bluuebunny/crossref_metadata_2025_split huggingface dataset:
68Ga-PSMA PET/CT in Patients With Biochemical Recurrence of Prostate Cancer
Authors: Zacho Helle D. , Nielsen Julie B. , Dettmann Katja , Haberkorn Uwe , Langkilde Niels C. , Jensen Jørgen B. , Petersen Lars J. 
Published: June 2018

Purpose of the Report
The aim of this study was to prospectively investigate the detection rate of 68Ga-PSMA PET/CT in biochemical recurrence (BCR) of prostate cancer and its impact on patient management.

Materials and Methods
Patients with BCR after curatively intended treatment of prostate cancer were included. Each patient underwent a 68Ga-PSMA PET/CT. Changes in patient management based on the results of 68Ga-PSMA PET/CT were assessed.

Results
Seventy patients were included. Sixty-four patients (91%) had radical prostatectomy, of whom 17 patients (24%) received salvage radiation therapy due to first biochemical relapse. Six patients (9%) underwent radiation therapy as the primary treatment. 68Ga-PSMA PET/CT detected recurrent disease in 37 patients (53%). The detection rate was 22% for prostate-specific antigen (PSA) levels up to 0.5 ng/mL compared with 83% for PSA levels greater than 0.5 ng/mL. Pathological uptake of 68Ga-PSMA was observed in 4 (16%) of 21, 4 (44%) of 9, 0 of 1, 7 (70%) of 10, and 22 (88%) of 25 patients with PSA levels from 0.2 to 0.3 ng/mL, 0.31 to 0.4 ng/mL, 0.41 to 0.5 ng/mL, 0.51 to 1 ng/mL, and greater than 1 ng/mL, respectively. Prostate-specific antigen was significantly higher in PSMA-positive patients than in PSMA-negative patients. In 15 (22%) of 69 patients, the results caused a definite change in patient management, and in another 15 (22%) of 69 patients, 68Ga-PSMA PET/CT guided the choice of treatment.

Conclusions

68Ga-PSMA PET/CT detects lesions in a large proportion of patients with BCR. Detection rates at low PSA levels (<0.5 ng/mL) were notably below the values reported in previous retrospective studies; however, detection rates improved with increasing PSA levels.
Factors That Affect Medical Students' Perception and Impression of a Plastic Surgery Program
Authors: Zuo Kevin J. , Retrouvey Helene , Wanzel Kyle R. 
Published: June 2018

Objective
Securing a residency training position in plastic surgery is highly competitive each year with a limited quota of positions and numerous qualified applicants. Although previous studies have highlighted the importance of residency programs and applicants seeking a “good fit,” it remains poorly understood what influences a medical student's impression and desire to train at a certain program over others. The objective of this cross-sectional study was to identify which specific potentially modifiable factors during elective rotations and program interviews were most important to Canadian medical students when ranking plastic surgery programs.

Methods
An electronic survey with 42 questions was administered to Canadian final year medical students who applied through the 2017 Canadian Residency Match Service to the plastic surgery training program at the University of Toronto. The survey consisted of 7-point Likert scale questions related to demographics, general factors affecting impression of a plastic surgery program, and specific factors related to the elective and interview experiences. Survey responses were collected anonymously for analysis.

Results
Twenty-three of 46 applicants completed the survey (50% response rate). The most important general factors affecting a medical student's impression and desire to train at a residency program were mentors at a specific program (weighted average, 6.39) and geographic location of a program (weighted average, 5.65). During elective rotations, the most important factors identified were overall impression of resident and staff collegiality (weighted average, 6.57), overall impression of resident happiness (weighted average, 6.52), and having a formal rotation-end debrief evaluation with the supervising staff (weighted average, 6.04). At program interviews, perceiving an atmosphere of collegiality (weighted average, 6.45) and opportunities to interact with residents and faculty at an organized social event (weighted average, 5.95) were considered of greatest importance.

Conclusions
Current applicants to plastic surgery in Canada prioritize resident happiness, program collegiality, and meaningful faculty relationships, such as those with a mentor, when ranking residency programs. Although finding a mutually “good fit” between applicant and program will remain a major aim, these findings indicate the importance of certain tangible, potentially modifiable factors that affect how medical students ultimately perceive and rank plastic surgery programs.
The Practice of Overlapping Colorectal Operations in a Tertiary Care Center Is Safe
Authors: Shogan Benjamin D. , Harmsen William S. , Dozois Eric J. , Nelson Heidi , Larson David W. 
Published: June 2018

Objective:
Determine the safety of overlapping surgery in a tertiary care colorectal surgery practice.

Summary:
Although overlapping surgery is common in academic centers, reports on outcomes of this practice are limited. The primary aim of this study was to investigate the safety of overlapping surgery in a dedicated tertiary care academic colorectal practice by comparing groups of patients who did or did not have their surgery performed in an overlapping fashion.

Methods:
Retrospective review of 1270 colorectal patients undergoing inpatient colorectal surgery at our institution. Eligible participants were all patients undergoing elective inpatient colorectal surgery by one of the colorectal surgeons at the Mayo Clinic Rochester between January 1, 2012 and December 31, 2015. Patients under the age of 18 or who underwent an emergent procedure were excluded. Data were abstracted using the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) database. Additionally, each subject's chart was reviewed and further abstracted. The safety of overlapping surgery on outcomes was assessed using multiple multivariable models.

Results:
One thousand two hundred seventy patients were included in the study cohort of whom 50.7% were female and the average age was 55.4 years. Overlapping surgery occurred in 576 patients (45%). There were no significant differences in demographic, surgical indications, procedures, or operative complexity between patients undergoing overlapping surgery and those who did not. Overall adverse events were significantly less likely in patients undergoing overlapping surgery compared with those who did not (18.4% vs 23.6%, P = 0.02). We found that overlapping surgery was associated with significantly less adverse events compared with patients not undergoing overlapping surgery using a model that controlled for the effect of the individual surgeon (OR 0.7, 95% CI 0.6 – 0.96; P = .02) and a multivariable propensity score (OR 0.7, 95% CI 0.5– 0.9; P = 01).

Conclusions:
Overlapping surgery in a tertiary care colorectal practice is safe and not associated with adverse patient outcomes.
Towards a framework for reporting self-guided interventions for people with cancer
Authors: Ugalde Anna , Kiss Nicole , Livingston Patricia , Aranda Sanchia 
Published: June 2018

Purpose of review
The purpose of this article is to provide an updated review exploring the recent developments in the field of self-guided interventions and describe the state of knowledge. This article builds on a previous systematic review on self-guided interventions, finding that the recent literature demonstrates that evidence for these interventions is mixed. The field is limited by descriptions of these interventions, and it is not possible to ascertain what aspects of interventions are more successful.

Recent findings
Development of a reporting framework whereby self-guided interventions could be clearly presented, would be a substantial contribution to understanding the evidence for these studies. Recent findings also support the need to understand patient adherence and engagement, which could be achieved within a reporting framework. Additionally, ensuring patient safety is paramount and all studies should develop strategies to ensure patients can engage with these studies in a way that allows them to access more help and support if required.

Summary
Self-guided interventions have potential for implementation and further translation because of being cost-effective and requiring few resources; and a reporting framework has the capacity to lead to clearer definitions and descriptions; and significantly improve the quality of evidence for these studies.
Impact of the Current Versus the Previous Diagnostic Threshold on the Outcome of Patients With Borderline Changes Suspicious for T Cell–mediated Rejection Diagnosed on Indication Biopsies
Authors: McRae Michael , Bouchard-Boivin François , Béland Stéphanie , Noël Réal , Côté Isabelle , Lapointe Isabelle , Lesage Julie , Latulippe Eva , Riopel Julie , Santoriello Dominick , Husain Syed A. , Désy Olivier , Houde Isabelle , Batal Ibrahim , De Serres Sacha A. 
Published: June 2018

Background
Since the borderline changes suspicious for acute T cell–mediated rejection (BL) category was broadened, there has been a debate regarding the right threshold for tubulitis and interstitial inflammation scores.

Methods
We studied a first cohort of 111 patients with BL found on an indication biopsy between 2006 and 2016 and compared those with scores of t1i0 (BLt1i0) to those with higher scores (BL≥t1i1). A second cohort of 56 patients with BL was used for external validation. We used a composite endpoint of death-censored graft failure or doubling of the serum creatinine level postbiopsy.

Results
In the first cohort, 68% (75/111) of the BL cases fell in the BLt1i0 group. At 5 years, the occurrence of the composite endpoint was 5% and 14% for BLt1i0 and BL≥t1i1, respectively. In contrast, the endpoint occurred in 5% of nonrejectors and 21% of patients with T cell–mediated rejection. In the validation cohort, 8% versus 36% of BLt1i0 and BL≥t1i1 reached the endpoint, respectively. Multivariable Cox modeling revealed that BLt1i0 patients had a prognosis similar to that of nonrejectors (adjusted hazard ratio, 0.6; 95% confidence interval, 0.1-2.2; P = 0.40) but better than that of patients with BL≥t1i1 (hazard ratio, 3.8; 95% confidence interval, 1.3-11.5; P = 0.02). Sensitivity analyses restricted to death-censored graft loss or using time posttransplant as the time of reference provided similar results.

Conclusions
In summary, patients with BLt1i0 have a different prognosis to that of BL≥t1i1 patients, which brings into question the current diagnostic thresholds.
Small Molecule Tyrosine Kinase Inhibitor Nintedanib Reduces Development of Cardiac Allograft Vasculopathy in Murine Aortic Allografts
Authors: Gocht Annika , Spriewald Bernd , Distler Jörg H.W. , Ramsperger-Gleixner Martina , Ensminger Stephan M. , Weyand Michael , Heim Christian 
Published: June 2018

Background
Nintedanib is a small molecule tyrosine kinase inhibitor that blocks the action of the platelet-derived growth factor receptor (PDGFR), the vascular endothelial growth factor receptor (VEGFR) and the fibroblast growth factor receptor. All of these receptors have been shown to be involved in the development of cardiac allograft vasculopathy (CAV) after heart transplantation. We therefore hypothesized that blocking these tyrosine kinase receptors with nintedanib could prevent CAV.

Methods
CBA/JRj (H2k) mice underwent an abdominal aortic transplantation with a graft derived from fully allogeneic C57BL/6JRj (H2b) mice. Nintedanib was given daily from the first day after transplantation until harvest on day 14 for polymerase chain reaction analysis of intragraft cytokine expression or harvest on day 30 for histological analysis of the graft.

Results
Nintedanib treatment resulted in significantly reduced neointima formation in the aortic graft compared with untreated control allografts. Interestingly, the immigration of smooth muscle cells into the neointima was markedly reduced while graft infiltrating macrophages and T cells were not altered in nintedanib-treated animals. The expression of the growth factor PDGF was significantly reduced in the nintedanib group going along with a distinctly reduced expression of the corresponding receptors PDGFR α and -β.

Conclusions
Treatment with nintedanib caused a significant reduction of CAV development after aortic transplantation in mice. We hypothesize the attenuated neointima formation in nintedanib-treated animals to be mediated by a direct inhibition of intimal smooth muscle cell proliferation via reduced expression of PDGF and the appropriate receptors PDGFR α + β.
Development of white matter fibre density and morphology over childhood: a longitudinal fixel-based analysis
Authors: Genc Sila , Smith Robert E , Malpas Charles B , Anderson Vicki , Nicholson Jan M , Efron Daryl , Sciberras Emma , Seal Marc L , Silk Timothy J 
Published: June 2018

AbstractPurposeWhite matter fibre development in childhood involves dynamic changes to microstructural organisation driven by increasing axon diameter, density, and myelination. However, there is a lack of longitudinal studies that have quantified advanced diffusion metrics to identify regions of accelerated fibre maturation, particularly across the early pubertal period. We applied a novel longitudinal fixel-based analysis (FBA) framework, in order to estimate microscopic and macroscopic white matter changes over time.MethodsDiffusion-weighted imaging (DWI) data were acquired for 59 typically developing children (27 female) aged 9 – 13 years at two time-points approximately 16 months apart (time-point 1: 10.4 ± 0.4 years, time-point 2: 11.7 ± 0.5 years). Whole brain FBA was performed using the connectivity-based fixel enhancement method, to assess longitudinal changes in fibre microscopic density and macroscopic morphological measures, and how these changes are affected by sex, pubertal stage, and pubertal progression. Follow-up analyses were performed in sub-regions of the corpus callosum to confirm the main findings using a Bayesian repeated measures approach.ResultsThere was a statistically significant increase in fibre density over time localised to medial and posterior commissural and association fibres, including the forceps major and bilateral superior longitudinal fasciculus. Increases in fibre cross-section were substantially more widespread. The rate of fibre development was not associated with age or sex. In addition, there was no significant relationship between pubertal stage or progression and longitudinal fibre development over time. Follow-up Bayesian analyses were performed to confirm the findings, which supported the null effect of the longitudinal pubertal comparison.ConclusionUsing a novel longitudinal fixel-based analysis framework, we demonstrate that white matter fibre density and fibre cross-section increased within a 16-month scan rescan period in specific regions. The observed increases might reflect increasing axonal diameter or axon count. Pubertal stage or progression did not influence the rate of fibre development in the early stages of puberty. Future work should focus on quantifying these measures across a wider age range to capture the full spectrum of fibre development across the pubertal period.
Empowering conservation practice with efficient and economical genotyping from poor quality samples
Authors: Natesh Meghana , Taylor Ryan W. , Truelove Nathan , Hadly Elizabeth A. , Palumbi Stephen , Petrov Dmitri , Ramakrishnan Uma 
Published: June 2018

AbstractModerate to high density genotyping (100+ SNPs) is widely used to determine and measure individual identity, relatedness, fitness, population structure and migration in wild populations.However, these important tools are difficult to apply when high-quality genetic material is unavailable. Most genomic tools are developed for high quality DNA sources from labor medical settings. As a result, most genetic data from market or field settings is limited to easily amplified mitochondrial DNA or a few microsatellites.To enable genotyping in conservation contexts, we used next-generation sequencing of multiplex PCR products from very low-quality DNA extracted from feces, hair, and cooked samples. We demonstrated utility and wide-ranging potential application in endangered wild tigers and tracking commercial trade in Caribbean queen conch.We genotyped 100 SNPs from degraded tiger samples to identify individuals, discern close relatives, and detect population differentiation. Co-occurring carnivores do not amplify (e.g. Indian wild dog/Dhole) or are monomorphic (e.g. leopard). 62 SNPs from conch fritters and field-collected samples were used to test relatedness and detect population structure.We provide proof-of-concept for a rapid, simple, cost-effective, and scalable method (for both samples and number of loci), a framework that can be applied to other conservation scenarios previously limited by low quality DNA samples. These approaches provide a critical advance for wildlife monitoring and forensics, open the door to field-ready testing, and will strengthen the use of science in policy decisions and wildlife trade.
A high-quality grapevine downy mildew genome assembly reveals rapidly evolving and lineage-specific putative host adaptation genes
Authors: Dussert Yann , Mazet Isabelle D. , Couture Carole , Gouzy Jérôme , Piron Marie-Christine , Kuchly Claire , Bouchez Olivier , Rispe Claude , Mestre Pere , Delmotte François 
Published: June 2018

ABSTRACTDowny mildews are obligate biotrophic oomycete pathogens that cause devastating plant diseases on economically important crops. Plasmopara viticola is the causal agent of grapevine downy mildew, a major disease in vineyards worldwide. We sequenced the genome of Pl. viticola with PacBio long reads and obtained a new 92.94 Mb assembly with high continuity (359 scaffolds for a N50 of 706.5 kb) due to a better resolution of repeat regions. This assembly presented a high level of gene completeness, recovering 1,592 genes encoding secreted proteins involved in plant-pathogen interactions. Pl. viticola had a two-speed genome architecture, with secreted protein-encoding genes preferentially located in gene-sparse, repeat-rich regions and evolving rapidly, as indicated by pairwise dN/dS values. We also used short reads to assemble the genome of Plasmopara muralis, a closely related species infecting grape ivy (Parthenocissus tricuspidata). The lineage-specific proteins identified by comparative genomics analysis included a large proportion of RxLR cytoplasmic effectors and, more generally, genes with high dN/dS values. We identified 270 candidate genes under positive selection, including several genes encoding transporters and components of the RNA machinery potentially involved in host specialization. Finally, the Pl. viticola genome assembly generated here will allow the development of robust population genomics approaches for investigating the mechanisms involved in adaptation to biotic and abiotic selective pressures in this species.DATA AVAILABILITYRaw reads and genome assemblies have been deposited in GenBank (BioProjects PRJNA329579 for Pl. viticola and PRJNA448661 for Pl. muralis). Genome assemblies, gene annotations and analysis files (e.g. orthology relationships, full tables for GO enrichment analyses, pairwise dN/dS values and branch-site tests) have been deposited in Dataverse (Pl. viticola assembly and annotation: doi.org/10.15454/4NYHD6, Pl. muralis assembly and annotation: doi.org/10.15454/Q1QJYK, analysis files: doi.org/10.15454/8NZ8X9). Links to the data and information about the grapevine downy mildew genome project can be found at http://grapevine-downy-mildew-genome.com/.
Mutations in Kinesin Family Member 6 Reveal Specific Role in Ependymal Cell Function and Human Neuro-Cranial Development
Authors: Konjikusic Mia J. , Yeetong Patra , Ittiwut Rungnapa , Suphapeetiporn Kanya , Wallingford John B. , Gurnett Christina A. , Shotelersuk Vorasuk , Gray Ryan S. 
Published: June 2018

ABSTRACTCerebrospinal fluid flow is crucial for neurodevelopment and homeostasis of the ventricular system of the brain, with localized flow being established by the polarized beating of the ependymal cell (EC) cilia. Here, we report a homozygous one base-pair deletion, c.1193delT (p.Leu398Glnfs*2), in the Kinesin Family Member 6 (KIF6) gene in a child displaying neurocranial defects and intellectual disability. To test the pathogenicity of this novel human KIF6 mutation we engineered an analogous C-terminal truncating mutation in mouse. These mutant mice display severe, postnatal-onset hydrocephalus. We generated a Kif6-LacZ transgenic mouse strain and report expression specifically and uniquely within the ependymal cell (EC) layer of the brain, without labeling other multiciliated mouse tissues. Analysis of Kif6 mutant mice with scanning electron microscopy (SEM) and immunofluorescence (IF) revealed a reduction in EC cilia, without effect on other multiciliated tissues. Consistent with our findings in mice, defects of the ventricular system and EC cilia were observed in kif6 mutant zebrafish. Overall, this work describes the first clinically-defined KIF6 homozygous null mutation in human and defines KIF6 as a conserved mediator of neuro-cranial morphogenesis with a specific role in the maintenance of EC cilia in vertebrates.AUTHOR SUMMARYCerebrospinal fluid flow is crucial for neurodevelopment and homeostasis of the ventricular system of the brain. Localized flows of cerebrospinal fluid throughout the ventricular system of the brain are established from the polarized beating of the ependymal cell (EC) cilia. Here, we identified a homozygous truncating mutation in KIF6 in a child displaying neuro-cranial defects and intellectual disability. To test the function of KIF6 in vivo, we engineered mutations of Kif6 in mouse. These Kif6 mutant mice display severe hydrocephalus, coupled with a loss of EC cilia. Similarly, we observed hydrocephalus and a reduction in EC cilia in kif6 mutant zebrafish. Overall, this work describes the first clinically-defined KIF6 mutation in human, while our animal studies demonstrate the pathogenicity of mutations in KIF6 and establish KIF6 as a conserved mediator of neuro-cranial development and EC cilia maintenance in vertebrates.
Free-living Bacterial Communities Are Mostly Dominated by Oligotrophs
Authors: Gao Yingnan , Wu Martin 
Published: June 2018

AbstractIn response to resource availability, bacteria have evolved two distinct ecological strategies. Copiotrophic bacteria grow fast and are heavily favored by selection where the resource is abundant. In contrast, oligotrophic bacteria grow slowly but more efficiently and are highly adaptive in nutrient-poor environments (Koch, 2001). Although oligotrophs and copiotrophs are ubiquitous, except for a few well-characterized environments like the open ocean and animal gut, the relative abundance of oligotrophic and copiotrophic bacteria and their importance in the global ecosystem are still unclear. In addition, although several studies have demonstrated the impact of nutrient availability on the bacterial community structure under experimental conditions (Klappenbach et al., 2000, Nemergut et al., 2016), the role of nutrients in shaping the structures of bacterial communities in their natural habitats remains largely unknown. Using the ribosomal RNA operon (rrn) copy number to capture the bacterial ecological strategy, we analyzed 44,045 samples from two large bacterial community repositories that cover 78 environmental types. Here we show that animal-associated microbiota are dominated by copiotrophs while plant-associated and free-living bacterial communities are mostly dominated by oligotrophs. Our results suggest that nutrient availability plays an important role in determining the structure and ecological strategy of bacterial communities in nature. We demonstrate that the average and distribution of rrn copy number are simple yet robust predictors of the ecological strategy of bacterial communities that can be applied to all sequence-based microbial surveys to link the community structure and function.