bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomics and random forests in patients with complex congenital heart disease
Authors: Michel Miriam , Laser Kai Thorsten , Dubowy Karl-Otto , Scholl-Bürgi Sabine , Michel Erik 
Published: October 2022

IntroductionIt is increasingly common to simultaneously determine a large number of metabolites in order to assess the metabolic state of, or clarify biochemical pathways in, an organism (“metabolomics”). This approach is increasingly used in the investigation of the development of heart failure. Recently, the first reports with respect to a metabolomic approach for the assessment of patients with complex congenital heart disease have been published. Classical statistical analysis of such data is challenging.ObjectiveThis study aims to present an alternative to classical statistics with respect to identifying relevant metabolites in a classification task and numerically estimating their relative impact.MethodsData from two metabolomic studies on 20 patients with complex congenital heart disease and Fontan circulation and 20 controls were reanalysed using random forest (RF) methodology. Results were compared to those of classical statistics.ResultsRF analysis required no elaborate data pre-processing. The ranking of the variables with respect to classification impact (subject diseased, or not) was remarkably similar irrespective of the evaluation method used, leading to identical clinical interpretation.ConclusionIn metabolomic classification in adult patients with complex congenital heart disease, RF analysis as a one-step method delivers the most adequate results with minimum effort. RF may serve as an adjunct to traditional statistics also in this small but crucial-to-monitor patient group.
Multi-omics insights into potential mechanism of SGLT2 inhibitors cardiovascular benefit in diabetic cardiomyopathy
Authors: Xi Yangbo , Chen Dongping , Dong Zhihui , Zhang Jinhua , Lam Hingcheung , He Jiading , Du Keyi , Chen Can , Guo Jun , Xiao Jianmin 
Published: October 2022

BackgroundMetabolic and energy disorders are considered central to the etiology of diabetic cardiomyopathy (DCM). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) can effectively reduce the risk of cardiovascular death and heart failure in patients with DCM. However, the underlying mechanism has not been elucidated.MethodsWe established a DCM rat model followed by treatment with empagliflozin (EMPA) for 12 weeks. Echocardiography, blood tests, histopathology, and transmission electron microscopy (TEM) were used to evaluate the phenotypic characteristics of the rats. The proteomics and metabolomics of the myocardium in the rat model were performed to identify the potential targets and signaling pathways associated with the cardiovascular benefit of SGLT2i.ResultsThe diabetic rat showed pronounced DCM characterized by mitochondrial pleomorphic, impaired lipid metabolism, myocardial fibrosis, and associated diastolic and systolic functional impairments in the heart. To some extent, these changes were ameliorated after treatment with EMPA. A total of 43 proteins and 34 metabolites were identified as targets in the myocardium of diabetic rats treated with EMPA. The KEGG analysis showed that arachidonic acid is associated with the maximum number of related pathways and may be a potential target of EMPA treatment. Fatty acid (FA) metabolism was enhanced in diabetic hearts, and the perturbation of biosynthesis of unsaturated FAs and arachidonic acid metabolism was a potential enabler for the cardiovascular benefit of EMPA.ConclusionSGLT2i ameliorated lipid accumulation and mitochondrial damage in the myocardium of diabetic rats. The metabolomic and proteomic data revealed the potential targets and signaling pathways associated with the cardiovascular benefit of SGLT2i, which provides a valuable resource for the mechanism of SGLT2i.
Evidence of the climate control of strong seismicity in the Italian Apennines through groundwater recharge
Authors: Bragato Pier Luigi 
Published: October 2022

This work explores the possibility that the destructive earthquakes occurring along the Apennine Chain in Italy are systematically triggered by groundwater recharge. The focus is on multi-year transitions toward phases of wet climate rather than on short-term heavy rainfall occurring in a few days or seasonally. The analysis takes into consideration the earthquakes with a moment magnitude of Mw ≥5.8 that have occurred since 1901. Their time distribution is compared with the fluctuations of the self-calibrated Palmer Drought Severity Index (scPDSI), an indicator of soil moisture, here assumed to be a proxy for groundwater recharge. It is found that the scPDSI evolved through six main oscillations lasting from 11 to 25 years, and that, with one exception, the strongest earthquake in each phase is placed within 2 years from the maximum of soil moisture. Based on a statistical test for pairs of point processes, such a coincidence indicates a significant synchrony between the two phenomena. In particular, the two strongest earthquakes of the study period (the 1915 Marsica earthquake and the 1980 Irpinia–Basilicata earthquake, with moment magnitudes of Mw 7.1 and 6.8, respectively) occurred exactly in the year of two of the largest peaks of scPDSI. The connection between wet climate conditions and the occurrence of strong earthquakes is further investigated by comparing the time distribution of Mw ≥6.1 historical earthquakes that have occurred since 1200 AD with the evolution of the Great Aletsch Glacier in Switzerland, representative of water accumulation at the continental level. Even in this case, the earthquakes clustered during time periods of increased precipitation and lower water evaporation, corresponding to the extreme phases of the Little Ice Age. The agreement of the results at different time scales and using different climate indexes leads to postulate a significant and systematic role of groundwater recharge in the triggering of large earthquakes along the Apennines. It is also suggested that the earthquakes might be triggered by pore-pressure propagation, where the necessary hydraulic continuity is made possible by the intersection of the shallow karst structures with the seismogenic faults.
A multi-proxy approach to detect the pore pressure and the origin of overpressure in sedimentary basins: An example from the Gulf of Suez rift basin
Authors: Radwan Ahmed E. 
Published: October 2022

The pore pressure gradient and fracture gradient (PPFG) are critical parameters for drilling mud weight design in the energy industry. Successful drilling operations can be achieved successfully through the understanding of the pore pressure and fracture pressure in the subsurface succession. The scope of this research is to use an integrated approach that encompasses well-logging, basin modeling, drilling-based interpretations, and reservoir measurement methods to gain a reasonable PPFG model and decrease the drilling uncertainties in the El Morgan oil field in the Gulf of Suez. Moreover, it investigates the overpressure generation mechanisms in the basin, which have not been studied before in this area. In this work, PPFGs of more than 16 km of cumulative thick sedimentary succession were modeled and evaluated using an integrated approach. This study utilizes Eaton’s sonic and resistivity-based methods for pore pressure evaluation, while vertical stress was calculated based on the composite density profile. The study revealed that the top geo-pressure was detected at a depth of 1,030 m of Tortonian sediments. Late Miocene sediments reveal hard over-pressure with a maximum gradient of 0.55 PSI/feet, while Middle Miocene sediments exhibit mildly over-pressured, normal, and sub-normal pore pressure zones. The lowest pore pressure values were measured in the Langhian-Serravalian Kareem reservoir with a gradient of 0.29 PSI/feet. With the exception of a slight difference in the reservoir section, the pore pressure profiles in the northern and southern parts of the El Morgan oil field are relatively similar. Reservoir connectivity is believed to be the main reason behind pore pressure magnitude differentiation in the Middle Miocene reservoirs. The key mechanism for generating overpressure has been identified as disequilibrium compaction, and reservoir overcharging may contribute as an excess-pressure generation mechanism at the reservoir level. The presented approach can be applied in PPFG studies for both development and exploratory geomechanical studies in other areas of the Gulf of Suez basin or elsewhere in the world.
Neurodegeneration of the cornea and retina in patients with type 1 diabetes without clinical evidence of diabetic retinopathy
Authors: Carmichael Josie , Fadavi Hassan , Tavakoli Mitra 
Published: October 2022

AimDiabetic retinopathy (DR) is widely considered the earliest and most common microvascular complication of diabetes. However, recent studies have shown that retinal nerve fiber layer and corneal nerve abnormalities may be present in diabetic patients without retinopathy. This preliminary study aimed to establish if structural and functional changes in the nerve fiber layer of the retina and cornea occur in patients with type 1 diabetes (T1DM) without retinopathy.MethodsTwenty patients with T1DM, without clinical evidence of retinopathy (Age: 47.0 ± 2.5 years; Duration diabetes: 27.0 ± 3 years) and 15 age-matched healthy control subjects underwent detailed medical neurological examinations. Ophthalmic examinations using Spectral Domain Optical coherence tomography (SD-OCT), Standard Automated Perimetry (SAP), Flicker Defined Form High Edge Perimetry (FDF), Corneal Confocal Microscopy (CCM) and Non-contact corneal Aesthesiometry (NCCA) were performed to quantify the structure and function of the nerves in the retina and cornea, respectively.ResultsAt the structural level, retinal nerve fiber layer thickness (RNFL) was significantly reduced in the superior nasal (p=0.001) and inferior temporal (p=0.004) sectors, in diabetic patients. Retinal ganglion layer function was reduced in the patient group when assessed using Flicker Defined Form Perimetry (FDF), but this was not significant. The function of the cornea assessed by corneal sensitivity, using a non-contact corneal aesthesiometer (NCCA), was significantly reduced (p=0.001). Structural assessment of corneal nerves using corneal confocal microscopy (CCM) showed reduction at corneal nerve fiber density (CNFD) (p=0.01), branch density (CNBD) (p=0.006) and length (CNFL) (p=0.01) in patients with diabetes. Compared to control subjects, the percentage of abnormality in patients with T1DM for RNFL was 32% while the FDF was abnormal in 61% of patients. Corneal abnormality was observed in 47% for NCCA, 28% for CNFD, and 17% for CNFL. There was no correlation between neuronal damage in the retina and cornea.ConclusionsNeuronal abnormalities were observed in both the retina and cornea of diabetic patients without evidence of retinopathy. The prevalence of structural and functional changes was higher in the retina compared to the cornea. This preliminary study suggests that structural neuronal changes may occur in parallel and correlate with functional changes. The assessment of corneal and retinal nerve structure may be clinically useful for detecting and monitoring the earliest stages of diabetic microvascular abnormalities.
Dose–response relationship between Chinese visceral adiposity index and type 2 diabetes mellitus among middle-aged and elderly Chinese
Authors: Pan Liang , Xu Qianqian , Liu Jianmin , Gao Yang , Li Jun , Peng Hongye , Chen Linli , Wang Miyuan , Mai Gang , Yang Shuo 
Published: October 2022

IntroductionChina has the largest population of diabetic patients (about 116 million) in the world. As a novel model of the fat index for Chinese people, the Chinese visceral adiposity index (CVAI) was considered a reliable indicator to assess the dysfunction of visceral fat. This study aimed to explore the dose–response relationship between CVAI and type 2 diabetes mellitus (T2DM) in the Chinese population, considering CVAI as a continuous/categorical variable.MethodBaseline and follow-up data were collected from waves 2011 and 2015, respectively, of the China Health and Retirement Longitudinal Study (CHARLS). Multivariate logistic regression models were used to explore the relationship between CVAI and T2DM. We built three models to adjust the possible effect of 10 factors (age, gender, education level, location, marital status, smoking status, drinking status, sleep time, systolic blood pressure (SBP), and diastolic blood pressure (DBP)) on the outcome. The restricted cubic splines were used to examine possible non-linear associations and visualize the dose–response relationship between CVAI and T2DM.ResultsA total of 5,014 participants were included, with 602 (12.00%) T2DM patients. The last CVAI quartile group (Q4) presented the highest risk of T2DM (OR, 2.17, 95% CI, 1.67–2.83), after adjusting for all covariates. There was a non-linear (U-shaped) relationship between the CVAI and the risk of T2DM (p for non-linear &lt;0.001) in the restricted cubic spline regression model. CVAI was a risk factor of T2DM when it exceeded 92.49; every interquartile range (IQR) increment in the CVAI was associated with a 57% higher risk of developing T2DM (OR = 1.57, 95% CI = 1.36–1.83) after adjusting for potential confounders. The area under the receiver operating characteristic curve (AUC) (95% confidence interval) for CVAI was 0.623, and the optimal cutoff point was 111.2. There was a significant interaction between CVAI and gender by stratified analysis.ConclusionCVAI was closely associated with the risk of T2DM and might possibly be a potential marker in predicting T2DM development. The outcome suggested that it might be better to maintain CVAI within an appropriate range.
Pond greenhouse gas emissions controlled by duckweed coverage
Authors: Rabaey Joseph , Cotner James 
Published: October 2022

Freshwaters are significant contributors of greenhouse gases to the atmosphere, including carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O). Small waterbodies such as ponds are now recognized to have disproportionate greenhouse gas emissions relative to their size, but measured emissions from ponds have varied by several orders of magnitude. To assess drivers of variation in pond greenhouse gas dynamics, we measured concentrations and emissions of CO2, CH4, and N2O across 26 ponds in Minnesota, United States, during the ice-free season. The studied ponds differed in land-use, from urban stormwater ponds to natural forested ponds. The ponds were all sources of greenhouse gases, driven by large CH4 emissions (mean 704 [sd 840] mg CH4-C m−2 d−1). CO2 fluxes were variable, but on average a sink (mean −25.9 [sd 862] mg CO2-C m−2 d−1), and N2O emissions were generally low (mean 0.398 [sd 0.747] mg N2O-N m−2 d−1). Duckweed coverage on the water surfaces ranged from 0% to 100% coverage, and had the largest influence on water chemistry and greenhouse gas dynamics across the ponds. Duckweed covered ponds (ponds with greater than 85% coverage) had higher phosphorus levels and increased anoxia compared to ponds without duckweed (ponds with less than 12% coverage), leading to higher CH4 concentrations and overall greenhouse gas emissions in the duckweed ponds. Duckweed ponds had a mean emission rate in CO2 equivalents of 30.9 g C m−2 d−1 compared to 11.0 g C m−2 d−1 in non-duckweed ponds.
Preimplantation genetic testing for recurrent autosomal dominant osteogenesis imperfecta associated with paternal gonosomal mosaicism
Authors: Bai Haiyan , Li Xiaofang , Liu Xitong , Shi Wenhao , He Bin , Wei Ruiyang , Shi Juanzi 
Published: October 2022

Research Question: How to prevent the transfer of a mutation causing osteogenesis imperfecta (OI) to offspring in a couple with recurrent adverse pregnancy outcomes, when the male partner is a gonosomal mosaic carrier.Design: High-throughput sequencing and first-generation DNA sequencing were performed using the tissues from an aborted fetus and its parents. Regions 2 Mb upstream and downstream of the COL1A1 gene were subjected to multiplex PCR to identify single nucleotide polymorphisms (SNPs) and family haplotypes associated with the disease-causing mutation. Single-cell whole-genome amplification and sequencing were performed on trophoblasts cultured in vitro for 5–6 days to construct embryonic SNP haplotypes, and first-generation sequencing was used for pathogenic locus verification and aneuploidy screening. Preimplantation genetic testing for monogenic disorders (PGT-M) was also performed.Results: The aborted fetus was heterozygous for the COL1A1 mutation c.1454G&gt;A (chr17-48272089, p.Gly485Asp) suspected to cause OI. The variant was also detected in the peripheral blood cells and sperm of the male partner, who appeared to be a gonosomal mosaic carrier of the mutation. Three morphologically usable blastocysts were obtained in vitro and successfully expanded after a trophectoderm biopsy. Two blastocysts were unusable owing to aneuploidy; however, one was euploid and did not carry the paternal mutation. Post-transfer gestation was confirmed by systematic B-scan ultrasound, and amniocentesis findings were consistent with the PGT-M results.Conclusion: Parental gonadal mosaicism was the cause of recurrent terminated pregnancies due to fetal skeletal dysplasia. Using PGT-M to select embryos without the paternal pathogenic mutation prevented the vertical transmission of OI in this family, and a successful pregnancy was achieved.
Th17 cells in primary Sjögren’s syndrome negatively correlate with increased Roseburia and Coprococcus
Authors: Xin Xiaohong , Wang Qian , Qing Jianbo , Song Wenzhu , Gui Yanni , Li Xiaofeng , Li Yafeng 
Published: October 2022

BackgroundDysbiosis of the gut microbiota is closely related to chronic systemic inflammation and autoimmunity, playing an essential role in the pathogenesis of primary Sjögren’s syndrome (pSS). Abnormalities in the proportions of blood T lymphocyte subtype, that is Th17/Treg, were detected in pSS patients. We aimed to determine the associations between gut microbiota and Th17/Treg in pSS.Method98 pSS patients and 105 healthy controls (NC) were enrolled between Dec 1, 2018, and Aug 31, 2019. The baseline information and clinical parameters on pSS patients and healthy controls were collected. 16S rRNA sequencing was performed to characterize the gut microbiome and identify gut microbes that are differentially abundant between patients and healthy controls. Lastly, associations between relative abundances of specific bacterial taxa in the gut and clinical outcome parameters were evaluated.ResultsPatients with pSS show decreased gut microbial diversity and richness, decreased abundance of butyrate producing bacteria, such as Roseburia and Coprococcus, and increased abundance of other taxa, such as Eubacterium rectale and Roseburia inulinivorans. These bacteria are enriched with functions related to glycolytic and lipogenic, energy, substance, galactose, pentose metabolism pathways and glucuronate interconversions, decreased with functions related to peptidoglycan biosynthesis, pyrimidine metabolism pathways. An integrative analysis identified pSS-related specific bacterial taxa in the gut, for which the abundance of Eubacterium rectale is negatively correlated with Th17/Treg. Furthermore, the pathways of biosynthesis of secondary metabolites, biosynthesis of amino acids, peptidoglycan biosynthesis and pyrimidine, galactose, pentose, microbial metabolism in diverse environments, glyoxylate and dicarboxylate metabolism are associated with Treg or Th17/Treg.ConclusionsPrimary Sjögren’s syndrome could lead to decreased gut microbial diversity and richness of intestinal flora in patients. The proportions of Th17 and Treg cells induced by microbiota were predictive pSS manifestations and accounted for the pSS severity.
Factors associated with hemorrhagic fever with renal syndrome based maximum entropy model in Zhejiang Province, China
Authors: Zhang Rong , Zhang Ning , Liu Ying , Liu Tianxiao , Sun Jimin , Ling Feng , Wang Zhen 
Published: October 2022

BackgroundHemorrhagic fever with renal syndrome (HFRS) is a serious public health problem in China. The geographic distribution has went throughout China, among which Zhejiang Province is an important epidemic area. Since 1963, more than 110,000 cases have been reported.MethodsWe collected the meteorological factors and socioeconomic indicators of Zhejiang Province, and constructed the HFRS ecological niche model of Zhejiang Province based on the algorithm of maximum entropy.ResultsModel AUC from 2009 to 2018, is 0.806–0.901. The high incidence of epidemics in Zhejiang Province is mainly concentrated in the eastern, western and central regions of Zhejiang Province. The contribution of digital elevation model ranged from 2009 to 2018 from 4.22 to 26.0%. The contribution of average temperature ranges from 6.26 to 19.65%, Gross Domestic Product contribution from 7.53 to 21.25%, and average land surface temperature contribution with the highest being 16.73% in 2011. In addition, the average contribution of DMSP/OLS, 20-8 precipitation and 8-20 precipitation were all in the range of 9%. All-day precipitation increases with the increase of rainfall, and the effect curve peaks at 1,250 mm, then decreases rapidly, and a small peak appears again at 1,500 mm. Average temperature response curve shows an inverted v-shape, where the incidence peaks at 17.8°C. The response curve of HFRS for GDP and DMSP/OLS shows a positive correlation.ConclusionThe incidence of HFRS in Zhejiang Province peaked in areas where the average temperature was 17.8°C, which reminds that in the areas where temperature is suitable, personal protection should be taken when going out as to avoid contact with rodents. The impact of GDP and DMSP/OLS on HFRS is positively correlated. Most cities have good medical conditions, but we should consider whether there are under-diagnosed cases in economically underdeveloped areas.