bluuebunny/crossref_metadata_2025 huggingface dataset:
Unifying the Notions of Modularity and Core–Periphery Structure in Functional Brain Networks during Youth
Authors: Gu Shi , Xia Cedric Huchuan , Ciric Rastko , Moore Tyler M , Gur Ruben C , Gur Raquel E , Satterthwaite Theodore D , Bassett Danielle S
Published: June 2019

At rest, human brain functional networks display striking modular architecture in which coherent clusters of brain regions are activated. The modular account of brain function is pervasive, reliable, and reproducible. Yet, a complementary perspective posits a core–periphery or rich-club account of brain function, where hubs are densely interconnected with one another, allowing for integrative processing. Unifying these two perspectives has remained difficult due to the fact that the methodological tools to identify modules are entirely distinct from the methodological tools to identify core–periphery structure. Here, we leverage a recently-developed model-based approach—the weighted stochastic block model—that simultaneously uncovers modular and core–periphery structure, and we apply it to functional magnetic resonance imaging data acquired at rest in 872 youth of the Philadelphia Neurodevelopmental Cohort. We demonstrate that functional brain networks display rich mesoscale organization beyond that sought by modularity maximization techniques. Moreover, we show that this mesoscale organization changes appreciably over the course of neurodevelopment, and that individual differences in this organization predict individual differences in cognition more accurately than module organization alone. Broadly, our study provides a unified assessment of modular and core–periphery structure in functional brain networks, offering novel insights into their development and implications for behavior.
Mycobacterium chimaera Encephalitis Following Cardiac Surgery: A New Syndrome
Authors: Lau Darren , Cooper Ryan , Chen Justin , Sim Valerie L , McCombe Jennifer A , Tyrrell Gregory J , Bhargava Ravi , Adam Benjamin , Chapman Erin , Croxen Matthew A , Garady Cherif , Antonation Kym , van Landeghem Frank K H , Ip Shannon , Saxinger Lynora
Published: June 2019

We report the cases of 3 patients with fatal, disseminated Mycobacterium chimaera infections following cardiac surgeries. Progressive neurocognitive decline and death were explained by active granulomatous encephalitis, with widespread involvement of other organs. This syndrome is clinically elusive and, thus, may have caused deaths in prior reported series.
Uncovering the mouse olfactory long non-coding transcriptome with a novel machine-learning model
Authors: Camargo Antonio P , Nakahara Thiago S , Firmino Luiz E R , Netto Paulo H M , do Nascimento João B P , Donnard Elisa R , Galante Pedro A F , Carazzolle Marcelo F , Malnic Bettina , Papes Fabio
Published: June 2019

Very little is known about long non-coding RNAs (lncRNAs) in the mammalian olfactory sensory epithelia. Deciphering the non-coding transcriptome in olfaction is relevant because these RNAs have been shown to play a role in chromatin modification and nuclear architecture reorganization, processes that accompany olfactory differentiation and olfactory receptor gene choice, one of the most poorly understood gene regulatory processes in mammals. In this study, we used a combination of in silico and ex vivo approaches to uncover a comprehensive catalogue of olfactory lncRNAs and to investigate their expression in the mouse olfactory organs. Initially, we used a novel machine-learning lncRNA classifier to discover hundreds of annotated and unannotated lncRNAs, some of which were predicted to be preferentially expressed in the main olfactory epithelium and the vomeronasal organ, the most important olfactory structures in the mouse. Moreover, we used whole-tissue and single-cell RNA sequencing data to discover lncRNAs expressed in mature sensory neurons of the main epithelium. Candidate lncRNAs were further validated by in situ hybridization and RT-PCR, leading to the identification of lncRNAs found throughout the olfactory epithelia, as well as others exquisitely expressed in subsets of mature olfactory neurons or progenitor cells.
Platypnoea–orthodeoxia syndrome after pulmonary lobectomy: a rare entity with a difficult diagnosis
Authors: Krasas Athanasios , Tzifa Afroditi , Mallios Dimitrios , Iliadis Kosmas
Published: June 2019

Platypnoea–orthodeoxia syndrome (POS) is a rare clinical entity. It is characterized by position-dependent dyspnoea and oxygen desaturation in the upright position with orthodeoxia resolving in the supine position, and is mainly associated with cardiac defects. Only 9 cases of post-lobectomy POS have been reported in the literature. We describe a case of POS in a woman who underwent a lobectomy and in whom POS was diagnosed and treated.
Computations of Eigenvalues and Resonances on Perturbed Hyperbolic Surfaces with Cusps
Authors: Levitin Michael , Strohmaier Alexander
Published: June 2019

In this paper we describe a simple method that allows for a fast direct computation of the scattering matrix for a surface with hyperbolic cusps from the Neumann-to-Dirichlet map on the compact manifold with boundary obtained by removing the cusps. We illustrate that even if the Neumann-to-Dirichlet map is obtained by a finite element method (FEM) one can achieve good accuracy for the scattering matrix. We give various interesting examples of how this can be used to investigate the behaviour of resonances under conformal perturbations or when moving in Teichmüller space. For example, based on numerical experiments we rediscover the four arithmetic surfaces of genus one with one cusp. This demonstrates that it is possible to identify arithmetic objects using FEM. All the videos accompanying this paper are available with its online version, or externally either at http://michaellevitin.net/hyperbolic.html or as a dedicated YouTube playlist.
Living with the Dead as a Way of Life: A Materialist Historiographical Approach to Cemetery Asceticism in Indian Buddhist Monasticisms
Authors: Witkowski Nicholas
Published: June 2019

This study challenges the long-standing scholarly conception that ascetic practice was incompatible with the institutional imperatives of the Indian Buddhist monastery in the “middle period.” Drawing upon the rich narrative tradition in Indian Buddhist law codes (Vinaya), I employ a new hermeneutical approach in order to demonstrate that cemetery (śmaśāna) asceticism remained central to the Buddhist monastic lifestyle. I begin with an extended methodological discussion that locates my approach—what I call materialist historiography—in a genealogy of scholarship that reads literary texts for an anthropology of everyday life. I then draw from a wide range of Vinaya narratives to argue that, despite the increasingly vocal presence of a Brahmanical purity party, the ascetic practices of residing in the cemetery, meditating on corpses, scavenging for goods on the charnel ground, and stripping corpses of their funeral shrouds remained an everyday affair in the monastery.
Genetic parameters of plasma and ruminal volatile fatty acids in sheep fed alfalfa pellets and genetic correlations with enteric methane emissions1
Authors: Jonker Arjan , Hickey Sharon M , McEwan John C , Rowe Suzanne J , Janssen Peter H , MacLean Sarah , Sandoval Edgar , Lewis Sarah , Kjestrup Holly , Molano German , Agnew Michael , Young Emilly A , Dodds Ken G , Knowler Kevin , Pinares-Patiño Cesar S
Published: June 2019

Animal-to-animal variation in methane (CH4) emissions determined in respiration chambers has a genetic basis, but rapid phenotyping methods that can be applied on-farm are required to enable increased genetic progress by the farming industry. Fermentation of carbohydrates in the rumen results in the formation of VFA with hydrogen (H2) as a byproduct that is used for CH4 formation. Generally, fermentation pathways leading to acetate are associated with the most H2 production, less H2 formation is associated with butyrate production, and propionate and valerate production are associated with reduced H2 production. Therefore, VFA may constitute a potential correlated proxy for CH4 emissions to enable high-throughput animal screening. The objective of the present study was to determine the genetic parameters for ruminal and plasma VFA concentrations in sheep fed alfalfa (Medicago sativa L.) pellets and their genetic (rg) and phenotypic (rp) correlations with CH4 emissions. Measurements of CH4 emissions in respiration chambers and ruminal (stomach tubing 18 h from last meal) and blood plasma (3 h post-feeding) VFA concentrations were made on 1,538 lambs from 5 birth years (2007 and 2009 to 2012) aged between 5 and 10 mo, while the animals were fed alfalfa pellets at 2.0 times maintenance requirements in 2 equal size meals (0900 and 1500 h). These measurements were repeated twice (rounds) 14 d apart. Mean (± SD) CH4 production was 24.4 ± 3.08 g/d, and the mean CH4 yield was 15.8 ± 1.51 g/kg DMI. Mean concentration of total ruminal VFA was 52.2 mM, with concentrations of acetate, propionate and butyrate of 35.97, 8.83, and 4.02 mM, respectively. Ruminal total VFA concentration had heritability (h2) and repeatability estimates (± SE) of 0.24 ± 0.05 and 0.35 ± 0.03, respectively, and similar estimates were found for acetate, propionate, and butyrate. Blood plasma concentrations of VFA had much lower estimates of h2 and repeatability than ruminal VFA. Genetic correlations with CH4 yield were greatest for total concentrations of ruminal VFA and acetate, with 0.54 ± 0.12 and 0.56 ± 0.12, respectively, which were much greater than their corresponding rp. The rp and rg of ruminal VFA proportions and blood VFAs with CH4 emissions were in general lower than for ruminal VFA concentrations. However, minor ruminal VFA proportions had also moderate rg with CH4 yield. Pre-feeding concentrations of total VFA and acetate were the strongest correlated proxies to select sheep that are genetically low CH4 emitters.
Impact of porcine reproductive and respiratory syndrome virus on muscle metabolism of growing pigs1
Authors: Helm Emma T , Curry Shelby M , De Mille Carson M , Schweer Wesley P , Burrough Eric R , Zuber Elizabeth A , Lonergan Steven M , Gabler Nicholas K
Published: June 2019

Porcine reproductive and respiratory syndrome (PRRS) virus is one of the most economically significant pig pathogens worldwide. However, the metabolic explanation for reductions in tissue accretion observed in growing pigs remains poorly defined. Additionally, PRRS virus challenge is often accompanied by reduced feed intake, making it difficult to discern which effects are virus vs. feed intake driven. To account for this, a pair-fed model was employed to examine the effects of PRRS challenge and nutrient restriction on skeletal muscle and liver metabolism. Forty-eight pigs were randomly selected (13.1 ± 1.97 kg BW) and allotted to 1 of 3 treatments (n = 16 pigs/treatment): 1) PRRS naïve, ad libitum fed (Ad), 2) PRRS-inoculated, ad libitum fed (PRRS+), and 3) PRRS naïve, pair-fed to the PRRS-inoculated pigs’ daily feed intake (PF). At days postinoculation (dpi) 10 and 17, 8 pigs per treatment were euthanized and tissues collected. Tissues were assayed for markers of proteolysis (LM only), protein synthesis (LM only), oxidative stress (LM only), gluconeogenesis (liver), and glycogen concentrations (LM and liver). Growth performance, feed intake, and feed efficiency were all reduced in both PRRS+ and PF pigs compared with Ad pigs (P < 0.001). Furthermore, growth performance and feed efficiency were additionally reduced in PRRS+ pigs compared with PF pigs (P < 0.05). Activity of most markers of LM proteolysis (μ-calpain, 20S proteasome, and caspase 3/7) was not increased (P > 0.10) in PRRS+ pigs compared with Ad pigs, although activity of m-calpain was increased in PRRS+ pigs compared with Ad pigs (P = 0.025) at dpi 17. Muscle reactive oxygen species production was not increased (P > 0.10) in PRRS+ pigs compared with Ad pigs. However, phosphorylation of protein synthesis markers was decreased in PRRS+ pigs compared with both Ad (P < 0.05) and PF (P < 0.05) pigs. Liver gluconeogenesis was not increased as a result of PRRS; however, liver glycogen was decreased (P < 0.01) in PRRS+ pigs compared with Ad and PF pigs at both time points. Taken together, this work demonstrates the differential impact a viral challenge and nutrient restriction have on metabolism of growing pigs. Although markers of skeletal muscle proteolysis showed limited evidence of increase, markers of skeletal muscle synthesis were reduced during PRRS viral challenge. Furthermore, liver glycogenolysis seems to provide PRRS+ pigs with glucose needed to fuel the immune response during viral challenge.
Effect of Sugarcane Cultivar and Foliar Insecticide Treatment on Infestations of the Invasive Sugarcane Thrips, Fulmekiola serrata (Thysanoptera: Thripidae), in Florida
Authors: Beuzelin J M , VanWeelden M T , Soto-Adames F N , Sandhu H S , Davidson R W , Baucum L , Swanson S
Published: June 2019

Fulmekiola serrata (Kobus) was observed infesting sugarcane, Saccharum spp. hybrids, in the United States for the first time in January 2017 in Florida. Field studies were conducted to determine F. serrata infestation levels on popular sugarcane cultivars and to determine the efficacy of foliar insecticide treatments that could be used for management. Cultivar evaluations comparing six and five commercial cultivars representing >46% of the sugarcane production area in Florida were conducted in 2017 and 2018, respectively. Fulmekiola serrata infestation levels did not differ among cultivars in 2017. However, infestation levels on CP 00-1101 were greater than on CP 96-1252 grown on organic soils, and infestation levels on CP 96-1252 were greater than on CPCL 97-2730 grown on mineral soils in 2018. Three insecticide evaluations, two in 2017 and one in 2018, were conducted. The pyrethroid lambda-cyhalothrin, which is registered for use on sugarcane, was consistently associated with the greatest decreases in F. serrata infestation levels. The neonicotinoids imidacloprid and thiamethoxam, as well as the butenolide flupyradifurone, decreased infestation levels but to a lesser extent than did lambda-cyhalothrin. The spinosyn spinetoram was associated with the lowest decreases in F. serrata infestation levels. Our results supported short-term F. serrata management recommendations: Popular Florida sugarcane cultivars should be considered equally susceptible to F. serrata until additional evaluations are conducted and F. serrata outbreaks can be treated with lambda-cyhalothrin when infestations stress the crop beyond acceptable levels.
EU General Court considers ‘MARRY ME’ descriptive for online dating
Authors: Ling Peter
Published: June 2019

General Court, Marry Me Group AG v EUIPO, T-332/18
Neymar dribbles past free riding: General Court confirms invalidity of a mark featuring the name of the Brazilian football star on the ground of bad faith
Authors: Giannino Michele
Published: June 2019

General Court of the EU, Third Chamber, Judgment of 14 May 2014, T-795/17, Carlos Moreira v EUIPO (Neymar), EU:T:2019:329
The Evolution of Public Policy and Judicial Function in English Law
Authors: Brekoulakis Stavros
Published: June 2019

This article is concerned with the function of English judges in employing the doctrine of public policy to decide cases under common law. For the first time, the article offers a critical appraisal of the recent evolution of public policy and decision making under English law from a structured doctrine of legal rules and limited judicial discretion to an open-ended principle of subjective evaluations. The main thesis of the article is that the latest judicial amendment of the nature of the public policy inquiry constitutes a radical and unnecessary departure from generally accepted propositions on the appropriate function of English judges in addressing issues of public policy.
Integrating Drones into a Natural-Resource Curriculum at Stephen F. Austin State University
Authors: Unger Daniel R , Kulhavy David L , Hung I-Kuai , Zhang Yanli , Stephens Williams Pat
Published: June 2019

Faculty within the Arthur Temple College of Forestry and Agriculture (ATCOFA) at Stephen F. Austin State University in Nacogdoches, Texas are integrating drone technology into their curriculum to introduce students to the use of high-end technology within a natural-resource-based decisionmaking process. Drones are currently being integrated across the curriculum within ATCOFA, including 10 geographic information systems (GIS) courses for students pursuing the B.S. in Spatial Science and within six non-GIS specific courses for students pursuing the B.S. in Forestry. Results indicate that drone technology can be an effective tool in enhancing a student’s academic experience and provides students with a skill set required for future natural-resource professionals.
Safety and Tolerability of Clofazimine in a Cohort of Children With Odontogenic Mycobacterium abscessus Infection
Authors: Adler-Shohet Felice C , Singh Jasjit , Nieves Delma , Ashouri Negar , Tran M Tuan , Flores M Cathy , Arrieta Antonio
Published: June 2019

Mycobacterium abscessus infections can be challenging to treat. Clofazimine has excellent in vitro activity against M abscessus, but reports of its use, particularly in children, have been limited. In this study, clofazimine was given to 27 children during an outbreak of odontogenic mycobacterial infections and seemed to be well tolerated as part of a multidrug regimen.
In vitro and in vivo characterization of two nonsporulating Aspergillus fumigatus clinical isolates from immunocompetent patients
Authors: Zhang Zheng , Jiang Yuan , Chen Jun , Chen Peiying , Kong Qingtao , Lu Ling , Sang Hong
Published: June 2019

Aspergillus fumigatus is a pathogenic fungus responsible for invasive aspergillosis (IA). Typically, it can produce abundant conidia to survive and spread. The infection by A. fumigatus usually occurs in immunocompromised patients due to failed clearance of inhaled conidia. However, the incidence of aspergillosis in immunocompetent hosts has been increasing, the pathogenesis of which is still unknown. Our team previously obtained two clinical nonsporulating A. fumigatus isolates from non-immunocompromised patients, which only have the form of hyphae. This present study demonstrated the in vitro and in vivo characteristics of the two nonsporulating A. fumigatus isolates and verified that their conidiation defects are associated to abolished expression of the sporulation-related central regulatory pathway brlA gene. In addition, we confirmed the mutation site of brlA gene (c.657_660delTCCT) contributes to the nonsporulating phenotype in one clinical isolate. Plate assay showed that the two nonsporulating isolates have a similar resistance to antifungal drugs, cell wall disturbing substances, and oxidative stress compared with the wild-type reference Af293. Most important of all, we employed an immunocompetent mouse model to mimic the pathogenesis of pulmonary aspergillosis in non-immunocompromised patients. It revealed that the hyphae of two nonsporulating isolates and Af293 have similar virulence in immunocompetent hosts. Interestingly, the hyphae fragments of Af293 but not conidia are able to induce invasive aspergillosis in immunocompetent mice. In conclusion, our study indicate that the form of hyphae may play a dominant causative role in pulmonary aspergillosis of immunocompetent hosts rather than conidia.
Radio pulsar polarization as a coherent sum of orthogonal proper mode waves
Authors: Dyks J
Published: June 2019

Radio pulsar polarization exhibits a number of complex phenomena that are classified into the realm of ‘beyond the rotating vector model’ (RVM). It is shown that these effects can be understood in geometrical terms, as a result of coherent and quasi-coherent addition of elliptically polarized natural mode waves. The coherent summation implies that the observed tracks of polarization angle (PA) do not always correspond to the natural propagation mode (NPM) waves. Instead, they are statistical average of coherent sum of the NPM waves, and can be observed at any (and frequency-dependent) distance from the natural modes. Therefore, the observed tracks of PA can wander arbitrarily far from the RVM, and may be non-orthogonal. For equal amplitudes of the NPM waves two pairs of orthogonal polarization modes (OPMs), displaced by 45°, can be observed, depending on the width of lag distribution. Observed pulsar polarization mainly results from two independent effects: the change of mode amplitude ratio and the change of phase lag. In the core region both effects are superposed on each other, which can produce so complex behaviour as observed in the cores of PSR B1933+16, B1237+25, and J0437−4715. Change of the phase lag with frequency ν is mostly responsible for the observed strong evolution of these features with ν. The coherent addition of orthogonal natural waves is a useful interpretive tool for the observed radio pulsar polarization.
Genius Architect or Clever Thief—How Plasmodiophora brassicae Reprograms Host Development to Establish a Pathogen-Oriented Physiological Sink
Authors: Malinowski Robert , Truman William , Blicharz Sara
Published: June 2019

When plants are infected by Plasmodiophora brassicae, their developmental programs are subjected to extensive changes and the resultant clubroot disease is associated with formation of large galls on underground tissue. The pathogen’s need to build an efficient feeding site as the disease progresses drives these changes, ensuring successful production of resting spores. This developmental reprogramming is an outcome of interactions between the pathogen and the infected host. During disease progression, we can observe alteration of growth regulator dynamics, patterns of cell proliferation and differentiation, increased cell expansion, and eventual cell wall degradation as well as the redirection of nutrients toward the pathogen. Recently, detailed studies of anatomical changes occurring during infection and studies profiling transcriptional responses have come together to provide a clearer understanding of the sequence of events and processes underlying clubroot disease. Additionally, genome sequencing projects have revealed P. brassicae’s potential for the production of signaling molecules and effectors as well as its requirements and capacities with respect to taking up host nutrients. Integration of these new findings together with physiological studies can significantly advance our understanding of how P. brassicae brings about reprogramming of host development. This article summarizes the current state of knowledge on cellular changes induced by P. brassicae infection and aims to explain their impact and importance for both the host and the pathogen.
Pediatric metabolic syndrome
Authors: Felix Abigail , John Rita Marie
Published: June 2019

Although the prevalence of obesity and its related complications are increasing among pediatric patients, appropriate management can prevent chronic disease. This article will present an overview of metabolic syndrome, pediatric metabolic syndrome guidelines, pathophysiology, associated risk factors, and clinical practice implications.
Assessing for and managing chronic insomnia in primary care settings
Authors: Cadet Myriam , Tucker Lorna , Allen Deborah H. , Lawal Ekaete , Dickson Darlene , Denis Anne Marie
Published: June 2019

Chronic insomnia is the most common sleep disorder. Improper or delayed diagnosis can lead to serious health problems. Early accurate assessment is essential to guide and provide safe treatment. This article reviews assessment and management of insomnia in the primary care setting.
Pediatric Patient-Reported Outcomes Measurement Information System is Equivalent to Scoliosis Research Society-22 in Assessing Health Status in Adolescent Idiopathic Scoliosis
Authors: Fedorak Graham T. , Larkin Kevin , Heflin John A. , Xu Julie , Hung Man
Published: June 2019

Study Design.

This was a correlational study.

Objective.

Determine the range of pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) scores for patients treated for adolescent idiopathic scoliosis (AIS) and assess correlation with Scoliosis Research Society-22 (SRS-22) domain scores.

Summary of Background Data.

Patient reported outcome (PRO) measures are important metrics for measuring health status in diverse patient populations. PROMIS is increasingly being used in orthopedic practice. Existing literature compares PROMIS measures favorably to legacy measures in numerous adult orthopedic conditions. This study sought to define the range of PROMIS mobility, pain interference, and peer relationships scores for adolescents treated for AIS. Furthermore, correlations between these domains and equivalent domains in the legacy PRO, SRS-22, were determined.

Methods.

Pediatric PROMIS and SRS-22 were obtained at routine clinical visits for AIS at a tertiary care children's hospital from January 2017 to October 2017. Spearman correlations were performed to examine the associations between three pediatric PROMIS domains and the SRS-22 domains. Only patients who completed both PRO measures were included in the analyses. Radiographic measurements were performed at each visit assessing sagittal and coronal deformity and overall spinal balance.

Results.

One hundred thirteen patients with a mean age of 14.4 (standard deviation [SD] = 2.1) years completed the assessments. The mean pediatric PROMIS domain scores included: mobility 50.9 (interquartile range [IQR] 36.2–65.6); pain interference 45.9 (IQR 28.9–62.9); peer relations 52.6 (IQR 38.3–64.9).

PROMIS mobility was strongly correlated with SRS-22 function (r = 0.65; P < 0.001). PROMIS pain interference was strongly correlated with SRS-22 pain (r = 0.70; P < 0.001). PROMIS peer relations was moderately correlated with SRS-22 Mental Health (r = 0.41; P < 0.001) and self-image (r = 0.34; P < 0.001).

Conclusion.

In AIS patients pediatric PROMIS pain interference and mobility correlate strongly with SRS-22 pain and function domains, while PROMIS peer relationships demonstrates moderate correlations with SRS-22 mental health and self-image.

Level of Evidence: 2
Cost-effectiveness of Operative versus Nonoperative Treatment of Adult Symptomatic Lumbar Scoliosis an Intent-to-treat Analysis at 5-year Follow-up
Authors: Carreon Leah Y. , Glassman Steven D. , Lurie Jon , Shaffrey Christopher I. , Kelly Michael P. , Baldus Christine R. , Bratcher Kelly R. , Crawford Charles H. , Yanik Elizabeth L. , Bridwell Keith H.
Published: June 2019

Study Design.

Secondary analysis using data from the NIH-sponsored study on adult symptomatic lumbar scoliosis (ASLS) that included randomized and observational arms.

Objective.

The aim of this study was to perform an intent-to-treat cost-effectiveness study comparing operative (Op) versus nonoperative (NonOp) care for ASLS.

Summary of Background Data.

The appropriate treatment approach for ASLS continues to be ill-defined. NonOp care has not been shown to improve outcomes. Surgical treatment has been shown to improve outcomes, but is costly with high revision rates.

Methods.

Patients with at least 5-year follow-up data were included. Data collected every 3 months included use of NonOp modalities, medications, and employment status. Costs for index and revision surgeries and NonOp modalities were determined using Medicare Allowable rates. Medication costs were determined using the RedBook and indirect costs were calculated based on reported employment status and income. Qualityadjusted life year (QALY) was determined using the SF6D.

Results.

There were 81 of 95 cases in the Op and 81 of 95 in the NonOp group with complete 5-year follow-up data. Not all patients were eligible 5-year follow-up at the time of the analysis. All patients in the Op and 24 (30%) in the NonOp group had surgery by 5 years. At 5 years, the cumulative cost for Op was $96,000 with a QALY gain of 2.44 and for NonOp the cumulative cost was $49,546 with a QALY gain of 0.75 with an incremental cost-effectiveness ratio (ICER) of $27,480 per QALY gain.

Conclusion.

In an intent-to-treat analysis, neither treatment was dominant, as the greater gains in QALY in the surgery group come at a greater cost. The ICER for Op compared to NonOp treatment was above the threshold generally considered cost-effective in the first 3 years of the study but improved over time and was highly cost-effective at 4 and 5 years.

Level of Evidence: 2
Synergistic anti-tumour effects of Clostridium butyricum in combination with apatinib in CT26 colorectal tumour-bearing mice
Authors: Xin Meng , Xie Qi , Ma Lin , An Ge , Xiao Junjuan , Li Junwei , Liu Xiaolin , Gao Peng , Liang Jing , Li Yan
Published: June 2019

To investigate the synergistic antitumour effect of Clostridium butyricum combined with apatinib on colorectal cancer in mice. Murine colorectal carcinoma cell line CT26.WT cells were xenografted into the skin of BALB/c mice. Tumour-bearing mice were randomly divided into four groups, and given different treatment options (PBS control; C. butyricum; apatinib; C. butyricum + apatinib). Real-time PCR was used to detect C. butyricum content in the intestine of mice given C. butyricum. The effects of various regimens on tumour growth were monitored, and CD31, proliferating cell nuclear antigen (PCNA), Bcl-2 and cleaved caspase-3 expressions in tumour were analysed by immunohistochemistry. C. butyricum combined with apatinib significantly inhibits tumour growth with decreased CD31, PCNA and Bcl-2 expressions, and increased cleaved caspase-3 expressions. Our study confirms that C. butyricum combined with apatinib in the treatment of xenografted colon tumour in mice can significantly inhibit tumour growth and promote cell apoptosis than apatinib alone treatments, providing the reference for clinical treatments.
Evolutionarily conserved resistance to phagocytosis observed in melanoma cells is insensitive to upregulation of pro-phagocytic signals and to CD47 blockade
Authors: Anderson Katie L. , Snyder Kristin M. , Ito Daisuke , Lins Debra C. , Mills Lauren J. , Weiskopf Kipp , Ring Nan G. , Ring Aaron M. , Shimizu Yoji , Mescher Matthew F. , Weissman Irving L. , Modiano Jaime F.
Published: June 2019

Therapeutic activation of macrophage phagocytosis has the ability to restrain tumour growth through phagocytic clearance of tumour cells and activation of the adaptive immune response. Our objective for this study was to evaluate the effects of modulating pro- and anti-phagocytic pathways in malignant melanoma. In order to identify evolutionarily conserved mechanisms of resistance that may be important for melanoma cell survival, we utilized a multi-species approach and examined the phagocytosis of human, mouse, and dog melanoma cells. We observed that melanoma cells from all three species displayed unexpected resistance to phagocytosis that could not be fully mitigated by blockade of the ‘don’t eat me’ signal CD47 or by chemotherapeutic enhancement of known ‘eat me’ signals. Additionally, CD47 blockade failed to promote anti-melanoma immune responses or tumour regression in vivo. This melanoma resistance to phagocytosis was not mediated by soluble factors, and it was unaffected by siRNA-mediated knockdown of 47 prospective ‘don’t eat me’ signals or by CRISPR-Cas-mediated CD47 knockout. Unexpectedly, CD47 knockout also did not enhance phagocytosis of lymphoma cells, but it eliminated the pro-phagocytic effect of CD47 blockade, suggesting that the pro-phagocytic effects of CD47 blockade are due in part to Fc receptor engagement. From this study, we conclude that melanoma cells possess an evolutionarily conserved resistance to macrophage phagocytosis. Further investigation will be needed to overcome the mechanisms that mediate melanoma cell resistance to innate immunity.
Role of BIOCHIP Indirect Immunofluorescence Test in Cutaneous Vesiculobullous Diseases
Authors: Tirumalae Rajalakshmi , Kalegowda Inchara Yeliur
Published: June 2019

BIOCHIP mosaics for indirect immunofluorescence in cutaneous vesiculobullous diseases provide antibody profiles in a single run and can be an alternative to performing multistep assays. There is scanty data regarding their utility. BIOCHIP tests performed over 4 years were compared with biopsy and/or direct immunofluorescence (DIF). Of 209 BIOCHIP tests, 108 were positive. Pemphigus vulgaris and Bullous pemphigoid were the commonest. Dsg3 was the commonest positive substrate in pemphigus group (86%) with 100% sensitivity. Intercellular space pattern on BIOCHIP primate esophagus was seen only in 49%. BP 180 was the commonest positive substrate in pemphigoid (95%) with 78% sensitivity. In 68 cases, corresponding biopsy/DIF was available with concordance of 89% in pemphigus and 93% in pemphigoid groups. In 40 cases where BIOCHIP was positive without biopsy/DIF, 97.5% were concordant with clinical diagnosis. Among the negative results, 13 had biopsy/DIF that were diagnostic. The overall positivity of BIOCHIP was 92% for pemphigus and 84% for pemphigoid groups. Indirect immunofluorescence by BIOCHIP method shows good concordance with histopathology/DIF. However, the sensitivity of some of the substrates varies. It is an effective screening tool to identify cases requiring further ELISA/immunoblots or where biopsy is not feasible.
Adjustment for Urinary Creatinine or Serum Lipids for Analytes Assayed in Pooled Specimens
Authors: Weinberg Clarice R. , Shi Min , O’Brien Katie M. , Umbach David M.
Published: June 2019

Background:

For case–control studies, pooling biologic specimens (cases with cases and controls with controls) can make it affordable to study a biomarker that is expensive to assay, while conserving quantities of archived specimens. For a fixed number of participants, pooling designs incur little loss of estimation precision, and they can even improve precision by enabling inclusion of more participants with the same number of assays. A limitation that has discouraged the use of these methods in environmental epidemiology, however, is the lack of a valid way to adjust for creatinine (urinary dilution) when assaying a biomarker in urine or to adjust for serum lipids when assaying a lipophilic biomarker in serum. We aimed to develop practical strategies to accomplish those adjustments.

Methods:

Our strategies either differentially dilute specimens before pooling equal aliquots or, alternatively, pool deliberately unequal aliquots from each specimen, where prior determinations of the adjustment factor in each individual specimen inform their differential dilution or unequal aliquot volumes. In addition, we show how to modify these strategies if, instead of just adjusting for creatinine per se, one needs to account for factors that influence creatinine. We carry out simulations under several causal scenarios.

Results:

We demonstrate that the proposed strategies perform well in estimating the same adjusted association parameter as would be estimated by using individually-assayed specimens.

Conclusion:

By implementing the proposed strategies when forming specimen pools, one can greatly improve the efficiency of case–control studies that involve an expensive-to-assay exposure measured in biospecimens.
Practical Approach and Safety of Hyaluronic Acid Fillers
Authors: Rohrich Rod J. , Bartlett Erica L. , Dayan Erez
Published: June 2019

Soft-tissue filler use has grown considerably related to the increasing popularity of minimally invasive cosmetic procedures. Hyaluronic acid products are currently the most utilized soft-tissue fillers. Proper working knowledge of individual products, limitations to use, and anatomic principles can improve outcomes. Prevention is key to minimize complications; however, when present, complications must be managed methodically. Complications are categorized based on the timing of presentation and include early, late, and delayed. Vascular compromise and tissue necrosis are among the most devastating complications seen with filler use. Nodules can be related to an inflammatory or infectious etiology but should be distinguished as treatment varies. Hyaluronidase is mandatory to have available as a reversal agent for hyaluronic acid products and can be used in treatment for many complications and untoward sequela.
USE OF CHOROIDAL VASCULARITY INDEX FOR CHOROIDAL STRUCTURAL EVALUATION IN CENTRAL SEROUS CHORIORETINOPATHY WITH CHOROIDAL NEOVASCULARIZATION
Authors: Kim Rae-Young , Chung Doh Hoon , Kim Mirinae , Park Young-Hoon
Published: June 2019

Purpose:

To evaluate choroidal vascular structure in eyes with central serous chorioretinopathy (CSC) by assessing the choroidal vascular index (CVI).

Methods:

We retrospectively analyzed the medical records of 117 eyes with CSC. Subjects were divided into 4 groups according to clinical characteristics: 1) acute CSC (N = 29), 2) non-neovascularized chronic CSC without flat irregular pigment epithelial detachment (N = 49), 3) non-neovascularized chronic CSC with flat irregular pigment epithelial detachment (N = 21), and 4) chronic CSC with choroidal neovascularization (N = 18). Subfoveal choroidal area (1,500 mm) of swept source optical coherence tomography scans were divided into luminal and stromal areas by the image binarization technique. The CVI was defined as the ratio of the luminal to the total subfoveal choroidal area.

Results:

The CVI was significantly lower in eyes of Group 4 than those of other groups (all P < 0.05). The subfoveal choroidal thickness was significantly lower in Group 4 than in Groups 1 and 2 (P < 0.05), but regression analysis showed no association with the CVI.

Conclusion:

Decreased CVI may reflect choroidal vascular structure changes in eyes with choroidal neovascularization complicating CSC. These findings suggest that the CVI could be useful for evaluating choroidal vascular changes in eyes with CSC.
Bilateral Necrotizing Herpes Simplex Keratitis in an Immunocompetent Patient With Genetic Analysis of Herpes Simplex Virus 1
Authors: Yoshida Masaaki , Hosogai Mayumi , Yokokura Shunji , Sato Kota , Hariya Takehiro , Kobayashi Wataru , Okabe Tatsu , Todokoro Daisuke , Nakazawa Toru
Published: June 2019

Purpose:

To report a case of severe bilateral necrotizing herpes simplex keratitis (HSK) in an immunocompetent patient, with genotyping of the underlying herpes simplex virus 1 (HSV-1).

Methods:

Genetic analyses of HSV-1 in tear samples were performed with polymerase chain reaction-based restriction fragment length polymorphism, targeting the viral genes unique short (US)2, US4 (glycoprotein G), and US7 (glycoprotein I).

Results:

A 64-year-old woman with no history of atopy or immune disorders manifested bilateral keratitis with geographic ulcer. Her initial visual acuity was 20/1000 (OD) and 20/20 (OS). Polymerase chain reaction testing of a tear sample revealed the presence of HSV-1 in both eyes, and the patient was diagnosed with bilateral HSK. Both eyes progressed to necrotizing keratitis during the treatment course. Continuous intensive treatment, at first with acyclovir ointment and oral valacyclovir and later with steroid eye drops for stromal keratitis, finally improved the patient's condition. However, after 2 years, her visual acuity was limited to 20/250 (OD) and 20/60 (OS) because of corneal opacity from scarring. We found that the strain in the current case had a genotype combination of C/A/B (for US2/US4/US7), a known pattern in Japan, in both eyes.

Conclusions:

We successfully performed an unprecedented genetic analysis of an HSV-1 strain isolated from a case of bilateral necrotizing HSK in an immunocompetent patient. The association of the HSV-1 genotype with the clinical manifestation remains unclear, calling for more data from new cases, especially from different geographic regions.
Optical Coherence Tomography Assessment of Risk Factors for Visual Acuity Decline After Trabeculectomy in Patients With Advanced Open-Angle Glaucoma
Authors: Asaoka Kei , Kunimatsu-Sanuki Shiho , Kokubun Taiki , Nakazawa Toru
Published: June 2019

Précis:

Thinning of the macular retinal nerve fiber layer (mRNFL) and ganglion cell complex in the papillomacular bundle area contributed significantly to visual acuity (VA) decline in advanced glaucoma patients after trabeculectomy.

Purpose:

To identify structural parameters that could predict VA decline after trabeculectomy in patients with advanced open-angle glaucoma.

Patients and Methods:

Retrospective review of 74 eyes of 74 patients with advanced glaucoma (defined as mean deviation −12 dB or worse) and best-corrected VA (BCVA) of ≥40/200. All patients underwent trabeculectomy between 2013 and 2016. Measurements included intraocular pressure, BCVA, visual field parameters, and optical coherence tomography-derived parameters [(in both the overall macula and within the papillomacular bundle (PMB)], including mRNFL thickness (mRNFLT), ganglion cell layer/inner plexiform layer thickness, and ganglion cell complex thickness. Measurements were obtained before and after surgery, and follow-up was at least 6 months. We grouped the patients according to whether they underwent VA decline of >3 lines of BCVA after 6 months. We then compared the VA-decline group and the stable-VA group and performed a receiver operating characteristic analysis to determine optimal cut-off values for predicting VA decline.

Results:

The VA-decline group comprised 7 eyes (9.5%) and had lower preoperative mean deviation (P=0.021) and thinner mRNFL, ganglion cell layer/inner plexiform layer, and ganglion cell complex in the PMB (P=0.003, 0.135, and 0.023, respectively) than the stable-VA group. The cut-off values for predicting VA decline were 9.5 μm for mRNFLT in the PMB.

Conclusions:

This study found that thin mRNFLT in the PMB were risk factors for VA decline after trabeculectomy.
Endemic Mycoses in Children
Authors: Yeoh Daniel K. , Butters Coen , Curtis Nigel
Published: June 2019

The endemic mycoses are a group of infections caused by fungi with a distinct geographic distribution, defined by climatic and environmental conditions. The systemic endemic mycoses, namely histoplasmosis, blastomycosis, talaromycosis, coccidioidomycosis and paracoccidioidomycosis, occur after the inhalation of fungal spores. The cutaneous endemic mycoses, including sporotrichosis, mycetoma, entomophthoramycosis and chromoblastomycosis, enter the host via traumatic inoculation of the skin. Clinical presentation varies between these relatively heterogeneous infections, as does the susceptibility of immunosuppressed patients to disease. An understanding of the geographic range, typical manifestations, diagnostic methods, and treatment of the endemic mycoses is key in assessing patients presenting with atypical infections who may have traveled to endemic areas.
Using a Systems Engineering Framework to Evaluate Proton Pump Inhibitor Prescribing in Critically Ill Patients
Authors: Tischendorf Jessica S. , Knobloch Mary J. , Musuuza Jackson S. , Safdar Nasia
Published: June 2019

Proton pump inhibitors (PPIs) are a risk factor for hospital-acquired Clostridium difficile infection (CDI). Much PPI use is inappropriate, and interventions to reduce PPI use, such as for stress ulcer prophylaxis in all critically ill patients, are essential to reduce CDI rates. This mixed-methods study in a combined medical-surgical intensive care unit at a tertiary academic medical center used a human factors engineering approach to understand barriers and facilitators to optimizing PPI prescribing in these patients. We performed chart review of patients for whom PPIs were prescribed to evaluate prescribing practices. Semistructured provider interviews were conducted to determine barriers and facilitators to reducing unnecessary PPI use. Emergent themes from provider interviews were classified according to the Systems Engineering Initiative for Patient Safety model. In our intensive care unit, 25% of PPI days were not clinically indicated. Barriers to optimizing PPI prescribing included inadequate provider education, lack of institutional guidelines for stress ulcer prophylaxis, and strong institutional culture favoring PPI use. Potential facilitators included increased pharmacy oversight, provider education, and embedded decision support in the electronic medical record. Interventions addressing barriers noted by front line providers are needed to reduce unnecessary PPI use, and future studies should assess the impact of such interventions on CDI rates.
Meaningful Use: Does Physician Participation Move the Needle on Quality Metrics?
Authors: Brooks Kevin , Sarzynski Erin , Houdeshell-Putt Laura , Polverento Molly , Given Charles , Oberst Kathleen
Published: June 2019

Introduction:

To determine the association between pattern of participation in the Meaningful Use (MU) initiative and self-reported clinical quality metrics.

Methods:

We used state-level Medicaid electronic health record (EHR) incentive program data to categorize physicians based on receipt of MU payments (single year vs. multiple years) and self-reported quality metrics from 2011 to 2016.

Results:

Among 4,198 participating physicians, only 36% received more than one EHR incentive payment. Physicians participating for a single year had better cancer-screening metrics. By comparison, physicians who participated for multiple years reported better medication-related metrics and chronic disease management metrics.

Conclusions:

Nature of participation may have varying degrees of influence on types of clinical quality metrics. Sustained participation may support management of chronic conditions. Administrative claims data will help to elucidate our findings.
GATAD2B-related intellectual disability due to parental mosaicism and review of literature
Authors: Kaur Parneet , Mishra Shivani , Rajesh Shimoga M. , Girisha Katta M. , Shukla Anju
Published: June 2019

GATA zinc finger domain-containing 2B (GATAD2B) encodes p66beta, a subunit of transcription repressor complex methyl-CpG-binding protein-1 histone deacetylase complex/nucleosome remodelling and deacetylase, and mediates gene silencing. Pathogenic variants in GATAD2B are known to cause mental retardation, autosomal dominant 18, characterized by intellectual disability, limited speech development, generalized hypotonia and dysmorphism. Till date, 17 cases of GATAD2B-related intellectual disability, resulting either from loss-of-function variants in GATAD2B or microdeletions spanning GATAD2B, have been reported. Singleton exome sequencing was performed for index patient. The pathogenic variant identified was validated and segregation analysis was performed by Sanger sequencing. In this study, we report on an additional subject with GATAD2B-related intellectual disability identified through whole exome sequencing. The clinically unaffected father harboured the pathogenic variant in a mosaic state. We review the existing phenotypic and genotypic information for the individuals with this condition. GATAD2B-related intellectual disability is a rare condition with subtle yet recognizable clinical features. In this article, we highlight a consistent clinical profile of subjects with GATAD2B-related intellectual disability.