bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of the COVID‐19 lockdown with smoking, drinking and attempts to quit in England: an analysis of 2019–20 data
Authors: Jackson Sarah E. , Garnett Claire , Shahab Lion , Oldham Melissa , Brown Jamie
Published: October 2020

Aim

To examine changes in smoking, drinking and quitting/reduction behaviour following the COVID‐19 lockdown in England.

Design/setting

Monthly cross‐sectional surveys representative of the adult population in England, aggregated before (April 2019–February 2020) versus after (April 2020) lockdown.

Participants

A total of 20 558 adults (≥ 16 years).

Measurements

The independent variable was the timing of the COVID‐19 lockdown (before versus after March 2020). Dependent variables were: prevalence of smoking and high‐risk drinking, past‐year cessation and quit attempts (among past‐year smokers), past‐year attempts to reduce alcohol consumption (among high‐risk drinkers) and use of evidence‐based (e.g. prescription medication/face‐to‐face behavioural support) and remote support [telephone support/websites/applications (apps)] for smoking cessation and alcohol reduction (among smokers/high‐risk drinkers who made a quit/reduction attempt). Covariates included age, sex, social grade, region and level of nicotine and alcohol dependence (as relevant).

Findings

The COVID‐19 lockdown was not associated with a significant change in smoking prevalence [17.0% (after) versus 15.9% (before), odds ratio (OR) = 1.09, 95% CI = 0.95–1.24], but was associated with increases in quit attempts [39.6 versus 29.1%, adjusted odds ratio (ORadj) = 1.56, 95% CI = 1.23–1.98], quit success (21.3 versus 13.9%, ORadj = 2.01, 95% CI = 1.22–3.33) and cessation (8.8 versus 4.1%, ORadj = 2.63, 95% CI = 1.69–4.09) among past‐year smokers. Among smokers who tried to quit, there was no significant change in use of evidence‐based support (50.0 versus 51.5%, ORadj = 1.10, 95% CI = 0.72–1.68) but use of remote support increased (10.9 versus 2.7%, ORadj = 3.59, 95% CI = 1.56–8.23). Lockdown was associated with increases in high‐risk drinking (38.3 versus 25.1%, OR = 1.85, CI = 1.67–2.06), but also alcohol reduction attempts by high‐risk drinkers (28.5 versus 15.3%, ORadj = 2.16, 95% CI = 1.77–2.64). Among high‐risk drinkers who made a reduction attempt, use of evidence‐based support decreased (1.2 versus 4.0%, ORadj = 0.23, 95% CI = 0.05–0.97) and there was no significant change in use of remote support (6.9 versus 6.1%, ORadj = 1.32, 95% CI = 0.64–2.75).

Conclusions

Following the March 2020 COVID‐19 lockdown, smokers and high‐risk drinkers in England were more likely than before lockdown to report trying to quit smoking or reduce alcohol consumption and rates of smoking cessation and use of remote cessation support were higher. However, high‐risk drinking prevalence increased post‐lockdown and use of evidence‐based support for alcohol reduction by high‐risk drinkers decreased with no compensatory increase in use of remote support.
Effect of Khat (Catha edulisForsk) extract on testicular maturation in pre‐pubertal and pubertal rats: A morphological and biochemical study
Authors: Abou‐Elhamd Alaa S. , Sumayli Saud , Steger Klaus , Ali Asaad Khaled Mohamed , Zayed Ahmed E.
Published: October 2020

The present study aimed at analysing the effect of Khat plant extract on rat testicular development. Thirty‐two weaned male albino rats (4 weeks old) were divided into four groups consisting of eight animals each. While control animals received normal saline, rats of groups I, II and III received 100, 200 and 300 mg Khat extract per kg body weight dissolved in distilled water by oral gavage daily for 8 weeks, respectively. Blood samples were collected in separate heparinized tubes by cardiac puncture from each rat and processed for measuring plasma levels of reproductive hormones LH, FSH, testosterone and prolactin. Five‐µm sections were stained with haematoxylin and eosin and examined by light microscope. Some sections were immunostained for protamine‐1 representing a biomarker for intact sperm differentiation. The present study clearly demonstrated that Khat extract has a pronounced effect on testicular maturation of developing albino rats at both the morphological and functional levels. Khat‐treated groups revealed a significantly low serum testosterone level and severe impairment of spermatogenesis when compared with control animals. The current findings also verified, for the first time, that the final stages of sperm maturation (spermiogenesis) were strongly impaired after administration of Khat extract to experimental rats particularly at a higher dose (300 mg/kg body weight). This was proved by the very weak, if any, expression of protamine‐1 in the maturing spermatids in Khat‐treated rats.
Fatty acid‐binding protein 3 controls contact hypersensitivity through regulating skin dermal Vγ4+ γ/δ T cell in a murine model
Authors: Kobayashi Shuhei , Phung Hai The , Kagawa Yoshiteru , Miyazaki Hirofumi , Takahashi Yu , Asao Atsuko , Maruyama Takashi , Yoshimura Akihiko , Ishii Naoto , Owada Yuji
Published: October 2020

Background

Fatty acid‐binding protein 3 (FABP3) is a cytosolic carrier protein of polyunsaturated fatty acids (PUFAs) and regulates cellular metabolism. However, the physiological functions of FABP3 in immune cells and how FABP3 regulates inflammatory responses remain unclear.

Methods

Contact hypersensitivity (CHS) induced by 2,4‐dinitrofluorobenzene (DNFB) and fluorescein isothiocyanate was applied to the skin wild‐type and Fabp3−/− mice. Skin inflammation was assessed using FACS, histological, and qPCR analyses. The development of γ/δ T cells was evaluated by a co‐culture system with OP9/Dll1 cells in the presence or absence of transgene of FABP3.

Results

Fabp3‐deficient mice exhibit a more severe phenotype of contact hypersensitivity (CHS) accompanied by infiltration of IL‐17‐producing Vγ4+ γ/δ T cells that critically control skin inflammation. In Fabp3−/− mice, we found a larger proportion of Vγ4+ γ/δ T cells in the skin, even though the percentage of total γ/δ T cells did not change at steady state. Similarly, juvenile Fabp3−/− mice also contained a higher amount of Vγ4+ γ/δ T cells not only in the skin but in the thymus when compared with wild‐type mice. Furthermore, thymic double‐negative (DN) cells expressed FABP3, and FABP3 negatively regulates the development of Vγ4+ γ/δ T cells in the thymus.

Conclusions

These findings suggest that FABP3 functions as a negative regulator of skin inflammation through limiting pathogenic Vγ4+ γ/δ T‐cell generation in the thymus.
Post‐operative outcomes in the elderly following colorectal cancer surgery
Authors: Park Hyerin , Parys Simon , Tan Jonathan , Entriken Fiona , Hodder Rupert
Published: October 2020

Background

Despite the prevalence of colorectal cancer in the elderly, there has been a lack of recent studies examining surgical outcomes in these patients. Post‐operative outcomes of colorectal cancer surgeries in those aged 80 and above will be compared to those younger than 80.

Methods

A retrospective study was conducted of adults receiving surgical resections at a single tertiary centre for colorectal cancer diagnosed between January 2017 and December 2019. Patient demographics, mode of presentation, tumour demographics, operative data and post‐operative outcomes were investigated.

Results

Of the 326 patients included, 56 were aged 80 and above. Older patients were more likely to be female (P = 0.02), present with surgical emergencies or from other workup rather than through screening (P = 0.002), have more locally advanced cancers (P = 0.009) and receive less neoadjuvant therapy (P = 0.016). Despite this, they had comparable outcomes to those younger than 80 in terms of length of stay (P = 0.21) and rates of complications including mortality (P = 0.67).

Conclusion

With appropriate patient selection and management, elderly patients can achieve comparable post‐operative outcomes to their younger counterparts.
Early management of hypokalaemia in severely malnourished children under five could help to reduce deaths in developing countries
Authors: Shahid Abu Sadat Mohammad Sayeem Bin , Alam Tahmina , Shahrin Lubaba , Shahunja K. M. , Sarmin Monira , Afroze Farzana , Waliur Rahman Muhammad , Faruque A. S. G. , Ahmed Tahmeed , Chisti Mohammod Jobayer
Published: October 2020

Aim

This study evaluated the factors associated with hypokalaemia and their outcomes, in severely malnourished children under 5 years of age.

Methods

We focused on 407 severely malnourished children under five who were admitted to the Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh, from April 2011 to June 2012. The cases were 139 with hypokalaemia, and the comparisons were 268 without hypokalaemia.

Results

Cases were older than the comparisons, with a poor socio‐economic status and a higher death rate of 12% vs 7%. They were more likely to present with a history of measles, diarrhoea, lethargy, lower pulse rates, hyponatraemia, metabolic acidosis, hypocalcaemia, hypomagnesaemia, higher height or length, severe underweight, severe wasting and leucocytosis on admission. At discharge, cases had lower potassium levels and a higher proportion had persistent hypokalaemia. Cases received longer treatment with ampicillin and micronutrients. After adjusting for confounders, hypokalaemia was independently associated with poor socio‐economic status, diarrhoea, lower pulse rates, hypocalcaemia, metabolic acidosis and leucocytosis.

Conclusion

Identifying simple clinical signs, like diarrhoea and lower pulse rates, and laboratory parameters, such as hypocalcaemia and metabolic acidosis, may enable the early management of hypokalaemia in severely malnourished children under 5 years. This could reduce morbidity and mortality.
Sophisticated electoral accountability
Authors: Belmonte Alessandro
Published: October 2020

How does voter sophistication affect electoral accountability and policy‐making? This paper studies this question in a political‐economic model where a politician in office, with career concerns, can conceal relevant information for policy‐making. Voters have a different level of electoral sophistication, yet all care about the provision of a public good. Sophistication helps voters to formulate correct electoral and economic decisions and can be developed by investing in education. Where this ability is low, voters misjudge the behavior of the politician in office who cheats the electorate, misappropriates public funds, and, nonetheless, obtains re‐election. I discuss the implications of this equilibrium. First, political deception deters aware, sophisticated voters from investing in education, which restricts future political expertise and electoral accountability. Second, fully revealed information deters cheating and can help less sophisticated societies embark on economic enhancing trajectories. In an infinite‐horizon extension of the model, I underline a potential complementarity between accountability and sophistication that can be used to explain divergent equilibria in the long‐run.
The values of open data
Authors: Inkpen Rob , Gauci Ritienne , Gibson Andy
Published: October 2020

This paper explores the values of open data in the context of differential power relations in academia and, in particular, the significance of open data policies for early career researchers and career development.
Toxicological analysis of azide and cyanide for azide intoxications using gas chromatography
Authors: Bruin Maaike A. C. , Dekker Douwe , Venekamp Nikkie , Tibben Matthijs , Rosing Hilde , de Lange Dylan W. , Beijnen Jos H. , Huitema Alwin D. R.
Published: October 2020

Azide is a highly toxic chemical agent to human being. Accidental, but also intentional exposure to azide occurs. To be able to confirm azide ingestion, we developed a method to identify and quantify azide in biological matrices. Cyanide was included in the method to evaluate suggested in vivo production of cyanide after azide ingestion. Azide in biological matrices was first derivatized by propionic anhydride to form propionyl azide. Simultaneously, cyanide was converted into hydrogen cyanide. After thermal rearrangement of propionyl azide, ethyl isocyanate was formed, separated together with hydrogen cyanide by gas chromatography (GC) and detected using a nitrogen phosphorous detector (NPD). The method was linear from 1.0‐100 µg/mL for both analytes, and azide was stable in human plasma at −20°C for at least 49 days. Azide was measured in the gastric content of two cases of suspected azide ingestion (case 1:1.2 mg/mL, case 2:1.5 mg/mL). Cyanide was only identified in the gastric content of case 1 (approximately 1.4 µg/mL). Furthermore, azide was quantified in plasma (19 µg/mL), serum (24 µg/mL), cell pellet (21 µg/mL) and urine (3.0 µg/mL) of case 2. This method can be used to confirm azide and cyanide exposure, and azide concentrations can be quantified in several biological matrices.
Lipid antigens in bile from patients with chronic liver diseases activate natural killer T cells
Authors: Valestrand L , Berntsen N L , Zheng F , Schrumpf E , Hansen S H , Karlsen T H , Blumberg R S , Hov J R , Jiang X , Melum E
Published: October 2020

Natural killer T (NKT) cells are an abundant subset of liver lymphocytes activated by lipid antigens presented on CD1d molecules that are expressed by cholangiocytes. We aimed to determine if bile from patients with chronic liver diseases contains antigenic lipids that can activate NKT cells. Using murine invariant (24.7, 24.8 and DN32.D3) and non-invariant (14S.6, 14S.7 and 14S.10) NKT hybridomas we investigated the presence of lipid antigens in bile collected from the gallbladder of patients undergoing liver transplantation due to end-stage liver disease. Biliary microbiota profiles were generated using 16S rRNA amplicon sequencing. We found that the patient bile samples contain antigens that activate both invariant and non-invariant NKT hybridomas (24.7, 24.8, DN32.D3, 14S.6, 14S.7 and 14S.10), as demonstrated by activation of at least one hybridoma by eight of 10 bile samples. Activation at high dilutions suggests that some antigens are highly potent. We used the non-invariant NKT hybridoma 14S.6 to screen 21 additional patient bile samples for NKT-reactivity and demonstrated that 12 of 21 bile samples resulted in activation, three of which gave a strong activation. Four of 12 activating bile samples contained microbial DNA. Our results reveal an immunological pathway that could be of critical importance in biliary immunology.
Revisiting B cell tolerance and autoantibodies in seropositive and seronegative autoimmune rheumatic disease (AIRD)
Authors: Pouw J N , Leijten E F A , van Laar J M , Boes M
Published: October 2020

Autoimmune rheumatic diseases (AIRD) are categorized seropositive or seronegative, dependent upon the presence or absence of specific autoreactive antibodies, including rheumatoid factor and anti-citrullinated protein antibodies. Autoantibody-based diagnostics have proved helpful in patient care, not only for diagnosis but also for monitoring of disease activity and prediction of therapy responsiveness. Recent work demonstrates that AIRD patients develop autoantibodies beyond those contained in the original categorization. In this study we discuss key mechanisms that underlie autoantibody development in AIRD: defects in early B cell development, genetic variants involved in regulating B cell and T cell tolerance, environmental triggers and antigen modification. We describe how autoantibodies can directly contribute to AIRD pathogenesis through innate and adaptive immune mechanisms, eventually culminating in systemic inflammation and localized tissue damage. We conclude by discussing recent insights that suggest distinct AIRD have incorrectly been denominated seronegative.
Older age does not influence the success of weight loss through the implementation of lifestyle modification
Authors: Leyden Eimear , Hanson Petra , Halder Louise , Rout Lucy , Cherry Ishbel , Shuttlewood Emma , Poole Donna , Loveder Mark , Abraham Jenny , Kyrou Ioannis , Randeva Harpal S. , Lam FT , Menon Vinod , Barber Thomas M.
Published: October 2020

Objective

Age is sometimes a barrier for acceptance of patients into a hospital‐based obesity service. Our aim was to explore the effect of age on the ability to lose weight through lifestyle interventions, implemented within a hospital‐based obesity service.

Design

Retrospective study.

Patients

We included a cohort of randomly selected patients with morbid obesity (n = 242), who attended our hospital‐based obesity service during 2005‐2016 and received only lifestyle weight loss interventions.

Measurements

Primary outcome measures were percentage weight loss (%WL) and percentage reduction in body mass index (%rBMI) following implemented lifestyle interventions. Data were stratified according to patient age at referral: group 1 (age < 60 years, n = 167) and group 2 (age ≥ 60 years, n = 75). Weight loss was compared between groups, and correlations with age at referral were explored.

Results

The duration of hospital‐based weight loss interventions ranged between 1 and 143 months (mean: 38.9 months; SD: 32.3). Baseline BMI at referral differed significantly between groups 1 and 2 (49.7 kgm−2 [SD: 8.7] vs 46.9 kgm−2 [SD: 6.1], respectively; P < .05). Following implemented lifestyle interventions, between groups 1 and 2 there were no differences in %WL (6.9% [SD: 16.7] vs 7.3% [SD: 11.60], respectively; P = NS) or %rBMI (8.1% [SD: 14.9] vs 7.8% [SD: 11.7], respectively; p = NS). Overall, there was no significant correlation between patient age at referral and %WL (r = −.13, p = NS).

Conclusions

Older age does not influence the success of weight loss through the implementation of lifestyle modification within a hospital‐based obesity service. Therefore, age per se should not influence clinical decisions regarding acceptance of patients to hospital‐based obesity services.
Molecular diagnosis based on comprehensive genetic testing in 800 Chinese families with non‐syndromic inherited retinal dystrophies
Authors: Liu Xiaozhen , Tao Tianchang , Zhao Lin , Li Genlin , Yang Liping
Published: October 2020

Importance

Inherited retinal dystrophies (IRDs) are a group of monogenic diseases, one of the leading causes of blindness.

Background

Introducing a comprehensive genetic testing strategy by combining single gene Sanger sequencing, next‐generation sequencing (NGS) including whole exome sequencing (WES), and a specific hereditary eye disease enrichment panel (HEDEP) sequencing, to identify the disease‐causing variants of 800 Chinese probands affected with non‐syndromic IRDs.

Design

Retrospective analysis.

Participants

Eight hundred Chinese non‐syndromic IRDs probands and their families.

Methods

A total of 149 patients were subjected to Sanger sequencing. Of the 651 patients subjected to NGS, 86 patients underwent WES and 565 underwent HEDEP. Patients that likely carried copy number variations (CNVs) detected by HEDEP were further validated by multiplex ligation‐dependent probe amplification (MLPA) or quantitative fluorescence PCR (QF‐PCR).

Main Outcome Measures

The diagnostic rate.

Results

(Likely) pathogenic variants were determined in 481 cases (60.13% detection rate). The detection rates of single gene Sanger sequencing, WES and HEDEP were 86.58%, 31.40% and 56.99%, respectively. Approximately 11.64% of 481 cases carried autosomal dominant variants, 72.97% carried AR variants and 15.39% were found to be X‐linked. CNVs were confirmed by MLPA or QF‐PCR in 17 families. Fourteen genes that each caused disease in 1% or more of the cohort were detected, and these genes were collectively responsible for disease in almost one half (46.38%) of the families.

Conclusions and Relevance

Sanger sequencing is ideal to detect pathogenic variants of clinical homogeneous diseases, whereas NGS is more appropriate for patients without an explicit clinical diagnosis.
Liquid‐based shaking of core needle biopsy samples for the molecular characterisation of tumours: A fallback in cytopathology
Authors: L'Imperio Vincenzo , Corral Lilia , Pagni Fabio
Published: October 2020

Cytological specimens may be the ideal source of nucleic acids for the molecular characterization of tumors in the next generation sequencing (NGS) era. Liquid‐based shaking of core needle biopsy samples could enhance the diagnostic yield, allowing additional material to be examined in parallel with histopathology.
Effusion cytology of a mucinous borderline ovarian tumour: Pitfall or controversy? A case report with insight into the newly proposed International System for Reporting Serous Fluid Cytology
Authors: Razack Rubina , Mohosho Mokoena Martins , Barnardt Pieter , Schubert Pawel Tomasz
Published: October 2020

A case report of effusion cytology of a mucinous neoplasm is illustrated. The authors share their insight into adapting the newly proposed international system for reporting serous fluid cytology.
Is the use of the atypical squamous cells of undetermined significance category still necessary in cytological triage?
Authors: Confortini Massimo
Published: October 2020

The balance between specificity and sensitivity in triage cytology must take into account that the first is the crucial point for the process of cervical cancer screening using HPV primary screening test. As the use of HPV as the primary screening test has completely changed the role of the Pap test in the screening algorithm, should “The Bethesda System for Reporting Cervical Cytology” be reviewed? In particular, is the use of the ASC‐US category still truly necessary?
Myeloperoxidase andCYBAgenetic variants in polycystic ovary syndrome
Authors: Ma Wandi , Li Suiyan , Liu Hongwei , Bai Huai , Liu Qingqing , Hu Kaifeng , Guan Linbo , Fan Ping
Published: October 2020

Background

Oxidative stress plays a pivotal role in the pathogenesis of polycystic ovary syndrome (PCOS). Genetic variations in myeloperoxidase (MPO;G‐463A) and NADPH oxidase p22phox subunit (CYBA;C242T) cause inter‐individual variability in enzyme activities. Here, we investigated the associations between MPO activity and theMPO G‐463AandCYBA C242Tpolymorphisms in Chinese women with PCOS.

Methods

This case‐control study included 1003 patients with PCOS and 810 controls. TheG‐463AandC242Tpolymorphisms were detected by polymerase chain reaction and restriction analysis, and clinical, hormonal, metabolic and oxidative stress parameters and MPO activity were analysed.

Results

The frequencies of theGA + AAgenotype andAallele frequency of theMPO G‐463Apolymorphism were significantly higher in the PCOS group than in the control group. Logistic regression analysis showed that theMPO‐463Aallele is a risk factor for PCOS (OR = 1.261, 95% CI: 1.042‐1.526,P = .017). Patients with theAAgenotype tended to have higher plasma MPO activity than those with theGGgenotype. No statistical significance was found in the genotype and allele frequencies of theCYBA C242Tpolymorphism between the PCOS and control groups. However, we demonstrated that the coexistence of theMPO Aallele (GA + AAgenotypes) and theCYBA CCgenotype was associated with an increased risk of PCOS when compared with the wild‐typeGG/CCgenotypes (OR = 1.302, 95% CI: 1.030‐1.646,P = .027).

Conclusion

TheMPO G‐463Avariant, but notCYBA C242Tvariant, is associated with a risk of PCOS in Chinese women.
A novel somatic PLCG2 variant associated with resistance to BTK and SYK inhibition in chronic lymphocytic leukemia
Authors: Raghunathan Vikram , Fan Guang , Kittai Adam S. , Okada Craig , Danilov Alexey V. , Spurgeon Stephen E.
Published: October 2020

The treatment of chronic lymphocytic leukemia (CLL) has been transformed by the use of targeted small molecules inhibiting components of the B cell receptor (BCR) signaling pathway (Haematologica, 103, 2018 and e204; Curr Hematol Malig Rep, 14, 2019, 302). Chief among these is ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), which produces deep, durable responses in CLL with good tolerability (Haematologica, 103, 2018 and e204). Though prolonged exposure to the drug can exert selective pressure on CLL cells and allow for the emergence of drug‐resistant clones, primary ibrutinib treatment failure is rare (Expert Rev Hematol, 11 and 2018, 185; N Engl J Med, 370, 2014 and 2352; N Engl J Med, 373, 2015 and 25, 2425; Blood, 128, 2016 and 2199). Activating mutations in the gene PLCG2, which encodes a downstream target of BTK, appear to enable constitutive BCR signaling and have been associated with ibrutinib resistance (Int J Cancer, 146 and 2020, 85; J Clin Oncol, 35, 2017 and 1437; Blood, 126, 2015 and 61). In recent years, novel investigational agents have targeted other components of the BCR pathway. Among these is entospletinib, an orally bioavailable, selective inhibitor of splenic tyrosine kinase (SYK) (Blood, 126, 2015 and 1744), which lies upstream of the enzyme phospholipase C‐gamma‐2 (PLCG2). Here, we describe a patient who was found to harbor a novel somatic variant of PLCG2 and experienced a lack of treatment response to both ibrutinib and entospletinib.
The Framingham cardiovascular risk score and 5‐year progression of multiple sclerosis
Authors: Petruzzo Martina , Reia Antonio , Maniscalco Giorgia T. , Luiso Fabrizio , Lanzillo Roberta , Russo Cinzia Valeria , Carotenuto Antonio , Allegorico Lia , Palladino Raffaele , Brescia Morra Vincenzo , Moccia Marcello
Published: October 2020

Background and purpose

Cardiovascular risk factors and comorbidities can affect the prognosis of multiple sclerosis (MS). The Framingham risk score is an algorithm that can estimate the 10‐year risk of developing macrovascular disease. Our objectives were to evaluate the possible association between the Framingham risk score at baseline and MS relapses, disability, and disease‐modifying therapy (DMT) choices over a 5‐year follow‐up.

Methods

This is a retrospective cohort study including 251 MS subjects. At baseline, we calculated the Framingham risk score considering the following variables: age, sex, diabetes, smoking, systolic blood pressure, and body mass index. MS outcomes including relapses, disability, and treatments were collected over 5 years. Cox proportional regression models were employed to estimate hazard ratios (HRs).

Results

A one‐point increase in the Framingham risk score was associated with 31% higher risk of relapse (HR = 1.31; 95% confidence interval [CI] = 1.03, 1.68), 19% higher risk of reaching of EDSS 6.0 (HR = 1.19; 95% CI = 1.05, 3.01), and 62% higher risk of DMT escalation (HR = 1.62; 95% CI = 1.22, 3.01).

Conclusions

Higher cardiovascular risk was associated with higher risk of relapses, disability, and DMT escalation in MS. Early identification, correction, and treatment of cardiovascular comorbidities should be carefully considered within MS management.
Short‐term protein restriction at advanced age stimulates FGF21 signalling, energy expenditure and browning of white adipose tissue
Authors: Dommerholt Marleen B. , Blankestijn Maaike , Vieira‐Lara Marcel A. , van Dijk Theo H. , Wolters Henk , Koster Mirjam H. , Gerding Albert , van Os Ronald P. , Bloks Vincent W. , Bakker Barbara M. , Kruit Janine K. , Jonker Johan W.
Published: October 2020

Dietary protein restriction has been demonstrated to improve metabolic health under various conditions. However, the relevance of ageing and age‐related decline in metabolic flexibility on the effects of dietary protein restriction has not been addressed. Therefore, we investigated the effect of short‐term dietary protein restriction on metabolic health in young and aged mice. Young adult (3 months old) and aged (18 months old) C57Bl/6J mice were subjected to a 3‐month dietary protein restriction. Outcome parameters included fibroblast growth factor 21 (FGF21) levels, muscle strength, glucose tolerance, energy expenditure (EE) and transcriptomics of brown and white adipose tissue (WAT). Here, we report that a low‐protein diet had beneficial effects in aged mice by reducing some aspects of age‐related metabolic decline. These effects were characterized by increased plasma levels of FGF21, browning of subcutaneous WAT, increased body temperature and EE, while no changes were observed in glucose homeostasis and insulin sensitivity. Moreover, the low‐protein diet used in this study was well‐tolerated in aged mice indicated by the absence of adverse effects on body weight, locomotor activity and muscle performance. In conclusion, our study demonstrates that a short‐term reduction in dietary protein intake can impact age‐related metabolic health alongside increased FGF21 signalling, without negatively affecting muscle function. These findings highlight the potential of protein restriction as a strategy to induce EE and browning of WAT in aged individuals.
Hepatocellular carcinoma and other complications of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis in Japan: A structured review of published works
Authors: Eguchi Yuichiro , Wong Gabriel , Lee I‐Heng , Akhtar Omar , Lopes Ricardo , Sumida Yoshio
Published: October 2020

Aims

Hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality in Japan. As the treatment of viral hepatitis improves, non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH) are rapidly becoming leading causes of HCC in Japan. This structured review aims to characterize the morbidity and mortality of HCC and other malignant and non‐malignant complications among Japanese NAFLD and NASH patients.

Methods

An English and Japanese structured search of published works was undertaken in PubMed, Embase, and Ichushi Web databases, identifying 6553 studies, 34 of which met predefined inclusion criteria.

Results

Hepatocellular carcinoma was the most common incident malignancy among NAFLD/NASH patients, with higher incidence in patients with advanced/severe fibrosis (F3/F4) of 10.5%–20.0%. Although NASH results in a lower HCC cumulative incidence than hepatitis C virus (HCV) (11.3% vs. 30.5%), they have similar impacts on health outcomes, including overall mortality.

Among Japanese NASH patients, HCC was found to be the main driver of mortality (40.0% in 2.7 years in NASH‐HCC). With longer follow‐up, higher mortality rates are observed in F3/4 patients: 25.0% in NASH F3/F4 versus 0.0% in NASH F0/2 over 7.7 years. The NASH‐HCC patients also have a higher post‐operative mortality than HCV‐HCC patients.

Additionally, NAFLD/NASH patients had higher rates of cardiovascular disease than non‐NAFLD/NASH controls, and slightly higher rates of gastric cancer than HCV patients.

Conclusion

Hepatocellular carcinoma is the most common malignancy and cause of death among NAFLD/NASH patients in Japan, with higher mortality observed among those with advanced disease and complications. Early identification and effective treatments are needed.
Intestinal permeability and small intestine bacterial overgrowth in excess weight adolescents
Authors: Cortez Ana Paula Bidutte , Fisberg Mauro , de Morais Mauro Batista
Published: October 2020

Background

Increased intestinal permeability may be associated with certain disorders, such as obesity and small intestine bacterial overgrowth (SIBO).

Objective

This study aimed to investigate intestinal permeability and SIBO in excess weight adolescents.

Methods

This cross‐sectional study included 67 adolescents with excess weight and 66 normal weight adolescents. Excess weight was defined as a body mass index for age (BMI/age) > +1 SD, which includes having excess body weight and obesity. SIBO was diagnosed by a breath test after the ingestion of lactulose according to the production of hydrogen and methane. Zonulin (haptoglobin) was considered an indicator of intestinal permeability.

Results

Adolescents with excess weight had a higher height/age Z‐score (median [25th; 75th percentile]: +0.6 [−0.4; +1.0]) than those in the normal weight group (−0.1 [−0.6; +0.7]; P = .014). Zonulin (mg/mL) in the excess weight (2.3 [1.5; 3.8]) adolescents was higher than that in the normal weight (1.6 [1.0; 2.2]) adolescents (P < .001). SIBO was diagnosed in 23.3% (31/133) of the adolescents. The adolescents with SIBO had a lower (P < .05) BMI/age (+0.6 [−0.6; +1.9]) and height/age (−0.3 [−0.7; +0.3]) than the adolescents without SIBO (+1.3 [+0.1; +2.6] and +0.2 [−0.5; +1.0], respectively). No association was found between zonulin and SIBO.

Conclusion

Excess weight is associated with increased intestinal permeability. No relationship was found between SIBO and intestinal permeability; however, SIBO was related to lower BMI and height for age Z‐scores.
Do Austrian Programmes Facilitate Labour Market Integration of Refugees?
Authors: Ortlieb Renate , Eggenhofer‐Rehart Petra , Leitner Sandra , Hosner Roland , Landesmann Michael
Published: October 2020

This study examines two programmes aimed at integrating refugees into the Austrian labour market: a short‐term Skills Assessment and a longer‐term Integration Year that includes an internship and training. The theoretical framework draws on the concepts of social field and forms of capital proposed by Pierre Bourdieu. Using data from a large‐scale refugee survey in early 2019, we find that Austria’s short‐term Skills Assessment fails to increase refugees’ employment chances. The Integration Year positively helps employment, but this outcome is limited to refugee women. We conclude that integration programmes only help if they provide refugees with both cultural and social capital. Implications for research and practice are discussed.
The state of nursing research from 2000 to 2019: A global analysis
Authors: Yanbing Su , Hua Liu , Chao Liu , Fenglan Wang , Zhiguang Duan
Published: October 2020

Aim

This study aims to present a general bibliometric overview of the development status of global nursing research from 2000 to 2019.

Design

A longitudinal bibliometric analysis of nursing research was conducted.

Methods

Nursing research publications (N = 88,665) were obtained from Web of Science. Bibliometric method was used to map the output and citation impact trends of countries/regions, institutions, disciplines, and journals and analyse the research collaboration among countries/regions and institutions.

Results

The global paper output in nursing research increased steadily over the past two decades and it varied in different countries/regions with the USA being far ahead of the others. The paper output and cross‐border collaboration are mainly distributed in several developed countries like the USA, the UK, Australia, and Canada. The University of Pennsylvania, Harvard University, University of Toronto, and University of North Carolina at Chapel Hill have high academic influence in the field of nursing. Increasing attention from academic fields has been paid to research on nursing. Journal of Advanced Nursing is the most prolific and most cited journal in nursing field.

Conclusion

Nursing research has developed steadily over the last two decades. Both the scientific output and research collaboration are disproportionally distributed between high‐income countries/regions and low‐ and middle‐income countries/regions. Most research and collaboration have taken place in a few developed countries across North America, Europe, and Oceania.

Impact

The study highlighted the need for policy makers and funding agencies, especially those from low‐ and middle‐income countries/regions, to allocate research funding that supports the nursing higher education and international cooperation so as to promote the development of high‐quality nursing research in those countries/regions. At the same time, researchers from non‐English‐speaking countries/regions should attach more importance to publishing papers in English, strengthening the academic exchanges with international nursing colleagues and better integrating into the international academic community.
A self‐management support intervention on knee functional status and health‐related quality of life among middle‐age women: A randomized controlled trial
Authors: Bunsanong Thippawan , Chaimongkol Nujjaree
Published: October 2020

Aim

To determine the effectiveness of a self‐management support intervention on knee functional status and health‐related quality of life among middle‐age women with knee osteoarthritis.

Design

Randomized controlled trial.

Methods

The participants were 40 middle‐aged women who had been clinically diagnosed with knee osteoarthritis for more than 3 months and randomly assigned into intervention and control groups equally. After IRB approval code 02‐05‐2562 was obtained, data collection was carried out from July – November 2019 at the Outpatient Department of Orthorpedics, Thasala Hospital, Thailand. The modified Thai version of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the Short Form Survey (SF‐36) were used to measure knee functional status and health‐related quality of life at baseline (T1), immediately after completing the intervention (T2) and 4 weeks after the intervention (T3). The participants in the intervention group received a self‐management support program developed by the researcher based on the Individual and Family Self‐Management Theory and a review of related literature plus routine care. The implementation consisted of eight sessions over 4 weeks. The control group received only routine care from the hospital. Two‐way repeated measure ANOVAs were used to analyze the data.

Results

The findings revealed that the participants in the intervention group had better knee functional status and HRQOL than those in the control group at follow‐up. Additionally, in the intervention group, both knee functional status and HRQOL significantly improved from pre‐ to post‐intervention and follow‐up.

Conclusions

The findings indicate that this self‐management support intervention is effective.

Impact

For women, the prevalence rate of knee OA rises dramatically post‐menopause due to lower oestrogen levels. Policy makers and healthcare providers could obtain and promote this intervention as part of standard practice. This should lead to improved knee functional status and HRQOL among middle‐aged women.

Thai Trial Registration number: TCTR20191223003. on February 5th, 2019
Generalized evidence for Bergmann’s rule: body size variation in a cosmopolitan owl genus
Authors: Romano Andrea , Séchaud Robin , Roulin Alexandre
Published: October 2020

Aim

The eco‐geographical Bergmann's rule predicts that animals have smaller body size in warmer regions than in cold environments because of thermoregulatory reasons. Although this rule has been widely investigated, intraspecific analyses on cosmopolitan taxa are rare. We examined whether geographical variation in wing length, a proxy of body size, shows a Bergmannian pattern and can be explained by three mechanisms known to affect animal body size (heat conservation, resource availability and starvation resistance) in seven species of nocturnal raptors of the genus Tyto.

Location

World.

Taxon

Genus Tyto.

Methods

We measured wing length of 9,033 museum specimens covering the entire distributional range of each species and linked it with geographical (absolute latitude, elevation) and climatic predictors associated with heat conservation, resource availability and starvation resistance hypotheses of spatial variation in body size.

Results

All the species show a trend of increasing wing length with increasing latitude and/or elevation, and in five of them either or both geographical predictors are statistically significant. In all the species showing a Bergmannian pattern, wing length significantly decreases with temperature, thus supporting the heat conservation hypothesis. Conversely, we found less generalized support for the other hypotheses, although in some species significant trends between wing length and proxies of climatic seasonality and/or primary productivity emerged.

Main conclusions

Consistent clines in body shrinking in warm environments are observed in species living in different continents at different latitudinal and temperature ranges, as well as exploiting different habitats. These findings thus support the hypothesis that body size is, at least partly, selected for heat maintenance depending on the thermal environment, even in nocturnal species which are not directly exposed to solar radiation. However, different selective pressures may also have concomitantly acted to promote body size evolution in this bird group.
Relationship between dominant frequency, organization index, and left atrial size in patients with atrial fibrillation
Authors: Choi You‐jung , Sohn Jang J. , Kwon Soonil , Lee So‐Ryoung , Cha Myung‐Jin , Choi Eue‐Keun , Kim Hee C. , Oh Seil
Published: October 2020

Introduction

Frequency domain analysis is a methodology for quantifying the organization of atrial fibrillation (AF) pattern to understand the pathophysiology of the electrical mechanism. We aimed to investigate whether the dominant frequency (DF) and organization index (OI) can indicate left atrial (LA) dilatation in patients with AF.

Methods and Results

This observational, retrospective, single‐center cohort study assessed 100 patients with persistent AF. The study population was divided into two groups based on an anterior–posterior LA dimension (LAD of 50 mm) measured by transthoracic echocardiography. The groups were one‐to‐one propensity score‐matched. Frequency domain analysis was performed using signals at leads II and V1 on surface electrocardiogram to calculate the DF and OI. In all patients, the DF was shown to have an inverse relationship with LAD (R = –.369, p < .001 in lead II; R = –.330, p = .001 in lead V1), while the OI was directly associated with LAD (R = .234, p = .190 in lead II; R = .283, p = .004 in lead V1). However, no significant relationship between the signal amplitude and LAD was observed. Compared to patients with LAD ≤ 50 mm, those with LAD > 50 mm had a lower DF (5.057 ± 0.740 vs. 4.542 ± 0.898, p = .002) and higher OI (0.261 ± 0.104 vs. 0.322 ± 0.116, p = .007) in lead V1. These findings were consistent with those found in lead II.

Conclusion

Patients with persistent AF and a larger LA size had a significantly higher OI and lower DF than those with a smaller LA size. Atrial electrical properties of structural remodeling are associated with increased organization of atrial signals.
Melatonin synergizes BRAF‐targeting agent dabrafenib for the treatment of anaplastic thyroid cancer by inhibiting AKT/hTERT signalling
Authors: Liao Yina , Gao Yao , Chang An , Li Zongjuan , Wang Huayu , Cao Jing , Gu Wei , Tang Ranran
Published: October 2020

As a selective inhibitor of BRAF kinase, dabrafenib has shown potent anti‐tumour activities in patients with BRAFV600E mutant anaplastic thyroid cancer. However, the resistance of thyroid cancer cells to dabrafenib limited its therapeutic effect. The effects of melatonin and dabrafenib as monotherapy or in combination on the proliferation, cell cycle arrest, apoptosis, migration and invasion of anaplastic thyroid cancer cells were examined. The molecular mechanism involved in drug combinations was also revealed. Melatonin enhanced dabrafenib‐mediated inhibition of cell proliferation, migration and invasion, and promoted dabrafenib‐induced apoptosis and cell cycle arrest in anaplastic thyroid cancer cells. Molecular mechanistic studies further uncovered that melatonin synergized with dabrafenib to inhibit AKT and EMT signalling pathways. Furthermore, melatonin and dabrafenib synergistically inhibited the expression of hTERT, and the inhibition of cell viability and the induction of cell cycle arrest mediated by the combination of these two drugs were reversed by hTERT overexpression. Taken together, our results demonstrated that melatonin synergized the anti‐tumour effect of dabrafenib in human anaplastic thyroid cancer cells by inhibiting multiple signalling pathways, and provided new insights in exploring the potential therapeutic targets for the treatment of anaplastic thyroid cancer.
Neurotrophin‐3 stimulates stem Leydig cell proliferation during regeneration in rats
Authors: Yu Yige , Li Zengqiang , Ma Feifei , Chen Quanxu , Lin Liben , Xu Qiang , Li Yang , Xin Xiu , Pan Peipei , Huang Tongliang , Wang Yiyan , Fei Qianjin , Ge Ren‐Shan
Published: October 2020

Neurotrophin‐3 (NT‐3) acts as an important growth factor to stimulate and control tissue development. The NT‐3 receptor, TRKC, is expressed in rat testis. Its function in regulation of stem Leydig cell development and its underlying mechanism remain unknown. Here, we reported the role of NT‐3 to regulate stem Leydig cell development in vivo and in vitro. Ethane dimethane sulphonate was used to kill all Leydig cells in adult testis, and NT‐3 (10 and 100 ng/testis) was injected intratesticularly from the 14th day after ethane dimethane sulphonate injection for 14 days. NT‐3 significantly reduced serum testosterone levels at doses of 10 and 100 ng/testis without affecting serum luteinizing hormone and follicle‐stimulating hormone levels. NT‐3 increased CYP11A1‐positive Leydig cell number at 100 ng/testis and lowered Leydig cell size and cytoplasmic size at doses of 10 and 100 ng/testis. After adjustment by the Leydig cell number, NT‐3 significantly down‐regulated the expression of Leydig cell genes (Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Hsd11b1, Insl3, Trkc and Nr5a1) and the proteins. NT‐3 increased the phosphorylation of AKT1 and mTOR, decreased the phosphorylation of 4EBP, thereby increasing ATP5O. In vitro study showed that NT‐3 dose‐dependently stimulated EdU incorporation into stem Leydig cells and inhibited stem Leydig cell differentiation into Leydig cells, thus leading to lower medium testosterone levels and lower expression of Lhcgr, Scarb1, Trkc and Nr5a1 and their protein levels. NT‐3 antagonist Celitinib can antagonize NT‐3 action in vitro. In conclusion, the present study demonstrates that NT‐3 stimulates stem Leydig cell proliferation but blocks the differentiation via TRKC receptor.
Alpha‐fetoprotein accelerates the progression of hepatocellular carcinoma by promoting Bcl‐2 gene expression through an RA‐RAR signalling pathway
Authors: Zhang Chao , Zhang Jiangtao , Wang Jing , Yan Ying , Zhang Chuanbao
Published: October 2020

Previous studies have found that alpha‐fetoprotein (AFP) can promote the proliferation of hepatoma cells and accelerate the progression of hepatocellular carcinoma (HCC). However, the exact mechanism of action remains unclear. Recent bioinformatics studies have predicted the possible interaction between AFP and retinoic acid receptors (RARs). Thus, the purpose of this study was to investigate the molecular mechanism through which AFP promotes tumour cell proliferation by interfering with the RA‐RAR signal pathway. Our data indicated that AFP could significantly promote the proliferation and weaken ATRA‐induced apoptosis of hepatoma cells. Besides, cytoplasmic AFP interacts with RAR, disrupting its entrance into the nucleus, which in turn affects the expression of the Bcl‐2 gene. In addition, knockdown of AFP in HepG2 cells was synchronously associated with an incremental increase of RAR binding to DNA, as well as down‐regulation of Bcl‐2; the opposite effect was observed in AFP gene‐transfected HLE cells. Moreover, a similar effect of AFP was detected in tumour tissues with high serum AFP, but not in adjacent non‐cancerous liver tissues, or HCC tissues with low serum AFP levels. These results indicate that AFP acts as signalling molecule and prevents RAR from entering into the nucleus by interacting with RAR, thereby promoting the expression of Bcl‐2. Our data reveal a novel mechanism through which AFP regulates Bcl‐2 expression and further suggest that AFP may be used as a novel target for treating HCC.