bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Trial of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2831781 in Healthy Japanese and White Participants
Authors: Liefaard Lia , Hajduk Eva , van den Berg Frans , Panoilia Eirini , Bouma Gerben , Lisi Edoardo , Srinivasan Naren , Cui Yi , Gross Annette S. , Tarzi Ruth , Marks Daniel J.B. 
Published: September 2022

AbstractThis study investigated ethnic differences in the safety, tolerability, pharmacokinetics, and pharmacodynamics of GSK2831781, an anti–lymphocyte activation gene 3 (LAG3) monoclonal antibody, in healthy participants, and determined local tolerability and bioavailability following subcutaneous (SC) administration. A double‐blind, randomized study of (A) single intravenous (IV) doses of GSK2831781 450 mg or placebo in Japanese and White participants; and (B) single SC doses of GSK2831781 150 or 450 mg, or placebo in White participants, was conducted. Blood samples for analyses were collected before dosing and over 112 days after dosing. GSK2831781 was well tolerated in Japanese and White participants after both IV and SC doses, with the adverse event profile in Japanese being consistent with other populations. There were no injection site adverse events. There was no evidence of differences in systemic exposure among Japanese and White participants. Systemic exposure did not vary with body weight. SC bioavailability was 76.5%, as estimated using population pharmacokinetic modeling. Full and sustained target engagement and evidence of LAG3+ cell depletion (≈53%–66%) were observed in both populations and after both administration routes. No evidence of reduced circulating regulatory T cells (CD4+CD25+CD127lowFoxP3+) was observed. Following IV and SC administration, GSK2831781 depleted circulating LAG3+ T cells with no interethnic difference observed. There were no major impacts on circulating regulatory T cells.
Addressing pollination deficits in orchard crops through habitat management for wild pollinators
Authors: Garratt Michael P. D. , O'Connor Rory S. , Carvell Claire , Fountain Michelle T. , Breeze Tom D. , Pywell Richard , Redhead John W. , Kinneen Lois , Mitschunas Nadine , Truslove Louise , Xavier e Silva Celina , Jenner Nigel , Ashdown Caroline , Brittain Claire , McKerchar Megan , Butcher Charnee , Edwards Mike , Nowakowski Marek , Sutton Peter , Potts Simon G. 
Published: September 2022

AbstractThere is increasing evidence that farmers in many areas are achieving below maximum yields due to insufficient pollination. Practical and effective approaches are needed to maintain wild pollinator populations within agroecosystems so they can deliver critical pollination services that underpin crop production. We established nesting and wildflower habitat interventions in 24 UK apple orchards and measured effects on flower‐visiting insects and the pollination they provide, exploring how this was affected by landscape context. We quantified the extent of pollination deficits and assessed whether the management of wild pollinators can reduce deficits and deliver improved outcomes for growers over 3 years. Wildflower interventions increased solitary bee numbers visiting apple flowers by over 20%, but there was no effect of nesting interventions. Other pollinator groups were influenced by both local and landscape‐scale factors, with bumblebees and hoverflies responding to the relative proportion of semi‐natural habitat at larger spatial scales (1000 m), while honeybees and other flies responded at 500 m or less. By improving fruit number and quality, pollinators contributed more than £16 k per hectare. However, deficits (where maximum potential was not being reached due to a lack of pollination) were recorded and the extent of these varied across orchards, and from year to year, with a 22% deficit in output in the worst (equivalent to ~£14 k/ha) compared to less than 3% (equivalent to ~£2 k/ha) in the best year. Although no direct effect of our habitat interventions on deficits in gross output was observed, initial fruit set and seed set deficits were reduced by abundant bumblebees, and orchards with a greater abundance of solitary bees saw lower deficits in fruit size. The abundance of pollinators in apple orchards is influenced by different local and landscape factors that interact and vary between years. Consequently, pollination, and the extent of economic output deficits, also vary between orchards and years. We highlight how approaches, including establishing wildflower areas and optimizing the ratio of cropped and non‐cropped habitats can increase the abundance of key apple pollinators and improve outcomes for growers.
Tropical forest loss impoverishes arboreal mammal assemblages by increasing tree canopy openness
Authors: Cudney‐Valenzuela Sabine J. , Arroyo‐Rodríguez Víctor , Morante‐Filho José C. , Toledo‐Aceves Tarin , Andresen Ellen 
Published: September 2022

AbstractLandscape‐scale deforestation poses a major threat to global biodiversity, not only because it limits habitat availability, but also because it can drive the degradation of the remaining habitat. However, the multiple pathways by which deforestation directly and indirectly affects wildlife remain poorly understood, especially for elusive forest‐dependent species such as arboreal mammals. Using structural equation models, we assessed the direct and indirect effects of landscape forest loss on arboreal mammal assemblages in the Lacandona rainforest, Mexico. We placed camera traps in 100 canopy trees, and assessed the direct effect of forest cover and their indirect effects via changes in tree basal area and canopy openness on the abundance and diversity (i.e., species richness and exponential of Shannon entropy) of arboreal mammals. We found that forest loss had negative indirect effects on mammal richness through the increase of tree canopy openness. This could be related to the fact that canopy openness is usually inversely related to resource availability and canopy connectivity for arboreal mammals. Furthermore, independently of forest loss, the abundance and richness of arboreal mammals was positively related to tree basal area, which is typically higher in old‐growth forests. Thus, our findings suggest that arboreal mammals generally prefer old‐growth vegetation with relatively low canopy openness and high tree basal area. However, unexpectedly, forest loss was directly and positively related to the abundance and richness of mammals, probably due to a crowding effect, a reasonable possibility given the relatively short history (~40 years) of deforestation in the study region. Conversely, the Shannon diversity was not affected by the predictors we evaluated, suggesting that rare mammals (not the common species) are the ones most affected by these changes. All in all, our findings emphasize that conservation measures ought to focus on increasing forest cover in the landscape, and preventing the loss of large trees in the remaining forest patches.
Quantifying flow and nonflow management impacts on an endangered fish by integrating data, research, and expert opinion
Authors: Yackulic Charles B. , Archdeacon Thomas P. , Valdez Richard A. , Hobbs Monika , Porter Michael D. , Lusk Joel , Tanner Ashley , Gonzales Eric J. , Lee Debbie Y. , Haggerty Grace M. 
Published: September 2022

AbstractManagers charged with recovering endangered species in regulated river segments often have limited flexibility to alter flow regimes and want estimates of the expected population benefits associated with both flow and nonflow management actions. Disentangling impacts on different life stages from concurrently applied actions is essential for determining the effectiveness of each action, but difficult without models that integrate multiple information sources. Here, we develop and fit an integrated population model for endangered Rio Grande Silvery Minnow (Hybognathus amarus) in the Middle Rio Grande, New Mexico. We integrate catch per unit effort monitoring data collected during 2002–2018 with population estimates, data collected during rescue of minnow from drying pools, habitat availability estimates, laboratory results, releases of hatchery reared minnow, and expert opinion. We use expert elicitation to develop a larval carrying capacity index as an informed proxy for the complex interactions among flow, habitat, and life history in this species. We evaluate the model using out‐of‐sample forecasts of 2019 and 2020, develop an algorithm to identify supplemental water releases that maximize benefits to the minnow, and quantify the effectiveness of various actions. Experts generally agreed on the duration and timing of flow requirements and disagreed regarding the importance of different magnitudes. The integrated model with the larval carrying capacity index outperformed two alternative models in forecasting catch in 2019 and 2020. The model estimates that minnow abundance varied by more than three orders of magnitude between 2002 and 2018 and that in a few years recruitment was limited by spawner abundance. Evaluation of the expected benefits of flow and nonflow management actions to fall population abundance across different years suggests that efficient addition of water to the base hydrograph is the most effective action in most, but not all years. Many actions are effective only under certain hydrologic and population conditions and the effectiveness of different actions varies in different sections of the study area. Widespread water extraction and river regulation combined with periodic drought and ongoing climate change may necessitate creative management of federally listed fish species in arid systems informed by thorough analyses of management effectiveness.
Predation risk regulates prey assortative mating by reducing the expected reproductive value of mates
Authors: Torsekar Viraj R. , Zaguri Moshe , Hawlena Dror 
Published: September 2022

AbstractMany animals exhibit size assortative mating (SAM), but how predation affects it remains largely unknown. We hypothesized that predation risk may turn prey less choosy, disrupting SAM, or reduce the expected reproductive value of mates, maintaining SAM but with different size ratio between mates. Using a manipulative field experiment, we found that desert isopods under risk of scorpion predation maintained SAM, but that males that choose and fight over females were on average smaller for a given female size. Less pairs were formed in risky sites, but there were no differences in female sizes and progeny number, size and age near and away from scorpion burrows. Our complementary behavioral experiments revealed that bigger males stayed longer near safe burrows, and won more male–male contests than smaller conspecifics. Our findings highlight that prey can anticipate future costs of predation and use this information to assess the expected reproductive value of mates.
Insulin‐like growth factor binding protein 7 (IGFBP7), a link between heart failure and senescence
Authors: Bracun Valentina , van Essen Bart , Voors Adriaan A. , van Veldhuisen Dirk J. , Dickstein Kenneth , Zannad Faiez , Metra Marco , Anker Stefan , Samani Nilesh J. , Ponikowski Piotr , Filippatos Gerasimos , Cleland John G.F. , Lang Chim C. , Ng Leong L. , Shi Canxia , de Wit Sanne , Aboumsallem Joseph Pierre , Meijers Wouter C. , Klip IJsbrand T. , van der Meer Peter , de Boer Rudolf A. 
Published: September 2022

AbstractAimsInsulin like growth factor binding protein 7 (IGFBP7) is a marker of senescence secretome and a novel biomarker in patients with heart failure (HF). We evaluated the prognostic value of IGFBP7 in patients with heart failure and examined associations to uncover potential new pathophysiological pathways related to increased plasma IGFBP7 concentrations.Methods and resultsWe have measured plasma IGFBP7 concentrations in 2250 subjects with new‐onset or worsening heart failure (BIOSTAT‐CHF cohort). Higher IGFBP7 plasma concentrations were found in older subjects, those with worse kidney function, history of atrial fibrillation, and diabetes mellitus type 2, and in subjects with higher number of HF hospitalizations. Higher IGFBP7 levels also correlate with the levels of several circulating biomarkers, including higher NT‐proBNP, hsTnT, and urea levels. Cox regression analyses showed that higher plasma IGFBP7 concentrations were strongly associated with increased risk of all three main endpoints (hospitalization, all‐cause mortality, and combined hospitalization and mortality) (HR 1.75, 95% CI 1.25–2.46; HR 1.71, 95% CI 1.39–2.11; and HR 1.44, 95% CI 1.23–1.70, respectively). IGFBP7 remained a significant predictor of these endpoints in patients with both reduced and preserved ejection fraction. Likelihood ratio test showed significant improvement of all three risk prediction models, after adding IGFBP7 (P < 0.001). A biomarker network analysis showed that IGFBP7 levels activate different pathways involved in the regulation of the immune system. Results were externally validated in BIOSTAT‐CHF validation cohort.ConclusionsIGFPB7 presents as an independent and robust prognostic biomarker in patients with HF, with both reduced and preserved ejection fraction. We validate the previously published data showing IGFBP7 has correlations with a number of echocardiographic markers. Lastly, IGFBP7 pathways are involved in different stages of immune system regulation, linking heart failure to senescence pathways.
A mathematical optimization model using red deer algorithm for resource discovery in CloudIoT
Authors: Goudarzi Parisa , Rahmani Amir Masoud , Mosleh Mohammad 
Published: September 2022

AbstractThe Internet of Things (IoT) and cloud computing are new concepts in revolutionized communication and information technologies. Different technologies, for example, transportation and healthcare, can benefit from Cloud of Things (CloudIoT) for mobile and fixed resource applications with great promises. Fixed and mobile resources are very important items in the CloudIoT paradigm because of the need for an appropriate discovery mechanism. In the present study, a mathematical optimization model is proposed for the minimization of bandwidth, cost, and response time of CloudIoT platforms with a special focus on the role of mobile and fixed resources in resource discovery. Additionally, this study presents a heuristic resource discovery algorithm using a mathematical optimization model (RDMOM). The mixed‐integer non‐linear programming is used to design the discovery mechanism. Furthermore, the optimization problem is solved using the red deer algorithm. Finally, the simulation results show a significant reduction in the latency, resource efficiency, and energy consumption, as well as an improvement in availability and success ratio, compared to previous algorithms. The RDMOM algorithm significantly improves the success ratio, energy consumption, resource efficiency, availability, and latency, respectively, by 18%, 21%, 24%, 17%, and 21% in comparison to other algorithms.
The effects of radial cracks on the fire performance of heritage timber
Authors: Harun Georgette , Chorlton Bronwyn , Richter Franz , Gales John 
Published: September 2022

AbstractHeritage timber buildings are found worldwide and their irreplaceable nature makes them of high value. A common occurrence on heritage timber members is radial shrinkage cracks resulting from changing moisture contents over time. There is little information available that can be used to assess the fire performance of heritage timber members (which has unique differences from contemporary timber), and to the author's awareness, no information regarding how the presence of radial cracks affects the fire performance and char depth of a timber member. The purpose of this study is to provide an evaluation of the effects of radial cracking on the fire performance of timber members, including its effect on char depth, time to ignition, and residual strength. Full‐scale heritage Pine timber members were procured from a 115‐year‐old building undergoing demolition and then subjected to a pool fire. Cracked samples were also extracted from the members and tested in a Cone Calorimeter apparatus relative to solid samples. It was found that the presence of cracks did allow for deeper charring with the full‐scale tests showing 64% greater char depth in the cracked region and the Cone Calorimeter tests showing 29% greater char depth on the cracked samples. Four‐point bending tests of the full‐scale members subjected to a pool fire showed that the effect of the fire exposure and the cracks did not significantly impact the capacity of the members (7.2% difference) but reduced the stiffness as the ultimate deflection increased by 43%. These results can help to inform practitioners who encounter heritage timber members to more accurately assess the fire performance of the member, such that they can make informed decisions on the level of fire protection required. The study also provides methodologies for the collection of heritage timber test materials.
The protective effects of rutin on the liver, kidneys, and heart by counteracting organ toxicity caused by synthetic and natural compounds
Authors: Rahmani Sohrab , Naraki Karim , Roohbakhsh Ali , Hayes A. Wallace , Karimi Gholamreza 
Published: September 2022

AbstractRutin is a flavonoid present in many plant species. Because of its antioxidant, anti‐inflammatory, and antiapoptotic properties, rutin is of interest for its potential protective effects against toxic agents. The hepatoprotective, renoprotective, and cardioprotective effects of rutin are reviewed. The antioxidant effects of rutin are elicited by enhancing antioxidant enzymes such as GST, GGT, CAT, GPx, SOD, and GR, activating the Nrf2/HO‐1 pathway, elevating GSH content, and the reduction in MDA. The anti‐inflammatory effects of rutin are mediated by the inhibition of IL‐1β, IL‐6, TGF‐β1, COX‐2, iNOS, TLR4, and XO. Rutin exerted its antiapoptotic effects by inhibition of free radicals, caspase‐3/‐7/‐9, hsp70, HMGB1, and p53, and the elevation of the antiapoptotic protein Bcl‐2. Rutin has potential therapeutic effectiveness against several toxicants, and its beneficial effects are more than likely mediated by its antioxidant, anti‐inflammatory, and/or antiapoptotic property.
Urine is a viral antigen reservoir in hepatitis E virus infection
Authors: Ying Dong , He Qiyu , Tian Weikun , Chen Yanling , Zhang Xiaoping , Wang Siling , Liu Chang , Chen Zihao , Liu Yu , Fu Lijuan , Yan Li , Wang Ling , Tang Zimin , Wang Lin , Zheng Zizheng , Xia Ningshao 
Published: September 2022

Background and Aims:
HEV ORF2 antigen (Ag) in serum has become a tool for diagnosing current HEV infection. Particularly, urinary shedding of HEV Ag has been gaining increasing interest. We aim to uncover the origin, antigenicity, diagnostic performance, and diagnostic significance of Ag in urine in HEV infection.

Approach and Results:
Clinical serum and urine samples from patients with acute and chronic HEV infection were analyzed for their Ag levels. Ag in urine was analyzed by biochemical and proteomic approaches. The origin of urinary Ag and Ag kinetics during HEV infection was investigated in mouse and rabbit models, respectively. We found that both the Ag level and diagnostic sensitivity in urine were higher than in serum. Antigenic protein in urine was an E2s‐like dimer spanning amino acids 453–606. pORF2 entered urine from serum in mice i.v. injected with pORF2. Ag in urine originated from the secreted form of pORF2 (ORF2S) that abundantly existed in hepatitis E patients’ serum. HEV Ag was specifically taken up by renal cells and was disposed into urine, during which the level of Ag was concentrated >10‐fold, resulting in the higher diagnosing sensitivity of urine Ag than serum Ag. Moreover, Ag in urine appeared 6 days earlier, lasted longer than viremia and antigenemia, and showed good concordance with fecal RNA in a rabbit model.

Conclusions:
Our findings demonstrated the origin and diagnostic value of urine Ag and provided insights into the disposal of exogenous protein of pathogens by the host kidney.
The relationship between internal and external factors about the outpatients’ choice of hospital: A cross‐sectional study from Jiaxing City, China
Authors: Yu Mingming , Zhao Guoyang , Tang Dan 
Published: September 2022

AbstractBackground and AimsExploring the mechanism influencing the choice of hospital among patients is important to render better care to them. The main purpose of this study is to evaluate the relationship between outpatients’ different internal factors (sociodemographic and psychological characteristics) and different external factors (provider characteristics) regarding their choice of hospital.MethodsThe data obtained via questionnaire was analyzed with a linear regression model to verify the relationship between outpatients’ internal and external factors. In addition, for external factors, we built a score reflecting a comprehensive hospital's “hard power” (diagnosis and treatment technology and expertise, i.e., to say, the curative capability) and “soft power” (whether the environment for seeing a doctor is convenient and cheap, etc.) factors which influence the choice of outpatients, and the factors were given different points and weighted according to the option's order of the questionnaire.ResultsWe did not see evidence that internal factors such as gender, age, birthplace, and having or not having medical insurance had an effect on the comprehensive external factors of the hospital's choice (p > 0.05). However, statistically significant differences were found (p < 0.001) that outpatients who usually resided near Jiaxing valued hospitals’ “hard power” to a greater extent than did outpatients who lived in Jiaxing city, otherwise, “soft power” was prioritized. Similarly, outpatients who recognized themselves as having serious diseases valued hospitals’ “hard power” to a greater extent than those with moderate or minor diseases, otherwise, “soft power” was prioritized (p = 0.03).ConclusionBy enhancing the hospital's “soft power,” the managers of small hospitals could attract different outpatients from large hospitals, such as outpatients with minor or moderate diseases. Moreover, the regional health service organizations should promote the building of first‐ and second‐level hospitals near cities to retain more outpatients and to achieve outpatients’ diversion from large tertiary hospitals.
Understanding the use of oral rehydration therapy: A narrative review from clinical practice to main recommendations
Authors: Aghsaeifard Ziba , Heidari Ghobad , Alizadeh Reza 
Published: September 2022

AbstractBackground and AimsFluid loss due to diarrhea remains a significant cause of mortality among children under the age of 5.MethodsOral rehydration therapy (ORT) is a first‐line therapeutic measure to compensate the volume loss due to diarrhea and vomiting among gastroenteritis patients. Despite adequate knowledge, the practice of ORT is limited, particularly in developing countries.ResultsSeveral recommendations are provided regarding the use of ORT to treat hypovolemia, however, the information regarding its adequate usage is restricted within the healthcare centers and professionals.ConclusionThis review highlights the importance of providing recommendations regarding the use of ORT. We also discuss the barriers and alternatives that might limit its use.