bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncological Outcomes After Anastomotic Leakage After Surgery for Colon or Rectal Cancer
Authors: Koedam Thomas W. A. , Bootsma Boukje T. , Deijen Charlotte L. , van de Brug Tim , Kazemier Geert , Cuesta Miguel A. , Fürst Alois , Lacy Antonio M. , Haglind Eva , Tuynman Jurriaan B. , Daams Freek , Bonjer Hendrik J. 
Published: March 2020

Objective:
The aim of this study was to evaluate oncological outcome for patients with and without anastomotic leakage after colon or rectal cancer surgery.

Summary of Background Data:
The role of anastomotic leakage in oncological outcome after colorectal cancer surgery is still topic of debate and impact on follow-up and consideration for further treatment remains unclear.

Methods:
Patients included in the international, multicenter, non-inferior, open label, randomized, controlled trials COLOR and COLOR II, comparing laparoscopic surgery for curable colon (COLOR) and rectal (COLOR II) cancer with open surgery, were analyzed. Patients operated by abdominoperineal excision were excluded. Both univariate and multivariate analyses were performed to investigate the impact of leakage on overall survival, disease-free survival, local and distant recurrences, adjusted for possible confounders. Primary endpoints in the COLOR and COLOR II trial were disease-free survival and local recurrence at 3-year follow-up, respectively, and secondary endpoints included anastomotic leakage rate.

Results:
For colon cancer, anastomotic leakage was not associated with increased percentage of local recurrence or decreased disease-free-survival. For rectal cancer, an increase of local recurrences (13.3% vs 4.6%; hazard ratio 2.96; 95% confidence interval 1.38–6.34; P = 0.005) and a decrease of disease-free survival (53.6% vs 70.9%; hazard ratio 1.67; 95% confidence interval 1.16–2.41; P = 0.006) at 5-year follow-up were found in patients with anastomotic leakage.

Conclusion:
Short-term morbidity, mortality, and long-term oncological outcomes are negatively influenced by the occurrence of anastomotic leakage after rectal cancer surgery. For colon cancer, no significant effect was observed; however, due to low power, no conclusions on the influence of anastomotic leakage on outcomes after colon surgery could be reached. Clinical awareness of increased risk of local recurrence after anastomotic leakage throughout the follow-up is mandatory.

Trial Registration: Registered with ClinicalTrials.gov, number NCT00387842 and NCT00297791.
Correlation between universal BCG vaccination policy and reduced mortality for COVID-19
Authors: Miller Aaron , Reandelar Mac Josh , Fasciglione Kimberly , Roumenova Violeta , Li Yan , Otazu Gonzalo H. 
Published: March 2020

AbstractCOVID-19 has spread to most countries in the world. Puzzlingly, the impact of the disease varies in different countries. This variation is attributed to differences in cultural norms, mitigation efforts, and health infrastructure. Here, we propose that national differences in COVID-19 impact could be partially explained by different national policies with respect to Bacillus Calmette-Guérin (BCG) vaccination. BCG vaccination has been reported to offer broad protection from other respiratory infections besides tuberculosis. We compared BCG vaccination policies with the morbidity and mortality for COVID-19 for middle-high and high-income countries. We found that countries without universal policies of BCG vaccination (Italy, the Netherlands, USA) have been more severely affected compared to countries with universal and long-standing BCG policies. The difference cannot be accounted for by differences in disease onset, adoption of early social distancing policies, state of health services, nor income level. Reduced mortality suggests BCG vaccination could be a potential new tool in the fight against COVID-19.
Codon usage and evolutionary rates of the 2019-nCoV genes
Authors: Dilucca Maddalena , Forcelloni Sergio , Pavlopoulou Athanasia , Georgakilas Alexandros G. , Giansanti Andrea 
Published: March 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (2019-nCoV), which first broke out in Wuhan (China) in December of 2019, causes a severe acute respiratory illness with a mortality ranging from 3% to 6%. To better understand the evolution of the newly emerging 2019-nCoV, in this paper, we analyze the codon usage pattern of 2019-nCoV. For this purpose, we compare the codon usage of 2019-nCoV with that of other 30 viruses belonging to the subfamily of orthocoronavirinae. We found that 2019-nCoV shows a rich composition of AT nucleotides that strongly influences its codon usage, which appears to be not optimized to human host. Then, we study the evolutionary pressures influencing the codon usage and evolutionary rates of the sequences of five conserved genes that encode the corresponding proteins (viral replicase, spike, envelope, membrane and nucleocapsid) characteristic of coronaviruses. We found different patterns of both mutational bias and nature selection that affect the codon usage of these genes at different extents. Moreover, we show that the two integral membrane proteins proteins (matrix and envelope) tend to evolve slowly by accumulating nucleotide mutations on their genes. Conversely, genes encoding nucleocapsid (N), viral replicase and spike proteins are important targets for the development of vaccines and antiviral drugs, tend to evolve faster as compared to other ones. Taken together, our results suggest that the higher evolutionary rate observed for these two genes could represent a major barrier in the development of antiviral therapeutics 2019-nCoV.
Negative selection may cause grossly altered but broadly stable karyotypes in metastatic colorectal cancer
Authors: Cross William , Nowinski Salpie , Cresswell George D , Mossner Maximilian , Banerjee Abhirup , Lu Bingxin , Williams Marc , Vlachogiannis Georgios , Gay Laura , Baker Ann-Marie , Kimberley Christopher , Whiting Freddie , Belnoue-Davis Hayley , Martinez Pierre , Traki Maria , Walther Viola , Smith Kane , Fernandez-Mateos Javier , Yara Erika , Oliveira Erica , Milite Salvatore , Caravagna Giulio , James Chela , Elia George , Berner Alison , Choi Ryan Changho , Ramagiri Pradeep , Chauhan Ritika , Matthews Nik , Murphy Jamie , Antoniou Anthony , Clark Susan , Mitchison Miriam , Aleong Jo-Anne Chin , Domingo Enric , Spiteri Inmaculada , McDonald Stuart AC , Shibata Darryl , Lacle Miangela M , Wang Lai Mun , Moorghen Morgan , Tomlinson Ian PM , Novelli Marco , Jansen Marnix , Watson Alan , Wright Nicholas A , Bridgewater John , Rodriguez-Justo Manuel , Barnes Chris P , Kocher Hemant , Leedham Simon J , Sottoriva Andrea , Graham Trevor A 
Published: March 2020

AbstractAneuploidy, the loss and gain of whole and part chromosomes, is near-ubiquitous in cancer genomes and likely defines cancer cell biology. However, the temporal evolutionary dynamics that select for aneuploidy remain uncharacterised. Here we perform longitudinal genomic analysis of 755 samples from a total of 167 patients with colorectal-derived neoplastic lesions that represent distinct stages of tumour evolution through metastasis and treatment. Adenomas typically had few copy number alterations (CNAs) and most were subclonal, whereas cancers had many clonal CNAs, suggesting that progression goes through a CNA bottleneck. Individual CRC glands from the same tumour typically had very similar karyotypes, despite evidence of ongoing instability at the cell level in patient tumours, cell lines and organoids. CNAs in metastatic lesions sampled from liver and other organs, after chemotherapy or targeted therapies, and in late recurrences were typically similar to the primary tumour. Mathematical modelling and statistical inference indicated that these data are consistent with the action of negative selection on CNAs that ‘traps’ cancer cell genomes on a fitness peak defined by the specific pattern of chromosomal aberrations. These data suggest that the initial progression of colorectal cancer requires the traversal of a rugged fitness landscape and subsequent CNA evolution, including metastatic dissemination and therapeutic resistance, is constrained by negative selection.
Inter-domain dynamics drive cholesterol transport by NPC1 and NPC1L1 proteins
Authors: Saha Piyali , Shumate Justin L. , Caldwell Jenna G. , Elghobashi-Meinhardt Nadia , Lu Albert , Zhang Lichao , Olsson Niclas E. , Elias Joshua E. , Pfeffer Suzanne R. 
Published: March 2020

AbstractTransport of LDL-derived cholesterol from lysosomes into the cytoplasm requires NPC1 protein; NPC1L1 mediates uptake of dietary cholesterol. We introduced single disulfide bonds into NPC1 and NPC1L1 to explore the importance of inter-domain dynamics in cholesterol transport. Using a sensitive method to monitor lysosomal cholesterol efflux, we find that NPC1’s N-terminal domain need not release from the rest of the protein for efficient cholesterol export. Either introducing single disulfide bonds to constrain lumenal/extracellular domains or shortening a cytoplasmic loop abolishes transport activity by both NPC1 and NPC1L1. The widely prescribed cholesterol uptake inhibitor, Ezetimibe, blocks NPC1L1; we show that interface residues that lie at the interface between NPC1L1’s three extracellular domains comprise the drug’s binding site. These data support a model in which cholesterol passes through the cores of NPC1/NPC1L1 proteins; concerted movement of various domains is needed for transfer and Ezetimibe blocks transport by binding to multiple domains simultaneously.
HamHeat: A fast and simple package for calculating Hamming distance from multiple sequence data for heatmap visualization
Authors: Rakov Alexey V. , Schifferli Dieter M. , Liu Shu-Lin , Mastriani Emilio 
Published: March 2020

AbstractThe problem of fast calculation of Hamming distance inferred from many sequence datasets is still not a trivial task. Here, we present HamHeat, as a new software package to efficiently calculate Hamming distance for hundreds of aligned protein or DNA sequences of a large number of residues or nucleotides, respectively. HamHeat uses a unique algorithm with many advantages, including its ease of use and the execution of fast runs for large amounts of data. The package consists of three consecutive modules. In the first module, the software ranks the sequences from the most to the least frequent variant. The second module uses the most common variant as the reference sequence to calculate the Hamming distance of each additional sequence based on the number of residue or nucleotide changes. A final module formats all the results in a comprehensive table that displays the sequence ranks and Hamming distances.Availability and implementationHamHeat is based on Python 3 and AWK, runs on Linux system and is available under the MIT License at:https://github.com/alexeyrakov/HamHeat.Contactrakovalexey@gmail.com
Widespread coexistence of self-compatible and self-incompatible phenotypes in a diallelic self-incompatibility system inLigustrum vulgare(Oleaceae)
Authors: De Cauwer Isabelle , Vernet Philippe , Billiard Sylvain , Godé Cécile , Bourceaux Angélique , Ponitzki Chloé , Saumitou-Laprade Pierre 
Published: March 2020

AbstractThe breakdown of self-incompatibility (SI) in angiosperms is one of the most commonly observed evolutionary transitions. While multiple examples of SI breakdown have been documented in natural populations, there is strikingly little evidence of stable within-population polymorphism with both inbreeding (self-compatible) and outcrossing (self-incompatible) individuals. This absence of mating system polymorphism corroborates theoretical expectations that predict that in/outbreeding polymorphism is possible only under very restricted conditions. However, theory also predicts that a diallelic sporophytic SI system facilitates the maintenance of such polymorphism. We tested this prediction by studying the mating system ofLigustrum vulgareL., an entomophilous hermaphroditic species of the Oleaceae family. Using stigma tests with controlled pollination and paternity assignment of open-pollinated progenies, we confirmed the existence of two self-incompatibility groups in this species. We also demonstrated the existence of self-compatible individuals in different populations of Western Europe arising from a mutation affecting the expression of the pollen component of SI. We then estimated the selfing rate in a garden experiment. Our results finally show that the observed low frequency of self-compatible individuals in natural populations is compatible with theoretical predictions only if inbreeding depression is very high.
Ergothioneine, a metabolite of the gut bacteriumLactobacillus reuteri, protects against stress-induced sleep disturbances
Authors: Matsuda Yoshiki , Ozawa Nobuyuki , Shinozaki Takiko , Wakabayashi Ken-ichi , Suzuki Kosuke , Kawano Yusuke , Ohtsu Iwao , Tatebayashi Yoshitaka 
Published: March 2020

AbstractThe relationships between depression and gut microbiota, particularly those involving the immune system, have become a major focus of recent research. Here, we analyzed changes in gut microbiota and their sulfur metabolites in the feces of a depression rat model using the modified 14-day social defeat stress (SDS) paradigm. Our results showed that SDS increased fecalLactobacillus reuteriin correlation with ergothioneine levels at around day 11, which continued for at least one month following SDS administration. In vitro study further revealed thatL. reuteriis capable of producing ergothioneine. Although the known anti-inflammatory and anti-oxidative actions of ergothioneine suggested that the increased fecal ergothioneine levels may be related to intestinal anti-inflammatory defense mechanisms, no change was observed in the plasma ergothioneine levels during the same observation period, indicating that the defense mechanisms may not be sufficiently reflected in the body. As ergothioneine is a natural ingredient that is absorbed mainly from the upper gastrointestinal tract, we hypothesized that oral ergothioneine may exert antidepressant effects. As expected, oral administration of ergothioneine prior to and during the SDS paradigm had a preventative effect on SDS-induced depressive behaviors, such as social avoidance and depression-like sleep abnormalities, particularly those of rapid eye movement sleep. These findings indicate that ergothioneine, a metabolite ofL. reuteri, may be a common substance in the microbiota-gut-brain axis that prevents stress-induced sleep disturbances, especially those associated with depression.
Systematics of a radiation of Neotropical suboscines (Aves: Thamnophilidae:Epinecrophylla)
Authors: Johnson Oscar , Howard Jeffrey T. , Brumfield Robb T. 
Published: March 2020

AbstractThe stipple-throated antwrens of the genusEpinecrophylla(Aves: Thamnophilidae) are represented by eight species primarily found in the lowlands of the Amazon Basin and the Guiana Shield. The genus has a long and convoluted taxonomic history, with many attempts made to address the taxonomy and systematics of the group. Here we employ massively parallel sequencing of thousands of ultraconserved elements (UCEs) to provide both the most comprehensive subspecies-level phylogeny ofEpinecrophyllaantwrens and the first population-level genetic analyses for most species in the genus. Most of our analyses are robust to a diversity of phylogenetic and population genetic methods, but we show that even with thousands of loci we are unable to confidently place the western Amazonian taxonpyrrhonota. We uncovered phylogenetic relationships between taxa and patterns of population structure that are discordant with both morphology and current taxonomy. For example, we found deep genetic breaks between taxa in theornatagroup currently regarded as species, and in thehaematonotaandleucophthalmagroups we found paraphyly at the species and subspecies levels, respectively. Our population genetics analyses showed extensive admixture between some taxa despite their deep genetic divergence. We present a revised taxonomy for the group, discuss the biogeographic patterns that we uncover, and suggest areas for further study.
Tissue interactions govern pattern formation in the posterior lateral line of medaka
Authors: Seleit Ali , Gross Karen , Onistschenko Jasmin , Hoang Oi Pui , Theelke Jonas , Centanin Lázaro 
Published: March 2020

AbstractVertebrate organs are arranged in a stereotypic, species-specific position along the animal body plan. Substantial morphological variation exists between related species, especially so in the vastly diversified teleost clade. It is still unclear how tissues, organs and systems can accommodate such diverse scaffolds. Here, we use the sequential formation of neuromasts in the posterior lateral line (pLL) system of medaka fish to address tissue-interactions defining a pattern. We show that the pLL pattern is established independently of its neuronal wiring, and demonstrate that the neuromast precursors that constitute the pLL behave as autonomous units during pattern construction. We uncover the necessity of epithelial integrity for correct pLL patterning by disruptingkeratin 15(krt15) and creating epithelial lesions that lead to novel neuromast positioning. By usingkrt15/wtchimeras, we determined that the new pLL pattern depends exclusively on the mutant epithelium, which instructswtneuromast to locate ectopically. Inducing epithelial lesions by 2-photon laser ablation during pLL morphogenesis phenocopieskrt15genetic mutants and reveals that epithelial integrity defines the final position of the embryonic pLL neuromasts. Our results show that a fine-balance between primordium intrinsic properties and instructive interactions with the surrounding tissues is necessary to achieve proper organ morphogenesis and patterning. We speculate that this logic likely facilitates the accommodation of sensory modules to changing and diverse body plans.
Purine metabolism regulates DNA repair and therapy resistance in glioblastoma
Authors: Zhou Weihua , Yao Yangyang , Scott Andrew J. , Wilder-Romans Kari , Dresser Joseph J. , Werner Christian K. , Sun Hanshi , Pratt Drew , Sajjakulnukit Peter , Zhao Shuang G. , Davis Mary , Morgan Meredith A. , Rehemtualla Alnawaz , Nelson Barbara S. , Halbrook Christopher J. , Zhang Li , Gatto Francesco , Xiong Jianping , Castro Maria G. , Lowenstein Pedro , Chandrasekaran Sriram , Lawrence Theodore S. , Lyssiotis Costas A. , Wahl Daniel R. 
Published: March 2020

AbstractIntratumoral genomic heterogeneity in glioblastoma (GBM) is a barrier to overcoming therapy resistance, and new strategies that are effective independent of genotype are urgently needed. By correlating intracellular metabolite levels with radiation resistance across dozens of genomically-distinct models of GBM, we found that purine metabolites strongly correlated with radiation resistance. Inhibiting purine, but not pyrimidine, synthesis radiosensitized GBM cells and patient-derived neurospheres by impairing DNA repair in a nucleoside-dependent fashion. Likewise, administration of exogenous purine nucleosides protected sensitive GBM models from radiation by promoting DNA repair. Combining an FDA-approved inhibitor ofde novopurine synthesis with radiation arrested growth in GBM xenograft models and depleted intratumoral guanylates. High expression of the rate-limiting enzyme ofde novoGTP synthesis was associated with shorter survival in GBM patients. Together, these findings indicate that inhibitingde novopurine synthesis may be a promising strategy to overcome therapy resistance in this genomically heterogeneous disease.
North American Breeding Bird Survey status and trend estimates to inform a wide-range of conservation needs, using a flexible Bayesian hierarchical generalized additive model
Authors: Smith Adam C. , Edwards Brandon P.M. 
Published: March 2020

ABSTRACTThe status and trend estimates derived from the North American Breeding Bird Survey (BBS), are critical sources of information for bird conservation. However, the estimates are partly dependent on the statistical model used. Therefore, multiple models are useful because not all of the varied uses of these estimates (e.g. inferences about long-term change, annual fluctuations, population cycles, recovery of once declining populations) are supported equally well by a single statistical model. Here we describe Bayesian hierarchical generalized additive models (GAM) for the BBS, which share information on the pattern of population change across a species’ range. We demonstrate the models and their benefits using data a selection of species; and we run a full cross-validation of the GAMs against two other models to compare predictive fit. The GAMs have better predictive fit than the standard model for all species studied here, and comparable predictive fit to an alternative first difference model. In addition, one version of the GAM described here (GAMYE) estimates a population trajectory that can be decomposed into a smooth component and the annual fluctuations around that smooth. This decomposition allows trend estimates based only on the smooth component, which are more stable between years and are therefore particularly useful for trend-based status assessments, such as those by the IUCN. It also allows for the easy customization of the model to incorporate covariates that influence the smooth component separately from those that influence annual fluctuations (e.g., climate cycles vs annual precipitation). For these reasons and more, this GAMYE model is a particularly useful model for the BBS-based status and trend estimates.LAY SUMMARYThe status and trend estimates derived from the North American Breeding Bird Survey are critical sources of information for bird conservation, but they are partly dependent on the statistical model used.We describe a model to estimate population status and trends from the North American Breeding Bird Survey data, using a Bayesian hierarchical generalized additive mixed-model that allows for flexible population trajectories and shares information on population change across a species’ range.The model generates estimates that are broadly useful for a wide range of common conservation applications, such as IUCN status assessments based on trends or changes in the rates of decline for species of concern; and the estimates have better or similar predictive accuracy to other models., and
Homeostatic Plasticity Requires Remodeling of the Homer-Shank Interactome
Authors: Heavner Whitney E. , Speed Haley , Lautz Jonathan D. , Gniffke Edward P. , Immendorf Karen B. , Welsh John P. , Smith Stephen E.P. 
Published: March 2020

AbstractNeurons maintain constant levels of excitability using homeostatic scaling, which adjusts relative synaptic strength in response to large changes in overall activity. It is still unknown how homeostatic scaling affects network-level protein interactions in the synapse despite extensive reporting of individual scaling-associated transcriptomic and proteomic changes. Here, we assessed a glutamatergic synapse protein interaction network (PIN) composed of 380 binary interactions among 21 protein members to identify protein complexes altered by synaptic scaling in vitro and in vivo. In cultured cortical neurons, we observed widespread bidirectional PIN alterations during up- and downscaling that reflected rapid glutamate receptor shuttling via synaptic scaffold remodeling. Sensory deprivation of the barrel cortex caused a PIN response that reflected changes in mGluR tone and NMDAR-dependent metaplasticity, consistent with emerging models of homeostatic plasticity in the barrel cortex that restore excitatory/inhibitory balance. Mice lackingHomer1orShank3Bdid not undergo normal PIN rearrangements, suggesting that these Autism Spectrum Disorder (ASD)-linked proteins serve as structural hubs for synaptic homeostasis. Our approach demonstrates how changes in the protein content of synapses during homeostatic plasticity translate into functional PIN alterations that mediate changes in neuron excitability.