bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR‐128‐3p inhibits high‐glucose‐induced peritoneal mesothelial cells fibrosis via PAK2/SyK/TGF‐β1 axis
Authors: Zhang Yao , Xiao Wu‐Hao , Huang Yi‐Xiong , Yang Yi‐Ya , Ouyang Sha‐Xi , Liang Yu‐Mei , Liu Kang‐Han 
Published: July 2022

AbstractAimTo elucidate the mechanism of miR‐128‐3p in peritoneal fibrosis (PF).MethodsPeritoneal mesothelial cells (PMCs) were dealt with high glucose (HG) for 3 days. The expressions of miR‐128‐3p, p21‐activated kinase 2 (PAK2), spleen tyrosine kinase (SyK), and transforming growth factor‐β1 (TGF‐β1) were detected with quantitative real‐time reverse transcription polymerase chain reaction. The levels of IL‐1β, TNF‐α, IL‐6, and monocyte chemotactic protein‐1 in supernatant were measured by ELISA. Proteins of TGF‐β1, SyK, PAK2, α‐SMA, collagen I, vimentin, ERK/AP‐1, and IκBα/NF‐κB pathway related proteins were measured by Western blot. The correlation between miR‐128‐3p and PAK2 was found by bioinformatics analysis and luciferase reporter gene analysis.ResultsmiR‐128‐3p was decreased while PAK2, SyK, and TGF‐β1 were increased in HG‐induced PMCs. Moreover, miR‐128‐3p inhibited HG‐induced fibrosis and inflammation in PMCs by targeting PAK2. PAK2 activated SyK, which induced TGF‐β1 expression through ERK/AP‐1 and IκBα/NF‐κB pathways to promote HG‐induced fibrosis of PMCs.ConclusionmiR‐128‐3p inhibited HG‐induced PMCs fibrosis via PAK2/SyK/TGF‐β1 axis.
Environmental DNA methylation of Lymnaea stagnalis varies with age and is hypermethylated compared to tissue DNA
Authors: Zhao Beilun , van Bodegom Peter M. , Trimbos Krijn B. 
Published: July 2022

AbstractEnvironmental DNA (eDNA) approaches contributing to species identifications are quickly becoming the new norm in biomonitoring and ecosystem assessments. Yet, information such as age and health state of the population, which is vital to species biomonitoring, has not been accessible from eDNA. DNA methylation has the potential to provide such information on the state of a population. Here, we measured the methylation of eDNA along with tissue DNA (tDNA) of Lymnaea stagnalis at four life stages. We demonstrate that eDNA methylation varies with age and allows distinguishing among age classes. Moreover, eDNA was globally hypermethylated in comparison to tDNA. This difference was age‐specific and connected to a limited number of eDNA sites. This differential methylation pattern suggests that eDNA release with age is partially regulated through DNA methylation. Our findings help to understand mechanisms involved in eDNA release and shows the potential of eDNA methylation analysis to assess age classes. Such age class assessments will encourage future eDNA studies to assess fundamental processes of population dynamics and functioning in ecology, biodiversity conservation and impact assessments.
A novel form of precise segmentectomy—Triumphal arch‐like anatomical segmentectomy
Authors: Zheng Yixiong , Zhang Shuliang , Zeng Taidui , Chen Maohui , Huang Guanglei , Xu Chi , Xu Guobing , Zheng Wei , Chen Chun , Zheng Bin 
Published: July 2022

AbstractThe increasingly accurate sublobar anatomical resection is constantly being explored and practiced. Surgeons try to preserve as much viable lung tissue as possible. Sublobar resection of the target tissue is similar with a cone‐shaped structure which penetrates deeply into the pulmonary parenchyma and runs through the lobe at both ends. This has not previously been described. The remaining lung tissue resembles the Triumphal Arch in Paris, France. Here, we describe triumphal arch‐like sublobectomy in detail, aiming to provide clinicians with an idea to explore this novel sublobectomy under similar conditions.
A randomized controlled trial on virtual reality distraction during venous cannulation in young children
Authors: Thybo Kasper H. , Friis Susanne M. , Aagaard Gitte , Jensen Claus S. , Dyekjær Charlotte D. , Jørgensen Casper Haslund , Walther‐Larsen Søren 
Published: July 2022

AbstractBackground and ObjectivesPain management in children is often inadequate, and the single most common painful procedure in children who are hospitalized is needle procedures. Virtual reality (VR) has been shown to decrease anxiety and pain in children undergoing painful procedures primarily in children from the age of 7 years. Our aim for this study is to investigate patient satisfaction and pain reduction by using a three‐dimensional VR interactive game as a distraction in 4–7 years old children during venous cannulation.MethodsIn this randomized clinical trial, we enrolled 106 children aged 4–7 years who were scheduled for venous cannulation. Patients assigned to the control group were adherent to standard of care, including topical numbing cream, positioning, and distraction in this group by games of choice on a tablet/smartphone. In the study group, children were adherent to standard of care and were distracted by an interactive VR game. Primary outcomes were patient satisfaction and the procedural pain assessed by using Wong–Baker Faces Pain Rating Scale; secondary outcomes were the procedural time and any adverse events.ResultsWe found an overall high level of patient satisfaction with our regime of topical numbing cream, positioning, and distraction. The primary outcome of pain during the procedure was median 20 mm (IQR 0–40) and 20 mm (IQR 0–55) (Wong–Baker 0–100 mm) in the VR group and the control group, respectively (difference: 0 mm, 95%CI: 0–20, p = .19). No significant difference was found in procedural times. The number of adverse effects was low, with no significant difference between the two groups.ConclusionsVR distraction is an acceptable form of distraction for children 4–7 years old when combined with topical numbing cream and positioning during preoperative venous cannulation. No difference was found between VR‐ and smartphone/tablet distraction.
The clinical utility of ongoing sonographic cervix length surveillance in pregnancies prescribed vaginal progesterone therapy
Authors: Ninkov Tatiana , Nathan Elizabeth A. , Belcher Cathryn N. , White Scott W. , Newnham John P. 
Published: July 2022

BackgroundVaginal progesterone therapy significantly reduces preterm birth (PTB) rates in those high‐risk pregnancies with a sonographic short cervix (≤25 mm) and/or a history of spontaneous PTB. Cervical length (CL) is routinely measured at the midtrimester morphology scan; however, CL surveillance thereafter is not currently recommended. Progesterone's precise mechanism of action remains unknown, though if it indeed influences CL, shortening after treatment initiation could indicate therapeutic failure and risk of PTB.AimsThe aim was to explore the utility of serial transvaginal ultrasound (TVU) measurement of CL at 16, 19 and 22 weeks for predicting PTB in high‐risk pregnancies prescribed progesterone therapy.MethodsA retrospective cohort study was conducted involving women who attended the King Edward Memorial Hospital PTB Prevention Clinic from 2015 to 2019 and were prescribed progesterone therapy. CL was measured at 16, 19 and 22 weeks by TVU. CL change across three time points was assessed using linear mixed models; then relationships between CL change between 16–19 and 19–22 weeks and PTB were analysed using logistic regression models.ResultsTerm birth was most likely when CL did not decrease across both time periods. The addition of 16–19 week decrease in CL to a model, including CL at 19 weeks alone, for predicting PTB increased sensitivity from 43.2 to 56.3%, specificity from 73.2 to 77.4%, and overall accuracy from 61.7 to 70.2%.ConclusionFor high‐risk women prescribed vaginal progesterone therapy, serial measurement of the cervix at 16 and 19 weeks improves clinical ability to predict PTB from current recommendations of 19‐week measurement alone.
Multi‐centre randomised trial of invasive and less invasive surfactant delivery methods showed similar spirometry results at 5–9 years of age
Authors: Göpel Wolfgang , Kribs Angela , Roll Claudia , Wieg Christian , Teig Norbert , Hoehn Thomas , Welzing Lars , Vochem Matthias , Hoppenz Marc , Bührer Christoph , Mehler Katrin , Hubert Mechthild , Eichhorn Joachim , Schmidtke Susanne , Rausch Tanja Katrin , König Inke Regina , Härtel Christoph , Roth Bernd , Herting Egbert 
Published: July 2022

AbstractAimWe explored whether subnormal forced expiratory volume within 1 s (FEV1) at 5–9 years of age was lower in children born preterm who received less invasive surfactant administration (LISA) rather than surfactant via an endotracheal tube.MethodsThe multi‐centre, randomised Nonintubated Surfactant Application trial enrolled 211 preterm infants born at 23–26 weeks of gestation from 13 level III neonatal intensive care units from April 2009 to March 2012. They received surfactant via LISA (n = 107) or after conventional endotracheal intubation (n = 104). The follow‐up assessments were carried out by a single team blinded to the group assignments. The main outcome was FEV1 < 80% of predicted values.ResultsSpirometry was successful in 102/121 children. The other children died or were lost to follow‐up. Median FEV1 was 93% (interquartile range 80%–113%) of predicted values in the LISA group and 86% (interquartile range 77–102%) in the control group (p = 0.685). Rates of FEV1 < 80% were 11/57 (19%) and 15/45 (33%), respectively, which was an absolute risk reduction of 14% (95% confidence interval −3.1% to 31.2%, p = 0.235). There were no differences in other outcome measures.ConclusionThe proportion of children aged 5–9 years with subnormal FEV1 was not significantly different between the groups.
Antenatal and neonatal risk factors in very preterm children were associated with language difficulties at 9 years of age
Authors: Taskila Hanna‐Leena , Heikkinen Minna , Yliherva Anneli , Välimaa Taina , Hallman Mikko , Kaukola Tuula , Kallankari Hanna 
Published: July 2022

AbstractAimThis Finnish study compared language and reading abilities between schoolchildren born at a very low gestational age (VLGA) of <32 weeks and at term and analysed any associations between antenatal and neonatal risk factors and language skills in the VLGA group.MethodsWe prospectively followed 76 children born at a VLGA and 50 children born at term when they reached a mean age of 9.0 (8.1–10.0) years. They attended mainstream schools and had no severe neurosensory disabilities. Receptive language ability, rapid naming and word reading were evaluated using standardised tests.ResultsChildren in the VLGA group had lower scores for receptive language abilities (median 55.0 vs. 57.0, p = 0.01) and word reading (mean 4.4 vs. 5.1, p = 0.03) than the children in the term group. In the VLGA group, foetal growth restriction was associated with lower scores for rapid naming, early intraventricular haemorrhage was associated with poor word reading and respiratory distress syndrome was associated with poor rapid naming (p < 0.05).ConclusionSchoolchildren born at a VLGA had more difficulties with receptive language abilities and word reading than children born at term. Foetal growth restriction and early neonatal morbidities were associated with language difficulties.
How are policies implemented in children's services? Developing an initial programme theory to evaluate the implementation of the new Child Sexual Exploitation guidance in Wales
Authors: Usubillaga Juan , Diaz Clive , Forrester Donald 
Published: July 2022

AbstractAlthough children's social care is an area rich in guidance, there is very little research looking at the implementation of new policies in the United Kingdom. In this article, we report on the first stage of a realist evaluation of the implementation of the new Safeguarding Children from Child Sexual Exploitation guidance in Wales. We discuss the development of an initial programme theory, for which we conducted semi‐structured interviews with practitioners and managers in three local authorities. We developed programme theories across three areas: policy nature and development, implementation plans and organizational context. Findings suggest that, for policies to produce a significant impact on practice, they need to be sufficiently different to social workers' current perceptions of practice. Second, we found that the coordination between national and local policies is critical for successful implementation as contradictions between them might lead to confusion in what local teams should prioritize. Finally, our findings highlight the importance of effective communication of policy changes, as well as a supportive organizational culture to strengthen implementation in local contexts. These findings illustrate the complexity of policy implementation and the need for policymakers to consider the meaningful involvement of local practitioners in national policy development.
Magnetic resonance imaging has a limited role in investigating odynophagia if examination is normal: A binary logistic regression analysis of 484 patients presenting to a tertiary head and neck clinic
Authors: Wright Oliver , Zhang Ting Ting , Gyimah Dominic Ayi , Davies‐Husband Cameron 
Published: July 2022

AbstractIntroductionInvestigation of head and neck cancers places a significant burden on the National Health Service and effective resource allocation is of perpetual importance. Existing risk calculators are designed to stratify the likelihood of underlying malignancy according to symptoms, but are less relevant in secondary care as they do not integrate clinical examination findings (e.g. naso‐endoscopy). We looked to evaluate the utility of magnetic resonance imaging (MRI) in investigating patients with unilateral odynophagia and a normal clinical examination.MethodsA retrospective analysis was conducted over a 54‐month period; 484 consecutively‐recruited adult patients who underwent MRI of the neck for suspected malignancy were included. Imaging reports, case notes, and histopathology results were reviewed. Patients with previously diagnosed/treated malignancy, undergoing surveillance, or those with pathology of the salivary glands, oral cavity or thyroid gland, were excluded. A multivariate binary logistical regression model was performed to calculate the odds ratios and probabilities of malignancy for each presenting symptom, with and without negative nasoendoscopy findings.ResultsThe overall incidence of malignancy within the cohort was 173/484 patients (35.7%; 95% CI 31.5%–40.2%) with no cases of malignancy in patients presenting with odynophagia and a normal nasoendoscopy (0/39). The presence of a neck lump was significantly associated with malignancy, (odds ratio [OR] 2.03, p = .001; 95% CI 1.59–2.58), as was dysphagia (OR 1.52, p = .009; 95% CI 1.11–2.11). Conversely, globus was found to have an inverse association (OR 0.41, p < .001; 95% CI 0.24–0.70).SummaryNew patients presenting with odynophagia alone and normal endoscopy or globus have a low likelihood of underlying malignancy, justifying reassurance and follow‐up in the event of persistent symptoms. Contrariwise, patients with a neck lump, dysphagia, odynophagia and multiple concurrent aerodigestive tract symptoms, or an abnormal endoscopy have a high likelihood of underlying malignancy and should be investigated accordingly.
Differential effects of metformin‐mediated BSEP repression on pravastatin and bile acid pharmacokinetics in humans: A randomized controlled trial
Authors: Metry Melissa , Krug Samuel A. , Karra Vijaya Kumari , Kane Maureen A. , Fink Jeffrey C. , Shu Yan , Wang Hongbing , Polli James E. 
Published: July 2022

AbstractMetformin has been shown to repress transcription of the bile salt export pump (BSEP) in human primary hepatocytes. The primary objective of this study was to assess the effect of oral metformin on the human pharmacokinetics (PKs) of two BSEP probe substrates: pravastatin and chenodeoxycholic acid (CDCA; also known as chenodiol). Endogenous bile acid levels were assessed as a secondary measure of metformin impact. An open‐label, randomized, single‐dose, placebo‐controlled, fasted, crossover PK study was conducted in 12 healthy adult volunteers. Metformin (500 mg b.i.d.) or placebo (b.i.d.) was administered orally for 6 days. On day 7, a single dose of the BSEP substrates pravastatin (80 mg) and CDCA (250 mg) were administered orally. Plasma samples were quantified for pravastatin, CDCA, and endogenous bile acids. Compared to placebo, metformin increased pravastatin plasma exposure, did not impact CDCA plasma exposure, and reduced conjugated primary bile acid levels in the blood. These results are consistent with metformin repressing BSEP expression. This differential effect reflects the degree of enterohepatic recirculation of victim substrates.
Bringing pharmacomicrobiomics to the clinic through well‐designed studies
Authors: Steiner Heidi E. , Patterson Hayley K. , Giles Jason B. , Karnes Jason H. 
Published: July 2022

AbstractPharmacomicrobiomic studies investigate drug‐microbiome interactions, such as the effect of microbial variation on drug response and disposition. Studying and understanding the interactions between the gut microbiome and drugs is becoming increasingly relevant to clinical practice due to its potential for avoiding adverse drug reactions or predicting variability in drug response. The highly variable nature of the human microbiome presents significant challenges to assessing microbes’ influence. Studies aiming to explore drug‐microbiome interactions should be well‐designed to account for variation in the microbiome over time and collect data on confounders such as diet, disease, concomitant drugs, and other environmental factors. Here, we assemble a set of important considerations and recommendations for the methodological features required for performing a pharmacomicrobiomic study in humans with a focus on the gut microbiome. Consideration of these factors enable discovery, reproducibility, and more accurate characterization of the relationships between a given drug and the microbiome. Furthermore, appropriate interpretation and dissemination of results from well‐designed studies will push the field closer to clinical relevance and implementation.
‘Much more convenient, just as effective’: Experiences of starting continuous glucose monitoring remotely following Type 1 diabetes diagnosis
Authors: Tanenbaum Molly L. , Zaharieva Dessi P. , Addala Ananta , Prahalad Priya , Hooper Julie A. , Leverenz Brianna , Cortes Ana L. , Arrizon‐Ruiz Nora , Pang Erica , Bishop Franziska , Maahs David M. 
Published: July 2022

AbstractAimInitiating continuous glucose monitoring (CGM) shortly after Type 1 diabetes diagnosis has glycaemic and quality of life benefits for youth with Type 1 diabetes and their families. The SARS‐CoV‐2 pandemic led to a rapid shift to virtual delivery of CGM initiation visits. We aimed to understand parents' experiences receiving virtual care to initiate CGM within 30 days of diagnosis.MethodsWe held focus groups and interviews using a semi‐structured interview guide with parents of youth who initiated CGM over telehealth within 30 days of diagnosis during the SARS‐CoV‐2 pandemic. Questions aimed to explore experiences of starting CGM virtually. Groups and interviews were audio‐recorded, transcribed and analysed using thematic analysis.ResultsParticipants were 16 English‐speaking parents (age 43 ± 6 years; 63% female) of 15 youth (age 9 ± 4 years; 47% female; 47% non‐Hispanic White, 20% Hispanic, 13% Asian, 7% Black, 13% other). They described multiple benefits of the virtual visit including convenient access to high‐quality care; integrating Type 1 diabetes care into daily life; and being in the comfort of home. A minority experienced challenges with virtual care delivery; most preferred the virtual format. Participants expressed that clinics should offer a choice of virtual or in‐person to families initiating CGM in the future.ConclusionMost parents appreciated receiving CGM initiation education via telehealth and felt it should be an option offered to all families. Further efforts can continue to enhance CGM initiation teaching virtually to address identified barriers.
Developing services to support the delivery of care to people with early‐onset type 2 diabetes
Authors: Misra Shivani , Gable David , Khunti Kamlesh , Barron Emma , Young Bob , Kar Partha , Valabhji Jonathan 
Published: July 2022

AbstractEarly‐onset type 2 diabetes occurring in childhood or early adulthood carries a significant excess burden of microvascular diabetes complications, cardiovascular disease and premature death, compared to later onset type 2 diabetes along with adverse pregnancy outcomes in women of child‐bearing age. National audit data in England reveal that 122,780 individuals under the age of 40 years are currently living with type 2 diabetes, with an over‐representation of people from minority ethnicities and those in the most socioeconomically deprived quintiles. A diagnosis of type 2 diabetes earlier in life poses some unique challenges to healthcare providers that are not routinely encountered when type 2 diabetes presents later. These include; (1) the need to ensure correct diabetes classification in an age group that carries a higher probability of other types of diabetes, (2) overcoming difficulties in engaging with individuals who are of working age or in full‐time education, (3) appreciating and addressing the lower attainment of diabetes treatment targets and (4) proactively supporting women of child‐bearing age to optimise their future pregnancy outcomes through better preparation for pregnancy, including achieving optimum glycaemic control at the time of conception. Meanwhile, approaches to prevent type 2 diabetes in younger age groups are challenged by difficulties in identifying those at highest risk, by poorer attendance at lifestyle interventions to prevent or delay the onset of type 2 diabetes and by attenuation of associated weight loss in those that do attend. In this article, we discuss the importance of recognising and addressing the distinct challenges in delivering healthcare to those with early‐onset type 2 diabetes, the greater challenges in preventing type 2 diabetes at younger ages, and key components of strategies that might address these challenges to drive improvements in pregnancy outcomes, microvascular and cardiovascular outcomes.