bluuebunny/crossref_metadata_2025_split huggingface dataset:
A National Survey on the Use of Electronic Directly Observed Therapy for Treatment of Tuberculosis
Authors: Macaraig Michelle , Lobato Mark N. , McGinnis Pilote Kara , Wegener Donna 
Published: July 2017

Context:
An increasing number of tuberculosis (TB) programs are adopting electronic directly observed therapy (eDOT), the use of technology to supervise patient adherence remotely. Pilot studies show that treatment adherence and completion were similar with eDOT compared with the standard in-person DOT.

Objective:
In December 2015, the National Tuberculosis Controllers Association administered an online survey to determine the extent to which eDOT is used in the United States.

Participants:
Sixty-eight Centers for Disease Control and Prevention (CDC)–funded health department TB programs across the United States and a convenient sample of local health department TB programs.

Results:
Fifty-six (82%) of 68 CDC-funded health department TB programs and an additional 57 local TB programs responded to the survey. Forty-seven (42%) of 113 TB programs are currently using eDOT, 41 (36%) are planning to implement it in the next year, and 25 (22%) have no plans to implement eDOT. Of the 47 TB programs using eDOT, 31 (66%) use synchronous video DOT, 4 (9%) asynchronous video DOT, 11 (23%) a combination of both, and 1 (2%) ingestible sensor to conduct electronic observations. Forty-one (87%) indicated that treatment adherence and 40 (85%) indicated that treatment completion were about the same or higher than in-person DOT. More than 80% indicated that eDOT resulted in program cost savings, and almost all (91%) reported benefits in patient and staff satisfaction. However, 25 (53%) of the 47 TB programs that use eDOT encountered technical challenges and 37 (79%) offer eDOT to less than a third of their patients.

Conclusions:
Results from this survey indicate that eDOT is a promising tool that can be utilized to efficiently and effectively manage TB treatment. Findings will inform other TB programs interested in implementing eDOT. However, further evaluation is needed to assess eDOT acceptability to understand barriers to eDOT implementation from the patient and provider perspectives.
Quantification of Immune Dysregulation by Next-generation Polymerase Chain Reaction to Improve Sepsis Diagnosis in Surgical Patients
Authors: Almansa Raquel , Ortega Alicia , Ávila-Alonso Ana , Heredia-Rodríguez Maria , Martín Silvia , Benavides Diana , Martín-Fernandez Marta , Rico Lucia , Aldecoa César , Rico Jesús , López de Cenarruzabeitia Iñigo , Beltrán de Heredia Juan , Gomez-Sanchez Esther , Aragón Marta , Andrés Cristina , Calvo Dolores , Andaluz-Ojeda David , Liu Pilar , Blanco-Antona Francisco , Blanco Lydia , Gómez-Herreras Jose Ignacio , Tamayo Eduardo , Bermejo-Martin Jesus F. 
Published: July 2017

Objectives:
To quantify immunological dysfunction in surgical patients with presence/absence of sepsis using a droplet digital polymerase chain reaction (ddPCR) transcriptomic analysis. The study also aims to evaluate this approach for improving identification of sepsis in these patients.

Background:
Immune dysregulation is a central event in sepsis. Quantification of the expression of immunological genes participating in the pathogenesis of sepsis could represent a new avenue to improve its diagnosis.

Methods:
Expression of 6 neutrophil protease genes (MMP8, OLFM4, LCN2/NGAL, LTF, PRTN3, MPO) and also of 5 genes involved in the immunological synapse (HLA-DRA, CD40LG, CD3E, CD28, ICOS) was quantified in blood from 101 surgical patients with sepsis, 53 uninfected surgical patients, and 16 blood donors by using ddPCR. Areas under receiver operating characteristic curves (AUROC) and multivariate regression analysis were employed to test individual genes and gene ratios to identify sepsis, in comparison with procalcitonin.

Results:
Sepsis-induced overexpression of neutrophil protease genes and depressed expression of immunological synapse genes. MMP8/HLA-DRA, LCN2/HLA-DRA outperformed procalcitonin in differentiating between patients with sepsis and surgical controls in the AUROC analysis: LCN2/HLA-DRA: 0.90 (0.85–0.96), MMP8/HLA-DRA: 0.89 (0.84–0.95), procalcitonin: 0.80 (0.73–0.88) (AUROC, confidence interval 95%), and also in the multivariate analysis: LCN2/HLA-DRA: 8.57 (2.25–32.62); MMP8/HLA-DRA: 8.03 (2.10–30.76), procalcitonin: 4.20 (1.15–15.43) [odds ratio (confidence interval 95%)]. Gene expression levels of HLA-DRA were an independent marker of hospital mortality.

Conclusions:
Quantifying the transcriptomic ratios MMP8/HLA-DRA, LCN2/HLA-DRA by ddPCR is a promising approach to improve sepsis diagnosis in surgical patients.
Plasma Proenkephalin and Poor Long-Term Outcome in Renal Transplant Recipients
Authors: Kieneker Lyanne M. , Hartmann Oliver , Struck Joachim , Bergmann Andreas , Gansevoort Ron T. , Joosten Michel M. , van den Berg Else , de Boer Rudolf A. , Bakker Stephan J.L. 
Published: July 2017

Background
Proenkephalin (pro-ENK), a stable and reliable surrogate marker for unstable enkephalins, was found to be associated with acute kidney injury and chronic renal failure in previous studies. We aimed to investigate whether pro-ENK is linked to chronic kidney injury and poor long-term outcome in renal transplant recipients (RTR).

Methods
We included 664 stable RTR and 95 healthy kidney donors. Pro-ENK was measured in plasma with a double monoclonal sandwich immunoassay. Graft failure was defined as return to dialysis therapy or retransplantation.

Results
Median pro-ENK was 110 pmol/L (interquartile range [IQR], 85-148 pmol/L) in RTR and 48 pmol/L (IQR, 42-55 pmol/L) in kidney donors. Pro-ENK was correlated with estimated glomerular filtration rate (GFR) (r
s = −0.80, P < 0.001) in RTR and with measured GFR (r
s = −0.74, P < 0.001) in kidney donors. During a median follow-up of 3.1 years (IQR, 2.7-3.9 years), 45 RTR developed graft failure and 76 died. Pro-ENK was positively associated with risk (hazard ratio [HR] per standard deviation increment of the logarithm of pro-ENK; 95% confidence interval [CI]) of graft failure (HR, 4.80; 95% CI, 3.55-6.48) and mortality (HR, 1.50; 95% CI, 1.22-1.85). After adjustment of age, sex, and estimated GFR, the association of pro-ENK with graft failure remained significant (HR, 2.36; 95% CI, 1.37-4.06), whereas no significant association of pro-ENK with risk of all-cause mortality was observed (HR, 1.34; 95% CI, 0.90-2.09).

Conclusions
Plasma pro-ENK is associated with kidney function as reflected by correlations with measured GFR in both RTR and kidney donors. In addition, pro-ENK was independently associated with increased risk of graft failure in RTR. Pro-ENK may aid in identification of RTR at risk for late graft failure.
High Intrapatient Variability of Tacrolimus Levels and Outpatient Clinic Nonattendance Are Associated With Inferior Outcomes in Renal Transplant Patients
Authors: Goodall Dawn L. , Willicombe Michelle , McLean Adam G. , Taube David 
Published: July 2017

Background
Nonadherence to immunosuppressants is associated with rejection and allograft loss. Intrapatient variability (IPV) of immunosuppression levels is a marker of nonadherence. This study describes the impact of IPV of tacrolimus levels in patients receiving a tacrolimus monotherapy immunosuppression protocol.

Methods
We retrospectively analyzed the outpatient tacrolimus levels of kidney-only transplant patients taken between 6 and 12 months posttransplant. IPV was determined using the coefficient of variance.

Results
Six hundred twenty-eight patients with a mean number of 8.98 ± 3.81 tacrolimus levels and a mean follow-up of 4.72 ± 2.19 years were included. Multivariate analysis showed death was associated with increasing age (1.04 [1.01-1.07], P = 0.0055), diabetes at time of transplant (2.79 [1.44-5.41], P = 0.0024), and rejection (2.34 [1.06-5.19], P = 0.036). Variables associated with graft loss included the highest variability group (2.51 [1.01-6.27], P = 0.048), mean tacrolimus level less than 5 ng/mL (4.32 [1.94-9.63], P = 0.0003), a high clinic nonattendance rate (1.10 [1.01-1.20], P = 0.03), and rejection (9.83 [4.62-20.94], P < 0.0001). Independent risk factors for rejection were de novo donor-specific antibody (3.15 [1.84-5.39], P < 0.0001), mean tacrolimus level less than 5 ng/mL (2.57 [1.27-5.19], P = 0.00860, and a high clinic nonattendance rate (1.11 [1.05-1.18], P = 0.0005).

Conclusions
This study shows that high tacrolimus IPV and clinic nonattendance are associated with inferior allograft survival. Interventions to minimize the causes of high variability, particularly nonadherence are essential to improve long-term allograft outcomes.
Divergence times in demosponges (Porifera): first insights from new mitogenomes and the inclusion of fossils in a birth-death clock model
Authors: Schuster Astrid , Vargas Sergio , Knapp Ingrid S. , Pomponi Shirley A. , Toonen Robert J. , Erpenbeck Dirk , Wöerheide Gert 
Published: July 2017

AbstractApproximately 80% of all recent sponge species belong to the class Demospongiae. Yet, despite their diversity and importance, accurate divergence times are still unknown for most demosponge clades. The estimation of demosponge divergence time is key to answering fundamental questions like e.g. the origin of Demospongiae, their diversification and historical biogeography. Molecular sequence data alone is not informative on an absolute time scale, and therefore needs to be “calibrated” with additional data such as fossils. Here, we apply the fossilized birth-death model (FBD), which has the advantage, compared to strict node dating with the oldest fossil occurrences, that it allows for the inclusion of young and old fossils in the analysis of divergence time. We use desma-bearing sponges, a diverse group of demosponges that form rigid skeletons and have a rich and continuous fossil record dating back to the Cambrian (∼500 Ma), aiming to date the demosponge radiation and constrain the timing of key evolutionary events, like the transition from marine to freshwater habitats. To do so, we assembled mitochondrial genomes of six desma-bearing demosponges from size-selected reduced-representation genomic libraries and apply a fossilized birth-death model including 30 fossils and 33 complete demosponge mitochondrial genomes to infer a dated phylogeny of Demospongiae. Our study supports a Neoproterozoic origin of Demospongiae. Novel age estimates for the split of freshwater and marine sponges dating back to the Carboniferous and the previously assumed Recent (∼18 Ma) diversification of freshwater sponges is supported. Moreover, we provide detailed age estimates for a possible diversification of Tetractinellidae (∼315 Ma), the Astrophorina (∼240 Ma), the Spirophorina (∼120 Ma) and the family Corallistidae (∼188 Ma) all of which are considered as key groups for dating the Demospongiae, due to their extraordinary rich and continuous fossil history.
NMDA-receptor antibodies alter cortical microcircuit dynamics
Authors: Rosch RE , Wright S , Cooray G , Papadopoulou M , Goyal S , Lim M , Vincent A , Upton AL , Baldeweg T , Friston KJ 
Published: July 2017

AbstractNMDA-receptor antibodies (NMDAR-Ab) cause an autoimmune encephalitis with a diverse range of electroencephalographic (EEG) abnormalities. NMDAR-Ab are believed to disrupt receptor function, but how blocking this excitatory neurotransmitter can lead to paroxysmal EEG abnormalities – or even seizures – is poorly understood. Here, we show that NMDAR-Ab change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity, and predispose to paroxysmal EEG abnormalities. Based on local field potential recordings in a mouse model, we first validate a dynamic causal model of NMDAR-Ab effects on cortical microcircuitry. Using this model, we then identify the key synaptic parameters that best explain EEG paroxysms in paediatric patients with NMDAR-Ab encephalitis. Finally, we use the mouse model to show that NMDAR-Ab- related changes render microcircuitry critically susceptible to overt EEG paroxysms, when these key parameters are changed. These findings offer mechanistic insights into circuit-level dysfunction induced by NMDAR-Ab.
Whole Genome Sequencing in Psychiatric Disorders: the WGSPD Consortium
Authors: Sanders Stephan J. , Neale Benjamin M. , Huang Hailiang , Werling Donna M. , An Joon-Yong , Dong Shan ,   Whole Genome Sequencing for Psychiatric Disorders, Abecasis Goncalo , Arguello P. Alexander , Blangero John , Boehnke Michael , Daly Mark J. , Eggan Kevin , Geschwind Daniel H. , Glahn David C. , Goldstein David B. , Gur Raquel E. , Handsaker Robert E. , McCarroll Steven A. , Ophoff Roel A. , Palotie Aarno , Pato Carlos N. , Sabatti Chiara , State Matthew W. , Willsey A. Jeremy , Hyman Steven E. , Addington Anjene M. , Lehner Thomas , Freimer Nelson B. 
Published: July 2017

AbstractAs technology advances, whole genome sequencing (WGS) is likely to supersede other genotyping technologies. The rate of this change depends on its relative cost and utility. Variants identified uniquely through WGS may reveal novel biological pathways underlying complex disorders and provide high-resolution insight into when, where, and in which cell type these pathways are affected. Alternatively, cheaper and less computationally intensive approaches may yield equivalent insights. Understanding the role of rare variants in the noncoding gene-regulating genome, through pilot WGS projects, will be critical to determine which of these two extremes best represents reality. With large cohorts, well-defined risk loci, and a compelling need to understand the underlying biology, psychiatric disorders have a role to play in this preliminary WGS assessment. The WGSPD consortium will integrate data for 18,000 individuals with psychiatric disorders, beginning with autism spectrum disorder, schizophrenia, bipolar disorder, and major depressive disorder, along with over 150,000 controls.
Solution structure of sperm lysin yields novel insights into molecular dynamics of rapid protein evolution
Authors: Wilburn Damien B. , Tuttle Lisa M. , Klevit Rachel E. , Swanson Willie J. 
Published: July 2017

AbstractProtein evolution is driven by the sum of different physiochemical and genetic processes that usually results in strong purifying selection to maintain biochemical functions. However, proteins that are part of systems under arms race dynamics often evolve at unparalleled rates that can produce atypical biochemical properties. In the marine mollusk abalone, lysin and VERL are a pair of rapidly coevolving proteins that are essential for species-specific interactions between sperm and egg. Despite extensive biochemical characterization of lysin, including crystal structures of multiple orthologs, it was unclear how sites under positive selection may facilitate recognition of VERL. Using a combination of targeted mutagenesis and multidimensional NMR, we present a high-definition solution structure of sperm lysin from red abalone (Haliotis rufescens). Unapparent from the crystallography data, multiple NMR-based analyses conducted in solution reveal clustering of the N-and C-termini to form a nexus of 13 positively selected sites that constitute a VERL binding interface. Evolutionary rate was found to be a significant predictor of backbone flexibility, which may be critical for lysin bioactivity and / or accelerated evolution. These flexible, rapidly evolving segments that constitute the VERL binding interface were also the most distorted regions of the crystal structure relative to what was observed in solution. While lysin has been the subject of extensive biochemical and evolutionary analyses for more than 30 years, this study highlights the enhanced insights gained from applying NMR approaches to rapidly evolving proteins.SignificanceThe fertilization of eggs by sperm is a critical biological process for nearly all sexually reproducing organisms to propagate their genetic information. Despite the importance of fertilization, the molecules that mediate egg-sperm interactions have been characterized for only a few species, and the biochemical mechanisms underlying these interactions are even less well understood. In the marine mollusk abalone, sperm lysin interacts with egg VERL in a species-specific manner to facilitate fertilization. In this report, we characterized the solution structure and molecular evolution of sperm lysin from red abalone (Haliotis rufescens), and identified the VERL binding interface as well as important lysin dimer interactions that have emerged as part of an incessant sexual arms race.
Effects of fragmentation on the seed predation and dispersal by rodents differ among species with different seed size
Authors: CHEN Qiong , TOMLINSON Kyle W. , CAO Lin , WANG Bo 
Published: July 2017

AbstractFragmentation influences the population dynamics and community composition of vertebrate animals. Fragmentation effects on rodent species in forests may, in turn, affect seed predation and dispersal of many plant species. Previous studies have usually addressed this question by monitoring a single species, and their results are contradictory. Very few studies have discussed the fragmentation effect on rodent–seed interaction among tree species with different seed sizes, which can significantly influence rodent foraging preference and seed fate. Given that fruiting periods for many coexisting plant species overlap, the changing foraging preference of rodents may substantially alter plant communities. In this study, we monitored the dispersal and predation by rodents of 9600 seeds, belonging to 4 Fagaceae species with great variation in seed size, in both the edge and interior areas of 12 tropical forest fragments ranging in area from 6.3 to 13872.9 ha in Southwest China. The results showed that forest fragmentation altered the seed fates of all the species, but the intensity and even the direction of fragmentation effect differed between species with large versus small seeds. For the seeds harvested, fragment size showed negative effects in forest interiors but positive effects at edges for the 2 large‐seeded species, but showed little effect for the 2 small‐seeded species. For the seeds removed, negative effects of fragment size only existed among the small‐seeded species. The different fragmentation effect on seed dispersal and predation among plant species may, in turn, translate into the composition differences of the regeneration of the whole fragmented forest.
Conflicts of Interest in Emergency Medicine
Authors: Geiderman Joel Martin , Iserson Kenneth V. , Marco Catherine A. , Jesus John , Venkat Arvind 
Published: July 2017

AbstractConflicts of interest (COIs) are common in the practice of emergency medicine and may be present in the areas of clinical practice, relations with industry, expert witness testimony, medical education, research, and organizations. A COI occurs when there is dissonance between a primary interest and another interest. The concept of professionalism in medicine places the patient as the primary interest in any interaction with a physician. We contend that patient welfare is the ultimate interest in the entire enterprise of medicine. Recognition and management of potential, real, and perceived COIs is essential to the ethical practice of emergency medicine. This paper discusses how to recognize, address, and manage them.
Holocene Brahmaputra River path selection and variable sediment bypass as indicators of fluctuating hydrologic and climate conditions in Sylhet Basin, Bangladesh
Authors: Sincavage Ryan , Goodbred Steven , Pickering Jennifer 
Published: July 2017

AbstractThe Holocene stratigraphy of Sylhet basin, a tectonically influenced sub‐basin within the Ganges‐Brahmaputra‐Meghna delta (GMBD), provides evidence for autogenic and allogenic controls on fluvial system behaviour. Using Holocene lithology and stratigraphic architecture from a dense borehole network, patterns of bypass‐dominated and extraction‐enhanced modes of sediment transport and deposition have been reconstructed. During a ~3‐kyr mid‐Holocene occupation of Sylhet basin by the Brahmaputra River, water and sediment were initially (~7.5–6.0 ka) routed along the basin's western margin, where limited downstream facies changes reflect minimal mass extraction and bypass‐dominated transport to the basin outlet. Sediment‐dispersal patterns became increasingly depositional ~6.0–5.5 ka with the activation of a large (~2250 km2) splay that prograded towards the basin centre while maintaining continued bypass along the western pathway. Beginning ~5.0 ka, a second splay system constructed an even larger (~3800 km2) lobe into the most distal portions of the basin along the Shillong foredeep. This evolution from a bypass‐dominated system to one of enhanced mass extraction is well reflected in (i) the rapid downstream fining of deposited sand and (ii) a change in facies from amalgamated channel deposits to mixed sands and muds within discrete depositional lobes. The persistence of sediment bypass suggests that seasonal flooding of the basin by local runoff exerts a hydrologic barrier to overbank flow and is thus a principal control on river path selection. This control is evidenced by (i) repeated, long‐term preference for occupying a course along the basin margin rather than a steeper path to the basin centre and (ii) the persistence of an under‐filled, topographically low basin despite sediment load sufficient to fill the basin within a few hundred years. The progradation of two 10–20‐m thick, sandy mega‐splays into the basin interior reflects an alternative mode of sediment dispersal that appears to have operated only in the mid‐Holocene (~6.0–4.0 ka) during a regional weakening of the summer monsoon. The reduced water budget at that time would have lowered seasonal water levels in the basin, temporarily lessening the hydrologic barrier effect and facilitating splay development into the basin interior. Overall, these results place basin hydrology as a first‐order control on fluvial system behaviour, strongly modifying the perceived dominance of tectonic subsidence. Such coupling of subsidence, fluvial dynamics and local hydrology have been explored through tank experiments and modelling; this field study demonstrates that complex, emergent behaviours can also scale to the world's largest fluvial system.