bluuebunny/crossref_metadata_2025 huggingface dataset:
Glioma-derived extracellular vesicles promote tumor progression by conveying WT1
Authors: Tsutsui Taishi , Kawahara Hironori , Kimura Ryouken , Dong Yu , Jiapaer Shabierjiang , Sabit Hemragul , Zhang Jiakang , Yoshida Takeshi , Nakada Mitsutoshi , Hanayama Rikinari
Published: May 2020

Glioma persists as one of the most aggressive primary tumors of the central nervous system. Glioma cells are known to communicate with tumor-associated macrophages/microglia via various cytokines to establish the tumor microenvironment. However, how extracellular vesicles (EVs), emerging regulators of cell–cell communication networks, function in this process is still elusive. We report here that glioma-derived EVs promote tumor progression by affecting microglial gene expression in an intracranial implantation glioma model mouse. The gene expression of thrombospondin-1 (Thbs1), a negative regulator of angiogenesis, was commonly downregulated in microglia after the addition of EVs isolated from different glioma cell lines, which endogenously expressed Wilms tumor-1 (WT1). Conversely, WT1-deficiency in the glioma-derived EVs significantly attenuated the Thbs1 downregulation and suppressed the tumor progression. WT1 was highly expressed in EVs obtained from the cerebrospinal fluid of human patients with malignant glioma. Our findings establish a novel model of tumor progression via EV-mediated WT1–Thbs1 intercellular regulatory pathway, which may be a future diagnostic or therapeutic target.
Clinical Impact of Accelerate Pheno Rapid Blood Culture Detection System in Bacteremic Patients
Authors: Dare Ryan K , Lusardi Katie , Pearson Courtney , McCain Kelsey D , Daniels K Baylee , Van Serena , Rico Juan Carlos , Painter Jacob , Lakkad Mrinmayee , Rosenbaum Eric R , Bariola J Ryan
Published: May 2020

Background

Accelerate Pheno blood culture detection system (AXDX) provides rapid identification and antimicrobial susceptibility testing results. Limited data exist regarding its clinical impact. Other rapid platforms coupled with antimicrobial stewardship program (ASP) real-time notification (RTN) have shown improved length of stay (LOS) in bacteremia.

Methods

A single-center, quasi-experimental study of bacteremic inpatients before and after AXDX implementation was conducted comparing clinical outcomes from 1 historical and 2 intervention cohorts (AXDX and AXDX + RTN).

Results

Of 830 bacteremic episodes, 188 of 245 (77%) historical and 308 (155 AXDX, 153 AXDX + RTN) of 585 (65%) intervention episodes were included. Median LOS was shorter with AXDX (6.3 days) and AXDX + RTN (6.7 days) compared to historical (8.1 days) (P = .001). In the AXDX and AXDX + RTN cohorts, achievement of optimal therapy (AOT) was more frequent (93.6% and 95.4%, respectively) and median time to optimal therapy (TTOT) was faster (1.3 days and 1.4 days, respectively) compared to historical (84.6%, P ≤ .001 and 2.4 days, P ≤ .001, respectively). Median antimicrobial days of therapy (DOT) was shorter in both intervention arms compared to historical (6 days each vs 7 days; P = .011). Median LOS benefit during intervention was most pronounced in coagulase-negative Staphylococcus bacteremia (P = .003).

Conclusions

LOS, AOT, TTOT, and total DOT significantly improved after AXDX implementation. Addition of RTN did not show further improvement over AXDX and an already active ASP. These results suggest that AXDX can be integrated into healthcare systems with an active ASP even without the resources to include RTN.
Isavuconazole Is as Effective as and Better Tolerated Than Voriconazole for Antifungal Prophylaxis in Lung Transplant Recipients
Authors: Samanta Palash , Clancy Cornelius J , Marini Rachel V , Rivosecchi Ryan M , McCreary Erin K , Shields Ryan K , Falcione Bonnie A , Viehman Alex , Sacha Lauren , Kwak Eun Jeong , Silveira Fernanda P , Sanchez Pablo G , Morrell Matthew , Clarke Lloyd , Nguyen M Hong
Published: May 2020

Background

Invasive fungal infections (IFIs) are common following lung transplantation. Isavuconazole is unstudied as prophylaxis in organ transplant recipients. We compared effectiveness and tolerability of isavuconazole and voriconazole prophylaxis in lung transplant recipients.

Methods

A single-center, retrospective study of patients who received isavuconazole (September 2015–February 2018) or voriconazole (September 2013–September 2015) for antifungal prophylaxis. IFIs were defined by EORTC/MSG criteria.

Results

Patients received isavuconazole (n = 144) or voriconazole (n = 156) for median 3.4 and 3.1 months, respectively. Adjunctive inhaled amphotericin B (iAmB) was administered to 100% and 41% of patients in the respective groups. At 1 year, 8% of patients receiving isavuconazole or voriconazole developed IFIs. For both groups, 70% and 30% of IFIs were caused by molds and yeasts, respectively, and breakthrough IFI (bIFI) rate was 3%. Outcomes did not significantly differ for patients receiving or not receiving iAmB. Independent risk factors for bIFI and breakthrough invasive mold infection (bIMI) were mold-positive respiratory culture and red blood cell transfusion >7 units at transplant. Bronchial necrosis >2 cm from anastomosis and basiliximab induction were also independent risk factors for bIMI. Isavuconazole and voriconazole were discontinued prematurely due to adverse events in 11% and 36% of patients, respectively (P = .0001). Most common causes of voriconazole and isavuconazole discontinuation were hepatotoxicity and lack of oral intake, respectively. Patients receiving ≥90 days prophylaxis had fewer IFIs at 1 year (3% vs 9%, P = .02). IFIs were associated with increased mortality (P = .0001) and longer hospitalizations (P = .0005).

Conclusions

Isavuconazole was effective and well tolerated as antifungal prophylaxis following lung transplantation.
Ulysses’ journey home to Ithaca: a new metaphor for understanding the General Theory
Authors: Togati Teodoro Dario
Published: May 2020

This paper argues that in order to remedy the lack of alternative methods in current macroeconomics it is necessary to clarify the ontology of Keynes’s General Theory. One of the reasons why Keynes lost his generality battle is that he left many gaping holes in the ‘correct’ articulation of his research programme—especially in terms of the specification of hard-core ‘cosmological’ beliefs concerning stability, value and aggregate behaviour—yet to be filled by the post-Keynesian literature. In order to start filling the gaps, this paper proposes a new agenda called ‘The General Theory 4.0’ based on the new ‘Ulysses’ journey’ metaphor, which, it shows, is better than alternative ones, such as Farmer’s ‘windy boat’ and Akerlof and Shiller’s ‘rollercoaster’, for improving understanding of Keynes’s book.
Riskscapes and the socio-spatial challenges of climate change
Authors: Davies Anna , Hooks Gregory , Knox-Hayes Janelle , Liévanos Raoul S
Published: May 2020

Anthropogenic climate change is increasing the frequency and severity of the physical threats to human and planetary wellbeing. However, climate change risks, and their interaction with other “riskscapes”, remain understudied. Riskscapes encompass different viewpoints on the threat of loss across space, time, individuals and collectives. This Special Issue of the Cambridge Journal of Regions, Economy, and Society enhances our understanding of the multifaceted and interlocking dimensions of climate change and riskscapes. It brings together rigorous and critical international scholarship across diverse realms on inquiry under two, interlinked, themes: (i) governance and institutional responses and (ii) vulnerabilities and inequalities. The contributors offer a forceful reminder that when considering climate change, social justice principles cannot be appended after the fact. Climate change adaptation and mitigation pose complex and interdependent social and ethical dilemmas that will need to be explicitly confronted in any activation of “Green New Deal” strategies currently being developed internationally. Such critical insights about the layered, unequal and institutional dimensions of risks are of paramount import when considering other riskscapes pertaining to conflict and war, displaced people and pandemics like the 2019–2020 global COVID-19 pandemic.
Neuroimmune interactions in cardiovascular diseases
Authors: Carnevale Daniela , Lembo Giuseppe
Published: May 2020

Our body is continuously in contact with external stimuli that need a fine integration with the internal milieu in order to maintain the homoeostasis. Similarly, perturbations of the internal environment are responsible for the alterations of the physiological mechanisms regulating our main functions. The nervous system and the immune system represent the main interfaces between the internal and the external environment. In carrying out these functions, they share many similarities, being able to recognize, integrate, and organize responses to a wide variety of stimuli, with the final aim to re-establish the homoeostasis. The autonomic nervous system, which collectively refers to the ensemble of afferent and efferent neurons that wire the central nervous system with visceral effectors throughout the body, is the prototype system controlling the homoeostasis through reflex arches. On the other hand, immune cells continuously patrol our body against external enemies and internal perturbations, organizing acute responses and forming memory for future encounters. Interesting to notice, the integration of the two systems provides a further unique opportunity for fine tuning of our body’s homoeostasis. In fact, the autonomic nervous system guides the development of lymphoid and myeloid organs, as well as the deployment of immune cells towards peripheral tissues where they can affect and control several physiological functions. In turn, every specific immune cell type can contribute to regulate neural circuits involved in cardiovascular function, metabolism, and inflammation. Here, we review current understanding of the cross-regulation between these systems in cardiovascular diseases.
Revisiting the Past in the Age of Posts: Rememory in Toni Morrison’s God Help the Child and Gisèle Pineau’s Femmes des Antilles
Authors: Gras Delphine
Published: May 2020

In this article, I examine how Toni Morrison and Gisèle Pineau provide timely pieces against the historical amnesia characteristic of post-racial discourse in the USA and in France. Studying Morrison’s God Help the Child (2015) and Pineau’s Femmes des Antilles: Traces et Voix (1998) side by side reveals how Morrison’s rememory is a global concept as pertinent today as when first coined in Beloved (1987). The term’s original use in the context of slavery also suggests a lens through which to read Morrison’s non-slavery era works like God Help the Child. What ultimately comes to the fore in both authors’ potent expositions of the specter of slavery haunting black women in the USA, France, and the West Indies is a rejection of historical silencing.
Appraisal of the PIBD-classes Criteria: A Multicentre Validation
Authors: Ledder Oren , Sonnino Micol , Birimberg-Schwartz Liron , Escher Johanna C , Russell Richard K , Orlanski-Meyer Esther , Matar Manar , Assa Amit , Tzion Raffi Lev , Shteyer Eyal , Griffiths Anne , Turner Dan
Published: May 2020

Introduction

The PIBD-classes criteria were developed to standardise the classification of children with inflammatory bowel disease [IBD], from Crohn’s disease [CD], through IBD-unclassified [IBD-U], to typical ulcerative colitis [UC]. We aimed to further validate the criteria and to explore possible modifications.

Methods

This was a multicentre retrospective cohort study of children diagnosed with IBD with at least 1 year of follow-up. Clinical, radiological, endoscopic, and histological data were recorded at diagnosis and latest follow-up, as well as the 23 items of the PIBD-classes criteria. The PIBD-classes criteria were assessed for redundant items, and a simplified algorithm was proposed and validated on the original derivation cohort from which the PIBD-classes algorithm was derived.

Results

Of the 184 included children [age at diagnosis 13 ± 3 years, 55% males], 122 [66%] were diagnosed by the physician with CD, 17 [9%] with IBD-U, and 45 [25%] with UC. There was high agreement between physician-assigned and PIBD-classes generated diagnosis for CD [93%; eight patients moved to IBD-U] and for UC [84%; six moved to IBD-U and one to CD]. A simplified version of the algorithm with only 19 items is suggested, with comparable performance to the original algorithm [81% sensitivity and 81% specificity vs 78% and 83% for UC; and 79% and 95% vs 80% and 95% for CD, respectively].

Conclusions

The PIBD-classes algorithm is a useful tool to facilitate standardised objective classification of IBD subtypes in children. A modified version of the PIBD-classes maintains accuracy of classification with a simplified algorithm.
Admission of patients with STEMI since the outbreak of the COVID-19 pandemic: a survey by the European Society of Cardiology
Authors: Pessoa-Amorim Guilherme , Camm Christian F , Gajendragadkar Parag , De Maria Giovanni Luigi , Arsac Celine , Laroche Cecile , Zamorano José Luis , Weidinger Franz , Achenbach Stephan , Maggioni Aldo P , Gale Chris P , Poppas Athena , Casadei Barbara
Published: May 2020

Aims

The COVID-19 pandemic required a significant redeployment of worldwide healthcare resources. Fear of infection, national lockdowns and altered healthcare priorities have the potential to impact utilisation of healthcare resources for non-communicable diseases. To survey health professionals’ views of the impact of the COVID-19 pandemic on the rate and timing of admission of patients with ST-elevation myocardial infarction (STEMI), the European Society of Cardiology (ESC) administered an internet-based questionnaire to cardiologists and cardiovascular nurses across 6 continents.

Methods and results

3101 responses were received from 141 countries across 6 continents. 88.3% responded that their country was in “total lockdown” and 7.1% in partial lockdown. 78.8% responded that the number of patients presenting with STEMI was reduced since the coronavirus outbreak and 65.2% indicated that the reduction in STEMI presentations was >40%. Approximately 60% of all respondents reported that STEMI patients presented later than usual and 58.5% that >40% of STEMI patients admitted to hospital presented beyond the optimal window for primary percutaneous intervention (PCI) or thrombolysis. Independent predictors of the reported higher rate of delayed STEMI presentation were a country in total lockdown, >100 COVID-19 cases admitted locally, and the complete restructuring of the local cardiology service.

Conclusion

The survey indicates that the impact of COVID-19 on STEMI presentations is likely to be substantial, with both lower presentations and a higher rate of delayed presentations occurring. This has potentially important ramifications for future healthcare and policy planning in the event of further waves of this pandemic.
Comparison of health care utilization among users of public and private community health centres in urban China
Authors: Shen Menghan , He Wen , Li Linyan , Wu Yushan
Published: May 2020

Background

In China, the government has encouraged the participation of private sector facilities in primary care to improve health care quality.

Objective

We compare health care utilization patterns among patients who select private versus public community health centres (CHCs) for reimbursed outpatient services.

Methods

This paper uses data from the Urban Employee Basic Medical Insurance scheme from 2013 to 2016 in one of the largest cities in China. We used a Poisson model and a logistic model to examine outcomes on monthly outpatient visits and the probability of hospitalization, respectively.

Results

Compared with being a user of a public CHC, being a user of a private CHC is associated with a 26.2% lower incidence rate of outpatient visits to hospitals [95% confidence interval (CI): 30.1–21.8%] and no difference in rates of visits to CHCs or hospitalization. Among patients with diabetes or hypertension, being a user of a private CHC is associated with a 12.9% lower incidence rate of outpatient visits to CHCs (95% CI: 19.8–5.4%), a 25.6% lower incidence rate of outpatient visits to hospitals (95% CI: 21.4–19.5%) and 22.3% higher odds of hospitalization (95% CI: 3.5–44.7%).

Conclusion

Being a user of a private CHC is associated with a reduction in outpatient visits to hospitals, which aligns with the goal of reducing hospital congestion at the outpatient level. For patients with chronic diseases, being a user of a private CHC is associated with a higher probability of hospitalization. More research is needed to understand the reason for this difference.
Shared Intimacies: Women’s Sexuality in Foreign Workers’ Camps, 1940–1945
Authors: Fauroux Camille
Published: May 2020

By examining judicial records as well as corporate archives, this article argues that the camp played an important role in the management of foreign workers’ sexuality in Nazi Germany. A means of housing foreigners or controlling the workforce, the segregation of workers along racial and gendered lines in barracks also ensured their reproducing bodies could be controlled to avoid their ‘settling down’ on Reich territory. This microhistorical study of French women living in Berlin between 1940 and 1945 argues that although camp housing was primarily intended to control heterosexuality, it also had profound consequences for queer relationships. In illuminating this previously unacknowledged aspect of biopolitics in Nazi Germany, the article addresses issues of spatial domination and agency in romantic and sexual encounters.
Driver License Renewal Laws and Older Adults’ Daily Driving, United States, 2003–2017
Authors: Shen Sijun , Ratnapradipa Kendra L , Pervall Gina C , Sweeney Meredith , Zhu Motao
Published: May 2020

Objectives

Around the world, aging populations pose significant concerns regarding their community mobility and transportation safety. Most previous studies in the United States have focused on the associations between driver license renewal laws and crash outcomes among older adults (65 years and older). Few studies have evaluated the impact of driver license renewal laws on older adults’ community mobility. This study aimed to identify the associations between driver license renewal laws and older males’ and females’ daily driving likelihood and duration.

Method

The 2003–2017 American Time Use Survey data were merged with driver license renewal legislation using ages 55–64 to control for effects of non-licensure factors (e.g., gasoline price). Weighted Poisson and linear regression models were used to estimate the associations of various driver licensure provisions with older males’ and females’ daily driving likelihood and duration.

Results

A shorter in-person renewal period and the presence of mandatory reporting laws for physicians were associated with a lower daily driving likelihood and shorter driving duration among females aged 75 years or older. The presence of mandatory reporting laws was also associated with reduced daily driving likelihood and duration for males aged 65–74 years.

Discussion

Policymakers should be aware that males and females may respond differently to older driver licensure laws, which may require distinct interventions to preserve their mobility. Future studies should consider the gender disparities when examining the association between driver licensure policies and older adults’ transportation safety and mobility.
A non-conventional proximal inflow for the radial artery coronary graft
Authors: Gatti Giuseppe , Taffarello Pierpaolo , De Groodt Jasmina , Benussi Bernardo
Published: May 2020

Despite good outcomes, the use of the radial artery as a coronary graft is not widespread. Concerns regarding its low versatility and the risk of hand ischaemia, as well as the lack of reliable information regarding the best storage solution of the graft, and regarding the treatment for preventing spasms have limited its use. In this manuscript, the (numerous) benefits and (few) drawbacks of the proximal inflow for the radial artery from the in situ right internal thoracic artery proximal stump are discussed. Outcomes are reported from a limited series of patients undergoing totally arterial myocardial revascularization using this composite graft and both internal thoracic arteries.
The effect of insurance status on overall survival among children and adolescents with cancer
Authors: Wang Xiaoyan , Ojha Rohit P , Partap Sonia , Johnson Kimberly J
Published: May 2020

Background

Differences in access, delivery and utilisation of health care may impact childhood and adolescent cancer survival. We evaluated whether insurance coverage impacts survival among US children and adolescents with cancer diagnoses, overall and by age group, and explored potential mechanisms.

Methods

Data from 58 421 children (aged ≤14 years) and adolescents (15–19 years), diagnosed with cancer from 2004 to 2010, were obtained from the National Cancer Database. We examined associations between insurance status at initial diagnosis or treatment and diagnosis stage; any treatment received; and mortality using logistic regression, Cox proportional hazards (PH) regression, restricted mean survival time (RMST) and mediation analyses.

Results

Relative to privately insured individuals, the hazard of death (all-cause) was increased and survival months were decreased in those with Medicaid [hazard ratio (HR) = 1.27, 95% confidence interval (CI): 1.22 to 1.33; and −1.73 months, 95% CI: −2.07 to −1.38] and no insurance (HR = 1.32, 95% CI: 1.20 to 1.46; and −2.13 months, 95% CI: −2.91 to −1.34). The HR for Medicaid vs. private insurance was larger (pinteraction <0.001) in adolescents (HR = 1.52, 95% CI: 1.41 to 1.64) than children (HR = 1.16, 95% CI: 1.10 to 1.23). Despite statistical evidence of PH assumption violation, RMST results supported all interpretations. Earlier diagnosis for staged cancers in the Medicaid and uninsured populations accounted for an estimated 13% and 19% of the survival deficit, respectively, vs. the privately insured population. Any treatment received did not account for insurance-associated survival differences in children and adolescents with cancer.

Conclusions

Children and adolescents without private insurance had a higher risk of death and shorter survival within 5 years following cancer diagnosis. Additional research is needed to understand underlying mechanisms.
Higher risk of dementia in English older individuals who are overweight or obese
Authors: Ma Yixuan , Ajnakina Olesya , Steptoe Andrew , Cadar Dorina
Published: May 2020

Background

Several risk factors contribute to dementia, but the role of obesity remains unclear. This study investigated whether increased body weight or central obesity were associated with a higher risk of developing dementia in a representative sample of older English adults.

Methods

We studied 6582 participants from the English Longitudinal Study of Ageing (ELSA) who were aged ≥50 years and were dementia-free at baseline, that being either wave 1 (2002–2003) for study members who started at wave 1, or at either wave 2 (2004–2005) or 4 (2008–2009) for those who began the study as refreshment samples. Body mass index (BMI) was measured at baseline and categorized into normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2) and obese (≥30 kg/m2). Central obesity was defined as a waist circumference (WC) >88 cm for women and >102 cm for men. Cumulative incidence of dementia was ascertained based on physician-diagnosed dementia, an overall score >3.38 on the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and Hospital Episodes Statistics (HES) data at every ELSA wave from baseline until wave 8 (2016–2017). Cox proportional hazards models were used to assess the association between baseline BMI levels or abdominal obesity in relation to dementia incidence during the mean follow-up period of 11 years.

Results

From the overall sample, 6.9% (n = 453) of participants developed dementia during the follow-up period of maximum 15 years (2002–2017). Compared with participants with normal weight, those who were obese at baseline had an elevated risk of dementia incidence [hazard ratio (HR) = 1.34, 95% confidence interval (CI) 1.07–1.61] independent of sex, baseline age, apolipoprotein E-ε4 (APOE-ε4), education, physical activity, smoking and marital status. The relationship was slightly accentuated after additionally controlling for hypertension and diabetes (HR = 1.31, 95% CI 1.03–1.59). Women with central obesity had a 39% greater risk of dementia compared with non-central obese women (HR = 1.39, 95% CI 1.12–1.66). When compared with a normal BMI and WC group, the obese and high WC group had 28% (HR = 1.28, 95% CI 1.03–1.53) higher risk of dementia.

Conclusions

Our results suggest that having an increased body weight or abdominal obesity are associated with increased dementia incidence. These findings have significant implications for dementia prevention and overall public health.
Improving Replicability, Reproducibility, And Reliability In Preclinical Research: A Shared Responsibility
Authors: Cheleuitte-Nieves Christopher , Lipman Neil S
Published: May 2020

Reproducible and reliable scientific investigation depends on the identification and consideration of various intrinsic and extrinsic factors that may affect the model system used. The impact of these factors must be managed during all phases of a study: planning, execution, and reporting. The value of in vivo (animal) research has come under increasing scrutiny over the past decade because of multiple reports documenting poor translatability to human studies. These failures have been attributed to various causes, including poor study design and execution as well as deficiencies in reporting. It is important to recognize that achieving reproducible and reliable preclinical research results is a joint responsibility that requires a partnership between the investigative team and the animal care and use program staff. The myriad of intrinsic factors, such as species, strain/substrain, age, sex, physiologic and health status, and extrinsic factors, including temperature, humidity, lighting, housing system, and diet, need to be recognized and managed during study planning and execution, as they can influence animal physiology and biological response. Of equal importance is the need to document and report these details. The ARRIVE and PREPARE guidelines were developed by concerned scientists, veterinarians, statisticians, journal editors, and funding agencies to assist investigative teams and scientific journals manage and report on intrinsic and extrinsic factors to improve reproducibility and reliability. This issue of the ILAR Journal will focus on the various extrinsic factors that have been recognized to confound animal research.
Holding Animal-Based Research to Our Highest Ethical Standards: Re-seeing Two Emergent Laboratory Practices and the Ethical Significance of Research Animal Dissent
Authors: Fenton Andrew
Published: May 2020

“Animal-based research should be held to the highest ethical standards” is becoming an increasingly common refrain. Though I think such a commitment is what we should expect of those using animals in science, much as we would if the participants were humans, some key insights of discussions in applied ethics and moral philosophy only seem to slowly impact what reasonably qualifies as the highest standards in animal research ethics. Early in my paper, I will explain some of these insights and loosely tie them to animal research ethics. Two emergent practices in laboratory animal science, positive reinforcement training and “rehoming,” will then be discussed, and I will defend the view that both should be mandatory on no more ethical grounds than what is outlined in the first section. I will also provide reasons for foregrounding the moral significance of dissent and why, most of the time, an animal research subject’s sustained dissent should be respected. Taken together, what I will defend promises to change how at least some animals are used in science and what happens to them afterwards. But I will also show how an objective ethics requires nothing less. Ignoring these constraints in the scientific use of animals comes at the cost of abandoning any claim to adhering to our highest ethical standards and, arguably, any claim to the moral legitimacy of such scientific use.
Harm-Benefit Analyses Can Be Harmful
Authors: Niemi Steven M
Published: May 2020

Harm-benefit analyses (HBAs) are becoming de rigueur with some governmental regulatory agencies and popular with local institutional animal care and use committees (or their equivalents), the latter due, in part, to the adoption of HBAs as an international accreditation standard. Such analyses are employed as an attempt to balance potential or actual pain or distress imposed on laboratory animals against scientists’ justifications for those impositions. The outcomes of those analyses are then supposed to be included in an official assessment of whether a given animal protocol should be approved as proposed. While commendable in theory as a means to avoid or minimize animal suffering, HBAs come with a flawed premise. Establishing an accurate prediction of benefit, especially for so-called “basic” research (vs “applied” research, such as in vivo testing for product development or batch release), is often impossible given the uncertain nature of experimental outcomes and the eventual value of those results. That impossibility, in turn, risks disapproving a legitimate research proposal that might have yielded important new knowledge if it had been allowed to proceed. Separately, the anticipated harm to which the animal would be subjected should similarly be scrutinized with an aim to refine that harm regardless of purported benefits if the protocol is approved. The intentions of this essay are to reflect on the potential harm and benefit of the HBA itself, highlight how HBAs may be helpful in advancing refinements, and propose alternative approaches to both parts of the equation in the assessment process.
Constructing co-occurrence network embeddings to assist association extraction for COVID-19 and other coronavirus infectious diseases
Authors: Oniani David , Jiang Guoqian , Liu Hongfang , Shen Feichen
Published: May 2020

Objective

As coronavirus disease 2019 (COVID-19) started its rapid emergence and gradually transformed into an unprecedented pandemic, the need for having a knowledge repository for the disease became crucial. To address this issue, a new COVID-19 machine-readable dataset known as the COVID-19 Open Research Dataset (CORD-19) has been released. Based on this, our objective was to build a computable co-occurrence network embeddings to assist association detection among COVID-19–related biomedical entities.

Materials and Methods

Leveraging a Linked Data version of CORD-19 (ie, CORD-19-on-FHIR), we first utilized SPARQL to extract co-occurrences among chemicals, diseases, genes, and mutations and build a co-occurrence network. We then trained the representation of the derived co-occurrence network using node2vec with 4 edge embeddings operations (L1, L2, Average, and Hadamard). Six algorithms (decision tree, logistic regression, support vector machine, random forest, naïve Bayes, and multilayer perceptron) were applied to evaluate performance on link prediction. An unsupervised learning strategy was also developed incorporating the t-SNE (t-distributed stochastic neighbor embedding) and DBSCAN (density-based spatial clustering of applications with noise) algorithms for case studies.

Results

The random forest classifier showed the best performance on link prediction across different network embeddings. For edge embeddings generated using the Average operation, random forest achieved the optimal average precision of 0.97 along with a F1 score of 0.90. For unsupervised learning, 63 clusters were formed with silhouette score of 0.128. Significant associations were detected for 5 coronavirus infectious diseases in their corresponding subgroups.

Conclusions

In this study, we constructed COVID-19–centered co-occurrence network embeddings. Results indicated that the generated embeddings were able to extract significant associations for COVID-19 and coronavirus infectious diseases.
Semiochemicals Affecting Attraction of Ambrosia Beetle Euwallacea fornicatus (Coleoptera: Curculionidae: Scolytinae) to Quercivorol: Developing Push-Pull Control
Authors: Byers John A , Maoz Yonatan , Fefer Daniela , Levi-Zada Anat
Published: May 2020

Euwallacea fornicatus (Eichhoff), the polyphagous shot hole borer (PSHB), is an ambrosia beetle infesting avocado Persea americana Mill. limbs in North America and Israel. We conducted field experiments with sticky traps in avocado orchards to develop push–pull semiochemical methods of managing PSHB. Traps baited with 10-fold increasing doses (0.01 to 100× or 1.26 µg to 12.6 mg/d) of attractant quercivorol were previously shown to increasingly capture female PSHB (males flightless). We converted trap catch of this relationship to a standardized effective attraction radius (EAR) that predicts capture power of baited-traps regardless of insect flight density. Earlier, piperitone and verbenone were shown to strongly inhibit attraction of PSHB to quercivorol-traps. We tested increasing numbers of 1× piperitone dispensers at 0.75-m distance surrounding a quercivorol-trap and found PSHB catch to decline exponentially. Increasing decadic doses (0.01 to 10×) of either verbenone or piperitone released at 1× quercivorol-traps caused a sigmoidal first-order kinetic-decay in catch. Verbenone (1×) placed at increasing distances (0, 0.25, 0.5, 1, and 2 m) from a 1× quercivorol-trap became increasingly ineffective in reducing catch of PSHB. We found no evidence that ethanol released from 7.5 to 480 mg/d affected attraction of PSHB, but Scobicia chevrieri (Villa and Villa) (Coleoptera: Bostrichidae) was increasingly attracted. Due to their relatively short-range (<0.5 m) inhibition of attractive sources, piperitone, and verbenone dispensers should be placed on avocado trunks where PSHB aggregations occur before the flight season.
On the Provision of Unemployment Insurance when Workers are Ex-Ante Heterogeneous
Authors: Setty Ofer , Yedid-Levi Yaniv
Published: May 2020

Labor market outcomes demonstrate considerable variation between and within skill groups. We construct a general equilibrium model with incomplete markets and exogenous differences that matches these facts. We study the role of exogenous heterogeneity in choosing the optimal replacement rate and the maximum benefit for an unemployment insurance (UI) system. The optimal average replacement rate is 27%, compared to 0% in a model without exogenous heterogeneity. The relatively generous choice is due to the redistributive role of UI, which is a manifestation of two elements. First, workers who are unemployed more often receive positive net transfers from the UI system because they draw resources more frequently. Second, the existence of a cap on benefits makes UI progressive. Our main result holds in the presence of a generous progressive taxation system.
The Role of National Human Rights Institutions in Implementing Decisions of the Inter-American System: Three Recent Examples from Costa Rica
Authors: Solano Carboni Montserrat
Published: May 2020

This practice note reflects on the potential role that national human rights institutions could play to promote implementation of judgments and decisions from supranational human rights bodies. In particular, it reflects on the experience the author had as head of one such institution in Costa Rica and the role she played promoting compliance by Costa Rica with cases decided by the Inter-American Court. She writes about the changing landscape of national human rights institutions in the Americas region and their potential in the future to impact implementation.
Accountability for Sexual and Gender-based Violence During Mass Repression and in Conflict
Authors: Kravetz Daniela
Published: May 2020

This article examines how national courts in Argentina and Guatemala are applying the international criminal law framework to address sexual violence perpetrated during mass repression and in conflict. It focuses on the emerging domestic jurisprudence in both countries and explores the challenges to prosecuting sexual and gender-based violence at the domestic level and the lessons learned from these experiences.
The protective role of m1A during stress-induced granulation
Authors: Alriquet Marion , Calloni Giulia , Martínez-Limón Adrían , Delli Ponti Riccardo , Hanspach Gerd , Hengesbach Martin , Tartaglia Gian G. , Vabulas R. Martin
Published: May 2020

Post-transcriptional methylation of N6-adenine and N1-adenine can affect transcriptome turnover and translation. Furthermore, the regulatory function of N6-methyladenine (m6A) during heat shock has been uncovered, including the enhancement of the phase separation potential of RNAs. In response to acute stress, e.g. heat shock, the orderly sequestration of mRNAs in stress granules (SGs) is considered important to protect transcripts from the irreversible aggregation. Until recently, the role of N1-methyladenine (m1A) on mRNAs during acute stress response remains largely unknown. Here we show that the methyltransferase complex TRMT6/61A, which generates the m1A tag, is involved in transcriptome protection during heat shock. Our bioinformatics analysis indicates that occurrence of the m1A motif is increased in mRNAs known to be enriched in SGs. Accordingly, the m1A-generating methyltransferase TRMT6/61A accumulated in SGs and mass spectrometry confirmed enrichment of m1A in the SG RNAs. The insertion of a single methylation motif in the untranslated region of a reporter RNA leads to more efficient recovery of protein synthesis from that transcript after the return to normal temperature. Our results demonstrate far-reaching functional consequences of a minimal RNA modification on N1-adenine during acute proteostasis stress.
Dynamic Viral Severe Acute Respiratory Syndrome Coronavirus 2 RNA Shedding in Children: Preliminary Data and Clinical Consideration from a Italian Regional Center
Authors: De Ioris Maria A , Scarselli Alessia , Ciofi degli Atti Marta L , Ravà Lucilla , Smarrazzo Andrea , Concato Carlo , Romani Lorenza , Scrocca Raffaella , Geremia Caterina , Carletti Michaela , Calò Carducci Francesca I , Bernardi Stefania , Coltella Luana , Santilli Veronica , Chiurchiu Sara , Peschiaroli Emanuela , Mariani Rosanna , Marabotto Caterina , Perrotta Daniela , Villani Alberto , Rossi Paolo , D’Argenio Patrizia , Campana Andrea , Raponi Massimiliano
Published: May 2020

We evaluated severe acute respiratory syndrome coronavirus 2 RNA clearance in 22 children. The estimation of positivity at day 14 was 52% for nasopharyngeal swab and 31% for stool samples. These data underline the significance of nasopharyngeal and stoolsample for detecting infected children. Additional studies are needed for transmissibility.
Anal fistula communicating to anterior abdominal wall treated with ksharasutra (medicated seton): a rare case study
Authors: Bhat Punchoor Ramesh , PN Deepthirani , Kiliyankandy Sandeep , Kizhakkayil Sathiajith
Published: May 2020

A case of anal fistula communication to anterior abdominal wall treated using ‘Medicated Seton’ called ‘Ksharasutra’ is reported here. Sushruta mentioned about Ksharasutra in his text book Sushruta Samhita in 500 BC. A 54-year-old male came with recurrent abscess in the lower abdominal wall and underwent incision and drainage three times earlier. Scar on lower abdomen and active sinuses on right and left ischiorectal fossa were noted. Internal opening was felt at anal mucosa posteriorly. Transrectal ultrasonography revealed posterior anal fistula, extending to left gluteum and traced till left ramus. Seton was placed in the tract from 5’o clock position to internal opening at 6’o clock position. Every week Ksharasutra changed for 8 weeks. This healed internal opening, right and left ischiorectal sinuses. Left tract toward groin and lower abdomen wall showed fibrosis. Same was confirmed through review scan. Six years of follow-up has shown no signs of recurrence.
Tracheostomy in a patient with COVID-19: a case report
Authors: Zvrko Elvir , Radunovic Ljubica , Pavicevic Vladimir
Published: May 2020

Some of coronavirus disease 2019 (COVID-19) patients with prolonged ventilation may require tracheostomy, which is an aerosol-generating procedure and poses a significant risk of viral transmission. We report our experience of the management of a patient with COVID-19 who underwent surgical tracheostomy and describe several essential infection control principles. In our patient, on the 14th day after intubation, an open tracheostomy was carried out because of the prolonged tracheal intubation and unsuccessful extubation attempts. Meticulous attention was paid during surgery to decrease the infection risk. Appropriate protection, infection control and teamwork are essential to perform open tracheostomy in COVID-19 positive patients safely with minimal risks to healthcare professionals.
Joint venture and joint operating agreements in Iran: legal aspects
Authors: Shiravi Abdolhossein , Vafaei Mahdi Abbasi
Published: May 2020

Under current Iranian laws and regulations there is a requirement for an upstream petroleum contract to be managed by a joint venture entity and so the conclusion of a joint venture agreement (JVA) is compulsory in such petroleum projects. In this research article we first discuss the rules governing JVAs and the statutory requirements of such agreements in Iran. Then, by studying the relevant rules, we consider the advantages and disadvantages of the both unincorporated and incorporated forms of JVA and finally we discuss some of the implications of the JVA regarding tax, accounting procedures and fiduciary duties. We also consider the role played by unincorporated joint ventures and the joint operating agreement (JOA) in Iran.
The chromatin-modifying protein HUB2 is involved in the regulation of lignin composition in xylem vessels
Authors: Zhang Bo , Sztojka Bernadette , Seyfferth Carolin , Escamez Sacha , Miskolczi Pál , Chantreau Maxime , Bakó László , Delhomme Nicolas , Gorzsás András , Bhalerao Rishikesh P , Tuominen Hannele
Published: May 2020

PIRIN2 (PRN2) was earlier reported to suppress syringyl (S)-type lignin accumulation of xylem vessels of Arabidopsis thaliana. In the present study, we report yeast two-hybrid results supporting the interaction of PRN2 with HISTONE MONOUBIQUITINATION2 (HUB2) in Arabidopsis. HUB2 has been previously implicated in several plant developmental processes, but not in lignification. Interaction between PRN2 and HUB2 was verified by β-galactosidase enzymatic and co-immunoprecipitation assays. HUB2 promoted the deposition of S-type lignin in the secondary cell walls of both stem and hypocotyl tissues, as analysed by pyrolysis-GC/MS. Chemical fingerprinting of individual xylem vessel cell walls by Raman and Fourier transform infrared microspectroscopy supported the function of HUB2 in lignin deposition. These results, together with a genetic analysis of the hub2 prn2 double mutant, support the antagonistic function of PRN2 and HUB2 in deposition of S-type lignin. Transcriptome analyses indicated the opposite regulation of the S-type lignin biosynthetic gene FERULATE-5-HYDROXYLASE1 by PRN2 and HUB2 as the underlying mechanism. PRN2 and HUB2 promoter activities co-localized in cells neighbouring the xylem vessel elements, suggesting that the S-type lignin-promoting function of HUB2 is antagonized by PRN2 for the benefit of the guaiacyl (G)-type lignin enrichment of the neighbouring xylem vessel elements.
Optical spectra of FO Aquarii during low and high accretion rates
Authors: Kennedy M R , Garnavich P M , Littlefield C , Marsh T R , Callanan P , Breton R P , Augusteijn T , Wagner R M , Ashley R P , Neric M
Published: May 2020

Between 2016 May and 2018 September, the intermediate polar (IP) FO Aquarii exhibited two distinct low states and one failed low state. We present optical spectroscopy of FO Aquarii throughout this period, making this the first detailed study of an accretion disc during a low state in any IP. Analysis of these data confirm that the low states are the result of a drop in the mass transfer rate between the secondary star and the magnetic white dwarf primary, and are characterized by a decrease in the system’s brightness coupled with a change of the system’s accretion structures from an accretion disc-fed geometry to a combination of disc-fed and ballistic stream-fed accretion, and that effects from accretion on to both magnetic poles become detectable. The failed low state only displays a decrease in brightness, with the accretion geometry remaining primarily disc-fed. We also find that the WD appears to be exclusively accretion disc-fed during the high state. There is evidence for an outflow close to the impact region between the ballistic stream and the disc which is detectable in all of the states. Finally, there is marginal evidence for narrow high-velocity features in the H α emission line during the low states which may arise due to an outflow from the WD. These features may be evidence of a collimated jet, a long predicted yet elusive feature of cataclysmic variables.
DES16C3cje: A low-luminosity, long-lived supernova
Authors: Gutiérrez C P , Sullivan M , Martinez L , Bersten M C , Inserra C , Smith M , Anderson J P , Pan Y-C , Pastorello A , Galbany L , Nugent P , Angus C R , Barbarino C , Carollo D , Chen T-W , Davis T M , Della Valle M , Foley R J , Fraser M , Frohmaier C , González-Gaitán S , Gromadzki M , Kankare E , Kokotanekova R , Kollmeier J , Lewis G F , Magee M R , Maguire K , Möller A , Morrell N , Nicholl M , Pursiainen M , Sollerman J , Sommer N E , Swann E , Tucker B E , Wiseman P , Aguena M , Allam S , Avila S , Bertin E , Brooks D , Buckley-Geer E , Burke D L , Carnero Rosell A , Carrasco Kind M , Carretero J , Costanzi M , da Costa L N , De Vicente J , Desai S , Diehl H T , Doel P , Eifler T F , Flaugher B , Fosalba P , Frieman J , García-Bellido J , Gerdes D W , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , James D J , Kuehn K , Kuropatkin N , Lahav O , Lima M , Maia M A G , March M , Menanteau F , Miquel R , Morganson E , Palmese A , Paz-Chinchón F , Plazas A A , Sako M , Sanchez E , Scarpine V , Schubnell M , Serrano S , Sevilla-Noarbe I , Soares-Santos M , Suchyta E , Swanson M E C , Tarle G , Thomas D , Varga T N , Walker A R , Wilkinson R ,   (DES Collaboration)
Published: May 2020

We present DES16C3cje, a low-luminosity, long-lived type II supernova (SN II) at redshift 0.0618, detected by the Dark Energy Survey (DES). DES16C3cje is a unique SN. The spectra are characterized by extremely narrow photospheric lines corresponding to very low expansion velocities of ≲1500 km s−1, and the light curve shows an initial peak that fades after 50 d before slowly rebrightening over a further 100 d to reach an absolute brightness of Mr ∼ −15.5 mag. The decline rate of the late-time light curve is then slower than that expected from the powering by radioactive decay of 56Co, but is comparable to that expected from accretion power. Comparing the bolometric light curve with hydrodynamical models, we find that DES16C3cje can be explained by either (i) a low explosion energy (0.11 foe) and relatively large 56Ni production of 0.075 M⊙ from an ∼15 M⊙ red supergiant progenitor typical of other SNe II, or (ii) a relatively compact ∼40 M⊙ star, explosion energy of 1 foe, and 0.08 M⊙ of 56Ni. Both scenarios require additional energy input to explain the late-time light curve, which is consistent with fallback accretion at a rate of ∼0.5 × 10−8 M⊙ s−1.