bluuebunny/crossref_metadata_2025_split huggingface dataset:
A targeted multi-omics approach reveals paraoxonase-1 as a determinant of obesity-associated fatty liver disease
Authors: Diels Sara , Cuypers Bart , Tvarijonaviciute Asta , Derudas Bruno , Van Dijck Evelien , Verrijken An , Van Gaal Luc F. , Laukens Kris , Lefebvre Philippe , Ceron Jose J. , Francque Sven , Vanden Berghe Wim , Van Hul Wim 
Published: August 2021

Abstract
Background
The multifactorial nature of non-alcoholic fatty liver disease cannot be explained solely by genetic factors. Recent evidence revealed that DNA methylation changes take place at proximal promoters within susceptibility genes. This emphasizes the need for integrating multiple data types to provide a better understanding of the disease’s pathogenesis. One such candidate gene is paraoxonase-1 (PON1). Substantial interindividual differences in PON1 are apparent and could influence disease risk later in life. The aim of this study was therefore to determine the different regulatory aspects of PON1 variability and to examine them in relation to the predisposition to obesity-associated fatty liver disease.

Results
A targeted multi-omics approach was applied to investigate the interplay between PON1 genetic variants, promoter methylation, expression profile and enzymatic activity in an adult patient cohort with extensive metabolic and hepatic characterisation including liver biopsy. Alterations in PON1 status were shown to correlate with waist-to-hip ratio and relevant features of liver pathology. Particularly, the regulatory polymorphism rs705379:C > T was strongly associated with more severe liver disease. Multivariable data analysis furthermore indicated a significant association of combined genetic and epigenetic PON1 regulation. This identified relationship postulates a role for DNA methylation as a mediator between PON1 genetics and expression, which is believed to further influence liver disease progression via modifications in PON1 catalytic efficiency.

Conclusions
Our findings demonstrate that vertical data-integration of genetic and epigenetic regulatory mechanisms generated a more in-depth understanding of the molecular basis underlying the development of obesity-associated fatty liver disease. We gained novel insights into how NAFLD classification and outcome are orchestrated, which could not have been obtained by exclusively considering genetic variation.
Abnormal sleep physiology in children with 15q11.2-13.1 duplication (Dup15q) syndrome
Authors: Saravanapandian Vidya , Nadkarni Divya , Hsu Sheng-Hsiou , Hussain Shaun A. , Maski Kiran , Golshani Peyman , Colwell Christopher S. , Balasubramanian Saravanavel , Dixon Amos , Geschwind Daniel H. , Jeste Shafali S. 
Published: August 2021

Abstract
Background
Sleep disturbances in autism spectrum disorder (ASD) represent a common and vexing comorbidity. Clinical heterogeneity amongst these warrants studies of the mechanisms associated with specific genetic etiologies. Duplications of 15q11.2-13.1 (Dup15q syndrome) are highly penetrant for neurodevelopmental disorders (NDDs) such as intellectual disability and ASD, as well as sleep disturbances. Genes in the 15q region, particularly UBE3A and a cluster of GABAA receptor genes, are critical for neural development, synaptic protein synthesis and degradation, and inhibitory neurotransmission. During awake electroencephalography (EEG), children with Dup15q syndrome demonstrate increased beta band oscillations (12–30 Hz) that likely reflect aberrant GABAergic neurotransmission. Healthy sleep rhythms, necessary for robust cognitive development, are also highly dependent on GABAergic neurotransmission. We therefore hypothesized that sleep physiology would be abnormal in children with Dup15q syndrome.

Methods
To test the hypothesis that elevated beta oscillations persist in sleep in Dup15q syndrome and that NREM sleep rhythms would be disrupted, we computed: (1) beta power, (2) spindle density, and (3) percentage of slow-wave sleep (SWS) in overnight sleep EEG recordings from a cohort of children with Dup15q syndrome (n = 15) and compared them to age-matched neurotypical children (n = 12).

Results
Children with Dup15q syndrome showed abnormal sleep physiology with elevated beta power, reduced spindle density, and reduced or absent SWS compared to age-matched neurotypical controls.

Limitations
This study relied on clinical EEG where sleep staging was not available. However, considering that clinical polysomnograms are challenging to collect in this population, the ability to quantify these biomarkers on clinical EEG—routinely ordered for epilepsy monitoring—opens the door for larger-scale studies. While comparable to other human studies in rare genetic disorders, a larger sample would allow for examination of the role of seizure severity, medications, and developmental age that may impact sleep physiology.

Conclusions
We have identified three quantitative EEG biomarkers of sleep disruption in Dup15q syndrome, a genetic condition highly penetrant for ASD. Insights from this study not only promote a greater mechanistic understanding of the pathophysiology defining Dup15q syndrome, but also lay the foundation for studies that investigate the association between sleep and cognition. Abnormal sleep physiology may undermine healthy cognitive development and may serve as a quantifiable and modifiable target for behavioral and pharmacological interventions.
Efficacy of damage control surgery and staged endoscopic pancreatic ductal double stenting therapy for severe pancreatic head injury: a case report
Authors: Nagashima Futoshi , Inoue Satoshi , Matsui Daisaku , Bansyoutani Yuki , Tokuda Rina , Fuzisaki Osamu , Kobayashi Makoto 
Published: August 2021

Abstract
Background
A high-grade pancreatic injury is a life-threatening injury that is associated with high mortality and morbidity. It is currently unclear which treatment strategy results in good clinical outcomes.

Case presentation
A 23-year-old Japanese woman sustained severe injury in a motor vehicle accident. Abdominal computed tomography revealed severe pancreatic head injury with extravasation of contrast media. Since it was not possible to insert an endoscopic pancreatic stenting tube into the main pancreatic duct, damage control surgery was performed. On day 3, we could insert the endoscopic pancreatic stenting tube from the ampulla of Vater and an endoscopic nasopancreatic drainage tube in the distal pancreatic duct from the accessory ampulla before the second operation. Drainage tubes were placed around the pancreatic head in the second operation. The endoscopic nasopancreatic drainage tube tube was converted to endoscopic pancreatic stenting tube on day 9. On day 51, the patient was discharged on foot from our hospital without serious complications.

Conclusion
Early and effective hemostasis, staged pancreatic duct drainage with stenting, and surgical external drainage around the pancreas in combination with an endoscopic procedure and damage control surgery were considered appropriate therapeutic strategy for high-grade pancreatic injury.
Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulate regenerative wound healing via transforming growth factor-β receptor inhibition
Authors: Zhang Yan , Pan Yingjin , Liu Yanhong , Li Xiheng , Tang Liang , Duan Mengna , Li Jiang , Zhang Guokun 
Published: August 2021

AbstractBackgroundScar formation is a common consequence of skin wound healing, and no effective treatment exists. Umbilical cord blood mesenchymal stem cells (UCB-MSCs) can improve wound healing; however, the role of UCB-MSCs remains unclear and whether they can ameliorate scar formation has not been fully elucidated.MethodsTo determine the function of UCB-MSCs, we examined and compared the therapeutic effects of UCB-MSCs and UCB-MSC-derived exosomes (UCB-MSC-exo) on skin healing in rats. Moreover, UCB-MSC-exo-specific miRNAs were identified and their effects in inhibiting the human dermal fibroblast (HDF) differentiation into myofibroblasts were investigated.ResultsBoth UCB-MSCs and UCB-MSC-exo accelerated wound closure; reduced scar formation; improved the regeneration of skin appendages, nerves, and vessels; and regulated the natural distribution of collagen fibers in wound healing. Additionally, UCB-MSC-exo suppressed the excessive formation of myofibroblasts and collagen I and increased the proliferation and migration of skin cells in vivo and in vitro. Functional analysis showed that UCB-MSC-derived miRNAs were closely related to the transforming growth factor-β (TGF-β) signaling pathway, which could induce myofibroblast differentiation. We identified abundant miRNAs that were highly expressed in UCB-MSC-exo. miR-21-5p and miR-125b-5p were predicted to contribute to TGF-β receptor type II (TGFBR2) and TGF-β receptor type I (TGFBR1) inhibition, respectively. Using miRNA mimics, we found that miR-21-5p and miR-125b-5p were critical for anti-myofibroblast differentiation in the TGF-β1-induced HDF.ConclusionThe effect of UCB-MSCs in stimulating regenerative wound healing might be achieved through exosomes, which can be, in part, through miR-21-5p- and miR-125b-5p-mediated TGF-β receptor inhibition, suggesting that UCB-MSC-exo might represent a novel strategy to prevent scar formation during wound healing.
Investigating the correlation of muscle function tests and sarcomere organization in C. elegans
Authors: Lesanpezeshki Leila , Qadota Hiroshi , Darabad Masoud Norouzi , Kashyap Karishma , Lacerda Carla M. R. , Szewczyk Nathaniel J. , Benian Guy M. , Vanapalli Siva A. 
Published: August 2021

AbstractBackgroundCaenorhabditis eleganshas been widely used as a model to study muscle structure and function. Its body wall muscle is functionally and structurally similar to vertebrate skeletal muscle with conserved molecular pathways contributing to sarcomere structure, and muscle function. However, a systematic investigation of the relationship between muscle force and sarcomere organization is lacking. Here, we investigate the contribution of various sarcomere proteins and membrane attachment components to muscle structure and function to introduceC.elegansas a model organism to study the genetic basis of muscle strength.MethodsWe employ two recently developed assays that involve exertion of muscle forces to investigate the correlation of muscle function to sarcomere organization. We utilized a microfluidic pillar-based platform called NemaFlex that quantifies the maximum exertable force and a burrowing assay that challenges the animals to move in three dimensions under a chemical stimulus. We selected 20 mutants with known defects in various substructures of sarcomeres and compared the physiological function of muscle proteins required for force generation and transmission. We also characterized the degree of sarcomere disorganization using immunostaining approaches.ResultsWe find that mutants with genetic defects in thin filaments, thick filaments, and M-lines are generally weaker, and our assays are successful in detecting the functional changes in response to each sarcomere location tested. We find that the NemaFlex and burrowing assays are functionally distinct informing on different aspects of muscle physiology. Specifically, the burrowing assay has a larger bandwidth in phenotyping muscle mutants, because it could pick ten additional mutants impaired while exerting normal muscle force in NemaFlex. This enabled us to combine their readouts to develop an integrated muscle function score that was found to correlate with the score for muscle structure disorganization.ConclusionsOur results highlight the suitability of NemaFlex and burrowing assays for evaluating muscle physiology ofC.elegans. Using these approaches, we discuss the importance of the studied sarcomere proteins for muscle function and structure. The scoring methodology we have developed enhances the utility of C.elegansas a genetic model to study muscle function.
Distributional health and financial consequences of increased cigarette tax in Iran: extended cost-effectiveness analysis
Authors: Raei Behzad , Emamgholipour Sara , Takian Amirhossein , Yaseri Mehdi , Abdoli Ghahreman , Alizadeh Ahad 
Published: August 2021

AbstractBackgroundTo assess the potential impact of a tax-induced cigarette price increase on financial and health outcomes by different socioeconomic groups.MethodsIn a modeled condition using pooled cross-section data from Household Income and Expenditure Survey (2002–2017) and Iran 2019 population data, a methodology of an extended cost effectiveness analysis (ECEA) was applied to model the impact on cigarette consumption of hypothetically increased cigarette tax. The methodology was employed to evaluate: [1] health benefits (premature deaths averted); [2] health expenditures regarding smoking-related disease treatment averted; [3] additional tax revenues raised; [4] change in household expenditures on cigarettes; and [5] financial risk protection among male Iranian smokers in a time span of 60 years following a one-time increase in cigarette price of 75%. The Stata version 15.1 (StataCorp., College Station, TX, USA) was used to perform the relevant analysis and estimate regression models.ResultsA 75% increase in cigarettes price through taxation would reduce the number of smokers by more than half a million, 11% of them in the poorest quintile; save about 1.9 million years of life (11% of which would be gained in the lowest quintile compared to 20% in the highest one); eliminate a total of US$196.4 million of health expenditures (9% of which would benefit the bottom quintile). Such a policy could raise the additional annual tax revenues by roughly US$ 1 billion, where the top two quintiles bear around 46% of the total tax burden. We estimated that the tax increase would avert an estimated 56,287 cases of catastrophic expenditure that wholly concentrated among the bottom two expenditure quintiles.ConclusionIncreasing cigarette tax can provide health and financial benefits, and would be pro-poor in terms of health gains, Out-of-Pocket (OOP) savings, and financial risk protection against smoking-related diseases.
Escherichia coli AraJ boosts utilization of arabinose in metabolically engineered cyanobacterium Synechocystis sp. PCC 6803
Authors: Ranade Saurabh , He Qingfang 
Published: August 2021

AbstractLignocellulosic biomass can serve as an inexpensive and renewable source of carbon for the biosynthesis of commercially important compounds. L-arabinose is the second most abundant pentose sugar present in the plant materials. Model cyanobacterium Synechocystis sp. PCC 6803 is incapable of catabolism of L-arabinose as a source of carbon and energy. In this study, all the heterologous genes expressed in Synechocystis were derived from Escherichia coli K-12. Initially we constructed four Synechocystis strains that expressed AraBAD enzymes involved in L-arabinose catabolism, either in combination with or without one of the three arabinose transporters, AraE, AraFGH or AraJ. Among the recombinants, the strain possessing AraJ transporter was observed to be the most efficient in terms of dry biomass production and L-arabinose consumption. Later, an additional strain was generated by the expression of AraJ in the AraE-possessing strain. The resultant strain was shown to be advantageous over its parent. This study demonstrates that AraJ, a protein with hitherto unknown function plays a role in the uptake of L-arabinose to boost its catabolism in the transgenic Synechocystis strains. The work also contributes to the current knowledge regarding metabolic engineering of cyanobacteria for the utilization of pentose sugars.
Novel phenotypes of coronavirus disease: a temperature-based trajectory model
Authors: Shen Yanfei , Chen Dechang , Huang Xinmei , Cai Guolong , Xu Qianghong , Hu Caibao , Yan Jing , Liu Jiao 
Published: August 2021

Abstract
Background
Coronavirus disease has heterogeneous clinical features; however, the reasons for the heterogeneity are poorly understood. This study aimed to identify clinical phenotypes according to patients’ temperature trajectory.

Method
A retrospective review was conducted in five tertiary hospitals in Hubei Province from November 2019 to March 2020. We explored potential temperature-based trajectory phenotypes and assessed patients’ clinical outcomes, inflammatory response, and response to immunotherapy according to phenotypes.

Results
A total of 1580 patients were included. Four temperature-based trajectory phenotypes were identified: normothermic (Phenotype 1); fever, rapid defervescence (Phenotype 2); gradual fever onset (Phenotype 3); and fever, slow defervescence (Phenotype 4). Compared with Phenotypes 1 and 2, Phenotypes 3 and 4 had a significantly higher C-reactive protein level and neutrophil count and a significantly lower lymphocyte count. After adjusting for confounders, Phenotypes 3 and 4 had higher in-hospital mortality (adjusted odds ratio and 95% confidence interval 2.1, 1.1–4.0; and 3.3, 1.4–8.2, respectively), while Phenotype 2 had similar mortality, compared with Phenotype 1. Corticosteroid use was associated with significantly higher in-hospital mortality in Phenotypes 1 and 2, but not in Phenotypes 3 or 4 (p for interaction < 0.01). A similar trend was observed for gamma-globulin.

Conclusions
Patients with different temperature-trajectory phenotypes had different inflammatory responses, clinical outcomes, and responses to corticosteroid therapy.
A parallel hybrid accelerated extragradient algorithm for pseudomonotone equilibrium, fixed point, and split null point problems
Authors: Arfat Yasir , Kumam Poom , Khan Muhammad Aqeel Ahmad , Ngiamsunthorn Parinya Sa , Kaewkhao Attapol 
Published: August 2021

AbstractThis paper provides iterative construction of a common solution associated with the classes of equilibrium problems (EP) and split convex feasibility problems. In particular, we are interested in the EP defined with respect to the pseudomonotone bifunction, the fixed point problem (FPP) for a finite family of "Equation missing"-demicontractive operators, and the split null point problem. From the numerical standpoint, combining various classical iterative algorithms to study two or more abstract problems is a fascinating field of research. We, therefore, propose an iterative algorithm that combines the parallel hybrid extragradient algorithm with the inertial extrapolation technique. The analysis of the proposed algorithm comprises theoretical results concerning strong convergence under a suitable set of constraints and numerical results.
Boundary value problem for nonlinear fractional differential equations of variable order via Kuratowski MNC technique
Authors: Benkerrouche Amar , Baleanu Dumitru , Said Souid Mohammed , Hakem Ali , Inc Mustafa 
Published: August 2021

AbstractIn the present research study, for a given multiterm boundary value problem (BVP) involving the Riemann-Liouville fractional differential equation of variable order, the existence properties are analyzed. To achieve this aim, we firstly investigate some specifications of this kind of variable-order operators, and then we derive the required criteria to confirm the existence of solution and study the stability of the obtained solution in the sense of Ulam-Hyers-Rassias (UHR). All results in this study are established with the help of the Darbo’s fixed point theorem (DFPT) combined with Kuratowski measure of noncompactness (KMNC). We construct an example to illustrate the validity of our observed results.
On the perturbations of maps obeying Shannon–Whittaker–Kotel’nikov’s theorem generalization
Authors: Antuña Almudena , Guirao Juan L. G. , López Miguel A. 
Published: August 2021

AbstractLet$f: \mathbb{R}\rightarrow \mathbb{R}$f:R→Rbe a map and$\tau \in \mathbb{R}^{+}$τ∈R+. The mapfobeys the Shannon–Whittaker–Kotel’nikov theorem generalization (SWKTG) if$f(t)=\lim_{n\to \infty } ( \sum_{k\in \mathbb{Z}} f^{ \frac{1}{n}} (\frac{k}{\tau } ) \operatorname{sinc} (\tau t-k) )^{n}$f(t)=limn→∞(∑k∈Zf1n(kτ)sinc(τt−k))nfor every$t\in \mathbb{R}$t∈R. The aim of the present paper is to characterize the perturbations of the mapfthat obeys SWKTG. Our results enlarge the catalog of maps that can be recomposed using SWKTG. We underline that maps obeying SWKTG play a central role in applications to chemistry and signal theory between other fields.
Metapangenomics reveals depth-dependent shifts in metabolic potential for the ubiquitous marine bacterial SAR324 lineage
Authors: Boeuf Dominique , Eppley John M. , Mende Daniel R. , Malmstrom Rex R. , Woyke Tanja , DeLong Edward F. 
Published: August 2021

AbstractBackgroundOceanic microbiomes play a pivotal role in the global carbon cycle and are central to the transformation and recycling of carbon and energy in the ocean’s interior. SAR324 is a ubiquitous but poorly understood uncultivated clade of Deltaproteobacteria that inhabits the entire water column, from ocean surface waters to its deep interior. Although some progress has been made in elucidating potential metabolic traits of SAR324 in the dark ocean, very little is known about the ecology and the metabolic capabilities of this group in the euphotic and twilight zones. To investigate the comparative genomics, ecology, and physiological potential of the SAR324 clade, we examined the distribution and variability of key genomic features and metabolic pathways in this group from surface waters to the abyss in the North Pacific Subtropical Gyre, one of the largest biomes on Earth.ResultsWe leveraged a pangenomic ecological approach, combining spatio-temporally resolved single-amplified genome, metagenomic, and metatranscriptomic datasets. The data revealed substantial genomic diversity throughout the SAR324 clade, with distinct depth and temporal distributions that clearly differentiated ecotypes. Phylogenomic subclade delineation, environmental distributions, genomic feature similarities, and metabolic capacities revealed strong congruence. The four SAR324 ecotypes delineated in this study revealed striking divergence from one another with respect to their habitat-specific metabolic potentials. The ecotypes living in the dark or twilight oceans shared genomic features and metabolic capabilities consistent with a sulfur-based chemolithoautotrophic lifestyle. In contrast, those inhabiting the sunlit ocean displayed higher plasticity energy-related metabolic pathways, supporting a presumptive photoheterotrophic lifestyle. In epipelagic SAR324 ecotypes, we observed the presence of two types of proton-pumping rhodopsins, as well as genomic, transcriptomic, and ecological evidence for active photoheterotrophy, based on xanthorhodopsin-like light-harvesting proteins.ConclusionsCombining pangenomic and both metagenomic and metatranscriptomic profiling revealed a striking divergence in the vertical distribution, genomic composition, metabolic potential, and predicted lifestyle strategies of geographically co-located members of the SAR324 bacterial clade. The results highlight the utility of metapangenomic approaches employed across environmental gradients, to decipher the properties and variation in function and ecological traits of specific phylogenetic clades within complex microbiomes.