bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Repeated Sterilization by Different Methods on Strength of Carbon Fiber Rods Used in External Fixator Systems
Authors: Unal Omer Kays , Poyanli Oguz Sukru , Sur Unal Ulku , Mutlu Hasan Huseyin , Ozkut Afsar Timucin , Esenkaya Irfan 
Published: May 2018

Objectives:
We aimed to study the effects of repeated sterilization, using different methods, on the carbon fiber rods of external fixator systems.

Methods:
We used a randomized set of 44 unused, unsterilized, and identical carbon fiber rods (11 × 200 mm), randomly assigned to 2 groups: unsterilized (4 rods) and sterilized (40 rods). The sterilized rods were divided into 2 groups, those sterilized in an autoclave and those sterilized using hydrogen peroxide. These were further divided into 5 subgroups based on the number of sterilization repetition to which the fibers were subjected (25, 50, 75, 100, and 200). A bending test was conducted to measure the maximum bending force, maximum deflection, flexural strength, maximum bending moment and bending rigidity. We also measured the surface roughness of the rods.

Results:
An increase in the number of sterilization repetition led to a decrease in maximum bending force, maximum bending moment, flexural strength, and bending rigidity, but increased maximum deflection and surface roughness (P < 0.01). The effect of the number of sterilization repetition was more prominent in the hydrogen peroxide group.

Conclusions:
This study revealed that the sterilization method and number of sterilization repetition influence the strength of the carbon fiber rods. Increasing the number of sterilization repetition degrades the strength and roughness of the rods.
Poly(ADP-ribose) polymerase 1 Searches DNA via a ‘Monkey Bar’ Mechanism
Authors: Rudolph Johannes , Mahadevan Jyothi , Dyer Pam , Luger KarolinKarolin 
Published: May 2018

AbstractPoly(ADP-ribose) polymerase 1 (PARP1) is both a first responder to DNA damage and a chromatin architectural protein. How PARP1 rapidly finds DNA damage sites in the context of a nucleus filled with undamaged DNA, to which it also binds, is an unresolved question. Here we show that PARP1 association with DNA is diffusion-limited, and release of PARP1 from DNA is promoted by binding of an additional DNA molecule that facilitates a “monkey bar” mechanism, also known as intersegment transfer. The WGR-domain of PARP1 is essential to this mechanism, and a point mutation (W589A) recapitulates the altered kinetics of the domain deletion. Demonstrating the physiological importance of the monkey bar mechanism for PARP1 function, the W589A mutant accumulates at sites of DNA damage more slowly following laser micro-irradiation than wild-type PARP1. Clinically relevant inhibitors of PARP1 did not alter the rate or mechanism of the release of PARP1 from DNA.
The Roles of Neighborhood Composition and Autism Prevalence on Vaccination Exemption Pockets: A Population-wide Study
Authors: Gromis Ashley , Liu Kayuet 
Published: May 2018

AbstractThe number of children entering schools without mandated vaccinations has increased in high-income countries due to the rise of nonmedical exemptions from school vaccination requirements. Herd immunity is threatened when unvaccinated children are concentrated in spatial pockets. It is often assumed that these exemption clusters are merely the result of population composition. On the other hand, despite the role of vaccine-autism controversy to the current wave of anti-vaccine movement, we do not know if exemption clusters are associated with local autism rates. Our spatial analysis of California shows that while racial/ethnic composition is associated with the locations of large exemption pockets, other sociodemographic factors and access to health care resources have limited geographical span. We decouple the race/ethnicity effect from that of unobserved socioeconomic status by examining families in poverty. Using unique address-level data on the locations of the majority of children with an autism diagnosis, we show that the prevalence of autism is not associated with the locations of large pockets of vaccination exemptions. In addition, we find charter schools in most exemption clusters; potential spillovers from charter schools to neighboring public schools are evaluated. Exemption pockets are not merely the result of population composition and community-level interventions are needed to maintain herd immunity.HighlightsAutism prevalence rates are not associated with the locations of large exemption pockets.The average exemption rate in charter schools (7.5%) was higher than private schools.Proportion non-Hispanic white has the strongest association with large exemption clusters.Population composition cannot fully explain the exemption clusters.
Interpreting HIV Diagnostic Histories into Infection Time Estimates: Analytical Framework and Online Tool
Authors: Grebe Eduard , Facente Shelley N. , Bingham Jeremy , Pilcher Christopher D. , Powrie Andrew , Gerber Jarryd , Priede Gareth , Chibawara Trust , Busch Michael P. , Murphy Gary , Kassanjee Reshma , Welte Alex ,   on behalf of the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA)
Published: May 2018

AbstractBackgroundIt is frequently of epidemiological and/or clinical interest to estimate the date of HIV infection or time-since-infection of individuals. Yet, for over 15 years, the only widely-referenced infection dating algorithm that utilises diagnostic testing data to estimate time-since-infection has been the ‘Fiebig staging’ system. This defines a number of stages of early HIV infection through various standard combinations of contemporaneous discordant diagnostic results, using tests of different sensitivity.ObjectiveTo develop a new, more nuanced infection dating algorithm, we generalised the Fiebig approach to accommodate positive and negative diagnostic results generated on the sameordifferent dates, and arbitrary current or future tests – as long as the test sensitivity is known. For this purpose, test sensitivity is conceptualised as the probability that a specimen will produce a positive result, expressed as a function of time since infection. This can be summarised as a median ‘diagnostic delay’ parameter, together with a measure of inter-subject variability.MethodsThe present work outlines the analytical framework for infection date estimation using subject-level diagnostic testing histories, and data on test sensitivity. We introduce a publicly-available online HIV infection dating tool that implements this estimation method, bringing together 1) curatorship of HIV test performance data, and 2) infection date estimation functionality, to calculate plausible intervals within which infection likely became detectable for each individual. The midpoints of these intervals are interpreted as infection time ‘point estimates’ and referred to as Estimated Dates of Detectable Infection (EDDIs).ResultsIn many settings, including most research studies, detailed diagnostic testing data are routinely recorded, and can provide reasonably precise estimates of the timing of HIV infection. We present a simple logic to the interpretation of ‘diagnostic testing histories’ into ‘infection time estimates’, either as a point estimate (EDDI) or an interval (earliest plausible to latest plausible dates of detectable infection), along with a publicly-accessible online tool that supports wide application of this logic.ConclusionsThis tool, available athttps://tools.incidence-estimation.org/idt/, is readily updatable as test technology evolves, given the simple architecture of the system and its nature as an open source project.
Fyn is Involved in Erythropoietin Signaling Pathway and Interfaces Oxidation to Regulate Erythropoiesis
Authors: Beneduce E , Matte A , De Falco L , Mbiandjeu TSC , Chiabrando D , Tolosano E , Federti E , Petrillo S , Mohandas N , Siciliano A , Babu AW , Menon V , Ghaffari S , Iolascon A , De Franceschi L 
Published: May 2018

ABSTRACTErythropoiesis is a complex multistep process responsible of the production of circulating mature erythrocytes and involved the production of reactive oxygen species (ROS) during erythroid differentiation. Here, we document that Fyn, a Src-family-kinase, participates in erythropoietin (EPO) signaling pathway, by the reducing extent of Tyr-phosphorylation of EPO-R and by decreasing STAT5 activity. The importance of Fyn in EPO cascade is also supported by the increased sensitivity of Fyn−/−mice to stress erythropoiesis. Fyn−/−mouse erythroblasts adapt to the induced stress by the activation of the redox-related-transcription-factor Nrf2. However, the absence of the Nrf2 physiologic repressor Fyn resulted in the persistent activation of Nrf2 and accumulation of non-functional proteins. This is paralleled by ROS induced over-activation of Jak2-Akt-mTOR pathway and repression of autophagy and perturbation of lysosomal-clearance during Fyn−/−reticulocyte maturation. Treatment with Rapamycin, a mTOR inhibitor and autophagy activator, ameliorates Fyn−/−mouse baseline erythropoiesis and restored the erythropoietic response to phenylhydrazine. Taken together these findings have enabled to identify the novel multimodal action of Fyn in the developmental program of erythropoiesis.
Sex-specific impact of patterns of imageable tumor growth on survival of primary glioblastoma patients
Authors: Whitmire Paula , Rickertsen Cassandra R. , Hawkins-Daarud Andrea , Carrasco Eduardo , Lorence Julia , De Leon Gustavo , Curtin Lee , Bayless Spencer , Clark-Swanson Kamala , Peeri Noah C. , Corpuz Christina , Lewis-de los Angeles Christine Paula , Bendok Bernard R. , Gonzalez-Cuyar Luis , Vora Sujay , Mrugala Maciej , Hu Leland S. , Wang Lei , Porter Alyx , Kumthekar Priya , Johnston Sandra K. , Egan Kathleen M. , Gatenby Robert , Canoll Peter , Rubin Joshua B. , Swanson Kristin R. 
Published: May 2018

BackgroundSex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences.MethodsCombining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients. Pretreatment MR images of 494 glioblastoma patients (299 males and 195 females) were segmented to quantify tumor volumes. Cox proportional hazard (CPH) models and Student’s t-tests were used to assess which variables were associated with survival outcomes.ResultsAmong males, tumor (T1Gd) radius was a predictor of overall survival (HR=1.027, p=0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR=1.011, p<0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p=0.010 t-test), but tumor size was not correlated with female overall survival (p=0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p=0.004, F p=0.001, t-test). Additionally, extent of resection, tumor laterality, and IDH1 mutation status were also found to have sex-specific effects on overall survival.ConclusionDespite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes, which emphasizes the importance of considering sex as a biological factor when determining patient prognosis and treatment approach.
Psychophysical Scaling Reveals a Unified Theory of Visual Memory Strength
Authors: Schurgin Mark W. , Wixted John T. , Brady Timothy F. 
Published: May 2018

AbstractAlmost all models of visual memory implicitly assume that errors in mnemonic representations are linearly related to distance in stimulus space. Here, we show that neither memory nor perception are appropriately scaled in stimulus space; instead, they are based on a transformed similarity representation that is non-linearly related to stimulus space. This result calls into question a foundational assumption of extant models of visual working memory. Once psychophysical similarity is taken into account, aspects of memory that have been thought to demonstrate a fixed working memory capacity of ~3-4 items and to require fundamentally different representations -- across different stimuli, tasks, and types of memory -- can be parsimoniously explained with a unitary signal detection framework. These results have significant implications for the study of visual memory and lead to a substantial reinterpretation of the relationship between perception, working memory and long-term memory.
Replication stress induced by CCNE1 overexpression creates a dependency on XRCC2 at the replication fork
Authors: Doberstein Kai , Karst Alison , Kroeger Paul T , Drapkin Ronny 
Published: May 2018

SummaryAcross multiple cancer types, genome instability has been linked to aberrant over-expression ofCCNE1due to premature cell cycle entry and replication stress. Using a gain-of-function screen, we found thatXRCC2cooperates withCCNE1in the neoplastic transformation ofTP53mutant cells. A pan-cancer analysis of TCGA data revealed a striking correlation betweenCCNE1andXRCC2expression and knockdown of XRCC2 in Cyclin E1 overexpressing cell lines is synthetic lethal. Immunopurification of XRCC2 showed that it interacts with the Minichromosome Maintenance Complex Component 7 (MCM7) protein. This interaction appears to be critical for protecting replication forks as knockdown of XRCC2 leads to a strong increase in MCM7 ubiquitination with concomitant decrease in MCM7 protein levels, and reduced replication fork speed. Importantly, Overexpression of MCM7 rescues the effect of XRCC2 knockdown. Our data describe a new dependency of Cyclin E1 overexpressing tumors on factors that stabilize the replication fork.
Evaluation of the antimicrobial activity and cytotoxicity of different components of natural origin present in essential oils
Authors: García-Salinas Sara , Elizondo Hellen , Arruebo Manuel , Mendoza Gracia , Irusta Silvia 
Published: May 2018

AbstractThe antimicrobial action of different components present in essential oils including carvacrol, cinnamaldehyde, thymol, squalene, rosmarinic acid, tyrosol, eugenol and β-Caryophyllene against Gram-positive and Gram-negative bacteria is here reported. Planktonic bacteria as well as a model of biofilm forming bacteria were challenged against those components being carvacrol, cinnamaldehyde and thymol the components with the highest antimicrobial action in both different settings. The potential synergy of some of those components against pathogenic bacteria was also analyzed. The antimicrobial mechanism of the different components was analyzed by means of flow cytometry and by electronic and confocal microscopy. Finally, subcytotoxic doses against mammalian cell lines are here reported to highlight the reduced cytotoxicity of those components against eukaryotic cells. Carvacrol, cinnamaldehyde and thymol showed the highest antimicrobial action of all the natural origin compounds tested and lower cytotoxicity against eukaryotic cells than conventional antiseptics such as chlorhexidine. The high inhibition in biofilm forming activity of those components highlight also their demonstrate benefits in reducing pathogenic microorganisms.ImportanceThe use and misuse of antibiotics has led to the emergence of antibiotic resistance to human and animal pathogens. Compounds from natural sources such as animals, plants, and microorganisms have been proposed as renewed potential antimicrobial alternatives. The comparative antimicrobial action of different components commonly present in essential oils including carvacrol, cinnamaldehyde, thymol, squalene, rosmarinic acid, tyrosol, eugenol and β-Caryophyllene against S. aureus and E. coli is here reported. Carvacrol, cinnamaldehyde and thymol are the components with the highest antimicrobial action. Bacteria membrane disruption represents the bactericidal mechanism attributable to these compounds. In addition, the presence of carvacrol, cinnamaldehyde and thymol hinders S. aureus biofilm formation and partially eliminates preformed biofilms. Those components are less toxic to human cells than chlorhexidine.
Phosphorylation of HspB1 regulates its mechanosensitive molecular chaperone interaction with native filamin C
Authors: Collier Miranda P. , Alderson T. Reid , de Villiers Carin P. , Nicholls Daisy , Gastall Heidi Y. , Allison Timothy M. , Degiacomi Matteo T. , Fuerst Dieter O. , van de Ven Peter F.M. , Djinovic-Carugo Kristina , Baldwin Andrew J. , Watkins Hugh , Gehmlich Katja , Benesch Justin L.P. 
Published: May 2018

AbstractSmall heat-shock proteins (sHsps; HspBs) are molecular chaperones involved in the cellular stress response and a range of basal functions. Despite a multitude of targets, sHsp interactions are not well understood due their heterogeneous structures and weak binding affinities. The most widely expressed human sHsp, HspB1, is prevalent in striated muscle, where the actin cross-linker filamin C (FLNC, γ-filamin, ABP-L) is a putative binding partner. Musculoskeletal HspB1 is phosphorylated in response to a variety of cues, including mechanical stress, which promotes oligomer disassembly and association with myoarchitectural elements. Here, we report the up-regulation and interaction of both proteins in the hearts of a mouse model of heart failure, with HspB1 being phosphorylated and FLNC increasingly associated with the sarcomeric Z-disc. We used a combination of structural approaches to reveal that phosphorylation of HspB1 results in increased availability of the residues surrounding the phosphosite, facilitating their interaction with folded FLNC domains equivalent to a force-sensing region in the paralog filamin A. By employing native mass spectrometry, we show that domains 18 to 21 of FLNC are extensible under conditions mimicking force, with phosphorylated HspB1 stabilising an intermediate from further unfolding. These findings report on conformations accessible during the cycles of mechanical extension central to filamin function, and are consistent with an interaction between the chaperone and a native target that is strengthened upon the application of force. This may represent a new mode of molecular chaperone activity, allowing HspB1 to protect FLNC from over-extension during mechanical stress.
The spatial correspondence and genetic influence of inter-hemispheric connectivity with white matter microstructure
Authors: Mollink Jeroen , Smith Stephen M. , Elliott Lloyd T. , Kleinnijenhuis Michiel , Hiemstra Marlies , Alfaro-Almagro Fidel , Marchini Jonathan , van Cappellen van Walsum Anne-Marie , Jbabdi Saad , Miller Karla L. 
Published: May 2018

AbstractMicroscopic features (i.e., microstructure) of axons affect neural circuit activity through characteristics such as conduction speed. Deeper understanding of structure-function relationships and translating this into human neuroscience has been limited by the paucity of studies relating axonal microstructure in white matter pathways to functional connectivity (synchrony) between macroscopic brain regions. Using magnetic resonance imaging data in 11354 subjects, we constructed multi-variate models that predict the functional connectivity of pairs of brain regions from the microstructural signature of white matter pathways that connect them. Microstructure-derived models provide predictions of functional connectivity that were significant in up to 86% of the brain region pairs considered. These relationships are specific to the relevant white matter pathway and have high reproducibility. The microstructure-function relationships are associated to genetic variants (single-nucleotide polymorphisms), co-located with genes DAAM1 and LPAR1, that have previously been reported to play a role in neural development. Our results demonstrate that variation in white matter microstructure across individuals consistently and specifically predicts functional connectivity, and that this relationship is underpinned by genetic variability.
Resistance Training does not Induce Uniform Adaptations to Quadriceps Muscles
Authors: Mangine Gerald T. , Redd Michael J. , Gonzalez Adam M. , Townsend Jeremy R. , Wells Adam J , Jajtner Adam R. , Beyer Kyle S. , Boone Carleigh H. , La Monica Michael B. , Stout Jeffrey R. , Fukuda David H. , Ratamess Nicholas A. , Hoffman Jay R. 
Published: May 2018

AbstractResistance training may differentially affect morphological adaptations along the length of uni-articular and bi-articular muscles. The purpose of this study was to compare changes in muscle morphology along the length of the rectus femoris (RF) and vastus lateralis (VL) in response to resistance training. Following a 2-wk preparatory phase, 15 resistance-trained men (24.0 ± 3.0 y, 90.0 ± 13.8 kg, 174.9 ± 20.7 cm) completed pre-training (PRE) assessments of muscle thickness (MT), pennation angle (PA), cross-sectional area (CSA), and echo-intensity in the RF and VL at 30, 50, and 70% of each muscle’s length; fascicle length (FL) was estimated from respective measurements of MT and PA within each muscle and region. Participants then began a high intensity, low volume (4 × 3 − 5 repetitions, 3min rest) lower-body resistance training program, and repeated all PRE-assessments after 8 weeks (2 d · wk−1) of training (POST). Although three-way (muscle [RF, VL] × region [30, 50, 70%] × time [PRE, POST]) repeated measures analysis of variance did not reveal significant interactions for any assessment of morphology, significant simple (muscle × time) effects were observed for CSA (p = 0.002) and FL (p = 0.016). Specifically, average CSA changes favored the VL (2.96 ± 0.69 cm2, pp < 0.001) over the RF (0.59 ± 0.20 cm2, p = 0.011), while significant decreases in average FL were noted for the RF (–1.03 ± 0.30 cm, p = 0.004) but not the VL (–0.05 ± 0.36 cm, p = 0.901). No other significant differences were observed. The findings of this study demonstrate the occurrence of non-homogenous adaptations in RF and VL muscle size and architecture following 8 weeks of high-intensity resistance training in resistance-trained men. However, training does not appear to influence region-specific adaptations in either muscle.
Effects of water decontamination methods and bedding material on the gut microbiota
Authors: Bidot Willie A. , Ericsson Aaron C. , Franklin Craig L. 
Published: May 2018

AbstractRodent models are invaluable to understanding health and disease in many areas of biomedical research. Unfortunately, many models suffer from lack of phenotype reproducibility. Our laboratory has shown that differences in gut microbiota (GM) can modulate phenotypes of models of colon cancer and inflammatory bowel disease. We and others have also shown that a number of factors associated with rodent research, including vendor, cage system, and bedding can alter GM. The objective of this study was to expand these studies to examine the effect of additional bedding materials and methods of water decontamination on GM diversity and composition. To this end, Crl:CD1 (ICR) mice were housed on corn cob or compressed paper chip bedding and provided water that was decontaminated by four commonly used procedures: reverse osmosis, autoclaving, sulfuric acid treatment, or hydrochloric acid treatment. Feces was collected at day 0, and at day 28 (endpoint), fecal and cecal samples were collected. DNA was extracted from samples, amplified by PCR using conserved bacterial primer sets and subjected to next generation sequencing. Sequence data were analyzed using Qiime and groups were compared using principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA). Two factor PERMANOVA of cecal GM data revealed significant changes when comparing bedding and water decontamination methods, while no significant effects were noted in the fecal GM data. Subsequent PERMANOVA and PCoA of cecal data revealed that several combinations of bedding and water decontamination methods resulted in differing GM, highlighting the complexity by which environmental factors interact to modulate GM.