bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revisiting the use of graph centrality models in biological pathway analysis
Authors: Naderi Yeganeh Pourya , Richardson Chrsitine , Saule Erik , Loraine Ann , Taghi Mostafavi M. 
Published: June 2020

AbstractThe use of graph theory models is widespread in biological pathway analyses as it is often desired to evaluate the position of genes and proteins in their interaction networks of the biological systems. In this article, we argue that the common standard graph centrality measures do not sufficiently capture the informative topological organizations of the pathways, and thus, limit the biological inference. While key pathway elements may appear both upstream and downstream in pathways, standard directed graph centralities attribute significant topological importance to the upstream elements and evaluate the downstream elements as having no importance.We present a directed graph framework, Source/Sink Centrality (SSC), to address the limitations of standard models. SSC separately measures the importance of a node in the upstream and the downstream of a pathway, as a sender and a receiver of biological signals, and combines the two terms for evaluating the centrality. To validate SSC, we evaluate the topological position of known human cancer genes and mouse lethal genes in their respective KEGG annotated pathways and show that SSC-derived centralities provide an effective framework for associating higher positional importance to the genes with higher importance from a priori knowledge. While the presented work challenges some of the modeling assumptions in the common pathway analyses, it provides a straight-forward methodology to extend the existing models. The SSC extensions can result in more informative topological description of pathways, and thus, more informative biological inference.
Regulation of heterogeneous cancer-associated fibroblasts: the molecular pathology of activated signaling pathways
Authors: Yoshida Go J. 
Published: June 2020

AbstractAccumulating evidence indicates that intratumoral heterogeneity contributes to the development of resistance to anticancer therapeutics. Fibroblasts, which are components of the paraneoplastic stroma, play a crucial role in the wound-healing process. Activated fibroblasts accumulate in the wound and are involved in many aspects of the tissue remodeling cascade that initiates the repair process and prevents further tissue damage. The pathophysiological roles of cancer-associated fibroblasts (CAFs) in the heterogeneous tumor microenvironment have attracted increasing interest. CAFs play crucial roles in tumor progression and the response to chemotherapy. Several cytokines and chemokines are involved in the conversion of normal fibroblasts into CAFs, and some of these form a feedback loop between cancer cells and CAFs. In addition, the physical force between tumor cells and CAFs promotes cooperative invasion or co-migration of both types of cells. Pro-inflammatory cytokines, such as leukemia inhibitory factor (LIF) and interleukin-6 (IL-6), are secreted by both cancer cells and CAFs, and mediate the epigenetic modification of CAFs. This enhances the pro-tumorigenic function of CAFs mediated by promoting actomyosin contractility and extracellular matrix remodeling to form the tracks used for collective cancer cell migration. The concept of intra-tumoral CAF heterogeneity refers to the presence of inflammatory CAFs with low levels of α-smooth muscle actin (α-SMA) and high levels of IL-6 expression, which are in striking contrast to transforming growth factor-β (TGF-β)-dependent myofibroblastic CAFs with high α-SMA expression levels. CAF populations that suppress tumor growth and progression through stroma-specific Hedgehog (Hh) activation have been detected in different murine tumor models including those of the bladder, colon, and pancreas. A new therapeutic strategy targeting CAFs is the “stromal switch,” in which tumor-promoting CAFs are changed into tumor-retarding CAFs with attenuated stromal stiffness. Several molecular mechanisms that can be exploited to design personalized anticancer therapies targeting CAFs remain to be elucidated. Strategies aimed at targeting the tumor stroma as well as tumor cells themselves have attracted academic attention for their application in precision medicine. This novel review discusses the role of the activation of EGFR, Wnt/β-catenin, Hippo, TGF-β, and JAK/STAT cascades in CAFs in relation to the chemoresistance and invasive/metastatic behavior of cancer cells. For instance, although activated EGFR signaling contributes to collective cell migration in cooperation with CAFs, an activated Hippo pathway is responsible for stromal stiffness resulting in the collapse of neoplastic blood vessels. Therefore, identifying the signaling pathways that are activated under specific conditions is crucial for precision medicine.
Catalogue of stage-specific transcripts in Ixodes ricinus and their potential functions during the tick life-cycle
Authors: Vechtova Pavlina , Fussy Zoltan , Cegan Radim , Sterba Jan , Erhart Jan , Benes Vladimir , Grubhoffer Libor 
Published: June 2020

Abstract
Background
The castor bean tick Ixodes ricinus is an important vector of several clinically important diseases, whose prevalence increases with accelerating global climate changes. Characterization of a tick life-cycle is thus of great importance. However, researchers mainly focus on specific organs of fed life stages, while early development of this tick species is largely neglected.

Methods
In an attempt to better understand the life-cycle of this widespread arthropod parasite, we sequenced the transcriptomes of four life stages (egg, larva, nymph and adult female), including unfed and partially blood-fed individuals. To enable a more reliable identification of transcripts and their comparison in all five transcriptome libraries, we validated an improved-fit set of five I. ricinus-specific reference genes for internal standard normalization of our transcriptomes. Then, we mapped biological functions to transcripts identified in different life stages (clusters) to elucidate life stage-specific processes. Finally, we drew conclusions from the functional enrichment of these clusters specifically assigned to each transcriptome, also in the context of recently published transcriptomic studies in ticks.

Results
We found that reproduction-related transcripts are present in both fed nymphs and fed females, underlining the poorly documented importance of ovaries as moulting regulators in ticks. Additionally, we identified transposase transcripts in tick eggs suggesting elevated transposition during embryogenesis, co-activated with factors driving developmental regulation of gene expression. Our findings also highlight the importance of the regulation of energetic metabolism in tick eggs during embryonic development and glutamate metabolism in nymphs.

Conclusions
Our study presents novel insights into stage-specific transcriptomes of I. ricinus and extends the current knowledge of this medically important pathogen, especially in the early phases of its development.
Transplantation of human dental pulp stem cells ameliorates diabetic polyneuropathy in streptozotocin-induced diabetic nude mice: the role of angiogenic and neurotrophic factors
Authors: Hata Masaki , Omi Maiko , Kobayashi Yasuko , Nakamura Nobuhisa , Miyabe Megumi , Ito Mizuho , Makino Eriko , Kanada Saki , Saiki Tomokazu , Ohno Tasuku , Imanishi Yuka , Himeno Tatsuhito , Kamiya Hideki , Nakamura Jiro , Ozawa Shogo , Miyazawa Ken , Kurita Kenichi , Goto Shigemi , Takebe Jun , Matsubara Tatsuaki , Naruse Keiko 
Published: June 2020

Abstract
Background
Dental pulp stem cells (DPSCs) have high proliferation and multi-differentiation capabilities that maintain their functionality after cryopreservation. In our previous study, we demonstrated that cryopreserved rat DPSCs improved diabetic polyneuropathy and that the efficacy of cryopreserved rat DPSCs was equivalent to that of freshly isolated rat DPSCs. The present study was conducted to evaluate whether transplantation of cryopreserved human DPSCs (hDPSCs) is also effective for the treatment of diabetic polyneuropathy.

Methods
hDPSCs were isolated from human impacted third molars being extracted for orthodontic reasons. Eight weeks after the induction of diabetes in nude mice, hDPSCs (1 × 105/limb) were unilaterally transplanted into the hindlimb skeletal muscle, and vehicle (saline) was injected into the opposite side as a control. The effects of hDPSCs were analyzed at 4 weeks after transplantation.

Results
hDPSC transplantation significantly ameliorated reduced sensory perception thresholds, delayed nerve conduction velocity, and decreased the blood flow to the sciatic nerve in diabetic mice 4 weeks post-transplantation. Cultured hDPSCs secreted the vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) proteins. A subset of the transplanted hDPSCs was localized around the muscle bundles and expressed the human VEGF and NGF genes at the transplanted site. The capillary/muscle bundle ratio was significantly increased on the hDPSC-transplanted side of the gastrocnemius muscles in diabetic mice. Neutralizing antibodies against VEGF and NGF negated the effects of hDPSC transplantation on the nerve conduction velocity in diabetic mice, suggesting that VEGF and NGF may play roles in the effects of hDPSC transplantation on diabetic polyneuropathy.

Conclusions
These results suggest that stem cell transplantation with hDPSCs may be efficacious in treating diabetic polyneuropathy via the angiogenic and neurotrophic mechanisms of hDPSC-secreted factors.
Health economic evaluation of an internet intervention for depression (deprexis), a randomized controlled trial
Authors: Gräfe Viola , Moritz Steffen , Greiner Wolfgang 
Published: June 2020

Abstract
Background
Depressive disorders often remain undiagnosed or are treated inadequately. Online-based programs may reduce the present treatment gap for depressive disorders and reduce disease-related costs. This study aimed to examine the potential of the internet intervention “deprexis” to reduce the total costs of statutory health insurance. Changes in depression severity, health-related quality of life and impairment in functioning were also examined.

Method
A total of 3805 participants with, at minimum, mild depressive symptoms were randomized to either a 12-week online intervention (deprexis) or a control condition. The primary outcome measure was statutory health insurance costs, estimated using health insurers’ administrative data. Secondary outcomes were: depression severity, health-related quality of life, and impairment in functioning; assessed on patient’s self-report at baseline, post-treatment, and three-months’ and nine-months’ follow-up.

Results
In both groups, total costs of statutory health insurance decreased during the study period, but changes from baseline differed significantly. In the intervention group total costs decreased by 32% from 3139€ per year at baseline to 2119€ in the study year (vs. a mean reduction in total costs of 13% in the control group). In comparison to the control group, the intervention group also showed a significantly greater reduction in depression severity, and impairment in functioning and a significantly greater increase in health-related quality of life.

Conclusion
The study underlines the potential of innovative internet intervention programs in treating depressive disorders. The results suggest that the use of deprexis over a period of 12 weeks leads to a significant improvement in symptoms with a simultaneous reduction in the costs of statutory health insurance.
Multidisciplinary team approach in acute myocardial infarction patients undergoing veno-arterial extracorporeal membrane oxygenation
Authors: Hong David , Choi Ki Hong , Cho Yang Hyun , Cho Su Hyun , Park So Jin , Kim Darae , Park Taek Kyu , Lee Joo Myung , Song Young Bin , Choi Jin-Oh , Hahn Joo-Yong , Choi Seung-Hyuk , Choi Jin-Ho , Sung Kiick , Gwon Hyeon-Cheol , Jeon Eun-Seok , Yang Jeong Hoon 
Published: June 2020

Abstract
Background
Limited data are available on the impact of a specialized extracorporeal membrane oxygenation (ECMO) team on clinical outcomes in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). This study evaluated whether specialized ECMO team is associated with improved in-hospital mortality in AMI patients undergoing veno-arterial (VA) ECMO.

Methods
A total of 255 AMI patients who underwent VA-ECMO were included. In January 2014, a multidisciplinary ECMO team was founded at our institution. Eligible patients were classified into a pre-ECMO team group (n = 131) and a post-ECMO team group (n = 124). The primary outcome was in-hospital mortality.

Results
In-hospital mortality (pre-ECMO team vs. post-ECMO team, 54.2% vs. 33.9%; p = 0.002) and cardiac intensive care unit mortality (pre-ECMO team vs. post-ECMO team, 51.9% vs. 30.6%; p = 0.001) were significantly lower after the implementation of a multidisciplinary ECMO team. On multivariable logistic regression model, implementation of the multidisciplinary ECMO team was associated with reduction of in-hospital mortality [odds ratio: 0.37, 95% confidence interval (CI) 0.20–0.67; p = 0.001]. Incidence of all-cause mortality [58.3% vs. 35.2%; hazard ratio (HR): 0.49, 95% CI 0.34–0.72; p < 0.001) and readmission due to heart failure (28.2% vs. 6.4%; HR: 0.21, 95% CI 0.08–0.58; p = 0.003) at 6 months of follow-up were also significantly lower in the post-ECMO team group than in the pre-ECMO team group.

Conclusions
Implementation of a multidisciplinary ECMO team was associated with improved clinical outcomes in AMI patients complicated by CS. Our data support that a specialized ECMO team is indispensable for improving outcomes in patients with AMI complicated by CS.
Continuous renal replacement therapy and transplant-free survival in acute liver failure: protocol for a systematic review and meta-analysis
Authors: Robinson Andrea M. , Karvellas C. J. , Dionne Joanna C. , Featherstone Robin , Sebastianski Meghan , Vandermeer Ben , Rewa Oleksa G. 
Published: June 2020

Abstract
Background
Acute liver failure is a rare syndrome with significant morbidity and mortality, particularly in absence of transplantation as a rescue therapy. An important mechanism contributing to mortality is hyperammonemia which drives cerebral edema and raised intracranial pressure. Multiple therapies for managing hyperammonemia have been trialed. Continuous renal replacement therapy is effective in treating hyperammonemia in other disease states (notably inborn errors of metabolism). Its efficacy in acute liver failure has been suggested but further investigation is required to prove this. The objective of this systematic review will be to determine the efficacy of continuous renal replacement therapy in patients with acute liver failure and its effect on mortality and transplant-free survival.

Methods
MEDLINE, EMBASE, Web of Science, and Cochrane Database will be searched. Identified studies will include all patients with acute liver failure in a critical care unit treated with continuous renal replacement therapy. Primary outcome will be effectiveness of ammonia clearance and mortality. Patients treated with any other modality of ammonia lowering therapy (such as plasma exchange or Molecular Adsorbent Recirculating System) will be excluded. Narrative synthesis of the identified studies will occur and if clinical homogeneity is identified, data will be pooled for meta-analysis using a DerSimonian-Laird random effects model.

Discussion
We present a protocol for a systematic review seeking to establish a link between transplant-free survival in acute liver failure and the use of continuous renal replacement therapy. Given the anticipated paucity of literature on this subject, both narrative and quantitative syntheses are planned.

Systematic review registration
(PROSPERO) CRD42019122520, registered April 16, 2019.
Lyapunov-type inequalities for generalized one-dimensional Minkowski-curvature problems
Authors: Liu Haidong 
Published: June 2020

AbstractIn this paper, we consider some types of scalar equations and systems of generalized one-dimensional Minkowski-curvature problems. Using an inequality technique, we establish several new Lyapunov-type inequalities for the problems considered. Our results extend the existing work in the literature.
A new family of orthogonal polynomials in three variables
Authors: Aktaş Rabia , Area Iván , Güldoğan Esra 
Published: June 2020

AbstractIn this paper we introduce a six-parameter generalization of the four-parameter three-variable polynomials on the simplex and we investigate the properties of these polynomials. Sparse recurrence relations are derived by using ladder relations for shifted univariate Jacobi polynomials and bivariate polynomials on the triangle. Via these sparse recurrence relations, second order partial differential equations are presented. Some connection relations are obtained between these polynomials. Also, new results for the four-parameter three-variable polynomials on the simplex are given. Finally, some generating functions are derived.
Proposal for a EN 149 acceptable reprocessing method for FFP2 respirators in times of severe shortage
Authors: Widmer Andreas F. , Richner Gilles 
Published: June 2020

Abstract
Introduction
Transmission of SARS-CoV-2 to health care workers (HCW) poses a major burden in the current COVID-19 pandemic. Unprotected exposure to a COVID-19 patient is a key risk factor for HCWs. Transmission mainly occurs by droplet transmission, or by aerosol generating procedures. Respirators such as filtering face piece masks (FFP2), also called respirators, are required to prevent transmission during aerosol generating procedures, as part of the personal protective equipment (PPE) for HCWs. However, many HCW were infected due to lack of PPE, or failure to use them. Therefore, the worldwide shortage of respirators triggered the development of reprocessing used FFP2 respirators or N95 respirators as standard in the US. Our proposal with H2O2 plasma sterilization for decontamination allows to reprocess FFP2, while they still meet the filtration efficiency required by EN 149. The protocol is simple, uses available resources in hospitals and can be rapidly implemented to decrease the shortage of respirators during this crisis. The goal of the study was the evaluate if respirators can be reprocessed and still fulfill the requirements for filtration efficiency outlined by EN 149.

Methods
Used FFP2 respirators – Model 3 M Aura™ 1862+ − were sterilized using a low temperature process hydrogen peroxide (H2O2), V-PRO® maX Low Temperature, a FDA (Food and Drug Administration) approved method to decontaminate FFP2 respirators. Decontaminated respirators were further checked for residual peroxide by a single-gas detector for H2O2. The total inward leakage of the protective respirators was quantitatively tested with 10 test persons in an atmosphere charged with paraffin aerosol according to the European Standard EN 149. The fit factor was calculated as the inverse of the total inward leakage.

Results
Ten new and ten decontaminated FFP2 respirators were tested for filtration efficiency. None of the respirators exceeded the maximum acceptable concentration of peroxide. More than 4000 respirators have been reprocessed so far, at cost of approximately 0.3 Euro/piece.

Conclusions
FFP2 respirators can be safely reprocessed once after decontamination with plasma peroxide sterilization, whereafter they still fulfill EN 149 requirements. This allows to almost double the current number of available FFP2 respirators.
A silent outbreak of vancomycin-resistant Enterococcus faecium in a neonatal intensive care unit
Authors: Marom Ronella , Mandel Dror , Haham Alon , Berger Irit , Ovental Amit , Raskind Craig , Grisaru-Soen Galia , Adler Amos , Lellouche Jonathan , Schwartz David , Carmeli Yehuda , Schechner Vered 
Published: June 2020

Abstract
Objective
To describe the containment of a widespread silent outbreak of vancomycin-resistant Enterococcus faecium (VRE-fm) in the Tel-Aviv Medical Center (TASMC) neonatal intensive care unit (NICU).

Methods
Setting - an NICU, participants - 49 cases of VRE-fm-colonized neonatal inpatients.

Results
A newborn was transferred from the TASMC NICU to another hospital and screened positive for VRE-fm upon arrival. All TASMC NICU patients were then immediately screened for VRE and 21/38 newborns were identified as VRE carriers. Interventional measures were strictly enforced. By the end of the outbreak, 49 cases of VRE carriage had been identified. There were no VRE clinical infections. The source of the outbreak was not identified.

Conclusion
Our study highlights the importance of screening implementation in a NICU setting since this outbreak could have been prevented by active screening of all out-born transfer patients and by having adopted mandatory screening into the NICU’s routine procedures. Screening for multi-drug resistant organisms upon admission of all transferred patients to the NICU has been implemented.
Genomic and transcriptomic insights into methanogenesis potential of novel methanogens from mangrove sediments
Authors: Zhang Cui-Jing , Pan Jie , Liu Yang , Duan Chang-Hai , Li Meng 
Published: June 2020

AbstractBackgroundMethanogens are crucial to global methane budget and carbon cycling. Methanogens from the phylum Euryarchaeota are currently classified into one class and seven orders, including two novel methanogen taxa,MethanofastidiosaandMethanomassiliicoccales. The relative importance of the novel methanogens to methane production in the natural environment is poorly understood.ResultsHere, we used a combined metagenomic and metatranscriptomic approach to investigate the metabolic activity of methanogens in mangrove sediments in Futian Nature Reserve, Shenzhen. We obtained 13 metagenome-assembled genomes (MAGs) representing one class (Methanofastidiosa) and five orders (Methanomassiliicoccales,Methanomicrobiales,Methanobacteriales,Methanocellales, andMethanosarcinales) of methanogens, including the two novel methanogens. Comprehensive annotation indicated the presence of an H2–dependent methylotrophic methanogenesis pathway inMethanofastidiosaandMethanomassiliicoccales. Based on the functional gene analysis, hydrogenotrophic and methylotrophic methanogenesis are the dominant pathways in mangrove sediments. MAG mapping revealed that hydrogenotrophicMethanomicrobiales were the most abundant methanogens and that methylotrophicMethanomassiliicoccaleswere the most active methanogens in the analyzed sediment profile, suggesting their important roles in methane production.ConclusionsPartial or near-complete genomes of two novel methanogen taxa,MethanofastidiosaandMethanomassiliicoccales, in natural environments were recovered and analyzed here for the first time. The presented findings highlight the ecological importance of the two novel methanogens and complement knowledge of how methane is produced in mangrove ecosystem. This study implies that two novel methanogens play a vital role in carbon cycle.