bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Maxillary Skeletal Expansion on Upper Airway Airflow: A Computational Fluid Dynamics Analysis
Authors: Zhao Tingting , Zhang Xiaotie , Ngan Peter , Yuan Wenjun , Chen Xiong , Hua Fang , He Hong 
Published: August 2019

Abstract
The effect of maxillary skeletal expansion (MSE) on upper airway in adolescent patients is not clear. The purpose of this study was to determine the upper airway airflow with MSE treatment using computational fluid dynamics analysis. Three-dimensional upper airway finite element models fabricated from cone beam computed tomography images were obtained before and after treatment in an adolescent patient with maxillary constriction. Turbulent analyses were applied. The nasal cavity (NC) was divided into 6 planes along the y-axis and the pharynx was divided into 7 planes in the z-axis. Changes in cross-sectional area, airflow velocity, pressure, and total resistance at maximum expiration and maximum inspiration were determined at each plane after MSE treatment. The greatest increase in area occurred in the oropharynx which was around 40.65%. The average increase in area was 7.42% in the NC and 22.04% in the pharynx. The middle part of pharynx showed the greatest increase of 212.81 mm2 and 217.99 mm2 or 36.58% and 40.66%, respectively. During both inspiration and expiration, airflow pressure decreased in both the NC and pharynx, which ranged from −11.34% to −23.68%. In the NC, the average velocity decrease was -0.18 m/s at maximum expiration (ME) and −0.13 m/s at maximum inspiration (MI). In the pharynx, the average velocity decrease was -0.07 m/s for both ME and MI. These results suggest that treatment of maxillary constriction using MSE appliance may show positive effects in improvement of upper airway cross-sectional areas and reduction of upper airway resistance and velocity.
Closed and Open Reduction of Nasal Fractures
Authors: James Joanne Grace , Izam Azza Shafiqah , Nabil Syed , Rahman Normastura Abd , Ramli Roszalina 
Published: August 2019

Aim:
The objective of this review was to determine the different types of surgical intervention in the management of nasal bone fractures, the outcomes, and complications associated with each intervention.

Methods:
A search was conducted using the PubMed and Cochrane Database of Systematic Review databases from January 1, 1997 until September 9, 2017. The search strategy was constructed using the Population Intervention Comparison Outcome framework with keywords related to nasal fracture and its treatment. Two sets of independent researchers performed the analysis. Qualitative analysis was performed using the Methodological Index for Non-Randomized Studies and National Institute for Clinical Excellence methodology for randomized controlled trial checklists.

Results:
The 4276 titles were obtained from PubMed database alone. Exclusion was made based on the title, abstract and full-text analysis. Finally, 23 papers were included and analyzed. Of the 23 papers, 13 (56.5%) were retrospective record review, 2 (8.7%) were randomized clinical trial or a randomized study and 8 case series (34.8%). 16 (69.6%) studies addressed closed reduction, 3 studies (13%) on open reduction and 4 studies (17.4%) addressed both open and closed reduction. The main focus in the outcome in all studies was accuracy of the anatomical reduction of the nasal bones. Three studies (13.0%) reported restoration of function such as breathing comfort or release in respiratory obstruction and another 3 (13.0%) addressed both cosmetic and breathing outcomes. Residual deformity was the most described complications in the studies (30.4%). In general, most of the studies were not of high quality as they lacked in some key elements in the Methodological Index for Non-Randomized Studies checklist.

Conclusion:
Both closed and open reduction provided good outcomes in cosmetic and breathing. Septoplasty is recommended to be performed simultaneously with fracture reduction.
Effect of a Mandibular Advancement Device on the Upper Airway in a Patient With Obstructive Sleep Apnea
Authors: Flores-Orozco Elan Ignacio , Tiznado-Orozco Gaby Esthela , Díaz-Peña Rogelio , Orozco Esteban Isaí Flores , Galletti Cosimo , Gazia Francesco , Galletti Francesco 
Published: August 2019

Abstract
The authors present a case of a 33-year-old male patient with obstructive sleep apnea syndrome who was treated with a mandibular advancement device with excellent results. The aim of this study is to underline the importance of new instruments that allow evaluating the upper airway with greater precision, such as cone beam tomography. Given the diagnosis and treatment, the upper airway was assessed using cone beam tomography; an increase in UA volume of 22% was observed (initial volume 22,962 mm3), along with a 28% increase in area (initial area 971 mm2). The evaluation of the UA using teleradiography also showed an increase in the points evaluated, with the midpoint of the soft palate presenting the greatest increase.
Clivus Intraosseous Meningioma Mimicking Chordoma
Authors: Abuzayed Bashar , Alawneh Khaled , Al Qawasmeh Majdi , Raffee Liqaa 
Published: August 2019

Abstract
A 78-year-old woman with progressive worsening vertigo and new onset of diplopia. Neurological examination revealed bilateral abducens nerve paralysis and gait disturbance with truncal ataxia. Neuroimaging revealed a mass lesion within the clivus with brain stem compression. The patient was operated with provisional diagnosis of clivus chordoma by neuro-navigation-guided extended endoscopic endonasal approach. Subtotal resection of the tumor was achieved with no intra- or postoperative complications. Histopathologic examination revealed intraosseous meningioma (WHO grade I). To the authors’ best knowledge this is the first case reporting clivus site of intraosseous meningioma.
A Virtual Crossmatch-based Strategy Facilitates Sharing of Deceased Donor Kidneys for Highly Sensitized Recipients
Authors: Roll Garrett R. , Webber Allison B. , Gae David H. , Laszik Zoltan , Tavakol Mehdi , Mayen Luis , Cunniffe Kelly , Syed Shareef , Hirose Ryutaro , Freise Chris , Feng Sandy , Roberts John P. , Ascher Nancy L. , Stock Peter G. , Rajalingam Raja 
Published: August 2019

Background.
It is estimated that 19.2% of kidneys exported for candidates with >98% calculated panel reactive antibodies are transplanted into unintended recipients, most commonly due to positive physical crossmatch (PXM). We describe the application of a virtual crossmatch (VXM) that has resulted in a very low rate of transplantation into unintended recipients.

Methods.
We performed a retrospective review of kidneys imported to our center to assess the reasons driving late reallocation based on the type of pretransplant crossmatch used for the intended recipient.

Results.
From December 2014 to October 2017, 254 kidneys were imported based on our assessment of a VXM. Of these, 215 (84.6%) were transplanted without a pretransplant PXM. The remaining 39 (15.4%) recipients required a PXM on admission using a new sample because they did not have an HLA antibody test within the preceding 3 months or because they had a recent blood transfusion. A total of 93% of the imported kidneys were transplanted into intended recipients. There were 18 late reallocations: 9 (3.5%) due to identification of a new recipient medical problem upon admission, 5 (2%) due to suboptimal organ quality on arrival, and only 4 (1.6%) due to a positive PXM or HLA antibody concern. A total of 42% of the recipients of imported kidneys had a 100% calculated panel reactive antibodies. There were no hyperacute rejections and very infrequent acute rejection in the first year suggesting no evidence for immunologic memory response.

Conclusions.
Seamless sharing is within reach, even when kidneys are shipped long distances for highly sensitized recipients. Late reallocations can be almost entirely avoided with a strategy that relies heavily on VXM.
Further Evidence That the Soluble Urokinase Plasminogen Activator Receptor Does Not Directly Injure Mice or Human Podocytes
Authors: Harel Efrat , Shoji Jun , Abraham Vivek , Miller Loan , Laszik Zoltan G. , King Andrew , Dobi Dejan , Szabo Gyula , Hann Byron , Sarwal Minnie M. , Craik Charles S. , Vincenti Flavio 
Published: August 2019

Background.
The role of the soluble urokinase plasminogen activator receptor (suPAR) in focal segmental glomerulosclerosis (FSGS) as the circulating factor or as a predictor of recurrence after transplantation remains controversial. Previously published studies in mice and isolated podocytes produced conflicting results on the effect of suPAR on podocyte injury, effacement of foot processes, and proteinuria. These discordant results were in part due to diverse experimental designs and different strains of mice. The aim of our study was to determine the reasons for the inconsistencies of the previous studies results with suPAR by using uniform methods and studies in different strains of mice.

Methods.
We utilized a primary culture of human podocytes and 2 mouse models, the wild type (WT) and the urokinase plasminogen activator receptor (uPAR) KO (uPAR−/−), in an attempt to resolve the reported conflicting results.

Results.
In both WT and uPAR−/− mouse models, injection of recombinant uPAR, even at a high dose (100 μg), did not induce proteinuria, effacement of podocytes, or disruption of the cytoskeleton. Injection of suPAR resulted in its deposition exclusively in the glomerular endothelial cells and not in the podocytes of WT mice and was not detected at the uPAR KO mice. Kidneys from patients with recurrent FSGS had negative immunostaining for uPAR. We also evaluated the effect of recombinant uPAR on primary culture of human podocytes. uPAR did not result in podocytes damage.

Conclusions.
suPAR by itself is not the cause for direct podocyte injury, in vitro or in vivo. These findings suggest a more complex and still poorly understood role of suPAR in FSGS.
PGRMC1 phosphorylation and cell plasticity 1: glycolysis, mitochondria, tumor growth
Authors: Thejer Bashar M. , Adhikary Partho P. , Kaur Amandeep , Teakel Sarah L. , Van Oosterum Ashleigh , Seth Ishith , Pajic Marina , Hannan Kate M. , Pavy Megan , Poh Perlita , Jazayeri Jalal A. , Zaw Thiri , Pascovici Dana , Ludescher Marina , Pawlak Michael , Cassano Juan C. , Turnbull Lynne , Jazayeri Mitra , James Alexander C. , Coorey Craig P. , Roberts Tara L. , Kinder Simon J. , Hannan Ross D. , Patrick Ellis , Molloy Mark P. , New Elizabeth J. , Fehm Tanja N. , Neubauer Hans , Goldys Ewa M. , Weston Leslie A. , Cahill Michael A. 
Published: August 2019

SUMMARYProgesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms. Here, we demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of the Warburg effect. This was associated with increased PI3K/Akt activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/Akt activation. Mutation of Y180F strongly attenuated mouse xenograft tumor growth. An accompanying paper demonstrates altered metabolism, mutation incidence, and epigenetic status in these cells, indicating that PGRMC1 phosphorylation strongly influences cancer biology.
PGRMC1 phosphorylation and cell plasticity 2: genomic integrity and CpG methylation
Authors: Thejer Bashar M. , Adhikary Partho P. , Teakel Sarah L. , Fang Johnny , Weston Paul A. , Gurusinghe Saliya , Anwer Ayad G. , Gosnell Martin , Jazayeri Jalal A. , Ludescher Marina , Gray Lesley-Ann , Pawlak Michael , Wallace Robyn H. , Pant Sameer D. , Wong Marie , Fischer Tamas , New Elizabeth J. , Fehm Tanja N. , Neubauer Hans , Goldys Ewa M. , Quinn Jane C. , Weston Leslie A. , Cahill Michael A. 
Published: August 2019

SUMMARYProgesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation. Here, we show that mutagenic manipulation of PGRMC1 phosphorylation alters cell metabolism, genomic stability, and CpG methylation. Each of several mutants elicited distinct patterns of genomic CpG methylation. Mutation of S57A/Y180/S181A led to increased net hypermethylation, reminiscent of embryonic stem cells. Pathways enrichment analysis suggested modulation of processes related to animal cell differentiation status and tissue identity, as well as cell cycle control and ATM/ATR DNA damage repair regulation. We detected different genomic mutation rates in culture. A companion manuscript shows that these cell states dramatically affect protein abundances, cell and mitochondrial morphology, and glycolytic metabolism. We propose that PGRMC1 phosphorylation status modulates cellular plasticity mechanisms relevant to early embryological tissue differentiation.
The Gut Microbiota composition of Feral and Tamworth Pigs determined using High-Throughput Culturomics and Metagenomics Reveals Compositional Variations When Compared to the Commercial Breeds
Authors: Fenske Gavin J. , Ghimire Sudeep , Antony Linto , Christopher-Hennings Jane , Scaria Joy 
Published: August 2019

AbstractBacterial communities in the hindguts of pigs have a profound impact on health and disease. Yet very limited studies have been performed outside intensive swine farms to determine pig gut microbiome composition in natural populations. Feral pigs represent a unique situation where the microbiome structure can be observed outside the realm of modern agriculture. Additionally, Tamworth pigs that freely forage were included to characterize the microbiome structure of this rare breed. In this study, gut microbiome of feral and Tamworth pigs were determined using metagenomics and culturomics. Tamworth pigs are highly dominated by Bacteroidetes primarily composed of the genus Prevotella whereas feral samples were more diverse with almost equal proportions of Firmicutes and Bacteroidetes. In total, 46 distinct species were successfully isolated from 1000 colonies selected. The combination of metagenomics and culture techniques facilitated a greater retrieval of annotated genes than either method alone. Furthermore, the naturally raised Tamworth pig microbiome contained more number of antibiotic resistance genes when compared to feral pig microbiome. The single medium based pig microbiota library we report is a resource to better understand pig gut microbial ecology and function by assembling simple to complex microbiota communities in bioreactors or germfree animal models.
Association between Drusen Burden Determined by OCT and Genetic Risk in Early and Intermediate Age-Related Macular Degeneration
Authors: Seddon Johanna M. , Dossett James , Widjajahakim Rafael , Rosner Bernard 
Published: August 2019

ABSTRACTPURPOSETo determine associations between macular drusen parameters derived from an automatic optical coherence tomography (OCT) algorithm, age-related macular degeneration (AMD) stage and genetic variants.METHODSEyes classified as early or intermediate AMD with OCT imaging and genetic data were selected (n=239 eyes). Drusen area and volume measurements were estimated using the Zeiss Cirrus advanced retinal pigment epithelium (RPE) analysis algorithm in a 5mm diameter (perifoveal) zone centered on the fovea. Associations between drusen measurements and common genetic variants in the complement and high density lipoprotein (HDL) lipid pathways and theARMS2variant were calculated using generalized estimating equations and linear mixed models adjusting for age, sex, smoking, BMI, and education.RESULTSWhen compared to eyes with no measurable drusen, drusen area ≥ the median was independently associated with a higher number of risk alleles forCFHrisk score, risk variants inC3andARMS2/HTRA1. Similar results were obtained for drusen volume. When all genes were analyzed in the same model, onlyCFHscore andARMS2/HTRA1were associated with drusen measurements. HDL pathway genes were not significantly related to drusen parameters. Early and intermediate AMD stages were associated with OCT derived drusen area and volume.CONCLUSIONGenetic variants inCFHandARMS2/HTRA1, commonly associated with advanced AMD, were independently associated with higher drusen burden determined by OCT in eyes with early and intermediate AMD. The automatic RPE algorithm using OCT provides a quantitative classification of non-advanced AMD. Drusen morphology and other OCT-derived sub-phenotypes are biomarkers that could provide early anatomic endpoints for clinical trials.
Dual RNA-seq provides insight into the biology of the neglected intracellular human pathogenOrientia tsutsugamushi
Authors: Mika-Gospodorz Bozena , Giengkam Suparat , Westermann Alexander J. , Wongsantichon Jantana , Kion-Crosby Willow , Chuenklin Suthida , Wang Loo Chien , Sunyakumthorn Piyanate , Sobota Radoslaw M. , Subbian Selvakumar , Vogel Jörg , Barquist Lars , Salje Jeanne 
Published: August 2019

SummaryEmerging and neglected diseases pose challenges as their biology is frequently poorly understood, and genetic tools often do not exist to manipulate the responsible pathogen. Organism agnostic sequencing technologies offer a promising approach to understand the molecular processes underlying these diseases. Here we apply dual RNA-seq toOrientia tsutsugamushi(Ot), an obligate intracellular bacterium and the causative agent of the vector-borne human disease scrub typhus. Half the Ot genome is composed of repetitive DNA, and there is minimal collinearity in gene order between strains. Integrating RNA-seq, comparative genomics, proteomics, and machine learning, we investigated the transcriptional architecture of Ot, including operon structure and non-coding RNAs, and found evidence for wide-spread post-transcriptional antisense regulation. We compared the host response to two clinical isolates and identified distinct immune response networks that are up-regulated in response to each strain, leading to predictions of relative virulence which were confirmed in a mouse infection model. Thus, dual RNA-seq can provide insight into the biology and host-pathogen interactions of a poorly characterized and genetically intractable organism such as Ot.
Long-termin vivoimaging ofDrosophilalarvae
Authors: Kakanj Parisa , Eming Sabine A. , Partridge Linda , Leptin Maria 
Published: August 2019

AbstractTheDrosophilalarva has been used to investigate many processes in cell biology, including morphogenesis, physiology, responses to drugs and new therapeutic compounds. Despite its enormous potential as a model system, it has technical limitations in cases where longer-term live imaging is necessary, because of the lack of efficient methods for immobilising larvae for extended periods. We describe here a simple procedure for anaesthetisation and long-termin vivoimaging of the epidermis and other larval organs including gut, imaginal discs, neurons, fat body, tracheae and haemocytes, and show a procedure for probing cell properties by laser ablation. We include a survey of different anaesthetics, showing that short exposure to diethyl ether is the most effective for long-term immobilisation of larvae. This method does not require specific expertise beyond basicDrosophilagenetics and husbandry, and confocal microscopy. It enables high-resolution studies of many systemic and sub-cellular processes in larvae.
Cell culture dimensionality influences mesenchymal stem cell fate through cadherin-2 and cadherin-11
Authors: Passanha Fiona R , Geuens Thomas , Konig Simon , van Blitterswijk Clemens A , LaPointe Vanessa LS 
Published: August 2019

ABSTRACTThe acquisition of a specific cell fate is one of the core aims of tissue engineering and regenerative medicine. Significant evidence shows that aggregate cultures have a positive influence on fate decisions, presumably through cell-cell interactions, but little is known about the specific mechanisms. To investigate the difference between cells cultured as a monolayer and as aggregates, we started by looking at cadherin expression, an important protein involved in cell adhesion, during the differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) in aggregate and monolayer cultures. We observed that proliferating hMSCs in monolayer culture express cadherin-2 and undergo a switch to cadherin-11 over time, which was not evident in the aggregate cultures. By knocking down cadherin-2 and cadherin-11, we found that both cadherins were required for adipogenic differentiation in a monolayer as well as aggregate culture. However, during osteogenic differentiation, low levels of cadherin-2 were found to be favorable for cells cultured as a monolayer and as aggregates, whereas cadherin-11 was dispensable for cells cultured as aggregates. Together, these results provide compelling evidence for the important role that cadherins play in regulating the differentiation of hMSCs and how this is affected by the dimensionality of cell culture.
Prevalence and mutational determinants of high tumor mutation burden in breast cancer
Authors: Barroso-Sousa R. , Jain E. , Cohen O. , Kim D. , Buendia-Buendia J. , Winer E. , Lin N. , Tolaney S.M. , Wagle N. 
Published: August 2019

AbstractBackgroundHigh tumor mutation burden (TMB) has been associated with benefit to immunotherapy in multiple tumor types. However, the prevalence of hypermutated breast cancer is not well described. The aim of this study is to evaluate frequency, mutational patterns, and genomic profile of hypermutated breast cancer.Patients and MethodsWe used de-identified data from individuals with primary or metastatic breast cancer from six different publicly available genomic studies. The prevalence of hypermutated breast cancer was determined among 3969 patients’ samples that underwent whole exome sequencing or gene panel sequencing. Samples were classified as having high TMB if they had ≥10 mutations per megabase (mut/Mb). An additional 8 patients were identified from a Dana-Farber Cancer Institute cohort for inclusion in the hypermutated cohort. Among patients with high TMB, the mutational patterns, and genomic profile were determined. A subset of patients was treated with regimens containing PD-1 inhibitors.ResultsThe median TMB was 2.63 mut/Mb. Median TMB significantly varied according to tumor subtype (HR-/HER2-> HER2+ > HR+/HER2-,p< 0.05) and sample type (metastatic > primary,p2.2×10−16). Hypermutated tumors were found in 198 patients (5%), with an enrichment in metastatic versus primary tumors (8.4% versus 2.9%, p = 6.5 × 10−14). APOBEC activity (59.2%), followed by mismatch repair deficiency (MMRd; 36.4%), were the most common mutational processes among hypermutated tumors. Three patients with hypermutated breast cancer—including two with a dominant APOBEC activity signature and one with a dominant MMRd signature—treated with pembrolizumab-based therapies derived an objective and durable response to therapy.ConclusionHypermutation occurs in 5% of all breast cancers, with an enrichment in metastatic tumors. Different mutational signatures are present in this population, with APOBEC activity being the most common dominant process. Preliminary data suggest that hypermutated breast cancers are more likely to benefit from PD-1 inhibitors.Key MessageHigh tumor mutation burden is found in 5% of all breast cancers and is more common in metastatic tumors. While different mutational signatures are present in hypermutated tumors, APOBEC activity is the most common dominant process. Preliminary data suggest that those tumors are more likely to benefit from PD-1 inhibitors.