bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amifostine Prophylaxis in Irradiated Breast Reconstruction
Authors: Luby Alexandra O. , Subramanian Chitra , Buchman Lauren K. , Lynn Jeremy V. , Urlaub Kevin M. , Nelson Noah S. , Donneys Alexis , Cohen Mark S. , Buchman Steven R. 
Published: December 2019

Background
Indications for adjuvant radiation therapy (XRT) in breast cancer have expanded. Although highly effective, XRT damages surrounding tissues and vasculature, often resulting in delayed or compromised breast reconstruction. Thus, effective yet safe methods of radiation injury prophylaxis would be desirable. Amifostine is a Food and Drug Administration–approved radioprotectant; however, concerns about its potential to also protect cancer remain. The purpose of this study was to evaluate the oncologic safety of amifostine (AMF) in vitro and determine its effect on human breast cancer cells in the setting of XRT.

Methods
One ER+/PR+/Her2− (MCF-7) and two ER−/PR−Her2− (MDA-MB-231, MDA-MB-468) breast cancer cell lines were investigated. Female fibroblasts were used as controls. Cells were treated with WR-1065, the active metabolite of AMF, 20 minutes before 0Gy, 10Gy, or 20Gy XRT. Live and dead cells were quantified; percent cell death was calculated.

Results
WR-1065 treatment significantly preserved viability and reduced healthy female fibroblasts death after XRT compared with untreated controls. All three breast cancer cells lines exhibited radiosensitivity with substantial cell death. Cancer cells retained their radiosensitivity despite WR-1065 pretreatment, achieving the same degree of cell death as untreated controls.

Conclusions
This study demonstrated the proficiency of AMF to selectively protect healthy cells from XRT while breast cancer cells remained radiosensitive. These results support the oncologic safety of AMF in breast cancer in vitro. Further investigation is now warranted in vivo to ascertain the translational potential of using AMF as a radioprotectant to improve breast reconstruction after radiation treatment.
Oblique Plane Cutting of Cone Beam Computed Tomography Analysis on the Safe Zone for Micro-Implants of Maxillary Molar Region
Authors: Wang Chao , Wang Guobao , Xin Ce , You Qingling , Wu Jun 
Published: December 2019

Objective:To explore the safe zone for micro-implants of the maxillary molar region by oblique plane cutting mode of cone beam computed tomography (CBCT).Methods:Thirty-nine patients with orthodontic alignment were enrolled with CBCT. In this study, the areas between the maxillary second premolar and the first molar were analyzed by the image reconstruction with CS 3D Imaging Software. The alveolar ridge bone width and the minimum interradicular space were measured at the height of 8, 10, and 12 mm from archwire under the 2 cutting modes of the oblique plane and coronal plane, respectively. The statistical analysis was performed.Results:The bone widths of alveolar ridge between the maxillary second premolar and the first molar were statistically significant under the 2 cutting modes of the oblique plane and coronal plane. The bone width was gradually decreased to the cranial side with the fixed measurement point and the interradicular space was gradually increased. The differences were statistically significant.Conclusion:The oblique plane cutting of CBCT is more representative of the alveolar bone than the coronal plane. There is sufficient safe zone between the maxillary second premolar and the first molar for most patients to implant the micro-implants. However, the individual differences present large and CBCT needs to be taken before the implantation.
Long-term Survival of 10,116 Korean Live Liver Donors
Authors: Hong Suk Kyun , Choe Sunho , Yi Nam-Joon , Shin Aesun , Choe Eun Kyung , Yoon Kyung Chul , Lee Kwang-Woong , Suh Kyung-Suk 
Published: December 2019

Objective:
To evaluate the long-term mortality of Korean live liver donors using data from a national donor registry by comparing it with the mortality of the general population.

Summary of Background Data:
Although live liver donors generally have a healthy status, their long-term mortality has not been properly addressed in a large donor registry.

Methods:
Data of 10,116 live liver donors were drawn from a mandated national registry of Korean live liver donors between 2000 and 2015. Matched controls were selected from the Korean National Health Insurance System-National Sample Cohort (NHIS-NSC). Median (range) follow-up of liver donors was 5.7 (0–15.9) years. Donors were 1:3 individually matched to controls by sex and 5-year age group; potential controls were from the whole NHIS-NSC (Control 1) or from NHIS-NSC after excluding people with contraindications to be organ donors (Control 2) (donor, n = 7538; Control 1, n = 28,248; Control 2, n = 28,248).

Results:
Fifty-three deaths occurred after donation. Ten-year cumulative mortality of live liver donors was 0.9%. The most common cause of death was suicide (n = 19) followed by cancer (n = 9) and traffic accident (n = 7). In the matched control analysis, overall risk of death was significantly lower in donors than in Control 1 (P < 0.001), but higher than in Control 2 (P < 0.001).

Conclusions:
Liver donors have increased long-term mortality risk compared to similar healthy controls without contraindications to be organ donors. Therefore, long-term follow-up, including psychosocial support, is needed for live liver donors.
Idiopathic Intracranial Hypertension and Anemia: A Matched Case–Control Study
Authors: Lin Weijie Violet , Berry Shauna , Nakawah Mohammad Obadah , Sadaka Ama , Lee Andrew G. 
Published: December 2019

Background:
An association between idiopathic intracranial hypertension (IIH) and anemia has been speculated from previous case reports and case series. Retrospective studies to date have not used matched case controls to compare standardized complete blood count (CBC) values for the presence of anemia.

Methods:
At our tertiary care facility, 50 patients with IIH were matched with 50 case–control patients to compare CBC values from laboratory affiliates with standardized ranges.

Results:
No significant difference was found for any CBC parameters for IIH vs control patients. For female IIH and control patients as well as male IIH patients, values for red blood cell count, hemoglobin (HGB), and hematocrit (HCT) tended to trend on the lower end of “normal” range, whereas this was not seen in male control patients.

Conclusions:
In this retrospective, matched case–control study, no significant association was found between IIH and anemia when comparing standardized CBC values. In accordance with previous studies, the prevalence of anemia may be relatively higher in the IIH population due to a prominent demographic overlap of females of child-bearing age.
Linguistic generalization and compositionality in modern artificial neural networks
Authors: Baroni Marco 
Published: December 2019

In the last decade, deep artificial neural networks have achieved astounding performance in many natural language-processing tasks. Given the high productivity of language, these models must possess effective generalization abilities. It is widely assumed that humans handle linguistic productivity by means of algebraic compositional rules: are deep networks similarly compositional? After reviewing the main innovations characterizing current deep language-processing networks, I discuss a set of studies suggesting that deep networks are capable of subtle grammar-dependent generalizations, but also that they do not rely on systematic compositional rules. I argue that the intriguing behaviour of these devices (still awaiting a full understanding) should be of interest to linguists and cognitive scientists, as it offers a new perspective on possible computational strategies to deal with linguistic productivity beyond rule-based compositionality, and it might lead to new insights into the less systematic generalization patterns that also appear in natural language.This article is part of the theme issue ‘Towards mechanistic models of meaning composition’.
How the brain composes morphemes into meaning
Authors: Gwilliams Laura 
Published: December 2019

Morphemes (e.g. [tune], [-ful], [-ly]) are the basic blocks with which complex meaning is built. Here, I explore the critical role that morpho-syntactic rules play in forming the meaning of morphologically complex words, from two primary standpoints: (i) how semantically rich stem morphemes (e.g. explode, bake, post) combine with syntactic operators (e.g. -ion, -er, -age) to output a semantically predictable result; (ii) how this process can be understood in terms of mathematical operations, easily allowing the brain to generate representations of novel morphemes and comprehend novel words. With these ideas in mind, I offer a model of morphological processing that incorporates semantic and morpho-syntactic operations in service to meaning composition, and discuss how such a model could be implemented in the human brain.This article is part of the theme issue ‘Towards mechanistic models of meaning composition’.
No consistent evidence for microbiota in murine placental and fetal tissues
Authors: Theis Kevin R. , Romero Roberto , Greenberg Jonathan M. , Winters Andrew D. , Garcia-Flores Valeria , Motomura Kenichiro , Ahmad Madison M. , Galaz Jose , Arenas-Hernandez Marcia , Gomez-Lopez Nardhy 
Published: December 2019

ABSTRACTThe existence of a placental microbiota andin uterocolonization of the fetus has been the subject of recent debate. The objective of this study was to determine whether the placental and fetal tissues of mice harbor bacterial communities. Bacterial profiles of the placenta and fetal brain, lung, liver, and intestine were characterized through culture, qPCR, and 16S rRNA gene sequencing. These profiles were compared to those of the maternal mouth, lung, liver, uterus, cervix, vagina, and intestine, as well as to background technical controls. Positive bacterial cultures from placental and fetal tissues were rare; of the 165 total bacterial cultures of placental tissues from the 11 mice included in this study, only nine yielded at least a single colony, and five of those nine positive cultures came from a single mouse. Cultures of fetal intestinal tissues yielded just a single bacterial isolate:Staphylococcus hominis, a common skin bacterium. Bacterial loads of placental and fetal brain, lung, liver, and intestinal tissues were not higher than those of DNA contamination controls and did not yield substantive 16S rRNA gene sequencing libraries. From all placental or fetal tissues (N = 49), there was only a single bacterial isolate that came from a fetal brain sample having a bacterial load higher than that of contamination controls and that was identified in sequence-based surveys of at least one of its corresponding maternal samples. Therefore, using multiple modes of microbiologic inquiry, there was not consistent evidence of bacterial communities in the placental and fetal tissues of mice.IMPORTANCEThe prevailing paradigm in obstetrics has been the sterile womb hypothesis, which posits that fetuses are first colonized by microorganisms during the delivery process. However, some are now suggesting that fetuses are consistently colonized by microorganismsin uteroby microbial communities that inhabit the placenta and intra-amniotic environment. Given the established causal role of microbial invasion of the amniotic cavity (i.e. intra-amniotic infection) in pregnancy complications, especially preterm birth, if thein uterocolonization hypothesis were true, there are several aspects of current understanding that will need to be reconsidered including the magnitude of intra-amniotic microbial load required to cause disease and their potential influence on the ontogeny of the immune system. However, acceptance of thein uterocolonization hypothesis is premature. Herein, we do not find consistent evidence for placental and fetal microbiota in mice using culture, qPCR, and DNA sequencing.
The proteomic inventory reveals the chloroplast ribosome as nexus within a diverse protein network
Authors: Westrich Lisa Désirée , Gotsmann Vincent Leon , Herkt Claudia , Ries Fabian , Kazek Tanja , Trösch Raphael , Ramundo Silvia , Nickelsen Jörg , Armbruster Laura , Wirtz Markus , Storchová Zuzana , Raeschle Markus , Willmund Felix 
Published: December 2019

ABSTRACTChloroplast gene expression is tightly regulated and majorly controlled on the level of protein synthesis. Fine-tuning of translation is vital for plant development, acclimation to environmental challenges and for the assembly of major protein complexes such as the photosynthesis machinery. However, many regulatory mediators and the interaction network of chloroplast ribosomes are not known to date. We report here on a deep proteomic analysis of the plastidic ribosome interaction network inChlamydomonas reinhardtiicells. Affinity-purification of ribosomes was achieved via endogenous affinity tagging of the chloroplast-encoded protein Rpl5, yielding a specific enrichment of >650 chloroplast-localized proteins. The ribosome interaction network was validated for several proteins and provides a new source of mainly conserved factors directly linking translation with central processes such as protein folding, photosystem biogenesis, redox control, RNA maturation, energy and metabolite homeostasis. Our approach provided the first evidence for the existence of a plastidic co-translational acting N-acetyltransferase (cpNAT1). Expression of tagged cpNAT1 confirmed its ribosome-association, and we demonstrated the ability of cpNAT1 to acetylate substrate proteins at their N-terminus. Our dataset establishes that the chloroplast protein synthesis machinery acts as nexus in a highly choreographed, spatially interconnected protein network and underscores its wide-ranging regulatory potential during gene expression.ONE-SENTENCE SUMMARYAffinity purification ofChlamydomonas reinhardtiichloroplast ribosomes and subsequent proteomic analysis revealed a broad spectrum of interactors ranging from global translation control to specific pathways.
Background selection does not mimic the patterns of genetic diversity produced by selective sweeps
Authors: Schrider Daniel R. 
Published: December 2019

1AbstractIt is increasingly evident that natural selection plays a prominent role in shaping patterns of diversity across the genome. The most commonly studied modes of natural selection are positive selection and negative selection, which refer to directional selection for and against derived mutations, respectively. Positive selection can result in hitchhiking events, in which a beneficial allele rapidly replaces all others in the population, creating a valley of diversity around the selected site along with characteristic skews in allele frequencies and linkage disequilibrium (LD) among linked neutral polymorphisms. Similarly, negative selection reduces variation not only at selected sites but also at linked sites—a phenomenon called background selection (BGS). Thus, discriminating between these two forces may be difficult, and one might expect efforts to detect hitchhiking to produce an excess of false positives in regions affected by BGS. Here, we examine the similarity between BGS and hitchhiking models via simulation. First, we show that BGS may somewhat resemble hitchhiking in simplistic scenarios in which a region constrained by negative selection is flanked by large stretches of unconstrained sites, echoing previous results. However, this scenario does not mirror the actual spatial arrangement of selected sites across the genome. By performing forward simulations under more realistic scenarios of BGS, modeling the locations of protein-coding and conserved noncoding DNA in real genomes, we show that the spatial patterns of variation produced by BGS rarely mimic those of hitchhiking events. Indeed, BGS is not substantially more likely than neutrality to produce false signatures of hitchhiking. This holds for simulations modeled after both humans andDrosophila, and for several different demographic histories. These results demonstrate that appropriately designed scans for hitchhiking need not consider background selection’s impact on false positive rates. However, we do find evidence that BGS increases the false negative rate for hitchhiking—an observation that demands further investigation.
Non-shared dispersal networks with heterogeneity promote species coexistence in hierarchical competitive communities
Authors: Zhang Helin , Liao Jinbao 
Published: December 2019

AbstractThe competition-colonization trade-off has been a classic paradigm to understand the maintenance of biodiversity in natural ecosystems. However, species-specific dispersal heterogeneities are not well integrated into our general understanding of how spatial coexistence emerges between competitors. Combining both network and metapopulation approaches, we construct a spatially explicit, patch-occupancy dynamic model for communities with hierarchically preemptive competition, to explore species coexistence in shared vs. non-shared dispersal networks with contrasting heterogeneities (including regular, random, exponential and scale-free networks). Our model shows that species with the same demography (i.e. identical colonization and extinction rates) cannot coexist stably in shared networks (i.e. the same dispersal pathways), regardless of dispersal heterogeneity. In contrast, increasing dispersal heterogeneity (even at very low levels of heterogeneity) in non-shared networks can greatly promote spatial coexistence, owing to the segregation-aggregation mechanism by which each species is restricted to self-organized clusters with a core of the most connected patches. However, these competitive patterns are largely mediated by species life-history attributes, for example, a unimodal biodiversity response to an increase of species dispersal rate emerges in non-shared heterogeneous networks, with species richness peaking at intermediate dispersal levels. Interestingly, increasing network size can foster species coexistence, leading to a monotonic increase in species-area curves. This strongly suggests that, unexpectedly, many more species can co-occur than the number of limiting resources. Overall, this modelling study, filling the gap between network structure and spatial competition, provides new insights into the coexistence mechanisms of spatial heterogeneity.
Spergulin-A strives intra-macrophage leishmanicidal activity by regulating the host P2X7R-P38MAPK axis
Authors: Mukherjee Niladri , Banerjee Saswati , Amin Sk. Abdul , Jha Tarun , Datta Sriparna , Saha Krishna Das 
Published: December 2019

ABSTRACTCurrent drugs are inadequate for the treatment of visceral leishmaniasis an immunosuppressive ailment caused byLeishmania donovani. Regrettably, there is no plant-origin antileishmanial drug present. P2X7R is constitutively present on macrophage surfaces and can be a putative therapeutic target in intra-macrophage pathogens with function attributes towards inflammation, host cell apoptosis, altered redox, and phagolysosomal maturation by activating p38MAPK. Here we demonstrated that the initial interaction of Spergulin-A (SpA), a triterpenoid saponin with RAW 264.7 macrophages was mediated through P2X7R involving the signaling cascade intermediates Ca++, P38MAPK, and NF-κβ. P38MAPK involvement is shown to have specific and firm importance in leishmanial killing with increased NF-κBp65. Phago-lysosomal maturation by Sp A also campaigns for another contribution of P2X7R.In vivoevaluation of the anti-leishmanial activity of Sp A was monitored through expression analyses of P2X7R, P38MAPK, and NF-κβ in murine spleen and bone-marrow macrophages and advocated Sp A of being a natural compound of leishmanicidal functions which acted through the P2X7R-P38MAPK axis.SIGNIFICANCE OR IMPORTANCEPreciously, this manuscript demonstrated previously unreported initial interaction of Spergulin-A, a triterpenoid saponin isolated fromGlinus oppositifoliuswith macrophages through P2X7R involving the signaling cascade intermediates Ca++, P38MAPK, and NF-κβ. Signaling interaction is shown to have specific importance in the leishmanial killing. Phago-lysosomal maturation also campaigns for another contribution of P2X7R.In vivoevaluation was monitored through P2X7R, P38MAPK, and NF-κβ in murine spleen and bone-marrow macrophages and advocated Sp A of being a natural compound of leishmanicidal functions which acted through the P2X7R-P38MAPKaxis. The result supports that Spergulin-A can provide new lead molecules for the development of alternative drugs against VL. We feel very strongly that this work can be very interesting as it describes a detailed evaluation of leishmanicidal effect by Sp A and thus has every potential to attract a lot of workers especially in the fields of pharmacology, drug development, immunology, as well as parasitology.
Nilotinib activates endothelial TLR4 to exacerbate atherosclerosis
Authors: Qu Dan , Huo Mingyu , Wang Li , Lau Chi-Wai , Tian Xiao Yu , Huang Yu 
Published: December 2019

AbstractThe use of nilotinib (Tasigna®), a second-generation tyrosine kinase inhibitor for treating chronic myeloid leukemia, increases risks for atherosclerosis. Here, we demonstrate that in endothelial cells, nilotinib activated TLR4, triggerd expression of inflammatory molecules, and increased monocyte attachment, which were all inhibited by knockdown of TLR4 or TLR4 inhibitor, CLI-095. Orally administered nilotinib profoundly accelerated atherosclerotic lesion formation in ApoE−/−mice, while co-administration of CLI-095 effectively reduced lesion areas. Our findings reveal TLR4 activation as an underlying mechanism of the pro-atherosclerotic effect of nilotinib and suggest TLR4 inhibition as an effective therapeutic approach to address vascular safety issue of nilotinib.
OLGenie: Estimating Natural Selection to Predict Functional Overlapping Genes
Authors: Nelson Chase W. , Ardern Zachary , Wei Xinzhu 
Published: December 2019

AbstractPurifying (negative) natural selection is a hallmark of functional biological sequences, and can be detected in protein-coding genes using the ratio of nonsynonymous to synonymous substitutions per site (dN/dS). However, when two genes overlap the same nucleotide sites in different frames, synonymous changes in one gene may be nonsynonymous in the other, perturbingdN/dS. Thus, scalable methods are needed to estimate functional constraint specifically for overlapping genes (OLGs). We propose OLGenie, which implements a modification of the Wei-Zhang method. Assessment with simulations and controls from viral genomes (58 OLGs and 176 non-OLGs) demonstrates low false positive rates and good discriminatory ability in differentiating true OLGs from non-OLGs. We also apply OLGenie to the unresolved case of HIV-1’s putativeantisense proteingene, showing significant purifying selection. OLGenie can be used to study known OLGs and to predict new OLGs in genome annotation. Software and example data are freely available athttps://github.com/chasewnelson/OLGenie.