bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of dose and route of administration of the P‐glycoprotein inhibitor, valspodar (PSC‐833) and the P‐glycoprotein and breast cancer resistance protein dual‐inhibitor, elacridar (GF120918) as dual infusion in rats
Authors: Rowbottom Christopher , Pietrasiewicz Alicia , Tuczewycz Taras , Grater Richard , Qiu Daniel , Kapadnis Sudarshan , Trapa Patrick
Published: March 2021

Transporters can play a key role in the absorption, distribution, metabolism, and excretion of drugs. Understanding these contributions early in drug discovery allows for more accurate projection of the clinical pharmacokinetics. One method to assess the impact of transporters in vivo involves co‐dosing specific inhibitors. The objective of the present study was to optimize the dose and route of administration of a P‐glycoprotein (P‐gp) inhibitor, valspodar (PSC833), and a dual P‐gp/breast cancer resistance protein (BCRP) inhibitor, elacridar (GF120918), by assessing the transporters’ impact on brain penetration and absorption. A dual‐infusion strategy was implemented to allow for flexibility with dose formulation. The chemical inhibitor was dosed intravenously via the femoral artery, and a cassette of known substrates was infused via the jugular vein. Valspodar or elacridar was administered as 4.5‐hour constant infusions over a range of doses. To assess the degree of inhibition, the resulting ratios of brain and plasma concentrations, Kp's, of the known substrates were compared to the vehicle control. These data demonstrated that doses greater than 0.9 mg/hr/kg valspodar and 8.9 mg/hr/kg elacridar were sufficient to inhibit P‐gp‐ and BCRP‐mediated efflux at the blood‐brain barrier in rats without any tolerability issues. Confirmation of BBB restriction by efflux transporters in preclinical species allows for subsequent prediction in humans based upon the proteomic expression at rodent and human BBB. Overall, the approach can also be applied to inhibition of efflux at other tissues (gut absorption, liver clearance) or can be extended to other transporters of interest using alternate inhibitors.
Trade‐offs in destination choices among the urban populations in three Southeast Asian countries
Authors: Zander Kerstin K. , Garnett Stephen T.
Published: March 2021

Internal migration of the urban population is substantial with diverse drivers, barriers, and reasons for destination choices. Whereas internal mobility in Organisation for Economic Co‐operation and Development (OECD) countries is well‐studied under the umbrella of residential, labour, amenity, and retirement migration, such research in non‐OECD countries is rare and limited to the economic aspects of migration. In this study, we assess the relative importance of social, environmental, and amenity factors in urban peoples' destination choices within three countries (Indonesia, Malaysia, and the Philippines) through an online survey. Concerns about safety and high living costs at potential destinations were among the most important factors in mobility decisions, whereas amenities were the least important. A high risk from climatic hazards, particularly from severe ones such as flooding and typhoons, was also an influential destination disincentive, particularly for people in Malaysia and the Philippines, that is, likely to grow in importance as climate change accelerates unabated. To maintain the attractiveness of highly exposed cities and regions to skilled people, urban planners must minimise these risks, for example, through crime control, flood disaster management, and early warning systems.
Impact of biochar and lignite‐based amendments on microbial communities and greenhouse gas emissions from agricultural soil
Authors: Li Changjian , Xiong Yunwu , Zou Jiaye , Dong Li , Ren Ping , Huang Guanhua
Published: March 2021

Understanding the responses of the microbial community and greenhouse gas (GHG) emissions to the incorporation of different organic amendments is essential for their proper utilization. In this study, laboratory‐incubated microcosm experiments were conducted to investigate the short‐term effects of pine‐wood biochar and lignite‐based amendment on the microbial communities and GHG emissions from agricultural soil. Soils amended at five different application rates were incubated for 19 d under the conditions of 60% water‐filled pore space and 25 °C. Microbial biomass in the amended soil after incubation was measured by the solid colony counting method, and the soil microbial diversity was assayed using a Biolog EcoPlate. The biochar and lignite‐based amendment had distinct effects on the soil microbial communities and GHG emissions. The microbial community growth and utilization of C sources were improved by the biochar but restrained by the lignite‐based amendment in most cases. The biochar and lignite‐based amendment had a minor impact on methane emissions. Carbon dioxide emissions were promoted by the biochar and inhibited by the lignite‐based amendment during the short‐term incubation period. Nitrous oxide emissions decreased with the application rate of biochar but increased with the rate of lignite‐based amendment. The addition of biochar at a rate of 3–4% and lignite‐based amendment at a rate of <1% has the potential to improve soil quality. Salt leaching is required to avoid accumulation when the biochar and lignite‐based amendments are applied. The findings can provide a reference for the application of biochar and lignite‐based amendment in silt loam soil.
The Australian bushfire disaster: How to avoid repeating this catastrophe for biodiversity
Authors: Celermajer Danielle , Lyster Rosemary , Wardle Glenda M. , Walmsley Rachel , Couzens Ed
Published: March 2021

Bushfires in Australia in the “Black Summer” of 2019–2020 shocked the world. Research is allowing us to begin to appreciate the scale of the catastrophe for humans, other animals, and the environment. If we are to anticipate, mitigate, and prevent further catastrophes and to protect biodiversity as best we can, we must develop a comprehensive picture of the impacts of these recent bushfires, understand their causes, and trace where responsibility for their catastrophic impact on biodiversity falls. This opinion piece argues that doing so requires an analysis that combines legal, philosophical, and scientific lenses. Correlatively, a comprehensive response demands the rapid introduction of a range of scientific, legal, political, economic, and cultural changes, not simply to reduce fossil fuel emissions and better protect biodiversity, but to disable the ideological conditions that enable the existing policy framework.

This article is categorized under:

Climate, Ecology, and Conservation > Conservation Strategies
Donor insulin therapy in intensive care predicts early outcomes after pancreas transplantation
Authors: Shapey Iestyn M. , Summers Angela , Khambalia Hussein , Yiannoullou Petros , Fullwood Catherine , Hanley Neil A. , Augustine Titus , Rutter Martin K. , van Dellen David
Published: March 2021

Aims/hypothesis

Approximately 50% of organ donors develop hyperglycaemia in intensive care, which is managed with insulin therapy. We aimed to determine the relationships between donor insulin use (DIU) and graft failure in pancreas transplantation.

Methods

UK Transplant Registry organ donor data were linked with national data from the UK solid pancreas transplant programme. All pancreas transplants performed between 2004 and 2016 with complete follow-up data were included. Logistic regression models determined associations between DIU and causes of graft failure within 3 months. Area under the receiver operating characteristic curve (aROC) and net reclassification improvement (NRI) assessed the added value of DIU as a predictor of graft failure.

Results

In 2168 pancreas transplant recipients, 1112 (51%) donors were insulin-treated. DIU was associated with a higher risk of graft loss from isolated islet failure: OR (95% CI), 1.79 (1.05, 3.07), p = 0.03, and this relationship was duration/dose dependent. DIU was also associated with a higher risk of graft loss from anastomotic leak (2.72 [1.07, 6.92], p = 0.04) and a lower risk of graft loss from thrombosis (0.62 [0.39, 0.96], p = 0.03), although duration/dose-dependent relationships were only identified in pancreas transplant alone/pancreas after kidney transplant recipients with grafts failing due to thrombosis (0.86 [0.74, 0.99], p = 0.03). The relationships between donor insulin characteristics and isolated islet failure remained significant after adjusting for potential confounders: DIU 1.75 (1.02, 2.99), p = 0.04; duration 1.08 (1.01, 1.16), p = 0.03. In multivariable analyses, donor insulin characteristics remained significant predictors of lower risk of graft thrombosis in pancreas transplant alone/pancreas after kidney transplant recipients: DIU, 0.34 (0.13, 0.90), p = 0.03; insulin duration/dose, 0.02 (0.001, 0.85), p = 0.04. When data on insulin were added to models predicting isolated islet failure, a significant improvement in discrimination and risk reclassification was observed in all models: no DIU aROC 0.56; DIU aROC 0.57, p = 0.86; NRI 0.28, p < 0.00001; insulin duration aROC 0.60, p = 0.47; NRI 0.35, p < 0.00001.

Conclusions/interpretation

DIU predicts graft survival in pancreas transplant recipients. This assessment could help improve donor selection and thereby improve patient and graft outcomes.

Graphical abstract
Repositioning HIV protease inhibitors and nucleos(t)ide RNA polymerase inhibitors for the treatment of SARS-CoV-2 infection and COVID-19
Authors: von Hentig Nils
Published: March 2021

Aims

SARS-CoV-2 is a single-stranded RNA virus which is part of the ß-coronavirus family (like SARS 2002 and MERS 2012). The high prevalence of hospitalization and mortality, in addition to the lack of vaccines and therapeutics, forces scientists and clinicians around the world to evaluate new therapeutic options. One strategy is the repositioning of already known drugs, which were approved drugs for other indications.

Subject and method

SARS-CoV-2 entry inhibitors, RNA polymerase inhibitors, and protease inhibitors seem to be valuable targets of research. At the beginning of the pandemic, theClinicalTrials.govwebpage listedn=479 clinical trials related to the antiviral treatment of SARS-CoV-2 (01.04.2020, “SARS-CoV-2,” “COVID-19,” “antivirals,” “therapy”), of whichn=376 are still accessible online in January 2021 (10.01.2021). Taking into account further studies not listed in the CTG webpage, this narrative review appraises HIV protease inhibitors and nucleos(t)ide RNA polymerase inhibitors as promising candidates for the treatment of COVID-19.

Results

Lopinavir/ritonavir, darunavir/cobicistat, remdesivir, tenofovir-disoproxilfumarate, favipriravir, and sofosbuvir are evaluated in clinical studies worldwide. Study designs show a high variability and results often are contradictory. Remdesivir is the drug, which is deployed in nearly 70% of the reviewed clinical trials, followed by lopinavir/ritonavir, favipiravir, ribavirine, and sofosbuvir.

Discussion

This review discusses the pharmacological/clinical background and questions the rationale and study design of clinical trials with already approved HIV protease inhibitors and nucleos(t)ide RNA polymerase inhibitors which are repositioned during the SARS-CoV-2 pandemic worldwide. Proposals are made for future study design and drug repositioning of approved antiretroviral compounds.
Different wear in two highly cross-linked polyethylene liners in THA: wear analysis with EBRA
Authors: Dammerer D. , Keiler A. , Putzer D. , Lenze F. , Liebensteiner M. , Thaler M.
Published: March 2021

Introduction

The purpose of this study was (1) to compare early wear rates in bedding-in periods of two highly cross-linked polyethylene liners frequently used in THA and (2) to evaluate risk factors indicating a possible higher wear rate.

Materials and methods

1120 patients who received a Crossfire or a Marathon highly cross-linked (HXLPE) ultra-high-molecular-weight polyethylene liner in primary THA at our Department between 2004 and 2018 were retrospectively reviewed. Patients with (1) only alumina heads on HXLPE acetabular bearings, (2) a minimum of four radiographs per patient for EBRA analysis, (3) no osteolysis around the acetabular cup and (4) no dislocations that occurred during the study period were included.

Results

A total of 328 patients (female: 183; male: 145; Marathon: 179; Crossfire: 149) fulfilled the inclusion criteria. Mean follow-up was 24 (range 7–51) months. With 0.22 (SD 0.27) mm mean total wear for the Marathon was three times greater than for the Crossfire, namely 0.07 (SD 0.14) mm. Mean cup migration during the investigated follow-up period was 0.7 (SD 0.8) mm for the Pinnacle and 0.5 mm (SD 0.7) for the Trident PSL cups.

Conclusion

Initial early wear of highly cross-linked polyethylene in combination with alumina heads differs strongly between products. Long-term survivorship of these liners should be observed to determine whether early wear has an impact on aseptic loosening.

Level of evidence

Level III (retrospective comparative study with prospective cohort).
The conduction velocity-potassium relationship in the heart is modulated by sodium and calcium
Authors: King D. Ryan , Entz Michael , Blair Grace A. , Crandell Ian , Hanlon Alexandra L. , Lin Joyce , Hoeker Gregory S. , Poelzing Steven
Published: March 2021

Abstract

The relationship between cardiac conduction velocity (CV) and extracellular potassium (K+) is biphasic, with modest hyperkalemia increasing CV and severe hyperkalemia slowing CV. Recent studies from our group suggest that elevating extracellular sodium (Na+) and calcium (Ca2+) can enhance CV by an extracellular pathway parallel to gap junctional coupling (GJC) called ephaptic coupling that can occur in the gap junction adjacent perinexus. However, it remains unknown whether these same interventions modulate CV as a function of K+. We hypothesize that Na+, Ca2+, and GJC can attenuate conduction slowing consequent to severe hyperkalemia. Elevating Ca2+ from 1.25 to 2.00 mM significantly narrowed perinexal width measured by transmission electron microscopy. Optically mapped, Langendorff-perfused guinea pig hearts perfused with increasing K+ revealed the expected biphasic CV-K+ relationship during perfusion with different Na+ and Ca2+ concentrations. Neither elevating Na+ nor Ca2+ alone consistently modulated the positive slope of CV-K+ or conduction slowing at 10-mM K+; however, combined Na+ and Ca2+ elevation significantly mitigated conduction slowing at 10-mM K+. Pharmacologic GJC inhibition with 30-μM carbenoxolone slowed CV without changing the shape of CV-K+ curves. A computational model of CV predicted that elevating Na+ and narrowing clefts between myocytes, as occur with perinexal narrowing, reduces the positive and negative slopes of the CV-K+ relationship but do not support a primary role of GJC or sodium channel conductance. These data demonstrate that combinatorial effects of Na+ and Ca2+ differentially modulate conduction during hyperkalemia, and enhancing determinants of ephaptic coupling may attenuate conduction changes in a variety of physiologic conditions.
The gastric disease of Napoleon Bonaparte: brief report for the bicentenary of Napoleon’s death on St. Helena in 1821
Authors: Lugli Alessandro , Carneiro Fatima , Dawson Heather , Fléjou Jean-François , Kirsch Richard , van der Post Rachel S. , Vieth Michael , Svrcek Magali
Published: March 2021

After the defeat at the battle of Waterloo on June 18, 1815, Napoleon Bonaparte was sent into exile to the Island of St. Helena where he died 6 years later on May 5, 1821. One day after his death, Napoleon’s personal physician, Dr. Francesco Antommarchi, performed the autopsy in the presence of Napoleon’s exile companions and the British medical doctors. Two hundred years later, mysteries still surround the cause of his death and different hypotheses have been postulated in the medical and historical literature. The main reasons seem to be the presence of several autopsy reports, their interpretation and perhaps the greed for thrill and mystery. Therefore, for the bicentenary of Napoleon’s death, an international consortium of gastrointestinal pathologists assembled to analyse Napoleon’s autopsy reports based on the level of medical evidence and to investigate if the autopsy reports really do not allow a final statement.
Management of Dysphagia in Nursing Homes: A National Survey
Authors: Engh Mina C. N. , Speyer Renée
Published: March 2021

The management of dysphagia may differ by country and clinical setting. The purpose of this study was to describe the management and care pathways for elderly people with dysphagia in nursing homes across Norway using an online survey. A national survey was developed that consisted of 23 questions covering various areas related to dysphagia care in nursing homes: background information of respondents, nursing homes, and residents and staff; screening and assessment of dysphagia including use of specialist consultation; management, practice patterns, and interventions targeting residents with dysphagia; training of staff; and perceived quality of current clinical practices in their nursing home. A total of 121 respondents completed the online survey, resulting in an overall response rate of 23.2%. Substantial discrepancies in dysphagia management were identified between nursing homes. In approximately 75% of nursing homes, residents were not routinely screened or assessed for swallowing problems. Although nursing homes used a broad range of strategies and routines for people with eating and swallowing difficulties, bolus modification seemed standard practice. Oral hygiene strategies were lacking in over 80% of nursing homes, and almost 50% did not have access to external experts, including speech therapists. Although nursing home staff rated the overall quality of care for people with eating and swallowing problems as high, their rating seemed mainly based on care for malnutrition and not directly aimed at dysphagia. The survey identified an evident need for training and upskilling staff in Norwegian nursing homes and raising awareness of the serious consequences and comorbidities that can result from dysphagia.
Project ACCLAIM: Intervention Effect on Community Knowledge, Attitudes and Beliefs of Maternal and Child Health and HIV/AIDS in Eswatini, Uganda and Zimbabwe
Authors: Bandopadhay N. , Woelk G. B. , Kieffer M. P. , Mpofu D. ,   the Project ACCLAIM Study Group, Woelk Godfrey , Kieffer Mary Pat , Mpofu Dephine , Chouraya Caspian , Kudiabor Kwashie , Khumalo Philisiwe , Bitarakwate Edward , Kajungu Eliab Natumanya , Mahomva Agnes , Musarandega Reuben
Published: March 2021

The ACCLAIM Study aimed to assess the effect of a package of community interventions on the demand for, uptake of, and retention of HIV-positive pregnant/postpartum women in maternal and child health (MCH) and prevention of mother-to-child HIV transmission (PMTCT) services. The study occurred from 2013 to 2015 in Eswatini, Uganda, and Zimbabwe. The three interventions were: (1) a social learning and action component for community leaders, (2) community days, and (3) peer discussion groups. Household cross-sectional surveys on community members’ MCH and PMTCT knowledge, attitudes, and beliefs were analyzed pre- and post-intervention, using MCH, HIV stigma, and gender-equitable men (GEM) indicators. We used t-tests to measure the significance of mean pre- vs. post-intervention score changes stratified by gender within each intervention arm and generalized linear models to compare mean score changes of the cumulative intervention arms with the community leaders-only intervention. Response rates were over 85% for both surveys for men and women, with a total of 3337 pre-intervention and 3162 post-intervention responses. The combined package of three interventions demonstrated a significantly greater increase in MCH scores for both women (diff = 1.34, p ≤ 0.001) and men (diff = 2.03, p < 0.001). The arms that included interventions for both community leader engagement and community days (arms 2 and 3)led to a greater increase in mean GEM scores compared to the community leader engagement intervention alone (arm 1), for both women (diff = 1.32, p = 0.002) and men (diff = 1.37, p = 0.004). Our findings suggest that a package of community interventions may be most effective in increasing community MCH/HIV knowledge and improving gender-equitable norms.
Cellulose dissolution in aqueous NaOH–ZnO: effect of pulp pretreatment at macro and molecular levels
Authors: Väisänen Saija , Kosonen Harri , Ristolainen Matti , Vuorinen Tapani
Published: March 2021

This paper discusses the effect of hydrolytic pretreatments on pulp dissolution in the aqueous NaOH–ZnO solvent system. Eight samples were studied. They consisted of a never-dried softwood kraft pulp that was hydrolyzed under seven different conditions as well as the pulp without hydrolysis as a reference. The dissolution of the pulps was evaluated both at the macro level as well as at the molecular level based on their reactivity with 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxo-piperidium (4-AcNH-TEMPO+). The fiber properties (i.e. the extent of fibrillation, amount of fines and fiber width, coarseness, and length) as well as the chemical composition (hemicellulose and cellulose contents) and the viscosity of the pulps was investigated. The results show that hydrolysis at medium consistency (10%) was successful in increasing the solubility of cellulose. Hydrolysis at high consistency (50%), on the other hand, increased the solubility only to some extent. With extended treatment time the fibers formed aggregates and their dissolution became poor. This phenomenon could be overcome by mechanically refining the fibers after the hydrolysis. Moreover, comparison of the viscosity of the pulp over the degree of oxidation revealed that the viscosity needed to decrease below ca. 400 ml/g in order for the outer layers of the fibers to dissolve. Finally, when pulps with similar viscosities where compared against each other, the ones with the higher glucomannan contents formed gels over time. This was true also for the pulp with the lowest viscosity and the highest solubility of the studied samples.
Labour market information and social justice: a critical examination
Authors: Staunton Tom , Rogosic Karla
Published: March 2021

Labour Market Information forms a central place in career practice and how individuals enact their careers. This paper makes use of Alvesson and Sandberg’s (Constructing research questions: doing interesting research.Sage, Thousand Oaks, 2013) methodology of focussing research on theoretical assumptions to construct a critical literature review on the relationship between Labour Market Information and career guidance. This paper presents six theoretical conceptions from the career literature: Contact, Rationalism, Nomad, Adaptability, Constructivist and Social Justice. We will argue for the need to move towards more constructivist understandings of Labour Market Information as well understandings linked to more critical understandings of the labour market.
How Do Firms Respond to Reduced Labor Costs? Evidence from the 2007 Swedish Payroll Tax Reform
Authors: Daunfeldt Sven-Olov , Gidehag Anton , Rudholm Niklas
Published: March 2021

One way for policymakers to reduce labor costs and stimulate the recruitment of marginalized groups of labor in a highly unionized economy is to lower payroll taxes. However, the efficiency of this policy instrument has been questioned, and previous evaluations have mostly found small employment effects for such reforms. We investigate the effects of a payroll tax cut in Sweden that decreased firms’ labor costs in relation to the number of young employees that they had employed when the reform was implemented in 2007. We find that most firms received small labor cost savings as a result of the reform, but those that received larger cost savings increased their number of employees significantly more than firms that received no, or minor, labor cost savings. Our findings also suggest that the payroll tax cut increased the total wages paid to incumbent workers, but the wage effect was too small to offset the positive extensive-margin employment effect of the reform. In total, we find that the Swedish payroll tax reform created 18,100 jobs over the period 2006–2008; most of these jobs were within the targeted group of young employees.
Health-promoting behaviors mediate the relationship between eHealth literacy and health-related quality of life among Chinese older adults: a cross-sectional study
Authors: Li Shaojie , Cui Guanghui , Yin Yongtian , Wang Shiyuan , Liu Xinyao , Chen Lei
Published: March 2021

Purpose

The aim of this study was to examine the association between eHealth literacy and health-related quality of life (HRQoL) and explore whether health-promoting behaviors mediate the association between eHealth literacy and HRQoL among Chinese older adults.

Methods

An anonymous cross-sectional survey was conducted among 2300 adults aged 60 or older from Jinan, China. The eHealth Literacy Scale, Short-Form Health-Promoting Lifestyle Profile, and Short-Form Health Survey (SF-12) were used to measure eHealth literacy, health-promoting behaviors, and HRQoL. Multivariate linear regression analyses were conducted to test the association between eHealth literacy, health-promoting behaviors, and HRQoL. The mediation analyses, composed of PROCESS analysis and bootstrapping method, were preformed to test both total (c), direct (c'), and indirect effects (a*b) of eHealth literacy on HRQOL through health-promoting behaviors.

Results

Regression analyses indicated that eHealth literacy (B = 0.487,p < 0.001) was significantly positively associated with health-promoting behaviors, and health-promoting behaviors (B = 0.257,p < 0.001) were associated with HRQoL. The mediation analyses indicated that eHealth literacy had a significant direct (c' = 0.183,p < 0.001) and indirect effect on older adults’ HRQoL through health-promoting behaviors (a*b = 0.125, bootstrapped 95% confidence interval (CI) = 0.094–0.157). The indirect effect accounted for 40.6% of the total effect (c = 0.308, bootstrapped 95% CI 0.241–0.376) of eHealth literacy on HRQoL.

Conclusions

Health-promoting behaviors mediated the association between eHealth literacy and HRQoL in Chinese older adults. The establishment of interventions focused on health-promoting behavior may be an effective way to help older adults with low eHealth literacy improve their HRQoL.
A Liberal Theory of Property
Authors: Dagan Hanoch
Published: March 2021

Property enhances autonomy for most people, but not for all. Because it both empowers and disables, property requires constant vigilance. A Liberal Theory of Property addresses key questions: how can property be justified? What core values should property law advance, and how do those values interrelate? How is a liberal state obligated to act when shaping property law? In a liberal polity, the primary commitment to individual autonomy dominates the justification of property, founding it on three pillars: carefully delineated private authority, structural (but not value) pluralism, and relational justice. A genuinely liberal property law meets the legitimacy challenge confronting property by expanding people's opportunities for individual and collective self-determination while carefully restricting their options of interpersonal domination. The book shows how the three pillars of liberal property account for core features of existing property systems, provide a normative vocabulary for evaluating central doctrines, and offer directions for urgent reforms.
Disarming the xenophobic everyday: Muslim migrants and the horizons of urban mutuality in Durban
Authors: Kirby Benjamin , Sibanda Francis , Charway Fred
Published: March 2021

This article explores the everyday lives that African migrants in Durban, South Africa share with other residents of the city. In conversation with Obvious Katsaura's work on ‘ethno-mutualism’, we use the example of ordinary greeting practices to show how Durban's urban everyday has been hijacked by xenophobic sensibilities. By demonstrating how the act of excluding migrants from these practices threatens to render the quotidian city uninhabitable for them, we shed light on the importance of mundane forms of social interaction for building a sense of identity and belonging. We then consider several ways in which African migrants develop and participate in Muslim forms of sociality that assist them in ‘disarming’ the urban everyday: from providing a platform for building solidarity with fellow migrants to mediating a ‘sense of welcome’ from the established Indian South African community. Elaborating on this, we delineate how forms of reciprocity emerge through the interactions between migrant and Indian Muslims that reproduce the ambient life of the city as a shared habitat, opening up new possibilities for entanglement. As such, our analysis contributes to emerging conversations about urban mutuality and migrant religious practices in the everyday lives of African cities.
Supplementing conjugated linoleic acid in breeder hens diet increased conjugated linoleic acid incorporation in liver and alters hepatic lipid metabolism in chick offspring
Authors: Fu Chun-Yan , Zhang Yan , Wang Wen-Bin , Shi Tian-Hong , Liu Xue-Lan , Wei Xiang-Fa , Yan Pei-Pei
Published: March 2021

This experiment was designed to investigate the effect of supplementing conjugated linoleic acid (CLA) in breeder hens diet on development and hepatic lipid metabolism of chick offspring. Hy-Line Brown breeder hens were allocated into two groups, supplemented with 0 (control (CT)) or 0·5 % CLA for 8 weeks. Offspring chicks were grouped according to the mother generation and fed for 7 d. CLA treatment had no significant influence on development, egg quality and fertility of breeder hens but darkened the egg yolks in shade and increased yolk sac mass compared with the CT group. Addition of CLA resulted in increased body mass and liver mass and decreased deposition of subcutaneous adipose tissue in chick offspring. The serum TAG and total cholesterol levels of chick offspring were decreased in CLA group. CLA treatment increased the incorporation of both CLA isomers (c9t11 and t10c12) in the liver of chick offspring, accompanied by the decreased hepatic TAG levels, related to the significant reduction of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) enzyme activities and the increased carnitine palmitoyltransferase-1 (CPT1) enzyme activity. Meanwhile, CLA treatment reduced the mRNA expression of genes related to fatty acid biosynthesis (FAS, ACC and sterol regulatory element-binding protein-1c) and induced the expression of genes related to β-oxidative (CPT1, AMP-activated protein kinase and PPARα) in chick offspring liver. In summary, the addition of CLA in breeder hens diet significantly increased the incorporation of CLA in the liver of chick offspring, which further regulate hepatic lipid metabolism.
Prostate cryoablation combined with androgen deprivation therapy for newly diagnosed metastatic prostate cancer: a propensity score-based study
Authors: wang Ning , Ye Yangtian , Deng Minhua , Zhao Diwei , Jiang Lijuan , Chen Dong , Wu Zhiming , Wang Yanjun , Li ZhiYong , Yang Zhenyu , Li Jibin , Zhou Fangjian , Li Yonghong
Published: March 2021

Background

Several studies showed that androgen deprivation therapy (ADT) plus local treatment of prostate could improve metastatic prostate cancer (mPCa) patients’ survival. To date there are few studies analyzed the value of prostate cryoablation in mPCa. The objective of our analysis is to evaluate the oncological results and clinical value of prostate cryoablation combined with ADT compared with ADT alone in newly diagnosed mPCa patients.

Methods

Newly diagnosed mPCa patients undergoing cryoablation plus ADT (group A) between January 2011 and November 2018 were identified. Patients receiving ADT alone (group B) were selected from the same institutional prostate cancer database by propensity score matching based on clinical characteristics. Oncological results and clinical value in symptom control and primary lesion treatment were compared.

Results

Fifty-four patients were included in each group. Prostate cryoablation was well tolerated. The median follow-up time was 40 (27–53) and 39 (31–54) months in group A and group B, respectively. Patients in group A had a lower median prostate-specific antigen (PSA) nadir (0.025 ng/mL vs. 0.230 ng/mL, p = 0.001), longer median failure-free survival (FFS) (39 months vs. 21 months, p = 0.005), and median metastatic castration-resistant prostate cancer (mCRPC)-free survival (39 months vs. 21 months, p = 0.007). No difference in cancer-specific survival and overall survival was found between the two groups. Multivariate Cox analysis showed combination therapy reduced the risk of FFS by 45.8% (HR = 0.542 [95% CI 0.329–0.893]; p = 0.016). Patients in group A had better clinical relief of urinary symptoms (79.1 vs. 59.1%, p = 0.044) and required less treatment of primary lesions for symptomatic relief (13.0 vs. 31.5%, p = 0.021).

Conclusions

Prostate cryoablation plus ADT decreases PSA nadir, prolongs FFS and mCRPC-free survival, relieves urinary symptoms and reduces the need for treating primary lesions in newly diagnosed mPCa patients compared to ADT alone.
Long noncoding RNA ERLR mediates epithelial-mesenchymal transition of retinal pigment epithelial cells and promotes experimental proliferative vitreoretinopathy
Authors: Yang Shuai , Li Hui , Yao Haipei , Zhang Yao , Bao Huiqian , Wu Liangjing , Zhang Conghui , Li Min , Feng Le , Zhang Jingfa , Zheng Zhi , Xu Guotong , Wang Fang
Published: March 2021

Proliferative vitreoretinopathy (PVR) is a disease that causes severe blindness and is characterized by the formation of contractile fibrotic subretinal or epiretinal membranes. The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a hallmark of PVR. This work aims to examine the role of a long noncoding RNA (lncRNA) named EMT-related lncRNA in RPE (ERLR, LINC01705-201 (ENST00000438158.1)) in PVR and to explore the underlying mechanisms. In this study, we found that ERLR is upregulated in RPE cells stimulated with transforming growth factor (TGF)-β1 as detected by lncRNA microarray and RT-PCR. Further studies characterized full-length ERLR and confirmed that it is mainly expressed in the cytoplasm. In vitro, silencing ERLR in RPE cells attenuated TGF-β1-induced EMT, whereas overexpressing ERLR directly triggered EMT in RPE cells. In vivo, inhibiting ERLR in RPE cells reduced the ability of cells to induce experimental PVR. Mechanistically, chromatin immunoprecipitation (ChIP) assays indicated that the transcription factor TCF4 directly binds to the promoter region of ERLR and promotes its transcription. ERLR mediates EMT by directly binding to MYH9 protein and increasing its stability. TCF4 and MYH9 also mediate TGF-β1-induced EMT in RPE cells. Furthermore, ERLR is also significantly increased in RPE cells incubated with vitreous PVR samples. In clinical samples of PVR membranes, ERLR was detected through fluorescent in situ hybridization (FISH) and colocalized with the RPE marker pancytokeratin (pan-CK). These results indicated that lncRNA ERLR is involved in TGF-β1-induced EMT of human RPE cells and that it is involved in PVR. This finding provides new insights into the mechanism and treatment of PVR.
Impairment in inflammasome signaling by the chronic Pseudomonas aeruginosa isolates from cystic fibrosis patients results in an increase in inflammatory response
Authors: Phuong Melissa S. , Hernandez Rafael E. , Wolter Daniel J. , Hoffman Lucas R. , Sad Subash
Published: March 2021

Pseudomonas aeruginosa is a common respiratory pathogen in cystic fibrosis (CF) patients which undergoes adaptations during chronic infection towards reduced virulence, which can facilitate bacterial evasion of killing by host cells. However, inflammatory cytokines are often found to be elevated in CF patients, and it is unknown how chronic P. aeruginosa infection can be paradoxically associated with both diminished virulence in vitro and increased inflammation and disease progression. Thus, we investigated the relationship between the stimulation of inflammatory cell death pathways by CF P. aeruginosa respiratory isolates and the expression of key inflammatory cytokines. We show that early respiratory isolates of P. aeruginosa from CF patients potently induce inflammasome signaling, cell death, and expression of IL-1β by macrophages, yet little expression of other inflammatory cytokines (TNF, IL-6 and IL-8). In contrast, chronic P. aeruginosa isolates induce relatively poor macrophage inflammasome signaling, cell death, and IL-1β expression but paradoxically excessive production of TNF, IL-6 and IL-8 compared to early P. aeruginosa isolates. Using various mutants of P. aeruginosa, we show that the premature cell death of macrophages caused by virulent bacteria compromises their ability to express cytokines. Contrary to the belief that chronic P. aeruginosa isolates are less pathogenic, we reveal that infections with chronic P. aeruginosa isolates result in increased cytokine induction due to their failure to induce immune cell death, which results in a relatively intense inflammation compared with early isolates.
Population genomics and conservation management of a declining tropical rodent
Authors: von Takach Brenton , Penton Cara E. , Murphy Brett P. , Radford Ian J. , Davies Hugh F. , Hill Brydie M. , Banks Sam C.
Published: March 2021

Conservation management is improved by incorporating information about the spatial distribution of population genetic diversity into planning strategies. Northern Australia is the location of some of the world’s most severe ongoing declines of endemic mammal species, yet we have little genetic information from this regional mammal assemblage to inform a genetic perspective on conservation assessment and planning. We used next-generation sequencing data from remnant populations of the threatened brush-tailed rabbit-rat (Conilurus penicillatus) to compare patterns of genomic diversity and differentiation across the landscape and investigate standardised hierarchical genomic diversity metrics to better understand brush-tailed rabbit-rat population genomic structure. We found strong population structuring, with high levels of differentiation between populations (FST = 0.21–0.78). Two distinct genomic lineages between the Tiwi Islands and mainland are also present. Prioritisation analysis showed that one population in both lineages would need to be conserved to retain at least ~80% of alleles for the species. Analysis of standardised genomic diversity metrics showed that approximately half of the total diversity occurs among lineages (δ = 0.091 from grand totalγ = 0.184). We suggest that a focus on conserving remnant island populations may not be appropriate for the preservation of species-level genomic diversity and adaptive potential, as these populations represent a small component of the total diversity and a narrow subset of the environmental conditions in which the species occurs. We also highlight the importance of considering both genomic and ecological differentiation between source and receiving populations when considering translocations for conservation purposes.
Organic matter and water from asteroid Itokawa
Authors: Chan Q. H. S. , Stephant A. , Franchi I. A. , Zhao X. , Brunetto R. , Kebukawa Y. , Noguchi T. , Johnson D. , Price M. C. , Harriss K. H. , Zolensky M. E. , Grady M. M.
Published: March 2021

Understanding the true nature of extra-terrestrial water and organic matter that were present at the birth of our solar system, and their subsequent evolution, necessitates the study of pristine astromaterials. In this study, we have studied both the water and organic contents from a dust particle recovered from the surface of near-Earth asteroid 25143 Itokawa by the Hayabusa mission, which was the first mission that brought pristine asteroidal materials to Earth’s astromaterial collection. The organic matter is presented as both nanocrystalline graphite and disordered polyaromatic carbon with high D/H and 15N/14N ratios (δD =  + 4868 ± 2288‰; δ15N =  + 344 ± 20‰) signifying an explicit extra-terrestrial origin. The contrasting organic feature (graphitic and disordered) substantiates the rubble-pile asteroid model of Itokawa, and offers support for material mixing in the asteroid belt that occurred in scales from small dust infall to catastrophic impacts of large asteroidal parent bodies. Our analysis of Itokawa water indicates that the asteroid has incorporated D-poor water ice at the abundance on par with inner solar system bodies. The asteroid was metamorphosed and dehydrated on the formerly large asteroid, and was subsequently evolved via late-stage hydration, modified by D-enriched exogenous organics and water derived from a carbonaceous parent body.
A survey of clinicians on the use of artificial intelligence in ophthalmology, dermatology, radiology and radiation oncology
Authors: Scheetz Jane , Rothschild Philip , McGuinness Myra , Hadoux Xavier , Soyer H. Peter , Janda Monika , Condon James J.J. , Oakden-Rayner Luke , Palmer Lyle J. , Keel Stuart , van Wijngaarden Peter
Published: March 2021

Artificial intelligence technology has advanced rapidly in recent years and has the potential to improve healthcare outcomes. However, technology uptake will be largely driven by clinicians, and there is a paucity of data regarding the attitude that clinicians have to this new technology. In June–August 2019 we conducted an online survey of fellows and trainees of three specialty colleges (ophthalmology, radiology/radiation oncology, dermatology) in Australia and New Zealand on artificial intelligence. There were 632 complete responses (n = 305, 230, and 97, respectively), equating to a response rate of 20.4%, 5.1%, and 13.2% for the above colleges, respectively. The majority (n = 449, 71.0%) believed artificial intelligence would improve their field of medicine, and that medical workforce needs would be impacted by the technology within the next decade (n = 542, 85.8%). Improved disease screening and streamlining of monotonous tasks were identified as key benefits of artificial intelligence. The divestment of healthcare to technology companies and medical liability implications were the greatest concerns. Education was identified as a priority to prepare clinicians for the implementation of artificial intelligence in healthcare. This survey highlights parallels between the perceptions of different clinician groups in Australia and New Zealand about artificial intelligence in medicine. Artificial intelligence was recognized as valuable technology that will have wide-ranging impacts on healthcare.
Smaller bladder capacity and stronger bladder contractility in patients with ketamine cystitis are associated with elevated TRPV1 and TRPV4
Authors: Yang Hsueh-Hui , Jhang Jia-Fong , Hsu Yung-Hsiang , Jiang Yuan-Hong , Zhai Wei-Jun , Kuo Hann-Chorng
Published: March 2021

Stronger contractility and smaller bladder capacity are common symptoms in ketamine cystitis (KC). This study investigates the association between expression levels of transient receptor potential cation channel subfamily V (TRPV) proteins and the clinical characteristics of KC. Bladder tissues were obtained from 24 patients with KC and four asymptomatic control subjects. Video urodynamic parameters were obtained before surgical procedures. The TRPV proteins were investigated by immunoblotting, immunofluorescence staining, and immunohistochemistry. The Pearson test was used to associate the expression levels of TRPV proteins with clinical characteristics of KC. The expression level of TRPV1 and TRPV4 was significantly higher in the severe KC bladders than in mild KC or control bladders. The TRPV1 proteins were localized in all urothelial cell layers, and TRPV4 was located in the basal cells and lamina propria. The expression of TRPV1 was negatively associated with maximal bladder capacity (r = − 0.66,P = 0.01). The expression of TRPV4 was positively associated with the velocity of detrusor pressure rise to the maximum flow rate (r = 0.53,P = 0.01). These observations suggest smaller bladder capacity and stronger contractility in KC are associated with an elevated expression of TRPV1 and TRPV4, respectively.
Effect of Ni2O3 on diamond crystal growth in an Fe–Ni–C system under high temperature and high pressure
Authors: Mu Peiyang , Zhou Guangtong , Chen Liangchao , Zhang Zhuangfei , Zhang Yuewen , Shen Weixia , Wang Qianqian , Wan Biao , Fang Chao , Jia Xiaopeng
Published: March 2021

In this paper, the oxygen-containing diamond large single crystals were successfully synthesized by adding Ni2O3 to the Fe–Ni–C system under HPHT. The oxygen affects the P–T conditions for diamond synthesis, and morphology of diamond.
A dual-rotator fluorescent probe for analyzing the viscosity of mitochondria and blood
Authors: Fu Manlin , Sun Yue , Kenry  , Zhang Miao , Zhou Haihua , Shen Wei , Hu Yi , Zhu Qing
Published: March 2021

A novel mitochondria-targeting molecular rotator FD was designed to visualize changes in viscosity under hypoxic conditions in vitro and in vivo.
Acceptor-mediated regioselective enzyme catalyzed sialylation: chemoenzymatic synthesis of GAA-7 ganglioside glycan
Authors: Tseng Hsin-Kai , Su Yung-Yu , Chang Ting-Wei , Liu Hsin-Chien , Li Pei-Jhen , Chiang Pei-Yun , Lin Chun-Cheng
Published: March 2021

The glycan of GAA-7 was facilely synthesized by enzymatic glycosylation through changing the nonreducing acceptor into GalNH2 or GalAz to successfully switch the regioselectivity of PmST1.
Synthetic heparan sulfate ligands for vascular endothelial growth factor to modulate angiogenesis
Authors: Jain Prashant , Shanthamurthy Chethan D. , Leviatan Ben-Arye Shani , Yehuda Sharon , Nandikol Sharvani S. , Thulasiram Hirekodathakallu V , Padler-Karavani Vered , Kikkeri Raghavendra
Published: March 2021

We have identified GlcNHAc(6-O-SO3−)-IdoA(2-O-SO3−) (HT-2,6S-NAc) tetrasaccharide as a potential ligand to target VEGF165 mediated angiogenesis.
Synthesis of nano-ZSM-5 zeolite via a dry gel conversion crystallization process and its application in MTO reaction
Authors: Chen Xueshuai , Jiang Rongli , Gao Yu , Zhou Zihan , Wang Xingwen
Published: March 2021

Nano-sized ZSM-5 with superior catalytic properties was synthesized from LAPONITE® as one of the Si sources by a dry gel conversion method.
Targeted synthesis of a CrIII–O–VV core oxo-bridged complex: spectroscopic, magnetic and electrical properties
Authors: Androš Dubraja Lidija , Žilić Dijana , Olujić Kristina , Pavić Luka , Molčanov Krešimir , Pajić Damir
Published: March 2021

The results of vibrational, electronic, structural, thermal, magnetic and impedance spectroscopy studies are presented in the first reported compound with a CrIII–O–VV bridge.
Exploring the interactions between protein coronated CdSe quantum dots and nanoplastics
Authors: Chakraborty Debolina , Naik Sanjay , Kumar Sanjit , Chandrasekaran N. , Mukherjee Amitava
Published: March 2021

QDs after protein coronation can undergo sequential interaction with other pollutants which may alter the physiochemical property of the QDs and influence the stability of the corona proteins.
Iridium-catalysed borylation of pyrene – a powerful route to novel optoelectronic materials
Authors: Zhang Yufeng , Tan Leibo , Shi Junqing , Ji Lei
Published: March 2021

We summarized the Ir-catalysed borylation of PAHs, especially pyrene, and the optoelectronic materials generated by following this chemistry. The optoelectronic properties of pyrene derivatives have also been discussed.