bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safeguarding Access to Justice in the Age of the Online Court
Authors: Denvir Catrina , Selvarajah Amanda Darshini 
Published: August 2021

AbstractIn 2016 Her Majesty's Courts and Tribunals Service embarked on a significant modernisation programme with a view to developing online courts. In pursuit of this ambition the Courts and Tribunals (Online Procedure) Bill seeks to introduce new procedural rules to govern the online jurisdiction, giving the Lord Chancellor and an Online Procedure Rule Committee the power to mandate which proceedings will be conducted online and what assistance will be provided to users. In this study we analyse survey data and case decisions to highlight the importance of channel plurality and digital support in light of the shift to online courts. Our findings identify the groups most at risk of digital exclusion, and the expectations the judiciary sets in relation to internet access, capability, and the design of online systems. We conclude by detailing what our findings mean for safeguarding access to justice in the digital age.
The world of ribonucleases from pseudomonads: a short trip through the main features and singularities
Authors: Apura Patrícia , Gonçalves Luis G. , Viegas Sandra C. , Arraiano Cecília M. 
Published: August 2021

SummaryThe development of synthetic biology has brought an unprecedented increase in the number molecular tools applicable into a microbial chassis. The exploration of such tools into different bacteria revealed not only the challenges of context dependency of biological functions but also the complexity and diversity of regulatory layers in bacterial cells. Most of the standardized genetic tools and principles/functions have been mostly based on model microorganisms, namely Escherichia coli. In contrast, the non‐model pseudomonads lack a deeper understanding of their regulatory layers and have limited molecular tools. They are resistant pathogens and promising alternative bacterial chassis, making them attractive targets for further studies. Ribonucleases (RNases) are key players in the post‐transcriptional control of gene expression by degrading or processing the RNA molecules in the cell. These enzymes act according to the cellular requirements and can also be seen as the recyclers of ribonucleotides, allowing a continuous input of these cellular resources. This makes these post‐transcriptional regulators perfect candidates to regulate microbial physiology. This review summarizes the current knowledge and unique properties of ribonucleases in the world of pseudomonads, taking into account genomic context analysis, biological function and strategies to use ribonucleases to improve biotechnological processes.
Age patterns of intra‐pair DNA methylation discordance in twins: Sex difference in epigenomic instability and implication on survival
Authors: Tan Qihua , Li Shuxia , Sørensen Mette , Nygaard Marianne , Mengel‐From Jonas , Christensen Kaare 
Published: August 2021

AbstractAging is a biological process linked to specific patterns and changes in the epigenome. We hypothesize that age‐related variation in the DNA methylome could reflect cumulative environmental modulation to the epigenome which could impact epigenomic instability and survival differentially by sex. To test the hypothesis, we performed sex‐stratified epigenome‐wide association studies on age‐related intra‐pair DNA methylation discordance in 492 twins aged 56–80 years. We identified 3084 CpGs showing increased methylation variability with age (FDR < 0.05, 7 CpGs withp < 1e‐07) in male twins but no significant site found in female twins. The results were replicated in an independent cohort of 292 twins aged 30–74 years with 37% of the discovery CpGs successfully replicated in male twins. Functional annotation showed that genes linked to the identified CpGs were significantly enriched in signaling pathways, neurological functions, extracellular matrix assembly, and cancer. We further explored the implication of discovery CpGs on individual survival in an old cohort of 224 twins (220 deceased). In total, 264 CpGs displayed significant association with risk of death in male twins. In female twins, 175 of the male discovery CpGs also showed non‐random correlation with mortality. Intra‐pair comparison showed that majority of the discovery CpGs have higher methylation in the longer‐lived twins suggesting that loss of DNA methylation during aging contributes to increased risk of death which is more pronounced in male twins. In conclusion, age‐related epigenomic instability in the DNA methylome is more evident in males than in females and could impact individual survival and contribute to sex difference in human lifespan.
Pancreatic solid pseudopapillary neoplasm: a single‐institution study
Authors: Kotecha Krishna , Pandya Advait , Gill Anthony J. , Mittal Anubhav , Samra Jaswinder 
Published: August 2021

AbstractBackgroundsSolid pseudopapillary neoplasms (SPNs) are a distinct but rare form of low‐grade pancreatic neoplasia, accounting for 0.3%–2.7% of all pancreatic tumours. They are most common in young females. Local recurrence and distant metastasis are reported but extremely rare, and are usually resectable with curative intent. We report the clinicopathological features and long‐term outcomes of SPNs following surgical resection from a single institution.MethodsA total of 1296 patients undergoing pancreatic resection during the 30 years period from 1991 to 2020 were retrospectively reviewed, and those with a confirmed pathological diagnosis of pancreatic SPN on review were included.ResultsTwenty‐two patients (1.7% of all patients undergoing resection), were identified. Twenty patients (91%) were female. Unlike previous studies, most patients (91%) were symptomatic at diagnosis. On diagnostic CT, cystic components were visible in 16 patients (73%), calcifications were found in two patients (9%), haemorrhage in one patient (5%) and a defined capsule was seen in four patients (18%). Surgical resection was undertaken on all cases, with distal pancreatectomy the most commonly performed (n = 11, 50%). One patient (4.7%) had nodal involvement, nine patients had an incomplete tumour capsule (41%) and seven patients (32%) had tumour extension into the pancreatic parenchyma. Despite this, no patients had disease recurrence at 10 years. One patient died within 5 years of heart failure unrelated to the SPN process; no patients died within 10 years of the disease.ConclusionWe confirm a high proportion of female patients. Interestingly, a high proportion of our cohort was investigated for symptomatic disease. Despite a high proportion of tumours with an incomplete capsule, and extension into the pancreatic parenchyma, our findings indicated that SPN patients have excellent survival after margin‐negative surgical resection.
Tapentadol and oxycodone reduce cingulate glutamate in healthy volunteers
Authors: Hansen Tine Maria , Frøkjær Jens Brøndum , Mark Esben Bolvig , Drewes Asbjørn Mohr 
Published: August 2021

Tapentadol and oxycodone are commonly used analgesics. Preclinical studies have shown that oxycodone modulates brain metabolites related to opioid pathways, whereas tapentadol also affects noradrenergic activity. However, knowledge about the function of the medications in the human brain is limited. The aim was to investigate effects of tapentadol and oxycodone on brain glutamate, the most important neurotransmitter in pain processing. Magnetic resonance spectroscopy was obtained in 21 healthy subjects from the anterior cingulate cortex, prefrontal cortex, and insula at baseline and after 14 days of treatment with either 50 mg tapentadol, 10 mg oxycodone (equipotent dose, both extended release) or placebo twice daily in a randomized double‐blind cross‐over study. Compared to baseline, decreased glutamate/creatine levels were identified in anterior cingulate cortex after tapentadol (1.26 ± 0.14vs. 1.35 ± 0.18,P = .04) and oxycodone (1.26 ± 0.10vs. 1.35 ± 0.12,P = .05) treatments, both with 7% reduction. This indicates that both analgesics modulate the glutamatergic system at the supraspinal level in humans.
Lack of pharmacokinetic interaction between the HIV‐1 maturation inhibitor GSK3640254 and combination oral contraceptives in healthy women
Authors: Pene Dumitrescu Teodora , Greene Thomas J. , Joshi Samit R. , Xu Jianfeng , Johnson Mark , Halliday Fiona , Butcher Laurie , Zimmerman Eric , Webster Lindsey , Pham Theresa T. , Lataillade Max , Min Sherene 
Published: August 2021

AimsGSK3640254 is a next‐generation maturation inhibitor likely to be coadministered with combined oral contraceptives in HIV‐positive women.MethodsThis phase I, open‐label, 1‐way study assessed pharmacokinetic and pharmacodynamic interactions of GSK3640254 200 mg and ethinyl oestradiol 0.03 mg/levonorgestrel 0.15 mg once daily in healthy female participants who received ethinyl oestradiol/levonorgestrel for 10 days with a moderate‐fat meal after which GSK3640254 was added from Days 11 to 21. Primary endpoints were area under the plasma concentration–time curve to the end of the dosing interval (AUC0‐t), maximum observed concentration (Cmax) and plasma concentration at the end of the dosing interval (Cτ) for ethinyl oestradiol and levonorgestrel. Serum follicle‐stimulating hormone, luteinizing hormone and progesterone concentrations were determined. Adverse events were monitored.ResultsAmong 23 enrolled participants, 17 completed the study. Geometric least squares mean ratios (with vs. without GSK3640254) of AUC0‐t, Cmax and Cτ were 0.974, 0.970 and 1.050 for ethinyl oestradiol and 1.069, 1.032 and 1.083 for levonorgestrel, respectively. Three participants had elevated progesterone levels, which occurred before GSK3640254 administration in 2 participants. No participants had elevated follicle‐stimulating hormone or luteinizing hormone values. Fourteen participants (61%) reported adverse events. Four participants reported asymptomatic elevated transaminase levels meeting liver‐stopping criteria; of these, 3 events occurred before GSK3640254 administration and led to study withdrawal.ConclusionEthinyl oestradiol/levonorgestrel plus GSK3640254 coadministration did not affect steady‐state pharmacokinetics or pharmacodynamics of ethinyl oestradiol and levonorgestrel in healthy female participants. No major tolerability findings were reported. Elevated liver transaminase levels were probably due to ethinyl oestradiol/levonorgestrel.
Medical prescription forms of opioid cough suppressants falsified by the patients before and after they switched from over‐the‐counter to prescription‐only in France
Authors: Jouanjus Emilie , Gibaja Valérie , Fabre Florence , Lapeyre‐Mestre Maryse ,   OSIAP Working Group on opioid cough suppressants
Published: August 2021

AimsThe French Ministry of Health scheduled opioid cough suppressants as prescription‐only drugs on 12 July 2017. The present study assessed the impact of this regulation on the diversion modalities of the concerned drugs and the related drug pholcodine by analysing the national OSIAP (Ordonnances Suspectes Indicateur d'Abus Possible) database.MethodsMedical prescriptions with at least 1 mention of codeine, dextromethorphan, ethylmorphine, noscapine or pholcodine for cough suppression recorded in 2013–2019 were extracted from OSIAP. Annual mentioning rates were estimated by dividing numbers of mentions over those of prescriptions recorded the year considered. A descriptive analysis compared the characteristics of prescriptions before and after 12 July 2017.ResultsOverall, 832 mentions of the requested drugs were retrieved on 827 prescription forms. Codeine was the most frequent (n = 809, 8.7%) with 6 additional mentions of codeine/ethylmorphine combination, followed by dextromethorphan (n = 11, 0.1%) and pholcodine (n = 6, 0.1%). There was no mention of noscapine. Annual mentioning rates varied between 0 and 0.3% for all drugs except codeine. Codeine mentioning rates ranged between 0.3% (n = 2) and 0.7% (n = 9) before 12 July 2017 and increased to 10.1% (n = 61) thereafter in 2017, 16.1% (n = 314) in 2018, and 19.8% (n = 414) in 2019. The profile of subjects evolved accordingly with an increased male/female ratio (10.0 vs. 1.5 before) and decreased age (23 vs. 40 y before, P < .001).DiscussionThe sharp increase of recourse to falsified prescription forms indicates that codeine diversion continues despite restricted access, whereas the other drugs studied do not seem to have been impacted.
Efficacy and safety of roxadustat for anaemia in dialysis‐dependent and non‐dialysis‐dependent chronic kidney disease patients: A systematic review and meta‐analysis
Authors: Zheng Li , Tian Jinhui , Liu Deping , Zhao Yan , Fang Xiaoyong , Zhang Yatong , Liu Yuming 
Published: August 2021

AimsRenal anaemia is a common complication of chronic kidney disease (CKD). Roxadustat is the first‐in‐class oral hypoxia‐inducible factor prolyl hydroxylase inhibitor for the treatment of anaemia. In this systematic review, we aimed to investigate the efficacy and safety of roxadustat in the treatment of anaemia in CKD patients.MethodsPubMed, Cochrane Library, Embase, and ClinicalTrials.gov databases were searched from their inception to February 2021 for randomised controlled trials (RCTs) that compared the efficacy and safety of roxadustat to those of an erythropoiesis‐stimulating agent (ESA) or a placebo in treating anaemia in CKD patients.ResultsNine RCTs involving 2743 patients were found. The meta‐analysis showed that roxadustat increased haemoglobin (Hb) level by 0.91 g/dL (95% confidence interval [CI]: 0.47–1.34, P < .05), transferrin level by 0.50 mg/dL (95% CI: 0.34–0.65, P < .05), and total iron‐binding capacity by 50.64 μg/dL (95% CI: 36.21–65.07, P < .05) in CKD patients. Decreases in hepcidin (mean difference [MD] = −23.16, 95% CI: −37.12 to −9.19, P < .05) and ferritin (MD = ‐38.35, 95% CI: −67.41 to −9.29, P < .05) levels were also observed. There was no significant difference in the incidence of adverse events (AEs) (OR: 1.12, 95% CI: 0.95–1.32, P = .17) between the roxadustat and control groups; however, the incidence of serious AEs in the roxadustat group was significantly higher than that in the ESA group (OR: 1.33, 95% CI: 1.06–1.68, P < .05).ConclusionRoxadustat can significantly improve renal anaemia in CKD patients by increasing Hb level and iron metabolism. However, attention must be paid to the risk of SAEs during treatment.
To remember, or not to remember? Potential impact of memory modification on narrative identity, personal agency, mental health, and well‐being
Authors: Zawadzki Przemysław , Adamczyk Agnieszka K. 
Published: August 2021

AbstractMemory modification technologies (MMTs)—interventions within the memory affecting its functions and contents in specific ways—raise great therapeutic hopes but also great fears. Ethicists have expressed concerns that developing and using MMTs may endanger the very fabric of who we are—our personal identity. This threat has been mainly considered in relation to two interrelated concerns: truthfulness and narrative self‐constitution. In this article, we propose that although this perspective brings up important matters concerning the potential aftermaths of MMT utilization, it fails to tell the whole story. We suggest that capturing more tangible potential consequences of MMT use, namely, its psychological ramifications is crucial both in ethical considerations and in making decisions regarding the permissibility of such interventions. To this end, we first examine what current MMTs are capable of and what are the prospects of emerging MMTs. Subsequently, we outline the relationship between memory and personal identity; specifically, we indicate that concepts of self‐defining memories and narrative identity are crucial to considering how MMTs may influence one's psychological functioning. On this basis, we analyze potential consequences of narrative disruption that may be the result of the use of MMTs; more precisely, we consider its potential effects on mental health, well‐being, and personal agency, and outline the ethical dilemmas that decision‐makers face in this context. We conclude by considering the broader cultural context that may have influence on policymaking regarding permissibility of memory modification interventions.
Mogamulizumab efficacy is underscored by its associated rash that mimics cutaneous T-cell lymphoma: a retrospective single-centre case series
Authors: Trum N.A. , Zain J. , Martinez X.U. , Parekh V. , Afkhami M. , Abdulla F. , Carson K.R. , Rosen S.T. , Bennett C.L. , Querfeld C. 
Published: August 2021

Summary
Background
Mogamulizumab is a humanized antibody against chemokine receptor type 4. It was recently approved by the US Food and Drug Administration for relapsed or refractory mycosis fungoides (MF) and Sézary syndrome (SS). The most commonly reported adverse event in the phase III licensing trial was drug eruption (28%), now termed mogamulizumab-associated rash (MAR). Clinical recommendations about MAR and its treatment differ between the current package insert and postapproval insights reported from two single-centre studies that focused on its characterization, but less so on outcomes and clinicopathological differentiation from cutaneous T-cell lymphoma (CTCL).
Objectives
To describe our experience in the diagnosis of MAR and treatment of patients with CTCL with mogamulizumab.
Methods
This is a single-centre retrospective case series study.
Results
We found a higher incidence of MAR in patients with CTCL (17 of 24, 68%) than previously reported. MAR development is associated with complete (11 of 17) or partial (four of 17) responses, with an overall response rate of 88%, compared with 29% (two of seven) in patients without MAR. Diagnosis of MAR may be obscured by its ability to mimic key CTCL features both clinically and histologically, but an absence of T-cell-receptor clonality and relatively decreased CD4 : CD8 ratio compared with baseline lesions strongly favour MAR over recurrent disease.
Conclusions
MAR has the potential to create a significant management problem for patients on mogamulizumab. Misidentification of MAR as recurrent CTCL may detrimentally result in the premature discontinuation of mogamulizumab in patients whose disease is historically hard to treat. Thorough clinicopathological investigation of new lesions during treatment with mogamulizumab is required to inform ideal treatment decisions and achieve better outcomes.
Characterisation of immune checkpoints in Richter syndrome identifies LAG3 as a potential therapeutic target
Authors: Gould Clare , Lickiss Jennifer , Kankanige Yamuna , Yerneni Satwica , Lade Stephen , Gandhi Maher K. , Chin Collin , Yannakou Costas K. , Villa Diego , Slack Graham W. , Markham John F. , Tam Constantine S. , Nelson Niles , Seymour John F. , Dickinson Michael , Neeson Paul J. , Westerman David , Blombery Piers 
Published: August 2021

SummaryRichter syndrome (RS), an aggressive lymphoma occurring in the context of chronic lymphocytic leukaemia/small lymphocytic lymphoma, is associated with poor prognosis when treated with conventional immunochemotherapy, therefore, improved treatments are required. Immune checkpoint blockade has shown efficacy in some B‐cell malignancies and modest responses in early clinical trials for RS. We investigated the immune checkpoint profile of RS as a basis to inform rational therapeutic investigations in RS.Formalin‐fixed, paraffin‐embedded biopsies of RS (n = 19), de novo diffuse large B‐cell lymphoma (DLBCL; n = 58), transformed indolent lymphomas (follicular [tFL], n = 16; marginal zone [tMZL], n = 24) and non‐transformed small lymphocytic lymphoma (SLL; n = 15) underwent gene expression profiling using the NanoString Human Immunology panel. Copy number assessment was performed using next‐generation sequencing. Immunohistochemistry (IHC) for LAG3 and PD‐1 was performed.LAG3 gene expression was higher in RS compared to DLBCL (P = 0·0002, log2FC 1·96), tFL (P < 0·0001, log2FC 2·61), tMZL (P = 0·0004, log2FC 1·79) and SLL (P = 0·0057, log2FC 1·45). LAG3 gene expression correlated with the gene expression of human leukocyte antigen Class I and II, and related immune genes and immune checkpoints. IHC revealed LAG3 protein expression on both malignant RS cells and tumour‐infiltrating lymphocytes. Our findings support the investigation of LAG3 inhibition to enhance anti‐tumour responses in RS.
Understanding the etiology of adolescent substance use through developmental perspectives
Authors: Trucco Elisa M. , Hartmann Sarah A. 
Published: August 2021

AbstractUsing alcohol, cigarettes, and marijuana during adolescence is associated with risks, yet there is no single cause for adolescent substance use. The etiology of substance use develops over time, across multiple levels of influence. Informed by developmental perspectives, in this review, we provide an overview of biological (e.g., genetic, neuroimaging), individual (e.g., temperament, behavior problems), and social (e.g., parents, peers) factors that increase the risk for and protection against this multifaceted phenomenon. We also highlight emerging areas of research, as well as preliminary work examining the etiology of adolescent substance use across levels of influence. Understanding early factors associated with the emergence of adolescent substance use can help inform prevention programs to reduce subsequent cognitive impairments and psychopathology. Adaptive individualized interventions addressing various domains linked to adolescent substance use are likely to have significant utility given the numerous pathways to adolescent substance use.
Liberalising audit markets for local government: The five forces at work in England and the Netherlands
Authors: de Widt Dennis , Llewelyn Iolo , Thorogood Tim 
Published: August 2021

AbstractBoth England and the Netherlands have seen efforts to liberalise their audit markets for local government in recent decades. According to economic theory, these should benefit buyers as increased competition produces lower prices and improved quality. Increasing the number of competing audit firms in markets traditionally dominated by few large firms is widely seen as a key ingredient to this process. However, liberalisation has taken different paths in England, compared to the Netherlands. In England, a national‐level collaborative purchasing arrangement has seen a small number of large firms competing, whilst in the Netherlands, a free market has led to the withdrawal by Big‐4 firms and rapidly growing market share by mid‐tier and small firms. In this paper, we analyse contrasting market developments in local public audit in England and the Netherlands and accordingly analyse the underlying factors through applying an established framework for market analysis from industrial economics, Porter's five forces framework, together with an institutional logics approach to further understand the factors involved. We find the Porter framework a useful tool to identify structural differences between markets but one that requires further analysis to explain underlying dynamics, which in the case of Dutch and English local public audit markets is effectively provided by the use of concepts from institutional logics including a historical contingency analysis.