bluuebunny/crossref_metadata_2025 huggingface dataset:
Antenatal corticosteroids for threatened labour facilitate thyroid maturation among preterm neonates
Authors: Hanaoka Shintaro , Iwanaga Kogoro , Tomotaki Seiichi , Niwa Fusako , Takita Junko , Kawai Masahiko
Published: June 2020

Objective

To examine the effect of antenatal corticosteroids (ANS) on the maturation of thyroid function in the preterm infants.

Context

ANS reduce mortality and morbidities in preterm neonates. Organ maturation by the glucocorticoids is the key, at least in part. However, the effect of ANS on thyroid is controversial.

Patients

A study group of 99 very low birthweight neonates (<34 weeks’ gestational age) with the exception of those born more than 7 days after ANS administration were divided into a complete group (n = 49) whose mothers completed two doses of betamethasone and who were born more than 24 hours after the completion of ANS administration, and an incomplete group (n = 50) who were not exposed to any ANS or were born within 24 hours after the completion of ANS administration. Serum‐free thyroxine and thyroid‐stimulating hormone (TSH) levels were measured, and thyrotropin‐releasing hormone (TRH) stimulation tests were performed at about 2 weeks of age.

Results

The incidence of hyperthyrotropinaemia (TSH > 15 mIU/L) in the complete group was significantly lower than in the incomplete group (6% vs 22%, P = .023). Exaggerated responses to TRH tests were more frequent in the incomplete group (17% vs 44%; P = .053). TSH30 was significantly lower in the complete group, (P = .046). Multivariate logistic regression analysis showed that the incidence of hyperthyrotropinaemia was associated with complete ANS administration (adjusted odds ratios 0.39).

Conclusions

ANS administration might facilitate thyroid maturation in preterm neonates.
Adaptive Block Coordinate Descent for Distortion Optimization
Authors: Naitsat Alexander , Zhu Yufeng , Zeevi Yehoshua Y.
Published: June 2020

We present a new algorithm for optimizing geometric energies and computing positively oriented simplicial mappings. Our major improvements over the state‐of‐the‐art are: (i) introduction of new energies for repairing inverted and collapsed simplices; (ii) adaptive partitioning of vertices into coordinate blocks with the blended local‐global strategy for more efficient optimization and (iii) introduction of the displacement norm for improving convergence criteria and for controlling block partitioning. Together these improvements form the basis for the Adaptive Block Coordinate Descent (ABCD) algorithm aimed at robust geometric optimization. ABCD achieves state‐of‐the‐art results in distortion minimization, even under hard positional constraints and highly distorted invalid initializations that contain thousands of collapsed and inverted elements. Starting with an invalid non‐injective initial map, ABCD behaves as a modified block coordinate descent up to the point where the current mapping is cleared of invalid simplices. Then, the algorithm converges rapidly into the chosen iterative solver. Our method is very general, fast‐converging and easily parallelizable. We show over a wide range of 2D and 3D problems that our algorithm is more robust than existing techniques for locally injective mapping.
VisualNeuro: A Hypothesis Formation and Reasoning Application for Multi‐Variate Brain Cohort Study Data
Authors: Jönsson Daniel , Bergström Albin , Forsell Camilla , Simon Rozalyn , Engström Maria , Walter Susanna , Ynnerman Anders , Hotz Ingrid
Published: June 2020

We present an application, and its development process, for interactive visual analysis of brain imaging data and clinical measurements. The application targets neuroscientists interested in understanding the correlations between active brain regions and physiological or psychological factors. The application has been developed in a participatory design process and has subsequently been released as the free software ‘VisualNeuro’. From initial observations of the neuroscientists' workflow, we concluded that while existing tools provide powerful analysis options, they lack effective interactive exploration requiring the use of many tools side by side. Consequently, our application has been designed to simplify the workflow combining statistical analysis with interactive visual exploration. The resulting environment comprises parallel coordinates for effective overview and selection, Welch's t‐test to filter out brain regions with statistically significant differences and multiple visualizations for comparison between brain regions and clinical parameters. These exploration concepts enable neuroscientists to interactively explore the complex bidirectional interplay between clinical and brain measurements and easily compare different patient groups. A qualitative user study has been performed with three neuroscientists from different domains. The study shows that the developed environment supports simultaneous analysis of more parameters, provides rapid pathways to insights and is an effective tool for hypothesis formation.
“Beauty won’t boil the pot:” Aesthetic discourse, memory, and urban development in Edinburgh
Authors: Ballard Tooley Christa
Published: June 2020

In 2005, a development proposal for the largest city center redevelopment in Edinburgh, Scotland since the 18thcentury was presented to the public. Intended for the medieval and recently industrial part of the city’s Old Town, the proposal sparked years of intense argument over appropriate development for the area. Perhaps no aspect of that debate has incited as much rancor as the question of aesthetics. Arguments over development aesthetics, which mobilized a broad spectrum of actors—from corporate leaders, to city councilors, heritage organization members, private architects, city planners, residents and lay observers—were dismissed by the development’s supporters as superficial and insignificant. Instead, I argue that this aesthetic transformation pursued by the developer was accurately perceived by many, in particular the area residents, as a means of spatialized forgetting. The industrial history of the area would be eclipsed by the physical transformations pursued in this development, and in response residents asserted a conflicting aesthetic ethic as native to the neighborhood. This article explores the discourse of aesthetics and its impacts upon this development process, concluding that such discourse represents a strategy of dispossession in neoliberalizing urban development.
Targeting epidermal growth factor‐overexpressing triple‐negative breast cancer by natural killer cells expressing a specific chimeric antigen receptor
Authors: Liu Yan , Zhou Yehui , Huang Kuo‐Hsiang , Fang Xujie , Li Ying , Wang Feifei , An Li , Chen Qingfei , Zhang Yunchao , Shi Aihua , Yu Shuang , Zhang Jingzhong
Published: June 2020

Objectives

Traditional cancer therapy and regular immunotherapy are ineffective for treating triple‐negative breast cancer (TNBC) patients. Recently, chimeric antigen receptor‐engineered natural killer cells (CAR NK) have been applied to target several hormone receptors on different cancer cells to improve the efficacy of immunotherapy. Furthermore, epidermal growth factor receptor (EGFR) is a potential therapeutic target for TNBC. Here, we demonstrated that EGFR‐specific CAR NK cells (EGFR‐CAR NK cells) could be potentially used to treat patients with TNBC exhibiting enhanced EGFR expression.

Materials and methods

We investigated the cytotoxic effects of EGFR‐CAR NK cells against TNBC cells in vitro and in vivo. The two types of EGFR‐CAR NK cells were generated by transducing lentiviral vectors containing DNA sequences encoding the single‐chain variable fragment (scFv) regions of the two anti‐EGFR antibodies. The cytotoxic and anti‐tumor effects of the two cell types were examined by performing cytokine release and cytotoxicity assays in vitro, and tumor growth assays in breast cancer cell line‐derived xenograft (CLDX) and patient‐derived xenograft (PDX) mouse models.

Results

Both EGFR‐CAR NK cell types were activated by TNBC cells exhibiting upregulated EGFR expression and specifically triggered the lysis of the TNBC cells in vitro. Furthermore, the two EGFR‐CAR NK cell types inhibited CLDX and PDX tumors in mice.

Conclusions

This study suggested that treatment with EGFR‐CAR NK cells could be a promising strategy for TNBC patients.
Bone mesenchymal stem cells are recruited via CXCL8‐CXCR2 and promote EMT through TGF‐β signal pathways in oral squamous carcinoma
Authors: Meng Lin , Zhao Yueqi , Bu Wenhuan , Li Xing , Liu Xinchen , Zhou Dabo , Chen Yumeng , Zheng Shize , Lin Quan , Liu Qilin , Sun Hongchen
Published: June 2020

Objectives

Bone mesenchymal stem cells (BMSCs) play critical roles in tumour microenvironment. However, molecular mechanisms of how BMSCs to be recruited and effect subsequent tumour progression are poorly understood in oral squamous cell carcinoma (OSCC).

Materials and Methods

The distribution of CXCL8 was detected by immunohistochemical staining in OSCC tissues. The chemotaxis of conditioned media from different epithelial cells to BMSCs was examined by trans‐well assay. Real‐time quantitative PCR (qPCR) and ELISA were used to detect the expression of related cytokines and chemokine receptors. The migration of BMSCs was observed in BALB/c nude mice. The roles of BMSCs in proliferation, migration and invasion of OSCC were detected by CCK‐8, flow cytometry and trans‐well assay. Epithelial‐mesenchymal transition (EMT)–related markers were analysed by qPCR and Western blot in vitro, and growth was evaluated in BALB/c nude mice using subcutaneously implanted OSCC in nude mouse model in vivo.

Results

Using OSCC, we show CXCL8, secreted by OSCC, binds to exclusively CXCR2 in BMSCs to facilitate migration of BMSCs to OSCC. TGF‐β secreted by BMSCs subsequently induces EMT of OSCC to promote their proliferation, migration and infiltration. We also showed that the Ras/Raf/Erk axis plays a critical role in tumour progression.

Conclusions

Our results provide the molecular basis for BMSC recruitment into tumours, and how this process leads to tumour progression and leads us to develop a novel OSCC treatment target.
Spatial prioritization of selected mining pitlakes from Eastern Coalfields region, India: A species distribution modelling approach
Authors: Das Snehangshu , Mukherjee Aparajita , Gupta Santanu
Published: June 2020

Pitlake conservation is still a naive idea in a developing country. Species distribution modelling approaches can prove to be a useful tool in protecting biodiversity. The current study considers the ecological health of pitlakes through models of three winter migratory waterfowl species, namely Anser indicus (bar‐headed goose), Nettapus coromandelianus (cotton pygmy goose) and Netta rufina (red‐crested pochard), providing practical information for conservation setups in and around selected pitlakes in Eastern India. The AUC ± SD (Standard deviation) values of MaxEnt models of target species, viz. A. indicus, N. coromandelianus, and N. rufina are 0.729 ± 0.026, 0.772 ± 0.012, and 0.732 ± 0.024, respectively. Thus through the evaluation of the respective models and ground truth verification criteria, three pitlakes have proven to hold excellent conditions for the survival of these winter migratory birds as compared to the 20 studied ones. Three zones were created in these three lakes based on their characteristics to support these species and their associates. A large chunk of the region falls under the proposed zone of conservation priority sites from each of the three pitlakes. The need of the hour is to fulfill the voids between researchers, policymakers, and Eastern Coalfield's administration and work towards implementing the proposed idea.
Safety, Tolerability, and Pharmacokinetics of Remdesivir, An Antiviral for Treatment of COVID‐19, in Healthy Subjects
Authors: Humeniuk Rita , Mathias Anita , Cao Huyen , Osinusi Anu , Shen Gong , Chng Estelle , Ling John , Vu Amanda , German Polina
Published: June 2020

Remdesivir (RDV), a single diastereomeric monophosphoramidate prodrug that inhibits viral RNA polymerases, has potent in vitro antiviral activity against severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). RDV received the US Food and Drug Administration (FDA)’s emergency use authorization in the United States and approval in Japan for treatment of patients with severe coronavirus disease 2019 (COVID‐19). This report describes two phase I studies that evaluated the safety and pharmacokinetics (PKs) of single escalating and multiple i.v. doses of RDV (solution or lyophilized formulation) in healthy subjects. Lyophilized formulation was evaluated for potential future use in clinical trials due to its storage stability in resource‐limited settings. All adverse events were grade 1 or 2 in severity. Overall, RDV exhibited a linear profile following single‐dose i.v. administration over 2 hours of RDV solution formulation across the dose range of 3–225 mg. Both lyophilized and solution formulations provided comparable PK parameters. High intracellular concentrations of the active triphosphate (~ 220‐fold to 370‐fold higher than the in vitro half‐maximal effective concentration against SARS‐CoV‐2 clinical isolate) were achieved following infusion of 75 mg or 150 mg lyophilized formulation over 30 minutes or 2 hours. Following multiple‐doses of RDV 150 mg once daily for 7 or 14 days, RDV exhibited a PK profile similar to single‐dose administration. Metabolite GS‐441524 accumulated ~ 1.9‐fold after daily dosing. Overall, RDV exhibited favorable safety and PK profiles that supported once‐daily dosing.
Primary cutaneous Ewing sarcoma with diffuse S100/SOX10 positivity and pseudoalveolar pattern: An extraordinarily rare case highlighting a potential pitfall with significant repercussions
Authors: Evangelou Zoi , Zhang Linsheng , Tafe Laura J. , Azzouz Lubna , Grada Zakaria , Linos Konstantinos
Published: June 2020

Primary cutaneous Ewing sarcoma is a very rare entity with less than 100 cases reported in the literature, sharing the same morphological and immunohistochemical characteristics as their osseous counterparts. Herein, to the best of our knowledge, we report the first case in English literature of a molecularly confirmed Ewing sarcoma with diffuse and strong SOX10 immunoreactivity. This exceedingly rare immunohistochemical finding along with the rarity of this tumor could easily lead to a misdiagnosis with significant repercussions. Our case highlights the difficulty in diagnosing primary cutaneous Ewing sarcoma as well as the pivotal role molecular diagnostics can play in specific scenarios.
Familiar words can serve as a semantic seed for syntactic bootstrapping
Authors: Babineau Mireille , de Carvalho Alex , Trueswell John , Christophe Anne
Published: June 2020

Young children can exploit the syntactic context of a novel word to narrow down its probable meaning. But how do they learn which contexts are linked to which semantic features in the first place? We investigate if 3‐ to 4‐year‐old children (n = 60) can learn about a syntactic context from tracking its use with only a few familiar words. After watching a 5‐min training video in which a novel function word (i.e., ‘ko’) replaced either personal pronouns or articles, children were able to infer semantic properties for novel words co‐occurring with the newly learned function word (i.e., objects vs. actions). These findings implicate a mechanism by which a distributional analysis, associated with a small vocabulary of known words, could be sufficient to identify some properties associated with specific syntactic contexts.
Progressive resistance training for adolescents with cerebral palsy: the STAR randomized controlled trial
Authors: Ryan Jennifer M , Lavelle Grace , Theis Nicola , Noorkoiv Marika , Kilbride Cherry , Korff Thomas , Baltzopoulos Vasilios , Shortland Adam , Levin Wendy ,   The Star Trial Team
Published: June 2020

Aim

To evaluate the effect of progressive resistance training of the ankle plantarflexors on gait efficiency, activity, and participation in adolescents with cerebral palsy (CP).

Method

Sixty‐four adolescents (10–19y; 27 females, 37 males; Gross Motor Function Classification System [GMFCS] levels I–III) were randomized to 30 sessions of resistance training (10 supervised and 20 unsupervised home sessions) over 10 weeks or usual care. The primary outcome was gait efficiency indicated by net nondimensional oxygen cost (NNcost). Secondary outcomes included physical activity, gross motor function, participation, muscle strength, muscle and tendon size, and muscle and tendon stiffness. Analysis was intention‐to‐treat.

Results

Median attendance at the 10 supervised sessions was 80% (range 40–100%). There was no between‐group difference in NNcost at 10 (mean difference: 0.02, 95% confidence interval [CI] –0.07 to 0.11, p=0.696) or 22 weeks (mean difference: –0.08, 95% CI –0.18 to 0.03, p=0.158). There was also no evidence of between‐group differences in secondary outcomes at 10 or 22 weeks. There were 123 adverse events reported by 27 participants in the resistance training group.

Interpretation

We found that 10 supervised sessions and 20 home sessions of progressive resistance training of the ankle plantarflexors did not improve gait efficiency, muscle strength, activity, participation, or any biomechanical outcome among adolescents with CP.

What this paper adds

Thirty sessions of progressive resistance training of the ankle plantarflexors over 10 weeks did not improve gait efficiency among ambulatory adolescents with cerebral palsy.

Resistance training did not improve muscle strength, activity, or participation.

Ninety percent of participants experienced an adverse event.

Most adverse events were expected and no serious adverse events were reported.
Adiposity and physical activity are related to heart rate variability: the African‐PREDICT study
Authors: Köchli Sabrina , Schutte Aletta E. , Kruger Ruan
Published: June 2020

Background

Physical inactivity contributes significantly to the development of obesity‐related cardiovascular disease. Adiposity may lead to reduced heart rate variability (HRV), whereas increased physical activity (PA) has the potential to improve autonomic activity. These associations remain largely unexplored in healthy individuals. We therefore investigated whether adiposity and physical activity (PA) are associated with reduced heart rate variability (HRV) in young adults.

Materials and methods

We examined 403 black and 461 white healthy adults (aged 20‐30 years) for HRV, including standard deviation of normal RR intervals (SDNN) and root mean square of successive differences (RMSSD). We measured adiposity, PA levels and blood pressure (BP). Body mass index (BMI) of ≥ 30 kg/m2 indicated obesity.

Results

Participants with obesity had lower mean HRV than normal weight (SDNN [95% CI]; 138 [131‐145]s vs 161 [158‐165]ms), where those with the highest PA had higher SDNN (164 [160‐169]ms) and RMSSD (51 [49‐53]ms) than the least active individuals (150 [146‐155]s) and 46 [44‐48]ms)(all P < .01). BMI, waist circumference and body fat associated with lower SDNN (P < .001). With each unit increase of vigorous PA, a favourable higher RMSSD was found (P < .05). One unit increase in diastolic BP was associated with decreased SDNN and RMSSD (P < .001). These findings remained significant in multivariable‐adjusted analyses.

Conclusions

Adiposity and low PA associated independently with depressed autonomic activity in young healthy adults. Sympathovagal imbalance seems to already contribute to elevated diastolic BP at young ages. Our study supports population‐based prevention programmes in young adults, improving PA and healthy diet, to curb the development of cardiovascular disease.
Association between diabetes mellitus and lung cancer: Meta‐analysis
Authors: Yi Zi‐Han , Luther Yannick , Xiong Guo‐Hang , Ni Yue‐Li , Yun Fang , Chen Jing , Yang Zhe , Zhang Qiao , Kuang Ying‐Min , Zhu Yue‐Chun
Published: June 2020

Background

This study aimed to summarize the association between diabetes mellitus (DM) and the incidence of lung cancer using a meta‐analysis of cohort studies.

Materials and methods

We systematically searched PubMed, Embase and the Cochrane Library to identify potential cohort studies. Relative risk (RR) was used to calculate the association between DM and the risk of lung cancer. Subgroup analysis, sensitivity analysis and test for publication bias were performed. Twenty cohort studies were selected.

Results

The participants with DM showed little or no significant effect on the risk of lung cancer (RR: 1.10; 95% CI: 0.99‐1.23; P = .087). DM was not associated with the risk of lung cancer in men (RR: 1.11; 95%CI: 0.92‐1.35; P = .270), but a significant association was observed in women (RR: 1.18; 95%CI: 1.10‐1.28; P < .001). Subgroup analysis suggested that smoker status was confounding variables that could bias the relationship between DM and the incidence of lung cancer.

Conclusions

This meta‐analysis suggests that DM has no significant impact on the incidence of lung cancer in men but has a harmful effect on women.
Fabrication method to maintain mouthguard thickness regardless of the model angle
Authors: Takahashi Mutsumi , Bando Yogetsu
Published: June 2020

Background/Aim

The safety and effectiveness of mouthguards depend on the sheet material and thickness. The aim of this study was to investigate the fabrication method for a mouthguard with appropriate thickness using a single sheet regardless of the model angle.

Materials and methods

Mouthguards were thermoformed using 4.0 mm thick ethylene vinyl acetate sheets and a vacuum forming machine. The working models were three hard plaster models trimmed so that the angle of the anterior teeth to the model base was 90°, 100°, and 110°. The model position was 40 mm from the front of the forming unit. The sheet was softened until it sagged 15 mm, after which the sheet frame was lowered to cover the model. Next, the vacuum was turned on and held for 30 seconds for the control. Under the forming conditions in which the model position (MP) was moved, after the model was covered with the sheet, a scissors handle was positioned at the rear of the model and used to push it forward 20 mm, and then, the vacuum switch was turned on for 30 seconds. Six specimens were formed for each condition. Mouthguard thickness after formation was measured using a specialized caliper. The differences in mouthguard thickness due to forming conditions and model angle were analyzed.

Results

The MP was significantly thicker than the control in each model (P < .01). The mouthguard thickness tended to decrease as the model angle increased. The average thickness of the labial surface in the MP was 3 mm or more and was not affected by the model angle.

Conclusions

This study suggested that the fabrication method in which moving the model forward by 20 mm just before formation could produce a mouthguard with approximately 3 mm thickness on the labial side with a single sheet regardless of the model angle.
Transition to dental practice: Newly graduated dentists' views of being successful in dental practice
Authors: Leadbeatter Delyse , Madden Jacalyn , Ross Benjamin , Russell Elara
Published: June 2020

Background

The transition of dental graduates to the workforce is of interest to dental educators. The ways dentists think about success and successful practice tend to be tied to business parameters, patient flow and job satisfaction. These measures are narrow, however, and there is scant literature exploring success in ways that connects with professional identity formation. This study aims to add to scholarly understanding about the experiences of newly graduated dentists by asking: What is the variation in the ways new graduate dentists experience success in practice?

Methods

The qualitative methodology used in this study is phenomenography. Phenomenography studies the variation in the way a group of people experience a common phenomenon. In‐depth, semi‐structured interviews were conducted with 12 new dentists who had graduated from the University of Sydney.

Results

Five increasingly sophisticated, qualitatively distinct categories of description were identified: the day runs smoothly, keeping busy, providing quality patient care, generating personal meaning and having a sense of connection and belonging.

Conclusions

This study gives insights into the complex ways newly graduated dentists think about successful dentistry. It broadens our view of successful practice beyond commercial aspects to include practitioner identity. Importantly, sense of responsibility, the practice environment and mentorship emerge as key players in this transitional career stage.
Accountability and (mis)trust in education systems: Private supplementary tutoring and the ineffectiveness of regulation in Myanmar
Authors: Liu Junyan , Bray Mark
Published: June 2020

Private supplementary tutoring, widely known as shadow education, has been viewed by many families around the world as a necessary complement to schooling. The analysis presented draws on questionnaire and interview data from secondary school students, teachers, principals, parents and other stakeholders in Myanmar. Parents displayed institutional mistrust in their perception of the inadequacy of public schooling to meet their children's needs. Organisational and interpersonal mistrust were also evident. The matters of mistrust relate to the theme of accountability in education, which requires systems for regulation and monitoring. The regulations on tutoring in Myanmar were widely ignored and were arguably worse than useless. The article is grounded in the context of Myanmar but has considerable insights for the wider literature.
Inner retinal layer thinning in radiologically isolated syndrome predicts conversion to multiple sclerosis
Authors: Aly L. , Havla J. , Lepennetier G. , Andlauer T. F. M. , Sie C. , Strauß E.‐M. , Hoshi M.‐M. , Kümpfel T. , Hiltensperger M. , Mitsdoerffer M. , Mühlau M. , Zimmer C. , Hemmer B. , Korn T. , Knier B.
Published: June 2020

Background and purpose

Individuals with radiologically isolated syndrome (RIS) are at increased risk of converting to multiple sclerosis (MS). Early identification of later converters is crucial for optimal treatment decisions. The purpose of this study was to assess the predictive potential of optical coherence tomography (OCT) measures in individuals with RIS regarding conversion to MS.

Methods

This prospective observational cohort study included 36 individuals with RIS and 36 healthy controls recruited from two German MS centers. All individuals received baseline OCT and clinical examination and were longitudinally followed over up to 6 years. The primary outcome measure was the conversion to MS.

Results

During clinical follow‐up of 46 (26–58) months (median, 25%–75% interquartile range), eight individuals with RIS converted to MS. Individuals converting to MS showed a thinning of the peripapillary retinal nerve fiber layer (pRNFL) and the common ganglion cell and inner plexiform layer (GCIP) at baseline and during follow‐up. Individuals with a pRNFL of 99 µm or lower or a GCIP of 1.99 mm3 or lower were at a 7.5‐ and 8.0‐fold risk for MS conversion, respectively, compared to individuals with higher measures. After correction for other known risk factors, Cox proportional hazards regression revealed a hazard ratio of 1.08 for conversion to MS for each 1 µm decline in pRNFL.

Conclusions

Reduction of the pRNFL might be a novel and independent risk factor for conversion to MS in individuals with RIS. OCT might be useful for risk stratification and therapeutic decision‐making in individuals with RIS.
Interictal intracranial electroencephalography for predicting surgical success: The importance of space and time
Authors: Wang Yujiang , Sinha Nishant , Schroeder Gabrielle M. , Ramaraju Sriharsha , McEvoy Andrew W. , Miserocchi Anna , de Tisi Jane , Chowdhury Fahmida A. , Diehl Beate , Duncan John S. , Taylor Peter N.
Published: June 2020

Objective

Predicting postoperative seizure freedom using functional correlation networks derived from interictal intracranial electroencephalography (EEG) has shown some success. However, there are important challenges to consider: (1) electrodes physically closer to each other naturally tend to be more correlated, causing a spatial bias; (2) implantation location and number of electrodes differ between patients, making cross‐subject comparisons difficult; and (3) functional correlation networks can vary over time but are currently assumed to be static.

Methods

In this study, we address these three challenges using intracranial EEG data from 55 patients with intractable focal epilepsy. Patients additionally underwent preoperative magnetic resonance imaging (MRI), intraoperative computed tomography, and postoperative MRI, allowing accurate localization of electrodes and delineation of the removed tissue.

Results

We show that normalizing for spatial proximity between nearby electrodes improves prediction of postsurgery seizure outcomes. Moreover, patients with more extensive electrode coverage were more likely to have their outcome predicted correctly (area under the receiver operating characteristic curve > 0.9, P « 0.05) but not necessarily more likely to have a better outcome. Finally, our predictions are robust regardless of the time segment analyzed.

Significance

Future studies should account for the spatial proximity of electrodes in functional network construction to improve prediction of postsurgical seizure outcomes. Greater coverage of both removed and spared tissue allows for predictions with higher accuracy.
Orbitofrontal involvement in a neuroCOVID‐19 patient
Authors: Le Guennec Loïc , Devianne Julia , Jalin Laurence , Cao Albert , Galanaud Damien , Navarro Vincent , Boutolleau David , Rohaut Benjamin , Weiss Nicolas , Demeret Sophie
Published: June 2020

Neurological manifestations of coronavirus disease 19 (COVID‐19) such as encephalitis and seizures have been reported increasingly, but our understanding of COVID‐19‐related brain injury is still limited. Herein we describe prefrontal involvement in a patient with COVID‐19 who presented prior anosmia, raising the question of a potential trans‐olfactory bulb brain invasion.
Disentangling types of liquidity and testing limits‐to‐arbitrage theories in the CDS–bond basis
Authors: Augustin Patrick , Schnitzler Jan
Published: June 2020

We disentangle asset‐specific, market, and funding liquidity in the CDS–bond basis outside and during the 2007–9 global financial crisis. Our findings stress the importance of separating different types of liquidity, since all three measures have independently negative impacts on the basis. Funding liquidity emerges as the economically most important liquidity metric. While asset‐specific liquidity is cross‐correlated in both the cash and derivative markets, funding and market liquidity only matter for the cash market. We exploit the decomposition of the basis to test predictions of limits‐to‐arbitrage theories. We find strong evidence in favor of margin‐based asset pricing and flight‐to‐quality effects.
Relational Lockdown and Relational Trauma† in the Time of Coronavirus: A Reflection from a UK Family Therapist
Authors: Rivett Mark
Published: June 2020

Like a meteor hitting the earth’s surface, 44, 131‡ unexpected deaths have shaken, disturbed, and saddened the core of our nation. This reflection considers the consequences of the coronavirus crisis in the UK with particular reference to the impact on families and on the practice of family therapists. The perspective presented can only be partial because of the fast‐changing situation and the limited access to alternative perspectives that are available during this period of relational lockdown. The author provides a systemic understanding of what has happened and what is happening.
Environmental, social and governance reporting in annual reports: A textual analysis
Authors: Baier Philipp , Berninger Marc , Kiesel Florian
Published: June 2020

Considering environmental, social, and governance (ESG) factors becomes increasingly important for companies and investors. However, “ESG” is not clearly defined so far and, therefore, it is difficult to measure the ESG activity of companies. We analyze the extent and changes in 10‐K reports and proxy statements on ESG, using a textual analysis and creating an ESG dictionary. The results show an average of 4.0 % ESG words on total words in the reports. The ESG word list with 482 items can be used to quantitatively examine the extent of ESG reporting, which will be helpful especially for SRI investors. Our classification of 40 subcategories allows a highly granular analysis of different ESG related aspects. Moreover, indications for a relation between changes in reporting and real events, especially negative media presence, are detected. Regulatory bodies have to be aware of the use of such words and how they are used.
A Visual Analytics System for Space–Time Dynamics of Regional Income Distributions Utilizing Animated Flow Maps and Rank‐based Markov Chains
Authors: Rey Sergio , Han Su Yeon , Kang Wei , Knaap Elijah , Cortes Renan Xavier
Published: June 2020

Regional income convergence and divergence has been an active field of research for more than 20 years, and research papers in this field are still being produced at a prodigious rate. Despite their importance for the study of dynamics of income distribution, interactive visualization tools revealing spatiotemporal dimensions of the income data have been sparsely developed. This study introduces a visual analytics system for the space–time analysis of income dynamics. We use state‐level US income data from 1929 to 2009 to demonstrate the visual analytics system and its utility for exploring similar data. The system consists of two modules, visualization and analytics. The visualization module, a Web‐based front‐end called Rank‐Path Visualizer (RPV), draws inspiration from the cartographic technique of flow mapping, originally developed by Tobler and embodied in his canonical Flow Mapper application.
Characterizing functionally integrated regions in the Central Yangtze River Megaregion from a city‐network perspective
Authors: Gao Peng , He Dan , Sun Zhijing , Ning Yuemin
Published: June 2020

The past decade has witnessed a blossoming of megaregional plans throughout China. However, it is still unclear whether megaregions delineated in these plans are based on a functionally integrated foundation or imagined by the government. This study takes the Central Yangtze River Megaregion (CYRM)—a cross‐jurisdictional megaregion planned as a leading regional integration platform in Central China—as a case to examine the mismatch between the governmentally designated regions and functionally integrated regions. Specifically, this research employs the community detection algorithm to identify functionally integrated regions within the CYRM based on producer services networks, then associate the formation of these network‐based regions with territorial factors. The results show that the integration of identified first‐tier functional regions is subject to the provincial administrative divisions; whereas, the locally planned regions comply with the second‐tier functionally integrated regions spatially. Besides, the regression results indicate that the territorial factors are significantly associated with the above spatial patterns. Hence, the region‐making practices initiated by the local governments rather than the central government, are more consistent with the conditions of regional economic development.
Transgender labour market outcomes: Evidence from the United States
Authors: Ciprikis Klavs , Cassells Damien , Berrill Jenny
Published: June 2020

Alternative labour market outcomes for men and women have been studied extensively in past literature. However, existing studies fail to directly compare labour market differences between transgender and non‐transgender people. We utilize data from the 2015 Behavioral Risk Factor Surveillance System in the United States to examine employment and wage differentials between transgender persons and non‐transgender people using the Fairlie decomposition method of 2005. Our findings suggest that transgender people are less likely than non‐transgender people to be employed, and are more likely than non‐transgender people to receive lower wages. While some of the difference in employment and wage gaps is explained by sociodemographic characteristics, part of the gap remains unexplained. Approximately 64 per cent of the employment differential and 43 per cent of the wage differential is unexplained and may be due to discrimination. Therefore, our findings highlight the importance of appropriate anti‐discrimination policy.
Management of pregnancy in women with factor VII deficiency: A case series
Authors: Lee Eun‐Ju , Burey Laura , Abramovitz Sharon , Desancho Maria T
Published: June 2020

Introduction

Inherited factor VII deficiency is the most common autosomal recessive inherited bleeding disorder, with an estimated incidence of one per 500 000 cases in the general population. Bleeding manifestations correlate poorly with circulating FVII levels. During pregnancy, increases in FVII levels can occur in women with mild‐moderate FVII deficiencies but not in those with severe deficiency.

Aim

We present five pregnant patients with FVII deficiency and describe the management during their pregnancies and peripartum periods.

Methods

Retrospective analysis of six pregnancies in five women with FVII deficiency followed during pregnancy and delivery at an academic medical centre between January 2013 and December 2019.

Results

Of the five patients, two had severe, one with moderate and two with mild FVII deficiency. Early postpartum haemorrhage (PPH) occurred in two patients. One of the two severe FVII‐deficient patients had PPH with a laceration at delivery despite replacement therapy with recombinant factor VII. The other PPH occurred in a patient with mild FVII deficiency who delivered twins by caesarean section under general anaesthesia. Neuraxial anaesthesia was utilized in only one woman with mild deficiency whose FVII level normalized at the end of the pregnancy.

Conclusions

Management of delivery for women with FVII deficiency should be addressed on a case‐by‐case basis at centres with expertise in rare bleeding disorders, maternal foetal medicine and obstetric anaesthesiology. These management discussions should factor the patient's bleeding history, third trimester PT, FVII level, multiple gestation and mode of delivery.
A Randomized Sham‐Controlled Cross‐Over Study on the Short‐Term Effect of Non‐Invasive Cervical Vagus Nerve Stimulation on Spinal and Supraspinal Nociception in Healthy Subjects
Authors: Alt Laura K. , Wach Katharina , Liebler Eric J. , Straube Andreas , Ruscheweyh Ruth
Published: June 2020

Objective

The aim of the present study was to test the effects of vagus nerve stimulation (VNS) on the descending pain inhibition, quantified by the nociceptive flexor (RIII) reflex and the conditioned pain modulation (CPM) paradigm, and on supraspinal nociceptive responses, assessed by pain intensity and unpleasantness ratings and late somatosensory evoked potentials (SEPs), in healthy subjects.

Background

Non‐invasive vagus nerve stimulation (nVNS) showed promising effects on headache and pain treatment. Underlying mechanisms are only incompletely understood but may include the activation of the descending pain inhibitory system and/or the modification of emotional responses to pain.

Methods

Twenty‐seven adult, healthy, and pain‐free subjects participated in this double‐blind cross‐over study conducted at a university research center. They received 4 minutes of cervical nVNS or sham stimulation in randomized order. RIII reflexes, pain ratings, and SEPs were assessed before, during, and 5, 15, 30, and 60 minutes after nVNS/sham stimulation, followed by CPM testing. The primary outcome was the nVNS effect on the RIII reflex size. Three subjects were excluded after the preparatory session (before randomization), 1 subject was excluded after outlier analysis, leaving 23 for analysis.

Results

RIII reflex areas were 917.1 ± 563.8 µV × ms (mean ± SD) before, 952.4 ± 467.4 µV × ms during and 929.2 ± 484.0 µV × ms immediately after nVNS and 858.4 ± 489.2 µV × ms before, 913.9 ± 539.7 µV × ms during and 862.4 ± 476.0 µV × ms after sham stimulation, revealing no differences between the immediate effects of nVNS and sham stimulation (F [3,66] = 0.67, P = .574). There also were no effects of nVNS over sham on RIII reflex areas up to 60 minutes after nVNS (F [1.7,37.4] = 1.29, P = .283). Similarly, there was no statistically significant effect of nVNS on pain intensity ratings and thresholds, RIII reflex thresholds, late SEP amplitudes, and the CPM effect, compared to sham. Pain unpleasantness ratings statistically significantly decreased from 4.4 ± 2.4 (NRS 0‐10) to 4.1 ± 2.5 during nVNS compared to sham stimulation (F [1,22] = 8.74, P = .007), but there were no longer lasting effects (5‐60 minutes after stimulation).

Conclusions

The present study does not support an acute effect of nVNS on descending pain inhibition, pain intensity perception or supraspinal nociception in healthy adults. However, there was a small effect on pain unpleasantness during nVNS, suggesting that nVNS may preferentially act on affective, not somatosensory pain components.
Congenital mesoblastic nephroma is characterised by kinase mutations including EGFR internal tandem duplications, the ETV6–NTRK3 fusion, and the rare KLHL7–BRAF fusion
Authors: Zhao Manli , Yin Minzhi , Kuick Chik Hong , Chen Huiyi , Aw Sze Jet , Merchant Khurshid , Ng Eileen Hui Qi , Gunaratne Sandini , Loh Amos Hong Pheng , Gu Weizhong , Tang Hongfeng , Chang Kenneth Tou En
Published: June 2020

Aims

Congenital mesoblastic nephroma (CMN) is histologically classified into classic, cellular and mixed subtypes. The aims of this study were to characterise the clinical, pathological and molecular features of a series of CMNs, and to determine the utility of pan‐Trk and epidermal growth factor receptor (EGFR) immunohistochemistry as surrogate markers for NTRK gene fusions and EGFR internal tandem duplications (ITDs).

Methods and results

Twenty‐two archival CMN cases (12 classic, five cellular, and five mixed) were tested for the ETV6–NTRK3 fusion and EGFR ITD transcripts by the use of reverse transcriptase polymerase chain reaction (PCR), and next‐generation sequencing‐based anchored multiplex PCR. All 12 classic CMNs had EGFR ITD. Of the five cellular CMNs, four had the ETV6–NTRK3 fusion and one had the KLHL7–BRAF fusion. Of the five mixed CMNs, four had EGFR ITD, and one had the ETV6–NTRK3 fusion. Pan‐Trk immunoreactivity was 100% sensitive and 94.1% specific for the presence of NTRK rearrangement. However, EGFR staining was only 62.5% sensitive and 33.3% specific for EGFR ITD.

Conclusions

EGFR ITD is a consistent genetic event in classic CMN. A majority of cellular CMNs have the ETV6–NTRK3 fusion. Rare cellular CMNs may harbour non‐canonical mutations such as the KLHL7–BRAF fusion, which was found in one case. Mixed CMNs may have either EGFR ITD or the ETV6–NTRK3 fusion. Pan‐Trk immunohistochemistry is a sensitive, albeit not perfectly specific, marker for NTRK rearrangement. EGFR immunohistochemistry is not helpful as a marker of EGFR ITD.
Clinical and histological features of secondary carcinomas in gastrointestinal tract biopsies
Authors: Rosty Christophe , Pai Rish K , Graham Rondell P
Published: June 2020

Background

Secondary carcinoma involving the gastrointestinal (GI) tract is an uncommon finding in biopsy specimens. The diagnosis can be challenging for tumours mimicking a primary carcinoma and when the clinical context is unknown.

Methods and results

A multicentre retrospective study was performed to evaluate the clinical and histological features of a series of secondary carcinoma in GI biopsies. A total of 197 cases from 190 patients (median age = 67 years; 57% females) were reviewed. In 16% of patients, the primary carcinoma was unknown. Most lesions presented endoscopically as mucosal or submucosal masses (58%). In 13%, the endoscopy was non‐suspicious for malignancy. The most common tumours were carcinomas of the breast (38%), kidney (13%), lung (12%), prostate (8%) and ovary (7%). The sites of involvement were the stomach (34%), colon (27%), rectum (18%), duodenum (13%), oesophagus (5%), jejunum (3%) and anus (0.5%). Histological patterns of infiltration were mucosal (76%), submucosal (41%), lymphatic (14%), and epithelial colonisation (8%). Submucosal infiltration was found significantly more frequently in carcinomas of the prostate (67%) and lung (62%), compared with carcinomas of the ovary (27%) and breast (23%). Histological obstructive changes were observed in 36% of all cases, with the highest rate in prostate carcinoma (53%) and the lowest rate in kidney carcinoma (8%).

Conclusion

Awareness of the main clinical and histological patterns of secondary carcinomas in GI tract biopsies may help pathologists to raise the possibility of this uncommon diagnosis and confirm it with the judicious use of immunohistochemistry.
Treatment outcomes of integrase inhibitors, boosted protease inhibitors and nonnucleoside reverse transcriptase inhibitors in antiretroviral‐naïve persons starting treatment
Authors: Mocroft A , Neesgard B , Zangerle R , Rieger A , Castagna A , Spagnuolo V , Antinori A , Lampe FC , Youle M , Vehreschild JJ , Mussini C , Borghi V , Begovac J , Duvivier C , Gunthard HF , Rauch A , Tiraboschi J , Chkhartishvili N , Bolokadze N , Wit F , Wasmuth JC , De Wit S , Necsoi C , Pradier C , Svedhem V , Stephan C , Petoumenos K , Garges H , Rogatto F , Peters L , Ryom L ,   the RESPOND study group
Published: June 2020

Objectives

Although outcomes of antiretroviral therapy (ART) have been evaluated in randomized controlled trials, experiences from subpopulations defined by age, CD4 count or viral load (VL) in heterogeneous real‐world settings are limited.

Methods

The study design was an international multicohort collaboration. Logistic regression was used to compare virological and immunological outcomes at 12 ± 3 months after starting ART with an integrase strand transfer inhibitor (INSTI), contemporary nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI/b) with two nucleos(t)ides after 1 January 2012. The composite treatment outcome (cTO) defined success as VL < 200 HIV‐1 RNA copies/mL with no regimen change and no AIDS/death events. Immunological success was defined as a CD4 count > 750 cells/μL or a 33% increase where the baseline CD4 count was ≥ 500 cells/μL. Poisson regression compared clinical failures (AIDS/death ≥ 14 days after starting ART). Interactions between ART class and age, CD4 count, and VL were determined for each endpoint.

Results

Of 5198 ART‐naïve persons in the International Cohort Consortium of Infectious Diseases (RESPOND), 45.4% started INSTIs, 26.0% PI/b and 28.7% NNRTIs; 880 (17.4%) were aged > 50 years, 2539 (49.4%) had CD4 counts < 350 cells/μL and 1891 (36.8%) had VL > 100 000 copies/mL. Differences in virological and immunological success and clinical failure among ART classes were similar across age groups (≤ 40, 40–50 and > 50 years), CD4 count categories (≤ 350 vs. > 350 cells/μL) and VL categories at ART initiation (≤ 100 000 vs. > 100 000 copies/mL), with all investigated interactions being nonsignificant (P > 0.05).

Conclusions

Differences among ART classes in virological, immunological and clinical outcomes in ART‐naïve participants were consistent irrespective of age, immune suppression or VL at ART initiation. While confounding by indication cannot be excluded, this provides reassuring evidence that such subpopulations will equally benefit from contemporary ART.