bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tandem Orthotopic Living Donor Liver Transplantation Followed by Same Donor Haploidentical Hematopoietic Stem Cell Transplantation for DOCK8 Deficiency
Authors: Freeman Alexandra F. , Yazigi Nada , Shah Nirali N. , Kleiner David E. , Parta Mark , Atkinson Prescott , Heller Theo , Holland Steven M. , Kaufman Stuart S. , Khan Khalid M. , Hickstein Dennis D. 
Published: February 2019

Background.An 11-year-old girl with dedicator of cytokinesis 8 (DOCK8) deficiency was proposed for potentially curative hematopoietic stem cell transplantation (HSCT), the donor being her haploidentical mother. However, end-stage liver disease caused by chronicCryptosporidiuminfection required liver transplantation before HSCT.Methods.Consequently, a staged approach of a sequential liver transplant followed by a HSCT was planned with her mother as the donor for both liver and HSCT.Results.The patient successfully underwent a left-lobe orthotopic liver transplant; however, she developed a biliary leak delaying the HSCT. Notably, the recipient demonstrated 3% donor lymphocyte chimerism in her peripheral blood immediately before HSCT. Haploidentical-related donor HSCT performed 2 months after liver transplantation was complicated by the development of acyclovir-resistant herpes simplex virus viremia, primary graft failure, and sinusoidal obstruction syndrome. The patient died from sinusoidal obstruction syndrome–associated multiorgan failure withCandidasepsis on day +40 following HSCT.Conclusions.We discuss the many considerations inherent to planning for HSCT preceded by liver transplant in patients with primary immunodeficiencies, including the role of prolonged immunosuppression and the risk of infection before immune reconstitution. We also discuss the implications of potential recipient sensitization against donor stem cells precipitated by exposure of the recipient to the donor lymphocytes from the transplanted organ.
Dementia Reported Missing
Authors: Lissemore Frances M. , Shatzman Stephanie , Clark Nicholas , Nash Jessica , Miller Rachel , Lerner Alan J. 
Published: February 2019

Background:
Persons with dementia (PWD) reported missing are known to be at high risk for mortality. Analysis of online search engines’ reports of missing PWD may show patterns in the data of this relatively common event and the broad patterns relevant to mortality risk factors.

Methods:
We searched Google news for PWD reported missing for 2015. Demographics, personal details, and outcomes were recorded.

Results:
Of 673 cases, 67 were found deceased, 525 alive, and the remainder had unknown outcomes. Mortality did not differ significantly by race/ethnicity for cases with known outcomes, but cases with unknown outcomes were significantly overrepresented among non-Caucasians (P<0.001; analysis of variance). Duration missing predicted mortality (P<0.001; χ2), and mortality was lower if a photograph was provided (P<0.05; χ2). Five states had no reports and some appeared to have fewer reports that would be expected based on estimates of dementia prevalence.

Conclusions:
Duration missing was the strongest predictor of mortality. Likelihood of mortality was not predicted by use of missing person alerts, and this may be a consequence of inconsistent reporting and follow-up of cases across states. Prevalence and mortality may likewise be underestimated because of the variability in usage and reporting of relevant search terms and definitions. Online resources and social media can provide information about trends and outcomes related to missing persons with dementia, but greater consistency is needed in definitions, searching, and reporting.
Therapeutic noninvasive brain stimulation in Alzheimer's disease and related dementias
Authors: Buss Stephanie S. , Fried Peter J. , Pascual-Leone Alvaro 
Published: February 2019

Purpose of review
Alzheimer's disease is a progressive neurodegenerative disease without effective pharmacological treatment. Noninvasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES), are increasingly being investigated for their potential to ameliorate the symptoms of Alzheimer's disease and related dementias (ADRD).

Recent findings
A comprehensive literature review for primary research reports that investigated the ability of TMS/tES to improve cognition in ADRD patients yielded a total of 20 reports since 2016. Eight studies used repetitive TMS and 12 used transcranial direct current stimulation, the most common form of tES. Eight of the studies combined NIBS with cognitive training. Promising results should encourage continued investigation, however there is currently insufficient evidence to support widespread adoption of NIBS-based clinical treatments for ADRD.

Summary
NIBS remains an active area of investigation for treatment of ADRD, though the predominance of small, heterogeneous, proof-of-principle studies precludes definitive conclusions. We propose the establishment of a consortium to achieve the benefits of large-scale, controlled studies using biomarker-based diagnostic characterization of participants, development of neurophysiological markers to verify target engagement, and standardization of parameters.
A curated transcriptome dataset collection to investigate inborn errors of immunity
Authors: Bougarn Salim , Boughorbel Sabri , Chaussabel Damien , Marr Nico 
Published: February 2019

ABSTRACTPrimary immunodeficiencies (PIDs) are a heterogeneous group of inherited disorders, frequently caused by loss-of-function and less commonly by gain-of-function mutations, which can result in susceptibility to a broad or a very narrow range of infections but also in inflammatory, allergic or malignant diseases. Owing to the wide range in clinical manifestations and variability in penetrance and expressivity, there is an urgent need to better understand the underlying molecular, cellular and immunological phenotypes in PID patients in order to improve clinical diagnosis and management. Here we have compiled a manually curated collection of public transcriptome datasets mainly obtained from human whole blood, peripheral blood mononuclear cells (PBMCs) or fibroblasts of patients with PIDs and of control subjects for subsequent meta-analysis, query and interpretation. A total of nineteen (19) datasets derived from studies of PID patients were identified and retrieved from the NCBI Gene Expression Omnibus (GEO) database and loaded in GXB, a custom web application designed for interactive query and visualization of integrated large-scale data. The dataset collection includes samples from well characterized PID patients that were stimulated ex vivo under a variety of conditions to assess the molecular consequences of the underlying, naturally occurring gene defects on a genome-wide scale. Multiple sample groupings and rank lists were generated to facilitate comparisons of the transcriptional responses between different PID patients and control subjects. The GXB tool enables browsing of a single transcript across studies, thereby providing new perspectives on the role of a given molecule across biological systems and PID patients. This dataset collection is available at: http://pid.gxbsidra.org/dm3/geneBrowser/list.
Lifelong genetically lowered sclerostin and risk of cardiovascular disease
Authors: Bovijn Jonas , Krebs Kristi , Chen Chia-Yen , Boxall Ruth , Censin Jenny C. , Ferreira Teresa , Pulit Sara L. , Glastonbury Craig A. , Laber Samantha , Millwood Iona Y. , Lin Kuang , Li Liming , Chen Zhengming , Milani Lili , Walters Robin G. , Mägi Reedik , Neale Benjamin M. , Lindgren Cecilia M. , Holmes Michael V. 
Published: February 2019

AbstractBackgroundInhibition of sclerostin is a novel therapeutic approach to lowering fracture risk. However, phase III randomised controlled trials (RCTs) of romosozumab, a monoclonal antibody that inhibits sclerostin, suggest an imbalance of serious cardiovascular events.MethodsWe used two independent genetic variants (rs7209826 and rs188810925) in SOST (encoding sclerostin) associated with bone mineral density (BMD) as proxies for therapeutic inhibition of sclerostin. We estimated the effects on risk of osteoporosis, fracture, coronary heart disease (CHD) and a further 22 cardiometabolic risk factors and diseases, by combining data from up to 478,967 participants of European ancestry from three prospective cohorts and up to 1,030,836 participants from nine GWAS consortia. In addition, we performed meta-analyses of cardiovascular outcome data from phase III RCTs of romosozumab.ResultsMeta-analysis of RCTs identified a higher risk of cardiac ischemic events in patients randomised to romosozumab (25 events among 4,298 individuals; odds ratio [OR] 2·98; 95% confidence interval [CI], 1·18 to 7·55; P=0·017). Scaled to the equivalent dose of romosozumab (210mg/month; 0·09 g/cm2 higher BMD), the SOST variants associated with lower risk of fracture (OR, 0·59; 95% CI, 0·54-0·66; P= 1·4×10−24), and osteoporosis (OR, 0·43; 95% CI, 0·36-0·52; P=2·4×10−18). The SOST variants associated with higher risk of myocardial infarction and/or coronary revascularisation (69,649 cases; OR, 1·18; 95% CI, 1·06-1·32; P=0·003) and type 2 diabetes (OR 1·15; 95% CI, 1·05-1·27; P=0·003), higher systolic blood pressure (1·3mmHg; 95% CI 0·8-1·9; P=5·9×10−6) and waist-to-hip-ratio adjusted for BMI (0·05 SDs; 95% CI, 0·02 to 0·08; P=8·5×10−4).ConclusionsGenetically and therapeutically lowered sclerostin leads to higher risk of cardiovascular events. Rigorous evaluation of the cardiovascular safety of romosozumab and other sclerostin inhibitors is warranted.
National HIV testing and diagnosis coverage in sub-Saharan Africa: a new modeling tool for estimating the “first 90” from program and survey data
Authors: Maheu-Giroux M , Marsh K , Doyle C , Godin A , Lanièce Delaunay C , Johnson LF , Jahn A , Abo K , Mbofana F , Boily MC , Buckeridge DL , Hankins C , Eaton JW 
Published: February 2019

AbstractObjectiveHIV testing services (HTS) are a crucial component of national HIV responses. Learning one’s HIV diagnosis is the entry point to accessing life-saving antiretroviral treatment and care. Recognizing the critical role of HTS, theJoint United Nations Programme on HIV/AIDS(UNAIDS) launched the 90-90-90 targets stipulating that by 2020, 90% of people living with HIV know their status, 90% of those who know their status receive antiretroviral therapy, and 90% of those on treatment have a suppressed viral load. Countries will need to regularly monitor progress on these three indicators. Estimating the proportion of people living with HIV who know their status (i.e., the “first 90”), however, is difficult.MethodsWe developed a mathematical model (henceforth referred to as “F90”) that formally synthesizes population-based survey and HTS program data to estimate HIV status awareness over time. The proposed model uses country-specific HIV epidemic parameters from the standard UNAIDS Spectrum model to produce outputs that are consistent with other national HIV estimates. The F90 model provides estimates of HIV testing history, diagnosis rates, and knowledge of HIV status by age and sex. We validate the F90 model using both in-sample comparisons and out-of-sample predictions using data from three countries: Côte d’Ivoire, Malawi, and Mozambique.ResultsIn-sample comparisons suggest that the F90 model can accurately reproduce longitudinal sex-specific trends in HIV testing. Out-of-sample predictions of the fraction of PLHIV ever tested over a 4-to-6-year time horizon are also in good agreement with empirical survey estimates. Importantly, out-of-sample predictions of HIV knowledge are consistent (i.e., within 4% points) with those of the fully calibrated model in the three countries, when HTS program data are included. The F90 model’s predictions of knowledge of status are higher than available self-reported HIV awareness estimates, however, suggesting –in line with previous studies– that these self-reports are affected by non-disclosure of HIV status awareness.ConclusionKnowledge of HIV status is a key indicator to monitor progress, identify bottlenecks, and target HIV responses. The F90 model can help countries track progress towards their “first 90” by leveraging surveys of HIV testing behaviors and annual HTS program data.
Testing models of mRNA localization reveals robustness regulated by reducing transport between cells
Authors: Harrison J. U. , Parton R. M. , Davis I. , Baker R. E. 
Published: February 2019

AbstractRobust control of gene expression in both space and time is of central importance in the regulation of cellular processes, and for multicellular development. However, the mechanisms by which robustness is achieved are generally not identified or well understood. For example, mRNA localization by molecular-motor-driven transport is crucial for cell polarization in numerous contexts, but the regulatory mechanisms that enable this process to take place in the face of noise or significant perturbations are not fully understood. Here we use a combined experimental-theoretical approach to characterize the robustness ofgurken/TGF-alphamRNA localization inDrosophilaegg chambers, where the oocyte and 15 surrounding nurse cells are connected in a stereotypic network via intracellular bridges known as ring canals. We construct a mathematical model that encodes simplified descriptions of the range of steps involved in mRNA localization, including production and transport between and within cells until the final destination in the oocyte. Using Bayesian inference, we calibrate this model using quantitative single molecule fluorescence in situ hybridization data. By analyzing both the steady state and dynamic behaviours of the model, we provide estimates for the rates of different steps of the localization process, as well as the extent of directional bias in transport through the ring canals. The model predicts that mRNA synthesis and transport must be tightly balanced to maintain robustness, a prediction which we tested experimentally using an over-expression mutant. Surprisingly, the over-expression mutant fails to display the anticipated degree of overaccumulation of mRNA in the oocyte predicted by the model. Through careful model-based analysis of quantitative data from the over-expression mutant we show evidence of saturation of transport of mRNA through ring canals. We conclude that this saturation engenders robustness of the localization process, in the face of significant variation in the levels of mRNA synthesis.Statement of significanceFor development to function correctly and reliably across a population, gene expression must be controlled robustly in a repeatable manner. How this robustness is achieved is not well understood. We use modelling to better study the localization of polarity determining transcripts (RNA) in fruit fly development. By calibrating our model with quantitative imaging data we are able to make experimentally testable predictions, comparison of which with data from a genetic mutant, reveals evidence that saturation of RNA transport contributes to the robustness of RNA localization.
Multiscale analysis of a non-periodic epidemic time series using wavelet transform
Authors: Gaudart Jean , Rebaudet Stanislas , Texier Gaetan , Barrais Robert , Piarroux Renaud , Giorgi Roch 
Published: February 2019

SummaryThe aim of the present study was to develop a method for multiscale analysis of non-stationary and non-periodic epidemic time series. Indeed, the epidemiologists may need to know the features, at different resolutions, of short duration outbreaks that did not exhibit periodic cycles. Among of the large number of wavelets, we have developed a continuous wavelet that shows an analogous shape to the Haar wavelet, and leads to precise time localization. We applied the wavelet transform to the cholera epidemic, which began in October 2010 in Haiti. We determined the wavelet spectra of both the cholera case toll and rainfall time series, from September 01, 2010, to November 20, 2012 (812 days). The relationship between case toll and rainfall was analyzed using cross-wavelet spectra at different lags. Cholera case toll scalogram highlighted four epidemic bursts. Cross-wavelet analysis highlighted an absence of relationship between the first epidemic burst and rainfall, but a clear relationship between the following epidemic bursts and rainfall after a 3 to 8 day lag.
The role of “spillover” in antibiotic resistance
Authors: Olesen Scott W. , Lipsitch Marc , Grad Yonatan H. 
Published: February 2019

ABSTRACTAntibiotic use is a key driver of antibiotic resistance. Understanding the quantitative association between antibiotic use and resulting resistance is important for predicting future rates of antibiotic resistance and for designing antibiotic stewardship policy. However, the use-resistance association is complicated by “spillover”, in which one population’s level of antibiotic use affects another population’s level of resistance via the transmission of bacteria between those populations. Spillover is known to have effects at the level of families and hospitals, but it is unclear if spillover is relevant at larger scales. We used mathematical modeling and analysis of observational data to address this question. First, we used dynamical models of antibiotic resistance to predict the effects of spillover. Whereas populations completely isolated from one another do not experience any spillover, we found that if even 1% of interactions are between populations, then spillover may have large consequences: the effect of a change in antibiotic use in one population on antibiotic resistance in that population could be reduced by as much as 50%. Then, we quantified spillover in observational antibiotic use and resistance data from US states and European countries for 3 pathogen-antibiotic combinations, finding that increased interactions between populations were associated with smaller differences in antibiotic resistance between those populations. Thus, spillover may have an important impact at the level of states and countries, which has ramifications for predicting the future of antibiotic resistance, designing antibiotic resistance stewardship policy, and interpreting stewardship interventions.
More accuracy estimation of the worm burden in the ascariasis of children in Kinshasa
Authors: Tshima Guyguy Kabundi , Mulumba Paul Madishala 
Published: February 2019

ABSTRACTThe present study aims to give a better estimate of the worm burden (ascariasis) to address accurately the impact of intestinal parasitosis on the children growth in Africa.The study was conducted on 20 subjects aged 10 months to 10 years (Mean ± SD: 5.6 ± 2.3 years). They were treated with 10 mg/kg of Pyrantel pamoate. The next day, the stools were collected, washed and filtered to harvest all adult ascaris. In total, 141 ascaris (71 males and 70 females) were extracted for 879.9 g of stool. The geometric mean of eggs counted was 29 by 2 mg of stool. The daily eggs laying per female was estimated to 202,500 eggs/days (CI95%: 128,800 – 276,200).Statistical analysis shows that the parasitic worm burden was proportional both to the number eggs counted per unit of stool volume, and to age of infested subject. A regression model based on these two parameters, with a coefficient of determination equal to 59 %, was retained. Thus, for an old subject respectively of 1, 5 and 10 years, at which 1 egg of ascaris in approximately 2 mg of a preparation would lodge a respective parasitic mass of 1, 3 and 9 g. The results are in the form of confidence interval. For example, for a 5 years old subject with an average of 10 eggs (CI95% = 5.6 - 14.4) after reading of 2 separated preparations coming from the same specimen, the estimated parasitic load is laying between 7 and 11 g.
The ‘hidden side’ of spin labeled oligonucleotides: Molecular Dynamics study focusing on the EPR-silent components of base pairing
Authors: Chandra Dantu Sarath , Sicoli Giuseppe 
Published: February 2019

AbstractNitroxide labels are combined with nucleic acid structures and studied using electron paramagnetic resonance experiments (EPR). As X-ray/NMR structures are unavailable with the nitroxide labels, detailed residue level information, down to atomic resolution, about the effect of these nitroxide labels on local RNA structures is currently lacking. This information is critical to evaluate the choice of spin label. In this study, we compare and contrast the effect of TEMPO-based (NT) and rigid spin (Ç) labels (in both 2’-O methylated and not-methylated forms) on RNA duplexes. We also investigate sequence-dependent effects of NT label on RNA duplex along with the more complex G-quadruplex RNA. Distances measured from molecular dynamics simulations between the two spin labels are in agreement with the EPR experimental data. To understand the effect of labeled oligonucleotides on the structure, we studied the local base pair geometries and global structure in comparison with the unlabeled structures. Based on the structural analysis, we can conclude that TEMPO-based and Ç labels do not significantly perturb the base pair arrangements of the native oligonucleotide. When experimental structures for the spin labelled DNA/RNA molecules are not available, general framework offered by the current study can be used to provide information critical to the choice of spin labels to facilitate future EPR studies.Graphical abstract
Islands of retroelements are the major components ofDrosophilacentromeres
Authors: Chang Ching-Ho , Chavan Ankita , Palladino Jason , Wei Xiaolu , Martins Nuno M. C. , Santinello Bryce , Chen Chin-Chi , Erceg Jelena , Beliveau Brian J. , Wu Chao-Ting , Larracuente Amanda M. , Mellone Barbara G. 
Published: February 2019

AbstractCentromeres are essential chromosomal regions that mediate kinetochore assembly and spindle attachments during cell division. Despite their functional conservation, centromeres are amongst the most rapidly evolving genomic regions and can shape karyotype evolution and speciation across taxa. Although significant progress has been made in identifying centromere-associated proteins, the highly repetitive centromeres of metazoans have been refractory to DNA sequencing and assembly, leaving large gaps in our understanding of their functional organization and evolution. Here, we identify the sequence composition and organization of the centromeres ofDrosophila melanogasterby combining long-read sequencing, chromatin immunoprecipitation for the centromeric histone CENP-A, and high-resolution chromatin fiber imaging. Contrary to previous models that heralded satellite repeats as the major functional components, we demonstrate that functional centromeres form on islands of complex DNA sequences enriched in retroelements that are flanked by large arrays of satellite repeats. Each centromere displays distinct size and arrangement of its DNA elements but is similar in composition overall. We discover that a specific retroelement,G2/Jockey-3, is the most highly enriched sequence in CENP-A chromatin and is the only element shared among all centromeres.G2/Jockey-3is also associated with CENP-A in the sister speciesDrosophila simulans, revealing an unexpected conservation despite the reported turnover of centromeric satellite DNA. Our work reveals the DNA sequence identity of the active centromeres of a premier model organism and implicates retroelements as conserved features of centromeric DNA.