bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trespassing on the Law: Critical legal engineering as a strategy for action research
Authors: Kusiak Joanna 
Published: January 2021

AbstractThis paper proposes critical legal engineering (CLE) as a new methodology for legal‐geographic action research. While legal geography is on the rise, geographers rarely participate in legal or judicial process, and when they do – for example, as court expert witnesses – they merely respond to the pre‐established agendas of the legal system. I argue that legal geographers’ knowledge on the nature of law and its relations with society is a source of power that could allow them to set legal agendas and pluralise legal discussions. CLE assumes that legal geographers can put forward technical legal arguments, thus using law’s own tools to implement normative agendas implied in critical research. However, CLE demands a dialectical attitude that preserves the contradiction between political ends and legal technology – while pursuing both of them at the same time. As I show, CLE can realise critical agendas in three ways. First, it co‐opts the legitimacy provided by the legal system, lending it to the agendas that are otherwise perceived as “too radical.” Second, elevated by the law these radical agendas may gain greater power to influence political‐economic realities even before the legal outcomes are decided. Finally, CLE draws out of “technical” legal discussions into the heat of the public debate, thus politicising the law. Having developed this methodological proposition in the course of my research on urban movements, I illustrate it with the strategy of Berlin's campaign Deutsche Wohnen & Co. Enteignen (DWE), which has crafted a legal argumentation based on Article 15 of the German Constitution to pursue re‐municipalisation (or de‐privatisation) of housing.
Low‐intensity shockwave therapy for the management of chronic prostatitis/chronic pelvic pain syndrome: a systematic review and meta‐analysis
Authors: Mykoniatis Ioannis , Pyrgidis Nikolaos , Sokolakis Ioannis , Sountoulides Petros , Hatzichristodoulou Georgios , Apostolidis Apostolos , Hatzichristou Dimitrios 
Published: January 2021

ObjectivesTo perform a systematic review and meta‐analysis aiming to improve the level of evidence and determine the efficacy and safety of low‐intensity shockwave therapy (LiST) in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).MethodsWe searched PubMed, Cochrane Library and Scopus databases from inception to November 2020 for randomised controlled trials (RCTs) exploring the role of LiST for the management of CP/CPPS. We performed a random‐effects meta‐analysis of RCTs comparing LiST vs sham therapy on CP/CPPS symptoms at different time‐points after treatment. Weighted mean differences (WMDs) with the corresponding confidence intervals (CIs) were estimated. Furthermore, we assessed the strength of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42020208813).ResultsWe included five sham RCTs and one non‐sham RCT. In the meta‐analysis of sham RCTs, both the National Institute of Health Chronic Prostatitis Symptom Index (NIH‐CPSI) pain domain score and the numeric pain rating scale improved significantly after LiST vs sham therapy at the assessment directly after treatment protocol completion (WMD 3.2, 95% CI 0.88–5.52, I2 = 90%; and WMD 1.43, 95% CI 0.85–2.01, I2 = 32%, respectively), at 1 month (WMD 4.4, 95% CI 2.84–5.95, I2 = 68%, and WMD 2.59, 95% CI 1.92–3.27, I2 = 83%, respectively), and at 3 months after last treatment session (WMD 3.61, 95% CI 1.49–5.74, I2 = 90%, and WMD 2.64, 95% CI 2.13–3.16, I2 = 71%, respectively). Similarly, the NIH‐CPSI total and quality‐of‐life domain scores improved significantly after LiST compared to sham therapy for the same time‐points. Conversely, the long‐term efficacy of LiST, as well as the effect of LiST on lower urinary tract symptoms and erectile function, was clinically insignificant.ConclusionsLiST is an effective treatment modality for the improvement of pain and quality of life in patients with CP/CPPS. Therefore, it should be recommended as a part of individualised treatment strategies in such patients.
Local anaesthetic transperineal (LATP) prostate biopsy using a probe‐mounted transperineal access system: a multicentre prospective outcome analysis
Authors: Lopez J. Francisco , Campbell Angus , Omer Altan , Stroman Luke , Bondad Jasper , Austin Tom , Reeves Thomas , Phelan Curtis , Leiblich Aaron , Philippou Yiannis , Lovegrove Catherine E. , Ranasinha Nithesh , Bryant Richard J. , Leslie Tom , Hamdy Freddie C. , Brewster Simon , Bell C. Richard , Popert Rick , Hodgson Dominic , Elsaghir Mohammed , Eddy Ben , Bolomytis Stefanos , Persad Raj , Reddy Utsav D. , Foley Charlotte , van Rij Simon , Lam Wayne , Lamb Alastair D. 
Published: January 2021

ObjectivesTo assess the feasibility of local anaesthetic transperineal (LATP) technique using a single‐freehand transperineal (TP) access device, and report initial prostate cancer (PCa) detection, infection rates, and tolerability.Patients and methodsObservational study of a multicentre prospective cohort, including all consecutive cases. LATP was performed in three settings: (i) first biopsy in suspected PCa, (ii) confirmatory biopsies for active surveillance, and (iii) repeat biopsy in suspected PCa. All patients received pre‐procedure antibiotics according to local hospital guidelines. Local anaesthesia was achieved by perineal skin infiltration and periprostatic nerve block without sedation. Ginsburg protocol principles were followed for systematic biopsies including cognitive magnetic resonance imaging‐targeted biopsies when needed using the PrecisionPoint™ TP access device. Procedure‐related complications and oncological outcomes were prospectively and consecutively collected. A validated questionnaire was used in a subset of centres to collect data on patient‐reported outcome measures (PROMs).ResultsSome 1218 patients underwent LATP biopsies at 10 centres: 55%, 24%, and 21% for each of the three settings, respectively. Any grade PCa was diagnosed in 816 patients (67%), of which 634 (52% of total) had clinically significant disease. Two cases of sepsis were documented (0.16%) and urinary retention was observed in 19 patients (1.6%). PROMs were distributed to 419 patients, with a 56% response rate (n = 234). In these men, pain during the biopsy was described as either ‘not at all’ or ‘a little’ painful by 64% of patients. Haematuria was the most common reported symptom (77%). When exploring attitude to re‐biopsy, 48% said it would be ‘not a problem’ and in contrast 8.1% would consider it a ‘major problem’. Most of the patients (81%) described the biopsy as a ‘minor or moderate procedure tolerable under local anaesthesia’, while 5.6% perceived it as a ‘major procedure that requires general anaesthesia’.ConclusionOur data suggest that LATP biopsy using a TP access system mounted to the ultrasound probe achieves excellent PCa detection, with a very low sepsis rate, and is safe and well tolerated. We believe a randomised controlled trial comparing LATP with transrectal ultrasound‐guided biopsy (TRUS) to investigate the relative trade‐offs between each biopsy technique would be helpful.
GNOM‐dependent endocytosis maintains polar localisation of the borate exporter BOR1 in Arabidopsis
Authors: Yoshinari Akira , Toda Yosuke , Takano Junpei 
Published: January 2021

Background InformationPlants use transporters polarly localised in the plasma membrane for the directional transport of nutrients. The boric acid/borate (B) exporter BOR1 is localised polarly in the inner lateral domain of the plasma membrane in various root cells for efficient translocation of B under B limitation. With a high B supply, BOR1 is ubiquitinated and transported to vacuoles for degradation. The polar localisation and vacuolar targeting of BOR1 are maintained by different endocytosis mechanisms.ResultsWe demonstrated that one of the most utilised inhibitors in endosomal recycling, brefeldin A (BFA), inhibits the polar localisation of BOR1. BFA inhibits a subset of guanine‐nucleotide exchange factors (ARF‐GEFs), regulators of vesicle formation. Using a transgenic line expressing BFA‐resistant engineered GNOM, we identified GNOM as the key ARF‐GEF in endocytosis and maintenance of the polar localisation of BOR1.Conclusions and SignificanceWe found that BFA inhibits the polar localisation of BOR1 by inhibiting GNOM activity. Our results suggest that GNOM‐dependent endocytosis contributes to the maintenance of the polar localisation of BOR1 under B limitation. We propose a model of BOR1 transcytosis initiated from GNOM‐dependent endocytosis.
An econometric analysis of salience theory
Authors: Balcombe Kelvin , Fraser Iain , Sharma Abhijit 
Published: January 2021

AbstractIn this paper, we econometrically examine the performance of salience theory (ST) for explaining observed behavior outside of a fully defined state contingent setting. Using a well‐known dataset, we find that only a minority of people act consistently in the way proposed by ST when confronted with lottery choices for which only marginal probabilities are presented. By estimating the implied dependence structure of payoffs consistent with ST, only a minority of people infer independent payoffs when attaching probabilities to states, a finding at odds with ST. Instead, a majority treat lotteries as having positively correlated payoffs which raise questions about the independence assumption in ST. Finally, we also find that ST explains choice behavior less consistently than expected utility. Thus, ST should not be assumed to be superior to the most prominent models within the literature when employed outside of particular contexts.
Corosolic acid inhibits colorectal cancer cells growth as a novel HER2/HER3 heterodimerization inhibitor
Authors: Zhang Bi‐Ying , Zhang Lei , Chen Yi‐Meng , Qiao Xin , Zhao Shu‐Ling , Li Ping , Liu Jin‐Feng , Wen Xiaodong , Yang Jie 
Published: January 2021

Background and PurposeColorectal cancer is the third most common cancer worldwide. HER2 and HER3 are two members of human epidermal receptor family of tyrosine kinase receptors (RTKs) and associated with poor survival in colorectal cancer. They have been observed as important therapeutic targets in various types of cancer. Corosolic acid, a natural pentacyclic triterpene, has been demonstrated to have a significant anti‐cancer activity. However, the target of corosolic acid has not yet been explored. This study aimed to reveal the direct targets of corosolic acid underlying its anti‐cancer activities.Experimental ApproachThe targets of corosolic acid were revealed by the phospho‐RTK array, bio‐layer interferometry, co‐immunoprecipitation, and proximity ligation assay. The inhibitory action of corosolic acid on HER2/HER3 heterodimerization and related downstream signalling were investigated in HCT116 and SW480 cells. In addition, the chemo‐preventive effects of corosolic acid were validated in both HCT116 xenograft model and AOM/DSS model.Key ResultsOur results demonstrated that corosolic acid could prevent NRG1‐induced HER2/HER3 heterodimerization and suppress the phosphorylation of both HER2 and HER3. Furthermore, HER2 and HER3 could regulate the downstream signalling pathways of RalA/RalBP1/CDK1 and PI3K/Akt/PKA, respectively, resulting in the changes in phosphorylation of Drp1 and mitochondrial dynamics. corosolic acid exhibited anti‐cancer activity in both HCT116 xenograft model and AOM/DSS model.Conclusions and ImplicationsCollectively, our results demonstrated corosolic acid directly targeted HER2 and HER3 heterodimerization and inhibited mitochondrial fission via regulating RalA/RalBP1/CDK1 and PI3K/Akt/PKA pathways, revealing a novel mechanism underlying the beneficial effects of corosolic acid on colorectal cancer.
Advancing Measurement and Research on Youths’ Prosocial Behavior in the Digital Age
Authors: Armstrong‐Carter Emma , Telzer Eva H. 
Published: January 2021

AbstractWidespread access to digital and social media has drastically altered the nature of youth’s interpersonal connections. In this context, the opportunities children and adolescents have to help people around them are rapidly evolving. In this article, we review emerging literature on how digital media influences youth’s prosocial development in new ways. Then we propose the next steps for advancing the field’s understanding of youth’s prosocial behavior in the digital age. We advocate for extending existing measures to capture experiences that are increasingly relevant for children and adolescents today, with a focus on current events, including the COVID‐19 pandemic, and social and political activism. We also provide a research agenda to advance the understanding of prosocial development.
Pharmacogenetics of inhaled corticosteroids and exacerbation risk in adults with asthma
Authors: Edris Ahmed , de Roos Emmely W. , McGeachie Michael J. , Verhamme Katia M. C. , Brusselle Guy G. , Tantisira Kelan G. , Iribarren Carlos , Lu Meng , Wu Ann Chen , Stricker Bruno H. , Lahousse Lies 
Published: January 2021

AbstractBackgroundInhaled corticosteroids (ICS) are a cornerstone of asthma treatment. However, their efficacy is characterized by wide variability in individual responses.ObjectiveWe investigated the association between genetic variants and risk of exacerbations in adults with asthma and how this association is affected by ICS treatment.MethodsWe investigated the pharmacogenetic effect of 10 single nucleotide polymorphisms (SNPs) selected from the literature, including SNPs previously associated with response to ICS (assessed by change in lung function or exacerbations) and novel asthma risk alleles involved in inflammatory pathways, within all adults with asthma from the Dutch population–based Rotterdam study with replication in the American GERA cohort. The interaction effects of the SNPs with ICS on the incidence of asthma exacerbations were assessed using hurdle models adjusting for age, sex, BMI, smoking and treatment step according to the GINA guidelines. Haplotype analyses were also conducted for the SNPs located on the same chromosome.Resultsrs242941 (CRHR1) homozygotes for the minor allele (A) showed a significant, replicated increased risk for frequent exacerbations (RR = 6.11, P < 0.005). In contrast, rs1134481 T allele within TBXT (chromosome 6, member of a family associated with embryonic lung development) showed better response with ICS. rs37973 G allele (GLCCI1) showed a significantly poorer response on ICS within the discovery cohort, which was also significant but in the opposite direction in the replication cohort.Conclusionrs242941 in CRHR1 was associated with poor ICS response. Conversely, TBXT variants were associated with improved ICS response. These associations may reveal specific endotypes, potentially allowing prediction of exacerbation risk and ICS response.
Adoptive transfer of immunomodulatory M2 macrophages suppresses experimental autoimmune encephalomyelitis in C57BL/6 mice via blockading NF-κB pathway
Authors: Chu F , Shi M , Lang Y , Chao Z , Jin T , Cui L , Zhu J 
Published: January 2021

SummaryMacrophages play important roles in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), and M2 macrophage may have anti-inflammatory effects. In this study, we elucidated the roles of M1 and M2 macrophages in the pathogenesis of EAE and the effects of treatment with M2 macrophages that target certain proinflammatory cytokines and with immunomodulatory preparations that beneficially influence the disease course. We found macrophages increased at the onset of clinical signs in the EAE group, consistent with an increased proportion of M1 macrophages and low numbers of M2 macrophages. As the disease progressed and the symptoms worsened, M1 macrophages decreased and M2 macrophages gradually increased until the peak. In the recovery stage, M2 macrophages gradually decreased. Treatment with M2 macrophages inhibited the nuclear factor kappa B (NF-κB) pathway, alleviated the symptoms of EAE, reduced inflammatory cell infiltration and demyelination in the central nervous system and decreased the numbers of macrophages in the spleens. BAY-11-7082, an NF-κB blocking agent, could reduce the total number of macrophages both in vivo and in vitro, effectively prevented EAE development and significantly inhibited EAE symptoms in mice. Our study demonstrates that macrophages may play a crucial role in the pathogenesis of EAE, while M2 macrophages have anti-inflammatory effects. Transfer of M2 macrophages to EAE mice can block the NF-κB pathway successfully and relieve EAE symptoms. Application of NF-κB blockers is useful in the prevention and treatment of EAE.
Immune complexome analysis reveals the presence of immune complexes and identifies disease-specific immune complex antigens in saliva samples from patients with Sjögren's syndrome
Authors: Yamane K , Nakamura H , Hamasaki M , Minei Y , Aibara N , Shimizu T , Kawakami A , Nakashima M , Kuroda N , Ohyama K 
Published: January 2021

SummarySjögren's syndrome (SS) is a chronic autoimmune disease that mainly damages the salivary and lacrimal glands. Immune complex (IC) formation triggers local inflammation through IC deposition and decreased antigen function. Some ICs can leak from the lesion and into the saliva, but no salivary ICs have been reported to date. We used immune complexome analysis to comprehensively identify antigens incorporated into IC (IC-antigens) in saliva samples from patients with SS (n = 9) or with xerostomia (n = 7). Neutrophil defensin 1 (67%), small proline-rich protein 2D (67%), myeloperoxidase (44%), neutrophil elastase (44%), cathepsin G (33%), nuclear mitotic apparatus 1 (33%) and phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma (33%) were identified as new IC-antigens specifically and frequently detected in the saliva of SS patients. Of these, neutrophil defensin 1, myeloperoxidase, neutrophil elastase and cathepsin G are neutrophil intracellular proteins, which suggests that repeated destruction of neutrophils due to abnormal autoimmunity may be involved in the pathogenesis of SS. We also analyzed serum samples from three SS patients. There was little overlap of IC-antigens between two of the samples (fewer than 30% of the IC-antigens in the saliva samples), suggesting that many ICs are formed locally and independently of the circulation. In addition, we found that four SS-specific salivary antigens show sequence homology with several proteins of oral microbiomes but no antigen has homology with Epstein–Barr virus proteins. The homology between some IC-antigens and oral microbiome proteins may indicate the impact of oral infection on local autoimmunity through molecular mimicry theory.
Copeptin is increased by nausea and vomiting during hypertonic saline infusion in healthy individuals
Authors: Brooks Emily , Bachmeier Caroline , Vorster Juanita , Sorbello Jane , Peer Faseeha , Chikani Viral , Dimeski Goce , Ungerer Jacobus , Pretorius Carel , Inder Warrick 
Published: January 2021

SummaryObjectiveMeasurement of hypertonic saline‐stimulated copeptin has recently been described for the differentiation of polyuria‐polydipsia syndrome. This study aims to determine the copeptin response to intravenous 3% hypertonic saline, including evaluation of adverse effects, in a local cohort of healthy adults >18 years in Australia.DesignProspective clinical study.MethodsTwenty healthy volunteers (10 males and 10 females) were recruited. Participants underwent infusion of 3% hypertonic saline via a previously described standardized protocol, until the plasma sodium was ≥150 mmol/L, with measurement of plasma copeptin.ResultsMean peak sodium was 152 mmol/L ± SD 1.4 with osmolality 315 mmol/kg ± SD 3.9. Median volume of hypertonic saline infused to reach target sodium ≥ 150 mmol/L was 1536 mL (IQR 1362, 1992). Mean rate of plasma sodium rise was 5.9 mmol/L/hour ± SD 1.5. Hypertonic saline‐stimulated copeptin had non‐parametrical distribution with median of 33.8 pmol/L (IQR 27.6, 63.6). Overall median symptom burden was 6/10 (range 3/10‐9/10). Copeptin was significantly higher for those who experienced nausea and/or vomiting (n = 13) (median 39.0 pmol/L; IQR 32.5, 90), compared to those participants who did not experience either (median 20.0 pmol/L; IQR 13.0, 31.0) (P = 0.003). There were no serious adverse events.ConclusionHypertonic saline‐stimulated copeptin measurements were similar in our population compared with previously reported reference intervals in healthy volunteers. There is a wide range of stimulated copeptin measurements in the healthy population. Nausea and vomiting are common adverse effects which enhance the copeptin response.
Fragile X premutation and associated health conditions: A review
Authors: Tassanakijpanich Nattaporn , Hagerman Randi J. , Worachotekamjorn Juthamas 
Published: January 2021

AbstractFragile X syndrome (FXS) is the most common single gene disorder, which causes autism and intellectual disability. The fragile X mental retardation 1 (FMR1) gene is silenced when cytosine‐guanine‐guanine (CGG) triplet repeats exceed 200, which is the full mutation that causes FXS. Carriers of FXS have a CGG repeat between 55 and 200, which is defined as a premutation and transcription of the gene is overactive with high levels of the FMR1 mRNA. Most carriers of the premutation have normal levels of fragile X mental retardation protein (FMRP) and a normal intelligence, but in the upper range of the premutation (120–200) the FMRP level may be lower than normal. The clinical problems associated with the premutation are caused by the RNA toxicity associated with increased FMR1 mRNA levels, although for some mildly lowered FMRP can cause problems associated with FXS. The RNA toxicity causes various health problems in the carriers including but not limited to fragile X‐associated tremor/ataxia syndrome, fragile X‐associated primary ovarian insufficiency, and fragile X‐associated neuropsychiatric disorders. Since some individuals with neuropsychiatric problems do not meet the severity for a diagnosis of a “disorder” then the condition can be labeled as fragile X premutation associated condition (FXPAC). Physicians must be able to recognize these health problems in the carriers and provide appropriate management.