bluuebunny/crossref_metadata_2025 huggingface dataset:
Boosting innate immunity:Asaiabacteria expressing a protein fromWolbachiadetermine macrophage activation and killing ofLeishmania
Authors: Varotto-Boccazzi Ilaria , Epis Sara , Arnoldi Irene , Corbett Yolanda , Gabrieli Paolo , Paroni Moira , Nodari Riccardo , Basilico Nicoletta , Sacchi Luciano , Gramiccia Marina , Gradoni Luigi , Tranquillo Vito , Bandi Claudio
Published: June 2020

Leishmaniases are severe vector-borne diseases affecting humans and animals, caused byLeishmaniaprotozoans. Immune polarization plays a major role in determining the outcome ofLeishmaniainfections: hosts displaying M1-polarized macrophages are protected, while those biased on the M2 side acquire a chronic infection, that could develop into an overt and potentially deadly disease. The identification of the factors involved in M1 polarization is essential for the design of therapeutic and prophylactic interventions, including vaccines. Infection by the filarial nematodeDirofilaria immitiscould be one of the factors that interfere with leishmaniasis in dogs. Indeed, filarial nematodes induce a partial skew of the immune response towards M1, likely caused by their bacterial endosymbionts,Wolbachia. Here we have examined the potential ofAsaiaWSP, a bacterium engineered for the expression of theWolbachiasurface protein (WSP), as an inductor of M1 macrophage activation andLeishmaniakilling. Macrophages stimulated withAsaiaWSPdisplayed a strong leishmanicidal activity, comparable to that determined by the choice-drug amphotericin B. Additionally,AsaiaWSPdetermined the expression of markers of classical macrophage activation, including M1 cytokines, ROS and NO, and an increase in phagocytosis activity.Asaianot expressing WSP also induced macrophage activation, although at a lower extent compared toAsaiaWSP. In summary, our study, while providing a strong evidence for the immune-stimulating properties ofWolbachia, highlights the translational potential ofAsaiaWSPin the areas of the immune-prophylaxis and therapy of leishmaniases, as well as of other diseases that could be subverted by M1 macrophage activation.
Application of dielectric spectroscopy in the dynamically changing biological system – case ofNeocaridina davidishrimp starvation
Authors: Wlodarczyk Agnieszka , Wlodarczyk Patryk
Published: June 2020

In this work, dielectric studies onNeocaridina davidishrimps have been presented. The effect of starvation on dielectric properties such as conductivity or permittivity have been shown. It was found that the onset frequency of electrode polarization depends on starvation period, which is probably related to the cytoplasm viscosity. In the dielectric spectra of shrimps two relaxation processes have been identified i.e. α and β process. The α process is probably related to the counter ion polarization while β process to the mobility of macromolecules present in the body of a shrimp, mainly to the amount of lipids. It was also found that there is a difference in dielectric response between control group and the group regenerated after 14 day starvation period. Basing on dielectric response, one can conclude that the viscosity of cytoplasm of regenerated shrimps is higher and the cells are rich in the lipid droplets when compared to control group.
Role for both myeloid and plasmacytoid DC in driving primary T helper cell response toBurkholderia pseudomalleiin healthy individuals
Authors: Reddi Durga , Durant Lydia , Bernardo David , Noble Alistair , English Nicholas R. , Hendy Philip , Clark Graeme C. , Prior Joann L. , Williamson E. Diane , Knight Stella C.
Published: June 2020

Burkholderia pseudomalleiis a Gram-negative bacterium that causes melioidosis, an infectious disease endemic to south-east Asia. AsB. pseudomalleiis antibiotic-resistant, the need for cell-based vaccines and therapies is crucial to managing melioidosis. Dendritic cells (DC) provide the first line of defense to infection and direct downstream immune responses. Using practical volumes of fresh healthy donor blood, we show that heat-killedB. pseudomalleiactivated and stimulated expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 from both myeloid and plasmacytoid DC. Furthermore,B. pseudomallei-pulsed DC induced activation and proliferation of CD4+T-cells. Thus, both DC subsets are important for driving primary T helper cell responses toB. pseudomalleiin healthy individuals and have the potential to be targeted for future therapies and vaccines.

Author Summary

Melioidosis is an infectious disease endemic to south-east Asia and northern Australia caused by the bacteriumBurkholderia pseudomallei. Melioidosis presents a significant public health threat because it has no effective vaccine or cure, leading to a high mortality rate of between 10-50%. We highlight the possibility of immune-based strategies targetingBurkholderia pseudomalleito better treat and prevent melioidosis. Specifically, we show that dendritic cells-the sentinel cells of the immune system-respond toB. pseudomalleiin healthy individuals and in turn can orchestrate downstream protective immune responses. Thus, dendritic cells may be key players in the development of both vaccines and therapeutics for melioidosis as well as other bacteria-driven diseases.
Crosstalk between Nitric Oxide and Retinoic Acid pathways is essential for amphioxus pharynx development
Authors: Caccavale F , Annona G , Subirana L , Escriva H , Bertrand S , D’Aniello S
Published: June 2020

During animal ontogenesis, body axis patterning is finely regulated by complex interactions between several signaling pathways. Nitric Oxide (NO) and Retinoic Acid (RA) are potent morphogens that play a pivotal role in vertebrate development. Their involvement in axial patterning of head and pharynx shows conserved features in the chordate phylum. Indeed, in the cephalochordate amphioxus NO and RA are crucial for the correct development of pharyngeal structures. Here we demonstrate the functional cooperation between NO and RA occurring in amphioxus embryogenesis. During neurulation, NO modulates RA production through the transcriptional regulation of Aldh1a.2 that irreversibly converts retinaldehyde into RA. On the other hand, RA regulates the transcription of Nos genes, probably through RA Response Elements found in their regulatory regions. The reciprocal regulation of NO and RA pathways results to be essential for the normal pharyngeal development in amphioxus and suggests that this regulatory crosstalk could be conserved in vertebrates.
Chemogenetics reveal an anterior cingulate-thalamic pathway for attending to task-relevant information
Authors: Bubb Emma J. , Aggleton John P. , O’Mara Shane M. , Nelson Andrew J.D.
Published: June 2020

In a changing environment, we need to decide when to select items that resemble previously rewarded stimuli and when it is best to switch to other stimulus types. Here, we used chemogenetic techniques to provide causal evidence that activity in the rodent anterior cingulate cortex and its efferents to the anterior thalamic nuclei modulate the ability to attend to reliable predictors of important outcomes. Rats were tested on an attentional set-shifting paradigm that first measures the ability to master serial discriminations involving a constant stimulus dimension that reliably predicts reinforcement (intradimensional-shift), followed by the ability to shift attention to a previously irrelevant class of stimuli when reinforcement contingencies change (extradimensional-shift). Chemogenetic silencing of the anterior cingulate cortex (Experiment 1) as well as selective inactivation of anterior cingulate efferents to the anterior thalamic nuclei (Experiment 2) impaired intradimensional learning but, facilitated two sets of extradimensional-shifts. This pattern of results signals the loss of a cortico-thalamic system for cognitive control that preferentially processes stimuli resembling those previously associated with reward. Previous studies highlight a separate prefrontal system that promotes switching to hitherto inconsistent predictors of reward when contingencies change. Competition between these two systems regulates cognitive flexibility and choice.
Twist regulates Yorkie to guide lineage reprogramming of syncytial alary muscles
Authors: Rose Marcel , Bartle-Schultheis Jakob , Domsch Katrin , Reim Ingolf , Schaub Christoph
Published: June 2020

The genesis of syncytial muscles is typically considered as a paradigm for an irreversible developmental process. Notably, transdifferentiation of syncytial muscles is naturally occurring duringDrosophiladevelopment. The ventral longitudinal heart-associated musculature (VLM) arises by a unique mechanism that revokes the differentiated fate from the so-called alary muscles and comprises at least two distinct steps: syncytial muscle cell fragmentation into single myoblasts and direct reprogramming into founder cells of the VLM lineage. Here we provide evidence that the mesodermal master regulatortwistplays a key role during this reprogramming process. Acting downstream ofDrosophilaTbx1 (Org-1) in the alary muscle lineage, Twist is crucially required for the derepression of the Hippo pathway effector Yki and thus for the initiation of syncytial muscle dedifferentiation and fragmentation. Subsequently, cell-autonomous FGFR-Ras-MAPK signaling in the resulting mono-nucleated myoblasts is maintaining Twist expression, thereby stabilizing nuclear Yki activity and inducing their lineage switch into the founder cells of the VLM.
An expanding manifold in transmodal regions characterizes adolescent reconfiguration of structural connectome organization
Authors: Park Bo-yong , Bethlehem Richard A. I. , Paquola Casey , Larivière Sara , Cruces Raul R. , de Wael Reinder Vos ,   Neuroscience in Psychiatry Network (NSPN) Consortium, Bullmore Edward T. , Bernhardt Boris C.
Published: June 2020

Abstract

Adolescence is a critical time for the continued maturation of brain networks. Here, we assessed structural connectome development in a large longitudinal sample ranging from childhood to young adulthood. By projecting high-dimensional connectomes into compact manifold spaces, we identified a marked expansion of structural connectomes with the strongest effects in transmodal regions during adolescence. Findings reflected increased within-module connectivity together with increased segregation, indicating increasing differentiation of higher-order association networks from the rest of the brain. Projection of subcortico-cortical connectivity patterns into these manifolds showed parallel alterations in pathways centered on the caudate and thalamus. Connectome findings were contextualized via spatial transcriptome association analysis, highlighting genes enriched in cortex, thalamus, and striatum. Statistical learning of cortical and subcortical manifold features at baseline and their maturational change predicted measures of intelligence at follow-up. Our findings demonstrate that connectome manifold learning can bridge the conceptual and empirical gaps between macroscale network reconfigurations, microscale processes, and cognitive outcomes in adolescent development.

Impact

Manifold learning of longitudinal brain network data provides novel insights into adolescent structural connectome maturation, and how multiple scales of cortical and subcortical organization interact in typical neurodevelopment.
Probing machine-learning classifiers using noise, bubbles, and reverse correlation
Authors: Thoret Etienne , Andrillon Thomas , Léger Damien , Pressnitzer Daniel
Published: June 2020

Background

Many scientific fields now use machine-learning tools to assist with complex classification tasks. In neuroscience, automatic classifiers may be useful to diagnose medical images, monitor electrophysiological signals, or decode perceptual and cognitive states from neural signals. However, such tools often remain black-boxes: they lack interpretability. A lack of interpretability has obvious ethical implications for clinical applications, but it also limits the usefulness of these tools to formulate new theoretical hypotheses.

New method

We propose a simple and versatile method to help characterize the information used by a classifier to perform its task. Specifically, noisy versions of training samples or, when the training set is unavailable, custom-generated noisy samples, are fed to the classifier. Multiplicative noise, so-called “bubbles”, or additive noise are applied to the input representation. Reverse correlation techniques are then adapted to extract either the discriminative information, defined as the parts of the input dataset that have the most weight in the classification decision, and represented information, which correspond to the input features most representative of each category.

Results

The method is illustrated for the classification of written numbers by a convolutional deep neural network; for the classification of speech versus music by a support vector machine; and for the classification of sleep stages from neurophysiological recordings by a random forest classifier. In all cases, the features extracted are readily interpretable.

Comparison with Existing Methods

Quantitative comparisons show that the present method can match state-of-the art interpretation methods for convolutional neural networks. Moreover, our method uses an intuitive and well-established framework in neuroscience, reverse correlation. It is also generic: it can be applied to any kind of classifier and any kind of input data.

Conclusions

We suggest that the method could provide an intuitive and versatile interface between neuroscientists and machine-learning tools.

Highlights

The heuristics of black-box classifiers can be probed with noisy inputs

The relevant features can be visualised in the input representation space

The method applies to any kind of data such as 2D images or 1D time series

It applies to any classifier such as deep neural networks, support vector machines, random forests
Moderate adolescent chronic intermittent ethanol exposure sex-dependently disrupts synaptic transmission and kappa opioid receptor function in the basolateral amygdala of adult rats
Authors: Przybysz Kathryn R. , Gamble Meredith E. , Diaz Marvin R.
Published: June 2020

Adolescent alcohol exposure is associated with many negative outcomes that persist into adulthood, including altered affective and reward-related behaviors. However, the long-term neurological disruptions underlying these behavioral states are not fully understood. The basolateral amygdala (BLA) plays a critical role in many of these behaviors, and shifts in the excitatory/inhibitory balance in this area are capable of directly modulating their expression. While changes to BLA physiology have been demonstrated during the acute withdrawal phase following adolescent ethanol exposure, no studies to date have examined whether these persist long-term. The kappa opioid receptor (KOR) system is a neuromodulatory system that acts as a prominent mediator of negative affective behaviors, and alterations of this system have been implicated in the behavioral profile caused by chronic alcohol exposure in adulthood. Notably, in the BLA, the KOR system undergoes functional changes between adolescence and adulthood, but whether BLA KORs are functionally disrupted by adolescent ethanol exposure has not been examined. In this study, we exposed male and female Sprague-Dawley rats to a vapor inhalation model of moderate adolescent chronic intermittent ethanol (aCIE) and examined the long-term effects on GABAergic and glutamatergic neurotransmission within the adult BLA using whole-cell patch-clamp electrophysiology. We also assessed how KOR activation modulated these neurotransmitter systems in aCIE versus control rats using the selective KOR agonist, U69593. This investigation revealed that aCIE exposure disrupted basal glutamate transmission in females by increasing spontaneous excitatory postsynaptic current (sEPSC) frequency, while having no effects on glutamate transmission in males or GABA transmission in either sex. Interestingly, we also found that aCIE exposure unmasked a KOR-mediated suppression of spontaneous inhibitory postsynaptic current (sIPSC) frequency and sEPSC amplitude only in males, with no effects of aCIE exposure on KOR function in females. Together, these data suggest that moderate-level adolescent ethanol exposure produces long-term changes to BLA physiology and BLA KOR function, and that these changes are sex-dependent. This is the first study to examine persistent adaptations to both BLA physiology and KOR function following adolescent alcohol exposure, and opens a broad avenue for future investigation into other neurobiological and behavioral consequences of adolescent ethanol exposure-induced disruptions of these systems.
Marine Dadabacteria exhibit genome streamlining and phototrophy-driven niche partitioning
Authors: Graham Elaina D. , Tully Benjamin J.
Published: June 2020

The remineralization of organic material via heterotrophy in the marine environment is performed by a diverse and varied group of microorganisms that can specialize in the type of organic material degraded and the niche they occupy. The marineDadabacteriaare cosmopolitan in the marine environment and belong to a candidate phylum for which there has not been a comprehensive assessment of the available genomic data to date. Here in, we assess the functional potential of the oligotrophic, marineDadabacteriain comparison to terrestrial, coastal, and subsurface members of the phylum. Our analysis reveals that the marineDadabacteriahave undergone a genome streamlining event, reducing their genome size and the nitrogen content of their DNA and predicted proteome, relative to their terrestrial counterparts. Collectively, theDadabacteriahave the potential to degrade microbial particulate organic matter, specifically peptidoglycan and phospholipids. The marineDadabacteriabelong to two clades with distinct ecological niches in global metagenomic data: a shallow clade with the potential for photoheterotrophy through the use of proteorhodopsin, present predominantly in surface waters up to 100m depth; and a deep clade lacking the potential for photoheterotrophy that is more abundant in the deep photic zone.
openPFGE: An open source and low cost pulsed-field gel electrophoresis equipment
Authors: Lagos-Susaeta Diego , Salazar Oriana , Asenjo Juan A.
Published: June 2020

DNA electrophoresis is a fundamental technique in molecular biology that allows the separation of DNA molecules up to ~50 Kbp. Pulsed-field gel electrophoresis [PFGE] is a variation of the conventional DNA electrophoresis technique that allows the separation of very large DNA molecules up to ~10 Mbp. PFGE equipment is very expensive and it becomes an access barrier to many laboratories. Also, just a few privative designs of the equipment are available and it becomes difficult for the community to improve or customize their functioning. Here, we provide an open source PFGE equipment capable of the separation of DNA molecules up to, at least, ~2 Mbp and at low cost: USD$850, about 3% of the price of typical commercial equipment.

Specifications table
Current infection control behaviour patterns in the UK, and how they can be improved by 'Germ Defence', an online behavioural intervention to reduce the spread of COVID-19 in the home.
Authors: Ainsworth Ben , Miller Sascha , Denison-Day James , Stuart Beth , Groot Julia , Rice Cathy , Bostock Jennifer , Hu Xiao-Yang , Morton Kate , Towler Lauren , Moore Michael , Willcox Merlin L , Chadborn Tim , Gold Natalie , Amlot Richard , Little Paul , Yardley Lucy
Published: June 2020

Background: Germ Defence (https://germdefence.org/) is a freely available website providing behavioural advice for infection control within households, using behaviour change techniques. This observational study reports current infection control behaviours in the home in UK and international users of the website, and examine how they might be improved to reduce the spread of COVID-19.
Method: 28,285 users sought advice from four website pathways (to protect themselves generally, to protect others if the user was showing symptoms, to protect themselves if household members were showing symptoms, and to protect a household member who is at high risk) and completed outcome measures of current infection control behaviours within the home (self-isolation, social distancing, putting shopping/packages aside, wearing face-covering, cleaning and disinfecting, handwashing), and intentions to change these behaviours.
Results: Current user behaviours mean scores varied across all infection control measures but were between 'sometimes' and 'quite often', except handwashing ('very often'). Behaviours were similar regardless of the website pathway used. After using Germ Defence, users recorded intentions to improve infection control behaviour across all website pathways and for all behaviours.
Conclusions: Self-reported infection control behaviours other than handwashing are lower than is optimal for infection prevention, although reported handwashing is much higher. The advice using behaviour change techniques in Germ Defence led to intentions to improve these behaviours. This has been shown previously to reduce the incidence, severity and transmission of infections. These findings suggest that promoting Germ Defence within national and local public health guidance could reduce COVID-19 transmission.
Impact of data-driven online financial consumption on supply chain services
Authors: Li Lei , Dai Yaxuan , Sun Yudong
Published: June 2020

Purpose

Employing big data analysis tools, this study examines the significance of supply chain integration affecting online financial consumption, analyzes the online financial consumption demand of mobile phone consumers, promotes the optimization of supply chain services with consumers as the focus and proposes full integration of a mobile phone supply chain in terms of product, logistics and marketing, in order to improve the supply and demand relationship between consumers and suppliers; the overall objective is to promote further development of online financial consumption.

Design/methodology/approach

In this study, TF-IDF (term frequency–inverse document frequency) and cosine similarity text analysis are used for analyzing online demand for mobile phone products, studying the influence of supply chain services on consumption demand and identifying strategies for promoting overall optimization of the supply chain to meet online financial consumption demands of consumers; the study analyzes online reviews on mobile phone topics from the JingDong (JD) platform and Weibo platform.

Findings

Research results show that online demand for mobile phone products is greatly influenced by supply chain links such as product design, logistics transportation and marketing promotion. The consumption demand for different mobile phone products has different emphases, but the differences are not significant. The overall improvement of the supply chain should focus on product research and development, logistics layout optimization and marketing promotion, in order to meet and guide the online financial demand of consumers and improve the effectiveness of supply chain management.

Research limitations/implications

This study only considered data from China's largest online mobile phone sales platform and Weibo text data owing to the data sensitivity involved.

Originality/value

There are few supply chain optimization studies based on online financial consumption reviews from customers. Therefore, this study integrates online consumption trends into a supply chain analysis framework to explore strategies for promoting supply chain optimization according to customer demands, improving the benign interaction of participants in the supply chain and promoting the development of online financial consumption.
Concentration and Competition in the Australian Banking Industry: A Bresnahan–Lau Structure–Conduct–Performance Assessment*
Authors: Inchauspe Julian , Cronje Tom
Published: June 2020

This study assesses the impact on competitiveness of banking takeovers in Australia, to inform regulators and contribute to the mergers and acquisitions body of international evidence. New industrial organisation theories and empirical evidence suggest that more concentration may or may not lead to decreased competition. We assess competitiveness with the Bresnahan–Lau conduct coefficient. We find that the 2008 takeover of St. George had no significant effect, whereas that of BankWest in 2012 attracted a marginally small deadweight efficiency loss. Overall, the sector is found to be fairly competitive, a result that we associate with intense price competition under low switching costs.
DNA barcoding of the South Korean Tettigoniidae (Orthoptera) using collection specimens reveals three potential species complexes
Authors: Kim Seon Yi , Kang Tae Hwa , Kim Tae Woo , Seo Hong Yul
Published: June 2020

We carried out DNA barcoding on 24 Korean tettigonid species of 19 genera deposited in the National Institute of Biological Resources to reevaluate the preliminary identification of each specimen. Sequence divergence of DNA barcodes obtained from 113 samples of the 24 species ranged from 0 to 30.4%, the intraspecific variation was 0–7.3%, and the interspecific divergence was 1.1–30.4%; we could not examine the barcoding gap. In the neighbor‐joining tree, the branch length among individuals of Tettigonia ussuriana, Paratlanticus ussuriensis, and Hexacentrus japonicus were relatively longer than those in other species. The detailed analysis of the morphological characters and DNA barcodes of the above three species revealed that these three species represent species complexes. The T. ussuriana complex comprised T. jungi, T. uvarovi, and T. ussuriana. Paratlanticus ussuriensis cluster contained four species; one cluster was identified as P. palgongensis based on morphological characteristics, but the other three clusters, including the P. ussuriensis cluster, require further detailed taxonomic analysis. Lastly, two species clusters were identified within the Hexacentrus japonicus clade. Based on the 99% sequence similarity obtained by blast search of the NCBI GenBank database, one of the clusters was identified as H. unicolor. Thus, the DNA barcoding revealed the presence of at least three cryptic species in Korean Tettigoniidae, although more detailed taxonomic analyses are required to establish their status. Therefore, we suggest that DNA barcoding is a very useful tool for increasing the identification accuracy of insect collections.
Effects of dietary choline, betaine, and L‐carnitine on the generation of trimethylamine‐N‐oxide in healthy mice
Authors: Yu Zhu‐Lin , Zhang Ling‐Yu , Jiang Xiao‐Ming , Xue Chang‐Hu , Chi Naiqiu , Zhang Tian‐Tian , Wang Yu‐Ming
Published: June 2020

Trimethylamine‐N‐oxide (TMAO) is considered to have negative effect on human health. Different precursors of TMAO, such as choline, betaine, and L‐carnitine, are commonly found in daily foods. The aim of the present study was to compare the ability of different precursors to be metabolized into TMAO, as well as the possible effect of chronic administration with TMAO precursors on TMAO production. The rate of TMAO generation after single gavage with different precursors was L‐carnitine > choline >betaine. Moreover, the serum TMAO level of mice increased more than twofold after administration with choline for 3 weeks compared with L‐carnitine and betaine groups, which was accompanied by the change of intestinal flora. After the gavage of choline chloride, the production for TMAO was 2.8 and 1.6 times higher in chronic choline‐treated group compared with L‐carnitine and betaine groups, respectively. In addition, administration with choline increased the lowest TMAO level after intraperitoneal injection of trimethylamine (TMA) hydrochloride among the three treated groups. These findings indicated that different TMAO precursors had different ability to form TMAO in vivo, and long‐term dietary intervention would affect the metabolism of precursors to generate TMA and the TMA oxidation to form TMAO, suggesting that TMAO levels in vivo could be regulated by dietary intervention.

Practical Application

Diverse TMAO precursors exhibited different ability to be converted into TMAO in vivo. The ability of choline to produce TMAO was stronger than that of betaine and L‐carnitine. Long‐term dietary intervention would affect the metabolism of precursors to generate TMA and the TMA oxidation to form TMAO, suggesting that TMAO levels in vivo could be regulated by adjustment of dietary structure.
Identification of LBX2 as a novel causal gene of lung adenocarcinoma
Authors: Hu Jingwen , Bai Yongkang , Zhang Quanli , Li Ming , Yin Rong , Xu Lin
Published: June 2020

Background

Lung adenocarcinoma (LUAD) is the most predominant histological type of lung cancer with a poor prognosis. In this study, we demonstrate that LBX2 regulates cell proliferation, migration and invasion and the potential molecular mechanism in LUAD.

Methods

The Cancer Genome Atlas dataset was accessed to screen for novel genes and immunohistochemistry (IHC) assays were performed to determine the association between LBX2 expression and clinicopathological features of LUAD. 5‐ethynyl‐2′‐deoxyuridine, colony formation and Real Time xCELLigence analysis system were used to evaluate the cell proliferation abilities of LUAD. Wound healing, transwell and Matrigel assays were used to detect cell migration and invasion capacities. Xenograft tumor models were used to assess the oncogenic role of LBX2 in vivo.

Results

We found that LBX2 was hyperexpressed in LUAD and correlated with clinicopathological features and poor prognosis in LUAD patients. Knockdown of LBX2 inhibited cell proliferation, migration and invasion of LUAD, whereas ectopic expression of LBX2 enhanced tumor growth, migration, and invasion. We further found that LBX2 might participate in epithelial‐to‐mesenchymal transition (EMT) progression and influence EMT‐related gene expression.

Conclusions

The current study suggests that LBX2 plays an oncogenic role in LUAD and may participate in tumor proliferation, migration, and invasion through EMT progression.

Key points

Significant findings of the study

LBX2 might participate in LUAD cell proliferation, migration and invasion via EMT progression.

What this study adds

LBX2 may represent a potential biomarker and a promising therapeutic target for LUAD.
Follow‐up of an occult tuberculosis scar cancer after resection of metastatic lesions
Authors: Sun Mengyao , Xu Yinghui , Wang Xu , Sun Chao , Guo Ye , Shao Guoguang , Yang Zhiguang , Liu Yunpeng , Zhang Peng , Qiu Shi , Ma Kewei
Published: June 2020

A 61‐year‐old Chinese man with a history of tuberculosis was found to have a large mass in the left lower lobe and multiple ground‐glass nodules (GGNs) on lung computed tomography (CT). Post‐operative pathology showed lung squamous carcinoma in the left lower lobe and mediastinal lymph node metastases, which were confirmed as lung adenocarcinoma. Multiple gene sequencing was performed, and no relationship was observed between the two primary sites. Chemotherapy consisting of four cycles of gemcitabine plus cisplatin were prescribed for this patient after the operation. After a period of two‐year follow‐up, the lung adenocarcinoma was found to have progressed with new metastases in the right cervical lymph nodes which had the same pathology and gene mutation as the metastatic mediastinal lymph nodes removed two years previously. Meanwhile, a primary lesion was found following PET‐CT scan, and the tuberculosis scar was determined as its point of origin. In conclusion, we have found that a tuberculosis scar is a risk factor of lung cancer, especially adenocarcinoma, and more attention should be paid to close monitoring and follow‐up by clinicians.
Out‐of‐hospital Respiratory Measures to Identify Patients With Serious Injury: A Systematic Review
Authors: Daya Mohamud R. , Cheney Tamara P. , Chou Roger , Fu Rongwei , Newgard Craig D. , O'Neil Maya E. , Wasson Ngoc , Hart Erica L. , Totten Annette M.
Published: June 2020

Objectives

The objective was to systematically review the published literature on the diagnostic accuracy of out‐of‐hospital respiratory measures for identifying patients with serious injury, focusing on measures feasible for field triage by emergency medical services personnel.

Methods

We searched Ovid MEDLINE, CINAHL, and the Cochrane databases from January 1, 1996, through August 31, 2017. We included studies on the diagnostic accuracy (sensitivity, specificity, and area under the receiver operating characteristic curve [AUROC]) for all respiratory measures used to identify patients with serious injury (resource use, serious anatomic injury, and mortality). We assessed studies for risk of bias and strength of evidence (SOE). We performed meta‐analysis for measures with sufficient data.

Results

We identified 46 articles reporting results of 44 studies. Out‐of‐hospital respiratory measures included respiratory rate, pulse oximetry, and airway support. Meta‐analysis was only possible for respiratory rate, which demonstrated a pooled sensitivity for serious injury of 13% (95% confidence interval [CI] = 5 to 29, I2 = 97.8%), specificity of 96% (95% CI = 83 to 99, I2 = 99.6%), and AUROC of 0.70 (95% CI = 0.66 to 0.79, I2 = 16.6%). For oxygen saturation, sensitivity ranged from 13% to 63%; specificity, 85% to 99%; and AUROC, 0.53 to 0.76. Need for airway support had a sensitivity of 8% to 53% and specificity of 61% to 100%; studies did not report AUROC. Across respiratory measures, the SOE was low. Other respiratory measures (pH, end‐tidal carbon dioxide [CO2], and sublingual partial pressure of CO2) were reported only in emergency department studies.

Conclusions

Data on the accuracy of out‐of‐hospital respiratory measures for field triage are limited and of low quality. Based on available research, respiratory rate, oxygen saturation, and need for airway intervention all have low sensitivity, high specificity, and poor to fair discrimination for identifying seriously injured patients.
Association Between Emergency Physician Length of Stay Rankings and Patient Characteristics
Authors: Chang Cindy Y. , Baugh Christopher W. , Brown Calvin A. , Weiner Scott G.
Published: June 2020

Objective

Emergency physicians are commonly compared by their patients’ length of stay (LOS). We test the hypothesis that LOS is associated with patient characteristics and that accounting for these features impacts physician LOS rankings.

Methods

This was a retrospective observational study of all encounters at an emergency department in 2010 to 2015. We compared the characteristics of patients seen by physicians in different quartiles of LOS. Primary outcome was variation in patient characteristics at time of physician assignment (age, sex, comorbidities, Emergency Severity Index [ESI], and chief complaint) across LOS quartiles. We also quantified the change in LOS rankings after accounting for difference in characteristics of patients seen by different physicians.

Results

A total of 264,776 encounters seen by 62 attending physicians met inclusion criteria. Physicians in the longest LOS quartile saw patients who were older (age = 49.1 vs 48.6 years, difference = +0.5 years, 95% confidence interval [CI] = 0.3 to 0.7) with more comorbidities (Gagne score = 1.3 vs. 0.9, difference = +0.4, 95% CI = 0.4 to 0.4) and higher acuity (ESI = 2.8 vs. 2.9, difference = −0.1, 95% CI = 0.1 to 0.1) than physicians in the shortest LOS quartile. The odds ratio (OR) of physicians in the longest LOS quartile seeing patients over age 50 compared to the shortest LOS quartile was 1.1 (95% CI = 1.0 to 1.1); the OR of physicians in the longest LOS quartile seeing patients with ESI of 1 or 2 was also 1.1 (95% CI = 1.0 to 1.1). Accounting for variation in patient characteristics seen by different physicians resulted in substantial reordering of physician LOS rankings: 62.9% (39/62) of physicians reclassified into a different quartile with mean absolute percentile change of 25.8 (95% CI = 20.3 to 31.3). A total of 62.5% (10/16) of physicians in the shortest LOS quartile and 56.3% (9/16) in the longest LOS quartile moved into a different quartile after accounting for variation in patient characteristics.

Conclusions

Length of stay was significantly associated with patient characteristics, and accounting for variation in patient characteristics resulted in substantial reordering of relative physician rankings by LOS. Comparisons of emergency physicians by LOS that do not account for patient characteristics should be reconsidered.
Happily partnered older adults’ relationship‐enhancing behaviours
Authors: Rahn Alison , Bennett Cary , Jones Tiffany , Lykins Amy
Published: June 2020

Objective

Relationship‐enhancing behaviours that contribute to older adults’ well‐being are scarcely considered in “active ageing” discourses despite relationship quality having been repeatedly linked to health outcomes. This paper explores such behaviours in older adults.

Methods

Cross‐sectional data were collected in 2016 from 168 partnered baby boomers (born 1946 to 1965) using an online survey. The 36 qualitative and quantitative questions were analysed using mixed methods.

Results

Participants were predominantly women (85%), with a mean age of 62 years (SD = 5.2). Relationship‐enhancing behaviours included verbal and non‐verbal cues, physical affection and pleasurable sexual activities. A couple's shared bed was an important relationship setting.

Conclusion

For happily partnered older adults, relationship quality improves personal well‐being. As a social determinant of healthy ageing, health policies and programs are needed to support older adults’ relationship quality. To this end, the development of targeted relationship interventions for delivery in health settings is warranted.
Information on early medical abortion for women using an audiovisual animation vs face‐to‐face consultation: A consortium randomized and quasi‐randomized trial
Authors: Reynolds‐Wright John J. , Belleuvre Florence , Daberius Anette , Faucher Philippe , Gemzell‐Danielsson Kristina , Cameron Sharon T.
Published: June 2020

Introduction

There is some evidence that audiovisual formats can be an effective way of providing information about early medical abortion (EMA). A short animation (3 minutes) was developed about EMA in three languages that summarized the EMA process for use in the UK, France and Sweden.

Material and methods

We conducted a multicenter randomized controlled trial to compare information on EMA delivered by an animated film vs a face‐to‐face consultation. Women requesting EMA (≤9 weeks’ gestation) from abortion clinics in Edinburgh (UK), Paris (France) and Stockholm (Sweden) were recruited. The primary outcome was women’s recall of prespecified key information on EMA. Secondary outcomes were acceptability of mode of information delivery, clarity and helpfulness of information rated on a Likert scale. The study was prospectively registered with clinicaltrials.gov, ID number: NCT03417362.

Results

172 women completed the study (Edinburgh = 50, Paris = 78, Stockholm = 48). There was no statistically significant difference in recall scores between the animation and standard arms in Edinburgh and Stockholm sites. However, the difference between arms at the Paris site was statistically significant (P = .007) in favor of the animation. All participants in the animation arm rated it as an acceptable way to receive information on EMA.

Conclusions

A “short” audiovisual animation can adequately and acceptably deliver key information about EMA. This intervention could be used routinely to provide standardized and high‐quality information to women seeking EMA.
Making the business case for corporate social responsibility and perceived trustworthiness: A cross‐stakeholder analysis
Authors: Peifer Jared L. , Newman David T.
Published: June 2020

The business case for corporate social responsibility (CSR) suggests that by doing good (i.e., engaging in CSR) a firm will do well (i.e., be profitable), and this notion has permeated the linguistic sensemaking of firm actors. But how are firms that articulate business‐case justifications evaluated by various stakeholders? We hypothesize that the way firms communicate their CSR engagement (i.e., accompanied by business‐case justifications or not) differentially impacts stakeholders’ perceived integrity, benevolence and ability trustworthiness of the firm. Conducting the same online experiment with two separate samples from the United States, we replicate three results; business‐case justification for CSR reduces benevolence trustworthiness among employees, increases ability trustworthiness among investors, and has no effect on perceived trustworthiness among consumers. We discuss the implications of our findings for the CSR literature and encourage future researchers to more carefully scrutinize the implications of justifying CSR with the business case.
Non‐invasive and surgical penile enhancement interventions for aesthetic or therapeutic purposes: a systematic review
Authors: Romero‐Otero Javier , Manfredi Celeste , Ralph David , Osmonov Daniar , Verze Paolo , Castiglione Fabio , Serefoglu Ege Can , Bozzini Giorgio , García‐Gómez Borja
Published: June 2020

Objective

To systematically review the literature in order to investigate the efficacy and safety of surgical and non‐invasive penile enhancement procedures for aesthetic and therapeutic purposes.

Methods

A systematic search for papers investigating penile enhancement procedures was performed using the MEDLINE database. Articles published from January 2010 to December 2019, written in English, including >10 cases, and reporting objective length and/or girth outcomes, were included. Studies without primary data and conference abstracts were excluded. The main outcome measure was objective length and/or girth improvement. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement.

Results

Out of 220 unique records, a total of 57 were reviewed. Eighteen studies assessed interventions for penile enhancement in 1764 healthy men complaining of small penis. Thirty‐nine studies investigated 2587 men with concomitant pathologies consisting mostly of Peyronie's disease and erectile dysfunction. Twenty‐five studies evaluated non‐invasive interventions and 32 studies assessed surgical interventions, for a total of 2192 and 2159 men, respectively. Non‐invasive interventions, including traction therapies and injection of fillers, were safe and mostly efficacious, whereas surgical interventions were associated with minor complications and mostly increased penile dimensions and/or corrected penile curvature. Overall, the quality of studies was low, and standardized criteria to evaluate and report efficacy and safety of procedures, as well as patient satisfaction, were missing.

Conclusion

The quality of the studies on penile enhancement procedures published in the last decade is still low. This prevents us from establishing recommendations based on scientific evidence regarding the efficacy and safety of interventions that are performed to increase the penis size for aesthetic or therapeutic indications.
Modelling neurodegenerative diseases with 3D brain organoids
Authors: Chang Yujung , Kim Junyeop , Park Hanseul , Choi Hwan , Kim Jongpil
Published: June 2020

Neurodegenerative diseases are incurable and debilitating conditions characterized by the deterioration of brain function. Most brain disease models rely on human post‐mortem brain tissue, non‐human primate tissue, or in vitro two‐dimensional (2D) experiments. Resource limitations and the complexity of the human brain are some of the reasons that make suitable human neurodegenerative disease models inaccessible. However, recently developed three‐dimensional (3D) brain organoids derived from pluripotent stem cells (PSCs), including embryonic stem cells and induced PSCs, may provide suitable models for the study of the pathological features of neurodegenerative diseases. In this review, we provide an overview of existing 3D brain organoid models and discuss recent advances in organoid technology that have increased our understanding of brain development. Moreover, we explain how 3D organoid models recapitulate aspects of specific neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, and explore the utility of these models, for therapeutic applications.
Reduced survival in patients who return to dialysis after kidney allograft failure
Authors: Bisigniano Liliana , Laham Gustavo , Giordani Maria Cora , Tagliafichi Viviana , Hansen Krogh Daniela , Maceira Alberto , Rosa‐Diez Guillermo Javier
Published: June 2020

Background

The outcome of patients who return to dialysis after Kidney allograft failure (KAF) remains unclear. Our aim was to compare the outcome of KAF patients vs two different types of transplant naive incident dialysis (TNID) patients, those on the waiting list (WL) and those with a kidney transplant contraindication (KTC).

Methods

We performed an observational study using data from the Argentinian Dialysis Registry between 2005 and 2016. We compare mortality between KAF, WL, and KTC.

Results

We included 75 722 patients of which 2734 were KAF. Survival between the three cohorts (KAF vs WL (n = 14 630) vs KTC (n = 58 358) revealed a significant difference (log‐rank test: P < .0001) indicating worse survival for KTC patients and best survival for WL. We found that KAF patients had as poor outcome as KTC patients after multivariate adjustment. Cox regression showed that age >65 years: HR: 1.845 (1.79‐1.89) P < .0001, transient catheter: HR: 1.303 (1.26‐1.34) P < .0001, diabetic: HR: 1.273 (1.22‐1.31) P < .0001, hepatitis C: HR: 1.156 (1.09‐1.22) P < .0001, and albumin: HR: 1.247 (1.21‐1.28) P < .0001 were associated with mortality.

Conclusion

Patients who return to dialysis after KAF have higher mortality than WL patients and similar to KTC patients.
Moving attention along the mental number line in preschool age: Study of the operational momentum in 3‐ to 5‐year‐old children's non‐symbolic arithmetic
Authors: Haman Maciej , Lipowska Katarzyna
Published: June 2020

People tend to underestimate subtraction and overestimate addition outcomes and to associate subtraction with the left side and addition with the right side. These two phenomena are collectively labeled 'operational momentum' (OM) and thought to have their origins in the same mechanism of 'moving attention along the mental number line'. OM in arithmetic has never been tested in children at the preschool age, which is critical for numerical development. In this study, 3–5 years old were tested with non‐symbolic addition and subtraction tasks. Their level of understanding of counting principles (CP) was assessed using the give‐a‐number task. When the second operand's cardinality was 5 or 6 (Experiment 1), the child's reaction time was shorter in addition/subtraction tasks after cuing attention appropriately to the right/left. Adding/subtracting one element (Experiment 2) revealed a more complex developmental pattern. Before acquiring CP, the children showed generalized overestimation bias. Underestimation in addition and overestimation in subtraction emerged only after mastering CP. No clear spatial‐directional OM pattern was found, however, the response time to rightward/leftward cues in addition/subtraction again depended on stage of mastering CP. Although the results support the hypothesis about engagement of spatial attention in early numerical processing, they point to at least partial independence of the spatial‐directional and magnitude OM. This undermines the canonical version of the number line‐based hypothesis. Mapping numerical magnitudes to space may be a complex process that undergoes reorganization during the period of acquisition of symbolic representations of numbers. Some hypotheses concerning the role of spatial‐numerical associations in numerical development are proposed.