bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation signatures to predict the cervicovaginal microbiome status
Authors: Nené Nuno R. , Barrett James , Jones Allison , Evans Iona , Reisel Daniel , Timms John F. , Paprotka Tobias , Leimbach Andreas , Franchi Dorella , Colombo Nicoletta , Bjørge Line , Zikan Michal , Cibula David , Widschwendter Martin 
Published: November 2020

Abstract
Background
The composition of the microbiome plays an important role in human health and disease. Whether there is a direct association between the cervicovaginal microbiome and the host’s epigenome is largely unexplored.

Results
Here we analyzed a total of 448 cervicovaginal smear samples and studied both the DNA methylome of the host and the microbiome using the Illumina EPIC array and next-generation sequencing, respectively. We found that those CpGs that are hypo-methylated in samples with non-lactobacilli (O-type) dominating communities are strongly associated with gastrointestinal differentiation and that a signature consisting of 819 CpGs was able to discriminate lactobacilli-dominating (L-type) from O-type samples with an area under the receiver operator characteristic curve (AUC) of 0.84 (95% CI = 0.77–0.90) in an independent validation set. The performance found in samples with more than 50% epithelial cells was further improved (AUC 0.87) and in women younger than 50 years of age was even higher (AUC 0.91). In a subset of 96 women, the buccal but not the blood cell DNA showed the same trend as the cervicovaginal samples in discriminating women with L- from O-type cervicovaginal communities.

Conclusions
These findings strongly support the view that the epithelial epigenome plays an essential role in hosting specific microbial communities.
The eIF4E homolog 4EHP (eIF4E2) regulates hippocampal long-term depression and impacts social behavior
Authors: Wiebe Shane , Meng Xiang Qi , Kim Sung-Hoon , Zhang Xu , Lacaille Jean-Claude , Aguilar-Valles Argel , Sonenberg Nahum 
Published: November 2020

Abstract
Background
The regulation of protein synthesis is a critical step in gene expression, and its dysfunction is implicated in autism spectrum disorder (ASD). The eIF4E homologous protein (4EHP, also termed eIF4E2) binds to the mRNA 5′ cap to repress translation. The stability of 4EHP is maintained through physical interaction with GRB10 interacting GYF protein 2 (GIGYF2). Gene-disruptive mutations in GIGYF2 are linked to ASD, but causality is lacking. We hypothesized that GIGYF2 mutations cause ASD by disrupting 4EHP function.

Methods
Since homozygous deletion of either gene is lethal, we generated a cell-type-specific knockout model where Eif4e2 (the gene encoding 4EHP) is deleted in excitatory neurons of the forebrain (4EHP-eKO). In this model, we investigated ASD-associated synaptic plasticity dysfunction, ASD-like behaviors, and global translational control. We also utilized mice lacking one copy of Gigyf2, Eif4e2 or co-deletion of one copy of each gene to further investigate ASD-like behaviors.

Results
4EHP is expressed in excitatory neurons and synaptosomes, and its amount increases during development. 4EHP-eKO mice display exaggerated mGluR-LTD, a phenotype frequently observed in mouse models of ASD. Consistent with synaptic plasticity dysfunction, the mice displayed social behavior impairments without being confounded by deficits in olfaction, anxiety, locomotion, or motor ability. Repetitive behaviors and vocal communication were not affected by loss of 4EHP in excitatory neurons. Heterozygous deletion of either Gigyf2, Eif4e2, or both genes in mice did not result in ASD-like behaviors (i.e. decreases in social behavior or increases in marble burying). Interestingly, exaggerated mGluR-LTD and impaired social behaviors were not attributed to changes in hippocampal global protein synthesis, which suggests that 4EHP and GIGYF2 regulate the translation of specific mRNAs to mediate these effects.

Limitations
This study did not identify which genes are translationally regulated by 4EHP and GIGYF2. Identification of mistranslated genes in 4EHP-eKO mice might provide a mechanistic explanation for the observed impairment in social behavior and exaggerated LTD. Future experiments employing affinity purification of translating ribosomes and mRNA sequencing in 4EHP-eKO mice will address this relevant issue.

Conclusions
Together these results demonstrate an important role of 4EHP in regulating hippocampal plasticity and ASD-associated social behaviors, consistent with the link between mutations in GIGYF2 and ASD.
COVID-19 pneumonia: the great radiological mimicker
Authors: Duzgun Selin Ardali , Durhan Gamze , Demirkazik Figen Basaran , Akpinar Meltem Gulsun , Ariyurek Orhan Macit 
Published: November 2020

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread worldwide since December 2019. Although the reference diagnostic test is a real-time reverse transcription-polymerase chain reaction (RT-PCR), chest-computed tomography (CT) has been frequently used in diagnosis because of the low sensitivity rates of RT-PCR. CT findings of COVID-19 are well described in the literature and include predominantly peripheral, bilateral ground-glass opacities (GGOs), combination of GGOs with consolidations, and/or septal thickening creating a “crazy-paving” pattern. Longitudinal changes of typical CT findings and less reported findings (air bronchograms, CT halo sign, and reverse halo sign) may mimic a wide range of lung pathologies radiologically. Moreover, accompanying and underlying lung abnormalities may interfere with the CT findings of COVID-19 pneumonia. The diseases that COVID-19 pneumonia may mimic can be broadly classified as infectious or non-infectious diseases (pulmonary edema, hemorrhage, neoplasms, organizing pneumonia, pulmonary alveolar proteinosis, sarcoidosis, pulmonary infarction, interstitial lung diseases, and aspiration pneumonia). We summarize the imaging findings of COVID-19 and the aforementioned lung pathologies that COVID-19 pneumonia may mimic. We also discuss the features that may aid in the differential diagnosis, as the disease continues to spread and will be one of our main differential diagnoses some time more.
The 100 top-cited meta-analyses of diagnostic accuracy in radiology journals: a bibliometric analysis
Authors: Yaxley Kaspar L. , To Minh-Son 
Published: November 2020

Abstract
Purpose
To identify the 100 top-cited meta-analyses of diagnostic accuracy studies published in radiology, medical imaging and nuclear medicine journals.

Methods
A PubMed search with pre-defined criteria was performed. The 100 top-cited articles meta-analyses were retrieved, using a custom Python script and the Scopus Application Programming Interface (Elsevier). Publication, citation and affiliation details were extracted from each meta-analysis. No formal statistical analysis was performed.

Results
The top meta-analysis was cited 394 times, the 100th meta-analysis 38 times. The USA was the top country represented in the papers (33 meta-analyses) followed by The Netherlands, China and Germany. The journal Radiology published 24 studies. The most common modality reported was positron emission tomography (PET) or PET computed tomography (36 instances), followed by magnetic resonance imaging (30 instances) and computed tomography (27 instances). Cardiac (19 meta-analyses), abdominal (18 meta-analyses), followed by neurological (12 meta-analyses) investigations were the most frequently encountered in the top 100 cited meta-analyses.

Conclusions
The 100 top-cited meta-analyses encompass a broad range of imaging modalities and body regions. This may comprise a useful resource for identifying influential evidence-based diagnostic accuracy information in radiology.
Application of adipose-derived stem cells in photoaging: basic science and literature review
Authors: Chen Shidie , He Zhigang , Xu Jinghong 
Published: November 2020

AbstractPhotoaging is mainly induced by continuous exposure to sun light, causing multiple unwanted skin characters and accelerating skin aging. Adipose-derived stem cells(ADSCs) are promising in supporting skin repair because of their significant antioxidant capacity and strong proliferation, differentiation, and migration ability, as well as their enriched secretome containing various growth factors and cytokines. The identification of the mechanisms by which ADSCs perform these functions for photoaging has great potential to explore therapeutic applications and combat skin aging. We also review the basic mechanisms of UV-induced skin aging and recent improvement in pre-clinical applications of ADSCs associated with photoaging. Results showed that ADSCs are potential to address photoaging problem and might treat skin cancer. Compared with ADSCs alone, the secretome-based approaches and different preconditionings of ADSCs are more promising to overcome the current limitations and enhance the anti-photoaging capacity.
Ventilator-associated pneumonia in patients with SARS-CoV-2-associated acute respiratory distress syndrome requiring ECMO: a retrospective cohort study
Authors: Luyt Charles-Edouard , Sahnoun Tarek , Gautier Melchior , Vidal Pauline , Burrel Sonia , Pineton de Chambrun Marc , Chommeloux Juliette , Desnos Cyrielle , Arzoine Jeremy , Nieszkowska Ania , Bréchot Nicolas , Schmidt Matthieu , Hekimian Guillaume , Boutolleau David , Robert Jérôme , Combes Alain , Chastre Jean 
Published: November 2020

Abstract
Background
The data on incidence, clinical presentation, and outcomes of ventilator-associated pneumonia (VAP) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia requiring mechanical ventilation (MV) are limited. We performed this retrospective cohort study to assess frequency, clinical characteristics, responsible pathogens, and outcomes of VAP in patients COVID-19 pneumonia requiring MV between March 12th and April 24th, 2020 (all had RT-PCR-confirmed SARS-CoV-2 infection). Patients with COVID-19-associated acute respiratory distress syndrome (ARDS) requiring ECMO were compared with an historical cohort of 45 patients with severe influenza-associated ARDS requiring ECMO admitted to the same ICU during the preceding three winter seasons.

Results
Among 50 consecutive patients with Covid-19-associated ARDS requiring ECMO included [median (IQR) age 48 (42–56) years; 72% male], 43 (86%) developed VAP [median (IQR) MV duration before the first episode, 10 (8–16) days]. VAP-causative pathogens were predominantly Enterobacteriaceae (70%), particularly inducible AmpC-cephalosporinase producers (40%), followed by Pseudomonas aeruginosa (37%). VAP recurred in 34 (79%) patients and 17 (34%) died. Most recurrences were relapses (i.e., infection with the same pathogen), with a high percentage occurring on adequate antimicrobial treatment. Estimated cumulative incidence of VAP, taking into account death and extubation as competing events, was significantly higher in Covid-19 patients than in influenza patients (p = 0.002). Despite a high P. aeruginosa-VAP rate in patients with influenza-associated ARDS (54%), the pulmonary infection recurrence rate was significantly lower than in Covid-19 patients. Overall mortality was similar for the two groups.

Conclusions
Patients with severe Covid-19-associated ARDS requiring ECMO had a very high late-onset VAP rate. Inducible AmpC-cephalosporinase-producing Enterobacteriaceae and Pseudomonas aeruginosa frequently caused VAP, with multiple recurrences and difficulties eradicating the pathogen from the lung.
Valorization of organic waste fractions: a theoretical study on biomethane production potential and the recovery of N and P in Austria
Authors: Rosenfeld Daniel C. , Lindorfer Johannes , Ellersdorfer Markus 
Published: November 2020

Abstract
Background
Due to climate change and the rising world population, sustainable energy and fertilizer production faces many challenges. The utilization of organic waste fractions is one possible solution for promoting sustainability. Organic waste fractions have a high potential for biomethane production, which could positively contribute to the current energy mix. Furthermore, organic waste fractions could be used for nutrient recovery (i.e., the recovery of N and P) concurrently to their use in biomethane production. This study examined the theoretical potential of organic waste fractions for valorization in Austria. Further, it provides a theoretical overview of biomethane production and nutrient-recovery potential.

Results
This analysis revealed a total substrate potential of 13 Mt per year in Austria, with the highest contribution from manure. Over 900 million Nm3 of biomethane could potentially be produced from organic waste fractions. Furthermore, developing organic waste fractions as an energy source could improve the impact of the natural gas consuming sectors on climate, reducing 2.4 Mt of CO2 emissions annually. Regarding nutrient recovery, more than 60 kt of N and 20 kt of P could potentially be recovered per year.

Conclusion
The study shows a high potential for producing biomethane from organic waste fractions in Austria. The overall production potential could substitute up to 11% of the Austrian natural gas demand, which could highly decrease the CO2 emissions from fossil energy carriers. Furthermore, a high nutrient recovery potential was identified for an inclusive implementation of an efficient recovery.
Sulfadiazine plasma concentrations in women with pregnancy-acquired compared to ocular toxoplasmosis under pyrimethamine and sulfadiazine therapy: a case–control study
Authors: Reiter-Owona Ingrid , Hlobil Harald , Enders Martin , Klarmann-Schulz Ute , Gruetzmacher Barbara , Rilling Veronika , Hoerauf Achim , Garweg Justus G. 
Published: November 2020

Abstract
Background
Dosing recommendations for the treatment of pregnancy-acquired toxoplasmosis are empirical and widely based on experimental data. There are no pharmacological data on pregnant women with acute Toxoplasma gondii infection under treatment with pyrimethamine (PY) and sulfadiazine (SA) and our study intends to tighten this gap.

Methods
In this retrospective case–control study, we included 89 pregnant women with primary Toxoplasma infection (PT) treated with PY (50 mg first dose, then 25 mg/day), SA (50 mg/kg of body weight/day), and folinic acid (10–15 mg per week). These were compared to a group of 17 women with acute ocular toxoplasmosis (OT) treated with an initial PY dose of 75 mg, thereafter 25 mg twice a day but on the same SA and folinic acid regimen. The exact interval between drug intake and blood sampling and co-medication had not been recorded. Plasma levels of PY and SA were determined 14 ± 4 days after treatment initiation using liquid chromatography–mass spectrometry and compared using the Mann–Whitney U test at a p < 0.05 level.

Results
In 23 PT patients (26%), SA levels were below 20 mg/l. Fifteen of these 23 patients (17% of all patients) in parallel presented with PY levels below 700 µg/l. Both drug concentrations differed remarkably between individuals and groups (PY: PT median 810 µg/l, 95% CI for the median [745; 917] vs. OT 1230 µg/l [780; 1890], p = 0.006; SA: PT 46.2 mg/l [39.9; 54.4] vs. OT 70.4 mg/l [52.4; 89], p = 0.015) despite an identical SA dosing scheme.

Conclusions
SA plasma concentrations were found in the median 34% lower in pregnant women with PT compared to OT patients and fell below a lower reference value of 50 mg/l in a substantial portion of PT patients. The interindividual variability of plasma concentrations in combination with systematically lower drug levels and possibly a lower compliance in pregnant women may thus account for a still not yet supportable transmission risk. Systematic drug-level testing in PT under PY/SA treatment deserves to be considered.
Cerebrospinal fluid α-synuclein predicts neurodegeneration and clinical progression in non-demented elders
Authors:   Alzheimer’s Disease Neuroimaging Initiative, Li Jie-Qiong , Bi Yan-Lin , Shen Xue-Ning , Wang Hui-Fu , Xu Wei , Tan Chen-Chen , Dong Qiang , Wang Yan-Jiang , Tan Lan , Yu Jin-Tai 
Published: November 2020

Abstract
Background
Accumulating reports have suggested that α-synuclein is involved in the pathogenesis of Alzheimer’s disease (AD). As the cerebrospinal fluid (CSF) α-synuclein has been suggested as a potential biomarker of AD, this study was set out to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in non-demented elders.

Methods
The associations between CSF α-synuclein and other AD biomarkers were investigated at baseline in non-demented Chinese elders. The predictive values of CSF α-synuclein for longitudinal neuroimaging change and the conversion risk of non-demented elders were assessed using linear mixed effects models and multivariate Cox proportional hazard models, respectively, in the Alzheimer’s disease Neuroimaging Initiative (ADNI) database.

Results
The CSF α-synuclein levels correlated with AD-specific biomarkers, CSF total tau and phosphorylated tau levels, in 651 Chinese Han participants (training set). These positive correlations were replicated in the ADNI database (validation set). Using a longitudinal cohort from ADNI, the CSF α-synuclein concentrations were found to increase with disease severity. The CSF α-synuclein had high diagnostic accuracy for AD based on the “ATN” (amyloid, tau, neurodegeneration) system (A + T+ versus A − T − control) (area under the receiver operating characteristic curve, 0.84). Moreover, CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia.

Conclusions
CSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in non-demented elders. This finding indicates that CSF α-synuclein is a potentially useful early biomarker for AD.
Perinatal environment shapes microbiota colonization and infant growth: impact on host response and intestinal function
Authors: Selma-Royo M. , Calatayud Arroyo M. , García-Mantrana I. , Parra-Llorca A. , Escuriet R. , Martínez-Costa C. , Collado M. C. 
Published: November 2020

AbstractBackgroundEarly microbial colonization triggers processes that result in intestinal maturation and immune priming. Perinatal factors, especially those associated with birth, including both mode and place of delivery are critical to shaping the infant gut microbiota with potential health consequences.MethodsGut microbiota profile of 180 healthy infants (n= 23 born at home andn= 157 born in hospital, 41.7% via cesarean section [CS]) was analyzed by 16S rRNA gene sequencing at birth, 7 days, and 1 month of life. Breastfeeding habits and infant clinical data, including length, weight, and antibiotic exposure, were collected up to 18 months of life. Long-term personalized in vitro models of the intestinal epithelium and innate immune system were used to assess the link between gut microbiota composition, intestinal function, and immune response.ResultsMicrobiota profiles were shaped by the place and mode of delivery, and they had a distinct biological impact on the immune response and intestinal function in epithelial/immune cell models. Bacteroidetes andBifidobacteriumgenus were decreased in C-section infants, who showed higherz-scores BMI and W/L during the first 18 months of life. Intestinal simulated epithelium had a stronger epithelial barrier function and intestinal maturation, alongside a higher immunological response (TLR4 route activation and pro-inflammatory cytokine release), when exposed to home-birth fecal supernatants, compared with CS. Distinct host response could be associated with different microbiota profiles.ConclusionsMode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier, and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants.Trial registrationNCT03552939.
The effect of statin treatment on intratumoral cholesterol levels and LDL receptor expression: a window-of-opportunity breast cancer trial
Authors: Feldt Maria , Menard Julien , Rosendahl Ann H. , Lettiero Barbara , Bendahl Pär-Ola , Belting Mattias , Borgquist Signe 
Published: November 2020

AbstractBackgroundDeregulated lipid metabolism is common in cancer cells and the mevalonate pathway, which synthesizes cholesterol, is central in lipid metabolism. This study aimed to assess statin-induced changes of the intratumoral levels of cholesterol and the expression of the low-density lipoprotein receptor (LDLR) to enhance our understanding of the role of the mevalonate pathway in cancer cholesterol metabolism.MethodsThis study is based on a phase II clinical trial designed as a window-of-opportunity trial including 50 breast cancer patients treated with 80 mg of atorvastatin/day for 2 weeks, between the time of diagnosis and breast surgery. Lipids were extracted from frozen tumor tissue sampled pre- and post-atorvastatin treatment. Intratumoral cholesterol levels were measured using a fluorometric quantitation assay. LDLR expression was evaluated by immunohistochemistry on formalin-fixed paraffin-embedded tumor tissue. Paired blood samples pre- and post-atorvastatin were analyzed for circulating low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1, and apolipoprotein B. In vitro experiments on MCF-7 breast cancer cells treated with atorvastatin were performed for comparison on the cellular level.ResultsIn the trial, 42 patients completed all study parts. From the paired tumor tissue samples, assessment of the cholesterol levels was achievable for 14 tumors, and for the LDLR expression in 24 tumors. Following atorvastatin treatment, the expression of LDLR was significantly increased (P= 0.004), while the intratumoral levels of total cholesterol remained stable. A positive association between intratumoral cholesterol levels and tumor proliferation measured by Ki-67 expression was found. In agreement with the clinical findings, results from in vitro experiments showed no significant changes of the intracellular cholesterol levels after atorvastatin treatment while increased expression of the LDLR was found, although not reaching statistical significance.ConclusionsThis study shows an upregulation of LDLR and preserved intratumoral cholesterol levels in breast cancer patients treated with statins. Together with previous findings on the anti-proliferative effect of statins in breast cancer, the present data suggest a potential role for LDLR in the statin-induced regulation of breast cancer cell proliferation.Trial registrationThe study has been registered at ClinicalTrials.gov (i.e., ID number:NCT00816244, NIH), December 30, 2008.