bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benzothiadiazole‐Substituted Aza‐BODIPY Dyes: Two‐Photon Absorption Enhancement for Improved Optical Limiting Performances in the Short‐Wave IR Range
Authors: David Sylvain , Chang Hao‐Jung , Lopes Cesar , Brännlund Carl , Le Guennic Boris , Berginc Gérard , Van Stryland Eric , Bondar Mykailo V. , Hagan David , Jacquemin Denis , Andraud Chantal , Maury Olivier 
Published: December 2020

AbstractAza‐boron dipyrromethenes (aza‐BODIPYs) presenting a benzothiadiazole substitution on upper positions are described. The strong electron‐withdrawing effect of the benzothiadiazole moiety permits enhancement of the accepting strength and improves the delocalization of the aza‐BODIPY core to attain a significant degree of electronic communication between the lower donating groups and the upper accepting groups. The nature of the intramolecular charge transfer is studied both experimentally and theoretically. Linear spectroscopy highlighted the strongly redshifted absorption and emission of the synthesized molecules with recorded fluorescence spectra over 1000 nm. Nonlinear optical properties were also investigated. Strong enhancement of the two‐photon absorption of the substituted dyes compared with the unsubstituted one (up to 4520 GM at 1300 nm) results in an approximately 15–20 % improvement of the optical power limiting performances. These dyes are therefore a good starting point for further improvement of optical power limiting in the short‐wave IR range.
Identification of Phenazine‐Based MEMO1 Small‐Molecule Inhibitors: Virtual Screening, Fluorescence Polarization Validation, and Inhibition of Breast Cancer Migration
Authors: Labrecque Courtney L. , Hilton Cassidy N. , Airas Justin , Blake Alexis , Rubenstein Kristen J. , Parish Carol A. , Pollock Julie A. 
Published: December 2020

AbstractPhosphorylation‐dependent protein–protein interactions play a significant role in biological signaling pathways; therefore, small molecules that are capable of influencing these interactions can be valuable research tools and have potential as pharmaceutical agents. MEMO1 (mediator of ErbB2‐cell driven motility) is a phosphotyrosine‐binding protein that interacts with a variety of protein partners and has been found to be upregulated in breast cancer patients. Herein, we report the first small‐molecule inhibitors of MEMO1 interactions identified through a virtual screening platform and validated in a competitive fluorescence polarization assay. Initial structure–activity relationships have been investigated for these phenazine‐core inhibitors and the binding sites have been postulated using molecular dynamics simulations. The most potent biochemical inhibitor is capable of disrupting the large protein interface with a KI of 2.7 μm. In addition, the most promising phenazine core compounds slow the migration of breast cancer cell lines in a scratch assay.
Pentafluoro‐3‐hydroxy‐pent‐2‐en‐1‐ones Potently Inhibit FNT‐Type Lactate Transporters from all Five Human‐Pathogenic Plasmodium Species
Authors: Walloch Philipp , Hansen Christian , Priegann Till , Schade Dennis , Beitz Eric 
Published: December 2020

AbstractThe protozoan parasite Plasmodium falciparum causes the most severe and prevailing form of malaria in sub‐Saharan Africa. Previously, we identified the plasmodial lactate transporter, PfFNT, a member of the microbial formate–nitrite transporter family, as a novel antimalarial drug target. With the pentafluoro‐3‐hydroxy‐pent‐2‐en‐1‐ones, we discovered PfFNT inhibitors that potently kill P. falciparum parasites in vitro. Four additional human‐pathogenic Plasmodium species require attention, that is, P. vivax, most prevalent outside of Africa, and the regional P. malariae, P. ovale and P. knowlesi. Herein, we show that the plasmodial FNT variants are highly similar in terms of protein sequence and functionality. The FNTs from all human‐pathogenic plasmodia and the rodent malaria parasite were efficiently inhibited by pentafluoro‐3‐hydroxy‐pent‐2‐en‐1‐ones. We further established a phenotypic yeast‐based FNT inhibitor screen, and found very low compound cytotoxicity and monocarboxylate transporter 1 off‐target activity on human cells, particularly of the most potent FNT inhibitor BH267.meta, allowing these compounds to proceed towards animal model malaria studies.
Quality of life among survivors of adolescent and young adult cancer in Canada: A Young Adults With Cancer in Their Prime (YACPRIME) study
Authors: Schulte Fiona S. M. , Chalifour Karine , Eaton Geoff , Garland Sheila N. 
Published: December 2020

BackgroundThe quality of life (QoL) among survivors of adolescent and young adult (AYA) cancer may be compromised compared with that in the general population. In this study, the authors: 1) assessed for differences in QoL among a national study of AYA cancer survivors compared with the Canadian population and 2) explored the factors associated with poorer QoL in AYA cancer survivors.MethodsFor the current research, data from the Young Adults With Cancer in Their Prime study were used. QoL was measured using physical and mental component scores from a 12‐item short‐form health status measure. A comparison group was derived from the Canadian Community Health Survey.ResultsAYAs (n = 195; 17.8% male; mean ± SD: 35.62 ± 6.89 years on study, 6.48 ± 5.73 years from treatment) were compared with a comparison sample (n = 665; 21.2% male). Among survivors, 31.8% reported poor physical health, and 49.7% reported poor mental health. Compared with the general population, AYAs had significantly lower physical health (F[1,818] = 52.80; P = .00) and mental health (F[1,818] = 83.54; P = .00), controlling for sex and age. Multivariable logistic regression analyses revealed that an annual income level <$40,000 (adjusted odds ratio [AOR], 8.32; 95% CI, 2.85‐24.30), poor sleep quality (AOR, 1.19; 95% CI, 1.06‐1.33), worse body image (AOR, 1.08; 95% CI, 1.02‐1.14), and higher social support (AOR, 1.02; 95% CI, 1.00‐1.05) were significantly associated with poor physical health. Poor sleep quality (AOR, 1.22; 95% CI, 1.08‐1.38), body image (AOR, 1.06; 95% CI, 1.01‐1.12), fear of cancer recurrence (AOR, 1.13; 95% CI, 1.06‐1.21) were associated with poor mental health.ConclusionsThe QoL of AYAs requires urgent attention. Sleep, body image, and social support may be important modifiable targets for intervention to improve their QoL.
Short‐term effects of wildfire in boreal peatlands: Does fire mitigate the linear footprint of oil and gas exploration?
Authors: Pinzon Jaime , Dabros Anna , Riva Federico , Glasier James R. N. 
Published: December 2020

AbstractExploration practices for oil sands developments in the boreal forest of western Canada create a network of thousands of kilometers of linear features, particularly seismic lines that dissect these forests posing significant environmental challenges. As wildfire is one of the prevalent stand‐replacing natural disturbances in the Canadian boreal forest, it is an important driver of environmental change and stand development that may contribute to the mitigation of such linear industrial footprint. Here, we evaluate the short‐term cumulative (also known as combined) effects of seismic lines and wildfire on biodiversity and site conditions. One year after the Horse River (Fort McMurray, Alberta, Canada) fire event in the spring of 2016, we compared dissected and undisturbed forests in burned and unburned boreal peatlands, assessing changes in overall stand structure and the responses of a variety of organisms. Soil moisture was significantly higher on seismic lines than in the adjacent forest, suggesting why most of the study sites within the fire perimeter showed little evidence of burning at the line in relation to the adjacent forest. Low fire severity on seismic lines seemed an important driver of local species diversity for ants, beetles, spiders, and plants in disturbed peatlands, resulting in similar species composition on seismic lines both within and outside the burned area, but different assemblages in burned and unburned adjacent forests. Our results suggest that fire did not erase seismic lines; rather, wildfire might increase the influence of this footprint on the recovering adjacent forest. Longer‐term monitoring will be necessary to understand how boreal treed peatlands respond to the cumulative effect of wildfire and linear disturbances.
Extreme rainfall events and cooling of sea turtle clutches: Implications in the face of climate warming
Authors: Laloë Jacques‐Olivier , Tedeschi Jamie N. , Booth David T. , Bell Ian , Dunstan Andy , Reina Richard D. , Hays Graeme C. 
Published: December 2020

AbstractUnderstanding how climate change impacts species and ecosystems is integral to conservation. When studying impacts of climate change, warming temperatures are a research focus, with much less attention given to extreme weather events and their impacts. Here, we show how localized, extreme rainfall events can have a major impact on a species that is endangered in many parts of its range. We report incubation temperatures from the world's largest green sea turtle rookery, during a breeding season when two extreme rainfall events occurred. Rainfall caused nest temperatures to drop suddenly and the maximum drop in temperature for each rain‐induced cooling averaged 3.6°C (n = 79 nests, min = 1.0°C, max = 7.4°C). Since green sea turtles have temperature‐dependent sex determination, with low incubation temperatures producing males, such major rainfall events may have a masculinization effect on primary sex ratios. Therefore, in some cases, extreme rainfall events may provide a “get‐out‐of‐jail‐free card” to avoid complete feminization of turtle populations as climate warming continues.
Elevated α‐hydroxybutyrate dehydrogenase as an independent prognostic factor for mortality in hospitalized patients with COVID‐19
Authors: Liu Zeming , Li Jinpeng , Li Man , Chen Sichao , Gao Rongfen , Zeng Guang , Chen Danyang , Wang Shipei , Li Qianqian , Hu Di , Zeng Wen , Guo Liang , Wu Xiaohui 
Published: December 2020

AbstractAimsMany studies have explored the clinical characteristics of patients with coronavirus disease (COVID‐19), especially patients with cardiovascular disease. However, associated mechanisms and markers remain to be further investigated. This study aimed to investigate the effect of α‐hydroxybutyrate dehydrogenase (α‐HBDH) levels on disease progression and prognosis of patients with COVID‐19.Methods and resultsOne thousand seven hundred and fifty‐one patients from the Leishenshan hospital in Wuhan were divided into elevated and normal groups by α‐HBDH level, and the clinical information between the two groups was compared retrospectively. The main outcome evaluation criteria included in‐hospital death and disease severity. Univariate and multivariate regression analyses, survival curves, logistic regression, and receiver operating characteristic curve models were performed to explore the relationship between elevated α‐HBDH and the two outcomes. Besides, curve fitting analyses were conducted to analyse the relationship between computed tomography score and survival. Among 1751 patients with confirmed COVID‐19, 15 patients (0.87%) died. The mean (SD) age of patients was 58 years in normal α‐HBDH group and 66 years in elevated α‐HBDH group (P < 0.001). The mortality during hospitalization was 0.26% (4 of 1559) for patients with normal α‐HBDH levels and 5.73% (11 of 192) for those with elevated α‐HBDH levels (P < 0.001). Multivariate Cox analysis confirmed an association between elevated α‐HBDH levels and higher risk of in‐hospital mortality [hazard ratio: 4.411, 95% confidence interval (95% CI), 1.127–17.260; P = 0.033]. Multivariate logistic regression for disease severity and α‐HBDH levels showed significant difference between both groups (odds ratio = 3.759; 95% CI, 1.895–7.455; P < 0.001). Kaplan–Meier curves also illustrated the survival difference between normal and elevated α‐HBDH patients (P < 0.001).ConclusionsOur study found that serum α‐HBDH is an independent risk factor for in‐hospital mortality and disease severity among COVID‐19 patients. α‐HBDH assessment may aid clinicians in identifying high‐risk individuals among COVID‐19 patients.
Side Effects of Insecticides on Leaf-Miners and Gall-Inducers Depend on Species Ecological Traits and Competition with Leaf-Chewers
Authors: Leroy Benjamin M.L. , Gossner Martin M. , Ferrini Gabriele , Seibold Sebastian , Lauer Florian P.M. , Petercord Ralf , Eichel Peter , Jaworek Jessica , Weisser Wolfgang W. 
Published: December 2020

Abstract
Internal feeding is considered to shield sessile herbivorous insects from exposure to nonsystemic insecticides aerially sprayed against forest defoliators, although this has not been tested. It is, however, established that leaf damage caused by defoliators affects the survivorship and oviposition behavior of sessile herbivores. Thus feeding ecology and competition may mediate nontarget effects of insecticides on these insects. We tested the ecological sensitivity of 3 guilds of sessile herbivores (upper-surface leaf-miners, lower-surface leaf-miners, and gall-inducers) to the lipophilic larvicides diflubenzuron and tebufenozide aerially applied either at operational rates (12 g active ingredient [a.i.]/ha and 69.6 g [a.i.]/ha, respectively) or at maximum legal rates (60 g [a.i.]/ha and 180 g [a.i.]/ha, respectively), in German oak forests. Diflubenzuron affected leaf-miners at different life stages depending on their position on the leaf but had no effect on gall-inducers. Tebufenozide showed a similar, but not significant, pattern in leaf-miners and did not affect gall-inducers. By reducing the incidence of chewing damage on leaves, both insecticides offset the negative effect of competition on leaf-miner and gall-inducers. The net outcome of insecticide treatment was positive for guilds avoiding exposure, but negative for upper-surface leaf-miners. Exposure to insecticides in situ can be mediated by subtle differences in species biology and species interactions, with potential implications for organisms usually considered safe in risk assessment studies. Environ Toxicol Chem 2021;00:1–17. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Strongly deleterious mutations are a primary determinant of extinction risk due to inbreeding depression
Authors: Kyriazis Christopher C. , Wayne Robert K. , Lohmueller Kirk E. 
Published: December 2020

AbstractHuman-driven habitat fragmentation and loss have led to a proliferation of small and isolated plant and animal populations with high risk of extinction. One of the main threats to extinction in these populations is inbreeding depression, which is primarily caused by recessive deleterious mutations becoming homozygous due to inbreeding. The typical approach for managing these populations is to maintain high genetic diversity, increasingly by translocating individuals from large populations to initiate a “genetic rescue.” However, the limitations of this approach have recently been highlighted by the demise of the gray wolf population on Isle Royale, which declined to the brink of extinction soon after the arrival of a migrant from the large mainland wolf population. Here, we use a novel population genetic simulation framework to investigate the role of genetic diversity, deleterious variation, and demographic history in mediating extinction risk due to inbreeding depression in small populations. We show that, under realistic models of dominance, large populations harbor high levels of recessive strongly deleterious variation due to these mutations being hidden from selection in the heterozygous state. As a result, when large populations contract, they experience a substantially elevated risk of extinction after these strongly deleterious mutations are exposed by inbreeding. Moreover, we demonstrate that, although genetic rescue is broadly effective as a means to reduce extinction risk, its effectiveness can be greatly increased by drawing migrants from small or moderate-sized source populations rather than large source populations due to smaller populations harboring lower levels of recessive strongly deleterious variation. Our findings challenge the traditional conservation paradigm that focuses on maximizing genetic diversity in small populations in favor of a view that emphasizes minimizing strongly deleterious variation. These insights have important implications for managing small and isolated populations in the increasingly fragmented landscape of the Anthropocene.
Effective supervision model for improved primary healthcare services: case of Egypt
Authors: Abdel‐Razik Madiha Said , El‐Aguizy Fayrouz , Wahby Ghada , Elsayad Ahmed Samir , Elhabashi Eman Moawad 
Published: December 2020

AbstractBackgroundIn Egypt, primary healthcare workers (PHCWs) often work in challenging situations and in relative isolation from the health system and specialists' experiences. Supervision is currently applied by PHCWs to present practice, control and upgrade knowledge and skills.ObjectivesTo assess the current supervision system in the Ministry of Health and Population (MOHP) at the central, governorate, district, and primary healthcare (PHC) facility levels.MethodsThe research setting is the MOHP‐PHC head quarter (HQ) and five governorates.DesignCross‐sectional analytical observational health system research qualitative and quantitative study of Egyptian health service and operations.SamplingThe multistage sampling technique was used to select districts (n = 25) units (n = 250), physicians (n = 250), and nurses (n = 250) from five randomly selected governorates that represent four Egypt regions.Data collectionFocus group discussions (FGDs) and self‐administered questionnaires.ResultsResponse rate to questionnaires were in total 73% (67% for physicians and 80% for nurses). FGDs demonstrated that PHC has an effective supervision system at central, governorate, and district levels. The effective supervision allowed overcoming barriers related to the shortage in PHCWs needed to cover 5364 PHC units in addition to mobile clinics. Supervisors use a standardized consistent checklist covering all items of service delivery. More than 95% of physicians and nurses appreciated receiving on‐the‐job training from the district supervisory teams.ConclusionEgypt MOHP‐PHC has an effective supervision model in place at the central, governorate and district levels that supports continuous communication between PHC facilities' staff and the health system enabling continuous personal and professional upgrade and development and improved problem‐solving skills at the facility level.
The uncertainty spillovers of China's economic policy: Evidence from time and frequency domains
Authors: Liu Tangyong , Gong Xu , Tang Lizhi 
Published: December 2020

AbstractIn this paper, we investigate the uncertainty spillovers among China's four important economic policies (i.e., fiscal, monetary, trade and exchange rate policy) during the period 2000–2020, based on the spillover framework of Diebold and Yilmaz, The Economic Journal, 2009, 119, 158–171 and Diebold and Yilmaz, International Journal of Forecasting, 2012, 28, 57–66. Considering the heterogeneity of shocks in frequency domain, we also use the frequency methodology of Baruník and Křehlík, Journal of Financial Econometrics, 2018, 16, 271–296. Our results are summarized as follows: (a) the uncertainty spillover between China's different economic policies is high (46.11%) and the low‐frequency spillover (24.90%) is higher than the high‐frequency spillover (19.65%); (b) fiscal policy acts as the mainly uncertainty transmitter on high‐frequency, while monetary policy on low‐frequency; (c) the uncertainty spillover increased in the global financial crisis (2007–2009) and the European debt crisis (2010–2011) and (d) we found that the increase in the former is due to long‐term shocks, while the latter is due to short‐term shocks.
Continuous ropivacaine subfascial wound infusion after cesarean delivery in pain management: A prospective randomized controlled double‐blind study
Authors: Rosetti Jérôme , Francotte Jacques , Noel Emmanuel , Drakopoulos Panagiotis , Rabbachin Nelson , de Brucker Michael 
Published: December 2020

AbstractObjectiveThe aim of this study is to analyze post‐cesarean morphine consumption using continuous ropivacaine subfascial wound infusion.MethodsAfter standardized spinal anesthesia (0.5% hyperbaric bupivacaine 8–10 mg combined with sufentanil 2–2.5 μg), women undergoing cesarean section (n = 69) were randomly allocated to receive either ropivacaine 0.2% (n = 35) or NaCl 0.9% (n = 34) infused through a subfascial wound catheter during 48 h in a multimodal analgesic approach. As primary outcome, opioid use by intravenous patient‐controlled analgesia was analyzed. Secondary outcomes were intensity of pain on visual analog scale at rest and at mobilization, postoperative nausea/vomiting, pruritus and time of first ambulation. Independent t test or Mann–Whitney U test, and Pearson's χ2 test or Fisher's exact test were used as appropriate.ResultsMorphine consumption was significantly lower in the ropivacaine group (21.52 ± 21.56 mg) compared with the placebo group (29.57 ± 22.38 mg; 95% confidence interval −18.8 to 2.76; p = 0.047). No significant differences were observed in pain evaluated by visual analog scale, except for pain at mobilization 6 h after surgery (ropivacaine versus placebo: 3.90 ± 2.66 versus 5.36 ± 2.55; p = 0.030). No significant differences were observed in the incidence of postoperative nausea/vomiting, pruritus, and time of first ambulation.ConclusionContinuous ropivacaine subfascial wound infusion results in less post‐cesarean morphine consumption.EudraCT trail registration number: 2017‐004797‐33.EudraCT link: https://www.clinicaltrialsregister.eu/ctr‐search/trial/2017‐004797‐33/BE#A
Burosumab for the Treatment of Tumor-Induced Osteomalacia
Authors: Jan de Beur Suzanne M , Miller Paul D , Weber Thomas J , Peacock Munro , Insogna Karl , Kumar Rajiv , Rauch Frank , Luca Diana , Cimms Tricia , Roberts Mary Scott , San Martin Javier , Carpenter Thomas O 
Published: December 2020

ABSTRACT
Tumor-induced osteomalacia (TIO) is caused by phosphaturic mesenchymal tumors producing fibroblast growth factor 23 (FGF23) and is characterized by impaired phosphate metabolism, skeletal health, and quality of life. UX023T-CL201 is an ongoing, open-label, phase 2 study investigating the safety and efficacy of burosumab, a fully human monoclonal antibody that inhibits FGF23, in adults with TIO or cutaneous skeletal hypophosphatemia syndrome (CSHS). Key endpoints were changes in serum phosphorus and osteomalacia assessed by transiliac bone biopsies at week 48. This report focuses on 14 patients with TIO, excluding two diagnosed with X-linked hypophosphatemia post-enrollment and one with CSHS. Serum phosphorus increased from baseline (0.52 mmol/L) and was maintained after dose titration from week 22 (0.91 mmol/L) to week 144 (0.82 mmol/L, p &lt; 0.0001). Most measures of osteomalacia were improved at week 48: osteoid volume/bone, osteoid thickness, and mineralization lag time decreased; osteoid surface/bone surface showed no change. Of 249 fractures/pseudofractures detected across 14 patients at baseline, 33% were fully healed and 13% were partially healed at week 144. Patients reported a reduction in pain and fatigue and an increase in physical health. Two patients discontinued: one to treat an adverse event (AE) of neoplasm progression and one failed to meet dosing criteria (receiving minimal burosumab). Sixteen serious AEs occurred in seven patients, and there was one death; all serious AEs were considered unrelated to treatment. Nine patients had 16 treatment-related AEs; all were mild to moderate in severity. In adults with TIO, burosumab exhibited an acceptable safety profile and was associated with improvements in phosphate metabolism and osteomalacia. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..