bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinal neurodegeneration, macular circulation and morphology of the foveal avascular zone in diabetic patients: quantitative cross‐sectional study using OCT‐A
Authors: Bontzos Georgios , Kabanarou Stamatina A. , Gkizis Ilias , Ragkousis Antonios , Xirou Tina , Peto Tunde
Published: January 2021

Purpose

Using OCT‐A to investigate the association between neurodegeneration and vascular morphology in diabetic retinopathy (DR).

Methods

Cross‐sectional study. One hundred and sixty‐two patients were enrolled and following fundoscopy were assigned to two groups according to DR severity: 54 patients to the group of no clinical signs of DR (noDR) and 54 to the non‐proliferative DR (NPDR) group. Fifty‐four age‐matched patients without known diabetes were recruited as the control group. Patients underwent full ophthalmic examination followed by OCT‐A. Central retinal thickness (CRT), vessel density (VD) in the superficial and deep retinal layers and foveal avascular zone (FAZ) area were measured. Additionally, ganglion cell complex (GCC) layer thickness along with global loss volume (GLV) and focal loss volume (FLV) indices was measured.

Results

In total, 85 men with mean age of 51.93 ± 9.03 and 77 women with age of 50.14 ± 10.35 were examined. Mean diabetes duration was 4.62 ± 2.16 years in the noDR group and 11.34 ± 2.73 years in the NPDR group (p < 0.001). Superficial VD (sVD) and deep VD (dVD) were significantly different only between noDR and NPDR groups (p < 0.001 for both comparisons), but no statistically significant difference was observed between the controls and the DR groups. Global loss volume was significantly higher in the NPDR (4.38 ± 2.22) compared to the noDR group (3.24 ± 1.76; p < 0.03). Focal loss volume was significantly higher in both noDR (1.22 ± 1.03) and NPDR (2.09 ± 1.72) groups compared to controls (0.95 ± 0.83; p < 0.001 between noDR and NPDR and p = 0.02 between control and noDR groups). Significant associations were found between GLV and deep VD (p < 0.01, r = −0.48), FLV and superficial VD (p < 0.01, r = −0.42) and FLV with deep VD (p < 0.01, r = −0.64).

Conclusion

In this study, we evaluated the impact of DR in both the vascular layers and neural components of the retina as expressed by FAZ, sVD, dVD and GCC thickness, FLV and GLV using OCT‐A. We found that FLV was significantly higher in both noDR and NPDR groups indicating that in progressive DR stages FLV values might be increased, which might serve as an early index of neuronal damage in patients with diabetes even in the absence of overt DR signs.
Inflammatory cytokines levels in aqueous humour and surgical outcomes of trabeculectomy in patients with prior acute primary angle closure
Authors: Yu Ping , Qian Tianwei , Gong Qiaoyun , Fu Mingshui , Bian Xiaolan , Sun Tao , Zhang Zhihua , Xu Xun
Published: January 2021

Purpose

To quantify the levels of three inflammatory cytokines in the aqueous humour of patients with prior acute primary angle closure (APAC) and investigate their correlation with surgical outcomes of trabeculectomy.

Methods

In this prospective cohort study, aqueous humour samples were collected from 44 prior APAC eyes. Analyte concentrations of monocyte chemoattractant protein‐1 (MCP‐1), vascular endothelial growth factor (VEGF) and interleukin‐6 (IL‐6) were measured using multiplexed immunoassay kits. Intraocular pressure was measured using Goldmann application tonometry.

Results

Forty‐four prior APAC eyes were followed up for 24 months after trabeculectomy and divided into success and failure groups according to surgical outcomes. Monocyte chemoattractant protein‐1 (MCP‐1) levels in the aqueous humour were significantly higher in the failure group (p = 0.0118). Univariate and multivariate analyses showed that MCP‐1 level was a significant risk factor for trabeculectomy outcomes (univariate analysis: p = 0.016, odds ratio = 14.538; multivariate analysis: p = 0.023, odds ratio = 13.718). When prior APAC eyes were divided according to MCP‐1 levels, the overall success rate was significantly higher in eyes with low MCP‐1 levels than eyes with high MCP‐1 levels (p = 0.0249).

Conclusion

In prior APAC patients, the MCP‐1 level in the aqueous humour predicts trabeculectomy results. Therefore, modulation of MCP‐1 expression may have potential clinical applications after filtration surgery.
Prognostic significance of atypical mitotic figures in smooth muscle tumors of uncertain malignant potential (STUMP) of the uterus and uterine adnexa
Authors: Travaglino Antonio , Raffone Antonio , Santoro Angela , Gencarelli Annarita , Angelico Giuseppe , Spadola Saveria , Marzullo Liberato , Zullo Fulvio , Insabato Luigi , Zannoni Gian Franco
Published: January 2021

We aimed to assess whether the presence of atypical mitotic figures (AMF) in smooth muscle tumors of uncertain malignant potential (STUMP) of the uterus and uterine adnexa is associated with increased risk of recurrence, and the association of AMF with the Stanford criteria, that is, significant cytologic atypia, mitotic index ≥ 10/10HPF, and coagulative tumor cell necrosis (CTCN). A systematic review was performed to identify all studies reporting the presence of AMF and oncologic outcomes in STUMP series. Fisher’s exact test was used to assess the association of AMF with the three Stanford parameters. Kaplan–Meier and Cox regression survival analyses with hazard ratio (HR) calculation were performed to assess the association between AMF and STUMP recurrence. A p‐value < 0.05 was considered significant. Five studies with 80 STUMPs were included, out of which 23.8% had AMF. AMF were significantly associated with the presence of significant atypia (p = 0.023), but not with the presence of a mitotic index ≥ 10/10HPF (p = 0.769), CTCN (p = 1), or more than one Stanford parameter (p = 0.171). AMF was not significantly associated with the risk of STUMP recurrence at both univariate (HR = 0.366; p = 0.188) and multivariate analyses (HR = 0.528; p = 0.463). In STUMP of the uterus and uterine adnexa, AMF are more common in the case of significant cytologic atypia, but do not seem to increase the risk of recurrence. Further studies are necessary in this regard.
Geographies of education: A journey
Authors: Kraftl Peter , Andrews William , Beech Suzanne , Ceresa Giulia , Holloway Sarah L. , Johnson Vicky , White Catherine
Published: January 2021

This paper provides a critical overview of scholarship on the geographies of education. The article explores some of the key roots, linguistic traditions, and conceptual underpinnings of what has become a burgeoning and diverse area of scholarship. It emphasises the different subdisciplinary areas to which research on geographies of education has contributed, including work on social reproduction, the relationship between education spaces and their “outsides,” the agency of learners, structural inequalities, learners’ experiences, materialities, and mobilities. The paper concludes with some suggestions about future work on geographies of education, identifying key areas of potential in terms of connection: with scholarship on geography education; with research going on outside geography; with scholarship on education spaces less well‐represented thus far (such as Further Education); and with research on and from non‐Anglophone contexts and the Majority Global South.
Trespassing on the Law: Critical legal engineering as a strategy for action research
Authors: Kusiak Joanna
Published: January 2021

This 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

Objectives

To 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).

Methods

We 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).

Results

We 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.

Conclusions

LiST 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

Objectives

To 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 methods

Observational 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).

Results

Some 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’.

Conclusion

Our 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 Information

Plants 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.

Results

We 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 Significance

We 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

In 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 Purpose

Colorectal 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 Approach

The 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 Results

Our 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 Implications

Collectively, 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.
Debate: Behavioural addictions and technology use – risk and policy recommendations for problematic online gambling and gaming
Authors: Kuss Daria , Gainsbury Sally
Published: January 2021

Digital technology allows people to connect and share similar interests across geographical and temporal borders. Two behavioural disorders related to Internet use have been officially recognised as mental health disorders: Gambling Disorder by the American Psychiatric Association and Gaming Disorder by the World Health Organization. The prevalence estimates and risk indicators of developing problems associated with excessive technology use differ considerably across countries. Individual, structural and situational factors need to be taken into consideration when evaluating existing study outcomes. Based on the current evidence base regarding prevention of problematic technology use including gaming and online gambling and reducing harm, whilst paying attention not to overpathologise everyday behaviours, we recommend a multi‐stakeholder approach, engaging researchers, clinicians, regulators and government bodies, community organisations and the industry. Implications for clinical practice include engaging in dialogue across experts and using evidence‐based treatment approaches to support those in need of professional help.
Advancing Measurement and Research on Youths’ Prosocial Behavior in the Digital Age
Authors: Armstrong‐Carter Emma , Telzer Eva H.
Published: January 2021

Widespread 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

Background

Inhaled corticosteroids (ICS) are a cornerstone of asthma treatment. However, their efficacy is characterized by wide variability in individual responses.

Objective

We investigated the association between genetic variants and risk of exacerbations in adults with asthma and how this association is affected by ICS treatment.

Methods

We 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.

Results

rs242941 (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.

Conclusion

rs242941 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

Macrophages 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

Sjögren'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

Objective

Measurement 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.

Design

Prospective clinical study.

Methods

Twenty 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.

Results

Mean 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.

Conclusion

Hypertonic 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

Fragile 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.
European native oysters and associated species richness in the presence of non‐native species in a southern North Sea estuary complex
Authors: Lown Alice E. , Hepburn Leanne J. , Heywood Jane L. , Cameron Tom C.
Published: January 2021

There are growing calls to restore populations of European native oysters (Ostrea edulis), on the premise that restored populations will support a range of ecosystem services with an emphasis placed on restored oyster habitats promoting biological diversity, however benefits associated with naturally occurring O. edulis remain unclear. We undertook biannual surveys in the Blackwater, Crouch, Roach and Colne Estuaries Marine Conservation Zone (BCRC.MCZ), a highly sedimented estuary complex in the southern North Sea, to investigate links between natural densities of O. edulis (0–4.2 m−2), the prevalence of other dominant habitat features such as non‐native slipper limpet (Crepidula fornicata), dead shell abundance and epibenthic macroinvertebrate species richness. Increased epibenthic species richness was associated with O. edulis, even at densities below the OSPAR Commission recognized definition of an oyster bed (5 oysters m−2). Our analysis predicts increased associated species richness with density of native oysters (e.g., +1.6 additional species at 1 oyster m−2 or + 2.8 species at 5 oysters m−2), but only in areas with lower density of C. fornicata. Where C. fornicata are at higher density, the potential benefits of oyster restoration for associated species were curtailed. This may explain the observed asymptotic relationship between oyster density and diversity at 1 oyster m−2. In these and other high Crepidula density areas we recommend extending native oyster habitat even at low density. This may be of particular interest to areas with the protozoan oyster parasite Bonamia ostreae, which spreads more easily in high‐density areas. These lower density thresholds should also be considered for future management decisions—closing harvests so they do not reduce density further and impair biodiversity services of the habitats. In conclusion, while C. fornicata may be a useful oyster settlement substrate, we find that it limits the potential increases in associated species gains of oyster restoration.
Endoscopic retrograde cholangiopancreatography and endoscopic ultrasound in children
Authors: Tagawa Manabu , Morita Atsushi , Imagawa Kazuo , Mizokami Yuji
Published: January 2021

Gastrointestinal endoscopy is fundamental to diagnostic and therapeutic procedures in pediatric gastroenterology. In the decades since endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) for hepatobiliary and pancreatic disease were introduced into clinical practice, there has been increasing interest in these procedures, and practice guidelines and position papers that clearly define the role of ERCP and EUS in children have been published. Based on the distinction of endoscopy between children and adults, this review focuses on the current state of ERCP and EUS procedures in children, including the types of endoscopes used in children, general anesthesia and radiation exposure, biliary and pancreatic indications, considerations of education and training for ERCP and EUS procedures in children, and expectations for development of endoscopes for children.
Data‐driven estimates of global litter production imply slower vegetation carbon turnover
Authors: He Yue , Wang Xuhui , Wang Kai , Tang Shuchang , Xu Hao , Chen Anping , Ciais Philippe , Li Xiangyi , Peñuelas Josep , Piao Shilong
Published: January 2021

Accurate quantification of vegetation carbon turnover time (τveg) is critical for reducing uncertainties in terrestrial vegetation response to future climate change. However, in the absence of global information of litter production, τveg could only be estimated based on net primary productivity under the steady‐state assumption. Here, we applied a machine‐learning approach to derive a global dataset of litter production by linking 2401 field observations and global environmental drivers. Results suggested that the observation‐based estimate of global natural ecosystem litter production was 44.3 ± 0.4 Pg C year−1. By contrast, land‐surface models (LSMs) overestimated the global litter production by about 27%. With this new global litter production dataset, we estimated global τveg (mean value 10.3 ± 1.4 years) and its spatial distribution. Compared to our observation‐based τveg, modelled τveg tended to underestimate τveg at high latitudes. Our empirically derived gridded datasets of litter production and τveg will help constrain global vegetation models and improve the prediction of global carbon cycle.
Morphological and molecular changes following neoadjuvant endocrine therapy of oestrogen receptor‐positive breast cancer: implications for clinical practice
Authors: Badr Nahla M , Spooner David , Steven Jane , Stevens Andrea , Shaaban Abeer M
Published: January 2021

Aims

Neoadjuvant endocrine therapy (NAET) is used in the management of oestrogen receptor (ER)‐positive breast cancer. The optimal method for histological assessment of response and the effect of NAET on the tumour morphology, grade and molecular profile remain unclear. The aim of this study is to investigate the NAET effect on tumour type, grade and molecular profile by analysing a well‐characterised cohort of breast cancer samples in a single large UK tertiary referral centre, and to provide guidance on the pathological assessment of those lesions to inform adjuvant management and prognosis.

Methods and results

A single large‐institution cohort of 132 patients who received NAET over a 13‐year period was identified. Comprehensive clinical, histopathological and follow‐up data were collected. A detailed histological review of a subset with residual post‐treatment carcinoma was undertaken. Two carcinomas (both of the lobular type) achieved complete pathological response. Central scarring was seen in 49.3% of tumours post‐treatment. Significant changes in tumour type (41.6%), tumour grade (downgrading in one‐third of tumours), and progesterone receptor (PR) expression (22.3%), with a switch to PR‐negative status in 17.6% of cases, were observed. The last of these was associated with an absence of tumour‐infiltrating lymphocytes (P = 0.005). Ten per cent of cases showed a change in HER2 expression (P = 0.002). The median patient survival was 60 months, and downgrading of tumours was associated with better overall survival (P = 0.05).

Conclusions

We propose a histological method for assessment of residual carcinoma following NAET, and recommend repeat ER/PR/HER2 testing to inform management and prognosis.
Impact of cucumber pomace fortification on the nutritional, sensorial and technological quality of soft wheat flour‐based noodles
Authors: Saad Ahmed M. , El‐Saadony Mohamed T. , Mohamed Alaa S. , Ahmed Alshaymaa I. , Sitohy Mahmoud Z.
Published: January 2021

The aim of the work was to study the effect of adding cucumber pomace powder (CP) to soft wheat flour used in noodle manufacture. CP is a rich source of minerals and fibres, having high contents of polyphenols and flavonoids were 1.6 mg g−1 GAE and 0.65 mg g−1 QE, respectively, besides its capability to inhibit bacterial and fungal growth and to scavenge DPPH˙ (74.44%). The dough rheological properties showed increased extensibility and water absorption but decreased elasticity with adding CP. CP addition significantly increased the mineral and polyphenols content in noodles, but decreased protein and carbohydrates. Noodles enriched with CP 6% have the best organoleptic properties and overall acceptability and were associated with high levels of essential minerals, reduced cooking time by 44% over the control and better nutritional value. No deteriorative changes in dried noodles occurred during 12 months. Cooked noodles enriched with CP 6% significantly reduced the microbial load.
3D Interactive Modeling of Pipe Failure in Water Supply Systems
Authors: Dawood Thikra , Elwakil Emad , Novoa Hector Mayol , Delgado José Fernando Gárate
Published: January 2021

The increased incidences of pipe breaks worldwide are posing a serious threat to potable water security in urban communities. The consequences may involve water loss and service interruptions, compromised water quality, infrastructure disruptions, and loss of revenue. Thus, creating failure assessment models is quite crucial to sustain water distribution networks (WDNs) and to optimize maintenance spending. This research paper aims at developing an assessment framework for water systems, as well as modeling the failure phenomena toward sustainable management of underground infrastructure. The city of El Pedregal in Peru was chosen to exemplify the methodology of the research due to the rapid pace of urbanization and growing economic activities in the region, which make water infrastructure even more critical. The framework is based on the application of modeling techniques stemming from statistical regression analysis (RA) and 3D schematic representation. First, the influential factors that lead to the deterioration of the WDNs are determined. Second, the RA technique is leveraged to evaluate and model the failure rate through consecutive simulation operations and a 3D surface plot. Finally, the efficacy of the model is investigated using different performance metrics, in conjunction with a residual analysis scheme. The validation results revealed the robustness of the model with R‐squared (R2) and the sum of squares error (SSE) of 0.9767 and 0.0008, respectively. The developed model is a predictive tool that can be used by municipal engineers as a preemptive measure against future pipeline bursts or leaks.
The miRNA‐15b/USP7/KDM6B axis engages in the initiation of osteoporosis by modulating osteoblast differentiation and autophagy
Authors: Lu Xiaohui , Zhang Yuantao , Zheng Yin , Chen Bin
Published: January 2021

Osteoporosis is a metabolic disease that results from oxidative stress or inflammation in renal disorders. microRNAs (miRNAs) are recently implicated to participate in osteoporosis, but the mechanism remains largely unexplored. Herein, we aimed to explore the potential role of miR‐15b in osteoblast differentiation and autophagy in osteoporosis. We established osteoporosis models through ovariectomy and determined that miR‐15b was highly expressed whereas USP7 and KDM6B were poorly expressed in tissue of osteoporosis mice. Treatment of silenced miR‐15b resulted in the elevation of decreased bone mineral density (BMD), the maximum elastic stress and the maximum load of osteoporosis mice. In osteoblasts, miR‐15 overexpression decreased proliferation but suppressed the cell differentiation and autophagy, accompanied with decreased expression of USP7. Mechanistically, miR‐15 bound and inhibited USP7 expression, while overexpression of USP7 promoted autophagy of osteoblasts. USP7, importantly, strengthened the stability of KDM6B and promoted KDM6B expression. MG132 protease inhibitor increased KDM6B and USP7 expression in osteoblasts. Silencing of KDM6B reversed the promoting effect on autophagy and proliferation induced by overexpression of USP7. Taken altogether, miR‐15b inhibits osteoblast differentiation and autophagy to aggravate osteoporosis by targeting USP7 to regulate KDM6B expression.
Family‐of‐origin rejection on suicidal ideation among a sexual minority sample
Authors: VanBergen Alexandra M. , Love Heather A.
Published: January 2021

Suicide is a leading cause of death in the United States. Among sexual minority populations, suicide risk is elevated; this can be explained by minority stress. One such source of minority stress is family‐of‐origin rejection, a known risk factor for suicide among lesbian, gay, and bisexual (LGB) adolescents; however, less is known about this association among sexual minority adults. While navigating the intersection of minority stress theory and the interpersonal theory of suicide, this study sought to evaluate the impact of family‐of‐origin rejection distress on suicidal ideation among a sample of adults with marginalized sexual orientations. Recruited for two larger studies, 325 LGB participants (64.3% cisgender, 35.7% transgender or nonbinary) completed an online survey concerning minority stressors, depressive symptoms, and suicide. Using cross‐sectional mediation analysis, family‐of‐origin rejection distress was indirectly associated with suicidal thoughts through depressive symptoms. Clinical implications and suggestions for future research are discussed.
Topical cream containing live lactobacilli decreases malodor‐producing bacteria and downregulates genes encoding PLP‐dependent enzymes on the axillary skin microbiome of healthy adult Nigerians
Authors: Onwuliri Victoria , Agbakoba Nneka R. , Anukam Kingsley C.
Published: January 2021

Background

Clinical data exist that support the utility of topical probiotics for certain dermatological diseases such as atopic dermatitis, acne, and psoriasis. However, there is paucity of data on the use of live lactobacilli to control axillary malodor. The objective of this study was to determine whether application of topical oil‐based cream containing live Lactobacilli could decrease malodor‐producing bacteria in the axilla of healthy subjects.

Aims

To determine the effects of topical cream with live lactobacilli on malodor‐producing bacteria in the axilla of healthy subjects.

Patients/Methods

Twenty‐five adult volunteers comprising 12 males and 13 females provided informed consent. Axillary skin swabs were collected before and after 14 days application of topical cream containing live Lactobacillus pentosus KCA1. Bacterial DNA was extracted, and V4 region of the 16S rRNA was amplified and sequenced in a pair‐end configuration on the Illumina MiSeq platform rendering 2 × 150 bp sequences. Microbial taxonomy to species level was generated using the Greengenes database. Linear discriminant analysis (LDA) effect size (LEfSe) was used to identify biologically and statistically significant differences in relative abundance.

Results

Actinobacteria decreased from 70% to 24%, and Firmicutes increased from 26.6% to 73.9% among the female participants. In males, Actinobacteria decreased from 65% to 38%, while Firmicutes increased from 24% to 57%. Corynebacterium decreased from 62.91% to 36.63%, while Lactobacillus increased from 0.06% to 23.11%. In males, unliked females, there were reduction of Staphylococcus species associated with malodor, notably Staphylococcus hominis, Staphylococcus hemolyticus, and Staphylococcus lugdunensis. Bacterial functional gene‐ Pyridoxal protein dependent enzymes involved in biotransformation of malodor precursor to volatile thioalcohols were down‐regulated.

Conclusions

Application of Lactobacillus pentosus KCA1 cream led to a significant decrease in the relative abundance of odor‐producing Corynebacterium species in both female and male subjects. Some species associated with malodor especially Corynebacterium striatum, Corynebacterium jeikeium, Corynebacterium tuberculostearicum, and Staphylococcus hominis decreased by 96%, 73%, 7%, and 20.8%, respectively, in males.
Factors associated with teaching efficacy among nurse educators in hospital settings
Authors: Shin Sujin , Kang Youngmi , Hwang Eun Hee , Kim Jeonghyun
Published: January 2021

Aims and objectives

The objective of this study was to examine differences in personal characteristics, core practice competency and role stress according to levels of teaching efficacy among clinical nurse educators working in general hospitals.

Background

In the clinical setting, successful adaptation to instruction among practicing clinical nurse educators is challenging.

Design

Secondary analysis of data through a cross‐sectional study design was adopted.

Methods

Originally, 565 nurses were recruited from general hospitals; 364 were included in this study. Participants were nurses with more than 1 year of experience in various settings from 16 general hospitals wherein nursing students trained for clinical practicum in five cities in South Korea. Self‐reported data were collected via the Teaching Efficacy, Core Practice Competency and Perceived Stress Scales assessing clinical education‐related teaching efficacy, core practice competency and role stress. In the analyses, comparison between nurses with high and low teaching efficacy was conducted. We have followed through the EQUATOR (e.g. STROBE) research checklist for the preparation of this manuscript.

Results

According to univariate analysis, levels of teaching efficacy were shown to be higher with age, longer clinical careers, in those undergoing a doctoral course or with a doctorate, previous experience in providing clinical education and enrolment in continuing education for clinical education. In the multivariate analysis, enrolment in continuing education for clinical education, assessment and intervention skills, critical thinking skills, teaching skills and role ambiguity were associated with level of teaching efficacy among nurse educators.

Conclusion

Based on the results of this study, we recommend that nursing administrators should foster the recognition of personal characteristics in potential clinical nurse educators or preceptors with high teaching efficacy.

Relevance to clinical practice

Nurses should be supported by providing them with opportunities for professional development to enhance teaching efficacy.