bluuebunny/crossref_metadata_2025 huggingface dataset:
Programmed cell death‐1 (PD‐1) and programmed death‐ligand 1 (PD‐L1) expression in PD‐1 inhibitor‐associated colitis and its mimics
Authors: Cassol Clarissa A , Owen Dwight , Kendra Kari , Braga Juarez R , Frankel Wendy L , Arnold Christina A
Published: April 2020

Aims

Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of advanced malignancies by boosting immune‐mediated destruction of neoplastic cells, but are associated with side effects stemming from generalised immune system activation against normal tissues. Checkpoint ligand expression in non‐tumoral cells of tissues affected by immune‐related adverse effects has been described in ICI‐associated hypophysitis, myocarditis, and acute interstitial nephritis. We aimed to investigate the tissue expression of the immune checkpoint receptor programmed cell death‐1 (PD‐1) and its ligand, programmed death‐ligand 1 (PD‐L1), in PD‐1 inhibitor‐associated colitis (PD1i colitis).

Methods and results

PD‐1 and PD‐L1 immunohistochemical expression levels were analysed in 15 cases of PD1i colitis and potential mimics—infectious colitis and inflammatory bowel disease (IBD). Increased epithelial expression of PD‐L1 was observed in PD1i colitis as compared with normal colon and infectious colitis, but the expression level was lower than that in IBD. Conversely, PD‐1 expression in inflammatory cells was higher in infectious colitis, intermediate in IBD, and minimal or absent in normal colon and in patients receiving PD‐1 inhibitors.

Conclusions

Although our results do not justify the use of PD‐L1 as a discriminatory marker of PD1i colitis against other entities within the differential diagnosis, they support the concept that PD1i colitis and IBD have similar pathogenetic mechanisms. They also highlight the fact that PD‐L1 epithelial overexpression is a commonly used mechanism of the gastrointestinal tract mucosa to protect itself from inflammatory‐mediated damage resulting from different aetiologies, which probably underpins the high incidence of gastrointestinal immune‐related adverse effects in patients receiving ICI therapies, in whom this mechanism is disrupted.
Effect of surface cleaning prior to chemical strengthening process of glass
Authors: Atılgan Semin , Özben Nahide , Sökmen İlkay , Wondraczek Lothar , Akman Suleyman
Published: April 2020

This work focuses on the effect of surface cleaning treatments of soda‐lime‐silicate float glasses before chemical strengthening where a compressive stress layer is introduced via ion exchange. As‐received and cleaned glass surfaces were subjected to two different treatments using demineralized water and acidic solutions were subjected to ion exchange in a molten KNO3 bath for 8 hours at 450°C. Precleaning treatment leads to a relative enhancement of the potassium surface concentration following chemical strengthening as compared to the uncleaned samples, also reflecting in altered surface stress profiles and case depth. These observations provide guidance for optimal pretreatment conditions of glass for chemical strengthening. Appropriate cleaning treatments can result in higher achievable fracture loads of subsequently chemically tempered glasses in ring‐on‐ring biaxial bending tests.
The value of 18F‐FDG PET/CT in diagnosing and localising deep sternal wound infection to guide surgical debridement
Authors: Liu Siwei , Zhang Jie , Yin Hongyan , Pang Lifang , Wu Bing , Shi Hongcheng
Published: April 2020

Deep sternal wound infection (DSWI) is a severe complication in patients after open heart surgery (OHS). But there is a lack of appropriate imaging tool to detect the infection sites, which may lead to incomplete debridement. The present study aims to investigate the value of 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (18F‐FDG PET/CT) in comparison with CT scan in diagnosing and localising DSWI. A total of 102 patients with DSWI after OHS were retrospectively collected from January 2012 to December 2017 in our hospital. All the patients had surgical debridements for DSWI with pretreatment imaging of either 18F‐FDG PET/CT or CT scan. The sensitivity, specificity, and accuracy of localising infection sites were compared between PET/CT and CT groups, with surgical, microbiological, and histopathological findings as the gold standard. The length of hospital stays and the rate of recurrence were also compared. Ten patients in the PET/CT group had a follow‐up PET/CT scan after debridement, and the correlations between the changes of PET/CT findings and surgical outcomes were analysed. 18F‐FDG PET/CT is more accurate than CT in diagnosing and localising DSWI after OHS, which leads to a more successful surgical debridement with a lower rate of recurrence and a shorter length of hospital stay. In addition, follow‐up PET/CT after debridement could evaluate the treatment effect.
Down‐regulated lncRNA SBF2‐AS1 in M2 macrophage‐derived exosomes elevates miR‐122‐5p to restrict XIAP, thereby limiting pancreatic cancer development
Authors: Yin Zi , Zhou Yu , Ma Tingting , Chen Sheng , Shi Ning , Zou Yiping , Hou Baohua , Zhang Chuanzhao
Published: April 2020

Evidence has indicated that M2 macrophages promote the progression of cancers, but few focus on the ability of M2 macrophage‐derived exosomes in pancreatic cancer (PC). This study aims to explore how M2 macrophages affect malignant phenotypes of PC through regulating long non‐coding RNA SET‐binding factor 2 antisense RNA 1 (lncRNA SBF2‐AS1)/microRNA‐122‐5p (miR‐122‐5p)/X‐linked inhibitor of apoptosis protein (XIAP) axis. THP‐1 cells were transformed into M1 macrophages by lipopolysaccharide and interferon‐γ treatment, and into M2 macrophages after interleukin‐4 treatment. The PANC‐1 PC cell line with the largest lncRNA SBF2‐AS1 expression was selected, and M2 macrophage‐derived exosomes were isolated and identified. A number of assays were applied for the examination of lncRNA SBF2‐AS1 expression, PC cell biological functions and subcellular localization of lncRNA SBF2‐AS1. XIAP expression was detected, along with the interaction among lncRNA SBF2‐AS1, miR‐122‐5p and XIAP. M2 macrophage exosomal lncRNA SBF2‐AS1 expression's effects on the tumorigenic ability of PANC‐1 cells in nude mice were also investigated. M2 macrophage‐derived exosomes promoted progression of PC cells. Overexpressed lncRNA SBF2‐AS1 promoted progression of PC cells. LncRNA SBF2‐AS1 was found to act as a competing endogenous RNA to repress miR‐122‐5p and up‐regulate XIAP. Constrained lncRNA SBF2‐AS1 in M2 macrophage‐derived exosomes contributed to restraining tumorigenic ability of PC cells. Collectively, our study reveals that constrained lncRNA SBF2‐AS1 in M2 macrophage‐derived exosomes increases miR‐122‐5p expression to restrain XIAP expression, which further inhibits PC progression.
Cold intolerance and neuropathic pain after peripheral nerve injury in upper extremity
Authors: Magistroni Ernesta , Parodi Giulia , Fop Fabrizio , Battiston Bruno , Dahlin Lars B.
Published: April 2020

Cold intolerance and pain can be a substantial problem in patients with peripheral nerve injury. We aimed at investigating the relationships among sensory recovery, cold intolerance, and neuropathic pain in patients affected by upper limb peripheral nerve injury (Sunderland type V) treated with microsurgical repair, followed by early sensory re‐education. In a cross‐sectional clinical study, 100 patients (male/female 81/19; age 40.5 ± 14.8 years and follow‐up 17 ± 5 months, mean ± SD), with microsurgical nerve repair and reconstruction in the upper extremity and subsequent early sensory re‐education, were evaluated, using Cold Intolerance Symptoms Severity questionnaire‐Italian version (CISS‐it, cut‐off pathology >30/100 points), CISS questionnaire‐12 item version (CISS‐12, 0‐46 points‐grouping: healthy that means no cold intolerance [0‐14], mild [15‐24], moderate [25‐34], severe [35‐42], very severe [43‐46] cold intolerance), probability of neuropathic pain (DouleurNeuropathique‐4; [DN4] 4/10), deep and superficial sensibility, tactile threshold (monofilaments), and two‐point discrimination (cutoff S2; Medical Research Council scale for sensory function; [MRC‐scale]). A high CISS score is associated with possible neuropathic pain (DN4 ≥ 4). Both a low CISS‐it score (ie, < 30) and DN4 < 4 is associated with good sensory recovery (MRC ≥ 2). In conclusion patients affected by upper limb peripheral nerve injuries with higher CISS scores more often suffer from cold intolerance and neuropathic pain, and the better their sensory recovery is, the less likely they are to suffer from cold intolerance and neuropathic pain.
Dynamic tongue area measurements in ultrasound images for adults with obstructive sleep apnea
Authors: Manlises Cyrel Ontimare , Chen Jeng‐Wen , Huang Chih‐Chung
Published: April 2020

Obstructive sleep apnea is a chronic breathing disorder where the recursive collapse of the upper airway causes cessation of airflow during sleep. Quantitative assessments of dynamic tongue motion may provide a better understanding of the mechanism of obstructive sleep apnea. Tongue area changes, in submental ultrasound images recorded during wakefulness from normal breathing by the Müller manoeuvre, were tracked using the modified optical flow‐based method. The results demonstrated that patients with obstructive sleep apnea had a larger mid‐sagittal tongue area compared to the control group (during normal breathing, p = .004, during the Müller manoeuvre p = .005, and differences between normal breathing and the Müller manoeuvre, p = .01). Tongue area measurements were significantly different in patients with varying severity of OSA during normal breathing and during the Müller manoeuvre, and had differences between normal breathing and the Müller manoeuvre (p = .005, p = .008 and p = .03, respectively). Patients with moderate or severe obstructive sleep apnea exhibited minimal movement of the tongue. In contrast, normal controls and patients with mild obstructive sleep apnea demonstrated bidirectional tongue motions during a transition from normal breathing to the Müller manoeuvre in wakefulness. Identifying different patterns of deformation and displacement of the tongue may have potential in evaluating the presence and the pathogenesis of OSA.
Meteorite transport—Revisited II
Authors: Wisdom Jack
Published: April 2020

In Wisdom (2017), I presented new simulations of meteorite transport from the chaotic zones associated with major resonances in the asteroid belt: the ν6 secular resonance, the 3:1 mean motion resonance with Jupiter, and the 5:2 mean motion resonance with Jupiter. I found that the observed afternoon excess (the fact that approximately twice as many meteorites fall in the afternoon as in the morning) of the ordinary chondrites is consistent with chaotic transport from the 3:1 resonance, contradicting prior reports. Here I report an additional study of the transport of meteorites from ν6 secular resonance and the 3:1 mean motion resonance. I use an improved integration algorithm, and study the evolution of more particles. I confirm that the afternoon excess of the ordinary chondrites is consistent with transport from the 3:1 resonance.
Mindfulness, complex interventions and conceptual clarity
Authors: Hancock Jason , Mattick Karen
Published: April 2020

How can we further develop mindfulness training in health professions education? Hancock and Mattick argue the answer lies in the complex interventions framework.
Transcriptome analysis and functional validation reveal a novel gene, BcCGF1, that enhances fungal virulence by promoting infection‐related development and host penetration
Authors: Zhang Ming‐Zhe , Sun Chen‐Hao , Liu Yue , Feng Hui‐Qiang , Chang Hao‐Wu , Cao Sheng‐Nan , Li Gui‐Hua , Yang Song , Hou Jie , Zhu‐Salzman Keyan , Zhang Hao , Qin Qing‐Ming
Published: April 2020

Simultaneous transcriptome analyses of both host plants and pathogens, and functional validation of the identified differentially expressed genes (DEGs) allow us to better understand the mechanisms underlying their interactions. Here, we analyse the mixed transcriptome derived from Botrytis cinerea (the causal agent of grey mould) infected tomato leaves at 24 hr after inoculation, a critical time point at which the pathogen has penetrated and developed in the leaf epidermis, whereas necrotic symptoms have not yet appeared. Our analyses identified a complex network of genes involved in the tomato–B. cinerea interaction. The expression of fungal transcripts encoding candidate effectors, enzymes for secondary metabolite biosynthesis, hormone and reactive oxygen species (ROS) production, and autophagy‐related proteins was up‐regulated, suggesting that these genes may be involved in the initial infection processes. Specifically, tomato genes involved in phytoalexin production, stress responses, ATP‐binding cassette transporters, pathogenesis‐related proteins, and WRKY DNA‐binding transcription factors were up‐regulated. We functionally investigated several B. cinerea DEGs via gene replacement and pathogenicity assays, and demonstrated that BcCGF1 was a novel virulence‐associated factor that mediates fungal development and virulence via regulation of conidial germination, conidiation, infection structure formation, host penetration, and stress adaptation. The fungal infection‐related development was controlled by BcCGF‐mediated ROS production and exogenous cAMP restored the mutant infection‐related development. Our findings provide new insights into the elucidation of the simultaneous tactics of pathogen attack and host defence. Our systematic elucidation of BcCGF1 in mediating fungal pathogenesis may open up new targets for fungal disease control.
Delayed attendance at routine eye examinations is associated with increased probability of general practitioner referral: a record linkage study in Northern Ireland
Authors: Wright David M , O'Reilly Dermot , Azuara‐Blanco Augusto , Curran Raymond , McMullan Margaret , Hogg Ruth E
Published: April 2020

Purpose

To investigate relationships between health and socio‐economic status with delayed attendance at routine eye examinations and risk of subsequent general practitioner (GP) referral in Northern Ireland.

Methods

We constructed a cohort of 132 046 community dwelling individuals aged ≥60 years, drawing contextual information from the 2011 Northern Ireland Census. Using linked administrative records of routine eye examinations between 2009 and 2014, we calculated 311 999 examination intervals. Multinomial models were used to estimate associations between contextual factors and examination interval (classified into three groups: early recall, on‐time, delayed attendance). Associations between examination interval and referral risk were estimated using logistic regression.

Results

Delayed attendance was recorded for 129 857 (41.6%) examination intervals, 53 759 (17.2%) delayed by ≥6 months. Female sex, poor general or mental health were each associated with delay, as were longer distances to optometry services among those aged ≥70 years (longest vs shortest: Relative Risk Ratio = 1.21 [1.14, 1.28]). Low income and residence in social housing were associated with reduced delay risk. There were 3347 (3.5%) and 11 401 (5.3%) GP referrals in the 60–69 and ≥70 years age groups respectively. Delayed attendance was associated with increased referral risk in both groups (Odds Ratios: 60–69 years = 1.30 [1.04, 1.61]; ≥70 years = 1.07 [1.01, 1.13]).

Conclusions

Poor health and longer distances to optometry services were associated with delayed attendance at routine eye examinations but low income was not. Delayed attendance was associated with increased GP referral risk, indicative of missed opportunities to detect potentially serious eye conditions.
High attenuation areas in pulmonary computed tomography: Their meaning and use in interstitial lung disease
Authors: Lau Kenneth K. , Nandurkar Dee
Published: April 2020

See related article
Sedimentary facies, fossil distribution and depositional setting of the late Ediacaran Tamengo Formation (Brazil)
Authors: Amorim Kamilla Borges , Afonso Jhon Willy Lopes , Leme Juliana de Moraes , Diniz Cleber Quidute Clemente , Rivera Laura Carolina Montenegro , Gómez‐Gutiérrez Juan Camilo , Boggiani Paulo César , Trindade Ricardo Ivan Ferreira
Published: April 2020

Mixed carbonate–siliciclastic deposits of the Tamengo Formation (terminal Ediacaran), record the rise of calcifying metazoans and the origin of exoskeletons in animals. To explore the relationships between environmental setting and the first appearance of calcified metazoans and their ecology, this study presents detailed sedimentological and stratigraphic data of eight sections that capture the final stages of the Ediacaran (550 to 543 Ma). This study combines stratigraphic characterization with detailed facies descriptions and evaluates lateral heterogeneity and overall ramp sedimentation integrated with fossil distribution. The Tamengo Formation represents a storm‐dominated ramp. The outer to mid‐ramp is composed of very fine‐grained siliciclastic rocks containing Corumbella body fossils and thin‐bedded mudstone/wackestone containing Cloudina. The mid‐inner ramp is dominated by wackestone/packstone with abundant Cloudina skeletal debris and ooid packstone/grainstone shoal deposits. Locally, fragments of Corumbella and Cloudina are found on the same horizon, which is a result of their high accumulation rate, resulting from the reworking and mixing of epifaunal organisms. In spite of taphonomic biases, the general distribution of Corumbella and Cloudina across the unit suggests that these organisms have been transported across ramp and/or probably show a differential response of fauna preservation. When compared to other occurrences worldwide, this dataset indicates an already complex ecosystem in the Ediacaran, where these early animals were capable of adapting to specific environmental niches.
Bayesian variable selection for multioutcome models through shared shrinkage
Authors: Kundu Debamita , Mitra Riten , Gaskins Jeremy T.
Published: April 2020

Variable selection over a potentially large set of covariates in a linear model is quite popular. In the Bayesian context, common prior choices can lead to a posterior expectation of the regression coefficients that is a sparse (or nearly sparse) vector with a few nonzero components, those covariates that are most important. This article extends the “global‐local” shrinkage idea to a scenario where one wishes to model multiple response variables simultaneously. Here, we have developed a variable selection method for a K‐outcome model (multivariate regression) that identifies the most important covariates across all outcomes. The prior for all regression coefficients is a mean zero normal with coefficient‐specific variance term that consists of a predictor‐specific factor (shared local shrinkage parameter) and a model‐specific factor (global shrinkage term) that differs in each model. The performance of our modeling approach is evaluated through simulation studies and a data example.
Novel HLA‐DPB1*14:01:11 allele, identified by next‐generation sequencing in a Saudi individual
Authors: Jawdat Dunia , Almutairi Yasser , Algharib Riyadh , Alaskar Ahmed S. , Hajeer Ali H.
Published: April 2020

HLA‐DPB1*14:01:11 differs from HLA‐DPB1*14:01:01:01 by a single synonymous nucleotide substitution in codon 52.
Novel HLA‐C*06:284 allele, identified by next‐generation sequencing in a Saudi individual
Authors: Jawdat Dunia , Mohammadi Mahammad , Haneef Loay , Alaskar Ahmed S. , Hajeer Ali H.
Published: April 2020

HLA‐C*06:284 differs from HLA‐C*06:02:01:02 by two single nucleotide substitutions in codon 24 (Ser > Thr).
Solid organ donation after death from listeria encephalitis: A case report
Authors: Douchy Thomas , Lagrou Katrien , Jochmans Ina , Sainz Barriga Mauricio , Monbaliu Diethard , Pirenne Jacques , Debaveye Yves
Published: April 2020

Despite organ shortage, organs from donors with listeria infections have been discarded for transplantation. We present the first‐reported case of liver transplantation following listeria encephalitis. The patient was admitted with progressing neurological symptoms after an episode of gastroenteritis. Rhombo‐encephalitis was diagnosed, and Listeria monocytogenes was found to be the causative pathogen. Despite proper antibiotic treatment and rapid clearance of bacteremia, he continued to deteriorate and became brain dead, after which organ donation was performed. At procurement, he had been treated with amoxicillin for 9 days. The recipient was treated with pipercillin/tazobactam for 21 days. Besides an anastomotic biliary stricture, necessitating endoscopic dilatation and stenting, further clinical course was uneventful and she is doing well eleven months post‐transplant. Our case suggests that listeria encephalitis is not an absolute contra‐indication to solid organ donation. We suggest that donors should be treated with adequate antibiotics for at least 48h prior to procurement and advocate confirmation of sterile blood cultures as a prerequisite for donation. According to listeriosis guidelines, we suggest that the recipient should be treated with targeted antibiotics for at least 2 weeks. The risk of transmission should, however, always be balanced carefully against the suspected waiting list mortality.
Impact of the COVID‐19 – a regional blood centre's perspective
Authors: Leung Jennifer N. S. , Lee Cheuk-Kwong
Published: April 2020

COVID‐19 pandemic has caused an overwhelming pressure to everyone around the world. Not only public healthcare system is overloaded with patients, but also public are panic, restricted in their mobility, and their daily life are completely changed. As a regional blood centre in part of China, the first 3 months of year 2020 were both painful and stressful in managing both the blood safety and supply. However, the experience gained and measures implemented to overcome blood shortage and gain donors’ confidence in safe blood donation were fruitful. All these should further be incorporated into the existing contingency plan in managing emerging infectious diseases and shared among colleagues in transfusion communities.
Lower bounds for Maass forms on semisimple groups
Authors: Brumley Farrell , Marshall Simon
Published: April 2020

Let$G$be an anisotropic semisimple group over a totally real number field$F$. Suppose that$G$is compact at all but one infinite place$v_{0}$. In addition, suppose that$G_{v_{0}}$is$\mathbb{R}$-almost simple, not split, and has a Cartan involution defined over$F$. If$Y$is a congruence arithmetic manifold of non-positive curvature associated with$G$, we prove that there exists a sequence of Laplace eigenfunctions on$Y$whose sup norms grow like a power of the eigenvalue.
Machine Learning Approaches for Performance Assessment of Nuclear Fuel Assemblies Subject to Seismic-Induced Impacts
Authors: Altieri Domenico , Robin-Boudaoud Marie-Cécile , Kessler Hannes , Pellissetti Manuel , Patelli Edoardo
Published: April 2020

In pressurized water nuclear reactors, the seismic performance of fuel assemblies is governed by their spacer grids (SGs) which may experience impacts with neighboring fuel assembly SGs or with the core barrel, depending on the intensity of the seismic event. Nonlinear dynamic analysis aiming at computing the maximum permanent deformation in a statistic framework is computationally demanding due to the different possible core configurations and the dimension of the dataset of seismic excitations. Hence, surrogate models trained by the physics-based dynamic model are proposed to analyze different scenarios, i.e., explore the space of potential core configurations and seismic excitations. Starting from ground motion records corresponding to six levels of seismic hazard, the dynamic excitation at the elevation of the reactor pressure vessel is obtained via transfer functions. Correlation between different seismic intensity measures and the maximum permanent deformation is evaluated. The performance of two well-established surrogate models, namely, artificial neural networks (ANN) and Gaussian process (GP) for regression problems is analyzed and discussed. Bayesian techniques are adopted to enhance the robustness of the trained surrogate models by training sets of neural networks and estimating the hyper-parameter of the GP.
Revisiting the Basis for Hip Fracture Prediction Through Bone Mineral Density Scans: Large Potential Errors and Improved Methods
Authors: Munsell, Jr. W. P.
Published: April 2020

Researchers have attempted to evaluate the likelihood of hip fracture as a function of an engineering concept called the moment of inertia, as applied to the cross-sectional area of hip bones. While the premise is sound, the results have been disappointing. Although several authors have acknowledged that errors may arise in the current methods investigators employ to determine the cross section moment of inertia (CSMI), none have looked critically at the sources, or even the magnitude, of those errors. This paper evaluates the nature of the error that can be introduced by the use of one-dimensional bone mineral density scans to estimate the CSMI and quantifies its impact on predictive calculations. In addition, this paper presents an improved method for approximating the mechanical section properties of highly complex cross sections. The factors affecting the accuracy of the proposed method are tested, and its error rate is also quantified. The method employs a two-dimensional analysis of digital images of the subject cross section and does not require extensive user expertise or investment in expensive finite element analysis programs to implement. The limited file space necessary to install the required code means that standard smart phones could be used to directly evaluate the most complex cross section in the field.
Continuous Phase Control of Vanadium Dioxide Films
Authors: Dai Jiguo , Annasiwatta Chandika , Bernussi Ayrton , Fan Zhaoyang , Berg Jordan M. , Ren Beibei
Published: April 2020

Vanadium dioxide (VO2) undergoes a metal-insulator transition (MIT) at approximately 68 °C, with associated sharp changes in its physical (e.g., optical, electrical, and mechanical) properties. This behavior makes VO2 films of interest in many potential applications, including memory devices, switches, sensors, and optical modulators. For ON/OFF like digital applications, an abrupt switching behavior is ideal. However, to continuously change VO2 metal/insulator phase ratio for analog-like operation, the intrinsic hysteresis characteristic of VO2 MIT renders the phase control becoming a formidable challenge. This paper considers the problem of controlling and tracking desired optical transmittance via continuous phase ratio change. The problem becomes worse while considering the differences of individual thin-film samples and the hysteresis associated with the phase change within a narrow temperature range. This paper reports a robust feedback controller using an optical transmittance measurement and based on an uncertainty and disturbance estimator (UDE) architecture. The proposed controller is capable of mitigating the adverse effect of hysteresis, while also compensating for various uncertainties. The effectiveness of the proposed methodology is demonstrated with experimental validation.
Effect of Aging on Trunk Muscle Function and Its Influence on Falls Among Older Adults
Authors: Porto Jaqueline M. , Spilla Sállua B. , Cangussu-Oliveira Luciana M. , Freire Júnior Renato C. , Nakaishi Ana Paula M. , de Abreu Daniela C.C.
Published: April 2020

The objective was to determine whether trunk muscle function is influenced by the aging process and to identify if the trunk can be an important factor in older people’s falls over a period of 1 year. The peak torque, rate of torque development, and torque steadiness of the trunk extensors and flexors were compared between a young group, older group (older adults with no episodes of falls), and older faller group (older adults who had suffered at least one fall episode over a period of 1 year) by one-way analysis of variance, followed by the post hoc Tukey test. The adjusted multivariate linear regression was applied to verify the association between the number of falls and the trunk parameters in older adults. The young group showed higher extensors and flexors peak torque and rate of torque development, and lower extensor torque steadiness at 10% when compared with older groups. Only trunk flexor peak torque showed a negative association with the number of future falls (p = .042), but there was no difference in trunk muscle function between the older group and the older faller group.
“Under One Banner”: The World Baseball Softball Confederation and the Gendered Politics of Olympic Participation
Authors: Maddox Callie Batts
Published: April 2020

In 2020, baseball and softball will return to the Olympics after a twelve-year absence. Leading the effort to secure reinstatement was the World Baseball Softball Confederation (WBSC), the international governing body for the two sports established in 2013 upon the merging of the International Baseball Federation and the International Softball Federation. Faced with continual threats of Olympic exclusion, the WBSC offers a unique model of global governance in that one federation is in charge of two very different sports. The history and work of the WBSC is made more complicated by the gendered bifurcation of baseball and softball, and systemic cultural beliefs that mark baseball as male and softball as female. Utilizing this gendered tension as a guiding framework, this article traces the emergence of the WBSC and suggests that the global governance of two sports under the single banner of the WBSC risks reproducing long-standing gender stereotypes and assumptions.
Ultraprecise single-molecule localization microscopy enables in situ distance measurements in intact cells
Authors: Coelho Simao , Baek Jongho , Graus Matthew S. , Halstead James M. , Nicovich Philip R. , Feher Kristen , Gandhi Hetvi , Gooding J. Justin , Gaus Katharina
Published: April 2020

Feedback SMLM achieves ultrahigh localization precision and in situ distance measurements on the biological relevant scales.
Electro-actuated valves and self-vented channels enable programmable flow control and monitoring in capillary-driven microfluidics
Authors: Arango Yulieth , Temiz Yuksel , Gökçe Onur , Delamarche Emmanuel
Published: April 2020

Capillary networks controlled by simple low-voltage gates open up new possibilities for fluid delivery in point-of-care assays.
On-demand regulation of photochromic behavior through various counterions for high-level security printing
Authors: Ma Yun , Yu Yaxin , She Pengfei , Lu Jinyu , Liu Shujuan , Huang Wei , Zhao Qiang
Published: April 2020

A facile strategy was proposed to achieve tunable coloration rates by varying counterions in zinc complexes for security printing.
A 1000-year-old mystery solved: Unlocking the molecular structure for the medieval blue from
Chrozophora tinctoria
, also known as folium
Authors: Nabais P. , Oliveira J. , Pina F. , Teixeira N. , de Freitas V. , Brás N. F. , Clemente A. , Rangel M. , Silva A. M. S. , Melo M. J.
Published: April 2020

A 1000-year-old mystery solved: The molecule behind the medieval blue from
Chrozophora tinctoria
, also known as folium.
Case series of coronavirus (SARS-CoV-2) in a military recruit school: clinical, sanitary and logistical implications
Authors: Baettig Sascha J , Parini A , Cardona I , Morand G B
Published: April 2020

Introduction

A new coronavirus, called Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2), has emerged from China in late 2019 and has now caused a worldwide pandemic. The impact of COVID-19 has not been described so far in a military setting. We therefore report a case series of infected patients in a recruit school in Switzerland and the herein associated challenges.

Methods

Retrospective review of COVID-19 cases among Swiss Armed Forces recruits in the early weeks of SARS-CoV-2 pandemic in the canton of Ticino, the southernmost canton of Switzerland. Positive cases were defined with two positive PCR testing for SARS-CoV-2 from nasopharyngeal swabs. Serological testing was performed with a commercially available kit according to manufacturers’ instructions.

Results

The first case was likely contaminated while skiing during weekend permission. He became symptomatic 4 days later, tested positive for SARS-CoV-2 and was put into isolation. He showed complete symptom resolution after 48 hours. Quarantine was ordered for all recruits with close contact in the past 2 days, a total of 55 persons out of 140 in the company. Seven out of nine recruits in one particular quarantine room became mildly symptomatic. SARS-CoV-2 PCR was positive in one of them. Seven days after initial diagnosis, the index patient and the other one from the quarantine retested positive for SARS-CoV-2, although they had been completely asymptomatic for over 96 hours. Serological testing revealed positive for both patients. All others showed negative IgM and IgG.

Conclusions

Young healthy recruits often showed a mild course of COVID-19 with rapid symptom decline but were persistent SARS-CoV-2 carriers. This illustrates how asymptomatic patients may be responsible for covert viral transmission. An early and prolonged establishment of isolation and quarantine for patients and close contacts is essential to slow down the spread of SARS-CoV-2, especially in the confined space of a military environment.
Seizure First Aid Training For people with Epilepsy (SAFE) frequently attending emergency departments and their significant others: results of a UK multi-centre randomised controlled pilot trial
Authors: Noble Adam J , Snape Dee , Nevitt Sarah , Holmes Emily A , Morgan Myfanwy , Tudur-Smith Catrin , Hughes Dyfrig A , Buchanan Mark , McVicar Jane , MacCallum Elizabeth , Goodacre Steve , Ridsdale Leone , Marson Anthony G
Published: April 2020

Objective

To determine the feasibility and optimal design of a randomised controlled trial (RCT) of Seizure First Aid Training For Epilepsy (SAFE).

Design

Pilot RCT with embedded microcosting.

Setting

Three English hospital emergency departments (EDs).

Participants

Patients aged ≥16 with established epilepsy reporting ≥2 ED visits in the prior 12 months and their significant others (SOs).

Interventions

Patients (and their SOs) were randomly allocated (1:1) to SAFE plus treatment-as-usual (TAU) or TAU alone. SAFE is a 4-hour group course.

Main outcome measures

Two criteria evaluated a definitive RCT’s feasibility: (1) ≥20% of eligible patients needed to be consented into the pilot trial; (2) routine data on use of ED over the 12 months postrandomisation needed securing for ≥75%. Other measures included eligibility, ease of obtaining routine data, availability of self-report ED data and comparability, SAFE’s effect and intervention cost.

Results

Of ED attendees with a suspected seizure, 424 (10.6%) patients were eligible; 53 (12.5%) patients and 38 SOs consented. Fifty-one patients (and 37 SOs) were randomised. Routine data on ED use at 12 months were secured for 94.1% patients. Self-report ED data were available for 66.7% patients. Patients reported more visits compared with routine data. Most (76.9%) patients randomised to SAFE received it and no related serious adverse events occurred. ED use at 12 months was lower in the SAFE+TAU arm compared with TAU alone, but not significantly (rate ratio=0.62, 95% CI 0.33 to 1.17). A definitive trial would need ~674 patient participants and ~39 recruitment sites. Obtaining routine data was challenging, taking ~8.5 months.

Conclusions

In satisfying only one predetermined ‘stop/go’ criterion, a definitive RCT is not feasible. The low consent rate in the pilot trial raises concerns about a definitive trial’s finding’s external validity and means it would be expensive to conduct. Research is required into how to optimise recruitment from the target population.

Trial registration number

ISRCTN13871327
Cognitive–behavioral therapy-based intervention to treat symptoms of anxiety in pregnancy in a prenatal clinic using non-specialist providers in Pakistan: design of a randomised trial
Authors: Surkan Pamela J , Hamdani Syed Usman , Huma Zill-e , Nazir Huma , Atif Najia , Rowther Armaan A , Chaudhri Rizwana , Zafar Shamsa , Mullany Luke C , Malik Abid , Rahman Atif
Published: April 2020

Introduction

Prenatal anxiety is a prevalent condition that is harmful for women and a strong predictor of postpartum depression. This trial assesses an intervention initiated in early pregnancy to mid pregnancy among women with clinical or subclinical symptoms of anxiety in Pakistan.

Methods and analysis

Happy Mother, Healthy Baby(HMHB) is a phase three, two-arm, single-blind, individual randomised clinical trial conducted in the outpatient department of Holy Family Hospital, a large public tertiary care facility affiliated with Rawalpindi Medical University (RMU). Pregnant women (enrolled at ≤22 weeks of gestation) receive six individual HMHB sessions based on cognitive–behavioral therapy (CBT) and relaxation techniques that are administered by non-specialist providers and tailored to address anxiety symptoms. Two to six booster sessions are given between the fifth consecutive weekly core session and the sixth core session that occurs in the third trimester. Apart from baseline data, data are collected in the third trimester, at birth and at 6-weeks postpartum. Primary outcomes include diagnoses of postpartum common mental disorders. Secondary outcomes include symptoms of anxiety and of depression, and birth outcomes including small-for-gestational age, low birth weight and preterm birth. An economic analysis will determine the cost effectiveness of the intervention.

Ethics

Ethics approval was obtained from the Johns Hopkins Bloomberg School of Health Institutional Review Board (Baltimore, USA), the Human Development Research Foundation Ethics Committee (Islamabad, Pakistan), the RMU Institutional Research Forum (Rawalpindi, Pakistan) and the National Institute of Mental Health-appointed Global Mental Health Data Safety and Monitoring Board.

Dissemination

Results from this trial will build evidence for the efficacy of a CBT-based intervention for pregnant women delivered by non-specialised providers. Identification of an evidence-based intervention for anxiety starting in early pregnancy to mid pregnancy may be transferable for use and scale-up in other low-income and middle-income countries.

Trial registration number

NCT03880032.
Validity of the Medi-StuNTS behavioural marker system: assessing the non-technical skills of medical students during immersive simulation
Authors: Phillips Emma Claire , Smith Samantha Eve , Clarke Benjamin , Hamilton Ailsa Lauren , Kerins Joanne , Hofer Johanna , Tallentire Victoria Ruth
Published: April 2020

Background

The Medical Students’ Non-Technical Skills (Medi-StuNTS) behavioural marker system (BMS) is the first BMS to be developed specifically for medical students to facilitate training in non-technical skills (NTS) within immersive simulated acute care scenarios. In order to begin implementing the tool in practice, validity evidence must be sought. We aimed to assess the validity of the Medi-StuNTS system with reference to Messick’s contemporary validity framework.

Methods

Two raters marked video-recorded performances of acute care simulation scenarios using the Medi-StuNTS system. Three groups were marked: third-year and fourth-year medical students (novices), final-year medical students (intermediates) and core medical trainees (experts). The scores were used to make assessments of relationships to the variable of clinical experience through expert–novice comparisons, inter-rater reliability, observability, exploratory factor analysis, inter-rater disagreements and differential item functioning.

Results

A significant difference was found between the three groups (p<0.005), with experts scoring significantly better than intermediates (p<0.005) and intermediates scoring significantly better than novices (p=0.001). There was a strong positive correlation between the two raters’ scores (r=0.79), and an inter-rater disagreement of more than one point in less than one-fifth of cases. Across all scenarios, 99.7% of skill categories and 84% of skill elements were observable. Factor analysis demonstrated appropriate grouping of skill elements. Inconsistencies in test performance across learner groups were shown specifically in the skill categories of situation awareness and decision making and prioritisation.

Conclusion

We have demonstrated evidence for several aspects of validity of the Medi-StuNTS system when assessing medical students’ NTS during immersive simulation. We can now begin to introduce this system into simulation-based education to maximise NTS training in this group.
Immune involvement of the contralateral hemisphere in a glioblastoma mouse model
Authors: Crommentuijn Matheus H W , Schetters Sjoerd T T , Dusoswa Sophie A , Kruijssen Laura J W , Garcia-Vallejo Juan J , van Kooyk Yvette
Published: April 2020

Background

Glioblastoma (GBM) is the most common and deadliest form of brain cancer in adults. Standard treatment, consisting of surgery and radiochemotherapy, only provides a modest survival benefit and is incapable of combating infiltrating GBM cells in other parts of the brain. New therapies in clinical trials, such as anti-programmed cell death 1 immunotherapy, have so far shown limited success in GBM. Moreover, it is unclear how the growth of GBM suppresses the immune system locally at the site of the brain tumor or if distant sites of tumor cell migration are also involved. Invasive GBM cells in brain tissue beyond the primary tumor limit the use of surgery, thus immunotherapy could be beneficial if activated/suppressed immune cells are present in the contralateral hemisphere.

Methods

Here, we used a syngeneic orthotopic GL26 GBM mouse model and multiparameter fluorescence-activated cell sorting analysis to study the phenotype of resident and infiltrating immune cells in both the brain tumor hemisphere and contralateral hemisphere.

Results

We show that lymphoid cells, including tumor antigen-specific CD8+tumor-infiltrating lymphocytes (TILs) are present in the tumor and are characterized by a tolerogenic phenotype based on high immune checkpoint expression. Massive infiltration of myeloid cells is observed, expressing immune checkpoint ligands, suggesting an immune-dependent coinhibitory axis limiting TIL responses. Surprisingly, these phenotypes are paralleled in the contralateral hemisphere, showing that infiltrating immune cells are also present at distant sites, expressing key immune checkpoints and immune checkpoint ligands.

Conclusion

Whole-brain analysis indicates active immune involvement throughout the brain, both at the site of the primary tumor and in the contralateral hemisphere. Using the right combination and timing, immune checkpoint blockade could have the potential to activate immune cells at the site of the brain tumor and at distant sites, thereby also targeting diffusely infiltrating GBM cells.
Functional and mechanistic advantage of the use of a bifunctional anti-PD-L1/IL-15 superagonist
Authors: Knudson Karin M , Hicks Kristin C , Ozawa Yohei , Schlom Jeffrey , Gameiro Sofia R
Published: April 2020

Background

Anti(α)-programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy fails to provide durable clinical benefit for most patients with carcinoma. Recent studies suggested that strategies to reduce immunosuppressive cells, promote systemic T-cell responses and lymphocyte trafficking to the tumor microenvironment (TME) may improve efficacy. N-809 is a first-in-class bifunctional agent comprising the interleukin (IL)-15 superagonist N-803 fused to two αPD-L1 domains. Thus, N-809 can potentially stimulate effector immune cells through IL-15 and block immunosuppressive PD-L1. Here, we examined the antitumor efficacy and immunomodulatory effects of N-809 versus N-803+αPD-L1 combination.

Methods

The ability of N-809 to block PD-L1 and induce IL-15-dependent immune effects was examined in vitro and in vivo. Antitumor efficacy of N-809 or N-803+αPD-L1 was evaluated in two murine carcinoma models and an extensive analysis of immune correlates was performed in the tumor and tumor-draining lymph node (dLN).

Results

We demonstrate that N-809 blocks PD-L1 and induces IL-15-dependent immune effects. N-809 was well-tolerated and reduced 4T1 lung metastasis, decreased MC38 tumor burden and increased survival versus N-803+αPD-L1. Compared with N-803+αPD-L1, N-809 enhanced natural killer (NK) and CD8+T-cell activation and function in the dLN and TME, relating to increased gene expression associated with interferon and cytokine signaling, lymphoid compartment, costimulation and cytotoxicity. The higher number of TME CD8+T cells was attributed to enhanced infiltration, not in situ expansion. Increased TME NK and CD8+T-cell numbers correlated with augmented chemokine ligands and receptors. Moreover, in contrast to N-803+αPD-L1, N-809 reduced immunosuppressive regulatory T cells (Treg), monocytic myeloid-derived suppressor cells (M-MDSC) and M2-like macrophages in the TME.

Conclusions

Our results suggest that N-809 functions by a novel immune mechanism to promote antitumor efficacy. Foremost, N-809 enhances intratumoral lymphocyte numbers by increasing trafficking via altered chemokine levels in the TME and chemokine receptor expression on CD8+T cells and NK cells. In addition, N-809 reduces immunosuppressive and pro-tumorigenic immune cells in the TME, including Treg, M2-like macrophages and M-MDSC. Overall, these novel effects of N-809 promote an inflamed TME, leading to lower tumor burden and increased survival. These results provide mechanistic insight and rationale supporting the potential clinical study of N-809 in patients with carcinoma.
Unexpected but transient tumour enlargement preceded complete regression and long‐term control after irradiation of squamous cell carcinoma in a red‐eared slider (Trachemys scripta elegans)
Authors: Baja Alexie J , Lewbart Gregory A , Luff Jennifer A , Nolan Michael W
Published: April 2020

A red‐eared slider with a chronic non‐healing ulcerative shell lesion was diagnosed with cutaneous squamous cell carcinoma (SCC). The animal underwent surgical debulking and adjuvant hypofractionated radiation therapy. The lesion initially responded, with near‐complete tumour regression, but then began growing again just a few months after finishing radiotherapy. Then, after several months with no additional tumour‐directed therapy, the lesion again regressed. Five years post‐irradiation and with no further treatment, the turtle now remains tumour‐free. This unusual pattern of disease regression, followed by transient growth and then long‐term local tumour control, suggests either a spontaneous remission or a pseudoprogression‐like phenomenon. Careful clinical follow‐up and reporting of future cases will aid in determining whether this pseudoprogression‐like event was random, versus being a common component of the chelonian response to irradiation of cutaneous SCC.
Age, body mass index, and weight gain do not increase sympathetic activity during pregnancy
Authors: Reyes Laura M. , Badrov Mark B. , Fu Qi , Steinback Craig D. , Davenport Margie H.
Published: April 2020

Associations between prepregnancy body mass index, gestational weight gain, maternal age, and basal sympathetic nervous system activity (SNA) in normotensive pregnant women have not been explored. Retrospective analysis of microneurography records from 74 normotensive pregnant women during their third trimester indicated that although pregnancy is associated with rapid weight gain, this does not influence SNA. There were also no associations between maternal age and SNA, but more studies are needed to confirm this interpretation.

Novelty Neither age nor excessive weight gain appears to influence sympathetic activity during normotensive pregnancy.