bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linear polyacrylamide is highly efficient in precipitating and purifying environmental and ancient DNA
Authors: Maixner Frank , Mitterer Christian , Jäger Heidi Y. , Sarhan Mohamed S. , Valverde Guido , Lücker Sebastian , Piombino‐Mascali Dario , Szikossy Ildikó , Molnár Erika , Pálfi György , Pap Ildikó , Cipollini Giovanna , Zink Albert 
Published: November 2021

Abstract

Nucleic acid extraction from complex environmental and ancient tissue material is prone to co‐extract inhibitory substances that make further molecular analysis difficult or impossible. This co‐extraction occurs in both solid‐phase and liquid‐phase/organic nucleic acid extraction protocols. Currently, the widely used method to overcome inhibition includes the addition of bovine serum albumin (BSA) to the downstream enzymatic reactions or the dilution of the nucleic acid extracts. BSA, however, seems to reduce the inhibitory effect of certain compounds only, and excessive dilution may change the original DNA composition.

In this study, we introduce an innovative new method using linear polyacrylamide (LPA) to efficiently precipitate and purify nucleic acids extracted from complex environmental and ancient tissue samples in one working step. The LPA method replaces the precipitation step in classic liquid‐phase/organic extraction protocols or can be easily applied as an additional post‐extraction step on impure DNA extracts. As a proof of concept, we experimented with this method on different ancient human mummy samples (bones, soft tissues and gut contents) from different time periods (5000 BC–1800 AD), as well as on complex environmental samples (e.g. soil, activated sludge and animal faeces) known to contain inhibitory compounds.

We demonstrated that LPA precipitates nucleic acids, even in an aqueous ethanol solution without the addition of chaotropic salts, resulting in the recovery of highly pure DNA from all tested samples that displayed inhibition with previously published extraction protocols. Compared to the current, most widely used silica‐based extraction method for ancient and sedimentary DNA, our LPA method resulted in comparable DNA qualities and overall DNA compositions (human endogenous content and microbial diversity).

In conclusion, our LPA method with its high purifying capacity provides an important alternative to the commonly used DNA extraction protocols in the environmental and ancient DNA (aDNA) fields.
Growth hormone receptor gene disruption in mature‐adult mice improves male insulin sensitivity and extends female lifespan
Authors: Duran‐Ortiz Silvana , List Edward O. , Ikeno Yuji , Young Jonathan , Basu Reetobrata , Bell Stephen , McHugh Todd , Funk Kevin , Mathes Samuel , Qian Yanrong , Kulkarni Prateek , Yakar Shoshana , Berryman Darlene E. , Kopchick John J. 
Published: November 2021

AbstractStudies in multiple species indicate that reducing growth hormone (GH) action enhances healthy lifespan. In fact, GH receptor knockout (GHRKO) mice hold the Methuselah prize for the world's longest‐lived laboratory mouse. We previously demonstrated that GHR ablation starting at puberty (1.5 months), improved insulin sensitivity and female lifespan but results in markedly reduced body size. In this study, we investigated the effects of GHR disruption in mature‐adult mice at 6 months old (6mGHRKO). These mice exhibited GH resistance (reduced IGF‐1 and elevated GH serum levels), increased body adiposity, reduced lean mass, and minimal effects on body length. Importantly, 6mGHRKO males have enhanced insulin sensitivity and reduced neoplasms while females exhibited increased median and maximal lifespan. Furthermore, fasting glucose and oxidative damage was reduced in females compared to males irrespective of Ghr deletion. Overall, disrupted GH action in adult mice resulted in sexual dimorphic effects suggesting that GH reduction at older ages may have gerotherapeutic effects.
Differences in lesion interpretation between radiologists in two countries: Lessons from a digital breast tomosynthesis training test set
Authors: Li Tong , Gandomkar Ziba , Trieu Phuong Dung (Yun) , Lewis Sarah J. , Brennan Patrick C. 
Published: November 2021

AbstractIntroductionIn many western countries, there is good evidence documenting the performance of radiologists reading digital breast tomosynthesis (DBT) images. However, the diagnostic efficiency of Chinese radiologists using DBT, particularly type of errors being made and type of cancers being missed, is understudied. This study aims to investigate the pattern of diagnostic errors across different lesion types produced by Chinese radiologists diagnosing from DBT images. Australian radiologists will be used as a benchmark.MethodsTwelve Chinese radiologists read a DBT test set and located each perceived cancer lesion. True positives, false positives (FP), true negatives and false negatives (FN) were generated. The same test set was also read by 14 Australian radiologists. Z‐scores and Pearson correlations were used to compare interpretation of lesions and identification of normal appearances between two groups of radiologists.ResultsArchitectural distortions (p < .001) and stellate masses (p = .02) were more difficult for Chinese radiologists to correctly diagnose compared to their Australian counterparts. Chinese readers categorised more FPs as discrete masses (p < .001) and fewer FPs as architectural distortions (p < .001) comparing with Australian radiologists. The percentages of FN for each cancer case were not correlated (r = 0.37, p = .18) but the percentages of FP for each normal case were moderately correlated (r = 0.52, p = .02) between two groups of readers.ConclusionsArchitectural distortions and stellate masses were challenging to Chinese radiologists when reading DBT. Our findings proposed the need of development of training and education programs focussing on imaging cases tailored for specific groups of readers with certain interpretation patterns.
Delineating the interactions between the cannabinoid CB2 receptor and its regulatory effectors; β‐arrestins and GPCR kinases
Authors: Patel Monica , Matti Christoph , Grimsey Natasha L. , Legler Daniel F. , Javitch Jonathan A. , Finlay David B. , Glass Michelle 
Published: November 2021

Background and PurposeThe cannabinoid CB2 receptor (CB2) is a promising therapeutic target for modulating inflammation. However, little is known surrounding the mechanisms underpinning CB2 desensitisation and regulation, particularly the role of GPCR kinases (GRKs). Here, we evaluated the role of six GRK isoforms in β‐arrestin recruitment to CB2. Mutagenesis of several distal C‐terminal aspartic acid residues was also performed in an attempt to delineate additional structural elements involved in the regulation of CB2.Experimental ApproachIn CB2‐expressing HEK 293 cells, β‐arrestin translocation was measured using real‐time BRET assays. G protein dissociation BRET assays were performed to assess the activation and desensitisation of CB2 in the presence of β‐arrestin 2.Key ResultsOverexpression of GRK isoforms 1–6 failed to considerably improve translocation of either β‐arrestin 1 or β‐arrestin 2 to CB2. Consistent with this, inhibition of endogenous GRK2/3 did not substantially reduce β‐arrestin 2 translocation. Mutagenesis of C‐terminal aspartic acid residues resulted in attenuation of β‐arrestin 2 translocation, which translated to a reduction in desensitisation of G protein activation.Conclusion and ImplicationsOur findings suggest that CB2 does not adhere to the classical GPCR regulatory paradigm, entailing GRK‐mediated and β‐arrestin‐mediated desensitisation. Instead, C‐terminal aspartic acid residues may act as phospho‐mimics to induce β‐arrestin activation. This study provides novel insights into the regulatory mechanisms of CB2, which may aid in our understanding of drug tolerance and dependence.
Nicotinic‐acid derivative BGP‐15 improves diastolic function in a rabbit model of atherosclerotic cardiomyopathy
Authors: Priksz Daniel , Lampe Nora , Kovacs Arpad , Herwig Melissa , Bombicz Mariann , Varga Balazs , Wilisicz Tician , Szilvassy Judit , Posa Aniko , Kiss Rita , Gesztelyi Rudolf , Raduly Arnold , Szekeres Reka , Sieme Marcel , Papp Zoltan , Toth Attila , Hamdani Nazha , Szilvassy Zoltan , Juhasz Bela 
Published: November 2021

Background and PurposeThe small molecule BGP‐15 has been reported to alleviate symptoms of heart failure and improve muscle function in murine models. Here, we investigated the acute and chronic effects of BGP‐15 in a rabbit model of atherosclerotic cardiomyopathy.Experimental ApproachRabbits were maintained on standard chow (control) or atherogenic diet (hypercholesterolemic) for 16 weeks. BGP‐15 was administered intravenously (once) or orally (for 16 weeks), to assess acute and chronic effects. Cardiac function was evaluated by echocardiography, endothelium‐dependent vasorelaxation was assessed and key molecules in the protein kinase G (PKG) pathway were examined by enzyme‐linked immunosorbent assay (ELISA) and western blot. Passive force generation was investigated in skinned cardiomyocytes.Key ResultsBoth acute and chronic BGP‐15 treatments improved the diastolic performance of the diseased heart. However, vasorelaxation and serum lipid markers were unaffected. Myocardial cyclic guanosine monophosphate (cGMP) levels were elevated in the BGP‐15‐treated group, along with preserved PKG activity and increased phospholamban Ser16‐phosphorylation. PDE5 expression decreased in the BGP‐15‐treated group and PDE1 was inhibited. Cardiomyocyte passive tension reduced in BGP‐15‐treated rabbits, the ratio of titin N2BA/N2B isoforms increased and PKG‐dependent N2B‐titin phosphorylation elevated.Conclusions and ImplicationsBGP‐15 treatment improves diastolic function, reduces cardiomyocyte stiffness and restores titin compliance in a rabbit model of atherosclerotic cardiomyopathy by increasing the activity of the cGMP‐PKG pathway. As BGP‐15 has been proven to be safe, it may be clinically useful in the treatment of diastolic dysfunction.
Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism
Authors: Jayasena Channa N. , Anderson Richard A. , Llahana Sofia , Barth Julian H. , MacKenzie Finlay , Wilkes Scott , Smith Neil , Sooriakumaran Prasanna , Minhas Sukhbinder , Wu Frederick C. W. , Tomlinson Jeremy , Quinton Richard 
Published: November 2021

AbstractMale hypogonadism (MH) is a common endocrine disorder. However, uncertainties and variations in its diagnosis and management exist. There are several current guidelines on testosterone replacement therapy that have been driven predominantly by single disciplines. The Society for Endocrinology commissioned this new guideline to provide all care providers with a multidisciplinary approach to treating patients with MH. This guideline has been compiled using expertise from endocrine (medical and nursing), primary care, clinical biochemistry, urology and reproductive medicine practices. These guidelines also provide a patient perspective to help clinicians best manage MH.
Challenges in the diagnosis and management of glucocorticoid‐induced osteoporosis in younger and older adults
Authors: Herath Madhuni , Langdahl Bente , Ebeling Peter R. , Milat Frances 
Published: November 2021

AbstractObjectiveGlucocorticoids constitute a considerable risk for developing osteoporosis in both younger and older adults. However, currently available bone imaging modalities and fracture‐risk assessment tools do not adequately capture the dramatic changes in bone microarchitecture, heterogeneity of glucocorticoid exposure, the impact of chronic disease and other osteoporosis risk factors on the assessment of osteoporosis in these individuals.DesignA narrative review is presented, following a systematic search of the literature from 2000 to 2021.ResultsOur current appreciation of glucocorticoid‐induced osteoporosis (GIO) is focused on older populations, with limited evidence to guide the investigation, risk assessment and treatment in premenopausal women and men less than 50 years. The impact of the underlying chronic disease on secondary osteoporosis in these younger adults is also poorly understood.ConclusionThrough this narrative review, we provide a comprehensive overview of and recommendations for optimising the management of this common cause of secondary osteoporosis younger and older adults.
The transcriptome of hand eczema assessed by tape stripping
Authors: Sølberg Julie B. K. , Quaade Anna S. , Jacobsen Stine B. , Andersen Jeppe D. , Kampmann Marie‐Louise , Morling Niels , Litman Thomas , Thyssen Jacob P. , Johansen Jeanne D. 
Published: November 2021

AbstractBackgroundNo biomarkers have been identified that can classify subtypes of hand eczema (HE). Although skin biopsies represent the gold standard for investigations of the skin, the invasive technique is not favorable when investigating skin from sensitive areas. Recent advances in the use of skin‐tape strips for molecular investigations enable noninvasive investigations of HE.ObjectiveBy using whole transcriptome sequencing (WTS), the molecular profile of HE according to different localizations on the hands, etiologies, and clinical/morphological subtypes was investigated.MethodsThirty adult, Danish HE patients, 12 with and 18 without concurrent atopic dermatitis (AD), as well as 16 controls were included. Tape strip samples were collected from lesional, nonlesional, and healthy skin. Total RNA was extracted and WTS was performed.ResultsThe largest molecular difference of HE patients with and without AD was found in nonlesional skin areas and included a downregulation ofCXCL8for HE patients without AD. Differences between allergic and irritant contact dermatitis included epidermal biomarkers such asEPHA1.ConclusionSkin tape strip samples could be used to assess the gene expression profile of HE on different localizations of the hands. The skin tape strip method identified new molecular markers that showed promising result for the identification of HE subtypes.
The Impact of COVID‐19 on the Dietary Diversity of Children and Adolescents: Evidence from a Rural/Urban Panel Study
Authors: Cui Yi , Si Wei , Zhao Qiran , Glauben Thomas , Feng Xiaolong 
Published: November 2021

AbstractThis paper offers the first empirical evidence of the impact of COVID‐19 on dietary diversity among children and adolescents in urban and rural families by using panel data collected in 2019 (before COVID‐19) and 2020 (during COVID‐19) in northern China. Our study uses panel data from 2,201 primary school students and 1,341 junior high‐school students to apply the difference in differences (DID) method to estimate the impact of COVID‐19 on dietary diversity among students in urban and rural families. We found that the dietary diversity score (DDS) of rural students decreased by 0.295 points (p < 0.01) compared with that of urban students during COVID‐19. Specifically, COVID‐19 significantly reduced the frequency of rural students' consumption of vegetables by 1.8 percent, protein‐rich foods such as soybean products and nuts by 6.0 percent, meats by 4.0 percent, aquatic products by 6.7 percent, and eggs by 5.3 percent, compared with urban students. Further, COVID‐19 had a significant negative effect on the dietary diversity of students from low‐ and middle‐income groups, with the DDS of the low‐income group decreasing by 0.31 points (p < 0.01) and that of the middle‐income group by 0.12 points (p < 0.1).
Hide‐and‐seek: Neurotropic squamous cell carcinoma of the periorbital region – a series of five cases and review of the literature
Authors: Morandi Evi M. , Rauchenwald Tina , Puelzl Petra , Zelger Bernhard W. , Zelger Bettina G. , Henninger Benjamin , Pierer Gerhard , Wolfram Dolores 
Published: November 2021

SummarySquamous cell carcinoma is the second most common malignancy of the skin after basal cell carcinoma and mainly found in sun‐exposed areas such as the face. This mostly locally destructive malignancy may show invasive growth and insidious mechanisms of dissemination such as perineural invasion. Periorbital squamous cell carcinoma is associated with perineural invasion in up to 14 % of cases. Specifically in this region, the proximity to cranial nerves and therefore the associated risk of progression to the central nervous system are associated with poor prognosis. The clinically concealed character of this entity often leads to a delay in diagnosis and consequently makes complete resection and reconstruction demanding. Careful clinical evaluation often hints at perineural invasion before obtaining histology.Aside from presenting five challenging cases, this work analyzes risk factors, clinical as well as histological features, and treatment options for periorbital squamous cell carcinoma with perineural invasion.
Drug eruptions with novel targeted therapies – immune checkpoint and EGFR inhibitors
Authors: Pospischil Isabella , Hoetzenecker Wolfram 
Published: November 2021

SummaryGiven the increasing use of novel targeted therapies, dermatologists are constantly confronted with novel cutaneous side effects of these agents. A rapid diagnosis and appropriate management of these side effects are crucial to prevent impairment of the patients’ quality of life and interruptions of essential cancer treatments. Immune checkpoint and EGFR inhibitors are frequently used targeted therapies for various malignancies and are associated with a distinct spectrum of cutaneous adverse events. Exanthematous drug eruptions represent a particular diagnostic challenge in these patients. Immune checkpoint inhibitors can elicit a plethora of immune‐related exanthemas, most commonly maculopapular, lichenoid, and psoriasiform eruptions. Additionally, autoimmune bullous dermatoses and exanthemas associated with connective tissue diseases may arise. In cases of severe, atypical or therapy‐resistant presentations an extensive dermatological investigation including a skin biopsy is recommended. Topical and systemic steroids are the mainstay of treatment. Papulopustular eruptions represent the major cutaneous adverse effect of EGFR inhibitor therapy, occurring in up to 90 % of patients within the first two weeks of therapy, depending on the agent. Besides topical antibiotics and steroids, oral tetracyclines are the first choice in systemic treatment and can also be used as prophylaxis.
The Existential‐Phenomenological Situation of Ideological Extremism
Authors: Zhao Steven 
Published: November 2021

AbstractIn this essay Steven Zhao provides an existential‐phenomenological account of radicalization and extremism. This elaboration is in response to what Zhao perceives to be the two problematically dominant perspectives of discourse on radicalization: the ideational perspective and the psychological perspective. The ideational perspective is risky because it offers an incomplete understanding of radicalization by presuming that it is the expression of cognitive errors. The psychological perspective, on the other hand, excessively individualizes radicalization as an exceptional psychological aberration that can riskily result in instructivistic preventative approaches in education. Zhao proposes the existential‐phenomenological elaboration as a supplemental articulation of radicalization that has potential to address the issues associated with these two dominant perspectives. According to this elaboration, ideological extremism is a relational phenomenon that constitutes a “dysfunctional” structure of intersubjectivity. Applying interrelated notion of subjectivity and intersubjectivity illuminates radicalization in a way that both widens the scope of ideational attributions/corrections and transcends the individualistic confines of psychopathology/psychological resilience. Ultimately, this elaboration seeks to enrich educational approaches to addressing radicalization such that preventative strategies are informed by the relational foundations intrinsic to both cognitive and psychological motivations of extremist behaviors and beliefs.
The Teacher Bandwidth Problem: MOOCs, Connectivism, and Collaborative Knowledge
Authors: Kotzee Ben , Palermos S. Orestis 
Published: November 2021

AbstractMassive Open Online Courses (MOOCs) have, in recent years, become increasingly popular. An important challenge facing MOOCs is the “teacher bandwidth problem”: in the MOOC environment, where there are potentially hundreds of thousands of students, it is impossible for a few teachers to interact with individual students — in other words, there is not enough “teacher bandwidth.” According to George Siemens and Stephen Downes's theory of “connectivism,” one can make up for the lack of teacher bandwidth by relying on collaboration between students. Philosophically speaking, however, this theory is underdeveloped. In this paper, Ben Kotzee and S. Orestis Palermos consider the question of learner collaboration in online courses, and the theory of connectivism, from the perspective of social epistemology. They note the similarities between Siemens and Downes's theory and virtue reliabilist theories of epistemic collaboration more broadly. The paper has two main aims: first, to offer an illustration of how it is possible to conceptualize learner collaboration in online settings as analogous to collaboration between scientists; and second, to expand on and clarify what Siemens and Downes had in mind when they proposed the theory of connectivism.
From analytic pragmatism to historical materialism: Frankfurt school critical theory and the Quine‐Duhem thesis
Authors: McNulty Jacob 
Published: November 2021

AbstractMy aim in this paper is to explore an affinity between early critical theory and analytical philosophy. The affinity is in a fairly unexpected area: philosophy of science. I argue that early critical theory embraces a view of science which is a natural if somewhat unfamiliar extension of the pragmatist one defended by Quine. In particular, I argue that Horkheimer has a version of the Quine‐Duhem thesis (“underdetermination of theory choice by the evidence”). How do the Frankfurt and analytical versions of the underdetermination thesis differ? Quine and others have taken the thesis to motivate a form of pragmatism. What this means is that it is certain interests that ultimately determine the choice of theory: chief among them, an interest in simplicity of our theories. However, the Critical Theorists offer us a distinctly historical materialist version of the underdetermination thesis, in which it is the imperatives of the prevailing mode of production, for example, capitalism, which are decisive. The result is an unfamiliar Marxist version of an otherwise familiar thesis from the analytic tradition.