bluuebunny/crossref_metadata_2025_split huggingface dataset:
The flavonoid resokaempferol improves insulin secretion from healthy and dysfunctional pancreatic β‐cells
Authors: Gautheron Guillaume , Péraldi‐Roux Sylvie , Vaillé Justine , Belhadj Sahla , Patyra Andrzej , Bayle Morgane , Youl Estelle , Omhmmed Soufiyan , Guyot Mélanie , Cros Gérard , Guichou Jean‐Francois , Uzan Benjamin , Movassat Jamileh , Quignard Jean‐François , Neasta Jérémie , Oiry Catherine 
Published: September 2024

Background and PurposeThe pharmacology of flavonoids on β‐cell function is largely undefined especially in the context of defective secretion of insulin. We sought to identify flavonoids that increased the insulin‐secreting function of β‐cells and to explore the underlying mechanisms.Experimental ApproachINS‐1 β‐cells in culture and islets of Langerhans isolated from control and diabetic male rats were used for insulin secretion experiments. Pharmacological and electrophysiological approaches were used for mechanistic studies.Key ResultsAmong a set of flavonoids, exposure of INS‐1 β‐cells to resokaempferol (ResoK) enhanced glucose‐stimulated insulin secretion and therefore we further characterised its activity and its pharmacological mechanism. ResoK glucose‐dependently enhanced insulin secretion in INS‐1 β‐cells and pancreatic islets isolated from rats. Mechanistically, whole cell patch clamp recordings in INS‐1 cells showed that ResoK rapidly and dose‐dependently enhanced the L‐type Ca2+ current whereas it was inactive towards T‐type Ca2+ current. Accordingly, pharmacological inhibition of L‐type Ca2+ current but not T‐type Ca2+ current blocked the effects of ResoK on glucose‐stimulated insulin secretion. ResoK was still active on dysfunctional β‐cells as it ameliorated glucose‐stimulated insulin secretion in glucotoxicity‐induced dysfunctional INS‐1 cells and in pancreatic islets isolated from diabetic rats.Conclusion and ImplicationsResoK is a glucose‐dependent activator of insulin secretion. Our results indicated that the effects of ResoK on insulin secretion involved its capacity to stimulate L‐type Ca2+ currents in cultured β‐cells. As ResoK was also effective on dysfunctional β‐cells, our work provides a new approach to stimulating insulin secretion, using compounds based on the structure of ResoK.
Protection of the genome and the central exome by peripheral non‐coding DNA against DNA damage in health, ageing and age‐related diseases
Authors: Qiu Guo‐Hua , Fu Mingjun , Zheng Xintian , Huang Cuiqin 
Published: September 2024

ABSTRACTDNA in eukaryotic genomes is under constant assault from both exogenous and endogenous sources, leading to DNA damage, which is considered a major molecular driver of ageing. Fortunately, the genome and the central exome are safeguarded against these attacks by abundant peripheral non‐coding DNA. Non‐coding DNA codes for small non‐coding RNAs that inactivate foreign nucleic acids in the cytoplasm and physically blocks these attacks in the nucleus. Damage to non‐coding DNA produced during such blockage is removed in the form of extrachromosomal circular DNA (eccDNA) through nucleic pore complexes. Consequently, non‐coding DNA serves as a line of defence for the exome against DNA damage. The total amount of non‐coding DNA/heterochromatin declines with age, resulting in a decrease in both physical blockage and eccDNA exclusion, and thus an increase in the accumulation of DNA damage in the nucleus during ageing and in age‐related diseases. Here, we summarize recent evidence supporting a protective role of non‐coding DNA in healthy and pathological states and argue that DNA damage is the proximate cause of ageing and age‐related genetic diseases. Strategies aimed at strengthening the protective role of non‐coding DNA/heterochromatin could potentially offer better systematic protection for the dynamic genome and the exome against diverse assaults, reduce the burden of DNA damage to the exome, and thus slow ageing, counteract age‐related genetic diseases and promote a healthier life for individuals.
Impact of glucagon‐like peptide‐1 receptor agonists on diabetic retinopathy: A meta‐analysis of clinical studies emphasising retinal changes as a primary outcome
Authors: Kapoor Ishani , Sarvepalli Swara M. , D'Alessio David A. , Hadziahmetovic Majda 
Published: September 2024

AbstractBackgroundTo determine if glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) are associated with the development and progression of diabetic retinopathy (DR).MethodsA systematic search was conducted on PubMed, Cochrane Library, and Embase from inception to February 2024 to identify clinical studies reporting the development of and changes in DR as the primary outcome in patients with type 2 diabetes taking GLP‐1RA, insulin, or oral antidiabetic medication (OAD). Two researchers independently completed the search and referred to a third as necessary. Data for meta‐analysis was pooled using a random‐effects model.ResultsAnalysis of seven studies representing 242 537 patients showed a significantly decreased risk of incidence of DR between GLP‐1RA and insulin use (RR = 0.66, 95% CI (0.48, 0.91), p = 0.01). There was no difference in the risk of DR complications (e.g., vitreous haemorrhage, retinal detachment, or requiring treatment with intravitreal injections, lasers, vitrectomy). Between GLP‐1RA and OAD use, there was no difference in the risk of incidence of DR, while there was a significantly increased risk of DR complications (RR = 1.39, 95% CI (1.07, 1.80), p = 0.01).ConclusionOur findings indicate no elevated risk of incidence of DR linked to GLP‐1RA compared to insulin. In fact, GLP‐1RA may offer potential advantages over insulin regarding the overall incidence of DR. The increased risk of DR requiring treatment and associated complications in the GLP‐1RA group compared to OAD may be due to the transient progression of DR associated with a rapid decrease in HbA1c – a phenomenon not specific to GLP‐1RA and warrants further investigation.
Unpacking the European Commission: Cabinet Composition and EU Policy‐Making
Authors: Daniel William T. , Hurka Steffen 
Published: September 2024

AbstractWe examine bureaucratic politics within the European Commission, using novel data on the backgrounds of individual members of Commissioners' cabinets. Although cabinet composition has become increasingly regulated in recent decades, its selection remains a key area for personalised political appointments within an organisation more commonly known for its collective responsibility and lack of individual influence. Using data on the personal and professional backgrounds of cabinet members since the first Barroso Commission, we trace how administrative reforms meant primarily to ‘de‐nationalise’ the selection of appointees have led to changes in cabinet composition. We then explore how cabinet composition impacts on the complexity of Commission proposals and its subsequent inter‐institutional negotiations. We find that whilst more diversity of Commission cabinets clearly enhances the input legitimacy of the EU's legislative process, it neither benefits nor threatens the quality of the Commission's policy proposals or how they are processed politically.
Efficacy and safety of RS plus bevacizumab versus RS plus fruquintinib as the third‐line therapy in patients with refractory metastatic colorectal cancer: A real‐world propensity score matching study
Authors: Zhou Yuwen , Xu Qian , Wang Jialing , Leng Wei‐Bing , Cao Peng , Chen Ye , Luo De‐Yun , Qiu Meng , Liu Jiyan 
Published: September 2024

AbstractBackgroundThis study aims to compare the effectiveness and safety of the combination of raltitrexed, S‐1 (RS), and fruquintinib with the combination of RS and bevacizumab in patients with refractory metastatic colorectal cancer (mCRC).MethodsThis retrospective cohort included mCRC patients who received the RS plus fruquintinib or regorafenib as the third‐line therapy from May 2019 to April 2023. A propensity score matching (PSM) analysis was used to balance the baseline characteristics of all patients. Overall survival (OS), progression‐free survival (PFS), tumor response, and safety of the two regimens were evaluated.ResultsOf the 153 patients enrolled, 123 patients received the RS plus bevacizumab and 30 patients received the RS plus fruquintinib. After PSM, 30 pairs were analyzed. Patients treated with RS plus fruquintinib had a longer PFS than those treated with RS plus bevacizumab before PSM (5.0 months vs. 4.3 months, p = 0.008) and after PSM (5.0 months vs. 4.4 months, p = 0.012). A longer OS was also observed in RS plus fruquintinib group before PSM and after PSM, but there was no statistic difference between two groups after PSM. Both objective response rate and disease control rate were higher in the RS plus fruquintinib cohort than those in the RS plus bevacizumab cohort before PSM, and the difference in values between the two groups reduced after PSM. The adverse effects (AEs) of both groups were well tolerated.ConclusionIn patients with refractory mCRC, RS plus fruquintinib demonstrated a superior OS, PFS than RS plus bevacizumab and had manageable AEs.
Dentoskeletal changes of long‐term oral appliance treatment in patients with obstructive sleep apnea: A systematic review and meta‐analysis
Authors: Chen Yanlong , Alhozgi Abdalgader I. , Almeida Fernanda R. 
Published: September 2024

AbstractPurposeThis systematic review and meta‐analysis aimed to evaluate the dental and skeletal effects of the long‐term oral appliance (OA) treatment in patients with obstructive sleep apnea (OSA) and provide insights for clinicians in treatment planning and decision‐making for OSA patients undergoing OA treatment.Materials and MethodsA comprehensive literature search was conducted in major databases up to April 2024. Studies were included if they assessed long‐term OA treatment (≥6 months) in adults with OSA using any type of mandibular advancement device (MADs) or tongue retaining device (TRD). Dental and skeletal changes, measured by dental cast and cephalometric analysis, were the primary outcomes.ResultsA total of 42 studies were included in the systematic review, with 23 included in the meta‐analysis. Long‐term OA treatment was associated with a significant decrease in overbite (0.87 mm, 95% CI: 0.69–1.05) and overjet (0.86 mm, 95% CI: 0.69–1.03). Subgroup analyses showed the decrease of overbite and overjet progressively changed over the years intervals. There was a significant retroclination of the upper incisors (U1‐SN, 2.58°, 95% CI: 1.07–4.08) and proclination of the lower incisors (L1‐MP, ‐2.67° (95% CI: ‐3.78–1.56). Skeletal changes were not significant.ConclusionOverbite and overjet gradually decreased in the long‐term OA treatment, which might predominantly result from the retroclination of the upper incisors and the proclination of the lower incisors. The skeletal patterns in the anteroposterior and vertical direction might remain relatively stable over time. There was a tendency for the clockwise rotation of the mandible.
Levels of matrix metalloproteinase‐1 (MMP‐1), MMP‐2, MMP‐3, osteopontin, pentraxin‐3, and thymic stromal lymphopoietin in crevicular fluid samples from peri‐implantitis, periodontitis, and healthy sites
Authors: Jansson Leif , Lundmark Anna , Modin Carolina , Gustafsson Anders , Yucel‐Lindberg Tülay 
Published: September 2024

AbstractAimPeriodontitis and peri‐implantitis are chronic inflammatory diseases characterized by the destruction of supporting tissues. Despite some similarities, it is essential to understand the differences in how these diseases elicit unique host responses within the oral tissues, including the production of selected matrix metalloproteinases (MMPs) and inflammatory mediators involved in tissue remodelling. The aim of this study was to evaluate the levels of proteolytic enzymes MMP‐1, MMP‐2, MMP‐3, as well as the inflammatory mediators osteopontin (OPN), pentraxin‐3 (PTX3), and thymic stromal lymphopoietin (TSLP) in crevicular fluid samples collected from healthy, periodontitis‐affected, and peri‐implantitis sites.MethodsGingival crevicular fluid (GCF) and peri‐implant crevicular fluid (PICF) samples were collected from healthy and diseased teeth and implant sites of 163 patients. The MMP‐1, MMP‐2, MMP‐3, OPN, PTX3, and TSLP levels were determined using commercially available immunoassays. A linear mixed model procedure was adopted for multilevel analyses, using biomarker levels as the outcome variable to compare two types of sites. The diagnostic accuracy of the biomarkers was evaluated by Youden's index to estimate the sensitivity, specificity and the area under curve (AUC).ResultsThe levels of MMP‐1, MMP‐2, MMP‐3, OPN, and TSLP were higher at sites with periodontitis and peri‐implantitis compared to the levels at sites with healthy teeth and healthy implants. No significant differences were observed in the levels of the measured markers between the sites diagnosed with periodontitis and those diagnosed with peri‐implantitis. The highest diagnostic potential at implant sites was found for MMP‐2 (AUC = 0.74) and TSLP (AUC = 0.72). The highest AUC (0.82) at tooth sites was found for OPN.ConclusionsThe findings indicate that the proteolytic enzyme MMP‐2 and the cytokine TSLP might be potential biomarkers for both periodontitis and peri‐implantitis, whereas the proinflammatory cytokine OPN may serve as a biomarker for periodontitis. Further studies are required to confirm the utility of these biomarkers and explore their potential clinical applications.
Predictability of sleep in insomnia: sleep patterns of patients from a sleep psychology clinic
Authors: Laroche Dave , Ivers Hans , Bastien Celyne H. , Vallières Annie 
Published: September 2024

SummaryThe present study aims at identifying sleep patterns in insomnia in a clinical sample using three strategies to define poor nights. Sleep diaries and self‐reported questionnaires were collected from 77 clinical patients with insomnia. The conditional probabilities of observing a poor night after 1, 2, or 3 consecutive poor nights were computed according to three strategies with same criteria for sleep onset latency, wake after sleep onset, and sleep efficiency, but varying criterion for total sleep time. Latent profile analyses were conducted to derive sleep patterns. Uni‐ and multivariate analyses were conducted to characterise the sleep patterns identified. A total of 1586 nights were analysed. The strategy used significantly influenced the average percentage of reported poor nights. Two to three sleep patterns were derived per strategy. Within each strategy, sleep patterns differed from each other on sleep variables and night‐to‐night variability. Results suggest the existence of sleep patterns in insomnia among individuals consulting in psychological clinics. Adding a total sleep time of 6‐h cut‐off as a criterion to define poor nights increases the accuracy of the strategy to define poor night and allows to identify sleep patterns of poor nights in insomnia.
Observed and expected reliability of echocardiographic volumetric methods and critical change values for quantification of mitral regurgitant fraction in dogs
Authors: Loughran Kerry A. , Kraus Marc S. , Achilles Erin J. , Huh Terry , Larouche‐Lebel Éva , Massey Laura K. , Gelzer Anna R. , Oyama Mark A. 
Published: September 2024

AbstractBackgroundReliability of echocardiographic calculations for stroke volume and mitral regurgitant fraction (RFMR) are affected by observer variability and lack of a gold standard. Variability is used to calculate critical change values (CCVs) that are thresholds representing real change in a measure not associated with observer variability.HypothesisObserved intra‐ and interobserver accuracy and variability in healthy dogs help model CCV for RFMR.AnimalsReliability cohort of 34 healthy dogs; allometric scaling cohort of 99 dogs with heart disease and 25 healthy dogs.MethodsAccuracy, variability, and CCV of 2 observers using geometric and flow‐based echocardiography were prospectively compared against a standard of RFMR = 0% and extrapolated across a range of expected RFMR values in the reliability cohort partly derived from cardiac dimensions predicted by the allometric cohort.ResultsAccuracy of methods to determine RFMR in descending order was 4‐chamber bullet (Bullet4CH), mitral inflow, cube formula, and Simpson's method of disks. Intraobserver variability was relatively high. The CCV for RFMR ranged from 28% to 88% and was inversely related to RFMR when extrapolated for use in affected dogs. For both observers, the Bullet4CH method had the lowest intraobserver CCV (Operator 1:28%, Operator 2:41%). Interobserver strength of agreement was low with intraclass correlation coefficients ranging from 0.210 to 0.413.Conclusions and Clinical ImportanceEchocardiographic volumetric methods used to calculate stroke volume and RFMR have low accuracy and high variability in healthy dogs. Extrapolation of observed CCV to a range of expected RFMR suggests observers and methods are not interchangeable and variability might hinder routine clinical usage. Individual observers should be aware of their own variability and CCV.
Pathology of IgA nephropathy: A global perspective
Authors: Roberts Ian S. D. 
Published: September 2024

AbstractWorldwide adoption of the Oxford Classification of IgA nephropathy (IgAN) has enabled comparison of pathology data from clinicopathological studies in different regions of the world. It is apparent that the frequency of Oxford Classification MEST‐C scores shows geographic variations. These in part reflect differences in the stage of disease at diagnosis, criteria for performing biopsies and inclusion in clinical studies, and pathologist reporting practice. However, there appears to be a true geographic difference in the frequency of glomerular inflammation and crescents with a 2–3 fold greater proportion of patients showing these changes in East Asia when compared to Europe and North America. This indicates that the pathology of IgAN is influenced by genetic background. Geographic differences in the pathology of IgAN might underly the reported differences in clinical presentation and outcome in different regions of the world, and has important implications for clinical trials and patient management.
B cell targeting in IgA nephropathy
Authors: Suzuki Yusuke 
Published: September 2024

AbstractThe “multi‐hit theory/4‐hit theory” pathogenesis hypothesis is widely accepted and IgA nephropathy (IgAN) is understood to be a disease originating from Hit 1, galactose deficient IgA1 (GdIgA1). The chronic repetitive activation of the complement pathway (alternative and lectin pathways) and the subsequent inflammation results in progressive glomerular damage that spills over into increased intraglomerular pressure and other hemodynamic changes, increased urinary protein, glomerulosclerosis, and tubulointerstitial fibrosis. The basic pathophysiology of this disease is the progression of a mixture of such acute and chronic pathologies. Currently, a number of new drugs has emerged as promising agents, such as complement regulators, endothelin receptor antagonists, and SGLT2 inhibitors, which are associated with each pathological step after glomerular deposition of GdIgA1/immune complexes. On the other hand, the molecular mechanisms of GdIgA1 production are gradually being elucidated, and the development of several novel therapeutic agents targeting the responsible B cells and their international clinical trials are progressing. These agents that inhibit or control the production of the Hit1, GdIgA1, are highly expected as essential therapies for this disease.The large body of clinical and basic research findings to date strongly suggest that nephritogenic GdIgA1 is a polymeric IgA1 of mucosal origin. In addition, the B cells involved in its nephritogenic GdIgA1 production are mainly differentiated mature B cells such as plasma cells, which may migrate to the bone marrow as well as the mucosa. The innate immune system in the mucosa, especially Toll‐like receptors (TLRs), is thought to be involved in their production. Among TLRs, TLT9 and TLR7, which recognize bacterial and viral unmethylated DNA and RNA, have been reported to be involved. The mucosal activation of these TLRs is associated with the production of APRIL (A Proliferation Inducing Ligand) and BAFF (B cell activating factor), which are TNF superfamily cytokines involved in B cell maturation, survival, and IgA class switching, and may also be involved in the production of nephritogenic GdIgA1. It is still inconclusive whether APRIL or BAFF is more closely involved in the production of nephritogenic GdIgA1. Phenotypes in transgenic animal models suggest BAFF involvement, however, a genome wide association study (GWAS) analysis of human IgAN has identified APRIL, not BAFF, as a candidate gene.Based on the above background, several international clinical trials are underway for drugs such as TLR regulators (hydroxychloroquine), anti‐APRIL drugs, anti‐BAFF drugs, APRIL/BAFF receptor (TACI) binding inhibitors, and cytoreductive drugs (proteasome inhibitors, anti‐CD38 antibodies) to inhibit nephritogenic GdIgA1 production in responsible B cells.This session will provide an overview of the responsible B cells, their GdIgA1 production mechanism, and ongoing drugs.
First patient diagnosed with lipoprotein glomerulopathy and Alport syndrome
Authors: Yang Lianlian , Yang Guang , Guo Hui 
Published: September 2024

AbstractAlport syndrome (AS) is one of the most common inherited kidney disorders, involving pathogenic variants of COL4A3, COL4A4 and COL4A5 genes that lead to disruption of the normal structure of collagen IV protein through improper chain or heterotrimer folding or degradation of heterotrimer components. Lipoprotein glomerulopathy (LPG) is an autosomal dominant disease involving APOE gene mutations disturbing lipoprotein metabolism. We report the first case with both AS and LPG in an 11‐year‐old girl. The patient presented with blepharedema, and decreased vision. Laboratory examinations showed hematemesis, proteinuria, hypoproteinemia, hyperlipidemia and progressive renal failure. Renal biopsy showed the changes of LPG and AS. Whole‐exome sequencing (WES) identified two pathogenic variants, c.127C > T in exon 3 of APOE gene, and c.930 + 1G > A in exon 15 of COL4A4 gene. We emphasize the importance of early completion of renal biopsy and WES for early diagnosis of LPG and AS.
An inquiry into the radial patterning of root hair cell distribution in eudicots
Authors: Lee Kyeonghoon , Hyun Jin‐Oh , Cho Hyung‐Taeg 
Published: September 2024

Summary

The root epidermis of tracheophytes consists of hair‐forming cells (HCs) and nonhair cells (NCs). The HC distribution pattern is classified into three types: random (Type I), vertically alternating (Type II), and radial (Type III). Type III is found only in core eudicots and is known to be position‐dependent in superrosids with HCs positioned between two underlying cortical cells. However, the evolution of Type III and the universality of its position dependency in eudicots remain unclear.

We surveyed the HC distribution in basal and Type III‐exhibiting core eudicots and conducted genomic analyses to get insight into whether eudicots share the same genetic network to establish Type III.

Our survey revealed no canonical Type III in basal eudicots but a reverse Type III, with NCs between two cortical cells and HCs on a single cortical cell, in Papaveraceae of basal eudicots. Type III‐exhibiting species from both superrosids and superasterids showed the canonical position dependency of HCs. However, some key components for Type III determination were absent in the genomes of Papaveraceae and Type III‐exhibiting superasterids.

Our findings identify a novel position‐dependent type of HC patterning, reverse Type III, and suggest that Type III emerged independently or diversified during eudicot evolution.