bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of gestational diabetes mellitus on the duration of breastfeeding in primiparous women: an observational cohort study
Authors: Laine Merja K. , Kautiainen Hannu , Gissler Mika , Pennanen Pirjo , Eriksson Johan G. 
Published: February 2021

Abstract
Background
The impact of gestational diabetes mellitus (GDM) on the duration of breastfeeding varies between shortening and no impact. Breastfeeding seems to reduce both maternal and offspring risk for type 2 diabetes and offspring risk for overweight or obesity later in life. The aim of our study was to evaluate in primiparous women whether GDM had an influence on the duration of breastfeeding, and further, to evaluate the factors that influenced on the duration of breastfeeding.

Methods
The study cohort (N = 1089) consisted of all primiparous women with a Finnish background excluding women with pre-existing diabetes mellitus who lived in the city of Vantaa, Finland, gave birth to a singleton living child between 2009 and 2015, and with valid data on breastfeeding available. The diagnosis of GDM was based on a standard 75 g 2-h oral glucose tolerance test. Data were obtained from Finnish national registers and from the medical records of the city of Vantaa.

Results
No differences were observed in the duration of breastfeeding between women diagnosed with GDM and without GDM, 7.5 (Standard Deviation [SD] 3.7) months versus 7.9 (SD 3.5) months (p = 0.17). Women diagnosed with GDM breastfed boys for a longer duration than girls (maternal age, pre-pregnancy body mass index, marital status, educational attainment, duration of pregnancy, and smoking habits adjusted p = 0.042). Women who breastfed < 6 months were younger, were more likely smokers, had shorter education, and higher pre-pregnancy body mass index than women who breastfed over 6 months (p <  0.001 for linearity).

Conclusions
In primiparous women GDM did not influence breastfeeding duration. The positive health effects of breastfeeding should be emphasized especially in young, overweight and less educated women in order to minimize the risk of obesity and type 2 diabetes for themselves and their offspring.
‘Resurgent’, ‘twin’ or ‘silent’ epidemic? A select data overview and observations on increasing psycho-stimulant use and harms in North America
Authors: Fischer Benedikt , O’Keefe-Markman Caroline , Lee Angelica , Daldegan-Bueno Dimitri 
Published: February 2021

AbstractIn the early 2000s, increasing prevalence of psycho-stimulant (e.g., crack/cocaine, methamphetamine) use and related harms, including severe adverse health outcomes, was observed among - mostly marginalized - populations of persons using illicit drugs in North America, underscoring an urgent need for interventions options towards improved prevention and treatment. By about 2010, however, the ‘opioid crisis’, featuring unprecedented use and public health burden, had accelerated into full force in North America, largely muting attention to the psycho-stimulant issue until recently. Recent surveillance data on drug use and related mortality/morbidity from the present decade has documented a marked resurgence of psycho-stimulant use and harms especially in at-risk populations, commonly in direct combination with opioids, across North America, resulting in a ‘twin epidemic’ comprised of opioids and psycho-stimulants We briefly review select epidemiological data indicators for these developments from the United States and Canada; in the latter jurisdiction, related evidence has been less prevalent and systematic but corroborating the same trends. Evidently, the (widely ongoing) focus on the ‘opioid epidemic’ as a ‘mono-type’ drug problem has become an anachronism that requires urgent and appropriate correction. We then briefly consider existing, evidence-based options for – prevention and treatment – interventions targeting psycho-stimulant use and harms, which are substantially more limited and/or less efficacious than those available for problematic opioid use, while presenting major gaps and challenges. The observed resurgence of psycho-stimulants may, indirectly, relate to recent efforts towards curtailing (medical) opioid availability, thereby accelerating demand and supply for both illicit opioids and psycho-stimulants. The presently unfolding ‘twin epidemic’ of opioids and psycho-stimulants, combined with limited intervention resources, presents an acute challenge for public health and may crucially undermine actively extensive efforts to reduce opioid-related health harms in North America.
Understanding the implementation of evidence-informed policies and practices from a policy perspective: a critical interpretive synthesis
Authors: Bullock Heather L. , Lavis John N. , Wilson Michael G. , Mulvale Gillian , Miatello Ashleigh 
Published: February 2021

Abstract
Background
The fields of implementation science and knowledge translation have evolved somewhat independently from the field of policy implementation research, despite calls for better integration. As a result, implementation theory and empirical work do not often reflect the implementation experience from a policy lens nor benefit from the scholarship in all three fields. This means policymakers, researchers, and practitioners may find it challenging to draw from theory that adequately reflects their implementation efforts.

Methods
We developed an integrated theoretical framework of the implementation process from a policy perspective by combining findings from these fields using the critical interpretive synthesis method. We began with the compass question: How is policy currently described in implementation theory and processes and what aspects of policy are important for implementation success? We then searched 12 databases as well as gray literature and supplemented these documents with other sources to fill conceptual gaps. Using a grounded and interpretive approach to analysis, we built the framework constructs, drawing largely from the theoretical literature and then tested and refined the framework using empirical literature.

Results
A total of 11,434 documents were retrieved and assessed for eligibility and 35 additional documents were identified through other sources. Eighty-six unique documents were ultimately included in the analysis. Our findings indicate that policy is described as (1) the context, (2) a focusing lens, (3) the innovation itself, (4) a lever of influence, (5) an enabler/facilitator or barrier, or (6) an outcome. Policy actors were also identified as important participants or leaders of implementation. Our analysis led to the development of a two-part conceptual framework, including process and determinant components.

Conclusions
This framework begins to bridge the divide between disciplines and provides a new perspective about implementation processes at the systems level. It offers researchers, policymakers, and implementers a new way of thinking about implementation that better integrates policy considerations and can be used for planning or evaluating implementation efforts.
Anterior cruciate ligament reconstruction in a rabbit model using a silk-collagen scaffold modified by hydroxyapatite at both ends: a histological and biomechanical study
Authors: Bi Fanggang , Chen Yangdi , Liu Junqi , Wang Yafei , Xu Danfeng , Tian Ke 
Published: February 2021

Abstract
Background
To investigate osteointegration at the graft-bone interface and the prevention of osteoarthritis after anterior cruciate ligament (ACL) reconstruction using a silk-collagen scaffold with both ends modified by hydroxyapatite (HA) in a rabbit model.

Methods
The HA/silk-collagen scaffold was fabricated using a degummed, knitted silk scaffold, collagen I matrix, and simulated body fluid (SBF). The HA/silk-collagen scaffold was rolled up to make a graft for replacing the native ACL in the experimental group (HA group), and the silk-collagen scaffold was used in the control (S group). All specimens were harvested at 16 weeks postoperatively to evaluate graft-bone healing and osteoarthritis prevention.

Results
Histological staining revealed the massive formation of more mature bone at the tendon-bone interface, and immunohistochemistry staining revealed more collagen I and osteocalcin deposition in the HA group than in the S group. Higher signals indicating more bone mineral formation were detected in the HA group than in the S group, which was consistent with the results of biomechanical testing. Better osteoarthritis prevention was also observed in the HA group, indicating a more stable knee joint in the HA group than in the S group.

Conclusion
The HA/silk-collagen scaffold promotes osteointegration at the tendon-bone interface after ACL reconstruction and has great potential for clinical applications.
Galli gigeriae endothelium corneum: its intestinal barrier protective activity in vitro and chemical composition
Authors: Li Shanshan , Zheng Meng , Zhang Zhentang , Peng Hengying , Dai Wenling , Liu Jihua 
Published: February 2021

AbstractBackgroundGalli gigeriae endothelium corneum (GGEC) has been effectively used for centuries for the treatment of functional dyspepsia (FD) in clinical practice in Asian countries. However, its potential mechanism and chemical composition remains undertermined.MethodsIn this study, the chemical profile of GGEC ethyl acetate extract (EAE) was evaluated by HPLC-Q-TOF–MS/MS. The effects of EAE on intestinal barrier function and inflammation were investigated in IEC-6 cells and RAW264.7 cells.ResultsThe results showed that 33 compounds were tentatively identified, including 12 soy isoflavones, 7 bile acids for the first time in EAE. EAE significantly reinforced intestinal barrier function via increasing the tight junction protein levels of ZO-1 and Occludin, reducing the mRNA expression levels of interleukin (IL)-1β and IL-6 in tumor necrosis factor alpha (TNF-α)-challenged IEC-6 cells. The scratch wound assay showed that EAE accelerated wound healing of IEC-6 cells. EAE evidently reduced the level of NO in a dose-dependent manner with an IC50value of 18.12 μg/mL, and the mRNA expression of TNF-α, IL-1β, IL-6, iNOS and COX-2 in LPS-treated RAW264.7 cells.ConclusionThis study revealed the intestinal barrier protective effects and chemical profile of GGEC, and the results indicated that GGEC strengthened the intestinal barrier by up-regulating protein expression of tight junctions and limiting inflammatory responses.
Dalfampridine in the treatment of multiple sclerosis: a meta-analysis of randomised controlled trials
Authors: Zhang Enyao , Tian Xin , Li Ruoming , Chen Chaoyang , Li Min , Ma Lingyun , Wei Ran , Zhou Ying , Cui Yimin 
Published: February 2021

Abstract
Background
Multiple sclerosis (MS) is a chronic illness involving the central nervous system (CNS) that is characterised by inflammation, demyelination, and degenerative changes. Dalfampridine is one of the available treatments for MS symptoms and comorbidities. This meta-analysis aimed to assess the safety and benefits of dalfampridine versus placebo in MS by summarising data deriving from previously published clinical randomised controlled studies (RCTs).

Results
A total of 9 RCTs were included in this meta-analysis, involving 1691 participants. There were significant differences between dalfampridine and placebo in terms of decreased 12-item Multiple Sclerosis Walking Scale score (weighted mean difference [WMD] =  − 3.68, 95% confidence interval [CI] [− 5.55, − 1.80], p = 0.0001), improved response to the timed 25-foot walk test (relative risk [RR] = 2.57, 95% CI [1.04, 6.33], p = 0.04), increased 6-min walk test (WMD = 18.40, 95% CI [1.30, 35.51], p = 0.03), increased 9-Hole Peg Test score (WMD = 1.33, 95% CI [0.60, 2.05], p = 0.0004), and increased Symbol Digit Modalities Test score (WMD = 4.47, 95% CI [3.91, 5.02], p < 0.00001). Significant differences in the incidence of side effects were also observed (RR = 1.12, 95% CI [1.04, 1.21], p = 0.002).

Conclusion
Dalfampridine exerts positive effects on walking ability, finger dexterity, and cognitive function. Treatment should be administered under the guidance of a physician or pharmacist given the higher incidence of adverse events.
A specific tRNA half, 5’tiRNA-His-GTG, responds to hypoxia via the HIF1α/ANG axis and promotes colorectal cancer progression by regulating LATS2
Authors: Tao En-Wei , Wang Hao-Lian , Cheng Wing Yin , Liu Qian-Qian , Chen Ying-Xuan , Gao Qin-Yan 
Published: February 2021

Abstract
Background
Currently, tRNA-derived small RNAs (tsRNAs) are recognized as a novel and potential type of non-coding RNAs (ncRNAs), which participate in various cellular processes and play an essential role in cancer progression. However, tsRNAs involvement in colorectal cancer (CRC) progression remains unclear.

Methods
Sequencing analyses were performed to explore the tsRNAs with differential expression in CRC. Gain- and loss-of functions of 5’tiRNA-His-GTG were performed in CRC cells and xenograft tumor to discover its role in the progression of CRC. Hypoxia culture and hypoxia inducible factor 1 subunit alpha (HIF1α) inhibitors were performed to uncover the biogenesis of 5’tiRNA-His-GTG. The regulation of 5’tiRNA-His-GTG for large tumor suppressor kinase 2 (LATS2) were identified by luciferase reporter assay, western blot, and rescue experiments.

Results
Here, our study uncovered the profile of tsRNAs in human CRC tissues and confirmed a specific tRNA half, 5’tiRNA-His-GTG, is upregulated in CRC tissues. Then, in vitro and in vivo experiments revealed the oncogenic role of 5’tiRNA-His-GTG in CRC and found that targeting 5’tiRNA-His-GTG can induce cell apoptosis. Mechanistically, the generation of 5’tiRNA-His-GTG seems to be a responsive process of tumor hypoxic microenvironment, and it is regulated via the HIF1α/angiogenin (ANG) axis. Remarkably, LATS2 was found to be an important and major target of 5’tiRNA-His-GTG, which renders 5’tiRNA-His-GTG to “turn off” hippo signaling pathway and finally promotes the expression of pro-proliferation and anti-apoptosis related genes.

Conclusions
In summary, the findings revealed a specific 5’tiRNA-His-GTG-engaged pathway in CRC progression and provided clues to design a novel therapeutic target in CRC.
Inhaled corticosteroids use in childhood respiratory diseases: an italian survey on pediatricians’ prescription habits
Authors: Cerimoniale Giovanni , Becherucci Paolo , Verga Maria Carmen , Di Mauro Giuseppe , Indinnimeo Luciana , Villani Alberto , Tosca Mariangela , Marseglia Gian Luigi , Duse Marzia , Biasci Paolo , Doria Mattia , Peroni Diego , Piacentini Giorgio , Di Cicco Maria , Pozzobon Gabriella , Lubrano Riccardo 
Published: February 2021

Abstract
Background
A national consensus document on inhaled corticosteroids (ICS) use in childhood, produced by the main Italian pediatric scientific societies, has been recently released. The aim of this study was to gather information on the current pediatricians’ ICS prescription habits in Italy for the management of the most common pediatric respiratory diseases, namely allergic rhinitis (AR), asthma, preschool wheezing and laryngitis.

Methods
From the 1st October 2018 to the 31st January 2019 a link to an online questionnaire was sent monthly through a newsletter to the members of the Italian Society of Pediatrics. The questionnaire included 18 items on ICS use in the most common pediatric respiratory diseases. Data collection and reporting was based on STROBE Statement Checklist for cross-sectional studies.

Results
One thousand-two questionnaires were returned from primary care pediatricians (39.1%), hospital pediatricians (38.7%), private practicers (16.4%), university pediatricians (3.1%) and Pediatrics residents (2.7%). We found a good adherence to the international guidelines on AR, with prevalent use of oral antihistamine (60.6%) in the secretive phenotype and nasal ICS in the obstructive phenotype (64.8%). In asthma exacerbations ICS are not used in 53.4% of cases, but they are used at high dose in 27.9% and at low dose in 18.7% of cases. In intermittent asthma, ICS are not chosen as a daily controller therapy in 54.1% of cases, while they are chosen as a low dose daily therapy in 44.5% of cases (high dose in 1.4%). In children with persistent asthma, ICS are chosen as a daily low dose therapy in 67.4% of cases and as a daily high dose therapy in 31%. In the management of preschool wheezing, when a long-term treatment is needed, ICS are chosen both alone and in association with antileukotrienes in 71.4% of cases. Children affected by recurrent asthma exacerbations and wheezing are closely followed up, in particular by their primary care pediatricians. The preference for certain molecules in the treatment of different respiratory diseases also emerged.

Conclusions
Pediatricians’ ICS prescription habits in Italy should be improved, especially in the management of asthma. Future surveys on a more numerous sample will be useful to analyze differences in prescription habits on the basis of pediatricians’ work settings and geographical distribution.
Could nutritional supplements act as therapeutic adjuvants in COVID-19?
Authors: Costagliola Giorgio , Spada Erika , Comberiati Pasquale , Peroni Diego G. 
Published: February 2021

Abstract
Background
The role of the immune system and inflammatory response in the pathogenesis of the severe manifestations of coronavirus disease 2019 (COVID-19) is well known. Currently, different therapies active on the immune system are used for the management of COVID-19. The involvement of the immune system also opens the opportunity for the use of nutritional supplements with antimicrobial and immunomodulatory activity.

Main aspects
Nutritional supplements with antimicrobial and immunomodulatory activity are promising therapeutic adjuvants for the treatment of COVID-19, and also for the prevention of viral spreading. In particular, the role of vitamin D, probiotics, lactoferrin, and zinc is of significant clinical interest, although there are only a few data on their use in COVID-19 patients. Their molecular actions, together with the results of studies performed on other respiratory infections, strongly suggest their potential utility in COVID-19. This article discusses the main properties of these nutritional supplements and their potential applicability in the prevention and treatment of COVID-19.

Conclusion
The supplementation with vitamin D, probiotics, lactoferrin and zinc could have a role both in preventing SARS-CoV-2 infection and in mitigating the clinical course in infected patients, contributing in the prevention of immune-mediated organ damage.
Diaphragm echodensity in mechanically ventilated patients: a description of technique and outcomes
Authors: Coiffard Benjamin , Riegler Stephen , Sklar Michael C. , Dres Martin , Vorona Stefannie , Reid W. Darlene , Brochard Laurent J. , Ferguson Niall D. , Goligher Ewan C. 
Published: February 2021

Abstract
Background
Acute increases in muscle sonographic echodensity reflect muscle injury. Diaphragm echodensity has not been measured in mechanically ventilated patients. We undertook to develop a technique to characterize changes in diaphragm echodensity during mechanical ventilation and to assess whether these changes are correlated with prolonged mechanical ventilation.

Methods
Diaphragm ultrasound images were prospectively collected in mechanically ventilated patients and in 10 young healthy subjects. Echodensity was quantified based on the right-skewed distribution of grayscale values (50th percentile, ED50; 85th percentile, ED85). Intra- and inter-analyzer measurement reproducibility was determined. Outcomes recorded included duration of ventilation and ICU complications (including reintubation, tracheostomy, prolonged ventilation, or death).

Results
Echodensity measurements were obtained serially in 34 patients comprising a total of 104 images. Baseline (admission) diaphragm ED85 was increased in mechanically ventilated patients compared to younger healthy subjects (median 56, interquartile range (IQR) 42–84, vs. 39, IQR 36–52, p = 0.04). Patients with an initial increase in median echodensity over time (≥ + 10 in ED50 from baseline) had fewer ventilator-free days to day 60 (n = 13, median 46, IQR 0–52) compared to patients without this increase (n = 21, median 53 days, IQR 49–56, unadjusted p = 0.03). Both decreases and increases in diaphragm thickness during mechanical ventilation were associated with increases in ED50 over time (adjusted p = 0.03, conditional R2 = 0.80) and the association between increase in ED50 and outcomes persisted after adjusting for changes in diaphragm thickness.

Conclusions
Many patients exhibit increased diaphragm echodensity at the outset of mechanical ventilation. Increases in diaphragm echodensity during the early course of mechanical ventilation are associated with prolonged mechanical ventilation. Both decreases and increases in diaphragm thickness during mechanical ventilation are associated with increased echodensity.
Multi-Round compared to Real-Time Delphi for consensus in core outcome set (COS) development: a randomised trial
Authors: Quirke Fiona A. , Healy Patricia , Bhraonáin Elaine Ní , Daly Mandy , Biesty Linda , Hurley Tim , Walker Karen , Meher Shireen , Haas David M. , Bloomfield Frank H. , Kirkham Jamie J. , Molloy Eleanor J. , Devane Declan 
Published: February 2021

Abstract
Background
The Delphi method is used in a wide variety of settings as a method of building consensus on important issues. Traditionally, the Delphi method uses multiple rounds of a survey to allow for feedback of other participants’ survey responses in between rounds. By informing participants about how others answer a question or prioritise specific topics, it allows for diverse opinions to inform the consensus process. For this reason, the Delphi method is popular as a consensus building approach in developing core outcome sets (COS), i.e. the minimum agreed set of standardised outcomes that should be measured and reported in studies on a specific health condition. In a COS setting, participants prioritise the importance of outcomes for inclusion in a COS. This usually involves participating in multiple rounds of a survey that can span several weeks or months. Challenges with participant retention have been highlighted in previous COS. We will compare a three-round with a Real-Time Delphi approach on prioritised outcomes. This trial is embedded within the COHESION study which is developing a COS for interventions treating neonatal encephalopathy.

Methods
One hundred and eighty stakeholders (parents/caregivers of infants diagnosed and treated with neonatal encephalopathy, healthcare providers and researchers) will be randomised using stratified randomisation to take part in either the Multi-Round or Real-Time Delphi. Stakeholders will rate the importance of the same set of outcomes in both arms. We will compare the prioritised outcomes at the end of both surveys as well as other parameters such as feedback, initial condition and iteration effects.

Discussion
This trial will provide evidence to inform decisions on the use of Multi-Round compared to Real-Time Delphi survey methods.

Trial registration
NCT04471103. Registered on 14 July 2020.