bluuebunny/crossref_metadata_2025 huggingface dataset:
1. Unregulated immigration and its opponents, from colonial America to the mid-nineteenth century
Authors: Gerber David A.
Published: March 2021

Colonial British North America was a melting pot for northern and western Europeans, with a majority white population from Great Britain. Colonial authorities encouraged immigration because of a need for labor. Immigration, both bonded and voluntary, supplemented the slave trade as a labor source. The same economic logic was present after the United States was founded in 1789, but, amid unregulated massive immigrations from northern and western Europe, suspicions based on race, nationality, and religion grew about the suitability of the immigrants for American citizenship, as did fears about their negative impact on American life. Thus, from the start, Americans looked in different directions when considering immigration. Immigrants were economically beneficial, yet too many of them were thought dangerous in variety of ways. In fear of immigrant political power, the American Party emerged in the 1850s, arguing unsuccessfully for extension of the period necessary for residence to become a citizen and vote.
3. Removing barriers and debating consequences
Authors: Gerber David A.
Published: March 2021

America emerged from World War II a more unified, confident society, experiencing dramatic economic expansion and exercising military and political supremecy as the world’s dominant superpower. Racism and restrictionism in immigration and refugee law and policy were a burden on claims to world leadership. Continuing economic expansion could be reinforced by immigrant labor. Support grew for more open immigration and refugee regimes without racial and nationality restrictions. A series of laws created foundations for an expansive refugee policy. The 1965 Immigration and Nationality Act ended restrictive quotas and racial deselections. The public was not overly enthusiastic about a re-inception of mass immigration, and was assured that this would not happen. However, when paired with unsettling political and economic change as modernization spread outside Europe, the unintended consequence of the 1965 law was intense controversy over unprecedented numbers of immigrants, both legal and illegal, principally from Asia and Latin America.
War and Religion: A Very Short Introduction
Authors: Mitchell Jolyon , Rey Joshua
Published: March 2021

War and Religion: A Very Short Introduction traces the history of religion and war. Is religion a force for war or a force for peace? From the crusades to Sri Lanka's civil war, religion has been involved in some of the most terrible wars in history. Yet from the Mahabharata to just war theory, religion has also provided ethical frameworks to moderate war, while some of the bravest pacifists have been deeply religious people. Ranging from ancient history to modern day conflicts, this VSI offers a nuanced view on these issues that have had such weight in the past, and which continue to shape the present and future.
Remembering wars
Authors: Mitchell Jolyon , Rey Joshua
Published: March 2021

‘Remembering wars’ discusses how war and religion mingle and shape one another and demonstrates how religion offers to meet the need for meaning in the overwhelming catastrophe of personal and national loss that war brings. There are three interesting different situations in which religious resources have been brought to bear on the remembrance of war, and equally have been shaped by it. The first one is the depiction of martyrdom and martyrs in the commemoration of the Battle of Karbala. The second one is the use of the cross in Great War memorials, while the third one is the Ghost Dance movement
Questioning religion and war
Authors: Mitchell Jolyon , Rey Joshua
Published: March 2021

‘Questioning religion and war’ explains how each faith—particularly Judaism, Christianity, and Islam—has a complex relationship to war and peace. It assesses whether or not religion in general does or does not tend to cause and intensify war in general. Those who are hostile to religion often claim it is inherently warlike. Those who favour religion conclude that it is a force for peace or, where it is implicated in war, it has been misunderstood and warped. Those who think religion inspires both war and the pursuit of peace want to promote the latter and discourage the former. These views have something in common: the idea that war is bad.
2. The moral virtues
Authors: Boyd Craig A. , Timpe Kevin
Published: March 2021

This chapter discusses the four cardinal virtues. Aristotle describes prudence, or practical wisdom, as ‘right reasoning about what is to be done’. He considered it as the most important of the cardinal virtues since it has all human activity under its purview. Justice is the second most important virtue and involves ‘giving to others what they deserve’. The final two moral virtues are fortitude and temperance. Fortitude, or courage, concerns one’s ‘fight or flight’ emotions. It helps one to do the ‘difficult thing’ that one struggles to face. And temperance, or self-control, helps one to moderate one’s desires for food, drink, and sex.
3. The intellectual virtues
Authors: Boyd Craig A. , Timpe Kevin
Published: March 2021

This chapter examines the intellectual virtues. The belief that there are specific intellectual virtues goes back as far as ancient Greece. Intellectual virtues are habits of the mind that facilitate the pursuit of truth, the avoidance of error, or other epistemic goods. Conversely, intellectual vices are habits of the mind that frustrate these goals. And it is possible that a person with intellectual virtue might not necessarily possess moral virtue. The chapter then considers different intellectual virtues: intellectual honesty; intellectual curiosity; intellectual open-mindedness; intellectual courage and perseverance; and intellectual charity.
6. The capital vices
Authors: Boyd Craig A. , Timpe Kevin
Published: March 2021

This chapter studies the capital vices and looks at the ways in which some of the virtues correct the harm that these vices do. A vice is a relatively stable disposition to behave badly; or in Aristotle’s words, ‘a vice is a bad habit of the soul’. The capital vices, as they are traditionally known, occupy an important role as a source for the other vices because their influence seems to afflict people to a greater degree than other vices. They often feed off one another and give birth to other vices. In their most typical listing, the capital vices are pride, envy, avarice, wrath, sloth, gluttony, and lust.
Conclusion
Authors: Boyd Craig A. , Timpe Kevin
Published: March 2021

This concluding chapter highlights some criticisms of the virtues. David Hume and Friedrich Nietzsche both challenged the traditional construal of the virtues and their role. Hume’s approach to morality was based upon ‘moral sentiment’ where moral feelings were central to one’s deliberation about ethics and so one’s practical reason was simply a means to best secure the satisfaction of one’s various desires. Nietzsche argues that the traditional virtues are merely terms used and cultivated by the weak to control the strong. He draws up a ‘genealogy of morals’ and concludes that terms like ‘good’ and ‘evil’ have no real meaning apart from self-descriptions of the people who employ them.
Hang on a second…
Authors: Morrison Leslie , Hohenkerk Catherine Y
Published: March 2021

Leslie Morrison and Catherine Hohenkerk consider the future direction of the leap second
Modelling giant molecular clouds
Authors: Anathpindika Sumedh
Published: March 2021

Sumedh Anathpindika reviews some recent results that shed new light on the dynamical evolution of giant molecular clouds and discusses the impact of ambient environment on their ability to form stars
New eyes and ideas for the chromosphere
Authors: Druett Malcolm , Snow Ben
Published: March 2021

An RAS Specialist Discussion Meeting organized by Malcolm Druett and Ben Snow on 13 November 2020 drew a broad international audience to explore a tricky layer of the Sun
Carrington's lost photograph
Authors: Cliver E W , Fletcher Lyndsay , Hudson H S
Published: March 2021

Ed Cliver, Lyndsay Fletcher and Hugh Hudson are looking for a photograph of Richard Carrington. Can you help?
Deep learning of gene relationships from single cell time-course expression data
Authors: Yuan Ye , Bar-Joseph Ziv
Published: March 2021

Time-course gene-expression data have been widely used to infer regulatory and signaling relationships between genes. Most of the widely used methods for such analysis were developed for bulk expression data. Single cell RNA-Seq (scRNA-Seq) data offer several advantages including the large number of expression profiles available and the ability to focus on individual cells rather than averages. However, the data also raise new computational challenges. Using a novel encoding for scRNA-Seq expression data, we develop deep learning methods for interaction prediction from time-course data. Our methods use a supervised framework which represents the data as 3D tensor and train convolutional and recurrent neural networks for predicting interactions. We tested our time-course deep learning (TDL) models on five different time-series scRNA-Seq datasets. As we show, TDL can accurately identify causal and regulatory gene–gene interactions and can also be used to assign new function to genes. TDL improves on prior methods for the above tasks and can be generally applied to new time-series scRNA-Seq data.
ZEAL: protein structure alignment based on shape similarity
Authors: Ljung Filip , André Ingemar
Published: March 2021

Motivation

Most protein-structure superimposition tools consider only Cartesian coordinates. Yet, much of biology happens on the surface of proteins, which is why proteins with shared ancestry and similar function often have comparable surface shapes. Superposition of proteins based on surface shape can enable comparison of highly divergent proteins, identify convergent evolution and enable detailed comparison of surface features and binding sites.

Results

We present ZEAL, an interactive tool to superpose global and local protein structures based on their shape resemblance using 3D (Zernike-Canterakis) functions to represent the molecular surface. In a benchmark study of structures with the same fold, we show that ZEAL outperforms two other methods for shape-based superposition. In addition, alignments from ZEAL were of comparable quality to the coordinate-based superpositions provided by TM-align. For comparisons of proteins with limited sequence and backbone-fold similarity, where coordinate-based methods typically fail, ZEAL can often find alignments with substantial surface-shape correspondence. In combination with shape-based matching, ZEAL can be used as a general tool to study relationships between shape and protein function. We identify several categories of protein functions where global shape similarity is significantly more likely than expected by random chance, when comparing proteins with little similarity on the fold level. In particular, we find that global surface shape similarity is particular common among DNA binding proteins.

Availability and implementation

ZEAL can be used online at https://andrelab.org/zeal or as a standalone program with command line or graphical user interface. Source files and installers are available at https://github.com/Andre-lab/ZEAL.

Supplementary information

Supplementary data are available at Bioinformatics online.
Heat-distribution in the body and wings of the morpho dragonflyZenithoptera lanei(Anisoptera: Libellulidae) and a possible mechanism of thermoregulation
Authors: Guillermo-Ferreira Rhainer , Gorb Stanislav N
Published: March 2021

Animals that live in hot environments must deal with extreme temperatures and overcome the constraints imposed by overheating. Some species exhibit remarkable adaptations to control body temperature, usually in the form of structures that act as thermal windows to cool down the body by dissipating heat. Here, we describe the case of the dragonfly Zenithoptera lanei, which inhabits open areas in the Neotropical Savannah and the Amazon. Males have striking and unique adaptations on the wings, not known in any other insect. The wings are covered with wax nanocrystals that reflect ultraviolet light and infrared radiation. Furthermore, the wing membrane is permeated by an intricate system of tracheae, another unique trait in Insecta. We hypothesized that these adaptations might be important not only for intraspecific communication, but also for thermoregulation. We analysed male body and wing temperatures and compared them with another dragonfly with common translucent wings. The results suggest that the dorsal wing surface acts as a cooling system, whereas the ventral surface might serve to elevate body temperature. Therefore, we conclude that Z. lanei possesses adaptations that are unique in nature; a complex system of thermoregulation with the dual function of cooling down or elevating body temperature, depending on wing position.
Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study
Authors: Aglago Elom K , Schalkwijk Casper G , Freisling Heinz , Fedirko Veronika , Hughes David J , Jiao Li , Dahm Christina C , Olsen Anja , Tjønneland Anne , Katzke Verena , Johnson Theron , Schulze Matthias B , Aleksandrova Krasimira , Masala Giovanna , Sieri Sabina , Simeon Vittorio , Tumino Rosario , Macciotta Alessandra , Bueno-de-Mesquita Bas , Skeie Guri , Gram Inger Torhild , Sandanger Torkjel , Jakszyn Paula , Sánchez Maria-Jose , Amiano Pilar , Colorado-Yohar Sandra M , Gurrea Aurelio Barricarte , Perez-Cornago Aurora , Mayén Ana-Lucia , Weiderpass Elisabete , Gunter Marc J , Heath Alicia K , Jenab Mazda
Published: March 2021

Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by the non-enzymatic reaction between amino acids and reducing sugars, or dicarbonyls as intermediate compounds. Experimental studies suggest that AGEs may promote colorectal cancer, but prospective epidemiologic studies are inconclusive. We conducted a case–control study nested within a large European cohort. Plasma concentrations of three protein-bound AGEs—Nε-(carboxy-methyl)lysine (CML), Nε-(carboxy-ethyl)lysine (CEL) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)—were measured by ultra-performance liquid chromatography–tandem mass spectrometry in baseline samples collected from 1378 incident primary colorectal cancer cases and 1378 matched controls. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression for colorectal cancer risk associated with CML, CEL, MG-H1, total AGEs, and [CEL+MG-H1: CML] and [CEL:MG-H1] ratios. Inverse colorectal cancer risk associations were observed for CML (OR comparing highest to lowest quintile, ORQ5 versus Q1 = 0.40, 95% CI: 0.27–0.59), MG-H1 (ORQ5 versus Q1 = 0.73, 95% CI: 0.53–1.00) and total AGEs (OR Q5 versus Q1 = 0.52, 95% CI: 0.37–0.73), whereas no association was observed for CEL. A higher [CEL+MG-H1: CML] ratio was associated with colorectal cancer risk (ORQ5 versus Q1 = 1.91, 95% CI: 1.31–2.79). The associations observed did not differ by sex, or by tumour anatomical sub-site. Although individual AGEs concentrations appear to be inversely associated with colorectal cancer risk, a higher ratio of methylglyoxal-derived AGEs versus those derived from glyoxal (calculated by [CEL+MG-H1: CML] ratio) showed a strong positive risk association. Further insight on the metabolism of AGEs and their dicarbonyls precursors, and their roles in colorectal cancer development is needed.
MSG07: An International Cohort Study Comparing Epidemiology and Outcomes of Patients With Cryptococcus neoformans or Cryptococcus gattii Infections
Authors: Baddley John W , Chen Sharon C-A , Huisingh Carrie , Benedict Kaitlin , DeBess Emilio E , Galanis Eleni , Jackson Brendan R , MacDougall Laura , Marsden-Haug Nicola , Oltean Hanna , Perfect John R , Phillips Peter , Sorrell Tania C , Pappas Peter G
Published: March 2021

Background

Cryptococcosis due to Cryptococcus neoformans and Cryptococcus gattii varies with geographic region, populations affected, disease manifestations, and severity of infection, which impact treatment.

Methods

We developed a retrospective cohort of patients diagnosed with culture-proven cryptococcosis during 1995–2013 from 5 centers in North America and Australia. We compared underlying diseases, clinical manifestations, treatment, and outcomes in patients with C. gattii or C. neoformans infection.

Results

A total of 709 patients (452 C. neoformans; 257 C. gattii) were identified. Mean age was 50.2 years; 61.4% were male; and 52.3% were white. Time to diagnosis was prolonged in C. gattii patients compared with C. neoformans (mean, 52.2 vs 36.0 days; P < .003), and there was a higher proportion of C. gattii patients without underlying disease (40.5% vs 10.2%; P < .0001). Overall, 59% had central nervous system (CNS) infection, with lung (42.5%) and blood (24.5%) being common sites. Pulmonary infection was more common in patients with C. gattii than in those with C. neoformans (60.7% vs 32.1%; P < .0001). CNS or blood infections were more common in C. neoformans–infected patients (P ≤ .0001 for both). Treatment of CNS disease with induction therapy of amphotericin B and flucytosine occurred in 76.4% of patients. Crude 12-month mortality was higher in patients with C. neoformans (28.4% vs 20.2%; odds ratio, 1.56 [95% confidence interval, 1.08–2.26]).

Conclusions

This study emphasizes differences in species-specific epidemiology and outcomes of patients with cryptococcosis, including underlying diseases, site of infection, and mortality. Species identification in patients with cryptococcosis is necessary to discern epidemiologic patterns, guide treatment regimens, and predict clinical progression and outcomes.
Perioperative platelet reduction after sutureless or stented valve implantation: results from the PERSIST-AVR controlled randomized trial
Authors: Lorusso Roberto , Jiritano Federica , Roselli Eric , Shrestha Malakh , Folliguet Thierry , Meuris Bart , Pollari Francesco , Fischlein Theodor ,   the PERSIST-AVR Investigators
Published: March 2021

OBJECTIVES

Platelet count reduction is a common but not fully understood phenomenon after aortic valve replacement (AVR) with bioprosthesis implantation. The aim of the present study was to investigate the occurrence and the clinical impact of platelet count reduction in patients receiving the Perceval bioprosthesis compared to those receiving standard sutured stented bioprosthetic aortic valve in a randomized, controlled AVR study.

METHODS

PERceval Sutureless Implant versus STandard Aortic Valve Replacement is a prospective, randomized, adaptive, open-label trial. Patients were randomized (March 2016–September 2018) to AVR with a sutureless or stented valve. Ad hoc analyses have been performed to evaluate the occurrence of platelet count reduction and the clinical impact of the platelet variations in the 2 groups.

RESULTS

The Perceval group showed a higher platelet reduction than the control group (46% vs 32%). The phenomenon was transient in both groups, with a slow recovery of the platelet count by hospital discharge. No differences were observed between groups regarding need of transfusions, blood loss, major bleeding and stroke events.

CONCLUSIONS

The Perceval sutureless aortic bioprosthesis implantation is associated with higher rate of transient platelet reduction as compared to stented bioprostheses for AVR. However, the platelet count reduction is transient and the decline does not affect the patient’s clinical outcomes. Current explanations for this phenomenon are speculative, and further investigations are required to elucidate it.

Clinical trial registration number

NCT02673697—ClinicalTrials.gov—4 February 2016.
The association between initial adhesion and cyanobacterial biofilm development
Authors: Faria Sara I , Teixeira-Santos Rita , Morais João , Vasconcelos Vitor , Mergulhão Filipe J
Published: March 2021

Although laboratory assays provide valuable information about the antifouling effectiveness of marine surfaces and the dynamics of biofilm formation, they may be laborious and time-consuming. This study aimed to determine the potential of short-time adhesion assays to estimate how biofilm development may proceed. The initial adhesion and cyanobacterial biofilm formation were evaluated using glass and polymer epoxy resin surfaces under different hydrodynamic conditions and were compared using linear regression models. For initial adhesion, the polymer epoxy resin surface was significantly associated with a lower number of adhered cells compared with glass (-1.27 × 105 cells.cm–2). Likewise, the number of adhered cells was significantly lower (-1.16 × 105 cells.cm–2) at 185 than at 40 rpm. This tendency was maintained during biofilm development and was supported by the biofilm wet weight, thickness, chlorophyll a content and structure. Results indicated a significant correlation between the number of adhered and biofilm cells (r = 0.800, p < 0.001). Moreover, the number of biofilm cells on day 42 was dependent on the number of adhered cells at the end of the initial adhesion and hydrodynamic conditions (R2 = 0.795, p < 0.001). These findings demonstrate the high potential of initial adhesion assays to estimate marine biofilm development.
Postharvest Bee Diversity is High but Declines Rapidly with Stand Age in Regenerating Douglas-Fir Forest
Authors: Rivers James W , Betts Matthew G
Published: March 2021

Concerns about long-term pollinator declines have made assessing bee communities a priority in nonagricultural ecosystems, including managed forests. We assessed wild bee communities in Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco) stands one to 15 years after clearcut harvest in western Oregon, USA, testing the hypothesis that bee diversity would be high initially and then decline with time-dependent reductions in floral resources. We captured 2,009 individual bees that represented 67 distinct species/morphospecies in 20 genera and five families. Asymptotic estimators of bee diversity representing Shannon and Simpson diversity were greater in communities during the second half of the early seral period, indicating older early seral stands were less diverse and contained more common and dominant bee species. In addition, observed species richness and bee abundance peaked at approximately three years postharvest and declined thereafter by 20% and 30% per year, respectively. Because floral resources declined in concert with reductions in bee diversity as stands aged, food appears to be a key driver of forest bee communities. Our results indicate that postharvest Douglas-fir stands supported a diversity of bees, including important crop pollinators, but their value to bees was restricted to a relatively short window at the beginning of the early seral period.
Older Adults’ Loneliness in Early COVID-19 Social Distancing: Implications of Rurality
Authors: Fuller Heather R , Huseth-Zosel Andrea
Published: March 2021

Objectives

Older adults face greater health risks due to coronavirus disease 2019 (COVID-19), yet preventative social distancing measures may cause increased social isolation, potentially heightening risk of loneliness. In this mixed-methods study we examine changes in older adults’ loneliness due to social distancing, explore variability in perceptions, and identify whether such changes differ by rurality.

Methods

A Midwestern sample of 76 older adults aged 70–97 (mean age = 82; 74% female; 95% White; 39% rural) completed a phone interview about their experiences with social distancing due to COVID-19. Interviews were conducted during early weeks of regional social distancing. Participants completed retrospective and current assessments of loneliness, including providing explanations of their responses.

Results

On average, loneliness increased during early social distancing, yet variability was evident. Those experiencing increased loneliness described a feeling of loss or lack of control, whereas those experiencing stability in loneliness identified adaptability in social connection modes or feeling accustomed to social isolation. Rural older adults experienced a significantly smaller increase in loneliness than their nonrural counterparts.

Discussion

These findings suggest nuanced experiences among older adults, but generally negative implications for loneliness. Interventions to address older adults’ social isolation and loneliness during COVID-19 are warranted.
Education-related inequalities in cause-specific mortality: first estimates for Australia using individual-level linked census and mortality data
Authors: Welsh Jennifer , Joshy Grace , Moran Lauren , Soga Kay , Law Hsei-Di , Butler Danielle , Bishop Karen , Gourley Michelle , Eynstone-Hinkins James , Booth Heather , Moon Lynelle , Biddle Nicholas , Blakely Antony , Banks Emily , Korda Rosemary J
Published: March 2021

Background

Socioeconomic inequalities in mortality are evident in all high-income countries, and ongoing monitoring is recommended using linked census-mortality data. Using such data, we provide the first estimates of education-related inequalities in cause-specific mortality in Australia, suitable for international comparisons.

Methods

We used Australian Census (2016) linked to 13 months of Death Registrations (2016–17). We estimated relative rates (RR) and rate differences (RD, per 100 000 person-years), comparing rates in low (no qualifications) and intermediate (secondary school) with high (tertiary) education for individual causes of death (among those aged 25–84 years) and grouped according to preventability (25–74 years), separately by sex and age group, adjusting for age, using negative binomial regression.

Results

Among 13.9 M people contributing 14 452 732 person-years, 84 743 deaths occurred. All-cause mortality rates among men and women aged 25–84 years with low education were 2.76 [95% confidence interval (CI): 2.61–2.91] and 2.13 (2.01–2.26) times the rates of those with high education, respectively. We observed inequalities in most causes of death in each age-sex group. Among men aged 25–44 years, relative and absolute inequalities were largest for injuries, e.g. transport accidents [RR = 10.1 (5.4–18.7), RD = 21.2 (14.5–27.9)]). Among those aged 45–64 years, inequalities were greatest for chronic diseases, e.g. lung cancer [men RR = 6.6 (4.9–8.9), RD = 57.7 (49.7–65.8)] and ischaemic heart disease [women RR = 5.8 (3.7–9.1), RD = 20.2 (15.8–24.6)], with similar patterns for people aged 65–84 years. When grouped according to preventability, inequalities were large for causes amenable to behaviour change and medical intervention for all ages and causes amenable to injury prevention among young men.

Conclusions

Australian education-related inequalities in mortality are substantial, generally higher than international estimates, and related to preventability. Findings highlight opportunities to reduce them and the potential to improve the health of the population.
Evaluation of the Mawid mobile healthcare application in delivering services during the COVID-19 pandemic in Saudi Arabia
Authors: Alanzi Turki M , Althumairi Arwa , Aljaffary Afnan , Alfayez Asma , Alsalman Demah , Alanezi Fahad , Alhodaib Hala , AlShammari Maha M , AL-Dossary Reem , Al-Rayes Saja , Hariri Beyan , AlThani Bashair
Published: March 2021

Purpose

The purpose of this study is to evaluate MAWID mobile application developed by the Ministry of Health, Saudi Arabia, which is used for primary care hospitals appointments management and for tracking and tracing COVID-19.

Participants and Methods

An online questionnaire-based survey was used for collecting data related to three major factors including Ease of Use, Satisfaction, and Benefits of MAWID application among its users. Out of total 2542 participants, 345 participants completed only a part of the survey, and 204 participants did not use the application. After removing, 549 invalid responses, a final sample of 1993 was included for the data analysis.

Results

82.1% of the participants referred MAWID as easy to use application, 79.8% were highly satisfied with the application, and majority of the participants reflected potential benefits of using the application. T-test results have revealed that significant differences existed between males and females, and young and older participants in relation to the Ease of Use and Satisfaction levels associated with MAWID application.

Conclusion

Mobile applications can be very effective in delivering the healthcare services during pandemics. However, there is a need for regular evaluation and assessment to trach the change in users′ needs and update the app according to the changing requirements.
Barriers to using clinical decision support in ambulatory care: Do clinics in health systems fare better?
Authors: Shi Yunfeng , Amill-Rosario Alejandro , Rudin Robert S , Fischer Shira H , Shekelle Paul , Scanlon Dennis P , Damberg Cheryl L
Published: March 2021

Objective

We quantify the use of clinical decision support (CDS) and the specific barriers reported by ambulatory clinics and examine whether CDS utilization and barriers differed based on clinics’ affiliation with health systems, providing a benchmark for future empirical research and policies related to this topic.

Materials and Methods

Despite much discussion at the theoretic level, the existing literature provides little empirical understanding of barriers to using CDS in ambulatory care. We analyze data from 821 clinics in 117 medical groups, based on in Minnesota Community Measurement’s annual Health Information Technology Survey (2014-2016). We examine clinics’ use of 7 CDS tools, along with 7 barriers in 3 areas (resource, user acceptance, and technology). Employing linear probability models, we examine factors associated with CDS barriers.

Results

Clinics in health systems used more CDS tools than did clinics not in systems (24 percentage points higher in automated reminders), but they also reported more barriers related to resources and user acceptance (26 percentage points higher in barriers to implementation and 33 points higher in disruptive alarms). Barriers related to workflow redesign increased in clinics affiliated with health systems (33 points higher). Rural clinics were more likely to report barriers to training.

Conclusions

CDS barriers related to resources and user acceptance remained substantial. Health systems, while being effective in promoting CDS tools, may need to provide further assistance to their affiliated ambulatory clinics to overcome barriers, especially the requirement to redesign workflow. Rural clinics may need more resources for training.
Dietary taurine attenuates hydrogen peroxide-impaired growth performance and meat quality of broilers via modulating redox status and cell death signaling
Authors: Xing Tong , Chen Xiangxing , Li Jiaolong , Zhang Lin , Gao Feng
Published: March 2021

Oxidative stress seriously affects poultry production. Nutritional manipulations have been effectively used to alleviate the negative effects caused by oxidative stress. This study investigated the attenuating effects and potential mechanisms of dietary taurine on the growth performance and meat quality of broiler chickens challenged with hydrogen peroxide (H2O2). Briefly, a total of 192 male Arbor Acres broilers (28 d old) were randomly categorized into three groups: non-injection of birds on basal diets (control), 10.0% H2O2 injection of birds on basal diets (H2O2), and 10.0% H2O2 injection of birds on basal diets supplemented with 5 g/kg taurine (H2O2 + taurine). Each group consisted of eight cages of eight birds per cage. Results indicated that H2O2 administration significantly reduced growth performance and impaired breast meat quality by decreasing ultimate pH and increasing shear force value (P < 0.05). Dietary taurine improved the body weight gain and feed intake and decreased feed/gain ratio of H2O2-challenged broilers. Meanwhile, oxidative stress induced by intraperitoneal injection of H2O2 suppressed the nuclear factor-κB (NF-κB) signaling and initiated autophagy and apoptosis. Compared with the H2O2 group, taurine supplementation restored the redox status in the breast muscle by decreasing levels of reactive oxygen species and contents of oxidative products and increasing antioxidant capacity (P < 0.05). Moreover, upregulated mRNA expression of NF-κB signaling-related genes, including NF-κB subunit 1 (p50) and B-cell CLL/lymphoma 2 (Bcl-2), and enhanced protein expression of NF-κB were observed in the H2O2 + taurine group (P < 0.05). Additionally, dietary taurine decreased the expression of caspase family, beclin1, and microtubule-associated protein 1light chain 3 beta (LC3-II; P < 0.05), thereby rescuing autophagy and apoptosis in breast muscle induced by H2O2. Collectively, dietary supplementation with taurine effectively improves growth performance and breast meat quality of broilers challenged with H2O2, possibly by protecting against oxidative injury and modulating cell death signaling.
Alteration of Termite Locomotion and Allogrooming in Response to Infection by Pathogenic Fungi
Authors: Hassan Ali , Huang Qiuying , Mehmood Nasir , Xu Huan , Zhou Wei , Gao Yongyong
Published: March 2021

Termites, being vulnerable to parasitic or pathogenic infections due to large number of individuals living together in colonies, have evolved various behavioral and physiological tactics to resist the infections by those pathogens. Locomotion can help termites collect information on parasites and accordingly exhibit hygienic behaviors. Termites inevitably encounter entomopathogenic fungi during nesting and foraging. However, how these fungal pathogens influence locomotion of termites and how hygienic behavior benefits their survival remains unknown. Here, we examined locomotion alteration of the termite Reticulitermes chinensis (Isoptera: Rhinotermitidae) after infections with different concentrations of the entomopathogenic fungus Metarhizium anisopliae (Hypocreales: Clavicipitaceae). When R. chinensis was isolated, the low concentration (5 × 103 conidia/ml) significantly increased termite locomotion after 6, 12, and 24 h compared with control. However, the high concentrations (5 × 107, 5 × 109 conidia/ml) significantly decreased termite locomotion after 48 h, and termite survival was also significantly lower at 5 × 107 and 5 × 109 conidia/ml compared with the low concentrations and the control. When R. chinensis was in group, however, the locomotion significantly increased 24 h after exposure to 5 × 103 and 5 × 109 conidia/ml but was normalized after 48 h of exposure compared with the control. Allogrooming was significantly higher at 5 × 103 and 5 × 109 conidia/ml compared with the control. The fungal infection did not result in significantly higher mortality of the group termites probably owing to their allogrooming. These findings enhance our understanding on how a termite species copes with biotic stress (i.e., fungal infections) via adaptive behaviors.
The Past, Present, and Future of Special Economic Zones and Their Impact
Authors: Zeng Douglas Z
Published: March 2021

Special economic zones (SEZs) have been used by many developing countries as a policy tool to promote industrialization and economic transformation. Since the initiation of the first modern zone in Shannon, Ireland, special economic zones have evolved in many ways, from an initial ‘enclave’ nature towards today’s ‘Economic Zone 5.0’, which is built on emerging digital technologies and well integrated with urban development. The special economic zones represents a new unilateral compromise between the state and market, while still contributing to economic globalization, by presenting itself as a complementary or as an alternative approach to integrate with the global market in addition to the international economic law instruments. Despite the prevalence of special economic zones worldwide, their performance and impact on the economy and structural transformation are quite mixed. Among the many lessons learned from successful special economic zone programmes, the key elements include a strategic location, integration of zone strategy with the overall development strategy, understanding the market and leveraging comparative advantage, and, most importantly, ensuring that zones are ‘special’ in terms of a business-friendly environment—especially a sound legal and regulatory framework and an embodiment of sustainability and resiliency towards various external shocks like today’s COVID-19 pandemic.
Sudden Mortality in Captive White-Tailed Deer With Atypical Infestation of Winter Tick
Authors: Machtinger Erika T , Springer Hayley R , Brown Jessica E , Olafson Pia U
Published: March 2021

In October 2020, three captive male white-tailed deer, Odocoileus virginianus [Zimmermann] (artiodactyla: Cervidae), were found dead in central Pennsylvania and a fourth was euthanized due to extreme lethargy. The deer presented with high burdens of Dermacentor albipictus (Packard) (Ixoda: Ixodidae) (winter tick). There were no other clinical symptoms and deer were in otherwise good physical condition with no observed alopecia. Winter tick epizootics have been associated with mortalities of moose, Alces alces [Linnaeus] (artiodactyla: cervidae), and more recently elk, Cervus canadensis [Erxleben] (artiodactyla: cervidae), in Pennsylvania, but have not been reported in white-tailed deer. Mild winters are favorable to winter ticks and deer producers and managers should be aware of possible infestations as a result.
Persistence of the Swiss Needle Cast Outbreak in Oregon Coastal Douglas-Fir and New Insights from Research and Monitoring
Authors: Shaw David C , Ritóková Gabriela , Lan Yung-Hsiang , Mainwaring Doug B , Russo Andrew , Comeleo Randy , Navarro Sarah , Norlander Daniel , Smith Ben
Published: March 2021

Swiss needle cast (SNC), caused by Nothophaeocryptopus gaeumannii, is a foliage disease of Douglas-fir (Pseudotsuga menziesii), that reduces growth in native stands and exotic plantations worldwide. An outbreak of SNC began in coastal Oregon in the mid-1990s and has persisted since that time. Here we review the current state of knowledge after 24 years of research and monitoring, with a focus on Oregon, although the disease is significant in coastal Washington and has recently emerged in southwestern British Columbia. We present new insights into SNC distribution, landscape patterns, disease epidemiology and ecology, host-pathogen interactions, trophic and hydrologic influences, and the challenges of Douglas-fir plantation management in the presence of the disease. In Oregon, the SNC outbreak has remained geographically contained but has intensified. Finally, we consider the implications of climate change and other recently emerged foliage diseases on the future of Douglas-fir plantation management.
Lyman-alpha radiation pressure: an analytical exploration
Authors: Tomaselli G M , Ferrara A
Published: March 2021

We study radiation pressure due to Ly α line photons, obtaining and exploring analytical expressions for the force-multiplier, MF(NH, Z) = Fα/(Lα/c), as a function of gas column density, NH, and metallicity, Z, for both dust-free and dusty media, employing a WKB approach for the latter case. Solutions for frequency offset emission to emulate non-static media moving with a bulk velocity v have also been obtained. We find that, in static media, Ly α pressure dominates over both photoionization and dust-mediated UV radiation pressure in a very wide parameter range (16 < log NH < 23; −4 < log [Z/Z⊙] < 0). For example, it overwhelms the other two forces by $\lower.5ex\hbox{$\,\, \buildrel\gt \over \sim \,\,$}10$ (300) times in standard (low-Z) star-forming clouds. Thus, in agreement with previous studies, we conclude that Ly α pressure plays a dominant role in the initial acceleration of the gas around luminous sources, and must be implemented in galaxy formation, evolution and outflow models and simulations.
BIMG-07. PHARMACOLOGICAL ASCORBATE ENHANCES RADIATION AND TEMOZOLOMIDE EFFECTIVENESS IN GLIOBLASTOMA BY A MECHANISM MEDIATED BY REDOX ACTIVE IRON
Authors: Allen Bryan , Petronek Michael , Monga Varun , Bodeker Kellie , Smith Brian , Buettner Garry , Greenlee Jeremy , Smith Mark , Spitz Douglas , Cullen Joseph , Magnotta Vincent , Buatti John
Published: March 2021

Pharmacological ascorbate (P-AscH-; high dose intravenous infusions of vitamin C generating milli-molar plasma concentrations) has re-emerged as an anti-cancer therapy. Phase 1 clinical trials combining P-AscH- with chemotherapy and ionizing radiation demonstrate safety and promising clinical outcomes in a variety of malignancies. In a first-in-human trial, subjects with newly diagnosed glioblastoma (GBM) and undetectable MGMT promoter methylation were treated with P-AscH-, ionizing radiation, and temozolomide. Results demonstrate median progression-free survival (PFS) of 10 months and median overall survival (OS) of 23 months, comparing favorably to historical GBM patients expressing MGMT. P-AscH-‘s anti-cancer mechanism is dependent upon the presence of redox active labile iron. In the presence of redox active iron, the formation of hydrogen peroxide, which causes oxidative stress and eventual cell death, selectively forms in cancer cells. Treatment with P-AscH- increased cancer cells’ labile iron pool, further enhancing sensitivity to P-AscH-. We investigated the capability of MR imaging (T2* relaxation time) to measure the redox active iron and predict response to P-AscH-. T2* relaxation time is influenced by in-field inhomogeneities, such as redox active paramagnetic iron. The active phase 2 trial evaluating P-AscH-, radiation, and temozolomide for GBM, obtains T2* imaging prior to (baseline) and immediately after ascorbate infusion (NCT02344355). A preliminary analysis of the baseline scan for the first 15 subjects suggests those with faster GBM T2* relaxation times (≤ 58 ms) have more redox active labile iron pools as well as an improved median PFS (11.4 months) compared to those with slower T2* relaxation times (> 58 ms; median PFS of 8.5 months). Pre-clinical studies evaluating the effectiveness of iron nano-particle supplementation in GBM animal models are on-going. (Supported by P01 CA217797, R01 CA169046, U01 CA140206, T32 CA078586, P30 CA086862, as well as the Gateway for Cancer Research grant G-17–1500.)
BIMG-13. A NOVEL RADIOPHARMACEUTICAL ([18F]DASA-23) TO MONITOR PYRUVATE KINASE M2 INDUCED GLYCOLYTIC REPROGRAMMING IN GLIOBLASTOMA
Authors: Beinat Corinne , Patel Chirag , Haywood Tom , Murty Surya , Naya Lewis , Hayden-Gephart Melanie , Khalighi Mehdi , Massoud Tarik , Iagaru Andrei , Davidzon Guido , Thomas Reena , Nagpal Seema , Recht Lawrence , Gambhir Sanjiv
Published: March 2021

BACKGROUND

Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain, making it an important biomarker of cancer glycolytic re-programming. We describe the bench-to-bedside development, validation, and translation of a novel positron emission tomography (PET) tracer to study PKM2 in GBM. Specifically, we evaluated 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and GBM patients.

METHODS

[18F]DASA-23 was synthesized with a molar activity of 100.47 ± 29.58 GBq/µmol and radiochemical purity >95%. We performed initial testing of [18F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next we produced [18F]DASA-23 under current Good Manufacturing Practices United States Food and Drug Administration (FDA) oversight, and evaluated it in healthy volunteers and a pilot cohort of patients with gliomas.

RESULTS

In mouse imaging studies, [18F]DASA-23 clearly delineated the U87 GBM from the surrounding healthy brain tissue and had a tumor-to-brain ratio (TBR) of 3.6 ± 0.5. In human volunteers, [18F]DASA-23 crossed the intact blood-brain barrier and was rapidly cleared. In GBM patients, [18F]DASA-23 successfully outlined tumors visible on contrast-enhanced magnetic resonance imaging (MRI). The uptake of [18F]DASA-23 was markedly elevated in GBMs compared to normal brain, and it was able to identify a metabolic non-responder within 1-week of treatment initiation.

CONCLUSION

We developed and translated [18F]DASA-23 as a promising new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These encouraging results warrant further clinical evaluation of [18F]DASA-23 to assess its utility for imaging therapy-induced normalization of aberrant cancer metabolism.
BIMG-20. METABOLIC BIOMARKERS IN MICRODIALYSATE OF IDH-1 MUTANT TUMORS
Authors: Rajani Karishma , Carlstrom Lucas , Jacobs Joshua , Schroeder Mark , Olson Ian , Hainy Matthew , Oh Juhee , Elmquist William , Sarkaria Jann , Burns Terry
Published: March 2021

Glioblastoma (GBM) is a common deadly malignant brain cancer of the central nervous system, with a median survival of 12–15 months. Scientific advancements are lacking in developing effective therapies for both primary GBM, as well as secondary GBMs, that typically originate as malignant transformation of lower-grade isocitrate dehydrogenase (IDH) 1-mutant tumors. The unique metabolomic profile of IDH1-mutant tumors presents opportunities to develop biomarker signatures of therapeutic efficacy. Microdialysis is an extracellular fluid sampling collection technique utilizing a perfused semipermeable catheter to permit diffusion of molecules between brain interstitium and the perfusate. We hypothesized that microdialysis may identify a metabolomics-based biomarker response to therapy in IDH1-mutant tumors. To test this hypothesis, orthotopic xenografts were generated from patient-derived xenografts (PDX) harboring mutant IDH-1 (R132H). Perfusates were collected from intra-cranial tumors in athymic nude mice sampled at baseline and 72h post treatment with temozolomide (TMZ), an oral alkylating agent used to treat IDH1-mutant gliomas, compared with vehicle treatment. Perfusates were analyzed via untargeted metabolomic profiling using liquid chromatography-mass spectrometry. Tumor specific metabolites such as (D)-2 hydroxyglutarate, were detected in microdialysate from IDH-1 mutant tumor bearing mice compared to non-tumor bearing mice. We also found high levels of metabolites such as 5-methylthioadenosine, and dimethylarginine and wide range of amino acids in microdialysate from IDH-1 mutant tumor bearing mice. TMZ treatment induced changes to metabolites in creatine and histidine metabolism. Our results indicate that microdialysis is a feasible technology to identify metabolomics-based biomarkers in IDH1-mutant gliomas and their response to therapy. We suggest that in vivo intratumoral microdialysis over several days could yield metabolic pharmacodynamic biomarkers of value to therapeutic translation for IDH-mutant gliomas.