Miracle-dz/UniFAR-FTUs huggingface dataset:
Growth plate damage, a feature of juvenile idiopathic arthritis, can be induced by adenoviral gene transfer of oncostatin M: a comparative study in gene-deficient mice.

OBJECTIVE To investigate the involvement of proinflammatory and destructive mediators in oncostatin M (OSM)-induced joint pathology, using gene-deficient mice. METHODS An adenoviral vector expressing murine OSM was injected into the joints of naive wild-type mice and mice deficient for interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha (TNFalpha), or inducible nitric oxide synthase (iNOS). Reverse transcription-polymerase chain reaction was used to study gene expression. Inflammation and cartilage proteoglycan (PG) depletion were assessed by histology. OSM and IL-1 levels in synovial fluid from patients with juvenile idiopathic arthritis (JIA) were measured by enzyme-linked immunosorbent assay. RESULTS Adenoviral expression of murine OSM led to joint inflammation, bone apposition, chondrophyte formation, articular cartilage PG depletion, and VDIPEN neoepitope expression in wild-type mice. A unique and consistent observation was the focal PG depletion and disorganization of the growth plate cartilage during the first week of inflammation. Synovial IL-1beta, IL-6, TNFalpha, and iNOS gene expression was strongly induced. Of these factors, only deficiency in IL-1 markedly reduced inflammation and PG depletion and completely prevented growth plate damage. In addition, this is the first study in which OSM was detected in JIA synovial fluid. Most samples were also IL-1beta positive. CONCLUSION IL-1, but not IL-6, TNFalpha, or iNOS, plays an important role in joint disease induced by intraarticular gene transfer of OSM in mice. The effect of OSM on murine connective tissue and the presence of OSM in human synovial fluid make involvement of OSM in human arthropathies very likely.
HPTN 071 (PopART): A Cluster-Randomized Trial of the Population Impact of an HIV Combination Prevention Intervention Including Universal Testing and Treatment: Mathematical Model

Background The HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence. Methods and Findings The HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative three-year HIV incidence. We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data. We predict that, if targets are reached, HIV incidence over three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence. Conclusions The HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by >60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention.
Phase transition for the mixing time of the Glauber dynamics for coloring regular trees

We prove that the mixing time of the Glauber dynamics for random <i>k</i>-colorings of the complete tree with branching factor <i>b</i> undergoes a phase transition at <i>k</i> = <i>b</i>(1+<i>o</i><sub>b</sub>(1))/ln <i>b</i>. Our main result shows nearly sharp bounds on the mixing time of the dynamics on the complete tree with <i>n</i> vertices for <i>k</i> = <i>Cb</i>/ln<i>b</i> colors with constant <i>C</i>. For <i>C</i> ≥ 1 we prove the mixing time is <i>O</i>(<i>n</i><sup>1+<i>o</i><sub><i>b</i></sub>(1)</sup> ln<sup>2</sup> <i>n</i>). On the other side, for <i>C</i> < 1 the mixing time experiences a slowing down, in particular, we prove it is <i>O</i>(<i>n</i><sup>1/<i>C+o</i><sub><i>b</i></sub>(1)</sup> ln<sup>2</sup> <i>n</i>) and Ω(<i>n</i><sup>1/<i>C-o</i><sub><i>b</i></sub>(1)</sup>). The critical point <i>C</i> = 1 is interesting since it coincides (at least up to first order) to the so-called reconstruction threshold which was recently established by Sly. The reconstruction threshold has been of considerable interest recently since it appears to have close connections to the efficiency of certain local algorithms, and this work was inspired by our attempt to understand these connections in this particular setting.
No association between mitochondrial DNA copy number and colorectal adenomas

Despite previously reported associations between peripheral blood mtDNA copy number and colorectal cancer, it remains unclear whether altered mtDNA copy number in peripheral blood is a risk factor for colorectal cancer or a biomarker for undiagnosed colorectal cancer. Though colorectal adenomas are well‐recognized precursor lesions to colorectal cancer, no study has evaluated an association between mtDNA copy number and colorectal adenoma risk. Hence, we investigated an association between peripheral blood mtDNA copy number and incident, sporadic colorectal adenoma in 412 colorectal adenoma cases and 526 cancer‐free controls pooled from three colonoscopy‐based case–control studies that used identical methods for case ascertainment, risk factor determination, and biospecimen collection. We also evaluated associations between relative mtDNA copy number and markers of oxidative stress, including circulating F2‐isoprostanes, carotenoids, and fluorescent oxidation products. We measured mtDNA copy number using a quantitative real time polymerase chain reaction (PCR). We used unconditional logistic regression to analyze the association between mtDNA copy number and colorectal adenoma risk after multivariable adjustment. We found no association between logarithmically transformed relative mtDNA copy number, analyzed as a continuous variable, and colorectal adenoma risk (odds ratio = 1.02, 95%CI: 0.82–1.27; P = 0.86). There were no statistically significant associations between relative mtDNA copy number and other markers of oxidative stress. Our findings, taken together with those from previous studies, suggest that relative mtDNA copy number in peripheral blood may more likely be a marker of early colorectal cancer than of risk for the disease or of in vivo oxidative stress. © 2015 Wiley Periodicals, Inc.
Special Care Units and Traditional Care in Dementia: Relationship with Behavior, Cognition, Functional Status and Quality of Life – A Review

Background: Special care facilities for patients with dementia gain increasing attention. However, an overview of studies examining the differences between care facilities with respect to their effects on behavior, cognition, functional status and quality of life is lacking. Results: Our literature search resulted in 32 studies published until October 2012. Overall, patients with dementia who lived at special care units (SCUs) showed a significantly more challenging behavior, more agitation/aggression, more depression and anxiety, more cases of global cognitive impairment and a better psychosocial functioning. There was a tendency towards a better functional status in specialized care facilities, and a better quality of life was found in favor of the SCU group compared to the traditional nursing home (n-SCU) group. Longitudinal studies showed an increased number of neuropsychiatric cases, more patients displaying deteriorating behavior and resistance to care as well as less decline in activities of daily living (ADL) in the SCU group compared to the n-SCU group. Patients in small-scale, homelike SCUs showed more agitation and less ADL decline compared to SCU patients. Conclusion: This review shows that the patient characteristics in SCU and n-SCU settings and, to a minor extent, in SCU and small-scale, homelike SCU settings are different. Over time, there are differences between n-SCU, SCU and small-scale, homelike SCU facilities for some variables.
Takotsubo Cardiomyopathy: A New Form of Acute, Reversible Heart Failure

Several relatively recent case reports and series have described a condition featuring symptoms and signs of acute myocardial infarction without demonstrable coronary artery stenosis or spasm in which the heart takes on the appearance of a Japanese octopus fishing pot called a takotsubo (Figure 1). In takotsubo cardiomyopathy (also called transient apical ballooning and stress cardiomyopathy), left ventricular dysfunction, which can be remarkably depressed, recovers within a few weeks.1–4 Takotsubo cardiomyopathy occurs predominantly in postmenopausal women soon after exposure to sudden, unexpected emotional or physical stress. For instance, the incidence of takotsubo cardiomyopathy increased substantially in elderly women living near the epicenter of the Niigata earthquake.4 Although the left ventricular dysfunction is transient and there is no evidence of obstructive epicardial coronary disease, an increasing number of angioplasty procedures have been performed for presumed acute coronary syndromes. Concepts about the demographics, clinical features, prognosis, and management of this reversible form of left ventricular failure are still evolving. In this brief review, we summarize recent clinical reports and discuss an animal model that may clarify the pathogenesis of this condition.
Measuring Agreement and Discord among Hemagglutination Inhibition Assays Against Different Ophidian Paramyxovirus Strains in the Eastern Massasauga (Sistrurus catenatus catenatus)

Abstract At present, the hemagglutination inhibition (HI) assay is the sole commercially available serologic method available to detect exposure to ophidian paramyxovirus (OPMV) in snakes. During 2006, 26 eastern massasaugas (Sistrurus catenatus catenatus) were collected, and blood was sampled to determine their OPMV status. Samples from each snake were divided into 3 aliquots and tested by using commercially available HI assays against the 4 OPMV isolates used in the 3 laboratories that offer the service. All snakes were tested for antibodies by using HI assays against the green tree python (GTP), San Lucan rattlesnake (SLR), and Aruba Island rattlesnake (AIR) isolates. Twenty-five snakes were tested for antibodies against the western diamondback rattlesnake (WDR) isolate. All samples tested against the GTP and SLR were positive (26/26), whereas 56% (14/25) of the WDR assays were positive, and none (0/ 26) of the AIR assays yielded a positive result. There was 100% agreement between the GTP and SLR assays, and complete disagreement between the SLR and AIR, as well as the GTP and AIR assays. Kappa statistics for the GTP– WDR, SLR–WDR, GTP–AIR, SLR–AIR, and WDR–AIR indicated that the assays had less than chance agreement. The results demonstrate that current HI assays are not reliable as a sole diagnostic assay in the eastern massasauga. Furthermore, HI assays need to be evaluated by using other parameters to determine OPMV exposure in eastern massasaugas.
Recombination in Escherichia coli and the definition of biological species

The DNA sequence of part of the gnd (6-phosphogluconate dehydrogenase) gene was determined for eight wild strains of Escherichia coli and for Salmonella typhimurium. Since a region of the trp (tryptophan) operon and the phoA (alkaline phosphatase) gene have been sequenced from the same strains, the gene trees for these three regions were determined and compared. Gene trees are different from species or strain trees in that a gene tree is derived from a particular segment of DNA, whereas a species or strain tree should be derived from many such segments and is the tree that best represents the phylogenetic relationship of the species or strains. If there were no recombination in E. coli, the gene trees for different genes would not be statistically different from the strain tree or from each other. But, if the gene trees are significantly different, there must have been recombination. Methods are proposed that show these gene trees to be statistically different. Since the gene trees are different, we conclude that recombination is important in natural populations of E. coli. Finally, we suggest that gene trees can be used to create an operational means of defining bacterial species by using the biological species definition.
A performance comparison of the temporally-ordered routing algorithm and ideal link-state routing

We present a relative performance comparison of the temporally-ordered routing algorithm (TORA) with an ideal link state (ILS) routing algorithm. The performance metrics evaluated include bandwidth efficiency for both control and data, as well as end-to-end message packet delay and throughput. The routing algorithms are compared in the context of a dynamic, multihop, wireless network employing broadcast transmissions. The network parameters varied include network size, average rate of topological changes and average network connectivity. While the average network connectivity was found not to be a significant factor, the relative performance of TORA and ILS was found to be critically dependent on the network size, and the average rate of topological changes. The results further indicate that for a given available bandwidth-as either the size of network increases or the rate of network topological change increases, the performance of TORA eventually exceeds that of ILS.
Conditional Estimation for Generalized Linear Models When Covariates Are Subject‐Specific Parameters in a Mixed Model for Longitudinal Measurements

Summary. The relationship between a primary endpoint and features of longitudinal profiles of a continuous response is often of interest, and a relevant framework is that of a generalized linear model with covariates that are subject‐specific random effects in a linear mixed model for the longitudinal measurements. Naive implementation by imputing subject‐specific effects from individual regression fits yields biased inference, and several methods for reducing this bias have been proposed. These require a parametric (normality) assumption on the random effects, which may be unrealistic. Adapting a strategy of Stefanski and Carroll (1987, Biometrika74, 703–716), we propose estimators for the generalized linear model parameters that require no assumptions on the random effects and yield consistent inference regardless of the true distribution. The methods are illustrated via simulation and by application to a study of bone mineral density in women transitioning to menopause.
Methylation variation at IGF2 differentially methylated regions and maternal folic acid use before and during pregnancy

Folic acid (FA) supplementation before and during pregnancy has been associated with decreased risk of neural tube defects although recent reports suggest it may also increase the risk of other chronic diseases. We evaluated exposure to maternal FA supplementation before and during pregnancy in relation to aberrant DNA methylation at two differentially methylated regions (DMRs) regulating Insulin-like Growth Factor 2 (IGF2) expression in infants. Aberrant methylation at these regions has been associated with IGF2 deregulation and increased susceptibility to several chronic diseases. Using a self-administered questionnaire, we assessed FA intake before and during pregnancy in 438 pregnant women. Pyrosequencing was used to measure methylation at two IGF2 DMRs in umbilical cord blood leukocytes. Mixed models were used to determine relationships between maternal FA supplementation before or during pregnancy and DNA methylation levels at birth. Average methylation at the H19 DMR was 61.2%. Compared to infants born to women reporting no FA intake before or during pregnancy, methylation levels at the H19 DMR decreased with increasing FA intake (2.8%, p=0.03, and 4.9%, p=0.04, for intake before and during pregnancy, respectively). This methylation decrease was most pronounced in male infants (p=0.01). Methylation alterations at the H19 DMR are likely an important mechanism by which FA risks and/or benefits are conferred in utero. Because stable methylation marks at DMRs regulating imprinted genes are acquired before gastrulation, they may serve as archives of early exposures with the potential to improve our understanding of developmental origins of adult disease.
Characterization of the capsular polysaccharide of Burkholderia (Pseudomonas) pseudomallei 304b

Burkholderia (Pseudomonas) pseudomallei is the causative agent of melioidosis, a bacterial infection of considerable morbidity in areas of endemicity of Southeast Asia and northern Australia. Clinical isolates of B. pseudomallei have been demonstrated to produce a lipopolysaccharide (LPS) containing two separate and chemically distinct antigenic O polysaccharides against which infected patients produced antibodies. A putative capsular polysaccharide (CPS) has also been reported and is thought to be antigenically conserved based on results of serological studies with clinical B. pseudomallei isolates. In the present study, the CPS isolated from B. pseudomallei 304b from northeastern Thailand was found to have an [alpha]D of +99 degrees (water), was composed of D-galactose (D-Gal), 3-deoxy-D-manno-2-octulosonic acid (KDO), and O-acetyl 3:1:1), and was a linear unbranched polymer of repeating tetrasaccharide units having the following structure: -3)-2-O-Ac-beta-D-Galp-(1-4)-alpha-D-Galp-(1-3)-beta-D -Galp-(1-5)-beta-D-KDOp-(2-. Sera from 13 of 15 patients with different clinical manifestations of melioidosis but not normal controls recognize the CPS, which suggests that it is immunogenic and raises the possibility that it may have a role as a vaccine candidate and/or diagnostic agent.
Comparative assessment of 18F‐Mefway as a serotonin 5‐HT1A receptor PET imaging agent across species: Rodents, nonhuman primates, and humans

We have developed 18F‐trans‐Mefway (18F‐Mefway) for positron emission tomography (PET) imaging studies of serotonin 5‐HT1A receptors which are implicated in various brain functions. Translation of imaging the 5‐HT1A receptor in animal models to humans will facilitate an understanding of the role of the receptor in human brain disorders. We report comparative brain distribution of 18F‐Mefway in normal mice, rats, monkeys, and healthy human volunteers. Mefway was found to be very selective, with subnanomolar affinity for the 5‐HT1A receptor. Affinities of >55 nM were found for all other human‐cloned receptor subtypes tested. Mefway was found to be a poor substrate (>30 μM) for the multidrug resistance 1 protein, suggesting low likelihood of brain uptake being affected by P‐glycoprotein. Cerebellum was used as a reference region in all imaging studies across all species due to the low levels of 18F‐Mefway binding. Consistent binding of 18F‐Mefway in cortical regions, hippocampus, and raphe was observed across all species. 18F‐Mefway in the human brain regions correlated with the known postmortem distribution of 5‐HT1A receptors. Quantitation of raphe was affected by the resolution of the PET scanners in rodents, whereas monkeys and humans showed a raphe to cerebellum ratio of approximately 3. 18F‐Mefway appears to be an effective 5‐HT1A receptor imaging agent in all models, including humans. 18F‐Mefway therefore may be used to quantify 5‐HT1A receptor distribution in brain regions for the study of various CNS disorders. J. Comp. Neurol. 524:1457–1471, 2016. © 2015 Wiley Periodicals, Inc.
Accelerated sampling for the Indian Buffet Process

We often seek to identify co-occurring hidden features in a set of observations. The Indian Buffet Process (IBP) provides a non-parametric prior on the features present in each observation, but current inference techniques for the IBP often scale poorly. The collapsed Gibbs sampler for the IBP has a running time cubic in the number of observations, and the uncollapsed Gibbs sampler, while linear, is often slow to mix. We present a new linear-time collapsed Gibbs sampler for conjugate likelihood models and demonstrate its efficacy on large real-world datasets.
CD-HIT: accelerated for clustering the next-generation sequencing data

Summary: CD-HIT is a widely used program for clustering biological sequences to reduce sequence redundancy and improve the performance of other sequence analyses. In response to the rapid increase in the amount of sequencing data produced by the next-generation sequencing technologies, we have developed a new CD-HIT program accelerated with a novel parallelization strategy and some other techniques to allow efficient clustering of such datasets. Our tests demonstrated very good speedup derived from the parallelization for up to ∼24 cores and a quasi-linear speedup for up to ∼8 cores. The enhanced CD-HIT is capable of handling very large datasets in much shorter time than previous versions. Availability: http://cd-hit.org. Contact: liwz@sdsc.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Autonomous Regulation of Sex-Specific Developmental Programming in Mouse Fetal Germ Cells1

Abstract In mice, unique events regulating epigenetic programming (e.g., genomic imprinting) and replication state (mitosis versus meiosis) occur during fetal germ cell development. To determine whether these processes are autonomously programmed in fetal germ cells or are dependent upon ongoing instructive interactions with surrounding gonadal somatic cells, we isolated male and female germ cells at 13.5 days postcoitum (dpc) and maintained them in culture for 6 days, either alone or in the presence of feeder cells or gonadal somatic cells. We examined allele-specific DNA methylation in the imprinted H19 and Snrpn genes, and we also determined whether these cells remained mitotic or entered meiosis. Our results show that isolated male germ cells are able to establish a characteristic “paternal” methylation pattern at imprinted genes in the absence of any support from somatic cells. On the other hand, cultured female germ cells maintain a hypomethylated status at these loci, characteristic of the normal “maternal” methylation pattern in endogenous female germ cells before birth. Further, the surviving female germ cells entered first meiotic prophase and reached the pachytene stage, whereas male germ cells entered mitotic arrest. These results indicate that mechanisms controlling both epigenetic programming and replication state are autonomously regulated in fetal germ cells that have been exposed to the genital ridge prior to 13.5 dpc.