bluuebunny/crossref_metadata_2025_split huggingface dataset:
A strategic study of acupuncture for diabetic kidney disease based on meta-analysis and data mining
Authors: Yu Yunfeng , Hu Gang , Yang Xinyu , Yin Yuman , Tong Keke , Yu Rong 
Published: February 2024

ObjectiveThe specific benefit and selection of acupoints in acupuncture for diabetic kidney disease (DKD) remains controversial. This study aims to explore the specific benefits and acupoints selection of acupuncture for DKD through meta-analysis and data mining.MethodsClinical trials of acupuncture for DKD were searched in eight common databases. Meta-analysis was used to evaluate its efficacy and safety, and data mining was used to explore its acupoints selection.ResultsMeta-analysis displayed that compared with the conventional drug group, the combined acupuncture group significantly increased the clinical effective rate (risk ratio [RR] 1.35, 95% confidence interval [CI] 1.20 to 1.51, P &lt; 0.00001) and high-density lipoprotein cholesterol (mean difference [MD] 0.36, 95% CI 0.27 to 0.46, P &lt; 0.00001), significantly reduced the urinary albumin (MD –0.39, 95% CI –0.42 to –0.36, P &lt; 0.00001), urinary microalbumin (MD –32.63, 95% CI –42.47 to –22.79, P &lt; 0.00001), urine β2-microglobulin (MD –0.45, 95% CI –0.66 to –0.24, P &lt; 0.0001), serum creatinine (MD –15.36, 95% CI –21.69 to –9.03, P &lt; 0.00001), glycated hemoglobin A1c (MD –0.69, 95% CI –1.18 to –0.19, P = 0.006), fasting blood glucose (MD –0.86, 95% CI –0.90 to –0.82, P &lt; 0.00001), 2h postprandial plasma glucose (MD –0.87, 95% CI –0.92 to –0.82, P &lt; 0.00001), total cholesterol (MD –1.23, 95% CI –2.05 to –0.40, P = 0.003), triglyceride (MD –0.69, 95% CI –1.23 to –0.15, P = 0.01), while adverse events were comparable. Data mining revealed that CV12, SP8, SP10, ST36, SP6, BL20, BL23, and SP9 were the core acupoints for DKD treated by acupuncture.ConclusionAcupuncture improved clinical symptoms, renal function indices such as uALB, umALB, uβ2-MG, and SCR, as well as blood glucose and blood lipid in patients with DKD, and has a favorable safety profile. CV12, SP8, SP10, ST36, SP6, BL20, BL23, and SP9 are the core acupoints for acupuncture in DKD, and this program is expected to become a supplementary treatment for DKD.
Incidence of microvascular dysfunction is increased in hyperlipidemic mice, reducing cerebral blood flow and impairing remote memory
Authors: Hernandez Torres Luis Daniel , Rezende Flavia , Peschke Eva , Will Olga , Hövener Jan-Bernd , Spiecker Frauke , Özorhan Ümit , Lampe Josephine , Stölting Ines , Aherrahrou Zouhair , Künne Carsten , Kusche-Vihrog Kristina , Matschl Urte , Hille Susanne , Brandes Ralf P. , Schwaninger Markus , Müller Oliver J. , Raasch Walter 
Published: February 2024

IntroductionThe development of cognitive dysfunction is not necessarily associated with diet-induced obesity. We hypothesized that cognitive dysfunction might require additional vascular damage, for example, in atherosclerotic mice.MethodsWe induced atherosclerosis in male C57BL/6N mice by injecting AAV-PCSK9DY (2x1011 VG) and feeding them a cholesterol-rich Western diet. After 3 months, mice were examined for cognition using Barnes maze procedure and for cerebral blood flow. Cerebral vascular morphology was examined by immunehistology.ResultsIn AAV-PCSK9DY-treated mice, plaque burden, plasma cholesterol, and triglycerides are elevated. RNAseq analyses followed by KEGG annotation show increased expression of genes linked to inflammatory processes in the aortas of these mice. In AAV-PCSK9DY-treated mice learning was delayed and long-term memory impaired. Blood flow was reduced in the cingulate cortex (-17%), caudate putamen (-15%), and hippocampus (-10%). Immunohistological studies also show an increased incidence of string vessels and pericytes (CD31/Col IV staining) in the hippocampus accompanied by patchy blood-brain barrier leaks (IgG staining) and increased macrophage infiltrations (CD68 staining).DiscussionWe conclude that the hyperlipidemic PCSK9DY mouse model can serve as an appropriate approach to induce microvascular dysfunction that leads to reduced blood flow in the hippocampus, which could explain the cognitive dysfunction in these mice.
Key genes involved in nonalcoholic steatohepatitis improvement after bariatric surgery
Authors: Chen Xiyu , Deng Shi-Zhou , Sun Yuze , Bai Yunhu , Wang Yayun , Yang Yanling 
Published: February 2024

BackgroundNonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), one of the most prevalent chronic liver diseases. The effectiveness of bariatric surgery in treating NASH and preventing or even reversing liver fibrosis has been demonstrated in numerous clinical studies, but the underlying mechanisms and crucial variables remain unknown.MethodsUsing the GSE135251 dataset, we examined the gene expression levels of NASH and healthy livers. Then, the differentially expressed genes (DEGs) of patients with NASH, at baseline and one year after bariatric surgery, were identified in GSE83452. We overlapped the hub genes performed by protein-protein interaction (PPI) networks and DEGs with different expression trends in both datasets to obtain key genes. Genomic enrichment analysis (GSEA) and genomic variation analysis (GSVA) were performed to search for signaling pathways of key genes. Meanwhile, key molecules that regulate the key genes are found through the construction of the ceRNA network. NASH mice were induced by a high-fat diet (HFD) and underwent sleeve gastrectomy (SG). We then cross-linked the DEGs in clinical and animal samples using quantitative polymerase chain reaction (qPCR) and validated the key genes.ResultsSeven key genes (FASN, SCD, CD68, HMGCS1, SQLE, CXCL10, IGF1) with different expression trends in GSE135251 and GSE83452 were obtained with the top 30 hub genes selected by PPI. The expression of seven key genes in mice after SG was validated by qPCR. Combined with the qPCR results from NASH mice, the four genes FASN, SCD, HMGCS1, and CXCL10 are consistent with the biological analysis. The GSEA results showed that the ‘cholesterol homeostasis’ pathway was enriched in the FASN, SCD, HMGCS1, and SQLE high-expression groups. The high-expression groups of CD68 and CXCL10 were extremely enriched in inflammation-related pathways. The construction of the ceRNA network obtained microRNAs and ceRNAs that can regulate seven key genes expression.ConclusionIn summary, this study contributes to our understanding of the mechanisms by which bariatric surgery improves NASH, and to the development of potential biomarkers for the treatment of NASH.
Differentially expressed microRNAs targeting genes in key pathways in keratoconus
Authors: Nowak-Malczewska Dorota M. , Swierkowska Joanna , Gajecka Marzena 
Published: February 2024

Introduction: Keratoconus (KTCN) is a corneal ectasia, characterized by a progressive thinning and protrusion of the cornea, with a complex etiology involving genetic, behavioral, lifestyle, and environmental factors. Previous studies indicated that microRNAs (miRNAs) could be involved in KTCN pathogenesis. This in silico study aimed to identify precursor microRNAs (pre-miRNAs) differentially expressed in KTCN corneas and to characterize mature miRNAs and their target genes.Materials and methods: Expression levels of pre-miRNAs were retrieved from our previously obtained RNA sequencing data of 25 KTCN and 25 non-KTCN human corneas (PMID:28145428, PMID:30994860). Differential expression with FDR ≤0.01 and ≥1.5-fold changes were considered significant. Lists of target genes (target score ≥90) of mature miRNAs were obtained from miRDB. Revealed up-/downregulated miRNAs and their target genes were assessed in databases and literature. Enrichment analyses were completed applying the DAVID database.Results: From a total of 47 pre-miRNAs, six were remarkably upregulated (MIR184, MIR548I1, MIR200A, MIR6728, MIR429, MIR1299) and four downregulated (MIR6081, MIR27B, MIR23B, MIR23A) in KTCN corneas. Out of the 1,409 target genes, 220 genes with decreased and 57 genes with increased expression levels in KTCN samples vs non-KTCN samples were found. The extracellular matrix (ECM) organization, response to mechanical stimulus, regulation of cell shape, and signal transduction processes/pathways were identified as distinctive in enrichment analyses. Also, processes associated with the regulation of transcription and DNA binding were listed.Conclusion: Indicated miRNAs and their target genes might be involved in KTCN pathogenesis via disruption of crucial molecular processes, including ECM organization and signal transduction.
An integrative mechanistic model of thymocyte dynamics
Authors: Kulesh Victoria , Peskov Kirill , Helmlinger Gabriel , Bocharov Gennady 
Published: February 2024

BackgroundThe thymus plays a central role in shaping human immune function. A mechanistic, quantitative description of immune cell dynamics and thymic output under homeostatic conditions and various patho-physiological scenarios are of particular interest in drug development applications, e.g., in the identification of potential therapeutic targets and selection of lead drug candidates against infectious diseases.MethodsWe here developed an integrative mathematical model of thymocyte dynamics in human. It incorporates mechanistic features of thymocyte homeostasis as well as spatial constraints of the thymus and considerations of age-dependent involution. All model parameter estimates were obtained based on published physiological data of thymocyte dynamics and thymus properties in mouse and human. We performed model sensitivity analyses to reveal potential therapeutic targets through an identification of processes critically affecting thymic function; we further explored differences in thymic function across healthy subjects, multiple sclerosis patients, and patients on fingolimod treatment.ResultsWe found thymic function to be most impacted by the egress, proliferation, differentiation and death rates of those thymocytes which are most differentiated. Model predictions also showed that the clinically observed decrease in relapse risk with age, in multiple sclerosis patients who would have discontinued fingolimod therapy, can be explained mechanistically by decreased thymic output with age. Moreover, we quantified the effects of fingolimod treatment duration on thymic output.ConclusionsIn summary, the proposed model accurately describes, in mechanistic terms, thymic output as a function of age. It may be further used to perform predictive simulations of clinically relevant scenarios which combine specific patho-physiological conditions and pharmacological interventions of interest.
Case report: Successful treatment of an anti-D2R and DPPX antibody-associated autoimmune encephalitis patient with high-dose methylprednisolone and intravenous immunoglobulin
Authors: Lin Zhangliang , Zhou Feng , Ni Lili , Dong Shiye , Fu Guoping , Zhao Jiangman 
Published: February 2024

BackgroundAutoimmune encephalitis is a neurological condition caused by abnormal immune responses, manifesting as cognitive impairments, behavioral abnormalities, and seizures. Its diagnosis depends on the detecting neuronal surface antibodies in serum or cerebrospinal fluid. Despite recent advances in understanding, clinical recognition remains challenging, especially with rare antibodies such as anti-dopamine D2 receptor (D2R) and anti-dipeptidyl-peptidase-like protein 6 (DPPX) antibodies. Delayed diagnosis can lead to severe complications. This case presentation emphasizes the diagnostic intricacies and effective treatment of the anti-D2R and DPPX antibody-associated autoimmune encephalitis.Case descriptionThe patient presented with a 3-day history of fatigue and limb soreness followed by a 3-h episode of confusion and limb convulsions. Upon admission to our facility, the initial diagnosis included status epilepticus, aspiration pneumonia, metabolic acidosis, respiratory alkalosis, and suspected encephalitis. Despite receiving antiepileptic, anti-infection, and antivirus therapy, the patient’s condition deteriorated. Both computed tomography (CT) scan and magnetic resonance imaging (MRI) of the brain showed no significant abnormalities. No pathogen was identified in the cerebrospinal fluid (CSF). However, further CSF and serum examination revealed positive results of anti-D2R and anti-DPPX antibodies, confirming a diagnosis of anti-D2R and DPPX antibody-associated autoimmune encephalitis. The patient underwent a comprehensive treatment regimen, including high-dose methylprednisolone pulse therapy combined with intravenous immunoglobulin (IVIG), antiviral and anti-infection treatments, and antiepileptic medications. Significant clinical improvement was observed, and by the 18th day of admission, the patient was stable and coherent.ConclusionsThe current patient represents the first reported case of double-positive autoimmune encephalitis for anti-D2R and DPPX antibodies, with epilepsy as a prominent feature. High-dose methylprednisolone pulse therapy combined with IVIG has shown significant safety and efficacy in treating anti-D2R and DPPX antibody-positive autoimmune encephalitis-associated epilepsy.
Histidine-rich glycoprotein in metabolic dysfunction-associated steatohepatitis-related disease progression and liver carcinogenesis
Authors: Foglia Beatrice , Sutti Salvatore , Cannito Stefania , Rosso Chiara , Maggiora Marina , Casalino Alice , Bocca Claudia , Novo Erica , Protopapa Francesca , Ramavath Naresh Naik , Provera Alessia , Gambella Alessandro , Bugianesi Elisabetta , Tacke Frank , Albano Emanuele , Parola Maurizio 
Published: February 2024

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD), previously non-alcoholic fatty liver disease (NAFLD), is a leading cause of chronic liver disease worldwide. In 20%–30% of MASLD patients, the disease progresses to metabolic dysfunction-associated steatohepatitis (MASH, previously NASH) which can lead to fibrosis/cirrhosis, liver failure as well as hepatocellular carcinoma (HCC). Here we investigated the role of histidine-rich glycoprotein (HRG), a plasma protein produced by hepatocytes, in MASLD/MASH progression and HCC development.MethodsThe role of HRG was investigated by morphological, cellular, and molecular biology approaches in (a) HRG knock-out mice (HRG−/− mice) fed on a CDAA dietary protocol or a MASH related diethyl-nitrosamine/CDAA protocol of hepatocarcinogenesis, (b) THP1 monocytic cells treated with purified HRG, and (c) well-characterized cohorts of MASLD patients with or without HCC.ResultsIn non-neoplastic settings, murine and clinical data indicate that HRG increases significantly in parallel with disease progression. In particular, in MASLD/MASH patients, higher levels of HRG plasma levels were detected in subjects with extensive fibrosis/cirrhosis. When submitted to the pro-carcinogenic protocol, HRG−/− mice showed a significant decrease in the volume and number of HCC nodules in relation to decreased infiltration of macrophages producing pro-inflammatory mediators, including IL-1β, IL-6, IL-12, IL-10, and VEGF as well as impaired angiogenesis. The histopathological analysis (H-score) of MASH-related HCC indicate that the higher HRG positivity in peritumoral tissue significantly correlates with a lower overall patient survival and an increased recurrence. Moreover, a significant increase in HRG plasma levels was detected in cirrhotic (F4) patients and in patients carrying HCC vs. F0/F1 patients.ConclusionMurine and clinical data indicate that HRG plays a significant role in MASLD/MASH progression to HCC by supporting a specific population of tumor-associated macrophages with pro-inflammatory response and pro-angiogenetic capabilities which critically support cancer cell survival. Furthermore, our data suggest HRG as a possible prognostic predictor in HCC patients with MASLD/MASH-related HCCs.
Brain imaging derived phenotypes: a biomarker for the onset of inflammatory bowel disease and a potential mediator of mental complications
Authors: Li Fan , Zhao Qi , Tang Tongyu , Liu Yuyuan , Wang Zhaodi , Wang Zhi , Han Xiaoping , Xu Zifeng , Chang Yu , Li Yuqin 
Published: February 2024

Background and aimsInflammatory bowel disease (IBD), mainly categorized into Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic relapsing gastrointestinal disorder that significantly impairs patients’ quality of life. IBD patients often experience comorbidities such as anxiety and depression, and the underlying mechanisms and treatment strategies remain areas of investigation.MethodsWe conducted a Mendelian randomization(MR) analysis utilizing brain image derived phenotypes (IDP) from the UK Biobank database to investigate the causal relationships between IBD and alterations in brain structural morphology and connectivity of neural tracts. This study aimed to identify biological evidence linking IBD to psychiatric disorders such as anxiety and depression.ResultsSpecifically, the volume of grey matter in the Left Frontal Orbital Cortex exhibited a negative association with the onset of Crohn’s disease (odds ratio (OR) [95% confidence interval (CI)]: 0.315[0.180~0.551], adjusted P=0.001), while the volume of the superior frontal cortex in the right hemisphere showed a positive correlation with the development of Ulcerative colitis (OR [95% CI]: 2.285[1.793~2.911], adjusted P&lt;0.001), and the volume of lateral occipital cortex in the left hemisphere demonstrated a positive relationship with Crohn’s disease onset (OR [95% CI]: 1.709[1.671~1.747], adjusted P&lt;0.001). In the context of reverse causality, the onset of UC or CD has led to alterations in imaging derived phenotypes associated with five disorders (anxiety, depression, schizophrenia, bipolar disorder, pain) and three functions (memory, emotion, language).ConclusionOur study has demonstrated a causal relationship between IBD and IDPs. IDPs may serve as potential biomarkers for the progression of IBD and as predictive intermediaries for the development of neurological diseases in IBD patients.
Abnormal functional lymphoid tolerance and enhanced myeloid exocytosis are characteristics of resting and stimulated PBMCs in cystic fibrosis patients
Authors: Gaudin Clémence , Ghinnagow Reem , Lemaire Flora , Villeret Bérengère , Sermet-Gaudelus Isabelle , Sallenave Jean-Michel 
Published: February 2024

IntroductionCystic Fibrosis (CF) is the commonest genetically inherited disease (1 in 4,500 newborns) and 70% of people with CF (pwCF) harbour the F508Del mutation, resulting in misfolding and incorrect addressing of the channel CFTR to the epithelial membrane and subsequent dysregulation of fluid homeostasis. Although studies have underscored the importance and over-activation of myeloid cells, and in particular neutrophils in the lungs of people with CF (pwCF), relatively less emphasis has been put on the potential immunological bias in CF blood cells, at homeostasis or following stimulation/infection.MethodsHere, we revisited, in an exhaustive fashion, in pwCF with mild disease (median age of 15, median % FEV1 predicted = 87), whether their PBMCs, unprimed or primed with a ‘non specific’ stimulus (PMA+ionomycin mix) and a ‘specific’ one (live P.a =PAO1 strain), were differentially activated, compared to healthy controls (HC) PBMCs.Results1) we analysed the lymphocytic and myeloid populations present in CF and Control PBMCs (T cells, NKT, Tgd, ILCs) and their production of the signature cytokines IFN-g, IL-13, IL-17, IL-22. 2) By q-PCR, ELISA and Luminex analysis we showed that CF PBMCs have increased background cytokines and mediators production and a partial functional tolerance phenotype, when restimulated. 3) we showed that CF PBMCs low-density neutrophils release higher levels of granule components (S100A8/A9, lactoferrin, MMP-3, MMP-7, MMP-8, MMP-9, NE), demonstrating enhanced exocytosis of potentially harmful mediators.DiscussionIn conclusion, we demonstrated that functional lymphoid tolerance and enhanced myeloid protease activity are key features of cystic fibrosis PBMCs.
Association between the risk of malnutrition and sarcopenia at 4.2 years of follow-up in community-dwelling older adults
Authors: Vidaña-Espinoza Helen J. , López-Teros Miriam T. , Esparza-Romero Julián , Rosas-Carrasco Oscar , Luna-López Armando , Alemán Mateo Heliodoro 
Published: February 2024

IntroductionCurrently, there is only scarce evidence of a causal association between risk of malnutrition (RM) by the mini-nutritional assessment (MNA) and the incidence of sarcopenia. This study was designed to assess such an association at 4.2 years of follow-up in community-dwelling subjects over 60 years old.MethodsThe data used were from the FraDySMex cohort study. The exposition variables were RM diagnosed by the long forma of the MNA (MNA-LF) and short form (MNA-SF). The last one included the body mass index and calf circumference at baseline, while sarcopenia was diagnosed by the EWGSOP2 at follow-up and taken as the response variable. Several covariates involved in the association were also considered. A multiple logistic regression analysis was performed to test the association.ResultsAt baseline, 27.0 and 37.9% of subjects had RM by the MNA-LF and MNA-SF, respectively. The incidence of sarcopenia was 13.7%. The fat mass variable significantly modified the association, so it was tested in each stratum. Two independent models showed that subjects with RM by the MNA-LF in the normal fat mass stratum were at a higher risk for developing sarcopenia at follow-up than those without RM (OR 9.28; IC 95% 1.57–54.76) after adjusting for age, sex, and waist circumference. No association was found for the excess fat mass stratum subjects. Subjects with RM by the MNA-SF in the excess fat mass stratum were more likely to develop sarcopenia at follow-up than those without RM by the MNA-SF (OR 3.67; IC 95% 1.29–10.43). This association was not found in the subjects in the normal fat mass stratum.ConclusionThe association was dependent on the variable fat mass. The two forms of the MNA should not be applied indistinctly with older adults. Based on these results, it is clear that the risk of malnutrition precedes the onset of sarcopenia.
Retinal structure and vessel density changes in cerebral small vessel disease
Authors: Wang Dandan , Wang Lina , Wang Jinjin , Du Yang , Wang Kaiyue , Wang Meizi , Yang Liu , Zhao Xingquan 
Published: February 2024

BackgroundCerebral small vessel disease (CSVD) attaches people’s attention in recent years. In this study, we aim to explore retinal structure and vessel density changes in CSVD patients.MethodsWe collected information on retinal metrics assessed by optical coherence tomography (OCT) and OCT angiography and CSVD characters. Logistic and liner regression was used to analyze the relationship between retinal metrics and CSVD.ResultsVessel density of superficial retinal capillary plexus (SRCP), foveal density- 300 length (FD-300), radial peripapillary capillary (RPC) and thickness of retina were significantly lower in CSVD patients, the difference only existed in the thickness of retina after adjusted relevant risk factors (OR (95% CI): 0.954 (0.912, 0.997), p = 0.037). SRCP vessel density showed a significant downward trend with the increase of CSVD scores (β: −0.087, 95%CI: −0.166, −0.008, p = 0.031). SRCP and FD-300 were significantly lower in patients with lacunar infarctions and white matter hypertensions separately [OR (95% CI): 0.857 (0.736, 0.998), p = 0.047 and OR (95% CI): 0.636 (0.434, 0.932), p = 0.020, separately].ConclusionSRCP, FD-300 and thickness of retina were associated with the occurrence and severity of total CSVD scores and its different radiological manifestations. Exploring CSVD by observing alterations in retinal metrics has become an optional research direction in future.