bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of Empagliflozin vs Dapagliflozin for Kidney Outcomes in Type 2 Diabetes
Authors: Bonnesen Kasper , Heide-Jørgensen Uffe , Christensen Diana H. , Christiansen Christian F. , Lash Timothy L. , Hennessy Sean , Matthews Anthony A. , Pedersen Lars , Thomsen Reimar W. , Schmidt Morten 
Published: January 2025

ImportanceNo large randomized clinical trial has directly compared empagliflozin with dapagliflozin, leaving their comparative effectiveness regarding kidney outcomes unknown.ObjectiveTo compare kidney outcomes between initiation of empagliflozin vs dapagliflozin in adults with type 2 diabetes who were receiving antihyperglycemic treatment.Design, Setting, and ParticipantsThis target trial emulation used nationwide, population-based routinely collected Danish health care data to compare initiation of empagliflozin vs dapagliflozin in adults with type 2 diabetes who received antihyperglycemic treatment between June 1, 2014, and October 31, 2020. Data were analyzed from October 2023 to August 2024. Persons were followed up until an outcome, emigration, death, 6 years, or December 31, 2021, whichever occurred first.ExposureInitiation of empagliflozin vs dapagliflozin.Main Outcomes and MeasuresOutcomes included acute kidney injury, incident chronic kidney disease (stages G3 to G5 or stage A2 or A3), and progression of chronic kidney disease (≥40% decrease in estimated glomerular filtration rate from baseline). Risks of kidney outcomes were estimated in intention-to-treat and per-protocol analyses using an Aalen-Johansen estimator that adjusted for 56 potential confounders and considered death as a competing event.ResultsA total of 32 819 individuals who initiated treatment with empagliflozin and 17 464 with dapagliflozin were included (median [IQR] age, 63 [54-71] years; 18 872 female individuals [37.5%]; median [IQR] estimated glomerular filtration rate, 88 [73-104] mL/min/1.73 m2). After weighting, all measured covariates were well balanced between the groups. In intention-to-treat analyses, people who initiated treatment with empagliflozin and dapagliflozin exhibited comparable 6-year risks of acute kidney injury (18.2% vs 18.5%; risk ratio, 0.98; 95% CI, 0.91-1.06), chronic kidney disease stages G3 to G5 (11.8% vs 12.1%; risk ratio, 0.97; 95% CI, 0.89-1.05), chronic kidney disease stage A2 or A3 (14.8% vs 14.3%; risk ratio, 1.04; 95% CI, 0.93-1.15), and progression of chronic kidney disease (5.3% vs 5.7%; risk ratio, 0.94; 95% CI, 0.56-1.58). The primary analyses were supported by corresponding per-protocol analyses.Conclusions and RelevanceThe results of this cohort study suggest that people with type 2 diabetes who initiated treatment with empagliflozin and dapagliflozin had comparable long-term kidney outcomes.
Factors Associated With Semaglutide Initiation Among Adults With Obesity
Authors: Podolsky Meghan I. , Raquib Rafeya , Shafer Paul R. , Hempstead Katherine , Ellis Randall P. , Stokes Andrew C. 
Published: January 2025

ImportanceSemaglutide, a novel glucagon-like peptide-1 (GLP-1) receptor agonist medication, was approved for weight management in individuals with obesity in June 2021. There is limited evidence on factors associated with uptake among individuals in this subgroup without diabetes.ObjectiveTo explore factors associated with semaglutide initiation among a population of commercially insured individuals with obesity but no diagnosed diabetes.Design, Setting, and ParticipantsThis retrospective observational cohort study used data from the Merative MarketScan Commercial Claims and Encounters Database and included adults in the US aged 18 years or older with a first diagnosis of obesity in an outpatient or inpatient setting between June 5, 2021, and July 1, 2022. Inclusion criteria were no prior antiobesity medication, GLP-1, bariatric surgery, or diabetes-related claim in the 12 months prior to obesity diagnosis, and continuous enrollment in the 12 months preceding and 6 months following obesity diagnosis. Analysis was conducted from February to November 2024.ExposuresMedication classes prescribed, clinical diagnoses, and sociodemographic factors. Exposures were identified within the 12 months prior to obesity diagnosis.Main Outcomes and MeasuresFactors associated with incident semaglutide prescription within 6 months after obesity diagnoses were identified using a 10-fold cross-classified random forest model. The top 20 features of the model feature importance list were ranked in a Shapley Additive Explanations plot and used in a multivariable logistic regression model to quantify associations with semaglutide initiation.ResultsIn this study of 97 456 individuals, 58 124 (59.6%) were female, 26 582 (27.3%) were aged 45 to 54 years, 50 705 (52.0%) resided in the South region, and 49 390 (50.7%) were covered by preferred provider organization plans. Of all participants, 1963 (2.0%) initiated semaglutide within 6 months of their initial obesity diagnosis. The random forest model had an area under the receiver operating characteristic curve of 0.71 (95% CI, 0.69-0.74). The most important exposures identified via Shapley Additive Explanations were sex, use of antidepressants, and employer industry. The top 20 factors were used in the logistic regression model, and significant associations were found with semaglutide initiation, including being female (adjusted odds ratio [aOR], 2.30; 95% CI, 2.05-2.58), use of certain medication classes including antidepressants (aOR,1.62; 95% CI, 1.46-1.78), and being covered by a point-of-service plan (aOR, 1.78; 95% C, 1.42-2.22).Conclusions and RelevanceThis cohort study found that key sociodemographic, health care, and clinical factors are associated with receipt of semaglutide in those without diabetes. These findings suggest that insurance plan type and structure may be a crucial intervention point for improving equity in obesity treatment access.
Age at Menopause and Development of Type 2 Diabetes in Korea
Authors: Ko Byung-Joon , Jung Jin-Hyung , Han Kyungdo , Nam Ga Eun 
Published: January 2025

ImportanceThere is limited evidence regarding the association between age at menopause and incident type 2 diabetes (T2D).ObjectiveTo investigate whether age at menopause and premature menopause are associated with T2D incidence in postmenopausal Korean women.Design, Setting, and ParticipantsThis population-based cohort study was conducted among a nationally representative sample from the Korean National Health Insurance Service database of 1 125 378 postmenopausal women without T2D who enrolled in 2009. The median (IQR) follow-up was 8.4 (8.1-8.7) years. Data were analyzed in March 2024.ExposuresAge at menopause and premature menopause (menopause onset at age &amp;lt;40 years).Main Outcomes and MeasuresThe primary outcome was incident T2D. Multivariable Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% CIs for incident T2D by age at menopause, adjusting for potential confounders.ResultsOf 1 125 378 participants (mean [SD] age at enrollment, 61.2 [8.4] years), 113 864 individuals (10.1%) were diagnosed with T2D at least 1 year after enrollment. Women with menopause onset at ages younger than 40 years (premature menopause; HR, 1.13; 95% CI, 1.08-1.18) and ages 40 to 44 years (HR, 1.03; 95% CI, 1.00-1.06) had increased risk of T2D compared with those with onset at age 50 years or older, with adjustment for sociodemographic, lifestyle, cardiometabolic, psychiatric, and reproductive factors; a younger age at menopause was associated with increased risk of developing T2D (P for trend &amp;lt;.001). Body mass index, depressive disorder, and prediabetes modified the association in subgroup analyses; for example, for individuals with premature menopause vs those with menopause at ages 50 years or older, HRs were 1.54 (95% CI, 1.14-2.06) for a BMI less than 18.5 and 1.14 (95% CI, 1.00-1.30) for a BMI of 30 or greater (P &amp;lt; .001), 1.28 (95% CI, 1.12-1.45) for individuals with depression and 1.11 (95% CI, 1.07-1.16) for those without depression (P = .01), and 1.25 (95% CI, 1.18-1.33) for individuals who were not prediabetic and 1.04 (95% CI, 0.99-1.11) those who were prediabetic (P &amp;lt; .001).Conclusions and RelevanceIn this study, premature and early menopause were associated with a higher risk of T2D, highlighting the need for targeted public health strategies aimed at preventing or delaying T2D among postmenopausal women.
Effect of Pediatric Obesity Treatment on Long-Term Health
Authors: Putri Resthie R. , Danielsson Pernilla , Ekström Nils , Ericsson Åsa , Lindberg Louise , Marcus Claude , Hagman Emilia 
Published: January 2025

IMPORTANCEData regarding the long-term impact of treating childhood obesity on the risk of obesity-related events, including premature mortality, are limited.OBJECTIVETo evaluate the long-term effect of different responses to pediatric obesity treatment on critical health outcomes in young adulthood.Design, Setting, and ParticipantsThe study included a dynamic prospective cohort of children and adolescents with obesity within The Swedish Childhood Obesity Treatment Register (BORIS) and general population comparators, linked with national registers. Baseline data were collected between 1996 and 2019. Formal analyses for this study was conducted in 2023. Outcomes were assessed from individuals aged 18 to 30 years (2005 to 2020). Participants included children and adolescents aged 6 to 17 years receiving at least 1 year of obesity treatment. General population comparators were matched on a ratio of 1:5 on sex, year of birth, and geographical area.EXPOSUREPediatric obesity treatment response was based on changes in body mass index standard deviation score and categorized as poor, intermediate, and good response and obesity remission.MAIN OUTCOMESObesity-related events included type 2 diabetes (T2D), dyslipidemia, hypertension, depression or anxiety, and weight-loss bariatric surgery. Additionally, mortality was assessed.RESULTSOf 6713 individuals (3777 male [56%] and 2936 female [44%]), the median age at obesity treatment initiation was 12.1 (quartile 1; quartile 3: 10.1; 14.3) years and treatment duration was 3.0 (1.8; 4.9) years. For T2D, hypertension, dyslipidemia, weight-loss bariatric surgery, and depression or anxiety outcomes, unadjusted incidence rates tended to decrease with better treatment response and the lowest estimate was observed among general population comparators. Compared with poor response, obesity remission or a good response in obesity treatment was associated with reduced risk of mortality (adjusted hazard ratio [HR], 0.12; 95% CI, 0.03-0.46). Good response was also associated with lower risk of TD2 (HR, 0.42; 95% CI, 0.23-0.77), dyslipidemia (HR, 0.31; 95% CI, 0.13-0.75), and bariatric surgery (HR, 0.42; 95% CI, 0.30-0.58). Obesity remission showed similar reduced risk, but also a reduced risk of hypertension (HR, 0.40; 95% CI, 0.24-0.65). Treatment response was not associated with depression or anxiety.CONCLUSIONS AND RELEVANCEIn this study, beneficial pediatric obesity treatment response yielded enduring health benefits, markedly lowering future morbidity and mortality risks in young adulthood.
Outcomes of a Population-Based Congenital Cytomegalovirus Screening Program
Authors: Dunn Jessica K. E. , Chakraborty Pranesh , Reuvers Emily , Gallagher Lauren , Kernohan Kristin D. , Lacaria Melanie , Barton Michelle , Leifso Kirk , Pernica Jeffrey M. , Santander Emeril , Pigeon Marie , Cushing Sharon L. , MacCormick Johnna , Gantt Soren , Weber Stacey , Bitnun Ari , Brophy Jason 
Published: January 2025

ImportanceDetection of congenital cytomegalovirus (cCMV) infection has previously relied on targeted screening programs or clinical recognition; however, these approaches miss most cCMV-infected newborns and fail to identify those infants who are asymptomatic at birth but at risk for late-onset sensorineural hearing loss.ObjectiveTo determine the feasibility of using routinely collected newborn dried blood spots (DBS) in a population-based cCMV screen to identify infants at risk for hearing loss and describe outcomes of infants screened.Design, Setting, and ParticipantsThis diagnostic study of a population-based screening program in Ontario, Canada, took place from July 29, 2019, to July 31, 2023. All newborns with a DBS sample collected as part of routine care were screened using polymerase chain reaction (PCR) analysis for cCMV as a risk factor for hearing loss. Infants with positive DBS PCR results for cCMV were referred for confirmation of infection by urine PCR (the gold standard), as well as complete medical and audiologic assessments for sequelae of cCMV infection. Infants with possible or confirmed symptomatic cCMV were referred to pediatric infectious disease specialists for evaluation for potential treatment with valganciclovir.ExposureDetection of cCMV by polymerase chain reaction assay on a newborn DBS.Main Outcomes and MeasuresNumber of infants with positive screening results successfully retrieved and confirmed to have cCMV and the timeliness of retrieval and symptomatic evaluation.ResultsOf 565 987 infants born in the screening period, 551 034 (97.4%) received cCMV screening on the DBS (45.7% female, 54.3% male). Of these infants, 689 (0.13%) screened positive for cCMV; 601 (87.2%) had cCMV infection confirmed and a complete assessment of sequelae of their congenital infection. Ninety-six infants with completed assessments (16.0%) were deemed to have cCMV symptoms, and 63 of these (65.6%) began valganciclovir treatment. Sensorineural hearing loss was confirmed in 34 of 96 infants (35.4%).Conclusions and RelevanceThis program found acceptable and feasible implementation of a population-based screening program using routinely collected DBS samples, suggesting that it may serve as a template for jurisdictions considering universal cCMV screening. The program had a much lower than expected prevalence of cCMV-positive screens but still identified many children who would otherwise not have been diagnosed and who would benefit from ongoing audiologic surveillance.
AXL promotes malignant phenotypes in tumor cells and might be a potential antitumor target of natural products
Authors: Yuan Yuan , Wang Shan , Fu Jia‐Lei , Deng Xin‐Xin , Guo Yang , Guo Zheng‐Wang , Han Shu‐Yan 
Published: January 2025

AbstractAXL belongs to the TAM receptor tyrosine kinase family. Relying on binding its high‐affinity ligand—growth arrest‐specific protein 6 (Gas6)—AXL plays an important role in tumor initiation and progression. Traditional Chinese Medicine (TCM) has been clinically used in tumor treatment for a long time, and remarkable therapeutic efficacy has been achieved. Recent studies pointed out that some natural products derived from TCM could inhibit tumor growth by targeting AXL. The potential antitumor mechanisms of natural products targeting AXL still need to be understood. In this review, we discussed the relationship between the AXL axis and tumor malignant phenotype, including migration, invasion, drug resistance, and immunosuppression. The effects and mechanisms of natural products on targeting AXL in tumors also have been systematically summarized.
Transgenerational Plasticity of Maternal Hemolymph Trehalose in Aphids
Authors: Soma Naomi , Kikuta Shingo 
Published: January 2025

ABSTRACTAphids exhibit a unique reproductive strategy known as pseudoplacental viviparity, in which embryos develop internally and are thought to receive nutrients such as sugars and amino acids directly from the maternal hemolymph through an ovariole sheath, bypassing the need for traditional yolk storage. This system enables viviparous aphids to adapt to diverse and potentially stressful environments by transmitting maternal environmental cues that influence transgenerational plasticity. However, the mechanisms underlying this nutrient‐mediated plasticity are poorly understood. This study focused on the role of trehalose, a primary sugar in the maternal hemolymph, in facilitating adaptive plasticity. Trehalose serves as an energy source and may act as a carrier of environmental information from the mother to offspring, potentially influencing resilience and adaptability. The results showed that winged adult aphids have higher levels of trehalose than wingless morphs, and that these elevated trehalose levels are inherited by their first‐instar nymphs. This transfer may help the offspring of winged aphids survive in resource‐poor environments after migration. Gene expression analysis showed the upregulation of trehalose metabolism genes in winged adults, possibly to meet the increased energy demands of flight and reproduction. However, trehalose metabolism in embryos appears to be regulated independently of postnatal nutrient uptake. In vitro studies further suggested that trehalose can directly penetrate the oocyte sheath and embryo membrane, supporting a direct pathway for trehalose transfer. These findings highlight the adaptive role of trehalose in aphid development and suggest a potential mechanism for nutrient‐based transgenerational plasticity in aphids.
‘Let's talk about the weather’: The activist curriculum and global climate change education
Authors: Pountney Richard 
Published: January 2025

AbstractActivist movements have garnered significant global attention on a range of sustainability issues, often involving collectives of citizens coming together. Invoked is the idea of citizens informed to act, emerging not from a common‐sense understanding of everyday life, but rather from a deep political understanding of the world—one that is underpinned by a level of civics knowledge that provides the intellectual basis for engaging in public discussions and planning citizen action. Here, the possibility of transformative activist curricular movements for climate education arises and whether to change the curriculum, or to see curriculum as change in itself. This paper examines what schools and teachers can do to develop children's understanding of and engagement with the issues, and to address their concerns, informed by John Dewey's notion of social action and his ideas on democracy and thinking. The discussion draws on a global movement in climate education, and the case of a group of schools in England. The two cases, chosen as illustrative, are theorised by means of Maton's semantic variation theory to identify how the systems of meaning in these, and similar, contexts can be made accessible. How the sustainable development goals (SDGs) of quality education (SDG4) and climate action (SDG13) can be achieved, including the design of the curriculum by teachers, is examined. The need for an activist curriculum is discussed, one that is integrated and embedded rather than inserted, in which young people can engage with and respond to the issues that they face. Such a curriculum posits the school as both democratic and open, in the sense of having boundaries that are fluid and permeable to the concerns of society, while also giving access to disciplinary knowledge that is the basis of conceptual understanding of the problems of, as well as the solutions to, climate change.
Assessing Human Ribosomal DNA Variation and Its Association With Phenotypic Outcomes
Authors: Rodriguez‐Algarra Francisco , Whittaker Elliott , del Castillo del Rio Sandra , Rakyan Vardhman K. 
Published: January 2025

ABSTRACTAlthough genome‐scale analyses have provided insights into the connection between genetic variability and complex human phenotypes, much trait variation is still not fully understood. Genetic variation within repetitive elements, such as the multi‐copy, multi‐locus ribosomal DNA (rDNA), has emerged as a potential contributor to trait variation. Whereas rDNA was long believed to be largely uniform within a species, recent studies have revealed substantial variability in the locus, both within and across individuals. This variation, which takes the form of copy number, structural arrangement, and sequence differences, has been found to be associated with human phenotypes. This review summarizes what is currently known about human rDNA variation, its causes, and its association with phenotypic outcomes, highlighting the technical challenges the field faces and the solutions proposed to address them. Finally, we suggest experimental approaches that can help clarify the elusive mechanisms underlying the phenotypic consequences of rDNA variation.
The Impact of the Institutional Quality on the Development of Sustainable Innovation: A Multilevel Analysis
Authors: Ibrahimi Agnesë , Krasniqi Besnik , Berisha Gentrit , Rexhepi Gadaf 
Published: January 2025

ABSTRACTWhat causes sustainable innovation has been the subject of recent academic and policy debate. This study examines whether the relationship between firm characteristics and sustainable innovation differs in European and non‐European countries with different institutional contexts. Drawing on institutional theory and leveraging data from the 2020 Eurobarometer survey involving 15,000 interviews in 36 European and non‐European countries, multilevel econometric analysis of firms in these countries reveals a robust connection between sustainable innovation and firm‐specific factors and institutional quality. We combine the firm‐level data from Eurobarometer 2020 with multiple sources of country‐level data to measure the impact of institutional quality on ‐sustainable innovation. Using a multilevel logistic regression model the findings indicate that small and medium‐sized enterprises tend to develop more sustainable innovations, and countries with superior institutional quality and institutional trust foster an environment conducive to sustainable innovation. The paper concludes with implications for theory and policy, suggesting how governments can influence the growth and development of sustainable innovation.
Using mixed methods in feasibility studies: The example of brief transactional analysis psychotherapy for depression
Authors: Vos Joel , van Rijn Biljana 
Published: January 2025

AbstractIntroductionFew guidelines exist on how to conduct Phase 1 feasibility studies in psychological therapies. It may be theoretically argued that small‐size feasibility studies are best studied with mixed methods. The primary aim of this study was to examine the feasibility of using mixed methods in feasibility studies. The secondary aim was to systematically explore the feasibility of a 16‐session treatment manual in transactional analysis psychotherapy (TAP) for depression developed in a prior Phase 0 study.MethodNine clients received therapy from three therapists, and sample characteristics were described using flowcharts and sociodemographic statistics. Interviews were conducted with clients and therapists to explore subjective experiences of changes and processes in therapy. Psychometric instruments measured the impact on mental health, quality of life and TAP‐specific outcomes. Therapist learning effects were examined through self‐reported TAP‐specific competencies. The analyses included reflexive thematic analysis, descriptive statistics, t‐tests and repeated measures ANOVA.ResultsThe results indicated that the clients experienced important changes, such as self‐insight, better coping strategies, self‐confidence and boundaries, mainly attributed to TAP and facilitated by helpful factors in TAP. Significant differences were reported in outcome measures, and analyses indicated increased competency in TAP‐specific skills. No negative side effects were mentioned.DiscussionThis study provides evidence for the feasibility of TAP for depression and the feasibility of using mixed methods in feasibility studies. Future researchers may want to use similar comprehensive mixed methods designs.