bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Factors of Survival After Neoadjuvant Treatment and Resection for Initially Unresectable Pancreatic Cancer
Authors: Klaiber Ulla , Schnaidt Eva S. , Hinz Ulf , Gaida Matthias M. , Heger Ulrike , Hank Thomas , Strobel Oliver , Neoptolemos John P. , Mihaljevic André L. , Büchler Markus W. , Hackert Thilo 
Published: March 2019

Objective:
To evaluate the impact of clinical and pathological parameters, including resection margin (R) status, on survival in patients undergoing pancreatic surgery after neoadjuvant treatment for initially unresectable pancreatic ductal adenocarcinoma (PDAC).

Background:
Prognostic factors are well documented for patients with resectable PDAC, but have not been described in detail for patients with initially unresectable PDAC undergoing resection after neoadjuvant therapy.

Methods:
Prospectively collected data of consecutive patients with initially unresectable pancreatic cancer treated by neoadjuvant treatment and resection were analyzed. The R status was categorized as R0 (tumor-free margin >1 mm), R1 ≤1 mm (tumor-free margin ≤1 mm), and R1 direct (microscopic tumor infiltration at margin). Clinicopathological characteristics and outcomes were compared among these groups and tested for survival prediction.

Results:
Between January, 2006 and February, 2017, 280 patients with borderline resectable (n = 18), locally advanced (n = 190), or oligometastatic (n = 72) disease underwent tumor resection after neoadjuvant treatment. Median overall survival from the time of surgery was 25.1 months for R0 (n = 82), 15.3 months for R1 ≤1 mm (n = 99), and 16.1 months for R1 direct (n = 99), with 3-year overall survival rates of 35.0%, 20.7%, and 18.5%, respectively (P = 0.0076). The median duration of the neoadjuvant treatment period was 5.1 months. In multivariable analysis, preoperative CA 19–9 levels, lymph node status, metastasis category, and vascular involvement were all significant prognostic factors for overall survival. The R status was not an independent prognostic factor.

Conclusions:
In patients undergoing resection after neoadjuvant therapy for initially unresectable PDAC, preoperative CA 19–9 levels, lymph node involvement, metastasis category, and vascular involvement, but not the R status, were independent prognostic factors of overall survival.
Practice Patterns Regarding Apical Support Procedures at Time of Hysterectomy for Pelvic Organ Prolapse
Authors: Hill Austin M. , Pauls Rachel N. , Crisp Catrina C. 
Published: March 2019

Objectives
We sought to understand practice patterns of non–female pelvic medicine and reconstructive surgery (FPMRS) clinicians regarding concurrent apical support procedures during hysterectomies when primarily performed for the treatment of pelvic organ prolapse. We also sought to describe differences between those receiving and not receiving apical support.

Methods
This retrospective study analyzed medical records of individuals undergoing hysterectomy for the primary indication of pelvic organ prolapse between 2012 and 2017 at all locations within the TriHealth system. Surgeries performed by board-certified FPMRS physicians were excluded. Comparisons were drawn between those who did and did not receive apical support.

Results
A total of 236 charts met the inclusion criteria. Of these, 66 (28%) received concurrent apical suspension, and 94 (39.8%) underwent no reconstructive procedures. The annual proportion of those receiving apical suspension did not differ over the course of the study period. On average, the addition of apical support added 39.9 minutes (P < 0.001) to the length of surgery. There was, however, no difference noted in estimated blood loss. Risk factors for recurrent prolapse including chronic constipation, pulmonary disease, and connective tissue disorders were similar between groups.

Conclusion
When excluding FPMRS surgeons, data from our institution showed that most patients undergoing hysterectomy for prolapse did not receive concurrent apical support. This suggests areas of potential improvement for adopting into clinical practice the new American College of Obstetricians and Gynecologists recommendations regarding the treatment of prolapse. Furthermore, this may represent an important opportunity for peer outreach and education by FPMRS surgeons.
Complement-mediated Damage to the Glycocalyx Plays a Role in Renal Ischemia-reperfusion Injury in Mice
Authors: Bongoni Anjan K. , Lu Bo , McRae Jennifer L. , Salvaris Evelyn J. , Toonen Erik J. M. , Vikstrom Ingela , Baz Morelli Adriana , Pearse Martin J. , Cowan Peter J. 
Published: March 2019

Background
Complement activation plays an important role in the pathogenesis of renal ischemia-reperfusion (IR) injury (IRI), but whether this involves damage to the vasculoprotective endothelial glycocalyx is not clear. We investigated the impact of complement activation on glycocalyx integrity and renal dysfunction in a mouse model of renal IRI.

Methods
Right nephrectomized male C57BL/6 mice were subjected to 22 minutes left renal ischemia and sacrificed 24 hours after reperfusion to analyze renal function, complement activation, glycocalyx damage, endothelial cell activation, inflammation, and infiltration of neutrophils and macrophages.

Results
Ischemia-reperfusion induced severe renal injury, manifested by significantly increased serum creatinine and urea, complement activation and deposition, loss of glycocalyx, endothelial activation, inflammation, and innate cell infiltration. Treatment with the anti-C5 antibody BB5.1 protected against IRI as indicated by significantly lower serum creatinine (P = 0.04) and urea (P = 0.003), tissue C3b/c and C9 deposition (both P = 0.004), plasma C3b (P = 0.001) and C5a (P = 0.006), endothelial vascular cell adhesion molecule-1 expression (P = 0.003), glycocalyx shedding (tissue heparan sulfate [P = 0.001], plasma syndecan-1 [P = 0.007], and hyaluronan [P = 0.02]), inflammation (high mobility group box-1 [P = 0.0003]), and tissue neutrophil (P = 0.0009) and macrophage (P = 0.004) infiltration.

Conclusions
Together, our data confirm that the terminal pathway of complement activation plays a key role in renal IRI and demonstrate that the mechanism of injury involves shedding of the glycocalyx.
Conformational gating in ammonia lyases
Authors: Lambrughi Matteo , Maršić Željka Sanader , Saez-Jimenez Veronica , Mapelli Valeria , Olsson Lisbeth , Papaleo Elena 
Published: March 2019

ABSTRACTAmmonia lyases (AL) are enzymes of industrial and biomedical interest. Knowledge of AL structure-dynamics-function relationship would be instrumental for making use of the application potential of these enzymes. We investigated, using microsecond molecular dynamics, the conformational changes in the proximity of the catalytic pocket of a 3-methylaspartate ammonia lyase (MAL) as a model system. In particular, we identified two regulatory elements in the MAL structure, i.e., the β5-α2 loop, and the helix-hairpin-loop subdomain. We showed that they undergo conformational changes switching from ‘occluded’ to ‘open’ states. We observed that these rearrangements are coupled to changes in the accessibility of the active site. The β5-α2 loop and the helix-hairpin-loop subdomain modulate the formation of tunnels from the protein surface to the substrate binding site, making the active site more accessible to the substrate when they are in an open state. We pinpointed a sequential mechanism, in which the helix-hairpin-loop subdomain needs to break a subset of intramolecular interactions first, to then allow the opening of the β5-α2 loop and, as a consequence, make the AL catalytic pocket accessible for the substrate. Our data suggest that protein dynamics need to be considered in the design of new AL variants for protein engineering and therapeutic purposes.
NanoDJ: A Dockerized Jupyter Notebook for Interactive Oxford Nanopore MinION Sequence Manipulation and Genome Assembly
Authors: Rodríguez-Pérez Héctor , Hernández-Beeftink Tamara , Lorenzo-Salazar José M. , Roda-García José L. , Pérez-González Carlos J. , Colebrook Marcos , Flores Carlos 
Published: March 2019

AbstractBackgroundThe Oxford Nanopore Technologies (ONT) MinION portable sequencer makes it possible to use cutting-edge genomic technologies in the field and the academic classroom.ResultsWe present NanoDJ, a Jupyter notebook integration of tools for simplified manipulation and assembly of DNA sequences produced by ONT devices. It integrates basecalling, read trimming and quality control, simulation and plotting routines with a variety of widely used aligners and assemblers, including procedures for hybrid assembly.ConclusionsWith the use of Jupyter-facilitated access to self-explanatory contents of applications and the interactive visualization of results, as well as by its distribution into a Docker software container, NanoDJ is aimed to simplify and make more reproducible ONT DNA sequence analysis. The NanoDJ package code, documentation and installation instructions are freely available at https://github.com/genomicsITER/NanoDJ.
The fungal endophyteFusarium solaniprovokes differential effects on the energy balance of twoLotusspecies
Authors: Nieva Amira S. , Vilas Juan M. , Gárriz Andrés , Maiale Santiago J. , Menéndez Ana B. , Erban Alexander , Kopka Joachim , Ruiz Oscar A. 
Published: March 2019

AbstractBackground and aimsThe interactions established between plants and endophytic fungi span acontinuumfrom beneficial to pathogenic associations. The aim of this work was to explore the mechanisms underlying the potentially beneficial effects provoked by a fungal strain in legume species of the genusLotus.MethodsThe ability to solubilise phosphorous was evaluated in nine fungal strains isolated from roots ofL. tenuis. A selected strain was further assessed for its ability to colonize plant roots in differentLotusspecies. The effects of the two interactions were assessed by analysis of the photosynthesis, sugar amount, and macronutrient status of leaves and roots.ResultsA fungal isolate identified asFusarium solanishows the highest phosphate-solubilisation activity and grows endophytically in roots ofL. japonicusandL. tenuis. Fungal invasion enhances plant growth inL. japonicusbut provokes a contrasting effect inL. tenuis. Photosynthesis, sugars and K content showed a differential effect in both plant species.ConclusionsOur results indicate neither of the plant species evaluated in this work were significantly stressed byF. solani. Thus, the differential responses observed are due to distinct mechanisms involving photosynthesis, potassium homeostasis, and carbohydrate metabolism that are employed by plants to maintain fitness during the endophytic interaction.
The haploinsufficient tumor suppressor Tip60 negatively regulates the oncogenic Aurora B kinase
Authors: Bose Arnab , Sudevan Surabhi , Rao Vinay J. , Shima Hiroki , Igarashi Kazuhiko , Kundu Tapas K. 
Published: March 2019

AbstractThe Aurora kinases represent a group of serine/threonine kinases which are crucial regulators of mitosis. Dysregulated Aurora kinase B (AurkB) expression, stemming from genomic amplification, increased gene transcription or overexpression of its allosteric activators, is capable of initiating and sustaining malignant phenotypes. Although AurkB level in cells is well-orchestrated, studies that relate to its stability or activity, independent of mitosis, are lacking. We report that AurkB undergoes acetylation in vitro by lysine acetyltransferases (KATs) belonging to different families, namely by p300 and Tip60. The haploinsufficient tumor suppressor Tip60 acetylates two highly conserved lysine residues within the kinase domain of AurkB which not only impinges the protein stability but also its kinase activity. These results signify a probable outcome on the increase in “overall activity” of AurkB upon Tip60 downregulation, as observed under cancerous conditions. The present work, therefore, uncovers an important functional interplay between AurkB and Tip60, frailty of which may be an initial event in carcinogenesis.
The transcriptional regulator Id2 is critical for adipose-resident regulatory T cell differentiation, survival and function
Authors: Frias Adolfo B. , Hyzny Eric J. , Buechel Heather M. , Beppu Lisa , Xie Bingxian , Jurczak Michael J. , D’Cruz Louise M. 
Published: March 2019

SUMMARYAdipose regulatory T cells (aTregs) have emerged as critical cells for the control of local and systemic inflammation. In this study, we show a distinctive role for the transcriptional regulator Id2 in the differentiation, survival and function of aTregs. Id2 was highly expressed in aTregs compared with high Id3 expression in lymphoid Tregs. Treg-specific deletion of Id2 resulted in a substantial decrease in aTregs, while Tregs in the spleen and lymph nodes were unaffected. Additionally, loss of Id2 resulted in decreased expression of aTreg associated markers including ST2, CCR2, KLRG1 and GATA3. Gene expression analysis revealed that Id2 expression was essential for the survival of aTregs and loss of Id2 increased cell death in aTregs due to increased Fas expression. Id2-mediated aTreg depletion resulted in increased systemic inflammation, increased inflammatory macrophages and CD8+ effector T cells and loss of glucose tolerance under standard diet conditions. Thus, we reveal an unexpected and novel function for Id2 in mediating differentiation, survival and function of adipose-resident Tregs, that when lost resulting in increased metabolic perturbation.
Evolutionary dynamics and diversification in changing environments
Authors: Alekseeva Evgeniia , Doebeli Michael , Ispolatov Iaroslav 
Published: March 2019

AbstractWe use adaptive dynamics models to study how changes in the abiotic environment affect patterns of evolutionary dynamics and diversity in evolving communities of organisms with complex phenotypes. The models are based on the logistic competition model and environmental changes are implemented as a temporal change of the carrying capacity as a function of phenotype. In general we observe that environmental changes cause a reduction in the number of species, in total population size, and in phenotypic diversity. The rate of environmental change is crucial for determining whether a community survives or undergoes extinction. Until some critical rate of environmental changes, species are able to follow evolutionarily the shifting phenotypic optimum of the carrying capacity, and many communities adapt to the changing conditions and converge to new stationary states. When environmental changes stop, such communities gradually restore their initial phenotypic diversity.
The Degree of Polymerization and Sulfation Patterns in Heparan Sulfate are Critical Determinants of Cytomegalovirus Entry into Host Cells
Authors: Hasan Mohammad H. , Mitra Dipanwita , Parmar Rinkuben C. , Fassero Lauren A. , Liang Quntao , Qiu Hong , Tiwari Vaibhav , Sharp Joshua S. , Wang Lianchun , Tandon Ritesh 
Published: March 2019

ABSTRACTSeveral enveloped viruses, including herpesviruses attach to host cells by initially interacting with cell surface heparan sulfate (HS) proteoglycans followed by specific coreceptor engagement which culminates in virus-host membrane fusion and virus entry. Interfering with HS-herpesvirus interactions has long been known to result in significant reduction in virus infectivity indicating that HS play important roles in initiating virus entry. In this study, we provide a series of evidence to prove that specific sulfations as well as the degree of polymerization (dp) of HS govern human cytomegalovirus (CMV) binding and infection. First, purified CMV extracellular virions preferentially bind to sulfated longer chain HS on a glycoarray compared to a variety of unsulfated glycosaminoglycans including unsulfated shorter chain HS. Second, the fraction of glycosaminoglycans (GAG) displaying higherdpand sulfation has a larger impact on CMV titers compared to other fractions. Third, cell lines deficient in specific glucosaminyl sulfotransferases produce significantly reduced CMV titers compared to wild-type cells and virus entry is compromised in these mutant cells. Finally, cells pretreated with a peptide that specifically binds sulfated-HS produce significantly reduced virus titers compared to the control peptide treated cells. Taken together, these results highlight the significance of HS chain length and sulfation patterns in CMV attachment and infectivity.IMPORTANCEHeparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It binds to a variety of protein ligands, including cytokines, chemokines, growth factors and morphogens and regulates a wide range of biological activities, including developmental processes, angiogenesis, blood coagulation, and tumor metastasis. The molecular diversity in HS chains generates unique binding sites for specific ligands and can offer preferential binding for a specific virus over other viruses or cellular ligands. In the current study human cytomegalovirus (CMV) was found to bind preferentially to uniquely sulfated and polymerized HS. The HS mimics designed with these properties inhibited CMV infection. The results were corroborated by parallel studies in mutant mouse cells as well as using peptide inhibition. Combined together, the data suggests that CMV preferentially attaches to uniquely modified HS and thus this virus-host interaction is amenable to targeting by specifically designed HS mimics or peptides.
TreeCluster: clustering biological sequences using phylogenetic trees
Authors: Balaban Metin , Moshiri Niema , Mai Uyen , Mirarab Siavash 
Published: March 2019

AbstractClustering homologous sequences based on their similarity is a problem that appears in many bioinformatics applications. The fact that sequences cluster is ultimately the result of their phylogenetic relationships. Despite this observation and the natural ways in which a tree can define clusters, most applications of sequence clustering do not use a phylogenetic tree and instead operate on pairwise sequence distances. Due to advances in large-scale phylogenetic inference, we argue that tree-based clustering is under-utilized. We define a family of optimization problems that, given a (not necessarily ultrametric) tree, return the minimum number of clusters such that all clusters adhere to constraints on their heterogeneity. We study three specific constraints that limit the diameter of each cluster, the sum of its branch lengths, or chains of pairwise distances. These three versions of the problem can be solved in time that increases linearly with the size of the tree, a fact that has been known by computer scientists for two of these three criteria for decades. We implement these algorithms in a tool called TreeCluster, which we test on three applications: OTU picking for microbiome data, HIV transmission clustering, and divide-and-conquer multiple sequence alignment. We show that, by using tree-based distances, TreeCluster generates more internally consistent clusters than alternatives and improves the effectiveness of downstream applications. TreeCluster is available athttps://github.com/niemasd/TreeCluster.
Substrate structure and computation guided engineering of a Lipase for Omega-3 fatty acid selectivity
Authors: Moharana Tushar Ranjan , Rao Nalam Madhusudhana 
Published: March 2019

AbstractOptimum health benefits of omega-3 fatty acids (ω-3 FAs) require it to be concentrated in its natural sources. Fatty acid selectivity of lipase governs the efficacy of the production of lipase-mediated ω-3 FAs concentrates. We attempted to improve the fatty acid selectivity of a lipase from thermophilic bacteriumGeobacillus thermoleovorans(GTL) by two approaches. In a semi-rational approach, six amino acid positions of GTL interacting with the substrate, were identified by docking and were subjected to site-saturation mutagenesis. Three best substitutions were incorporated into GTL(CM-GTL). Hydrolysis of oil by lipase was monitored in a pH-Stat and the fatty acids released at various time points were analyzed by GC-MS.CM-GTL showed a significant improvement in discrimination against DHA during hydrolysis. In the second approach based on rational design, the active site was narrowed by incorporating heavier amino acids in the lining of acyl-binding pocket to hinder access to bulky ω-3 FAs. For this purpose, two amino acids surrounding the opening of the acyl pocket were replaced with the next heavier amino acids and the affinities were evaluatedin silico.The double mutant, thus deigned, was found to be excellent in discriminating the ω-3 FAs during hydrolysis of triglycerides. Engineering the binding pocket of a complex substrate, such as a triglyceride, with the supportive information on substrate structure and its binding modes with the enzyme provided by computational methods, has resulted in designing two efficient lipase variants with improved substrate selectivity.
Operation of networked multi-carrier microgrid considering demand response
Authors: Amir Vahid , Jadid Shahram , Ehsan Mehdi 
Published: March 2019

Purpose
Microgrids are inclined to use renewable energy resources within the availability limits. In conventional studies, energy interchange among microgrids was not considered because of one-directional power flows. Hence, this paper aims to study the optimal day-ahead energy scheduling of a centralized networked multi-carrier microgrid (NMCMG). The energy scheduling faces new challenges by inclusion of responsive loads, integration of renewable sources (wind and solar) and interaction of multi-carrier microgrids (MCMGs).

Design/methodology/approach
The optimization model is formulated as a mixed integer nonlinear programing and is solved using GAMS software. Numerical simulations are performed on a system with three MCMGs, including combined heat and power, photovoltaic arrays, wind turbines and energy storages to fulfill the required electrical and thermal load demands. In the proposed system, the MCMGs are in grid-connected mode to exchange power when required.

Findings
The proposed model is capable of minimizing the system costs by using a novel demand side management model and integrating the multiple-energy infrastructure, as well as handling the energy management of the network. Furthermore, the novel demand side management model gives more accurate optimal results. The operational performance and total cost of the NMCMG in simultaneous operation of multiple carriers has been effectively improved.

Originality/value
Introduction and modeling of the multiple energy demands within the MCMG. A novel time- and incentive-based demand side management, characterized by shifting techniques, is applied to reshape the load curve, as well as for preventing the excessive use of energy in peak hours. This paper analyzes the need to study how inclusion of multiple energy infrastructure integration and responsive load can impact the future distribution network costs.