bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of a Farnesoid X-receptor Agonist on Postprandial Lipemia in Rats Fed a Supraphysiological Fat Dozes
Authors: Alekhin Yu. N. , Popova O. S. , Ponamarev V. S. , Parshin P. A. 
Published: May 2023

Introduction. One of the most progressive directions of the modern stage of development of biology is the deepening of knowledge about the mechanisms of regulation of metabolic processes, in particular about signal molecules that transmit information to the cell through ion channels and nuclear receptors associated with G-protein or with enzymatic activity. The nuclear Farnesoid X receptor (FXR) is mainly expressed in the liver and intestines, it regulates key genes that provide the processes of synthesis, transport and reabsorption of bile acids, and is also involved in the metabolism of lipids and carbohydrates.Aim. To evaluate the effect of a farnesoid X receptor agonist on postprandial lipemia in rats fed a supraphysiological fat diet.Materials and methods. An experimental, prospective, controlled, unblinded, randomized study was conducted to study the effect of a farnesoid X receptor agonist (obeticholic acid) on postprandial lipemia in rats receiving a diet containing a supraphysiological dose of fats.Results and discussion. It has been shown that when assessing postprandial lipemia, an oral test for tolerance to supraphysiological doses of fat with the determination of the initial lipid profile parameters and 4 hours after exercise has a sufficiently high information content. It was found that in animals that received a diet containing an increased amount of fat for 28 days, there was an imbalance in lipid metabolism with activation of their absorption in the intestine, but a "slow" reaction of the mechanisms of intermediate lipid metabolism, which was accompanied by the accumulation of triglycerides and cholesterol in the blood of hungry rats, chylomicrons and LDL. At 4 hours post-feeding, these animals showed abnormal increases in triglycerides and cholesterol.Conclusion. The use of obeticholic acid harmonizes lipid metabolism against the background of alimentary fat load, due to the activation of farnesoid X-receptors of the intestine and liver, which is manifested by a simultaneous increase in the intensity of lipid absorption processes and their intermediate metabolism. As a result, the risk of hyperchylomicronemia, hypercholesterolemia and hypertriglyceridemia is eliminated, the likelihood of developing secondary hyperlipedemia, insulin tolerance and functional overload (or pathology) of the liver is reduced.
Mapping of the podocin proximity-dependent proteome reveals novel components of the kidney podocyte foot process
Authors: Gerlach Gary F. , Imseis Zachary H. , Cooper Shamus L. , Santos Anabella N. , O’Brien Lori L. 
Published: May 2023

Introduction: The unique architecture of glomerular podocytes is integral to kidney filtration. Interdigitating foot processes extend from the podocyte cell body, wrap around fenestrated capillaries, and form specialized junctional complexes termed slit diaphragms to create a molecular sieve. However, the full complement of proteins which maintain foot process integrity, and how this localized proteome changes with disease, remain to be elucidated.Methods: Proximity-dependent biotin identification (BioID) enables the identification of spatially localized proteomes. To this end, we developed a novel in vivo BioID knock-in mouse model. We utilized the slit diaphragm protein podocin (Nphs2) to create a podocin–BioID fusion. Podocin–BioID localizes to the slit diaphragm, and biotin injection leads to podocyte-specific protein biotinylation. We isolated the biotinylated proteins and performed mass spectrometry to identify proximal interactors.Results and Discussion: Gene ontology analysis of 54 proteins specifically enriched in our podocin–BioID sample revealed ‘cell junctions,’ ‘actin binding,’ and ‘cytoskeleton organization’ as top terms. Known foot process components were identified, and we further uncovered two novel proteins: the tricellular junctional protein Ildr2 and the CDC42 and N-WASP interactor Fnbp1l. We confirmed that Ildr2 and Fnbp1l are expressed by podocytes and partially colocalize with podocin. Finally, we investigated how this proteome changes with age and uncovered a significant increase in Ildr2. This was confirmed by immunofluorescence on human kidney samples and suggests altered junctional composition may preserve podocyte integrity. Together, these assays have led to new insights into podocyte biology and support the efficacy of utilizing BioID in vivo to interrogate spatially localized proteomes in health, aging, and disease.
“There wasn’t a guidebook for this”: caring leadership during crisis
Authors: Steilen Kate , Stone-Johnson Corrie 
Published: June 2023

IntroductionIn this study, we seek to add to the descriptive literature on caring leadership through an examination of the work principals did to guide school communities through the COVID-19 pandemic. In this time, one essential role they played was as caretaker for all; not simply deciding, advising, or providing resources but responding with advocacy and compassion. Even so, they simultaneously had to consider traditional instructional leadership expectations including teacher observation and supervision as well as student evaluation.MethodsThis study examines the acts and expressions of caring leadership. Our research responds to one overarching question: What does caring leadership look like in action? Through close examination of 17 elementary principals’ recollections of work during the school closures of 2020, this study highlights the elements of their decisions and choices that embodied caring leadership as well as demonstrates how these moves both incorporated and exceeded traditional leadership work.ResultsOur findings highlight the centrality of caring leadership not merely as part of leaders’ work, but as the actual work itself. We extend a presumed tautology of caring leadership to explicate the discrete tasks undertaken by caring leaders to sustain the work of schools.DiscussionResearch on leadership practices frequently emphasizes professional work as relational and interactive to achieve instructional goals without acknowledging that much of the contemporary leadership work both centers on and draws strength from mutual, authentic caring for others to accomplish work. Thus, this investigation enhances research on leadership in education to recognize the caring work that principals perform and the value they ascribe to caring.
Patient-reported outcomes provide evidence for increased depressive symptoms and increased mental impairment in giant cell arteritis
Authors: Froehlich Matthias , Zahner Antonia , Schmalzing Marc , Gernert Michael , Strunz Patrick-Pascal , Hueper Sebastian , Portegys Jan , Schwaneck Eva Christina , Gadeholt Ottar , Kübler Andrea , Hewig Johannes , Ziebell Philipp 
Published: May 2023

ObjectivesThe spectrum of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) represents highly inflammatory rheumatic diseases. Patients mostly report severe physical impairment. Possible consequences for mental health have been scarcely studied. The aim of this study was to investigate psychological well-being in the context of GCA and PMR.MethodsCross-sectional study with N = 100 patients with GCA and/or PMR (GCA-PMR). Patient-reported outcomes (PROs) were measured using the Short Form 36 Version 2 (SF-36v2) and visual analog scale (VAS) assessment. Moreover, the Patient Health Questionnaire 9 (PHQ-9) was used in 35 of 100 patients to detect depression. To compare PROs with physician assessment, VAS was also rated from physician perspective. To assess a possible association with inflammation itself, serological parameters of inflammation (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]) were included.ResultsIn all scales of the SF-36v2 except General Health (GH) and in the physical and mental sum score (PCS, MCS), a significant impairment compared to the German reference collective was evident (MCS: d = 0.533, p &lt; 0.001). In the PHQ-9 categorization, 14 of the 35 (40%) showed evidence of major depression disorder. VAS Patient correlated significantly with PHQ-9 and SF-36 in all categories, while VAS Physician showed only correlations to physical categories and not in the mental dimensions. Regarding inflammatory parameters, linear regression showed CRP to be a complementary significant positive predictor of mental health subscale score, independent of pain.ConclusionPRO show a relevant impairment of mental health up to symptoms of major depression disorder. The degree of depressive symptoms is also distinctly associated with the serological inflammatory marker CRP.
Regional changes in brain apparent diffusion coefficient in fetuses with complex congenital heart disease and normal pregnancy assessed using diffusion-weighted imaging
Authors: Song Jia-Guang , Sun Cong , Zhu Mei , Zhu Jin-Xia , Zhang Nan , Wang Guang-Bin , Zhao Bin 
Published: May 2023

ObjectivesTo explore changes in brain apparent diffusion coefficient (ADC) in normal fetuses and fetuses with complex congenital heart disease (CHD) during the second and early third trimesters.MethodsThis single-center prospective study was conducted from May 2019 through October 2021. We measured and compared the mean ADC values between 23 fetuses with CHD and 27 gestational age (GA)-matched controls using covariance analyses. ADC density plots and histograms were used to compare brain characteristics. False-discovery rates (FDR, α = 0.05) correction was used for multiple testing.ResultsThe mean ADC in the frontal white matter, temporal white matter, parietal white matter, occipital white matter, cerebellar hemisphere, central area of the centrum semiovale, basal ganglia region, thalamus, and pons were not significantly different (all p &gt; 0.05). Based on histogram analysis, there were no significant differences between the controls and fetuses with CHD after FDR correction. However, the ADC density plots showed significant heterogeneity between the controls and fetuses with CHD.ConclusionThe mean ADC values and ADC histogram analysis did not differ between the CHD and normal groups. The ADC density plots may provide supplementary information and improve the sensitivity for detecting early brain changes in fetuses with CHD.
GABNet: global attention block for retinal OCT disease classification
Authors: Huang Xuan , Ai Zhuang , Wang Hui , She Chongyang , Feng Jing , Wei Qihao , Hao Baohai , Tao Yong , Lu Yaping , Zeng Fanxin 
Published: June 2023

IntroductionThe retina represents a critical ocular structure. Of the various ophthalmic afflictions, retinal pathologies have garnered considerable scientific interest, owing to their elevated prevalence and propensity to induce blindness. Among clinical evaluation techniques employed in ophthalmology, optical coherence tomography (OCT) is the most commonly utilized, as it permits non-invasive, rapid acquisition of high-resolution, cross-sectional images of the retina. Timely detection and intervention can significantly abate the risk of blindness and effectively mitigate the national incidence rate of visual impairments.MethodsThis study introduces a novel, efficient global attention block (GAB) for feed forward convolutional neural networks (CNNs). The GAB generates an attention map along three dimensions (height, width, and channel) for any intermediate feature map, which it then uses to compute adaptive feature weights by multiplying it with the input feature map. This GAB is a versatile module that can seamlessly integrate with any CNN, significantly improving its classification performance. Based on the GAB, we propose a lightweight classification network model, GABNet, which we develop on a UCSD general retinal OCT dataset comprising 108,312 OCT images from 4686 patients, including choroidal neovascularization (CNV), diabetic macular edema (DME), drusen, and normal cases.ResultsNotably, our approach improves the classification accuracy by 3.7% over the EfficientNetV2B3 network model. We further employ gradient-weighted class activation mapping (Grad-CAM) to highlight regions of interest on retinal OCT images for each class, enabling doctors to easily interpret model predictions and improve their efficiency in evaluating relevant models.DiscussionWith the increasing use and application of OCT technology in the clinical diagnosis of retinal images, our approach offers an additional diagnostic tool to enhance the diagnostic efficiency of clinical OCT retinal images.
MEG language mapping using a novel automatic ECD algorithm in comparison with MNE, dSPM, and DICS beamformer
Authors: Babajani-Feremi Abbas , Pourmotabbed Haatef , Schraegle William A. , Calley Clifford S. , Clarke Dave F. , Papanicolaou Andrew C. 
Published: June 2023

IntroductionThe single equivalent current dipole (sECD) is the standard clinical procedure for presurgical language mapping in epilepsy using magnetoencephalography (MEG). However, the sECD approach has not been widely used in clinical assessments, mainly because it requires subjective judgements in selecting several critical parameters. To address this limitation, we developed an automatic sECD algorithm (AsECDa) for language mapping.MethodsThe localization accuracy of the AsECDa was evaluated using synthetic MEG data. Subsequently, the reliability and efficiency of AsECDa were compared to three other common source localization methods using MEG data recorded during two sessions of a receptive language task in 21 epilepsy patients. These methods include minimum norm estimation (MNE), dynamic statistical parametric mapping (dSPM), and dynamic imaging of coherent sources (DICS) beamformer.ResultsFor the synthetic single dipole MEG data with a typical signal-to-noise ratio, the average localization error of AsECDa was less than 2 mm for simulated superficial and deep dipoles. For the patient data, AsECDa showed better test-retest reliability (TRR) of the language laterality index (LI) than MNE, dSPM, and DICS beamformer. Specifically, the LI calculated with AsECDa revealed excellent TRR between the two MEG sessions across all patients (Cor = 0.80), while the LI for MNE, dSPM, DICS-event-related desynchronization (ERD) in the alpha band, and DICS-ERD in the low beta band ranged lower (Cor = 0.71, 0.64, 0.54, and 0.48, respectively). Furthermore, AsECDa identified 38% of patients with atypical language lateralization (i.e., right lateralization or bilateral), compared to 73%, 68%, 55%, and 50% identified by DICS-ERD in the low beta band, DICS-ERD in the alpha band, MNE, and dSPM, respectively. Compared to other methods, AsECDa’s results were more consistent with previous studies that reported atypical language lateralization in 20-30% of epilepsy patients.DiscussionOur study suggests that AsECDa is a promising approach for presurgical language mapping, and its fully automated nature makes it easy to implement and reliable for clinical evaluations.
Association of modifiable lifestyle with colorectal cancer incidence and mortality according to metabolic status: prospective cohort study
Authors: Xie Peng , Wu Siqing , Kuo Zichong , Tian Huidong , He Qiangsheng , Li Yanfei , Mi Ningning , Hu Linmin , Zhao Haitong , Li Wenjing , Xia Bin , Yuan Jinqiu , Yang Kehu , Zhang Changhua , He Yulong 
Published: May 2023

BackgroundMetabolic syndrome has been linked to an increased risk of colorectal cancer (CRC) incidence and mortality, but whether adopting a healthy lifestyle could attenuate the risk of CRC conferred by metabolic syndrome remains unclear. The aim of the study is to investigate the individual and joint effects of modifiable healthy lifestyle and metabolic health status on CRC incidence and mortality in the UK population.MethodsThis prospective study included 328,236 individuals from the UK Biobank. An overall metabolic health status was assessed at baseline and categorized based on the presence or absence of metabolic syndrome. We estimated the association of the healthy lifestyle score (derived from 4 modifiable behaviors: smoking, alcohol consumption, diet, physical activity and categorized into “favorable,” “intermediate”, and “unfavorable”) with CRC incidence and mortality, stratified by metabolic health status.ResultsDuring a median follow-up of 12.5 years, 3,852 CRC incidences and 1,076 deaths from CRC were newly identified. The risk of incident CRC and its mortality increased with the number of abnormal metabolic factors and decreased with healthy lifestyle score (P trend = 0.000). MetS was associated with greater CRC incidence (HR = 1.24, 95% CI: 1.16 – 1.33) and mortality (HR = 1.24, 95% CI: 1.08 – 1.41) when compared with those without MetS. An unfavorable lifestyle was associated with an increased risk (HR = 1.25, 95% CI: 1.15 – 1.36) and mortality (HR = 1.36, 95% CI: 1.16 – 1.59) of CRC across all metabolic health status. Participants adopting an unfavorable lifestyle with MetS had a higher risk (HR = 1.56, 95% CI: 1.38 – 1.76) and mortality (HR = 1.75, 95% CI: 1.40 – 2.20) than those adopting a favorable healthy lifestyle without MetS.ConclusionThis study indicated that adherence to a healthy lifestyle could substantially reduce the burden of CRC regardless of the metabolic status. Behavioral lifestyle changes should be encouraged for CRC prevention even in participants with MetS.
Whole-genome informed circulating tumor DNA analysis by multiplex digital PCR for disease monitoring in B-cell lymphomas: a proof-of-concept study
Authors: Haider Zahra , Wästerlid Tove , Spångberg Linn Deleskog , Rabbani Leily , Jylhä Cecilia , Thorvaldsdottir Birna , Skaftason Aron , Awier Hero Nikdin , Krstic Aleksandra , Gellerbring Anna , Lyander Anna , Hägglund Moa , Jeggari Ashwini , Rassidakis Georgios , Sonnevi Kristina , Sander Birgitta , Rosenquist Richard , Tham Emma , Smedby Karin E. 
Published: June 2023

IntroductionAnalyzing liquid biopsies for tumor-specific aberrations can facilitate detection of measurable residual disease (MRD) during treatment and at follow-up. In this study, we assessed the clinical potential of using whole-genome sequencing (WGS) of lymphomas at diagnosis to identify patient-specific structural (SVs) and single nucleotide variants (SNVs) to enable longitudinal, multi-targeted droplet digital PCR analysis (ddPCR) of cell-free DNA (cfDNA).MethodsIn 9 patients with B-cell lymphoma (diffuse large B-cell lymphoma and follicular lymphoma), comprehensive genomic profiling at diagnosis was performed by 30X WGS of paired tumor and normal specimens. Patient-specific multiplex ddPCR (m-ddPCR) assays were designed for simultaneous detection of multiple SNVs, indels and/or SVs, with a detection sensitivity of 0.0025% for SV assays and 0.02% for SNVs/indel assays. M-ddPCR was applied to analyze cfDNA isolated from serially collected plasma at clinically critical timepoints during primary and/or relapse treatment and at follow-up.ResultsA total of 164 SNVs/indels were identified by WGS including 30 variants known to be functionally relevant in lymphoma pathogenesis. The most frequently mutated genes included KMT2D, PIM1, SOCS1 and BCL2. WGS analysis further identified recurrent SVs including t(14;18)(q32;q21) (IGH::BCL2), and t(6;14)(p25;q32) (IGH::IRF4). Plasma analysis at diagnosis showed positive circulating tumor DNA (ctDNA) levels in 88% of patients and the ctDNA burden correlated with baseline clinical parameters (LDH and sedimentation rate, p-value &lt;0.01). While clearance of ctDNA levels after primary treatment cycle 1 was observed in 3/6 patients, all patients analyzed at final evaluation of primary treatment showed negative ctDNA, hence correlating with PET-CT imaging. One patient with positive ctDNA at interim also displayed detectable ctDNA (average variant allele frequency (VAF) 6.9%) in the follow-up plasma sample collected 2 years after final evaluation of primary treatment and 25 weeks before clinical manifestation of relapse.ConclusionIn summary, we demonstrate that multi-targeted cfDNA analysis, using a combination of SNVs/indels and SVs candidates identified by WGS analysis, provides a sensitive tool for MRD monitoring and can detect lymphoma relapse earlier than clinical manifestation.
Fucoidan inhibits apoptosis and improves cardiac remodeling by inhibiting p53 transcriptional activation through USP22/Sirt 1
Authors: Wang Shuai , Bai Jie , Che Yilin , Qu Weikun , Li Jing 
Published: May 2023

Background: Humans with hypertensive heart disease are more likely to experience heart failure, arrhythmia, myocardial infarction, and sudden death, and it is crucial to treat this condition. Fucoidan (FO) is a natural substance derived from marine algae that has antioxidant and immunomodulatory activities. FO has also been shown to regulate apoptosis. However, whether FO can protect against cardiac hypertrophy is unknown.Methods: We investigated the effect of FO in hypertrophic models in vivo and in vitro. C57BL/6 mice were given an oral gavage of FO (300 mg/kg/day) or PBS (internal control) the day before surgery, followed by a 14-day infusion of Ang II or saline. AC-16 cells were treated with si-USP22 for 4 h and then treated with Ang II (100 nM) for 24 h. Systolic blood pressure (SBP) was recorded, echocardiography was used to assess cardiac function, and pathological changes in heart tissues were assessed by histological staining. Apoptosis levels were detected by TUNEL assays. The mRNA level of genes was assessed by qPCR. Protein expression was detected by immunoblotting.Results: Our data showed that USP22 expression was lowered in Ang II-infused animals and cells, which could promote cardiac dysfunction and remodeling. However, treatment with FO significantly upregulated the expression of USP22 and reduced the incidence of cardiac hypertrophy, fibrosis, inflammation, and oxidative responses. Additionally, FO treatment lowered p53 expression and apoptosis while increasing Sirt 1 and Bcl-2 expression.Conclusion: By reducing the level of Ang II-induced apoptosis through the regulation of USP22/Sirt 1 expression, FO treatment might improve cardiac function. According to this study, FO might be potential targeted approach for treating heart failure.