bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive mass budgets of high-altitude and debris-covered fragmented tributary glaciers in Gangotri Glacier System, Himalaya
Authors: Hussain Md. Arif , Azam Mohd. Farooq , Srivastava Smriti , Vinze Parul 
Published: November 2022

Glacier-wide mass balances (MBs) of the Gangotri, Chaturangi, Raktavaran, Meru, and Gangotri Glacier System are reconstructed with a temperature-index (T-index) model using bias-corrected ERA5 data at a daily temporal resolution over 1979–2020. The model output is calibrated against available geodetic MB for Gangotri Glacier System and validated with satellite-derived snow line altitudes (SLAs) for Gangotri Glacier. Gangotri and Meru glaciers show mean mass wastage of –0.88 ± 0.31 m w. e. a‒ˡ (meter water equivalent per year) and ‒0.17 ± 0.29 m w. e. a‒ˡ, respectively whereas the mass budgets of fragmented tributary Chaturangi and Raktavaran glaciers are positive with the mean values of 0.49 ± 0.17 m w. e. a‒ˡ and 0.62 ± 0.15 m w. e. a‒ˡ, respectively over 1979–2020. Gangotri Glacier’s tongue is covered by thick debris having several supra-glacial lakes and ice cliffs (considered as melting hotspots); therefore, despite the presence of thick debris, we assume the melting over this area as of a clean glacier. The whole Gangotri Glacier System shows a moderate wastage of ‒0.27 ± 0.25 m w. e. a‒ˡ. The positive MBs of the Raktavaran and Chaturangi glaciers are due to their high area-elevation distribution and heavily debris-covered tongues. The positive MBs on these fragmented tributary glaciers are due to non-climatic topographic reasons and should not be misunderstood as climate change deniers or compared with Karakoram Anomaly. Modelled MBs are most sensitive to the threshold temperature for melt. The altitudinal MB sensitivities to all model parameters become negligible above 6,200 m a.s.l.
Linear and nonlinear analyses of the association between low–density lipoprotein cholesterol and diabetes: The spurious U–curve in observational study
Authors: Ma Yujia , Zhou Zechen , Li Xiaoyi , Ding Kexin , Xiao Han , Wu Yiqun , Wu Tao , Chen Dafang 
Published: November 2022

ObjectiveHyperlipidemia is traditionally considered a risk factor for diabetes. The effect of low-density lipoprotein cholesterol (LDL-C) is counterintuitive to diabetes. We sought to investigate the relationship between LDL-C and diabetes for better lipid management.MethodsWe tested the shape of association between LDL-C and diabetes and created polygenic risk scores of LDL-C and generated linear Mendelian randomization (MR) estimates for the effect of LDL-C and diabetes. We evaluated for nonlinearity in the observational and genetic relationship between LDL-C and diabetes.ResultsTraditional observational analysis suggested a complex non-linear association between LDL-C and diabetes while nonlinear MR analyses found no evidence for a non-linear association. Under the assumption of linear association, we found a consistently protective effect of LDL-C against diabetes among the females without lipid-lowering drugs use. The ORs were 0.84 (95% CI, 0.72–0.97, P=0.0168) in an observational analysis which was more prominent in MR analysis and suggested increasing the overall distribution of LDL-C in females led to an overall decrease in the risk of diabetes (P=0.0258).ConclusionsWe verified the liner protective effect of LDL-C against diabetes among the females without lipid-lowering drug use. Non-linear associations between LDL-C against diabetes in observational analysis are not causal.
Microwell culture platform maintains viability and mass of human pancreatic islets
Authors: Kato Hiroyuki , Miwa Tatsuaki , Quijano Janine , Medrano Leonard , Ortiz Jose , Desantis Akiko , Omori Keiko , Wada Aya , Tatsukoshi Kentaro , Kandeel Fouad , Mullen Yoko , Ku Hsun Teresa , Komatsu Hirotake 
Published: November 2022

BackgroundTransplantation of the human pancreatic islets is a promising approach for specific types of diabetes to improve glycemic control. Although effective, there are several issues that limit the clinical expansion of this treatment, including difficulty in maintaining the quality and quantity of isolated human islets prior to transplantation. During the culture, we frequently observe the multiple islets fusing together into large constructs, in which hypoxia-induced cell damage significantly reduces their viability and mass. In this study, we introduce the microwell platform optimized for the human islets to prevent unsolicited fusion, thus maintaining their viability and mass in long-term cultures.MethodHuman islets are heterogeneous in size; therefore, two different-sized microwells were prepared in a 35 mm-dish format: 140 µm × 300 µm-microwells for &lt;160 µm-islets and 200 µm × 370 µm-microwells for &gt;160 µm-islets. Human islets (2,000 islet equivalent) were filtered through a 160 µm-mesh to prepare two size categories for subsequent two week-cultures in each microwell dish. Conventional flat-bottomed 35 mm-dishes were used for non-filtered islets (2,000 islet equivalent/2 dishes). Post-cultured islets are collected to combine in each condition (microwells and flat) for the comparisons in viability, islet mass, morphology, function and metabolism. Islets from three donors were independently tested.ResultsThe microwell platform prevented islet fusion during culture compared to conventional flat bottom dishes, which improved human islet viability and mass. Islet viability and mass on the microwells were well-maintained and comparable to those in pre-culture, while flat bottom dishes significantly reduced islet viability and mass in two weeks. Morphology assessed by histology, insulin-secreting function and metabolism by oxygen consumption did not exhibit the statistical significance among the three different conditions.ConclusionMicrowell-bottomed dishes maintained viability and mass of human islets for two weeks, which is significantly improved when compared to the conventional flat-bottomed dishes.
Decreased expression of Glucagon-like peptide-1 receptor and Sodium-glucose co-transporter 2 in patients with proliferative diabetic retinopathy
Authors: Chen Hui , Zhang Xiongze , Liao Nanying , Ji Yuying , Mi Lan , Gan Yuhong , Su Yongyue , Wen Feng 
Published: November 2022

PurposeTo investigate the expression of Glucagon-like peptide-1 receptor (GLP-1R), sodium-glucose co-transporter (SGLT) 1, SGLT2, Glucose transporter type 1 (GLUT1) and GLUT2 in patients with diabetic retinopathy (DR).MethodsWe obtained peripheral blood mononuclear cells (PBMCs) and vitreous samples from 26 proliferative DR (PDR) patients, 25 non-proliferative DR (NPDR) patients, 25 non-DR (NDR) patients, and 26 nondiabetic patients with idiopathic epiretinal membranes (ERMs, control). The protein level and mRNA expression level of GLP-1R were quantified by immunoblot and qRT-PCR and the levels of SGLT1, SGLT2, GLUT1, and GLUT2 expression were determined by PCR. Their association with clinical parameters and PBMCs/vitreous cytokine was analyzed. Furthermore, immunofluorescence staining of GLP-1R and SGLT2 was carried out on samples of fibrovascular membranes (FVMs) retrieved from 26 patients with PDR and 26 patients with ERMs.ResultsThe transcriptional levels of GLP-1R and SGLT2 in PBMCs were significantly more decreased in PDR patients than in patients without DR and controls, which was simultaneously associated with an increased level of expression of tumor necrosis factor (TNF)-α and interferon (IFN)-γ. The expression levels of GLUT1 and GLUT2 were tightly correlated with their SGLT partners, respectively. Further, Immunofluorescence staining showed no positive staining of GLP-1R and SGLT2 was detected in the FVMs from PDR.ConclusionsGLP-1R and SGLT2 were significantly decreased in PDR patients which was associated with an increased level of expression of TNF-α and IFN-γ. These findings implicate that defective GLP-1R and SGLT2 signaling may potentially correlate with immune response cytokines in patients with PDR.
Genetically supported causality between benign prostate hyperplasia and urinary bladder neoplasms: A mendelian randomization study
Authors: Du Wenzhi , Wang Tianyi , Zhang Wenxiu , Xiao Yu , Wang Xinghuan 
Published: November 2022

Background: Observational studies have suggested a possible association between benign prostate hyperplasia (BPH) and bladder cancer (BLCA). However, these studies are prone to errors and limitations or confounding factors, making them unsuitable for assessing the causal relationship between BPH and BLCA.Objective: Two-sample Mendelian randomization (MR) was performed to determine a possible association between genetically predicted BPH and the risk of BLCA.Methods: A two-sample MR analysis was performed utilizing the Integrative Epidemiology Unit genome-wide association (GWAS) database of the Medical Research Council, United Kingdom A series of control steps, including five primary methods, were performed to identify the most suitable instrumental variables (IVs) for MR analysis. Sensitivity analysis was conducted to avoid statistical errors, including heterogeneity and pleiotropic bias.Results: Genetic variants associated with BPH (P &lt; 5 × 10–8) and BLCA (P &lt; 5 × 10–6) were identified as instrumental variables and assessed using GWAS summary data (BPH, 4,670 cases vs. 458,340 controls; BLCA, 1,279 cases vs. 372,016 controls). BPH exhibited a positive effect on the occurrence of BLCA (inverse variance weighted (IVW), odds ratio (OR) = 1.095, 95% confidence interval (CI) = 1.030–1.165, p = 0.003), but there was no causal effect for BLCA on BPH (IVW, OR = 1.092, 95% CI = 0.814–1.465, p = 0.554).Conclusion: Genetically predicted BPH was associated with a higher risk of BLCA in all histological subtypes. In contrast, the evidence was not significant to back the causality of genetically induced BLCA on BPH. These findings indicate that BPH plays a key role in developing BLCA in the European population. Further studies are needed to uncover the underlying mechanisms.
Construction of a mitochondrial dysfunction related signature of diagnosed model to obstructive sleep apnea
Authors: Liu Qian , Hao Tao , Li Lei , Huang Daqi , Lin Ze , Fang Yipeng , Wang Dong , Zhang Xin 
Published: November 2022

Background: The molecular mechanisms underlying obstructive sleep apnea (OSA) and its comorbidities may involve mitochondrial dysfunction. However, very little is known about the relationships between mitochondrial dysfunction-related genes and OSA.Methods: Mitochondrial dysfunction-related differentially expressed genes (DEGs) between OSA and control adipose tissue samples were identified using data from the Gene Expression Omnibus database and information on mitochondrial dysfunction-related genes from the GeneCards database. A mitochondrial dysfunction-related signature of diagnostic model was established using least absolute shrinkage and selection operator Cox regression and then verified. Additionally, consensus clustering algorithms were used to conduct an unsupervised cluster analysis. A protein–protein interaction network of the DEGs between the mitochondrial dysfunction-related clusters was constructed using STRING database and the hub genes were identified. Functional analyses, including Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA), were conducted to explore the mechanisms involved in mitochondrial dysfunction in OSA. Immune cell infiltration analyses were conducted using CIBERSORT and single-sample GSEA (ssGSEA).Results: we established mitochondrial dysfunction related four-gene signature of diagnostic model consisted of NPR3, PDIA3, SLPI, ERAP2, and which could easily distinguish between OSA patients and controls. In addition, based on mitochondrial dysfunction-related gene expression, we identified two clusters among all the samples and three clusters among the OSA samples. A total of 10 hub genes were selected from the PPI network of DEGs between the two mitochondrial dysfunction-related clusters. There were correlations between the 10 hub genes and the 4 diagnostic genes. Enrichment analyses suggested that autophagy, inflammation pathways, and immune pathways are crucial in mitochondrial dysfunction in OSA. Plasma cells and M0 and M1 macrophages were significantly different between the OSA and control samples, while several immune cell types, especially T cells (γ/δ T cells, natural killer T cells, regulatory T cells, and type 17 T helper cells), were significantly different among mitochondrial dysfunction-related clusters of OSA samples.Conclusion: A novel mitochondrial dysfunction-related four-gen signature of diagnostic model was built. The genes are potential biomarkers for OSA and may play important roles in the development of OSA complications.
In silico and in vitro arboviral MHC class I-restricted-epitope signatures reveal immunodominance and poor overlapping patterns
Authors: Lopes-Ribeiro Ágata , Araujo Franklin Pereira , Oliveira Patrícia de Melo , Teixeira Lorena de Almeida , Ferreira Geovane Marques , Lourenço Alice Aparecida , Dias Laura Cardoso Corrêa , Teixeira Caio Wilker , Retes Henrique Morais , Lopes Élisson Nogueira , Versiani Alice Freitas , Barbosa-Stancioli Edel Figueiredo , da Fonseca Flávio Guimarães , Martins-Filho Olindo Assis , Tsuji Moriya , Peruhype-Magalhães Vanessa , Coelho-dos-Reis Jordana Grazziela Alves 
Published: November 2022

IntroductionThe present work sought to identify MHC-I-restricted peptide signatures for arbovirus using in silico and in vitro peptide microarray tools.MethodsFirst, an in-silico analysis of immunogenic epitopes restricted to four of the most prevalent human MHC class-I was performed by identification of MHC affinity score. For that, more than 10,000 peptide sequences from 5 Arbovirus and 8 different viral serotypes, namely Zika (ZIKV), Dengue (DENV serotypes 1-4), Chikungunya (CHIKV), Mayaro (MAYV) and Oropouche (OROV) viruses, in addition to YFV were analyzed. Haplotype HLA-A*02.01 was the dominant human MHC for all arboviruses. Over one thousand HLA-A2 immunogenic peptides were employed to build a comprehensive identity matrix. Intending to assess HLAA*02:01 reactivity of peptides in vitro, a peptide microarray was designed and generated using a dimeric protein containing HLA-A*02:01.ResultsThe comprehensive identity matrix allowed the identification of only three overlapping peptides between two or more flavivirus sequences, suggesting poor overlapping of virus-specific immunogenic peptides amongst arborviruses. Global analysis of the fluorescence intensity for peptide-HLA-A*02:01 binding indicated a dose-dependent effect in the array. Considering all assessed arboviruses, the number of DENV-derived peptides with HLA-A*02:01 reactivity was the highest. Furthermore, a lower number of YFV-17DD overlapping peptides presented reactivity when compared to non-overlapping peptides. In addition, the assessment of HLA-A*02:01-reactive peptides across virus polyproteins highlighted non-structural proteins as “hot-spots”. Data analysis supported these findings showing the presence of major hydrophobic sites in the final segment of non-structural protein 1 throughout 2a (Ns2a) and in nonstructural proteins 2b (Ns2b), 4a (Ns4a) and 4b (Ns4b).DiscussionTo our knowledge, these results provide the most comprehensive and detailed snapshot of the immunodominant peptide signature for arbovirus with MHC-class I restriction, which may bring insight into the design of future virus-specific vaccines to arboviruses and for vaccination protocols in highly endemic areas.
Circular RNA hsa_circ_0007990 as a blood biomarker for unruptured intracranial aneurysm with aneurysm wall enhancement
Authors: Wu Xiao-Bing , Wu You-Tao , Guo Xin-Xing , Xiang Chun , Chen Pei-Sheng , Qin Wang , Shi Zhong-Song 
Published: November 2022

BackgroundCircular RNAs (circRNAs) may involve the formation and rupture of intracranial aneurysms (IA). Inflammation plays a vital role in the development and progression of IA, which can be reflected by aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI). This study aims to evaluate the role of circRNAs as the blood inflammatory biomarker for unruptured IA (UIA) patients with AWE on HR-VWI.MethodsWe analyzed the circRNA expression profiles in the peripheral blood samples among subjects from saccular UIA with AWE, UIA without AWE, and healthy controls by the circRNA microarray. The differential expression of hsa_circ_0007990 was assessed. We constructed the hsa_circ_0007990-microRNA-mRNA network and the regulatory axis of hub genes associated with the AWE in UIA.ResultsEighteen patients harboring saccular UIAs with HR VWI and five healthy controls were included. We found 412 differentially expressed circRNAs between UIA patients and healthy controls by circRNA microarray. Two hundred thirty-one circRNAs were significantly differentially expressed in UIA patients with AWE compared with those without AWE. Twelve upregulated circRNAs were associated with AWE of UIA, including hsa_circ_0007990, hsa_circ_0114507, hsa_circ_0020460, hsa_circ_0053944, hsa_circ_0000758, hsa_circ_0000034, hsa_circ_0009127, hsa_circ_0052793, hsa_circ_0000301 and hsa_circ_0000729. The expression of hsa_circ_0007990 was increased gradually in the healthy control, UIA without AWE, and UIA with AWE confirmed by RT-PCR (P&lt;0.001). We predicted 4 RNA binding proteins (Ago2, DGCR8, EIF4A3, PTB) and period circadian regulator 1 as an encoding protein with hsa_circ_0007990. The hsa_circ_0007990-microRNA-mRNA network containing five microRNAs (miR-4717-5p, miR-1275, miR-150-3p, miR-18a-5p, miR-18b-5p), and 97 mRNAs was constructed. The five hub genes (hypoxia-inducible factor 1 subunit alpha, estrogen receptor 1, forkhead box O1, insulin-like growth factor 1, CREB binding protein) were involved in the inflammatory response.ConclusionDifferentially expressed blood circRNAs associated with AWE on HR-VWI may be the novel inflammatory biomarkers for assessing UIA patients. The mechanism of hsa_circRNA_0007990 for UIA progression needs to investigate further.
Bone fragility and sarcoidosis: An underestimated relationship
Authors: Caffarelli Carla , Cameli Paolo , Al Refaie Antonella , Giglio Elisa , Manzana Giulio , Mondillo Caterina , Noacco Yari , Olivieri Carmela , Bargagli Elena , Gonnelli Stefano 
Published: November 2022

IntroductionSarcoidosis is a chronic multisystem inflammatory disease which may affect any organ. Also bone can be involved both directly and indirectly. Data on BMD values and fragility fractures in sarcoidosis patients are few and heterogeneous. This study aimed to characterized the presence of fracture and the relative risk factors in patients with sarcoidosis.Materials and methodsIn this single center cross-sectional study we evaluated 252 sarcoidosis patients (54.7 ± 12.1 years) compared to sex-and age matched healthy controls. We measured BMD at lumbar spine, at femoral neck and at total hip. Moreover, the presence of fragility fractures was collected during osteoporosis visit and all radiological images were examined for the presence of any vertebral fracture according to Genant’s method’s. Lung function measurements, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, and diffusion capacity for carbon monoxide (DLCO) were assessed.ResultsBone Mineral Density T-scores were lower in patients affected by sarcoidosis with respect to those obtained in healthy controls, but the difference was statistically significant only for BMD-LS (p &lt; 0.01) and BMD-TH (p &lt; 0.05). Moreover, BMD values at all skeletal sites were significantly associated with DLCO (%) (p &lt; 0.05). The prevalence of fragility fracture was higher in patients with sarcoidosis than in healthy controls (30.6 vs. 12.3%). The patients with ≥3 vertebral fracture had lower values of FVC (%), FEV1 (%), and DLCO (%). Multiple regression analyses showed that BMI was positively associated with fragility fracture, while BMD-TH, DLCO(%) and therapy use was negatively associated.ConclusionsVertebral fractures represent a frequent complication in patients with sarcoidosis. Furthermore, the number of vertebral fractures was linked with a worsening in pulmonary functional tests. Therefore, the degree of severity of the sarcoidosis disease appears to be the main determinant of bone fragility.
Dynamic control of eye-head gaze shifts by a spiking neural network model of the superior colliculus
Authors: Alizadeh Arezoo , Van Opstal A. John 
Published: November 2022

IntroductionTo reorient gaze (the eye’s direction in space) towards a target is an overdetermined problem, as infinitely many combinations of eye- and head movements can specify the same gaze-displacement vector. Yet, behavioral measurements show that the primate gaze-control system selects a specific contribution of eye- and head movements to the saccade, which depends on the initial eye-in-head orientation. Single-unit recordings in the primate superior colliculus (SC) during head-unrestrained gaze shifts have further suggested that cells may encode the instantaneous trajectory of a desired straight gaze path in a feedforward way by the total cumulative number of spikes in the neural population, and that the instantaneous gaze kinematics are thus determined by the neural firing rates. The recordings also indicated that the latter is modulated by the initial eye position. We recently proposed a conceptual model that accounts for many of the observed properties of eye-head gaze shifts and on the potential role of the SC in gaze control.MethodsHere, we extend and test the model by incorporating a spiking neural network of the SC motor map, the output of which drives the eye-head motor control circuitry by linear cumulative summation of individual spike effects of each recruited SC neuron. We propose a simple neural mechanism on SC cells that explains the modulatory influence of feedback from an initial eye-in-head position signal on their spiking activity. The same signal also determines the onset delay of the head movement with respect to the eye. Moreover, the downstream eye- and head burst generators were taken to be linear, as our earlier work had indicated that much of the non-linear main-sequence kinematics of saccadic eye movements may be due to neural encoding at the collicular level, rather than at the brainstem.Results and discussionWe investigate how the spiking activity of the SC population drives gaze to the intended target location within a dynamic local gaze-velocity feedback circuit that yields realistic eye- and head-movement kinematics and dynamic SC gaze-movement fields.