bluuebunny/crossref_metadata_2025 huggingface dataset:
Compassion as an Agent of Historical Change
Authors: Barclay Katie
Published: November 2022

Compassion plays a significant role in many historiographies because of its capacity to explain human motivation and action. Within the history of judicial punishment in particular, compassion is a key agent of change—a feeling with explanatory power for historians. With its call to historicize feeling, the history of emotions troubles such accounts, undercutting the human universalism that compassion’s explanatory power relies on. This article argues that an emotions history of early modern compassion leads us to draw quite different conclusions about not just the operation of early modern punishment but especially what changed with the decline of corporeal punishment and the rise of human rights in the eighteenth century. It reminds historians that the history of emotions is important not just for those in this subdiscipline but for any who use emotion to explain historical events.
Cancer subtyping with heterogeneous multi-omics data via hierarchical multi-kernel learning
Authors: Wei Yifang , Li Lingmei , Zhao Xin , Yang Haitao , Sa Jian , Cao Hongyan , Cui Yuehua
Published: November 2022

Differentiating cancer subtypes is crucial to guide personalized treatment and improve the prognosis for patients. Integrating multi-omics data can offer a comprehensive landscape of cancer biological process and provide promising ways for cancer diagnosis and treatment. Taking the heterogeneity of different omics data types into account, we propose a hierarchical multi-kernel learning (hMKL) approach, a novel cancer molecular subtyping method to identify cancer subtypes by adopting a two-stage kernel learning strategy. In stage 1, we obtain a composite kernel borrowing the cancer integration via multi-kernel learning (CIMLR) idea by optimizing the kernel parameters for individual omics data type. In stage 2, we obtain a final fused kernel through a weighted linear combination of individual kernels learned from stage 1 using an unsupervised multiple kernel learning method. Based on the final fusion kernel, k-means clustering is applied to identify cancer subtypes. Simulation studies show that hMKL outperforms the one-stage CIMLR method when there is data heterogeneity. hMKL can estimate the number of clusters correctly, which is the key challenge in subtyping. Application to two real data sets shows that hMKL identified meaningful subtypes and key cancer-associated biomarkers. The proposed method provides a novel toolkit for heterogeneous multi-omics data integration and cancer subtypes identification.
Ultraliser: a framework for creating multiscale, high-fidelity and geometrically realistic 3D models for in silico neuroscience
Authors: Abdellah Marwan , Cantero Juan José García , Guerrero Nadir Román , Foni Alessandro , Coggan Jay S , Calì Corrado , Agus Marco , Zisis Eleftherios , Keller Daniel , Hadwiger Markus , Magistretti Pierre J , Markram Henry , Schürmann Felix
Published: November 2022

Ultraliser is a neuroscience-specific software framework capable of creating accurate and biologically realistic 3D models of complex neuroscientific structures at intracellular (e.g. mitochondria and endoplasmic reticula), cellular (e.g. neurons and glia) and even multicellular scales of resolution (e.g. cerebral vasculature and minicolumns). Resulting models are exported as triangulated surface meshes and annotated volumes for multiple applications in in silico neuroscience, allowing scalable supercomputer simulations that can unravel intricate cellular structure–function relationships. Ultraliser implements a high-performance and unconditionally robust voxelization engine adapted to create optimized watertight surface meshes and annotated voxel grids from arbitrary non-watertight triangular soups, digitized morphological skeletons or binary volumetric masks. The framework represents a major leap forward in simulation-based neuroscience, making it possible to employ high-resolution 3D structural models for quantification of surface areas and volumes, which are of the utmost importance for cellular and system simulations. The power of Ultraliser is demonstrated with several use cases in which hundreds of models are created for potential application in diverse types of simulations. Ultraliser is publicly released under the GNU GPL3 license on GitHub (BlueBrain/Ultraliser).

Significance

There is crystal clear evidence on the impact of cell shape on its signaling mechanisms. Structural models can therefore be insightful to realize the function; the more realistic the structure can be, the further we get insights into the function. Creating realistic structural models from existing ones is challenging, particularly when needed for detailed subcellular simulations. We present Ultraliser, a neuroscience-dedicated framework capable of building these structural models with realistic and detailed cellular geometries that can be used for simulations.
Early postoperative non-steroidal anti-inflammatory drugs and anastomotic leakage after oesophagectomy
Authors: Hirano Yuki , Konishi Takaaki , Kaneko Hidehiro , Itoh Hidetaka , Matsuda Satoru , Kawakubo Hirofumi , Uda Kazuaki , Matsui Hiroki , Fushimi Kiyohide , Daiko Hiroyuki , Itano Osamu , Yasunaga Hideo , Kitagawa Yuko
Published: November 2022

Background

Previous studies have suggested that postoperative non-steroidal anti-inflammatory drug (NSAID) use may increase the risk of anastomotic leakage after colorectal surgery. However, the association between NSAIDs and anastomotic leakage after oesophagectomy is unclear. The aim of this retrospective study was to assess the effect of early postoperative NSAID use on anastomotic leakage after oesophagectomy.

Methods

The Data of patients who underwent oesophagectomy for cancer between July 2010 and March 2019 were extracted from a Japanese nationwide inpatient database. Stabilized inverse probability of treatment weighting (IPTW), propensity score matching, and instrumental variable analyses were performed to investigate the association between NSAID use in the early postoperative period (defined as the day of and the day after surgery) and short-term outcomes, adjusting for potential confounders. The primary outcome was anastomotic leakage. The secondary outcomes were acute kidney injury, gastrointestinal bleeding, and mortality.

Results

Among 39 418 eligible patients, early postoperative NSAIDs were used by 16 211 individuals (41 per cent). Anastomotic leakage occurred in 5729 patients (15 per cent). In stabilized IPTW analyses, NSAIDs were not associated with anastomotic leakage (odds ratio 1.04, 95 per cent c.i. 0.97 to 1.10). The proportions of acute kidney injury and gastrointestinal bleeding, as well as 30-day mortality and in-hospital mortality, did not differ according to NSAID use. Propensity score matching and instrumental variable analyses demonstrated similar results.

Conclusion

Early postoperative NSAID use was not associated with anastomotic leakage or other complications in patients who underwent oesophagectomy.
Ideological Dilemmas in Social Work: Justice Social Workers in Scotland Talk about Gender in Practice
Authors: Kirkwood Steve , Mullins Eve , McCulloch Trish , Cree Viviene E
Published: November 2022

It has long been acknowledged that gender matters in social work, not least within justice social work, given the over-representation of men within the criminal justice system. Whilst there is significant theorising about the role of gender in criminal justice, there has been little empirical examination of how social workers understand and address gender in practice. This article sets out to redress this omission by introducing a novel study of the expressed views of justice social workers (JSWs) in Scotland on gender in their work. The findings are challenging. They demonstrate that JSWs talk about gender in complex and, at times, seemingly inconsistent ways; the concept of ideological dilemmas is used as a vehicle through which to interrogate this further. Our conclusions suggest that it is not necessary to resolve the conflicts and complexities that are an inevitable response to, and expression of, the multiple and often competing discourses within which JSW practitioners operate on a daily basis, but we do need to make space for these conflicts in practice. A person-centred approach to gender, and an intersectional approach to understanding personhood, offer a way forward, allowing insight into the complex and demanding environment within which JSWs function.
Risk and aversion coding in human habenula high gamma activity
Authors: Manssuer Luis , Ding Qiong , Zhang Yingying , Gong Hengfeng , Liu Wei , Yang Ruoqi , Zhang Chencheng , Zhao Yijie , Pan Yixin , Zhan Shikun , Li Dianyou , Sun Bomin , Voon Valerie
Published: November 2022

Neurons in the primate lateral habenula fire in response to punishments and are inhibited by rewards. Through its modulation of midbrain monoaminergic activity, the habenula is believed to play an important role in adaptive behavioural responses to punishment and underlie depressive symptoms and their alleviation with ketamine. However, its role in value-based decision-making in humans is poorly understood due to limitations with non-invasive imaging methods which measure metabolic, not neural, activity with poor temporal resolution.

Here, we overcome these limitations to more closely bridge the gap between species by recording local field potentials directly from the habenula in 12 human patients receiving deep brain stimulation treatment for bipolar disorder (n = 4), chronic pain (n = 3), depression (n = 3) and schizophrenia (n = 2). This allowed us to record neural activity during value-based decision-making tasks involving monetary rewards and losses.

High-frequency gamma (60–240 Hz) activity, a proxy for population-level spiking involved in cognitive computations, increased during the receipt of loss and decreased during receipt of reward. Furthermore, habenula high gamma also encoded risk during decision-making, being larger in amplitude for high compared to low risk. For both risk and aversion, differences between conditions peaked approximately between 400 and 750 ms after stimulus onset.

The findings not only demonstrate homologies with the primate habenula but also extend its role to human decision-making, showing its temporal dynamics and suggesting revisions to current models. The findings suggest that habenula high gamma could be used to optimize real-time closed-loop deep brain stimulation treatment for mood disturbances and impulsivity in psychiatric disorders.
Inborn errors of human IKAROS: LOF and GOF variants associated with primary immunodeficiency
Authors: Kuehn Hye Sun , Boast Brigette , Rosenzweig Sergio D
Published: November 2022

IKAROS/IKZF1 plays a pivotal role in lymphocyte differentiation and development. Germline mutations in IKZF1, which have been shown to be associated with primary immunodeficiency, can be classified through four different mechanisms of action depending on the protein expression and its functional defects: haploinsufficiency, dimerization defective, dominant negative, and gain of function. These different mechanisms are associated with variable degrees of susceptibility to infectious diseases, autoimmune disorders, allergic diseases, and malignancies. To date, more than 30 heterozygous IKZF1 germline variants have been reported in patients with primary immunodeficiency. Here we review recent discoveries and clinical/immunological characterization of IKAROS-associated diseases that are linked to different mechanisms of action in IKAROS function.
Evaluation of the US Definitions for Coronavirus Disease 2019 Community Risk Levels
Authors: Mokhtar Sina , Parpia Alyssa S , Lo Nathan C , Ndeffo-Mbah Martial L
Published: November 2022

The US Centers for Disease Control and Prevention (CDC) defines a county metric of coronavirus disease 2019 (COVID-19) community levels to inform public health measures. We find that the COVID-19 community levels vary frequently over time, which may not be optimal for decision making. Alternative metric formulations that do not compromise predictive ability are shown to reduce variability.
Reliability Analysis of the Cactus-Based Networks Based on Subsystem
Authors: Liu Xiaoqing , Zhou Shuming , Liu Jiafei , Zhang Hong
Published: November 2022

Multiprocessor systems play a significant role in big data era. As the probability of presence of processor failures in a multiprocessor system raises with the increase of the system scale, the effect of processor failure is worthy of quantifying. The subsystem reliability of a multiprocessor system is the probability that a fault-free subsystem of certain size still operate with the rise of individual faults. In this work, we employ the probabilistic fault model and the Principle of Inclusion-Exclusion (PIE) to establish the approximation and upper bound on the subsystem reliability of the cactus-based networks through decomposition into $(n-1)$-dimensional subsystems by fixing one position-pair. Numerical simulations show that the upper bound derived in this way is close to the approximation of the accurate subsystem reliability.
Natural parasites in conjunction with behavioral and color traits explain male agonistic behaviors in a lizard
Authors: Megía-Palma Rodrigo , Paranjpe Dhanashree , Cooper Robert D , Blaimont Pauline , Sinervo Barry
Published: November 2022

Male competition conforms to a cost–benefit model, because while aggression may increase reproductive prospects, it can also increase the risk of injury. We hypothesize that an additional cost in aggressive males would be an increase in parasite load associated with a high energy investment into sexual competition. Some of these infections, in turn, may downmodulate the level of host aggression via energetic trade-offs. We staged dyadic male contests in the lab to investigate the relationships of multiple parasites with the agonistic behavior of lizard hosts, Sceloporus occidentalis. We also included both color and behavioral traits from opponents in the analyses because (1) color patches of lizards may serve as intraspecific signals used by conspecifics to assess the quality of opponents, and (2) contests between male lizards fit classical models of escalated aggression, where lizards increase aggression displays in response to an opponent’s behavior. The results conform to our hypothesis because male lizards displayed more pushups when they had more ticks. Moreover, some parasites may modulate the levels of aggression because lizards infected by hematic coccidians performed fewer pushups. Interestingly, lizards also displayed fewer pushups when both the chroma and size of the opponent’s blue patch were greater. The results thus also supported the role of the blue patch of S. occidentalis as a sexual armament, because it contributed to the deterrence of aggression from opponent lizards. We revealed that natural parasitic infections in lizard hosts can contribute to their agonistic behavior. We encourage future studies to account for parasites in behavioral tests with lizards.
Intra-arrest partial carbon dioxide level and favorable neurological outcome after out-of-hospital cardiac arrest: a nationwide multicenter observational study in Japan (the JAAM-OHCA registry)
Authors: Matsuyama Tasuku , Ohta Bon , Kiyohara Kosuke , Kitamura Tetsuhisa
Published: November 2022

Aims

Little is known about whether guideline-recommended ventilation during cardiopulmonary resuscitation results in optimal partial carbon dioxide (pCO2) levels or favorable outcomes. This study aimed to evaluate the association between intra-arrest pCO2 level and the outcome after out-of-hospital cardiac arrest (OHCA).

Methods and results

We performed a secondary analysis of a multicenter observational study, including adult patients with OHCA who did not achieve a return of spontaneous circulation (ROSC) upon hospital arrival and whose blood gas analysis was performed before the ROSC between June 2014 and December 2017. The patients were categorized into four quartiles based on their intra-arrest carbon dioxide levels: Quartile 1 (<66.0 mmHg), Quartile 2 (66.1–87.2 mmHg), Quartile 3 (87.3–113.5 mmHg), and Quartile 4 (≥113.6 mmHg). The primary outcome was 1-month survival with favorable neurological outcomes defined as cerebral performance Category 1 or 2. Multivariate logistic regression analysis was used to evaluate the association between pCO2 and favorable neurological outcomes. During the study period, 20 913 patients were eligible for the analysis. The proportion of favorable neurological outcomes was 1.8% (90/5133), 0.7% (35/5232), 0.4% (19/5263), and 0.2% (9/5285) in Quartiles 1–4, respectively. Multivariable logistic regression analysis demonstrated that the probability of favorable neurological outcome decreased with increased intra-arrest carbon dioxide levels (i.e. Q1 vs. Q4, adjusted odds ratio 0.25, 95% confidence interval 0.16–0.55, P for trend <0.001).

Conclusion

Lower intra-arrest pCO2 levels were associated with a favorable neurological outcome.
Splitting the anterior mitral leaflet impairs left ventricular function in an ovine model
Authors: Brunel Laurencie , Williams Zoe A , Yastrebov Konstantin , Robinson Benjamin M , Wise Innes K , Paterson Hugh S , Bannon Paul G
Published: November 2022

OBJECTIVES

During mitral valve replacement, the anterior mitral leaflet is usually resected or modified. Anterior leaflet splitting seems the least disruptive modification. Reattachment of the modified leaflet to the annulus reduces the annulopapillary distance. The goal of this study was to quantify the acute effects on left ventricular function of splitting the anterior mitral leaflet and shortening the annulopapillary distance.

METHODS

In 6 adult sheep, a wire was placed around the anterior leaflet and exteriorized through the left ventricular wall to enable splitting the leaflet in the beating heart. Releasable snares to reduce annulopapillary distance were likewise positioned and exteriorized. A mechanical mitral prosthesis was inserted to prevent mitral incompetence during external manipulations of the native valve. Instantaneous changes in left ventricular function were recorded before and after shortening the annulopapillary distance, then before and after splitting the anterior leaflet.

RESULTS

After splitting the anterior leaflet, preload recruitable stroke work, stroke work, stroke volume, cardiac output, left ventricular end systolic pressure and mean pressure were significantly decreased by 26%, 23%, 12%, 9%, 15% and 11%, respectively. Shortening the annulopapillary distance was associated with significant decreases in the end systolic pressure volume relationship, preload recruitable stroke work, stroke work and left ventricular end systolic pressure by 67%, 33%, 15% and 13%, respectively. Shortening the annulopapillary distance after splitting the leaflet had no significant effect.

CONCLUSIONS

Splitting the anterior mitral leaflet acutely impaired left ventricular contractility and haemodynamics in an ovine model. Shortening the annulopapillary distance after leaflet splitting did not further impair left ventricular function.
International Investment Protection Made in Germany? On the Domestic and Foreign Policy Dynamics behind the First BITs
Authors: Venzke Ingo , Günther Philipp
Published: November 2022

The investment protection treaty concluded between Germany and Pakistan in 1959 is generally regarded as a milestone in the development of international investment law. It has entered the collective memory as the first bilateral investment treaty (BIT). In this article, we analyse archival sources to investigate why Germany and Pakistan concluded this agreement at that specific time and what makes this treaty the first of its kind. Through historical analysis, we trace the domestic and related foreign policies that led to the BIT and discuss the negotiation process. Our analysis shows that the BIT was so closely linked with the German federal investment guarantee scheme (Bundesgarantien) that it is best understood as an extension of that policy. This also helps us to specify the underlying rationale for the treaties. We further highlight the influence of the financial industry – especially of Hermann Josef Abs – on the genesis of the BIT, which was less decisive than is often suggested. We identify features of the 1959 BIT that do characterize it as a new international legal instrument, but nuance claims about its degree of innovation as well as underlying motivations, and counter considerable retrospective myth making.
Do students’ oral corrective feedback beliefs matter to teachers?
Authors: Ha Xuan Van
Published: November 2022

This study explores the impact of students’ beliefs on teachers’ beliefs regarding oral corrective feedback through a targeted professional development programme. The programme comprised a one-day seminar during which eleven high-school EFL teachers were presented with and discussed the findings of a study of their students’ feedback beliefs, and follow-up experiential learning activities through reflective practice for eight weeks. Data were collected from multiple sources over eighteen weeks. The findings revealed that the teachers did not explicitly acknowledge the influence of their students’ beliefs, but the comments in the follow-up interviews and written reflections showed considerable changes in their views about the workability of immediate feedback, the appropriate choices of feedback types, and the interaction among contextual factors, learner factors, feedback types, and error types. These changes were in the direction of their students’ feedback preferences, which were also aligned with research recommendations. Implications for teacher professional development are discussed.
Palliative care interventions and end-of-life care as reported by patients’ post-stroke and their families: a systematic review
Authors: Govind Natalie , Ferguson Caleb , Phillips Jane L , Hickman Louise
Published: November 2022

Aims

Internationally, there is an urgent need to implement guidelines supporting integration of palliative care into stroke clinical practice. Despite considerable advances in acute stroke management, ∼20% of all acute stroke patients die within the first 30 days. Palliative care is well established in diseases such as cancer or advanced heart failure, but evidence-based interventions of high quality are limited in stroke populations. This systematic review aims to identify and evaluate quantitative studies that describe palliative care interventions and end-of-life care as reported by patient’s post-stroke and their families.

Methods and results

A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines was conducted in Cumulative Index to Nursing and Allied Health Literature, PubMed, Cochrane, Embase, Ovid, Proquest, and Scopus from 1990 to April 2021. The National Heart, Lung and Blood Institute standardized quality rating tools for quality assessment were used. Seven studies were identified, and all used descriptive quantitative designs. There were no interventional studies. The results were synthesized narratively according to the elements of palliative care interventions and end-of-life care: symptom burden and satisfaction, loss of autonomy at the end of life, and acknowledging uncertainty.

Conclusion

This review highlights the limited empirical evidence that describes palliative care interventions and end-of-life care as reported by patient’s post-stroke and their families. Most of the current evidence focuses on the provision of care during the final days and hours of life, or end-of-life care, with little evidence to guide the integration of palliative care into post-stroke clinical care, especially for patients with an uncertain prognosis. Acute stroke is sudden, unexpected, and life-changing, and patients and families would benefit from well-designed targeted interventions to determine strategies that address the diverse palliative needs of this patient population.

Registration

PROSPERO CRD42021254536.
The impact of switching from single-use to reusable healthcare products: a transparency checklist and systematic review of life-cycle assessments
Authors: Keil Mattis , Viere Tobias , Helms Kevin , Rogowski Wolf
Published: November 2022

Background

Replacing single-use products with reusable ones may reduce the environmental impact of healthcare. This study aimed to broadly assess the environmental effects of that substitution.

Methods

A systematic review of comparative cradle-to-grave life-cycle assessments (LCAs) of single-use and reusable healthcare products was conducted. The main outcomes assessed were changes in the environmental impact that resulted after switching from single-use to reusable products. As no standardized transparency checklist was available, one was developed here using DIN ISO 14040/14044. The final checklist included 22 criteria used to appraise the included studies.

Results

After screening, 27 studies were included in the analysis. The healthcare products were assigned to four categories: invasive medical devices, non-invasive medical devices, protection equipment and inhalers. The outcomes revealed a reduction in mean effect sizes for all environmental impacts except water use. Non-invasive medical devices have greater relative mitigation potential than invasive devices. On average, information on 64% of the transparency checklist items was reported. Gaps included the reporting of data quality requirements.

Conclusions

Switching to reusable healthcare products is likely to reduce most impacts on the environment except water use, but the effect size differs among product categories. Possible study limitations include location bias, no systematic search of the grey literature and small samples for some impacts. This study’s strengths are its approach to product categories and developed transparency catalogue. This catalogue could be useful to inform and guide a future process towards creating a standardized transparency checklist for the systematic reviews of LCAs.
Antimicrobial activity of dominant Ligilactobacillus animalis strains in healthy canine feces and their probiotic potential
Authors: Lee Hong-Jae , Lee Joong-Bok , Park Seung-Yong , Choi In-Soo , Lee Sang-Won
Published: November 2022

The number of companion animals living with humans has continually increased over the last few decades, and so has the interest of owners and stakeholders in the animal food and probiotics industry. Currently, the probiotic bacteria added to the feed of companion animals predominantly originate from the lactic acid bacteria (LAB) used for humans; however, there are differences between the microbiota of humans and that of their companion animals. This study aimed to determine the dominant LAB in dog feces and investigate their functional properties. Ligilactobacillus animalis (formerly called Lactobacillus animalis) was identified as the dominant lactic acid bacterium in dog feces. It displayed various inhibitory effects against pathogenic and enteropathogenic bacteria. This finding suggests that Ligilactobacillus animalis can potentially be used in novel probiotics or as a food additive for dogs.
Conceptualizing Person-Centered Care in Elder Mistreatment Intervention: Use of a Well-Being Framework
Authors: Martinez Julia M , Homeier Diana C , Fowler Cherie , Wilber Kathleen H
Published: November 2022

Background and Objectives

Person-centered care (PCC) applied to elder mistreatment interventions is an approach to include victim priorities. Although PCC may improve outcomes by supporting choice, victim preferences are often difficult to support, especially in high-risk situations. We studied the adaptation of PCC structures and process to a pilot intervention, aimed at including client preferences in a multidisciplinary team’s plans to address complex elder mistreatment.

Research Design and Methods

Case study analysis was used to examine the process of integrating client priorities into a risk-reduction plan. A well-being framework was used to understand the relationship between safety and preferences. Purposive sampling identified a case study of a high-risk victim with history of refusing help who agreed to work with the Service Advocate, a member of a multidisciplinary team.

Results

PCC required a relationship of trust, honed over several weeks by prioritizing the clients’ perspective. Client preferences included remaining at home, continuing the relationship with the abuser, and maintaining a sense of mastery. Individualized definitions of “safety” were unrelated to elder mistreatment risk. Assistance included working with the suspected perpetrator, which is not offered by most elder mistreatment interventions, and resulted in some risk reduction. Reasons for refusing help were a desire for control and fear of loss of well-being assets.

Discussion and Implications

Individualized definitions of well-being should be considered in measuring intervention success. Future research could determine guidelines on what levels of elder mistreatment risk are acceptable, and how to monitor clients for safety while supporting autonomy.
Deep-learning-guided high-resolution subsurface reflectivity imaging with application to ground-penetrating radar data
Authors: Gao Kai , Donahue Carly , Henderson Bradley G , Modrak Ryan T
Published: November 2022

Subsurface reflectivity imaging is one of the most important geophysical characterization methods for revealing subsurface structures. In many cases, accurate subsurface reflectivity imaging is challenging because of, for example, random or coherent noise in the data and sparse source–receiver observation geometry. We develop a deep-learning-guided iterative imaging method to improve subsurface structure imaging. Specifically, we train a supervised neural network to infer a noise-free, high-resolution image from a noisy, low-resolution image and use this estimated image as guidance to regularize least-squares imaging. We develop a systematic method to generate high-quality synthetic training data (data-label pairs) to train the guidance neural network. The trained neural network can provide high-fidelity predictions even for field-data images that are not in the training data. We validate our new imaging method using one synthetic and two field ground-penetrating radar data examples, and find that our method can produce clean, high-resolution subsurface reflectivity images where existing single-pass and least-squares imaging methods fail due to noise and insufficient data coverage.
Artesunate ameliorates osteoarthritis cartilage damage by updating MTA1 expression and promoting the transcriptional activation of LXA4 to suppress the JAK2/STAT3 signaling pathway
Authors: Zhao Chengjin , Zhao Li , Zhou Yuhu , Feng Yangyang , Li Nannan , Wang Kunzheng
Published: November 2022

The objective of this study was to discuss the mechanism of artesunate (ART) in improving cartilage damage in osteoarthritis (OA) by regulating the expression levels of metastatic tumor antigen 1 (MTA1), lipoxin A4 (LXA4) and the downstream JAK2/STAT3 signaling pathway. The OA model in vitro was constructed by stimulating chondrocytes for 24 h with 10 ng/mL interleukin (IL)-1β, and cell proliferation and apoptosis, expression levels of Aggrecan, MTA1, LXA4, MMP3, MMP13 and Collagen II, and inflammatory cytokines in the culture supernatants were examined. Histopathological changes, inflammatory response and chondrocyte apoptosis of the cartilage tissues of OA mice were performed. In vitro cell experiments, ART enhanced cell proliferation capacity, accompanied by decreased apoptosis rate, decreased expression of MMP-3 and MMP-13, elevated expression of Collagen II and Aggrecan, as well as reduced levels of IL-6 and TNF-α in the cell supernatant. ART also ameliorated IL-1β-induced chondrocyte damage by upregulating MTA1. The LXA4 promoter region had two potential binding sites for MTA1. There was a positive correlation between MTA1 and LXA4. MTA1 enhanced the expression of LXA4 through transcription and blocked the activation of the JAK2/STAT3 signaling pathway. In vivo animal model experiments further showed that ART treatment alleviated cartilage tissue damage in OA model mice by upregulating MTA1. Our study demonstrates that ART improves the cartilage damage of OA by upregulating MTA1 expression and promoting the transcriptional activation of LXA4, and further blocking the JAK2/STAT3 signaling pathway.
Digital Peacebuilding: A Framework for Critical–Reflexive Engagement
Authors: Hirblinger Andreas Timo , Hansen Julie Marie , Hoelscher Kristian , Kolås Åshild , Lidén Kristoffer , Martins Bruno Oliveira
Published: November 2022

Existing research on digital technologies in peacebuilding exhibits both tech-solutionist and tech-problematizing traits that tend to understate their embeddedness in society and politics. We argue that the study of digital peacebuilding should instead reflexively engage with the coproduction of the technical and the social in both academia and practice. This requires asking how assumptions about technology are related to assumptions about the conflict and peacebuilding context on which these technologies are brought to bear, and with what consequences. Therefore, we propose a methodological framework that brings to the fore how technologies for peacebuilding and peacebuilding with technology are coproduced. First, we focus on the interrelated claims about peacebuilding and technology, and the coproduction of peacebuilding problems and technological solutions. Second, we inquire into the characteristics of the digital peacebuilding agendas built on these claims, including the dynamics of disruptive change and datafication that these agendas bring. Third, we consider the sticky effects of digital approaches, in terms of a politicization or depoliticization of peacebuilding efforts, and ask what kind of peace this may produce.
Forum: The Why and How of Global Governors: Relational Agency in World Politics
Authors: Hofferberth Matthias , Lambach Daniel , Koch Martin , Holzscheiter Anna , Deloffre Maryam Zarnegar , Reiners Nina , Ronit Karsten
Published: November 2022

Scholars of world politics can readily list the global governors of our time, but why and how did these particular actors gain agency in the first place? While there is impressive scholarship on single global governors and their respective impact, there is little comparative work and systematic theorization on what agency in world politics is and how actors gain it. This forum brings together contributions that apply relational frameworks to the question, focusing on the dynamics of self-agentification, delegation, and recognition. Individual contributions detail different empirical cases, from individuals to the G20, and introduce concepts for meso-level theorizing. Taken together, the contributions call for a more dynamic research agenda that not only allows scholars to reconstruct how agency emerges but also pushes us toward an agency-focused reframing of global governance, which is needed to ensure the continued relevance of the paradigm.
The effect of the acute phase of infection on absorption of and exposure to orally administered antibiotics in non-critically ill, hospitalized patients
Authors: Van Den Broek A K , Visser C E , Veenstra J , Van Den Berg B T J , Prins J M , Van Hest R M
Published: November 2022

Objectives

During the acute phase of infection, IV antibiotics are preferred to ensure adequate systemic exposure. To assess whether adequate exposure may also be achieved with oral antibiotics, we investigated exposure to oral antibiotics and PTA during the acute phase of infection and after defervescence.

Methods

We enrolled hospitalized, non-critically ill febrile patients treated with IV antibiotics other than amoxicillin or ciprofloxacin. The study consisted of two visits: when patients had received <24 h IV treatment; and when patients had become afebrile. On both visits, patients received one additional dose of 750 mg amoxicillin, or 500 mg ciprofloxacin, depending on the presumed infection, after which serial blood samples were obtained. The primary endpoint was the ratio of the AUC during the febrile and the afebrile phase. The AUCs were considered to be equivalent when the ratio of the mean AUCs and its 90% CI was contained within the acceptance interval of 80%–125%. The secondary endpoint was PTA.

Results

Forty-four patients (15 amoxicillin, 29 ciprofloxacin) completed both study visits. The median time between the two study visits was 65.8 h (range 33.8–427.4). The ratio of the mean AUCs (study visit 1/study visit 2) was 97% (90% CI of 80%–117%) for amoxicillin and 112% (90% CI of 108%–116%) for ciprofloxacin. The PTA for amoxicillin and ciprofloxacin did not differ between the two phases and was adequate to treat common pathogens.

Conclusions

The acute phase of infection in non-critically ill febrile patients does not influence the exposure to, or PTA of, orally administered amoxicillin and ciprofloxacin. This might justify earlier IV-to-oral switching.
Applying the indicator amino acid oxidation technique in the domestic cat: results of a pilot study and development of a non-steady state prediction model
Authors: Pezzali Julia Guazzelli , Rafii Mahroukh , Courtney-Martin Glenda , Cant John P , Shoveller Anna K
Published: November 2022

The aim of this study was to evaluate whether the indicator amino acid oxidation (IAAO) method could be applied in the domestic cat. Six adult male cats were used in a replicated 3 × 3 Latin square design. Three semi-synthetic diets were developed: a methionine (Met) and total sulfur AA (TSAA) deficient diet (T-BASAL; 0.24% Met+Cys − DM basis) and two Met and TSAA-sufficient diets in which either dl-Met (T-DLM) or 2-hydroxy-4-(methylthio)-butanoic acid (T-MHA) were supplemented, respectively, on an equimolar basis to meet the TSAA requirement (0.34%). After a 2-d diet adaptation, IAAO studies were performed. Cats were offered 13 small meals. The sixth meal contained a priming dose (4.8 mg/kg-BW) of l-[1-13C]-Phe and the remaining meals a constant dose (1.04 mg/kg-BW). Breath samples were collected every 25 min to measure 13CO2 enrichment. The following morning, fasted blood samples were collected. Cats returned to the T-BASAL top dressed with a dl-Met solution for 4 d prior to being fed a new dietary treatment. Isotopic steady state was evaluated through visual inspection. Data were analyzed using PROC GLIMMIX procedure in SAS 9.4. While 13CO2 enrichment was successfully captured in breath samples, cats failed to reach 13CO2 steady state. Thus, a non-steady state isotope model was developed and coded in ACSLX (V3.1.4.2) individually for each cat on each study day to predict 13CO2 enrichment, and then, calculate oxidation of l-[1-13C]-Phe (F13CO2). A higher predicted F13CO2 was observed for cats fed T-BASAL compared to the others (P < 0.05), while no differences were observed between T-DLM and T-MHA (P > 0.05). Cats fed T-DLM tended to have higher plasma Met concentrations compared to those fed T-BASAL with cats fed T-MHA intermediate (P = 0.0867). Plasma homocysteine concentrations were higher in cats fed T-BASAL compared to the others (P < 0.05), while threonine concentrations tended to be higher in cats fed T-BASAL compared to those fed T-MHA (P = 0.0750). In conclusion, short-term provision of a semi-synthetic diet deficient in Met may elicit a metabolic response aiming to conserve Met. The successful quantification of 13CO2 enrichment in breath and the higher predicted F13CO2 in cats fed a Met deficient diet suggest that the IAAO technique may be used in cats. Adaptations in the isotope protocol should be made to achieve 13CO2 steady state in breath and avoid mathematical modeling to predict F13CO2.
Surf4, cargo trafficking, lipid metabolism, and therapeutic implications
Authors: Shen Yishi , Gu Hong-Mei , Qin Shucun , Zhang Da-Wei
Published: November 2022

Surfeit 4 is a polytopic transmembrane protein that primarily resides in the endoplasmic reticulum (ER) membrane. It is ubiquitously expressed and functions as a cargo receptor, mediating cargo transport from the ER to the Golgi apparatus via the canonical coat protein complex II (COPII)-coated vesicles or specific vesicles. It also participates in ER–Golgi protein trafficking through a tubular network. Meanwhile, it facilitates retrograde transportation of cargos from the Golgi apparatus to the ER through COPI-coated vesicles. Surf4 can selectively mediate export of diverse cargos, such as PCSK9 very low-density lipoprotein (VLDL), progranulin, α1-antitrypsin, STING, proinsulin, and erythropoietin. It has been implicated in facilitating VLDL secretion, promoting cell proliferation and migration, and increasing replication of positive-strand RNA viruses. Therefore, Surf4 plays a crucial role in various physiological and pathophysiological processes and emerges as a promising therapeutic target. However, the molecular mechanisms by which Surf4 selectively sorts diverse cargos for ER–Golgi protein trafficking remain elusive. Here, we summarize the most recent advances in Surf4, focusing on its role in lipid metabolism.
Regulatory Convergence Between U.S. Antitrust Law and Eu Competition Law in International Air Transport—Taking Stock
Authors: Lykotrafiti Antigoni
Published: November 2022

This article takes stock of the regulatory convergence between US antitrust law and EU competition law in the field of international air transport. The analysis draws a distinction between domestic aviation and international aviation and sets the boundaries of regulatory convergence in international air transportation. Through a comparative analysis of the decisional practice of the U.S. Department of Transportation and the European Commission, it identifies instances of regulatory convergence in: (i) the definition of the relevant market in international airline alliance cases, (ii) the remedies imposed to immunize international airline alliances, and (iii) the duration of the antitrust immunity. It further identifies an instance of legislative convergence in the area of fair competition in international air transport. The analysis addresses the future of regulatory convergence in the post-Covid 19 era and emphasizes the role of the competition authorities in safeguarding consumer welfare.
Multiscale computational solid mechanics: data and machine learning
Authors: Su Tung-Huan , Huang Szu-Jui , Jean Jimmy Gaspard , Chen Chuin-Shan
Published: November 2022

Multiscale computational solid mechanics concurrently connects complex material physics and macroscopic structural analysis to accelerate the application of advanced materials in the industry rather than resorting to empirical constitutive models. The rise of data-driven multiscale material modeling opens a major paradigm shift in multiscale computational solid mechanics in the era of material big data. This paper reviews state-of-the-art data-driven methods for multiscale simulation, focusing on data-driven multiscale finite element method (data-driven FE2) and data-driven multiscale finite element-deep material network method (data-driven FE-DMN). Both types of data-driven multiscale methods aim to resolve the past challenge of concurrent multiscale simulation. Numerical examples are designed to demonstrate the effectiveness of data-driven multiscale simulation methods. Future research directions are discussed, including data sampling strategy and data generation technique for the data-driven FE2 method and generalization of data-driven FE-DMN method.
Impacts of methyl jasmonate onSelaginella martensii: volatiles, transcriptomics, phytohormones, and gas exchange
Authors: Wuyun Tana , Hõrak Hanna , Liu Bin , Talts Eero , Kilk Kalle , Kaurilind Eve , Li Caihong , Zhang Lu , Niinemets Ülo
Published: November 2022

Methyl jasmonate (MeJA) induces various defence responses in seed plants, but for early plant lineages, information on the potential of jasmonates to elicit stress signalling and trigger physiological modifications is limited. The spikemoss Selaginella martensii was exposed to a range of MeJA concentrations (0, 10, 25, and 50 mM), and biogenic volatile organic compound (BVOC) emissions, photosynthetic rate (A), and stomatal conductance (gs) were continuously measured. In addition, changes in phytohormone concentrations and gene expression were studied. Enhancement of methanol, lipoxygenase pathway volatiles and linalool emissions, and reductions in A and gs, were MeJA dose-dependent. Before MeJA treatment, the concentration of 12-oxo-phytodienoic acid (OPDA) was 7-fold higher than jasmonic acid (JA). MeJA treatment rapidly increased OPDA and JA concentrations (within 30 min), with the latter more responsive. Some genes involved in BVOC biosynthesis and OPDA-specific response were up-regulated at 30 min after MeJA spraying, whereas those in the JA signalling pathway were not affected. Although JA was synthesized in S. martensii, OPDA was prioritized as a signalling molecule upon MeJA application. MeJA inhibited primary and enhanced secondary metabolism; we propose that fast-emitted linalool could serve as a marker of elicitation of stress-induced metabolism in lycophytes.
Extending the ‘one-point method’ for estimations of leaf photosynthetic capacity to a broader temperature range
Authors: Oliveira Tony César de Sousa , Garcia Maquelle Neves , Veenendaal Elmar , Domingues Tomas Ferreira
Published: November 2022

We propose a temperature-dependent scaling factor for the ‘one-point method’ to mitigate the overestimation of the maximum carboxylation capacity of photosynthesis at high temperatures.
Stable ARMADILLO REPEAT KINESIN 2 in light inhibits hypocotyl elongation and facilitates light-induced cortical microtubule reorientation in Arabidopsis
Authors: Lan Miao , Kang Erfang , Liu Xianan , Fu Ying , Zhu Lei
Published: November 2022

Hypocotyls undergo different morphogenesis in light and dark conditions, with cortical microtubules being reoriented in response to light to coordinate cell growth status. Kinesins are microtubule-based motor proteins that are mostly responsible for transporting organelles and vesicles, although some can also regulate microtubule organization; however, it is currently not known whether they are involved in microtubule reorientation and hypocotyl elongation. In this study, we found that ARMADILLO REPEAT KINESIN 2 (ARK2) negatively regulated the hypocotyl elongation of Arabidopsis. The hypocotyl cells of plants with the ark2 null allele were longer than those of the wild type and had relatively more transversely arranged cortical microtubules. In addition, ARK2 co-localized with cortical microtubules and facilitated the light-induced reorientation of the cortical microtubule arrays. Interestingly, the ARK2 protein is stable in the light and degraded through the 26S proteasome pathway in the dark. Furthermore, we determined that ARK2 could interact with the E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), which contributed to down-regulation of ARK2 in darkness that might benefit hypocotyl growth in the dark.