bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of narasin supplementation on dry matter intake and rumen fermentation characteristics of Bos indicus steers fed a high-forage diet
Authors: Polizel Daniel M , Cappellozza Bruno I , Hoe Fernanda , Lopes Catarina N , Barroso José Paulo , Miszura Alexandre , Oliveira Gabriela B , Gobato Luiz , Pires Alexandre V 
Published: October 2019

Abstract
This study evaluated the effects of narasin on intake and rumen fermentation characteristics of Bos indicus steers offered a high-forage diet for 140 d. On day 0 of the study, 30 rumen-fistulated Nellore steers [initial body weight (BW) = 281 ± 21 kg] were assigned to 30 individual pens in a randomized complete block design according to their initial BW. Animals were randomly assigned to 1 of the 3 treatments: 1) forage-based diet without narasin (CONT; n = 10), 2) CONT diet plus 13 ppm of narasin (13NAR; n = 10), and 3) CONT diet plus 20 ppm of narasin (20NAR; n = 10). The forage used was Tifton-85 (Cynodon dactylon spp.), whereas the carrier for narasin was a 50:50 mixture of soybean hull:corn. The experimental period was divided into 5 periods of 28 d each. Throughout the experimental period, total dry matter intake (DMI) was recorded daily, whereas mineral salt intake was recorded weekly. Blood and ruminal fluid samples were collected on day 0 (prior to treatment feeding), 28, 56, 84, 112, and 140 of the study. Moreover, total tract apparent nutrient digestibility was performed for a 5-d period every 28 d. No treatment effects were observed on forage, mineral, concentrate, or total DMI (P ≥ 0.22). Nonetheless, 13NAR tended to have a greater mineral intake vs. 20NAR cohorts (P = 0.08) Narasin-supplemented animals had reduced rumen acetate, Ac:Pr ratio, as well as greater (P ≤ 0.02) rumen propionate concentrations vs. CONT cohorts. Moreover, 13NAR increased rumen propionate and decreased butyrate, Ac:Pr vs. 20NAR cohorts (P ≤ 0.01). Throughout the experimental period, narasin-supplemented animals had reduced ammonia concentrations vs. CONT cohorts (P &lt; 0.01), whereas no differences were observed between 13NAR and 20NAR (P = 0.80). No treatment or dose effects were observed (P ≥ 0.23) on DM, organic matter (OM), protein, neutral detergent fiber (NDF), acid detergent fiber (ADF), and mineral digestibility. Animals fed 13NAR had a reduced mean plasma urea concentration vs. CONT cohorts (P = 0.03), whereas no further differences were observed (P ≥ 0.12). In summary, narasin supplementation to beef steers offered a high-forage diet did not impact forage, mineral, and total DMI, as well as nutrient digestibility, whereas rumen fermentation characteristics, rumen ammonia, and plasma urea concentrations were positively impacted and lasted throughout the experimental period. Additionally, 13 ppm of narasin resulted in a reduced Ac:Pr ratio and rumen ammonia when compared to animals supplemented with 20 ppm.
Computer-assisted craniometric evaluation for diagnosis and follow-up of craniofacial asymmetries: SymMetric v. 1.0
Authors: Lopes Alho Eduardo Joaquim , Rondinoni Carlo , Furokawa Fabio Okuda , Monaco Bernardo A. 
Published: October 2019

AbstractPurposeThe current assessment of patients with craniofacial asymmetries is accomplished by physical examination, anamnesis and radiological imaging.We propose a semi-automated, computer-assisted craniofacial evaluation (SymMetric v 1.0) based on orthogonal photography of the patient’s head in 3 positions. The system is simple, low-cost, no-radiation or special resources needed. Although it does not substitute CT in cases of doubt between craniosynostosis and positional plagiocephaly, multiple numeric evaluations indicate regional deformities and severity of the asymmetry, which can help in the clinical decision of indicating or not the orthosis in positional deformities, determining treatment duration or evaluating surgical outcomes after correction.MethodsA Matlab-based tool was developed for digital processing of photographs taken in 3 positions (anterior, superior and lateral). The software guides the user to select visible and reproducible landmarks in each photograph acquisition and calculates multiple indexes and metrics, generating a set of comprehensive plots to offer the user an overview of head and facial symmetry across the orthogonal views. For purposes of demonstration, we evaluated 2 patients (one control and one with non-sinostotic deformity).ResultsThe results show a clear differentiation of the control and plagiocephalic patient metrics mainly in the superior view, showing potential for diagnosis of the condition, and also detected the clinical improvement during helmet treatment in the follow-up, 3 and 5 months after orthosis’ use.ConclusionWe presented a proof-of-concept for a low cost, no radiation evaluation system for craniofacial asymmetries, that can be useful in a clinical context for diagnosis and follow-up of patients.
NeuroMark: a fully automated ICA method to identify effective fMRI markers of brain disorders
Authors: Du Yuhui , Fu Zening , Sui Jing , Gao Shuang , Xing Ying , Lin Dongdong , Salman Mustafa , Rahaman Md Abdur , Abrol Anees , Chen Jiayu , Hong L Elliot , Kochunov Peter , Osuch Elizabeth A. , Calhoun Vince D. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2019

SummaryIncreasing sharing initiatives on neuroimaging data have provided unprecedented opportunities to study brain disorders. Standardized approaches for capturing reproducible and comparable biomarkers are greatly needed. Here, we propose a method,NeuroMark, which leverages a priori-driven independent component analysis to effectively extract functional brain network biomarkers from functional magnetic resonance imaging (fMRI) data.NeuroMarkautomatically estimates features adaptable to each individual and comparable across subjects by taking advantage of the replicated brain network templates extracted from 1828 healthy controls as guidance to initialize the individual-level networks. Four studies including 2454 subjects were conducted spanning six brain disorders (schizophrenia, autism spectrum disorder, depression, bipolar disorder, mild cognitive impairment and Alzheimer’s disease) to evaluate the proposed method from different perspectives (replication, cross-study comparison, subtle difference identification, and multi-disorder classification). Results demonstrate the great potential ofNeuroMarkin its feasibility to link different datasets/studies/disorders and enhance sensitivity in identifying biomarkers for patients with challenging mental illnesses.Significance StatementIncreasing evidence highlights that features extracted from resting fMRI data can be leveraged as potential biomarkers of brain disorders. However, it has been difficult to replicate results using different datasets, translate findings across studies, and differentiate brain disorders sharing similar clinical symptoms. It is important to systematically characterize the degree to which unique and similar impaired patterns are reflective of brain disorders. We propose a fully automated method (calledNeuroMark) that leverages priori-driven independent component analysis (ICA) using replicated brain network templates to estimate individual-subject network features. Evaluated by four studies involving six different brain disorders, we show thatNeuroMarkcan effectively link the comparison of biomarkers across different studies/datasets/disorders and enable classification between complex brain disorders, while also providing information about relevant aspects of whole brain functional connectivity.
Efficacy and safety of Nab-paclitaxel in breast cancer: a meta-analysis
Authors: Yadav Upendra , Kumar Pradeep , Rai Vandana 
Published: October 2019

AbstractWorldwide breast cancer is the leading cause of cancer related death in women. Paclitaxel is an effective drug used for the treatment of breast cancer but it has many side effects. Nab-paclitaxel (nanoparticle albumin-bound paclitaxel) is an FDA approved drug for the treatment of breast cancer. Currently many clinical trials are conducted to deliver nab-paclitaxel into the tumor cells. But the efficacy and safety of this nab-paclitaxel over conventional paclitaxel still remains questionable. So, we performed a meta-analysis to evaluate the efficacy and safety of nab-paclitaxel in breast cancer treatment.Electronic databases were searched for the suitable studies using key terms “nab-paclitaxel”, “paclitaxel”, and “clinical trial” with the combination of “breast cancer” up to August 11, 2019. Risk ratio (RR) and odds ratio (OR) with corresponding 95% confidence intervals (CIs) were calculated. All statistical analyses were performed by the Open Meta-Analyst program. A total of eight studies which fulfilled our criteria were included in this study. For efficacy we retrieved data of 12 months progression free survival, 24 months progression free survival, and overall survival (up to 3 years) and for the safety we took data of nausea, anemia, leukopenia, neutropenia, fatigue, diarrhea and pain.We did not found any difference in efficacy of nab-paclitaxel over paclitaxel (12 months progression free survival-RRFE= 0.86, 95%CI= 0.77-0.97, p= 0.02, I2= 25.07%; 24 months progression free survival-RRFE= 0.86, 95% CI= 0.64-1.16, p= 0.34, I2= 0%; and 3 years survival-RRFE= 1.20, 95%CI= 0.92-1.56, p= 0.16, I2= 37.55%). The meta-analysis of studies used nab-paclitaxel showed reduced adverse effect of anemia (ORFE= 1.66, 95% CI= 1.26-2.19; p= <0.001; I2= 0%) and leukopenia (ORFE= 1.37; 95%CI= 1.06-1.75; p= 0.01; I2= 48.63%). However, in case of other adverse effects no significant association was found with nab-paclitaxel (nausea-ORFE=1.15, 95%CI= 0.94-1.41, p= 0.15, I2= 50.12%; neutropenia-ORRE= 0.75, 95%CI= 0.30-1.87, p= 0.54, I2= 94.45%; fatigue-ORRE= 1.11, 95%CI= 0.77-1.62, p= 0.55, I2= 56.02; diarrhea-ORFE= 1.11, 95%CI= 0.77-1.62, p= 0.55; I2= 34.26; pain-ORRE= 1.15, 95%CI= 0.78-1.69, p= 0.45, I2= 52.96%).In conclusion the use of nab-paclitaxel has reduces the side effects of anemia and leukopenia in breast cancer treatment in comparison to paclitaxel but nab-paclitaxel has no effect on the overall survival of the patients.
BRAFmutation testing of MSI CRCs in Lynch syndrome diagnostics: performance and efficiency according to patient’s age
Authors: Bläker Hendrik , Haupt Saskia , Morak Monika , Holinski-Feder Elke , Arnold Alexander , Horst David , Sieber-Frank Julia , Seidler Florian , von Winterfeld Moritz , Alwers Elizabeth , Chang-Claude Jenny , Brenner Hermann , Roth Wilfried , Engel Christoph , Löffler Markus , Möslein Gabriela , Schackert Hans-Konrad , Weitz Jürgen , Perne Claudia , Aretz Stefan , Hüneburg Robert , Schmiegel Wolff , Vangala Deepak , Rahner Nils , Steinke-Lange Verena , Heuveline Vincent , von Knebel Doeberitz Magnus , Ahadova Aysel , Hoffmeister Michael , Kloor Matthias ,   the German Consortium for Familial Intestinal Cancer
Published: October 2019

AbstractBackground and aimsBRAFV600E mutations have been reported to be associated with sporadic microsatellite-unstable (MSI) colorectal cancer (CRC), while rarely detected in CRCs of Lynch syndrome (LS) patients. Therefore, current international diagnostic guidelines recommend somaticBRAFmutation testing in MLH1-deficient MSI CRC patients to exclude LS. As sporadicBRAF-mutant MSI CRC is a disease of the elderly, while LS-associated CRC usually occurs at younger age, we hypothesized that the efficacy ofBRAFtesting in LS diagnostics may be age-dependent.MethodsWe systematically compared the prevalence ofBRAFV600E mutations in LS-associated CRCs and MSI CRCs from population-based cohorts in different age groups as available from published studies, databases, and population-based patient cohorts. Cost calculations and sensitivity analysis of theBRAFtesting for exclusion of LS was performed.ResultsAmong 969 MSI CRCs from LS mutation carriers from the literature and German HNPCC Consortium, 15 (1.6%, 95% CI: 0.9-2.6%) harboredBRAFmutations. 6/7 LS patients withBRAF-mutant CRC and reported age were <50 years. Among unselected MSI CRCs, 44.8% (339/756) harboredBRAFmutations, 92.3% (313/339) of which were detected in patients >60 years. In MSI CRC patients <50,BRAFmutations were detected only in 0.6% (2/339), and the inclusion ofBRAFtesting led to increased costs and higher risk of missing LS patients (1.2%) compared to other age groups.ConclusionBRAFtesting in patients <50 years is cost-inefficient and carries the highest risk of missing LS patients among different age groups. We suggest direct referral of MSI CRC patients <50 years to genetic counseling without priorBRAFtesting.
Association of polygenic risk scores for coronary artery disease with subsequent events amongst established cases
Authors: Howe Laurence J. , Dudbridge Frank , Schmidt A. Floriaan , Finan Chris , Denaxas Spiros , Asselbergs Folkert W. , Hingorani Aroon D. , Patel Riyaz S. 
Published: October 2019

AbstractBackgroundThere is growing evidence that polygenic risk scores (PRS) can be used to identify individuals at high lifetime risk of coronary artery disease (CAD). Whether they can also be used to stratify risk of subsequent events among those surviving a first CAD event remains uncertain.MethodsUsing two subsamples of UK Biobank, defined at baseline as prevalent CAD (N=10,287) and without CAD (N=393,108), we evaluated associations between a CAD PRS and incident cardiovascular and fatal outcomes, during a median follow up of 7.8 years.ResultsA 1 S.D. higher PRS was associated with increased risk of incident MI in participants without CAD (OR 1.33; 95% C.I. 1.29, 1.38), but the effect estimate was markedly attenuated in those with prevalent CAD (OR 1.15; 95% C.I. 1.06, 1.25); heterogeneity P =0.0012. Additionally, among prevalent CAD cases, we found evidence of an inverse association between the CAD PRS and risk of all-cause death (OR 0.91; 95% C.I. 0.85, 0.98) compared to those without CAD (OR 1.01; 95% C.I. 0.99, 1.03); heterogeneity P =0.0041. A similar inverse association was found for ischaemic stroke (Prevalent CAD (OR 0.78; 95% C.I. 0.67, 0.90); without CAD (OR 1.09; 95% C.I. 1.04, 1.15), heterogeneity P <0.001).ConclusionsBias induced by case stratification and survival into UK Biobank may attenuate, or reverse, associations of polygenic risk scores derived from case-control studies or populations initially free of disease. Polygenic risk scores for subsequent events should be derived from new genome wide association studies conducted in patients with established disease.Key messagesCAD PRS are positively associated with incident myocardial infarction risk amongst established CAD cases.However, the effect size is attenuated compared to estimates from CAD-free populations.CAD PRS are inversely associated with mortality and stroke risk amongst established CAD cases.These associations may reflect index event bias induced by stratifying on case status.Dedicated GWAS of coronary disease progression are required to improve prediction of subsequent event risk.
C-terminal tail polyglycylation and polyglutamylation alter microtubule mechanical properties
Authors: Wall Kathryn P. , Hart Harold , Lee Thomas , Page Cynthia , Hawkins Taviare L. , Hough Loren 
Published: October 2019

ABSTRACTMicrotubules are biopolymers that perform diverse cellular functions. The regulation of microtubule behavior occurs in part through post-translational modification of both theα- andβ- subunits of tubulin. One class of modifications is the heterogeneous addition of glycine and glutamate residues to the disordered C-terminal tails of tubulin. Due to their prevalence in stable, high stress cellular structures such as cilia, we sought to determine if these modifications alter the intrinsic stiffness of microtubules. Here we describe the purification and characterization of differentially-modified pools of tubulin fromTetrahymena thermophila. We found that glycylation on theα-C-terminal tail is a key determinant of microtubule stiffness, but does not affect the number of protofilaments incorporated into microtubules. We measured the dynamics of the tail peptide backbone using nuclear magnetic resonance spectroscopy. We found that the spin-spin relaxation rate (R2) showed a pronounced decreased as a function of distance from the tubulin surface for theα-tubulin tail, indicating that theα-tubulin tail interacts with the dimer surface. This suggests that the interactions of theα-C-terminal tail with the tubulin body contributes to the stiffness of the assembled microtubule, providing insight into the mechanism by which glycylation and glutamylation can alter microtubule mechanical properties.SIGNIFICANCEMicrotubules are regulated in part by post-translational modifications including the heterogeneous addition of glycine and glutamate residues to the C-terminal tails. By producing and characterizing differentially-modified tubulin, this work provides insight into the molecular mechanisms of how these modifications alter intrinsic microtubule properties such as flexibility. These results have broader implications for mechanisms of how ciliary structures are able to function under high stress.
Cathepsin g degrades synovial fluid lubricin: relevance for osteoarthritis pathogenesis
Authors: Huang Shan , Thomsson Kristina A. , Jin Chunsheng , Alweddi Sally , Struglics André , Rolfson Ola , Björkman Lena I , Kalamajski Sebastian , Schmidt Tannin A. , Jay Gregory D. , Krawetz Roman , Karlsson Niclas G. , Eisler Thomas 
Published: October 2019

AbstractLubricin (PRG4) is a mucin type protein that plays an important role in maintaining normal joint function by providing lubrication and chondroprotection. Improper lubricin modification and degradation has been observed in idiopathic osteoarthritis (OA), while the detailed mechanism still remains unknown. We hypothesized that the protease cathepsin G (CG) may participate in degrading lubricin in synovial fluid (SF). The presence of endogenous CG in SF was confirmed in 16 patients with knee OA. Recombinant human lubricin (rhPRG4) and native lubricin purified from the SF of patients were incubated with exogenous CG and lubricin degradation was monitored using western blot, staining by Coomassie or Periodic Acid-Schiff in gels, and with proteomics. Full length lubricin (∼300 kDa), was efficiently digested with CG generating a 25-kDa protein fragment, originating from the densely glycosylated mucin domain (∼250 kDa). The 25-kDa fragment was present in the SF from OA patients, and the amount was increased after incubation with CG. A CG digest of rhPRG4 revealed 135 peptides and 72 glycopeptides, and confirmed that the protease could cleave in different domains of lubricin. Our results suggest that synovial CG may take part in the degradation of lubricin, which could affect the lubrication of OA joints.
Reconstructing the history of variation in effective population size along phylogenies
Authors: Brevet Mathieu , Lartillot Nicolas 
Published: October 2019

AbstractThe nearly-neutral theory predicts specific relations between effective population size (Ne) and patterns of divergence and polymorphism, which depend on the shape of the distribution of fitness effects (DFE) of new mutations. However, testing these relations is not straightforward, owing to the difficulty in estimating Ne. Here, we introduce an integrative framework allowing for an explicit reconstruction of the phylogenetic history of Ne, thus leading to a quantitative test of the nearly-neutral theory and an estimation of the allometric scaling of the ratios of non-synonymous over synonymous polymorphism (πN /πS) and divergence (dN/dS) with respect to Ne. As an illustration, we applied our method to primates, for which the nearly-neutral predictions were mostly verified. Under a purely nearly-neutral model with a constant DFE across species, we find that the variation in πN /πS and dN/dS as a function of Ne is too large to be compatible with current estimates of the DFE based on site frequency spectra. The reconstructed history of Ne shows a ten-fold variation across primates. The mutation rate per generation u, also reconstructed over the tree by the method, varies over a three-fold range and is negatively correlated with Ne. As a result of these opposing trends for Ne and u, variation in πS is intermediate, primarily driven by Ne but substantially influenced by u. Altogether, our integrative framework provides a quantitative assessment of the role of Ne and u in modulating patterns of genetic variation, while giving a synthetic picture of their history over the clade.Significance statementNatural selection tends to increase the frequency of mutants of higher fitness and to eliminate less fit genetic variants. However, chance events over the life of the individuals in the population are susceptible to introduce deviations from these trends, which are expected to have a stronger impact in smaller populations. In the long-term, these fluctuations, called random drift, can lead to the accumulation of mildly deleterious mutations in the genomes of living species, and for that reason, the effective population size (usually denoted Ne, and which captures the relative strength of drift, relative to selection) has been proposed as a major determinant of the evolution of genome architecture and content. A proper quantitative test of this hypothesis, however, is hampered by the fact that Ne is difficult to estimate in practice. Here, we propose a Bayesian integrative approach for reconstructing the broad-scale variation in Ne across an entire phylogeny, which in turns allows for quantifying how Ne correlates with life history traits and with various measures of genetic diversity and selection strength, between and within species. We apply this approach to the phylogeny of primates, and observe that selection is indeed less efficient in primates characterized by smaller effective population sizes.
A cost-efficient open source laser engine for microscopy
Authors: Schröder Daniel , Deschamps Joran , Dasgupta Anindita , Matti Ulf , Ries Jonas 
Published: October 2019

AbstractScientific-grade lasers are costly components of modern microscopes. For high-power applications, such as single-molecule localization microscopy, their price can become prohibitive. Here, we present an open-source high-power laser engine that can be built for a fraction of the cost. It uses affordable, yet powerful laser diodes at wavelengths of 405 nm, 488 nm and 640 nm and optionally a 561 nm diode-pumped solid-state laser. The light is delivered to the microscope via an agitated multimode fiber in order to suppress speckles. We provide the part lists, CAD files and detailed descriptions, allowing any research group to build their own laser engine.