bluuebunny/crossref_metadata_2025 huggingface dataset:
Circular RNA circCPA4 promotes tumorigenesis by regulating miR‐214‐3p/TGIF2 in lung cancer
Authors: Tao Wenhu , Cao Cheng , Ren Gaofei , Zhou Decun
Published: November 2021

Background

Lung cancer is the most prevalent malignancy in adults. Circular RNA (circRNA) circCPA4 (hsa_circ_0082374) is highly expressed in non‐small cell lung cancer (NSCLC). The purpose of this study was to explore the role and mechanism of circCPA4 in lung cancer.

Methods

CircCPA4, linear CPA4, TGF‐β‐induced factor homeobox 2 (TGIF2), and microRNA‐214‐3p (miR‐214‐3p) levels were measured by real‐time quantitative polymerase chain reaction (RT‐qPCR). The protein levels of TGIF2, Beclin1, and p62 were assessed by western blot assay. Colony numbers, migration, invasion, apoptosis, and cell cycle progression were examined by colony formation, wound‐healing, transwell, and flow cytometry assays, respectively. The binding relationship between miR‐214‐3p and circCPA4 or TGIF2 was predicted by StarBase or TargetScan and then verified by a dual‐luciferase reporter, RNA immunoprecipitation (RIP), and RNA pulldown assays. The biological role of circCPA4 on lung tumor growth was assessed by a xenograft tumor model in vivo, and TGIF2 and ki‐67 expression was assessed by immunohistochemistry.

Results

We determined that CircCPA4 and TGIF2 were increased, and miR‐214‐3p was decreased in lung cancer tissues and cells. Functionally, circCPA4 knockdown could suppress colony formation, migration, invasion, cell cycle progression, and expedite apoptosis of lung cancer cells in vitro. Mechanically, circCPA4 could regulate TGIF2 expression by sponging miR‐214‐3p. In addition, circCPA4 deficiency inhibited the tumor growth in lung cancer in the mouse model.

Conclusions

CircCPA4 could act as a sponge of miR‐214‐3p to upregulate TGIF2 expression, thereby promoting the progression of lung cancer cells. These findings suggested underlying therapeutic targets for the treatment of lung cancer.
Intrapleural treatment in patients with non‐small cell lung cancer with malignant pleural effusions in the real world
Authors: Pan Pengfei , Wu Fengjuan , Xu Zhiyun , Ji Xiang , Qi Qian , Huang Xiaomin , Zhao Ruyue , Liu Mingtao , Jiang Peng , Li Yu , Xu Lisheng
Published: November 2021

Background

The aim of the study was to assess the efficacy and side‐effects of intrapleural treatment in non‐small cell lung cancer (NSCLC) patients with malignant pleural effusions (MPEs).

Methods

The medical records of NSCLC patients with MPEs diagnosed in four Chinese hospitals from October 2014 to December 2019 were searched. The Kaplan–Meier method is used to calculate median overall survival (MOS) and subgroup analyses are done.

Results

A total of 285 patients were evaluated; 81.1% of patients received intrapleural treatment, and no patients received talc pleurodesis. MOS of the whole cohort was 21 months. Patients were divided into three groups: erythromycin group (EG; intrapleural treatment with drugs and erythromycin); intrathoracic treatment group (ITG; intrapleural treatment with drugs); control group (CG; no drug treatment in the pleural cavity). The MOS of patients in the EG, ITG and CG was 20, 22, and 19 months, respectively. Among patients who received only chemotherapy as systemic therapy, the MOS of intrathoracic administration group (IAG; i.e., EG and ITG) was longer than that of CG (12 vs. 6 months; p = 0.034), and the MOS of patients with a ratio of carcinoembryonic antigen in pleural effusion (PE‐CEA): CEA in blood (B‐CEA) ≤1 is worse than that of patients with a ratio >1 (4 vs. 12 months, p = 0.021) and that of CG (4 vs. 6 months, p = 0.442).

Conclusions

Intrapleural treatment can prolong the survival of NSCLC patients with MPE who do not receive targeted treatment or who only receive chemotherapy. The PE‐CEA: B‐CEA ratio can be used to predict the efficacy if intrapleural treatment is indicated.
Major adverse cardiac events after emergency department evaluation of chest pain patients with advanced testing: Systematic review and meta‐analysis
Authors: Mehta Prayag , McDonald Samuel , Hirani Raiz , Good Daniel , Diercks Deborah
Published: November 2021

Objectives

Our primary objective was to describe the risk of major adverse cardiac events (MACE) at 1, 6, and 12 months after a negative coronary computed tomography angiogram (cCTA), electrocardiogram (ECG) stress test, stress echocardiography, and myocardial perfusion scintigraphy (MPS) in low‐ to intermediate‐risk patients.

Methods

Initially, 952 articles were identified for screening, 81 met criteria for full‐text review, and once risk of bias was assessed, 33 articles were included in this meta‐analysis. We utilized a random‐effects model to assess pooled MACE event proportion for patients undergoing evaluation of acute coronary syndrome (ACS) when risk stratified to a low‐ to intermediate‐risk category after undergoing standard testing. Heterogeneity analysis was performed using Cochrane's Q‐test and I2 statistic.

Results

Twenty‐one studies evaluated follow‐up at 1 month with cCTA having a 0.09% (95% confidence interval [CI] = 0.03% to 0.26%) pooled MACE compared to 0.23% (95% CI = 0.01% to 5.8%) of the exercise stress testing (p = 1). MPS and cCTA had an overall event rate of 0.15% (95% CI = 0.06% to 0.41%) at 6 months (I2 = 0%). At 12 months, a subgroup analysis found a pooled cCTA MACE of 0.16% (95% CI = 0.04% to 0.65%) compared to 1.68% (95% CI = 0.01% to 2.6%) for stress echocardiography with low within‐group heterogeneity (I2 = 0%). Subgroup analysis of cCTA with no disease versus nonobstructive disease (<50% stenosis) did not find statistical difference in the MACE at both 1 month (0.17% [95% CI = 0.04% to 0.67%] vs. 0.06% [95% CI = 0.01% to 0.34%]) and 12 months (0.44% [95% CI = 0.09% to 2.2% vs. 0.54% [95% CI = 0.19% to 1.5%]).

Conclusions

Patients presenting with chest pain who have a coronary CTA showing < 50% stenosis, negative ECG stress test, stress echocardiography, or stress myocardial perfusion scan in the past 12 months can be discharged without any further risk stratification if their ECG and troponin are reassuring given low MACE.
Forecasting future prevalence and gender differences in binge drinking among young adults through 2040
Authors: Platt Jonathan M. , Jager Justin , Patrick Megan E. , Kloska Deborah , Schulenberg John , Rutherford Caroline , Keyes Katherine M.
Published: November 2021

Background

Binge drinking among adolescents and young adults has changed over time, but patterns differ by age and gender. Identifying high‐risk groups to target future efforts at reducing drinking in this population remains a public health priority. Forecasting methods can provide a better understanding of variation and determinants of future binge drinking prevalence.

Methods

We implemented regression‐based forecasting models to estimate the prevalence and gender differences in binge drinking among cohort groups of U.S. young adults, ages 18, 23–24, and 29–30 through 2040. Forecasting models were adjusted for covariates accounting for changes in demographic, Big‐5 social roles (e.g., residential independence), and drinking norms and related substance use, to understand the drivers of forecasted binge drinking estimates.

Results

From the last observed cohort group (years varied by age) through 2040, unadjusted binge drinking prevalence was forecasted to decrease from 26% (95% CI: 20, 33%) (2011–15) to 11% (95% CI: 4, 27%) at age 18, decrease from 38% (95% CI: 30, 45%) (2006–2010) to 34% (95% CI: 18, 55%) at ages 23/24, and increase from 32% (95% CI: 25, 40%) (2001–2005) to 35% (95% CI: 16, 59%) at ages 29/30. Gender‐stratified forecasts show a continuation in the narrowing of binge drinking prevalence between young men and women, though the magnitude of narrowing differs by age. Estimated trends were partially explained by changing norms regarding drinking and other substance use, though these indirect effects explained less of the total trend as age increased.

Conclusions

Understanding how covariates influence binge drinking trends can guide public health policies to leverage the most important determinants of future binge drinking to reduce the harm caused by binge drinking from adolescence to adulthood.
The sociology of compensation inequality in upper‐echelon positions: evidence from Australia
Authors: Safari Maryam , Birt Jacqueline , Xiang Yi
Published: November 2021

This paper explores the sociology of gender pay equality in leadership positions. Using a large compensation dataset, we examine the impact of gender pay inequality among directors and executives on firm performance. Based on a triangulation research design, quantitative outcomes are supplemented with semi‐structured interviews to study compensation expectations, negotiation skills and gender differences in teamwork on boards of directors. The findings show that remuneration transparency is becoming the norm. However, compensation inequalities still exist and undermine performance. The results indicate that diversity targets or specific policies regarding equality and equity of opportunity are insufficient if they are not supported by a cultural understanding and the application of equitable policies and procedures throughout the organisation.
Does stock market liberalisation restrain corporate financialisation?
Authors: Ying Qianwei , Zhu Yanyan , Yao Mengchao , Li Ziyang
Published: November 2021

We study the impact of stock market liberalisation through the Mainland China–Hong Kong Stock Connect (CHSC) program on the corporate financialisation of listed firms in Mainland China using the generalised difference‐in‐difference model in this paper. The empirical results show that implementing the CHSC program significantly reduces corporate financialisation of the listed firms in Mainland China by mitigating internal agency conflicts and enhancing external monitoring. Further analysis indicates that the inhibiting effect of stock market liberalisation through the CHSC program on corporate financialisation is more pronounced for firms without cross‐listing or qualified foreign institutional investors (QFII) ownership and firms with a more remarkable change of foreign ownership brought by the CHSC program.
Comparison of calcium hydroxide extrusion with syringe versus spiral filler delivery: A pilot study
Authors: Lai Gordon S. , Davis Scott , Gluskin Alan H. , Peters Christine I. , Peters Ove A.
Published: November 2021

This study aimed to evaluate Ca(OH)2 extrusion in relation to delivery technique, apical size and depth of placement. Plastic blocks had j‐shaped canals shaped to apical sizes #35 and #45 (n = 32 each). Amounts of calcium hydroxide extrusion was determined relative to apical taper, depth of insertion and whether syringe or spiral filler at 500 rpm was used. Blocks were immersed in pH‐sensitive gel and observed for colour change. Extent of extrusion was expressed in mm2. Extrusion occurred in 48/64 of the samples. At 3 mm from the canal terminus, the device affected the frequency of extrusion, with syringe placement causing extrusion significantly (P < 0.01) more frequently, irrespective of apical size. Extrusion was significantly greater at 2 mm short of the canal terminus (median 27.44 mm2) compared to 3 mm (median 19.69 mm2). Under in‐vitro conditions, a spiral filler at 500 rpm, 3 mm short of the apex, minimised extrusion of Ca(OH)2 from root canals.
In vitro antibacterial activity of endodontic bioceramic materials against dual and multispecies aerobic‐anaerobic biofilm models
Authors: Jerez‐Olate Christian , Araya Nancy , Alcántara Raúl , Luengo Luis , Bello‐Toledo Helia , González‐Rocha Gerardo , Sánchez‐Sanhueza Gabriela
Published: November 2021

The aim of this in vitro study was to evaluate the antibacterial activity of calcium silicate repair cements and sealers against a dual‐species planktonic aerobic model with different aging times and the ability to inhibit the formation of a mature 21‐day‐old multispecies anaerobic biofilm. The antibacterial activity of ProRoot MTA, MTA Angelus, Biodentine, BioRoot RCS and TotalFill BC sealer against a dual‐species aerobic planktonic model, as well as measuring how materials were affected by aging, was evaluated using the Modified Direct Contact Test. Subsequently, the ability to inhibit the formation of a mature multispecies anaerobic biofilm was evaluated using scanning electron microscopy complemented with confocal laser scanning microscopy. Biodentine and BioRoot RCS had higher antibacterial action, and Biodentine was able to maintain its antibacterial action after a prolonged aging period in vitro. Calcium silicate repair cement MTA ProRoot and Biodentine had higher antibiofilm action.
Letter: cross‐linkage between bacterial taxonomy and gene functions—a study of metagenome‐assembled genomes of gut microbiota in adult non‐alcoholic fatty liver disease
Authors: Han Weijia , Hou Jinlin
Published: November 2021

LINKED CONTENT

This article is linked to Canivet et al papers. To view these articles, visit https://doi.org/10.1111/apt.16262
Editorial: evolution of GLP‐1 receptor agonists as pharmacotherapy for NASH beyond diabetes mellitus and obesity
Authors: Kim Won
Published: November 2021

LINKED CONTENT

This article is linked to Flint et al papers. To view these articles, visit https://doi.org/10.1111/apt.16608 and https://doi.org/10.1111/apt.16669
Letter: a randomised clinical trial comparing the effects of pregabalin with those of placebo on functional dyspepsia
Authors: Chen Peng , Chen Fuchao , Lei Jiexin , Wu Yue , Benhong Zhou
Published: November 2021

LINKED CONTENT

This article is linked to Kotikula et al papers. To view these articles, visit https://doi.org/10.1111/apt.16588 and https://doi.org/10.1111/apt.16667
Editorial: statin use in patients with NAFLD—safety concerns, decreased awareness or both?
Authors: Mallet Maxime , Pais Raluca
Published: November 2021

LINKED CONTENT

This article is linked to Henson et al papers. To view these articles, visit https://doi.org/10.1111/apt.16646
Co‐curation: Archival interventions and voluntary sector records
Authors: Brewis Georgina , Ellis Paine Angela , Hardill Irene , Lindsey Rose , Macmillan Rob
Published: November 2021

There is a growing trend across the social sciences to engage with archives. Within human geography, this has stimulated a debate about the nature of archives, including moving from considering ‘archive as source’ to ‘archive as subject.’ We build on and extend this thinking, suggesting that an even more active appreciation of the dynamic nature of relationships between researchers, owners of records, and archival material is needed. This paper draws on an interdisciplinary study of voluntary action and welfare provision in England in the 1940s and 2010s to highlight how the different iterative processes involved in collaborative archival research are part of what we call co‐curation. Co‐curation involves the negotiated identification, selection, preparation, and interpretation of archival materials. This has implications for both research processes and outcomes.
Emotions and positionalities: Experiences from fieldwork among Danish Muslims
Authors: Koefoed Lasse , Simonsen Kirsten
Published: November 2021

This paper discusses epistemological and methodological considerations related to emotional experiences of conducting research among Muslims. It also involves considerations of positionalities and the issue of doing critical research on the basis of experiences. Through concrete examples, we unearth experiences from fieldwork, in this way uncovering emotions and prejudices from both researchers and research participants. Experiences then have a double meaning: both as the study of “their” experiences as living and acting minorities and as “our” methodological experiences and their influence on our studies. It includes recruitment, mutual prejudice, insecurity, and research roles in participatory research. The paper draws on research projects that we have undertaken and written about during the past 10 years involving our work with ethnic minorities (dominantly Muslims) in Copenhagen. Our approach is what we will call “critical phenomenology” and our methods involve in‐depth interviews, ethnographic observations, and participant observations. The major object of the studies, then, is “ordinary life,” that is, everyday life and embodied experiences from living as ethnic minorities in the city.
Prognostic importance of concomitant non‐regional lymph node and bone metastases in men with newly diagnosed metastatic prostate cancer
Authors: Heesterman Berdine L. , van der Poel Henk G. , Schoots Ivo G. , Mehra Niven , Aben Katja K. H.
Published: November 2021

Objectives

To evaluate the prognostic importance of concomitant non‐regional lymph node (NRLN) and bone metastases in men with synchronous metastatic hormone‐sensitive prostate cancer (mHSPC), and to determine whether M1b/M1c is the most appropriate M‐stage and evaluate the additional importance to the distinction in low/high volume disease.

Patients and Methods

All men diagnosed with synchronous mHSPC from 2010 to 2018 in the Netherlands were identified in the Netherlands Cancer Registry. Men were categorised as having NRLN (M1a), bone (M1b), NRLN and bone (M1c), or visceral metastases (M1c). For men diagnosed since October 2015 disease volume could be determined. Analyses were performed in this cohort (>5600 men) and repeated in the 2010–2018 cohort (>14 000 men). The primary outcome measure in this observational cohort study was overall survival (OS) and Cox regression was used to calculate hazard ratios (HRs).

Results

Compared to men with NRLN and bone metastases (reference group), OS of men with only NRLN (HR 0.70, 95% confidence interval [CI] 0.55–0.88) was better. This was also true for men with only bone metastases in the low‐volume subgroup (HR 0.75, 95% CI0.58–0.98), but not in the high‐volume subgroup (HR 0.99, 95% CI 0.84–1.18). In contrast, the OS of men with visceral metastases was worse (HR 2.20, 95% CI 1.75–2.77 + 0.97/month, 95% CI 0.96–0.98).

Conclusion

In men with low‐volume synchronous mHSPC, presence of concomitant NRLN and bone metastases (currently classified as M1c), is a poor prognostic sign. However, survival of men with visceral metastases (M1c) is worse. Implying that classifying concomitant NRLN and bone metastases as M1c or M1b is not appropriate. Adding a fourth M1‐category to the ninth edition of the Tumour‐Node‐Metastasis classification should be contemplated. Furthermore, definitions of metastatic burden need to be re‐evaluated.
CDK1/FBXW7 facilitates degradation and ubiquitination of MLST8 to inhibit progression of renal cell carcinoma
Authors: Zhang Encheng , Chen Siteng , Tang Heting , Fei Cheng , Yuan Zhihao , Mu Xingyu , Qin Yan , Liu Haixia , Fan Yu , Tan Mingyue , Wang Xiang
Published: November 2021

Recent studies have reported that MLST8 is upregulated in many malignant tumors. Nevertheless, the underlying molecular mechanism is still unclear. The aim of this work was to investigate how MLST8 contributes to the development and progression of clear cell renal cell carcinoma (ccRCC). MLST8 is an oncogenic protein in the TCGA database and ccRCC clinical specimens. We also ascertain that MLST8 interacts with FBXW7, which was universally regarded as an E3 ubiquitin ligase. MLST8 can be degraded and ubiquitinated by tumor suppressor FBXW7. FBXW7 recognizes a consensus motif (T/S) PXX (S/T/D/E) of MLST8 and triggers MLST8 degradation via the ubiquitin‐proteasome pathway. Strikingly, the activated cyclin dependent kinase 1 (CDK1) kinase engages in the MLST8 phosphorylation required for FBXW7‐mediated degradation. In vitro, we further prove that MLST8 is an essential mediator of FBXW7 inactivation‐induced tumor growth, migration, and invasion. Furthermore, the MLST8 and FBXW7 proteins are negatively correlated in human renal cancer specimens. Our findings suggest that MLST8 is a putative oncogene that functions via interaction with FBXW7, and inhibition MLST8 could be a potential future target in ccRCC treatment.
Child development in an ideological context: Through the lens of resistance and accommodation
Authors: Rogers Leoandra Onnie , Way Niobe
Published: November 2021

Every aspect of child development—from cognition to relationships—is shaped by macrolevel ideologies (e.g., white supremacy, patriarchy) that reflect the social hierarchies and embedded power structures of society. While ecological theories have long underscored the impact of macrosystems and cultures on humans, the field of child development has tended to overemphasize microsystems and often overlooks how ideologies of power shape developmental processes. In this article, we situate child development within and in response to the ideological context, which directs the field’s attention away from “fixing” individuals and microsystems and toward disrupting the macro‐ideologies that shape them. We ground this article in research on resistance and accommodation to such ideologies, revealing that humans have a natural capacity to resist what gets in the way of their ability to survive and thrive. We discuss questions that are necessary to address when integrating resistance and accommodation in the study of child development.
Socioeconomic status impacts genetic influences on the longitudinal dynamic relationship between temperament and general cognitive ability in childhood: The Louisville Twin Study
Authors: Finkel Deborah , Davis Deborah W. , Giangrande Evan J. , Womack Sean , Turkheimer Eric , Beam Christopher
Published: November 2021

The current analysis investigates genetic and environmental influences on the bidirectional relationships between temperament and general cognitive ability (GCA). Measures of GCA and three temperament factors (persistence, approach, and reactivity) were collected from 486 children ages 4–9 years (80% white, 50% female) from the Louisville Twin Study from 1976 to 1998. The results indicated a bidirectional dynamic model of temperament influencing subsequent GCA and GCA influencing subsequent temperament. The dynamic relationship between temperament and GCA arose primarily from shared genetic variance, particularly in families with higher socioeconomic status, where input from temperament contributed on average 20% to genetic variance in GCA versus 0% in lower SES families.
Young children’s overestimation of performance: A cross‐cultural comparison
Authors: Xia Mengtian , Poorthuis Astrid M. G. , Zhou Qiang , Thomaes Sander
Published: November 2021

Western literature suggests that young children overestimate their performance across a range of tasks. Research in non‐Western cultures, however, is lacking. In 2019, 101 Chinese (52% girls) and 98 Dutch (49% girls) children, ages 4 and 5, were asked to estimate how well they would perform on both a motor and a memory task. Children from both countries overestimated their performance to the same extent ( = .077 and .027 for the motor and memory tasks, respectively). They generally persevered in doing so despite receiving realistic performance feedback. Yet, children overestimated their peers’ performance about as much as their own performance, in some cases even more. This is the first demonstration of performance overestimation in children growing up in a non‐Western culture.
Diagnostic performance of serial serum total tryptase measurement to differentiate positive from negative allergy testing among patients with suspected perioperative hypersensitivity
Authors: Srisuwatchari Witchaya , Tacquard Charles A. , Borushko Anna , Viville Simon , Stenger Rodolphe , Ehrhard Yoann , Malinovsky Jean‐Marc , Mertes Paul‐Michel , Demoly Pascal , Chiriac Anca‐Mirela
Published: November 2021

Background

Serum total tryptase has been shown to increase during acute allergic reactions (acute tryptase, TA); however, few studies have investigated the values of TA or a combination of TA and baseline tryptase (TB) to discriminate positive from negative testing in perioperative hypersensitivity reaction (POH) allergy work‐up. The aim of this study was to determine the diagnostic performance of TA in order to differentiate positive from negative allergy testing suspected POH and analyse the diagnostic performance of serial tryptase levels using several formulas.

Methods

All patients from the University hospital of Montpellier and Strasbourg, France, who presented with suspected POH and underwent complete drug allergy work‐up between March 2011 and December 2019 with available TA and TB were included. Four formulas, including a change in TA > 11 (F1), or >2 + 1.2 × TB (F2), or >3 + TB (F3), or >120%TB (F4), were applied.

Results

One hundred and sixty‐two patients were included, and 131 of them (80.8%) had Grade III or IV reactions. Ninety patients had positive allergy testing. The optimal cut‐off value of TA to distinguish positive from negative allergy testing patients was 9.8 μg/L with an AUC of 0.817 (95% CI: 0.752–0.882, p < .001). The 93% PPV threshold for TA was 33 μg/L (95.8% specificity). Paired tryptase levels according to formulas F2 and F3 yielded the highest Youden index (0.54 and 0.53, respectively).

Conclusion

The optimal cut‐off point for TA for distinguishing positive from negative allergy testing suspected POH was 9.8 μg/L. TA value of 33 μg/L was required to achieve >90% PPV.
Clinical impact and immunological alterations in asthmatic patients allergic to grass pollen subjected to high urban pollution in Madrid
Authors: Feo‐Brito Francisco , Alfaya Arias Teresa , Amo‐Salas Mariano , Somoza Álvarez María Luisa , Haroun Díaz Elisa , Mayorga Mayorga Cristobalina , Fernández Santamaría Rubén , Urra Ardanaz José Miguel
Published: November 2021

Background

The prevalence of asthma has increased in recent decades. Among the reasons for this increase is environmental pollution. Pollutants cause bronchial inflammation and introduce modifications in the pollen, making it more allergenic.

Objective

Assess symptoms and medication requirements of asthmatic patients with grass allergies in Madrid (high urban pollution) and Ciudad Real (low pollution), and simultaneously evaluate the in vitro effects that pollen collected in both areas has on the immune cells of patients.

Methods

During two pollen seasons, patients from both cities were included. The patients recorded their symptoms and the asthma medication they took daily. In both cities, pollen data, pollutants and meteorological variables were evaluated. The response to different cell populations from patients in both areas were analysed after “in vitro” stimulation with pollen from both cities.

Results

The symptoms and medication use of the patients in Madrid was 29.94% higher. The NO2 concentration in Madrid was triple that of Ciudad Real (33.4 vs. 9.1 µg/m3 of air). All other pollutants had very similar concentrations during the study period. Pollen from the high pollution area caused a significant enhancement of T‐CD8+ and NK cells proliferation compared with pollen of low pollution area, independently of the patient's origin.

Conclusion

Asthmatic patients from Madrid have a worse clinical evolution than those from Ciudad Real because of higher levels of urban pollution, and this could be driven by the higher capacity of pollen of Madrid to activate T‐CD8+ and NK cells.
Running to save sight: The effects of exercise on retinal health and function
Authors: Chu‐Tan Joshua A. , Kirkby Max , Natoli Riccardo
Published: November 2021

The benefits of exercise to human health have long been recognised. However, only in the past decade have researchers started to discover the molecular benefits that exercise confers, especially to the central nervous system (CNS). These discoveries include the magnitude of molecular messages that are communicated from skeletal muscle to the CNS. Despite these advances in understanding, very limited studies have been conducted to decipher the molecular benefits of exercise in retinal health and disease. Here, we review the latest work on the effects of exercise on the retina and discuss its effects on the wider CNS, with a focus on demonstrating the potential applicability and comparative molecular mechanisms that may be occurring in the retina. This review covers the key molecular pathways where exercise exerts its effects: oxidative stress and mitochondrial health; inflammation; protein aggregation; neuronal health; and tissue crosstalk via extracellular vesicles. Further research on the benefits of exercise to the retina and its molecular messages within extracellular vesicles is highly topical in this field.
One dose of preoperative, intravenous, prophylactic antibiotics significantly lowers postoperative infection rate in septoplasty—a study of 772 operations
Authors: Lundberg Marie , Lilja Markus , Blomgren Karin , Kotisalmi Ida , Mäkitie Antti A. , Sainio Sara , Hytönen Maija
Published: November 2021

Objectives

Postoperative infection is the most common complication after septoplasty. Pre‐ or postoperative prophylactic antibiotics are commonly used, although no official guidelines exist.

Design

We retrospectively collected data on postoperative infections from 772 septoplasties performed in 2015, 2016 and 2018, and classified the infections according to surgical site infection (SSI) criteria by the Centers for Disease Control and Prevention (CDC). We evaluated the infections according to antibiotic use (preoperative or postoperative, both, or none) and accounted for patient and surgical confounding factors. We compared the results with three previous studies from our department to find out the trend in the occurrence of postoperative infections and in the use of antibiotics.

Results

Twenty‐nine cases (3.8%) fulfilled CDC infection criteria. Any kind of antibiotic prophylaxis reduced the risk of SSI (p = .018). One dose of intravenous cefuroxime before incision was the most effective preventive measure (p = .045). We found no significant effect of postoperative antibiotics. However, postoperative antibiotics lowered the infection rate to 1.8% compared to 6.1% among those not treated with any antibiotics. The only other factor reducing the risk of SSI was local anaesthesia compared with general anaesthesia.

Conclusion

Preoperative antibiotic prophylaxis effectively reduced postoperative infection rate after septoplasty.
Regular endoscopic surveillance and polypectomy is effective in managing rectal adenoma progression following colectomy and ileorectal anastomosis in patients with familial adenomatous polyposis
Authors: Anele Chukwuemeka C. , Xiang Jinpo , Martin Isabel , Hawkins Menna , Man Ripple , Clark Susan K. , Faiz Omar D. , Latchford Andrew
Published: November 2021

Aim

Total colectomy with ileorectal anastomosis (TC‐IRA) is a surgical option for patients with familial adenomatous polyposis (FAP). Regular endoscopic surveillance of the rectum is recommended to prevent rectal cancer. We aimed to document polyp progression in the rectum following TC‐IRA and evaluate the role of polypectomy during surveillance.

Method

Patients with FAP who underwent TC‐IRA between 1990 and 2017 were identified. Demographic, endoscopic and genetic data were retrieved. Cumulative rectal adenoma (polyp) counts were obtained, whilst accounting for any polypectomies during the study period. The rate of polyp progression and factors influencing secondary proctectomy were evaluated.

Results

One hundred and ninety‐nine patients fulfilled our inclusion criteria, of which 44% were male. The median age at colectomy was 19 (range 11–70) years and median preoperative rectal polyp count was 7 (range 0–50). All patients had an APC pathogenic variant, of which 151 (79%) were 5' of the mutation cluster region (MCR), 19 (10%) in the MCR, six (3%) were 3' of the MCR and 15 (8%) had a gross deletion. After a median follow‐up of 8.6 (range1–27) years and a median of 11 (range 2–37) flexible sigmoidoscopies per patient, the median rate of polyp progression was 5.5 polyps/year (range 0–70.2). There was no evidence of polyp regression. Eight (4%) patients underwent secondary proctectomy for neoplasia, of which one (0.5%) had rectal adenocarcinoma. A total of 13,527 polyps were removed, a median of 35 polyps/patient (range 0–829). The rate of polyp progression was not significantly associated with genotypic or phenotypic factors.

Conclusion

Progression of rectal adenoma burden following TC‐IRA appears to be slow and dependent on the length of follow‐up. In the modern era of stringent endoscopic surveillance and therapeutic procedures such as cold snare polypectomy, the rate of secondary proctectomy and the risk of rectal cancer after TC‐IRA are very low. These findings are important when counselling patients with regard to the choice of surgery for FAP and implementing endoscopic surveillance.
Revisiting the prevalence and population of children with neurological impairments in sub‐Saharan Africa
Authors: Olusanya Bolajoko O
Published: November 2021

This commentary is on the original article by Abuga et al. on pages 347–356 of this issue.
Estimate false‐negative RT‐PCR rates for SARS‐CoV‐2. A systematic review and meta‐analysis
Authors: Pecoraro Valentina , Negro Antonella , Pirotti Tommaso , Trenti Tommaso
Published: November 2021

Background

Molecular‐based tests used to identify symptomatic or asymptomatic patients infected by SARS‐CoV‐2 are characterized by high specificity but scarce sensitivity, generating false‐negative results. We aimed to estimate, through a systematic review of the literature, the rate of RT‐PCR false negatives at initial testing for COVID‐19.

Methods

We systematically searched Pubmed, Embase and CENTRAL as well as a list of reference literature. We included observational studies that collected samples from respiratory tract to detect SARS‐CoV‐2 RNA using RT‐PCR, reporting the number of false‐negative subjects and the number of final patients with a COVID‐19 diagnosis. Reported rates of false negatives were pooled in a meta‐analysis as appropriate. We assessed the risk of bias of included studies and graded the quality of evidence according to the GRADE method. All information in this article is current up to February 2021.

Results

We included 32 studies, enrolling more than 18,000 patients infected by SARS‐CoV‐2. The overall false‐negative rate was 0.12 (95%CI from 0.10 to 0.14) with very low certainty of evidence. The impact of misdiagnoses was estimated according to disease prevalence; a range between 2 and 58/1,000 subjects could be misdiagnosed with a disease prevalence of 10%, increasing to 290/1,000 misdiagnosed subjects with a disease prevalence of 50%.

Conclusions

This systematic review showed that up to 58% of COVID‐19 patients may have initial false‐negative RT‐PCR results, suggesting the need to implement a correct diagnostic strategy to correctly identify suspected cases, thereby reducing false‐negative results and decreasing the disease burden among the population.
Soil bacterial and fungal communities are linked with plant functional types and soil properties under different grazing intensities
Authors: Wang Zhen , Ding Yong , Jin Ke , Struik Paul C. , Sun Shixian , Ji Baoming , Zhang Yujuan , Li Xiliang
Published: November 2021

As a grassland management strategy in the typical steppe, livestock grazing can affect soil microbes and ecosystem functions via vegetation removal, trampling and manure deposition. However, the effects of grazing and its main consequences (e.g. the shifts in plant functional types and alterations in soil properties) on soil bacterial and fungal community composition remain unresolved. Taking advantage of a 5‐year grazing exclosure experiment that tested different grazing intensities [control: no grazing (G0); light: 0.75 sheep ha−1(G1); moderate: 1.50 sheep ha−1(G2); heavy: 2.25 sheep ha−1(G3); and overgrazing: 3.00 sheep ha−1(G4)], we examined grazing‐related changes in plant communities, soil chemistry and soil microbial communities. Grazing intensity affected the diversity and composition of soil bacterial and fungal communities via changes in plant species and soil nutrient contents. Increased grazing intensity reduced soil organic carbon (OC), suppressed the dominant bacterial phyla Proteobacteria and Bacteriodetes, and increased the abundance of oligotrophic bacteria in subordinate phyla (e.g. Verrucomicroba and Chloroflexi). Increased grazing intensity also promoted the dominant fungal phylum Ascomycetes because of the poor‐nutrient soil environment. The decreased soil carbon‐to‐nitrogen (C/N) ratio in the G2 treatment was associated with an effect on the fungal community composition. Structural equation modelling demonstrated that responses of the bacterial community to grazing intensity were related to changes in soil OC and soil pH, whereas the combination of C4plant community biomass and soil pH drove changes in the fungal community. Our study provides novel evidence that grazing affects plant functional group and soil chemistry through the soil pH and C/N ratio, which in turn affects bacterial and fungal communities.

Highlights

Heavy and overgrazing suppressed bacterial phylum Proteobacteria and increased fungal phylumAscomycete.

Soil OC was the predominant driver of changes in bacterial richness and community composition.

C4plant community biomass modulated fungal richness and community composition.
Web‐based decision support system for patient‐tailored selection of antiseizure medication in adolescents and adults: An external validation study
Authors: Hadady Levente , Klivényi Péter , Perucca Emilio , Rampp Stefan , Fabó Dániel , Bereczki Csaba , Rubboli Guido , Asadi‐Pooya Ali A. , Sperling Michael R. , Beniczky Sándor
Published: November 2021

Background and purpose

Antiseizure medications (ASMs) should be tailored to individual characteristics, including seizure type, age, sex, comorbidities, comedications, drug allergies, and childbearing potential. We previously developed a web‐based algorithm for patient‐tailored ASM selection to assist health care professionals in prescribing medication using a decision support application (https://epipick.org). In this validation study, we used an independent dataset to assess whether ASMs recommended by the algorithm are associated with better outcomes than ASMs considered less desirable by the algorithm.

Methods

Four hundred twenty‐five consecutive patients with newly diagnosed epilepsy were followed for at least 1 year after starting an ASM chosen by their physician. Patient characteristics were fed into the algorithm, blinded to the physician's ASM choices and outcome. The algorithm recommended ASMs, ranked in hierarchical groups, with Group 1 ASMs labeled as the best option for that patient. We evaluated retention rates, seizure freedom rates, and adverse effects leading to treatment discontinuation. Survival analysis contrasted outcomes between patients who received favored drugs and those who received lower ranked drugs. Propensity score matching corrected for possible imbalances between the groups.

Results

Antiseizure medications classified by the algorithm as best options had a higher retention rate (79.4% vs. 67.2%, p = 0.005), higher seizure freedom rate (76.0% vs. 61.6%, p = 0.002), and lower rate of discontinuation due to adverse effects (12.0% vs. 29.2%, p < 0.001) than ASMs ranked as less desirable by the algorithm.

Conclusions

Use of the freely available decision support system is associated with improved outcomes. This drug selection application can provide valuable assistance to health care professionals prescribing medication for individuals with epilepsy.
The epilepsy–autism spectrum disorder phenotype in the era of molecular genetics and precision therapy
Authors: Specchio Nicola , Di Micco Valentina , Trivisano Marina , Ferretti Alessandro , Curatolo Paolo
Published: November 2021

Autism spectrum disorder (ASD) is frequently associated with infants with epileptic encephalopathy, and early interventions targeting social and cognitive deficits can have positive effects on developmental outcome. However, early diagnosis of ASD among infants with epilepsy is complicated by variability in clinical phenotypes. Commonality in both biological and molecular mechanisms have been suggested between ASD and epilepsy, such as occurs with tuberous sclerosis complex. This review summarizes the current understanding of causal mechanisms between epilepsy and ASD, with a particularly genetic focus. Hypothetical explanations to support the conjugation of the two conditions include abnormalities in synaptic growth, imbalance in neuronal excitation/inhibition, and abnormal synaptic plasticity. Investigation of the probable genetic basis has implemented many genes, although the main risk supports existing hypotheses in that these cluster to abnormalities in ion channels, synaptic function and structure, and transcription regulators, with the mammalian target of rapamycin (mTOR) pathway and “mTORpathies” having been a notable research focus. Experimental models not only have a crucial role in determining gene functions but are also useful instruments for tracing disease trajectory. Precision medicine from gene therapy remains a theoretical possibility, but more contemporary developments continue in molecular tests to aid earlier diagnoses and better therapeutic targeting.
Extracellular vesicles from equine mesenchymal stem cells decrease inflammation markers in chondrocytes in vitro
Authors: Arévalo‐Turrubiarte Magdalena , Baratta Mario , Ponti Giovanna , Chiaradia Elisabetta , Martignani Eugenio
Published: November 2021

Background

Mesenchymal stem cells (MSCs) have been used therapeutically in equine medicine. MSCs release extracellular vesicles (EVs), which affect cell processes by inhibiting cell apoptosis and regulating inflammation. To date, little is known about equine EVs and their regenerative properties.

Objectives

To characterise equine MSC‐derived extracellular vesicles (EVs) and evaluate their effect on equine chondrocytes treated with pro‐inflammatory cytokines in vitro.

Study design

In vitro experiments with randomised complete block design.

Methods

Mesenchymal stem cells from bone marrow, adipose tissue, and synovial fluid were cultured in vitro. The MSC culture medium was centrifuged and filtered. Isolated particles were analysed for size and concentration (total number of particles per mL). Transmission electron microscopy analysis was performed to evaluate the morphology and CD9 expression of the particles. Chondrocytes from healthy equines were treated with the inflammatory cytokines interleukin (IL)‐1β and tumour necrosis factor‐alpha. MSC‐derived EVs from bone marrow and synovial fluid cells were added as co‐treatments in vitro. Gene expression analysis by real‐time PCR was performed to evaluate the effects of EVs.

Results

The particles isolated from MSCs derived from different tissues did not differ significantly in size and concentration. The particles had a round‐like shape and positively expressed CD9. EVs from bone marrow cells displayed reduced expression of metalloproteinase‐13.

Main limitations

Sample size and characterisation of the content of EVs.

Conclusions

EVs isolated from equine bone marrow MSCs reduced metalloproteinase 13 gene expression; this gene encodes an enzyme related to cartilage degradation in inflamed chondrocytes in vitro. EVs derived from MSCs can reduce inflammation and could potentially be used as an adjuvant treatment to improve tissue and cartilage repair in the articular pathologies.
Evidence for a role of extracellular heat shock protein 70 in epidermolysis bullosa acquisita
Authors: Tukaj Stefan , Mantej Jagoda , Sitko Krzysztof , Bednarek Marta , Zillikens Detlef , Ludwig Ralf J. , Bieber Katja , Kasperkiewicz Michael
Published: November 2021

Heat shock protein 90 (Hsp90) and Hsp70 are chaperones implicated in different inflammatory disorders, given their property to impact innate and adaptive immune responses. Here, we determined the so far unknown role of extracellular Hsp70 in epidermolysis bullosa acquisita (EBA), an anti‐type VII collagen autoantibody‐mediated blistering dermatosis. The in vivo pathophysiological relevance of extracellular Hsp70 was demonstrated in an anti‐type VII collagen antibody transfer‐induced EBA mouse model in which elevated blood levels of this chaperone were recorded. We found that Hsp70‐treated mice had a more intense clinical disease severity compared to controls that were paralleled by increased levels of cutaneous matrix metalloproteinase 9 and plasma hydrogen peroxide. The latter finding was confirmed in an independent reactive oxygen species release assay using EBA‐specific immune complexes combined with recombinant Hsp70. Finally, cell culture experiments using human naive peripheral blood mononuclear cells (PBMC) revealed that extracellular Hsp70 stimulated the secretion of the T cell–derived pro‐inflammatory cytokines IL‐6 and IL‐8. This work extends knowledge about the role of Hsps in autoimmune bullous diseases, suggesting that extracellular Hsp70 represents a pathophysiological factor and potential treatment target in EBA.
Quantifying socio‐economic novelty in fisheries social‐ecological systems
Authors: Ammar Yosr , Voss Rudi , Niiranen Susa , Blenckner Thorsten
Published: November 2021

Socio‐economic development has shaped fisheries social‐ecological systems (SES) worldwide across different scales. No work has yet undertaken how this development led to novel, not experienced before, systems structure in marine SES. Here, we quantify socio‐economic novelty as the degree of dissimilarity relative to a specific spatiotemporal baseline in the Baltic Sea fisheries SES between 1975 and 2015. We used catch by "gears," catch by "commercial groups" and trade ("import" and "export") as respective indicators of novelty at national, regional and international governance levels. We found that socio‐economic novelty increased over time nonlinearly in relation to the 1975–1979 baseline. The contribution to total novelty shifted from the dominance of “gears” and “commercial groups” in the late 1990s and early 2000s to “import” and “export” after the mid‐2000s, i.e. from national and regional levels to the international level. The fastest increase in novelty occurred with the trade dominance shift, primarily related to monetary value rather than quantity. Spatially, novelty emerged with a large difference across countries, and a major contribution by Sweden, Denmark and Poland. We identified the influence of different management interventions and governance actions on the emergence of novelty in the Baltic SES. The decreasing socio‐economic novelty at national and regional levels could indicate reduced variability due to management intervention in recent years which might decrease SES resilience to shocks. Calculating socio‐economic novelty and studying its drivers at different scales could provide a better understanding of SES complexity and inform urgently needed adaptation and transformation towards sustainable future pathways.