bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges in Microsurgical Reconstruction for Craniofacial Osteomyelitis With Resultant Osteonecrosis
Authors: Couto Rafael A. , Sinclair Nicholas R. , Lamaris Gregory , Durand Paul , Knackstedt Rebecca , Aliotta Rachel , Gastman Brian R. 
Published: June 2019

Introduction:
Chronic osteomyelitis is characterized by compromised blood supply and eventual osteonecrosis. Definitive treatment requires aggressive resection of affected bone. The resultant defect poses a unique challenge to reconstructive surgeons. Much of the literature on craniofacial osteomyelitis focuses on infection eradication, rather than subsequent reconstruction. This article reports representative cases from our experience with free flap reconstruction for defects secondary to chronic osteomyelitis of the craniofacial skeleton.

Methods/Results:
The authors selected 5 of the most difficult reconstructive cases of craniofacial osteomyelitis from our experience in a single tertiary referral institution with a follow-up of at least 6 months. Three of the 5 cases arose in the setting of previous head and neck cancer treated with resection and radiation therapy. One case had a previous surgical craniotomy complicated by osteomyelitis and multiple failed alloplastic reconstructions. The final case was due to multiple gunshots to the head, with subsequent cerebral and cranial abscess (>1000cc). In each case, the defect was successfully treated with free tissue transfer. Two cases required creation of recipient vessels with an arteriovenous loop.

Conclusions:
Free tissue transfer provides a versatile and effective tool in the reconstruction of extensive craniofacial osteomyelitis defects. Furthermore, the addition of vascularized tissue can protect against further episodes of osteomyelitis. Finally, arteriovenous loops can be employed successfully when prior radiation and infection of the wound bed precludes the use of local recipient target vessels.
Intraoperative Computed Tomography Scan for Orbital Fracture Reconstruction
Authors: Nazimi Abd Jabar , Khoo Soo Ching , Nabil Syed , Nordin Rifqah , Lan Tan Huann , Rajandram Rama Krsna , Rajaran Jothi Raamahlingam 
Published: June 2019

Abstract
Orbital fractures pose specific challenge in its surgical management. One of the greatest challenges is to obtain satisfactory reconstruction by correct positioning of orbital implant. Intraoperative computed tomography (CT) scan may facilitate this procedure. The aim of this study was to describe the early use of intraoperative CT in orbital fractures repair in our center. The authors assessed the revision types and rates that have occurred with this technique. With the use of pre-surgical planning, optical intraoperative navigation, and intraoperative CT, the impact of intraoperative CT on the management of 5 cases involving a total number of 14 orbital wall fractures were described. There were 6 pure orbital blowout wall fractures reconstructed, involving both medial and inferior wall of the orbit fracturing the transition zone and 8 impure orbital wall fractures in orbitozygomaticomaxillary complex fracture. 4 patients underwent primary and 1 had delayed orbital reconstruction. Intraoperative CT resulted in intraoperative orbital implant revision, following final navigation planning position, in 40% (2/5) of patients or 14% (2/14) of the fractures. In revised cases, both implant repositioning was conducted at posterior ledge of orbit. Intraoperative CT confirmed true to original reconstruction of medial wall, inferior wall and transition zone of the orbit. Two selected cases were illustrated. In conclusion, intraoperative CT allows real-time assessment of fracture reduction and immediate orbital implant revision, especially at posterior ledge. As a result, no postoperative imaging was indicated in any of the patients. Long-term follow-ups for orbital fracture patients managed with intraoperative CT is suggested.
Accelerated Biochemical Kinetic Model Fitting via the Asynchronous, Generalized Island Method
Authors: Medley J Kyle , Asifullah Shaik , Hellerstein Joseph , Sauro Herbert M 
Published: June 2019

Mechanistic kinetic models of biological pathways are an important tool for understanding biological systems. Constructing kinetic models requires fitting the parameters to experimental data. However, parameter fitting on these models is a non–convex, non–linear optimization problem. Many algorithms have been proposed to addressing optimization for parameter fitting including globally convergent, population–based algorithms. The computational complexity of the this optimization for even modest models means that parallelization is essential. Past approaches to parameter optimization have focused on parallelizing a particular algorithm. However, this requires re–implementing the algorithm usinga distributed computing framework, which requires a significant investment of time and effort. There are two major drawbacks of this approach: First, the choice of best algorithm may depend on the model. Given the large variety of optimization algorithms available, it is difficult to re–implement every potentially useful algorithm. Second, when new advances are made in a given optimization algorithm, the parallel implementation must be updated to take advantage of these advantages. Thus, there is a continual burden placed on the parallel implementation. The drawbacks of re–implementing algorithms lead us to a different approach to parallelizing parameter optimization. Instead of parallelizing the algorithms themselves, we run many instances of the algorithm on single cores. This provides great flexibility as to the choice of algorithms by allowing us to reuse previous implementations. Also, it does not require the creation and maintenance of parallel versions of optimization algorithms. This approach is known as the island method. To our knowledge, the utility of the island method for parameter fitting in systems biology has not been previously demonstrated. For the parameter fitting problem, we allow islands to exchange information about their “best” solutions so that all islands leverage the discoveries of the few. This turns out to be avery effective in practice, leading to super–linear speedups. That is, if a single processor finds the optimal value of parameters in time t, then N processors exchanging information in this way find the optimal value much faster than t/N. We show that the island method is able to consistently provide good speedups for these problems. We also benchmark the island method against a variety of large, challenging kinetic models and show that it is able to consistently improve the quality of fit in less time than a single–threaded implementation.Our software is available at https://github.com/sys-bio/sabaody under a Apache 2.0 license.Contactmailto:medjk@comcast.net
A Multidimensional Array Representation of State-Transition Model Dynamics
Authors: Krijkamp Eline M. , Alarid-Escudero Fernando , Enns Eva A. , Pechlivanoglou Petros , Hunink M.G. Myriam , Jalal Hawre J. 
Published: June 2019

ABSTRACTCost-effectiveness analyses often rely on cohort state-transition models (cSTMs). The cohort trace is the primary outcome of cSTMs, which captures the proportion of the cohort in each health state over time (state occupancy). However, the cohort trace is an aggregated measure that does not capture the information about the specific transitions among the health states (transition dynamics). In practice, these transition dynamics are crucial in many applications, such as incorporating transition rewards or computing various epidemiological outcomes that could be used for model calibration and validation (e.g. disease incidence and lifetime risk). In this manuscript we propose modifying the transitional cSTMs cohort trace computation to compute and store cSTMs dynamics that capture both state occupancy and transition dynamics. This approach produces a multidimensional matrix from which both the state occupancy and the transition dynamics can be recovered. We highlight the advantages and potential applications of this approach with an example coded in R to facilitate the implementation of our method.
Novel immune and stromal subtype classification system of lung adenocarcinoma based on tumor microenvironment
Authors: Zeng Zihang , Li Jiali , Zhang Nannan , Jiang Xueping , Gao Yanping , Xu Liexi , Liu Xingyu , Chen Jiarui , Gao Yuke , Han Linzhi , Ren Jiangbo , Gong Yan , Xie Conghua 
Published: June 2019

ABSTRACTBackgroundTumor microenvironment has complex effects on tumorigenesis and metastasis in lung adenocarcinoma (LUAD). However, there is still a lack of comprehensive understanding of the relationship between immune and non-immune stromal characteristics in tumor microenvironment.Patients and methodsEight cohort of 1681 lung caner patients were included in this study. The immune and non-immune stromal signatures of tumor microenvironment were identified by eigendecomposition and extraction algorithms. We developed a novel immune and stromal scoring system to quantify anti-tumor immune and promote-metastasis stromal activation, namely PMBT (prognostic model based on tumor microenvironment) as an R package. Tumors were classified into 4 subtypes according to PMBT system. Comprehensive analysis was performed in different subtypes.ResultsThe 4 subgroups had different mutation landscape, molecular, cellular characteristics and prognosis, which validated by 7 data sets containing 1175 patients. 19% patients was characterized by highly active anti-tumor reaction with high production of immunoactive mediators, immunocyte, low fibroblasts infiltration, low TGF-β, VEGFA, collagen and glucose catabolic, low immune checkpoint per T cell, tumor mutation burden, and favourable overall survival (all, P < 0.05) named high-immune and low-stromal activation subgroup (HL). Cellular paracrine network showed both high humoral and cellular immune interaction in HL group. The low-immune and high-stromal activation group (19%) had opposite characteristics with HL group. Moreover, the PMBT system showed the value to predict overall survival and immunotherapy responses (all, P < 0.05).ConclusionsDifferent molecular, cellular characteristics, mutation landscape and prognosis were discovered in the 4 subgroups. Our classification, PMBT system provided novel insight for clinical monitoring and treatment in LUAD.
Decomposing Retrosynthesis into Reactive Center Prediction and Molecule Generation
Authors: Liu Xianggen , Li Pengyong , Song Sen 
Published: June 2019

AbstractChemical retrosynthesis has been a crucial and challenging task in organic chemistry for several decades. In early years, retrosynthesis is accomplished by the disconnection approach which is labor-intensive and requires expert knowledge. Afterward, rule-based methods have dominated in retrosynthesis for years. In this study, we revisit the disconnection approach by leveraging deep learning (DL) to boost its performance and increase the explainability of DL. Concretely, we propose a novel graph-based deep-learning framework, named DeRetro, to predict the set of reactants for a target product by executing the process of disconnection and reactant generation orderly. Experimental results report that DeRetro achieves new state-of-the-art performance in predicting the reactants. In-depth analyses also demonstrate that even without the reaction type as input, DeRetro retains its retrosynthesis performance while other methods show a significant decrease, resulting in a large margin of 19% between DeRetro and previous state-of-the-art rule-based method. These results have established DeRetro as a powerful and useful computational tool in solving the challenging problem of retrosynthetic analysis.
Cortical temporal hierarchy is immature in middle childhood
Authors: Moraczewski Dustin , Nketia Jazlyn , Redcay Elizabeth 
Published: June 2019

AbstractThe development of successful social-cognitive abilities requires one to track, accumulate, and integrate knowledge of other people’s mental states across time. Regions of the brain differ in their temporal scale (i.e., a cortical temporal hierarchy) and those receptive to long temporal windows may facilitate social-cognitive abilities; however, the cortical development of long timescale processing remains to be investigated. The current study utilized naturalistic viewing to examine cortical development of long timescale processing and its relation to social-cognitive abilities in middle childhood – a time of expanding social spheres and increasing social-cognitive abilities. We found that, compared to adults, children exhibited reduced low-frequency power in the temporo-parietal junction (TPJ) and reduced specialization for long timescale processing within the TPJ and other regions broadly implicated in the default mode network and higher-order visual processing. Further, specialization for long timescales within the right dorsal medial prefrontal cortex became more ‘adult-like’ as a function of children’s comprehension of character mental states. These results suggest that cortical temporal hierarchy in middle childhood is immature and may be important for an accurate representation of complex naturalistic social stimuli during this age.
The mitochondrial HSP90 paralog TRAP1 forms an OXPHOS-regulated tetramer and is involved in maintaining mitochondrial metabolic homeostasis
Authors: Joshi Abhinav , Dai Joyce , Lee Jungsoon , Ghahhari Nastaran Mohammadi , Segala Gregory , Beebe Kristin , Tsai Francis T.F. , Neckers Len , Picard Didier 
Published: June 2019

AbstractBackgroundThe molecular chaperone TRAP1, the mitochondrial isoform of cytosolic HSP90, remains poorly understood with respect to its pivotal role in the regulation of mitochondrial metabolism. Most studies have found it to be an inhibitor of mitochondrial oxidative phosphorylation (OXPHOS) and an inducer of the Warburg phenotype of cancer cells. However, others have reported the opposite and there is no consensus on the relevant TRAP1 interactors. This calls for a more comprehensive analysis of the TRAP1 interactome and of how TRAP1 and mitochondrial metabolism mutually affect each other.ResultsWe show that the disruption of the gene for TRAP1 in a panel of cell lines dysregulates OXPHOS by a metabolic rewiring that induces the anaplerotic utilization of glutamine metabolism to replenish TCA cycle intermediates. Restoration of wild-type levels of OXPHOS requires full-length TRAP1. Whereas the TRAP1 ATPase activity is dispensable for this function, it modulates the interactions of TRAP1 with various mitochondrial proteins. Quantitatively by far the major interactors of TRAP1 are the mitochondrial chaperones mtHSP70 and HSP60. However, we find that the most stable stoichiometric TRAP1 complex is a TRAP1 tetramer, whose levels change in response to both a decline or an increase in OXPHOS.ConclusionsOur work provides a roadmap for further investigations of how TRAP1 and its interactors such as the ATP synthase regulate cellular energy metabolism. Our results highlight that TRAP1 function in metabolism and cancer cannot be understood without a focus on TRAP1 tetramers as potentially the most relevant functional entity.
Activity-dependent nucleation of dynamic microtubules at presynaptic boutons is required for neurotransmission
Authors: Qu Xiaoyi , Kumar Atul , Blockus Heike , Waites Clarissa , Bartolini Francesca 
Published: June 2019

SUMMARYControl of microtubule (MT) dynamics is critical for neuronal function. Whether MT nucleation is regulated at presynaptic boutons and influences overall presynaptic activity remains unknown. By visualizing MT dynamics at individual excitatory en passant boutons in axons of hippocampal neurons we found that MTs preferentially grow from presynaptic boutons as a result of γ-tubulin and augmin-dependent nucleation. MT nucleation at boutons is promoted by neuronal activity, functionally coupled to synaptic vesicle (SV) transport, and required for neurotransmission. Hence, en passant boutons act as hotspots for activity-dependent MT nucleation, which is required for neurotransmission by providing the tracks for a rate-limiting supply of SVs to sites of neurotransmitter release.HighlightsExcitatory boutons are hotspots for neuronal activity-induced γ-tubulin dependent MT nucleationThe augmin complex is required for the correct polarity of presynaptic de novo nucleated MTsPresynaptic MT nucleation promotes SV motility and exocytosis at sites of releaseIn BriefOur results demonstrate that excitatory en passant boutons are hotspots for neuronal activity-induced γ-tubulin- and augmin-dependent oriented MT nucleation, and that the resulting presynaptic de novo nucleated MTs promote inter-bouton SV motility which is rate-limiting for neurotransmitter release.
Response to starvation and microbial community composition in microbial fuel cells enriched on different electron donors
Authors: Saheb‐Alam Soroush , Persson Frank , Wilén Britt‐Marie , Hermansson Malte , Modin Oskar 
Published: June 2019

SummaryIn microbial fuel cells (MFCs), microorganisms generate electrical current by oxidizing organic compounds. MFCs operated with different electron donors harbour different microbial communities, and it is unknown how that affects their response to starvation. We analysed the microbial communities in acetate‐ and glucose‐fed MFCs and compared their responses to 10 days starvation periods. Each starvation period resulted in a 4.2 ± 1.4% reduction in electrical current in the acetate‐fed MFCs and a 10.8 ± 3.9% reduction in the glucose‐fed MFCs. When feed was resumed, the acetate‐fed MFCs recovered immediately, whereas the glucose‐fed MFCs required 1 day to recover. The acetate‐fed bioanodes were dominated by Desulfuromonas spp. converting acetate into electrical current. The glucose‐fed bioanodes were dominated by Trichococcus sp., functioning as a fermenter, and a member of Desulfuromonadales, using the fermentation products to generate electrical current. Suspended biomass and biofilm growing on non‐conductive regions within the MFCs had different community composition than the bioanodes. However, null models showed that homogenizing dispersal of microorganisms within the MFCs affected the community composition, and in the glucose‐fed MFCs, the Trichococcus sp. was abundant in all locations. The different responses to starvation can be explained by the more complex pathway requiring microbial interactions to convert glucose into electrical current.
Constitutive internalization across therapeutically targeted GPCRs correlates with constitutive activity
Authors: Hendrik Schmidt Jan , Perslev Mathias , Bukowski Lina , Stoklund Mikkel , Herborg Freja , Herlo Rasmus , Lindegaard Madsen Kenneth 
Published: June 2019

AbstractWhile the physiological function and mechanisms of agonist‐dependent G protein‐coupled receptor (GPCR) internalization have been extensively studied, the functional characterization of constitutive internalization of these critically important receptors has received less attention. Here we relate the constitutive internalization of more than 30 therapeutically targeted GPCRs to their agonist‐induced internalization. The constitutive internalization ranges from levels of bulk membrane endocytosis in some cases to levels of agonist‐induced internalization for other receptors. Moreover, for receptors with high constitutive internalization this occludes further agonist‐induced internalization. Additionally, Gq‐coupled GPCRs show a significantly higher rate of constitutive internalization than Gs‐ and Gi‐coupled receptors. Finally, we consolidate the proposed link between the constitutive internalization, as assessed by a cytometry‐based assay, and the constitutive activity of these receptors, as previously reported by a β‐arrestin recruitment assay across the range of pharmacologically relevant receptors. In summary, we provide a quantitative comparison of GPCR internalization across a range of pharmacologically relevant receptors providing generalized insight into the relations between constitutive internalization, constitutive activity and agonist‐induced internalization, which has so far relied on mutational studies in individual receptors.
Complexities of conducting research in adolescent refugees resettling in Australia
Authors: Hirani Kajal , Mutch Raewyn , Payne Donald , Cherian Sarah 
Published: June 2019

AbstractAdolescent refugees resettling in Australia are a vulnerable and marginalised population. Dedicated research to help better understand their health‐care needs remains scarce. There are multiple complexities which may deter health professionals from conducting research with this population. Health‐care system barriers, such as lack of adolescent‐ and refugee‐specific health‐care services, complicate comprehensive data collection. Limited investigator knowledge pertaining to culturally appropriate research in a population with limited English proficiency or a history of trauma can have an impact on adolescent participation and retention in research studies. Additional ethical and legal issues relating to adolescent consent and confidentiality, which include suicidality and physical or sexual abuse, can arise during research and cause potential harm to adolescents if not managed appropriately. This article highlights current knowledge and understanding relating to these issues along with recommendations to address barriers and safeguard adolescents, with the aim of promoting high‐quality research that will benefit resettling adolescent refugees.
Risk of chikungunya virus transmission associated with European travelers returning from southern Thailand (2008–2015)
Authors: Appassakij Hatsadee , Khuntikij Paiwon , Silpapojakul Khachornsakdi , Promwong Charuporn , Rujirojindakul Pairaya , Suddeaugrai Oranart , Chullasara Arthiya 
Published: June 2019

BACKGROUNDThe impact of the spread of chikungunya virus (CHIKV) by autochthonous transmission and blood transfusion in nonendemic areas via travelers returning from CHIKV‐affected locations is a concern.METHODSWe analyzed the risks of potential CHIKV importation and transfusion transmission from Thailand to Europe via travelers visiting southern Thailand from 2008 through 2015, using the web‐based European Up‐front Risk Assessment Tool.RESULTSThe risk of CHIKV importation by European travelers returning from Thailand from 2008 through 2015 varied depending on the year of travel, tourist destination, duration of stay, and time since last possible exposure. Specifically, the risks of acquiring CHIKV among travelers visiting Songkhla and Krabi for 1, 5, or 10‐30 days during the highest epidemic activity in 2009 were estimated to be 74.40, 371.99, and 706.77 (Songkhla) and 1.82, 9.08, and 17.25 (Krabi) per 100,000 travelers, respectively. In contrast, such risks were estimated to be fewer than 0.099 per 100,000 travelers in nonepidemic years. The 2009 yearly average rates of expected incidence among 4,059,988 European travelers who stayed for 1 or 10‐30 days in all six outbreak activity destinations were calculated to be, respectively, 4.01 × 10−6 or 1.20 × 10−4 cases per day, corresponding to the estimated rates of viremia and transfusion‐transmitted CHIKV via traveling blood donations of 3.21 × 10−5 and 0.61, and 9.62 × 10−4 and 3.34, respectively. Additionally, it is probable that 18 (0.0004%) Europeans acquired CHIKV in Thailand, representing a maximum attack rate of 0.0023%.CONCLUSIONThe extent of the expected risks and attack rates of CHIKV infection might reflect the travel preferences for popular destinations rather than the true risks of CHIKV transmission in travelers' home nonendemic countries. Nevertheless, preventive and blood‐safety intervention measures may be applied to returning travelers at risk for infection to reduce CHIKV transfusion threats in their home countries.