bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melatonin‐Supplemented Obese Female Mice Show Less Inflammation in Ovarian Adipocytes and Browning in Subcutaneous Adipocytes
Authors: Nagagata Brenda A. , Mandarim‐de‐Lacerda Carlos A. , Aguila Marcia Barbosa 
Published: December 2024

ABSTRACTWe hypothesized that melatonin (Mel) supplementation may offer therapeutic benefits for obesity, particularly in women. Therefore, the study evaluated Mel's effects on white adipose tissue (WAT) in diet‐induced obese female mice. Four‐week‐old C57BL/6 females were assigned to either a control diet (C group) or a high‐fat diet (HF group) for 6 weeks (n = 20/group). Following this, Mel was administered (10 mg/kg/day) for 8 weeks (n = 10/group), resulting in four groups: C, CMel, HF, and HFMel. The HF group developed obesity. HFMel displayed reduced fat pad size, lower plasma insulin, and improved glucose tolerance and insulin resistance compared to HF. In ovarian WAT (oWAT), HFMel versus HF showed reduced pro‐inflammatory markers, less endoplasmic reticulum (ER) stress, and smaller adipocyte size. In subcutaneous WAT (sWAT), HFMel versus HF demonstrated increased adipocyte multiloculation, higher uncoupling protein‐1 expression, and elevated thermogenic gene expression. Principal component analysis of gene expressions in oWAT and sWAT revealed significant differences: in oWAT, ER stress and inflammation markers were linked to the HF group, while HFMel and CMel clustered together, indicating a beneficial Mel effect. In sWAT, HFMel and CMel clustered on the opposite side of HF, which is associated with thermogenic gene expressions. In conclusion, the findings demonstrate that Mel supplementation in obese female mice, even when maintained on an HF diet, effectively modulated weight gain and reduced ovarian and subcutaneous fat accumulation. Mel supplementation positively influenced insulin resistance, inflammation, and ER stress while promoting thermogenesis in WAT in obese female mice.
Epigenetic Regulation by Histone Methylation and Demethylation in Freeze‐Tolerant Frog Kidney
Authors: Taiwo Olawale O. , Breedon Sarah A. , Storey Kenneth B. 
Published: December 2024

ABSTRACTThe wood frog (Rana sylvatica) endures whole‐body freezing over the winter, with extensive extracellular ice formation and halted physiological activities. Epigenetic mechanisms, including reversible histone lysine methylation, enable quick alterations in gene expression, helping to maintain viability during freeze‐thaw cycles. The present study evaluated eight histone lysine methyltransferases (KMTs), 10 histone lysine demethylases (KDMs), and 11 histone marks in wood frog kidneys. Using immunoblotting, significant changes in relative protein levels of multiple KMTs and KDMs were observed in response to freezing, with variable alterations during thawing. Specifically, the repressive methyl marks H3K27me1 and H4K20me3 significantly decreased during freezing, whereas H3K9me3, H3K27me3, and H3K36me2 decreased during thawing. These results demonstrate that the regulation of histone methylation and demethylation play crucial roles in controlling gene expression over the freeze‐thaw cycle and the maintenance of normal renal physiology.
20 Jahre nach der Entdeckung von Graphen: Zweidimensionale Materialien
Authors: Schubert Ulrich 
Published: December 2024

ZusammenfassungFeststoffe mit zweidimensionaler Ausdehnung aber nur wenigen Nanometern Dicke sind seit der Entdeckung von Graphen in den Fokus wissenschaftlichen Interesses gerückt. Es gelang nicht nur, Einzelschichten von anderen schichtartig aufgebauten Feststoffen zu exfolieren, sondern auch, neue Methoden zur Erzeugung und Stabilisierung von 2D‐Nanostrukturen zu entwickeln. Am Beispiel von Metalldichalkogeniden, hexagonalem Bornitrid, Silicen und Übergangsmetallcarbid/nitrid‐Phasen (MXene) werden in diesem Artikel exemplarisch Synthesemethoden und Eigenschaften von 2D‐Materialien vorgestellt.
Doping Control Analysis of Methylsulfonylmethane in Horses
Authors: Wong Jenny K. Y. , Choi Timmy L. S. , Wong Celia O. L. , Curl Peter , Wan Terence S. M. , Ho Emmie N. M. 
Published: December 2024

ABSTRACTMethylsulfonylmethane (MSM), also known as dimethyl sulfone, is a naturally occurring sulphur‐containing compound that can be found in plants, animals and humans. MSM can also be a metabolite of dimethyl sulfoxide (DMSO). Due to their anti‐inflammatory and analgesic effects, both MSM and DMSO are prohibited substances in horseracing. As both substances are naturally occurring, their misuse in horses is controlled by International Residue Limits (IRL) of 1200 and 15 μg/mL, respectively, in horse urine as established by the International Federation of Horseracing Authorities. The elimination of DMSO in horses has been reported; however, there has been no report on the elimination of MSM in horses. This paper describes a pilot study of an administration study of MSM in two geldings following one scoop (~15 g) of Pure MSM twice daily for six consecutive days. MSM in post‐administration urine and blood samples was quantified by gas chromatography–mass spectrometry after sample dilution, with additional protein precipitation for the blood samples. The elimination profiles of MSM in urine and blood are described. The maximum detection time in urine at the IRL of 1200 μg/mL was around 4.5 days after the last dose. Plasma MSM in both horses was around 120 μg/mL at 4.4 days after the last dose, which was the last blood sample collected. As such, 120 μg/mL may indicate a possible IRL for controlling MSM in horse blood. The analysis of DMSO in post‐MSM‐administration samples showed that DMSO is not a significant metabolite of MSM in horses.
B Cell Receptor Repertoire Analysis of the CD21lo B Cell Compartment in Healthy Individuals, Patients With Sjögren's Disease, and Patients With Radiographic Axial Spondyloarthritis
Authors: Wilbrink Rick , van der Weele Linda , Spoorenberg Anneke J. P. L. , de Vries Niek , Niewold Ilse T. G. , Verstappen Gwenny M. , Kroese Frans G. M. 
Published: December 2024

ABSTRACTB cells with low or absent expression of CD21 (CD21lo B cells) gained attention due to their expansion in the peripheral blood of patients with immune‐mediated, rheumatic diseases. This is not only observed in typical autoimmune diseases like systemic lupus erythematosus and Sjögren's disease (SjD) but also in radiographic axial spondyloarthritis (r‐axSpA), which is considered an autoinflammatory disease. To gain more insight into the origins of the heterogeneous CD21lo B‐cell population, and its relation to the plasmablast (PB) compartment, we profiled the B‐cell‐receptor (BCR) repertoire in CD27− and CD27+ fractions of CD21lo B cells and early PBs using next‐generation sequencing. Populations were sorted from peripheral blood of healthy individuals, SjD patients, and r‐axSpA patients (n = 10 for each group). In healthy individuals and both patient groups, our findings indicate that CD27−CD21lo B cells, which exhibit few mutations in their BCR, may develop into CD27+CD21lo B cells and PBs, both marked by considerably more mutations. Given the known expansion of circulating CD27−CD21lo B cells in SjD and r‐axSpA patients and clonal relationships with both CD27+CD21lo B cells and early PBs, these cells might actively contribute to (pathological) immune responses in rheumatic diseases with autoimmune and/or autoinflammatory characteristics.
Enhancing Equity in Genomics: Incorporating Measures of Structural Racism, Discrimination, and Social Determinants of Health
Authors: Rajagopalan Ramya M. , D'Antonio Matteo , Fujimura Joan H. 
Published: December 2024

AbstractThe everyday harms of structural racism and discrimination, perpetuated through institutions, laws, policies, and practices, constitute social determinants of health, but measures that account for their debilitating effects are largely missing in genetic studies of complex diseases. Drawing on insights from the social sciences and public health, we propose critical methodologies for incorporating tools that measure structural racism and discrimination within genetic analyses. We illustrate how including these measures may strengthen the accuracy and utility of findings for diverse communities, clarify elusive relationships between genetics and environment in a racialized society, and support greater equity within genomics and precision health research. This approach may also support efforts to build and sustain vital partnerships with communities and with other fields of research inquiry, centering community expertise and lived experiences and drawing on valuable knowledge from practitioners in the social sciences and public health to innovate biomedical and genomic study designs aimed at community health priorities.
The UN Declaration on the Rights of Indigenous Peoples and Genomics: Ethical Complementarity for Just Research
Authors: Garba Ibrahim , Carroll Stephanie Russo 
Published: December 2024

AbstractGovernance of biomedical research in the United States has been characterized by ethical individualism, a mode of reasoning that treats the individual person as the center of moral concern and analysis. However, genomics research raises ethics issues that uniquely affect certain genetically related communities as collectives, not merely as aggregates of individuals. This is especially true of identifiable populations—including Indigenous Peoples—that are often minoritized, socially marginalized, or geographically isolated. We propose an alternative, complementary framework based on the United Nations Declaration on the Rights of Indigenous Peoples (UNDRIP) (2007), which explicitly recognizes both individual and collective rights. We use the CARE Principles for Indigenous Data Governance as a case study to show how this UNDRIP‐based framework can complement the individual‐focused national standard for research oversight represented by the Belmont principles, thereby better protecting Indigenous Peoples’ rights and interests in genomic data.
Numerical Simulations of Heat and Mass Transfer Enhancement Over a Rotating Cone
Authors: Zaman Saquib Ul , Ahmad Sameed 
Published: December 2024

ABSTRACTIn this work, we investigate the combined effects of heat and mass exchange on the time‐dependent convectional flow of a rheological nanofluid across a rotating cone. A numerical arrangement of nonlinear differential equations is obtained for spinning cones with separator temperature boundary conditions by similarity transformation. The effect of different parameters on the velocity, temperature, and concentration profiles are discussed. Tangential velocity is observed to decrease with an increase in the Deborah number, whereas it increases with increasing values of the angular velocity ratio, relaxation to the retardation time ratio, and buoyancy parameter. Expansion in the Prandtl number is noted to decrease the boundary‐layer temperature and thickness. Nusselt number and skin disunion observations are also considered. It is discovered that the Nusselt number expands by expanding the lightness parameter and Prandtl number, whereas it increases by decreasing the Deborah number. We also noticed that the Sherwood number falls incrementally in Deborah and Prandtl numbers, but it upsurges with an increase in the buoyancy parameter. The effect of parameters on temperature is graphically displayed, and the face shear stress tabulated values and heat shift rate are included in tables.
Head‐to‐head comparison of palbociclib and ribociclib in first‐line treatment of HR‐positive/HER2‐negative metastatic breast cancer with real‐world data from the OPAL registry
Authors: Thill Marc , Zahn Mark‐Oliver , Welt Anja , Nusch Arnd , Zaiss Matthias , Engelken Kathrin , Kaltenecker Gabriele , Ringwald Kai , Gratzke Katja , Dille Stephanie , Kruggel Lisa , Jänicke Martina , Schulz Holger , Hagen Volker , Fricker Roland , Stickeler Elmar , Harbeck Nadia , Wöckel Achim , Decker Thomas 
Published: December 2024

AbstractCyclin‐dependent kinase 4/6 inhibitors (CDKIs) in combination with endocrine therapy (ET) are the standard‐of‐care in the first‐line treatment of HR‐positive, HER2‐negative metastatic breast cancer. In the absence of direct head‐to‐head trials comparing the efficacy and safety of the different CDKIs, the individual choice of treatment in everyday practice is complex. Inverse probability of treatment weighting was used to emulate a head‐to‐head comparison of palbociclib +ET (PALBO) and ribociclib +ET (RIBO) in patients recruited into the prospective, observational, multicenter registry platform OPAL (NCT03417115). Progression‐free survival (PFS), overall survival (OS) and quality of life surveys were analyzed, also for subgroups stratified by treatment‐free interval (TFI). A total of 623 patients with HR‐positive, HER2‐negative metastatic breast cancer received PALBO (n = 388) or RIBO (n = 235) in their first line of treatment. No difference between PALBO and RIBO was found for PFS (median 26.7 months [23.6, 30.7] vs. 27.0 months [21.1, 30.4], HR 1.01 [0.80, 1.27]) and OS (median 42.4 months [38.8, 50.3] vs. 49.3 months [36.9, NA], HR 0.96 [0.71, 1.28]). There was a trend for longer PFS and OS in patients with TFI <12 months receiving RIBO. Patients reported comparable side effects for both CDKIs. This head‐to‐head comparison revealed no difference in PFS and OS between PALBO and RIBO, however, a trend to longer PFS and OS with RIBO was observed in the subgroup of patients with TFI <12 months. Side effects experienced with PALBO and RIBO highlight the important toxicities to be addressed during treatment decision.
Genetic variants of FER and SULF1 in the fibroblast‐related genes are associated with non–small‐cell lung cancer survival
Authors: Lu Guojun , Liu Hongliang , Wang Huilin , Luo Sheng , Du Mulong , Christiani David C. , Wei Qingyi 
Published: December 2024

AbstractFibroblasts are important components in the tumor microenvironment and can affect tumor progression and metastasis. However, the roles of genetic variants of the fibroblast‐related genes (FRGs) in the prognosis of non–small‐cell lung cancer (NSCLC) patients have not been reported. Therefore, we investigated the associations between 26,544 single nucleotide polymorphisms (SNPs) in 291 FRGs and survival of NSCLC patients from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. In Cox regression multivariable analysis, we found that 661 SNPs were associated with NSCLC overall survival (OS). Then we validated these SNPs in another independent replication dataset of 984 patients from the Harvard Lung Cancer Susceptibility (HLCS) Study. Finally, we identified two independent SNPs (i.e., FER rs7716388 A>G and SULF1 rs11785839 G>C) that remained significantly associated with NSCLC survival with hazards ratios (HRs) of 0.87 (95% confidence interval [CI] = 0.77–0.98, p = 0.018) and 0.88 (95% CI = 0.79–0.99, p = 0.033), respectively. Combined analysis for these two SNPs showed that the number of protective alleles was associated with better OS and disease‐specific survival. Expression quantitative trait loci analysis indicated that the FER rs7716388 G allele was associated with the up‐regulation of FER mRNA expression levels in lung tissue. Our results indicated that these two functional SNPs in the FRGs may be prognostic biomarkers for the prognosis of NSCLC patients, and the possible mechanism may be through modulating the expression of their corresponding genes.
Exploiting NRF2‐ARE pathway activation in papillary renal cell carcinoma
Authors: Angori Silvia , Lakshminarayanan Harini , Banaei‐Esfahani Amir , Mühlbauer Katharina , Bolck Hella Anna , Kallioniemi Olli , Pietiäinen Vilja , Schraml Peter , Moch Holger 
Published: December 2024

AbstractPapillary renal cell carcinoma (pRCC) is the second most frequent renal cancer subtype but has no indicated targeted treatments. MET inhibition may be a treatment for MET‐driven pRCC, but there is a large group of non‐MET‐driven pRCC without targeted therapy. Activation of NRF2‐ARE pathway has been suggested to be involved in pRCC. To study the relevance of the NRF2‐ARE pathway, we characterized 60 pRCCs by copy number analysis and Whole Exome Sequencing. Because stabilisation of NRF2 results in enhanced expression of NQO1, a reductase that prevents production of reactive oxygen species, protein expression of NQO1 was analysed by immunohistochemistry (IHC) from tissue microarrays (TMAs) and by enzymatic activity assay. Finally, patient‐derived pRCC cells (PDCs) were applied for drug profiling with 18 NRF2‐ARE pathway inhibitors. We identified MET mutations in 5%, and mutations in four genes of NRF2‐ARE pathway (NFE2L2, KEAP1, CUL3 and BACH1) in 10% of 60 pRCC samples. IHC analysis of TMAs of 638 renal cancers showed the correlation of the expression of NQO1 with poor survival outcome (p < .001) and high tumour grade (p < .001) and stage (p < .001) in pRCC. NQO1 mRNA, protein levels and enzymatic activity were increased in 56% of matched pRCC tissue samples and patient‐derived cells (PDCs, n = 9). Drug screening revealed that Brusatol and Convallatoxin are potential novel drugs for pRCC. Inhibition of NRF2 represents a novel therapeutic approach for MET‐independent pRCC patients.
Measuring the Uncertainty Impacts During the Systems Engineering Lifecycle
Authors: Flanigan David , Dixon Jeffery 
Published: December 2024

ABSTRACTUncertainty is a large part of the systems engineering development process. Particularly absent is the quantification of uncertainty of the threat, operating environment, and friendly force factors at each step of this lifecycle. This paper will explore a methodology to quantify the amount of uncertainty and the interdependencies of the uncertainty factors during the development. Included for consideration are internal and external factors and their contribution to the overall system uncertainty. An illustrative example is provided to exercise this methodology.
Informing the Delineation of Input Uncertainty Space in Exploratory Modelling Using a Heuristic Approach
Authors: Moallemi Enayat A. , Elsawah Sondoss , Ryan Michael J. 
Published: December 2024

ABSTRACTExploratory modelling is an emerging approach which can address the challenge of model‐based decision making in dealing with input model uncertainties. Exploratory modelling samples from an input uncertainty space and generates extensive computational experiments to analyse possible model behaviours in an output solution space. The way that the input uncertainty space is delineated influences the results of exploratory modelling and its computational cost. In this article, we show the statistical significance of the implication of the size of an input uncertainty space on the resulted output solution space. We also propose a heuristic approach which informs the delineation of input uncertainties by screening the relevant model behaviour in the solution space. An illustrative example of an aircraft fleet management system is used to demonstrate the implementation of our approach in practice. We conclude that the delineation of input uncertainty space can be a way to control simulations in exploratory modelling and to enhance the efficiency of the exploration process and the confidence of the final results.
Comparison of diagnoses made by dentistry students and by artificial intelligence dentists
Authors: Bahadir Hasibe Sevilay , Keskin Neslihan Büşra , Çakmak Emine Şebnem Kurşun , Güneç Gürkan , Cesur Aydin Kader , Sari Saliha Kübra 
Published: December 2024

AbstractObjectivesThe introduction of artificial intelligence (AI) about great changes in the field of dentistry, but it has not yet been fully determined in which areas it will make a positive contribution to dentistry students. The objective of our study was to compare the diagnostic accuracy of undergraduate students (fourth‐year dentistry students [4DS] and final‐year dentistry students [5DS]) and AI when examining panoramic radiographs.MethodsFifty panoramic radiographs and 1602 teeth were examined by 50 4DS who had not received a clinical practice internship, 50 5DS, and an AI application. The participants and the AI application evaluated the teeth seen in each radiograph one by one in terms of caries, fillings, teeth with root canal treatment, periodontal loss, extractions, crowns, teeth with apical lesions, and impacted and extracted teeth. Findings were recorded in an Excel chart. Chi‐square analysis was used to compare diagnostic success between the groups.ResultsThe results indicate that there was a statistically significant difference in the identified accuracy of caries, fillings, and extractions between the AI application and undergraduate students (p < 0.05). Although AI showed more identified accuracy in teeth with apical lesions, impacted teeth, and teeth with root canal treatment than in undergraduate students, there was no significant difference between them (p > 0.05).ConclusionAI exhibited better results than undergraduate students especially in the detection of caries and fillings. AI could improve undergraduates’ accuracy in detecting caries, fillings, and extractions and help them make accurate treatment decisions. In cases where dentistry students are examining patients using panoramic radiographs, employing AI programs during their clinical training to confirm and strengthen the student's diagnosis may be a promising new development.
Glucose‐induced self‐assembly in structurally diverse polyoxyethylene based nonionic surfactants for enhanced anticancer drug solubilization
Authors: Kuperkar Ketan , Prajapati Virendra , Marangoni Gerrard , Bahadur Pratap 
Published: December 2024

AbstractThis study investigates the influence of glucose in inducing the micellar growth/transition in several structurally diverse, longer, and shorter chain polyoxyethylene (POE)‐based nonionic surfactants, commercially known as Kolliphor® HS15 (Solutol), Kolliphor EL®, Akypo®, Brij®‐78, Pluronic® (P103 and F77), Tetronic® (T1304), and Tyloxapol® in aqueous solution environment. It was observed that the addition of glucose induces dehydration of the POE moieties or chains in the tested systems, thereby enhancing the inter‐micellar interactions via hydrogen bonding in the hydrophilic part of the selected surfactants. This dehydration leads to an interesting clouding behavior across all the studied surfactant systems. Also, the dynamic light scattering (DLS) technique accounted for the probable self‐assembly and micellar growth in water and 1 M glucose (fix) across various temperatures. Being pharmaceutical excipients, these micellar entities were successfully employed to assay the hydrophobic anticancer drug curcumin (Cur) solubilized, as confirmed by the peak intensity variation from UV–visible spectroscopy. Cur solubilization into glucose‐containing micelles revealed enhanced solubility expressed in terms of drug loading efficiency (DL%), encapsulation efficiency (EE%), partition coefficient (log P), and standard free energy of solubilization (ΔG°), which is due to the glucose‐induced hydrophobicity in the examined nonionic micellar systems.