bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virtual Surgical Planning for Reconstruction of Giant Ameloblastoma of the Mandible
Authors: Moro Alessandro , Pelo Sandro , Gasparini Giulio , Saponaro Gianmarco , Todaro Mattia , Pisano Giusi , D'Amato Giuseppe , Doneddu Piero 
Published: June 2020

Abstract
Ameloblastoma is a histologically benign tumor that behaves aggressively because of its tendency to invade local structures, and it has a high probability of local recurrence. If neglected, ameloblastomas can grow substantially over the course of years, reaching the size of giant ameloblastomas. This large size can lead to deformities in facial appearance and impairments in speaking, swallowing, eating, and breathing.
Surgical planning can be challenging because of the extension of the tumor and the consequent reconstructive issues.
In this article, we present our experience with the reconstruction of 2 cases of giant ameloblastomas planned on the basis of occlusal casts and acrylic splints. In these patients, computerized planning was rendered complex and potentially inaccurate because of the dimensions of the tumor, the loss of anatomical landmarks, and the loss of occlusal landmarks. The cases were successfully reconstructed, but the technique can be flawed. A 3-dimensional virtual model of the mandible can be used as a template to develop cutting guides for reconstruction with free fibular flaps. This will allow us to overcome limitations, standardize the procedure, and achieve optimal functional and aesthetic results.
Understanding Breast Implant Illness, Before and After Explantation
Authors: Wee Corinne E. , Younis Joseph , Isbester Kelsey , Smith Arvin , Wangler Brooke , Sarode Anuja L. , Patil Nirav , Grunzweig Katherine , Boas Samuel , Harvey Donald J. , Kumar Anand R. , Feng Lu-Jean 
Published: June 2020

Background
Breast implant illness (BII) after aesthetic breast augmentation remains a poorly defined syndrome encompassing a wide spectrum of symptoms. While previously published series have observed overall symptomatic improvement after breast implant removal,
1–3
there is a lack of studies evaluating changes in specific symptoms over time. The purpose of this study was to gain an understanding of symptoms associated with BII, and to evaluate how these symptoms change after removal of breast implants and total capsulectomy (explantation). We hypothesized that patients presenting with BII would experience both immediate and sustained improvement in constitutional symptoms after explantation.

Methods
A retrospective study of all patients who underwent explantation by a single surgeon over 2 years was conducted. Repeated-measures analysis of variance accounting for dependency was used to compare symptoms before and after surgery. Multivariate analyses and linear regression models were used to examine the impact of patient- and implant-related factors on changes in symptoms.

Results
Seven hundred fifty patients met inclusion criteria. Mean preoperative survey score (26.19 ± 11.24) was significantly different from mean postoperative survey score at less than 30 days (9.49 ± 7.56) and greater than 30 days (9.46 ± 7.82, P < 0.001). Patients with a BMI greater than 30 or those with clinically detectable contracture on examination showed greater improvement on their survey scores (P = 0.039, 0.034, respectively).

Conclusions
Although BII encompasses a large range of symptoms, subjects in this study demonstrated significant and sustained improvement in 11 common symptom domains. This improvement was demonstrable within the first 30 days postoperatively and was maintained beyond 30 days. The study demonstrated a strong association of explantation and specific symptom improvement within the patient population studied. Future investigation will further elucidate possible biologic phenomena to better characterize the pathophysiology and mechanism of BII.
Dynamic impact of transfusion ratios on outcomes in severely injured patients: Targeted machine learning analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios randomized clinical trial
Authors: Nguyen Minh , Pirracchio Romain , Kornblith Lucy Z. , Callcut Rachael , Fox Erin E. , Wade Charles E. , Schreiber Martin , Holcomb John B. , Coyle Jeremy , Cohen Mitchell , Hubbard Alan 
Published: June 2020

BACKGROUNDMassive transfusion protocols to treat postinjury hemorrhage are based on predefined blood product transfusion ratios followed by goal-directed transfusion based on patient's clinical evolution. However, it remains unclear how these transfusion ratios impact patient outcomes over time from injury.METHODSThe Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) is a phase 3, randomized controlled trial, across 12 Level I trauma centers in North America. From 2012 to 2013, 680 severely injured patients required massive transfusion. We used semiparametric machine learning techniques and causal inference methods to augment the intent-to-treat analysis of PROPPR, estimating the dynamic relationship between transfusion ratios and outcomes: mortality and hemostasis at different timepoints during the first 24 hours after admission.RESULTSIn theintention-to-treat analysis, the 1:1:1 group tended to have decreased mortality, but with no statistical significance. For patients in whom hemostasis took longer than 2 hours, the 1:1:1 ratio was associated with a higher probability of hemostasis, statistically significant from the 4thhour on. In the per-protocol,actual-transfusion-ratios-received analysis,during four successive time intervals, no significant association was found between the actual ratios and mortality. When comparing patient groups who received both high plasma/PRBC and high platelet/PRBC ratios to the group of low ratios in both, the relative risk of achieving hemostasis was 2.49 (95% confidence interval, 1.19–5.22) during the third hour after admission, suggesting a significant beneficial impact of higher transfusion ratios of plasma and platelets on hemostasis.CONCLUSIONOur results suggest that the impact of transfusion ratios on hemostasis is dynamic. Overall, the transfusion ratios had no significant impact on mortality over time. However, receiving higher ratios of platelets and plasma relative to red blood cells hastens hemostasis in subjects who have yet to achieve hemostasis within 3 hours after hospital admission.LEVEL OF EVIDENCETherapeutic IV.
Sex-related Differences in Tau Positron Emission Tomography (PET) and the Effects of Hormone Therapy (HT)
Authors: Wisch Julie K. , Meeker Karin L. , Gordon Brian A. , Flores Shaney , Dincer Aylin , Grant Elizabeth A. , Benzinger Tammie L. , Morris John C. , Ances Beau M. 
Published: June 2020

Importance:
Female sex is a major risk factor for late-onset Alzheimer disease (AD), and sex hormones have been implicated as a possible protective factor. Neuroimaging studies that evaluated the effects of sex hormones on brain integrity have primarily emphasized neurodegenerative measures rather than amyloid and tau burden.

Objective:
We compared cortical amyloid and regional tau positron emission tomography (PET) deposition between cognitively normal males and females. We also compared preclinical AD pathology between females who have and have not used hormone therapy (HT). Finally, we compared the effects of amyloid and tau pathology on cognition, testing for both sex and HT effects.

Design, Setting, and Participants:
We analyzed amyloid, tau, and cognition in a cognitively normal cross-sectional cohort of older individuals (n=148) followed at the Knight Alzheimer Disease Research Center. Amyloid and tau PET, medication history, and neuropsychological testing were obtained for each participant.

Results:
Within cognitively normal individuals, there was no difference in amyloid burden by sex. Whether or not we controlled for amyloid burden, female participants had significantly higher tau PET levels than males in multiple regions, including the rostral middle frontal and superior and middle temporal regions. HT accounted for a small reduction in tau PET; however, males still had substantially lower tau PET compared with females. Amyloid PET and tau PET burden were negatively associated with cognitive performance, although increasing amyloid PET did not have a deleterious effect on cognitive performance for women with a history of HT.

Conclusions and Relevance:
Regional sex-related differences in tau PET burden may contribute to the disparities in AD prevalence between males and females. The observed decreases tau PET burden in HT users has important implications for clinical practice and trials and deserves future consideration in longitudinal studies.
SARS-CoV-2 ORF8 can fold into human factor 1 catalytic domain binding site on complement C3b: Predict functional mimicry
Authors: Singh Jasdeep , Kar Sudeshna , Hasnain Seyed Ehtesham , Ganguly Surajit 
Published: June 2020

AbstractPathogens are often known to use host factor mimicry to take evolutionary advantage. As the function of the non-structural ORF8 protein of SARS-CoV-2 in the context of host-pathogen relationship is still obscure, we investigated its role in host factor mimicry using computational protein modelling techniques. Modest sequence similarity of ORF8 of SARS-CoV-2 with the substrate binding site within the C-terminus serine-protease catalytic domain of human complement factor 1 (F1; PDB ID: 2XRC), prompted us to verify their resemblance at the structural level. The modelled ORF8 protein was found to superimpose on the F1 fragment. Further, protein-protein interaction simulation confirmed ORF8 binding to C3b, an endogenous substrate of F1, via F1-interacting region on C3b. Docking results suggest ORF8 to occupy the binding groove adjacent to the conserved “arginine-serine” (RS) F1-mediated cleavage sites on C3b. Comparative H-bond interaction dynamics indicated ORF8/C3b binding to be of higher affinity than the F1/C3b interaction. Hence, ORF8 is predicted to inhibit C3b proteolysis by competing with F1 for C3b binding using molecular mimicry with a possibility of triggering unregulated complement activation. This could offer a mechanistic premise for the unrestrained complement activation observed in large number of SARS-CoV-2 infected patients.
Peripheral electrical stimulation augments cerebral collateral circulation if performed within a critical time window
Authors: Ding Ming-Chieh , Kundu Aritra , Sullender Colin T. , Dunn Andrew 
Published: June 2020

AbstractIschemic stroke is one of the leading causes of death and disability in the world. Recent advances in acute stroke care have dramatically improved clinicians’ abilities to reperfuse occluded blood vessels. With these advances, the importance of adjunctive therapies to supplement or complement reperfusion therapy is receiving greater interest. Cerebral collateral circulation is one of such area that is now gaining greater interest in acute stroke care. In this study, we investigate the use of peripheral electrical stimulation to induce functional hyperemia in a mouse animal model in the setting of acute stroke. Using a laser speckle contrast imaging system, we evaluated the use of peripheral electrical stimulation at 1 hour and 3 hours after stroke induction. Results demonstrated that stimulation initiated 1 hour following stroke significantly increase collateral cerebral blood flow, while stimulation at 3 hours after stroke had no appreciable effect. These results suggest that augmentation cerebral collateral circulation may be possible in the setting of acute stroke although there may be a critical time window in which this would have to be initiated.
Observation of an α-synuclein liquid droplet state and its maturation into Lewy body-like assemblies
Authors: Hardenberg Maarten C. , Sinnige Tessa , Casford Sam , Dada Samuel , Poudel Chetan , Robinson Lizzy , Fuxreiter Monika , Kaminksi Clemens , Kaminski Schierle Gabriele S. , Nollen Ellen A. A. , Dobson Christopher M. , Vendruscolo Michele 
Published: June 2020

AbstractMisfolded α-synuclein is a major component of Lewy bodies, which are a hallmark of Parkinson’s disease. A large body of evidence shows that α-synuclein can self-assemble into amyloid fibrils, but the relationship between amyloid formation and Lewy body formation still remains unclear. Here we show, bothin vitroand in aC. elegansmodel of Parkinson’s disease, that α-synuclein undergoes liquid-liquid phase separation by forming a liquid droplet state, which converts into an amyloid-rich hydrogel. This maturation process towards the amyloid state is delayed in the presence of model synaptic vesiclesin vitro. Taken together, these results suggest that the formation of Lewy bodies is linked to the arrested maturation of α-synuclein condensates in the presence of lipids and other cellular components.
Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion
Authors: Zang Ruochen , Case James Brett , Gomez Castro Maria Florencia , Liu Zhuoming , Zeng Qiru , Zhao Haiyan , Son Juhee , Rothlauf Paul W. , Hou Gaopeng , Bose Sayantan , Wang Xin , Vahey Michael D. , Kirchhausen Tomas , Fremont Daved H. , Diamond Michael S. , Whelan Sean P.J. , Ding Siyuan 
Published: June 2020

AbstractCholesterol 25-hydroxylase (CH25H) is an interferon-stimulated gene (ISG) that shows broad antiviral activities against a wide range of enveloped viruses. Here, using an ISG screen against VSV-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses, we identified CH25H and its enzymatic product 25-hydroxycholesterol (25HC) as potent inhibitors of virus replication. Mechanistically, internalized 25HC accumulates in the late endosomes and blocks cholesterol export, thereby restricting SARS-CoV-2 spike protein catalyzed membrane fusion. Our results highlight a unique antiviral mechanism of 25HC and provide the molecular basis for its possible therapeutic development.
Gene Expression Imputation with Generative Adversarial Imputation Nets
Authors: Viñas Ramon , Azevedo Tiago , Gamazon Eric R. , Liò Pietro 
Published: June 2020

AbstractA question of fundamental biological significance is to what extent the expression of a subset of genes can be used to recover the full transcriptome, with important implications for biological discovery and clinical application. To address this challenge, we present GAIN-GTEx, a method for gene expression imputation based on Generative Adversarial Imputation Networks. In order to increase the applicability of our approach, we leverage data from GTEx v8, a reference resource that has generated a comprehensive collection of transcriptomes from a diverse set of human tissues. We compare our model to several standard and state-of-the-art imputation methods and show that GAIN-GTEx is significantly superior in terms of predictive performance and runtime. Furthermore, our results indicate strong generalisation on RNA-Seq data from 3 cancer types across varying levels of missingness. Our work can facilitate a cost-effective integration of large-scale RNA biorepositories into genomic studies of disease, with high applicability across diverse tissue types.
Comparison of CRISPR/Cas endonucleases forin vivoretinal gene editing
Authors: Li Fan , Wing Kristof , Wang Jiang-Hui , Luu Chi D. , Bender James A. , Chen Jinying , Wang Qi , Lu Qinyi , Nguyen Tran Minh Thuan , Young Kaylene M , Wong Raymond C.B. , Pébay Alice , Cook Anthony L. , Hung Sandy S.C. , Liu Guei-Sheung , Hewitt Alex W. 
Published: June 2020

ABSTRACTCRISPR/Cas has opened the prospect of direct gene correction therapy for some inherited retinal diseases. Previous work has demonstrated the utility of adeno-associated virus (AAV) mediated delivery to retinal cellsin vivo; however, with the expanding repertoire of CRISPR/Cas endonucleases, it is not clear which of these are most efficacious for retinal editingin vivo. We sought to compare CRISPR/Cas endonuclease activity using both single and dual AAV delivery strategies for gene editing in retinal cells. Plasmids of a dual vector system with SpCas9, SaCas9, Cas12a, CjCas9 and sgRNA targetingYFPand a single vector system with SaCas9/YFP sgRNA were generated and validated in YFP-expressing HEK293A cell by flow cytometry and T7E1 assay. Paired CRISPR/Cas endonuclease and its best performing sgRNA was then packaged into an AAV2 capsid derivative, AAV7m8, and injected intravitreally into CMV-Cre::Rosa26-YFP mice. SpCas9 and Cas12a achieved better knockout efficiency than SaCas9 and CjCas9. Moreover, no significant difference inYFPgene editing was found between single and dual CRISPR/SaCas9 vector systems. With a marked reduction of YFP-positive retinal cells, AAV7m8 delivered SpCas9 was found to have the highest knockout efficacy among all investigated endonucleases. We demonstrate that the AAV7m8-mediated delivery of CRISPR/SpCas9 construct achieves the most efficient gene modification in neurosensory retinal cellsin vitroandin vivo.
Loss of hepatic aldolase B activates Akt and promotes hepatocellular carcinogenesis by destabilizing Aldob/Akt/PP2A protein complex
Authors: He Xuxiao , Li Min , Yu Hongming , Liu Guijun , Wang Ningning , Yin Chunzhao , Tu Qiaochu , Narla Goutham , Tao Yongzhen , Cheng Shuqun , Yin Huiyong 
Published: June 2020

AbstractLoss of hepatic fructose-1, 6-bisphosphate aldolase B (Aldob) leads to a paradoxical upregulation of glucose metabolism to favor hepatocellular carcinogenesis but the upstream signaling events remain poorly defined. Akt is highly activated in HCC and targeting Akt is being explored as a potential therapy for HCC. Herein we demonstrate that Aldob suppresses Akt activity through a protein complex containing Aldob, Akt, and protein phosphatase 2A (PP2A), leading to inhibition of cell viability, cell cycle progression, glucose metabolism and tumor growth. Interestingly, Aldob directly interacts with phosphorylated Akt (p-Akt) and promotes the recruitment of PP2A to dephosphorylate p-Akt, and this scaffolding effect of Aldob is independent of its enzymatic activity. Loss of Aldob or disruption of Aldob/Akt interaction in Aldob R304A mutant restores Akt activity and tumor promoting effects. Consistently, Aldob and p-Akt expression are inversely correlated in human HCC tissues, and Aldob downregulation coupled with p-Akt upregulation predicts a poor prognosis for HCC. We have further discovered that a specific small-molecule activator of PP2A (SMAP) efficiently attenuates HCC tumorigenesis in Aldob-deficient cell lines and xenografts. Our work reveals a novel non-glycolytic role of Aldob in negative regulation of Akt activation, suggesting that inhibiting Akt activity and reactivating PP2A may be a potential therapeutic approach for HCC treatment.
Virtual manipulation of bird tail postures demonstrates drag minimisation when gliding
Authors: Song Jialei , Cheney Jorn A. , Usherwood James R. , Bomphrey Richard J. 
Published: June 2020

AbstractAerodynamic function of the avian tail has previously been studied using observations of bird flight, physical models in wind tunnels, theoretical modelling and flow visualization. However, none of these approaches has provided rigorously quantitative evidence concerning tail functions since: appropriate manipulation and controls cannot be achieved using live animals; and the aerodynamic interplay with wings and body challenges reductive theoretical or physical modelling approaches. Here, we have developed a comprehensive analytical drag model, calibrated by high-fidelity computational fluid dynamics (CFD), and used it to investigate the aerodynamic action of the tail by virtually manipulating its posture. The bird geometry used for CFD was reconstructed previously using stereo photogrammetry of a freely gliding barn owl and validated against wake measurements. Using this CFD-calibrated drag model, we predicted the drag production for 16 gliding flights with a range of tail postures. These observed postures are set in the context of a wider parameter sweep of theoretical postures, where the tail spread and elevation angles were manipulated virtually. The observed postures of our gliding bird corresponded to near minimal total drag.Author SummaryThe aerodynamic contribution of bird tails is challenging to study; strong interactions between wings, body and tail make models isolating the contributions of different body parts difficult to interpret. Further, methods for direct manipulation are limited, and confounding compensation is likely in live, free-flying birds. To circumvent these issues, we applied high-fidelity CFD to a range of measured gliding owl geometries in order to develop a comprehensive analytical drag model. This enabled the drag implications of virtually-manipulated tail postures to be explored. The theoretical postures that cause minimum drag match those used by owls. The drag model demonstrates the importance of the viscous component of drag, which is of particular relevance to fliers at the scale of birds and, increasingly, smaller UAVs.
The changing value of higher education as a currency of opportunity
Authors: Wright Ewan , Wei Haitao 
Published: June 2020

PurposeThe worldwide expansion of higher education participation has destabilised the value of higher education as a currency of opportunity. An increasing number of graduates are experiencing the precarity of unemployment, under-employment and low salaries. This study aimed to investigate how university students in China understand and respond to the changing relationship between higher education and career opportunities.Design/methodology/approachThe research team conducted 100 in-depth interviews with final-year undergraduates at one elite and one lower-tier university in a metropolitan city in Guangdong Province.FindingsThe students were acutely aware of fierce competition in the graduate labour market. When asked “what matters most” for post-graduation career prospects, they identified elite universities and high-status fields of study as “traditional” currencies of opportunity. Nonetheless, to stand out in a competitive environment, they perceived a growing need to supplement higher education credentials through university experiences (internships, student governance, study abroad programmes), party membership, personal connections and (overseas) postgraduate education. Moreover, in a “race to the top”, they discussed how qualitatively distinctive university experiences and elite postgraduate education are “new” currencies of opportunity for high-status professional employment.Originality/valueThe study demonstrates how intensified competition for graduate employment can result in an “opportunity trap”. The students were participating in an “arms race” to accumulate positional advantages for their post-graduation careers. The net impact of such efforts on a systemic level is to create an upward spiral in what students are expected to do in preparation for their post-graduation careers and further destabilise the value of higher education as a currency of opportunity.