bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurodegenerative phosphoprotein signaling landscape in models of SCA3
Authors: Sowa Anna S. , Popova Taissia G. , Harmuth Tina , Weber Jonasz J. , Pereira Sena Priscila , Schmidt Jana , Hübener-Schmid Jeannette , Schmidt Thorsten 
Published: March 2021

AbstractSpinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disorder resulting from an aberrant expansion of a polyglutamine stretch in the ataxin-3 protein and subsequent neuronal death. The underlying intracellular signaling pathways are currently unknown. We applied the Reverse-phase Protein MicroArray (RPMA) technology to assess the levels of 50 signaling proteins (in phosphorylated and total forms) using three in vitro and in vivo models expressing expanded ataxin-3: (i) human embryonic kidney (HEK293T) cells stably transfected with human ataxin-3 constructs, (ii) mouse embryonic fibroblasts (MEF) from SCA3 transgenic mice, and (iii) whole brains from SCA3 transgenic mice. All three models demonstrated a high degree of similarity sharing a subset of phosphorylated proteins involved in the PI3K/AKT/GSK3/mTOR pathway. Expanded ataxin-3 strongly interfered (by stimulation or suppression) with normal ataxin-3 signaling consistent with the pathogenic role of the polyglutamine expansion. In comparison with normal ataxin-3, expanded ataxin-3 caused a pro-survival stimulation of the ERK pathway along with reduced pro-apoptotic and transcriptional responses.
Identification of novel sublingual parameters to analyze and diagnose microvascular dysfunction in sepsis: the NOSTRADAMUS study
Authors: Rovas Alexandros , Sackarnd Jan , Rossaint Jan , Kampmeier Stefanie , Pavenstädt Hermann , Vink Hans , Kümpers Philipp 
Published: March 2021

Abstract
Background
The availability of handheld, noninvasive sublingual video-microscopes allows for visualization of the microcirculation in critically ill patients. Recent studies demonstrate that reduced numbers of blood-perfused microvessels and increased penetration of erythrocytes into the endothelial glycocalyx are essential components of microvascular dysfunction. The aim of this study was to identify novel microvascular variables to determine the level of microvascular dysfunction in sepsis and its relationship with clinical variables.

Methods
This observational, prospective, cross-sectional study included 51 participants, of which 34 critically ill sepsis patients were recruited from intensive care units of a university hospital. Seventeen healthy volunteers served as controls. All participants underwent sublingual videomicroscopy by sidestream darkfield imaging. A new developed version of the Glycocheck™ software was used to quantify vascular density, perfused boundary region (PBR-an inverse variable of endothelial glycocalyx dimensions), red blood cell (RBC) velocity, RBC content, and blood flow in sublingual microvessels with diameters between 4 and 25 µm.

Results
A detailed analysis of adjacent diameter classes (1 µm each) of vessels between 4 and 25 µm revealed a severe reduction of vascular density in very small capillaries (5–7 µm), which correlated with markers of sepsis severity. Analysis of RBC velocity (VRBC) revealed a strong dependency between capillary and feed vessel VRBC in sepsis patients (R2 = 0.63, p < 0.0001) but not in healthy controls (R2 = 0.04, p = 0.43), indicating impaired capillary (de-)recruitment in sepsis. This finding enabled the calculation of capillary recruitment and dynamic capillary blood volume (CBVdynamic). Moreover, adjustment of PBR to feed vessel VRBC further improved discrimination between sepsis patients and controls by about 50%. By combining these dynamic microvascular and glycocalyx variables, we developed the microvascular health score (MVHSdynamic™), which decreased from 7.4 [4.6–8.7] in controls to 1.8 [1.4–2.7] in sepsis patients (p < 0.0001) and correlated with sepsis severity.

Conclusion
We introduce new important diameter-specific quantification and differentiated analysis of RBC kinetics, a key to understand microvascular dysfunction in sepsis. MVHSdynamic, which has a broad bandwidth to detect microvascular (dys-) function, might serve as a valuable tool to detect microvascular impairment in critically ill patients.
Coagulation phenotypes in sepsis and effects of recombinant human thrombomodulin: an analysis of three multicentre observational studies
Authors: Kudo Daisuke , Goto Tadahiro , Uchimido Ryo , Hayakawa Mineji , Yamakawa Kazuma , Abe Toshikazu , Shiraishi Atsushi , Kushimoto Shigeki 
Published: March 2021

Abstract
Background
A recent randomised trial showed that recombinant thrombomodulin did not benefit patients who had sepsis with coagulopathy and organ dysfunction. Several recent studies suggested presence of clinical phenotypes in patients with sepsis and heterogenous treatment effects across different sepsis phenotypes. We examined the latent phenotypes of sepsis with coagulopathy and the associations between thrombomodulin treatment and the 28-day and in-hospital mortality for each phenotype.

Methods
This was a secondary analysis of multicentre registries containing data on patients (aged ≥ 16 years) who were admitted to intensive care units for severe sepsis or septic shock in Japan. Three multicentre registries were divided into derivation (two registries) and validation (one registry) cohorts. Phenotypes were derived using k-means with coagulation markers, platelet counts, prothrombin time/international normalised ratios, fibrinogen, fibrinogen/fibrin-degradation-products (FDP), D-dimer, and antithrombin activities. Associations between thrombomodulin treatment and survival outcomes (28-day and in-hospital mortality) were assessed in the derived clusters using a generalised estimating equation.

Results
Four sepsis phenotypes were derived from 3694 patients in the derivation cohort. Cluster dA (n = 323) had severe coagulopathy with high FDP and D-dimer levels, severe organ dysfunction, and high mortality. Cluster dB had severe disease with moderate coagulopathy. Clusters dC and dD had moderate and mild disease with and without coagulopathy, respectively. Thrombomodulin was associated with a lower 28-day (adjusted risk difference [RD]: − 17.8% [95% CI − 28.7 to − 6.9%]) and in-hospital (adjusted RD: − 17.7% [95% CI − 27.6 to − 7.8%]) mortality only in cluster dA. Sepsis phenotypes were similar in the validation cohort, and thrombomodulin treatment was also associated with lower 28-day (RD: − 24.9% [95% CI − 49.1 to − 0.7%]) and in-hospital mortality (RD: − 30.9% [95% CI − 55.3 to − 6.6%]).

Conclusions
We identified four coagulation marker-based sepsis phenotypes. The treatment effects of thrombomodulin varied across sepsis phenotypes. This finding will facilitate future trials of thrombomodulin, in which a sepsis phenotype with high FDP and D-dimer can be targeted.
Molecular and computational approaches to map regulatory elements in 3D chromatin structure
Authors: Lee Beoung Hun , Rhie Suhn K. 
Published: March 2021

AbstractEpigenetic marks do not change the sequence of DNA but affect gene expression in a cell-type specific manner by altering the activities of regulatory elements. Development of new molecular biology assays, sequencing technologies, and computational approaches enables us to profile the human epigenome in three-dimensional structure genome-wide. Here we describe various molecular biology techniques and bioinformatic tools that have been developed to measure the activities of regulatory elements and their chromatin interactions. Moreover, we list currently available three-dimensional epigenomic data sets that are generated in various human cell types and tissues to assist in the design and analysis of research projects.
Proton pump inhibitors use and risk of developing spontaneous bacterial peritonitis in cirrhotic patients: A systematic review and meta-analysis
Authors: Alhumaid Saad , Al Mutair Abbas , Al Alawi Zainab , Zaidi Abdul Rehman Zia , Rabaan Ali A. , Elhazmi Alyaa , Al-Omari Awad 
Published: March 2021

Abstract
Background
Spontaneous bacterial peritonitis (SBP) is one of the most common infectious diseases in patients with cirrhosis and is associated with serious prognosis. A prevailing dogma posits that SBP is exacerbated by the frequent use of proton pump inhibitors (PPIs).

Aims
To re-assess the association between PPIs use and SBP incidence with larger and better-quality data.

Method
The studies were identified by searching Proquest, Medline, and Embase for English language articles published between January 2008 and March 2020 using the following keywords alone or in combination: anti-ulcer agent, antacid, proton pump inhibitor, proton pumps, PPI, omeprazole, rabeprazole, lansoprazole, pantoprazole, esomeprazole, peritonitis, spontaneous bacterial peritonitis, SBP, ascites, cirrhosis, ascitic and cirrhotic. Three authors critically reviewed all of the studies retrieved and selected those judged to be the most relevant. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Sub-group analyses were done to decrease the heterogeneity.

Results
A total of twenty-three studies: seven case–control, and sixteen cohorts, involving 10,386 patients were analyzed. The overall results showed a statistically significant association between SBP and PPIs use (pooled odds ratio (OR): 1.80, 95% CI of 1.41 to 2.31). Substantial heterogeneity was observed. On subgroup analysis involving cohort studies, the association was weaker (OR: 1.55 with 95% CI of 1.16 to 2.06 p < 0.00001) but still statistically significant and with high heterogeneity (Chi2p = 57.68; I2 = 74%). For case–control studies, the OR was 2.62 with a 95% CI of 1.94 to 3.54. The funnel plot was asymmetric and Egger’s test confirmed asymmetry suggesting publication bias (intercept = − 0.05, SE = 0.27, P = 0.850 two-tailed).

Conclusion
This meta-analysis sheds light on the conflicting results raised by previous studies regarding the association of SBP with PPIs use. Our meta-analysis showed that there is a weak association, although statistically significant, between SBP and PPIs use. However, the magnitude of the possible association diminished when analysis focused on higher quality data that were more robust. Thus, this updated meta-analysis suggests judicious use of PPIs among cirrhotic patients with ascites.
Resistance-induced brain activity changes during cycle ergometer exercises
Authors: Lin Ming-An , Meng Ling-Fu , Ouyang Yuan , Chan Hsiao-Lung , Chang Ya-Ju , Chen Szi-Wen , Liaw Jiunn-Woei 
Published: March 2021

Abstract
Background
EEGs are frequently employed to measure cerebral activations during physical exercise or in response to specific physical tasks. However, few studies have attempted to understand how exercise-state brain activity is modulated by exercise intensity.

Methods
Ten healthy subjects were recruited for sustained cycle ergometer exercises at low and high resistance, performed on two separate days a week apart. Exercise-state EEG spectral power and phase-locking values (PLV) are analyzed to assess brain activity modulated by exercise intensity.

Results
The high-resistance exercise produced significant changes in beta-band PLV from early to late pedal stages for electrode pairs F3-Cz, P3-Pz, and P3-P4, and in alpha-band PLV for P3-P4, as well as the significant change rate in alpha-band power for electrodes C3 and P3. On the contrary, the evidence for changes in brain activity during the low-resistance exercise was not found.

Conclusion
These results show that the cortical activation and cortico-cortical coupling are enhanced to take on more workload, maintaining high-resistance pedaling at the required speed, during the late stage of the exercise period.
Heterogeneous field network for power distribution grid based on HPLC and RF adaptive communications technology
Authors: Huang Rui , Xiao Yu , Liu Mouhai , Liu Zhaoyang , Liu Xiaoping , Xu Huiting , Gao Yunpeng , Yang Maotao , Ye Liuqing 
Published: March 2021

AbstractIn order to improve the connection rate and transmission efficiency of field network for power distribution grid, a dual-mode heterogeneous field network with high-speed power line broadband carrier and micro-power radio frequency wireless communication capabilities was designed. First, the topological structure of the field network, the networking process of the central node and the free nodes and the dynamic maintenance mechanism of the network were discussed in detail. Secondly, the routing measurement mechanism for creating a hybrid routing table and the improved layer limit shortest path routing algorithm were presented. On this basis, each node in the network could choose the optimal communication media at any given moment to create communication links with the adaptive data transfer speed according to the real-time hybrid routing table. Finally, the dual-mode heterogeneous field network was applied to the electricity consumption information collection system and tested in the laboratory and jobsite. The test results show that the dual-mode field network was more effective than the single-mode field network in shortening the reading meter time and increasing networking success rate.
Computation of solutions to linear difference and differential equations with a prescribed asymptotic behavior
Authors: Baumann Hendrik , Hanschke Thomas 
Published: March 2021

AbstractLinear differential equations usually arise from mathematical modeling of physical experiments and real-world problems. In most applications these equations are linked to initial or boundary conditions. But sometimes the solution under consideration is characterized by its asymptotic behavior, which leads to the question how to infer from the asymptotic growth of a solution to its initial values. In this paper we show that under some mild conditions the initial values of the desired solution can be computed by means of a continuous-time analogue of a modified matrix continued fraction. For numerical applications we develop forward and backward algorithms which behave well in most situations. The topic is closely related to the theory of special functions and its extension to higher-dimensional problems. Our investigations result in a powerful tool for solving some classical mathematical problems. To demonstrate the efficiency of our method we apply it to Poincaré type and Kneser’s differential equation.
Generalized degenerate Bernoulli numbers and polynomials arising from Gauss hypergeometric function
Authors: Kim Taekyun , Kim Dae San , Jang Lee-Chae , Lee Hyunseok , Kim Hanyoung 
Published: March 2021

AbstractA new family of p-Bernoulli numbers and polynomials was introduced by Rahmani (J. Number Theory 157:350–366, 2015) with the help of the Gauss hypergeometric function. Motivated by that paper and in the light of the recent interests in finding degenerate versions, we construct the generalized degenerate Bernoulli numbers and polynomials by means of the Gauss hypergeometric function. In addition, we construct the degenerate type Eulerian numbers as a degenerate version of Eulerian numbers. For the generalized degenerate Bernoulli numbers, we express them in terms of the degenerate Stirling numbers of the second kind, of the degenerate type Eulerian numbers, of the degenerate p-Stirling numbers of the second kind and of an integral on the unit interval. As to the generalized degenerate Bernoulli polynomials, we represent them in terms of the degenerate Stirling polynomials of the second kind.
Pre-Cambrian roots of novel Antarctic cryptoendolithic bacterial lineages
Authors: Albanese Davide , Coleine Claudia , Rota-Stabelli Omar , Onofri Silvano , Tringe Susannah G. , Stajich Jason E. , Selbmann Laura , Donati Claudio 
Published: March 2021

AbstractBackgroundCryptoendolithic communities are microbial ecosystems dwelling inside porous rocks that are able to persist at the edge of the biological potential for life in the ice-free areas of the Antarctic desert. These regions include the McMurdo Dry Valleys, often accounted as the closest terrestrial counterpart of the Martian environment and thought to be devoid of life until the discovery of these cryptic life-forms. Despite their interest as a model for the early colonization by living organisms of terrestrial ecosystems and for adaptation to extreme conditions of stress, little is known about the evolution, diversity, and genetic makeup of bacterial species that reside in these environments. Using the Illumina Novaseq platform, we generated the first metagenomes from rocks collected in Continental Antarctica over a distance of about 350 km along an altitudinal transect from 834 up to 3100 m above sea level (a.s.l.).ResultsA total of 497 draft bacterial genome sequences were assembled and clustered into 269 candidate species that lack a representative genome in public databases. Actinobacteria represent the most abundant phylum, followed by Chloroflexi and Proteobacteria. The “CandidatusJiangella antarctica” has been recorded across all samples, suggesting a high adaptation and specialization of this species to the harshest Antarctic desert environment.The majority of these new species belong to monophyletic bacterial clades that diverged from related taxa in a range from 1.2 billion to 410 Ma and are functionally distinct from known related taxa.ConclusionsOur findings significantly increase the repertoire of genomic data for several taxa and, to date, represent the first example of bacterial genomes recovered from endolithic communities. Their ancient origin seems to not be related to the geological history of the continent, rather they may represent evolutionary remnants of pristine clades that evolved across the Tonian glaciation. These unique genomic resources will underpin future studies on the structure, evolution, and function of these ecosystems at the edge of life.
Genetic-variant hotspots and hotspot clusters in the human genome facilitating adaptation while increasing instability
Authors: Long Xi , Xue Hong 
Published: March 2021

Abstract
Background
Genetic variants, underlining phenotypic diversity, are known to distribute unevenly in the human genome. A comprehensive understanding of the distributions of different genetic variants is important for insights into genetic functions and disorders.

Methods
Herein, a sliding-window scan of regional densities of eight kinds of germline genetic variants, including single-nucleotide-polymorphisms (SNPs) and four size-classes of copy-number-variations (CNVs) in the human genome has been performed.

Results
The study has identified 44,379 hotspots with high genetic-variant densities, and 1135 hotspot clusters comprising more than one type of hotspots, accounting for 3.1% and 0.2% of the genome respectively. The hotspots and clusters are found to co-localize with different functional genomic features, as exemplified by the associations of hotspots of middle-size CNVs with histone-modification sites, work with balancing and positive selections to meet the need for diversity in immune proteins, and facilitate the development of sensory-perception and neuroactive ligand-receptor interaction pathways in the function-sparse late-replicating genomic sequences. Genetic variants of different lengths co-localize with retrotransposons of different ages on a “long-with-young” and “short-with-all” basis. Hotspots and clusters are highly associated with tumor suppressor genes and oncogenes (p < 10−10), and enriched with somatic tumor CNVs and the trait- and disease-associated SNPs identified by genome-wise association studies, exceeding tenfold enrichment in clusters comprising SNPs and extra-long CNVs.

Conclusions
In conclusion, the genetic-variant hotspots and clusters represent two-edged swords that spearhead both positive and negative genomic changes. Their strong associations with complex traits and diseases also open up a potential “Common Disease-Hotspot Variant” approach to the missing heritability problem.
Video-feedback promotes sensitive limit-setting in parents of twin preschoolers: a randomized controlled trial
Authors: Euser Saskia , Vrijhof Claudia I. , Van den Bulk Bianca G. , Vermeulen Rachel , Bakermans-Kranenburg Marian J. , van IJzendoorn Marinus H. 
Published: March 2021

AbstractBackgroundPrimary aim of the current randomized controlled trial was to test the effectiveness of the parenting intervention ‘Video-feedback to promote Positive Parenting and Sensitive Discipline’ (VIPP-SD) in a sample of parents of preschool-aged twins, as well as differential susceptibility to intervention efforts, that is, whether more temperamentally reactive parents would profit more from the VIPP-SD than parents with lower reactivity.MethodsThe sample consisted of 202 families with same-sex twins [N = 404 children, mean age 45 months (SD = 6.81)]. Randomization was done at the family level in a 2:3 ratio, with 83 families (41%) randomized to the VIPP-SD group, and 119 families (59%) to the control group. After two pre-tests in year 1 and year 2 of the study, the VIPP-SD was implemented in the third year, with a post-test assessment 1 month after the five intervention sessions. Parental sensitivity was observed during structured play in which parent and child copied a drawing together in a computerized Etch-A-Sketch paradigm. Parental limit-setting was observed in a ‘don’t touch’ task in which the parent required from the child to abstain from playing with attractive toys. Parents interacted with each of their twins in separate sessions.ResultsThe VIPP-SD intervention had a positive impact on the level of parents’ positive limit-setting in interaction with their preschool twins, and this positive effect was most pronounced when the parents completed at least five intervention sessions. However, the intervention did not enhance parental sensitivity during structured play. Parents with higher reactivity were not more open to the impact of the intervention, thus for this temperamental marker differential susceptibility in adults was not supported.ConclusionsThe current study is unique in targeting families with twin preschoolers, providing proof of principle that coaching parents with video-feedback promotes parental sensitive limit-setting to both children. It remains to be seen whether this finding can be replicated in families with non-twin siblings, or other parental susceptibility markers.Trial registrationTrial NL5172 (NTR5312), 2015-07-20.