bluuebunny/crossref_metadata_2025_split huggingface dataset:
XGBLC: an improved survival prediction model based on XGBoost
Authors: Ma Baoshan , Yan Ge , Chai Bingjie , Hou Xiaoyu 
Published: September 2021

AbstractMotivationSurvival analysis using gene expression profiles plays a crucial role in the interpretation of clinical research and assessment of disease therapy programs. Several prediction models have been developed to explore the relationship between patients’ covariates and survival. However, the high-dimensional genomic features limit the prediction performance of the survival model. Thus, an accurate and reliable prediction model is necessary for survival analysis using high-dimensional genomic data.ResultsIn this study, we proposed an improved survival prediction model based on XGBoost framework called XGBLC, which used Lasso-Cox to enhance the ability to analyze high-dimensional genomic data. The novel first- and second-order gradient statistics of Lasso-Cox were defined to construct the loss function of XGBLC. We extensively tested our XGBLC algorithm on both simulated and real-world datasets, and estimated the performance of models with 5-fold cross-validation. Based on 20 cancer datasets from The Cancer Genome Atlas (TCGA), XGBLC outperforms five state-of-the-art survival methods in terms of C-index, Brier score and AUC. The results show that XGBLC still keeps good accuracy and robustness by comparing the performance on the simulated datasets with different scales. The developed prediction model would be beneficial for physicians to understand the effects of patient’s genomic characteristics on survival and make personalized treatment decisions.Availability and implementationThe implementation of XGBLC algorithm based on R language is available at: https://github.com/lab319/XGBLCSupplementary informationSupplementary data are available at Bioinformatics online.
Multiomix: a cloud-based platform to infer cancer genomic and epigenomic events associated with gene expression modulation
Authors: Camele Genaro , Menazzi Sebastian , Chanfreau Hernán , Marraco Agustin , Hasperué Waldo , Butti Matias D , Abba Martin C 
Published: September 2021

Abstract

Motivation
Large-scale cancer genome projects have generated genomic, transcriptomic, epigenomic and clinicopathological data from thousands of samples in almost every human tumor site. Although most omics data and their associated resources are publicly available, its full integration and interpretation to dissect the sources of gene expression modulation require specialized knowledge and software.

Results
We present Multiomix, an interactive cloud-based platform that allows biologists to identify genetic and epigenetic events associated with the transcriptional modulation of cancer-related genes through the analysis of multi-omics data available on public functional genomic databases or user-uploaded datasets. Multiomix consists of an integrated set of functions, pipelines and a graphical user interface that allows retrieval, aggregation, analysis and visualization of different omics data sources. After the user provides the data to be analyzed, Multiomix identifies all significant correlations between mRNAs and non-mRNA genomics features (e.g. miRNA, DNA methylation and CNV) across the genome, the predicted sequence-based interactions (e.g. miRNA–mRNA) and their associated prognostic values.

Availability and implementation
Multiomix is available at https://www.multiomix.org. The source code is freely available at https://github.com/omics-datascience/multiomix.

Supplementary information
Supplementary data are available at Bioinformatics online.
Blood DNA methylation provides an accurate biomarker ofKMT2B-related dystonia and predicts onset
Authors: Mirza-Schreiber Nazanin , Zech Michael , Wilson Rory , Brunet Theresa , Wagner Matias , Jech Robert , Boesch Sylvia , Škorvánek Matej , Necpál Ján , Weise David , Weber Sandrina , Mollenhauer Brit , Trenkwalder Claudia , Maier Esther M , Borggraefe Ingo , Vill Katharina , Hackenberg Annette , Pilshofer Veronika , Kotzaeridou Urania , Schwaibold Eva Maria Christina , Hoefele Julia , Waldenberger Melanie , Gieger Christian , Peters Annette , Meitinger Thomas , Schormair Barbara , Winkelmann Juliane , Oexle Konrad 
Published: September 2021

AbstractDystonia is a prevalent, heterogeneous movement disorder characterized by involuntarily abnormal postures. Biomarkers of dystonia are notoriously lacking.Here, a biomarker is reported for histone lysine methyltransferase (KMT2B)-deficient dystonia, a leading subtype among the individually rare monogenic dystonias. It was derived by applying a support vector machine to an episignature of 113 DNA CpG sites, which, in blood cells, showed significant epigenome-wide association with KMT2B deficiency and at least 1× log-fold change of methylation. This classifier was accurate both when tested on the general population and on samples with various other deficiencies of the epigenetic machinery, thus allowing for definitive evaluation of variants of uncertain significance and identifying patients who may profit from deep brain stimulation, a highly successful treatment in KMT2B-deficient dystonia.Methylation was increased in KMT2B deficiency at all 113 CpG sites. The coefficients of variation of the normalized methylation levels at these sites also perfectly classified the samples with KMT2B-deficient dystonia. Moreover, the mean of the normalized methylation levels correlated well with the age at onset of dystonia (P = 0.003)—being lower in samples with late or incomplete penetrance—thus serving as a predictor of disease onset and severity. Similarly, it may also function in monitoring the recently envisioned treatment of KMT2B deficiency by inhibition of DNA methylation.
Midbrain organoids with anSNCAgene triplication model key features of synucleinopathy
Authors: Mohamed Nguyen-Vi , Sirois Julien , Ramamurthy Janani , Mathur Meghna , Lépine Paula , Deneault Eric , Maussion Gilles , Nicouleau Michael , Chen Carol X -Q , Abdian Narges , Soubannier Vincent , Cai Eddie , Nami Harris , Thomas Rhalena A , Wen Dingke , Tabatabaei Mahdieh , Beitel Lenore K , Singh Dolt Karamjit , Karamchandani Jason , Stratton Jo Anne , Kunath Tilo , Fon Edward A , Durcan Thomas M 
Published: September 2021

AbstractSNCA, the first gene associated with Parkinson’s disease, encodes the α-synuclein protein, the predominant component within pathological inclusions termed Lewy bodies. The presence of Lewy bodies is one of the classical hallmarks found in the brain of patients with Parkinson’s disease, and Lewy bodies have also been observed in patients with other synucleinopathies. However, the study of α-synuclein pathology in cells has relied largely on two-dimensional culture models, which typically lack the cellular diversity and complex spatial environment found in the brain. Here, to address this gap, we use three-dimensional midbrain organoids, differentiated from human-induced pluripotent stem cells derived from patients carrying a triplication of the SNCA gene and from CRISPR/Cas9 corrected isogenic control iPSCs. These human midbrain organoids recapitulate key features of α-synuclein pathology observed in the brains of patients with synucleinopathies. In particular, we find that SNCA triplication human midbrain organoids express elevated levels of α-synuclein and exhibit an age-dependent increase in α-synuclein aggregation, manifested by the presence of both oligomeric and phosphorylated forms of α-synuclein. These phosphorylated α-synuclein aggregates were found in both neurons and glial cells and their time-dependent accumulation correlated with a selective reduction in dopaminergic neuron numbers. Thus, human midbrain organoids from patients carrying SNCA gene multiplication can reliably model key pathological features of Parkinson’s disease and provide a powerful system to study the pathogenesis of synucleinopathies.
Circulating Omentin-1 levels and altered iron balance in chronic haemodialysis patients
Authors: Bolignano Davide , Dounousi Evangelia , Presta Pierangela , Greco Marta , Duni Anila , Crugliano Giuseppina , Pappas Charalambos , Pappas Ethymios , Dragone Francesco , Lakkas Lampros , Foti Daniela Patrizia , Andreucci Michele , Coppolino Giuseppe 
Published: September 2021

ABSTRACT

Background
Iron deficiency is highly prevalent among patients undergoing chronic haemodialysis (HD) but its correct identification is often problematic as common biomarkers of iron status, such as transferrin saturation (TSAT) and ferritin, can be altered by inflammation or malnutrition.

Methods
In this pilot multicentre study, we aimed at evaluating circulating levels of Omentin-1, a novel fat depot-specific adipokine that is also involved in iron regulation, in a cohort of 85 chronic HD patients with relation to their iron status.

Results
Omentin-1 levels in HD were statistically higher than in healthy controls (P = 0.03) and there was a significant, growing trend in all iron parameters across Omentin-1 tertiles (P &lt; 0.001). Compared with patients with optimal iron status, Omentin-1 levels were lower in subjects categorized according to TSAT ≤20% or serum ferritin ≤200 μg/L (both P &lt; 0.001) and even more reduced in 19 patients (22%) simultaneously displaying low levels of both markers (P &lt; 0.001). In this latter group, Omentin-1 levels increased in parallel to all other iron markers after iron correction by i.v. supplementation. At multivariate regression analyses, ferritin (β = 0.71; P &lt; 0.001) and TSAT (β = 0.32; P = 0.03) remained the sole independent predictors of Omentin-1 levels. This biomarker also showed a remarkable diagnostic capacity at receiver operating characteristic analyses in identifying iron-depleted HD patients according to a criterion of TSAT ≤20% [area under the curve (AUC) 0.827], ferritin ≤200 μg/L (AUC 0.863) or low levels of both parameters (AUC 0.907).

Conclusions
Findings obtained indicate that Omentin-1 is somewhat involved in iron balance regulation and might be a candidate biomarker for diagnosing and managing altered iron conditions in HD patients.
PD-1 inhibitors in esophageal cancer: a systematic review of the oncological outcomes associated with PD-1 blockade and the evolving therapeutic paradigm
Authors: Whooley J , Alazzawi M , Donlon N E , Bolger J C , Robb W B 
Published: September 2021

Abstract
Patients with esophageal or gastroesophageal junction (GEJ) cancer who fail to respond to chemoradiotherapy have a poor clinical prognosis. Recent clinical trials have investigated the use of immune checkpoint inhibitors in these patients. The use of programmed cell death protein 1 (PD-1) inhibitors has emerged as exciting therapeutic options in the curative and palliative setting of other solid tumors. We assessed the efficacy and safety of PD-1 inhibitors in esophageal and GEJ cancers. This systematic review was performed in accordance with the PRISMA guidelines. A comprehensive electronic literature search from the EMBASE, Pubmed, Scopus, MEDLINE, and Google Scholar databases was conducted up to 25 July 2021. This review identified 11 eligible studies reporting outcomes of 3451 patients treated with PD-1 blockade compared with 2286 patients treated with either a placebo or the standard regimen of chemotherapy. Clinically significant improvements in median overall survival have been demonstrated in advanced and metastatic esophageal and GEJ cancer while maintaining acceptable safety profiles. Promising survival data have also recently emerged from PD-1 blockade in the adjuvant setting. PD-1 blockade in esophageal and GEJ cancer has delivered impressive survival benefit while remaining well tolerated. Its use in the adjuvant setting will further advance treatment options, and more advancements in this area of therapy are highly anticipated. However, further characterization of the PD-1/programmed death ligand-1 pathway and elucidation of biomarkers to predict response are required to optimize patient selection.
Automated left atrial volume measurement by two-dimensional speckle-tracking echocardiography: feasibility, accuracy, and reproducibility
Authors: Florescu Diana R , Badano Luigi P , Tomaselli Michele , Torlasco Camilla , Târtea Georgică C , Bălșeanu Tudor A , Volpato Valentina , Parati Gianfranco , Muraru Denisa 
Published: September 2021

Abstract

Aims
A byproduct of left atrial (LA) strain analysis is the automated measurement of LA maximal volume (LAVmax), which may decrease the time of echocardiography reporting, and increase the reproducibility of the LAVmax measurement. However, the automated measurement of LAVmax by two-dimensional speckle-tracking analysis (2DSTE) has never been validated. Accordingly, we sought to (i) assess the feasibility of automated LAVmax measurement by 2DSTE; (ii) compare the automated LAVmax by 2DSTE with conventional two-dimensional (2DE) biplane and three-dimensional echocardiography (3DE) measurements; and (iii) evaluate the accuracy and reproducibility of the three echocardiography techniques.

Methods and results
LAVmax (34–197 mL) were obtained from 198/210 (feasibility 94%) consecutive patients (median age 67 years, 126 men) by 2DSTE, 2DE, and 3DE. 2DE and 2DSTE measurements resulted in similar LAVmax values [bias = 1.5 mL, limits of agreement (LOA) ± 7.5 mL], and slightly underestimated 3DE LAVmax (biases = −5 mL, LOA ± 17 mL and −6 mL, LOA ± 16 mL, respectively). LAVmax by 2DSTE and 2DE were strongly correlated to those obtained by cardiac magnetic resonance (CMR) (r = 0.946 and r = 0.935, respectively; P &lt; 0.001). However, LAVmax obtained by 2DSTE (bias = −9.5 mL, LOA ± 16 mL) and 2DE (bias = −8 mL, LOA ± 17 mL) were significantly smaller than those measured by CMR. Conversely, 3DE LAVmax were similar to CMR (bias = −2 mL, LOA ± 10 mL). Excellent intra- and inter-observer intraclass correlations were found for 3DE (0.995 and 0.995), 2DE (0.990 and 0.988), and 2DSTE (0.990 and 0.989).

Conclusion
Automated LAVmax measurement by 2DSTE is highly feasible, highly reproducible, and provided similar values to conventional 2DE calculations in consecutive patients with a wide range of LAVmax.
Causal relation of tricuspid regurgitation for heart failure outcomes: a mediation analysis of echocardiographic predictors
Authors: Hakuno Daihiko , Fukae Tomoaki , Takahashi Masashi , Sueyoshi Koichiro 
Published: September 2021

AbstractAimsAlthough significant tricuspid regurgitation (TR) is critically associated with heart failure (HF) prognosis, the predictors for large TR impact on HF outcomes remain unknown. This study aimed to identify echocardiographic predictors for a causal relation of TR to HF outcomes.Methods and resultsIn a retrospective, acute HF cohort of 462 patients, multivariate logistic regression analysis was performed to determine subgroups with strong association of greater-than-moderate TR with HF readmission or cardiovascular death in a year. We then conducted causal mediation analysis according to persistent atrial fibrillation (Af) or mitral regurgitation (MR) to identify the echocardiographic predictors. The association of TR with HF outcomes was prominent in subgroups of females, with Af, the enlarged indexed tricuspid annular diameter (TADi) or right atrial area, or within certain ranges of the left ventricular ejection fraction, indexed right ventricular end-systolic area, or fractional area change (FAC). Causal mediation analysis found that the TR impact was significant in patients with Af. Furthermore, combination of TADi ≥2.1 cm/m2 and FAC ≥30%, which accounted for half of TR patients, predicted a much larger TR impact irrespective of Af and MR. Its prediction ability was superior to that of the modified Model for End-stage Liver Disease score.ConclusionThe causal impact and burden of TR on HF outcomes was significant in patients with Af, and combining TADi ≥2.1 cm/m2 with FAC ≥30% could provide superior echocardiographic prediction of larger TR impact in HF patients.
Comparative analysis ofMalassezia furfurmitogenomes and the development of a mitochondria-based typing approach
Authors: Theelen Bart , Christinaki Anastasia C , Dawson Thomas L , Boekhout Teun , Kouvelis Vassili N 
Published: September 2021

ABSTRACTMalassezia furfur is a yeast species belonging to Malasseziomycetes, Ustilaginomycotina and Basidiomycota that is found on healthy warm-blooded animal skin, but also involved in various skin disorders like seborrheic dermatitis/dandruff and pityriasis versicolor. Moreover, Malassezia are associated with bloodstream infections, Crohn's disease and pancreatic carcinoma. Recent advances in Malassezia genomics and genetics have focused on the nuclear genome. In this work, we present the M. furfur mitochondrial (mt) genetic heterogenicity with full analysis of 14 novel and six available M. furfur mt genomes. The mitogenome analysis reveals a mt gene content typical for fungi, including identification of variable mt regions suitable for intra-species discrimination. Three of them, namely the trnK–atp6 and cox3–nad3 intergenic regions and intron 2 of the cob gene, were selected for primer design to identify strain differences. Malassezia furfur strains belonging to known genetic variable clusters, based on AFLP and nuclear loci, were assessed for their mt variation using PCR amplification and sequencing. The results suggest that these mt regions are excellent molecular markers for the typing of M. furfur strains and may provide added value to nuclear regions when assessing evolutionary relationships at the intraspecies level.
Thermal expansivity, heat capacity and bulk modulus of the mantle
Authors: Stixrude Lars , Lithgow-Bertelloni Carolina 
Published: September 2021

SUMMARYWe derive exact expressions for the thermal expansivity, heat capacity and bulk modulus for assemblages with arbitrarily large numbers of components and phases, including the influence of phase transformations and chemical exchange. We illustrate results in simple two-component, two-phase systems, including Mg–Fe olivine-wadsleyite and Ca–Mg clinopyroxene-orthopyroxene and for a multicompontent model of mantle composition in the form of pyrolite. For the latter we show results for the thermal expansivity and heat capacity over the entire mantle pressure–temperature regime to 40 GPa, or a depth of 1000 km. From the thermal expansivity, we derive a new expression for the phase buoyancy parameter that is valid for arbitrarily large numbers of phases and components and which is defined at every point in pressure–temperature space. Results reveal regions of the mantle where the magnitude of the phase buoyancy parameter is larger in magnitude than for those phase transitions that are most commonly included in mantle convection simulations. These regions include the wadsleyite to garnet and ferropericlase transition, which is encountered along hot isentropes (e.g. 2000 K potential temperature) in the transition zone, and the ferropericlase and stishovite to bridgmanite transition, which is encountered along cold isentropes (e.g. 1000 K potential temperature) in the shallow lower mantle. We also show the bulk modulus along a typical mantle isentrope and relate it to the Bullen inhomogeneity parameter. All results are computed with our code HeFESTo, updates and improvements to which we discuss, including the implementation of the exact expressions for the thermal expansivity, heat capacity and bulk modulus, generalization to allow for pressure dependence of non-ideal solution parameters and an improved numerical scheme for minimizing the Gibbs free energy. Finally, we present the results of a new global inversion of parameters updated to incorporate more recent results from experiment and first principles theory, as well as a new phase (nal phase), and new species: Na-majorite and the NaAlO2 end-member of ferropericlase.
Relationship between glucose homeostasis and obesity in early life—a study of Italian children and adolescents
Authors: Balkhiyarova Zhanna , Luciano Rosa , Kaakinen Marika , Ulrich Anna , Shmeliov Aleksey , Bianchi Marzia , Chioma Laura , Dallapiccola Bruno , Prokopenko Inga , Manco Melania 
Published: September 2021

Abstract
Epidemic obesity is the most important risk factor for prediabetes and type 2 diabetes (T2D) in youth as it is in adults. Obesity shares pathophysiological mechanisms with T2D and is likely to share part of the genetic background. We aimed to test if weighted genetic risk scores (GRSs) for T2D, fasting glucose (FG) and fasting insulin (FI) predict glycaemic traits and if there is a causal relationship between obesity and impaired glucose metabolism in children and adolescents. Genotyping of 42 SNPs established by genome-wide association studies for T2D, FG and FI was performed in 1660 Italian youths aged between 2 and 19 years. We defined GRS for T2D, FG and FI and tested their effects on glycaemic traits, including FG, FI, indices of insulin resistance/beta cell function and body mass index (BMI). We evaluated causal relationships between obesity and FG/FI using one-sample Mendelian randomization analyses in both directions. GRS-FG was associated with FG (beta = 0.075 mmol/l, SE = 0.011, P = 1.58 × 10−11) and beta cell function (beta = −0.041, SE = 0.0090 P = 5.13 × 10−6). GRS-T2D also demonstrated an association with beta cell function (beta = −0.020, SE = 0.021 P = 0.030). We detected a causal effect of increased BMI on levels of FI in Italian youths (beta = 0.31 ln (pmol/l), 95%CI [0.078, 0.54], P = 0.0085), while there was no effect of FG/FI levels on BMI. Our results demonstrate that the glycaemic and T2D risk genetic variants contribute to higher FG and FI levels and decreased beta cell function in children and adolescents. The causal effects of adiposity on increased insulin resistance are detectable from childhood age.
The interspecific competition presents greater nutrient facilitation compared with intraspecific competition through AM fungi interacting with litter for two host plants in karst soil
Authors: Guo Yun , He Yuejun , Wu Pan , Wu Bangli , Lin Yan , He Minhong , Han Xu , Xia Tingting , Shen Kaiping , Kang Liling , Tan Qiyu , Ren Wenda , Sun Yan , Li Qing 
Published: September 2021

AbstractLitter is the crucial carrier of soil nutrition transformation. The influence of arbuscular mycorrhizal (AM) fungi on nutrient acquisition in plants has been widely recognized. However, in nutrient-deficient karst habitat, how competitive plants utilize nutrients regulated by AM fungi via litter remain largely unknown. The experimental treatments included the inoculation with or without Glomus etunicatum, the litter addition by the mixed leaves of Broussonetia papyrifera and Carpinus pubescens or no addition, and the competition through the intraspecific competition of B. papyrifera and C. pubescens, respectively, and the interspecific competition mixed both plants. AM fungi differently affected plant on nutrient acquisition, increasing nutrients acquisitions of B. papyrifera in intra- and interspecific competitions while decreasing for C. pubescens. Litter presented opposite influences on N acquisitions of both plants in interspecific competition with AM fungi, being positive for C. pubescens and negative for B. papyrifera, respectively. Under the interaction of AM fungi and litter, nitrogen (N), phosphorus (P) and potassium (K) acquisitions by B. papyrifera and N acquisition by C. pubescens in interspecific competition were all greater than intraspecific competition. In the interspecific competition, the competitive ability of plants on nutrient absorption presented significant species difference, which of B. papyrifera on P and K was significantly increased, while was converse for C. pubescens on K. In conclusion, these results suggest that the interspecific competition presents greater nutrient facilitation compared with intraspecific competition through AM fungi interacting with litter for plants in karst soil.