bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence of Percentage Weight-Bearing on Foot Radiographs
Authors: Shelton Trevor J. , Singh Sohni , Bent Robinson Eduardo , Nardo Lorenzo , Escobedo Eva , Jackson Lyle , Kreulen Christopher D. , Giza Eric 
Published: October 2018

Introduction: Clinical decisions are often made on weight-bearing radiographs. However, it is unknown whether various weight-bearing conditions alter specific radiographic measurements. The purpose of this study was to determine whether percentage weight-bearing influences radiographic measurements of the normal foot. Methods: A prospective study with 20 healthy individuals had radiographs of the foot under 5 weight-bearing conditions (non–weight-bearing, 10% body weight, 25% body weight, 50% body weight, and 100% body weight). Measurements were made of hallux valgus angle (HVA), 1-2 intermetatarsal angle (IMA), talonavicular coverage angle (TNCA), talocalcaneal angle (TCA), forefoot width, LisFranc distance, cuboid height to ground (CHG), and talo–first metatarsal angle (TMA) of each weight-bearing condition. Statistical differences of each measurement for each weight-bearing condition were determined. Results: The TNCA and TCA increased significantly, whereas the CHG decreased significantly with increased percentage body weight. There were no differences in HVA, IMA, forefoot width, LisFranc distance, and TMA with increased percentage body weight. Conclusions: This study shows an increase in TNCA and TCA, and decrease in CHG, demonstrating a flattening of the medial arch, increasing hindfoot valgus, and midfoot external rotation and abduction with increasing percentage body weight applied to a foot. Percentage weight-bearing does not change radiographs in the foot between 25% and 100% weight-bearing. The clinical relevance of this finding is that graduated postinjury or postoperative weight-bearing regimens may only be relevant if the patient is either less than or greater than 25% of body weight on their extremity. Levels of Evidence: Case Series, Level IV: Prospective
An unconventional path to greater social-communication skills and independence for an adolescent on the autism spectrum
Authors: Trembath David , Bala Rachel J , Tamblyn Joanne , Westerveld Marleen F 
Published: October 2018

Background In 2015, a father took his 14-year-old son who is on the autism spectrum on a six-month journey aimed to develop his son’s social-communication and independent living skills. The duo travelled across 10 countries, meeting people and practising these skills. This study examined their goals, motivations for, and outcomes of the journey. Method We used intrinsic case study methodology with mixed methods, including interviews with parents and professionals; analyses of filmed interactions between the son, his father and strangers during the journey; and descriptive analysis of parent-reported changes in their son’s participation at home, school and in the community using the Participation and Environment Measure – Children and Youth. Results Qualitative analysis of the interviews with parents and professionals revealed a set of insightful goals and motivations, focusing on creating an optimal environment for the son’s development. Parents reported increases in their son’s social-communication and independent living skills, but also unexpected changes in his perspective and self-belief. The former findings were consistent with those arising from video analysis, whereby social-pragmatic skills critical to good conversations (staying on topic, body position, eye contact) all increased over the course of the journey, while abrupt topic changes and conversational prompts reduced. Participation and inclusion across home, school and community settings all increased over the same period. Conclusion While this study makes no claims regarding causation, the findings indicate that the journey was associated with positive changes for the son and his parents, leading to greater expectations for, and progress towards, independence following the journey. Implications of the findings for supporting young people on the autism spectrum in regular community settings are discussed.
CD16+ monocytes give rise to CD103+RALDH2+TCF4+ dendritic cells with unique transcriptional and immunological features
Authors: Wacleche Vanessa Sue , Cattin Amélie , Goulet Jean-Philippe , Gauchat Dominique , Gosselin Annie , Cleret-Buhot Aurélie , Zhang Yuwei , Tremblay Cécile L. , Routy Jean-Pierre , Ancuta Petronela 
Published: October 2018

Abstract
Classical CD16− vs intermediate/nonclassical CD16+ monocytes differ in their homing potential and biological functions, but whether they differentiate into dendritic cells (DCs) with distinct contributions to immunity against bacterial/viral pathogens remains poorly investigated. Here, we employed a systems biology approach to identify clinically relevant differences between CD16+ and CD16− monocyte-derived DCs (MDDCs). Although both CD16+ and CD16− MDDCs acquire classical immature/mature DC markers in vitro, genome-wide transcriptional profiling revealed unique molecular signatures for CD16+ MDDCs, including adhesion molecules (ITGAE/CD103), transcription factors (TCF7L2/TCF4), and enzymes (ALDH1A2/RALDH2), whereas CD16− MDDCs exhibit a CDH1/E-cadherin+ phenotype. Of note, lipopolysaccharides (LPS) upregulated distinct transcripts in CD16+ (eg, CCL8, SIGLEC1, MIR4439, SCIN, interleukin [IL]-7R, PLTP, tumor necrosis factor [TNF]) and CD16− MDDCs (eg, MMP10, MMP1, TGM2, IL-1A, TNFRSF11A, lysosomal-associated membrane protein 1, MMP8). Also, unique sets of HIV-modulated genes were identified in the 2 subsets. Further gene set enrichment analysis identified canonical pathways that pointed to “inflammation” as the major feature of CD16+ MDDCs at immature stage and on LPS/HIV exposure. Finally, functional validations and meta-analysis comparing the transcriptome of monocyte and MDDC subsets revealed that CD16+ vs CD16− monocytes preserved their superior ability to produce TNF-α and CCL22, as well as other sets of transcripts (eg, TCF4), during differentiation into DC. These results provide evidence that monocyte subsets are transcriptionally imprinted/programmed with specific differentiation fates, with intermediate/nonclassical CD16+ monocytes being precursors for pro-inflammatory CD103+RALDH2+TCF4+ DCs that may play key roles in mucosal immunity homeostasis/pathogenesis. Thus, alterations in the CD16+/CD16− monocyte ratios during pathological conditions may dramatically influence the quality of MDDC-mediated immunity.
Understanding the role of the family physician in early psychosis intervention
Authors: Anderson Kelly K. , Archie Suzanne , Booth Richard G. , Cheng Chiachen , Lizotte Daniel , MacDougall Arlene G. , Norman Ross M. G. , Ryan Bridget L. , Terry Amanda L. , Rodrigues Rebecca 
Published: October 2018

BackgroundThe family physician is key to facilitating access to psychiatric treatment for young people with first-episode psychosis, and this involvement can reduce aversive events in pathways to care. Those who seek help from primary care tend to have longer intervals to psychiatric care, and some people receive ongoing psychiatric treatment from the family physician.AimsOur objective is to understand the role of the family physician in help-seeking, recognition and ongoing management of first-episode psychosis.MethodWe will use a mixed-methods approach, incorporating health administrative data, electronic medical records (EMRs) and qualitative methodologies to study the role of the family physician at three points on the pathway to care. First, help-seeking: we will use health administrative data to examine access to a family physician and patterns of primary care use preceding the first diagnosis of psychosis; second, recognition: we will identify first-onset cases of psychosis in health administrative data, and look back at linked EMRs from primary care to define a risk profile for undetected cases; and third, management: we will examine service provision to identified patients through EMR data, including patterns of contacts, prescriptions and referrals to specialised care. We will then conduct qualitative interviews and focus groups with key stakeholders to better understand the trends observed in the quantitative data.DiscussionThese findings will provide an in-depth description of first-episode psychosis in primary care, informing strategies to build linkages between family physicians and psychiatric services to improve transitions of care during the crucial early stages of psychosis.Declaration of interestNone.
Occurrence of Treatment-Related Cardiotoxicity and Its Impact on Outcomes Among Children Treated in the AAML0531 Clinical Trial: A Report From the Children’s Oncology Group
Authors: Getz Kelly D. , Sung Lillian , Ky Bonnie , Gerbing Robert B. , Leger Kasey J. , Leahy Allison Barz , Sack Leah , Woods William G. , Alonzo Todd , Gamis Alan , Aplenc Richard 
Published: October 2018

PurposeLate cardiotoxicity after pediatric acute myeloid leukemia therapy causes substantial morbidity and mortality. The impact of early-onset cardiotoxicity on treatment outcomes is less well understood. Thus, we evaluated the risk factors for incident early cardiotoxicity and the impacts of cardiotoxicity on event-free survival (EFS) and overall survival (OS).MethodsCardiotoxicity was ascertained through adverse event monitoring over the course of follow-up among 1,022 pediatric patients with acute myeloid leukemia treated in the Children’s Oncology Group trial AAML0531. It was defined as grade 2 or higher left ventricular systolic dysfunction on the basis of Common Terminology Criteria for Adverse Events (version 3) definitions.ResultsApproximately 12% of patients experienced cardiotoxicity over a 5-year follow-up, with more than 70% of incident events occurring during on-protocol therapy. Documented cardiotoxicity during on-protocol therapy was significantly associated with subsequent off-protocol toxicity. Overall, the incidence was higher among noninfants and black patients, and in the setting of a bloodstream infection. Both EFS (hazard ratio [HR], 1.6; 95% CI, 1.2 to 2.1; P = .004) and OS (HR, 1.6; 95% CI, 1.2 to 2.2, P = .005) were significantly worse in patients with documented cardiotoxicity. Impacts on EFS were equivalent whether the incident cardiotoxicity event occurred in the absence (HR, 1.6; 95% CI, 1.1 to 2.2; P = .017) or presence of infection (HR, 1.6; 95% CI, 1.0 to 2.7; P = .069) compared with patients without documented cardiotoxicity. However, the reduction in OS was more pronounced for cardiotoxicity not associated with infection (HR, 1.7; 95% CI, 1.2 to 2.5; P = .004) than for infection-associated cardiotoxicity (HR, 1.3; 95% CI, 0.7 to 2.4; P = .387).ConclusionEarly treatment-related cardiotoxicity may be associated with decreased EFS and OS. Cardioprotective strategies are urgently needed to improve relapse risk and both short- and long-term mortality outcomes.
Controversies in Vitamin D: Summary Statement From an International Conference
Authors: Giustina Andrea , Adler Robert A , Binkley Neil , Bouillon Roger , Ebeling Peter R , Lazaretti-Castro Marise , Marcocci Claudio , Rizzoli Rene , Sempos Christopher T , Bilezikian John P 
Published: October 2018

AbstractContextVitamin D is classically recognized as a regulator of calcium and phosphorus metabolism. Recent advances in the measurement of vitamin D metabolites, diagnosis of vitamin D deficiency, and clinical observations have led to an appreciation that along with its role in skeletal metabolism, vitamin D may well have an important role in nonclassical settings. Measurement of the circulating form of vitamin D that best describes total body stores, namely 25-hydroxyvitamin D, can be unreliable despite many sophisticated methodologies that have been proposed and implemented. Likewise, evidence from clinical studies showing a beneficial role of vitamin D in different disease states has been controversial and at times speculative. Moreover, the target concentrations of 25-hydroxyvitamin D to address a number of putative links between vitamin D inadequacy and nonskeletal diseases are further areas of uncertainty.SettingTo address these issues, an international conference on “Controversies in Vitamin D” was held in Pisa, Italy, in June 2017. Three main topics were addressed: (i) vitamin D assays and the definition of hypovitaminosis D; (ii) skeletal and extraskeletal effects of vitamin D; (iii) therapeutics of vitamin D.ResultsThis report provides a summary of the deliberations of the expert panels of the conference.ConclusionsDespite great advances in our appreciation of vitamin D metabolism, measurements, biological actions on classical and nonclassical tissues, and therapeutics, all of which this report summarizes, much more work remains to be done so that our knowledge base can become even more secure.
Reconstruction of destruction – in vitro reconstitution methods in autophagy research
Authors: Moparthi Satish Babu , Wollert Thomas 
Published: October 2018

ABSTRACT
Autophagy is one of the most elaborative membrane remodeling systems in eukaryotic cells. Its major function is to recycle cytoplasmic material by delivering it to lysosomes for degradation. To achieve this, a membrane cisterna is formed that gradually captures cargo such as organelles or protein aggregates. The diversity of cargo requires autophagy to be highly versatile to adapt the shape of the phagophore to its substrate. Upon closure of the phagophore, a double-membrane-surrounded autophagosome is formed that eventually fuses with lysosomes. In response to environmental cues such as cytotoxicity or starvation, bulk cytoplasm can be captured and delivered to lysosomes. Autophagy thus supports cellular survival under adverse conditions. During the past decades, groundbreaking genetic and cell biological studies have identified the core machinery involved in the process. In this Review, we are focusing on in vitro reconstitution approaches to decipher the details and spatiotemporal control of autophagy, and how such studies contributed to our current understanding of the pathways in yeast and mammals. We highlight studies that revealed the function of the autophagy machinery at a molecular level with respect to its capacity to remodel membranes.
Fast P(RMNE): Fast forensic DNA probability of random man not excluded calculation
Authors: Ricke Darrell O. , Schwartz Steven 
Published: October 2018

High throughput sequencing (HTS) of DNA forensic samples is expanding from the sizing of short tandem repeats (STRs) to massively parallel sequencing (MPS). HTS panels are expanding from the FBI 20 core Combined DNA Index System (CODIS) loci to include SNPs. The calculation of random man not excluded, P(RMNE), is used in DNA mixture analysis to estimate the probability that a person is present in a DNA mixture. This calculation encounters calculation artifacts with expansion to larger panel sizes. Increasing the floating-point precision of the calculations allows for increased panel sizes but with a corresponding increase in computation time. The Taylor series higher precision libraries used fail on some input data sets leading to algorithm unreliability. Herein, a new formula is introduced for calculating P(RMNE) that scales to larger SNP panel sizes while being computationally efficient (patent pending).
Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis
Authors: Heneghan Carl J. , Aronson Jeffrey K. , Spencer Elizabeth , Holman Bennett , Mahtani Kamal R. , Perera Rafael , Onakpoya Igho 
Published: October 2018

Background: Oral hormone pregnancy tests (HPTs), such as Primodos, containing ethinylestradiol and high doses of norethisterone, were given to over a million women from 1958 to 1978, when Primodos was withdrawn from the market because of concerns about possible teratogenicity. We aimed to study the association between maternal exposure to oral HPTs and congenital malformations. Methods: We have performed a systematic review and meta-analysis of case-control and cohort studies that included data from pregnant women and were exposed to oral HPTs within the estimated first three months of pregnancy, if compared with a relevant control group. We used random-effects meta-analysis and assessed the quality of each study using the Newcastle–Ottawa Scale for non-randomized studies. Results: We found 16 case control studies and 10 prospective cohort studies, together including 71 330 women, of whom 4209 were exposed to HPTs. Exposure to oral HPTs was associated with a 40% increased risk of all congenital malformations: pooled odds ratio (OR) = 1.40 (95% CI 1.18 to 1.66; P<0.0001; I2 = 0%). Exposure to HPTs was associated with an increased risk of congenital heart malformations: pooled OR = 1.89 (95% CI 1.32 to 2.72; P = 0.0006; I2=0%); nervous system malformations OR = 2.98 (95% CI 1.32 to 6.76; P = 0.0109 I2 = 78%); gastrointestinal malformations, OR = 4.50 (95% CI 0.63 to 32.20; P = 0.13; I2 = 54%); musculoskeletal malformations, OR = 2.24 (95% CI 1.23 to 4.08; P= 0.009; I2 = 0%); the VACTERL syndrome (Vertebral defects, Anal atresia, Cardiovascular anomalies, Tracheoesophageal fistula, Esophageal atresia, Renal anomalies, and Limb defects), OR = 7.47 (95% CI 2.92 to 19.07; P < 0.0001; I2 = 0%). Conclusions: This systematic review and meta-analysis shows that use of oral HPTs in pregnancy is associated with increased risks of congenital malformations.
Team- and individual-level motivation in complex primary care system change: A realist evaluation of the Salud Mesoamerica Initiative in El Salvador
Authors: Munar Wolfgang , Wahid Syed S. , Mookherji Sangeeta , Innocenti Cinzia , Curry Leslie 
Published: October 2018

Background:We study the role of individual and team-level motivation in explaining large-scale primary care performance improvements in El Salvador, one of the top-performing countries in the Salud Mesoamerica Initiative.Methods:Case study with outlier sampling of high-performing, community health teams in El Salvador. Design includes scoping review of literature, document review, non-participant observation, and qualitative analysis of in-depth interviews following a realist case study protocol.Results:The interplay between program interventions and organizational, community and policy contexts trigger multi-level motivational mechanisms that operate in complex, dynamic fashion. Interventions like performance measurement and team-based, in-kind incentives foster motivation among individual members of high-performing teams, which may be moderated by working conditions, supervision practices, and by the stress exerted by the interventions themselves. Individuals report a strong sense of public service motivation and an overarching sense of commitment to the community they serve. At the interpersonal level, the linkage between performance measurement and in-kind incentives triggers a sense of collective efficacy and increases team motivation and improvement behaviors. The convening of learning forums and performance dialogue increases the stakes for high-performing teams, helps them make sense of performance data, and leads to performance information utilization for healthcare improvements. Closeness to communities creates strong emotional linkages among team members that further increases collective efficacy and social identity. Such changes in individuals, team, and organizational behaviors can contribute to improved delivery of primary care services and explain the gains in performance demonstrated by the program.Conclusions:This case suggests that primary care systems that rely on multi-disciplinary teams for the provision of care can benefit from performance measurement and management interventions that leverage individual and team-level motivation. Realist evaluation can help prioritize policy-relevant research and enhance the design and evaluation of large-scale performance reforms in primary care systems in low- and middle-income settings.
Functional specialization in the middle temporal area for smooth pursuit initiation
Authors: Bakhtiari Shahab , Pack Christopher C. 
Published: October 2018

Smooth pursuit eye movements have frequently been used to model sensorimotor transformations in the brain. In particular, the initiation phase of pursuit can be understood as a transformation of a sensory estimate of target velocity into an eye rotation. Despite careful laboratory controls on the stimulus conditions, pursuit eye movements are frequently observed to exhibit considerable trial-to-trial variability. In theory, this variability can be caused by the variability in sensory representation of target motion, or by the variability in the transformation of sensory information to motor commands. Previous work has shown that neural variability in the middle temporal (MT) area is likely propagated to the oculomotor command, and there is evidence to suggest that the magnitude of this variability is sufficient to account for the variability of pursuit initiation. This line of reasoning presumes that the MT population is homogeneous with respect to its contribution to pursuit initiation. At the same time, there is evidence that pursuit initiation is strongly linked to a subpopulation of MT neurons (those with strong surround suppression) that collectively generate less motor variability. To distinguish between these possibilities, we have combined human psychophysics, monkey electrophysiology, and computational modeling to examine how the pursuit system reads out the MT population during pursuit initiation. We find that the psychophysical data are best accounted for by a model that gives stronger weight to surround-suppressed MT neurons, suggesting that variability in the initiation of pursuit could arise from multiple sources along the sensorimotor transformation.