bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Bleeding Phenotype of Inherited Factor VII Deficiency in Children With a Bleeding Assessment Tool and Global Assays
Authors: Toret Ersin , Ay Yilmaz , Karapinar Tuba H. , Oymak Yeşim , Kavakli Kaan , Vergin Raziye C. 
Published: July 2019

Introduction:
Inherited factor VII (FVII) deficiency is the most common of the rare bleeding disorders and shows a heterogenous distribution of bleeding phenotypes independent of factor activity level. The bleeding score (BS) evaluates the phenotype of patients with rare bleeding disorders. Thromboelastography (TEG) and thrombin generation assays (TGAs) are 2 methods to evaluate global hemostasis, and controversially both tests are useful for identifying different bleeding tendency phenotypes. The purpose of this study was to investigate the use of the BS and global assays (TEG and TGAs) to predict the bleeding phenotype of inherited FVII deficiency.

Materials and Methods:
A total of 27 patients with FVII deficiency were evaluated with the BS and global hemostasis assays.

Results:
The BS was compatible with disease severity according to the FVII activity level (P<0.05) but the BS and bleeding grade of patients did not show a statistically significant correlation with factor activity level (P>0.05). No significant correlation was observed between the factor activity level and any TEG parameter (P>0.05). The factor activity level was negatively correlated with the lag time of the TGA on the contrary positively correlated with the peak thrombin time of the TGA (P<0.05).

Conclusions:
The global assays do not successfully predict the bleeding phenotype. The BS is a more suitable tool than conventional and global assays for predicting the bleeding phenotype.
Investing in Skilled Specialists to Grow Hospital Infrastructure for Quality Improvement
Authors: Padula William V. , Nagarajan Madhuram , Davidson Patricia M. , Pronovost Peter J. 
Published: July 2019

Objectives
Hospitals can reduce labor costs by hiring lowest skill possible for the job, stretching clinical hours, and reducing staff not at bedside. However, these labor constraints designed to reduce costs may paradoxically increase costs. Specialty staff, such as board-certified clinicians, can redesign health systems to evaluate the needs of complex patients and prevent complications. The aim of the study was to evaluate whether investing in skilled specialists for supporting hospital quality infrastructure improves value and performance.

Methods
We evaluated pressure injury rates as an indicator of performance in a retrospective observational cohort of 55 U.S. academic hospitals from the Vizient clinical database between 2007 and 2012. Pressure injuries were defined by U.S. Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicator 3 (PSI-03) for stage 3, 4, and unstageable pressure injuries not present on admission in hospitalized adults. We compared ratios of board-certified wound care nurses per 1000 hospital beds to hospital-acquired pressure injury rates in these hospitals using mixed-effects regression of hospital quarters.

Results
High-performing hospitals invested in prevention infrastructure with skilled specialists and observed performance improvements. Regression indicated that by adding one board-certified wound care nurse per 1000 hospital beds, hospitals had associated decreases in pressure injury rates by −17.7% relative to previous quarters, controlling for other interruptions. Highest performers supplied fewer skilled specialists and achieve improved outcomes.

Conclusions
Skilled specialists bring important value to health systems as a representation of investment in infrastructure, and the proportion of these specialists could be scaled relative to the hospital’s patient capacity. Policy should support hospitals to make investments in infrastructure to drive down patient costs and improve quality.
Mandibular Distraction Osteogenesis
Authors: Sahoo Nanda Kishore , Issar Yuvraj , Thakral Ankur 
Published: July 2019

Abstract
Mandibular hypoplasia is a common dentofacial deformity requiring a combination of orthodontic and surgical treatment. Before the introduction of distraction osteogenesis various orthognathic surgical procedures were carried out to treat mandibular hypoplasia. Orthognathic procedures like corpus lengthening by bilateral sagittal split ramus osteotomy and genioplasty are commonly practised all over the world to address the high esthetic demands and functional problems. But hardly there are any established orthognathic surgical procedures to address the deficiency of the posterior part of the mandible that is ramus and condyle. Transverse mandibular deficiency is one of the most difficult problems to be addressed surgically.
With the advent of distraction osteogenesis there is a change in concept of addressing mandibular deficiency. Mandibular corpus distraction was first performed by McCarthy et al using an extraoral unidirectional distraction device. The precision of bone lengthening with extraoral distracters did not accurately match the device settings. Since then due to sustained research and design and collaboration with the manufacturers, clinicians have developed various devices to improve the results of mandibular lengthening. Distractor devices of various shape and size are developed for intraoral use in specific anatomical locations of mandible.
This presentation will focus on use of intraoral distraction devices on different anatomical locations of mandible. The surgical methods of corpus, ramus, ramuscondylar unit, and symphyseal distraction osteogenesis and associated complications will be discussed in detail.
One-Step Triple-Layer Reconstruction of an Exposed Calvarium in a Patient With Radiated Tinea Capitis
Authors: Shay Tamir , Har-Shai Lior , Cohen Avi A. , Ad-El Dean D. 
Published: July 2019

Abstract
Full-thickness large scalp defects with underlying exposed calvarium pose a significant reconstructive challenge. Traditional reconstructive techniques are usually not an option in patients with irradiated scalp with thin skin and reduced laxity.
Dermal substitutes-based reconstruction techniques have been described in recent years. A common approach is the staged methodology, with the initial application of skin substitute followed by a split-thickness skin graft few weeks later; however, this method involves a prolonged period of local wound management prior to skin grafting and is often associated with complications that interfere with wound healing.
This report describes a single-stage triple-layer technique for the reconstruction of a large scalp defect with exposed bone in a patient with a history of radiation treatment, using 3 turnover pericranial flaps in conjunction with a Matriderm dermal substitute and split-thickness skin graft. This immediate multilayered reconstruction provides a long-lasting structural and aesthetic outcome, with minimal donor site morbidity and reduced complications.
Frontal Sinus Preservation During Cerebrospinal Fluid Leak Repair
Authors: Bozkurt Gülpembe , Zocchi Jacopo , Russo Federico , Pietrobon Giacomo , Karligkiotis Apostolos , Elhassan Hassan Ahmed , Seyhun Nurullah , Bignami Maurizio , Castelnuovo Paolo 
Published: July 2019

Background:
To validate the repair of frontal sinus cerebrospinal fluid (CSF) leaks with preservation of frontal sinus drainage pathway (FSDP), independently of the approach used, and to establish the indications and limits of the endoscopic approach.

Methods:
A retrospective evaluation of patients undergoing surgery for frontal sinus CSF leaks was performed. Demographics, indications for both endoscopic/combined endoscopic and open approaches, complications, methods for maintaining FSDP, and perioperative outcomes were examined.

Results:
Fifty-three patients (average age 45 years) with frontal sinus CSF leaks were treated surgically from 2000 to 2018. All CSF leak repairs were successful at the 1st attempt with a mean follow-up of 76.8 months (range 4–227 months). Etiology was spontaneous (14), traumatic (26), and iatrogenic (13). In 17 patients, a purely endoscopic approach was performed, while an endoscopic endonasal orbital transposition procedure was added in 4 out of this group. In 23 patients, a combined endoscopic and osteoplastic procedure was employed, while in 13 patients a combined craniotomy and endoscopic procedure was performed. All frontal sinuses remained patent except for 2 cranialization patients.

Conclusion:
With contemporary endoscopic instrumentation and techniques, endoscopic closure of frontal sinus CSF leaks even in the far superolateral wall is feasible in selected patients. However, the surgeon should consider the option of combining an external approach when required. Preserving the FSDP should be the main aim regardless of the approach.
Pancreas Retransplant After Pancreas Graft Failure in Simultaneous Pancreas-kidney Transplants Is Associated With Better Kidney Graft Survival
Authors: Parajuli Sandesh , Arunachalam Annamalai , Swanson Kurtis J. , Aziz Fahad , Garg Neetika , Bath Natalie , Redfield Robert R. , Kaufman Dixon , Djamali Arjang , Odorico Jon , Mandelbrot Didier A. 
Published: July 2019

Background.
Simultaneous pancreas-kidney (SPK) transplant is usually the best option for the diabetic end-stage renal disease patient. There is limited information about kidney graft outcomes in SPK recipients with isolated pancreas graft failure who do versus do not undergo pancreas retransplantation.

Methods.
Patients were divided into 2 groups based on whether they underwent pancreas retransplant (ReTx+) or not (ReTx−). Kidney graft function and survival were the primary endpoints.

Results.
One hundred and nine patients satisfied our selection criteria, 25 in ReTx+ and 84 in ReTx−. Mean interval from SPK to pancreas failure was significantly shorter in the ReTx+ compared with the ReTx− group, 19.3 ± 36.7 versus 45.7 ± 47.0 months (P = 0.01), respectively. There was no significant difference in kidney graft follow-up post SPK between 2 groups (P = 0.48). At last follow-up, 15 of the 25 (60%) of the repeat pancreas graft had failed, with a mean graft survival among these failed pancreas graft of 2.6 ± 2.7 years, ranging from 0 to 8.1 years. Uncensored kidney graft failure was significantly lower in the ReTx+ group compared with the ReTx− group, 44% versus 67% (P = 0.04). Death-censored kidney graft failure was also lower in the ReTx+ group, 24% versus 48% (P = 0.04). The difference in patient survival did not reach statistical significance. In adjusted Cox regression analysis, rejection as a cause of pancreas failure was associated with increased risk of death-censored kidney graft failure, and pancreas retransplantation was associated with decreased risk of kidney graft failure. A similar pattern was seen after 1:1 matching for the interval between SPK and pancreas graft failure.

Conclusions.
Even though ReTx+ patients accept the risks associated with repeat pancreas surgery, providers should consider this option in suitable otherwise healthy patients.
Early-Career Coordinated Distributed Experiments: Empowerment Through Collaboration
Authors: Pastor Ada , Hernández-del Amo Elena , Giménez-Grau Pau , Fillol Mireia , Pereda Olatz , Flores Lorea , Sanpera-Calbet Isis , Bravo Andrea G. , Martín Eduardo J. , Poblador Sílvia , Arroita Maite , Rasines-Ladero Rubén , Ruiz Celia , del Campo Rubén , Abril Meritxell , Reyes Marta , Casas-Ruiz Joan Pere , Fernández Diego , de Castro-Català Núria , Tornero Irene , Palacin-Lizarbe Carlos , Arce María Isabel , Mora-Gómez Juanita , Gómez-Gener Lluís , Monroy Silvia , Freixa Anna , Lupon Anna , González-Ferreras Alexia María , Estévez Edurne , Rodríguez-Lozano Pablo , Solagaistua Libe , Rodríguez-Castillo Tamara , Aristi Ibon , Martínez Aingeru , Catalán Núria 
Published: July 2019

AbstractCoordinated distributed experiments (CDEs) enable the study of large-scale ecological patterns in geographically dispersed areas, while simultaneously providing broad academic and personal benefits for the participants. However, the effective involvement of early-career researchers (ECRs) presents major challenges. Here, we analyze the benefits and challenges of the first CDE exclusively led and conducted by ECRs (i.e. ECR-CDE), which sets a baseline for similar CDEs, and we provide recommendations for successful CDE execution. ECR-CDEs achieve most of the outcomes identified in conventional CDEs as well as extensive benefits for the young cohort of researchers, including: (i) receiving scientific credit, (ii) peer-training in new concepts and methods, (iii) developing leadership and communication skills, (iv) promoting a peer network among ECRs, and (v) building on individual engagement and independence. We also discuss the challenges of ECR-CDEs, which are mainly derived from the lack of independence and instability of the participants, and we suggest mechanisms to address them, such as resource re-allocation and communication strategies.
Principles of Cell Circuits for Tissue Repair and Fibrosis
Authors: Adler Miri , Mayo Avi , Zhou Xu , Franklin Ruth , Meizlish Matthew , Medzhitov Ruslan , Kallenberger Stefan , Alon Uri 
Published: July 2019

AbstractTissue-repair is a protective response after injury, but repetitive or prolonged injury can lead to fibrosis, a pathological state of excessive scarring. To pinpoint the dynamic mechanisms underlying fibrosis, it is important to understand the principles of the cell circuits that carry out tissue-repair. In this study, we establish a cell-circuit framework for the myofibroblast-macrophage circuit in wound-healing, including the accumulation of scar-forming extracellular matrix. We find that fibrosis results from multistability between three outcomes, which we term ‘hot fibrosis’ characterized by many macrophages, ‘cold fibrosis’ lacking macrophages, and normal wound-healing. The cell-circuit framework clarifies several unexplained phenomena including the paradoxical effect of macrophage depletion, the limited time-window in which removing inflammation leads to healing, the effects of cellular senescence, and why scar maturation takes months. We define key parameters that control the transition from healing to fibrosis, which may serve as potential targets for therapeutic reduction of fibrosis.
Plant defense resistance in natural enemies of a specialist insect herbivore
Authors: Zhang Xi , van Doan Cong , Arce Carla C.M. , Hu Lingfei , Gruenig Sandra , Parisod Christian , Hibbard Bruce E. , Hervé Maxime , Robert Christelle A.M. , Machado Ricardo A.R. , Erb Matthias 
Published: July 2019

AbstractPlants defend themselves against herbivores through the production of toxic and deterrent metabolites. Adapted herbivores can tolerate and sequester these metabolites, allowing them to feed on defended plants and become toxic to their own enemies. Can herbivore natural enemies overcome sequestered plant defense metabolites to prey on adapted herbivores? To address this question, we studied how entomopathogenic nematodes cope with benzoxazinoid defense metabolites that are produced by grasses and sequestered by a specialist maize herbivore, the western corn rootworm. We find that nematodes from US maize fields in regions in which the western corn rootworm was present over the last 50 years are behaviorally and metabolically resistant to sequestered benzoxazinoids and more infective towards the western corn rootworm than nematodes from other parts of the world. Exposure of a benzoxazinoid-susceptible nematode strain to the western corn rootworm for five generations results in higher behavioral and metabolic resistance and benzoxazinoid-dependent infectivity towards the western corn rootworm. Thus, herbivores that are exposed to a plant defense sequestering herbivore can evolve both behavioral and metabolic resistance to plant defense metabolites, and these traits are associated with higher infectivity towards a defense sequestering herbivore. We conclude that plant defense metabolites that are transferred through adapted herbivores may result in the evolution of resistance in herbivore natural enemies. Our study also identifies plant defense resistance as a novel target for the improvement of biological control agents.
Enhanced targeted resequencing by optimizing the combination of enrichment technology and DNA fragment length
Authors: Iadarola Barbara , Xumerle Luciano , Lavezzari Denise , Paterno Marta , Marcolungo Luca , Beltrami Cristina , Fortunati Elisabetta , Mei Davide , Vetro Annalisa , Guerrini Renzo , Parrini Elena , Rossato Marzia , Delledonne Massimo 
Published: July 2019

AbstractWhole-exome sequencing (WES) enrichment platforms are usually evaluated by measuring the depth of coverage at target regions. However, variants called in WES are reported in the variant call format (VCF) file, which is filtered by minimum site coverage and mapping quality. Therefore, genotypability (base calling calculated by combining depth of coverage with the confidence of read alignment) should be considered as a more informative parameter to assess the performance of WES. We found that the mapping quality of reads aligned to difficult target regions was improved by increasing the DNA fragment length well above the average exon size. We tested three different DNA fragment lengths using four major commercial WES platforms and found that longer DNA fragments achieved a higher percentage of callable bases in the target regions and thus improved the genotypability of many genes, including several associated with clinical phenotypes. DNA fragment size also affected the uniformity of coverage, which in turn influences genotypability, indicating that different platforms are optimized for different DNA fragment lengths. Finally, we found that although the depth of coverage continued to increase in line with the sequencing depth (overall number of reads), base calling reached saturation at a depth of coverage that depended on the enrichment platform and DNA fragment length. This confirmed that genotypability provides better estimates for the optimal sequencing depth of each fragment size/enrichment platform combination.
Global Analysis of Human mRNA Folding Disruptions in Synonymous Variants Demonstrates Significant Population Constraint
Authors: Gaither Jeffrey B.S. , Lammi Grant E. , Li James L. , Gordon David M. , Kuck Harkness C. , Kelly Benjamin J. , Fitch James R. , White Peter 
Published: July 2019

ABSTRACTBackgroundIn most organisms the structure of an mRNA molecule is crucial in determining speed of translation, half-life, splicing propensities and final protein configuration. Synonymous variants which distort this wildtype mRNA structure may be pathogenic as a consequence. However, current clinical guidelines classify synonymous or “silent” single nucleotide variants (sSNVs) as largely benign unless a role in RNA splicing can be demonstrated.ResultsWe developed novel software to conduct a global transcriptome study in which RNA folding statistics were computed for 469 million SNVs in 45,800 transcripts using an Apache Spark implementation of ViennaRNA in the cloud. Focusing our analysis on the subset of 17.9 million sSNVs, we discover that variants predicted to disrupt mRNA structure have lower rates of incidence in the human population. Given that the community lacks tools to evaluate the potential pathogenic impact of sSNVs, we introduce a “Structural Predictivity Index” (SPI) to quantify this constraint due to mRNA structure.ConclusionsOur findings support the hypothesis that sSNVs may play a role in genetic disorders due to their effects on mRNA structure. Our RNA-folding scores provide a means of gauging the structural constraint operating on any sSNV in the human genome. Given that the majority of patients with rare or as yet to be diagnosed disease lack a molecular diagnosis, these scores have the potential to enable discovery of novel genetic etiologies. Our RNA Stability Pipeline as well as ViennaRNA structural metrics and SPI scores for all human synonymous variants can be downloaded from GitHub https://github.com/nch-igm/rna-stability.
Aerobic methoxydotrophy: growth on methoxylated aromatic compounds by Methylobacterium
Authors: Lee Jessica A. , Stolyar Sergey , Marx Christopher J. 
Published: July 2019

AbstractPink-pigmented facultative methylotrophs have long been studied for their ability to grow on reduced single-carbon (C1) compounds. The C1 groups that support methylotrophic growth may come from a variety of sources. Here, we describe a group of Methylobacterium strains that can engage in methoxydotrophy: they can metabolize the methoxy groups from several aromatic compounds that are commonly the product of lignin depolymerization. In addition, these organisms can utilize the full aromatic ring as a growth substrate, a phenotype that has rarely been described in Methylobacterium. We demonstrated growth on p-hydroxybenzoate, protocatechuate, vanillate, and ferulate in laboratory culture conditions. We also used comparative genomics to explore the evolutionary history of this trait, finding that the capacity for aromatic catabolism is likely ancestral to two clades of Methylobacterium, but has also been acquired horizontally by closely related organisms. In addition, we surveyed the published metagenome data to find that the most abundant group of aromatic-degrading Methylobacterium in the environment is likely the group related to M. nodulans, and they are especially common in soil and root environments. The demethoxylation of lignin-derived aromatic monomers in aerobic environments releases formaldehyde, a metabolite that is a potent cellular toxin but that is also a growth substrate for methylotrophs. We found that, whereas some known lignin-degrading organisms excrete formaldehyde as a byproduct during growth on vanillate, Methylobacterium do not. This observation is especially relevant to our understanding of the ecology and the bioengineering of lignin degradation.