bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Effectiveness of Different Interventions of Perivascular Hyaluronidase
Authors: Lee Won , Oh Wook , Oh Seung Min , Yang Eun-Jung 
Published: January 2020

Background:
Soft-tissue necrosis caused by vascular compromise is a frequent and troublesome complication of hyaluronic acid filler injection. Hyaluronidase has been proposed as a treatment for this condition. This study aimed to determine the effective dose and administration interval of hyaluronidase injection in a skin necrosis animal model.

Methods:
New Zealand rabbits were used to simulate the hyaluronic acid–associated vascular occlusion model. Hyaluronic acid filler (0.1 ml) was injected into the central auricular artery to create an occlusion. Three rabbit auricular flaps were injected with 500 IU of hyaluronidase once (group A) and three flaps each were injected at 15-minute intervals with 250 IU of hyaluronidase twice (group B), 125 IU of hyaluronidase four times (group C), 100 IU of hyaluronidase five times (group D), and 75 IU of hyaluronidase seven times (group E), all at 24 hours after occlusion. No intervention was administered after occlusion in the control group. Flap fluorescence angiography was performed immediately after hyaluronidase injection and on postoperative days 2, 4, and 7. Flap necrotic areas were analyzed.

Results:
All control and experimental flaps demonstrated total occlusion after hyaluronic acid injection. The average total survival rate (positive area/total area ×100 percent) of control flaps was 37.61 percent. For experimental groups, the average total survival rates were 74.83 percent, 81.49 percent, 88.26 percent, 56.48 percent, and 60.69 percent in groups A through E, respectively.

Conclusion:
A better prognosis can be obtained by administering repeated doses rather than a single high dose of hyaluronidase.
Risk of Intracranial Extension of Craniofacial Dermoid Cysts
Authors: Overland Joseph , Hall Courtney , Holmes Anthony , Burge Jonathan 
Published: January 2020

Background:
Dermoid cysts are benign lesions lined by keratinizing squamous epithelium that also contain epidermal adnexa (hair follicles, hair shafts, sebaceous glands, and both apocrine and eccrine sweat glands) and mesodermal derivatives (smooth muscle fibers, vascular stroma, nerves, and collagen fibers). Craniofacial dermoid cysts represent approximately 7 percent of all dermoids and have an incidence ranging between 0.03 and 0.14 percent.

Methods:
The authors conducted a single-center, consecutive, nonrandomized comparative case series over a 20-year period of all patients treated surgically for craniofacial dermoid at the Royal Children’s Hospital in Melbourne, Australia. Six hundred forty-seven patients had craniofacial dermoids and adequate information to be included in the study. The authors also conducted a thorough review of the literature using the MEDLINE and Embase databases.

Results:
Six hundred forty-seven patients amounted to 655 lesions in our case series. The age at surgery ranged from 2 months to 18 years, with an average age of 25.65 months. The depth of the lesions was stratified using a classification system, and the risk of intracranial extension was assessed using these data. Midline nasal lesions are established as high risk by other studies, but frontal, temporal, and occipital lesions were found to be as risky if not more risky for intracranial extension.

Conclusions:
Several classification systems for craniofacial dermoid cysts have used both broader anatomical locations and physical characteristics to group these lesions and identify those warranting preoperative imaging. The authors propose a system using more specific classification of anatomical location to assist in the prompt identification of high-risk lesions and facilitate sound preoperative planning.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, V.
Free Tissue Transfer with Distraction Osteogenesis and Masquelet Technique Is Effective for Limb Salvage in Patients with Gustilo Type IIIB Open Fractures
Authors: Abdou Salma A. , Stranix John T. , Daar David A. , Mehta Devan D. , McLaurin Toni , Tejwani Nirmal , Saadeh Pierre B. , Levine Jamie P. , Leucht Philipp , Thanik Vishal D. 
Published: January 2020

Summary:
Osteocutaneous reconstruction can be challenging because of concomitant injuries and limited donor sites. There is a paucity of data on limb salvage outcomes following combined soft-tissue reconstruction and bone transport or Masquelet procedures. The authors reviewed a consecutive series of open tibia fracture patients undergoing soft-tissue reconstruction with either distraction osteogenesis or Masquelet technique. Endpoints were perioperative flap complications and bone union. Fourteen patients with Gustilo type IIIB open tibia fractures were included. Half of the group received muscle flaps and the remaining half received fasciocutaneous flaps. Ten patients (71.4 percent) underwent distraction osteogenesis and the remaining patients underwent Masquelet technique. Average bone gap length was 65.7 ± 31.3 mm (range, 20 to 120 mm). In the bone transport group, the average external fixation duration was 245 days (range, 47 to 686 days). In the Masquelet group, the average duration of the first stage of this two-stage procedure (i.e., time from cement spacer placement to bone grafting) was 95 days (range, 42 to 181 days). Bone union rate, as determined by radiographic evidence, was 85.7 percent. There was one complete flap failure (7.1 percent). One patient underwent below-knee amputation after failing bone transport and developing chronic osteomyelitis and subsequent infected nonunion. Our case series demonstrates that nonosteocutaneous flap methods of limb reconstruction are a viable option in patients with segmental long bone defects, with a bone union rate of 85 percent and a limb salvage rate over 90 percent in patients with Gustilo type IIIB fractures.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Antenatal Intracellular Concentrations of Tenofovir Diphosphate and Emtricitabine Triphosphate and Associations Between Tenofovir Diphosphate and Severe Adverse Pregnancy Outcomes: IMPAACT-PROMISE (1077BF) Trial
Authors: Aizire Jim , Brooks Kristina M. , Mirochnick Mark , Flynn Patricia M. , Butler Kevin , Kiser Jennifer J. , Siberry George K. , Fenton Terry , Cababasay Mae , Fowler Mary G. ,   for the PROMISE Study Team
Published: January 2020

Background:
In the Promoting Maternal and Infant Survival Everywhere (PROMISE) trial, tenofovir disoproxil fumarate (TDF) use was associated with moderate or severe adverse pregnancy/neonatal outcomes. This study characterized tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) concentrations in dried blood spots (DBS) and assessed association between severe adverse pregnancy/neonatal outcomes and TFV-DP concentration.

Methods:
Retrospective case–control study of PROMISE trial arm-C women randomized to receive TDF, FTC, and ritonavir-boosted lopinavir (LPV/r), who took at least 1 dose of TDF + FTC and had week-4 postrandomization DBS drawn before delivery. Cases, defined as severe adverse pregnancy/neonatal outcomes (very preterm delivery before 34 weeks of gestation, stillbirth ≥20 weeks of gestation, or infant death before 14 days-of-age), were matched to controls (1:2 ratio) by site and gestational age at entry. Week 4 and week 8 DBS samples were assayed for TFV-DP and FTC-TP by liquid chromatography and tandem mass spectrometry. Associations were tested using Wilcoxon rank test and conditional logistic regression.

Results:
Of 447 PROMISE arm-C women, 33 met case definitions, and overall, 22 cases and 44 controls were analyzed. Median (interquartile range) concentrations of TFV-DP at weeks 4 and 8 were 706 (375–1023) fmol/punch and 806 (414–1265) fmol/punch, respectively. Odds ratio (95% confidence interval) for severe adverse pregnancy/neonatal outcome with natural log of TFV-DP concentrations as the predictor were 1.27 (0.74 to 2.18) and 1.74 (0.66 to 4.60) at weeks 4 and 8, respectively. Median (interquartile range) concentrations of FTC-TP at weeks 4 and 8 were 0.27 (0.05–0.36) pmol/punch and 0.29 (0.05–0.40) pmol/punch, respectively.

Conclusions:
TFV-DP concentrations in DBS appeared not to be associated with severe adverse pregnancy/neonatal outcomes, although sample size was limited.
Significance of Best Spirometry in the First Year After Bilateral Lung Transplantation: Association With 3-Year Outcomes
Authors: Mohanka Manish R. , Kanade Rohan , Garcia Heriberto , Mahan Luke , Bollineni Srinivas , Mullins Jessica , Joerns John , Kaza Vaidehi , Torres Fernando , Zhang Song , Banga Amit 
Published: January 2020

Background.
Spirometry is the cornerstone of monitoring allograft function after lung transplantation (LT). We sought to determine the association of variables on best spirometry during the first year after bilateral LT with 3-year posttransplant survival.

Methods.
We reviewed charts of patients who survived at least 3 months after bilateral LT (n = 157; age ± SD: 54 ± 13 y, male:female = 91:66). Best spirometry was calculated as the average of 2 highest measurements at least 3 weeks apart during the first year. Airway obstruction was defined as forced expiratory volume in 1-second (FEV1)/forced vital capacity (FVC) ratio <0.7. Survival was compared based on the ventilatory defect and among groups based on the best FEV1 and FVC measurements (>80%, 60%–80%, and <60% predicted). Primary outcome was 3-year survival.

Results.
Overall, 3-year survival was 67% (n = 106). Obstructive defect was uncommon (7%) and did not have an association with 3-year survival (72% versus 67%, P = 0.7). Although one-half patients achieved an FVC>80% predicted (49%), 1 in 5 (19%) remained below 60% predicted. Irrespective of the type of ventilatory defect, survival worsened as the best FVC (% predicted) got lower (>80: 80.8%; 60–80: 63.3%; <60: 40%; P < 0.001). On multivariate logistic regression analysis, after adjusting for age, gender, transplant indication, and annual bronchoscopy findings, best FVC (% predicted) during the first year after LT was independently associated with 3-year survival.

Conclusions.
A significant proportion of bilateral LT patients do not achieve FVC>80% predicted. Although the type of ventilatory defect on best spirometry does not predict survival, failure to achieve FVC>80% predicted during the first year was independently associated with 3-year mortality.
LPS-induced Airway-centered Inflammation Leading to BOS-like Airway Remodeling Distinct From RAS-like Fibrosis in Rat Lung Transplantation
Authors: Takahagi Akihiro , Sato Masaaki , Chen-Yoshikawa Toyofumi F. , Miyamoto Ei , Saito Masao , Gochi Fumiaki , Hamaji Masatsugu , Yoshizawa Akihiko , Terasaki Yasuhiro , Urushiyama Hirokazu , Aoyama Akihiro , Sonobe Makoto , Date Hiroshi 
Published: January 2020

Background.
Localization of inflammatory stimuli may direct lung allografts to different phenotypes of chronic dysfunction, such as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). We hypothesized that airway stimulation with lipopolysaccharide (LPS) in rats leads to airway-centered inflammation similar to human BOS.

Methods.
Rat left lung transplantation was conducted (donor: Brown Norway, recipient: Lewis). Allotransplant recipients received cyclosporine A (CsA) until postoperative day 56 with airway instillation of LPS (Allo-LPS, n = 8), phosphate buffered saline (Allo-PBS, n = 5) from days 35 to 46 (3 times a wk), or no further treatment (n = 4). Some allotransplant recipients received CsA until day 14 and were immunosuppression free after day 15 until day 56. Bronchial and pleural fibrosis were semiquantified; alveolar fibrosis was evaluated with a histological scale.

Results.
The Allo-LPS group had significantly increased International Society for Heart and Lung Transplantation rejection grades (grade A, P = 0.005; grade B, P = 0.004), bronchial obstructive proportion (0.34 ± 0.04% [Allo-LPS] versus 0.11 ± 0.04% [Allo-PBS], P = 0.006), and airway resistance (3.05 ± 1.78 cm H2O·s/mL [Allo-LPS] versus 0.83 ± 0.58 cm H2O·s/mL [Allo-PBS], P = 0.007) compared with other groups. Allotransplant recipients that underwent a short course of CsA developed RAS-like fibrosis involving the airways, alveoli, and pleura.

Conclusions.
Airway instillation of LPS in allografts under immunosuppression resulted in BOS-like airway-centered inflammation and fibrosis distinct from RAS-like diffuse fibrosis, which was induced by a shortened course of immunosuppression. We propose novel animal models for BOS and RAS after lung transplantation.
CXCL9 Predicts Severity at the Onset of Chronic Graft-versus-host Disease
Authors: Giesen Nicola , Schwarzbich Mark-Alexander , Dischinger Katharina , Becker Natalia , Hummel Manuela , Benner Axel , Radujkovic Aleksandar , Müller-Tidow Carsten , Dreger Peter , Luft Thomas 
Published: January 2020

Background.
Chronic graft-versus-host disease (cGVHD) represents a double-edged sword. In its nonsevere form, cGVHD associates with better control of the malignant disease, thus highlighting graft-versus-leukemia effects. However, severe cGVHD leads to debilitating morbidity and increased nonrelapse mortality. The prediction of severe cGVHD, in particular at disease onset, is therefore of high importance for ensuing clinical decisions and overall success of allogeneic stem cell transplantations. CXC-chemokine ligand 9 (CXCL9) is an interferon-inducible chemokine of the CXC family and is increased in cGVHD. Endothelial activation and stress index (EASIX) was shown to predict death after acute graft-versus-host disease. We explored CXCL9 and EASIX as predictors of severe cGVHD.

Methods.
Sera and clinical data of 480 patients were available who survived at least 6 months following allogeneic stem cell transplantation without steroid-refractory acute graft-versus-host disease and without early relapse. CXCL9 and EASIX were measured on day +100 and onset of cGVHD.

Results.
Development of nonsevere cGVHD was significantly associated with improved overall survival (hazard ratio 0.53, P < 0.001). CXCL9 serum levels at the onset of cGVHD predicted the development of severe cGVHD later on (hazard ratio 1.33, P = 0.02). In contrast, EASIX at the onset of cGVHD was not associated with cGVHD severity but was a significant independent risk factor for overall mortality and nonrelapse mortality.

Conclusions.
CXCL9 levels at the onset of cGVHD can help to predict severe courses of the disease and have potential for optimizing tailored administration of immunosuppressive therapy.
Nasal Pressure Injuries Due to Nasal Continuous Positive Airway Pressure Treatment in Newborns
Authors: Dai Tian , Lv Limin , Liu Xiaojuan , Chen Jin , Ye Yalan , Xu Lixuan 
Published: January 2020

PURPOSE:
The purpose of this study was to calculate incidence, severity, and risk factors of nasal pressure injuries due to nasal continuous positive airway pressure (NCPAP) treatment in newborns.

DESIGN:
A prospective observational study.

SUBJECTS AND SETTING:
Newborns admitted between March 2017 and February 2018 to the neonatal intensive care unit of the First Affiliated Hospital of Xiamen University, Xiamen, China.

METHODS:
All newborns' noses were examined during NCPAP application. Every NCPAP-related nasal pressure injury including occurrence date, injury severity, outcomes, and pressure injury treatment methods was recorded. These data were collected twice a week by a research nurse. Nasal pressure injuries were classified using the National Pressure Ulcer Advisory Panel/European Pressure Ulcer Advisory Panel pressure injury classification system.

RESULTS:
During the study period, 429 newborns received NCPAP treatment via nasal prongs. Nasal pressure injuries were observed in 149 (34.7%); 99 (66.44%) were classified as Stage 1, 48 (32.31%) were Stage 2, and 2 (1.25%) cases were classified as deep tissue injury. The risk of nasal pressure injury was significantly higher when gestational age was less than 32 weeks (odds ratio [OR], 3.728; 95% confidence interval [CI], 1.18-11.77; P ≤ .025) and in those who received NCPAP treatment for more than 6 days (OR, 0.262; 95% CI, 0.087-0.787; P ≤ .017). The mean interval between the application of NCPAP and onset of nasal pressure injury was 4.72 days (SD, 4.78; range, 0-30 days).

CONCLUSIONS:
Nasal pressure injuries are a prevalent complication of NCPAP use, especially in preterm newborns. Our results identified a gestational age of less than 32 weeks and longer use of NCPAP are important factors associated with nasal pressure injuries. Methods to prevent the development of injuries such as the use of a prophylactic dressing along and replacement of binasal prongs with nasal masks are advocated.
Vertebrate palaeophysiology
Authors: Cubo Jorge , Huttenlocker Adam K. 
Published: January 2020

Physiology is a functional branch of the biological sciences, searching for general rules by which explanatory hypotheses are tested using experimental procedures, whereas palaeontology is a historical science dealing with the study of unique events where conclusions are drawn from congruence among independent lines of evidence. Vertebrate palaeophysiology bridges these disciplines by using experimental data obtained from extant organisms to infer physiological traits of extinct ones and to reconstruct how they evolved. The goal of this theme issue is to understand functional innovations imprinted on modern vertebrate clades, and how to infer (or ‘retrodict’) physiological capacities in their ancient relativesa posteriori.As such, the present collection of papers deals with different aspects of a rapidly growing field to understand innovations in: phospho-calcic metabolism, acid–base homeostasis, thermometabolism, respiratory physiology, skeletal growth, palaeopathophysiology, genome size and metabolic rate, and it concludes with a historical perspective. Sometimes, the two components (physiological mechanism and palaeobiological inference) are proposed in separate papers. Other times, the two components are integrated in a single paper. In all cases, the approach was comparative, framed in a phylogenetic context, and included rigorous statistical methods that account for evolutionary patterns and processes.This article is part of the theme issue ‘Vertebrate palaeophysiology’.
The evolution of mechanisms involved in vertebrate endothermy
Authors: Legendre Lucas J. , Davesne Donald 
Published: January 2020

Endothermy, i.e. the endogenous production of metabolic heat, has evolved multiple times among vertebrates, and several strategies of heat production have been studied extensively by physiologists over the course of the twentieth century. The independent acquisition of endothermy by mammals and birds has been the subject of many hypotheses regarding their origin and associated evolutionary constraints. Many groups of vertebrates, however, are thought to possess other mechanisms of heat production, and alternative ways to regulate thermogenesis that are not always considered in the palaeontological literature. Here, we perform a review of the mechanisms involved in heat production, with a focus on cellular and molecular mechanisms, in a phylogenetic context encompassing the entire vertebrate diversity. We show that endothermy in mammals and birds is not as well defined as commonly assumed by evolutionary biologists and consists of a vast array of physiological strategies, many of which are currently unknown. We also describe strategies found in other vertebrates, which may not always be considered endothermy, but nonetheless correspond to a process of active thermogenesis. We conclude that endothermy is a highly plastic character in vertebrates and provides a guideline on terminology and occurrences of the different types of heat production in vertebrate evolution.This article is part of the theme issue ‘Vertebrate palaeophysiology’.
The relationship between genome size and metabolic rate in extant vertebrates
Authors: Gardner Jacob D. , Laurin Michel , Organ Chris L. 
Published: January 2020

Genome size has long been hypothesized to affect the metabolic rate in various groups of animals. The mechanism behind this proposed association is the nucleotypic effect, in which large nucleus and cell sizes influence cellular metabolism through surface area-to-volume ratios. Here, we provide a review of the recent literature on the relationship between genome size and metabolic rate. We also conduct an analysis using phylogenetic comparative methods and a large sample of extant vertebrates. We find no evidence that the effect of genome size improves upon models in explaining metabolic rate variation. Not surprisingly, our results show a strong positive relationship between metabolic rate and body mass, as well as a substantial difference in metabolic rate between endothermic and ectothermic vertebrates, controlling for body mass. The presence of endothermy can also explain elevated rate shifts in metabolic rate whereas genome size cannot. We further find no evidence for a punctuated model of evolution for metabolic rate. Our results do not rule out the possibility that genome size affects cellular physiology in some tissues, but they are consistent with previous research suggesting little support for a direct functional connection between genome size and basal metabolic rate in extant vertebrates.
This article is part of the theme issue ‘Vertebrate palaeophysiology’.
Machine learning approaches for fracture risk assessment: a comparative analysis of genomic and phenotypic data in 5,130 older men
Authors: Wu Qing , Nasoz Fatma , Jung Jongyun , Bhattarai Bibek , Han Mira V 
Published: January 2020

AbstractThe study aims were to develop fracture prediction models by using machine learning approaches and genomic data, as well as to identify the best modeling approach for fracture prediction. The genomic data of Osteoporotic Fractures in Men, cohort Study (n= 5,130), was analyzed. After a comprehensive genotype imputation, genetic risk score (GRS) was calculated from 1,103 associated SNPs for each participant. Data were normalized and split into a training set (80%) and a validation set (20%) for analysis. Random forest, gradient boosting, neural network, and logistic regression were used to develop prediction models for major osteoporotic fractures separately, with GRS, bone density and other risk factors as predictors. For model training, the synthetic minority over-sampling technique was used to account for low fracture rate, and 10-fold cross-validation was employed for hyperparameters optimization. In the testing set, the area under the ROC curve (AUC) and accuracy were used to assess the model performance. The McNemar test was employed for pairwise comparisons to examine the accuracy difference between models. The results showed that the prediction performance of gradient boosting was the best, with AUC of 0.71 and an accuracy of 0.88, and the GRS ranked as the 7th most important variable in the model. The performance of random forest and neural network were also better than that of logistic regression. Pairwise comparisons showed that the accuracy difference between models was significant. This study suggested that improving fracture prediction can be achieved by incorporating genetic profiling and by utilizing the gradient boosting approach.