bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone Tissue Engineering in the Growing Calvaria Using Dipyridamole-Coated, Three-Dimensionally–Printed Bioceramic Scaffolds: Construct Optimization and Effects on Cranial Suture Patency
Authors: Maliha Samantha G. , Lopez Christopher D. , Coelho Paulo G. , Witek Lukasz , Cox Madison , Meskin Alan , Rusi Sejndi , Torroni Andrea , Cronstein Bruce N. , Flores Roberto L. 
Published: November 2019

Background:
Three-dimensionally–printed bioceramic scaffolds composed of β-tricalcium phosphate delivering the osteogenic agent dipyridamole can heal critically sized calvarial defects in skeletally mature translational models. However, this construct has yet to be applied to growing craniofacial models. In this study, the authors implanted three-dimensionally–printed bioceramic/dipyridamole scaffolds in a growing calvaria animal model and evaluated bone growth as a function of geometric scaffold design and dipyridamole concentration. Potential adverse effects on the growing suture were also evaluated.

Methods:
Bilateral calvarial defects (10 mm) were created in 5-week-old (approximately 1.1 kg) New Zealand White rabbits (n = 16 analyzed). Three-dimensionally–printed bioceramic scaffolds were constructed in quadrant form composed of varying pore dimensions (220, 330, and 500 μm). Each scaffold was coated with collagen and soaked in varying concentrations of dipyridamole (100, 1000, and 10,000 μM). Controls consisted of empty defects. Animals were killed 8 weeks postoperatively. Calvariae were analyzed using micro–computed tomography, three-dimensional reconstruction, and nondecalcified histologic sectioning.

Results:
Scaffold-induced bone growth was statistically greater than bone growth in empty defects (p = 0.02). Large scaffold pores, 500 μm, coated in 1000 μM dipyridamole yielded the most bone growth and lowest degree of scaffold presence within the defect. Histology showed vascularized woven and lamellar bone along with initial formation of vascular canals within the scaffold lattice. Micro–computed tomographic and histologic analysis revealed patent calvarial sutures without evidence of ectopic bone formation across all dipyridamole concentrations.

Conclusion:
The authors present an effective pediatric bone tissue-engineering scaffold design and dipyridamole concentration that is effective in augmentation of calvarial bone generation while preserving cranial suture patency.
The Alignment of the Nose in Rhinoplasty: Fix Down Concept
Authors: Taş Süleyman 
Published: November 2019

Background:
The current literature on rhinoplasty focuses mainly on the nasal profile (sagittal plane); however, the nose is a three-dimensional structure, and alignment of the nose in consideration of other aspects is important to achieve an aesthetic result. The author aimed to introduce the fix down concept, which includes fix down technique and the adjunct maneuvers for achieving alignment of the nose in three anatomical planes and improving the results of rhinoplasty in terms of symmetry.

Methods:
Between March of 2017 and December of 2017, a total of 102 patients (78 women and 24 men), 13 revision and 89 primary cases, underwent septorhinoplasty with the fix down concept. The noses were evaluated in coronal, sagittal, and axial planes and classified according to their deformities.

Results:
The functional and aesthetic results were satisfactory for the patients, examiners, and surgeon. No revisions were necessary during the follow-up period. In addition to the fix down technique, ethmoid bone grafting (16 patients), fix up technique (eight patients), dissection of the levator labii superioris alaeque nasi muscle (14 patients), plication of this muscle (four patients), superior-based transposition flap (39 patients), rim grafts (17 patients), mucosa grafts (12 patients), double-layer grafts (nine patients), maxillary deepening (five patients), maxillary augmentation with cartilage/bone grafts (21 patients), and supratip onlay grafts (seven patients) were used as adjunctive maneuvers to achieve symmetry in the frontal, base, and profile views.

Conclusion:
The presented fix down concept will help to provide three-dimensional symmetric noses for rhinosurgeons.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Interventions to reduce acute hepatitis C virus in HIV-positive MSM
Authors: Elliott Tamara , Cooke Graham S. , Garvey Lucy 
Published: November 2019

Purpose of review
The WHO has set ambitious targets for hepatitis C virus (HCV) elimination by 2030. In this review, we explore the possibility of HCV micro-elimination in HIV-positive (+) MSM, discussing strategies for reducing acute HCV incidence and the likely interventions required to meet these targets.

Recent findings
With wider availability of directly acting antivirals (DAAs) in recent years, reductions in acute HCV incidence have been reported in some cohorts of HIV+ MSM. Recent evidence demonstrates that treatment in early infection is well tolerated, cost effective and may reduce the risk of onward transmission. Modelling studies suggest that to reduce incidence, a combination approach including behavioural interventions and access to early treatment, targeting both HIV+ and negative high-risk groups, will be required. HCV vaccine trials have not yet demonstrated efficacy in human studies, however phase one and two studies are ongoing.

Summary
Some progress towards the WHO HCV elimination targets has been reported. Achieving sustained HCV elimination is likely to require a combination approach including early access to DAAs in acute infection and reinfection, validated and reproducible behavioural interventions and an efficacious HCV vaccine.
Facing increased sexually transmitted infection incidence in HIV preexposure prophylaxis cohorts: what are the underlying determinants and what can be done?
Authors: Kenyon Chris , Van Dijck Christophe , Florence Eric 
Published: November 2019

Purpose of review
The combined incidence of chlamydia, gonorrhoea and syphilis in MSM PrEP (preexposure prophylaxis) cohorts now frequently exceeds 100 per 100 person years. The efficacy of antiretroviral PrEP in reducing HIV transmission has led to efforts to find similar biomedical ways reduce sexually transmitted infection (STI) incidence. We review the recent evidence for these and other strategies.

Recent findings
Doxycycline PrEP/postexposure prophylaxis has been shown to reduce the incidence of syphilis and chlamydia but not gonorrhoea. A meningococcal vaccine has been found to result in a lower incidence of gonorrhoea. Novel insights into the role of the pharynx in the transmission of gonorrhoea have led to clinical trials of oral antiseptics to reduce the spread of gonorrhoea. Intensified STI screening has been introduced in a number of clinics. Serious concerns have however been raised about the emergence of resistance to each of these strategies. This is particularly true for doxycycline PrEP which is not advocated by any guidelines we reviewed.

Summary
Randomized controlled trials are urgently required to ascertain the benefits and risks of interventions to reduce STIs in MSM PrEP cohorts.
Comparison of Quantitative Perfusion and Function Parameters of Gated-SPECT Myocardial Perfusion Imaging in Patients With Concordant and Discordant Left Bundle-Branch Block
Authors: Ghaedian Tahereh , Behbudnia Tuba , Dehghani Pooyan 
Published: November 2019

Background
Patients with left bundle-branch block (LBBB) can be classified to discordant LBBB (dLBBB) and concordant LBBB (cLBBB) according to T-wave orientation in lateral leads. This classification indicates different functional left ventricular (LV) parameters with worse prognosis in dLBBB patients. However, there are no data regarding the impact of this classification on perfusion status of the left ventricle. The aim of this study is to evaluate and compare the SPECT myocardial perfusion imaging (MPI) findings of LV perfusion and function between dLBBB and cLBBB patients.

Methods
All patients who were referred for SPECT MPI during an 11 months' period were evaluated. Patients with evidence of LBBB on standard baseline 12-lead ECG were included, and their demographic, medical history, and imaging data were recorded. Quantitative perfusion and function parameters of LV included summed stress score, summed rest score, summed difference score, total perfusion deficit (TPD) at both phases with delta TPD, ejection fraction, end-diastolic volume, end-systolic volume, summed motion score, summed thickening score, phase SD, and phase histogram bandwidth. All baseline ECGs were further assessed by a cardiologist to categorize patients as the cLBBB or dLBBB group according to concordance of the T wave with QRS complex in lateral leads.

Results
Finally, 97 patients with 46 cLBBB and 51 dLBBB cases were included. Baseline characteristics and cardiovascular risk factors including diabetes mellitus, hypertension, hyperlipidemia, history of coronary artery disease (CAD), family history of CAD, and smoking were not significantly different between the 2 groups. However, summed stress score (12.2 vs 6.7), summed difference score (4.0 vs 2.6), stress TPD (11.0 vs 6.4), and delta TPD (4.8 vs 3.9) were significantly higher in dLBBB patients. In addition, functional parameters were also significantly worse in dLBBB patients with lower ejection fraction and higher end-diastolic volume, end-systolic volume, summed motion score, and summed thickening score in these patients. Mean phase SD and phase histogram bandwidth were also significantly higher in dLBBB patients.

Conclusions
This study revealed that LBBB patients with discordant T wave in lateral leads have significantly higher ischemic scores and worse functional parameters with more dyssynchrony in gated SPECT MPI.
Solitary Bone Langerhans Cell Histiocytosis Demonstrated on Multimodality Imaging in an Adult
Authors: Zhao Yu , Zhou Yi , Tian Rong , Su Minggang 
Published: November 2019

Abstract
Multimodality imaging was performed on a 53-year-old woman who was suspected with malignant bone tumor in her left femoral midshaft on radiograph. An MRI demonstrated the lesion showed hypointensity on T1-weighted and high intensity on T2-weighted fat-saturated images. It was more extensive on MRI than that on radiograph, especially in bone marrow and parosteal soft tissue. The lesion accumulated radiotracer on bone scan and 18F-FDG PET/CT. Finally, a Langerhans cell histiocytosis was confirmed after surgery. The case cautions us Langerhans cell histiocytosis should be in the differential diagnosis spectrum in an adult with unexplained unifocal bone lesion on 18F-FDG PET/CT.
Adrenocortical Scintigraphy With SPECT/CT for the Diagnosis of Hepatic Adrenal Rest
Authors: Kawasaki Masako , Yoshimura Mana , Sugimoto Katsutoshi , Takeuchi Hirohito , Saito Kazuhiro 
Published: November 2019

Abstract
Hepatic adrenal rest include ectopic adrenal tissue in the liver and adrenohepatic fusion. Long-lasting hyperstimulation of that tissue induces hyperplasia sometimes simulating true tumors. True autonomic tumors originating from ectopic adrenal tissue with or without hyperfunction are rare. Hepatic adrenal rest sometimes has similar imaging findings to lipid-rich hepatocellular carcinoma or angiomyolipoma, containing obvious lipid component. But in our cases, tumors showed hypervascular patterns similar to hepatocellular adenoma or carcinoma. Therefore, adrenocortical scintigraphy with SPECT/CT should be taken into consideration to diagnose tumoral lesions in the posterior segment of the right hepatic lobe with or without an obvious lipid component.
Nivolumab-Induced Subcutaneous Fat Necrosis
Authors: Bhargava Peeyush , Flynt Lesley , Marcal Leonardo 
Published: November 2019

Abstract
A 59-year-old woman with history of metastatic melanoma, currently on nivolumab, presents for a restaging FDG PET/CT scan. New subcutaneous hypermetabolic foci are seen in bilateral lower extremities, suggestive of recurrent melanoma. She is referred for percutaneous image-guided biopsy for definitive diagnosis of progressive disease. Ultrasound shows the subcutaneous foci to be hyperechoic (fat density), and biopsy of the right thigh nodule shows fat necrosis with no evidence of tumor. Fat necrosis, an immune-related adverse event, can be FDG-avid and mimic malignancy on PET/CT scan.
Patent foramen ovale and stroke: current evidence and treatment options
Authors: Favilla Christopher G. , Messé Steven R. 
Published: November 2019

Purpose of review
Recent data have changed the landscape of patent foramen ovale (PFO) closure for secondary stroke prevention. This review synthesizes the data and provides a framework for optimal management of stroke patients with PFO.

Recent findings
The cumulative evidence indicates that PFO closure reduces the risk of recurrent stroke in carefully selected young cryptogenic stroke patients, with an annualized risk reduction of ∼0.6%. The benefit of PFO closure is particularly evident in patients with embolic appearing strokes, large right-to-left shunt, or an associated atrial septal aneurysm. There may be little or no benefit in patients with small deep infarcts, a small PFO, or an indication for long-term anticoagulation. Closure is accompanied by a small risk of major procedural complication and atrial fibrillation.

Summary
The annual risk of stroke from PFO is low relative to other stroke mechanisms, but the life-time cumulative risk in young patients who have experienced a prior stroke may be substantial, in which case the absolute benefit of closure is likely impactful. PFO is highly prevalent in the general population, present in about one in four adults, and should not be considered to be the cause of the stroke until a thorough workup has excluded alternative mechanisms.
Multi-site clonality analyses uncovers pervasive subclonal heterogeneity and branching evolution across melanoma metastases
Authors: Rabbie Roy , Ansari-Pour Naser , Cast Oliver , Lau Doreen , Scott Francis , Welsh Sarah J. , Parkinson Christine , Khoja Leila , Moore Luiza , Tullett Mark , Wong Kim , Ferreira Ingrid , Martínez Gómez Julia M. , Levesque Mitchell , Gallagher Ferdia A. , Jiménez-Sánchez Alejandro , Riva Laura , Miller Martin L. , Allinson Kieren , Campbell Peter J. , Corrie Pippa , Wedge David C. , Adams David J. 
Published: November 2019

AbstractMetastatic melanoma carries a poor prognosis despite modern systemic therapies. Understanding the evolution of the disease could help inform patient management. Through whole-genome sequencing of 13 melanoma metastases sampled at autopsy from a treatment naïve patient and by leveraging the analytical power of multi-sample analyses, we reveal that metastatic cells may depart the primary tumour very early in the disease course and follow a branched pattern of evolution. Truncal UV-induced mutations that often swamp downstream analyses of heterogeneity, were found to be replaced by APOBEC-associated mutations in the branches of the evolutionary tree. Multi-sample analyses from a further 7 patients confirmed that branched evolution was pervasive, representing an important mode of melanoma dissemination. Our analyses illustrate that combining cancer cell fraction estimates across multiple metastases provides higher resolution phylogenetic reconstructions relative to single sample analyses and highlights the limitations of accurately inferring inter-tumoural heterogeneity from a single biopsy.
Age-related differences in structural and functional prefrontal networks during a logical reasoning task
Authors: Ziaei Maryam , Bonyadi Mohammad Reza , Reutens David C. 
Published: November 2019

AbstractIn logical reasoning, difficulties in inhibition of currently-held beliefs may lead to unwarranted conclusions, known as belief bias. Aging is associated with difficulties in inhibitory control, which may lead to deficits in inhibition of currently-held beliefs. No study to date, however, has investigated the underlying neural substrates of age-related differences in logical reasoning and the impact of belief load. The aim of the present study was to delineate age differences in brain activity during a syllogistic logical reasoning task while the believability load of logical inferences was manipulated. Twenty-nine, healthy, younger and thirty, healthy, older adults (males and females) completed a functional magnetic resonance imaging experiment in which they were asked to determine the logical validity of conclusions. Unlike younger adults, older adults engaged a large-scale network including anterior cingulate cortex (ACC) and inferior frontal gyrus (IFG) during conclusion stage. Our functional connectivity results suggest that while older adults engaged the ACC network to overcome their intuitive responses for believable inferences, the IFG network contributed to higher control over responses during both believable and unbelievable conditions. Our functional results were further supported by structure-function-behavior analyses indicating the importance of cingulum bundle and uncinate fasciculus integrity in rejection of believable statements. These novel findings lend evidence for age-related differences in belief bias, with potentially important implications for decision making where currently-held beliefs and given assumptions are in conflict.
Evaluating molecular modeling tools for thermal stability using an independently generated dataset
Authors: Huang Peishan , Chu Simon K. S. , Frizzo Henrique N. , Connolly Morgan P. , Caster Ryan W. , Siegel Justin B. 
Published: November 2019

ABSTRACTEngineering proteins to enhance thermal stability is a widely utilized approach for creating industrially relevant biocatalysts. Computational tools that guide these engineering efforts remain an active area of research with new data sets and develop algorithms. To aid in these efforts, we are reporting an expansion of our previously published data set of mutants for a β-glucosidase to include both measures of TM and ΔΔG, to complement the previously reported measures of T50 and kinetic constants (kcat and KM). For a set of 51 mutants, we found that T50 and TM are moderately correlated with a Pearson correlation coefficient (PCC) of 0.58, indicated the two methods capture different physical features. The performance of predicted stability using five computational tools are also evaluated on the 51 mutants dataset, none of which are found to be strong predictors of the observed changes in T50, TM, or ΔΔG. Furthermore, the ability of the five algorithms to predict the production of isolatable soluble protein is examined, which revealed that Rosetta ΔΔG, ELASPIC, and DeepDDG are capable of predicting if a mutant could be produced and isolated as a soluble protein. These results further highlight the need for new algorithms for predicting modest, yet important, changes in thermal stability as well as a new utility for current algorithms for prescreening designs for the production of soluble mutants.
Thermodynamic modelling of synthetic communities predicts minimum free energy requirements for sulfate reduction and methanogenesis
Authors: Delattre Hadrien , Chen Jing , Wade Matthew , Soyer Orkun S 
Published: November 2019

ABSTRACTMicrobial communities are complex dynamical systems harbouring many species interacting together to implement higher-level functions. Among these higher-level functions, conversion of organic matter into simpler building blocks by microbial communities underpins biogeochemical cycles and animal and plant nutrition, and is exploited in biotechnology. A prerequisite to predicting the dynamics and stability of community-mediated metabolic conversions, is the development and calibration of appropriate mathematical models. Here, we present a generic, extendable thermodynamic model for community dynamics accounting explicitly for metabolic activities of composing microbes, system pH, and chemical exchanges. We calibrate a key parameter of this thermodynamic model, the minimum energy requirement associated with growth-supporting metabolic pathways, using experimental population dynamics data from synthetic communities composed of a sulfate reducer and two methanogens. Our findings show that accounting for thermodynamics is necessary in capturing experimental population dynamics of these synthetic communities that feature relevant species utilising low-energy growth pathways. Furthermore, they provide the first estimates for minimum energy requirements of methanogenesis and elaborates on previous estimates of lactate fermentation by sulfate reducers. The open-source nature of the developed model and demonstration of its use for estimating a key thermodynamic parameter should facilitate further thermodynamic modelling of microbial communities.
Satellite cell depletion in early adulthood attenuates muscular dystrophy pathogenesis
Authors: Boyer Justin G. , Han Sarah , Prasad Vikram , Khalil Hadi , Vagnozzi Ronald J. , Molkentin Jeffery D. 
Published: November 2019

AbstractSatellite cells are skeletal muscle resident stem cells that regenerate adult myofibers following an acute injury to muscle. Despite the assumption that the loss of satellite cells would be detrimental in a chronic regeneration-inducing muscle disease such as muscular dystrophy, this assumption has never been tested using mouse genetics. Here we generated a novel model of satellite cell ablation and crossed it with mouse models of muscular dystrophy to directly investigate how critical these cells are in maintaining muscle during a chronic degenerative disorder. Satellite cell deletion in 2-week-old young dystrophic mice provided noticeable improvements in histopathology and function, although at this early timepoint it was utimately detrimental because muscle size was not sufficient to permit survival. However, depletion of satellite cells beginning at 2 months of age in dystrophic mice provided similar histological and functional improvements but without compromising muscle size. The improved profile showed fewer damaged fibers, less myofiber central nucleation, increased sarcolemma integrity, decreased fibrosis and a dramatic size increase in the remaining myofibers. At the functional level, young adult dystrophic mice lacking satellite cells performed significantly better than those with satellite cells when exercised on a treadmill. Thus, loss of satellite cells during early adulthood in dystrophic mice produces an unexpected protective effect.