bluuebunny/crossref_metadata_2025 huggingface dataset:
A quantum-enhanced precision medicine application to support data-driven clinical decisions for the personalized treatment of advanced knee osteoarthritis: development and preliminary validation of precisionKNEE_QNN
Authors: Heidari Nima , Olgiati Stefano , Meloni Davide , Pirovano Federico , Noorani Ali , Slevin Mark , Azamfirei Leonard
Published: December 2021

Background

The clinical problem of knee osteoarthritis is that, although some novel therapies are safe and effective, the response is variable, and defining the features that predict individual response remains a challenge. Variational quantum-classical and quantum machine learning (QML) algorithms based on parameterized quantum circuits (PQC) are promising experimental technologies which can improve the efficiency of precision medicine clinical decision support systems (CDSS) based on real-world data stored in large unstructured databases. In this paper we tested a quantum neural network (QNN) application to support precision data-driven clinical decisions to select personalized treatments for advanced knee osteoarthritis.

Methods

Following patients’ consent and Research Ethics Committee approval, we collected clinico-demographic data before and after the treatment from 170 patients eligible for knee arthroplasty (Kellgren-Lawrence grade ≥ 3, OKS ≤ 27, Age ≥ 64 and idiopathic aetiology of arthritis) treated over a 2 year period with a single injection of microfragmented fat. Gender classes were balanced (76 M, 94 F) to mitigate gender bias. A patient with an improvement ≥ 7 OKS has been considered a Responder. We trained our QNN Classifier on a randomly selected training subset of 113 patients to classify responders from non-responders (73 R, 40 NR) in pain and function at 1 year. Outliers were hidden from the training dataset but not from the validation set. We ran our QNN Classifier on a IBM quantum simulator to reduce the error due to noise.

Results

We tested our QNN Classifier on a randomly selected test subset of 57 patients (34 R, 23 NR) including outliers. The No Information Rate was equal to 0.59. Our application correctly classified 28 Responders out of 34 and 6 non-Responders out of 23 (Sensitivity = 0.82, Specificity = 0.26, F1 Statistic= 0.71). The Positive (LR+) and Negative (LR-) Likelihood Ratios were respectively 1.11 and 0.68. The Diagnostic Odds Ratio (DOR) was equal to 2.

Conclusions

Preliminary clinical and technical results of a QNN Classifier tested on a relatively small knee osteoarthritis dataset show that quantum machine learning applied to data-driven clinical decisions is a promising technology. Our results need further research validation with larger, real-world unstructured datasets, and clinical validation with an AI Clinical Trial to test model efficacy, safety, clinical significance and relevance at a public health level.
Residual insecticide surface treatment for preventing malaria: a systematic review protocol
Authors: Munn Zachary , Stone Jennifer C. , Barker Timothy Hugh , Price Carrie , Pollock Danielle , Kabaghe Alinune Nathanael , Gimnig John E. , Stevenson Jennifer C.
Published: December 2021

Introduction

Malaria presents a significant global public health burden, although substantial progress has been made, with vector control initiatives such as indoor residual surface spraying with insecticides and insecticide treated nets. There now exists many different approaches to apply residual insecticide to indoor and outdoor surfaces in malaria endemic settings. This review aims to synthesise the best available evidence regarding full or partial indoor or outdoor residual insecticide surface treatment for preventing malaria.

Methods and Analysis

This review will comprehensively search the literature (both published and unpublished) for any studies investigating the effectiveness of residual insecticide surface treatment for malaria. Studies will be screened to meet the inclusion criteria by a minimum of two authors, followed by assessment of risk of bias (using appropriate risk of bias tools for randomised and non-randomised studies) and extraction of relevant information using structured forms by two independent authors. Meta-analysis will be carried out where possible for epidemiological outcomes such as malaria, anaemia, malaria related mortality, all-cause mortality and adverse effects. Certainty in the evidence will be established with GRADE assessments.

Ethics and Dissemination

A full review report will be submitted to the Vector Control & Insecticide Resistance Unit, Global Malaria Program, WHO. A version of this report will be submitted for publication in an open access peer-reviewed journal. The report will inform the development of WHO recommendations regarding residual insecticide treatment for malaria. This systematic review does not require ethics approval as it is a review of primary studies.

Registration

PROSPERO, ID 293194 (in progress as of 24thNovember, 2021)
Genuine Selective Caspase-2 Inhibition with new Irreversible Small Peptidomimetics
Authors: Bosc Elodie , Anastasie Julie , Soualmia Feryel , Coric Pascale , Kim Ju Youn , Lacin Gullen , Duplus Eric , Tixador Philippe , Brugg Bernard , Reboud-Ravaux Michelle , Bouaziz Serge , Karin Michael , El Amri Chahrazade , Jacotot Etienne
Published: December 2021

Caspase-2 (Casp2) is a promising therapeutic target in several human diseases including nonalcoholic steatohepatitis (NASH) and Alzheimer’s disease (AD). However, the design of active-site-directed inhibitor selective to individual caspase family members is challenging because caspases have extremely similar active sites. Here we present new peptidomimetics derived from the VDVAD pentapeptide structure, harboring non-natural modifications at the P2 position and an irreversible warhead. Enzyme kinetics shows that these new compounds, such as LJ2 or its specific isomer LJ2a, and LJ3a, strongly and irreversibly inhibit Casp2 with genuine selectivity. According to Casp2 role in cellular stress responses, LJ2 inhibits cell death induced by microtubule destabilization or hydroxamic acid-based deacetylase inhibition. The most potent peptidomimetic, LJ2a, inhibits human Casp2 with a remarkably high inactivation rate (k3/Ki ~ 5 500 000 M−1s−1) and the most selective inhibitor, LJ3a, has a near to 1000 times higher inactivation rate on Casp2 as compared to Casp3. Structural analysis of LJ3a shows that spatial configuration of Cα at the P2 position determines inhibitor efficacy. In transfected human cell lines overexpressing site-1 protease (S1P), sterol regulatory element-binding protein 2 (SREBP2) and Casp2, LJ2a and LJ3a fully inhibit SREBP2 activation, suggesting a potential to prevent NASH development. Furthermore, in primary hippocampal neurons treated with β-amyloid oligomers, submicromolar concentrations of LJ2a and of LJ3a prevent synapse loss, indicating a potential for further investigations in AD treatment.
A novel framework for analysis of the shared genetic background of correlated traits
Authors: Svishcheva Gulnara R. , Tiys Evgeny S. , Elgaeva Elizaveta E. , Feoktistova Sofia G. , Timmers Paul R. H. J. , Sharapov Sodbo Zh. , Axenovich Tatiana I. , Tsepilov Yakov A.
Published: December 2021

We propose a novel effective framework for analysis of the shared genetic background for a set of genetically correlated traits using SNP-level GWAS summary statistics. This framework called SHAHER is based on the construction of a linear combination of traits by maximizing the proportion of its genetic variance explained by the shared genetic factors. SHAHER requires only full GWAS summary statistics and matrices of genetic and phenotypic correlations between traits as inputs. Our framework allows both shared and unshared genetic factors to be to effectively analyzed. We tested our framework using simulation studies, compared it with previous developments, and assessed its performance using three real datasets: anthropometric traits, psychiatric conditions and lipid concentrations. SHAHER is versatile and applicable to summary statistics from GWASs with arbitrary sample sizes and sample overlaps, allows incorporation of different GWAS models (Cox, linear and logistic) and is computationally fast.
Introduction ofloxPsites by electroporation in the mouse genome; a simple approach for conditional allele generation in complex targeting loci
Authors: Bernas Guillaume , Ouellet Mariette , Barrios Andréa , Jamann Hélène , Larochelle Catherine , Lévy Émile , Schmouth Jean-François
Published: December 2021

Background

The discovery of the CRISPR-Cas9 system and its applicability in mammalian embryos has revolutionized the way we generate genetically engineered animal models. To date, models harbouring conditional alleles (i.e.: twoloxPsites flanking an exon or a critical DNA sequence of interest) remain the most challenging to generate as they require simultaneous cleavage of the genome using two guides in order to properly integrate the repair template. In the current manuscript, we describe a modification of the sequential electroporation procedure described by Horiiet al(2017). We demonstrate production of conditional allele mouse models for eight different genes via one of two alternative strategies: either by consecutive sequential electroporation (strategy A) or non-consecutive sequential electroporation (strategy B).

Results

By using strategy A, we demonstrated successful generation of conditional allele models for three different genes (Icam1, Lox, andSar1b), with targeting efficiencies varying between 5 to 13%. By using strategy B, we generated five conditional allele models (Loxl1, Pard6a, Pard6g, Clcf1, andMapkapk5), with targeting efficiencies varying between 3 to 25%.

Conclusion

Our modified electroporation-based approach, involving one of the two alternative strategies, allowed the production of conditional allele models for eight different genes via two different possible paths. This reproducible method will serve as another reliable approach in addition to other well-established methodologies in the literature for conditional allele mouse model generation.
In silico evidence of superantigenic features in ORF8 protein from COVID-19
Authors: Gómez-Icazbalceta Guillermo , Hussain Zubair , Vélez-Alavez Marcela
Published: December 2021

Very early on COVID-19 pandemic outbreak, it was noted that the some of the virus-induced clinical conditions resembled features of toxaemia caused by the toxic shock syndrome toxin type 1, which is a soluble superantigen produced byStaphylococcus aureus. Among all SARS proteins, the ORF8 protein from SARS-2 virus is significantly different from other known SARS-like coronaviruses, and therefore could exhibit unique pathogenic properties. We assess if ORF8 protein bears super antigenic features usingin silicotools. We show that ORF8 has properties of an extracellular soluble protein and shares a significant degree of amino acid sequence identity with toxic shock syndrome toxin. Besides, docking and binding affinity analyses between monomeric and homodimeric ORF-8 with Vβ 2.1 and TRBV11-2 reveal strong interaction and high binding affinity. ORF8-TRBV11-2 strong interaction can contribute to the observed clonal expansion of that chain during COVID-19-associated multisystem inflammatory syndrome. Taken together, the evidence presented here supports the hypothesis that ORF8 protein from SARS-2 bears super antigenic properties.
Connectome-wide association analysis identified significant brain functional alteration in adults with attention-deficit/hyperactivity disorder
Authors: Liu Lu , Chen Di , Huang Fang , Jia Tianye , Pan Meirong , Zhao Mengjie , Bu Xuan , Wang Yufeng , Cao Miao , Qian Qiujin , Feng Jianfeng
Published: December 2021

Adults with attention-deficit/hyperactivity disorder (ADHD), as an extreme-phenotype of ADHD, is still facing problems of inconsistency and undeciphered mechanisms for its neuropathology. To address this matter, our present study performed connecotome-wide voxel-based analyses with the resting-state fMRI data of 84 adults with ADHD and 89 healthy controls. We found that functional connectivity patterns of the left precuneus and the left middle temporal significantly altered in ADHD populations serving as potential neural biomarkers to distinguish ADHD with healthy controls, with subsequent seed-based analysis revealing the dysfunction of functional connections both intra- and inter-default mode and attention networks, among which middle temporal gyrus plays the key role of ‘bridge’ linking the default mode and attention networks. After cognitive behavioral therapy, two of these ADHD-altered functional connections ameliorated accompanied with improvement of ADHD core symptoms. Additionally, imaging genetic analyses also revealed close relationships between the observed brain functional alterations and ADHD-risk genes. Taken together, our findings suggested the interference of default mode on attention networks in adults with ADHD, which would be severing as a potential biomarker for both ADHD pathogenesis and treatment effects.
Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2
Authors: Li Changzhi , Zhou Hongjuan , Guo Lingling , Xie Dehuan , He Huiping , Zhang Hong , Liu Yixiu , Peng Lixia , Zheng Lisheng , Lu Wenhua , Mei Yan , Liu Zhijie , Huang Jie , Wang Mingdian , Shu Ditian , Ding Liuyan , Lang Yanhong , Luo Feifei , Wang Jing , Huang Bijun , Huang Peng , Gao Song , Chen Jindong , Qian Chao-Nan
Published: December 2021

The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social and economic stability. In this study, we established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus S protein and its host receptor ACE2. This platform is a rapid, sensitive, specific, and high throughput system. With this platform, we screened two compound libraries of 2,864 molecules and identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S-protein and the human cell ACE2 receptor. This data suggests that TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug.

SIGNIFICANCE

The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19. In this present study, we screened two compound libraries of 2,864 molecules and identified a potent inhibitor (TS-984) for blocking the coronavirus S-protein and the human cell ACE2 receptor. TS-984 might have the potential to be developed into an effective anti-coronavirus drug for treating COVID-19.
A unified model for the biogenesis of mitochondrial outer membrane multi-span proteins
Authors: Zhou Jialin , Jung Martin , Dimmer Kai S. , Rapaport Doron
Published: December 2021

The mitochondrial outer membrane (MOM) harbors proteins that traverse the membrane via several helical segments, so-called multi-span proteins. Two contradicting mechanisms were suggested to describe their integration into the MOM. The first proposes that the mitochondrial import (MIM) complex facilitates this process and functions as an insertase, whereas the second suggests that such proteins can integrate into the lipid phase without the assistance of import factors in a process that is enhanced by phosphatidic acid. To resolve this discrepancy and obtain new insights on the biogenesis of these proteins, we addressed this issue using yeast mitochondria and the multi-span protein Om14. Testing different truncation variants, we show that only the full-length protein contains all the required information that assure targeting specificity. Employing a specific insertion assay and several single and double deletion strains, we show that neither the import receptor Tom70 nor any other protein with a cytosolically exposed domain have a crucial contribution to the biogenesis process. We further demonstrate that Mim1 and Porin are required for optimal membrane integration of Om14 but none of them is absolutely required. Unfolding of the newly synthesized protein, its optimal hydrophobicity, as well as higher fluidity of the membrane dramatically enhanced the import capacity of Om14. Collectively, our findings suggest that MOM multi-span proteins can follow different biogenesis pathways in which proteinaceous elements and membrane behavior contribute to a variable extent to the combined efficiency.

Zhou et al. provide new insights to the biogenesis of mitochondrial outer membrane proteins. They demonstrate that such proteins can follow various routes where both proteinaceous elements and membrane behavior regulate the efficiency and specificity of this process.
Institutional ethnoracial discrimination and microaggressions among a diverse sample of undergraduates at a minority-serving university: a gendered racism approach
Authors: Lui Florence , Anglin Deidre M.
Published: December 2021

Purpose

Ethnoracial minorities report a variety of discriminatory experiences due to systemic racism. Yet, few studies have examined whether gender and race/ethnicity interact to predict institutional discrimination and racial microaggressions through an intersectional approach.

Design/methodology/approach

A predominantly female (60%), ethnoracial minority (20.8% Black, 31.6% Asian, 30.8% Latina/o, 8.2% White, 6.6% Middle Eastern) sample of 895 undergraduates attending a minority-serving public university in an urban setting completed self-report measures of sociodemographic characteristics, experiences of racial microaggressions and institutional discrimination.

Findings

Significant (p < 0.05) gender × race/ethnicity interaction effects were found in several institutional discrimination domains: Males reported more police/court discrimination overall, but gender differences in police/court discrimination were less pronounced for non-Black vs Black students. While males tended to report more institutional discrimination than females, the reverse was true for the Middle Eastern group: Middle Eastern females reported institutional discrimination in more domains and more discrimination getting hired than their male counterparts. There was a significant race/ethnicity × gender interaction effect for environmental microaggressions: White males reported more environmental microaggressions than White females, but gender differences were not found in the overall sample.

Originality/value

This study is the first to the authors’ knowledge to assess the interactive effects of gender and ethnicity on the type of microaggressions experienced in a diverse sample that includes individuals of Middle Eastern descent. The authors highlight the range of discriminatory events that ethnoracially minoritized undergraduates experience, even at a minority-serving institution.
A relationship between bias, lean tools, and waste
Authors: Purushothaman Mahesh Babu , Seadon Jeff , Moore Dave
Published: December 2021

Purpose

This study aims to highlight the system-wide potential relationships between forms of human bias, selected Lean tools and types of waste in a manufacturing process.

Design/methodology/approach

A longitudinal single-site ethnographic case study using digital processing to make a material receiving process Lean was adopted. An inherent knowledge process with internal stakeholders in a stimulated situation alongside process requirements was performed to achieve quality data collection. The results of the narrative analysis and process observation, combined with a literature review identified widely used Lean tools, wastes and biases that produced a model for the relationships.

Findings

The study established the relationships between bias, Lean tools and wastes which enabled 97.6% error reduction, improved on-time accounting and eliminated three working hours per day. These savings resulted in seven employees being redeployed to new areas with delivery time for products reduced by seven days.

Research limitations/implications

The single site case study with a supporting literature survey underpinning the model would benefit from testing the model in application to different industries and locations.

Practical implications

Application of the model can identify potential relationships between a group of human biases, 25 Lean tools and 10 types of wastes in Lean manufacturing processes that support decision makers and line managers in productivity improvement. The model can be used to identify potential relationships between forms of human biases, Lean tools and types of wastes in Lean manufacturing processes and take suitable remedial actions. The influence of biases and the model could be used as a basis to counter implementation barriers and reduce system-wide wastes.

Originality/value

To the best of the authors’ knowledge, this is the first study that connects the cognitive perspectives of Lean business processes with waste production and human biases. As part of the process, a relationship model is derived.
Investigating the role of employee psychological well-being and psychological empowerment with relation to work engagement and sustainable employability
Authors: Rahi Samar
Published: December 2021

Purpose

This study aims to gain insight into how employee psychological and human resource (HR) practices impact employee work engagement behavior. In addition to that, the research model of this study has tested the moderating relationship of affective employee commitment between employee work engagement and sustainable employability.

Design/methodology/approach

The research model is empirically tested with data set of 311 responses retrieved from an employee working in private organizations. Sample size of this study is computed with prior power analysis. Data were analyzed with partial least square-based structural equation modeling (SEM).

Findings

Findings of the SEM revealed that altogether psychological well-being, psychological empowerment, HR compensation, HR training, transformational leadership and job enrichment have explainedR266.1% variance in employee work engagement. Concerning individual impact size psychological well-being has shown medium level effect size (f2) in measuring employee work engagement. However, all other exogenous variables have shown a small effect in determining employee work engagement. The moderating effect of commitment is confirmed in such a way that the relationship between employee work engagement and sustainable employability will be higher when affective commitment is higher.

Practical implications

This research has synthesized HR literature into four core dimensions of HR practices and, hence contributes to HR literature. Similarly, this research contributes to well-being theory while integrating employee psychological well-being into the research model. For HR practitioners this research revealed that psychological well-being, psychological empowerment, affective employee commitment, transformational leadership, HR compensation and HR training are core factors, which influence employee behavior toward work engagement and sustainable employability.

Originality/value

The current research is unique as it investigates sustainable employability phenomenon with an integrated research model that combines employee psychological and HR factors. The concept of sustainable employability is less studied, and therefore this research fills the research gap in this context.
Impact of media multitasking on executive function in adolescents: behavioral and self-reported evidence from a one-year longitudinal study
Authors: Luo Jiutong , Yeung Pui-Sze , Li Hui
Published: December 2021

Purpose

The longitudinal impact of media multitasking on the development of executive function has been understudied, as most of the existing studies are cross-sectional. This longitudinal study addresses this research gap and uses multiple measures, i.e. behavioral and self-reported, to explore the impact of media multitasking on the executive function of Chinese adolescents.

Design/methodology/approach

This study followed 99 Chinese adolescents (Mage = 14.41, SD = 1.10; 42 boys and 57 girls) for one year using both behavioral (2-back, Stroop Color and Number-letter tasks) and self-reported (questionnaire) measures. The adolescents were categorized as either heavy/high media multitaskers (HMMs; 19 boys and 29 girls) or light/low media multitaskers (LMMs; 23 boys and 28 girls). They were tested at baseline, 6 months later and 12 months later.

Findings

The results indicated that the accuracy scores for all cognitive tasks differed with age, but the switch-cost in the shifting task and the self-reported measures of executive function did not. And there were consistent differences between the HMMs and LMMs in the self-reported measures and 2-back accuracy. However, the interaction effect was found only in shifting ability, indicating a decline in the LMMs' self-reported problematic shifting behavior in daily life.

Originality/value

This study used behavioral and self-reported measures to confirm the longitudinal impact of media multitasking on executive function. The impact of media multitasking on executive function is more apparent in daily-life behavior than in cognitive task performance.
Elastic properties and litho‐fluid facies estimation from pre‐stack seismic data through bidirectional long short‐term memory networks
Authors: Aleardi Mattia
Published: December 2021

One of the main goals of pre‐stack seismic inversion is the estimation of elastic properties (i.e. P‐, S‐ wave velocities and density) and litho‐fluid classes in the investigated area. To this end, many inversion strategies have been proposed, but the most popular is based on a two‐step inversion approach: First, elastic properties are inferred from pre‐stack data, and then a classification algorithm is used to convert the outcomes of the first stage into litho‐fluid facies. In this work, we propose an alternative approach based on recurrent neural networks. We train two bidirectional long short‐term memory networks to predict the inverse mappings from pre‐stack seismic data to elastic properties, and litho‐fluid classes. In the elastic inversion, we also use a Monte Carlo simulation approach to properly propagate onto the model space both the uncertainties related to noise contamination in the data and to the modelling error introduced by the network approximation. One crucial aspect of any machine‐learning inversion strategy is the definition of an appropriate training set. In this case, the models forming the training and validation examples are drawn according to a previously defined elastic and facies prior models derived from actual well log recordings. In particular, we assume a Gaussian‐mixture elastic prior, and we also take into account the uncertainties affecting the estimation of the transition probabilities of facies. We invert each seismic gather independently, and in this context, the generation of the training set, and the learning process can be accomplished with a very limited computational effort on a common notebook. Once trained, the networks estimate the elastic properties, the litho‐fluid facies and the related uncertainties from the pre‐stack data in near real‐time. Synthetic and field data inversions are used to validate the proposed method. The network predictions are also benchmarked against the outcomes of a more standard two‐step approach that combines a linear elastic inversion and a subsequent point‐wise Bayesian classification. Our results demonstrate that the implemented algorithm guarantees more accurate elastic property estimations and facies predictions than the standard inversion strategy. In particular, the predictions provided by the long short‐term memory network are less affected by erroneous assumptions on the noise statistics and prior model and by errors in the estimated source wavelet.
Ultrasound‐guided multiple‐injection costotransverse block for mastectomy and primary reconstructive surgery. A study protocol
Authors: Holm Ulrik H. U. , Andersen Christian H. S. , Hansen Christian K. , Tanggaard Katrine , Børglum Jens , Nielsen Martin Vedel
Published: December 2021

Background

Post‐operative pain amelioration following breast cancer surgery is inconsistent. The novel multiple‐injection costotransverse block (MICB) mimics the thoracic paravertebral block by possible anaesthetising the ventral rami of the thoracic spinal nerves and the sympathetic trunk. Proof of concept has been determined in a cadaveric study and needs further clinical testing.

Methods

This double‐blinded, randomised and placebo‐controlled study investigates the efficacy of the ultrasound‐guided MICB versus placebo in 36 patients undergoing unilateral mastectomy and primary subpectoral reconstruction surgery. Oral pre‐operative medicine is standardised for all patients. Active group is pre‐operatively administered MICB with three injections of each 10 ml of ropivacaine (5 mg/ml). The placebo group is pre‐operatively administered three injections of each 10 ml of saline (0.9%). Standard general anaesthesia is induced and 30 min before emergence 0.2 μg/kg total body weight sufentanil IV, 1 g of paracetamol IV and 4 mg of ondansetron IV (post‐operative nausea and vomiting, PONV, prophylaxis) will be administered. All patients are provided with a patient‐controlled analgesia pump with morphine. The primary aim is total morphine consumption in the first 24 post‐operative hours. Secondary aims are pain intensity, duration of the block, patient satisfaction, side effects, time to ambulation, time to discharge, and quality of recovery.

Discussion

Recruitment began in November 2019 and is expected to finish ultimo 2021. Results are expected to be published in an international peer‐reviewed medical journal. The results will hopefully provide a substantial contribution to the knowledge of these new ‘intertransverse process blocks’ providing regional anaesthesia of the thoracic wall.
Profiling of extracellular vesicle‐bound miRNA to identify candidate biomarkers of chronic alcohol drinking in nonhuman primates
Authors: Lewis Sloan A. , Doratt Brianna , Sureshchandra Suhas , Pan Tianyu , Gonzales Steven W. , Shen Weining , Grant Kathleen A. , Messaoudi Ilhem
Published: December 2021

Background

Long‐term alcohol drinking is associated with numerous health complications including susceptibility to infection, cancer, and organ damage. However, due to the complex nature of human drinking behavior, it has been challenging to identify reliable biomarkers of alcohol drinking behavior prior to signs of overt organ damage. Recently, extracellular vesicle‐bound microRNAs (EV‐miRNAs) have been found to be consistent biomarkers of conditions that include cancer and liver disease.

Methods

In this study, we profiled the plasma EV‐miRNA content by miRNA‐Seq from 80 nonhuman primates after 12 months of voluntary alcohol drinking.

Results

We identified a list of up‐ and downregulated EV‐miRNA candidate biomarkers of heavy drinking and those positively correlated with ethanol dose. We overexpressed these candidate miRNAs in control primary peripheral immune cells to assess their potential functional mechanisms. We found that overexpression of miR‐155, miR‐154, miR‐34c, miR‐450a, and miR‐204 led to increased production of the inflammatory cytokines TNFα or IL‐6 in peripheral blood mononuclear cells after stimulation.

Conclusion

This exploratory study identified several EV‐miRNAs that could serve as biomarkers of long‐term alcohol drinking and provide a mechanism to explain alcohol‐induced peripheral inflammation.
PolyI:C attenuates transforming growth factor‐β signaling to induce cytostasis of surrounding cells by secreted factors in triple‐negative breast cancer
Authors: Tamura Yusuke , Tsutsumi Shuichi , Miyazono Kohei , Koinuma Daizo
Published: December 2021

The activation of RIG‐I‐like receptor (RLR) signaling in cancer cells is widely recognized as a critical cancer therapy method. The expected mechanism of RLR ligand‐mediated cancer therapy involves the promotion of cancer cell death and strong induction of interferon (IFN)‐β that affects the tumor microenvironment. We have recently shown that activation of RLR signaling in triple‐negative breast cancer cells (TNBC) attenuates transforming growth factor‐β (TGF‐β) signaling, which partly contributes to the promotion of cancer cell pyroptosis. However, the consequences of suppression of TGF‐β signaling by RLR ligands with respect to IFN‐β‐mediated tumor suppression are not well characterized. This study showed that transfection of a typical RLR ligand polyI:C in cancer cells produces significant levels of IFN‐β, which inhibits the growth of the surrounding cancer cells. In addition, IFN‐β‐induced cell cycle arrest in surrounding cancer cells was inhibited by the expression of constitutively active Smad3. Constitutively active Smad3 suppresses IFN‐β expression through the alleviation of IFN regulatory factor 3 binding to the canonical target genes, as suggested by ChIP sequencing analysis. Based on these findings, a new facet of the protumorigenic function of TGF‐β that suppresses IFN‐β expression is suggested when RLR‐mediated cancer treatment is used in TNBC.
The post‐war generation remembers: A mixed‐method study exploring children’s attitudes towards World War II commemoration
Authors: Mitima‐Verloop Huibertha B. , Boelen Paul A. , Mooren Trudy T. M.
Published: December 2021

This study investigated how children, a post‐war generation without direct connection to war, relate to the commemoration of World War II (WWII). Seven group interviews were held among pupils in the Netherlands, aged 9 to 18 (n = 55) and, subsequently, questionnaires were administered to other pupils (n = 374). Results revealed that children are affected by the collective narrative of WWII, and connect to commemoration on a social and emotional level. Comprehension, tangibility, inclusiveness and a right atmosphere are key elements to appreciate a commemoration. Insights from this study may help societies practice more appealing remembrances with post‐war generations.
Rational Redundancy in Referring Expressions: Evidence from Event‐related Potentials
Authors: Tourtouri Elli N. , Delogu Francesca , Crocker Matthew W.
Published: December 2021

In referential communication, Grice's Maxim of Quantity is thought to imply that utterances conveying unnecessary information should incur comprehension difficulties. There is, however, considerable evidence that speakers frequently encode redundant information in their referring expressions, raising the question as to whether such overspecifications hinder listeners’ processing. Evidence from previous work is inconclusive, and mostly comes from offline studies. In this article, we present two event‐related potential (ERP) experiments, investigating the real‐time comprehension of referring expressions that contain redundant adjectives in complex visual contexts. Our findings provide support for both Gricean and bounded‐rational accounts. We argue that these seemingly incompatible results can be reconciled if common ground is taken into account. We propose a bounded‐rational account of overspecification, according to which even redundant words can be beneficial to comprehension to the extent that they facilitate the reduction of listeners’ uncertainty regarding the target referent.
Trends in an emerging artisanal fishery of the African cyprinid Rastrineobola argentea in Lake Nabugabo, Uganda
Authors: Groves Veronica , Sharpe Diana M. T. , Nkalubo Winnie , Chapman Lauren J.
Published: December 2021

Fishing pressure can have strong impacts on fish populations, driving declines in abundance and, occasionally, changing life history traits. However, much of our current understanding of these phenomena derives from studies conducted decades or even centuries after the onset of fishing. Newly established fisheries provide an excellent opportunity to understand this critical early phase. Temporal trends in catch data and life history traits of the cyprinid fish Rastrineobola argentea (Pellegrin), now the target of a burgeoning artisanal fishery in Lake Nabugabo, Uganda, were analysed. Results showed that the R. argentea fishery intensified and became more selective during the first decade since its establishment (2008–2019), while catch‐per‐unit‐effort of R. argentea (fisheries‐independent abundance) at repeatedly sampled sites in the lake decreased over this same time period. Size‐adjusted egg volume and ovary mass increased significantly over the time period, which may reflect a density‐dependent response to a fisheries‐induced population decline.
Salvage of infected tunneled hemodialysis catheters using 70% ethanol lock solution: A brief report
Authors: Visweswaran Kasi , Ravi Ranjani , Daniel David Jasper , Krishnaswamy Sampathkumar , Akhil Remyasri
Published: December 2021

Tunneled hemodialysis catheters are the lifeline to patients on maintenance hemodialysis with failed arteriovenous fistulas. However, thrombosis and infection are the main causes of reduced longevity of these accesses. According to IDSA guidelines, catheter‐related infection with Pseudomonas and fungi are absolute indications for catheter removal. Considering the cost and difficulties in catheter replacement, for those in whom all accesses are exhausted, retaining the same catheter may be lifesaving. We would like to present two patients in whom, 70% ethanol instillation was used to eradicate infection with these organisms as confirmed by repeat cultures post procedure. Hemodialysis is being successfully continued through the same catheter.
Administration of adipose stromal vascular fraction attenuates acute rejection in donation after circulatory death rat renal transplantation
Authors: Wang Xinning , Zhou Changcheng , Liu Jingyu , Mao Liang , Yang Tianli , Hong Xi , Jiang Nan , Jia Ruipeng
Published: December 2021

Objective

Stem cell therapy represents a new approach to induce immune tolerance in solid organ transplantation. However, the time‐consuming process of stem cell expending limits the range of stem cell treatment. Uncultured adipose stromal vascular fraction is considered an attractive cell source for cell‐based therapy. This study aimed to evaluate the effect of stromal vascular fraction on the immune system in donation after circulatory death rat renal transplantation.

Methods

Stromal vascular fraction cells and splenocytes were co‐cultured to evaluate the effect of stromal vascular fraction on splenocyte proliferation and viability. Sprague–Dawley rats were used as donors. and Wistar rats as recipients to establish a donation after a circulatory death rat renal transplantation model. Warm ischemia time was 5 min. Stromal vascular fraction was administered in the rat model following the intra‐arterial route. The spleens and grafts of recipients were harvested on days 1, 3 and 7 post‐transplantation for assessing acute rejection, infiltration of inflammatory cells, indoleamine 2, 3‐dioxygenase expression and T‐cell frequency in the spleen.

Results

Stromal vascular fraction could inhibit proliferation and induce apoptosis of splenocytes in vitro (P < 0.05). The administration of stromal vascular fraction could significantly reduce acute rejection and infiltration of CD8+ T cells and mononuclear macrophages in grafts, and increase indoleamine 2, 3‐dioxygenase expression (P < 0.05). The frequency of CD8+ T cells decreased, and the frequency of CD25+Foxp3+ regulatory T cells increased in the spleen of the acute rejection + stromal vascular fraction group on day 7 post‐transplantation (P < 0.05).

Conclusion

Administration of the adipose stromal vascular fraction could attenuate acute rejection in donation after circulatory death renal transplantation by increasing the ratio of regulatory T cells and enhancing indoleamine 2, 3‐dioxygenase expression.
Evaluation of patient satisfaction for telehealth (telephone and video) in rheumatology outpatients during COVID‐19 pandemic
Authors: Oh Yumi , Hennessey Ashleigh , Young Laurel , Barrett Claire
Published: December 2021

Background

Telehealth in rheumatology has been a topic of interest for many years, but the COVID‐19 pandemic placed it in the forefront.

Aims

To evaluate patient perception of rheumatology telehealth and determine predictive factors for future telehealth acceptability.

Methods

A questionnaire containing 30 questions was sent to public and private rheumatology patients who attended telehealth appointments between April and May 2020. The questionnaire aimed to obtain information on baseline demographics, traditional appointment details, telehealth appointment details and appointment satisfaction using a 5‐point Likert scale. Descriptive statistical analysis was conducted.

Results

The questionnaire was sent to 1452 patients, of whom 494 (34%) patients responded. More than 70% of responses indicated overall satisfaction in specialist care through telehealth, and 88.7% perceived this suitable during a pandemic. Less than 50% of patients were agreeable for future telehealth either through telephone or video conference after the pandemic is over. Higher odds ratio for future telehealth acceptability was associated with visual impairment, perceived cost‐effectiveness and previous time lost at work for a face‐to‐face appointment.

Conclusion

During the unprecedented time of the pandemic, telehealth appointments (telephone/video) assisted in providing ongoing patient care remotely, with high level of satisfaction seen in this study. The patient's experience and perception of telehealth was strongly influenced by financial incentives, and certain subgroups of patients were more accepting for future telehealth appointments. Nevertheless, low level of future telehealth acceptability also highlighted the potential dissatisfaction among patients in telehealth compared with the traditional appointments.
Epigenetic regulation of natural killer cell memory*
Authors: Lau Colleen M. , Wiedemann Gabriela M. , Sun Joseph C.
Published: December 2021

Immunological memory is the underlying mechanism by which the immune system remembers previous encounters with pathogens to produce an enhanced secondary response upon re‐encounter. It stands as the hallmark feature of the adaptive immune system and the cornerstone of vaccine development. Classic recall responses are executed by conventional T and B cells, which undergo somatic recombination and modify their receptor repertoire to ensure recognition of a vast number of antigens. However, recent evidence has challenged the dogma that memory responses are restricted to the adaptive immune system, which has prompted a reevaluation of what delineates “immune memory.” Natural killer (NK) cells of the innate immune system have been at the forefront of these pushed boundaries, and have proved to be more “adaptable” than previously thought. Like T cells, we now appreciate that their “natural” abilities actually require a myriad of signals for optimal responses. In this review, we discuss the many signals required for effector and memory NK cell responses and the epigenetic mechanisms that ultimately endow their enhanced features.
Silencing and activating anergic B cells*
Authors: Tanaka Shinya , Ise Wataru , Baba Yoshihiro , Kurosaki Tomohiro
Published: December 2021

Despite the existence of central tolerance mechanisms, including clonal deletion and receptor editing to eliminate self‐reactive B cells, moderately self‐reactive cells still survive in the periphery (about 20% of peripheral B cells). These cells normally exist in a functionally silenced state called anergy; thus, anergy has been thought to contribute to tolerance by active‐silencing of potentially dangerous B cells. However, a positive rationale for the existence of these anergic B cells has recently been suggested by discoveries that broadly neutralizing antibodies for HIV and influenza virus possess poly‐ and/or auto‐reactivity. Given the conundrum of generating inherent holes in the immune repertoire, retaining weakly self‐reactive BCRs on anergic B cells could allow these antibodies to serve as an effective defense against pathogens, particularly in the case of pathogens that mimic forbidden self‐epitopes to evade the host immune system. Thus, anergic B cells should be brought into a silenced or activated state, depending on their contexts. Here, we review recent progress in our understanding of how the anergic B cell state is controlled in B cell–intrinsic and B cell–extrinsic ways.
Catheter ablation versus medical therapy for atrial fibrillation: Penny‐wise Pound‐foolish
Authors: Kowlgi Gurukripa N. , Deshmukh Abhishek J.
Published: December 2021

Catheter ablation for atrial fibrillation has emerged as a mainstay for the management of atrial fibrillation. It has been shown to be clinically effective and cost‐effective in multiple trials.
Characteristics and outcomes of ventricular tachycardia and premature ventricular contractions ablation in patients with prior mitral valve surgery
Authors: Khalil Fouad , Toya Takumi , Madhavan Malini , Badawy Mohamed , Ahmad Ali , Kapa Suraj , Mulpuru Siva K. , Siontis Konstantinos C. , DeSimone Christopher V. , Deshmukh Abhishek J. , Cha Yong‐Mei , Friedman Paul A. , Munger Thomas , Asirvatham Samuel J. , Killu Ammar M.
Published: December 2021

Background

Data regarding ventricular tachycardia (VT) or premature ventricular complex (PVC) ablation following mitral valve surgery (MVS) is limited. Catheter ablation (CA) can be challenging given perivalvular substrate in the setting of mitral annuloplasty or prosthetic valves.

Objective

To investigate the characteristics, safety, and outcomes of radiofrequency CA in patients with prior MVS and ventricular arrhythmias (VA).

Methods

We identified consecutive patients with prior MVS who underwent CA for VT or PVC between January 2013 and December 2018. We investigated the mechanism of arrhythmia, ablation approach, peri‐operative complications, and outcomes.

Results

In our cohort, 31 patients (77% men, mean age 62.3 ± 10.8 years, left ventricular ejection fraction 39.2 ± 13.9%) with prior MVS underwent CA (16 VT; 15 PVC). Access to the left ventricle was via transseptal approach in 17 patients, and a retrograde aortic approach was used in 13 patients. A combined transseptal and retrograde aortic approach was used in one patient, and a percutaneous epicardial approach was combined with trans‐septal approach in one patient. Heterogenous scar regions were present in 94% of VT patients and scar‐related reentry was the dominant mechanism of VT. Forty‐seven percent of PVC patients had abnormal substrate at the site targeted for ablation. Clinical VA substrates involved the peri‐mitral area in six patients with VT and five patients with PVC ablation. No procedure‐related complications were reported. The overall recurrence‐free rate at 1‐year was 72.2%; 67% in the VT group and 78% in the PVC group. No arrhythmia‐related death was documented on long‐term follow‐up.

Conclusion

CA of VAs can be performed safely and effectively in patients with MVS.