bluuebunny/crossref_metadata_2025_split huggingface dataset:
The potential DNA methylation markers of cardiovascular disease in patients with type 2 diabetes
Authors: He Yunbiao , Chen Xia , Liu Mingliang , Zuo Lei , Zhai Zhiyu , Zhou Long , Li Guangzhen , Chen Li , Qi Guolong , Jing Chunxia , Hao Guang 
Published: October 2023

Abstract
Background
DNA methylation is associated with cardiovascular (CV) disease. However, in type 2 diabetes (T2D) patients, the role of gene methylation in the development of CV disease is under-studied. We aimed to identify the CV disease-related DNA methylation loci in patients with T2D and to explore the potential pathways underlying the development of CV disease using a two-stage design.

Methods
The participants were from the Jinan Diabetes Cohort Study (JNDCS), an ongoing longitudinal study designed to evaluate the development of CV risk in patients with T2D. In the discovery cohort, 10 diabetic patients with CV events at baseline were randomly selected as the case group, and another 10 diabetic patients without CV events were matched for sex, age, smoking status, and body mass index as the control group. In 1438 T2D patients without CV disease at baseline, 210 patients with CV events were identified after a mean 6.5-year follow-up. Of whom, 100 patients who experienced CV events during the follow-up were randomly selected as cases, and 100 patients who did not have CV events were randomly selected as the control group in the validation cohort. Reduced representation bisulfite sequencing and Targeted Bisulfite Sequencing were used to measure the methylation profiles in the discovery and validation cohort, respectively.

Results
In the discover cohort, 127 DMRs related to CV disease were identified in T2D patients. Further, we validated 23 DMRs mapped to 25 genes, of them, 4 genes (ARSG, PNPLA6, NEFL, and CRYGEP) for the first time were reported. There was evidence that the addition of DNA methylation data improved the prediction performance of CV disease in T2D patients. Pathway analysis identified some significant signaling pathways involved in CV comorbidities, T2D, and inflammation.

Conclusions
In this study, we identified 23 DMRs mapped to 25 genes associated with CV disease in T2D patients, of them, 4 DMRs for the first time were reported. DNA methylation testing may help identify a high CV-risk population in T2D patients.
Effects of µ-Conotoxin GIIIB on the cellular activity of mouse skeletal musculoblast: combined transcriptome and proteome analysis
Authors: Wu Han-xi , He Pei-min , Jia Rui 
Published: October 2023

Abstractµ-Conotoxin GIIIB (µ-CTX GIIIB) is a polypeptide containing three disulfide bridges, produced by the sea snail Conus geographus. This study was aimed to explored the cytotoxic effects of µ-CTX GIIIB on mouse skeletal musculoblast (Sol8). Sol8 cells were exposed to ouabain and veratridine to establish the cell injury model, and then treated with µ-CTX GIIIB. CCK-8 was adopted to evaluate the cytotoxicity of µ-CTX GIIIB. Then, proteomics and transcriptome were conducted, and the explore the differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) affected by µ-CTX GIIIB were found. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to investigate the affected signaling pathways. µ-CTX GIIIB increased the cell survival rate of injured Sol8 cells. We found and identified 1,663 DEGs and 444 DEPs influenced by µ-CTX GIIIB. 106 pairs of correlated DEGs and DEPs were selected by combining transcriptome and proteome data. The results of KEGG and GO analysis showed that µ-CTX GIIB affected the cell cycle, apoptosis, DNA damage and repair, lipid metabolism and other biological processes of Sol8 cells. µ-CTX GIIIB could affected cell cycle regulation, DNA damage repair, and activation of tumor factors, with potential carcinogenic effects. Our results provide an important basis for the study of in vitro toxicity, the mechanism of toxicity and injury prevention by µ-CTX GIIIB.
Myeloid PTP1B deficiency protects against atherosclerosis by improving cholesterol homeostasis through an AMPK-dependent mechanism
Authors: Oliver Helk , Ruta Dekeryte , Thompson Dawn , Kamli-Salino Sarah , Philip Sam , Wilson Heather M. , Mody Nimesh , Delibegovic Mirela 
Published: October 2023

Abstract
Objective
Atherosclerosis is a chronic inflammatory process induced by the influx and entrapment of excess lipoproteins into the intima media of arteries. Previously, our lab demonstrated that systemic PTP1B inhibition protects against atherosclerosis in preclinical LDLR−/− models. Similarly, it was shown that myeloid-specific PTP1B ablation decreases plaque formation and ameliorates dyslipidaemia in the ApoE−/− model of atherosclerosis. We hypothesized that the relevant improvements in dyslipidaemia following modification of PTP1B activation may either result from changes in hepatic cholesterol biosynthesis and/or increased uptake and degradation by liver-resident macrophages. We examined this in animal models and patients with coronary artery disease.

Methods
In this study, we determined the cholesterol-lowering effect of myeloid-PTP1B deletion in mice fed a high-fat high-cholesterol diet and examined effects on total cholesterol levels and lipoprotein profiles. We also determined the effects of PTP1B inhibition to oxLDL-C challenge on foam cell formation and cholesterol efflux in human monocytes/macrophages.

Results
We present evidence that myeloid-PTP1B deficiency significantly increases the affinity of Kupffer cells for ApoB containing lipoproteins, in an IL10-dependent manner. We also demonstrate that PTP1B inhibitor, MSI-1436, treatment decreased foam cell formation in Thp1-derived macrophages and increased macrophage cholesterol efflux to HDL in an AMPK-dependent manner. We present evidence of three novel and distinct mechanisms regulated by PTP1B: an increase in cholesterol efflux from foam cells, decreased uptake of lipoproteins into intra-lesion macrophages in vitro and a decrease of circulating LDL-C and VLDL-C in vivo.

Conclusions
Overall, these results suggest that myeloid-PTP1B inhibition has atheroprotective effects through improved cholesterol handling in atherosclerotic lesions, as well as increased reverse cholesterol transport.
Trial registration Research registry, researchregistry 3235. Registered 07 November 2017, https://www.researchregistry.com/browse-the-registry#home/registrationdetails/5a01d0fce7e1904e93e0aac5/.
Astrocyte interferon-gamma signaling dampens inflammation during chronic central nervous system autoimmunity via PD-L1
Authors: Smith Brandon C. , Tinkey Rachel A. , Brock Orion D. , Mariam Arshiya , Habean Maria L. , Dutta Ranjan , Williams Jessica L. 
Published: October 2023

AbstractMultiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS). Infiltrating inflammatory immune cells perpetuate demyelination and axonal damage in the CNS and significantly contribute to pathology and clinical deficits. While the cytokine interferon (IFN)γ is classically described as deleterious in acute CNS autoimmunity, we and others have shown astrocytic IFNγ signaling also has a neuroprotective role. Here, we performed RNA sequencing and ingenuity pathway analysis on IFNγ-treated astrocytes and found that PD-L1 was prominently expressed. Interestingly, PD-1/PD-L1 antagonism reduced apoptosis in leukocytes exposed to IFNγ-treated astrocytes in vitro. To further elucidate the role of astrocytic IFNγ signaling on the PD-1/PD-L1 axis in vivo, we induced the experimental autoimmune encephalomyelitis (EAE) model of MS in Aldh1l1-CreERT2, Ifngr1fl/fl mice. Mice with conditional astrocytic deletion of IFNγ receptor exhibited a reduction in PD-L1 expression which corresponded to increased infiltrating leukocytes, particularly from the myeloid lineage, and exacerbated clinical disease. PD-1 agonism reduced EAE severity and CNS-infiltrating leukocytes. Importantly, PD-1 is expressed by myeloid cells surrounding MS lesions. These data support that IFNγ signaling in astrocytes diminishes inflammation during chronic autoimmunity via upregulation of PD-L1, suggesting potential therapeutic benefit for MS patients.
In vitro investigation of the effect of proinflammatory cytokines on mouse choroid plexus membrane transporters Ncbe and NKCC1
Authors: Johnsen Laura Øllegaard , Friis Kathrine Abildskov , Damkier Helle Hasager 
Published: October 2023

AbstractIntraventricular hemorrhage is a potentially life-threatening condition. Approximately 20% of patients develop posthemorrhagic hydrocephalus with increased ventricular volume and intracranial pressure. Hydrocephalus develops partially due to increased secretion of cerebrospinal fluid by the choroid plexus. During hemorrhage a multitude of factors are released into the cerebrospinal fluid. Many of these have been implicated in the hypersecretion. In this study, we have investigated the isolated effect of inflammatory components, on the abundance of two membrane transporters involved in cerebrospinal fluid secretion by the choroid plexus: the Na+-dependent Cl−/HCO3− exchanger, Ncbe, and the Na+, K+, 2Cl− cotransporter, NKCC1. We have established a primary choroid plexus epithelial cell culture from 1 to 7 days old mouse pups. Seven days after seeding, the cells formed a monolayer. The cells were treated with either tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL-1β), or interleukin 6 (IL-6) to mimic inflammation. The data show that treatment with TNFα, and IL-1β only transiently increased NKCC1 abundance whereas the effect on Ncbe abundance was a transient decrease. IL-6 however significantly increased NKCC1 (242%), the phosphorylated NKCC1 (147%), as well as pSPAK (406%) abundance, but had no effect on Ncbe. This study suggests that the inflammatory pathway involved in hypersecretion primarily is mediated by activation of basolateral receptors in the choroid plexus, mainly facilitated by IL-6. This study highlights the complexity of the pathophysiological circumstances occurring during intraventricular hemorrhage.
The clinical significance of some serum tumor markers among chronic patients with Helicobacter pylori infections in Ibb Governorate, Yemen
Authors: Saeed Marwan K. , Al-Ofairi B. A. , Hassan Mohammed A. , Al-Jahrani M. A. , Abdulkareem Ahmed M. 
Published: October 2023

Abstract
Background
Helicobacter pylori (H. pylori) is a carcinogenic bacterium, it is the greatest risk factor for gastric cancer (GC), according to these evidences, there may be a certain association between chronic H. pylori infections and serum levels of tumor markers. This study was conducted to determine serum levels of some tumor markers, namely carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and cancer antigen 72-4 (CA72-4) in patients with chronic H. pylori infections and evaluate the association between serum tumor marker levels and chronic patients with H. pylori infections in Ibb Governorate, Yemen.

Subjects and methods
This study involved 200 patients who had been diagnosed with H. pylori infections using a serum immunochromatography antibody test. Stool and blood samples were collected from all patients to confirm the presence of H. pylori through detection of serum H. pylori IgG antibody and stool antigen test (SAT). Additionally, serum samples were analyzed to measurement the level of certain tumor markers CEA, CA19-9 and CA72-4. These tests were conducted at various Hospitals, Gastroenterology and Hepatology clinics in Ibb governorate, Yemen from October 2019 to November 2020.

Results
The findings of current study showed that the prevalence of H. pylori infections by rapid anti H. pylori test were 200 (100%), 157 (78.5%) by serum H. pylori IgG antibody and 108 (54%) by SAT. In addition, the results showed that 42 (21%) of the patients had abnormal level of CEA, 30 (15%) had abnormal level of CA19-9 and 31 (15.5%) had abnormal level of CA72-4. Most importantly, the results indicated that the serum tumor marker levels CEA, CA19-9 and CA72-4 were correlated with the levels of serum H. pylori IgG antibody as well as positive results from the SAT (P < 0.05). Furthermore, the results indicated that serum tumor marker levels were associated with different infection status. Finally, the results indicated that the serum levels of tumor markers were associated with older ages, symptomatic patients and long duration of H. pylori infections (P < 0.05).

Conclusion
The findings of this study indicated that there is a significant association between chronic H. pylori infections and the serum levels of tumor markers (CEA, CA19-9 and CA72-4). This suggests that the patients with active chronic H. pylori infection may have an increased risk of developing GC. Therefore, monitoring and early detection of H. pylori infection and tumor markers levels in these patients may be crucial for identifying individuals at higher risk and implementing appropriate interventions.
Robust, scalable, and informative clustering for diverse biological networks
Authors: Gaiteri Chris , Connell David R. , Sultan Faraz A. , Iatrou Artemis , Ng Bernard , Szymanski Boleslaw K. , Zhang Ada , Tasaki Shinya 
Published: October 2023

AbstractClustering molecular data into informative groups is a primary step in extracting robust conclusions from big data. However, due to foundational issues in how they are defined and detected, such clusters are not always reliable, leading to unstable conclusions. We compare popular clustering algorithms across thousands of synthetic and real biological datasets, including a new consensus clustering algorithm—SpeakEasy2: Champagne. These tests identify trends in performance, show no single method is universally optimal, and allow us to examine factors behind variation in performance. Multiple metrics indicate SpeakEasy2 generally provides robust, scalable, and informative clusters for a range of applications.
Global analysis of suppressor mutations that rescue human genetic defects
Authors: Ünlü Betül , Pons Carles , Ho Uyen Linh , Batté Amandine , Aloy Patrick , van Leeuwen Jolanda 
Published: October 2023

Abstract
Background
Genetic suppression occurs when the deleterious effects of a primary “query” mutation, such as a disease-causing mutation, are rescued by a suppressor mutation elsewhere in the genome.

Methods
To capture existing knowledge on suppression relationships between human genes, we examined 2,400 published papers for potential interactions identified through either genetic modification of cultured human cells or through association studies in patients.

Results
The resulting network encompassed 476 unique suppression interactions covering a wide spectrum of diseases and biological functions. The interactions frequently linked genes that operate in the same biological process. Suppressors were strongly enriched for genes with a role in stress response or signaling, suggesting that deleterious mutations can often be buffered by modulating signaling cascades or immune responses. Suppressor mutations tended to be deleterious when they occurred in absence of the query mutation, in apparent contrast with their protective role in the presence of the query. We formulated and quantified mechanisms of genetic suppression that could explain 71% of interactions and provided mechanistic insight into disease pathology. Finally, we used these observations to predict suppressor genes in the human genome.

Conclusions
The global suppression network allowed us to define principles of genetic suppression that were conserved across diseases, model systems, and species. The emerging frequency of suppression interactions among human genes and range of underlying mechanisms, together with the prevalence of suppression in model organisms, suggest that compensatory mutations may exist for most genetic diseases.
Increasing design flexibility by manually adapting the solution space for crashworthiness
Authors: Ascia Paolo , Lange Volker A. , Duddeck Fabian 
Published: October 2023

AbstractThe solution space methodology, as presented in 2013, was meant to guide developers at the very beginning of the development process of a new mechanically crashworthy car. Several attempts were already made to use this methodology at later development stages. However, they all encountered problems related to its very strict and demanding corridors, thus constricting the design parameters. To allow more flexibility, two different approaches were proposed to relax the initial strict conditions. The first introduced temporal dependencies to widen the corridors. The second locally changed the corridors to adapt to the needs of the development, introducing dependencies between components. We, on the contrary, propose a new method to increase flexibility without introducing any kind of dependencies. We manage this by computing the intervals of solution space under user-defined conditions, hence selecting a custom set of independent corridors that fits the data gathered during development; i.e.: force-deformation curves that can be measured during a drop-tower test simulation. This new methodology of the adaptive solution space allows designers to edit the corridors, in order to have more flexibility for fulfilling high-level requirements when independently designing new components.
Myocardial glucose suppression may interfere with the detection of inflammatory cells with FDG-PET as suggested in a canine model of myocardial infarction
Authors: Wilk Benjamin , Smailovic Haris , Sullivan Rebecca , Sistermans Erik R. , Butler John , Jago Hannah , Kovacs Michael , Wisenberg Gerald , Thiessen Jonathan D. , Prato Frank S. 
Published: October 2023

Abstract
Background
After myocardial infarction, fibrosis and an ongoing dysregulated inflammatory response have been shown to lead to adverse cardiac remodeling. FDG PET is an imaging modality sensitive to inflammation as long as suppression protocols are observed while gadolinium enhanced MRI can be used to determine extracellular volume (ECV), a measure of fibrosis. In patients, glucose suppression is achieved variously through a high fat diet, fasting and injection of heparin. To emulate this process in canines, a heparin injection and lipid infusion are used, leading to similar fatty acids in the blood. The aim of this study was to examine the effect of glucose suppression on the uptake of FDG in the infarcted myocardial tissue and also on the determination of ECV in both the infarcted tissue and in the myocardium remote to the zone of infarction during a long constant infusion of FDG and Gd-DTPA.

Results
Extracellular volume was affected neither by suppression nor the length of the constant infusion in remote and infarcted tissue. Metabolic rate of glucose in infarcted tissue decreased during and after suppression of glucose uptake by lipid infusion and heparin injection. An increase in fibrosis and inflammatory cells was found in the center of the infarct as compared to remote tissue.

Conclusion
The decrease in the metabolic rate of glucose in the infarcted tissue suggests that inflammatory cells may be affected by glucose suppression through heparin injection and lipid infusion.
Regulation of appetite-related neuropeptides by herbal medicines: research using microarray and network pharmacology
Authors: Lee Ji Hwan , Jang Dongyeop , Lee Myong Jin , Shin Myoung-Sook , Kim Chang-Eop , Park Jun Yeon , Kang Ki Sung 
Published: October 2023

AbstractAnorexia means loss of appetite and is a state whereby a desire to eat is either reduced or eliminated resulting in reducing or stopping food intake. Sipjeondaebo-tang (SDT) and Hyangsayukgunja-tang (HYT) are prescriptions known to have appetite-improving effects, but studies on their mechanisms and active components are insufficient. The hypothalamus is the center of appetite control, and various appetite control mechanisms are known. We used mouse hypothalamic neuronal GT1-7 cells as appetite control center cells and analyzed the difference in efficacy between SDT and HYT using microarray and network pharmacology. Microarray analysis showed that SDT and HYT affect the regulation of genes related to appetite control in the digestive tract and central nervous system. Using network pharmacology, we analyzed the differential expression of neuropeptide Y receptors, glucagon, corticotropin-releasing hormone receptors 1, and 5-hydroxytryptamine receptor 4 among the 17 anorexia-related genes selected from the comparative toxicogenomics database and also analyzed the active components that affect gene expression. In conclusion, the appetite-related genes contributed to anorexia control, and the difference in the action mechanism of the two complex prescriptions could be explained.
High mobility group box-1: a potential therapeutic target for allergic rhinitis
Authors: Wu Shuhua , Yu Yangyang , Zheng Zhong , Cheng Qi 
Published: October 2023

AbstractAllergic rhinitis (AR) is a prevalent chronic inflammatory disease of the nasal mucosa primarily characterized by symptoms, such as nasal itching, sneezing, runny nose, and nasal congestion. It has a high recurrence rate and low cure rate, with a lack of effective drugs for treatment. The current approach to management focuses on symptom control. High mobility group box-1 (HMGB1) is a highly conserved non-histone protein widely present in the nucleus of eukaryotes. It is recognized as a proinflammatory agent, and recent studies have demonstrated its close association with AR. Here, we will elaborate the role and mechanism of HMGB1 in AR, so as to reveal the potential value of HMGB1 in the occurrence and development of AR, and provide a new target for clinical research on the treatment of AR.
Variations in ecosystem service value in response to land use changes in Dhaka and Gazipur Districts of Bangladesh
Authors: Sorker Raihan , Khan Mohammad Wahidur , Kabir Alamgir , Nawar Nowshin 
Published: October 2023

AbstractUrban sprawl is a global phenomenon that has resulted in a substantial impact on ecosystem services. This study assessed how land use changes have affected the ecosystem services in Dhaka and Gazipur districts, two important economic centers of Bangladesh. This study analyzed changes in land use categories and their effects on ecosystem services during a thirty-year period, from 1990 to 2020, using LandSat data and published coefficient values. Additionally, a sensitivity analysis was undertaken to evaluate the ramifications of altering these coefficients on the resultant estimated values. The study revealed that in both Dhaka and Gazipur districts, the expansion of settlement areas and the reduction in tree vegetation cover have led to a significant decline in the overall value of ecosystem services. Over a 30-year timeframe, Gazipur experienced a more substantial loss in tree vegetation cover compared to Dhaka, whereas Dhaka witnessed a greater increase in settlement areas than Gazipur. Remarkably, during the most recent decade (2010–2020), the Gazipur district encountered heightened urban expansion and a more significant reduction in tree vegetation compared to Dhaka. The loss of the entire ecosystem service value was significant, amounting to USD 206.24 million for Dhaka and USD 381.27 million for Gazipur. This loss was primarily attributed to the decline in agricultural land, water bodies, rivers, and a reduction in tree vegetation. The study recommends that a more responsible land-use plan be created to protect tree vegetation, sustainable agriculture, and water bodies, which have the highest ecosystem service value in the study area. Overall, this study highlights the need for sustainable land-use techniques and offers insightful information about how urbanization affects ecosystem services in the investigated areas.