bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-way relation-enhanced hypergraph representation learning for anti-cancer drug synergy prediction
Authors: Liu Xuan , Song Congzhi , Liu Shichao , Li Menglu , Zhou Xionghui , Zhang Wen
Published: August 2022

Motivation

Drug combinations have exhibited promise in treating cancers with less toxicity and fewer adverse reactions. However, in vitro screening of synergistic drug combinations is time-consuming and labor-intensive because of the combinatorial explosion. Although a number of computational methods have been developed for predicting synergistic drug combinations, the multi-way relations between drug combinations and cell lines existing in drug synergy data have not been well exploited.

Results

We propose a multi-way relation-enhanced hypergraph representation learning method to predict anti-cancer drug synergy, named HypergraphSynergy. HypergraphSynergy formulates synergistic drug combinations over cancer cell lines as a hypergraph, in which drugs and cell lines are represented by nodes and synergistic drug–drug–cell line triplets are represented by hyperedges, and leverages the biochemical features of drugs and cell lines as node attributes. Then, a hypergraph neural network is designed to learn the embeddings of drugs and cell lines from the hypergraph and predict drug synergy. Moreover, the auxiliary task of reconstructing the similarity networks of drugs and cell lines is considered to enhance the generalization ability of the model. In the computational experiments, HypergraphSynergy outperforms other state-of-the-art synergy prediction methods on two benchmark datasets for both classification and regression tasks and is applicable to unseen drug combinations or cell lines. The studies revealed that the hypergraph formulation allows us to capture and explain complex multi-way relations of drug combinations and cell lines, and also provides a flexible framework to make the best use of diverse information.

Availability and implementation

The source data and codes of HypergraphSynergy can be freely downloaded from https://github.com/liuxuan666/HypergraphSynergy.

Supplementary information

Supplementary data are available at Bioinformatics online.
Vitamin K1 and progression of cardiovascular calcifications in hemodialysis patients: The VitaVasK randomized controlled trial
Authors: Saritas Turgay , Reinartz Sebastian , Krüger Thilo , Ketteler Markus , Liangos Orfeas , Labriola Laura , Stenvinkel Peter , Kopp Christoph , Westenfeld Ralf , Evenepoel Pieter , Siepmann Robert , Wied Stephanie , Hilgers Ralf-Dieter , Schurgers Leon , Floege Jürgen ,   for the VitaVasK Investigators
Published: August 2022

Background

Cardiovascular calcifications are prevented by matrix Gla protein (MGP), a vitamin K-dependent protein. Hemodialysis patients exhibit marked vitamin K deficiency. The randomized, prospective, open-label, multicenter VitaVasK trial analyzed whether vitamin K1 supplementation reduces progression of coronary artery calcifications (CAC) and thoracic aortic calcifications (TAC).

Methods

Patients with preexisting CAC were randomized to continue on standard care or to additionally receive 5 mg vitamin K1 orally thrice weekly. Hierarchically ordered primary end points were progression of TAC and CAC in computed tomography scans at 18 months. Linear mixed effects models with repeated measures at baseline, 12 and 18 months assessed treatment effects after adjusting for study site.

Results

Of 60 randomized patients, 20 dropped out for reasons unrelated to vitamin K1, resulting in 23 control and 17 vitamin K1 patients. The trial was stopped early due to slow recruitment. At 18 months, the average TAC progression was 56% lower in the vitamin K1 compared to the control group (p = 0.039). CAC significantly progressed within the control group, but not within the vitamin K1 group. Average progression at 18 months was 68% lower in the vitamin K1 compared to the control group (p = 0.072). Vitamin K1 reduced plasma levels of pro-calcific uncarboxylated-MGP by 69% at 18 months. No treatment-related adverse events were noted.

Conclusion

Vitamin K1 intervention is a potent, safe and cost-effective approach to correct vitamin K deficiency and to potentially reduce cardiovascular calcification in this high-risk population.
SGLT-2 inhibitors in nephrotic-range proteinuria: emerging clinical evidence
Authors: Kalay Zeynepgul , Sahin Ozgun E , Copur Sidar , Danacı Senem , Ortiz Alberto , Yau Kevin , Cherney David Z I , Kanbay Mehmet
Published: August 2022

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a class of novel oral anti-hyperglycemic agents which are increasingly used in clinical practice. SGLT-2 inhibitors improve glycemic control and cardiorenal outcomes, promote weight loss, and reduce blood pressure. Randomized controlled trials have demonstrated that SGLT-2 inhibitors reduce proteinuria and delay progression of kidney disease in patients with albuminuria. However, whether SGLT-2 inhibitors have similar benefits in patients with nephrotic-range proteinuria has not been well established. Evidence to date has been limited to case reports, case series and secondary analyses of randomized controlled trials. This is the first comprehensive review on the effectiveness of SGLT-2 inhibitors for the treatment of patients with nephrotic-range albuminuria or proteinuria. Overall findings support a likely beneficial role of SGLT-2 inhibitors in reducing proteinuria and delaying chronic kidney disease progression in patients with nephrotic-range proteinuria.
Intravascular molecular imaging: translating pathophysiology of atherosclerosis into human disease conditions
Authors: Seguchi Masaru , Aytekin Alp , Lenz Tobias , Nicol Philipp , Klosterman Grace R , Beele Alicia , Sabic Emina , Utsch Léa , Alyaqoob Aseel , Gorpas Dimitris , Ntziachristos Vasilis , Jaffer Farouc A , Rauschendorfer Philipp , Joner Michael
Published: August 2022

Progression of atherosclerotic plaque in coronary arteries is characterized by complex cellular and non-cellular molecular interactions. Within recent years, atherosclerosis has been recognized as inflammation-driven disease condition, where progressive stages are characterized by morphological changes in plaque composition but also relevant molecular processes resulting in increased plaque vulnerability. While existing intravascular imaging modalities are able to resolve key morphological features during plaque progression, they lack capability to characterize the molecular profile of advanced atherosclerotic plaque. Because hybrid imaging modalities may provide incremental information related to plaque biology, they are expected to provide synergistic effects in detecting high risk patients and lesions. The aim of this article is to review existing literature on intravascular molecular imaging approaches, and to provide clinically oriented proposals of their application. In addition, we assembled an overview of future developments in this field geared towards detection of patients at risk for cardiovascular events.
‘This was the better way’: The Restoration Afterlives of Ben Jonson’s Comic Designs
Authors: Cameron John H , Goossen Jonathan
Published: August 2022

The dramatists of the Restoration stage reveal the guiding influence of Ben Jonson, giving his plays a strong comedic afterlife, particularly with respect to his construction of his plots and his sense of comedic design. This article explores that influence by first considering the influences on Jonson’s own concept of comic design, particularly as derived from Aristotle, and the late-antique grammarians Euanthius and Donatus. Jonson follows Aristotle’s distinction of comedy from tragedy on the basis of the ‘laughable’ moral quality of its characters. When paired with Jonson’s own didactic bent, this distinction shaped his ‘humours’-based approach to character, and his plots’ exposure and mockery of those characters. Daniël Heinsius’s commentaries on Aristotle’s Poetics show clear consonance with Jonson’s tight integration of his humorous characters into densely unified plots by way of the trickster characters’ hoaxes. Jonson also finds in Scaliger’s unique concept of catastasis, the penultimate movement of comic plot, a definitive tactic for achieving that integration and exposure. In the light of these claims, we look at three of Jonson’s plays, Every Man Out of His Humour (1599), Volpone (1605) and Epicene, or the Silent Woman (1609), which depict his developing techniques of character, exposure hoaxes and catastasis. This leads to the later seventeenth century and John Dryden’s attentive analysis of Jonson’s comic plots, especially that of Epicene. We then show how the Jonsonian traits singled out by Dryden were used and adapted by William Wycherley in The Country Wife (1675) and William Congreve in The Way of the World (1700).
Productivity of ClonalIlex paraguariensisGenotypes in a Semi-Hydroponic System Is Reduced by Shading
Authors: de Aguiar Natália Saudade , Moreno Gabira Mônica , de Cássia Tomasi Jéssica , Mendes Duarte Manoela , Marcolino Vieira Leandro , José Lavoranti Osmir , Wendling Ivar
Published: August 2022

Yerba mate (Ilex paraguariensis A. St.-Hil.) is a South American tree cultivated in systems with or without shading at different intensities; however, there is no consensus about shading effect on leaf biomass production. Therefore, we evaluated yerba mate clones under different shading levels over one year to determine the influence of shading and genotype on biomass production. Two yerba mate genotypes (EC22 and EC40), cultivated in a semi-hydroponic system, were subjected to five shading levels (0%, 40%, 51%, 76%, and 82%) in a greenhouse. We determined total fresh biomass (branches and leaves) and fresh biomass of young and mature leaves on six harvests. Biomass production was influenced by harvest season, genotype, and shading levels. Spring and summer harvests provided higher biomass production than the other seasons. EC40 genotype produced higher total fresh and young leaf biomass than EC22. Although we observed differences among genotypes and harvest seasons, shading was the factor that most influenced biomass production. Total fresh biomass productivity was reduced 6.8 times between 0% and 82% shading for the EC40 genotype. Thus, we do not recommend high levels of shade, such as 76% and 82%, in this new yerba mate cultivation system.
Ecoregional Variation of Crimean Pine (Pinus nigrasubspeciespallasiana[Lamb.] Holmboe) Stand Growth
Authors: Seki Mehmet , Sakici Oytun Emre
Published: August 2022

Investigation and numerical determination of the effects of ecologically different regions on forest growth are important issues to be considered for sustainable forest management. In this study, differences in growth patterns of Crimean pine (Pinus nigra subsp. pallasiana [Lamb.] Holmboe) stands among the ecoregions located in the Kastamonu region of northwestern Turkey were investigated. For this purpose, stand-level growth models for dominant height, number of trees, basal area, and volume were fitted using the data from 274 sample plots and 293 stem analysis in even-aged, pure, and productive Crimean pine stands. The nonlinear extra sum of squares method and graphical examinations revealed that growth characteristics of these Crimean pine stands were affected by ecoregional differences. Ecoregion-based growth models, which are more flexible and have the ability to reflect the ecoregional differences in growth patterns, were found to be superior to regional models. Applying general models without any ecoregional classification resulted in biases of 5.3%, 23.1%, 5.5%, and 6.2% in the estimates of dominant height, number of trees, basal area, and volume of Crimean pine stands, respectively. The results showed that ecological differences must be considered in studies on forest growth modeling and forest management.
The measurement and modification of hypoxia in colorectal cancer: overlooked but not forgotten
Authors: Fletcher Teddy , Thompson Alex J , Ashrafian Hutan , Darzi Ara
Published: August 2022

Tumour hypoxia is the inevitable consequence of a tumour’s rapid growth and disorganized, inefficient vasculature. The compensatory mechanisms employed by tumours, and indeed the absence of oxygen itself, hinder the ability of all treatment modalities. The clinical consequence is poorer overall survival, disease-free survival, and locoregional control. Recognizing this, clinicians have been attenuating the effect of hypoxia, primarily with hypoxic modification or with hypoxia-activated pro-drugs, and notable success has been demonstrated. However, in the case of colorectal cancer (CRC), there is a general paucity of knowledge and evidence surrounding the measurement and modification of hypoxia, and this is possibly due to the comparative inaccessibility of such tumours. We specifically review the role of hypoxia in CRC and focus on the current evidence for the existence of hypoxia in CRC, the majority of which originates from indirect positron emission topography imaging with hypoxia selective radiotracers; the evidence correlating CRC hypoxia with poorer oncological outcome, which is largely based on the measurement of hypoxia inducible factor in correlation with clinical outcome; the evidence of hypoxic modification in CRC, of which no direct evidence exists, but is reflected in a number of indirect markers; the prognostic and monitoring implications of accurate CRC hypoxia quantification and its potential in the field of precision oncology; and the present and future imaging tools and technologies being developed for the measurement of CRC hypoxia, including the use of blood-oxygen-level-dependent magnetic resonance imaging and diffuse reflectance spectroscopy.
Immigration Experience and Cognitive Function Trajectories Among Older Chinese Immigrants
Authors: Tang Fengyan , Li Ke , Rauktis Mary E , Buckley Tommy D , Chi Iris
Published: August 2022

Objectives

Although a number of studies have documented cognitive health among older immigrants in the United States, little is known about how the life-course immigration experiences are associated with cognitive trajectories among older Chinese immigrants. We assess patterns of cognitive functioning and change over time and examine whether age at migration, reasons for migration, acculturation, perceived discrimination, and preferred dialects are related to cognitive trajectories.

Methods

The sample comprised 2,075 participants from the Population Study of Chinese Elderly (PINE), who completed a battery of cognitive tests at four time points (2011–2019). Latent class growth analysis and multinomial logistic regression were utilized.

Results

Three latent classes of cognitive trajectories were identified: the low functioning with the fastest decline (LCF, 12%), the moderate functioning with a medium decline rate (MCF, 39%), and the high functioning with the slowest decline (HCF, 48%). Perceiving more discrimination reduced, whereas speaking Taishanese increased the odds of being in the LCF and MCF. High acculturation only distinguished MCF from HCF after controlling for the known factors of cognitive health such as age, education, and social engagement.

Discussion

This study identifies a group of older Chinese immigrants who are especially vulnerable to cognitive impairment and indicates that the risk of cognitive decline appears to be elevated with lower levels of acculturation and unidentified racial discrimination. More research is needed to fully understand the underlying mechanisms that link the life-course immigration experiences to cognitive health outcomes in later life.
Memory, community and the end of empire on the Isle of Dogs, 1980–2004
Authors: Gleeson Finn
Published: August 2022

How might we best understand the place of imperial memory in contemporary British history? Recent scholarship has tended to characterize this through one of two binary categories, pointing to either imperial ‘amnesia’ or imperial ‘nostalgia’. This article contends that sustained and detailed case studies can offer us a more sophisticated and nuanced understanding of the production of memory. It uses the example of the Island History Trust, established to help local residents of London’s Docklands protest and later adjust to the losses brought about by deindustrialization, outward migration and financialized redevelopment overseen by Margaret Thatcher’s Conservative government. Within this narrative of social and economic displacement, however, was hidden another story: residents’ lament for the empowerment and enrichment that they had in earlier life derived from their proximity to the imperial port. The Trust’s left-wing practitioners had a complex relationship with the foundational place of empire in local identity; while they perceived it as being connected to an ‘endemic’ racism among residents, they also knew it signified great pride and dignity for many. This article traces the Trust’s shifting representations of empire over time. They celebrated the imperial port when it signified residents’ enrichment, criticized it when addressing the far-right British National Party’s popularity and obscured its connection to racism when mourning the disappearing community for posterity. The article argues that case studies like this can help begin the vital work of moving past simplistic and binary analyses of imperial ‘amnesia’ or ‘nostalgia’, and towards a history of imperial memory that appreciates its fluidity, messiness and political contingency. This, it argues, is vital if we are to effectively understand the politics of imperial memory in the present.
About a Play: Stanley Middleton’s Pentrich Revolution
Authors: Steedman Carolyn
Published: August 2022

A school play about the Pentrich Revolution (1817) and Jeremiah Brandreth its ‘leader’, scripted in 1970–71 by teacher and novelist Stanley Middleton, reveals the history of teaching about Pentrich, to adults and children, over the previous century. Middleton’s use of the Nottinghamshire dialect to write history, in the play and his many novels, is a focus of the article.
The deep sea and me
Authors: Barnhill Kelsey Archer
Published: August 2022

In this perspective, I reflect on my path to the deep sea, a field, and ecosystem that are often hard to access. Growing up in a coastal town, the seashore was my playground, but it was not until I was 18 years old that I was inspired to be a deep-sea scientist. From a Bachelor of Arts in the United States to a Master of Science in Norway and currently a PhD programme in Scotland, I have let the deep sea lead my career path with the help of supportive mentors and peers. Now, as an early career scientist with over 100 d of at-sea experience working on science, mapping, and outreach teams, I highlight the key moments that allowed me to enter the field. Looking to Horizon 2050, I share my goals for the future of deep-sea science. I hope to see a new age of ocean exploration with an increased commitment to advancing technologies, a more diverse, inclusive, and international team offshore and onshore, and a more engaged public through placing a larger focus on the deep sea in educational curricula.
Affine Anosov Representations and Proper Actions
Authors: Ghosh Sourav , Treib Nicolaus
Published: August 2022

We define the notion of affine Anosov representations of word hyperbolic groups into the affine group $\textsf {SO}^0(n+1,n)\ltimes {\mathbb {R}}^{2n+1}$. We then show that a representation $\rho $ of a word hyperbolic group is affine Anosov if and only if its linear part $\mathtt {L}_\rho $ is Anosov in $\textsf {SO}^0(n+1,n)$ with respect to the stabilizer of a maximal isotropic plane and $\rho (\Gamma )$ acts properly on $\mathbb {R}^{2n+1}$.
Discrimination by Legal Design? UK Supreme Court in Mencap v Tomlinson-Blake Finds Care Workers are Not Protected by Minimum Wage Law for Sleep-in Shifts
Authors: Hayes Ljb
Published: August 2022

In Mencap v Tomlinson Blake the Supreme Court finds that the UK’s statutory national minimum wage scheme excludes care workers from protection during sleep-in shifts. UK employment rights thus move further from international labour standards, including ILO Convention 189. This commentary argues that Mencap points to discrimination by legal design. The Supreme Court gives expansive and uncritical regard to the wording and circumstances of a 1998 Low Pay Commission report that recommends residential care workers be excluded from protection as a ‘special treatment’. It shows that care workers’ entitlement to statutory protection is dependent on their contractual arrangements and does not consider inequality of bargaining power. The judgment erases caring labour of its cognitive and professional skills and puts care workers at a particular disadvantage. The care sector is notorious for the poor functioning of its labour market as well as for low pay. Care workers are mainly women and are disproportionately black and minority ethnic women. The discriminatory intent of Parliament, as explored by the Supreme Court in Mencap, reveals that the UK’s statutory minimum wage scheme is currently unable to provide workers with the dignity that would come from assigning a minimum value to the full range of care work.
Proceedings of the 2021 American Burn Association State and Future of Burn Science Meeting
Authors:   The 2021 American Burn Association State and Future of Burn Science Working Group, Shupp Jeffrey W , Holmes James H , Moffatt Lauren T , Phelan Herbert A , Sousse Linda , Romanowski Kathleen S , Jeschke Marc , Kowalske Karen J , Badger Karen , Allely Rebekah , Cartotto Robert , Burmeister David M , Kubasiak John C , Wolf Steven E , Wallace Katherine F , Gillenwater Justin , Schneider Daniel M , Hultman C Scott , Wiechman Shelley A , Bailey J Kevin , Powell Heather M , Travis Taryn E , Supp Dorothy M , Carney Bonnie C , Johnson Laura S , Johnson Laura S , Chung Kevin K , Chung Kevin K , Kahn Steven A , Gibson Angela L F , Christy Robert J , Carter Jeffrey E , Carson Joshua S , Palmieri Tina L , Kopari Nicole M , Blome-Eberwein Sigrid A , Hickerson William L , Parry Ingrid , Cancio Jill M , Suman Oscar , Schulman Carl I , Lamendella Regina , Hill David M , Wibbenmeyer Lucy A , Nygaard Rachel M , Wagner Anne Lambert , Carter and Damien W , Greenhalgh David G , Lawless Mary Beth , Carlson Deborah L , Harrington David T
Published: August 2022

Periodically, the American Burn Association (ABA) has convened a State of the Science meeting on various topics representing multiple disciplines within burn care and research. In 2021 at the request of the ABA President, meeting development was guided by the ABA’s Burn Science Advisory Panel (BSAP) and a subgroup of meeting chairs. The goal of the meeting was to produce both an evaluation of the current literature and ongoing studies, and to produce a research agenda and/or define subject matter-relevant next steps to advance the field(s). Members of the BSAP defined the topics to be addressed and subsequently solicited for nominations of expert speakers and topic leaders from the ABA’s Research Committee. Current background literature for each topic was compiled by the meeting chairs and the library then enhanced by the invited topic and breakout discussion leaders. The meeting was held in New Orleans, LA on November 2nd and 3rd and was formatted to allow for 12 different topics, each with two subtopics, to be addressed. Topic leaders provided a brief overview of each topic to approximately 100 attendees, followed by expert-lead breakout sessions for each topic that allowed for focused discussion among subject matter experts and interested participants. The breakout and topic group leaders worked with the participants to determine research needs and associated next steps including white papers, reviews and in some cases collaborative grant proposals. Here, summaries from each topic area will be presented to highlight the main foci of discussion and associated conclusions.
Nationwide Termite Pest Survey Conducted in Taiwan as a Citizen Science Project
Authors: Huang Shih-Ying , Chiu Chun-I , Tsai Yi-Ying , Li Wei-Jie , Wu Chia-Chien , Li Hou-Feng
Published: August 2022

Information regarding the species composition and dispersal flight season of termites is crucial for termite management. The major obstacles to collecting such information are a lack of access to private buildings and shortage of workers to monitor and report on termite swarming. To overcome these difficulties, we launched a citizen science project in which members of the public and pest management professionals were invited to collect termite samples. We created the website, Taiwan Termite Identification Service, on which populace could log the collection information, and ship termite samples to our laboratory for identification. We also established a Facebook group, called the “Termite Forum,” to publicize this project. A total of 3024 samples were collected from 2015 to 2020, and we identified the species of >93% of the samples. Based on 1499 samples collected from buildings, five structural termite pests were identified, and species composition in each county of Taiwan is available. According to 844 dispersal flight events, termite dispersal flight timing peak and degree of centralization were estimated using a Gaussian model. The collected data demonstrated that the invasive termite species, Coptotermes gestroi (Wasmann) (Blattodea: Rhinotermitidae), continued northward expansion. The first intercepted alate of Schedorhinotermes sp. (Blattodea: Rhinotermitidae) indicated that it may be a new invasive pest from Southeast Asia. This study reports on a successful case of a citizen science project where urban pest data were collected on a national scale.
Electrophysiologically Determined Spectral Responses in Lobesia botrana (Lepidoptera: Tortricidae)
Authors: Crook Damon J , Chiesa Serena G , Warden Melissa L , Nadel Hannah , Ioriatti Claudio , Furtado Mandy
Published: August 2022

Electrophysiological methods were used to test the visual sensitivity of European grapevine moth, Lobesia botrana (Lepidoptera: Tortricidae) to wavelengths ranging from 300 to 700 nm. For male and females tested, a main, peak response occurred in the 460–540 nm range (blue-green wavelengths) with females having a generally lower response to wavelengths in that range. A second smaller peak was observed for both sexes at the 340–420 nm range. A general linear model indicated that males, virgin females, and mated females did not react differently to changes in wavelength. No moths showed any obvious sensitivity to wavelengths between 580 and 700 nm. Based on our retinal recording data we suggest that UV light traps (≤480 nm) could be utilized alongside pheromone traps when monitoring L. botrana in high risk areas.
Active Choice vs. Inertia? An Exploratory Assessment of the European Microsoft Case’s Choice Screen
Authors: Vasquez Duque Omar
Published: August 2022

In January 2009, the European Commission accused Microsoft of extending its monopoly from the operating system market to the browsers market by preinstalling Internet Explorer (IE) and setting it as the users’ default. Microsoft settled the case agreeing to display a choice screen to its users located in the European Economic Area, Croatia, and Switzerland, whose default web browser was Internet Explorer. The remedy would allow Microsoft’s users to freely choose whatever internet browser they preferred. After March 2010, IE’s market share did go down in the EEA, Croatia, and Switzerland. It seems straightforward to attribute IE’s decline to the choice screen itself. However, when considering other developed jurisdictions as a comparison group, the impact of the choice screen on IE’s market share is negligible (roughly, between 1.4 and 2 percent). This finding invites us to assess the potential causes of default effects and the effectiveness of strategies that analysts, policymakers, and enforcers have assumed to be effective. This work argues that the theory of harm and the remedies that may address consumers’ inertia should be re-examined. Primarily, which types of consumers may stick to default applications, whether choice screens may change the users’ preferences after they have familiarized themselves with an experience good, whether choice screens have so far facilitated the development of competing applications, as well as the reach of choice screens.
Comparing Land Manager and Community Perceptions of a Colorado Prescribed Fire Outreach Program
Authors: McGrath Novak Katie , McCaffrey Sarah , Schultz Courtney A
Published: August 2022

Researchers and practitioners often emphasize the importance of effective community engagement around forest management projects to address possible barriers to implementation related to a lack of social acceptance. Using qualitative methods, we examined a public outreach program to understand the goals and perceptions of those providing and receiving information about forest management. We found that many community members were initially drawn to learn about wildfire risk mitigation, but their informational needs shifted toward broader forest ecology over time, suggesting that communication strategies and topics must also evolve over time. Some common terms used by land management professionals were unclear to public audiences, sometimes leading to feelings of dissatisfaction with outreach. One-on-one meetings and experiential group learning were perceived by information providers and community members to be useful strategies for outreach. Our findings can be used to improve ongoing outreach in this study area and inform similar efforts elsewhere.

Study Implications: We interviewed community members and land management professionals to understand what they believe to be effective forms of public outreach related to prescribed fire. We found that community members’ goals for learning changed over time, requiring outreach efforts to cover a range of topics and strategies. Community members were unfamiliar with some agency jargon, leading to confusion and dissatisfaction with outreach. One-on-one meetings and experiential group learning were widely considered to be the most useful outreach strategies. Our work can be applied to improve similar outreach programs in other areas in the future.
Opportunistic Pathogens in Cystic Fibrosis: Epidemiology and Pathogenesis of Lung Infection
Authors: Blanchard Ana C , Waters Valerie J
Published: August 2022

Cystic fibrosis (CF) is one of the most common life-shortening genetic diseases in Caucasians. Due to abnormal accumulation of mucus, respiratory failure caused by chronic infections is the leading cause of mortality in this patient population. The microbiology of these respiratory infections includes a distinct set of opportunistic pathogens, including Pseudomonas aeruginosa, Burkholderia spp., Achromobacter spp., Stenotrophomonas maltophilia, anaerobes, nontuberculous mycobacteria, and fungi. In recent years, culture-independent methods have shown the polymicrobial nature of lung infections, and the dynamics of microbial communities. The unique environment of the CF airway predisposes to infections caused by opportunistic pathogens. In this review, we will highlight how the epidemiology and role in disease of these pathogens in CF differ from that in individuals with other medical conditions. Infectious diseases (ID) physicians should be aware of these differences and the specific characteristics of infections associated with CF.
Mid-regional Proadrenomedullin Biomarker Predicts Coronavirus Disease 2019 Clinical Outcomes: A US-Based Cohort Study
Authors: Atallah Natalie J , Panossian Vahe S , Atallah Christine J , Schwabe Andrej , Johannes Sascha , Wiemer Jan , Mansour Michael K
Published: August 2022

Background

Mid-regional proadrenomedullin (MR-proADM) is a biomarker released following endothelial damage. Studies have shown a correlation in predicting coronavirus disease 2019 (COVID-19) outcomes with MR-proADM levels. Our study aimed to investigate baseline MR-proADM as a predictor of a wider range of clinical outcomes of varying severity in patients admitted with COVID-19, and to compare to other biomarkers.

Methods

Data from the Boston Area COVID-19 Consortium (BACC) Bay Tocilizumab Trial was used in this study. Patients with biomarker determinations, and not admitted to the intensive care unit (ICU) on admission, were included. MR-proADM cutoff of 0.87 nmol/L was assessed in predicting clinical outcomes.

Results

Of 182 patients, 11.0% were mechanically ventilated or dead within 28 days. Of patients with MR-proADM >0.87 nmol/L, 21.1% were mechanically ventilated or dead within 28 days, compared with 4.5% of those with MR-proADM ≤0.87 nmol/L (P < .001). The sensitivity, specificity, negative predictive value, and positive predictive value of MR-proADM cutoff of 0.87 nmol/L in predicting mechanical ventilation or death were 75%, 65%, 95%, and 21%, respectively, with an area under the receiver operating characteristic curve of 0.76. On multivariable logistic regression analysis, MR-proADM >0.87 nmol/L was independently associated with mechanical ventilation or death, ICU admission, prolonged hospitalization beyond day 4, and day 4 COVID-19 ordinal scale equal to or worse than day 1.

Conclusions

MR-proADM functions as a valuable biomarker for the early risk stratification and detection of severe disease progression of patients with COVID-19. In the prediction of death, MR-proADM performed better compared to many other commonly used biomarkers.
Accuracy of C-reactive Protein and Procalcitonin for Diagnosing Bacterial Infections Among Subjects With Persistent Fever in the Tropics
Authors: Van Duffel Lukas , Yansouni Cedric P , Jacobs Jan , Van Esbroeck Marjan , Ramadan Kadrie , Buyze Jozefien , Tsoumanis Achilleas , Barbé Barbara , Boelaert Marleen , Verdonck Kristien , Chappuis Francois , Bottieau Emmanuel
Published: August 2022

Background

In low-resource settings, inflammatory biomarkers can help identify patients with acute febrile illness who do not require antibiotics. Their use has not been studied in persistent fever (defined as fever lasting for ≥7 days at presentation).

Methods

C-reactive protein (CRP) and procalcitonin (PCT) levels were measured in stored serum samples of patients with persistent fever prospectively enrolled in Cambodia, the Democratic Republic of Congo, Nepal, and Sudan. Diagnostic accuracy was assessed for identifying all bacterial infections and the subcategory of severe infections judged to require immediate antibiotics.

Results

Among 1838 participants, CRP and PCT levels were determined in 1777 (96.7%) and 1711 (93.1%) samples, respectively, while white blood cell (WBC) count was available for 1762 (95.9%). Areas under the receiver operating characteristic curve for bacterial infections were higher for CRP (0.669) and WBC count (0.651) as compared with PCT (0.600; P <.001). Sensitivity for overall and severe bacterial infections was 76.3% (469/615) and 88.2% (194/220) for CRP >10 mg/L, 62.4% (380/609) and 76.8% (169/220) for PCT >0.1 µg/L, and 30.5% (184/604) and 43.7% (94/215) for WBC >11 000/µL, respectively. Initial CRP level was <10 mg/L in 45% of the participants who received antibiotics at first presentation.

Conclusions

In patients with persistent fever, CRP and PCT showed higher sensitivity for bacterial infections than WBC count, applying commonly used cutoffs for normal values. A normal CRP value excluded the vast majority of severe infections and could therefore assist in deciding whether to withhold empiric antibiotics after cautious clinical assessment.
Cerulean Warblers exhibit parallel migration patterns and multiple migratory stopovers within the Central American Isthmus
Authors: Raybuck Douglas W , Boves Than J , Stoleson Scott H , Larkin Jeffery L , Bayly Nicholas J , Bulluck Lesley P , George Gregory A , Slankard Kate G , Kearns Laura J , Petzinger Sharon , Cox John J , Buehler David A
Published: August 2022

The Cerulean Warbler (Setophaga cerulea) is a declining Nearctic–Neotropical migratory songbird of conservation concern. Implementing full annual cycle conservation strategies to facilitate recovery has been difficult because we know little about the migratory period or strength of migratory connectivity between North American breeding and South American nonbreeding regions. Between 2014 and 2017, we deployed geolocators on 282 males at 14 study sites throughout the species’ range to (1) evaluate the strength and pattern of connectivity between breeding and nonbreeding regions, (2) identify approximate routes and stopover regions, and (3) document migration phenology. We obtained data from 26 birds and observed moderate migratory connectivity overall but documented strong parallel migration for birds breeding in two longitudinally disparate regions. Most (14 of 15; 93%) Appalachian breeders spent the stationary nonbreeding period in the Colombian/Venezuelan Andes, whereas most (5 of 7; 71%) Ozark-breeders spent the stationary nonbreeding period in Peru/Ecuador. The majority of spring migration (62%) was spent in Central America at multiple stopover locations between Panama and southern Mexico. The 2 migratory periods were approximately equal in duration: 38 ± 2 days (SE) in fall and 42 ± 2 days (SE) in spring. Based on the observed connectivity pattern, conservation of Appalachian-breeding populations during the stationary nonbreeding period should focus on forest conservation and restoration in pre-montane/lower montane forests of Colombia and Venezuela, whereas Ozark-breeding population conservation should focus on forest conservation and restoration efforts in Ecuador and Peru. Further conservation efforts are also needed on the breeding grounds, especially for the most sharply declining populations. And finally, conservation of forests used by Cerulean Warblers during stopover periods throughout Central America and southern Mexico, in southeastern United States coastal areas, and in the Mississippi Alluvial Valley will benefit individuals from multiple breeding locations and populations.
Genome-Transcriptome-Functional Connectivity-Cognition Link Differentiates Schizophrenia From Bipolar Disorder
Authors: Chen Jiayu , Fu Zening , Bustillo Juan R , Perrone-Bizzozero Nora I , Lin Dongdong , Canive Jose , Pearlson Godfrey D , Stephen Julia M , Mayer Andrew R , Potkin Steven G , van Erp Theo G M , Kochunov Peter , Elliot Hong L , Adhikari Bhim M , Andreassen Ole A , Agartz Ingrid , Westlye Lars T , Sui Jing , Du Yuhui , Macciardi Fabio , Hanlon Faith M , Jung Rex E , Turner Jessica A , Liu Jingyu , Calhoun Vince D
Published: August 2022

Background and Hypothesis

Schizophrenia (SZ) and bipolar disorder (BD) share genetic risk factors, yet patients display differential levels of cognitive impairment. We hypothesized a genome-transcriptome-functional connectivity (frontoparietal)-cognition pathway linked to SZ-versus-BD differences, and conducted a multiscale study to delineate this pathway.

Study Designs

Large genome-wide studies provided single nucleotide polymorphisms (SNPs) conferring more risk for SZ than BD, and we identified their regulated genes, namely SZ-biased SNPs and genes. We then (a) computed the polygenic risk score for SZ (PRSSZ) of SZ-biased SNPs and examined its associations with imaging-based frontoparietal functional connectivity (FC) and cognitive performances; (b) examined the spatial correlation between ex vivo postmortem expressions of SZ-biased genes and in vivo, SZ-related FC disruptions across frontoparietal regions; (c) investigated SZ-versus-BD differences in frontoparietal FC; and (d) assessed the associations of frontoparietal FC with cognitive performances.

Study Results

PRSSZ of SZ-biased SNPs was significantly associated with frontoparietal FC and working memory test scores. SZ-biased genes’ expressions significantly correlated with SZ-versus-BD differences in FC across frontoparietal regions. SZ patients showed more reductions in frontoparietal FC than BD patients compared to controls. Frontoparietal FC was significantly associated with test scores of multiple cognitive domains including working memory, and with the composite scores of all cognitive domains.

Conclusions

Collectively, these multiscale findings support the hypothesis that SZ-biased genetic risk, through transcriptome regulation, is linked to frontoparietal dysconnectivity, which in turn contributes to differential cognitive deficits in SZ-versus BD, suggesting that potential biomarkers for more precise patient stratification and treatment.
Levetiracetam Attenuates Adolescent Stress-induced Behavioral and Electrophysiological Changes Associated With Schizophrenia in Adult Rats
Authors: Cavichioli Andreza M , Santos-Silva Thamyris , Grace Anthony A , Guimarães Francisco S , Gomes Felipe V
Published: August 2022

Background and Hypothesis

Stress during adolescence is a major risk factor for schizophrenia. We have found previously in rats that adolescent stress caused, in adulthood, behavioral changes and enhanced ventral tegmental area (VTA) dopamine system activity, which were associated with dysregulation of the excitatory-inhibitory (E/I) balance in the ventral hippocampus (vHip). Levetiracetam, an anticonvulsant drug, regulates the release of neurotransmitters, including glutamate, via SV2A inhibition. It also modulates parvalbumin interneuron activity via Kv3.1 channels. Therefore, levetiracetam could ameliorate deficits in the E/I balance. We tested whether levetiracetam attenuate the adolescent stress-induced behavioral changes, vHip hyperactivity, and enhanced VTA dopamine system activity in adult rats.

Study Design

Male Sprague-Dawley rats were subjected to a combination of daily footshock (postnatal day [PD] 31–40), and three 1 h-restraint stress sessions (at PD31, 32, and 40). In adulthood (PD62), animals were tested for anxiety responses (elevated plus-maze and light-dark box), social interaction, and cognitive function (novel object recognition test). The activity of vHip pyramidal neurons and VTA dopamine neurons was also recorded.

Study Results

Adolescent stress produced anxiety-like responses and impaired sociability and cognitive function. Levetiracetam (10 mg/kg) reversed these changes. Levetiracetam also reversed the increased VTA dopamine neuron population activity and the enhanced firing rate of vHip pyramidal neurons induced by adolescent stress.

Conclusions

These findings suggest that levetiracetam attenuates the adverse outcomes associated with schizophrenia caused by stress during adolescence.
History of ECT in Schizophrenia: From Discovery to Current Use
Authors: de Mangoux Gonzague Corbin , Amad Ali , Quilès Clélia , Schürhoff Franck , Pignon Baptiste
Published: August 2022

Eighty years ago, schizophrenia was the first indication for electroconulsive therapy (ECT), and likewise ECT was one of the first treatments used for schizophrenia. This paper presents the history of ECT in the treatment of schizophrenia and its evolution, from it’s discovery in the 20th century, which is an example of empiricism with a sequence of “shock” therapies. Following this discovery, the use ECT in schizophrenia has been in expansion during several decades, in a context of lack of efficacy of the treatment in schizophrenia. Then, after World War II and the derivative use of ECT in Germany, the use of ECT has decline during several decades. However, in the last decades, the use of ECT in schizophrenia has reemerged. Indeed, among patients in schizophrenia, rates of resistance to treatment have always been and still are high. In 2017, the concept of “ultra-treatment resistant schizophrenia” was defined when clozapine was tried and failed; and ECT, that had been long since abandoned in the treatment of schizophrenia until recent renewed interest, has emerged especially concerning the add-on of ECT to clozapine. However, ECT remains highly stigmatized and underutilized. This article looks at the history of the practice of ECT in schizophrenia with a historical and clinical approach and makes connections between the history of the treatment and its influence on its current recommendation and practice.
Effect of supplemental methionine on health and performance of receiving beef heifers
Authors: Grant Madeline S , Speer Hannah F , Luchini N Daniel , Blasi Dale A , Titgemeyer Evan C
Published: August 2022

Methionine supplementation can improve immune function in transition dairy cattle. Our objective was to determine if supplemental methionine could improve health and performance of newly received growing cattle. Crossbred heifers (n = 384; 222 kg initial body weight; southeastern U.S. origin) were received in four truckloads (blocks) over 9 d. Heifers were weighed at arrival. The following day (d 0) cattle were vaccinated for viral and clostridial diseases, received 2.5 mg tulathromycin/kg body weight, and were stratified within the blocks by arrival body weight to 1 of 8 pens containing 12 heifers each. Within blocks, pens were assigned to 1 of 2 treatments: 0 (control) or 0.1725% Smartamine M to provide 0.1035% metabolizable methionine to the diet. Cattle were limit-fed at 2.2% of body weight daily (dry matter basis) on a diet containing 40% wet corn gluten feed, 34.5% dry-rolled corn, 10% corn silage, 7.5% supplement, 4% alfalfa hay, and 4% prairie hay. Pen weights were measured weekly to determine the feed offered the following week. Individual body weight and tail-vein blood samples were collected on d 0, 14, and 45. Plasma haptoglobin was measured to assess acute-phase protein response. Incidences of morbidity (1.6% for control, 2.6% for Smartamine M) and mortality (0.5% for both control and Smartamine M) were low. Between d 0 and 45, no differences were observed for average daily gain (1.24 vs. 1.27 kg/d; control vs. Smartamine M, P = 0.55) or gain:feed (0.107 vs. 0.110, P = 0.28), although dry matter intake was 1.3% greater (P < 0.01) for control than Smartamine M due to differences in diet dry matter concentration. An interaction between treatment and linear effect of day was detected for plasma haptoglobin (P < 0.05); over time, haptoglobin increased more for control (2.15, 2.28, and 2.95 mg/mL at 0, 14, and 45 d) than for Smartamine M (2.35, 2.37, and 2.58 mg/mL). Supplemental methionine may alleviate acute-phase protein responses in stressed receiving cattle.