bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cedazuridine/decitabine: from preclinical to clinical development in myeloid malignancies
Authors: Patel Anand A. , Cahill Kirk , Saygin Caner , Odenike Olatoyosi 
Published: April 2021

Abstract
Since the US Food and Drug Administration (FDA) approvals of parenteral decitabine and azacitidine, DNA methyltransferase inhibitors, otherwise referred to as DNA hypomethylating agents (HMAs), have been a mainstay in the treatment of higher-risk myelodysplastic syndromes. The development of oral HMAs has been an area of active interest; however, oral bioavailability has been quite poor due to rapid metabolism by cytidine deaminase (CDA). This led to the development of the novel CDA inhibitor cedazuridine, which was combined with an oral formulation of decitabine. Preclinical work demonstrated a pharmacokinetic and pharmacodynamic profile approximate to parenteral decitabine, leading to early-phase clinical trials of oral cedazuridine-decitabine (C-DEC) in myelodysplastic syndromes and chronic myelomonocytic leukemia (CMML). A combination of oral decitabine 35 mg with oral cedazuridine 100 mg was established as the recommended phase 2 dose. Phase 2 data confirmed bioequivalence of C-DEC when compared with parenteral decitabine, and a larger phase 3 trial has demonstrated similar results, leading to the FDA approval of C-DEC for use in intermediate/high-risk myelodysplastic syndrome (MDS) and CMML. This review will focus upon the current role of HMA therapy in MDS/CMML, preclinical and clinical development of C-DEC, and potential roles of oral HMA therapy in myeloid malignancies moving forward.
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 aimsTo 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

Abstract
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

AbstractBackgroundTheRhododendron 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.ResultsReflectance 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.ConclusionsOur 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundThe 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.MethodsWe 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.ResultsOur 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.ConclusionOur 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

Abstract
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

Abstract
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.