bluuebunny/crossref_metadata_2025 huggingface dataset:
An algebraic and suboptimal solution of constrained model predictive control via tangent hyperbolic function
Authors: Dursun Ufuk , Yıldız Taşçıkaraoğlu Fatma , Üstoğlu İlker
Published: June 2020

In this paper, we propose a novel method to solve the model predictive control (MPC) problem for linear time‐invariant (LTI) systems with input and output constraints. We establish an algebraic control rule to solve the MPC problem to overcome the computational time of online optimization methods. For this purpose, we express system constraints as a continuous function through the tangent‐hyperbolic function, hence the optimization problem is reformulated. There are two steps for the solution of the optimization problem. In the first step, the optimal control signal is determined by the use of the necessary condition for optimality, assuming that there is only input constraint. In the latter, the solution obtained in the first step is revised to keep the system states in a feasible region. It is shown that the solution is suboptimal. The proposed solution method is simulated for three different sample systems, and the results are compared with the classical MPC, which show that the new algebraic method dramatically reduces the computational time of MPC.
‘Just don’t tell them what’s in it’: Ethics, edible insects and sustainable food choice in schools
Authors: Jones Verity
Published: June 2020

Supporting young people with global crises mitigation strategies is essential, yet loaded with ethical dilemmas for the educator. This study explores whether young people will make ethical decisions regarding the sustainability of food choice in schools, and based on the processes identified, what educators’ needs are in supporting transformative learning. This study is the first of its kind, where young people under the age of 14 have been tasting edible insects and discussing their role in a more sustainable diet. The article draws on mixed‐method research with over 180 young people and their teachers in three schools in Wales and examines responses to a possible introduction of edible insects into school canteens. Highlighted is the complexity of sustainable food choices—likely to be identifiable with other young people and educators in western countries. The article considers how educators and policy makers may need to frame routes to positive sustainable action and the associated impacts these may have on personal, social, political and environmental spheres.
Aggregation‐induced integrated stress response rejuvenates culture‐expanded human mesenchymal stem cells
Authors: Bijonowski Brent M. , Fu Qin , Yuan Xuegang , Irianto Jerome , Li Yan , Grant Samuel C. , Ma Teng
Published: June 2020

Protein homeostasis is critical for cellular function, as loss of homeostasis is attributed to aging and the accumulation of unwanted proteins. Human mesenchymal stem cells (MSCs) have shown promising therapeutic potential due to their impressive abilities to secrete inflammatory modulators, angiogenic, and regenerative cytokines. However, there exists the problem of human MSC expansion with compromised therapeutic quality. Duringin vitro expansion, human MSCs are plated on stiff plastics and undergo culture adaptation, which results in aberrant proliferation, shifts in metabolism, and decreased autophagic activity. It has previously been shown that three‐dimensional (3D) aggregation can reverse some of these alterations by heightening autophagy and recovering the metabolic state back to a naïve phenotype. To further understand the proteostasis in human MSC culture, this study investigated the effects of 3D aggregation on the human MSC proteome to determine the specific pathways altered by aggregation. The 3D aggregates and 2D cultures of human MSCs derived from bone marrow (bMSC) and adipose tissue (ASC) were analyzed along with differentiated human dermal fibroblasts (FB). The proteomics analysis showed the elevated eukaryotic initiation factor 2 pathway and the upregulated activity of the integrated stress response (ISR) in 3D aggregates. Specific protein quantification further determined that bMSC and ASC responded to ISR, while FB did not. 3D aggregation significantly increased the ischemic survival of bMSCs and ASCs. Perturbation of ISR with small molecules salubrinal and GSK2606414 resulted in differential responses of bMSC, ASC, and FB. This study indicates that aggregation‐based preconditioning culture holds the potential for improving the therapeutic efficacy of expanded human MSCs via the establishment of ISR and homeostasis.
Increased metal tolerance and bioaccumulation of zinc and cadmium in Chlamydomonas reinhardtii expressing a AtHMA4 C‐terminal domain protein
Authors: Ibuot Aniefon , Webster Rachel E. , Williams Lorraine E. , Pittman Jon K.
Published: June 2020

The use of microalgal biomass for metal pollutant bioremediation might be improved by genetic engineering to modify the selectivity or capacity of metal biosorption. A plant cadmium (Cd) and zinc (Zn) transporter (AtHMA4) was used as a transgene to increase the ability of Chlamydomonas reinhardtii to tolerate 0.2 mM Cd and 0.3 mM Zn exposure. The transgenic cells showed increased accumulation and internalization of both metals compared to wild‐type. AtHMA4 was expressed either as the full‐length (FL) protein or just the C‐terminal (CT) tail, which is known to have metal‐binding sites. Similar Cd and Zn tolerance and accumulation was observed with expression of either the FL protein or CT domain, suggesting that enhanced metal tolerance was mainly due to increased metal binding rather than metal transport. The effectiveness of the transgenic cells was further examined by immobilization in calcium alginate to generate microalgal beads that could be added to a metal contaminated solution. Immobilization maintained metal tolerance, while AtHMA4‐expressing cells in alginate showed a concentration‐dependent increase in metal biosorption that was significantly greater than alginate beads composed of wild‐type cells. This demonstrates that expressing AtHMA4 FL or CT has great potential as a strategy for bioremediation using microalgal biomass.
Sustainability disclosure and financial analysts' accuracy: The European case
Authors: Ferrer Elena , López‐Arceiz Francisco J. , del Rio Cristina
Published: June 2020

This study aims to analyze whether the adoption of Directive 2014/95/EU on sustainability disclosure has contributed to more truthful reporting to financial analysts in terms of risks and firms' performance. Financial analysts, as requesters of sustainability reports, are expected to have produced more accurate forecasts as a result of this legal reform. To investigate this, we have examined analysts' earnings per share (EPS) forecasts for 434 companies, 241 of which are classified as low sustainability companies, from 2008 to 2017. To detect a possible increase in EPS forecast accuracy after the enforcement of the directive, we perform an analysis based on panel regression specifications. The results show that EPS forecast accuracy has increased due to the higher levels of both sustainability disclosure and reporting quality after the enforcement of Directive 2014/95/EU.
Clinical outcomes among unresectable, locally advanced, and metastatic cutaneous squamous cell carcinoma patients treated with systemic therapy
Authors: Cowey C. Lance , Robert Nicholas J. , Espirito Janet L. , Davies Kalatu , Frytak Jennifer , Lowy Israel , Fury Matthew G.
Published: June 2020

Prior studies of conventional chemotherapy or epidermal growth factor receptor inhibitors for advanced (ie, locally advanced cutaneous squamous cell carcinoma [laCSCC] or metastatic [mCSCC]) cutaneous squamous cell cancer enrolled ≤ 40 patients. This retrospective, observational study assessed real‐world treatment patterns and clinical outcomes in patients with unresectable laCSCC or mCSCC using electronic health records of patients who initiated first‐line (1L) systemic treatment from 1 January 2008 to 31 December 2015, with follow‐up to 30 September 2017. The median duration of follow‐up from 1L treatment was 10.1 months (range 0.03‐67.6 months). Duration of therapy (DOT) and overall survival (OS) were assessed using Kaplan‐Meier analysis. Response rate was calculated as the proportion of patients who achieved physician‐assessed‐response. Eighty‐two patients were identified (17 laCSCC and 65 mCSCC). Median age at 1L treatment initiation was 75 years; 85% were male, 88% had an Eastern Cooperative Oncology Group performance status of 1, and 84% had received radiotherapy. The most common 1L regimens were carboplatin + paclitaxel (27%) and cetuximab monotherapy (24%). The median 1L DOT was 4.1 months for laCSCC and 2.3 months for mCSCC. The physician‐assessed response rate for 1L therapy was 17.6% for laCSCC, and 18.5% for mCSCC. The median OS from 1L treatment initiation was 16.2 months for laCSCC, and 15.3 months for mCSCC. Only 24 patients (29%) received second‐line therapy. This is the largest retrospective data set regarding patients with advanced CSCC treated with anticancer systemic therapy prior to approval of the anti‐programmed cell death‐1 antibody, cemiplimab. Efficacy was low in both laCSCC and mCSCC. These data provide historic benchmarks for outcomes in patients with advanced CSCC prior to Food and Drug Administration approval of cemiplimab‐rwlc.
Financial Impact of Abusive Head Trauma to Age 17
Authors: Steinbeigle Ryan , Barr Marilyn , Barr Ronald G. , Miller Ted R.
Published: June 2020

In order to illustrate the medical and financial impact arising from the care of a severely injured victim of abusive head trauma (AHT) from incident through to adulthood, a complete review of all medical financial files for the injured child beginning at the time custody of the child was transferred to the paternal grandparents (2.5 months of age) through to age 17 was conducted. Cost data were extracted from the insurance explanation of benefits or the family's bank statements. Costs were divided into seven categories and adjusted for inflation using the gross domestic product medical care deflator. Medical costs from 2.5 months to 18 years of age totaled $261 499, with $106 607 of out‐of‐pocket expenditures by the child's paternal grandparents and $154 892 covered by insurance. Costs were highly variable from year to year as reflected in the standard deviation of annual costs of $16 877. The cost of caring for a seriously injured victim of AHT is substantial. The costs may be highly variable and unpredictable from year to year making it difficult for families to plan financially.

Key Practitioner Messages

The financial impact of AHT on a family can be substantial and unaffordable.

The financial impact for a family varies wildly from year to year.

The often unaffordability of caring for a victim of AHT limits the quality and access to care in households with lower incomes.
Uncovering Biological Application of Brazilian Green Propolis: A Phenotypic Screening againstSchistosoma mansoni
Authors: A. de L. Paula Lucas , Santos Mario F. C. , Pagotti Mariana C. , Faleiros Renata , Ramos Henrique P. , Veneziani Rodrigo C. S. , Bastos Jairo K. , Caffrey Conor R. , Ambrosio Sérgio R. , Magalhães Lizandra G.
Published: June 2020

The chemotherapy of schistosomiasis remains centered in the use of praziquantel, however, there has been growing resistant parasites to this drug. Thus, the aim of this work was to evaluatein vitroschistosomicidal activity of the hexanes/dichloromethane 1 : 1 extract of Brazilian green propolis (Pex), as well as its major isolated compounds artepillin C, caffeic acid, coumaric acid and drupanin againstSchistosoma mansoni. The Pex was active by displaying an IC50value of 36.60 (26.26–51.13) μg mL−1at 72 h against adult worms ofS. mansoni. The major isolated compounds were inactive with IC50values >100 μM, however, the combination of the isolated compounds (CM) in the same range found in the extract was active with an IC50value of 41.17 (39.89–42.46) μg mL−1at 72 h. Pex and CM induced alteration in the tegument ofS. mansoni, and caffeic acid caused alteration in egg's maturation. Pex displayedin vitroactivity against adult worms’ and eggs’ viability ofS. mansoni, which opens new perspectives to better understand the synergistic and/or additive effects promoted by both Pex extract and CM against schistosomiasis features.
European Bifurcation Club white paper on stenting techniques for patients with bifurcated coronary artery lesions
Authors: Burzotta Francesco , Lassen Jens Flensted , Louvard Yves , Lefèvre Thierry , Banning Adrian P. , Daremont Olivier , Pan Manuel , Hildick‐Smith David , Chieffo Alaide , Chatzizisis Yiannis S. , Džavík Vladimír , Gwon Hyeon‐Cheol , Hikichi Yutaka , Murasato Yoshinobu , Koo Bon Kwon , Chen Shao‐Liang , Serruys Patrick , Stankovic Goran
Published: June 2020

Background

Defining the optimal conduction of percutaneous‐coronary‐intervention (PCI) to treat bifurcation lesions has been the subject of many clinical studies showing that the applied stenting technique may influence clinical outcome. Accordingly, bifurcation stenting classifications and technical sequences should be standardized to allow proper reporting and comparison.

Methods

The European Bifurcation Club (EBC) is a multidisciplinary group dedicated to optimize the treatment of bifurcations and previously created a classification of bifurcation stenting techniques that is based on the first stent implantation site. Since some techniques have been abandoned, others have been refined and dedicated devices became available, EBC promoted an international task force aimed at updating the classification of bifurcation stenting techniques as well as at highlighting the best practices for most popular techniques. Original descriptive images obtained by drawings, bench tests and micro‐computed‐tomographic reconstructions have been created in order to serve as tutorials in both procedure reporting and clinical practice.

Results

An updated Main‐Across‐Distal‐Side (MADS)‐2, classification of bifurcation stenting techniques has been realized and is reported in the present article allowing standardized procedure reporting in both clinical practice and scientific studies. The EBC‐promoted task force deeply discussed, agreed on and described (using original drawings and bench tests) the optimal steps for the following major bifurcation stenting techniques: (a) 1‐stent techniques (“provisional” and “inverted provisional”) and (b) 2‐stent techniques (“T/TAP,” “culotte,” and “DK‐crush”).

Conclusions

The present EBC‐promoted paper is intended to facilitate technique selection, reporting and performance for PCI on bifurcated lesions during daily clinical practice.
Myocardial ischemia due to a recanalized chronic coronary thrombus: Angiographic and optical coherence tomography imaging insights
Authors: Sacchetta Giorgio , Scalise Renato Francesco Maria , Garcia Ruiz Victoria , Barrano Giombattista , Garro Nadia , Costa Francesco , Contarini Marco
Published: June 2020

Chronic organized thrombus as a result of prior untreated myocardial infarction can determine myocardial ischemia. This entity appears as an angiographically irregular and hazy image; optical coherence tomography is useful to evaluate these ambiguous lesions and guide interventional treatment.
Meadow fescue seeding rate impacts mixtures with alfalfa on marginal sites
Authors: Cherney J.H. , Cherney D.J.
Published: June 2020

Alfalfa (Medicago sativa L.)–grass mixtures are often used to provide high‐quality dairy forage in the northeastern United States. Meadow fescue (Festuca pratensis Huds.) is popular as a companion for alfalfa in the region because of its high nutritive value. We aimed to evaluate alfalfa–meadow fescue mixtures in northern environments that are unsuited to alfalfa production. Our study was conducted in the year after seeding at two northern New York sites. A reduced‐lignin [fall dormancy (FD) = 4] and a conventional alfalfa (FD = 3) were seeded with diploid and tetraploid meadow fescue varieties in replicated plots, with five seeding rates for meadow fescue. Dry matter yield increased linearly with increased meadow fescue seeding rate. The meadow fescue percentage of mixtures had a curvilinear response to meadow fescue seeding rate, increasing from 44% at the 0.5 lb acre–1 seeding rate to 67.4% at the 4 lb acre–1 rate. Tetraploid meadow fescue had a smaller grass percentage in mixtures and higher nutritive value than a diploid meadow fescue. Reduced‐lignin alfalfa was not greatly different in nutritive value from a conventional cultivar under unfavorable environmental conditions for alfalfa production. We conclude that meadow fescue should be seeded at a very low rate (1 lb acre–1) with alfalfa in northern environments that are unsuitable for alfalfa. Moreover, reduced‐lignin alfalfa (FD = 4) may not result in large increases in nutritive value compared with conventional cultivars selected for high nutritive value on marginal northern sites better suited to FD 3 cultivars.
Opening the Third Century of Polyhalide Chemistry: Thermally Stable Complex with “Trapped” Dichlorine
Authors: Usoltsev Andrey N. , Adonin Sergey A. , Kolesov Boris A. , Novikov Alexander S. , Fedin Vladimir P. , Sokolov Maxim N.
Published: June 2020

Unlike polyhalides of heavier halogens, polychlorides still remain exotic curiosities. Herein, we report preparation and investigation of complexes Cat2{[TeCl6](Cl2)} (cat=1‐methylpyridinium (1) and tetramethylammonium (2)) where dichlorine units are “trapped” by chlorotellurate(IV) anions via a system of non‐covalent Cl⋅⋅⋅Cl interactions. Complex 2 reveals a record thermal stability (>100 °C) for inclusion compounds with Cl2, indications that such compounds can be used as solid Cl2 source.
Functionalized Cannabinoid Subtype 2 Receptor Ligands: Fluorescent, PET, Photochromic and Covalent Molecular Probes
Authors: Basagni Filippo , Rosini Michela , Decker Michael
Published: June 2020

Cannabinoid subtype 2 receptors (CB2Rs) are G protein‐coupled receptors (GPCRs) belonging to the endocannabinoid system, a complex network of signalling pathways leading to the regulation of key physiological processes. Interestingly, CB2Rs are strongly up‐regulated in pathological conditions correlated with the onset of inflammatory events like cancer and neurodegenerative diseases. Therefore, CB2Rs represent an important biological target for therapeutic as well as diagnostic purposes. No CB2R‐selective drugs are yet on the market, thus underlining a that deeper comprehension of CB2Rs’ complex activation pathways and their role in the regulation of diseases is needed. Herein, we report an overview of pharmacological and imaging tools such as fluorescent, positron emission tomography (PET), photochromic and covalent selective CB2R ligands. These molecular probes can be used in vitro as well as in vivo to investigate and explore the unravelled role(s) of CB2Rs, and they can help to design suitable CB2R‐targeted drugs.
Hybrid molecules based on 1,3,5‐triazine as potential therapeutics: A focused review
Authors: Prasher Parteek , Sharma Mousmee , Aljabali Alaa A. A. , Gupta Gaurav , Negi Poonam , Kapoor Deepak N. , Singh Inderbir , Zacconi Flavia C. , de Jesus Andreoli Pinto Terezinha , da Silva Mateus Webba , Bakshi Hamid A. , Chellappan Dinesh Kumar , Tambuwala Murtaza M. , Dua Kamal
Published: June 2020

Majority of the representative drugs customarily interact with multiple targets manifesting unintended side effects. In addition, drug resistance and over expression of the cellular efflux‐pumps render certain classes of drugs ineffective. With only a few innovative formulations in development, it is necessary to identify pharmacophores and novel strategies for creating new drugs. The conjugation of dissimilar pharmacophoric moieties to design hybrid molecules with an attractive therapeutic profile is an emerging paradigm in the contemporary drug development regime. The recent decade witnessed the remarkable biological potential of 1,3,5‐triazine framework in the development of various chemotherapeutics. The appending of the 1,3,5‐triazine nucleus to biologically relevant moieties has delivered exciting results. The present review focuses on 1,3,5‐triazine based hybrid molecules in the development of pharmaceuticals.
Evaluation of longitudinal steroid profiling with the ADAMS adaptive model for detection of transdermal, intramuscular, and subcutaneous testosterone administration
Authors: Nair Vinod S. , Husk Jacob , Miller Geoffrey D. , van Eenoo Peter , Crouch Andre , Eichner Daniel
Published: June 2020

The steroidal module of the Athlete Biological Passport (ABP) has been used since 2014 for the longitudinal monitoring of urinary testosterone and its metabolites in order to identify samples suspicious for the use of synthetic forms of endogenous anabolic androgenic steroids (EAAS). Samples identified by the module may then be confirmed by isotope ratio mass spectrometry (IRMS) to establish clearly the exogenous origin of testosterone and/or metabolites in the sample. To examine the detection capability of the steroidal ABP model, testosterone administration studies were performed with various doses and three routes of administration – transdermal, intramuscular, and subcutaneous with 15 subjects for each route of administration. Urine samples were collected before, during, and after administration and steroid profiles were analyzed using the steroidal ABP module in ADAMS. A subset of samples from each mode of administration was also analyzed by IRMS. The steroidal ABP module was more sensitive to testosterone use than population‐based thresholds and with high dose administrations there was very good agreement between the IRMS results and samples flagged by the module. However, with low dose administration the ABP module was unable to identify samples where testosterone use was still detectable by IRMS analysis. The testosterone/epitestosterone (T/E) ratio was the most diagnostic parameter for longitudinal monitoring with the exception of low testosterone excretors for whom the 5α‐androstane‐3α, 17β‐diol/epitestosterone (5αAdiol/E) ratio may provide more sensitivity.
River food chains lead to riparian bats and birds in two mid‐order rivers
Authors: Jackson Breeanne K. , Stock Sarah L. , Harris Leila S. , Szewczak Joseph M. , Schofield Lynn N. , Desrosiers Michelle A.
Published: June 2020

River regulation can modify natural flow regimes with deleterious effects on aquatic communities. While the effects of flow manipulation on the physical environment and populations and assemblages of aquatic organisms have been described thoroughly, how and to what extent river regulation influences ecosystem processes like food web architecture is less studied. Emergent aquatic insect prey can provide an important food resource to riparian consumers like birds and bats with concomitant consequences for nutrient cycling through aquatic–terrestrial food webs, thus potentially increasing the spatial influence of river regulation into the riparian zone and beyond. We used naturally abundant stable isotopes of carbon and nitrogen to compare food web architecture (trophic position and reliance on an aquatic nutritional pathway) leading to birds and bats between a regulated river, the Tuolumne River downstream of Hetch Hetchy Reservoir, and an adjacent unregulated river, the Merced River, located in Yosemite National Park on the west slope of the Sierra Nevada, California, USA. We found that both birds and bats derived >50% of their nutrition from food webs originating in photosynthesis by algae. In addition, birds and bats occupied a similar trophic position to predatory fish in other systems. Both birds and bats seemed to rely more strongly on an aquatic nutritional pathway during the dryer year of our study period, underscoring the potential importance of emergent aquatic prey as a water subsidy in dry systems and in dry years. In the Tuolumne River, reservoir managers strive to simulate characteristics of the natural flow regime, including seasonal scouring flows and prolonged floodplain inundation. Although we found no conclusive evidence of an effect of river regulation on food web responses, our study suggests that nutrient cycling through aquatic–terrestrial food webs expands the potential influence of river regulation to organisms and ecosystems typically characterized as terrestrial.
Highly competent native snake hosts extend the range of an introduced parasite beyond its invasive Burmese python host
Authors: Miller Melissa A. , Kinsella John M. , Snow Ray W. , Falk Bryan G. , Reed Robert N. , Goetz Scott M. , Mazzotti Frank J. , Guyer Craig , Romagosa Christina M.
Published: June 2020

Invasive Burmese pythons (Python bivittatus) have introduced a nonnative pentastomid parasite (Raillietiella orientalis) to southern Florida that has spilled over to infect native snakes. However, the extent of spillover, regarding prevalence and intensity, is unknown. We examined native snakes (n = 523) and invasive pythons (n = 1003) collected from Florida to determine the degree to which parasite spillover is occurring. We found R. orientalis has infected 13 species of native snakes collected from areas of sympatry with pythons. Prevalence and infection intensity of R. orientalis were significantly higher among native snakes compared with pythons. Moreover, adult female pentastomes achieved larger sizes and represented a greater proportion of the overall parasite population in native snakes vs. pythons, indicating native snakes are more competent hosts of R. orientalis than pythons. We also examined native snakes from regions of allopatry with pythons to determine how far R. orientalis has spread. We found an infected native snake 348 km north of the northernmost infected python. Our data show that native snakes are highly competent hosts of R. orientalis and have facilitated the rapid spread of this nonnative pentastome beyond the range of its invasive host.
Statin intensity and risk for cardiovascular events after heart transplantation
Authors: Golbus Jessica R. , Adie Sarah , Yosef Matheos , Murthy Venkatesh L. , Aaronson Keith D. , Konerman Matthew C.
Published: June 2020

Aims

Statins improve survival and reduce rejection and cardiac allograft vasculopathy after heart transplantation (HT). The impact of different statin intensities on clinical outcomes has never been assessed. We set out to determine the impact of statin exposure on cardiovascular outcomes after HT.

Methods and results

We performed a retrospective study of 346 adult patients who underwent HT from 2006 to 2018. Statin intensity was determined longitudinally after HT based on American College of Cardiology/American Heart Association (ACC/AHA) guidelines. The primary outcome was the time to the first primary event defined as the composite of heart failure hospitalization, myocardial infarction, revascularization, and all‐cause mortality. Secondary outcomes included time to significant rejection and time to moderate–severe cardiac allograft vasculopathy. Adverse events were evaluated for subjects on high‐intensity statin therapy. A Cox proportional hazards model was used to evaluate the relationship between clinical variables, statin intensity, and outcomes. Most subjects were treated with low‐intensity statin therapy although this declined from 89.9% of the population at 1month after HT to 42.8% at 5years after HT. History of ischaemic cardiomyopathy, significant acute rejection, older donor age, and lesser statin intensity (p ≤ 0.001) were associated with reduced time to the primary outcome in a multivariable Cox model. Greater intensity of statin therapy was most beneficial early after HT. There were no statin‐related adverse events for the 14 subjects on high‐intensity statin therapy.

Conclusions

Greater statin intensity was associated with a reduction in adverse cardiovascular outcomes after HT.
Mortality and pathophysiology of acute kidney injury according to time of occurrence in acute heart failure
Authors: Diebold Matthias , Kozhuharov Nikola , Wussler Desiree , Strebel Ivo , Sabti Zaid , Flores Dayana , Shrestha Samyut , Martin Jasmin , Staub Daniel , Venge Per , Mueller Christian , Breidthardt Tobias
Published: June 2020

Aims

Acute kidney injury (AKI) during acute heart failure (AHF) is common and associated with increased morbidity and mortality. The underlying pathophysiological mechanism appears to have prognostic relevance; however, the differentiation of true, structural AKI from hemodynamic pseudo‐AKI remains a clinical challenge.

Methods and results

The Basics in Acute Shortness of Breath Evaluation Study (NCT01831115) prospectively enrolled adult patients presenting with AHF to the emergency department. Mortality of patients was prospectively assessed. Haemoconcentration, transglomerular pressure gradient (n = 231) and tubular injury patterns (n = 253) were evaluated to investigate pathophysiological mechanisms underlying AKI timing (existing at presentation vs. developing during in‐hospital period). Of 1643 AHF patients, 755 patients (46%) experienced an episode of AKI; 310 patients (19%; 41% of AKI patients) presented with community‐acquired AKI (CA‐AKI), 445 patients (27%; 59% of AKI patients) developed in‐hospital AKI. CA‐AKI but not in‐hospital AKI was associated with higher mortality compared with no‐AKI (adjusted hazard ratio 1.32 [95%‐CI 1.01–1.74]; P = 0.04). Independent of AKI timing, haemoconcentration was associated with a lower two‐year mortality. Transglomerular pressure gradient at presentation was significantly lower in CA‐AKI compared to in‐hospital AKI and no‐AKI (P < 0.01). Urinary NGAL ratio concentrations were significantly higher in CA‐AKI compared to in‐hospital AKI (P < 0.01) or no‐AKI (P < 0.01).

Conclusions

CA‐AKI but not in‐hospital AKI is associated with increased long‐term mortality and marked by decreased transglomerular pressure gradient and tubular injury, probably reflecting prolonged tubular ischemia due to reno‐venous congestion. Adequate decongestion, as assessed by haemoconcentration, is associated with lower long‐term mortality independent of AKI timing.
Diagnosis of isolated cardiac sarcoidosis based on new guidelines
Authors: Kawai Hideki , Sarai Masayoshi , Kato Yasuchika , Naruse Hiroyuki , Watanabe Ayumi , Matsuyama Takahiro , Takahashi Hiroshi , Motoyama Sadako , Ishii Junnichi , Morimoto Shin‐ichiro , Toyama Hiroshi , Ozaki Yukio
Published: June 2020

Aims

In the updated guidelines for cardiac sarcoidosis (CS) proposed by the Japanese Circulation Society (JCS), the definition of isolated CS (iCS) was established for the first time. This prompted us to examine the characteristics of patients with CS including iCS according to them by reviewing patients undergoing 18F‐fluoro‐2‐deoxyglucose positron‐emission tomography/computerized tomography (FDG‐PET/CT), compared with those with CS determined by the conventional international criteria.

Methods and results

From 2013 to 2019, 94 patients (61 ± 15 years, 50 female patients) with suspected CS underwent whole‐body and cardiac FDG‐PET/CT scanning. In contrast to 22 patients with CS based on the international criteria, 34 [27 with systemic sarcoidosis including cardiac involvement (sCS) and 7 with clinical iCS] were diagnosed with CS according to the new JCS guidelines (P = 0.012), and 60 were not (4 suspected iCS, 13 systematic sarcoidosis without cardiac involvement, and 43 no sarcoidosis). In addition to 26 of 34 patients with CS, corticosteroids were also started in 6 of 60 without CS according to clinical need.

Conclusions

Diagnostic yield with the new JCS guidelines was higher, with approximately 1.5‐fold of the patients diagnosed with CS compared with the previous international criteria and clinical iCS accounting for approximately 20% of the whole CS cohort. In addition to 75% of the patients with sCS or clinical iCS in the updated guidelines, 10% in whom CS was not documented were also started on corticosteroids for clinical indications such as reduced cardiac function or arrhythmia.
Long‐term impact of new‐onset atrial fibrillation complicating acute myocardial infarction on heart failure
Authors: Luo Jiachen , Xu Siling , Li Hongqiang , Li Zhiqiang , Liu Baoxin , Qin Xiaoming , Gong Mengmeng , Shi Beibei , Wei Yidong
Published: June 2020

Aims

New‐onset atrial fibrillation (NOAF) complicating acute myocardial infarction (AMI) has been associated with poor survival, but the clinical implication of NOAF on heart failure (HF) is still not well characterized. We aimed to investigate the relationship between NOAF complicating AMI and HF hospitalization.

Methods and results

Adult AMI patients identified in the New‐Onset Atrial Fibrillation Complicating Acute Myocardial Infarction in Shanghai registry who, discharged alive, had complete echocardiography and follow‐up data from February 2014 to March 2018 were included. Patients were divided according to the presence of NOAF. The outcome measures were HF hospitalization and death during the observational period (until 10 April 2019). Cox proportional hazard models were performed in the whole population and propensity score‐matched (PSM) cohort to assess the adjusted hazard ratio (HR) and 95% confidence interval (CI). Overall, 2075 patients (mean age: 65.2 ± 12.3 years, 77.3% were men) with AMI were analysed, of whom 228 (11.0%) developed NOAF. Advanced age, admission HF (Killip II–IV), impaired renal function, decreased left ventricular ejection fraction, increased heart rate, and left atrial enlargement were independent predictors of NOAF. Over a median observational period of 2.7 years, the annual incidence rates of HF hospitalization were 18.4% and 2.8% for patients with NOAF and sinus rhythm, respectively. After adjustment for confounders, NOAF was significantly associated with HF hospitalization (HR: 3.14, 95% CI: 2.30–4.28, P < 0.001). Similar results were obtained when accounting for the competing risk of all‐cause death (subdistribution HR: 3.06, 95% CI: 2.18–4.30, P < 0.001) or from the PSM cohort (HR: 2.82, 95% CI: 1.99–4.00, P < 0.001). Patients with persistent NOAF (HR: 5.81, 95% CI: 3.59–9.41) were at significantly higher risk of HF hospitalization when compared with those with transient one (HR: 2.61, 95% CI: 1.84–3.70, P interaction = 0.008). Although post‐MI NOAF was significantly related to cardiovascular death (annual incidence rates for NOAF and sinus rhythm were 9.4% and 2.3%, respectively; HR: 1.97, 95% CI: 1.36–2.85, P < 0.001), such an association was attenuated when HF hospitalization (modelled as a time‐varying covariate) and antithrombotic treatment were adjusted (HR: 1.37, 95% CI: 0.92–2.02, P = 0.121).

Conclusions

In patients with AMI, NOAF is strongly associated with an increased long‐term risk of HF hospitalization. Our findings suggest that strengthened secondary prevention of HF should be considered in this high‐risk population.
Synthesis of Non‐Symmetric Ruthenium(II) POCOP Pincer Complexes and Their Bimetallic Derivatives by π‐Coordination of Arenophile Fragments
Authors: Roque‐Ramires Manuel A. , Shen Longzhu , Le Lagadec Ronan
Published: June 2020

A series of neutral 16‐electron square pyramidal ruthenium(II) complexes of the general formula [Ru(POCOP)(X)(CO)] (X = Cl, H) have readily been obtained in good yields from [RuCl2(COD)]n and different POCOP pincer ligands based on the naphthoresorcinate backbone. The molecular structure of two of the compounds was unequivocally determined by single‐crystal X‐ray diffraction, showing different stereochemistries upon the coordination of chloride or hydride ligand. The observed discrepancies are explained by DFT calculations. The regiospecific η6‐coordination of a second 12‐electron organometallic fragment on the exo aromatic ring of the POCOP pincer ligand was achieved under mild conditions, and the corresponding [(MLn)Ru(POCOP)(X)(CO)]PF6 (MLn = [RuCp]+, [RuCp*]+ and [FeCp*]+) bimetallic sandwich‐like species were obtained as air‐stable solids.
Synthesis and Conformational Analysis of 2‐O‐Silyl Protected Nucleosides from Unprotected Nucleobases and Sugar Epoxides
Authors: Ahmed Ajaz , Rasool Faheem , Singh Gurpreet , Katoch Meenu , Mukherjee Debaraj
Published: June 2020

Synthesis of orthogonally protected 2‐silyl nucleosides were achieved by trans opening of sugar epoxides with nucleobases catalyzed by trimethylsilyltrifluoromethanesulfonate using hexamethyldisilazane both as solvent and silylating agent. Both α and β nucleosides were obtained with complete stereocontrol only by changing the epoxide stereochemistry. The synthesized nucleosides exist in different chair conformations depending upon the nature of protecting groups present in the sugar moiety as determined from coupling constants in the proton NMR. All the synthesized nucleosides were screened for biofilm inhibition activity against four bacterial pathogens and compound 7c was found to be most potent against Salmonella typhimurium with 1.22 µm biofilm inhibitory activity taking ciprofloxacin as control.
Subacute cannabidiol alters genome‐wide DNA methylation in adult mouse hippocampus
Authors: Wanner Nicole M , Colwell Mathia , Drown Chelsea , Faulk Christopher
Published: June 2020

Use of cannabidiol (CBD), the most abundant non‐psychoactive compound found in cannabis (Cannabis sativa), has recently increased as a result of widespread availability of CBD‐containing products. CBD is FDA‐approved for the treatment of epilepsy and exhibits anxiolytic, antipsychotic, prosocial, and other behavioral effects in animal studies and clinical trials, however, the underlying mechanisms governing these phenotypes are still being elucidated. The epigenome, particularly DNA methylation, is responsive to environmental input and can govern persistent patterns of gene regulation affecting phenotype across the life course. In order to understand the epigenomic activity of cannabidiol exposure in the adult brain, 12‐week‐old male wild‐type a/a Agouti viable yellow (Avy) mice were exposed to either 20 mg/kg CBD or vehicle daily by oral administration for 14 days. Hippocampal tissue was collected and reduced‐representation bisulfite sequencing (RRBS) was performed. Analyses revealed 3,323 differentially methylated loci (DMLs) in CBD‐exposed animals with a small skew toward global hypomethylation. Genes for cell adhesion and migration, dendritic spine development, and excitatory postsynaptic potential were found to be enriched in a gene ontology term analysis of DML‐containing genes, and disease ontology enrichment revealed an overrepresentation of DMLs in gene sets associated with autism spectrum disorder, schizophrenia, and other phenotypes. These results suggest that the epigenome may be a key substrate for CBD's behavioral effects and provides a wealth of gene regulatory information for further study.
Roles of Chk2/CHEK2 in guarding against environmentally induced DNA damage and replication‐stress
Authors: Mustofa Md. Kawsar , Tanoue Yuki , Tateishi Chie , Vaziri Cyrus , Tateishi Satoshi
Published: June 2020

Checkpoint kinase 2 (human CHEK2; murine Chk2) is a critical mediator of the DNA damage response and has established roles in DNA double strand break (DSB)‐induced apoptosis and cell cycle arrest. DSBs may be invoked directly by ionizing radiation but may also arise indirectly from environmental exposures such as solar ultraviolet (UV) radiation. The primary forms of DNA damage induced by UV are DNA photolesions (such as cyclobutane pyrimidine dimers CPD and 6‐4 photoproducts) which interfere with DNA synthesis and lead to DNA replication fork stalling. Persistently stalled and unresolved DNA replication forks can “collapse” to generate DSBs that induce signaling via Chk2 and its upstream activator the ataxia telangiectasia‐mutated (ATM) protein kinase. This review focuses on recently defined roles of Chk2 in protecting against DNA replication‐associated genotoxicity. Several DNA damage response factors such as Rad18, Nbs1 and Chk1 suppress stalling and collapse of DNA replication forks. Defects in the primary responders to DNA replication fork stalling lead to generation of DSB and reveal “back‐up” roles for Chk2 in S‐phase progression and genomic stability. In humans, there are numerous variants of the CHEK2 gene, including CHEK2*1100delC. Individuals with the CHEK2*1100delC germline alteration have an increased risk of developing breast cancer and malignant melanoma. DNA replication fork‐stalling at estrogen‐DNA adducts and UV‐induced photolesions are implicated in the etiology of breast cancer and melanoma, respectively. It is likely therefore that the Chk2/CHEK2‐deficiency is associated with elevated risk for tumorigenesis caused by replication‐associated genotoxicities that are exacerbated by environmental genotoxins and intrinsic DNA‐damaging agents.
Fuzzy reliability‐redundancy allocation problem of the overspeed protection system
Authors: Taghiyeh Sajjad , Mahmoudi Morteza , Fadaie Saber , Tohidi Hossein
Published: June 2020

System reliability is defined as the probability of satisfactory performance of a system under stated conditions for a specified period of time. According to this definition, four parameters, including probability, satisfactory performance, specific conditions, and time should be exactly characterized to evaluate the system reliability accurately. However, due to the uncertainty involved in real situations, it is hardly possible to assess the aforementioned parameters precisely. In this article, two general and distinct approaches, including Zadeh's extension principle and modification of fuzzy parametric programming (FPP), are proposed to take into account such uncertainty in a famous reliability problem called the overspeed protection system. According to Zadeh's extension principle, a pair of nonlinear programming problems is formulated to compute α‐level cuts of fuzzy system reliability. The membership function of fuzzy system reliability can then be constructed analytically by numerating different values of α. This fuzzy system reliability presents flexibility for further system analysis. In the second approach, from a different point of view, a variant of FPP is improved that provides a crisp value as a system reliability measure. The rewarding point of the latter procedure is to handle the problem in a computationally easier way.
Duration of untreated eating disorder and relationship to outcomes: A systematic review of the literature
Authors: Austin Amelia , Flynn Michaela , Richards Katie , Hodsoll John , Duarte Tiago Antunes , Robinson Paul , Kelly Jonathan , Schmidt Ulrike
Published: June 2020

Objective

This systematic review assesses the average duration of untreated eating disorder (DUED) in help‐seeking populations at the time of first eating disorder (ED) treatment and investigates the relationship between DUED and symptom severity/clinical outcomes.

Method

PRISMA guidelines were followed throughout. Selected studies provided information on either: (i) length of DUED, (ii) components of DUED, (iii) cross‐sectional associations between DUED and symptom severity, (iv) associations between DUED and clinical outcomes, or (v) experimental manipulation of DUED. Study quality was assessed.

Results

Fourteen studies from seven countries were included. Across studies, average DUED weighted by sample size was 29.9 months for anorexia nervosa, 53.0 months for bulimia nervosa and 67.4 months for binge eating disorder. A younger age at time of first treatment was indicative of shorter DUED. Retrospective studies suggest that a shorter DUED may be related to a greater likelihood of remission. Manipulation of DUED by shortening service‐related delays may improve clinical outcomes.

Conclusions

Data on length of DUED provide a benchmark for early intervention in EDs. Preliminary evidence suggests DUED may be a modifiable factor influencing outcomes in EDs. To accurately determine the role of DUED, definition and measurement must be uniformly operationalised.

Highlights

This systematic review is the first to examine duration of untreated eating disorder (DUED) across different eating disorders. Definitions and measurement of DUED and its components vary considerably between studies.

Across different eating disorders average DUED weighted by sample size ranges from approximately two and a half years (for anorexia nervosa) to nearly 6 years (for binge eating disorder).

DUED appears to be related to age such that younger patients have shorter DUED.
Detrital zircon U–Pb–Hf data from Cambrian sandstones of the Ougarta Mountains Algeria: Implication for palaeoenvironment
Authors: Wang Qian , Spencer Christopher J. , Hamdidouche Rachid , Zhao Guochun , Evans Noreen J. , McDonald Bradley J.
Published: June 2020

We report new detrital zircon U–Pb ages and Hf isotopic signatures of detrital zircons in Cambrian sedimentary rocks from the Ougarta Mountains of Algeria in the West African Craton (WAC) in order to provide constraints on the palaeo‐catchments of the Early Palaeozoic river systems draining Gondwana. The Cambrian sedimentary samples from the Ougarta Mountains have near‐identical age spectra with a dominant age peak at 618 Ma and an additional age peak at 2,035 Ma. The oldest detrital zircon grain is 3,407 Ma. The εHf(t) values of the 618 Ma age peak spans from εHf(t) +12 to −25 with a dominant mode at −1; the εHf(t) of the Palaeoproterozoic zircon ranges from 6 to −27 with an average of −10; the pre‐2,300 Ma zircon Hf lie along a crustal evolution trajectory (176Lu/177Hf = 0.01) back to the depleted mantle at ~3,100 Ma. The maximum depositional age of the sandstones in the Sebkhet el Melah Formation is constrained by the youngest detrital zircon age of 559 ± 13 Ma and by the underlying volcaniclastic rocks dated at 555 ± 7 Ma (Late Ediacaran to the Early Cambrian). The 618 and 2,035 Ma age peaks are consistent with a proximal provenance from the WAC, and it is possible that recycling of eroded material from the Cadomian arc and Pan‐African rocks may have been a potential source of the Ediacaran detrital zircons analysed herein. There were four (0.9%) Stenian detrital zircons identified in this study, and our results are consistent with the lack of WAC Stenian detrital zircon noted in previous studies, except those reported from a single Middle Cambrian sample in Morocco. Correlative sedimentary successions further to the east contain ubiquitous ca. 1.0 Ga detrital zircon that was likely supplied from the Trans‐Gondwana Mountain chain. It is noteworthy that the WAC and Sahara Metacraton are surrounded on three sides by Neoproterozoic orogenic systems, with the Rokelide, Dahomeyide, Pharuside, Anti‐Atlas, and Brasiliano orogens (reconstructed position from Gondwana palaeogeography) around the WAC and the Dahomeyide, Pharuside, East African orogen, and Oubangides orogens around the Sahara Metacraton. We posit these orogenic belts acted as drainage divides that controlled sediment routing pathways. Additionally, the occurrence of Stenian detrital zircon in Morocco could be explained by longshore drift coming from the east (present‐day coordinates).