bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Orlistat on Sterol Metabolism in Obese Patients
Authors: Kwon Yu-Jin , Kwon Go Eun , Lee Hye Sun , Choi Man Ho , Lee Ji-Won 
Published: February 2022

BackgroundOrlistat, a reversible inhibitor of pancreatic and gastric lipase, is known to have anti-obesity and antioxidant properties. Cholesterol intermediates and metabolites have diverse and important functions in cardiovascular disease. Therefore, we aimed to evaluate the effect of orlistat on sterol metabolism in overweight and obese adults after weight loss during the intervention or weight loss at 12 weeks.MethodsA total of 51 (27 in the control group and 24 in the experimental group), patients with a BMI of 27 or greater were randomly assigned in a 1:1 ratio to receive either orlistat (120 mg) three times a day plus phentermine hydrochloride (37.5 mg) once daily or a placebo three times a day plus phentermine hydrochloride (37.5 mg) once daily. The primary study outcome was sterol metabolism.ResultsThe experimental group exhibited significantly decreased metabolic signatures of serum sterols, free cholesterol, sitosterol, 7α-hydroxycholesterol (7α-OHC), and 7β-OHC at 12 weeks. The experimental group also exhibited significantly decreased metabolic ratios of sitosterol and 7α-OHC to cholesterol at 12 weeks. Regarding changes in sterol signatures from baseline to 6-month follow-up, free cholesterol, plant sterols, and cholesterol precursors tended to decrease with weight loss during the intervention and increase again as the weight was regained in both groups.ConclusionOrlistat treatment improves oxysterol metabolism in overweight and obese adults. Our findings support that orlistat plays a crucial role in the process of endothelial dysfunction and atherosclerosis via oxysterol modulation.
Ketoconazole- and Metyrapone-Induced Reductions on Urinary Steroid Metabolites Alter the Urinary Free Cortisol Immunoassay Reliability in Cushing Syndrome
Authors: Vega-Beyhart Arturo , Laguna-Moreno Javier , Díaz-Catalán Daniela , Boswell Laura , Mora Mireia , Halperin Irene , Casals Gregori , Hanzu Felicia A. 
Published: February 2022

IntroductionTwenty-four-hour urinary free cortisol (24h-UFC) is the most used test for follow-up decision-making in patients with Cushing syndrome (CS) under medical treatment. However, 24h-UFC determinations by immunoassays (IA) are commonly overestimated because of steroid metabolites’ cross-reaction. It is still uncertain how ketoconazole (KTZ)- and metyrapone (MTP)-induced changes on the urinary steroid metabolites can alter the 24h-UFC*IA determinations’ reliability.Methods24h-UFC was analyzed by IA and gas chromatography-mass spectrometry (GC-MS) in 193 samples (81 before treatment, 73 during KTZ, and 39 during MTP) from 34 CS patients. In addition, urinary steroidome was analyzed by GC-MS on each patient before and during treatment.ResultsBefore treatment, 24h-UFC*IA determinations were overestimated by a factor of 1.75 (95% CI 1.60–1.94) compared to those by GC-MS. However, during KTZ treatment, 24h-UFC*IA results were similar (0.98:1) to those by GC-MS (95% CI, 0.83–1.20). In patients taking MTP, IA bias only decreased 0.55, resulting in persistence of an overestimation factor of 1.33:1 (95% CI, 1.09–1.76). High method agreement between GC-MS and IA before treatment (R2 = 0.954) declined in patients under KTZ (R2 = 0.632) but not in MTP (R2 = 0.917). Upper limit normal (ULN) reductions in patients taking KTZ were 27% larger when using 24h-UFC*IA compared to 24h-UFC*GC-MS, which resulted in higher false efficacy and misleading biochemical classification of 15% of patients. Urinary excretion changes of 22 urinary steroid metabolites explained 86% of the 24h-UFC*IA interference. Larger urinary excretion reductions of 6β-hydroxy-cortisol, 20α-dihydrocortisol, and 18-hydroxy-cortisol in patients with KTZ elucidated the higher 24h-UFC*IA bias decrement compared to MTP-treated patients.ConclusionKTZ and MTP alter the urinary excretion of IA cross-reactive steroid metabolites, thus decreasing the cross-reactive interference of 24h-UFC*IA determinations present before treatment. Consequently, this interference reduction in 24h-UFC*IA leads to loss of method agreement with GC-MS and high risk of overestimating the biochemical impact of KTZ and MTP in controlling CS because of poor reliability of reference ranges and ULN.
Numerical Investigations of Injection Timing Effects on a Gasoline Direct Injection Engine Performance: Part A, In-Cylinder Combustion Process
Authors: Yan Yuchao , Yang Ruomiao , Sun Xiaoxia , Li Ruijie , Liu Zhentao 
Published: February 2022

Gasoline direct injection (GDI) engine are widely adopted in the automobile industry since its advantage in the fuel economy. Injection Timing (IT) is an important parameter for the GDI engine, having a great impact on the spray atomization, mixture evenness, combustion characteristics, and therefore performance of the GDI engine. With the motive of IT optimization, a three-dimensional CFD model of a single cylinder 4-stroke spark ignition GDI engine with bore of 84 mm and compression ratio of 10.3 was utilized to analyze the detailed process at different IT (270, 280, 290, 300-degree CA BTDC), while the other conditions were invariant like rotate speed at 2000 RPM. The spray, turbulence, G-equation combustion were included. The result indicated that delayed IT tended to reduce drop-wall impingement significantly but still intensified unevenness of mixture concertation severely, resulting in fuel-rich region appeared around cylinder. Because the duration available for mixing was shortened, which dominantly intensified the unevenness of the mixture. The combustion was deteriorated as the IT delayed because the excessive equivalence ratio region severely slowed flame propagation and frozen at the most uneven region, which finally degraded thermal efficiency and engine performance. In conclusion, this paper demonstrated the whole process from injection to combustion, revealing that droplet-wall impingement and available duration for mixing are dominant trade-off factors for mixture formation and following combustion process, as the IT changes.
Effect of Electroacupuncture at Zusanli (ST36) on Intestinal Microbiota in Rats With Chronic Atrophic Gastritis
Authors: Huang Wanyi , Yau Yuenming , Zhu Jingru , Wang Yingjie , Dai Zhipeng , Gan Huijuan , Qian Linchao , Yang Zongbao 
Published: February 2022

Background: Electroacupuncture is a common treatment for chronic atrophic gastritis (CAG) in China. We aimed to determine the effects of electroacupuncture at zusanli (ST36) on intestinal microbiota in CAG rats.Methods: In total, 42 SD rats were randomly divided into normal (NC, 10 rats) and model (MG, 32 rats) groups. Rats in the MG group were established as CAG disease models. After that, the rats in the MG group were randomly divided into CAG (10 rats), electroacupuncture (EA, 10 rats), and Vitacoenzyme (Vit, 10 rats) groups. Rats in the NC and CAG groups were subjected to a 30-min/d confinement for 4 weeks. Rats in the EA group were given electroacupuncture at zusanli for 30 min/d for 4 weeks. Rats in the Vit group were given Vitacoenzyme solution 10 ml/(kg d) for 4 weeks. Histopathological changes in the gastric mucosa were observed with hematoxylin and eosin staining, and the gene expression level of p53, Bcl-2, and c-myc was determined using the qPCR method. The 16S rDNA sequencing technique was used to determine structural changes and relative abundance expression of intestinal flora.Results: Compared with the NC group, gastric mucosal pathology in the CAG group revealed significant inflammatory infiltration, and the gastric mucosal lesions in the electroacupuncture group were improved remarkably; the expression of p53 and c-myc genes in the CAG group increased (p &lt; 0.05), while the expression of Bcl-2 genes decreased (p &lt; 0.05) in the EA group, that of p53 and c-myc genes decreased (p &lt; 0.05), and that of Bcl-2 genes increased (p &lt; 0.05). The abundance of bacteria such as Lactobacillus, Desulfobacterota, and Bacteroides pectinophilus group in the CAG group increased (p &lt; 0.05), while that of bacteria such as Gastranaerophilales, Romboutsia, and Blautia decreased (p &lt; 0.05). The relative abundance of Desulfobacterota and Helicobacter in the EA group decreased (p &lt; 0.05), while that of probiotic bacteria such as Oscillospirales, Romboutsia, and Christensenellaceae increased (p &lt; 0.05).Conclusion: Electroacupuncture at zusanli can promote the repair of pathological damage to the gastric mucosa in rats with CAG, and the mechanism might relate to the reduction in the relative abundance of harmful bacteria, increase in the relative abundance of intestinal probiotics, and regulation of the intestinal microbiota.
The Prognostic Value of GNG7 in Colorectal Cancer and Its Relationship With Immune Infiltration
Authors: Fang Can , Zhong Rulei , Qiu Chenyang , Zou Bing-bing 
Published: February 2022

Background: G Protein Subunit Gamma 7 (GNG7) is an important gene that regulates cell proliferation and induces apoptosis. However, the correlation between GNG7 expression and immune infiltration as well as patient prognosis of colorectal cancer (CRC) remains unclear.Methods: The GNG7 expression differences between tumor tissues and normal tissues were explored via the Oncomine database, Tumor Immune Estimation Resource (TIMER) site and UALCAN database. Then, the influence of GNG7 on clinical prognosis were evaluated, using the PrognoScan database. In addition, the relationship between GNG7 and tumor-related immune infiltration as well as gene marker sets of immune infiltration was investigated via TIMER, TISIDB and GEPIA.Results: We found that GNG7 expression was down-regulated in multiple malignant tumors including colorectal cancer (CRC) and the GNG7 expression was associated with tumor stage, histology subtype, lymph node metastasis and poor prognosis in colorectal cancer (CRC). In addition, the expression of GNG7 was significantly associated with infiltration level of multiple immune cells, immunomodulatory factors as well as part of the immune cell markers.Conclusion: GNG7 displays validated prognostic value in CRC and was associated with its immune cell infiltration and immunoregulation. These results suggest that GNG7 is a potential prognostic marker and is associated with tumor immune infiltration, thus providing a new perspective for the immunotherapy of CRC.
Molecular Characteristics and Distribution of Adult Human Corneal Immune Cell Types
Authors: Li Yanxiu , Jeong Joyce , Song Weitao 
Published: February 2022

BackgroundThe limbus is located at a 2-mm-wide area between the bulbar conjunctiva and the cornea and has been suggested to be the niche of corneal epithelial stem cells and immune cells. Like the skin and intestines, the cornea is also an important mucosal surface, and immune cells on the cornea play critical roles in immune surveillance to ensure barrier surface homeostasis and protection from various environmental damage and infections. Single-cell RNA sequencing (scRNA-seq) analysis of protein tyrosine phosphatase receptor type C positive (PTPRC+) hematopoietic cells from the corneal limbus could provide a single cell atlas of all the immune cell subsets.MethodsWe performed single-cell RNA sequencing to generate transcriptomic profile for 804 sort-purified hematopoietic cells from the corneal limbus of three healthy donors.ResultsOur analysis identified a primary transcriptomic pattern for multiple immune cell subtypes, including naive T cells, antiviral effector CD8+ T cells, and innate immune cells such as IDO1+ mature regulatory dendritic cells (mregDCs), macrophages, monocytes, and basophils in the human corneal limbus.ConclusionOverall, single-cell transcriptomic analysis of limbal immune cells suggested the possible contribution of these cells on the adaptive and innate immune response of the human cornea.
Associations of HER2 Mutation With Immune-Related Features and Immunotherapy Outcomes in Solid Tumors
Authors: Wang Deqiang , Chen Xiaofeng , Du Yian , Li Xiaoqin , Ying Leqian , Lu Yi , Shen Bo , Gao Xuan , Yi Xin , Xia Xuefeng , Sui Xinbing , Shu Yongqian 
Published: February 2022

BackgroundHER2 is one of the most extensively studied oncogenes in solid tumors. However, the association between tumor microenvironment (TME) and HER2 mutation remains elusive, and there are no specific therapies for HER2-mutated tumors. Immune checkpoint inhibitors (ICIs) have been approved for some tumor subgroups that lack targeted therapies, while their effects are still unclear in HER2-mutated tumors. We examined whether HER2 mutation impacts treatment outcomes of ICIs in solid tumors via its association with anticancer immunity.MethodsMulti-omics data of solid tumors from The Cancer Genome Atlas (TCGA), the Asian Cancer Research Group and the Affiliated Hospital of Jiangsu University were used to analyze the association between HER2 mutations and tumor features. Data of patients with multiple microsatellite-stable solid tumors, who were treated by ICIs including antibodies against programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), or cytotoxic T lymphocyte-associated protein 4 (CTLA-4) in eight studies, were collected to investigate the effects of HER2 mutations on immunotherapy outcomes.ResultsThe mutation rate of HER2 varied in solid tumors of TCGA, with an overall incidence of 3.13%, ranged from 0.39% to 12.2%. Concurrent HER2 mutations and amplifications were rare (0.26%). HER2 mutation was not associated with HER2 protein expression but was positively associated with microsatellite instability, tumor mutation and neoantigen burdens, infiltrating antitumor immune cells, and signal activities of antitumor immunity. Of 321 ICI-treated patients, 18 carried HER2 mutations (5.6%) and showed improved objective response rates compared with those with HER2 wild-type (44.4% vs. 25.7%, p=0.081), especially in the anti-PD-1/anti-PD-L1 subgroup (62.5% vs. 28.4%, p=0.04). Heterogeneity was observed among tumor types. Patients with HER2 mutations also had superior overall survival than those with HER2 wild-type (HR=0.47, 95%CI: 0.23-0.97, p=0.04), especially in the presence of co-mutations in ABCA1 (HR = 0.23, 95% CI: 0.07-0.73, p=0.013), CELSR1 (HR = 0.24, 95% CI: 0.08-0.77, p=0.016), LRP2 (HR = 0.24, 95% CI: 0.07-0.74, p=0.014), or PKHD1L1 (HR = 0.2, 95% CI: 0.05-0.8, p=0.023).ConclusionsHER2 mutations may improve the TME to favor immunotherapy. A prospective basket trial is needed to further investigate the impacts of HER2 mutations on immunotherapy outcomes in solid tumors.
Integrating Clinics, Laboratory, and Imaging for the Diagnosis of Common Variable Immunodeficiency-Related Granulomatous–Lymphocytic Interstitial Lung Disease
Authors: Cabanero-Navalon Marta Dafne , Garcia-Bustos Victor , Forero-Naranjo Leonardo Fabio , Baettig-Arriagada Eduardo José , Núñez-Beltrán María , Cañada-Martínez Antonio José , Forner Giner Maria José , Catalán-Cáceres Nelly , Martínez Francés Manuela , Moral Moral Pedro 
Published: February 2022

BackgroundGranulomatous–lymphocytic interstitial lung disease (GLILD) is a distinct clinic-radio-pathological interstitial lung disease (ILD) that develops in 9% to 30% of patients with common variable immunodeficiency (CVID). Often related to extrapulmonary dysimmune disorders, it is associated with long-term lung damage and poorer clinical outcomes. The aim of this study was to explore the potential use of the integration between clinical parameters, laboratory variables, and developed CT scan scoring systems to improve the diagnostic accuracy of non-invasive tools.MethodsA retrospective cross-sectional study of 50 CVID patients was conducted in a referral unit of primary immune deficiencies. Clinical variables including demographics and comorbidities; analytical parameters including immunoglobulin levels, lipid metabolism, and lymphocyte subpopulations; and radiological and lung function test parameters were collected. Baumann’s GLILD score system was externally validated by two observers in high-resolution CT (HRCT) scans. We developed an exploratory predictive model by elastic net and Bayesian regression, assessed its discriminative capacity, and internally validated it using bootstrap resampling.ResultsLymphadenopathies (adjusted OR 9.42), splenomegaly (adjusted OR 6.25), Baumann’s GLILD score (adjusted OR 1.56), and CD8+ cell count (adjusted OR 0.9) were included in the model. The larger range of values of the validated Baumann’s GLILD HRCT scoring system gives it greater predictability. Cohen’s κ statistic was 0.832 (95% CI 0.70–0.90), showing high concordance between both observers. The combined model showed a very good discrimination capacity with an internally validated area under the curve (AUC) of 0.969.ConclusionModels integrating clinics, laboratory, and CT scan scoring methods may improve the accuracy of non-invasive diagnosis of GLILD and might even preclude aggressive diagnostic tools such as lung biopsy in selected patients.
Decline in Antibody Concentration 6 Months After Two Doses of SARS-CoV-2 BNT162b2 Vaccine in Solid Organ Transplant Recipients and Healthy Controls
Authors: Hamm Sebastian Rask , Møller Dina Leth , Pérez-Alós Laura , Hansen Cecilie Bo , Pries-Heje Mia Marie , Heftdal Line Dam , Hasselbalch Rasmus Bo , Fogh Kamille , Madsen Johannes Roth , Almagro Armenteros Jose Juan , Knudsen Andreas Dehlbæk , Poulsen Johan Runge , Frikke-Schmidt Ruth , Hilsted Linda Maria , Sørensen Erik , Ostrowski Sisse Rye , Harboe Zitta Barrella , Perch Michael , Sørensen Søren Schwartz , Rasmussen Allan , Bundgaard Henning , Garred Peter , Iversen Kasper , Nielsen Susanne Dam 
Published: February 2022

BackgroundPrevious studies have indicated inferior responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination in solid organ transplant (SOT) recipients. We examined the development of anti-receptor-binding domain (RBD) immunoglobulin G (IgG) after two doses of BNT162b2b in SOT recipients 6 months after vaccination and compared to that of immunocompetent controls.MethodsWe measured anti-RBD IgG after two doses of BNT162b2 in 200 SOT recipients and 200 matched healthy controls up to 6 months after first vaccination. Anti-RBD IgG concentration and neutralizing capacity of antibodies were measured at first and second doses of BNT162b2 and 2 and 6 months after the first dose. T-cell responses were measured 6 months after the first dose.ResultsIn SOT recipients, geometric mean concentration (GMC) of anti-RBD IgG increased from first to second dose (1.14 AU/ml, 95% CI 1.08–1.24 to 11.97 AU/ml, 95% CI 7.73–18.77) and from second dose to 2 months (249.29 AU/ml, 95% CI 153.70–385.19). Six months after the first vaccine, anti-RBD IgG declined (55.85 AU/ml, 95% CI 36.95–83.33). At all time points, anti-RBD IgG was lower in SOT recipients than that in controls. Fewer SOT recipients than controls had a cellular response (13.1% vs. 59.4%, p &lt; 0.001). Risk factors associated with humoral non-response included age [relative risk (RR) 1.23 per 10-year increase, 95% CI 1.11–1.35, p &lt; 0.001], being within 1 year from transplantation (RR 1.55, 95% CI 1.30–1.85, p &lt; 0.001), treatment with mycophenolate (RR 1.54, 95% CI 1.09–2.18, p = 0.015), treatment with corticosteroids (RR 1.45, 95% CI 1.10–1.90, p = 0.009), kidney transplantation (RR 1.70, 95% CI 1.25–2.30, p = 0.001), lung transplantation (RR 1.63, 95% CI 1.16–2.29, p = 0.005), and de novo non-skin cancer comorbidity (RR 1.52, 95% CI, 1.26–1.82, p &lt; 0.001).ConclusionImmune responses to BNT162b2 are inferior in SOT recipients compared to healthy controls, and studies aiming to determine the clinical impact of inferior vaccine responses are warranted.
The Trend of Drug Therapy on Uveitic Macular Edema: A Bibliometric Analysis of the 100 Most Cited Articles
Authors: Chen Si , Kong Jinfeng , Feng Lei 
Published: February 2022

BackgroundMacular edema is the most common cause of impaired vision due to uveitis. Although various medications are available, not all uveitis patients with macular edema are satisfied with the treatment results. Therefore, solving this gap becomes the utmost concern worldwide. This study attempted to use bibliometric analysis to compare the valuable information in the top 100 highly cited studies in the field of drug therapy for uveitic macular edema (UME) and then determine the research hot spots and trends in this field.MethodsIn this study, the Science Citation Index Expanded (SCIE) of Web of Science (WOS) was used to collect the top 100 most cited studies on UME and analyze the literature from different countries/regions, institutions, and journals. The visualization knowledge maps is generated by VOSviewer and Citespace software.ResultsThe top 100 highly cited studies are from 34 countries/regions. The United States has the largest number of publications, followed by the England, Spain and Germany. The top three institutions publishing highly cited literature are all from the England: University of London, University College London, and Moorfields Eye Hospital NHS Foundation Trust. Ophthalmology is the most widely published journal with 14 papers. The total number of citations is 1,371, meaning that Ophthalmology is the most authoritative journal in the field of UME drug therapy. The top two articles with the most cited times are from the United States, accounting for 36.5% of the total cited times of the top 10 articles. Keywords were divided into three clusters: the corticosteroid administration pathway, biological agents, and clinical trials. Uveitis, cystoid macular edema, efficacy, dexamethasone, and triamcinolone acetonide appeared more frequently in keywords. Researches on local and long-acting drug has gradually becoming the hot spots and trends.ConclusionThis study concludes that bibliometric analysis can intuitively and quickly obtain the frontiers and hot spots of research in the field of UME drug therapy. Corticosteroid administration, biological agents, and clinical trials are considered the potential focus of future research.