bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconfiguration of brain network architectures between resting state and complexity-dependent cognitive reasoning
Authors: Hearne Luke J. , Cocchi Luca , Zalesky Andrew , Mattingley Jason B. 
Published: July 2017

AbstractOur capacity for higher cognitive reasoning has a measureable limit. This limit is thought to arise from the brain’s capacity to flexibly reconfigure interactions between spatially distributed networks. Recent work, however, has suggested that reconfigurations of task-related networks are modest when compared with intrinsic ‘resting state’ network architecture. Here we combined resting state and task-driven functional magnetic resonance imaging to examine how flexible, task-specific reconfigurations associated with increasing reasoning demands are integrated within a stable intrinsic brain topology. Human participants (21 males and 28 females) underwent an initial resting state scan, followed by a cognitive reasoning task involving different levels of complexity, followed by a second resting state scan. The reasoning task required participants to deduce the identity of a missing element in a 4 × 4 matrix, and item difficulty was scaled parametrically as determined by relational complexity theory. Analyses revealed that external task engagement was characterized by a significant change in functional brain modules. Specifically, resting state and null-task demand conditions were associated with more segregated brain network topology, whereas increases in reasoning complexity resulted in merging of resting state modules. Further increments in task complexity did not change the established modular architecture, but impacted selective patterns of connectivity between fronto-parietal, subcortical, cingulo-opercular and default-mode networks. Larger increases in network efficiency within the newly established task modules were associated with higher reasoning accuracy. Our results shed light on the network architectures that underlie external task engagement, and highlight selective changes in brain connectivity supporting increases in task complexity.Significance StatementHumans have clear limits in their ability to solve complex reasoning problems. It is thought that such limitations arise from flexible, moment-to-moment reconfigurations of functional brain networks. It is less clear how such task-driven adaptive changes in connectivity relate to stable, intrinsic networks of the brain and behavioral performance. We found that increased reasoning demands rely on selective patterns of connectivity within cortical networks that emerged in addition to a more general, task-induced modular architecture. This task-driven architecture reverted to a more segregated resting state architecture both immediately before and after the task. These findings reveal how flexibility in human brain networks is integral to achieving successful reasoning performance across different levels of cognitive demand.
Multiplexed Gene Synthesis in Emulsions for Exploring Protein Functional Landscapes
Authors: Plesa Calin , Sidore Angus M. , Lubock Nathan B. , Zhang Di , Kosuri Sriram 
Published: July 2017

AbstractNext-generation sequencing has engendered an expanding suite of functional assays that can test sequence-function relationships at unprecedented scales in pooled formats (multiplex). Such assays are currently constrained by the short length of oligonucleotide (oligo) pools, which limit potential applications. Here we report a simple, low-cost, and scalable method called DropSynth that assembles gene libraries from oligo pools for use in multiplexed functional assays. DropSynth utilizes a library of barcoded beads to isolate and concentrate oligos needed for a gene’s synthesis in a pooled format. These bead-bound oligos are then emulsified, processed, and assembled into genes within the emulsion droplets. We synthesized ~1000 phylogenetically diverse orthologs of phosphopantetheine adenylyltransferase (PPAT) and tested their fitness in a multiplexed functional assay. While the majority of orthologs complement, those that do not are broadly distributed across the phylogenetic tree. Synthetic errors in our assemblies allow us to explore local landscapes around the designed orthologs revealing constrained mutations for complementing orthologs as well as gain-of-function mutations for low-fitness orthologs. This broad mutational scanning approach is complementary to deep mutational scanning and helps us understand proteins by probing evolutionarily divergent sequences that share function.
Multi-scale immune selection and the transmission-diversity feedback ofPlasmodium falciparummalaria
Authors: Holding Thomas , Valletta John Joseph , Recker Mario 
Published: July 2017

AbstractAntigenic diversity is a key factor underlying the complex epidemiology ofPlasmodium falciparummalaria. Within-host clonal antigenic variation limits host exposure to the parasite’s antigenic repertoire, while the high degree of diversity at the population-level requires multiple exposures for hosts to acquire anti-disease immunity. This diversity is predominantly generated through mitotic and meiotic recombination between individual genes and multi-gene repertoires and is therefore expected to respond dynamically to changes in transmission and immune selection. We hypothesised that this coupling creates a positive feedback mechanism whereby infection and disease transmission promotes the generation of diversity, which itself facilitates immune evasion and hence further infection and transmission. To investigate the link between diversity and malaria prevalence in more detail we developed an individual-based model in which antigenic diversity emerges as a dynamic property from the underlying transmission processes. We show that the balance between stochastic extinction and the generation of new antigenic variants is intrinsically linked to within-host and between-host immune selection, which in turn determines the level of diversity that can be maintained in a given population. We further show that the transmission-diversity feedback can lead to temporal lags in the response to natural or intervention-induced perturbations in transmission rates. These results will add to our understanding of the epidemiological dynamics ofP. falciparummalaria in different transmission settings and will have important implications for monitoring and assessing the effectiveness of disease control efforts.
Bifurcation analysis of metabolic pathways: an illustration from yeast glycolysis
Authors: Overal Gosse , Teusink Bas , Bruggeman Frank J. , Hulshof Josephus , Planqué Robert 
Published: July 2017

AbstractIn microorganisms such as bacteria or yeasts, metabolic rates are tightly coupled to growth rate, and therefore to fitness. Although the topology of central pathways are largely conserved across organisms, the enzyme kinetics and their parameters generally vary. This prevents us to understand and predict (changes in) metabolic dynamics. The analytical treatment of metabolic pathways is generally restricted to small models, containing maybe two to four equations. Since such small core models involve much coarse graining, their biological interpretation is often hampered. In this paper we aim to bridge the gap between analytical, more in-depth treatment of small core models and biologically more realistic and detailed models by developing new methods. We illustrate these methods for a model of glycolysis inSaccharo-myces cerevisiaeyeast, arguably the best characterised metabolic pathway in the literature. The model is more involved than in previous studies, and involves both ATP/ADP and NADH/NAD householding.A detailed analysis of the steady state equations sheds new light on two recently studied biological phenomena in yeast glycolysis: whether it is to be expected that fructose-1,6-biphosphate (FBP) parameterises all steady states, and the occurrence of bistability between a regular steady state and imbalanced steady state in which glycolytic intermediates keep accumulating.This work shows that the special structure of metabolic pathways does allow for more in-depth bifurcation analyses than is currently the norm. We especially emphasise which of the techniques developed here scale to larger pathways, and which do not.
Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD
Authors: Atasoy Selen , Roseman Leor , Kaelen Mendel , Kringelbach Morten L. , Deco Gustavo , Carhart-Harris Robin L. 
Published: July 2017

ABSTRACTRecent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used ‘connectome-harmonic decomposition’, a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.
HtrA1 activation is driven by an allosteric mechanism of inter-monomer communication
Authors: Cabrera Alvaro Cortes , Melo Esther , Roth Doris , Topp Andreas , Delobel Frederic , Stucki Corinne , Chen Chia-yi , Jakob Peter , Banfai Balazs , Dunkley Tom , Schilling Oliver , Huber Sylwia , Iacone Roberto , Petrone Paula 
Published: July 2017

ABSTRACTThe human protease family HtrA is responsible for preventing protein misfolding and mislocalization, and a key player in several cellular processes. Among these, HtrA1 is implicated in several cancers, cerebrovascular disease and age-related macular degeneration. HtrA1 activation, although very relevant for drug-targeting this protease, remains poorly characterized. Our work provides a mechanistic step-by-step description of HtrA1 activation and regulation. We report that the HtrA1 trimer is regulated by an allosteric mechanism by which monomers relay the activation signal to each other, in a PDZ-domain independent fashion. Notably, we show that inhibitor binding is precluded if HtrA1 monomers cannot communicate with each other. Our study establishes how HtrA1 oligomerization plays a fundamental role in proteolytic activity. Moreover, it offers a structural explanation for HtrA1-defective pathologies as well as mechanistic insights into the degradation of complex extracellular fibrils such as tubulin, amyloid beta and tau that belong to the repertoire of HtrA1.HighlightsMonomeric HtrA1 is activated by a gating mechanism.Trimeric HtrA1 is regulated by PDZ-independent allosteric monomer cross-talk.HtrA1 oligomerization is key for proteolytic activity.Substrate-binding is precluded if monomers cannot communicate with each other.
A method for detecting rash and fever illness‐associated viruses using multiplex reverse transcription polymerase chain reaction
Authors: Matsushima Yuki , Shimizu Tomomi , Doi Ikuko , Mizukoshi Fuminori , Nagasawa Koo , Ryo Akihide , Shimizu Hideaki , Kobayashi Masae , Funatogawa Keiji , Nagata Noriko , Ishikawa Mariko , Komane Ayako , Okabe Nobuhiko , Mori Yoshio , Takeda Makoto , Kimura Hirokazu 
Published: July 2017

ABSTRACTIn this study, a new multiplex RT‐PCR method for detecting various viral genes in patients with rash and fever illnesses (RFIs) was constructed. New primer sets were designed for detection of herpes simplex viruses 1 and 2 (HSV1 and 2), and Epstein–Barr virus (EBV). The newly designed and previously reported primer sets were used to detect 13 types of RFI‐associated viruses by multiplex RT‐PCR assay systems. Moreover, to eliminate non‐specific PCR products, a double‐stranded specific DNase was used to digest double‐stranded DNA derived from the templates in clinical specimens. RFI‐associated viruses were detected in 77.0% of the patients (97/126 cases) by the presented method, multiple viruses being identified in 27.8% of the described cases (35/126 cases). Detected viruses and clinical diagnoses were compatible in 32.5% of the patients (41/126 cases). Sensitivity limits for these viruses were estimated to be 101–103 copies/assay. Furthermore, non‐specific PCR products were eliminated by a double‐stranded specific DNase with no influence on sensitivity. These results suggest that this method can detect various RFI‐associated viruses in clinical specimens with high sensitivity and specificity.
Continuing competence assessment and maintenance in occupational therapy: Scoping review with stakeholder consultation
Authors: Myers Christine T. , Schaefer Nancy , Coudron Ashley 
Published: July 2017

Background/aimContinuing competence activities hold the promise of improving health‐care service quality, especially given concerns about system inefficiencies and fragmentation. The aim of this scoping review was to describe the assessment and maintenance of occupational therapists’ continuing competence and identify knowledge gaps for future research. A secondary aim was comparing scoping review findings with those from other health‐care fields and considering possible impact of varying international regulations.MethodsA series of database searches retrieved peer‐reviewed and grey literature on assessment and maintenance of occupational therapy continuing competence from 1995 to 2015. Themes were developed and findings shared with stakeholders, whose comments drove a second phase: searching for reviews related to continuing competence from allied health, medicine, and nursing, and reviewing websites and documents concerning regulatory requirements for occupational therapy continuing competence in seven English‐speaking nations.ResultsTwenty‐seven sources from the scoping review search met inclusion criteria. Stakeholder consultation validated the themes and preliminary knowledge gaps. Research into other health‐care specialties corresponded to findings from the scoping review. The website/document review of occupational therapy regulatory requirements revealed wide variation on both the state/province and national levels.ConclusionsThis scoping review highlights gaps in research on effective methods and assessment of occupational therapy continuing competence. Findings suggest a need for research on approaches to continuing competence that incorporate the translation of evidence to practice and address the influence of external factors. Regulatory agencies may address the quality of occupational therapy services by incorporating a variety of professional development options into requirements.
Association between universal hepatitis B prison vaccination, vaccine uptake and hepatitis B infection among people who inject drugs
Authors: Palmateer Norah E. , Goldberg David J. , Munro Alison , Taylor Avril , Yeung Alan , Wallace Lesley A. , Mitchell Alan , Shepherd Samantha J. , Gunson Rory N. , Aitken Celia , Hutchinson Sharon J. 
Published: July 2017

AbstractBackground and aimsIn Scotland, hepatitis B virus (HBV) vaccination for all prisoners was introduced in 1999; here, we examine the impact of this programme among people who inject drugs (PWID) in the community. This study aimed to compare rates of HBV vaccine uptake before and after implementation of the prison programme and to estimate the determinants of vaccine uptake, the levels of ever/current HBV infection and the associations between vaccine uptake and ever/current HBV infection.DesignData collected via serial cross‐sectional surveys were used to compare the proportion who reported being vaccinated over time. For the 2013–14 survey, rates of ever/current HBV infection were calculated and the associations between vaccine uptake and ever/current HBV infection were examined using logistic regression.SettingServices providing injecting equipment and drug treatment and street sites in Glasgow (1993–2002) and throughout Scotland (2008–14).ParticipantsMore than 10 000 PWID in total were recruited in the surveys.MeasurementsParticipants completed a questionnaire (all years) to ascertain self‐reported vaccine uptake and provided a blood spot (in 2013–14), tested for HBV core antibodies (anti‐HBc) and surface antigen (HBsAg).FindingsAmong recent‐onset PWID in Glasgow, vaccine uptake increased from 16% in 1993 to 59% in 2008–14 (P < 0.001). Among all PWID in Scotland, uptake increased further from 71% in 2008–09 to 77% in 2013–14 (P < 0.001) and was associated with incarceration [adjusted odds ratio (aOR) = 2.91, 95% confidence interval (CI) = 2.23–3.79]. The prevalence of anti‐HBc and HBsAg in Scotland was 2.6 and 0.3%, respectively, among PWID who had commenced injecting in the decade since the programme's introduction. Vaccination was associated with reduced odds of ever (aOR = 0.60, CI = 0.37–0.97) and current (aOR = 0.40, CI = 0.16–0.97) HBV infection.ConclusionsIn Scotland, uptake of hepatitis B virus (HBV) vaccination among people who inject drugs (PWID) in the community has increased since the 1999 introduction of universal prison vaccination, and current levels of HBV infection among PWID are low compared with other European countries.
Comparison of perioperative and functional outcomes of robotic partial nephrectomy for cT1a vs cT1b renal masses
Authors: Reynolds Christopher R. , Delto Joan C. , Paulucci David J. , Weinstein Corey , Badani Ketan , Eun Daniel , Abaza Ronney , Porter James , Bhandari Akshay , Hemal Ashok K. 
Published: July 2017

ObjectiveTo compare perioperative and functional outcomes of patients with cT1a or cT1b renal masses undergoing robotic partial nephrectomy (RPN) in a large multi‐institutional studyPatients and MethodsThe present retrospective Institutional Review Board‐approved multi‐institutional study utilised a prospectively maintained database to identify patients undergoing RPN by six surgeons for a solitary cT1a (n = 1 307) or cT1b (n = 377) renal mass from 2006 to 2016. Perioperative and renal function outcomes at discharge and at a median follow‐up of 12.2 months were compared in univariable and multivariable regression analyses adjusting for surgeon performing the procedure and date of surgery.ResultsIn univariable analysis, cT1b masses were associated with longer operative time (190.0 vs 159.0 min, P < 0.001), longer warm ischaemia time (18.8 vs 15.0 min, P < 0.001), higher estimated blood loss (150.0 vs 100.0 mL, P < 0.001), more intraoperative complications (5.6% vs 2.4%, P = 0.034), and more surgical postoperative complications (10.1% vs 5.7%, P =0.002). Results were similar in multivariable analysis with additional findings including more overall postoperative complications (odds ratio 1.55, P = 0.015) and longer length of stay (P < 0.001) associated with cT1b masses. There were no differences in the risk of progression of chronic kidney disease stage at 12.2 months, positive surgical margins, or major postoperative complications.ConclusionsAlthough our study shows a longer operative time, longer warm ischemia time, and higher complication rate for patients undergoing RPN for cT1b renal masses, the magnitude of these differences is small. RPN should be considered for cT1b lesions when anatomical and spatial location allow for a feasible procedure.
Baseline and longitudinal plasma caveolin‐1 level as a biomarker in active surveillance for early‐stage prostate cancer
Authors: Basourakos Spyridon P. , Davis John W. , Chapin Brian F. , Ward John F. , Pettaway Curtis A. , Pisters Louis L. , Navai Neema , Achim Mary F. , Wang Xuemei , Chen Hsiang‐Chun , Choi Seungtaek , Kuban Deborah , Troncoso Patricia , Hanash Sam , Thompson Timothy C. , Kim Jeri 
Published: July 2017

ObjectivesTo evaluate the role of caveolin‐1 (Cav‐1) as a predictor of disease reclassification (DR) in men with early prostate cancer undergoing active surveillance (AS).Patients and MethodsWe analysed archived plasma samples prospectively collected from patients with early prostate cancer in a single‐institution AS study. Of 825 patients enrolled, 542 had ≥1 year of follow‐up. Baseline and longitudinal plasma Cav‐1 levels were measured using an enzyme‐linked immunosorbent assay. Tumour volume or Gleason grade increases were criteria for DR. Logistic regression analyses were used to assess associations between clinicopathological characteristics and reclassification risk.ResultsIn 542 patients, 480 (88.6%) had stage cT1c disease, 542 (100.0%) had a median prostate‐specific antigen level of 4.1 ng/mL, and 531 (98.0%) had a median Cancer of the Prostate Risk Assessment score of 1. In all, 473 (87.3%) had a Gleason score of 3+3. After a median of 3.1 years of follow‐up, disease was reclassified in 163 patients (30.1%). The mean baseline Cav‐1 level was 2.2 ± 8.5 ng/mL and the median 0.2 ng/mL (range, 0–85.5 ng/mL). In univariate analysis, baseline Cav‐1 was a significant predictor for risk of DR (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.24–2.65; P = 0.002). In multivariate analysis, with adjustments for age, tumour length, group risk stratification and number of positive cores, reclassification risk associated with Cav‐1 remained significant (OR 1.91, 95% CI 1.28–2.84; P = 0.001).ConclusionBaseline plasma Cav‐1 level was an independent predictor of disease classification. New methods for refining AS and intervention may result.
Safety and performance of a novel collagenated xenogeneic bone block for lateral alveolar crest augmentation for staged implant placement
Authors: Ortiz‐Vigón Alberto , Suarez Iñaki , Martínez‐Villa Sergio , Sanz‐Martín Ignacio , Bollain Juan , Sanz Mariano 
Published: July 2017

AbstractObjectivesTo evaluate the performance and safety of placing a collagenated xenogeneic bone block (CXBB) graft for the lateral bone augmentation of the alveolar crest prior to implant placement.Material & MethodsIn patients with single or multiple tooth gaps and a severe horizontal collapse of the alveolar ridge, a ridge augmentation procedure was performed using CXBB fixated with osteosynthesis screws to the atrophic bone crest and complemented with deproteinized bovine bone mineral particles (DBBM) and a native bilayer collagen membrane (NBCM). Patients were examined with CBCT prior to and 24 weeks after the augmentation. Twenty‐six weeks postoperatively, a re‐entry procedure was performed to evaluate the bone width and availability for adequate implant placement.ResultsFifteen patients received 28 CXBB, and in 13 patients, a re‐entry procedure was performed. Eleven patients (84.6%) gained enough bone volume for implant insertion without additional contouring or secondary bone augmentation. The mean crest width at baseline was 2.83 mm (SD 0.57), and the mean crest width at re‐entry was 6.90 mm (SD 1.22), with a mean ridge width increase of 4.12 mm (SD 1.32). Soft tissue dehiscence occurred during the follow‐up in 5 of 14 patients (35.7%) at various time points. In addition, there was a high incidence of early implant loss (30.8% [patient‐based]).ConclusionsCXBB achieved significant horizontal crestal width gains allowing a secondary implant placement in the majority of the patients. However, the occurrence of soft tissue dehiscence may notably affect the outcome of the subsequent implant therapy.