bluuebunny/crossref_metadata_2025 huggingface dataset:
MEK Inhibition Reverses Aberrant Signaling in Melanoma Cells through Reorganization of NRas and BRAF in Self Nanoclusters
Authors: Yakovian Oren , Sajman Julia , Arafeh Rand , Neve-Oz Yair , Alon Michal , Samuels Yardena , Sherman Eilon
Published: December 2020

Hotspot mutations of the oncogenes BRAF and NRas are the most common genetic alterations in cutaneous melanoma. Still, the nanoscale organization and signal coupling of these proteins remain incompletely understood, particularly upon expression of oncogenic NRas mutants. Here we employed single-molecule localization microscopy to study the nanoscale organization of NRas and BRAF at the plasma membrane (PM) of melanoma cells. NRas and BRAF resided in self-clusters that did not associate well in resting cells. In EGF-activated cells, NRas clusters became more diffused while overall protein levels at the PM increased; thus allowing enhanced association of NRas and BRAF and downstream signaling. In multiple melanoma cell lines, mutant NRas resided in more pronounced self-clusters relative to wild-type (WT) NRas yet associated more with the clustered and more abundant BRAF. In cells resistant to trametinib, a clinical MEK inhibitor (MEKi), a similar coclustering of NRas and BRAF was observed upon EGF activation. Strikingly, treatment of cells expressing mutant NRas with trametinib reversed the effect of mutant NRas expression by restoring the nonoverlapping self-clusters of NRas and BRAF and by reducing their PM levels and elevated pERK levels caused by mutant NRas. Our results indicate a new mechanism for signal regulation of NRas in melanoma through its nanoscale dynamic organization and a new mechanism for MEKi function in melanoma cells carrying NRas mutations but lacking MEK mutations.

Significance:

Nanoscale dynamic organization of WT and mutant NRas relative to BRAF serves as a regulatory mechanism for NRas signaling and may be a viable therapeutic target for its sensitivity to MEKi.
USP24 Is a Cancer-Associated Ubiquitin Hydrolase, Novel Tumor Suppressor, and Chromosome Instability Gene Deleted in Neuroblastoma
Authors: Bedekovics Tibor , Hussain Sajjad , Zhang Ying , Ali Asma , Jeon Young J. , Galardy Paul J.
Published: December 2020

Deubiquitinating enzymes are increasingly recognized to play important roles in cancer, with many acting as oncogenes or tumor suppressors. In this study, we employed a bioinformatics approach to screen for enzymes from this family involved in cancer and found USP24 as a potent predictor of poor outcomes in neuroblastoma, an aggressive childhood cancer. USP24 resides in a region commonly deleted in neuroblastoma, yet was independently associated with poor outcomes in this disease. Deletion of Usp24 in a murine model resulted in degradation of collapsin response mediator protein 2 (CRMP2), a regulator of axon growth, guidance, and neuronal polarity. Cells lacking USP24 had significant increases in spindle defects, chromosome missegregation, and aneuploidy, phenotypes that were rescued by the restoration of CRMP2. USP24 prevented aneuploidy by maintaining spindle-associated CRMP2, which is required for mitotic accuracy. Our findings further indicate that USP24 is a tumor suppressor that may play an important role in the pathogenesis of neuroblastoma.

Significance:

This study identifies the chromosome instability gene USP24 as frequently deleted in neuroblastoma and provides important insight into the pathogenesis of this aggressive childhood cancer.
Posttraumatic Stress Disorder and Likelihood of Hormone Therapy Use among Women in the Nurses' Health Study II: A 26-Year Prospective Analysis
Authors: Lawn Rebecca B. , Nishimi Kristen M. , Kim Yongjoo , Jung Sun Jae , Roberts Andrea L. , Sumner Jennifer A. , Thurston Rebecca C. , Chibnik Lori B. , Rimm Eric B. , Ratanatharathorn Andrew D. , Jha Shaili C. , Koenen Karestan C. , Tworoger Shelley S. , Kubzansky Laura D.
Published: December 2020

Background:

Posttraumatic stress disorder (PTSD) is associated with higher risk of certain chronic diseases, including ovarian cancer, but underlying mechanisms remain unclear. Although prior work has linked menopausal hormone therapy (MHT) use with elevated ovarian cancer risk, little research considers PTSD to likelihood of MHT use. We examined whether PTSD was prospectively associated with greater likelihood of initiating MHT use over 26 years.

Methods:

Using data from the Nurses' Health Study II, with trauma and PTSD (symptoms and onset date) assessed by screener in 2008 and MHT assessed via biennial survey (from 1989), we performed Cox proportional regression models with women contributing person-years from age 36 years. Relevant covariates were assessed at biennial surveys. We considered potential effect modification by race/ethnicity, age at baseline, and period (1989–2002 vs. 2003–2015).

Results:

Over follow-up, 22,352 of 43,025 women reported initiating MHT use. For example, compared with women with no trauma, the HR for initiating MHT was 1.18 for those with trauma/1–3 PTSD symptoms [95% confidence interval (CI), 1.13–1.22] and 1.31 for those with trauma/4–7 PTSD symptoms (95% CI, 1.25–1.36; P trend < 0.001), adjusting for sociodemographic factors. Associations were maintained when adjusting for reproductive factors and health conditions. We found evidence of effect modification by age at baseline.

Conclusions:

Trauma and number of PTSD symptoms were associated with greater likelihood of initiating MHT use in a dose–response manner.

Impact:

MHT may be a pathway linking PTSD to altered chronic disease risk. It is important to understand why women with PTSD initiate MHT use.
Genome Methylation Accurately Predicts Neuroendocrine Tumor Origin: An Online Tool
Authors: Hackeng Wenzel M. , Dreijerink Koen M.A. , de Leng Wendy W.J. , Morsink Folkert H.M. , Valk Gerlof D. , Vriens Menno R. , Offerhaus G. Johan A. , Geisenberger Christoph , Brosens Lodewijk A.A.
Published: December 2020

Purpose:

The primary origin of neuroendocrine tumor metastases can be difficult to determine by histopathology alone, but is critical for therapeutic decision making. DNA methylation–based profiling is now routinely used in the diagnostic workup of brain tumors. This has been enabled by the availability of cost-efficient array-based platforms. We have extended these efforts to augment histopathologic diagnosis in neuroendocrine tumors.

Experimental Design:

Methylation data was compiled for 69 small intestinal, pulmonary, and pancreatic neuroendocrine tumors. These data were used to build a ridge regression calibrated random forest classification algorithm (neuroendocrine neoplasm identifier, NEN-ID). The model was validated during 3 × 3 nested cross-validation and tested in a local and an external cohort (n = 198 cases).

Results:

NEN-ID predicted the origin of tumor samples with high accuracy (>95%). In addition, the diagnostic approach was determined to be robust across a range of possible confounding experimental parameters, such as tumor purity and array quality. A software infrastructure and online user interface were built to make the model available to the scientific community.

Conclusions:

This DNA methylation–based prediction model can be used in the workup for patients with neuroendocrine tumors of unknown primary. To facilitate validation and clinical implementation, we provide a user-friendly, publicly available web-based version of NEN-ID.
MEK-ing the Most of It: Strategies to Co-target Gαq and MAPK in Uveal Melanoma
Authors: Neelature Sriramareddy Sathya , Smalley Keiran S.M.
Published: December 2020

Most uveal melanomas harbor mutations in Gαq and show constitutive MAPK activation. Although MEK inhibition has some efficacy against uveal melanoma, clinical responses are typically poor. The Gαq inhibitor-MEK inhibitor combination showed prolonged suppression of MAPK signaling in preclinical uveal melanoma models and led to improved therapeutic responses.

See related article by Hitchman et al., p. 1476
Cost Effectiveness of Whole Population BRCA Genetic Screening for Cancer Prevention in Israel
Authors: Michaan Nadav , Leshno Moshe , Safra Tamar , Sonnenblick Amir , Laskov Ido , Grisaru Dan
Published: December 2020

With the growing technical ease and reduction in genetic screening costs, whole population BRCA screening may be a feasible option. Our objective was to investigate the cost effectiveness of whole population screening for BRCA mutations in Israel, for varying degrees of BRCA carrier state. Lifetime costs of whole female population screening for BRCA mutation carrier state versus nonscreening were compared using a Markovian process decision analysis model. Model parameters including ovarian and breast cancer risks were obtained from previously published data. Screening and other treatment-related costs were received from the Israeli Ministry of Health pricing list according to specified codes. Quality-adjusted life years were used for cost-effectiveness analysis. Sensitivity analysis was conducted to evaluate model uncertainties, specifically varying degrees of BRCA prevalence. Results show that whole population BRCA screening in Israel is cost effective across a wide range of BRCA prevalence rates with an incremental cost-effectiveness ratio of 81,493 new Israeli Shekels for a BRCA prevalence of 2.5%, increasing to 250,000 new Israeli Shekels for a 0.75% prevalence rate, per quality-adjusted life year gained. Discount rate and population BRCA prevalence and rate of risk reduction salpingo-oophorectomy are the most influential parameters in the model. Whole population screening for BRCA mutations should be offered as part of general health screening strategies by national medical insurance providers, even for non-Ashkenazi Jews. Our algorithm can be applied for other countries, adjusting local costs of screening and treatment.

Prevention Relevance:

Whole population BRCA mutation screening in Israel is cost effective across a wide prevalence rate and should be offered as part of general health screening strategies by national medical insurance providers for cancer prevention.
Therapy of Established Tumors with Rationally Designed Multiple Agents Targeting Diverse Immune–Tumor Interactions: Engage, Expand, Enable
Authors: Fabian Kellsye P. , Malamas Anthony S. , Padget Michelle R. , Solocinski Kristen , Wolfson Benjamin , Fujii Rika , Abdul Sater Houssein , Schlom Jeffrey , Hodge James W.
Published: December 2020

Immunotherapy of immunologically cold solid tumors may require multiple agents to engage immune effector cells, expand effector populations and activities, and enable immune responses in the tumor microenvironment (TME). To target these distinct phenomena, we strategically chose five clinical-stage immuno-oncology agents, namely, (i) a tumor antigen–targeting adenovirus-based vaccine (Ad-CEA) and an IL15 superagonist (N-803) to activate tumor-specific T cells, (ii) OX40 and GITR agonists to expand and enhance the activated effector populations, and (iii) an IDO inhibitor (IDOi) to enable effector-cell activity in the TME. Flow cytometry, T-cell receptor (TCR) sequencing, and RNA-sequencing (RNA-seq) analyses showed that in the CEA-transgenic murine colon carcinoma (MC38-CEA) tumor model, Ad-CEA + N-803 combination therapy resulted in immune-mediated antitumor effects and promoted the expression of costimulatory molecules on immune subsets, OX40 and GITR, and the inhibitory molecule IDO. Treatment with Ad-CEA + N-803 + OX40 + GITR + IDOi, termed the pentatherapy regimen, resulted in the greatest inhibition of tumor growth and protection from tumor rechallenge without toxicity. Monotherapy with any of the agents had little to no antitumor activity, whereas combining two, three, or four agents had minimal antitumor effects. Immune analyses demonstrated that the pentatherapy combination induced CD4+ and CD8+ T-cell activity in the periphery and tumor, and antitumor activity associated with decreased regulatory T-cell (Treg) immunosuppression in the TME. The pentatherapy combination also inhibited tumor growth and metastatic formation in 4T1 and LL2-CEA murine tumor models. This study provides the rationale for the combination of multimodal immunotherapy agents to engage, enhance, and enable adaptive antitumor immunity.
Auditory Outcome after Cochlear Implantation in Children with DFNB7/11 Caused by Pathogenic Variants in TMC1 Gene
Authors: Gallo Samanta , Trevisi Patrizia , Rigon Chiara , Caserta Ezio , Seif Ali Dario , Bovo Roberto , Martini Alessandro , Cassina Matteo
Published: December 2020

Introduction: Non-syndromic hereditary hearing loss is characterized by extreme genetic heterogeneity. So far, more than 100 pathogenic or likely pathogenic variants in TMC1 gene have been reported in patients with autosomal recessive hearing loss (HL) DFNB7/11. The prevailing auditory phenotype of individuals with DFNB7/11 is congenital, profound, bilateral HL, but the functional outcome after cochlear implantation (CI) described in the literature is variable. The objective of this work is to evaluate the auditory outcome after CI in pediatric patients with DFNB7/11, born to non-consanguineous parents. Methods: A retrospective analysis of genetic and audiological data of DFNB7/11 patients followed up in a single Italian otolaryngology clinic was performed. Cases with biallelic pathogenic variants in TMC1 were selected from the cohort of children with non-syndromic hearing loss who had undergone CI and had been molecularly characterized by multigene panel testing. All patients underwent extensive audiological assessment, and the auditory outcome after CI was evaluated. Results: DFNB7/11 was diagnosed in a total of 3 patients from 2 non-consanguineous families; a novel disease-causing variant in TMC1 was detected [c.962G>A p.(Trp321*)]. All the affected children showed the typical DFNB7/11 phenotype characterized by prelingual, severe-to-profound HL. The patients showed an excellent functional outcome after CI; speech perception, nonverbal cognition, and speech performance were comparable to those of patients with DFNB1 deafness. Discussion/Conclusion: Our results do not support the variable auditory outcome reported in the literature, which may be affected by several social and environmental factors and by the genetic background.
Microbiome: A Supportive or a Leading Actor in Lung Cancer?
Authors: Martins Diana , Mendes Fernando , Schmitt Fernando
Published: December 2020

Lung cancer is still the leading cause of cancer death worldwide. Despite the major diagnostic and therapeutic innovations, the effect on mortality has been modest and the overall survival is still poor. Better understanding of the pathology of these tumors is necessary in order to develop personalized therapeutic strategies in lung cancer patients. Human microbiome has been associated with normal physiology and function, and increasing evidence points towards a key role of the microbiome in promoting the progression of lung disease. Studies have shown that although poorly understood, lung has a distinctive microbiome that may an important role in lung cancer development and progression, and interactions between microbial populations have the potential to influence disease, suggesting that microbiome can be an emerging target in cancer therapeutics. We will review mechanisms how the lung microbiota influences carcinogenesis, focusing on the bacterial dysbiosis and inflammation. Moreover, we will discuss the link between the microbiome and cancer and the consequences induced by the immune system, as the host microbiota plays an essential role in activating and modulating the immune response. We summarize current research advances in the lung microbiome and demonstrate the potential to exploit microbiome as a mechanism to prevent carcinogenesis and modulate therapeutic strategy, suggesting microbiome as a valuable approach in lung cancer patients.
Phylogenetic Characterization of the 5′ Untranslated Region of Untypable HCV Genotypes Circulating in Pakistan
Authors: Ghani Usman , Rehman Irshad Ur , Ali Muhammad , Khan Ayyaz , Ullah Sana , Ali Liaqat , Butt Sadia
Published: December 2020

Introduction: Commercial methods for HCV genotyping is challenged by the increased prevalence of untypable genotypes in Pakistan. Objective: The aim of the current study was to perform nucleotide sequencing of 5′ UTR region for genotyping of viral isolates circulating in Peshawar, Pakistan. Methods: The total number of commercially untypable samples were 94 in which 18 samples were sequenced for the characterization of 5′ UTR region. Post-sequencing analysis was performed for genotype identification (n = 18) and molecular phylogenetic analysis. Results: The current study reveals different genotypes, that is, 10/18 viral isolates were found to be genotype 3a (55.55%), 3 isolates (genotype 3b, 16.66%), 2 isolates (genotype 6h/6g, 11.11%), 2 (6g/d, 11.11%), and 1 sample (genotype 1c, 5.55%). In addition, genotype 3a is the dominant representative of HCV circulating in Pakistan and has been increasing across the country. Conclusion: The current study also reveals that genotype 6 (2 were genotype 6h/6g and 2 were 6g/d) is also circulating in Pakistan and not restricted to South China and Hong Kong.
Intravenous Hydrogen Therapy With Intracisternal Magnesium Sulfate Infusion in Severe Aneurysmal Subarachnoid Hemorrhage
Authors: Takeuchi Satoru , Kumagai Kosuke , Toyooka Terushige , Otani Naoki , Wada Kojiro , Mori Kentaro
Published: December 2020

Background and Purpose:

Poor-grade subarachnoid hemorrhage still has a poor prognosis. This randomized controlled clinical trial evaluated intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy in patients with poor-grade subarachnoid hemorrhage.

Methods:

Thirty-seven patients with poor-grade subarachnoid hemorrhage were randomized to Mg+H
2
, Mg, and control groups. Mg and Mg+H
2
groups received intracisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days. Mg+H
2
group also received intravenous hydrogen-rich solution infusion for 14 days. Primary outcome measures were occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures were modified Rankin Scale and Karnofsky performance status at 3 and 12 months, Barthel index at 12 months, and serum and cerebrospinal fluid malondialdehyde and neuron-specific enolase.

Results:

Serum neuron-specific enolase levels were significantly lower in the Mg+H
2
group from days 3 to 14 than in the control group. Cerebrospinal fluid neuron-specific enolase levels were also significantly lower in the Mg+H
2
group from days 3 to 7 than in the control group. Incidences of cerebral vasospasm and delayed cerebral ischemia were significantly higher in the control group than in other groups. Modified Rankin Scale and Karnofsky performance status did not significantly differ between the three groups at 3 months. Modified Rankin Scale scores 0 to 2 were more common in the Mg and Mg+H
2
groups at 1 year. Barthel index was higher in the Mg+H
2
group than in the control group.

Conclusions:

Intracisternal magnesium sulfate infusion started immediately after surgery reduces the incidence of cerebral vasospasm and delayed cerebral ischemia and improves clinical outcomes without complications in patients with poor-grade subarachnoid hemorrhage. Intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy decreases serum malondialdehyde and neuron-specific enolase and improves Barthel index, indicating hydrogen has additional effects.

Registration:

URL:
https://www.umin.ac.jp/ctr/index.htm
. Unique identifier: UMIN000014696.
Utility of Severity-Based Prehospital Triage for Endovascular Thrombectomy
Authors: Zhao Henry , Smith Karen , Bernard Stephen , Stephenson Michael , Ma Henry , Chandra Ronil V. , Phan Thanh , Bladin Christopher F. , Churilov Leonid , Crompton Douglas , Dewey Helen M. , Wijeratne Tissa , Cloud Geoffrey , Thijs Vincent , Kleinig Timothy J. , Ng Jo Lyn , Williams Cameron , Alemseged Fana , Ng Felix , Mitchell Peter J. , Parsons Mark W. , Yassi Nawaf , Davis Stephen M. , Campbell Bruce C.V.
Published: December 2020

Background and Purpose:

Severity-based assessment tools may assist in prehospital triage of patients to comprehensive stroke centers (CSCs) for endovascular thrombectomy (EVT), but criticisms regarding diagnostic inaccuracy have not been adequately addressed. This study aimed to quantify the benefits and disadvantages of severity-based triage in a large real-world paramedic validation of the Ambulance Clinical Triage for Acute Stroke Treatment (ACT-FAST) algorithm.

Methods:

Ambulance Victoria paramedics assessed the prehospital ACT-FAST algorithm in patients with suspected stroke from November 2017 to July 2019 following an 8-minute training video. All patients were transported to the nearest stroke center as per current guidelines. ACT-FAST diagnostic accuracy was compared with hospital imaging for the presence of large vessel occlusion (LVO) and need for CSC-level care (LVO, intracranial hemorrhage, and tumor). Patient-level time saving to EVT was modeled using a validated Google Maps algorithm. Disadvantages of CSC bypass examined potential thrombolysis delays in non-LVO infarcts, proportion of patients with false-negative EVT, and CSC overburdening.

Results:

Of 517 prehospital assessments, 168/517 (32.5%) were ACT-FAST positive and 132/517 (25.5%) had LVO. ACT-FAST sensitivity and specificity for LVO was 75.8% and 81.8%, respectively. Positive predictive value was 58.8% for LVO and 80.0% when intracranial hemorrhage and tumor (CSC-level care) were included. Within the metropolitan region, 29/55 (52.7%) of ACT-FAST-positive patients requiring EVT underwent a secondary interhospital transfer. Prehospital bypass with avoidance of secondary transfers was modeled to save 52 minutes (95% CI, 40.0–61.5) to EVT commencement. ACT-FAST was false-positive in 8 patients receiving thrombolysis (8.1% of 99 non-LVO infarcts) and false-negative in 4 patients with EVT requiring secondary transfer (5.4% of 74 EVT cases). CSC bypass was estimated to over-triage 1.1 patients-per-CSC-per-week in our region.

Conclusions:

The overall benefits of an ACT-FAST algorithm bypass strategy in expediting EVT and avoiding secondary transfers are estimated to substantially outweigh the disadvantages of potentially delayed thrombolysis and over-triage, with only a small proportion of EVT patients missed.
Silver Lining to Extreme Weather Events? Democracy and Climate Change Mitigation
Authors: Peterson Lauri
Published: December 2020

Long-standing meteorological research has established that anthropogenic climate change increases the risk and intensity of extreme weather events, such as tropical cyclones, floods, and forest fires. However, comparatively little is known about the impact of such events on policy ambition. Studies on the topic emerged only recently and tend to focus on individual country cases. A comprehensive cross-country perspective is still missing. This article addresses the gap in the literature using large-scale analyses on the basis of country-level data from 2008 to 2017. The findings indicate that extreme weather events propel only highly functioning democracies to tackle climate change. Effects among remaining country cases are insignificant. This variation in the data can be attributed to democracies’ concern for the common good and the perspectives of those most affected by climate-related disasters.
The Impact of Power on Contact Zones and Receptivity
Authors: Ulf Christoph
Published: December 2020

The concept of contacts zones, as developed in Ulf 2009, employs differentiating factors to embed the actors involved in the transfers of goods and ideas in their cultural and socio-political environments. Power exerted between people who transfer goods and ideas and those who receive them, is decisive for how receptivity is shaped by their recipients. To discover where power is situated in the complex processes of intercultural interactions, this paper leads attention to the societal characteristics that have an impact on the cultural actors. Referring to the change from the Greek enoikismoi within the scattered settlements of the local population(s) in the hinterland between the Gulf of Taranto and Brindisi to the emergence of recognizable Greek settlements along the coastline from the 8th to the 7th century BC, the example of the feast is chosen to highlight the accompanying change of the scale of power and its exertion. In the terminology of contact zones, a dense contact zone lacking a dominant partner turns into a Middle Ground. From the definition of the various contact zones derives, that the receptivity changed from free adaptation of so far unknown cultural elements to their own intentions and needs to conscious and intentional misunderstandings of the other’s cultural forms and behaviour to gain advantage over the exchange partner. Thus power is a growing factor in their relationship and becomes the more important when the Middle Ground is replaced by a dense zone of contact where one partner is able to dominate. Thereby, it becomes clear that the relationships in cultural transfers are not tied up with ethnic conditions or cultural superiority and inferiority, but determined by the type of contact zones which in turn are characterized by the tools of power involved.
“The Grand Retinue” Phenomenon in Northern and Eastern Europe in the 10-11th Centuries
Authors: Stefanovich Petr
Published: December 2020

The author summarizes evidence of large professional armies in the service of the rulers of early medieval polities in Northern and Eastern Europe. Following František Graus, the author refers to that institution as “grand retinue” (Czech velkodružina, German Staatsgefolge). The rulers maintained these troops mainly by paying in cash collected as tribute from the populace. The late 10th-early 11th-century Poland and the “North Sea Empire” of Cnut the Great (1016-1035) provide the most compelling evidence on the grand retinue. In the 10-11th centuries Rus’, the princes also had armies of military servants, referred to as otroki (a Slavic word) or – more specifically – grid’ (term borrowed from Old Norse). Such troops played a major role during the emergence of the centralized political framework, but have disappeared or degenerated as early as the 12th century. Rus’ian records describe them as prosperous in the 11th century and show their decline during the 12-13th centuries. I interpret the Rus’ian “grand retinue” as an institution based on Scandinavian models, a result of the “transfer of knowledge” that occurred in Northern and Eastern Europe during the 10-11th centuries.
Vulner-ability: A Systematic Theological Approach to an Ambivalent Term
Authors: Leidinger Miriam
Published: December 2020

The term vulnerability is en vogue, both in theology and in mission studies. This contribution systematically analyses the concept and phenomenon of vulnerability and discusses its different aspects; namely materiality and embodiment, pain and suffering, and resilience and resistance. From a Christian theological point of view, these aspects of vulnerability resonate with key theological questions that lead to a closer look at the Christologies of Jürgen Moltmann, Jon Sobrino, and Graham Ward. The guiding questions are: How can we speak about the vulnerable human being in his or her relationship to Jesus Christ, the Son of God made flesh? And how is it possible vice versa to speak about the incarnated God in light of the vulnerability of all human beings? Finally, the argument culminates in a plea for a vulnerable theology in a wounded world.
The “Liturgy after the Liturgy” and Deep Solidarity. The Orthodox Understanding of Christian Witness and its Implications for Human Society
Authors: Sonea Cristian
Published: December 2020

The paper will investigate the orthodox understanding of mission as “liturgy after the Liturgy” and its consequences for human life. The Eucharistic Liturgy understood as an experience of God where the community of saints reveal the absolute model of unity must be replicated in the human society as another type of liturgy, a liturgy of solidarity. The research will present how starting from the Eucharistic community we can reach the community in solidarity.
Hugo Grotius and the Classical Law of Civil War
Authors: Kari Ville
Published: December 2020

This article explores the writings of Hugo Grotius on the law of civil war. First, the article takes a look at what Grotius wrote about the Dutch revolt, the civil war during which he himself lived and which he helped to legitimise. Second, the article notes how in legal practice the Dutch revolt also provided a valuable early precedent for the later scholars of the law of civil war, who were more concerned with questions of revolutionary prize jurisdiction and the problem of recognition. Third, the article explores the elements relating to these questions of civil war in Grotius’s volitional law of nations as presented in De iure belli ac pacis. These provided Grotius’s most enduring legacy for the later scholars on the law of civil war.
Chinese Perceptions of American Democracy: Late Qing Observers and Their Experiences with the Chinese Exclusion Act
Authors: Wong Sam , Wong Brian
Published: December 2020

Analysis of the writings of Kuang Qizhao and other Chinese self-strengtheners suggests that their emphasis on promoting education before democracy and continuing to endorse classical Confucianism were not signs of a retrograde kind of conservatism, but an entirely rational decision based on the actual experiences of late Qing observers of 19th Century American democracy. Observing the U.S. Congress’s passage of the Chinese Exclusion Act of 1882, Chinese officials observed the real dangers of demagogue led populism without an educated, moral citizenry and the apparent importance of Christianity to creating the moral foundation for an effective modern society. For Kuang, Confucianism was equivalent to Christianity to establish that moral basis, and not a conservative desire to preserve the old social order. Kuang would pass on his thoughts to some of China’s most important reformers and officials on his return home, suggesting he and the officials he associated with had a more realistic and sophisticated understanding of American society and democracy than is currently assumed.
‘Jewish Culture is Inseparable From the Struggle Against Reaction’: Forging an Australian Jewish Antifascist Culture in the 1940s
Authors: Kaiser Max
Published: December 2020

In the immediate postwar period Jewish communities worldwide sought to draw political lessons from the events of the Holocaust, the rise of fascism and the Second World War. A distinctive popular Jewish left antifascist politics developed as a way of memorialising the Holocaust, struggling against antisemitism and developing anti-racist and anti-assimilationist Jewish cultures. This article looks at the trilingual magazine Jewish Youth, published in Melbourne in the 1940s in English, Yiddish and Hebrew, as a prism through which to examine Jewish antifascist culture in Australia. Jewish Youth featured an oppositional political stance against antisemitism and fascism, tied often to Holocaust memorialisation; a conscious political and cultural minoritarianism and resistance to assimilation; and a certain fluctuating multilingualism, tied to its transnational situatedness and plurality of audiences.
‘The Antifascist Kick’: A Signifying Cultural Practice in the History of Transnational Antifascism?
Authors: Lundberg Victor
Published: December 2020

This article is based on an empirical study of ‘the antifascist kick’ as a formative cultural practice in the history of transnational antifascism. It scopes from the 1930s and the era of opposition to classic fascism, through to the twenty-first century where antifascism encounters political processes of globalization, fragmentation, neoliberalism, and neofascism. The article discusses the ‘antifascist kick’ in different historical contexts, from 1930s Sweden to Germany and the United States today. The article reveals that ‘the antifascist kick’ works in various cultural directions: as a political conception of those who are only worth contempt, as a symbolic representation of the antifascist struggle, and as a practical instruction for how to treat fascists in the streets.
Music Subculture versus Class Revolutionaries: Czech Antifascism in the Postsocialist Era
Authors: Daniel Ondřej
Published: December 2020

With its roots in the political, economic and social changes of 1989/1990, the Czech antifascist movement was initially characterized by its young supporters, who came mostly from subcultural and anarchist circles. When violent far-right skinheads increased their attacks in the country between 1990 and 1992, local antifascists were the main group to physically confront them. Three decades later, as a result of generational and tactical changes, Czech antifascists’ agenda is largely at odds with the class politics that drive important parts of the anarchist movement. At the same time, the antifascist movement retains some subcultural traits that have become depoliticized. Its strategy is now limited to monitoring far-right activists online and running cultural events. This study analyzes internal debates over the antifascist movement’s positions and reflects on their development over time.
Exile Dreams: Antifascist Jews, Antisemitism and the ‘Other Germany’
Authors: Koch Anna
Published: December 2020

This article examines the meanings antifascist German Jews invested in antifascism and highlights its role as an emotional place of belonging. The sense of belonging to a larger collective enabled antifascist Jews to hold onto their Germanness and believe in the possibility of an ‘other Germany’. While most German Jewish antifascists remained deeply invested in their home country in the 1930s, this idea of the ‘other Germany’ became increasingly difficult to uphold in the face of war and genocide. For some this belief received the final blow after the end of the Second World War when they returned and witnessed the construction of German states that fell short of the hopes they had nourished while in exile. Yet even though they became disillusioned with the ‘other Germany’, they remained attached to antifascism.
‘L’antisémitisme est l’auxiliaire obligatoire du fascisme’: Jewish Communists, Antifascism and Antisemitism in France, 1944-1960s
Authors: Grumberg Zoé
Published: December 2020

This article studies the discursive construction by Jewish communists of the struggle against antisemitism in France between 1944 and the 1960s. It shows that after the Holocaust, without denying the racial aspect of Nazi antisemitism, Jewish communists adopted the French Communist Party and the ussr’s antifascist analysis of antisemitism according to which antisemitism was the corollary of fascism, a strategy to divide people and the working class. However, after the War, Jewish communists’ fight against antisemitism was also shaped by their experiences as Jews during the Holocaust, by their commitment to defend Jewish interests and by their desire to be (re)integrated into the French nation. The author argues that through a specific Jewish and communist antifascist fight against antisemitism, Jewish communists managed to remain faithful to their multiples allegiances – to Jews, to the pcf, and to French universalism – and to reach multiples audiences that identified, at least temporarily, with antifascism.
Internationalisation of Higher Education: Building South-South Partnerships between China and Mexico
Authors: Hu Yiyun , Fan Lijun
Published: December 2020

As an important emerging economy, Mexico is significant to China for promoting world multipolarisation as well as an important partner in jointly building a community of shared future for mankind. Educational exchanges and co-operation are an indispensable part of friendly transactions between China and Mexico. Both countries have made many advancements in the fields of personnel turnover, the establishment of overseas co-operation centres, language promotion, and vocational and technical training. Both China and Mexico regard the other as an important education partner. In future co-operation, the two countries should continue to promote vocational education, improve the degree system, and pay attention to hidden safety issues.
Speaking Back: Reading a Christian Denomination’s Vision for Diversity through the Eyes of its Children and Congregations
Authors: Csinos David M.
Published: December 2020

This article analyzes the United Church of Canada’s vision for becoming intercultural through data generated by qualitative research into the theological meaning-making of children within United Church congregations. The author provides an overview of the broader research project through which this data was generated and background information about Canadian multiculturalism and the United Church’s response to the challenges of multiculturalism, particularly its 2006 document, ‘A Transformative Vision for the United Church of Canada.’ The author presents three points of critique of this document that come into focus when analyzed through the lens of children within United Church congregations. These points include the important step of intentionally listening to voices on the margins, the document’s neglect of individuals and contexts that hold hybrid cultural identities, and its tendency to overlook congregations that are intercultural.
Why French Academic Journals are Protesting
Authors: _ _ , Noûs Camille
Published: December 2020

Written by an anonymous collective of academics as well as an alliance of academic journals on strike, “Why French Academic Journals are Protesting” firstly operates as an archive of struggles unfolding in the world and on the future of research and higher education in France. Documenting a wave of transformations, from the bureaucratization of student-teacher relations and the commodification of university diplomas to the contractualisation of academic labor and cuts to employee benefits, the article exposes the loss of autonomisation and the diffusion of precarity in French academia. More than merely chronicling devastating legislative and administrative reforms, it acts as a testament of a unique form of scholarly disobedience or scholar-activism. In doing so, the author-activists open up a space of hope for alternative futures or perhaps even a sanctuary, wherein the university-as-it-were might be salvaged from or imagined beyond neoliberalism.
Taxonomic revision of Jumellea (Orchidaceae, Angraecinae) in the Mascarenes

Authors: PAILLER THIERRY , RAKOTOARIVELO FANNY PATRICKA , RAZAFIMANDIMBISON SYLVAIN G. , BYTEBIER BENNY , FLORENS F. B. VINCENT , MARTOS FLORENT , BAIDER CLÁUDIA
Published: December 2020

We present a taxonomic revision of the genus Jumellea (Angraecinae; Orchidaceae) in the Mascarenes based on morphological study and field observations. We examined 328 specimens mostly from the MAU, P and REU, and recognise nine species. We provide a key, morphological descriptions, distributions, habitats, phenologies and conservation assessments following the Red List categories and criteria (IUCN). All nine species are present on Réunion with two being endemic there, and five have been confirmed on Mauritius, none of them endemic. The single species recorded for Rodrigues is also the only one found on all three islands of the Mascarenes and Madagascar. Five species are endemic to the Mascarene Archipelago, whereas the other four also occur in Madagascar. All nine species qualify as threatened with extinction on at least one of the islands of the Mascarenes. Two species are probably extinct on one island, and only two species on Réunion are not threatened.
A Multiscale Local Gain Form Ensemble Transform Kalman Filter (MLGETKF)
Authors: Wang Xuguang , Chipilski Hristo G. , Bishop Craig H. , Satterfield Elizabeth , Baker Nancy , Whitaker Jeffrey S.
Published: December 2020

A new multiscale, ensemble-based data assimilation (DA) method, multiscale local gain form ensemble transform Kalman filter (MLGETKF), is introduced. MLGETKF allows simultaneous update of multiple scales for both the ensemble mean and perturbations through assimilating all observations at once. MLGETKF performs DA in independent local volumes, which lends the algorithm a high degree of computational scalability. The multiscale analysis is enabled through the rapid creation of many pseudoensemble perturbations via a multiscale ensemble modulation procedure. The Kalman gain that is used to update the raw background ensemble mean and perturbations is based on this modulated ensemble, which intrinsically includes multiscale model space localization. Experiments with a noncycled statistical model show that the full background covariance estimated by MLGETKF more accurately resembles the shape of the true covariance than a scale-unaware localization. The mean analysis from the best-performing MLGETKF is statistically significantly more accurate than the best-performing scale-unaware LGETKF. The accuracy of the MLGETKF analysis is more sensitive to small-scale band localization radius than large-scale band. MLGETKF is further examined in a cycling DA context with a surface quasigeostrophic model. The root-mean-square potential temperature analysis error of the best-performing MLGETKF is 17.2% lower than that of the best-performing LGETKF. MLGETKF reduces analysis errors measured in kinetic energy spectra space by 30%–80% relative to LGETKF with the largest improvement at large scales. MLGETKF deterministic and ensemble mean forecasts are more accurate than LGETKF for full and large scales up to 5–6-day lead time and for small scales up to 3–4-day lead time, gaining ~12 h–1 day of predictability.
Laparoscopic cholecystectomy with two incisions: an improved, feasible and safe technique with superior cosmetic outcomes
Authors: Xu Yongfu , Wang Aidong , Dai Qiqiang , Fang Zheping , Li Zhenyu
Published: December 2020

Objective

Conventional laparoscopic cholecystectomy (CLC) is usually performed with four incisions. Minimally invasive surgery for gallbladder disease with less pain and smaller scars has become increasingly popular. This study reported a new, two-incision laparoscopic cholecystectomy (TILC) using conventional instruments.

Methods

In this prospective study, 43 patients were recruited to undergo TILC and were compared with 43 historical cases undergoing CLC. We evaluated operative time, postoperative pain, cosmesis and complications.

Results

There was no significant difference in gender, age, body mass index, bile duct damage, blood loss and postoperative hospital stay between the two groups. The mean operation time was longer with TILC than with CLC, but the difference was not statistically different. Postoperative pain scores were significantly lower with TILC than with CLC. The mean cosmetic satisfaction score was significantly higher with TILC than that with CLC. There was no significant difference in the incidence of complications between the two groups.

Conclusion

Our work demonstrates that TILC generates less postoperative pain and significantly improved cosmesis for patients. TILC is a safe and feasible alternative to CLC.
Neural network adaptive backstepping fault tolerant control for unmanned airships with multi-vectored thrusters
Authors: Liu Shiqian , Whidborne James F
Published: December 2020

This paper presents the fault tolerant control (FTC) of an unmanned airship with multiple vectored thrusters in the presence of model parameter uncertainties and unknown wind disturbances. A fault tolerant control based on constrained adaptive backstepping (CAB) approach, combined with a radial basis function neural network (RBFNN) approximation, is proposed for the airship with thruster faults. A wind observer is designed to estimate the bounded wind disturbances. An adaptive fault estimator is proposed to estimate the unknown actuator faults. A weighted pseudo inverse based control allocation is incorporated to reconstruct and optimize the practical control inputs of the failed airship under constraints of actuator saturation. Rigorous stability analysis shows that trajectory tracking errors of the airship position and attitude converge to the desired set through Lyapunov theory. Numerical simulations demonstrate the fault tolerant trajectory tracking capability of the proposed NN-CAB controller under the actuator faults, even in the presence of aerodynamic coefficient uncertainties, and unknown wind disturbances.
“He May Do Harm . . .”: Translation and Meaning of 2 Sam 12.18
Authors: Jones Ethan
Published: December 2020

Three major English translations, NRSV, ESV, and NASB, render וְאֵיךְ נֹאמַר אֵלָיו מֵת הַיֶּלֶד וְעָשָׂה רָעָה׃‎ as “How then can we tell him the child is dead? He may do himself some harm.” These translations insert the reflexive pronoun “himself” as the object of עשׂה‎. While such a reading is possible, it is not at all probable when we take into account how reflexives are expressed in Biblical Hebrew, as well as the syntax and semantics of עשׂה‎. This article contributes to our understanding of 2 Sam 12.18 not by offering a new translation of וְעָשָׂה רָעָה‎, but by providing a linguistic explanation for why translators should reject the reflexive “harm himself” and instead render the phrase as “he may do harm” (so MEV).
The role of saline irrigation prior to wound closure in the reduction of surgical site infection: a systematic review and meta-analysis
Authors: Ambe Peter C. , Rombey Tanja , Rembe Julian-Dario , Dörner Johannes , Zirngibl Hubert , Pieper Dawid
Published: December 2020

Background

Surgical site infection (SSI) describes an infectious complication of surgical wounds. Although SSI is thought to be preventable, it still represents a major cause of morbidity and substantial economic burden on the health system. Wound irrigation (WI) might reduce the level of bacterial contamination, but current data on its role in reducing or preventing SSI is conflicting. Our aim was to investigate the effectiveness of WI with normal saline prior to wound closure for the reduction of SSI in patients undergoing abdominal surgery.

Methods

We conducted a systematic literature search in MEDLINE, EMBASE, and CENTRAL from inception to present, and cross-checked the reference lists of all included primary studies and relevant systematic reviews. (Quasi-) randomized controlled trials (RCTs) investigating the rate of SSI when using normal saline vs. no irrigation prior to wound closure following abdominal surgery were included. Primary outcome was the rate of SSI, secondary outcome the mean length of hospital stay (LOS).

Results

Four RCTs including a total of 1194 patients were included for analysis. All studies compared wound irrigation with normal saline with no wound irrigation prior to wound closure. Their risk of bias was moderate. The relative risk of developing a SSI was lower when wound irrigation with normal saline was performed prior to wound closure although the effect was not statistically significant (risk ratio 0.73, 95%-confidence level: 0.37 to 1.43). Similarly, there was no difference in the LOS amongst both intervention arms.

Conclusion

This systematic review could not identify an advantage for routine irrigation of abdominal wounds with normal saline over no irrigation prior to wound closure in preventing or reducing the rate of SSI.

Systematic review registration

PROSPERO registry number CRD42018082287.