bluuebunny/crossref_metadata_2025_split huggingface dataset:
Klotho Regulates Club Cell Senescence and Differentiation in Chronic Obstructive Pulmonary Disease
Authors: Li Min , Chen Bo , Sun Sibo , Wang Kai , Wang Yu , Wu Jianqing 
Published: February 2025

ABSTRACTChronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation and senescence. Previous studies showed that club cells and club cell secretory proteins (CCSP) have anti‐inflammatory roles, which reduced in COPD. Klotho (KL) decreased in human COPD lung tissue. KL‐deficient mice showed aging phenotypes, such as obvious emphysema and premature senility at the early stage, which are characteristics of COPD. However, little is known about the relationship between KL, club cells, and COPD. We speculated lack of KL would aggravate club cell senescence, which contributes to COPD inflammation. We collected COPD lung tissue using single‐cell RNA sequencing (scRNA‐seq), revealing club cells heterogeneity and cellular senescence in COPD. In addition, KL and CCSP expressions were downregulated in cigarette smoke (CS)‐induced COPD mice, associated with increasing age‐related markers. After KL knockout, more ciliated cells appeared where club cells disappeared. Furthermore, KL deficiency aggravated club cell senescence and CSE‐induced pulmonary inflammation. To investigate the specific regulation mechanism, hnRNPA2/B1 was recognised and identified it was the key molecule in KL‐regulated club cell senescence, and neddylation of club cell was a crucial factor contributing to hnRNPA2/B1 downregulation. In vitro, SA‐β‐gal staining suggested the aging phenotype was aggravated in hnRNPA2/B1‐silenced groups, and hnRNPA2/B1 over‐expressed achieved a rescue result. Thus, KL could regulate club cell senescence and differentiation. When CS stimulates the small airway epithelium, KL deficiency aggravates lung inflammation, club cell senescence and dysfunctional of ciliated cell. Targeting neddylation might be a promising strategy to reverse lung aging and club cell senescence. These results provide a mechanism about COPD‐linked lung inflammation.
Once‐Weekly Semaglutide Versus Once‐Daily Liraglutide for Weight Loss in Adults: A Meta‐Analysis of Randomized Controlled Trials
Authors: Hashmi Tallal Mushtaq , Ahmed Mushood , Haider Ali , Naseem Salman , Jafar Uzair , Hussain Munir , Iqbal Javed , Ali Waqar , Ahmed Raheel 
Published: February 2025

ABSTRACTThe effectiveness of glucagon‐like peptide‐1 receptor agonists in facilitating weight loss among patients with diabetes is widely recognized. However, there are limited data available on the relative effectiveness and safety of once‐weekly semaglutide versus once‐daily liraglutide. We conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) identified through a comprehensive search of the Cochrane Library, PubMed, and ScienceDirect databases from inception until July 2024. Statistical analysis was conducted using R version 4.4.1 with the “meta” package, employing a random effects model. Three RCTs with a total of 922 patients were included in our meta‐analysis. The results indicated that OW semaglutide significantly reduced body weight (WMD: −4.55; 95% CI: −6.43, −2.67, p < 0.01), HbA1c (WMD: −0.46; 95% CI: −0.84, −0.08; p = 0.02), and fasting plasma glucose levels (WMD: −1.23; 95% CI: −1.51, −0.95; p < 0.01) in comparison to OD liraglutide. The risk of severe adverse effects (OR, 1.66; 95% CI, 0.53–5.16; p = 0.38) and gastrointestinal adverse effects (OR, 1.84; 95% CI, 0.82–4.14; p = 0.14) was comparable between both groups. Once‐weekly semaglutide therapy results in a more pronounced loss in body weight, HbA1c, and fasting glucose levels compared to once‐daily liraglutide.
Dietary interventions for the management of type 2 diabetes mellitus in childhood and adolescence: A systematic review
Authors: Bhanot Alisha , Hawton Katherine , Perry Rachel , Miller‐Molloy Felix , Blest Francesca , Easter Shelley , Hamilton‐Shield Julian , Candler Toby 
Published: February 2025

AbstractAimsDespite the alarming increasing incidence of type 2 diabetes mellitus (T2DM) in children and young People (CYP), and its associated morbidities and poor long‐term prognosis, there remains uncertainty in its management. Dietary interventions have been shown to be effective in adults with T2DM, but little is known about their effectiveness in CYP. The aim of this systematic review is to provide up‐to‐date evidence regarding dietary interventions for T2DM in childhood and adolescence.MethodsFive databases Embase, MEDLINE, CENTRAL, Web of Science and CINAHL were searched from January 2000 to May 2023 for all studies involving dietary interventions in CYP under 19 years with T2DM. The primary outcome was glycaemic control as measured by HbA1c.ResultsOf 8352 search results, five papers met inclusion criteria. No randomised controlled trials were identified. Two interventional studies (n = 28) found very low energy diets (VLED) were associated with reduced HbA1c (16 mmol/mol (3.6%) reduction after 8 weeks), decreased requirement for pharmacotherapy and weight loss. However, benefits to HbA1c were not sustained over 2 years. From the observational studies, the most frequent self‐reported dietary strategies were limiting sweets and increasing fruit/vegetable intake, but efficacy was limited. Limiting fat intake was associated with improved HbA1c in women.ConclusionsThere is limited evidence and a lack of robust clinical trials to support the effectiveness of dietary interventions for CYP‐onset T2DM. With evidence of benefit in adulthood and encouraging initial results in the young, it is imperative that fully powered randomised trials with longer follow‐up are undertaken to determine efficacy.
GLP‐1 receptor agonists and cardiovascular events in metabolically healthy or unhealthy obesity
Authors: Bucci Tommaso , Alam Uazman , Fauchier Grégoire , Lochon Lisa , Bisson Arnaud , Ducluzeau Pierre Henri , Lip Gregory Y. H. , Fauchier Laurent 
Published: February 2025

AbstractAimsThe associations of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and outcomes among patients with obesity according to the presence of cardiovascular risk factors (metabolically healthy obesity (MHO) or metabolically unhealthy obesity (MUHO)) remain unclear. We examined the associations of GLP‐1RAs with mortality and adverse cardiovascular events in patients with MHO and MUHO.MethodsThe TriNetX network was utilized to select a cohort of patients with MHO or MUHO, and use or non‐use of GLP‐1RAs with propensity score matching (1:1). Cardiovascular events were identified during follow‐up.ResultsA total of 2 983 151 patients with obesity (512 434 with MHO and 2 470 717 with MUHO) were included in the study. Among these, 416 713 (13.9%) were GLP‐1RA users. After propensity score matching, GLP‐1RA use in MUHO was associated with a significantly lower risk of mortality (HR 0.580 [95% CI, 0.566–0.595]), ischemic stroke (HR 0.921 [0.890–0.953]), AF (HR 0.913 [0.888–0.938]) and hospitalization for HF (HR 0.925 [0.900–0.949]) during follow‐up compared with non‐use of GLP‐1RA. Patients with MHO had a markedly lower risk of clinical events than those with MUHO. A trend towards a lower risk of cardiovascular events associated with GLP‐1RA was seen among patients with MHO. There was no statistical interaction in the risk of cardiovascular outcomes with GLP‐1RA use for MHO and MUHO patients.ConclusionsThe use of GLP‐1RAs was associated with lower rates of cardiovascular events than no use in patients with MUHO. Similar but non‐statistically significant trends were seen in patients with MHO.
Novel pharmacotherapies for weight loss: Understanding the role of incretins to enable weight loss and improved health outcomes
Authors: Forst Thomas , De Block Christophe , Del Prato Stefano , Frias Juan , Lautenbach Anne , Ludvik Bernhard , Marinez Marina , Mathieu Chantal , Müller Timo D. , Schnell Oliver 
Published: February 2025

AbstractObesity and type 2 diabetes mellitus (T2D) are widespread diseases that significantly impact cardiovascular and renal morbidity and mortality. In the recent years, intensive research has been performed to assess the role of adipose tissue and body fat distribution in the development of metabolic and non‐metabolic complications in individuals with obesity. In addition to lifestyle modifications, glucagon‐like peptide‐1 receptor agonists (GLP‐1‐RA) have become a meaningful treatment expansion for the management of both disorders. In addition to improving metabolic control and reducing body weight, treatment with GLP‐1‐RAs reduces cardiovascular and renal events in individuals with obesity with and without diabetes. These important benefits of GLP‐1‐RAs have triggered new interest in other enteroendocrine and enteropancreatic peptides for treating obesity and its metabolic and non‐metabolic consequences. The first peptide dual‐agonist targeting glucose‐dependent insulinotropic polypeptide (GIP) and GLP‐1 receptors has been approved for the treatment of T2D and obesity. GIP/GLP‐1 dual‐agonism appear to provide better metabolic control and greater weight reduction compared with GLP‐1‐R mono‐agonism. Other peptide and non‐peptide co‐agonists are in clinical development for obesity, T2D, metabolic dysfunction‐associated steatotic liver disease (MASLD) and other metabolic disorders. This narrative review aims to summarize the available data on approved and emerging enteroendocrine and enteropancreatic based treatment approaches for obesity and metabolic disorders. In addition to available clinical efficacy measures, side effects, limitations and open challenges will also be addressed.
Impact of heart failure medications on cognitive function: A systematic review
Authors: Jahangiri Soodeh , Kazakov Eliot , Amancherla Saipranusha , Kalogeropoulos Andreas P. 
Published: February 2025

AbstractBackgroundHeart failure (HF) often coexists with cognitive impairment and accelerates cognitive decline. However, the impact of HF medications on cognition has received limited attention. This review evaluates the evidence on the cognitive effects of currently recommended medication classes for HF.MethodsSystematic review using PubMed and EMBASE following PRISMA guidelines, employing keywords related to HF, cognitive function and guideline‐recommended HF medications. Eligible studies were randomized controlled trials (RCT) or cohort studies assessing cognitive function in adult HF patients.ResultsThree cohort studies on ACEi/ARBs (N = 5080; 2 prospective, 1 retrospective) reported no significant impact on cognitive function to higher cognitive scores with ACEi/ARBs. Eight studies on sacubitril/valsartan (ARNI, N = 42,143; all observational studies or post‐hoc analyses of RCT) found either no effect on cognitive function or reduced risk of new‐onset dementia and improved cognitive outcomes with ARNI. Beta‐blockers (N = 40; 1 RCT) lacked significant cognitive effects; empagliflozin (SGLT2i, N = 162; 1 prospective) improved cognitive performance in patients with diabetes and HF with preserved ejection fraction; digoxin (N = 1172; 1 retrospective) was associated with enhanced cognitive function; and statins (N = 112,357; 2 retrospective), which are indicated in HF of ischemic aetiology, were not associated with a significant effect on cognition.ConclusionsGuideline‐recommended HF medication classes appear to have neutral effects on cognitive function, and some may even offer cognitive benefits. However, the limited number and mostly observational nature of studies prevent firm conclusions. Further research is necessary to better understand the cognitive impact of HF medications.
Long‐run peer effects and promotion: Evidence from 70‐plus years of career records in Japan
Authors: Arai Natsuki , Nakazawa Nobuhiko 
Published: February 2025

AbstractWe estimate long‐term peer effects in the workplace by investigating whether working with a future executive makes junior employees more likely to be promoted. Using data on career history at the Japanese central administration from 1946 to 2019, we find that long‐term peer effects are substantial and persistent—junior employees who work with a future executive during the first 5 years of their employment are more likely to be promoted to top executive than employees who do not. The empirical results are consistent with the mechanisms of increased human capital, the formation of social connections, and a reduction in information asymmetry.
Attack on Climate: The Persistent Effects of Authoritarianism on Climate Policy Equilibria
Authors: Surdea‐Hernea Vlad 
Published: February 2025

ABSTRACTIn this paper, I examine whether exposure to authoritarian rule, which often focuses on preventing the emergence of pro‐environmental groups that might threaten regime stability, persists after regime collapse and the onset of democratisation. Empirically, I exploit the post‐World War II division of Germany into two states, one of which became a liberal democracy and the other a Soviet‐style autocracy, in a geographic regression discontinuity design. I show that districts from the former East have lower climate policy equilibrium levels, which means that more climate‐ambitious political parties are less likely to receive strong electoral support. Crucially, these effects are independent of East Germans' preferences over other political conflicts, suggesting that authoritarian rule had a direct and persistent effect on environmental attitudes. Moreover, I show that the authoritarian legacy also manifests itself in increased polarisation over climate change policies, which, combined with lower demand for such measures, makes the former East Germany a breeding ground for climate‐sceptical political parties.
Doubt and Transformation in Education
Authors: Schaper Marieke 
Published: February 2025

AbstractFostering transformative experiences is a central goal of education. In this article, Marieke Schaper examines the relationship between doubt and transformation in education, specifically problematizing the idea that doubt can serve as a catalyst for transformative experiences in the classroom. Schaper's thesis is that doubt is not valuable by itself; it must encompass certain characteristics if it is to support meaningful transformation while avoiding the risks of transformative education. In making this argument, Schaper proposes the concept of aspirational doubt as an educationally valuable subcategory of doubt. She begins by engaging with the vast philosophical and psychological literature on doubt and, based on this analysis, identifies five main conceptions of doubt that wield influence. Next, she points to the ethical risks of using doubt as an educational catalyst, particularly for transformative purposes, but instead of rejecting the role of doubt in transformative education, she explores the potential of aspirational doubt to circumvent these risks. She concludes with a discussion of the practical implications for fostering aspirational doubt in the classroom.
The Effect of the Jigsaw Technique on Nursing Students' Learning of Employee Safety and Retention of Knowledge: A Randomized Controlled Research
Authors: Ordu Yadigar , Çalışkan Nurcan 
Published: February 2025

ABSTRACTThe purpose of this study was to determine the effect of the Jigsaw technique on nursing students' learning and retention of knowledge about employee safety. The study was conducted between December 2022 and January 2023 with 84 first‐year students enrolled in the Nursing Department of a state university in a province of Turkey. Data were collected using the Descriptive Characteristics Form and Employee Safety Research/Test Instrument. During the study, the experimental group (n = 42) learned about employee safety using the Jigsaw technique, while the control group (n = 42) used the traditional method. Then, the students filled out the data collection forms (Post‐test). Four weeks after the post‐test, students again filled out the data collection forms to evaluate the retest of knowledge (Retest). The data were analysed with SPSS 22.0 package program. It was determined that the mean research/test instrument score of the experimental group in the employee safety post‐test and retest was statistically significantly higher than the control group (p = 0.000). It was determined that the Jigsaw technique was effective in nursing students' learning of employee safety and retest of knowledge.
Gamma Transcranial Alternating Current Stimulation Has Frequency‐Dependent Effects on Human Motor Cortex Plasticity Induced by Theta‐Burst Stimulation
Authors: Liao Wei‐Yeh , Hand Brodie J. , Cirillo John , Sasaki Ryoki , Opie George M. , Goldsworthy Mitchell R. , Semmler John G. 
Published: February 2025

ABSTRACTLong‐term potentiation (LTP)‐like plasticity in primary motor cortex (M1) induced by intermittent theta burst stimulation (iTBS) can be enhanced by transcranial alternating current stimulation (tACS) at a gamma frequency of 70 Hz. Recent evidence suggests that there is some frequency specificity in the effects of tACS on motor function within the midgamma band (60–90 Hz). The purpose of this study was to examine the effect of different tACS frequencies within the gamma band on the neuroplastic response to iTBS. Seventeen healthy young adults performed four experimental sessions, where iTBS was combined with different tACS conditions (60, 75 and 90 Hz, sham) over M1 using a tACS‐iTBS costimulation approach. Motor evoked potential (MEP) amplitude and short‐interval intracortical inhibition (SICI) were assessed from a hand muscle before and after the intervention using transcranial magnetic stimulation with posterior–anterior (PA) and anterior–posterior (AP) coil orientations. Gamma tACS‐iTBS costimulation increased PA and AP MEPs when gamma tACS was applied at 90 Hz, but not at 75 or 60 Hz, compared with sham tACS. PA and AP SICI was reduced by tACS‐iTBS costimulation, but this was not influenced by gamma tACS frequency. Gamma tACS can increase LTP‐like plasticity when combined with iTBS over M1, with the largest effect observed when tACS was applied at higher gamma frequencies. The functional relevance of targeting higher gamma frequencies within different brain areas and study populations remains to be determined.
Heterozygous PNPT1 Variants Cause a Sensory Ataxic Neuropathy
Authors: Haddad Saif , Record Christopher J. , Self Eleanor , Skorupinska Mariola , Rossor Alexander M. , Laura Matilde , Ingle Gordon , Manzur Adnan , Muntoni Francesco , Blake Julian C. , Reilly Mary M. 
Published: February 2025

ABSTRACTBackgroundBiallelic variants in polyribonucleotide‐nucleotidyltransferase‐1 (PNPT1) have been associated with a range of phenotypes from syndromic hearing loss to Leigh's syndrome. More recently, heterozygous variants in PNPT1, have been reported in three families with cerebellar ataxia and prominent sensory neuropathy.MethodsWhole genome sequencing was performed in two families with autosomal dominant sensory ataxic neuropathy (SAN).ResultsSegregating heterozygous splice site (c.2014‐3C>G) and nonsense (p.Arg715Ter) variants were detected in both families. All patients initially presented with an isolated SAN clinically and neurophysiologically with subsequent variable cerebellar involvement.ConclusionWe report two heterozygous PNPT1 variants in two families with a predominant SAN, including the novel p.Arg715Ter. This strengthens the argument of PNPT1 causing dominant disease and highlights a new cause for dominantly inherited SAN.
GLP‐1 Agonists as Potential Neuromodulators in Development of Parkinson's Disease: A Nationwide Cohort Study
Authors: Gamborg Mads , Grand Mia Klinten , Arvedsen Jasmin , Meaidi Amani , Mørch Lina Steinrud 
Published: February 2025

ABSTRACTBackgroundParkinson's disease is a progressive neurodegenerative disorder with no cure. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) may have neuroprotective effects. However, long‐term real‐world studies are needed to clarify their potential impact on Parkinson's disease.MethodsThis nationwide cohort study included 33,462 patients (16,731 GLP‐1RA initiators and 16,731 propensity score‐matched dipeptidyl peptidase‐4 inhibitor [DPP‐4i] initiators) from 2007 to 2018, followed until 2022. Eligible participants were ≥ 50 years, had no prior cancer or Parkinson's disease, and were residents in Denmark for at least 10 years. Patients were followed until Parkinson's diagnosis, death, emigration, treatment discontinuation (no additional prescription within 180 days), switch to the other study drug, or end of follow‐up. Additional analyses included comparisons with insulin, competing risk of death, and the main analysis disregarding adherence.ResultsDuring follow‐up, 192 patients developed Parkinson's disease, including 93 during sustained treatment. After 10 years, sustained GLP‐1RA users had a lower hazard ratio (HR 0.57 (95% CI 0.37;0.85)) and absolute risk difference (−0.24 (95% CI −0.63 to 0.15)) compared to DPP‐4i users. Similar trends were found when using insulin as a comparator. A significant survival advantage was found among sustained users of GLP‐1RA (particularly when comparing with insulin). When not accounting for adherence, the results was not statistically significant.ConclusionsResults were suggestive for a potential neuroprotective effect of GLP‐1RAs against Parkinson's disease. Further studies are needed to assess biomarkers of disease progression, and evaluate safety in patients with Parkinson's disease, dosing, and effects when combined with other treatments in neurodegenerative diseases.
Impact of glucocorticoids on osteocytes and on the lacuno‐canalicular system of maxillary and mandibular alveolar bone
Authors: Rodriguez Juliana , Lacave Mariela , Sánchez Luciana Marina , De Lucca Romina Carmen , Tasat Deborah Ruth , Bozal Carola Bettina 
Published: February 2025

AbstractIn long bones, glucocorticoids are known to cause a decrease in bone formation and an increase in bone resorption, leading to a condition of osteoporosis also during growth. However, there are few studies on the effect of glucocorticoids on alveolar bone. The aim of the present study was to evaluate the impact of chronic administration of glucocorticoids on osteocytes and the lacuno‐canalicular system of maxillary and mandibular alveolar bone in growing rats. Male Wistar rats were administered intramuscular dexamethasone (7 mg/kg b.w.) or saline solution once a week for 5 weeks. After euthanasia, mandibles and upper maxillae were resected and processed for micro‐computed tomography, histological, and immunohistochemical evaluation. Glucocorticoids induced morphological changes in the lacuno‐canalicular system and apoptosis of alveolar bone osteocytes and had no effect on SOST/sclerostin osteocyte expression. Our findings suggest that the deleterious effect of glucocorticoids on alveolar bone is associated with osteocyte apoptosis and lacuno‐canalicular system changes, whereas Wnt/β catenin pathway regulation in osteocytes appears to play no significant role in the pathogenesis of glucocorticoid‐induced bone loss.