bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validating the regional estimates of changes in soil organic carbon by using the data from paired-sites: the case study of Mediterranean arable lands
Authors: Schillaci Calogero , Saia Sergio , Lipani Aldo , Perego Alessia , Zaccone Claudio , Acutis Marco 
Published: June 2021

AbstractBackgroundLegacy data are unique occasions for estimating soil organic carbon (SOC) concentration changes and spatial variability, but their use showed limitations due to the sampling schemes adopted and improvements may be needed in the analysis methodologies. When SOC changes is estimated with legacy data, the use of soil samples collected in different plots (i.e., non-paired data) may lead to biased results. In the present work, N = 302 georeferenced soil samples were selected from a regional (Sicily, south of Italy) soil database. An operational sampling approach was developed to spot SOC concentration changes from 1994 to 2017 in the same plots at the 0–30 cm soil depth and tested.ResultsThe measurements were conducted after computing the minimum number of samples needed to have a reliable estimate of SOC variation after 23 years. By applying an effect size based methodology, 30 out of 302 sites were resampled in 2017 to achieve a power of 80%, and an α = 0.05.A Wilcoxontestapplied to the variation of SOC from 1994 to 2017 suggested that there was not a statistical difference in SOC concentration after 23 years (Z = − 0.556; 2-tailed asymptotic significance = 0.578). In particular, only 40% of resampled sites showed a higher SOC concentration than in 2017.ConclusionsThis finding contrasts with a previous SOC concentration increase that was found in 2008 (75.8% increase when estimated as differences of 2 models built with non-paired data), when compared to 1994 observed data (Z = − 9.119; 2-tailed asymptotic significance < 0.001).This suggests that the use of legacy data to estimate SOC concentration dynamics requires soil resampling in the same locations to overcome the stochastic model errors. Further experiment is needed to identify the percentage of the sites to resample in order to align two legacy datasets in the same area.
A HIF1α-GPD1 feedforward loop inhibits the progression of renal clear cell carcinoma via mitochondrial function and lipid metabolism
Authors: Liu Ren , Feng Yuanfa , Deng Yulin , Zou Zhihao , Ye Jianheng , Cai Zhiduan , Zhu Xuejin , Liang Yingke , Lu Jianming , Zhang Hui , Luo Yong , Han Zhaodong , Zhuo Yangjia , Xie Qingling , Hon Chi Tin , Liang Yuxiang , Wu Chin-Lee , Zhong Weide 
Published: June 2021

Abstract
Background
Hypoxia signaling, especially the hypoxia inducible factor (HIF) pathway, is a major player in clear cell renal cell carcinoma (ccRCC), which is characterized by disorders in lipid and glycogen metabolism. However, the interaction between hypoxia and lipid metabolism in ccRCC progression is still poorly understood.

Methods
We used bioinformatic analysis and discovered that glycerol-3-phosphate dehydrogenase 1 (GPD1) may play a key role in hypoxia and lipid metabolism pathways in ccRCC. Tissue microarray, IHC staining, and survival analysis were performed to evaluate clinical function. In vitro and in vivo assays showed the biological effects of GPD1 in ccRCC progression.

Results
We found that the expression of GPD1 was downregulated in ccRCC tissues, and overexpression of GPD1 inhibited the progression of ccRCC both in vivo and in vitro. Furthermore, we demonstrated that hypoxia inducible factor-1α (HIF1α) directly regulates GPD1 at the transcriptional level, which leads to the inhibition of mitochondrial function and lipid metabolism. Additionally, GPD1 was shown to inhibit prolyl hydroxylase 3 (PHD3), which blocks prolyl-hydroxylation of HIF1α and subsequent proteasomal degradation, and thus reinforces the inhibition of mitochondrial function and phosphorylation of AMPK via suppressing glycerol-3-phosphate dehydrogenase 2 (GPD2).

Conclusions
This study not only demonstrated that HIF1α-GPD1 forms a positive feedforward loop inhibiting mitochondrial function and lipid metabolism in ccRCC, but also discovered a new mechanism for the molecular basis of HIF1α to inhibit tumor activity, thus providing novel insights into hypoxia-lipid-mediated ccRCC therapy.
Staphylococcus aureus ventilator-associated pneumonia in patients with COVID-19: clinical features and potential inference with lung dysbiosis
Authors: De Pascale Gennaro , De Maio Flavio , Carelli Simone , De Angelis Giulia , Cacaci Margherita , Montini Luca , Bello Giuseppe , Cutuli Salvatore Lucio , Pintaudi Gabriele , Tanzarella Eloisa Sofia , Xhemalaj Rikardo , Grieco Domenico Luca , Tumbarello Mario , Sanguinetti Maurizio , Posteraro Brunella , Antonelli Massimo 
Published: June 2021

Abstract
Background
Hospitalized patients with COVID-19 admitted to the intensive care unit (ICU) and requiring mechanical ventilation are at risk of ventilator-associated bacterial infections secondary to SARS-CoV-2 infection. Our study aimed to investigate clinical features of Staphylococcus aureus ventilator-associated pneumonia (SA-VAP) and, if bronchoalveolar lavage samples were available, lung bacterial community features in ICU patients with or without COVID-19.

Methods
We prospectively included hospitalized patients with COVID-19 across two medical ICUs of the Fondazione Policlinico Universitario A. Gemelli IRCCS (Rome, Italy), who developed SA-VAP between 20 March 2020 and 30 October 2020 (thereafter referred to as cases). After 1:2 matching based on the simplified acute physiology score II (SAPS II) and the sequential organ failure assessment (SOFA) score, cases were compared with SA-VAP patients without COVID-19 (controls). Clinical, microbiological, and lung microbiota data were analyzed.

Results
We studied two groups of patients (40 COVID-19 and 80 non-COVID-19). COVID-19 patients had a higher rate of late-onset (87.5% versus 63.8%; p = 0.01), methicillin-resistant (65.0% vs 27.5%; p < 0.01) or bacteremic (47.5% vs 6.3%; p < 0.01) infections compared with non-COVID-19 patients. No statistically significant differences between the patient groups were observed in ICU mortality (p = 0.12), clinical cure (p = 0.20) and microbiological eradication (p = 0.31). On multivariable logistic regression analysis, SAPS II and initial inappropriate antimicrobial therapy were independently associated with ICU mortality. Then, lung microbiota characterization in 10 COVID-19 and 16 non-COVID-19 patients revealed that the overall microbial community composition was significantly different between the patient groups (unweighted UniFrac distance, R2 0.15349; p < 0.01). Species diversity was lower in COVID-19 than in non COVID-19 patients (94.4 ± 44.9 vs 152.5 ± 41.8; p < 0.01). Interestingly, we found that S. aureus (log2 fold change, 29.5), Streptococcus anginosus subspecies anginosus (log2 fold change, 24.9), and Olsenella (log2 fold change, 25.7) were significantly enriched in the COVID-19 group compared to the non–COVID-19 group of SA-VAP patients.

Conclusions
In our study population, COVID-19 seemed to significantly affect microbiological and clinical features of SA-VAP as well as to be associated with a peculiar lung microbiota composition.
Flow Index: a novel, non-invasive, continuous, quantitative method to evaluate patient inspiratory effort during pressure support ventilation
Authors: Albani Filippo , Pisani Luigi , Ciabatti Gianni , Fusina Federica , Buizza Barbara , Granato Anna , Lippolis Valeria , Aniballi Eros , Murgolo Francesco , Rosano Antonio , Latronico Nicola , Antonelli Massimo , Grasso Salvatore , Natalini Giuseppe 
Published: June 2021

Abstract
Background
The evaluation of patient effort is pivotal during pressure support ventilation, but a non-invasive, continuous, quantitative method to assess patient inspiratory effort is still lacking. We hypothesized that the concavity of the inspiratory flow-time waveform could be useful to estimate patient’s inspiratory effort. The purpose of this study was to assess whether the shape of the inspiratory flow, as quantified by a numeric indicator, could be associated with inspiratory effort during pressure support ventilation.

Methods
Twenty-four patients in pressure support ventilation were enrolled. A mathematical relationship describing the decay pattern of the inspiratory flow profile was developed. The parameter hypothesized to estimate effort was named Flow Index. Esophageal pressure, airway pressure, airflow, and volume waveforms were recorded at three support levels (maximum, minimum and baseline). The association between Flow Index and reference measures of patient effort (pressure time product and pressure generated by respiratory muscles) was evaluated using linear mixed effects models adjusted for tidal volume, respiratory rate and respiratory rate/tidal volume.

Results
Flow Index was different at the three pressure support levels and all group comparisons were statistically significant. In all tested models, Flow Index was independently associated with patient effort (p < 0.001). Flow Index prediction of inspiratory effort agreed with esophageal pressure-based methods.

Conclusions
Flow Index is associated with patient inspiratory effort during pressure support ventilation, and may provide potentially useful information for setting inspiratory support and monitoring patient-ventilator interactions.
The global and promoter-centric 3D genome organization temporally resolved during a circadian cycle
Authors: Furlan-Magaril Mayra , Ando-Kuri Masami , Arzate-Mejía Rodrigo G. , Morf Jörg , Cairns Jonathan , Román-Figueroa Abraham , Tenorio-Hernández Luis , Poot-Hernández A. César , Andrews Simon , Várnai Csilla , Virk Boo , Wingett Steven W. , Fraser Peter 
Published: June 2021

Abstract
Background
Circadian gene expression is essential for organisms to adjust their physiology and anticipate daily changes in the environment. The molecular mechanisms controlling circadian gene transcription are still under investigation. In particular, how chromatin conformation at different genomic scales and regulatory elements impact rhythmic gene expression has been poorly characterized.

Results
Here we measure changes in the spatial chromatin conformation in mouse liver using genome-wide and promoter-capture Hi-C alongside daily oscillations in gene transcription. We find topologically associating domains harboring circadian genes that switch assignments between the transcriptionally active and inactive compartment at different hours of the day, while their boundaries stably maintain their structure over time. To study chromatin contacts of promoters at high resolution over time, we apply promoter capture Hi-C. We find circadian gene promoters displayed a maximal number of chromatin contacts at the time of their peak transcriptional output. Furthermore, circadian genes, as well as contacted and transcribed regulatory elements, reach maximal expression at the same timepoints. Anchor sites of circadian gene promoter loops are enriched in DNA binding sites for liver nuclear receptors and other transcription factors, some exclusively present in either rhythmic or stable contacts. Finally, by comparing the interaction profiles between core clock and output circadian genes, we show that core clock interactomes are more dynamic compared to output circadian genes.

Conclusion
Our results identify chromatin conformation dynamics at different scales that parallel oscillatory gene expression and characterize the repertoire of regulatory elements that control circadian gene transcription through rhythmic or stable chromatin configurations.
Global transcriptome landscape of the rabbit protozoan parasite Eimeria stiedae
Authors: Xie Yue , Xiao Jie , Zhou Xuan , Gu Xiaobin , He Ran , Xu Jing , Jing Bo , Peng Xuerong , Yang Guangyou 
Published: June 2021

Abstract
Background
Coccidiosis caused by Eimeria stiedae is a widespread and economically significant disease of rabbits. The lack of studies on the life-cycle development and host interactions of E. stiedae at the molecular level has hampered our understanding of its pathogenesis.

Methods
In this study, we present a comprehensive transcriptome landscape of E. stiedae to illustrate its dynamic development from unsporulated oocysts to sporulated oocysts, merozoites, and gametocytes, and to identify genes related to parasite-host interactions during parasitism using combined PacBio single-molecule real-time and Illumina RNA sequencing followed by bioinformatics analysis and qRT-PCR validation.

Results
In total, 12,582 non-redundant full-length transcripts were generated with an average length of 1808 bp from the life-cycle stages of E. stiedae. Pairwise comparisons between stages revealed 8775 differentially expressed genes (DEGs) showing highly significant description changes, which compiled a snapshot of the mechanisms underlining asexual and sexual biology of E. stiedae including oocyst sporulation between unsporulated and sporulated oocysts; merozoite replication between sporulated oocysts and merozoites; and gametophyte development and gamete generation between merozoites and gametocytes. Further, 248 DEGs were grouped into nine series clusters and five groups by expression patterns, and showed that parasite–host interaction-related genes predominated in merozoites and gametocytes and were mostly involved in steroid biosynthesis and lipid metabolism and carboxylic acid. Additionally, co-expression analyses identified genes associated with development and host invasion in unsporulated and sporulated oocysts and immune interactions during gametocyte parasitism.

Conclusions
This is the first study, to our knowledge, to use the global transcriptome profiles to decipher molecular changes across the E. stiedae life cycle, and these results not only provide important information for the molecular characterization of E. stiedae, but also offer valuable resources to study other apicomplexan parasites with veterinary and public significance.

Graphical Abstract
A case of lymphocytic esophagitis in a woman with multiple allergies
Authors: Wojas O. , Żalikowska-Gardocka M. , Krzych-Fałta E. , Szczepankiewicz B. , Samel-Kowalik P. , Samoliński B. , Przybyłkowski A. 
Published: June 2021

Abstract
Background
Lymphocytic esophagitis is a newly recognized entity of unknown origin. Dysphagia is defined as difficulty swallowing and represents a common symptom in the general population with a prevalence of approximately 20%. Chronic inflammation of the esophageal wall may manifest itself clinically and endoscopically, mimicking inflammation of another origin. However, little is known about the pathogenesis of the disease, as patients are seldom suspected and rarely diagnosed with lymphocytic esophagitis.

Case presentation
Here, we present a rare case of lymphocytic esophagitis in a patient with multiple allergies and suspected eosinophilic esophagitis. A 28-year-old woman with polyvalent sensitization to food and inhalant allergens presented with intermittent dysphagia, a sensation of a foreign body in the throat, itchiness of the oral cavity after ingesting certain foods, heartburn, and prolonged chewing time. A skin prick test showed positive results for birch-tree, alder, hazel, and rye pollen, as well as house dust mites. Apart from obesity (BMI 30 kg/m2), multiple pustules and excoriations on the skin, her physical examination was insignificant. Esophagogastroduodenoscopy (EGD) was performed revealing full-length but discrete trachealization of the esophagus. A barium swallow test showed slowing of esophageal peristalsis in the recumbent position. No esophageal pathology was observed. A histopathological analysis of mucosal samples revealed slight hyperplasia of the basal layer of the esophagus, and the stomach showed changes typical of chronic gastritis.

Conclusions
In summary, this clinical case illustrates that lymphocytic esophagitis, as a newly recognized entity, should be considered in the differential diagnosis of chronic dysphagia. Additionally, when treating allergic patients, clinicians should be aware that lymphocytic esophagitis, distinct from eosinophilic esophagitis, should be considered in the diagnosis of patients with atopy and upper gastrointestinal symptoms.
Psychometric validation and refinement of the Interoception Sensory Questionnaire (ISQ) in adolescents and adults on the autism spectrum
Authors: Suzman Evan , Williams Zachary J. , Feldman Jacob I. , Failla Michelle , Cascio Carissa J. , Wallace Mark T. , Niarchou Maria , Sutcliffe James S. , Wodka Ericka , Woynaroski Tiffany G. 
Published: June 2021

AbstractBackgroundIndividuals on the autism spectrum are reported to display alterations in interoception, the sense of the internal state of the body. The Interoception Sensory Questionnaire (ISQ) is a 20-item self-report measure of interoception specifically intended to measure this construct in autistic people. The psychometrics of the ISQ, however, have not previously been evaluated in a large sample of autistic individuals.MethodsUsing confirmatory factor analysis, we evaluated the latent structure of the ISQ in a large online sample of adults on the autism spectrum and found that the unidimensional model fit the data poorly. Using misspecification analysis to identify areas of local misfit and item response theory to investigate the appropriateness of the seven-point response scale, we removed redundant items and collapsed the response options to put forth a novel eight-item, five-response choice ISQ.ResultsThe revised, five-response choice ISQ (ISQ-8) showed much improved fit while maintaining high internal reliability. Differential item functioning (DIF) analyses indicated that the items of the ISQ-8 were answered in comparable ways by autistic adolescents and adults and across multiple other sociodemographic groups.LimitationsOur results were limited by the fact that we did not collect data for typically developing controls, preventing the analysis of DIF by diagnostic status. Additionally, while this study proposes a new 5-response scale for the ISQ-8, our data were not collected using this method; thus, the psychometric properties for the revised version of this instrument require further investigation.ConclusionThe ISQ-8 shows promise as a reliable and valid measure of interoception in adolescents and adults on the autism spectrum, but additional work is needed to examine its psychometrics in this population. A free online score calculator has been created to facilitate the use of ISQ-8 latent trait scores for further studies of autistic adolescents and adults (available athttps://asdmeasures.shinyapps.io/ISQ_score/).
From hypotonic maintenance fluid to severe hyponatremia: a case report
Authors: Denis M. , Di Giacomo A. , Lacotte E. , Porcheret F. , Letouzé N. , Lauzier B. , Goyer I. , Brossier D. 
Published: June 2021

AbstractBackgroundThe principles for maintenance intravenous fluid prescription in children were developed in the 1950s. These guidelines based on the use of hypotonic solutions have been challenged regularly for they seem to be associated with an increased risk of hospital-acquired hyponatremia.Case presentationWe report the case of a 4-week-old Caucasian child admitted for acute bronchiolitis who received hypotonic maintenance fluids and developed severe hyponatremia (94 mmol/L) with hyponatremic encephalopathy.ConclusionThis clinical situation can serve as a reminder of the latest recommendations from the American Academy of Pediatrics regarding the use of intravenous fluids that promote the use of isotonic fluids in children.
Rspo3 regulates the abnormal differentiation of small intestinal epithelial cells in diabetic state
Authors: Shan Ti-Dong , Yue Han , Sun Xue-Guo , Jiang Yue-Ping , Chen Li 
Published: June 2021

Abstract
Background
The complications caused by diabetes mellitus (DM) are the focus of clinical treatment. However, little is known about diabetic enteropathy (DE) and its potential underlying mechanism.

Methods
Intestinal epithelial cells (IECs) and intestinal epithelial stem cells (IESCs) were harvested from BKS.Cg-Dock7m+/+Leprdb/JNju (DM) mice, and the expression of R-Spondin 3 (Rspo3) was detected by RT-qPCR, Western blotting, immunohistochemistry, and immunofluorescence. The role of Rspo3 in the abnormal differentiation of IECs during DM was confirmed by knockdown experiments. Through miRNA expression profiling, bioinformatics analysis, and RT-qPCR, we further analyzed the differentiation-related miRNAs in the IECs from mice with DM.

Results
Abnormal differentiation of IECs was observed in the mice with DM. The expression of Rspo3 was upregulated in the IECs from the mice with DM. This phenomenon was associated with Rspo3 overexpression. Additionally, Rspo3 is a major determinant of Lgr5+ stem cell identity in the diabetic state. Microarray analysis, bioinformatics analysis, and luciferase reporter assays revealed that microRNA (miR)-380-5p directly targeted Rspo3. Moreover, miR-380-5p upregulation was observed to attenuate the abnormal differentiation of IECs by regulating Rspo3 expression.

Conclusions
Together, our results provide definitive evidence of the essential role of Rspo3 in the differentiation of IECs in DM.
Crucial mutation in the exoribonuclease domain of nsp14 of PEDV leads to high genetic instability during viral replication
Authors: Niu Xiaoyu , Kong Fanzhi , Hou Yixuan J. , Wang Qiuhong 
Published: June 2021

Abstract
Background
Coronavirus (CoV) nonstructural protein 14 (nsp14) has exoribonuclease (ExoN) activity, responsible for proofreading and contributing to replication fidelity. It has been reported that CoVs exhibit variable sensitivity to nsp14-ExoN deficiency. Betacoronavirus murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV were viable upon nsp14-ExoN deficiency. While betacoronavirus Middle East respiratory syndrome (MERS)-CoV and SARS-CoV-2 were non-viable with disabled nsp14-ExoN. In this study, we investigated the nsp14-ExoN deficiency of alphacoronavirus porcine epidemic diarrhea virus (PEDV) in viral pathogenesis using reverse genetics.

Results
Eight nsp14-ExoN deficient mutants, targeting the predicted active sites and the Zinc finger or mental-coordinating sites, of PEDV were designed. Only one mutant E191A with a mutation in the Mg2+-binding site was rescued using the infectious clone of PEDV PC22A strain (icPC22A). The passage no.1–3 (P1-3) of E191A grew to very low titers in Vero cells. To evaluate the pathogenesis of the E191A, 4 or 5-day-old gnotobiotic pigs were inoculated orally with 100 TCID50/pig of the E191A-P1, icPC22A, or mock. All mock pigs did not shed virus in feces or show clinical signs. All pigs inoculated with icPC22A shed high viral RNA levels, had severe diarrhea, and died by 6 days post-inoculation (dpi). In contrast, only 3 pigs (3/4, 75%) in the E191A-P1 group shed low levels of viral RNA and 2 pigs had moderate diarrhea at acute infection phase. At 22 dpi, each pig was challenged orally with 106 plaque forming unit of virulent icPC22A. All pigs in the mock group developed severe diarrhea and 2 of the 5 pigs died. Pigs in the E191A-P1 group had less severe diarrhea and no pigs died. Sanger sequencing analysis revealed that the viral genome in the fecal sample of one E191A-P1-inoculated pig and the P4 virus passaged in vitro lost the E191A mutation, suggesting the genetic instability of the E191A mutant.

Conclusion
The recombinant PEDV variants carrying mutations at the essential functional sites within nsp14-ExoN were either lethal or genetically unstable. Our finding further confirmed the critical role of nsp14-ExoN in CoV life cycle, suggesting that it may be a target for the design of universal anti-CoV drugs.