bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of botulinum neurotoxin in the treatment of erectile dysfunction refractory to phosphodiesterase inhibitors: Results of a randomized controlled trial
Authors: Abdelrahman Islam Fathy Soliman , Raheem Amr Abdel , Elkhiat Yaser , Aburahma Abdelrahman A. , Abdel‐Raheem Tarek , Ghanem Hussein 
Published: October 2021

AbstractBackgroundThere has been recent interest in the use of botulinum neurotoxin (BoNT) in the field of Andrology, whereby it has been investigated in the treatment of penile retraction and premature ejaculation.ObjectivesTo evaluate the safety and efficacy of intracavernosal BoNT‐A injection in the treatment of patients with erectile dysfunction (ED) refractory to oral phosphodiesterase inhibitors (PDE5Is).Patients and methodsA double‐blind randomized placebo‐controlled prospective comparative study conducted at one center and involved 70 patients with ED refractory to PDE5Is. At baseline, the following data were collected: erection hardness score (EHS), peak systolic velocity (PSV), end diastolic velocity (EDV), sexual health inventory for men (SHIM), and the sexual encounter profile 2&3 (SEP‐2&3) questionnaires. Treatment group (n = 35) received a single ICI of 100 units of BoNT‐A in 2 ml of saline and control group (n = 35) received a single ICI of 2 ml of saline. EHS, PSV, and EDV were assessed at 2 weeks post treatment. SHIM, SEP‐2, SEP‐3, and global assessment questionnaire (GAQ‐Q1&Q2) were completed at 2‐, 6‐, and 12‐weeks post treatment.ResultsTwo weeks post treatment, the treatment group showed a statistically significant improvement in the mean EHS, PSV, EDV, and GAQ‐Q1 positive responders (p < 0.001) compared to the control group. At 6‐ and 12‐weeks post treatment, the treatment group showed a statistically significant improvement in the SHIM scores, SEP‐2, and GAQ‐Q1&Q2 positive responders compared to the control group. At 6 weeks, where there was a 5‐point improvement in the mean SHIM score of the treatment group (10±5.9 from 5.4±1.7 at baseline) versus no improvement in the placebo group, 18 patients in the treatment group (53%) were able to have an erection hard enough for vaginal penetration versus only one patient in the control group.ConclusionBoNT‐A is safe and effective as a potential treatment for ED refractory to PDE5I therapy.
Metallographic and neutron diffraction analysis on microstructural evolution and control in ancient Indian high carbon steel
Authors: Park Jang‐Sik , Grazzi Francesco , Scherillo Antonella , Shinde Vasant 
Published: October 2021

AbstractDespite the credit attributed to India for the early production of high carbon steel, not much is known about Indian contribution to the implementation of a pertinent fabrication technique without which this special material might have little practical value. A metallographic examination of a small iron lump and an iron sheet, both excavated from the second BC to second AD century site at Junnar in India, provided evidence that the production of high carbon steel was stimulated by a sophisticated technique practiced for the control of carbide precipitation in such a peculiar material. In addition, neutron diffraction analysis on one of the objects, the iron sheet, produced key information defining the thermo‐mechanical treatments applied. An anisotropy in the orientation of cementite grains, similar to one of those documented for the so‐called Damascus swords, was also confirmed. A detailed account of the analytical results is presented, suggesting that a proper technique for the control of microstructural evolution in high carbon steel was fully established in India much earlier than the beginning of the Damascus steel tradition, which must have been inspired by technologies long practiced in India.
Art historical and archaeometric analyses of the ‘animal style’ gold and silver ornaments (fourth–third centuries bce) found in north‐west China
Authors: Liu Yan , Xi Tongyuan , Ma Jian , Liu Ruiliang , Kuerban Reheman , Yan Feng , Ma Yingxia , Yu Jianjun , Ji Juan , Yang Junchang 
Published: October 2021

AbstractThe archaeological visibility of the production and consumption of gold and silver ornaments increased substantially during the Iron Age. A large number of precious metalworks rendered with distinctive ‘animal style’ motifs have been recovered from elite tombs in north‐west China, and have attracted great interest when investigating the dynamics of exchange, mobility and transcultural encounters in Eurasian antiquity. However, little scientific research has been undertaken to examine the manufacturing techniques and metal composition of such ‘animal style’ artefacts found in north‐west China and its neighbouring areas in a broader Eurasian context. Using multiple non‐invasive analytical methods, we conducted a detailed scientific analysis of two groups of precious metals excavated from Dongheigou Tomb 12 (fourth–second centuries bce) and Xigou Tomb 1 (third–second centuries bce) in present‐day Balikun county, Xinjiang Uygur Autonomous Region. The results suggest that mould‐pressing technology was employed for the production of the ‘animal style’ appliqués found in these two tombs. The current analysis provides a definitive explanation for the traces of superficial crafting through their specific microstructure and the tool marks of manufacturing, and will thus be of significant interest for further research concerning the metallurgic knowledge and technological practice of precious metalworking industry in north‐west China and Central Asia.
Physicians' and pharmacists' views and experiences regarding use of direct oral anticoagulants in clinical practice
Authors: Capiau Andreas , Mehuys Els , Dhondt Eline , De Backer Tine , Boussery Koen 
Published: October 2021

AimDirect oral anticoagulants (DOACs) are increasingly used compared to vitamin K antagonists (VKAs). Guidelines advocate a structured multidisciplinary approach in the management of patients treated with DOACs. The aim of this study was to assess the views and experiences of physicians and pharmacists regarding DOAC use in clinical practice.MethodsAn online questionnaire was sent to both primary (general practitioners [GPs], community pharmacists) and secondary healthcare professionals (cardiologists, residents in internal medicine and hospital pharmacists) between March and July 2020. The questionnaire covered four topics: (i) current practice, (ii) prescribing behaviour (only for physicians), (iii) self‐perceived knowledge about DOACs and (iv) views and opinions about DOACs versus VKAs.ResultsIn total, 110 physicians and 111 pharmacists completed the survey. Healthcare professionals in secondary care had more experience with DOACs and felt more confident with higher self‐perceived knowledge about DOACs compared to their colleagues in primary care. Healthcare professionals' self‐perceived knowledge was more or less complementary, for example physicians felt less confident in managing drug–drug interactions (DDIs) where pharmacists reported being more confident in this topic. Physicians reported uncertainties on the potential impact of risk factors – such as older age, lower body weight and DDIs – on appropriate DOAC dosing.ConclusionComplementarity in physicians' and pharmacists' self‐perceived knowledge levels of DOACs may facilitate and necessitate future multidisciplinary collaboration initiatives for the management and follow‐up of DOAC patients.
Assessment of drug–drug interactions between moxonidine and antiepileptic drugs in the maximal electroshock seizure test in mice
Authors: Łukawski Krzysztof , Czuczwar Stanisław Jerzy 
Published: October 2021

AbstractHypertension is a common comorbid condition with epilepsy, and drug interactions between antihypertensive and antiepileptic drugs (AEDs) are likely in patients. Experimental studies showed that centrally active imidazoline compounds belonging to antihypertensive drugs can affect seizure susceptibility. The purpose of this study was to assess the effect of moxonidine, an I1‐imidazoline receptor agonist, on the anticonvulsant efficacy of numerous AEDs (carbamazepine, phenobarbital, valproate, phenytoin, oxcarbazepine, topiramate and lamotrigine) in the mouse model of maximal electroshock. Besides, the combinations of moxonidine and AEDs were investigated for adverse effects in the passive avoidance task and the chimney test. Drugs were administered intraperitoneally (ip). Moxonidine at doses of 1 and 2 mg/kg ip did not affect the convulsive threshold. Among tested AEDs, moxonidine (2 mg/kg) potentiated the protective effect of valproate against maximal electroshock. This interaction could be pharmacodynamic because the brain concentration of valproate was not significantly changed by moxonidine. The antihypertensive drug did not cause adverse effects when combined with AEDs. This study shows that moxonidine may have a neutral or positive effect on the anticonvulsant activity of AEDs in patients with epilepsy. The enhancement of the anticonvulsant action of valproate by moxonidine needs further investigations to elucidate potential mechanisms involved.
Assurance of corporate social responsibility reports: Does it reduce decoupling practices?
Authors: García‐Sánchez Isabel‐María , Hussain Nazim , Aibar‐Guzmán Cristina , Aibar‐Guzmán Beatriz 
Published: October 2021

AbstractRecent research shows the existence of a selective corporate social responsibility (CSR) disclosure strategy that creates a gap between CSR disclosure and actual performance. These CSR decoupling practices compromise the credibility of CSR reports and have triggered a demand for the adoption of credibility enhancement mechanisms, such as adherence to the global reporting initiative (GRI) reporting guidelines, and the external assurance of CSR reports. The effectiveness of such mechanisms is not clear, however. This paper draws on legitimacy theory and addresses the issue of symbolic versus substantive use of assurance, and compliance with GRI reporting standards, by analysing their effect on CSR decoupling using an international sample of 1,939 companies (15,219 observations from 2002 to 2017). Analysis of a sub‐sample of 708 firms (3,730 observations from 2011 to 2017) also shows that the application of GRI guidelines and the specific characteristics of the assurance provider—accountant, experience and specialisation—reduce CSR decoupling practices. The results provide researchers, managers, assurance providers, investors, stakeholders and regulators with additional insight into the value of the external assurance of sustainability reports and have important managerial and policy implications.
Caring by lying
Authors: MacKenzie Jordan 
Published: October 2021

AbstractCaring for loved ones with dementia can sometimes necessitate a loose relationship with the truth. Some might view such deception as categorically immoral, and a violation of our general truth‐telling obligations. I argue that this view is mistaken. This is because truth‐telling obligations may be limited by the particular relationships in which they feature. Specifically, within caregiving relationships, we are often permitted (and sometimes obligated) to deceive the people with whom we share them. Our standing to deceive follows from certain features of caregiving relationships. Specifically, they are relationships that involve obligations to promote a person's interests and values (and not simply their autonomy), that often permit us to assume the hypothetical consent of the person with whom we share them, and in which we are often entitled to act out of self‐interest. Once we appreciate these features, we will be able to recognize that the truth‐telling norms governing our relationships with loved ones with dementia do not represent a radical departure from our general truth‐telling obligations, but are instead consistent with truth‐telling norms that feature in other caregiving relationships. In addition, we will be able to understand why we may feel conflicted about lying to loved ones with dementia, even when lying is permissible.
Inequitable use of health services for Indigenous mothers who experience stillbirth in Australia
Authors: Callander Emily , Fox Haylee , Mills Kyly , Stuart‐Butler Deanna , Middleton Philippa , Ellwood David , Thomas Joseph , Flenady Vicki 
Published: October 2021

AbstractObjectivesThe purpose of this study was to identify differences in health service expenditure on Indigenous and non‐Indigenous women who experience a stillbirth, women's out‐of‐pocket costs, and health service use.MethodsThe project used a whole‐of‐population linked data set called “Maternity1000,” which includes all women who gave birth in Queensland, Australia, between July 1, 2012, and June 30, 2018 (n = 396 158). Multivariable analysis was undertaken to assess differences in mean health service expenditure; and number of health care services accessed between Indigenous and non‐Indigenous women who had a stillbirth from birth to twelve months postpartum. Costs are presented in 2019/20 Australian dollars.ResultsThere was a total of 1864 babies stillborn to women in Queensland between July 1, 2012, and June 30, 2018, with 135 being born to Indigenous women and 1729 born to non‐Indigenous women. There was significantly lower total expenditure per woman for Indigenous women compared with non‐Indigenous women ($16 083 and $18 811, respectively). This was consistent across public hospital inpatient ($12 564 compared with $14 075), outpatient ($1127 compared with $1470), community‐based services ($198 compared with $313), pharmaceuticals ($8 compared with $22), private hospital ($434 compared with $1265), and for individual out‐of‐pocket fees ($21 compared with $86). Mean expenditure on emergency department services per woman was higher for Indigenous women compared with non‐Indigenous women ($947 compared with $643). Indigenous women who experienced a stillbirth accessed fewer general practitioners, allied health, specialist, obstetrics, and outpatient services, and fewer pathology and diagnostic test than their non‐Indigenous counterparts.ConclusionsInequities in access to health services exist between Indigenous and non‐Indigenous women who experience a stillbirth.
Impact of major bleeding and thrombosis on 180‐day survival in patients with severe COVID‐19 supported with veno‐venous extracorporeal membrane oxygenation in the United Kingdom: a multicentre observational study
Authors: Arachchillage Deepa J. , Rajakaruna Indika , Scott Ian , Gaspar Mihaela , Odho Zain , Banya Winston , Vlachou Aikaterini , Isgro Graziella , Cagova Lenka , Wade Joshua , Fleming Lucy , Laffan Mike , Szydlo Richard , Ledot Stephane , Jooste Rachel , Vuylsteke Alain , Yusuff Hakeem 
Published: October 2021

SummaryBleeding and thrombosis are major complications in patients supported with extracorporeal membrane oxygenation (ECMO). In this multicentre observational study of 152 consecutive patients (≥18 years) with severe COVID‐19 supported by veno‐venous (VV) ECMO in four UK commissioned centres during the first wave of the COVID‐19 pandemic (1 March to 31 May 2020), we assessed the incidence of major bleeding and thrombosis and their association with 180‐day mortality. Median age (range) was 47 years (23–65) and 75% were male. Overall, the 180‐day survival was 70·4% (107/152). The rate of major bleeding was 30·9% (47/152), of which intracranial bleeding (ICH) was 34% (16/47). There were 96 thrombotic events (63·1%) consisting of venous 44·7% [68/152 of which 66·2% were pulmonary embolism (PE)], arterial 18·6% (13/152) and ECMO circuit thrombosis 9·9% (15/152). In multivariate analysis, only raised lactate dehydrogenase (LDH) at the initiation of VV ECMO was associated with an increased risk of thrombosis [hazard ratio (HR) 1·92, 95% CI 1·21‐3·03]. Major bleeding and ICH were associated with 3·87‐fold (95% CI 2·10–7·23) and 5·97‐fold [95% confidence interval (CI) 2·36–15·04] increased risk of mortality and PE with a 2·00‐fold (95% CI1·09–3·56) risk of mortality. This highlights the difficult balancing act often encountered when managing coagulopathy in COVID‐19 patients supported with ECMO.
Cyclic helix B peptide promotes random‐pattern skin flap survival via TFE3‐mediated enhancement of autophagy and reduction of ROS levels
Authors: Lou Junsheng , Zhang Haojie , Qi Jianjun , Xu Yu , Wang Xingyu , Jiang Jingtao , Hu Xinli , Ni Libin , Cai Yuepiao , Wang Xiangyang , Gao Weiyang , Xiao Jian , Zhou Kailiang 
Published: October 2021

Background and PurposeNecrosis of random‐pattern skin flaps limits their clinical application. Helix B surface peptide (HBSP) protects tissues from ischaemia–reperfusion injury but its short plasma half‐life limits its applications. Here, we have synthesized cyclic helix B peptide (CHBP) and investigated its role in flap survival and the underlying mechanisms.Experimental ApproachFlap viability was evaluated by survival area analysis, laser Doppler blood flow and histological analysis. RNA sequencing was used to identify mechanisms underlying the effects of CHBP. Levels of autophagy, oxidative stress, pyroptosis, necroptosis and molecules related to the AMP‐activated protein kinase (AMPK)–TRPML1–calcineurin signalling pathway were assayed with Western blotting, RT‐qPCR, immunohistochemistry and immunofluorescence.Key ResultsThe results indicated that CHBP promoted the survival of random‐pattern skin flaps. The results of RNA sequencing analysis indicated that autophagy, oxidative stress, pyroptosis and necroptosis were involved in the ability of CHBP to promote skin flap survival. Restoration of autophagy flux and enhanced resistance to oxidative stress contributed to inhibition of pyroptosis and necroptosis. Increased autophagy and inhibition of oxidative stress in the ischaemic flaps were regulated by transcription factor E3 (TFE3). A decrease in the levels of TFE3 caused a reduction in autophagy flux and accumulation of ROS and eliminated the protective effect of CHBP. Moreover, CHBP regulated the activity of TFE3 via the AMPK–TRPML1–calcineurin signalling pathway.Conclusion and ImplicationsCHBP promotes skin flap survival by up‐regulating autophagy and inhibiting oxidative stress in the ischaemic flap and may have potential clinical applications.
1‐Hydroxypyrene mediates renal fibrosis through aryl hydrocarbon receptor signalling pathway
Authors: Miao Hua , Wu Xia‐Qing , Wang Yan‐Ni , Chen Dan‐Qian , Chen Lin , Vaziri Nosratola D. , Zhuang Shougang , Guo Yan , Su Wei , Ma Shi‐Xing , Zhang Huan‐Qiao , Shang You‐Quan , Yu Xiao‐Yong , Zhao Yan‐Long , Mao Jia‐Rong , Gao Ming , Zhang Jin‐Hua , Zhao Jin , Zhang Yuan , Zhang Li , Zhao Ying‐Yong , Cao Gang 
Published: October 2021

Background and PurposeIn chronic kidney disease (CKD), patients inevitably reach end‐stage renal disease and require renal transplant. Evidence suggests that CKD is associated with metabolite disorders. However, the molecular pathways targeted by metabolites remain enigmatic. Here, we describe roles of 1‐hydroxypyrene in mediating renal fibrosis.Experimental ApproachWe analysed 5406 urine and serum samples from patients with Stage 1–5 CKD using metabolomics, and 1‐hydroxypyrene was identified and validated using longitudinal and drug intervention cohorts as well as 5/6 nephrectomised and adenine‐induced rats.Key ResultsWe identified correlations between the urine and serum levels of 1‐hydroxypyrene and the estimated GFR in patients with CKD onset and progression. Moreover, increased 1‐hydroxypyrene levels in serum and kidney tissues correlated with decreased renal function in two rat models. Up‐regulated mRNA expression of aryl hydrocarbon receptor and its target genes, including CYP1A1, CYP1A2 and CYP1B1, were observed in patients and rats with progressive CKD. Further we showed up‐regulated mRNA expression of aryl hydrocarbon receptor and its three target genes, plus up‐regulated nuclear aryl hydrocarbon receptor protein levels in mice and HK‐2 cells treated with 1‐hydroxypyrene, which caused accumulation of extracellular matrix components. Treatment with aryl hydrocarbon receptor short hairpin RNA or flavonoids inhibited mRNA expression of aryl hydrocarbon receptor and its target genes in 1‐hydroxypyrene‐induced HK‐2 cells and mice.Conclusion and ImplicationsMetabolite 1‐hydroxypyrene was demonstrated to mediate renal fibrosis through activation of the aryl hydrocarbon receptor signalling pathway. Targeting aryl hydrocarbon receptor may be an alternative therapeutic strategy for CKD progression.
The Appalachian area as a tectonostratigraphic analogue for the Barents Sea shelf
Authors: Martins Gustavo , Ettensohn Frank , Knutsen Stig‐Morten 
Published: October 2021

AbstractThe US Appalachian Basin and the Arctic Norwegian and Russian Barents Sea shelf (BSS) areas are two strategic provinces for the energy industry. The Appalachian Basin is a well‐studied, mature, onshore basin, whereas the offshore BSS is still considered a frontier area. This study suggests that the Appalachian Basin may be an appropriate analogue for understanding the BSS and contribute to development of a tectonostratigraphic framework for the area. Although the Appalachian and BSS areas reflect different times and settings, both areas began as passive margins that were subsequently subjected to subduction and continent collision associated with the closure of an adjacent ocean basin. As a result, both areas exhibited multi‐phase subduction‐type orogenies, a rising hinterland that sourced sediments, and a foreland‐basin sedimentary system that periodically overflowed onto an adjacent intracratonic area of basins and platforms with underlying basement structures. Foreland‐basin sedimentary systems in the Mid‐to‐Late Palaeozoic Appalachian Basin are composed of unconformity‐bound cycles related to specific orogenic pulses called tectophases. Each tectophase gave rise to a distinct sequence of lithologies related to flexural events in the orogen. In this study, similar sequences are recognised in both BSS foreland‐basin and adjacent intracratonic sedimentary sequences that formed in response to the Late Palaeozoic–Mesozoic Uralian–Pai–Khoi–Novaya Zemlya Orogeny, suggesting that the processes generating the sequences are analogous to the tectophase cycles in the Appalachian Basin. Hence, this pioneering use of the Appalachian area and its succession as large‐scale tectonostratigraphic analogues for the BSS may further enhance understanding of Upper Palaeozoic to Middle Jurassic stratigraphy across the BSS.