bluuebunny/crossref_metadata_2025 huggingface dataset:
Shadow thermodynamics of non-linear charged Anti-de Sitter black holes*
Authors: Du Yun-Zhi , Li Huai-Fan , Zhou Xiang-Nan , Guo Wei-Qi , Zhao Ren
Published: August 2022

It is well known that when vacuum polarization emerges in quantum electrodynamics, the non-linear interaction between electromagnetic fields should be considered. Moreover, the corresponding field of non-linear electrodynamics can have important effects on black hole physics. In this work, we focus on the relationship between an observable quantity, that is, the shadow radius, and the first-order phase transition of non-linear charged AdS black holes in the framework of Einstein-power-Yang-Mills gravity. The results show that, under a certain condition, there exists a first-order phase transition from the viewpoint of both the shadow radius and horizon radius, which depend on temperature (or pressure). From the viewpoint of the shadow radius, the phase transition temperature is higher than that from the viewpoint of the horizon radius under the same condition. This may be due to the non-linear Yang Mills charge and the gravitational effect. This indicates that the shadow radius can be regarded as a probe to reveal the thermodynamic phase transition information of black holes. The thermal profiles of coexistent large and small black hole phases when the system is undergoing the phase transition are presented for two different values of the non-linear Yang Mills charge parameter:

. Furthermore, the effects of the non-linear Yang Mills charge parameter on the shadow radius and thermal profile are investigated.
Time-resolved terahertz spectroscopy for probing the effects of low-temperature annealing on CsPbBr3 evaporated thin-films
Authors: Gatto Lorenzo , Treglia Antonella , Crippa Gabriele , Devetta Michele , Folpini Giulia , Petrozza Annamaria , Stagira Salvatore , Vozzi Caterina , Cinquanta Eugenio
Published: August 2022

The fine-tuning of the growth conditions and post-deposition treatments is of fundamental importance to improve the efficiency of photovoltaic devices based on all-inorganic metal halide perovskites like CsPbBr3. In this work, we used time-resolved terahertz spectroscopy (TRTS) in combination with optical characterization techniques, x-ray diffraction (XRD), and scanning electron microscopy, to probe the different properties induced by a low-temperature (180 °C) annealing treatment on evaporated CsPbBr3 thin-films. We observed a faster build-up and relaxation dynamics in the annealed sample, accompanied by a remarkable decrease of the photoluminescence intensity and minor changes in the photoconductivity and XRD measurements as compared to the as-deposited sample. We estimated for both the samples a mobility of

μ
=

1.7
±
0.5

×

10
2

cm2 V−1 s−1. Our results suggest that the lattice reorganization induced by low-temperature annealing of evaporated CsPbBr3 could lead to a different charge carrier-phonon coupling and to an increased contribution of non-radiative recombination channels. We found that TRTS can be effectively used to follow the changes induced by post-deposition thermal annealing of CsPbBr3.
Micromasers as quantum batteries
Authors: Shaghaghi Vahid , Singh Varinder , Benenti Giuliano , Rosa Dario
Published: August 2022

We show that a micromaser is an excellent model of quantum battery. A highly excited, pure, and effectively steady state of the cavity mode, charged by coherent qubits, can be achieved, also in the ultrastrong coupling regime of field-matter interaction. Stability of these appealing features against loss of coherence of the qubits and the effect of counter-rotating terms in the interaction Hamiltonian are also discussed.
Plasma-enabled electrochemical jet micromachining of chemically inert and passivating material
Authors: Lu Jiajun , Zhan Shunda , Liu Bowen , Zhao Yonghua
Published: August 2022

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

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.
Extracellular vesicles and seeding amplification: a step closer to a Parkinson’s disease blood test
Authors: Martinez-Valbuena Ivan , Kovacs Gabor G , Lang Anthony E.
Published: August 2022

This scientific commentary refers to ‘Detection of neuron-derived pathological α-synuclein in blood’ by Kluge et al. (https://doi.org/10.1093/brain/awac115).
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

The 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

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

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 < .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

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 >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

Aims

Ventricular 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 results

The 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 >50% (from 60.2 to 41.4%, P < 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.

Conclusion

Connexin 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 registration

Clinical 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

Aims

Activation 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 results

Patients 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 < 0.001) and procedural time (119 ± 28 vs. 132 ± 22 min, P = 0.001), similar procedural complication rates (3.6 vs. 3.8%, P > 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.

Conclusion

As 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

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

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

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

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.
A National Analysis of Discharge Disposition in Older Adults with Burns—Estimating the Likelihood of Independence at Discharge
Authors: Cobert Jason , Sheckter Clifford , Pham Tam N
Published: August 2022

Whereas older age predicts higher burn mortality, the impact of age on discharge disposition is less well defined in older adults with burns. This investigation assesses the relationship between older age and discharge disposition after burns in a nationally representative sample. We queried the 2007 to 2015 National Trauma Data Bank for non-fatal burn hospitalizations in older adults. Pre-defined age categories were 55 to 64 years (working-age comparison group), 65 to 74 years (young-old), 75 to 84 years (middle-old), and 85+ years (old-old). Covariables included inhalation injury, comorbidities, burn total body surface area, injury mechanism, and race/ethnicity. Discharge to non-independent living (nursing home, rehabilitation, and other facilities) was the primary outcome. Logistic regression assessed the association between older age and discharge to non-independent living. There were 25,840 non-fatal burn hospitalizations in older adults during the study period. Working-age encounters comprised 53% of admissions, young-old accounted for 28%, middle-old comprised 15% and old-old comprised 4%. Discharge to non-independent living increased with burn TBSA and older age in survivors. Starting in young-old, the majority (65 %) of patients with burns ≥20% TBSA were discharged to non-independent living. Adjusted odd ratios for discharge to non-independent living were 2.0 for young-old, 3.3 for middle-old, and 5.6 for old-old patients, when compared with working-age patients (all P < .001). Older age strongly predicts non-independent discharge after acute burn hospitalization. Matrix analysis of discharge disposition indicates a stepwise rise in discharge to non-independent living with higher age and TBSA, providing a realistic discharge framework for treatment decisions and expectations about achieving independent living after burn hospitalization.
Quantitative Analysis of Contrast-enhanced Mammography for Risk Stratification of Benign Versus Malignant Disease and Molecular Subtype
Authors: Cain Natalie , Rahbar Guita , Park Esther , Tang Maxine , Andrews-Tang Denise , Gupta Esha , Roth Antoinette , Lee-Felker Stephanie , Thomas Mariam
Published: August 2022

Objective

To assess quantitative enhancement of benign, high-risk, and malignant lesions and differences in molecular subtype and grade of malignant lesions on contrast-enhanced mammography (CEM).

Methods

This IRB-approved retrospective study included women who underwent CEM for diagnostic work-up of a breast lesion between 2014 and 2020. Inclusion criteria were women who had diagnostic work-up with CEM and had BI-RADS 1 or 2 with one year follow-up, BI-RADS 3 with tissue diagnosis or stability for 2 years, or BI-RADS 4 or 5 with tissue diagnosis. An enhancement ratio was calculated for all lesions. This was obtained by drawing a region of interest within the lesion and a second region of interest in the nonenhancing background tissue using a program developed with MATLAB. Descriptive statistics were evaluated using chi-squared tests, Fisher exact tests, and analysis of variance. A logistic regression model was used to predict cancer outcome using the enhancement ratio. Statistical significance was defined as P < 0.05.

Results

There were 332 lesions in 210 women that met study criteria. Of the 332 lesions, 50.9% (169/332) were malignant, 5.7% (19/332) were high-risk, and 43.4% (144/332) were benign. Enhancement intensity of malignant lesions was higher than benign lesions. Odds ratio for quantitative enhancement of malignant lesions was 30.15 (P < 0.0001). Enhancement ratio above 1.49 had an 84.0% sensitivity and 84.0% specificity for malignancy. HER2-enriched breast cancers had significantly higher mean enhancement ratios (P = 0.0062).

Conclusion

Quantitative enhancement on CEM demonstrated that malignant breast lesions had higher mean enhancement intensity than benign lesions.
Market Work and the Formation of the Omnivorous Consumer Subject
Authors: Pomiès Anissa , Arsel Zeynep
Published: August 2022

Omnivorousness is the tendency of culturally and economically privileged individuals to consume both highbrow and lowbrow products. Prior research explores omnivorousness as a manifestation of status distinction in which consumers deploy the aesthetic disposition—a generic and transposable ability to appreciate cultural products through a formal gaze—to lowbrow options. Existing work emphasizes the acquisition of the aesthetic disposition, but it does not explain how consumers transpose their generic disposition to specific cultural contexts and develop omnivorous tastes. Therefore, we study the formation of omnivorous consumer subjects and highlight its enabling conditions. Building on a 7-year ethnography of coffee consumption in France, we find that omnivorous subjects develop a dual and flexible cultural competence. First, they acquire a common appreciation of coffee during their primary socialization and enjoy the energizing and socializing functions of lowbrow coffee. Then, they develop a formal appreciation of coffee later in life as a result of market work conducted by market professionals. Specifically, market professionals do three types of market work: qualification, captation, and activation. Consumers respond to market work by transposing their aesthetic disposition to highbrow coffee and, therefore, enjoy its formal characteristics. We extend prior research on taste, omnivorousness, and consumer subject formation.
Analysis of cancer drug prices: a narrative review of literature
Authors: Shazad Mohammed , El-Dahiyat Faris , Javid Farideh , Zare Neda , Ozbek Besime , Stephenson John , Babar Zaheer-Ud-Din
Published: August 2022

Objectives

The objective of the literature review is to collect data on how cancer medication pricing affects affordability and availability around the world.

Key findings

A literature search was carried out between 12 October 2020 and 2 December 2020, articles were selected based on them being available as full texts online and written in English. The keywords used were: ‘cancer’, ‘medicines’, ‘drug’, ‘drugs’, ‘pharmaceuticals’, ‘price’, ‘prices’, ‘pricing’. The collective search produced a total of 10 725 articles. After a refining process, any articles considered unnecessary and potential duplications were eliminated, and 16 research articles were included in the final analysis. The results were included in the following categories: (a) high-income countries, (b) low- and middle-income countries (LMICs), (c) originator cancer drug prices, (d) generic drug prices, (e) breast and colorectal cancer drug pricing. The expensive pricing of oncology medications is typically expected to be an obstacle for developing nations; however, the soaring prices have been found increasingly challenging for high-income countries. Within Europe, variations exist between countries in government expenditure and cancer drug prices. Originator cancer drug prices tend to be most expensive in Sweden, Denmark, Switzerland and Germany whereas Greece, Spain, Portugal and the UK had among the lowest recorded prices. The high cost of cancer drugs coupled with low availability rates have resulted in restricted access for many LMICs as monthly medicinal costs are often greater than yearly incomes.

The literature has shown the increasing trend of cancer drug pricing. The synthesis has also shown that cancer treatments are unaffordable in many developing countries resulting in most cancer deaths occurring in LMICs. Furthermore, governments cannot effectively challenge patented drug prices until the expiry of the patent.
Evidence of a role for cAMP in mitochondrial regulation in ovarian granulosa cells
Authors: Kaseder Melanie , Schmid Nina , Eubler Katja , Goetz Katharina , Müller-Taubenberger Annette , Dissen Gregory A , Harner Max , Wanner Gerhard , Imhof Axel , Forne Ignasi , Mayerhofer Artur
Published: August 2022

In the ovary, proliferation and differentiation of granulosa cells (GCs) drive follicular growth. Our immunohistochemical study in a non-human primate, the Rhesus monkey, showed that the mitochondrial activity marker protein cytochrome c oxidase subunit 4 (COX4) increases in GCs in parallel to follicle size, and furthermore, its intracellular localization changes. This suggested that there is mitochondrial biogenesis and trafficking, and implicates the actions of gonadotropins, which regulate follicular growth and ovulation. Human KGN cells, i.e. granulosa tumour cells, were therefore used to study these possibilities. To robustly elevate cAMP, and thereby mimic the actions of gonadotropins, we used forskolin (FSK). FSK increased the cell size and the amount of mitochondrial DNA of KGN cells within 24 h. As revealed by MitoTracker™ experiments and ultrastructural 3D reconstruction, FSK treatment induced the formation of elaborate mitochondrial networks. H89, a protein kinase A (PKA) inhibitor, reduced the network formation. A proteomic analysis indicated that FSK elevated the levels of regulators of the cytoskeleton, among others (data available via ProteomeXchange with identifier PXD032160). The steroidogenic enzyme CYP11A1 (Cytochrome P450 Family 11 Subfamily A Member 1), located in mitochondria, was more than 3-fold increased by FSK, implying that the cAMP/PKA-associated structural changes occur in parallel with the acquisition of steroidogenic competence of mitochondria in KGN cells. In summary, the observations show increases in mitochondria and suggest intracellular trafficking of mitochondria in GCs during follicular growth, and indicate that they may partially be under the control of gonadotropins and cAMP. In line with this, increased cAMP in KGN cells profoundly affected mitochondrial dynamics in a PKA-dependent manner and implicated cytoskeletal changes.
Effectiveness and Safety of CT-Guided Facet Joint Cyst Rupture for Radicular Pain as First Choice Therapy: A Retrospective Analysis
Authors: Strohm Alexa , Braun Michael , Kloth Christopher , Sollmann Nico , Ozpeynirci Yigit , Pala Andrej , Beer Meinrad , Schmitz Bernd L , Rosskopf Johannes
Published: August 2022

Objective

To evaluate effectiveness and safety of computed tomography (CT)-guided cyst rupture with intraarticular contrast-enhanced injection of steroid and local anesthetic as first choice therapy in patients with facet joint cyst-induced radicular pain.

Design

Retrospective data set analysis.

Setting

University hospital.

Subjects

One hundred and twenty-one patients suffering from radicular pain attributable to facet joint cysts were included.

Methods

The rate of patients without following surgery was assessed and defined as surrogate to measure effectiveness. Patients’ characteristics, procedure-associated complications, technical aspects, and imaging findings on magnetic resonance imaging (MRI) were analyzed. A subgroup of 65 patients (54%) underwent telephone interview to assess pain relief and clinical outcome measured by Numeric Rating Scale and Oswestry Disability Index. Analyses between the groups with and without surgery were performed by Fisher exact test and two-sample unpaired t-test, respectively.

Results

The effectiveness of CT-guided cyst rupture was found to be 66.1%. Procedure-induced pain yielded in premature abort in two cases (1.7%). The detection of epidural contrast agent was statistically significantly associated with no need for surgery (P = .010). The cyst level was associated with the status of following surgery (P = .026), that is, cysts at lower lumbar spine were easier to rupture than cysts at other locations (cervical, thoracic, or upper lumbar spine). No further significant association was found.

Conclusions

CT-guided cyst rupture as the first-choice therapy in patients with cyst-induced radicular pain was safe and effective. Successful cyst rupture was associated with no need for surgery. Cysts at lower lumbar spine revealed the highest success rate.
Extended Release of Bupivacaine from Temperature-responsive Hydrogels Provides Multi-day Analgesia for Postoperative Pain
Authors: Heffernan John M , McLaren Alex C , Glass Christopher M , Overstreet Derek J
Published: August 2022

Objective

A local anesthetic that provides analgesia lasting at least three days could significantly improve postoperative pain management. This study evaluated the analgesic efficacy and safety of an extended-release formulation of bupivacaine based on the injectable hydrogel carrier poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide) (PNDJ).

Methods

The efficacy of PNDJ containing 4% bupivacaine (SBG004) given by peri-incisional subcutaneous injection (SBG004 SC) or wound filling instillation (SBG004 WF) was evaluated compared to saline, liposomal bupivacaine, bupivacaine collagen sponge, bupivacaine-meloxicam polyorthoester, and bupivacaine HCl in a porcine skin and muscle incision model. Mechanical allodynia was assessed by withdrawal from application of von Frey filaments, and local tolerance was evaluated by histology. Bupivacaine pharmacokinetics for SBG004 SC were measured in rabbits (16.5 mg bupivacaine/kg).

Results

Animals demonstrated less mechanical allodynia at incisions receiving SBG004 SC for up to 96 hours postoperatively. Incisions treated with SBG004 SC tolerated more force without a withdrawal indicative of pain compared to saline for 96 hours, and compared to SBG004 WF and all active controls at 24, 48, and 72 hours except bupivacaine-meloxicam polyorthoester at 72 hours. By 49 days, SBG004 was histologically absent and was replaced with granulation tissue infiltrated with immune cells in some areas. In rabbits, Cmax was 41.6 ± 9.7 ng/mL with t1/2 82.0 ± 35.8 hours (mean ± SD).

Conclusions

Peri-incisional SBG004 SC provided extended release of bupivacaine sufficient to reduce sensation of incisional pain for 96 hours, in vivo bupivacaine delivery for at least 7 days, and a favorable local and systemic toxicity profile.
Pulmonary arterial wall thickness increased in Behçet’s disease patients with major organ involvement: Is it a sign of severity?
Authors: Kutluğ Ağaçkıran Seda , Sünbül Murat , Doğan Zekeriya , Kocakaya Derya , Kayacı Semih , Direskeneli Haner , Alibaz-Oner Fatma
Published: August 2022

Objectives

Behçet’s disease (BD) is a unique systemic vasculitis mainly involving veins, in contrast to other vasculitides. Prior studies have shown that pulmonary arteries (PAs) have a similar structure to systemic veins. In this study we aimed to assess PA wall thickness by transthoracic echocardiography (TTE) in BD patients compared with healthy controls (HCs) and patients with non-inflammatory pulmonary embolism (NIPE).

Methods

Patients with BD (n = 77) and NIPE (n = 33) and HCs (n = 57) were studied. PA wall thickness was measured from the mid-portion of the main PA with TTE by two cardiologists blinded to cases.

Results

PA wall thickness was significantly lower in HCs [3.6 mm (s.d. 0.3)] compared with NIPE [4.4 mm (s.d. 0.5)] and BD [4.4 mm (s.d. 0.6)] (P < 0.001 for both). PA wall thickness was similar between BD and NIPE (P = 0.6). Among patients with BD, PA wall thickness was significantly higher in patients with major organ involvement compared with mucocutaneous limited disease [4.7 mm (s.d. 0.4) vs 3.7 (0.4), P < 0.001], HCs and NIPE (P < 0.001 and P = 0.006, respectively). PA wall thickness was comparable between patients with vascular and non-vascular major organ involvement [4.6 mm (s.d. 0.5) vs 4.7 (0.3), P = 0.3].

Conclusion

We observed that PA wall thickness was significantly higher in BD with major organ involvement compared with patients with only mucocutaneous limited disease, HCs and NIPE. These results suggest that increased PA wall thickness may be a sign of severe disease with major organ involvement in BD.
Blockade of Voltage-Dependent K+ Channels by Benztropine, a Muscarinic Acetylcholine Receptor Inhibitor, in Coronary Arterial Smooth Muscle Cells
Authors: Kang Minji , An Jin Ryeol , Li Hongliang , Zhuang Wenwen , Heo Ryeon , Park Seojin , Mun Seo-Yeong , Park Minju , Seo Mi Seon , Han Eun-Taek , Han Jin-Hee , Chun Wanjoo , Park Won Sun
Published: August 2022

We investigated the effect of the acetylcholine muscarinic receptor inhibitor benztropine on voltage-dependent K+ (Kv) channels in rabbit coronary arterial smooth muscle cells. Benztropine inhibited Kv currents in a concentration-dependent manner, with an apparent IC50 value of 6.11 ± 0.80 μM and Hill coefficient of 0.62 ± 0.03. Benztropine shifted the steady-state activation curves toward a more positive potential, and the steady-state inactivation curves toward a more negative potential, suggesting that benztropine inhibited Kv channels by affecting the channel voltage sensor. Train pulse (1 or 2 Hz)-induced Kv currents were effectively reduced by the benztropine treatment. Furthermore, recovery time constants of Kv current inactivation increased significantly in response to benztropine. These results suggest that benztropine inhibited vascular Kv channels in a use (state)-dependent manner. The inhibitory effect of benztropine was canceled by pretreatment with the Kv 1.5 inhibitor, but there was no obvious change after pretreatment with Kv 2.1 or Kv7 inhibitors. In conclusion, benztropine inhibited the Kv current in a concentration- and use (state)-dependent manner. Inhibition of the Kv channels by benztropine primarily involved the Kv1.5 subtype. Restrictions are required when using benztropine to patients with vascular disease.
Fertility Following Natural Disasters and Epidemics in Africa
Authors: Norling Johannes
Published: August 2022

This paper uses dozens of large-scale household surveys to measure average changes in fertility following hundreds of droughts, floods, earthquakes, tropical cyclones, other storms, and epidemics in Africa between 1980 and 2016. Droughts are the largest and longest-lasting type of disaster on average, and fertility decreases by between 3.5 and 6.8 percent in the five years after droughts. Fertility changes are smaller or less clear after other types of disasters. Comparisons between countries, rather than within countries, drive these findings. There is substantial geographic heterogeneity in the direction and magnitude of the changes in fertility after disasters, driven by characteristics of the disasters and survey respondents. Fertility decreases especially after more recent droughts and in areas prone to drought. Fertility also decreases after longer floods. Fertility decreases after epidemics for women near the start and end of their childbearing careers, but increases for women in their late twenties and early thirties.
Job attributes valued by physicians, PAs, and NPs
Authors: Gillette Chris , Everett Chris , Ostermann Jan , Garvick Sarah , Momen Jennifer , Boles Ginger , Crandall Sonia
Published: August 2022

Objective:

This study evaluated the relative importance of job-, community-, and individual-related factors that contribute to job choice among physicians, physician assistants (PAs), and NPs, to inform policy options to recruit clinicians to rural areas.

Methods:

A cross-sectional online survey of PA preceptors from three institutions in two states. Participants were asked to rate the importance of 16 job-, community-, and individual-related factors when choosing a job.

Results:

We received responses from 45 physicians, 74 PAs, and 15 NPs (24.2% response rate), who rated most job-, community-, and individual-related factors as important; ratings were similar across clinicians. PAs rated loan repayment programs and work hours higher than physicians, though the magnitude of the difference was small.

Conclusions:

Clinicians similarly rated many factors as important. A better understanding of the tradeoffs clinicians are willing to make between these factors when making a job choice is critical to increase the attractiveness of rural positions.