bluuebunny/crossref_metadata_2025 huggingface dataset:
Encouraging the resumption of economic activity after COVID-19: Evidence from a large scale-field experiment in China
Authors: Palacios Juan , Fan Yichun , Yoeli Erez , Wang Jianghao , Chai Yuchen , Sun Weizeng , Rand David G. , Zheng Siqi
Published: January 2022

Significance

When the COVID-19 pandemic ends and it becomes safe to resume economic behavior, we will need to find effective ways of communicating that it is truly safe to do so. In this study, we tested a simple “nudge” that informed people of the proportion of their neighbors who were planning to visit a restaurant over the weekend, so that those who felt that restaurants were very unsafe would realize that many others felt comfortable visiting them. Our nudge successfully motivated such hesitant individuals to increase restaurant visits by 37%, and additional analyses indicate they indeed felt that visiting restaurants was safer.
Function-guided proximity mapping unveils electrophilic-metabolite sensing by proteins not present in their canonical locales
Authors: Zhao Yi , Miranda Herrera Pierre A. , Chang Dalu , Hamelin Romain , Long Marcus J. C. , Aye Yimon
Published: January 2022

Significance

The cell is a hive of information flow in which metabolite signals and proteins translocate across subcompartments. Peering into this submicroscopic world is hugely challenging. Using a strategy termed Localis-rex, we identify subcellular locale-specific sensors of a native reactive electrophilic metabolite. Surprisingly, several proteins sense electrophiles in locales where they do not canonically reside. One example is the nuclear protein, CDK9. In the cytosol, the electrophilic-metabolite–modified CDK9 has no negative function. However, following nuclear translocation, the electrophilic-metabolite–modified CDK9 downregulates the transcriptional activator, RNA-Polymerase-II. This exquisitely-nuanced signaling modality highlights the need to assign means, motive, and opportunity to proteins involved in reactive metabolite signaling.
Modelling inductive charging of electric cars in an experimental setup: teaching physics concepts in the context of electromobility
Authors: Fösel Angela , Wilhelm Simon
Published: January 2022

Within the last 10 years, electromobilty has been and still is an emerging field of research. Besides the possibility of charging the batteries of the vehicles by cables, a lot of research has been conducted on charging them without cables. One of those possibilities is based on a wireless energy transfer using the physical phenomenon of induction, which is a relevant topic for all physics students. In this article, we present a modular experimental setup of an inductive chargeable car and of its charging station. Although a few articles discussing the concept of inductive charging for didactical reasons already exist, all of them focus on theoretical explanations or on practical realisations, but not with electromobility in mind. We present a new ansatz. We designed a sizeable, touchable model for showing the concept as well as the functionality of a technology that is an ongoing object of research. Likewise, we developed the modular experimental setup to have the opportunity to teach the physics phenomenon induction within the interesting and motivating context of electromobilty. Experiments, that students learning about induction could perform if given the modular experimental setup, are discussed. The paper is addressed to undergraduate students and educators teaching physics at university.
Is an extended barrier-free discharge under nanosecond-pulse excitation really diffuse?
Authors: Ren Chenhua , Huang Bangdou , Qiu Jintao , Zhang Cheng , Qi Bo , Chen Weijiang , Shao Tao
Published: January 2022

A homogeneous discharge with a large volume is a desirable plasma source for many applications. Nanosecond-pulsed high-voltage (HV) excitation is believed to be a promising strategy for obtaining homogeneous or diffuse discharges at atmospheric pressure. In this paper, using a knife–plate geometry driven by a nanosecond-pulsed generator, a diffuse plasma sheet with a gap distance of 1 cm and a length of 12 cm is generated in atmospheric air, maintaining a low gas temperature of ∼330 K. However, time-resolved images reveal that the discharge, which appears diffuse to the naked eye, actually consists of multiple individual streamers that propagate from knife (HV) to plate (ground). The appearance of two processes, namely primary and secondary streamers, is consistently verified by discharge images, electric field evolution and fluid simulation. This further proves that the entire discharge belongs to an intermediate state between corona and spark. This work aids a deeper understanding of the intrinsic characters of similar diffuse discharges and optimizing parameters in practical applications.
Defects, band bending and ionization rings in MoS2
Authors: Di Bernardo Iolanda , Blyth James , Watson Liam , Xing Kaijian , Chen Yi-Hsun , Chen Shao-Yu , Edmonds Mark T , Fuhrer Michael S
Published: January 2022

Chalcogen vacancies in transition metal dichalcogenides are widely acknowledged as both donor dopants and as a source of disorder. The electronic structure of sulphur vacancies in MoS2 however is still controversial, with discrepancies in the literature pertaining to the origin of the in-gap features observed via scanning tunneling spectroscopy (STS) on single sulphur vacancies. Here we use a combination of scanning tunnelling microscopy and STS to study embedded sulphur vacancies in bulk MoS2 crystals. We observe spectroscopic features dispersing in real space and in energy, which we interpret as tip position- and bias-dependent ionization of the sulphur vacancy donor due to tip induced band bending. The observations indicate that care must be taken in interpreting defect spectra as reflecting in-gap density of states, and may explain discrepancies in the literature.
Diagnosing topological phase transitions in 1D superconductors using Berry singularity markers
Authors: Kotetes Panagiotis
Published: January 2022

In this work I demonstrate how to characterize topological phase transitions in BDI symmetry class superconductors (SCs) in 1D, using the recently introduced approach of Berry singularity markers (BSMs). In particular, I apply the BSM method to the celebrated Kitaev chain model, as well as to a variant of it, which contains both nearest and next nearest neighbor equal spin pairings. Depending on the situation, I identify pairs of external fields which can detect the topological charges of the Berry singularities which are responsible for the various topological phase transitions. These pairs of fields consist of either a flux knob which controls the supercurrent flow through the SC, or, strain, combined with a field which can tune the chemical potential of the system. Employing the present BSM approach appears to be within experimental reach for topological nanowire hybrids.
Method for online matching of multiple identical targets using local homography matrix based on moving DLT
Authors: Wang Yue , Rui Jing , Zhang Xuefeng , Wang Xiangjun , Wu Xuangou
Published: January 2022

In the field of geometric measurement of stereo vision, problems such as interference sources and similarity of target characteristics increase the difficulty of the matching of multiple identical targets. An online matching method for multiple identical targets using local homography matrix based on moving direct linear transform is presented in this paper. Firstly, the matching feature point pairs between left and right background images are obtained in advance. Secondly, the left background image is evenly divided into multiple rectangular meshes, and the local homography matrix of each rectangular mesh is calculated offline. Thirdly, the mapping point of each target is estimated online by the local homography matrix corresponding to the rectangular mesh where the target is located, and the target point with the closest Euclidean distance to the mapping point is considered as the matching point. Computer simulation and quality experimental data proves effectiveness of the proposed method. Experimental results reflect that our method is better than existing matching methods based on Delaunay triangulation, and the root mean square error of image coordinates between the mapping points from our method and the actual matching points is less than 13 pixels when entire image size is 1920 pixels × 1200 pixels.
Abnormal data detection for industrial processes using adversarial autoencoders support vector data description
Authors: Qiu Kepeng , Song Weihong , Wang Peng
Published: January 2022

Abnormal data detection for industrial processes is essential in industrial process monitoring and is an important technology to ensure production safety. However, for most industrial processes, it is a challenge to establish an effective abnormal data detection model due to the following issues: (a) weak model performance due to the small amount of process data; (b) trade-offs between model sparsity and accuracy; and (c) weak generalization ability of abnormal data detection model. To address these issues, a method based on adversarial autoencoders support vector data description (AAESVDD) is presented in this work. First, a novel construction strategy is designed for a hybrid feature dataset based on the adversarial autoencoder (AAE). The hybrid feature dataset utilizes the latent feature and reconstruction residual extracted by the AAE to enhance the feature diversity of the process data. Then, combining the support vector data description (SVDD) and Bayesian optimization algorithm (BOA), an automatic detection model for abnormal data of the hybrid feature dataset is established. Meanwhile, a BOA objective function based on the criterion of the hybrid risk minimization is proposed to automatically optimize the model parameters, which further enhances the generalization ability of the SVDD-based model. Finally, the effectiveness of the proposed AAESVDD method is illustrated with the UCI benchmark datasets and an industrial penicillin fermentation process.
Experimental determination of k

Q
factors for two types of ionization chambers in scanned proton beams
Authors: Medin Joakim , Andreo Pedro , Palmans Hugo
Published: January 2022

Objective. Experimental determination of beam quality k

Q
factors for two types of Farmer ionization chambers, NE2571 and IBA FC65-G, in a scanned proton beam for three nominal energies (140 MeV, 180 MeV and 220 MeV) based on water calorimetry. Approach. Beam quality correction factors were determined comparing the results obtained with water calorimetry and ionometry. Water calorimetry was performed to determine the absorbed dose at a depth of measurement in water of 5 g cm−2, limited by the extension of the calorimeter glass vessel used. For the ionometry, two chambers of each type were included in the study. The ionization chambers were calibrated in terms of absorbed dose to water in 60Co at the Swedish Secondary Standard Dosimetry Laboratory, directly traceable to the BIPM, and were used according to the IAEA TRS-398 Code of Practice. Main results. The k

Q
values determined in the present work have been compared with the values tabulated in TRS-398 and its forthcoming update and also with those obtained in previous water calorimetric measurements and Monte Carlo calculations. All results were found to agree within the combined uncertainties of the different data. Significance. It is expected that the present work will serve as an experimental contribution to k

Q
-factors for the two chamber types and three scanned proton beam qualities used.
A half-wave superconducting transformer-rectifier flux pump using J
c(B) switches
Authors: Leuw Bradley , Geng Jianzhao , Rice James H P , Moseley Dominic A , Badcock Rodney A
Published: January 2022

High temperature superconducting (HTS) flux pumps can generate ultra-high currents (>1 kA) without the requirement for thermally inefficient room temperature current leads. Ultra-high currents enable physically smaller magnets with significantly less inductance unlocking new design opportunities. However, limited by intrinsically low electrical power efficiencies, existing HTS flux pumps cannot output high voltage or high power. In this work, we design, devise, and experimentally verify a transformer–rectifier type HTS flux pump using Jc(B) switching. We show that the rectification can be achieved by exploiting the HTS E-J relation with the application of DC magnetic fields. A quasi-persistent current of 54.5 A has been achieved at 77 K only limited by the load coil critical current. In addition, the electrical power efficiencies of both half-wave and full-wave flux pump are derived. We illustrate that the fundamental J
c(B) mechanism provides significantly higher efficiency than existing HTS flux pumps. This advancement will overthrow the common knowledge that HTS flux pumps could only be used for maintaining rather than fast ramping magnetic fields.
Gravitational waves of the QCD phase transition in a 5D soft wall model with Gauss-Bonnet correction
Authors: Rezapour S , Bitaghsir Fadafan K , Ahmadvand M
Published: January 2022

In this paper, we study the gravitational wave energy density spectrum of cosmological de/confinement phase transition at finite baryon chemical potential within a soft wall model of AdS/QCD with Gauss-Bonnet correction. Focusing on the approach of dilaton/radion dominance approximation, we find the dual bounce action and the duration of the phase transition at the nucleation temperature. We also consider the possibility of a supercooling period during the transition, obtain the quantities characterizing the gravitational wave spectrum through this approach, and discuss the detectability prospect of generated gravitational wave signals by gravitational wave experiments.
A test of galaxy cluster fundamental plane for the X-COP sample
Authors: Pradyumna S. , Desai Shantanu
Published: January 2022

We test the galaxy cluster fundamental plane using the X-COP sample of 12 clusters. The fundamental plane is given by the relation TX ∝ Ms
α rs
β, where TX, Ms, and rs correspond to the gas temperature, NFW halo mass, and scale radius, respectively. We did this analysis using two different temperatures: the error-weighted temperature in (50–500)h-1 kpc as well as the mass-weighted temperature in the same range.
With both these temperatures, we find a very tight fundamental plane with dispersion of about 0.02 dex. The best-fit values for α and β are in-between those expected from virial equilibrium and self-similarity solution for secondary infall and collapse, with α being closer to the virial expectation.
Our best-fit values are also consistent with a recent re-analyses of the fundamental plane for the CLASH sample, after excluding the hottest clusters.
The simulation of ELM suppression by ion cyclotron resonance heating in EAST using BOUT++
Authors: Li Y.L. , Xia T.Y. , Zou X.L. , Zhang X.J. , Zhou C. , Mao S.F. , Gui B. , Huang Y.Q. , Hu G.H. , Ye M.Y. , the EAST Team
Published: January 2022

Edge localized modes (ELMs) are completely suppressed by ion cyclotron resonant heating (ICRH) during H-mode discharge, which is first observed in the Experimental Advanced Superconducting Tokamak (EAST). The electromagnetic turbulence model in the BOUT++ framework is applied to the simulations, with the aim of obtaining the key physics mechanisms of ELM suppression by ICRH. The simulations, for the EAST experiment with no ELMs after ICRH, reveal that the radio frequency (RF) sheath plays a key role in the suppression of ELMs. The simulation results show that: (a) using the flow-balanced electric field, the ELM sizes are about 3.4% before ICRH, and 2.1% after ICRH. Although the smaller ELM is obtained with ICRH, it still belongs to relatively large ELMs; (b) instead of the flow-balance condition, the radial electric field E
r is calculated using the RF sheath model, and the ELM size is about 0.36% with ICRH, much closer to the small/no ELM regime. After considering the effect of ICRH, the larger E × B shear rate in the pedestal and scrape-off layer induced by the RF sheath reduces the linear growth rate, and enhances the nonlinear mode coupling. Furthermore, we find that there is an effective range of the sheath potential, in which the ELM can be well suppressed, but beyond this range the ELM may be only mitigated rather than suppressed. This can reasonably explain why the probability of ELM suppression by ICRH appearing in the experiments is low.
Accounting for local temperature effect substantially alters afforestation patterns
Authors: Windisch Michael Gregory , Humpenöder Florian , Lejeune Quentin , Schleussner Carl-Friedrich , Lotze-Campen Hermann , Popp Alexander
Published: January 2022

Human intervention in forested ecosystems is hoped to perform a fundamental shift within the next decade by reverting current forest loss—a major source of CO2 emissions—to net forest gain taking up carbon and thus aiding climate change mitigation. The demanded extensive establishment of forests will change the local surface energy fluxes, and with it the local climate, in addition to competing with food and fiber production for land and water. Scenario building models encompass this competition for resources but have turned a blind eye to the biogeophysical (BGP) local surface energy flux disturbance so far. We combine the benefit of CO2 sequestration of afforestation/reforestation (A/R) with the additional incentive or penalty of local BGP induced cooling or warming by translating the local BGP induced temperature change to a CO2 equivalent. We then include this new aspect in the land-use model Model for Agricultural Production and their Impact on the Environment (MAgPIE) via modifying the application of the price on greenhouse gases (GHGs). This enables us to use MAgPIE to produce A/R scenarios that are optimized for both their potential CO2 sequestration and the CO2 equivalent local BGP effect, as well as the socio-economic trade-offs of A/R. Here we show that optimal A/R patterns are substantially altered by taking the local BGP effects into account. Considering local cooling benefits of establishing forests triples (+203.4%) the viable global A/R area in 2100 from 116 to 351 Mha under the conditions of the shared socioeconomic pathway 2 (SSP2) scenario driven by the same GHG price. Three quarters (76.0%, +179 Mha) of the additionally forested area is established in tropical climates alone. Therefore, a further neglect of BGP effects in scenario building models undervalues the benefit of tropical forests while simultaneously running the risk of proposing counterproductive measures at high latitudes. However, the induced focus on tropical forestation intensifies the competition with food production where forests contribute most to mitigation. A/R related trade-offs need to be considered alongside their climate benefit to inhibit unintentional harm of mitigation efforts.
Generalized Carleson perturbations of elliptic operators and applications
Authors: Feneuil Joseph , Poggi Bruno
Published: January 2022

We extend in two directions the notion of perturbations of Carleson type for the Dirichlet problem associated to an elliptic real second-order divergence-form (possibly degenerate, not necessarily symmetric) elliptic operator. First, in addition to the classical perturbations of Carleson type, that we call additive Carleson perturbations, we introduce scalar-multiplicative and antisymmetric Carleson perturbations, which both allow non-trivial differences at the boundary. Second, we consider domains which admit an elliptic PDE in a broad sense: we count as examples the 1-sided NTA (a.k.a. uniform) domains satisfying the capacity density condition, the 1-sided chord-arc domains, the domains with low-dimensional Ahlfors-David regular boundaries, and certain domains with mixed-dimensional boundaries; thus our methods provide a unified perspective on the Carleson perturbation theory of elliptic operators.

Our proofs do not introduce sawtooth domains or the extrapolation method. We also present several applications to some Dahlberg-Kenig-Pipher operators, free-boundary problems, and we provide a new characterization of

A

∞

A_{\infty }

among elliptic measures.
Healthcare for older people in Central and South America
Authors: Robledo Luis Miguel GutiéRrez , Cano-GutiéRrez Carlos , Garcia Enrique Vega
Published: January 2022

Latin American countries (LAC), with their culturally and ethnically diverse populations, form a region that is difficult to define and to understand. The region’s health systems are deeply fragmented, which poses great challenges to overall equity levels in health. This is also one of the fastest ageing regions in the world, with increasing demands as well for acute and long-term care (LTC). Demographic and epidemiological transitions across the region are heterogeneous. In this context, health systems are in general, largely unprepared to face the challenge of promoting healthy ageing. This unpreparedness has been magnified by the Coronavirus disease-2019 pandemic. Here, we analyse the burden of disease in the older population and identify priorities to improve the care and quality of life for people living in LAC. Besides an adequately prepared workforce, we must remediate disparities and inequities; develop and implement integrated care; achieve patient-centred care and further develop palliative and end-of-life care; simultaneously, we must develop the structure and financing of LTC services and strengthen the role of public health making healthy ageing an essential component.
Investigation of Left Ventricular Strain and Its Morphological Basis During Different Stages of Diastolic and Systolic Dysfunction in Spontaneously Hypertensive Rat
Authors: Fu Liyun , Ruan Qinyun , You Ziling , Huang Huimei , Chen Yupeng , Cheng Sheng , Yan Lei , Cai Huang’e , Chen Yali , Lin Dongmei , Chen Huizhen , Huang Chunyan
Published: January 2022

Background

Myocardial fibrosis plays an important role in the pathogenesis of hypertensive cardiac dysfunction, and myocardial strain could detect early systolic abnormalities when left ventricular ejection fraction (LVEF) is preserved. The aim of this study was to investigate the characteristics of left ventricular multidirectional strain during different stages of heart dysfunction and the possible morphological basis in spontaneously hypertensive rats (SHRs).

Methods

SHRs and Wistar-Kyoto (WKY) rats were randomly divided into cages and observed for 3–25 months. Echocardiographic measurements, LV + dp/dtmax and left ventricular end-diastolic pressure (LVEDP), and histological collagen volume fraction (CVF) were observed in all rats.

Results

According to LVEF and LVEDP, SHRs were divided into normal cardiac function group (group A), diastolic dysfunction group (group B1), and systolic dysfunction group (group B2). In group A, myocardial strain and CVF showed no difference compared with the control group. In group B1, global longitudinal strain (GLS) and endocardial longitudinal strain (SL-endo) were lower than those in group A CVF-endo was increased (all P < 0.05). In group B2, global and layer-specific strain decreased significantly, along with the increased CVF-endo and CVF-epi (all P < 0.05). The decrease of GLS and SL-endo was moderately correlated with the increase of CVF-endo. The reduction of LVEF was correlated with the decrease of SC-endo (r = 0.65, P < 0.01).

Conclusions

Pathological myocardial fibrosis associated with hypertension develops from the inner to outer layer of myocardium, which is coincident with the impairment of myocardial deformation, where longitudinal strain is involved firstly and LVEF declines when all directions of strain are reduced.
LongPhase: an ultra-fast chromosome-scale phasing algorithm for small and large variants
Authors: Lin Jyun-Hong , Chen Liang-Chi , Yu Shu-Chi , Huang Yao-Ting
Published: January 2022

Motivation

Long-read phasing has been used for reconstructing diploid genomes, improving variant calling and resolving microbial strains in metagenomics. However, the phasing blocks of existing methods are broken by large Structural Variations (SVs), and the efficiency is unsatisfactory for population-scale phasing.

Results

This article presents a novel algorithm, LongPhase, which can simultaneously phase single nucleotide polymorphisms (SNPs) and SVs of a human genome in 10–20 min, 10× faster than the state-of-the-art WhatsHap, HapCUT2 and Margin. In particular, co-phasing SNPs and SVs produces much larger haplotype blocks (N50 = 25 Mbp) than those of existing methods (N50 = 10–15 Mbp). We show that LongPhase combined with Nanopore ultra-long reads is a cost-effective and highly contiguous solution, which can produce between one and 26 blocks per chromosome arm without the need for additional trios, chromosome-conformation and strand-seq data.

Availabilityand implementation

LongPhase is freely available at https://github.com/twolinin/LongPhase/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Functional variant rs2270363 on 16p13.3 confers schizophrenia risk by regulating NMRAL1
Authors: Wang Junyang , Li Shiwu , Li Xiaoyan , Liu Jiewei , Yang Jinfeng , Li Yifan , Li Wenqiang , Yang Yongfeng , Li Jiao , Chen Rui , Li Kaiqin , Huang Di , Liu Yixing , Lv Luxian , Li Ming , Xiao Xiao , Luo Xiong Jian
Published: January 2022

Recent genome-wide association studies have reported multiple schizophrenia risk loci, yet the functional variants and their roles in schizophrenia remain to be characterized. Here we identify a functional single nucleotide polymorphism (rs2270363: G>A) at the schizophrenia risk locus 16p13.3. rs2270363 lies in the E-box element of the promoter of NMRAL1 and disrupts binding of the basic helix–loop–helix leucine zipper family proteins, including USF1, MAX and MXI1.

We validated the regulatory effects of rs2270363 using reporter gene assays and electrophoretic mobility shift assay. Besides, expression quantitative trait loci analysis showed that the risk allele (A) of rs2270363 was significantly associated with elevated NMRAL1 expression in the human brain. Transcription factors knockdown and CRISPR-Cas9-mediated editing further confirmed the regulatory effects of the genomic region containing rs2270363 on NMRAL1. Intriguingly, NMRAL1 was significantly downregulated in the brain of schizophrenia patients compared with healthy subjects, and knockdown of Nmral1 expression affected proliferation and differentiation of mouse neural stem cells, as well as genes and pathways associated with brain development and synaptic transmission. Of note, Nmral1 knockdown resulted in significant decrease of dendritic spine density, revealing the potential pathophysiological mechanisms of NMRAL1 in schizophrenia. Finally, we independently confirmed the association between rs2270363 and schizophrenia in the Chinese population and found that the risk allele of rs2270363 was the same in European and Chinese populations.

These lines of evidence suggest that rs2270363 may confer schizophrenia risk by regulating NMRAL1, a gene whose expression dysregulation might be involved in the pathogenesis of schizophrenia by affecting neurodevelopment and synaptic plasticity.
Establishing gene regulatory networks from Parkinson’s disease risk loci
Authors: Farrow Sophie L , Schierding William , Gokuladhas Sreemol , Golovina Evgeniia , Fadason Tayaza , Cooper Antony A , O’Sullivan Justin M
Published: January 2022

The latest meta-analysis of genome-wide association studies identified 90 independent variants across 78 genomic regions associated with Parkinson’s disease, yet the mechanisms by which these variants influence the development of the disease remains largely elusive.

To establish the functional gene regulatory networks associated with Parkinson’s disease risk variants, we utilized an approach combining spatial (chromosomal conformation capture) and functional (expression quantitative trait loci) data.

We identified 518 genes subject to regulation by 76 Parkinson’s variants across 49 tissues, whicih encompass 36 peripheral and 13 CNS tissues. Notably, one-third of these genes were regulated via trans-acting mechanisms (distal; risk locus-gene separated by >1 Mb, or on different chromosomes). Of particular interest is the identification of a novel trans-expression quantitative trait loci–gene connection between rs10847864 and SYNJ1 in the adult brain cortex, highlighting a convergence between familial studies and Parkinson’s disease genome-wide association studies loci for SYNJ1 (PARK20) for the first time. Furthermore, we identified 16 neurodevelopment-specific expression quantitative trait loci–gene regulatory connections within the foetal cortex, consistent with hypotheses suggesting a neurodevelopmental involvement in the pathogenesis of Parkinson’s disease. Through utilizing Louvain clustering we extracted nine significant and highly intraconnected clusters within the entire gene regulatory network. The nine clusters are enriched for specific biological processes and pathways, some of which have not previously been associated with Parkinson’s disease.

Together, our results not only contribute to an overall understanding of the mechanisms and impact of specific combinations of Parkinson’s disease variants, but also highlight the potential impact gene regulatory networks may have when elucidating aetiological subtypes of Parkinson’s disease.
Stem cell-derived sensory neurons modelling inherited erythromelalgia: normalization of excitability
Authors: Alsaloum Matthew , Labau Julie I R , Liu Shujun , Effraim Philip R , Waxman Stephen G
Published: January 2022

Effective treatment of pain remains an unmet healthcare need that requires new and effective therapeutic approaches. NaV1.7 has been genetically and functionally validated as a mediator of pain. Preclinical studies of NaV1.7-selective blockers have shown limited success and translation to clinical studies has been limited. The degree of NaV1.7 channel blockade necessary to attenuate neuronal excitability and ameliorate pain is an unanswered question important for drug discovery. Here, we utilize dynamic clamp electrophysiology and induced pluripotent stem cell-derived sensory neurons (iPSC-SNs) to answer this question for inherited erythromelalgia, a pain disorder caused by gain-of-function mutations in Nav1.7. We show that dynamic clamp can produce hyperexcitability in iPSC-SNs associated with two different inherited erythromelalgia mutations, NaV1.7-S241T and NaV1.7-I848T. We further show that blockade of approximately 50% of NaV1.7 currents can reverse neuronal hyperexcitability to baseline levels.
Maternal soybean genistein on prevention of later-life breast cancer through inherited epigenetic regulations
Authors: Chen Min , Li Shizhao , Srinivasasainagendra Vinodh , Sharma Manvi , Li Zhenhai , Tiwari Hemant , Tollefsbol Trygve O , Li Yuanyuan
Published: January 2022

Breast cancer has strong developmental origins and maternal nutrition composition may influence later-life breast cancer risk in the offspring. Our study focused on a bioactive dietary component, genistein (GE) enriched in soybean products, to investigate specific timing of maternal GE exposure that may influence preventive efficacy of GE on offspring breast cancer later in life, and to explore the potential epigenetic mechanisms. Our results indicate a time-dependent effect of maternal GE exposure on early-life breast cancer development in offspring mice. Through integrated transcriptome and methylome analyses, we identified several candidate genes showing significantly differential gene expression and DNA methylation changes. We further found maternal long-term GE treatment can induce inherited epigenetic landmark changes in a candidate tumor suppressor gene, Trp63, resulting in transcriptional activation of Trp63 and induction of the downstream target genes. Our results suggest that maternal long-term exposure to soybean GE may influence early-life epigenetic reprogramming processes, which may contribute to its temporal preventive effects on breast cancer in the offspring. This study provides important mechanistic insights into an appropriate maternal administration of soybean products on prevention of breast cancer later in offspring life.
Predictive factors and prognosis of microscopic residual disease in non-small-cell lung cancer surgery
Authors: Rabinel Pierre , Vergé Romain , Cazaux Mathilde , Mazzoni Lucia , Renaud Claire , Rouch Axel , Brouchet Laurent
Published: January 2022

OBJECTIVES

We described patients with microscopic residual disease (R1) operated on for non-small-cell lung cancer (NSCLC) and investigated predictive factors for R1. We also examined prognostic factors for overall survival in these patients.

METHODS

From June 2003 to December 2019, a total of 2595 patients benefited from an anatomical resection operation for NSCLC in our department. All preoperative data were prospectively collected in Epithor, the French thoracic surgery national database. All pre-, per- and postoperative care followed the current recommendations. Tumours were classified by experienced pathologists according to the TNM classification and the resection status R. Survival information was collected retrospectively using the French national death register.

RESULTS

A total of 94 R1 patients (3.6%) and 2255 R0 patients (86.9%) were identified. R1 patients showed significant differences: They were older (p = 0.02), with a high rate of pneumonectomy(p < 0.001), more squamous cell carcinomas (p < 0.001) and more cases of advanced-stage disease (p < 0.001). We proved that incomplete resection was a poor and independent prognostic factor whereas complete resection had a significant impact on overall survival (HR: 4.66 [3.46–6.27]). Thus, we identified high clinical T status (odds ratio [OR]: 8.82 [5.00–15.56]), high clinical N status (OR: 3.54 [2.13–5.87), squamous cell carcinoma (OR: 3.86 [2.33–6.42]), obesity (OR 1.91 [1.04–3.52]) and low forced expiratory volume in 1 s (OR: 3.62 [1.70–7.68]) as risk factors for R1. No statistical differences were found according to the location of positive resection margin or treatment, whether adjuvant or neoadjuvant.

CONCLUSIONS

Incomplete resection was a poor prognostic factor for overall survival of patients operated on for NSCLC, particularly in the advanced stages of the disease. Identification of different predictive factors should help to avoid this situation.

subj collection: 152
Galectin 3 enhances platelet aggregation and thrombosis via Dectin-1 activation: a translational study
Authors: Chen Yufei , Fu Wanrong , Zheng Yunbo , Yang Jing , Liu Yangyang , Qi Zhiyong , Wu Meiling , Fan Zhichao , Yin Kanhua , Chen Yunfeng , Gao Wen , Ding Zhongren , Dong Jianzeng , Li Qi , Zhang Si , Hu Liang
Published: January 2022

Aims

Galectin-3, a β-galactoside-binding lectin, is abnormally increased in cardiovascular disease. Plasma Galectin-3 receives a Class II recommendation for heart failure management and has been extensively studied for multiple cellular functions. The direct effects of Galectin-3 on platelet activation remain unclear. This study explores the direct effects of Galectin-3 on platelet activation and thrombosis.

Methods and results

A strong positive correlation between plasma Galectin-3 concentration and platelet aggregation or whole blood thrombus formation was observed in patients with coronary artery disease (CAD). Multiple platelet function studies demonstrated that Galectin-3 directly potentiated platelet activation and in vivo thrombosis. Mechanistic studies using the Dectin-1 inhibitor, laminarin, and Dectin-1−/− mice revealed that Galectin-3 bound to and activated Dectin-1, a receptor not previously reported in platelets, to phosphorylate spleen tyrosine kinase and thus increased Ca2+ influx, protein kinase C activation, and reactive oxygen species production to regulate platelet hyperreactivity. TD139, a Galectin-3 inhibitor in a Phase II clinical trial, concentration dependently suppressed Galectin-3-potentiated platelet activation and inhibited occlusive thrombosis without exacerbating haemorrhage in ApoE−/− mice, which spontaneously developed increased plasma Galectin-3 levels. TD139 also suppressed microvascular thrombosis to protect the heart from myocardial ischaemia–reperfusion injury in ApoE−/− mice.

Conclusion

Galectin-3 is a novel positive regulator of platelet hyperreactivity and thrombus formation in CAD. As TD139 has potent antithrombotic effects without bleeding risk, Galectin-3 inhibitors may have therapeutic advantages as potential antiplatelet drugs for patients with high plasma Galectin-3 levels.
Improving cardiovascular magnetic resonance access in low- and middle-income countries for cardiomyopathy assessment: rapid cardiovascular magnetic resonance
Authors: Menacho Katia Devorha , Ramirez Sara , Perez Aylen , Dragonetti Laura , Perez de Arenaza Diego , Katekaru Diana , Illatopa Violeta , Munive Sara , Rodriguez Bertha , Shimabukuro Ana , Cupe Kelly , Bansal Rajiv , Bhargava Vivek , Rodriguez Ivonne , Seraphim Andreas , Knott Kris , Abdel-Gadir Amna , Guerrero Salomon , Lazo Marco , Uscamaita David , Rivero Marco , Amaya Neil , Sharma Sanjiv , Peix Amelia , Treibel Thomas , Manisty Charlotte , Mohiddin Sam , Litt Harold , Han Yuchi , Fernandes Juliano , Jacob Ron , Westwood Mark , Ntusi Ntobeko , Herrey Anna , Walker John Malcolm , Moon James
Published: January 2022

Aims

To evaluate the impact of a simplified, rapid cardiovascular magnetic resonance (CMR) protocol embedded in care and supported by a partner education programme on the management of cardiomyopathy (CMP) in low- and middle-income countries (LMICs).

Methods and results

Rapid CMR focused particularly on CMP was implemented in 11 centres, 7 cities, 5 countries, and 3 continents linked to training courses for local professionals. Patients were followed up for 24 months to assess impact. The rate of subsequent adoption was tracked. Five CMR conferences were delivered (920 attendees—potential referrers, radiographers, reporting cardiologists, or radiologists) and five new centres starting CMR. Six hundred and one patients were scanned. Cardiovascular magnetic resonance indications were 24% non-contrast T2* scans [myocardial iron overload (MIO)] and 72% suspected/known cardiomyopathies (including ischaemic and viability). Ninety-eighty per cent of studies were of diagnostic quality. The average scan time was 22 ± 6 min (contrast) and 12 ± 4 min (non-contrast), a potential cost/throughput reduction of between 30 and 60%. Cardiovascular magnetic resonance findings impacted management in 62%, including a new diagnosis in 22% and MIO detected in 30% of non-contrast scans. Nine centres continued using rapid CMR 2 years later (typically 1–2 days per week, 30 min slots).

Conclusions

Rapid CMR of diagnostic quality can be delivered using available technology in LMICs. When embedded in care and a training programme, costs are lower, care is improved, and services can be sustained over time.
Remote-delivered cardiac rehabilitation during COVID-19: a prospective cohort comparison of health-related quality of life outcomes and patient experiences
Authors: Candelaria Dion , Kirkness Ann , Farrell Maura , Roach Kellie , Gooley Louise , Fletcher Ashlee , Ashcroft Sarah , Glinatsis Helen , Bruntsch Christine , Roberts Jayne , Randall Sue , Gullick Janice , Ladak Laila Akbar , Soady Keith , Gallagher Robyn
Published: January 2022

Aims

Enforced suspension and reduction of in-person cardiac rehabilitation (CR) services during the coronavirus disease-19 (COVID-19) pandemic restrictions required rapid implementation of remote delivery methods, thus enabling a cohort comparison of in-person vs. remote-delivered CR participants. This study aimed to examine the health-related quality of life (HRQL) outcomes and patient experiences comparing these delivery modes.

Methods and results

Participants across four metropolitan CR sites receiving in-person (December 2019 to March 2020) or remote-delivered (April to October 2020) programmes were assessed for HRQL (Short Form-12) at CR entry and completion. A General Linear Model was used to adjust for baseline group differences and qualitative interviews to explore patient experiences. Participants (n = 194) had a mean age of 65.94 (SD 10.45) years, 80.9% males. Diagnoses included elective percutaneous coronary intervention (40.2%), myocardial infarction (33.5%), and coronary artery bypass grafting (26.3%). Remote-delivered CR wait times were shorter than in-person [median 14 (interquartile range, IQR 10–21) vs. 25 (IQR 16–38) days, P < 0.001], but participation by ethnic minorities was lower (13.6% vs. 35.2%, P < 0.001). Remote-delivered CR participants had equivalent benefits to in-person in all HRQL domains but more improvements than in-person in Mental Health, both domain [mean difference (MD) 3.56, 95% confidence interval (CI) 1.28, 5.82] and composite (MD 2.37, 95% CI 0.15, 4.58). From qualitative interviews (n = 16), patients valued in-person CR for direct exercise supervision and group interactions, and remote-delivered for convenience and flexibility (negotiable contact times).

Conclusion

Remote-delivered CR implemented during COVID-19 had equivalent, sometimes better, HRQL outcomes than in-person, and shorter wait times. Participation by minority groups in remote-delivered modes are lower. Further research is needed to evaluate other patient outcomes.
Comparison of various late gadolinium enhancement magnetic resonance imaging methods with high-definition voltage and activation mapping for detection of atrial cardiomyopathy
Authors: Eichenlaub Martin , Mueller-Edenborn Bjoern , Minners Jan , Figueras i Ventura Rosa M , Forcada Barbara Rubio , Colomer Anna Vallès , Hein Manuel , Ruile Philipp , Lehrmann Heiko , Schoechlin Simon , Allgeier Juergen , Bohnen Marius , Trenk Dietmar , Neumann Franz Josef , Arentz Thomas , Jadidi Amir
Published: January 2022

Aims

Atrial cardiomyopathy (ACM) is associated with increased arrhythmia recurrence rates after pulmonary vein isolation (PVI). We compare the most common left atrial (LA) late gadolinium enhancement magnetic resonance imaging (LGE-MRI)-methods [Utah-method and image intensity ratio (IIR)-methods] and endocardial voltage mapping for ACM-detection and outcome prediction after PVI for atrial fibrillation (AF).

Methods and results

In this prospective observational study, 37 ablation-naive patients (66 ± 9 years, 84% male) with persistent AF underwent LA-LGE-MRI and high-definition voltage and activation mapping (2129 ± 484 sites) in sinus rhythm prior to PVI. The MRI-post-processing-analyses were performed by two independent expert laboratories. Arrhythmia recurrence was recorded within 12 months following PVI. The global ACM-extent was highly variable: median LA low-voltage substrate (LA-LVS) was 12.9% at <1.0 mV and 2.7% at <0.5 mV; median LA-LGE-extent using the Utah-method was 18.3% and 0.03–93.1% using the IIR-methods. The LA activation time was significantly correlated with LA-LVS (r = 0.76 at <0.5 mV and r = 0.82 at <1.0 mV, both P < 0.0001), but not with LA-LGE-extent. The highest regional matching between LA-LVS <0.5 mV and LA-LGE was found for the anterior wall in 57% of patients using the Utah-method and in 59% using IIR 1.20. The corresponding values for the posterior wall were 19% and 38%, respectively. Arrhythmia recurrence occurred in 15(41%) patients. Freedom from arrhythmia was significantly lower in those with LA-LVS ≥2 cm2 at 0.5 mV but not in those with LGE ≥20% (Utah-stages III and IV): 43% vs. 81%, P = 0.009 and 50% vs. 67%, P = 0.338, respectively.

Conclusion

Comparison of the most common LA-LGE-MRI methods and endocardial voltage mapping revealed large discrepancies in global and regional ACM-extent.
Self-Enhanced False Memory Across the Life Span
Authors: Wang Jianqin , Otgaar Henry , Howe Mark L , Dong Qun , Zhou Chu
Published: January 2022

Objectives

The role of self in veridical memory has been extensively studied, but what is the role of self in false memory development across the life span? The current study examined the impact of self-reference on associative false memory in children, younger adults, and older adults, and further investigated possible mechanisms concerning how self-reference might affect false memory in different age groups.

Methods

Combining a self-reference manipulation with the Deese/Roediger–McDermott (DRM) paradigm, children, younger adults, and older adults encoded DRM word lists as paired with their own name, another person’s name, or a red square. Later their true and false recognition memory as well as recollection and familiarity were measured.

Results

A self-enhanced false memory effect was found in all age groups. That is, participants generated more false memories in the self-reference condition relative to the other-reference and neutral conditions. Furthermore, when examining its underlying memory mechanisms, we found that self-reference mainly increased false recollection in younger adults but facilitated familiarity of critical lures in older adults.

Discussion

Although self-reference increases false memory in both younger and older adults, the underlying mechanisms are different in that older adults have more self-relevant false familiarity while younger adults generate more self-relevant phantom recollection. The current study also has implications for eyewitness reports, suggesting that the self-relevance of memory may be one relevant factor to consider when evaluating potential risk factors of false memory.
Application of multiscale magnetotelluric data to mineral exploration: an example from the east Tennant region, Northern Australia
Authors: Jiang Wenping , Duan Jingming , Doublier Michael , Clark Andrew , Schofield Anthony , Brodie Ross C , Goodwin James
Published: January 2022

The footprint of a mineral system is potentially detectable at a range of scales and lithospheric depths, reflecting the size and distribution of its components. Magnetotellurics is one of a few techniques that can provide multiscale data sets to image and understand mineral systems. We have used long-period data from the Australian Lithospheric Architecture Magnetotelluric Project (AusLAMP) as a first-order reconnaissance survey to resolve large-scale lithospheric architecture for mapping areas of mineral potential in northern Australia. The 3-D resistivity model reveals a broad conductivity anomaly extending from the Tennant Creek district to the Murphy Province in the lower crust and upper mantle, representing a potential fertile source region for mineral systems. Results from a higher-resolution infill magnetotelluric survey reveal two prominent conductors in an otherwise resistive host whose combined responses result in the lithospheric-scale conductivity anomaly mapped in the AusLAMP model. Integration of the conductivity structure with deep seismic reflection data reveals a favourable crustal architecture linking the lower, fertile source regions with potential depositional sites in the upper crust. The enhanced conductivity likely resulted from the remnant (metallic) material deposited when fluids were present during the ‘ancient’ tectonic events. This observation strongly suggests that the deep-penetrating major faults potentially acted as pathways for transporting metalliferous fluids to the upper crust where they could form mineral deposits. This result and its integration with other geophysical and geochronological data sets suggest high prospectivity for major mineral deposits in the vicinity of these major faults, that is, Gulunguru Fault and Lamb Fault. In addition to these insights, interpretation of high-frequency magnetotelluric data acquired during the infill survey helps to characterize cover and assist with selecting targets for stratigraphic drilling which, in turn, can validate the models and improve our understanding of basement geology, cover sequences and mineral potential. This study demonstrates that integration of geophysical data from multiscale surveys is an effective approach to scale reduction during mineral exploration in covered terranes with limited geological knowledge.