bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantification of Environmental DNA (eDNA) shedding and decay rates for three commercially harvested fish species and comparison between eDNA detection and trawl catches
Authors: Kirtane Anish , Wieczorek Daniel , Noji Thomas , Baskin Liza , Ober Claire , Plosica Riley , Chenoweth Ashley , Lynch Katie , Sassoubre Lauren
Published: July 2021

Stock assessments are critical to inform decisions for sustainable fisheries management. Environmental DNA (eDNA) analysis is a potential tool for assessing fish biomass and populations to aid in stock assessments. To facilitate modeling of biomass based on eDNA data, shedding and decay rates are needed. We designed species‐specific, probe‐based qPCR assays for three economically important fish species: black sea bass (Centropristis striata), winter flounder (Pseudopleuronectes americanus), and summer flounder (Paralichthys dentatus). Winter flounder eDNA was measured using two qPCR assays (135 and 292 bp). We report the eDNA shedding and decay rates and the associated variability from two replicate experimental systems. The eDNA decay rates were not significantly different between all species. The eDNA shedding rates between the two replicate systems were significantly different for winter flounder (135 bp assay) and summer flounder. qPCR amplicon length did not affect the eDNA decay rates for winter flounder. The three new qPCR assays were tested in environmental waters alongside traditional trawl surveys. No eDNA from BSB, WF, or SF was detected by eDNA methods, and out of 13 bottom trawls over 6 days only 1 WF, 1 SF, and 2 BSB were caught. This research presents three new, efficient qPCR assays and shows agreement between eDNA methods and trawl surveys suggesting low abundance or absence of target fish.
Executive functions and depressive symptoms interplay in binge eating disorder: A structural equation model analysis
Authors: Rania Marianna , Aloi Matteo , de Filippis Renato , Carbone Elvira Anna , Caroleo Mariarita , De Fazio Pasquale , Segura‐Garcia Cristina
Published: July 2021

Objective

Executive functions (EF) have been so far investigated as potential endophenotypes for binge eating disorder (BED). However, major critical limitations in previous research, such as the influence of obesity and comorbid depression, prevented any consensus to be reached. The present study investigated the association between depressive symptoms, a broad range of EF and binge eating severity in individuals with obesity and with/without BED, and whether this association may be explained by a mediation or independency model.

Method

One hundred and seven participants completed clinical and psychometric examination. Associations between EF, depressive symptoms and binge eating severity were assessed through bivariate correlation analysis, and the magnitude, as well as the direction of associations between variables, was estimated with structural equation model.

Results

Two reliable models were tested; results showed that depressive symptoms exhibited significant direct and indirect effects on the severity of binge eating; conversely, EF did not show either significant direct or indirect effect on binge eating severity.

Conclusion

Depression contributes more than EF to psychopathology of BED. Thus, clinicians should routinely assess and, eventually, tailor depressive symptoms in treatment to improve the outcomes of patients with BED.
Evaluating Multiple Biochemical Markers in Xenopus laevis Tadpoles Exposed to the Pesticides Thiacloprid and Trifloxystrobin in Single and Mixed Forms
Authors: Uçkun Miraç , Özmen Murat
Published: July 2021

Pesticide exposure is thought to be one of the common reasons for the decline in amphibian populations, a phenomenon that is a major threat to global biodiversity. Although the single effects of pesticides on amphibians have been well studied, the effects of mixtures are not well known. The present study aimed to evaluate the acute toxicity of the insecticide thiacloprid and the fungicide trifloxystrobin on early developmental stages of Xenopus laevis using various biochemical markers (glutathione S-transferase, glutathione reductase, acetylcholinesterase, carboxylesterase, glutathione peroxidase, catalase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, Na+K+-adenosine triphosphatase [ATPase], Ca2+-ATPase, Mg2+-ATPase, and total ATPase). The median lethal concentrations (LC50s) of thiacloprid and trifloxystrobin were determined to be 3.41 and 0.09 mg a.i. L–1, respectively. Tadpoles were exposed to the LC50, LC50/2, LC50/10, LC50/20, LC50/50, and LC50/100 of these pesticides. Both pesticides significantly affected (inhibited/activated) the biomarkers even at low concentrations. The pesticides showed a synergistic effect when applied as a mixture and altered the biomarkers more than when applied individually. In conclusion, we can assume that tadpoles are threatened by these pesticides even at environmentally relevant concentrations. Our findings provide important data to guide management of the ecotoxicological effects of these pesticides on nontarget amphibians.  Environ Toxicol Chem 2021;40:2846–2860. © 2021 SETAC

Abstract

Evaluating multiple biochemical markers in Xenopus laevis tadpoles exposed to pesticides thiacloprid and trifloxystrobin in single and mixed forms. THI = thiacloprid; TFS = trifloxystrobin; LC50 = median lethal concentration.
Cytochrome P450 Inhibition by Antimicrobials and Their Mixtures in Rainbow Trout Liver Microsomes In Vitro
Authors: Pihlaja Tea L.M. , Niemissalo Sanna M. , Sikanen Tiina M.
Published: July 2021

Antimicrobials are ubiquitous in the environment and can bioaccumulate in fish. In the present study, we determined the half-maximal inhibitory concentrations (IC50) of 7 environmentally abundant antimicrobials (ciprofloxacin, clarithromycin, clotrimazole, erythromycin, ketoconazole, miconazole, and sulfamethoxazole) on the cytochrome P450 (CYP) system in rainbow trout (Oncorhynchus mykiss) liver microsomes, using 7-ethoxyresorufin O-deethylation (EROD, CYP1A) and 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylation (BFCOD, CYP3A) as model reactions. Apart from ciprofloxacin and sulfamethoxazole, all antimicrobials inhibited either EROD or BFCOD activities or both at concentrations <500 µM. Erythromycin was the only selective and time-dependent inhibitor of BFCOD. Compared with environmental concentrations, the IC50s of individual compounds were generally high (greater than milligrams per liter); but as mixtures, the antimicrobials resulted in strong, indicatively synergistic inhibitions of both EROD and BFCOD at submicromolar (~micrograms per liter) mixture concentrations. The cumulative inhibition of the BFCOD activity was detectable even at picomolar (~nanograms per liter) mixture concentrations and potentiated over time, likely because of the strong inhibition of CYP3A by ketoconazole (IC50 = 1.7 ± 0.3 µM) and clotrimazole (IC50 = 1.2 ± 0.2 µM). The results suggest that if taken up by fish, the mixtures of these antimicrobials may result in broad CYP inactivation and increase the bioaccumulation risk of any other xenobiotic normally cleared by the hepatic CYPs even at biologically relevant concentrations. Environ Toxicol Chem 2022;41:663–676. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Abstract

Synergistic and time-dependent inhibition of cytochrome P450 3A activity by antimicrobial mixtures was observed in rainbow trout liver microsomes in vitro even at trace-level concentrations.
InTACT: An adaptive and powerful framework for joint‐tissue transcriptome‐wide association studies
Authors: Bae Ye Eun , Wu Lang , Wu Chong
Published: July 2021

Transcriptome‐wide association studies (TWAS) that integrate transcriptomic reference data and genome‐wide association studies (GWAS) have successfully enhanced the discovery of candidate genes for many complex traits. However, existing methods may suffer from substantial power loss because they fail to effectively consider that expression of many genes tends to be consistent across tissues. Here we propose a computationally efficient testing method, referred to as Integrative Test for Associations via Cauchy Transformation (InTACT), that effectively combines information across multiple tissues and thus improves the power of identifying associated genes. Through simulation studies, we show that InTACT maintains high power while properly controls for Type 1 error rates. We applied InTACT to the largest GWAS of Alzheimer's disease (AD) to date and identified 227 genome‐wide significant genes, of which 130 were not identified by benchmark methods, TWAS and MultiXcan. Importantly, InTACT identified five novel loci for AD. We implemented InTACT in publicly available software, “InTACT.”
The Center's Highest Award
Authors: Gray Bradford H. , Solomon Mildred Z.
Published: July 2021

Prompted by a 2019 essay by Jonathan Moreno in the Hastings Center Report, the Center's board of directors undertook a careful examination of the name of its preeiminent award, the Henry Knowles Beecher Award, which has been given to twenty‐nine individuals who have made lifetime contributions to bioethics. citing new research that revealed that Beecher's earlier experimentation on drugs had involved nonconsenting adults, Moreno urged the Center to reevaluate honoring Beecher through this award. After reviewing the relevant published evidence and holding extensive discussions, the board decided to rename the award. We also took the opportunity to reframe the award to emphasize quality of scholarship and impact on thinking, practice, and policy rather than lifetime achievement. The new name—the Founders’ Award of The Hastings Center—reflects our desire to honor not only the Center's cofounders, Daniel Callahan and Willard Gaylin, but also others who helped found the field of bioethics.

With great pride, the Center has announced that Patricia King of the Georgetown University Law Center is the 2021 recipient of the Founders’ Award. A distinguished civil rights lawyer, King was instrumental in ensuring justice as one of the three principles of The Belmont Report.
Essential Reading for Bioethicists in the Anthropocene Era
Authors: Churchill Larry R. , Schenck David
Published: July 2021

The multiple emergencies of global heating require bioethicists to embrace the dormant, comprehensive bioethics legacy of Van Rensselaer Potter, moving beyond the current narrower focus of the field on medicine and health care. We recommend readings that expand the core literature of bioethics to address key environmental issues. These are Jessica Pierce and Andrew Jameton's The Ethics of Environmentally Responsible Health Care; Dale Jamieson's Reason in a Dark Time; and David Wallace‐Well's The Uninhabitable Earth. Because efforts to mitigate climate disasters are likely to be only partially successful, we also recommend the teachings of late Roman Stoicism and core texts of Buddhism, which provide ethical wisdom likely to be needed in the multiple crises of the Anthropocene.
A Realpolitik for Presidential Health: A Psychiatrist's Perspective
Authors: Appel Jacob M.
Published: July 2021

The health and fitness of United States presidents has been a matter of concern since the Constitutional Convention. Several United States presidents, including James Madison, James Garfield, and Woodrow Wilson, were significantly impaired during portions of their tenure. Yet how to address this issue has proved both ethically and politically challenging, increasingly so during our nation's current period of elevated polarization. This essay reviews the history of presidential impairment and the range of proposals that have been offered to address it. Ultimately, the essay argues that any effort to require the release of medical records or to evaluate the president while in office is likely to prove ineffective and politically unworkable, but also that providing the public with more medical information about candidates and presidents is unlikely to prove useful to voters in rendering their decisions.
It Is Time to Abandon the Dogma That Brain Death Is Biological Death
Authors: Miller Franklin G. , Nair‐Collins Michael , Truog Robert D.
Published: July 2021

Drawing on a recent case report of a pregnant, brain‐dead woman who gave birth to a healthy child after over seven months of intensive care treatment, this essay rejects the established doctrine in medicine that brain death constitutes the biological death of the human being. The essay describes three policy options with respect to determination of death and vital organ transplantation in the case of patients who are irreversibly comatose but remain biologically alive.
Activism and Bioethics: Taking a Stand on Things That Matter
Authors: Rogers Wendy A. , Scully Jackie Leach
Published: July 2021

The question of whether activism should be overtly embraced as part of the bioethicist's role deserves serious consideration. Like others, we agree that bioethics is inescapably partisan; bioethical deliberation is based on trying to determine morally relevant features of situations and morally justifiable outcomes. Where disagreement arises is over the degree to which bioethicists should be activists. Meyers argues for a somewhat circumscribed role, limited to action on ethically concerning institutional matters, for those who are financially independent of the institutions. We take a broader view, arguing that some issues are so morally egregious that there is a duty to take a stand against them, even if the prospects of success are dim. There is a need for further debate, sharing of experiences, and analysis of case studies, to support bioethicists who take a stand.
Leveraging green HRM for firm performance: The joint effects of CEO environmental belief and external pollution severity and the mediating role of employee environmental commitment
Authors: Ren Shuang , Jiang Kaifeng , Tang Guiyao
Published: July 2021

The topic of green human resource management (HRM) has drawn increasing attention of HRM scholars in the past decade. Recent research has called for more studies to identify the antecedents of green HRM used in organizations and explore the mediating mechanisms through which green HRM is related to performance outcomes. This study represents an effort to address these research needs by examining the joint effects of chief executive officer (CEO) environmental belief and external pollution severity on the use of green HRM and testing the mediating role of employee environmental commitment in the relationship between green HRM and firm performance. Drawing upon data collected from multiple sources (i.e., survey data from chief executive officer (CEOs), chief financial officers (CFOs), HR managers and employees, and archival data from government statistics), we found that CEO's environmental belief is significantly related to the use of green HRM, especially for companies operating in locations with severer pollution. Green HRM in turn has a positive relationship with the firm's environmental and financial performances via employee commitment to the environment. The findings highlight the often‐overlooked role of in the strategic HRM literature pertinent to environmental management and clarify the antecedents and influential mechanisms of green HRM at the firm level of analysis. We also discuss theoretical and practical implications in this study.
Preliminary assessment of health risks associated with consumption of grapevines contaminated with mining effluents in Turkey: Persistent trace elements and critical raw materials
Authors: Topal Murat , Arslan Topal E.Işıl , Öbek Erdal
Published: July 2021

In this study, some persistent trace elements and critical raw materials were investigated in grapevines contaminated with Pb–Zn mining effluents. The persistent trace elements under certain conditions remain without any change in form in the environment over long periods. The critical raw materials are the ones that have economic importance and have the risks associated with their supply. The health risks of persistent trace elements and critical raw materials in the leaves of grapevine that are consumed by humans were determined. The highest persistent trace elements concentrations followed the order of root > stem > leaf for Mn, Cu, Cd, Ni, and Cr while root > leaf > stem for Zn and leaf > root > stem for Pb. The maximum critical raw material concentrations for Co and V followed the order of root > stem > leaf. For Sb and La, these were leaf > root > stem and root > stem > leaf, respectively. The maximum critical raw materials concentrations for W was leaf > stem = root. The total maximum carcinogenic value was 0.146 for Cd while the total minimum carcinogenic value was 0.0054 for Pb. In this study, potential carcinogenic risk values in terms of ingestion of contaminated soil (Cr, Cd, and Ni) and dietary take of grapevine leaves (Ni, Cr, Cd, and Pb) are higher than acceptable levels (1 × 10−4 – 1 × 10−6). Maximum cancer risk on human health was determined as dietary intake of grapevine leaves. When hazard quotient for dietary (HQdie), hazard quotient for ingestion (HQing), and hazard quotient for inhalation (HQinh) values ​​of critical raw materials were examined, the maximum values ​​were observed for children. Also, the highest hazard quotient for dermal (HQder) value was determined for men. The hazard index and total hazard index values were >1 for critical raw materials. As a result, values >1 indicated potential non-carcinogenic human health risk associated with the consumption of grapevines contaminated with mining effluents. Actual region-specific exposure estimates for consumption of grapevines, however, were not evaluated. Integr Environ Assess Manag 2022;18:517–527. © 2021 SETAC

KEY POINTS

The total maximum carcinogenic value was 0.146 for cadmium in grapevines collected near an abandoned mine site in Turkey. The potential carcinogenic risk values in terms of ingestion of contaminated soil (Cr, Cd, and Ni) and dietary take of grapevine leaves (Ni, Cr, Cd, and Pb) are higher than acceptable levels. The hazard index and total hazard index values were greater than 1 for critical raw materials indicating potential non-carcinogenic human health risk associated with the consumption of grapevine leaves contaminated with mining effluents.
Intergenerational gestational surrogacy in a patient with ovarian dysgerminocarcinoma
Authors: Morris Joshua M. , Tillmanns Todd D. , Brezina Paul R.
Published: July 2021

A 20‐year‐old woman was diagnosed with an ovarian dysgerminoma on the right ovary and underwent fertility‐preserving right salpingo‐oophorectomy and staging. Eight months later she was found to have a left ovarian solid mass. She underwent controlled ovarian hyperstimulation and oocyte cryopreservation before total abdominal hysterectomy, left salpingo‐oophorectomy, and exploratory surgery were performed. The patient was optimally debulked, with no recurrent cancer to date. Thirty‐six oocytes were mature and cryopreserved using vitrification. Now, the patient's mother has undergone embryo transfer that resulted in a clinical pregnancy, acting as a gestational carrier, for her daughter. To our knowledge, this is the first case describing the uterine transfer of embryos into a gestational carrier where the embryos were generated using oocytes obtained through controlled ovarian hyperstimulation in the context of active ovarian cancer. In the appropriate clinical setting, women desiring future fertility with a diagnosis of ovarian cancer without the option of ovarian‐sparing surgery may be candidates for controlled ovarian hyperstimulation for the purposes of fertility preservation, especially if altruistic gestational carriers are available and willing.
Ranking intersecting distribution functions
Authors: Aaberge Rolf , Havnes Tarjei , Mogstad Magne
Published: July 2021

Second‐degree dominance has become a widely accepted criterion for ordering distribution functions according to social welfare. However, it provides only a partial ordering, and it may fail to rank distributions that intersect. To rank intersecting distribution functions, we propose a general approach based on rank‐dependent theory. This approach avoids making arbitrary restrictions or parametric assumptions about social welfare functions and allows researchers to identify the weakest set of assumptions needed to rank distributions according to social welfare. Our approach is based on two complementary sequences of nested dominance criteria. The first (second) sequence extends second‐degree stochastic dominance by placing more emphasis on differences that occur in the lower (upper) part of the distribution. The sequences characterize two separate systems of nested subfamilies of rank‐dependent social welfare functions. This allows us to identify the least restrictive rank‐dependent social preferences that give an unambiguous ranking of a given set of distribution functions. We also provide an axiomatization of the sequences of dominance criteria and the corresponding subfamilies of social welfare functions. We show the usefulness of our approach using two empirical applications; the first assesses the welfare implications of changes in household income distributions over the business cycle, while the second performs a social welfare comparison of the actual and counterfactual outcome distributions from a policy experiment.
Revisiting gender identity and relative income within households: A cautionary tale on the potential pitfalls of density estimators
Authors: Kuehnle Daniel , Oberfichtner Michael , Ostermann Kerstin
Published: July 2021

We show that Bertrand et al.'s (QJE, 2015, ) finding of a sharp drop in the relative income distribution within married couples at the point where wives start to earn more than their husbands is unstable across different estimation procedures and varies across contexts. We apply the estimators by McCrary (JoE, 2008, McC) and Cattaneo et al. (JASA, 2020, CJM) to administrative data from the United States and Germany and compare their performance in a simulation. Large bins cause McC to substantially overreject the null hypothesis, and mass points close to the potential discontinuity affect McC more than CJM.
Are there no wage returns to compulsory schooling in Germany? A reassessment
Authors: Cygan‐Rehm Kamila
Published: July 2021

This study replicates and challenges the finding of zero wage returns to compulsory schooling in Germany by Pischke and von Wachter (Review of Economics and Statistics, 90(3), 592–598), which is unusual in the literature yet widely cited and until now uncontradicted. I document that this finding is sensitive to minor changes in sample restrictions and model specification. Further results suggest that their estimates are potentially confounded by previously unconsidered institutional details. These findings render the conclusion that compulsory schooling in Germany yields no wage returns at a minimum controversial.
Liver‐specific decrease in Tff3 gene expression in infant mice perinatally exposed to 2,3,7,8‐tetrabromodibenzofuran or 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin
Authors: Kimura Eiki , Suzuki Go , Uramaru Naoto , Kakeyama Masaki , Maekawa Fumihiko
Published: July 2021

Polybrominated dibenzo‐p‐dioxins and dibenzofurans (PBDD/DFs) are byproducts of brominated flame retardants and can cause adverse health effects. Although exposure to polychlorinated (PC) DD/DFs induces toxic effects, including liver injury and neurobehavioral disorder, little is known about toxicities associated with PBDD/DF exposure. Thus, we examined effects of perinatal exposure to brominated congener on the infant mouse. Gene expression in several organs, such as the liver and brain, was analyzed in mouse offspring born to dams administered 2,3,7,8‐tetrabromodibenzofuran (TBDF; 9 or 45 μg/kg body weight) or 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD; 3 μg/kg body weight) on gestational day 12.5. An increase in liver size was observed in TBDF‐ or TCDD‐exposed offspring in infancy. Gene microarray analysis revealed that 163 and 36 genes were markedly upregulated and downregulated, respectively, in the liver of TBDF‐exposed mice compared with those in vehicle‐treated mice on postnatal day (PND) 5. Significant increases in Cyp1a1, Cyp1a2, Fmo3, and Pnliprp1 and decreases in Tff3, Ocstamp, Kcnk16, and Lgals2 mRNA levels in TBDF‐exposed offspring on PNDs 5 and 12 were confirmed by quantitative PCR. In particular, a significant reduction in Tff3 mRNA in the liver, but not in the brain, small intestine, colon, and kidney, was observed in offspring perinatally exposed to TBDF or TCDD. Ultrasonic calls of TBDF‐ or TCDD‐exposed offspring on PNDs 3–5 were impaired. Taken together, perinatal exposure to polyhalogenated dioxin/furan congeners disrupts gene expression patterns in the liver and ultrasonic calling during infancy. These results suggest that liver injury may contribute to neurobehavioral disorder.
Incorporating nanocrystalline cellulose into a multifunctional hydrogel for heart valve tissue engineering applications
Authors: Ma Nianfang , Cheung Daniel Y. , Butcher Jonathan T.
Published: July 2021

Functional tissue engineered heart valves (TEHV) have been an elusive goal for nearly 30 years. Among the persistent challenges are the requirements for engineered valve leaflets that possess nonlinear elastic tissue biomechanical properties, support quiescent fibroblast phenotype, and resist osteogenic differentiation. Nanocellulose is an attractive tunable biological material that has not been employed to this application. In this study, we fabricated a series of photocrosslinkable composite hydrogels mNCC‐MeGel (mNG) by conjugating TEMPO‐modified nanocrystalline cellulose (mNCC) onto the backbone of methacrylated gelatin (MeGel). Their structures were characterized by FTIR, 1HNMR and uniaxial compression testing. Human adipose‐derived mesenchymal stem cells (HADMSC) were encapsulated within the material and evaluated for valve interstitial cell phenotypes over 14 days culture in both normal and osteogenic media. Compared to the MeGel control group, the HADMSC encapsulated within mNG showed decreased alpha smooth muscle actin (αSMA) expression and increased vimentin and aggrecan expression, suggesting the material supports a quiescent fibroblastic phenotype. Under osteogenic media conditions, HADMSC within mNG hydrogels showed lower expression of osteogenic genes, including Runx2 and osteocalcin, indicating resistance toward calcification. As a proof of principle, the mNG hydrogel, combined with a viscosity enhancing agent, was used to 3D bioprint a tall, self‐standing tubular structure that sustained cell viability. Together, these results identify mNG as an attractive biomaterial for TEHV applications.
Elevation, oxygen, and the origins of viviparity
Authors: Watson Charles M. , Cox Christian L.
Published: July 2021

Research focused on understanding the evolutionary factors that shape parity mode evolution among vertebrates have long focused on squamate reptiles (snakes and lizards), which contain all but one of the evolutionary transitions from oviparity to viviparity among extant amniotes. While most hypotheses have focused on the role of cool temperatures in favoring viviparity in thermoregulating snakes and lizards, there is a growing appreciation in the biogeographic literature for the importance of lower oxygen concentrations at high elevations for the evolution of parity mode. However, the physiological mechanisms underlying how hypoxia might reduce fitness, and how viviparity can alleviate this fitness decrement, has not been systematically evaluated. We qualitatively evaluated previous research on reproductive and developmental physiology, and found that (1) hypoxia can negatively affect fitness of squamate embryos, (2) oxygen availability in the circulatory system of adult lizards can be similar or greater than an egg, and (3) gravid females can possess adaptive phenotypic plasticity in response to hypoxia. These findings suggest that the impact of hypoxia on the development and physiology of oviparous and viviparous squamates would be a fruitful area of research for understanding the evolution of viviparity. To that end, we propose an integrative research program for studying hypoxia and the evolution of viviparity in squamates.
Macrophage M1/M2 polarization dynamically adapts to changes in microenvironment and modulates alveolar bone remodeling after dental implantation
Authors: Liang Beilei , Wang Haicheng , Wu Di , Wang Zuolin
Published: July 2021

As one of the first arriving immune cells after dental implantation, Mϕs own the abilities to polarize into to a spectrum of diverse phenotypes, from “classically activated” M1 Mϕs to “alternatively activated” M2 Mϕs. Herein, it was hypothesized that Mϕ phenotypes dynamically adapt after dental implantation, and the changes ensue a cascade of coordinated interplay with the bone-forming osteoblast and the bone-resorbing osteoclast. Results showed that the remodelling process after dental implantation was similar with the standard response to tissue injury (exampled by tooth extraction models), only with the delay of bone regeneration phases. Additionally, Mϕ activation in both groups underwent a transition from M1 Mϕs dominated to M2-type dominated stage, but the persistence of M1 Mϕs occurred in rat model of dental implantation. Further research in vitro showed that M1 Mϕs are involved in osteoclast activities via secreting the highest levels of TNF-α and IL-1β, as well as being the potential precursor of osteoclasts. Besides, they also recruited BMSCs by secreting the highest levels of chemoattractants, CCL2 and VEGF. M2 Mϕs accelerated osteogenesis in the subsequent stage via their capability to secrete osteogenesis-related proteins, BMP-2 and TGF-β1. However, the osteogenic differentiation of BMSCs was inhibited when cultured in a high concentration of conditioned media from each Mϕ phenotype, meaning that the immune strategies should be controlled within the proper ranges. These results suggest that coordinated efforts by both M1 and M2 Mϕs for bone remodelling, which may highlight an optimization strategy for tissue engineering implants.
Comparing the effectiveness of Atazanavir/Ritonavir/Dolutegravir/Hydroxychloroquine and Lopinavir/Ritonavir/Hydroxychloroquine treatment regimens in COVID‐19 patients
Authors: Kalantari Saeed , Fard Soheil R. , Maleki Donya , Taher Mahshid T. , Yassin Zeynab , Alimohamadi Yousef , Minaeian Sara
Published: July 2021

The purpose of this study was to compare the effectiveness of Atazanavir/Ritonavir/Dolutegravir/Hydroxychloroquine and Lopinavir/Ritonavir/Hydroxychloroquine treatment regimens in COVID‐19 patients based on clinical and laboratory parameters. We prospectively evaluated the clinical and laboratory outcomes of 62 moderate to severe COVID‐19 patients during a 10‐day treatment plan. Patients were randomly assigned to either KH (receiving Lopinavir/Ritonavir [Kaletra] plus Hydroxychloroquine) or ADH (receiving Atazanavir/Ritonavir, Dolutegravir, and Hydroxychloroquine) groups. During this period, clinical and laboratory parameters and outcomes such as intensive care unit (ICU) admission or mortality rate were recorded. Compared to the KH group, after the treatment period, patients in the ADH group had higher activated partial thromboplastin time (aPTT) (12, [95% confidence interval [CI]: 6.97, 17.06), p = <0.01), international normalized ratio (INR) (0.17, [95% CI: 0.07, 0.27), p = <0.01) and lower C‐reactive protein (CRP) (−14.29, (95% CI: −26.87, −1.71), p = 0.03) and potassium (−0.53, (95% CI: −1.03, −0.03), p = 0.04) values. Moreover, a higher number of patients in the KH group needed invasive ventilation (6 (20%) vs. 1 (3.1%), p = 0.05) and antibiotic administration (27 (90%) vs. 21(65.6), p = 0.02) during hospitalization while patients in the ADH group needed more corticosteroid administration (9 (28.1%) vs. 2 (6.7%), p = 0.03). There was no difference in mortality rate, ICU admission rate, and hospitalization period between the study groups. Our results suggest that the Atazanavir/Dolutegravir treatment regimen may result in a less severe disease course compared to the Lopinavir/Ritonavir treatment regimen and can be considered as an alternative treatment option beside standard care. However, to confirm our results, larger‐scale studies are recommended.
The variants question: What is the problem?
Authors: Zella Davide , Giovanetti Marta , Benedetti Francesca , Unali Francesco , Spoto Silvia , Guarino Michele , Angeletti Silvia , Ciccozzi Massimo
Published: July 2021

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) originated in Wuhan, China in early December 2019 has rapidly widespread worldwide. Over the course of the pandemic, due to the advance of whole‐genome sequencing technologies, an unprecedented number of genomes have been generated, providing both invaluable insights into the ongoing evolution and epidemiology of the virus and allowing the identification of hundreds of circulating genetic variants during the pandemic. In recent months variants of SARS‐CoV‐2 that have an increased number of mutations on the Spike protein have brought concern all over the world. These have been called “variants of concerns” (VOCs), and/or “variants of interests” (VOIs) as it has been suggested that their genome mutations might impact transmission, immune control, and virulence. Tracking the spread of emerging SARS‐CoV‐2 variants is crucial to inform public health efforts and control the ongoing pandemic. In this review, a concise characterization of the SARS‐CoV‐2 mutational patterns of the main VOCs and VOIs circulating and cocirculating worldwide has been presented to determine the magnitude of the SARS‐CoV‐2 threat to better understand the virus genetic diversity and its potential impact on vaccination strategy.
Public awareness about coronavirus vaccine, vaccine acceptance, and hesitancy
Authors: Elgendy Marwa O. , Abdelrahim Mohamed E. A.
Published: July 2021

Measurement of the population's general knowledge of the coronavirus vaccine is very important to improve public acceptance and decrease vaccine hesitancy in confronting the disease. This study aimed to evaluate the knowledge, attitude, and practices of the participants towards the coronavirus vaccine. Data were collected using an online survey, in the form of a structured questionnaire, conducted during April–May 2021 in Egypt, and subjects from all over Egypt participated. The questionnaire was divided into three parts to assess the knowledge and attitude regarding coronavirus. The first part was to assess participants’ experience about coronavirus infection (eight items), the second was to assess the health beliefs about coronavirus and vaccine (16 items) and the third was to assess general knowledge, attitude, and practices of the participants towards vaccine (28 items). A total of 871 (465 females) participants participated, 81% of them were still committed to the precautionary measures for protection. Eighty‐eight percent of them accepted to take the vaccine. Eighty‐three percent of the participants answered that they will encourage family, friends, and colleagues to get the vaccine. Ninety‐four percent knew that the coronavirus vaccine provides immunity against infection for a period of 6–12 months. 91.9% believed that the current infection with coronavirus is one of the main contraindications to vaccination. Eighty‐nine percent believed that both pregnant women and chronic disease patients can get vaccinated and also that there is no specific age for a specific type of vaccination. Ninety‐four percent of them knew that subjects taking immunosuppressive drugs should be prescribed Sinopharm, not AstraZeneca vaccine. The median score of this survey was 20/22 regarding knowledge about the coronavirus vaccine. Overall, the study participants had good knowledge about the coronavirus vaccine and accepted to take the vaccine, which indicates the highly commendable efforts to confront the coronavirus.
Rapid immunoassay and clinical evaluation of the SARS‐CoV‐2 antibody assay on the real express‐6 analyzer
Authors: Zhang Shun , Ning Yingjun , Rong Yejing , Nie Yaxing , Xiong Zi , Li Rui , Jin Tong , Cai Ting
Published: July 2021

We developed a rapid and simple magnetic chemiluminescence enzyme immunoassay on the Real Express‐6 analyzer, which could simultaneously detect immunoglobulin G and immunoglobulin M antibodies against SARS‐CoV‐2 virus in human blood within 18 min, and which could be used to detect clinical studies to verify its clinical efficacy. We selected blood samples from 185 COVID‐19 patients confirmed by polymerase chain reaction and 271 negative patients to determine the clinical detection sensitivity, specificity, stability, and precision of this method. Meanwhile, we also surveyed the dynamic variance of viral antibodies during SARS‐CoV‐2 infection. This rapid immunoassay test has huge potential benefits for rapid screening of SARS‐CoV‐2 infection and may help clinical drug and vaccine development.
Contribution of HCN1 variant to sinus bradycardia: A case report
Authors: Yu Hangang , Gall Bryan , Newman Mackenzie , Hathaway Quincy , Brundage Kathleen , Ammer Amanda , Mathers Peter , Siderovski David , Hull Robert W.
Published: July 2021

Background

Missense mutations in the hyperpolarization‐activated cyclic nucleotide‐modulated (HCN) channel 4 (HCN4) are one of the genetic causes of cardiac sinus bradycardia.

Objective

To investigate possible HCN4 channel mutation in a young patient with profound sinus bradycardia.

Methods

Direct sequencing of HCN4 and whole‐exome sequencing were performed on DNA samples from the indexed patient (P), the patient's son (PS), and a family unrelated healthy long‐distance running volunteer (V). Resting heart rate was 31 bpm for P, 67 bpm for PS, and 50 bpm for V. Immunoblots, flow cytometry, and immunocytofluorescence confocal imaging were used to study cellular distribution of channel variants. Patch‐clamp electrophysiology was used to investigate the properties of mutant HCN1 channels.

Results

In P no missense mutations were found in the HCN4 gene; instead, we found two heterozygous variants in the HCN1 gene: deletion of an N‐terminal glycine triplet (72GGG74, “N‐del”) and a novel missense variant, P851A, in the C‐terminal region. N‐del variant was found before and shared by PS. These two variations were not found in V. Compared to wild type, N‐del and P851A reduced cell surface expression and negatively shifted voltage‐activation with slower activation kinetics.

Conclusion

Decreased channel activity HCN1 mutant channel makes it unable to contribute to early depolarization of sinus node action potential, thus likely a main cause of the profound sinus bradycardia in this patient.
Confocal Raman spectroscopic study of melt inclusions in olivine of mantle xenoliths from the Bultfontein kimberlite pipe (Kimberley cluster, South Africa): Evidence for alkali‐rich carbonate melt in the mantle beneath Kaapvaal Craton
Authors: Sharygin Igor S. , Golovin Alexander V. , Tarasov Alexey A. , Dymshits Anna M. , Kovaleva Elizaveta
Published: July 2021

Identifying the composition of primary/primitive mantle melts is crucial for understanding the mantle's evolution and mantle‐derived magmatism. Melt inclusions in mantle xenoliths provide key information about such melts. This study used confocal Raman spectroscopy to characterize mineral assemblage of unexposed crystallized secondary melt inclusions in the olivine from the xenoliths of the sheared garnet peridotites from the Bultfontein kimberlite pipe (Kimberley cluster, Kaapvaal Craton, South Africa). The studied peridotites originated from 112‐ to 146‐km mantle depths. In total, 16 minerals were identified among daughter crysatls, which include carbonates (calcite, magnesite, dolomite), alkali carbonates (eitelite, nyerereite, gregoryite/natrite, K–Na–Ca–carbonate (K,Na)2Ca(CO3)2 (K analogue of nyerereite), alkali carbonates with additional anions (northupite, bradleyite, burkeite), alkali sulfates (glauberite, thenardite, aphthitalite), apatite, tetraferriphlogopite, and magnetite. Several more daughter minerals gave distinct Raman spectra, but they were not determined due to the lack of similar spectra in the databases. Carbonates are predominant among the daughter minerals in the melt inclusions. Many daughter minerals are rich in alkalis. These facts indicate that melt(s), parental for the inclusions, is alkali‐rich carbonate in composition. Two possible models were suggested for the origin of these melt inclusions: (1) in situ fracturing of olivine and the mantle melt infiltration shortly before the sheared peridotites were entrained by the ascending kimberlitic magma; (2) infiltration of the transporting kimberlite melt into xenoliths during ascent. Both models imply that the alkali‐rich carbonate melt(s) that interacted with peridotites originated at a greater depth than the entrapment level of studied xenoliths (>150 km), that is, at the base of the lithosphere or in the asthenosphere. This melt is genetically related to the kimberlite magmatism that formed the Bultfontein pipe and points at the alkali‐rich carbonate composition of primary kimberlite melt.
Structural studies of ligand stabilized Ni/Ga clusters by means of vibrational spectroscopy and theoretical calculations
Authors: Mink János , Staiger Lena , Muhr Maximilian , Gemel Christian , Drees Markus , Hajba László , Mihály Judith , Németh Csaba , Lokshin Boris V. , Hemmer Karina , Schütz Max , Cokoja Mirza , Fischer Roland A.
Published: July 2021

In order to explain the different catalytic activity in hydrogenation of two new intermetallic Ni/Ga clusters, [Ga7](NiCp*)6 (1A) and [NiGa6](NiCp*)6 (1B) (Cp* = C5Me5), investigations of structure–function relationship have been performed based on Raman and infrared (IR) spectroscopy and theoretical (density functional theory [DFT] and normal coordinate) calculations. Full interpretation of the Raman, far‐IR, and mid‐IR spectra of these dark colored solids has been proposed. Based on the overview of metal–Cp* complexes, all the 14 characteristic Cp*− skeletal fundamental modes have been identified. By comparison of the NiCp* stretching and tilting external modes (350–380 cm−1), their force constants, and bond lengths, cluster 1B exhibited slightly stronger metal–ligand bonding. Vibrations of Ga7 and NiGa6 cluster cores showed that the stretching wavenumbers and force constants of NiGa (100–350 cm−1) and GaGa (60–250 cm−1) bonds are higher for cluster 1B, in agreement with the shorter averaged experimental and calculated bond lengths of GaGa bonds (2.873 and 2823 Å for clusters 1A and 1B, respectively). Cluster hydrogenation experiments with H2 and D2 showed strong NiH and ND stretching features (at 1750 and 1260 cm−1, respectively), and at the same time, characteristic bands of self‐hydrogenated Cp*H and remained nondegraded clusters have been detected. The extent of HD exchange in cluster deuteration was obtained about 1.5 times more effective with cluster 1B than cluster 1A. The stronger hydrogen or deuterium uptake by cluster 1B and the more intensive self‐hydrogenation of Cp* clearly support the higher hydrogenation activity of cluster 1B compared with that of 1A.
A multi‐institutional validation study of prognostic nomograms for retroperitoneal sarcoma
Authors: Squires Malcolm H. , Ethun Cecilia G. , Donahue Erin E. , Benbow Jennifer H. , Anderson Colin J. , Jagosky Megan H. , Salo Jonathan C. , Hill Joshua S. , Ahrens William , Prabhu Roshan S. , Livingston Michael B. , Gower Nicole L. , Needham Mckenzie , Trufan Sally J. , Fields Ryan C. , Krasnick Bradley A. , Bedi Meena , Abbott Daniel E. , Schwartz Patrick , Votanopoulos Konstantinos , Chouliaras Konstantinos , Grignol Valerie , Roggin Kevin K. , Tseng Jennifer , Poultsides George , Tran Thuy B. , Cardona Kenneth , Howard J. Harrison
Published: July 2021

Background and Objectives

Prognostic nomograms for patients undergoing resection of retroperitoneal sarcoma (RPS) include the Sarculator and Memorial Sloan Kettering (MSK) sarcoma nomograms. We sought to validate the Sarculator and MSK nomograms within a large, modern multi‐institutional cohort of patients with primary RPS undergoing resection.

Methods

Patients who underwent resection of primary RPS between 2000 and 2017 across nine high‐volume US institutions were identified. Predicted 7‐year disease‐free (DFS) and overall survival (OS) and 4‐, 8‐, and 12‐year disease‐specific survival (DSS) were calculated from the Sarculator and MSK nomograms, respectively. Nomogram‐predicted survival probabilities were stratified in quintiles and compared in calibration plots to observed survival outcomes assessed by Kaplan–Meier estimates. Discriminative ability of nomograms was quantified by Harrell's concordance index (C‐index).

Results

Five hundred and two patients underwent resection of primary RPS. Histologies included leiomyosarcoma (30%), dedifferentiated liposarcoma (23%), and well‐differentiated liposarcoma (15%). Median tumor size was 14.0 cm (interquartile range [IQR], 8.5–21.0 cm). Tumor grade distribution was: Grade 1 (27%), Grade 2 (17%), and Grade 3 (56%). Median DFS was 31.5 months; 7‐year DFS was 29%. Median OS was 93.8 months; 7‐year OS was 51%. C‐indices for 7‐year DFS, and OS by the Sarculator nomogram were 0.65 (95% confidence interval [CI]: 0.62–0.69) and 0.69 (95%CI: 0.65–0.73); plots demonstrated good calibration for predicting 7‐year outcomes. The C‐index for 4‐, 8‐, and 12‐year DSS by the MSK nomogram was 0.71 (95%CI: 0.67–0.75); plots demonstrated similarly good calibration ability.

Conclusions

In a diverse, modern validation cohort of patients with resected primary RPS, both Sarculator and MSK nomograms demonstrated good prognostic ability, supporting their ongoing adoption into clinical practice.
Rapid chiral discrimination of oncometabolite dl‐2‐hydroxyglutaric acid using derivatization and field asymmetric waveform ion mobility spectrometry/mass spectrometry
Authors: Fukui Serina , Sugiyama Eiji , Mizuno Hajime , Sakane Iwao , Asakawa Daiki , Saikusa Kazumi , Nishiya Yuki , Amano Yuri , Takahara Kentaro , Higo Daisuke , Toyo'oka Toshimasa , Todoroki Kenichiro
Published: July 2021

2‐Hydroxyglutaric acid is a chiral metabolite whose enantiomers specifically accumulate in different diseases. An enantiomeric excess of the d‐form in biological specimens reflects the existence of various pathogenic mutations in cancer patients, however, conventional methods using gas or liquid chromatography and capillary electrophoresis had not been used for large clinical studies because they require multiple analytical instruments and a long run time to separate the enantiomers. Here, we present a rapid separation method for dl‐2‐hydroxyglutaric acid using a chiral derivatizing reagent and field asymmetric waveform ion mobility spectrometry/mass spectrometry, which requires a single analytical instrument and <1 s for the separation. We compared three derivatization methods and found that a method using (S)‐1‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)pyrrolidin‐3‐amine enables the separation. In addition, we were able to detect dl‐2‐hydroxyglutaric acid in standard solution at lower concentrations than that previously reported for the serum. These results show the potential of the method to be used in clinical analysis.
Featured Front Cover
Authors: Zhang Jun , Huang Xiaozhong , Zhang Shengrui , Ren Xiuxiu , Xiao Yulin , Wang Jiale , Xiang Lixiong , Xu Qinghai , Birks Harry John Betteley
Published: July 2021

The cover image is based on the Original Article Cycles of grazing and agricultural activity during the historical period and its relationship with climatic and societal changes in northern China by Xiaozhong Huang et al., https://doi.org/10.1002/ldr.4007.

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Positive solutions for integral nonlinear boundary value problem in fractional Sobolev spaces
Authors: Azzaoui Bouchra , Tellab Brahim , Zennir Khaled
Published: July 2021

In the present paper, we consider an important problem from the point of view of application in sciences and engineering, namely, Riemann–Liouville nonlinear fractional boundary value problem. Under new minimal conditions on the parameters 0 ≤ s, τ ≤ 1, it is shown that, based on the upper and lower solutions method using Schauder fixed point theorem, the positive solutions in a Sobolev spaces exist. Moreover, our results are illustrated by a numerical example.