bluuebunny/crossref_metadata_2025 huggingface dataset:
Crucial role of neutron diffusion in the crust of accreting neutron stars
Authors: Chugunov A I , Shchechilin N N
Published: March 2020

Observed temperatures of transiently accreting neutron stars in the quiescent state are generally believed to be supported by deep crustal heating, associated with non-equilibrium exothermic reactions in the crust. Traditionally, these reactions are studied by considering nuclear evolution governed by compression of the accreted matter. Here, we show that this approach has a basic weakness; that is, in some regions of the inner crust the conservative forces, applied for matter components (nuclei and neutrons), are not in mechanical equilibrium. In principle, the force balance can be restored by dissipative forces; however, the required diffusion fluxes are of the same order as total baryon flux at Eddington accretion. We argue that redistribution of neutrons in the inner crust should be involved in realistic model of accreted crust.
Pervasive and CpG-dependent promoter-like characteristics of transcribed enhancers
Authors: Steinhaus Robin , Gonzalez Tonatiuh , Seelow Dominik , Robinson Peter N
Published: March 2020

The temporal and spatial expression of genes is controlled by promoters and enhancers. Findings obtained over the last decade that not only promoters but also enhancers are characterized by bidirectional, divergent transcription have challenged the traditional notion that promoters and enhancers represent distinct classes of regulatory elements. Over half of human promoters are associated with CpG islands (CGIs), relatively CpG-rich stretches of generally several hundred nucleotides that are often associated with housekeeping genes. Only about 6% of transcribed enhancers defined by CAGE-tag analysis are associated with CGIs. Here, we present an analysis of enhancer and promoter characteristics and relate them to the presence or absence of CGIs. We show that transcribed enhancers share a number of CGI-dependent characteristics with promoters, including statistically significant local overrepresentation of core promoter elements. CGI-associated enhancers are longer, display higher directionality of transcription, greater expression, a lesser degree of tissue specificity, and a higher frequency of transcription-factor binding events than non-CGI-associated enhancers. Genes putatively regulated by CGI-associated enhancers are enriched for transcription regulator activity. Our findings show that CGI-associated transcribed enhancers display a series of characteristics related to sequence, expression and function that distinguish them from enhancers not associated with CGIs.
Epistemology of Geometry
Authors: Eisenthal Joshua , Patton Lydia
Published: March 2020

From Euclid to Einstein, geometry has continually shown itself to be a remarkably rich area of philosophical inquiry. Major geometrical traditions find their roots in the Āryabhatīya of Āryabhata from the classical age of Indian mathematics, the Nine Chapters on the Mathematical Art from Han dynasty China, and in Euclid’s Elements of ancient Greece, conveyed via the Arabic textual tradition to medieval scholars. Ancient reasoning methods—characteristically relying on pictures or diagrams—have found a renaissance in the scholarship of the last few decades and are now seen as far more rigorous than has often been supposed. Much contemporary geometry traces back to the development of algebraic methods (spurred in the Western tradition through philosophers such as Descartes and Leibniz), and geometry today overlaps with many other areas of mathematics (including set theory, category theory, and homotopy type theory). In the interim, a number of traditions have risen to prominence. Kant regarded geometry as the paradigm example of the synthetic a priori, and Hilbert’s work on geometry set a new standard for the axiomatization of a mathematical theory. Having always been admired as a paradigm of science, there is a long-standing tradition of seeking out “geometrical formulations” of physical theories (including classical mechanics, electromagnetism, and quantum physics). The emergence of a plurality of non-Euclidean geometries—sending shock waves through mathematics, physics and philosophy—led in particular to the 19th-century “problem of space,” which then fed into Einstein’s theories of special and general relativity, radically transforming the physical application of geometrical notions. This article is organized into three major areas of the epistemology of geometry. The first, Geometrical Reasoning, concerns the epistemology of geometrical practice itself. The second, Geometry and Philosophy, concerns the various pathways between geometry and philosophical theorizing more generally, including the historical engagement between the two. And the third, Geometry and Physics, concerns the intimate connections between geometry and physics, especially (of course) the physics of space. The bibliography begins with a selection of general overviews and textbooks that can serve as entry points into more specific areas.
Canadian Foreign Policy
Authors: Carment David , Jamieson Brandon
Published: March 2020

In an era of instability, upheaval, and change Canada’s place in the world remains uncertain. This is an era of significant geopolitical shifts, nationalism, and identity politics. As a result, the institutions in which Canada has invested significant capital such as trade, political, and security organizations are being tested and stretched to the limit. In essence, Canada’s fate and future is structurally contingent on its relationship with the United States; a relationship that paradoxically is key to enhancing Canadian sovereignty while at the same time having the potential to reduce it. Canada’s foreign policy has been captivated by three or perhaps four ends: the establishment of peace and security through the rule of law, maintaining a harmonious and productive relationship with the United States, and ensuring economic prosperity and competitiveness through trade and investment. To these three core elements we might add enhancing national unity and its corollary strengthening Canadian sovereignty. While these ends remain largely unchanged, where we would find a great deal of variation over time is how various governments envision achieving them. The publications cited in this article examine these emerging issues as well as those grounded in overarching debates about Canada’s place in the world, its relationship to the United States, and the importance of international institutions in advancing Canadian interests and values. While some of the readings may be regarded as definitive and others seminal much of what is identified is intended to provide insights on different ways of thinking about Canada’s foreign policy, who shapes it, and to what end.
Ludwig van Beethoven
Authors: Wilson John D.
Published: March 2020

Few if any other composers in the history of European art music have inspired more words on paper than Ludwig van Beethoven. Even during his lifetime (b. 1770–d. 1827), Beethoven’s music inspired both heated debate and thoughtful reaction among some of the era’s most influential critics and philosophers, a discourse which would only intensify after his death and establish him as a singular force in musical thought and a formidable challenge for future composers. His seemingly all-encompassing absorption of the musical language of the 18th century, and his mastery over the full range of its expressive potential, attracted notice among connoisseurs, fortuitously as newly established concert-giving institutions and specialized journals began to conceive of and shape a canon of musical works. At the same time, many other listeners sensed that his music—in its dynamism and rude, often explosive contrasts—projected a sui generis compositional persona, a perception which spurred on his younger creative peers. If there is a red thread in the variegated written responses over the last 250 years, it is the tension between these two views of Beethoven, as a culmination of the past and as a finger pointing firmly toward the future. While words on Beethoven have surely been written in every language in which music is written about, the most essential ones for the modern student or scholar are in German and English, and serious research requires reading proficiency in both languages. Not all of the primary sources have been translated into English, to say nothing of important secondary literature, and in recent years the German academic publishing market has been robustly producing a number of fine compendia and reference works. English-language scholarship has historically distinguished itself, on the other hand, in biography and Sketch Studies. And while it might come as a surprise that there still remain neglected aspects of Beethoven’s body of work, it does not take long for the reader to realize that many words have been devoted to a relatively small corner of his output—namely a handful of Symphonies, String Quartets, piano Sonatas, and other instrumental works that embody what has come to be known as the “heroic style.” Much of the freshest recent scholarship, then, explores the previously marginalized works—music for dancing, singing, worship, the theater, political celebrations—while another belated but welcome development focuses on the historical, intellectual, and aesthetic contexts that shaped his music.
Territoriality
Authors: Kamath Ambika
Published: March 2020

Territoriality is a foundational concept in animal behavior and behavioral ecology. Territoriality is commonly defined as “the defense of an area,” wherein the area being defended is known as the “territory.” Territoriality serves as a framework that allows animal behaviorists and behavioral ecologists to describe and hypothesize links among diverse aspects of animals’ biology. The many facets and functions of territoriality include the acquisition of food, nest sites, and shelter, space-use and movement behavior, and interactions with mates and competitors. Thus, because territoriality encompasses behaviors that directly determine individuals’ survival and reproduction (i.e., their fitness), it offers a powerful approach to understanding the evolution of animal behavior. Territoriality has been used to describe animal behavior for many centuries, particularly in avian systems; conversely, many advances in how biologists conceive of and use territoriality have arisen in research on birds. Operational definitions of territory fall broadly into two categories—those that focus on animals’ behavior and those that focus on their ecological relationships. That said, the question of how to conceive of territory has long been a subject of contention, with widely varied opinions on how the term should be defined and whether and how it is useful for understanding animal behavior. Discussions and critiques of territoriality, from not only animal behavior and behavioral ecology but also from the social sciences, help to contextualize and sharpen how we use the concept to understand the evolution of animal behavior. Technological and statistical advances continue to change the ways in which territories are mapped and quantified, with different methods available for taxa of different sizes, habitats, and life histories. Research on territoriality can be divided into two large domains based on the function served by territory—foraging and mating—but these two functions are intimately linked through the socioecological hypothesis that proposes a relationship between resource distributions and mating systems. This hypothesis has served to structure much research on territoriality in the last half-century or so. Finally, territoriality is pertinent not just to within-species interactions but also to between-species interactions and species coexistence, with implications for macroecological and macroevolutionary patterns and processes.
Hebrew Literature and Music
Authors: Ben-Horin Michal
Published: March 2020

Literature and music have a long entwined history. Since Antiquity, music and poetry (a crystalized form of “literature” or the “poetic”) have been regarded as “twin sisters,” constituting a productive source of creation and inspiration. In the Romantic era (especially German Romanticism), this affinity reached one of its peaks, as demonstrated in the emergence of symbiotic musical-poetic forms and modes of aesthetic expression. From the perspective of cultural history, however, the scope of this relationship is even wider and can be traced back to the overlap between language and music. The compatibility of music and poetry has produced a range of scholarship elaborated in various traditions of knowledge and research disciplines, including semiotics, poetics, aesthetics, musicology, cultural studies, and critical theory. It is well known that sound is a central component of both musical and verbal sign systems. What happens to this sound, however, when we read a story? Moreover, whereas the connection between sounds and poems seems obvious, as shown in the field of research called prosody, which explores various phenomena such as rhythm and alliteration, metric and intonation, the connection between sounds and prose fiction is less obvious. This article focuses on a body of works—theoretical, methodological, and textual—dedicated to the exploration of literature and music relationships in general, in order to understand the relationship between Hebrew literature (including poetry, but mainly prose fiction) and music in particular. Compared to other national literatures, such as French, English, and, above all, German, the scholarly study of Hebrew literature and music is relatively young. Central domains of this study are the employment of sound and acoustic components (i.e., prosody), the incorporation of musical intertexts (i.e., texts that are connected to the realm of music, such as musical terminology, descriptions of music playing, allusions to musical repertoire and themes), and the shaping of analogies between musical forms and narrative structures (i.e., the sonata form or the counterpoint). Hebrew literature also has a history, of course, from the Bible and other ancient texts to medieval Hebrew poetry and up to modern Hebrew and contemporary Israeli literature. Viewing these poetic traditions through the specific lens of language/literature and music relationships, an emerging field of study dealing with representations of music in modern Hebrew and Israeli prose fiction will be discussed, alongside scholarship on the relationship between Hebrew poetry and music.
Resources
Authors: Soh Pek-Hooi
Published: March 2020

Management scholars have long argued that firm performance difference can be driven by strategic resources inside a firm. Most resources in organizations are considered as input factors required to perform a firm’s business functions and operations efficiently. There are other resources such as brand capital and organizational knowledge that are produced from the usage of inputs. Resources are said to be strategically important when their use enables the firm to create economic rents, resulting in the firm’s competitive advantage that no current and potential competitors can achieve. Examples of strategic resources are managerial skills, specialized knowledge, and organizational routines such as human resource and supply chain practices. Strategic resources arising from within firms and across partnering firms can also be uniquely accessed, combined, and utilized in order to drive firm performance and growth. Most empirical studies have focused on understanding how firms develop and transform rent-generating resources into a form of firm-specific assets that enable them to exploit new opportunities and achieve sustainable competitive advantage. Research inquiries on strategic resources have also led to the development of several important conceptual perspectives, such as the resource-based view, dynamic capabilities, core competence, and the knowledge-based view. The respective conceptualization of these perspectives has sparked many debates and critiques among the perspectives about the assumptions of resources and associated value and the extent to which different perspectives contribute to the usefulness of explaining persistent firm performance difference and prescribing pragmatic approaches to management.
Japanese Ceramics
Authors: Wilson Richard L.
Published: March 2020

From its inception in the late 19th century up to the 1970s, modern scholarship in Japanese ceramics was largely bifurcated into archaeology-based studies of pre- and early-historical wares and art-historical investigations of wares from later periods. The former relied on stratigraphic and typological methods. Extensive excavations began in the 1920s, and within two decades a chronology of prehistoric pottery up to the 3rd century had been established for all of the main islands. Successive generations of archaeologists have built on that foundation to create what must be the most complex prehistoric pottery classification system in the world. The efforts of art and craft historians, on the other hand, drew from premodern descriptions of local industries, and especially from the traditions of connoisseurship and collecting developed in the tea ceremony, which focused on form and provenance in a select group of utensils produced or collected in Japan. From the 1910s, influenced by Western aesthetics, the old hierarchy expanded into a “ceramic art” canon that included under- and overglaze decorated wares, notably in porcelain. Supported by a postwar enthusiasm for Japanese traditional culture and development-driven archaeology, ceramics as both art and artifact received broad exposure in exhibitions and publishing both domestically and overseas. Bridges between the archaeological and art-historical approaches appeared in the last two decades of the 20th century with the acceleration of kiln- and user-site excavations. With access to staggering amounts of information on how ceramics of all periods were made, traded, and used, art historians now embrace the findings if not the actual methods of the archaeologist. At the same time, mirroring trends in Western studies of material culture, Japanese ceramics studies as a whole have become more self-reflexive and context-sensitive, and now include critical inquiry into identity-making, collecting, consumer demand, and regionality. Scholarly interest in modern (post-1868) ceramics has also increased considerably since the mid-1990s. Japanese-language literature in every aspect of this field is vast, but here those contributions are limited to reference works, benchmark publications, and select topics that are not covered in English or other Western languages; when English is included in those works, it is noted in the respective entry.
What’s Hot in Clinical Infectious Diseases? 2019 IDWeek Summary
Authors: Moss Sean , Boucher Helen W
Published: March 2020

The year 2019 brought about a multitude of innovations in clinical infectious diseases. With the continued rise of antimicrobial resistance (AMR), advances in diagnostics and newly available antibiotics offer additional strategies for combating this threat, but the broken antibiotic market serves as an impediment to further developments. The IDSA and other stakeholders are working to create novel pull incentives to stabilize the pipeline. Ongoing needs include developing optimal stewardship practices, including by using narrow-spectrum antibiotics and shorter durations of therapy. In the area of solid organ transplantation, early data from transplanting Hepatitis C virus (HCV)-infected organs are encouraging and the American Society of Transplantation (AST) released new guidelines addressing several key issues. Lastly, 2019 saw a resurgence in Measles emphasizing the importance of vaccination.
Blood Pressure Screening by Outpatient Physical Therapists: A Call to Action and Clinical Recommendations
Authors: Severin Richard , Sabbahi Ahmad , Albarrati Ali , Phillips Shane A , Arena Sara
Published: March 2020

Hypertension (HTN) is among the leading global preventable risk factors for cardiovascular disease and premature mortality. Early detection and effective management of HTN have demonstrated significant reductions in mortality, morbidity rate, and health care costs. Furthermore, screening for HTN by nonphysician health care providers improves detection rates and medical management. As physical therapist practice advances to a more independent care model, physical therapists may serve as the first point of contact into the health care system, thereby necessitating a need for routine blood pressure (BP) monitoring. This is especially relevant in the outpatient physical therapist practice setting, where there is evidence for elevated BP measures among patients, yet omission of routine screening in this setting is well documented. Leading physical therapy professional organizations include statements in their guidelines that suggest that physical therapists have a duty to provide a standard of care that protects the safety and optimizes the overall health of patients under their care. Therefore, it is imperative not only that physical therapists include BP examination into routine practice protocols but that the knowledge and skills to accurately measure and interpret BP at rest and during exercise be integrated into the standard of care. The authors suggest that the profession of physical therapy proactively embrace their potential to address the national and worldwide HTN epidemic through routine assessment of BP, appropriate referral for elevated BP measures, and exploration of HTN management by physical therapists.
The benefits of non-invasive ventilation for community-acquired pneumonia: a meta-analysis
Authors: Klefti G. , Hill A.T.
Published: March 2020

There is an observed international increase in non-invasive ventilation (NIV) application as an alternative to endotracheal intubation (ETI) in non-chronic obsructive pulmonary disease (COPD) patients admitted with community-acquired pneumonia (CAP) despite the lack of strong evidence for its use. The aim of this study is the meta-analysis of data from randomized controlled trials (RCTs) on the effectiveness of NIV vs. standard medical care in adults admitted with severe CAP. Monthly electronic searches on CENTRAL and MEDLINE were performed between September 2017 and October 2019. Only RCTs comparing NIV to standard medical care for the treatment of CAP in adults were eligible for inclusion. The primary outcomes were the rate of ETI and the proportion of patients meeting the criteria of ETI as defined by the investigators. Secondary outcomes were the intensive care unit (ICU) and hospital mortality rate. Study eligibility was independently assessed by two investigators. The risk of bias of included studies was assessed using Cochrane’s Risk of bias Tool. Four RCTs involving a total of 218 participants were eligible for inclusion. Results from the meta-analysis showed that NIV significantly reduced rate of ETI (risk ratio (RR) = 0.46, 95% CI [0.26, 0.79]), the proportion of patients that met the criteria for ETI (RR = 0.28, 95% CI [0.16, 0.49]) and ICU mortality rate (RR = 0.3, 95% CI [0.09, 0.93]). No significant effect on hospital mortality rate was found (RR = 0.44, 95% CI [0.05, 3.67]). The authors rated quality of evidence based on GRADE criteria as ‘Moderate’ for the rate of intubation and proportion of patients meeting ETI criteria outcomes, but quality of evidence for ICU and hospital mortality rate as ‘Low’. This study provides evidence supporting the use of NIV as potential means of avoiding ETI and ICU mortality, in patients with acute respiratory failure due to CAP in the critical care setting. However, there is need for further larger international studies.
Computational modelling of social cognition and behaviour—a reinforcement learning primer
Authors: Lockwood Patricia L , Klein-Flügge Miriam C
Published: March 2020

Social neuroscience aims to describe the neural systems that underpin social cognition and behaviour. Over the past decade, researchers have begun to combine computational models with neuroimaging to link social computations to the brain. Inspired by approaches from reinforcement learning theory, which describes how decisions are driven by the unexpectedness of outcomes, accounts of the neural basis of prosocial learning, observational learning, mentalizing and impression formation have been developed. Here we provide an introduction for researchers who wish to use these models in their studies. We consider both theoretical and practical issues related to their implementation, with a focus on specific examples from the field.
Cannabidiol attenuates methamphetamine-induced conditioned place preference via the Sigma1R/AKT/GSK-3β/CREB signaling pathway in rats
Authors: Yang Genmeng , Liu Liu , Zhang Ruilin , Li Juan , Leung Chi-Kwan , Huang Jian , Li Yuanyuan , Shen Baoyu , Zeng Xiaofeng , Zhang Dongxian
Published: March 2020

Methamphetamine (METH) is a highly addictive psychostimulant. Cannabidiol (CBD) is an exogenous cannabinoid without psychostimulating activity, which has potential therapeutic effects on opioid addiction. However, it is unclear whether CBD has therapeutic effects on METH-induced motivational effects. The present study examines whether CBD has a protective effect on METH-induced conditioned place preference (CPP) in rats by regulating the Sigma1R and AKT-GSK3β-CREB signaling pathway. Seventy rats were equally and randomly divided into seven groups. The rat CPP model was established via the intraperitoneal injection (IP) of 2 mg/kg of METH. Next, the intraperitoneal injection of 10, 20, 40, and 80 mg/kg CBD was performed 1 h prior to the injection of saline or METH. The protein expression levels of Sigma1R, AKT, p-AKT, GSK-3β, p-GSK-3β, CREB, and p-CREB in the rats’ prefrontal cortex, nucleus accumbens, and hippocampus and ventral tegmental were detected using western blot analysis. CBD was found to inhibit METH-induced CPP in a dose-dependent fashion. The expression levels of Sigma1R, p-AKT, p-GSK3β, and p-CREB increased significantly in the METH-induced CPP model. Treatment involving different doses of CBD caused differential inhibitory responses in the cellular protein abundance of Sigma1R, p-AKT, p-GSK3β, and p-CREB across various brain regions. The present study found that METH can induce CPP in rats. When a pretreatment of CBD is applied, the CBD can weaken CPP in METH-induced rats by regulating the SigmaR1/AKT/GSK-3β/CREB signaling pathway. The results of this study indicate that CBD has a potential therapeutic effect on METH-induced rewarding effects.
Oxidative stress response associates with the teratogenic effects of benzyl butyl phthalate (BBP)
Authors: Song Ge , Wang Rui , Cui Yi , Hao Chan Juan , Xia Hong-Fei , Ma Xu
Published: March 2020

Benzyl butyl phthalate (BBP) is a persistent environmental pollutant. BBP exposure and the possible effects on human neural tube defects (NTDs) remain elusive. In this study, we found that the detection ratio of positive BBP and its metabolites in maternal urine was obviously higher in NTDs’ population than that in normal controls by GC-MS (P < 0.01, P < 0.05, respectively). Animal experiments showed that BBP treatment induced developmental toxicity in chick embryo by enhancing the levels of oxidative stress and cell apoptosis (P < 0.01). More interestingly, the supplement of high-dose choline (CHO, 10 5 μg/mL) could partially restore the teratogenic effects of BBP by inhibiting the occurrence of oxidative stress. Our data collectively suggest that BBP exposure may disturb neural tube development by strengthening oxidative stress. CHO can partially restore the toxicity effects of BBP. This study may provide new insight for NTD prevention.
CaCBL1 Acts as a Positive Regulator in Pepper Response toRalstonia solanacearum
Authors: Shen Lei , Yang Sheng , Yang Feng , Guan Deyi , He Shuilin
Published: March 2020

Bacterial wilt caused by Ralstonia solanacearum is an important disease of pepper (Capsicum annuum), an economically important solanaceous vegetable worldwide, in particular, under high temperature (HT) conditions. However, the molecular mechanism underlying pepper immunity against bacterial wilt remains poorly understood. Herein, CaCBL1, a putative calcineurin B-like protein, was functionally characterized in the pepper response to R. solanacearum inoculation (RSI) under HT (RSI/HT). CaCBL1 was significantly upregulated by RSI at room temperature (RSI/RT), HT, or RSI/HT. CaCBL1-GFP fused protein targeted to whole epidermal cells of Nicotiana benthamiana when transiently overexpressed. CaCBL1 silencing by virus-induced gene silencing significantly enhanced pepper susceptibility to RSI under RT or HT, while its transient overexpression triggered hypersensitive response mimic cell death and upregulation of immunity-associated marker genes, including CabZIP63, CaWRKY40, and CaCDPK15, the positive regulators in the pepper response to RSI or HT found in our previous studies. In addition, by chromatin immunoprecipitation PCR and electrophoretic mobility shift assay, CaCBL1 was found to be directly targeted by CaWRKY40, although not by CaWRKY27 or CaWRKY58, via the W-box-2 within its promoter, and its transcription was found to be downregulated by silencing of CaWRKY40 while it was enhanced by its transient overexpression. These results suggest that CaCBL1 acts as a positive regulator in pepper immunity against R. solanacearum infection, constituting a positive feedback loop with CaWRKY40.
Occurrence in Seeds and Potential Seed Transmission of Xanthomonas vasicola pv. vasculorum in Maize in the United States
Authors: Arias Silvina L. , Block Charles C. , Mayfield Derrick A. , Santillana Gem , Stulberg Michael J. , Broders Kirk D. , Jackson-Ziems Tamra A. , Munkvold Gary P.
Published: March 2020

This paper reports original evidence regarding the potential role of seed transmission of Xanthomonas vasicola pv. vasculorum in the epidemiology of bacterial leaf streak (BLS) in maize. We evaluated the occurrence of the pathogen on seeds from diseased fields and its subsequent transmission to seedlings. In 2016 and 2017, X. vasicola pv. vasculorum was detected by TaqMan PCR from 22 of 41 maize seed lots harvested from naturally infected fields in Colorado, Nebraska, and Iowa. However, many of the PCR-positive samples did not yield culturable X. vasicola pv. vasculorum colonies. The highest levels of seed contamination were detected in dent maize and popcorn from NE and CO. Seed transmission was evaluated in greenhouse grow-outs from eight seed lots, totaling more than 14,000 plants. Putative seed transmission events from naturally contaminated seed lots, estimated from PCR results, occurred at a frequency between 0.1 and 0.5% in 10-seedling pooled samples and at a frequency of 2.7% from individual plant assays. However, no seedling symptoms were observed during these assays and live X. vasicola pv. vasculorum colonies were not recovered from PCR-positive seedlings. In contrast, seed transmission was readily demonstrated from artificially contaminated seed lots, including typical symptoms and recovery of live bacteria. Seed transmission consistently occurred from seeds soaked in bacterial suspensions with concentrations of ≥106 CFU/ml, suggesting that a threshold population of the bacterium is necessary for the development of BLS symptoms and recovery of live bacteria. The low bacterial populations on naturally contaminated seeds apparently were not sufficient to result in diseased seedlings.
Evaluation of anti-cancer potency of silibinin on murine renal carcinoma RenCa cells in an animal model with an intact immune system
Authors: Yang Chao , Li Feng , Ma Jianbin , Zhang Hai-Bao , Jia Jing , Zeng Jin , Wang Xinyang , He Dalin , Guo Peng
Published: March 2020

Silibinin is a flavonoid extract isolated from milk thistle and has been proved to be a promising chemotherapeutic drug for cancer. However, most of those studies were performed on the human cancer cells, where the effects of silibinin could only be observed on an animal model with a deficient immune system. RenCa cells were isolated from a murine spontaneous renal cell carcinoma, which resembles many features of human renal cell carcinoma, and have been used to establish animal models with a sound immune response. Herein, we investigated the anti-cancer effects of silibinin on RenCa cells, revealing that it inhibited cell viability in both dose- and time-dependent manners. Silibinin slightly triggered apoptosis and significantly induced G2-M cell cycle arrest by downregulating cyclin B1 and CDK1 and increasing expression of p21WAF1/CIP1. Furthermore, silibinin significantly inhibited the growth of RenCa cell xenografts in vivo. In addition, we found that silibinin reduced programmed cell death 1 ligand 1 expression of RenCa cells in vivo and in vitro. Our findings demonstrate that silibinin can inhibit the growth of mouse tumor cells in an animal model with an intact immune system, and silibinin may decrease the immunosuppression effect of tumor cells. Our results provide new evidence for evaluation of Silibinin application in cancer therapy.
Emerging treatments in advanced urothelial cancer
Authors: Alhalabi Omar , Campbell Matthew , Shah Amishi , Siefker-Radtke Arlene , Gao Jianjun
Published: March 2020

Purpose of review

Urothelial carcinoma is one of the 10 most common forms of cancer in the world with more than half a million cases diagnosed yearly. The past few years have witnessed a revolution in understanding the biology of urothelial carcinoma and the development of promising therapies. In this review, we summarize the emerging therapeutic approaches in the management of advanced urothelial carcinoma.

Recent findings

Since 2016, the Food and Drug Administration (FDA) has approved five checkpoint inhibitors (CPIs), a fibroblast growth factor receptor (FGFR) inhibitor, and an antibody drug conjugate (ADC) for the treatment of advanced urothelial carcinoma. Additionally, the FDA has granted several breakthrough designations for other therapeutic strategies including other ADCs.

CPIs, anti-FGFR agents and ADCs are significant advancements that offer new treatment options to patients with advanced urothelial carcinoma. However, there remains a need to understand mechanisms of resistance, identify biomarkers to choose potential responders, and learn the best strategy to sequence these agents in regards to lines of therapy.
Influence of selected polymorphisms in disposition genes on lumefantrine pharmacokinetics when coadministered with efavirenz
Authors: Adegbola Adebanjo Jonathan , Rana Abutaima , Adeagbo Babatunde Ayodeji , Bolarinwa Rahman A. , Olagunju Adeniyi Ebenezer , Siccardi Marco , Owen Andrew , Bolaji Oluseye Oladotun
Published: March 2020

Background

Coadministration of artemether–lumefantrine and efavirenz has been shown to result in significant interactions. The influence of functional genetic polymorphisms in selected CYPs on the magnitude of this interaction was investigated in pregnant and nonpregnant adults.

Method

A standard 3-day regimen of artemether–lumefantrine was administered to each patient on steady-state efavirenz-based antiretroviral therapy (ART). Pharmacokinetic parameters were obtained from intensive plasma concentration–time data. Genotyping data were tested for compliance with Hardy–Weinberg equilibrium by Chi-square test. Linear regressions, Mann–Whitney U-test or Kruskal–Wallis tests were conducted to examine the association of lumefantrine plasma level with CYP2B6 c.516G>T, NR1I3 152c-1089T>C, CYP2B6 c.983T>C, CYP3A5*3 and CYP3A4*22.

Results

Among a total of 69 malaria–HIV coinfected patients (34 nonpregnant and 35 pregnant), median (interquartile range) age was 33 (27–36.5) years and body weight was 59.5 (50–67.5) kg. In nonpregnant group, CYP2B6 c.516G>T was significantly associated with lower log C
day 7 of lumefantrine using multivariate linear regressions (β = −0.239; P = 0.013). In 59% of women with CYP2B6 c.516T, C
day 7 of lumefantrine was below the target of 280 ng/mL compared to 47% in the noncarriers. CYP2B6 c.983T>C significantly associated with higher log C
day 7 of desbutyl lumefantrine in both pregnant (β = 0.383; P = 0.033) and nonpregnant (β = 0.395; P = 0.023) groups. Composite genotypes for both CYP2B6 Single-nucleotide polymorphisms strongly associated with lumefantrine plasma concentration. An associative trend between lumefantrine pharmacokinetics and NR1I3 152c-1089T>C genotypes indicated that 70% of the C
day 7 of lumefantrine in those with NR1I3 152c-1089TT genotype was below 280 ng/mL compared to 53% in those with NR1I3 152c-1089CC or CT genotype.

Conclusion

The findings revealed that the efavirenz–lumefantrine interaction was accentuated in the group with CYP2B6 c.516T, c.983C and NR1I3 152c-1089T alleles. This warrants further investigations of other drug–drug interactions for optimising dosing in genetically defined subgroups, particularly during drug development.
Use of Social Media to Teach Global Reconstructive Surgery: Initiation of a Secret Facebook Group
Authors: Deptula Peter L. , Auten Brieanne , Chang James
Published: March 2020

Background:

The ReSurge Global Training Program (RGTP) is a model for building reconstructive surgery capacity in low- and middle-income countries.
1
The aim of this study is to assess attitudes toward social media, to develop an initial RGTP Facebook Education Group, and to assess the early results of the group’s implementation.

Methods:

A survey of the RGTP community assessed group demographic, interests, concerns, and familiarity with Facebook from July to August of 2018. A “secret” Facebook group was launched on October 30, 2018. Narrated lectures were posted weekly to the group. Educational cases were shared on the group’s discussion page. Facebook “Group Insights” and individual post review were used to obtain group statistics.

Results:

Senior faculty were less likely to have an existing Facebook account (58% vs 93%, P < 0.05). Trainees were more confident using Facebook (97% vs 54%, P < 0.05) and favored viewing the training curriculum through Facebook (93.0%, P < 0.05). At 6 months, the group enrolled 103 members from 14 countries. Twenty-two lectures were posted, obtaining an average of 59.4 views (range, 36–78). Fourteen cases were presented for group discussion with an average of 61.1 views (range, 43–87).

Conclusions:

The RGTP Facebook group has continued to expand in its early months. This group allows our community to view RGTP’s training curriculum, while providing global access to expert opinion and collaboration. The secret Facebook group can be used as an effective and easy-to-use platform for educational outreach in global reconstructive surgery.
Acral Lentiginous Melanoma: Do Surgical Approach and Sentinel Lymph Node Biopsy Matter?
Authors: Walker Marc E. , Han Gang , Gabrick Kyle , Kanouzi Jack , Lo Ying-Chun , Galan Anjela , Clune James , Narayan Deepak , Ariyan Stephan , Han Dale
Published: March 2020

Background:

Management of acral lentiginous melanoma (ALM) remains controversial. Traditionally, ALM was managed with digit amputation (DA), resulting in significant morbidity, but recent evidence has advocated for digit sparing management. Furthermore, the significance of nodal metastasis for ALM is not well reported. The aims of this study were to determine if surgical approach for primary ALM impacts outcomes and to evaluate the predictive value of nodal status for ALM.

Methods:

Patients with localized ALM diagnosed from 1982 to 2017 were retrospectively identified. Clinicopathologic characteristics were correlated with surgical approach, nodal metastasis, overall survival, and recurrence-free survival.

Results:

There were 47 patients with ALM. Median age was 59 years, and median thickness was 3 mm. 51% of patients underwent wide local excision (WLE), 27.9% underwent DA, and 20.9% underwent partial digit amputation (PDA). ALM on the hand versus foot (OR: 12.7, 95%, confidence interval (CI), 2.0–80.1; P = 0.007) and subungual versus nonsubungual location (OR: 28.0, 95% confidence interval, 2.7–295.7; P = 0.006) were significantly associated with surgical approach (DA and PDA versus WLE). There were no significant differences in overall survival or recurrence-free survival between DA, PDA, or WLE cases (P = 0.481 and P = 0.778, respectively). There were no significant differences in overall survival or recurrence-free survival based on nodal status (P = 0.562 and P = 0.136, respectively).

Conclusions:

No significant differences in overall survival or recurrence-free survival were seen between ALM patients treated with DA, PDA, and WLE. Given these results, PDA or WLE may be options in select patients with digital ALM; however, careful consideration must be taken when deciding on the surgical approach.
Spreading Awareness: Bowel Perforation with Liposuction
Authors: Taha Ahmed A. , Tahseen Hossam
Published: March 2020

Complications with liposuction are not uncommon; some of these are very serious and can be life-threatening. In this case report, we represent a case of bowel perforation with liposuction.
Immediate Targeted Nipple–Areolar Complex Reinnervation: Improving Outcomes in Gender-affirming Mastectomy
Authors: Rochlin Danielle H. , Brazio Phil , Wapnir Irene , Nguyen Dung
Published: March 2020

Background:

Female-to-male mastectomy often renders the chest skin and nipple–areolar complex (NAC) insensate. We propose a new technique of preserving the intercostal nerves and using them to reinnervate the NAC after mastectomy.

Methods:

We performed a prospective analysis of transmasculine patients who underwent female-to-male mastectomy. The technique involves dissecting out the lateral intercostal nerves to length and performing a neurorrhaphy to nerve stumps at the base of the NAC. Sensory outcomes, as assessed with Semmes–Weinstein monofilaments, were compared to a cohort of patients who underwent mastectomy without neurotization.

Results:

Ten patients with a mean age of 17.5 years (range: 16–19 years) underwent mastectomy. The final follow-up was a mean of 15.4 ± 4.3 months for the treated group and 40.7 ± 12.9 months for the control group. Compared to control patients, treated patients had significant improvement in sensation at the nipple (P ≤ 0.0002), areola (P = 0.0001), and peripheral breast skin (P = 0.0001). For treated patients, there was no statistically significant difference in sensation between preoperative and postoperative sensation in all tested areas at final follow-up.

Conclusion:

This proof of concept study suggests that immediate reinnervation of the NAC after mastectomy enhances recovery of NAC sensation in patients undergoing female-to-male mastectomy and may be further generalized to women undergoing postmastectomy breast reconstruction.
Comparison of clinical and PET-derived prognostic factors in patients with non-Hodgkin lymphoma: a special emphasis on bone marrow involvement
Authors: Kupik Osman , Akin Serkan , Tuncel Murat , Eren Gülnihan , Türker Alev , Kars Ayşe , Erbaş Belkis
Published: March 2020

Objective

In patients with non-Hodgkin lymphoma (NHL), we investigated 18F FDG PET/computed tomography (CT) parameters, clinical findings, laboratory parameters, and bone marrow involvement (BMI) status for predictive methods in progression-free survival (PFS) and overall survival (OS), and whether 18F FDG PET/CT could take the place of bone marrow biopsy (BMB).

Methods

The performance of 18F FDG PET/CT (BMPET) was evaluated. The prognostic value of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), stage, international prognostic index (IPI) score, IPI risk, lactate dehydrogenase (LDH), B2 microglobulin, Ki67 proliferation index, and the presence of BMI was evaluated for OS and PFS. Kaplan–Meier curves were drawn for each designated cutoff value, and 5-year PFS and 7-year OS were evaluated using log-rank analysis.

Results

The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of BMPET and BMB to identify BMI were 69, 100, 86.1, 80, 100%, and 81.6, 100, 92.5, 89, 100%, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of BMPET in patients with Ki67- proliferation index >25% were all 100%. BMPET, IPI risk, MTV, and LDH were found to be independent prognostic predictors for PFS, whereas BMPET, SUVmax, and MTV for OS. Five-year PFS analysis estimated as follows: BMPET (+) = 22%, BMPET (−) = 80%, LDH ≤ 437 (U/L) = 86%, LDH > 437 (U/L) = 51%, MTV ≤ 56 (cm3) = 87%, MTV > 56 (cm3) = 49%, low IPI risk = 87%, intermediate IPI risk = 69%, high IPI risk = 25%. Seven-year OS analysis was found as: SUVmax ≤ 17.6 = 80%, SUVmax > 17.6 = 48%, MTV ≤ 56 (cm3) = 84.4%, MTV > 56 (cm3) = 45.8%, BMPET (−) = 72.5%, BMPET (+) = 42%.

Conclusion

In the Ki-67 proliferation index > 25% group, 18F FDG PET/CT was able to differentiate BMI independently from NHL subgroups. We recommend using this method with large patient groups. MTV and BMPET were independent prognostic indicators for OS and PFS and may help to determine high-risk patients.
A Multisite Study Demonstrates Positive Impacts to Systems Thinking Using a Table-top Simulation Experience
Authors: Sanko Jill S. , Gattamorta Karina , Young Judith , Durham Carol F. , Sherwood Gwen , Dolansky Mary
Published: March 2020

Background

Systems thinking (ST) is the ability to recognize, understand, and synthesize interactions and interdependencies in a set of components designed for a purpose. Systems thinking has been shown to improve systems and decrease error. Despite these benefits, ST has not yet been consistently integrated into all health care education programs.

Purpose

This study examined the impact of Friday Night at the ER (FNER), a table-top simulation designed to teach ST to a variety of prelicensure and postlicensure health care students.

Methods

A multisite study was conducted in 5 academic institutions targeting both graduate and prelicensure students enrolled in nursing, medicine, physical therapy, public health, psychology, and pharmacy programs.

Results

The FNER simulation was followed by statistically significant improvements in ST scores.

Conclusions

The FNER table-top simulation was found to improve ST in a wide variety of health-related majors.
The Moderating Role of Emotion Regulation in the Association Between Stressors With Psychological and Biological Measures in Adolescence
Authors: Klosowska Joanna Cecylia , Verbeken Sandra , Braet Caroline , Wijnant Kathleen , Debeuf Taaike , De Henauw Stefaan , Michels Nathalie
Published: March 2020

Objective

This study explored the role of emotion regulation (ER) as a moderator in the stressor–adjustment outcome relationship while identifying the relevant stressors.

Methods

In 214 adolescents (10–18 years; 51.4% boys), stressors (parent and peer relations, negative events), psychological outcomes (adolescent perceived stress, psychopathology symptoms, negative affect), and biological measures related to the stress response (hair cortisol [HC], heart rate variability [HRV]) as well as ER strategies—maladaptive (MalER), adaptive (AdER), and their ratio (Mal/AdER)—were measured and analyzed via linear regression, adjusted for age, sex, and socioeconomic status.

Results

Parental rejection and bullying were the stressors with the strongest association with psychological outcomes (β range = |0.217–0.352|, p < .05). In addition, parental rejection was associated with HC (β = 0.242, p = .035), whereas none of the stressors were associated with HRV. MalER was linked to all, and AdER to most psychological outcomes (β range = |0.21–0.49|, p < .05). MalER, but not AdER, was associated with HC (β = 0.25, p = .009), whereas none of the ER strategy types were associated with HRV. Moreover, several associations between stressors and psychological outcomes were moderated by MalER and Mal/AdER, whereas AdER’s role as a moderator was not confirmed.

Conclusions

The study confirmed that adolescents’ stressors are associated with both psychological and physiological outcomes and moderated by MalER or Mal/AdER. The lack of moderation by AdER directs toward the maladaptive shift theory. Investigations through a longitudinal, rather than a cross-sectional design, could further elucidate the current observations. Moreover, training in how to use ER effectively has a potential of increasing adolescents’ stress resilience.