bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma-enabled electrochemical jet micromachining of chemically inert and passivating material
Authors: Lu Jiajun , Zhan Shunda , Liu Bowen , Zhao Yonghua 
Published: August 2022

Abstract
Electrochemical jet machining (EJM) encounters significant challenges in the microstructuring of chemically inert and passivating materials because an oxide layer is easily formed on the material surface, preventing the progress of electrochemical dissolution. This research demonstrates for the first time a jet-electrolytic plasma micromachining (Jet-EPM) method to overcome this problem. Specifically, an electrolytic plasma is intentionally induced at the jet-material contact area by applying a potential high enough to surmount the surface boundary layer (such as a passive film or gas bubble) and enable material removal. Compared to traditional EJM, introducing plasma in the electrochemical jet system leads to considerable differences in machining performance due to the inclusion of plasma reactions. In this work, the implementation of Jet-EPM for fabricating microstructures in the semiconductor material 4H-SiC is demonstrated, and the machining principle and characteristics of Jet-EPM, including critical parameters and process windows, are comprehensively investigated. Theoretical modeling and experiments have elucidated the mechanisms of plasma ignition/evolution and the corresponding material removal, showing the strong potential of Jet-EPM for micromachining chemically resistant materials. The present study considerably augments the range of materials available for processing by the electrochemical jet technique.
Attention-wise masked graph contrastive learning for predicting molecular property
Authors: Liu Hui , Huang Yibiao , Liu Xuejun , Deng Lei 
Published: August 2022

Abstract

Motivation
Accurate and efficient prediction of the molecular property is one of the fundamental problems in drug research and development. Recent advancements in representation learning have been shown to greatly improve the performance of molecular property prediction. However, due to limited labeled data, supervised learning-based molecular representation algorithms can only search limited chemical space and suffer from poor generalizability.

Results
In this work, we proposed a self-supervised learning method, ATMOL, for molecular representation learning and properties prediction. We developed a novel molecular graph augmentation strategy, referred to as attention-wise graph masking, to generate challenging positive samples for contrastive learning. We adopted the graph attention network as the molecular graph encoder, and leveraged the learned attention weights as masking guidance to generate molecular augmentation graphs. By minimization of the contrastive loss between original graph and augmented graph, our model can capture important molecular structure and higher order semantic information. Extensive experiments showed that our attention-wise graph mask contrastive learning exhibited state-of-the-art performance in a couple of downstream molecular property prediction tasks. We also verified that our model pretrained on larger scale of unlabeled data improved the generalization of learned molecular representation. Moreover, visualization of the attention heatmaps showed meaningful patterns indicative of atoms and atomic groups important to specific molecular property.
Muscle synergy analysis yields an efficient and physiologically relevant method of assessing stroke
Authors: Funato Tetsuro , Hattori Noriaki , Yozu Arito , An Qi , Oya Tomomichi , Shirafuji Shouhei , Jino Akihiro , Miura Kyoichi , Martino Giovanni , Berger Denise , Miyai Ichiro , Ota Jun , Ivanenko Yury , d’Avella Andrea , Seki Kazuhiko 
Published: August 2022

AbstractThe Fugl-Meyer Assessment is widely used to test motor function in stroke survivors. In the Fugl-Meyer Assessment, stroke survivors perform several movement tasks and clinicians subjectively rate the performance of each task item. The individual task items in the Fugl-Meyer Assessment are selected on the basis of clinical experience, and their physiological relevance has not yet been evaluated. In the present study, we aimed to objectively rate the performance of task items by measuring the muscle activity of 41 muscles from the upper body while stroke survivors and healthy participants performed 37 Fugl-Meyer Assessment upper extremity task items. We used muscle synergy analysis to compare muscle activity between subjects and found that 13 muscle synergies in the healthy participants (which we defined as standard synergies) were able to reconstruct all of the muscle activity in the Fugl-Meyer Assessment. Among the standard synergies, synergies involving the upper arms, forearms and fingers were activated to varying degrees during different task items. In contrast, synergies involving posterior trunk muscles were activated during all tasks, which suggests the importance of posterior trunk muscle synergies throughout all sequences. Furthermore, we noted the inactivation of posterior trunk muscle synergies in stroke survivors with severe but not mild impairments, suggesting that lower trunk stability and the underlying activity of posterior trunk muscle synergies may have a strong influence on stroke severity and recovery. By comparing the synergies of stroke survivors with standard synergies, we also revealed that some synergies in stroke survivors corresponded to merged standard synergies; the merging rate increased with the impairment of stroke survivors. Moreover, the degrees of severity-dependent changes in the merging rate (the merging rate–severity relationship) were different among different task items. This relationship was significant for 26 task items only and not for the other 11 task items. Because muscle synergy analysis evaluates coordinated muscle activities, this different dependency suggests that these 26 task items are appropriate for evaluating muscle coordination and the extent of its impairment in stroke survivors. Overall, we conclude that the Fugl-Meyer Assessment reflects physiological function and muscle coordination impairment and suggest that it could be performed using a subset of the 37 task items.
E3 ubiquitin ligases STUB1/CHIP contributes to the Th17/Treg imbalance via the ubiquitination of aryl hydrocarbon receptor in rheumatoid arthritis
Authors: Wang Wen , Xiang Ting , Yang Yachen , Wang Zitao , Xie Jianmin 
Published: August 2022

Abstract
STIP1-homologous U-Box containing protein 1 (STUB1) is involved in the development of immune pathologies and the regulation of T cell. However, the potential role of STUB1 in the pathogenesis of rheumatoid arthritis (RA), especially in the regulation of T cells, remains elusive. Here we show that STUB1 promotes the imbalance of Th17/Treg cells through non-degradative ubiquitination of aryl hydrocarbon receptor (AHR). Using Western blot and flow cytometry analysis, we observe that the level of STUB1 was increased in RA patients compared with healthy controls. In particular, the expression of STUB1 protein was different in Th17 cells and Treg cells of RA patients. We also demonstrated that STUB1 facilitates Th17/Treg imbalance by up- or downregulating the expression of STUB1. In a subsequent series of in vitro experiments, we revealed that STUB1 promoted the imbalance of Th17 and Treg cells through non-degradative ubiquitination of AHR. Both knockdown of the AHR expression by siRNA and assays of CYP1A1 enzymatic activity by ethoxyresorufin-O-deethylase (EROD) supported this conclusion. Furthermore, we explored the ubiquitination sites of AHR responsible for STUB1-mediated ubiquitination and revealed that STUB1 promotes ubiquitination of AHR via K63 chains. Together, STUB1 may induce the imbalance of Th17/Treg cells via ubiquitination of AHR and serve as a potential therapeutic target for RA.
Targeted Versus Shotgun Metagenomic Sequencing-based Detection of Microorganisms in Sonicate Fluid for Periprosthetic Joint Infection Diagnosis
Authors: Hong Hyo-Lim , Flurin Laure , Thoendel Matthew J , Wolf Matthew J , Abdel Matthew P , Greenwood-Quaintance Kerryl E , Patel Robin 
Published: August 2022

Abstract

Background
Next-generation sequencing (NGS) is increasingly used for periprosthetic joint infection (PJI) diagnosis, but its clinical utility is poorly defined. Shotgun metagenomic sequencing (sNGS) has been reported to identify PJI pathogens undetected by culture in sonicate fluid. However, sNGS is complex and costly. Here, 16S ribosomal RNA (rRNA) gene-based targeted metagenomic sequencing (tNGS) was compared to sNGS of sonicate fluid for microbial detection and identification in patients with total hip arthroplasty (THA) and total knee arthroplasty (TKA) failure.

Methods
A convenience sample of sonicate fluids derived from patients who had undergone THA or TKA removal, enriched with culture negative PJI cases, was tested. Samples had been previously tested by sNGS. For tNGS, samples were extracted, amplified by polymerase chain reaction targeting the V1 to V3 regions of the 16S rRNA gene, and sequenced on an Illumina MiSeq.

Results
A total of 395 sonicate fluids, including 208 from subjects with PJI, were studied. Compared with sonicate fluid culture, tNGS had higher positive percent agreement (72.1 vs 52.9%, P &lt; .001), detecting potential pathogens in 48.0% of culture-negative PJIs. There was no difference between the positive percent agreement of tNGS (72.1%) and sNGS (73.1%, P = .83).

Conclusions
16S rRNA gene-based tNGS is a potential diagnostic tool for PJI pathogen identification in sonicate fluid from failed THAs and TKAs in culture-negative cases, with similar performance characteristics to sNGS.
Personalized ablation vs. conventional ablation strategies to terminate atrial fibrillation and prevent recurrence
Authors: Azzolin Luca , Eichenlaub Martin , Nagel Claudia , Nairn Deborah , Sanchez Jorge , Unger Laura , Dössel Olaf , Jadidi Amir , Loewe Axel 
Published: August 2022

Abstract

Aims
The long-term success rate of ablation therapy is still sub-optimal in patients with persistent atrial fibrillation (AF), mostly due to arrhythmia recurrence originating from arrhythmogenic sites outside the pulmonary veins. Computational modelling provides a framework to integrate and augment clinical data, potentially enabling the patient-specific identification of AF mechanisms and of the optimal ablation sites. We developed a technology to tailor ablations in anatomical and functional digital atrial twins of patients with persistent AF aiming to identify the most successful ablation strategy.

Methods and results
Twenty-nine patient-specific computational models integrating clinical information from tomographic imaging and electro-anatomical activation time and voltage maps were generated. Areas sustaining AF were identified by a personalized induction protocol at multiple locations. State-of-the-art anatomical and substrate ablation strategies were compared with our proposed Personalized Ablation Lines (PersonAL) plan, which consists of iteratively targeting emergent high dominant frequency (HDF) regions, to identify the optimal ablation strategy. Localized ablations were connected to the closest non-conductive barrier to prevent recurrence of AF or atrial tachycardia. The first application of the HDF strategy had a success of &gt;98% and isolated only 5–6% of the left atrial myocardium. In contrast, conventional ablation strategies targeting anatomical or structural substrate resulted in isolation of up to 20% of left atrial myocardium. After a second iteration of the HDF strategy, no further arrhythmia episode could be induced in any of the patient-specific models.

Conclusion
The novel PersonAL in silico technology allows to unveil all AF-perpetuating areas and personalize ablation by leveraging atrial digital twins.
Identification of Cx43 variants predisposing to ventricular fibrillation in the acute phase of ST-elevation myocardial infarction
Authors: Chevalier Philippe , Moreau Adrien , Bessière Francis , Richard Sylvain , Chahine Mohamed , Millat Gilles , Morel Elodie , Paganelli Franck , Lesavre Nathalie , Placide Leslie , Montestruc François , Ankou Bénédicte , Puertas Rosa Doñate , Asatryan Babken , Delinière Antoine ,   MAP-IDM Investigators
Published: August 2022

AbstractAimsVentricular fibrillation (VF) occurring in the acute phase of ST-elevation myocardial infarction (STEMI) is the leading cause of sudden cardiac death worldwide. Several studies showed that reduced connexin 43 (Cx43) expression and reduced conduction velocity increase the risk of VF in acute myocardial infarction (MI). Furthermore, genetic background might predispose individuals to primary VF (PVF). The primary objective was to evaluate the presence of GJA1 variants in STEMI patients. The secondary objective was to evaluate the arrhythmogenic impact of GJA1 variants in STEMI patients with VF.Methods and resultsThe MAP-IDM prospective cohort study included 966 STEMI patients and was designed to identify genetic predisposition to VF. A total of 483 (50.0%) STEMI patients with PVF were included. The presence of GJA1 variants increased the risk of VF in STEMI patients [from 49.1 to 70.8%, P = 0.0423; odds ratio (OR): 0.40; 95% confidence interval: 0.16–0.97; P = 0.04]. The risk of PVF decreased with beta-blocker intake (from 53.5 to 44.8%, P = 0.0085), atrial fibrillation (from 50.7 to 26.4%, P = 0.0022), and with left ventricular ejection fraction &gt;50% (from 60.2 to 41.4%, P &lt; 0.0001). Among 16 GJA1 variants, three novel heterozygous missense variants were identified in three patients: V236I, H248R, and I327M. In vitro studies of these variants showed altered Cx43 localization and decreased cellular communication, mainly during acidosis.ConclusionConnexin 43 variants are associated with increased VF susceptibility in STEMI patients. Restoring Cx43 function may be a potential therapeutic target to prevent PVF in patients with acute MI.Clinical trial registrationClinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00859300
Novel dual-reference approach facilitates the activation mapping and catheter ablation of premature atrial complexes with non-pulmonary vein and non-superior vena cava origins
Authors: Chen Mu , Yang Mei , Li Wei , Zhang Peng-Pai , Zhang Rui , Mo Bin-Feng , Gong Chang-Qi , Han Ya-Qin , Sun Xiang-Hua , Wang Qun-Shan , Lu Qiu-Fen , Sun Jian , Li Yi-Gang 
Published: August 2022

AbstractAimsActivation mapping of premature atrial complexes (PACs) proves challenging due to interference by mechanical bumping and non-targeted ectopies. This study aims to compare the mapping efficacy, instant success, and long-term recurrence of catheter ablation for PACs with non-pulmonary vein (PV) and non-superior vena cava (SVC) origins between the novel dual-reference approach (DRA) and the routine single-reference approach (SRA) of mapping.Methods and resultsPatients with symptomatic, drug-refractory PACs, or frequent residual PACs after atrial tachyarrhythmia ablation were enrolled. During activation mapping, the coronary sinus (CS) catheter was used as the only timing reference in the SRA group. In the DRA group, another catheter, which was spatially separated from the CS catheter, was used as the second reference. The timing difference between the two references was used to discriminate the targeted PACs from the uninterested rhythms. Procedural parameters and long-term recurrence were compared. A total of 188 patients (109 in SRA and 79 in DRA) were enrolled. The baseline characteristics were similar. Compared with the SRA group, the DRA group had less repeated mapping (1.2 ± 0.4 vs. 1.4 ± 0.5, P = 0.004), shorter mapping (15 ± 6 vs. 23 ± 7 min, P &lt; 0.001) and procedural time (119 ± 28 vs. 132 ± 22 min, P = 0.001), similar procedural complication rates (3.6 vs. 3.8%, P &gt; 0.999), higher instant success (96.2 vs. 87.2%, P = 0.039), and lower recurrence rate (15.2 vs. 29.3%, hazard ratio 1.943, P = 0.033) during a 24-month follow-up.ConclusionAs a novel strategy, the DRA shortens the procedural time and improves both instant and long-term success of PAC ablation, serving as a promising approach in mapping PACs with non-PV and non-SVC origins.
Scalable approaches for functional analyses of whole-genome sequencing non-coding variants
Authors: Kuksa Pavel P , Greenfest-Allen Emily , Cifello Jeffrey , Ionita Matei , Wang Hui , Nicaretta Heather , Cheng Po-Liang , Lee Wan-Ping , Wang Li-San , Leung Yuk Yee 
Published: August 2022

Abstract
Non-coding genetic variants outside of protein-coding genome regions play an important role in genetic and epigenetic regulation. It has become increasingly important to understand their roles, as non-coding variants often make up the majority of top findings of genome-wide association studies (GWAS). In addition, the growing popularity of disease-specific whole-genome sequencing (WGS) efforts expands the library of and offers unique opportunities for investigating both common and rare non-coding variants, which are typically not detected in more limited GWAS approaches. However, the sheer size and breadth of WGS data introduce additional challenges to predicting functional impacts in terms of data analysis and interpretation. This review focuses on the recent approaches developed for efficient, at-scale annotation and prioritization of non-coding variants uncovered in WGS analyses. In particular, we review the latest scalable annotation tools, databases and functional genomic resources for interpreting the variant findings from WGS based on both experimental data and in silico predictive annotations. We also review machine learning-based predictive models for variant scoring and prioritization. We conclude with a discussion of future research directions which will enhance the data and tools necessary for the effective functional analyses of variants identified by WGS to improve our understanding of disease etiology.
Cost-effectiveness Analysis of Subcutaneous Infliximab for Inflammatory Bowel Diseases in Sequential Biologic Treatment
Authors: Bouhnik Yoram , Atreya Raja , Casey Daniel , Górecki Michał , Baik Deborah , Yoon Sang Wook , Kwon Taek Sang , Jang Minyoung 
Published: August 2022

Abstract

Background
Inflammatory bowel disease (IBD) guidelines recommend tumor necrosis factor-α inhibitors (TNFis) for patients who have not responded to conventional therapy, and vedolizumab in case of inadequate response to conventional therapy and/or TNFis. Recent studies have shown that vedolizumab may also be effective in the earlier treatment lines. Therefore, we conducted cost-effectiveness analyses to determine the optimal treatment sequence in patients with IBD.

Methods
A Markov model with a 10-year time horizon compared the cost-effectiveness of different biologic treatment sequences in patients with moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD) from the UK and French perspectives. Subcutaneous formulations of infliximab, vedolizumab, and adalimumab were evaluated. Comparative effectiveness was based on a network meta-analysis of clinical trials and real-world evidence. Costs included pharmacotherapy, surgery, adverse events, and disease management.

Results
The results indicated that treatment sequences starting with infliximab were less costly and more effective than those starting with vedolizumab for patients with UC in the United Kingdom and France, and patients with just CD in France. For patients with CD in the United Kingdom, treatment sequences starting with infliximab resulted in better health outcomes with incremental cost-effectiveness ratios (ICERs) near the threshold.

Conclusions
Based on the ICERs, treatment sequences starting with infliximab are the dominant option for patients with UC in the United Kingdom, and patients with UC and CD in France. In UK patients with CD, ICERs were near the assumed “willingness to pay” threshold. These results reinforce the UK’s National Institute for Health and Care Excellence recommendations for using infliximab prior to using vedolizumab in biologics-naïve patients.
Software Application Profile: SUMnlmr, an R package that facilitates flexible and reproducible non-linear Mendelian randomization analyses
Authors: Mason Amy M , Burgess Stephen 
Published: August 2022

Abstract

Motivation
Mendelian randomization methods that estimate non-linear exposure-outcome relationships typically require individual-level data. This package implements non-linear Mendelian randomization methods using stratified summarized data, facilitating analyses where individual-level data cannot easily be shared, and additionally increasing reproducibility as summarized data can be reported. Dependence on summarized data means the methods are independent of the form of the individual-level data, increasing flexibility to different outcome types (such as continuous, binary or time-to-event outcomes).

Implementation
SUMnlmr is available as an R package (version 3.1.0 or higher).

General features
The package implements the previously proposed fractional polynomial and piecewise linear methods on stratified summarized data that can either be estimated from individual-level data using the package or supplied by a collaborator. It constructs plots to visualize the estimated exposure-outcome relationship, and provides statistics to assess preference for a non-linear model over a linear model.

Availability
The package is freely available from GitHub [https://github.com/amymariemason/SUMnlmr].
The promise and challenges of launching cyber-military strikes: Japan’s ‘cross-domain’ operational concepts
Authors: Katagiri Nori 
Published: August 2022

Abstract
I investigate three factors that keep countries from adopting the strategy of cross-domain warfare and launching cyber and military operations at the same time. I do so by disentangling the relationship between international law, cybersecurity norms, and the concept of cross-domain operations. My analysis of Japan’s cross-domain vision indicates how difficult it can be for norm-compliant countries to launch cross-domain operations. In Japan’s case, the reason for the challenge rests with flaws in its legal system and a long-standing commitment to international legal and normative regulations applied to cyberspace dynamics. The three factors are behind the reason why Japan has never carried out a cross-domain operation, even though other states have essentially done so. The analysis generates several strategic implications for other countries contemplating the use of cross-domain operations within their own legal and international parameters.