bluuebunny/crossref_metadata_2025 huggingface dataset:
Telemedicine in the management of patients with chronic respiratory failure
Authors: Shah Neeraj M. , Kaltsakas Georgios
Published: April 2021

Patients with chronic respiratory failure are often required to attend multiple hospital appointments, which may be difficult due to their physical disabilities and the amount of equipment they are required to bring. Their caregivers often struggle with the lack of immediate care available when the patient suffers difficulties at home. Telemedicine is an opportunity to bridge the gap between home and healthcare professionals by allowing the healthcare team to reach into patients’ homes to provide more frequent support. The evidence for the use of telemedicine in patients with chronic respiratory failure remains equivocal. Although the uptake of telemedicine has been slow, the SARS-CoV-2 pandemic has resulted in the rapid dissemination of telemedicine to allow the delivery of care to vulnerable patients while reducing the need for their attendance in hospital. Logistical and legal challenges to the delivery of telemedicine remain, but the pandemic may serve as a driver to ameliorate these challenges and facilitate wider use of this technology to improve the experience of patients with chronic respiratory failure.

Educational aims

To provide an overview of the rationale for delivering careviatelemedicine for patients with chronic respiratory failure.

To provide the evidence base for establishing a telemedicine service.

To highlight the potential opportunities and challenges in delivering a telemedicine service for patients with chronic respiratory failure.
A test of native plant adaptation more than one century after introduction of the invasive Carpobrotus edulis to the NW Iberian Peninsula
Authors: García Carlos , Campoy Josefina G. , Retuerto Rubén
Published: April 2021

Background

Although the immediate consequences of biological invasions on ecosystems and conservation have been widely studied, the long-term effects remain unclear. Invaders can either cause the extinction of native species or become integrated in the new ecosystems, thus increasing the diversity of these ecosystems and the services that they provide. The final balance of invasions will depend on how the invaders and native plants co-evolve. For a better understanding of such co-evolution, case studies that consider the changes that occur in both invasive and native species long after the introduction of the invader are especially valuable. In this work, we studied the ecological consequences of the more than one century old invasion of NW Iberia by the African plant Carpobrotus edulis. We conducted a common garden experiment to compare the reciprocal effects of competition between Carpobrotus plants from the invaded area or from the native African range and two native Iberian plant species (Artemisia crithmifolia and Helichrysum picardii) from populations exposed or unexposed to the invader.

Results

Exposure of H. picardii populations to C. edulis increased their capacity to repress the growth of Carpobrotus. The repression specifically affected the Carpobrotus from the invader populations, not those from the African native area. No effects of exposition were detected in the case of A. crithmifolia. C. edulis plants from the invader populations had higher growth than plants from the species' African area of origin.

Conclusions

We found that adaptive responses of natives to invaders can occur in the long term, but we only found evidence for adaptive responses in one of the two species studied. This might be explained by known differences between the two species in the structure of genetic variance and gene flow between subpopulations. The overall changes observed in the invader Carpobrotus are consistent with adaptation after invasion.
Differential expressions of anthocyanin synthesis genes underlie flower color divergence in a sympatric Rhododendron sanguineum complex
Authors: Ye Lin-Jiang , Mӧller Michael , Luo Ya-Huang , Zou Jia-Yun , Zheng Wei , Wang Yue-Hua , Liu Jie , Zhu An-Dan , Hu Jin-Yong , Li De-Zhu , Gao Lian-Ming
Published: April 2021

Background

TheRhododendron sanguineumcomplex is endemic to alpine mountains of northwest Yunnan and southeast Tibet of China. Varieties in this complex exhibit distinct flower colors even at the bud stage. However, the underlying molecular regulations for the flower color variation have not been well characterized. Here, we investigated this via measuring flower reflectance profiles and comparative transcriptome analyses on three coexisting varieties of theR. sanguineumcomplex, with yellow flush pink, bright crimson, and deep blackish crimson flowers respectively. We compared the expression levels of differentially-expressed-genes (DEGs) of the anthocyanin / flavonoid biosynthesis pathway using RNA-seq and qRT-PCR data. We performed clustering analysis based on transcriptome-derived Single Nucleotide Polymorphisms (SNPs) data, and finally analyzed the promoter architecture of DEGs.

Results

Reflectance spectra of the three color morphs varied distinctively in the range between 400 and 700 nm, with distinct differences in saturation, brightness, hue, and saturation/hue ratio, an indirect measurement of anthocyanin content. We identified 15,164 orthogroups that were shared among the three varieties. The SNP clustering analysis indicated that the varieties were not monophyletic. A total of 40 paralogous genes encoding 12 enzymes contributed to the flower color polymorphism. These anthocyanin biosynthesis-related genes were associated with synthesis, modification and transportation properties (RsCHS,RsCHI,RsF3H,RsF3′H,RsFLS,RsANS,RsAT,RsOMT,RsGST), as well as genes involved in catabolism and degradation (RsBGLU,RsPER,RsCAD). Variations in sequence andcis-acting elements of these genes might correlate with the anthocyanin accumulation, thus may contribute to the divergence of flower color in theR. sanguineumcomplex.

Conclusions

Our results suggested that the varieties are very closely related and flower color variations in theR. sanguineumcomplex correlate tightly with the differential expression levels of genes involved in the anabolic and catabolic synthesis network of anthocyanin. Our study provides a scenario involving intricate relationships between genetic mechanisms for floral coloration accompanied by gene flow among the varieties that may represent an early case of pollinator-mediated incipient sympatric speciation.
Possible associations between callers’ degree-of-worry and their socioeconomic status when contacting out-of-hours services: a prospective cohort study
Authors: Thilsted Sita LeBlanc , Folke Fredrik , Tolstrup Janne S. , Thygesen Lau Caspar , Gamst-Jensen Hejdi
Published: April 2021

Background

Telephone triage within out-of-hours (OOH) services aims to ascertain the urgency of a caller’s medical condition in order to determine the correct type of health care needed, ensuring patient safety. To improve the triage process by increasing patient-centred communication, a triage tool has been developed, whereby callers are asked to rate their degree-of-worry (DOW) as a measure of self-evaluated urgency. Studies show that low socioeconomic status (SES), being single and non-Western ethnicity are associated to low self-rated health and high morbidity and these factors may also be associated with high DOW. The aim of this paper was to examine if low SES, being single and non-Western ethnicity were associated to high DOW of callers contacting OOH services.

Methods

A prospective cohort study design, at the OOH services for the Capital Region of Denmark. Over 2 weeks, 6869 of 38,787 callers met the inclusion criteria: ≥18 years, patients themselves or close relative/friend, reported DOW, had a valid personal identification number and gave informed consent. Callers were asked to report their DOW (1 = minimal worry to 5 = maximal worry), which was dichotomized into low (1–3) and high (4, 5) DOW and linked to data from electronical medical records and Statistics Denmark. Socioeconomic factors (education and annual household income), marital status and ethnicity were assessed in relation to DOW by logistic regression.

Results

High DOW was reported by 38.2% of the participants. Low SES (low educational level; OR 1.5, 95% CI 1.3–1.7 and low annual household income; 1.5, 1.3–1.6) was associated with high DOW and so too was being single; 1.2, 1.1–1.3 and of non-Western ethnicity; 2.9, 2.5–3.4.

Conclusions

Knowledge of the association of low SES, marital status as single and non-Western ethnicity with high DOW among callers to OOH services may give call handlers a better understanding of callers’ DOW. If this does not correspond to the call handler’s perception of urgency, this knowledge may further encourage patient-centred communication, aid the triage process and increase patient safety. A better understanding of socioeconomic variables and their relation to callers’ DOW gives direction for future research to improve telephone triage of OOH services.
Active surveillance for thyroid Cancer: a qualitative study of barriers and facilitators to implementation
Authors: Jensen Catherine B. , Saucke Megan C. , Pitt Susan C.
Published: April 2021

Background

The 2015 American Thyroid Association guidelines supported active surveillance (AS) as a strategy for managing select low-risk thyroid cancers. Data examining physicians’ attitudes about the acceptability of this option are limited. This study aimed to characterize the barriers and facilitators to implementing AS as perceived by practicing endocrinologists and surgeons in the United States.

Methods

We conducted 24 semi-structured interviews probing physicians’ attitudes toward AS for patients with small, low-risk thyroid cancer. We used deductive content analysis guided by a well-known model of guideline implementation. Analysis characterized concepts and themes related to AS implementation as physician, guideline, or external factors. We performed member checking to validate results.

Results

The most prominent barriers to AS were related to physician factors, although guideline-specific and external barriers were also observed. Physician attitudes towards AS comprised the majority of physician-related barriers, while lack of knowledge about the guideline was also discussed. Participants’ concerns about the potential negative outcomes resulting from observing a cancer were notable as were the lack of confidence in performing and offering surveillance. Beliefs about patient expectations and lack of knowledge about the guideline were also identified as barriers to offering surveillance. Guideline-specific and external barriers included the vagueness of surveillance protocols, lack of data supporting active surveillance, and societal beliefs about cancer. Facilitators of active surveillance included patients’ desire to avoid surgery and shared decision-making.

Conclusions

Barriers and facilitators of active surveillance for low-risk thyroid cancers exist at multiple levels. Strategies to increase adoption of active surveillance should focus on physicians’ attitudes, patient expectations, data supporting surveillance outcomes, and promoting societal-level acceptance of surveillance.
Correlates of bullying perpetration among Lebanese adolescents: a national study
Authors: Awad Emmanuelle , Haddad Chadia , Sacre Hala , Hallit Rabih , Soufia Michel , Salameh Pascale , Obeid Sahar , Hallit Souheil
Published: April 2021

Background

Presently, 1 in 4 Lebanese adolescents is involved in bullying, with 12% being perpetrators. In Lebanon, around 90% of bullying incidents occur in schools. Given the lack of studies tackling bullying perpetration in Lebanon, this study aims to identify and target risk factors of bullying perpetration among Lebanese adolescents, which would serve future prevention and intervention programs.

Methods

This cross-sectional study took place between January and May 2019 in a proportionate random sample of schools from all Lebanese districts. A total of 1810 (90.5%) out of 2000 students accepted to participate.

Results

Results showed that 831 (49.1%, CI: 0.46–0.51) participants had bullied other people. A stepwise linear regression, using as the dependent variable the bullying perpetration score, showed that higher psychological (β = 0.12; 95% CI 0.083–0.176), sexual (β = 0.26; 95% CI 0.128–0.411), neglect (β = 0.08; 95% CI 0.051–0.120), physical abuse (β = 0.13; 95% CI 0.036–0.235), higher internet addiction (β = 0.07; 95% CI 0.057–0.097), higher social fear (β = 0.10; 95% CI 0.075–0.140), and having separated parents (β = 1.60; 95% CI 0.561–2.650) were significantly associated with more bullying perpetration. Higher social avoidance (β = − 0.03; 95% CI -0.062- -0.003) was significantly associated with less bullying perpetration.

Conclusion

The results revealed that bullying perpetration is significantly associated with parental status, child abuse, internet addiction, and social fear. Educational and relevant governmental institutions could use our findings to develop and implement efficient bullying prevention and intervention programs for all involved parties.
Lifestyle habits and depressive symptoms in Norwegian adolescents: a national cross-sectional study
Authors: Kleppang Annette Løvheim , Haugland Siri Håvås , Bakken Anders , Stea Tonje Holte
Published: April 2021

Background

This study’s purpose was to examine the association between a broad range of lifestyle habits and depressive symptoms in Norwegian adolescents.

Methods

This study was based on national, self-reported, cross-sectional data from the Ungdata Surveys, conducted in 2017–2019. The target group comprised 244,250 adolescents (ages 13–19). Binominal logistic regression was used to analyse the association between lifestyle habits (physical activity, social media use, gaming, dietary habits, smoking, smokeless tobacco, alcohol intoxication) and depressive symptoms. The outcome measure was defined as a high level of depressive symptoms (≥80th percentile). Separate analyses were performed for boys and girls, and all models were adjusted for perceived family economy, parental higher education and age.

Results

The odds of having depressive symptoms were significantly lower among those who reported being physically active at least 3 times per week (OR; boys: 0.81, girls: 0.83), used social media ≤3 h per day (OR; boys: 0.65, girls: 0.70), engaged in gaming ≤3 h per day (OR; boys: 0.72, girls: 0.77), were non-smokers (OR; boys: 0.74, girls: 0.72) and had not experienced alcohol intoxication during the previous 12 months (OR; boys: 0.66, girls: 0.67). Furthermore, the results indicated a significant inverse association between depressive symptoms and high consumption of a range of healthy food items and low consumption of unhealthy food and beverages among girls. Similar tendencies were found among boys (OR; 0.77–0.91). Finally, higher adherence to healthy lifestyle habits was associated significantly with lower odds of having depressive symptoms among both genders (OR; boys: 0.40, girls: 0.52).

Conclusions

A healthier lifestyle was associated with lower odds of having depressive symptoms. Additional research is needed to confirm a possible causal relationship.
Qualitative analysis of visual risk communication on twitter during the Covid-19 pandemic
Authors: Sleigh Joanna , Amann Julia , Schneider Manuel , Vayena Effy
Published: April 2021

Background

The Covid-19 pandemic is characterized by uncertainty and constant change, forcing governments and health authorities to ramp up risk communication efforts. Consequently, visuality and social media platforms like Twitter have come to play a vital role in disseminating prevention messages widely. Yet to date, only little is known about what characterizes visual risk communication during the Covid-19 pandemic. To address this gap in the literature, this study’s objective was to determine how visual risk communication was used on Twitter to promote the World Health Organisations (WHO) recommended preventative behaviours and how this communication changed over time.

Methods

We sourced Twitter’s 500 most retweeted Covid-19 messages for each month from January–October 2020 using Crowdbreaks. For inclusion, tweets had to have visuals, be in English, come from verified accounts, and contain one of the keywords ‘covid19’, ‘coronavirus’, ‘corona’, or ‘covid’. Following a retrospective approach, we then performed a qualitative content analysis of the 616 tweets meeting inclusion criteria.

Results

Our results show communication dynamics changed over the course of the pandemic. At the start, most retweeted preventative messages came from the media and health and government institutions, but overall, personal accounts with many followers (51.3%) predominated, and their tweets had the highest spread (10.0%, i.e., retweet count divided by followers). Messages used mostly photographs and images were found to be rich with information. 78.1% of Tweets contained 1–2 preventative messages, whereby ‘stay home’ and ‘wear a mask’ frequented most. Although more tweets used health loss framing, health gain messages spread more.

Conclusion

Our findings can inform the didactics of future crisis communication. The results underscore the value of engaging individuals, particularly influencers, as advocates to spread health risk messages and promote solidarity. Further, our findings on the visual characteristic of the most retweeted tweets highlight factors that health and government organisations should consider when creating visual health messages for Twitter. However, that more tweets used the emotive medium of photographs often combined with health loss framing raises concerns about persuasive tactics. More research is needed to understand the implications of framing and its impact on public perceptions and behaviours.
Central Australian Aboriginal women’s pregnancy, labour and birth outcomes following maternal smokeless tobacco (pituri) use, cigarette use or no-tobacco use: a prospective cohort study
Authors: Ratsch Angela , Bogossian Fiona , Steadman Kathryn
Published: April 2021

Background

Outcomes related to maternal smoked tobacco (cigarette) use have been substantially examined over the past 50 years with resultant public health education targeted towards the reduction of use during pregnancy. However, worldwide the effects of maternal smokeless tobacco use have been less well explored and in Australia, there has been no examination of maternal outcomes in relation to the use of Australian Nicotiana spp. (tobacco plant) as a smokeless tobacco, colloquially known as pituri. The aim of this study is to describe the maternal outcomes of a group of central Australian Aboriginal women in relation to their self-reported tobacco use.

Methods

Eligible participants were > 18 years of age, with a singleton pregnancy, > 28 weeks gestation, and who planned to birth at the Alice Springs Hospital (the major regional hospital for central Australia, in the Northern Territory, Australia). The sample consisted of 73 conveniently recruited women categorized by tobacco-use status as no-tobacco users (n = 31), pituri chewers (n = 19), and smokers (n = 23).

Results

There were differences in the groups in relation to teenage pregnancies; 35% of no-tobacco users, compared with 5% of pituri users, and 13% of smokers were <  20 years of age. The chewers had a higher rate (48%) of combined pre-existing and pregnancy-related elevated glucose concentrations compared with smokers (22%) and no-tobacco users (16%).The pituri chewers had the lowest rate (14%) of clinically significant post-partum hemorrhage (> 1000 ml) compared with 22% of smokers and 36% of the no-tobacco users.

Conclusions

This is the first research to examine pituri use in pregnancy and the findings indicate possible associations with a range of adverse maternal outcomes. The use of smokeless tobacco needs to be considered in maternal healthcare assessment to inform antenatal, intrapartum and postpartum care planning.

Implications for public health

Female smokeless tobacco use is a global phenomenon and is particularly prevalent in low and middle income countries and in Indigenous populations. The findings contribute to the developing knowledge around maternal smokeless tobacco use and maternal outcomes. Maternal screening for a broader range of tobacco and nicotine products is required.

Note to readers

In this research, the central Australian Aboriginal women chose the term ‘Aboriginal’ to refer to themselves, and ‘Indigenous’ to refer to the broader First Peoples. That choice has been maintained in the reporting of the research findings.
Influence of Angptl1 on osteoclast formation and osteoblastic phenotype in mouse cells
Authors: Ishida Masayoshi , Kawao Naoyuki , Mizukami Yuya , Takafuji Yoshimasa , Kaji Hiroshi
Published: April 2021

Background

Osteoblasts and osteoclasts play important roles during the bone remodeling in the physiological and pathophysiological states. Although angiopoietin family Angiopoietin like proteins (Angptls), including Angptl1, have been reported to be involved in inflammation, lipid metabolism and angiogenesis, the roles of Angptl1 in bone have not been reported so far.

Methods

We examined the effects of Angptl1 on the osteoblast and osteoclast phenotypes using mouse cells.

Results

Angptl1 significantly inhibited the osteoclast formation and mRNA levels of tartrate-resistant acid phosphatase and cathepsin K enhanced by receptor activator of nuclear factor κB ligand in RAW 264.7 and mouse bone marrow cells. Moreover, Angptl1 overexpression significantly enhanced Osterix mRNA levels, alkaline phosphatase activity and mineralization induced by bone morphogenetic protein-2 in ST2 cells, although it did not affect the expression of osteogenic genes in MC3T3-E1 and mouse osteoblasts. On the other hand, Angptl1 overexpression significantly reduced the mRNA levels of peroxisome proliferator-activated receptor γ and adipocyte protein-2 as well as the lipid droplet formation induced by adipogenic medium in 3T3-L1 cells.

Conclusions

The present study first indicated that Angptl1 suppresses and enhances osteoclast formation and osteoblastic differentiation in mouse cells, respectively, although it inhibits adipogenic differentiation of 3T3-L1 cells. These data suggest the possibility that Angptl1 might be physiologically related to bone remodeling.
Natural course of metabolically healthy phenotype and risk of developing Cardiometabolic diseases: a three years follow-up study
Authors:   for the Metabolic Syndrome Study Group, Elías-López Daniel , Vargas-Vázquez Arsenio , Mehta Roopa , Cruz Bautista Ivette , Del Razo Olvera Fabiola , Gómez-Velasco Donaji , Almeda Valdes Paloma , Aguilar-Salinas Carlos A.
Published: April 2021

Background

Whether the metabolically healthy obese (MHO) phenotype is a single, stable or a transitional, fluctuating state is currently unknown. The Mexican-Mestizo population has a genetic predisposition for the development of type 2 diabetes (T2D) and other cardiometabolic complications. Little is known about the natural history of metabolic health in this population. The aim of this study was to analyze the transitions over time among individuals with different degrees of metabolic health and body mass index, and evaluate the incidence of cardiometabolic outcomes according to phenotype.

Methods

The study population consisted of a metabolic syndrome cohort with at least 3 years of follow up. Participants were apparently-healthy urban Mexican adults ≥20 years with a body mass index (BMI) ≥20 kg/m2. Metabolically healthy phenotype was defined using the criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) metabolic syndrome criteria and the subjects were stratified into 4 groups according to their BMI and metabolic health. For cardiometabolic outcomes we estimated the incidence of cardiometabolic outcomes and standardized them per 1, 000 person-years of follow-up. Finally, to evaluate the risk for transition and development of cardiometabolic outcomes, we fitted Cox Proportional Hazard regression models.

Results

Amongst the 5541 subjects, 54.2% were classified as metabolically healthy and 45.8% as unhealthy. The MHO prevalence was 39.3%. Up to a third of the population changed from their initial category to another and the higher transition rate was observed in MHO (42.9%). We also found several novel factors associated to transition to metabolically unhealthy phenotype; socioeconomic status, number of pregnancies, a high carbohydrate intake, history of obesity and consumption of sweetened beverages. Similarly, visceral adipose tissue (VAT) was a main predictor of transition; loss of VAT ≥5% was associated with reversion from metabolically unhealthy to metabolically healthy phenotype (hazard ratio (HR) 1.545, 95%CI 1.266–1.886). Finally, we observed higher incidence rates and risk of incident T2D and hypertension in the metabolically unhealthy obesity (MUHO) and metabolically unhealthy lean (MUHL) phenotypes compared to MHO.

Conclusions

Metabolic health is a dynamic and continuous process, at high risk of transition to metabolically unhealthy phenotypes over time. It is imperative to establish effective processes in primary care to prevent such transitions.
Development and psychometric testing of quality nursing care scale in Mongolia
Authors: Tsogbadrakh Basbish , Kunaviktikul Wipada , Akkadechanunt Thitinut , Wichaikhum Orn-Anong , Gaalan Khulan , Badamdorj Oyungoo , Stark Azadeh
Published: April 2021

Background

Quality Nursing Care (QNC) is fundamental to the profession of nursing practice. Perception of QNC differ across the globe because of differences in social norms, cultural values and political ambiance and economy. This study aimed to develop a QNC instrument congruent with the Mongolian (QNCS-M) healthcare system and cultural values and societal norms.

Methods

Exploratory sequential mixed-method design was implemented to develop and assess performance of QNCS-M. First, we focused on developing the components of QNCS-M and their operational definitions. Second, we dedicated to ascertaining psychometric performance of QNCS-M. The field testing consisted of assessing the construct validity and internal consistency reliability. Correlation between QNCS-M and the criterion tool, Quality of Nursing Care Questionnaire-Registered Nurse was evaluated.

Results

The initial version of QNCS-M contained 66 items of which 7 (I-CVI < .78) were deleted after item-content validity assessment. The total-item correlation analysis yielded to exclusion of another 3 items (<.3). Additional 12 items were excluded after inter-item correlation (<.3, >.7). Results from Spearman rank-order correlation analysis of the remaining 44 items indicated relationship between social desirability and 6 items (r = −.09 tor = .11). These items were excluded to reduce the likelihood of potential information bias. A total of 38 items remained for exploratory factor analysis. Results from exploratory factor analysis yielded eigenvalues > 1.0 for the 9 domains. Three domains contained items fewer than 3. These domains and 2 items (factor loading <.4) were eliminated, yielding to 6 domains with 36-item. Results from internal consistency reliability yielded an overall Cronbach’s α = .92; the coefficient values for the 6 domains ranging between .72 and .85 and Pearson correlation for stability reliability yielded an acceptable (r = .82,P < .001).

Conclusion

Improving the quality of healthcare services delivered by nurses is a priority for the Mongolian government. The development of QNCS-M is a major stride in addressing this concern. The final version of QNCS-M which contains 36 items, loaded into 6 domains, was morphed to the specifics of the Mongolian healthcare systems and cultural values and societal norms. QNCS-M demonstrates a high level of content and construct validity with acceptable reliability.
InforMing the PAthway of COPD Treatment (IMPACT) trial: fibrinogen levels predict risk of moderate or severe exacerbations
Authors: Singh Dave , Criner Gerard J. , Dransfield Mark T. , Halpin David M. G. , Han MeiLan K. , Lange Peter , Lettis Sally , Lipson David A. , Mannino David , Martin Neil , Martinez Fernando J. , Miller Bruce E. , Wise Robert , Zhu Chang-Qing , Lomas David
Published: April 2021

Background

Fibrinogen is the first qualified prognostic/predictive biomarker for exacerbations in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial investigated fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI and UMEC/VI in patients with symptomatic COPD at risk of exacerbations. This analysis used IMPACT trial data to examine the relationship between fibrinogen levels and exacerbation outcomes in patients with COPD.

Methods

8094 patients with a fibrinogen assessment at Week 16 were included, baseline fibrinogen data were not measured. Post hoc analyses were performed by fibrinogen quartiles and by 3.5 g/L threshold. Endpoints included on-treatment exacerbations and adverse events of special interest (AESIs).

Results

Rates of moderate, moderate/severe, and severe exacerbations were higher in the highest versus lowest fibrinogen quartile (0.75, 0.92 and 0.15 vs 0.67, 0.79 and 0.10, respectively). The rate ratios (95% confidence interval [CI]) for exacerbations in patients with fibrinogen levels ≥ 3.5 g/L versus those with fibrinogen levels < 3.5 g/L were 1.03 (0.95, 1.11) for moderate exacerbations, 1.08 (1.00, 1.15) for moderate/severe exacerbations, and 1.30 (1.10, 1.54) for severe exacerbations. There was an increased risk of moderate/severe exacerbation (hazard ratio [95% CI]: highest vs lowest quartile 1.16 [1.04, 1.228]; ≥ 3.5 g/L vs < 3.5 g/L: 1.09 [1.00, 1.16]) and severe exacerbation (1.35 [1.09, 1.69]; 1.27 [1.08, 1.47], respectively) with increasing fibrinogen level. Cardiovascular AESIs were highest in patients in the highest fibrinogen quartile.

Conclusions

Rate and risk of exacerbations was higher in patients with higher fibrinogen levels. This supports the validity of fibrinogen as a predictive biomarker for COPD exacerbations, and highlights the potential use of fibrinogen as an enrichment strategy in trials examining exacerbation outcomes.

Trial registration: NCT02164513
Effect of ambient fine particulates (PM2.5) on hospital admissions for respiratory and cardiovascular diseases in Wuhan, China
Authors: Ren Zhan , Liu Xingyuan , Liu Tianyu , Chen Dieyi , Jiao Kuizhuang , Wang Xiaodie , Suo Jingdong , Yang Haomin , Liao Jingling , Ma Lu
Published: April 2021

Background

Positive associations between ambient PM2.5 and cardiorespiratory disease have been well demonstrated during the past decade. However, few studies have examined the adverse effects of PM2.5 based on an entire population of a megalopolis. In addition, most studies in China have used averaged data, which results in variations between monitoring and personal exposure values, creating an inherent and unavoidable type of measurement error.

Methods

This study was conducted in Wuhan, a megacity in central China with about 10.9 million people. Daily hospital admission records, from October 2016 to December 2018, were obtained from the Wuhan Information center of Health and Family Planning, which administrates all hospitals in Wuhan. Daily air pollution concentrations and weather variables in Wuhan during the study period were collected. We developed a land use regression model (LUR) to assess individual PM2.5 exposure. Time-stratified case-crossover design and conditional logistic regression models were adopted to estimate cardiorespiratory hospitalization risks associated with short-term exposure to PM2.5. We also conducted stratification analyses by age, sex, and season.

Results

A total of 2,806,115 hospital admissions records were collected during the study period, from which we identified 332,090 cardiovascular disease admissions and 159,365 respiratory disease admissions. Short-term exposure to PM2.5 was associated with an increased risk of a cardiorespiratory hospital admission. A 10 μg/m3 increase in PM2.5 (lag0–2 days) was associated with an increase in hospital admissions of 1.23% (95% CI 1.01–1.45%) and 1.95% (95% CI 1.63–2.27%) for cardiovascular and respiratory diseases, respectively. The elderly were at higher PM-induced risk. The associations appeared to be more evident in the cold season than in the warm season.

Conclusions

This study contributes evidence of short-term effects of PM2.5 on cardiorespiratory hospital admissions, which may be helpful for air pollution control and disease prevention in Wuhan.
SGLT2 inhibitors and lower limb complications: an updated meta‐analysis
Authors: Lin Chu , Zhu Xingyun , Cai Xiaoling , Yang Wenjia , Lv Fang , Nie Lin , Ji Linong
Published: April 2021

Background

To exam the associations between the use of sodium glucose co-transporter 2 inhibitor (SGLT2i) and the risk of lower limb complications, and to analyze the associated factors.

Methods

Pubmed, Medline, Embase, the Cochrane Center Register of Controlled Trials for Studies andClinicaltrial.govwere searched from the inception to November 2020. Randomized controlled trials of SGLT2i conducted in population containing diabetic patients with reports of amputation, peripheral arterial disease (PAD) and diabetic foot (DF) events were included. Random-effect model, fixed-effect model and meta-regression analysis were accordingly used.

Result

The numbers of SGLT2i users versus non-SGLT2i users in the analyses of amputation, PAD and DF were 40,925/33,414, 36,446/28,685 and 31,907/25,570 respectively. Compared with non-SGLT2i users, the risks of amputation and PAD were slightly increased in patients with canagliflozin treatment (amputation: OR = 1.60, 95% CI 1.04 to 2.46; PAD: OR = 1.53, 95 % CI 1.14 to 2.05). Meta-regression analyses indicated that greater weight reduction in SGLT2i users was significantly associated with the increased risks of amputation (β = − 0.461, 95% CI − 0.726 to − 0.197), PAD (β = − 0.359, 95% CI − 0.545 to − 0.172) and DF (β = − 0.476, 95% CI − 0.836 to − 0.116). Lower baseline diastolic blood pressure (β = − 0.528, 95% CI − 0.852 to − 0.205), more systolic blood pressure reduction (β = − 0.207, 95% CI − 0.390 to − 0.023) and more diastolic blood pressure reduction (β = − 0.312, 95% CI − 0.610 to − 0.015) were significantly associated with the increased risks of amputation, PAD and DF respectively in patients with SGLT2i treatment.

Conclusions

The risks of amputation and PAD were slightly increased in patients with canagliflozin treatment. Reductions in body weight and blood pressure were associated with lower limb complications in patients with SGLT2i treatment.
“Maskandi experience”: exploring the use of a cultural song for community engagement in preparation for a pilot Sterile Insect Technique release programme for malaria vector control in KwaZulu-Natal Province, South Africa 2019
Authors: Manana Pinky N. , Jewett Sara , Zikhali Jabulani , Dlamini Dumsani , Mabaso Nondumiso , Mlambo Zothile , Ngobese Roxanne , Munhenga Givemore
Published: April 2021

Background

An assessment of the Sterile Insect Technique (SIT) as a complementary malaria vector control tool, is at an advanced stage in South Africa. The technique involves the release of laboratory-reared sterilized male mosquitoes of the major malaria vector Anopheles arabiensis, raising social, ethical and regulatory concerns. Therefore, its implementation largely depends on community participation and acceptance. Against this background, it is critical that robust and effective community strategies are developed. This study describes the development of a cultural song to engage the community and increase awareness on SIT and malaria control in KwaZulu-Natal, South Africa.

Methods

An exploratory concurrent mixed-methods study was conducted to get opinions about the effectiveness of a cultural song developed to engage communities and increase acceptability of the SIT technology. Two self-administered surveys (expert and community) were conducted. Additionally, more in depth opinions of the song and its effectiveness in conveying the intended information were investigated through three community dialogue sessions with community members in the study area.

Results

A total of 40 experts and 54 community members participated in the survey. Four themes were identified in relation to the appropriateness and effectiveness of the song, with a fifth theme focused on recommendations for adaptations. Overall, the song was well received with the audience finding it entertaining and informative. Responses to unstructured questions posed after the song showed an increase in the knowledge on malaria transmission and SIT technology. In particular, the explanation that male mosquitoes do not bite allayed anxiety and fears about the SIT technology.

Conclusion

The song was deemed both culturally appropriate and informative in engaging community members about the SIT technology. It proved useful in promoting health messages and conveying SIT technology as a complementary malaria vector control tool. With minor adaptations, the song has potential as an area-wide community engagement tool in areas targeted for sterile male releases.
Occupational exposure to glyphosate and risk of lymphoma:results of an Italian multicenter case-control study
Authors: Meloni Federico , Satta Giannina , Padoan Marina , Montagna Andrea , Pilia Ilaria , Argiolas Alessandra , Piro Sara , Magnani Corrado , Gambelunghe Angela , Muzi Giacomo , Ferri Giovanni Maria , Vimercati Luigi , Zanotti Roberta , Scarpa Aldo , Zucca Mariagrazia , De Matteis Sara , Campagna Marcello , Miligi Lucia , Cocco Pierluigi
Published: April 2021

Background

The International Agency for Research on Cancer (IARC) recently classified glyphosate, the most used herbicide worldwide, as a probable human carcinogen. We inquired into the association between occupational exposure to glyphosate and risk of lymphoma subtypes in a multicenter case-control study conducted in Italy.

Methods

The Italian Gene-Environment Interactions in Lymphoma Etiology (ItGxE) study took place in 2011–17 in six Italian centres. Overall, 867 incident lymphoma cases and 774 controls participated in the study. Based on detailed questionnaire information, occupational experts classified duration, confidence, frequency, and intensity of exposure to glyphosate for each study subject. Using unconditional regression analysis, we modelled risk of major lymphoma subtypes associated with exposure to glyphosate adjusted by age, gender, education, and study centre.

Results

Very few study subjects (2.2%) were classified as ever exposed to glyphosate. Risk of follicular lymphoma (FL) was elevated 7-fold in subjects classified as ever exposed to glyphosate with medium-high confidence, 4.5-fold in association with medium-high cumulative exposure level, 12-fold with medium-high exposure intensity, and 6-fold with exposure for 10 days or more per year. Significant upward trends were detected with all the exposure metrics, but duration. The overall p-value for an upward trend with four independent metrics was 1.88 × 10− 4. There was no association with risk of lymphoma (any subtype), Non Hodgkin Lymphoma, B-cell lymphoma, or the major lymphoma subtypes other than FL.

Conclusions

Our findings provide limited support to the IARC decision to classify glyphosate as Group 2A human carcinogen.
Correction to: TRIM29 facilitates the epithelial-tomesenchymal transition and the progression of colorectal cancer via the activation of the Wnt/β-catenin signaling pathway
Authors: Sun Juntao , Zhang Tianyu , Cheng Mengmeng , Hong Liwen , Zhang Chen , Xie Mengfan , Sun Peijun , Fan Rong , Wang Zhengting , Wang Lei , Zhong Jie
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Tankyrases as modulators of pro-tumoral functions: molecular insights and therapeutic opportunities
Authors: Zamudio-Martinez Esteban , Herrera-Campos Ana Belén , Muñoz Alberto , Rodríguez-Vargas José Manuel , Oliver F. Javier
Published: April 2021

Tankyrase 1 (TNKS1) and tankyrase 2 (TNKS2) are two homologous proteins that are gaining increasing importance due to their implication in multiple pathways and diseases such as cancer. TNKS1/2 interact with a large variety of substrates through the ankyrin (ANK) domain, which recognizes a sequence present in all the substrates of tankyrase, called Tankyrase Binding Motif (TBM). One of the main functions of tankyrases is the regulation of protein stability through the process of PARylation-dependent ubiquitination (PARdU). Nonetheless, there are other functions less studied that are also essential in order to understand the role of tankyrases in many pathways. In this review, we concentrate in different tankyrase substrates and we analyze in depth the biological consequences derived of their interaction with TNKS1/2. We also examine the concept of both canonical and non-canonical TBMs and finally, we focus on the information about the role of TNKS1/2 in different tumor context, along with the benefits and limitations of the current TNKS inhibitors targeting the catalytic PARP domain and the novel strategies to develop inhibitors against the ankyrin domain. Available data indicates the need for further deepening in the knowledge of tankyrases to elucidate and improve the current view of the role of these PARP family members and get inhibitors with a better therapeutic and safety profile.
Plantar soft tissues and Achilles tendon thickness and stiffness in people with diabetes: a systematic review
Authors: Khor Benedictine Yen Chen , Woodburn James , Newcombe Lisa , Barn Ruth
Published: April 2021

Background

Diabetes mellitus is associated with changes in soft tissue structure and function. However, the directionality of this change and the extent to which either tissue thickness or stiffness contributes to the pathogenesis of diabetes‐related foot ulcerations is unclear. Hence, this systematic review aims to summarise the existing evidence for soft tissue structural differences in the feet of people with and without diabetes.

Methods

In compliance with MOOSE and PRISMA guidelines, AMED, CINAHL, MEDLINE, ProQuest Health & Medical Collection, ProQuest Nursing & Allied Health Database, and Web of Science electronic databases were systematically searched for studies published from database inception until 1st October 2020 [Prospero CRD42020166614]. Reference lists of included studies were further screened. Methodological quality was appraised using a modified critical appraisal tool for quantitative studies developed by McMaster University.

Results

A total of 35 non‐randomised observational studies were suitable for inclusion. Within these, 20 studies evaluated plantar tissue thickness, 19 studies evaluated plantar tissue stiffness, 9 studies evaluated Achilles tendon thickness and 5 studies evaluated Achilles tendon stiffness outcomes. No significant differences in plantar tissue thickness were found between people with and without diabetes in 55% of studies (11/20), while significantly increased plantar tissue stiffness was found in people with diabetes in 47% of studies (9/19). Significantly increased Achilles tendon thickness was found in people with diabetes in 44% of studies (4/9), while no significant differences in Achilles tendon stiffness were found between people with and without diabetes in 60% of studies (3/5).

Conclusions

This systematic review found some evidence of soft tissue structural differences between people with and without diabetes. However, uncertainty remains whether these differences independently contribute to diabetes‐related foot ulcerations. The heterogeneity of methodological approaches made it difficult to compare across studies and methodological quality was generally inadequate. High‐quality studies using standardised and validated assessment techniques in well‐defined populations are required to determine more fully the role of structural tissue properties in the pathogenesis of diabetes‐related foot ulcerations.
Plasma-derived exosomal miR-4732-5p is a promising noninvasive diagnostic biomarker for epithelial ovarian cancer
Authors: Liu Jingjing , Yoo Jigeun , Ho Jung Yoon , Jung Yuyeon , Lee Sanha , Hur Soo Young , Choi Youn Jin
Published: April 2021

Background

Exosomal miRNAs regulate gene expression and play important roles in several diseases. We used exosomal miRNA profiling to investigate diagnostic biomarkers of epithelial ovarian cancer (EOC).

Methods

In total, 55 individuals were enrolled, comprising healthy (n = 21) and EOC subjects (n = 34). Small mRNA (smRNA) sequencing and real-time PCR (RT-PCR) were performed to identify potential biomarkers. Receiver operating characteristic (ROC) curves were conducted to determine biomarker sensitivity and specificity.

Results

Using smRNA sequencing, we identified seven up-regulated (miR-4732-5p, miR-877-5p, miR-574-3p, let-7a-5p, let-7b-5p, let-7c-5p, and let-7f-5p) and two down-regulated miRNAs (miR-1273f and miR-342-3p) in EOC patients when compared with healthy subjects. Of these, miR-4732-5p and miR-1273f were the most up-regulated and down-regulated respectively, therefore they were selected for RT-PCR analysis. Plasma derived exosomal miR-4732-5p had an area under the ROC curve of 0.889, with 85.7% sensitivity and 82.4% specificity in distinguishing EOC patients from healthy subjects (p<0.0001) and could be a potential biomarker for monitoring the EOC progression from early stage to late stage (p = 0.018).

Conclusions

Plasma derived exosomal miR-4732-5p may be a promising candidate biomarker for diagnosing EOC.
Whole-genome sequencing with long reads reveals complex structure and origin of structural variation in human genetic variations and somatic mutations in cancer
Authors: Fujimoto Akihiro , Wong Jing Hao , Yoshii Yukiko , Akiyama Shintaro , Tanaka Azusa , Yagi Hitomi , Shigemizu Daichi , Nakagawa Hidewaki , Mizokami Masashi , Shimada Mihoko
Published: April 2021

Background

Identification of germline variation and somatic mutations is a major issue in human genetics. However, due to the limitations of DNA sequencing technologies and computational algorithms, our understanding of genetic variation and somatic mutations is far from complete.

Methods

In the present study, we performed whole-genome sequencing using long-read sequencing technology (Oxford Nanopore) for 11 Japanese liver cancers and matched normal samples which were previously sequenced for the International Cancer Genome Consortium (ICGC). We constructed an analysis pipeline for the long-read data and identified germline and somatic structural variations (SVs).

Results

In polymorphic germline SVs, our analysis identified 8004 insertions, 6389 deletions, 27 inversions, and 32 intra-chromosomal translocations. By comparing to the chimpanzee genome, we correctly inferred events that caused insertions and deletions and found that most insertions were caused by transposons andAluis the most predominant source, while other types of insertions, such as tandem duplications and processed pseudogenes, are rare. We inferred mechanisms of deletion generations and found that most non-allelic homolog recombination (NAHR) events were caused by recombination errors in SINEs. Analysis of somatic mutations in liver cancers showed that long reads could detect larger numbers of SVs than a previous short-read study and that mechanisms of cancer SV generation were different from that of germline deletions.

Conclusions

Our analysis provides a comprehensive catalog of polymorphic and somatic SVs, as well as their possible causes. Our software are available athttps://github.com/afujimoto/CAMPHORandhttps://github.com/afujimoto/CAMPHORsomatic.