bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of homozygous genotypes for a putatively lethal recessive mutation in the porcine argininosuccinate synthase 1 (ASS1) gene
Authors: Mármol‐Sánchez E. , Luigi‐Sierra M.G. , Quintanilla R. , Amills M. 
Published: November 2019

SummaryThe sequencing of the pig genome revealed the existence of homozygous individuals for a nonsense mutation in the argininosuccinate synthase 1 (ASS1) gene (rs81212146, c.944T>A, L315X). Paradoxically, an AA homozygous genotype for this polymorphism is expected to abolish the function of the ASS1 enzyme that participates in the urea cycle, leading to citrullinemia, hyperammonemia, coma and death. Sequencing of five Duroc boars that sired a population of 350 Duroc barrows revealed the segregation of the c.944T>A polymorphism, so we aimed to investigate its phenotypic consequences. Genotyping of this mutation in the 350 Duroc barrows revealed the existence of seven individuals homozygous (AA) for the nonsense mutation. These AA pigs had a normal weight despite the fact that mild citrullinemia often involves impaired growth. Sequencing of the region surrounding the mutation in TT, TA and AA individuals revealed that the A substitution in the second position of the codon (c.944T>A) is in complete linkage disequilibrium with a C replacement (c.943T>C) in the first position of the codon. This second mutation would compensate for the potentially damaging effect of the c.944T>A replacement. In fact, this is the most probable reason why pigs with homozygous AA genotypes at the 944 site of the ASS1 coding region are alive. Our results illustrate the complexities of predicting the consequences of nonsense mutations on gene function and phenotypes, not only because of annotation issues but also owing to the existence of genetic mechanisms that sometimes limit the penetrance of highly harmful mutations.
Depot medroxyprogesterone acetate and norethisterone enanthate differentially impact T‐cell responses and expression of immunosuppressive markers
Authors: Matubu Allen , Hillier Sharon L. , Meyn Leslie A. , Stoner Kevin A. , Mhlanga Felix , Mbizvo Mike , Maramba Aaron , Chirenje Zvavahera M. , Achilles Sharon L. 
Published: November 2019

AbstractProblemInjectable contraceptive use may impact immune cell responsiveness and susceptibility to infection. We measured responsiveness of T‐cells from women before and after initiating depot medroxyprogesterone acetate (DMPA) or norethisterone enanthate (Net‐En).Method of studyPeripheral blood mononuclear cells collected from women aged 18‐34 years prior to, at steady state, and nadir concentrations after initiating DMPA (n = 30) or Net‐En (n = 36) and from women initiating copper intrauterine device (CU‐IUD; n = 32) were stimulated with phorbol myristate acetate and analyzed using flow cytometry. We evaluated percentage change in T‐cells expressing programmed cell death‐1 (PD‐1) and cytotoxic T‐lymphocyte associated protein‐4 (CTLA‐4).ResultsCompared to baseline, there were decreased numbers of CD4+CTLA4+ (P < .001) and CD8+CTLA4+ (P < .01) T‐cells following ex vivo stimulation challenge at steady state DMPA concentrations and no differences at nadir concentrations (P = .781 and P = .463, respectively). In Net‐En users, no differences in CD4+CTLA4+ T‐cells at steady state (P = .087) and nadir concentrations (P = .217) were observed. DMPA users had fewer CD4+PD‐1+ (P < .001) and CD8+PD‐1+ (P < .001) T‐cells at nadir concentrations. Number of CD4+PD‐1+ and CD8+PD‐1+ T‐cells decreased at steady state concentration (P = .002 and P = .001, respectively) and at nadir concentrations after Net‐En initiation (P < .001 and P < .001). In CU‐IUD users, there were no changes in number of CD4+CTLA4+ (P = .426) and CD8+CTLA4+ (P = .169) and no changes in CD4+PD‐1+ (P = .083) and CD8+PD‐1+ (P = .936) compared to baseline.ConclusionActivation of T‐cells in response to ex vivo stimulation is suppressed at steady state DMPA concentration and resolves at nadir concentration, suggesting DMPA immunosuppressive effects may be transient.
A temporally stratified extension of space‐for‐time Cormack–Jolly–Seber for migratory animals
Authors: Hance Dalton J. , Perry Russell W. , Plumb John M. , Pope Adam C. 
Published: November 2019

AbstractUnderstanding drivers of temporal variation in demographic parameters is a central goal of mark‐recapture analysis. To estimate the survival of migrating animal populations in migration corridors, space‐for‐time mark–recapture models employ discrete sampling locations in space to monitor marked populations as they move past monitoring sites, rather than the standard practice of using fixed sampling points in time. Because these models focus on estimating survival over discrete spatial segments, model parameters are implicitly integrated over the temporal dimension. Furthermore, modeling the effect of time‐varying covariates on model parameters is complicated by unknown passage times for individuals that are not detected at monitoring sites. To overcome these limitations, we extended the Cormack–Jolly–Seber (CJS) framework to estimate temporally stratified survival and capture probabilities by including a discretized arrival time process in a Bayesian framework. We allow for flexibility in the model form by including temporally stratified covariates and hierarchical structures. In addition, we provide tools for assessing model fit and comparing among alternative structural models for the parameters. We demonstrate our framework by fitting three competing models to estimate daily survival, capture, and arrival probabilities at four hydroelectric dams for over 200 000 individually tagged migratory juvenile salmon released into the Snake River, USA.
One‐step targeted maximum likelihood estimation for time‐to‐event outcomes
Authors: Cai Weixin , van der Laan Mark J. 
Published: November 2019

AbstractResearchers in observational survival analysis are interested in not only estimating survival curve nonparametrically but also having statistical inference for the parameter. We consider right‐censored failure time data where we observe n independent and identically distributed observations of a vector random variable consisting of baseline covariates, a binary treatment at baseline, a survival time subject to right censoring, and the censoring indicator. We assume the baseline covariates are allowed to affect the treatment and censoring so that an estimator that ignores covariate information would be inconsistent. The goal is to use these data to estimate the counterfactual average survival curve of the population if all subjects are assigned the same treatment at baseline. Existing observational survival analysis methods do not result in monotone survival curve estimators, which is undesirable and may lose efficiency by not constraining the shape of the estimator using the prior knowledge of the estimand. In this paper, we present a one‐step Targeted Maximum Likelihood Estimator (TMLE) for estimating the counterfactual average survival curve. We show that this new TMLE can be executed via recursion in small local updates. We demonstrate the finite sample performance of this one‐step TMLE in simulations and an application to a monoclonal gammopathy data.
The palaeobiology of belemnites – foundation for the interpretation of rostrum geochemistry
Authors: Hoffmann René , Stevens Kevin 
Published: November 2019

ABSTRACTBelemnites are an extinct group of Mesozoic coleoid cephalopods with a fossil record ranging from the early Late Triassic [about 240 million years ago (Mya)] to the Cretaceous/Palaeogene boundary (65 Mya). Belemnites were widely distributed, highly abundant and diverse, and an important component of Mesozoic marine food webs. Their internal shells, specifically their low‐Mg calcite rostra, have been used as palaeoenvironmental carbonate archives for the last 70 years. This is primarily due to the assumption that the rostrum calcite formed in equilibrium with the oxygen isotope composition of ambient sea water. Of prime importance for the reliable interpretation of isotope data derived from these biogenic carbonates is a robust reconstruction of the palaeobiology of their producers. Here we provide a critical assessment of published reconstructions of belemnite soft‐body organization and their lifestyle and habitats. Different lines of evidence, including sedimentological, geochemical, morphological, and biomechanical data, point towards an outer shelf habitat of belemnites, for some taxa also including the littoral area. Belemnite habitat temperatures, oxygen content, salinities, and life span are constrained based on observations of the ecology and life history of modern coleoids. Belemnite habitat depth might have been largely controlled by food and temperature, with a temperature optimum between 10°C and 30°C. The distribution of modern coleoids is for most species restricted to well‐oxygenated water masses and a salinity between 27 and 37 psu. The trophic position of belemnites as both predators and prey is documented by unique fossil finds of stomach contents and soft tissue preservation, such as jaws, hooks, and ink sacs. Belemnites were medium‐sized predators in the epipelagic zone (not deeper than ∼200 m) hunting for crustaceans, other cephalopods, and fishes. Taxa with elongated rostra probably were fast and highly manoeuvrable swimmers. Forms with conical rostra represent slow but highly manoeuvrable swimmers, and forms with depressed rostra likely had a bottom‐related life habit. Predators of adult belemnites were sharks, bony fishes, and marine reptiles. Belemnites, like most of the modern coleoids, were relatively short lived, most likely living only for 1–2 years. Understanding the biomineralization of belemnite rostra is highly relevant for an improved interpretation of their geochemistry. Here we confirm that belemnite rostra are composed of low Mg‐calcite fibres, but they do not contain distinct types of laminae. These fibres are composed of two distinct calcite phases. One phase is a filigree network of tetrahedral organic‐rich calcite and the second phase is represented by organic‐poor calcite.
Influence of bio‐aging on corrosion behavior of different implant materials
Authors: Zhou Wen , Peng Xian , Zhou Xuedong , Li Mingyun , Ren Biao , Cheng Lei 
Published: November 2019

AbstractBackgroundDental implants and abutments are exposed to challenging oral environment. Corrosion of these materials can affect the overall performance of titanium implants.PurposeTo investigate the effects of biofilm‐induced bio‐aging on corrosion behavior of different implant materials surface.Materials and MethodsCommercial polished titanium (Polish), sand‐blasted, large grit, acid‐etched surface treated titanium (SLA), microarc oxidation (MAO), and hydroxyapatite (HA) coated titanium were bio‐aged with saliva biofilm for 30 days. Titanium surfaces topography, chemical composition, roughness, and water contact angle changes were evaluated. In addition, human gingival fibroblasts (HGFs) adhesion, Streptococcus sanguinis (S. sanguinis) biofilm formation were determined.ResultsSurface topography, roughness, and chemical composition have no significant changes for all groups after bio‐aging (P > .05). Water contact angle of bio‐aged SLA was greatly increased (P < .05). While other groups showed no sign of change (P > .05). Adhesion and proliferation of HGFs on the bio‐aged SLA titanium surfaces were decreased (P < .05), but increased on bio‐aged Polish and HA titanium (P < .05). S. sanguinis biofilm viability was promoted with bio‐aging in HA group (P < .05).ConclusionsBiological characteristics of Polish, SLA, and HA titanium surfaces were influenced by bio‐aging. While MAO group was relatively resistant to saliva biofilm bio‐aging.
Update of inflammasome activation in microglia/macrophage in aging and aging‐related disease
Authors: Hu Meng‐yan , Lin Yin‐yao , Zhang Bing‐jun , Lu Dan‐li , Lu Zheng‐qi , Cai Wei 
Published: November 2019

AbstractAging and aging‐related CNS diseases are associated with inflammatory status. As an efficient amplifier of immune responses, inflammasome is activated and played detrimental role in aging and aging‐related CNS diseases. Macrophage and microglia display robust inflammasome activation in infectious and sterile inflammation. This review discussed the impact of inflammasome activation in microglia/macrophage on senescence “inflammaging” and aging‐related CNS diseases. The preventive or therapeutic effects of targeting inflammasome on retarding aging process or tackling aging‐related diseases are also discussed.
Using vertebrate environmental DNA from seawater in biomonitoring of marine habitats
Authors: Sigsgaard Eva Egelyng , Torquato Felipe , Frøslev Tobias Guldberg , Moore Alec B. M. , Sørensen Johan Mølgård , Range Pedro , Ben‐Hamadou Radhouane , Bach Steffen Sanvig , Møller Peter Rask , Thomsen Philip Francis 
Published: November 2019

AbstractConservation and management of marine biodiversity depends on biomonitoring of marine habitats, but current approaches are resource‐intensive and require different approaches for different organisms. Environmental DNA (eDNA) extracted from water samples is an efficient and versatile approach to detecting aquatic animals. In the ocean, eDNA composition reflects local fauna at fine spatial scales, but little is known about the effectiveness of eDNA‐based monitoring of marine communities at larger scales. We investigated the potential of eDNA to characterize and distinguish marine communities at large spatial scales by comparing vertebrate species composition among marine habitats in Qatar, the Arabian Gulf (also known as the Persian Gulf), based on eDNA metabarcoding of seawater samples. We conducted species accumulation analyses to estimate how much of the vertebrate diversity we detected. We obtained eDNA sequences from a diverse assemblage of marine vertebrates, spanning 191 taxa in 73 families. These included rare and endangered species and covered 36% of the bony fish genera previously recorded in the Gulf. Sites of similar habitat type were also similar in eDNA composition. The species accumulation analyses showed that the number of sample replicates was insufficient for some sampling sites but suggested that a few hundred eDNA samples could potentially capture >90% of the marine vertebrate diversity in the study area. Our results confirm that seawater samples contain habitat‐characteristic molecular signatures and that eDNA monitoring can efficiently cover vertebrate diversity at scales relevant to national and regional conservation and management.
Changes in severity and impact of drooling after submandibular gland botulinum neurotoxin A injections in children with neurodevelopmental disabilities
Authors: Van Hulst Karen , Van Der Burg Jan JW , Jongerius Peter H , Geurts Alexander CH , Erasmus Corrie E 
Published: November 2019

AimsTo examine changes in objective and subjective drooling severity measures after submandibular botulinum neurotoxin A injection in children with neurodevelopmental disabilities, explore their relationship, and evaluate if clinically relevant responses relate to changes in the impact of drooling.MethodThis longitudinal, observational cohort study involved 160 children (92 males, 68 females; 3–17y, mean 9y 1mo, SD 3y 6mo) treated between 2000 and 2012 at the Radboud University Medical Center, Nijmegen, the Netherlands. Repeated measures analysis of variance was used to compare the 5‐minute Drooling Quotient (DQ5) and Visual Analogue Scale (VAS) for drooling severity pretreatment and posttreatment, and Pearson’s rho to assess their association. A parent questionnaire was used to assess drooling impact in responders (defined as ≥50% reduction in DQ5 and/or ≥2 SD reduction in VAS for drooling severity 8wks postintervention) and non‐responders.ResultsOne hundred and twelve children (70%) were responders. Their mean VAS for drooling severity and DQ5 scores were significantly lower 32 weeks postintervention compared to baseline. At baseline, the VAS for drooling severity‐DQ5 relationship was ‘weak’ (rs=0.15, p=0.060), whereas it was ‘fair’ at 8 weeks (rs=0.43, p=0.000) and 32 weeks (rs=0.30, p=0.000). For responders, a significant change was found regarding the impact of drooling on daily care and social interactions at 8 weeks after intervention; most of these effects were maintained at 32 weeks.InterpretationA clinically relevant response based on a combination of objective and subjective measures of drooling severity was accompanied by positive changes regarding the impact of drooling on daily care and social interactions.What this paper adds

Botulinum neurotoxin A injection into the submandibular glands reduced drooling severity in 70% of children with neurodevelopmental disabilities.

Objective (5‐minute Drooling Quotient) and subjective (Visual Analogue Scale for drooling severity) measures correlated 8 and 32 weeks after treatment.

Objective and subjective measures complemented each other when changes in drooling severity were assessed.

Reduced drooling severity was accompanied by positive changes with regard to the impact of drooling.
Observational analyses from ADVANCE and ADVANCE‐ON
Authors: Chalmers John , Woodward Mark 
Published: November 2019

AbstractAimsTo explain, and document, the epidemiological work associated with the action in diabetes and vascular disease: preterax and diamicron‐modified release controlled evaluation (ADVANCE) clinical trial.Materials and methodsADVANCE was designed as a randomized controlled multicentre factorial trial in high‐risk patients with diabetes. The two interventions were blood pressure lowering medications versus placebo, and intensive glucose control versus standard glucose control. Following termination of the trial, an observational study of surviving participants, able to join, was mounted: the ADVANCE ‐ observational study (ADVANCE‐ON). Other epidemiological analyses that were undertaken treated the trial as a cohort study, including using biomarkers from the blood samples taken from ADVANCE subjects as risk exposures.ResultsMore than 50 publications have reported epidemiological results from ADVANCE. The main results from ADVANCE‐ON suggested attenuated benefits of ADVANCE's blood pressure lowering treatment on all‐cause and cardiovascular death, but no such long‐term benefits for intensive glucose control, although this did give persistent benefit for end‐stage renal disease. The other epidemiological studies found, amongst other things, strong effects of NT‐terminal pro‐B‐type natriuretic peptide and high‐sensitivity cardiac troponin T on macrovascular events, microvascular events and all‐cause death.ConclusionsEmbedding post‐randomization and epidemiological analyses into clinical trials is worthwhile and can be highly productive in advancing scientific knowledge.
Urinalysis in patients with neuromyelitis optica spectrum disorder
Authors: Chen Z. G. , Huang J. , Fan R. , Weng R. H. , Shinohara R. T. , Landis J. R. , Chen Y. , Jiang Y. 
Published: November 2019

Background and purposeIncreasing evidence has demonstrated that aquaporin‐4 (AQP4) immunoglobulin G causes damage to the kidney in neuromyelitis optica spectrum disorder (NMOSD). However, changes in urinalysis in NMOSD have not been investigated thus far. Our objective was to evaluate the changes in urinalysis in NMOSD patients.MethodsCase data were collected from 44 patients with AQP4 antibody‐positive NMOSD, 53 patients with multiple sclerosis (MS) and 79 age‐ and sex‐matched healthy controls. Analyses of early morning urine and 24‐h urine samples comparing NMOSD with MS patients were conducted.ResultsIn the acute phase, urine pH levels (P < 0.001) and urine specific gravity levels (P < 0.001) from NMOSD patients were significantly higher and lower, respectively, than for MS patients. 24‐h urine sodium and 24‐h urine volume from NMOSD patients were significantly higher than for MS patients (both P = 0.001). A 24‐h urine volume higher than 2500 ml (odds ratio 11.7, 95% confidence interval 1.863–73.066) and a 24‐h urine sodium higher than 200 mmol (odds ratio 16.0, 95% confidence interval 2.122–120.648) are more likely to occur in NMOSD patients in the acute phase than in MS patients.ConclusionsThe urinalysis results were significantly different between NMOSD patients and MS patients. The pathophysiological changes in AQP4 antibody‐positive NMOSD patients were not limited to the central nervous system.
A novel optimal PID controller autotuning design based on the SLP algorithm
Authors: Pongfai Jirapun , Su Xiaojie , Zhang Huiyan , Assawinchaichote Wudhichai 
Published: November 2019

AbstractA novel optimal proportional integral derivative (PID) autotuning controller design based on a new algorithm approach, the “swarm learning process” (SLP) algorithm, is proposed. It improves the convergence and performance of the autotuning PID parameter by applying the swarm and learning algorithm concepts. Its convergence is verified by two methods, global convergence and characteristic convergence. In the case of global convergence, the convergence rule of a random search algorithm is employed to judge, and Markov chain modelling is used to analyse. The superiority of the proposed method, in terms of characteristic convergence and performance, is verified through the simulation based on the automatic voltage regulator and direct current motor control system. Verification is performed by comparing the results of the proposed model with those of other algorithms, that is, the ant colony optimization with a new constrained Nelder–Mead algorithm, the genetic algorithm (GA), the particle swarm optimization (PSO) algorithm, and a neural network (NN). According to the global convergence analysis, the proposed method satisfies the convergence rule of the random search algorithm. With respect to the characteristic convergence and performance, the proposed method provides a better response than the GA, the PSO, and the NN for both control systems.
Structural basis of the strong cell‐cell junction formed by cadherin‐23
Authors: Singaraju Gayathri S. , Sagar Amin , Kumar Anuj , Samuel Jesse S. , Hazra Jagadish P. , Sannigrahi Malay K. , Yennamalli Ragothaman M. , Ashish   , Rakshit Sabyasachi 
Published: November 2019

Cadherin‐23, a giant atypical cadherin, form homophilic interactions at the cell–cell junction of epithelial cells and heterophilic interactions with protocadherin‐15 at the tip links of neuroepithelial cells. While the molecular structure of the heterodimer is solved, the homodimer structure is yet to be resolved. The homodimers play an essential role in cell–cell adhesion as the downregulation of cadherin‐23 in cancers loosen the intercellular junction resulting in faster migration of cancer cells and a significant drop in patient survival. In vitro studies have measured a stronger aggregation propensity of cadherin‐23 compared to typical E‐cadherin. Here, we deciphered the unique trans‐homodimer structure of cadherin‐23 in solution and show that it consists of two electrostatic‐based interfaces extended up to two terminal domains. The interface is robust, with a low off‐rate of ~ 8 × 10−4 s−1 that supports its strong aggregation propensity. We identified a point mutation, E78K, that disrupts this binding. Interestingly, a mutation at the interface was reported in skin cancer. Overall, the structural basis of the strong cadherin‐23 adhesion may have far‐reaching applications in the fields of mechanobiology and cancer.