than at baseline (p = 0.011). No patients showed signs of overt cardiotoxicity. ECV early after RT was moderately positively correlated with maximum RT dose (ρ = 0.50, p = 0.036).

Conclusions
In EC patients, CT-derived myocardial ECV was increased after RT and may thus appear as a potential early biomarker of cardiotoxicity.
Workload for radiologists during on-call hours: dramatic increase in the past 15 years
Authors: Bruls R. J. M. , Kwee R. M. 
Published: November 2020

Abstract
Background
The objective of this study is to investigate the workload for radiologists during on-call hours and to quantify the 15-year trend in a large general hospital in Western Europe.

Methods
Data regarding the number of X-ray, ultrasound and computed tomography (CT) studies during on-call hours (weekdays between 6.00 p.m. and 7.00 a.m., weekends, and national holidays) between 2006 and 2020 were extracted from the picture archiving and communication system. All studies were converted into relative value units (RVUs) to estimate the on-call workload. The Mann–Kendall test was performed to assess the temporal trend.

Results
The total RVUs during on-call hours showed a significant increase between 2006 and 2020 (Kendall's tau-b = 0.657, p = 0.001). The overall workload in terms of RVUs during on-call hours has quadrupled. The number of X-ray studies significantly decreased (Kendall's tau-b = − 0.433, p = 0.026), whereas the number of CT studies significantly increased (Kendall's tau-b = 0.875, p < 0.001) between 2006 and 2020. CT studies which increased by more than 500% between 2006 and 2020 are CT for head trauma, brain CTA, brain CTV, chest CT (for suspected pulmonary embolism), spinal CT, neck CT, pelvic CT, and CT for suspected aortic dissection. The number of ultrasound studies did not change significantly (Kendall's tau-b = 0.202, p = 0.298).

Conclusions
The workload for radiologists during on-call hours increased dramatically in the past 15 years. The growing amount of CT studies is responsible for this increase. Radiologist and technician workforce should be matched to this ongoing increasing trend to avoid potential burn-out and to maintain quality and safety of radiological care.
Mesenchymal stem cells: amazing remedies for bone and cartilage defects
Authors: Kangari Parisa , Talaei-Khozani Tahereh , Razeghian-Jahromi Iman , Razmkhah Mahboobeh 
Published: November 2020

AbstractSkeletal disorders are among the leading debilitating factors affecting millions of people worldwide. The use of stem cells for tissue repair has raised many promises in various medical fields, including skeletal disorders. Mesenchymal stem cells (MSCs) are multipotent stromal cells with mesodermal and neural crest origin. These cells are one of the most attractive candidates in regenerative medicine, and their use could be helpful in repairing and regeneration of skeletal disorders through several mechanisms including homing, angiogenesis, differentiation, and response to inflammatory condition. The most widely studied sources of MSCs are bone marrow (BM), adipose tissue, muscle, umbilical cord (UC), umbilical cord blood (UCB), placenta (PL), Wharton’s jelly (WJ), and amniotic fluid. These cells are capable of differentiating into osteoblasts, chondrocytes, adipocytes, and myocytes in vitro. MSCs obtained from various sources have diverse capabilities of secreting many different cytokines, growth factors, and chemokines. It is believed that the salutary effects of MSCs from different sources are not alike in terms of repairing or reformation of injured skeletal tissues. Accordingly, differential identification of MSCs’ secretome enables us to make optimal choices in skeletal disorders considering various sources. This review discusses and compares the therapeutic abilities of MSCs from different sources for bone and cartilage diseases.
Differential expression of microRNAs in the hippocampi of male and female rodents after chronic alcohol administration
Authors: Choi Mi Ran , Han Jasmin Sanghyun , Jin Yeung-Bae , Lee Sang-Rae , Choi In Young , Lee Heejin , Cho Hyun , Kim Dai-Jin 
Published: November 2020

AbstractBackgroundWomen are more vulnerable than men to the neurotoxicity and severe brain damage caused by chronic heavy alcohol use. In addition, brain damage due to chronic heavy alcohol use may be associated with sex-dependent epigenetic modifications. This study aimed to identify microRNAs (miRNAs) and their target genes that are differentially expressed in the hippocampi of male and female animal models in response to alcohol.MethodsAfter chronic alcohol administration (3~3.5 g/kg/day) in male (control,n= 10; alcohol,n= 12) or female (control,n= 10; alcohol,n= 12) Sprague-Dawley rats for 6 weeks, we measured body weights and doublecortin (DCX; a neurogenesis marker) concentrations and analyzed up- or downregulated miRNAs using GeneChip miRNA 4.0 arrays. The differentially expressed miRNAs and their putative target genes were validated by RT-qPCR.ResultsAlcohol attenuated body weight gain only in the male group. On the other hand, alcohol led to increased serum AST in female rats and decreased serum total cholesterol concentrations in male rats. The expression of DCX was significantly reduced in the hippocampi of male alcohol-treated rats. Nine miRNAs were significantly up- or downregulated in male alcohol-treated rats, including upregulation of miR-125a-3p, let-7a-5p, and miR-3541, and downregulation of their target genes (Prdm5,Suv39h1,Ptprz1,Mapk9,Ing4,Wt1,Nkx3-1,Dab2ip,Rnf152,Ripk1,Lin28a,Apbb3,Nras, andAcvr1c). On the other hand, 7 miRNAs were significantly up- or downregulated in alcohol-treated female rats, including downregulation of miR-881-3p and miR-504 and upregulation of their target genes (Naa50,Clock,Cbfb,Arih1,Ube2g1, andGng7).ConclusionsThese results suggest that chronic heavy alcohol use produces sex-dependent effects on neurogenesis and miRNA expression in the hippocampus and that sex differences should be considered when developing miRNA biomarkers to diagnose or treat alcoholics.
Current laboratory and clinical practices in reporting and interpreting anti-nuclear antibody indirect immunofluorescence (ANA IIF) patterns: results of an international survey
Authors: Van Hoovels Lieve , Broeders Sylvia , Chan Edward K. L. , Andrade Luis , de Melo Cruvinel Wilson , Damoiseaux Jan , Viander Markku , Herold Manfred , Coucke Wim , Heijnen Ingmar , Bogdanos Dimitrios , Calvo-Alén Jaime , Eriksson Catharina , Kozmar Ana , Kuhi Liisa , Bonroy Carolien , Lauwerys Bernard , Schouwers Sofie , Lutteri Laurence , Vercammen Martine , Mayer Miroslav , Patel Dina , Egner William , Puolakka Kari , Tesija-Kuna Andrea , Shoenfeld Yehuda , de Sousa Maria José Rego , Hoyos Marcos Lopez , Radice Antonella , Bossuyt Xavier 
Published: November 2020

Abstract
Background
The International Consensus on Antinuclear Antibody (ANA) Patterns (ICAP) has recently proposed nomenclature in order to harmonize ANA indirect immunofluorescence (IIF) pattern reporting. ICAP distinguishes competent-level from expert-level patterns. A survey was organized to evaluate reporting, familiarity, and considered clinical value of ANA IIF patterns.

Methods
Two surveys were distributed by European Autoimmunity Standardization Initiative (EASI) working groups, the International Consensus on ANA Patterns (ICAP) and UK NEQAS to laboratory professionals and clinicians.

Results
438 laboratory professionals and 248 clinicians from 67 countries responded. Except for dense fine speckled (DFS), the nuclear competent patterns were reported by > 85% of the laboratories. Except for rods and rings, the cytoplasmic competent patterns were reported by > 72% of laboratories.
Cytoplasmic IIF staining was considered ANA positive by 55% of clinicians and 62% of laboratory professionals, with geographical and expertise-related differences.
Quantification of fluorescence intensity was considered clinically relevant for nuclear patterns, but less so for cytoplasmic and mitotic patterns. Combining IIF with specific extractable nuclear antigens (ENA)/dsDNA antibody testing was considered most informative.
Of the nuclear competent patterns, the centromere and homogeneous pattern obtained the highest scores for clinical relevance and the DFS pattern the lowest. Of the cytoplasmic patterns, the reticular/mitochondria-like pattern obtained the highest scores for clinical relevance and the polar/Golgi-like and rods and rings patterns the lowest.

Conclusion
This survey confirms that the major nuclear and cytoplasmic ANA IIF patterns are considered clinically important. There is no unanimity on classifying DFS, rods and rings and polar/Golgi-like as a competent pattern and on reporting cytoplasmic patterns as ANA IIF positive.
KRAS mutation effects on the 2-[18F]FDG PET uptake of colorectal adenocarcinoma metastases in the liver
Authors: Popovic M. , Talarico O. , van den Hoff J. , Kunin H. , Zhang Z. , Lafontaine D. , Dogan S. , Leung J. , Kaye E. , Czmielewski C. , Mayerhoefer M. E. , Zanzonico P. , Yaeger R. , Schöder H. , Humm J. L. , Solomon S. B. , Sofocleous C. T. , Kirov A. S. 
Published: November 2020

Abstract
Background
Deriving individual tumor genomic characteristics from patient imaging analysis is desirable. We explore the predictive value of 2-[18F]FDG uptake with regard to the KRAS mutational status of colorectal adenocarcinoma liver metastases (CLM).

Methods
2-[18F]FDG PET/CT images, surgical pathology and molecular diagnostic reports of 37 patients who underwent PET/CT-guided biopsy of CLM were reviewed under an IRB-approved retrospective research protocol. Sixty CLM in 39 interventional PET scans of the 37 patients were segmented using two different auto-segmentation tools implemented in different commercially available software packages. PET standard uptake values (SUV) were corrected for: (1) partial volume effect (PVE) using cold wall-corrected contrast recovery coefficients derived from phantom spheres with variable diameter and (2) variability of arterial tracer supply and variability of uptake time after injection until start of PET scan derived from the tumor-to-blood standard uptake ratio (SUR) approach. The correlations between the KRAS mutational status and the mean, peak and maximum SUV were investigated using Student’s t test, Wilcoxon rank sum test with continuity correction, logistic regression and receiver operation characteristic (ROC) analysis.
These correlation analyses were also performed for the ratios of the mean, peak and maximum tumor uptake to the mean blood activity concentration at the time of scan: SURMEAN, SURPEAK and SURMAX, respectively.

Results
Fifteen patients harbored KRAS missense mutations (KRAS+), while another 3 harbored KRAS gene amplification. For 31 lesions, the mutational status was derived from the PET/CT-guided biopsy. The Student’s t test p values for separating KRAS mutant cases decreased after applying PVE correction to all uptake metrics of each lesion and when applying correction for uptake time variability to the SUR metrics. The observed correlations were strongest when both corrections were applied to SURMAX and when the patients harboring gene amplification were grouped with the wild type: p ≤ 0.001; ROC area under the curve = 0.77 and 0.75 for the two different segmentations, respectively, with a mean specificity of 0.69 and sensitivity of 0.85.

Conclusion
The correlations observed after applying the described corrections show potential for assigning probabilities for the KRAS missense mutation status in CLM using 2-[18F]FDG PET images.
RNAi-mediated silencing of Trichinella spiralis serpin-type serine protease inhibitors results in a reduction in larval infectivity
Authors: Yi Nana , Yu Pengcheng , Wu Lijia , Liu Zhaokun , Guan Jingzhe , Liu Chang , Liu Mingxu , Lu Yixin 
Published: November 2020

AbstractTrichinella spiralisserpin-type serine protease inhibitors (TsSPIs) are expressed in adult worms (AW), newborn larvae (NBL) and muscle larvae (ML) ofT. spiralis, with the ML stage demonstrating the highest expression level. This study aims to determine TsSPI functions in larval viability and invasion of intestinal epithelial cells in vitro, as well as their development, survival, and fecundity in vivo via RNAi. TsSPI-specific siRNAs and dsRNA were transfected into ML by incubation. The silencing effect of TsSPI transcription and expression was determined using qPCR and western blot, respectively. After incubation in 60 ng/μL dsRNA–TsSPI for 3 days, larval TsSPI mRNA and protein expression levels were reduced by 68.7% and 68.4% (P < 0.05), respectively. dsRNA-mediated silencing of TsSPI significantly impacted larval invasion into intestinal epithelial cells in vitro but did not affect the survival rate of larvae. After challenge with dsRNA–TsSPI-treated ML, mice exhibited a 56.0% reduction in intestinal AW burden and 56.9% reduction in ML burden (P < 0.05), but NBL production of female AW remained the same (P > 0.05). Our results revealed that RNAi-mediated silencing of TsSPI expression inT. spiralissignificantly reduced larval infectivity and survival in the host but had no effect on the survival rate and fecundity. Furthermore, TsSPIs have no effect on the growth and reproduction of parasites but may be directly involved in regulating the interaction ofT. spiralisand the host. Therefore, TsSPIs are crucial in the process ofT. spiralislarval invasion and parasite survival in the host.