bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review of genetic ancestry as a risk factor for incidence of non-small cell lung cancer in the US
Authors: James Breanna A. , Williams Jennie L. , Nemesure Barbara 
Published: April 2023

Background: Non-Small Cell Lung Cancer (NSCLC), the leading cause of cancer-related death in the United States, is the most diagnosed form of lung cancer. While lung cancer incidence has steadily declined over the last decade, disparities in incidence and mortality rates persist among African American (AA), Caucasian American (CA), and Hispanic American (HA) populations. Researchers continue to explore how genetic ancestry may influence differential outcomes in lung cancer risk and development. The purpose of this evaluation is to highlight experimental research that investigates the differential impact of genetic mutations and ancestry on NSCLC incidence.Methods: This systematic review was conducted using PubMed and Google Scholar search engines. The following key search terms were used to select articles published between 2011 and 2022: “African/European/Latin American Ancestry NSCLC”; “Racial Disparities NSCLC”; “Genetic Mutations NSCLC”; “NSCLC Biomarkers”; “African Americans/Hispanic Americans/Caucasian Americans NSCLC incidence.” Systematic reviews, meta-analyses, and studies outside of the US were excluded. A total of 195 articles were initially identified and after excluding 156 which did not meet eligibility criteria, 38 were included in this investigation.Results: Studies included in this analysis focused on racial/ethnic disparities in the following common genetic mutations observed in NSCLC: KRAS, EGFR, TP53, PIK3CA, ALK Translocations, ROS-1 Rearrangements, STK11, MET, and BRAF. Results across studies varied with respect to absolute differential expression. No significant differences in frequencies of specific genetic mutational profiles were noted between racial/ethnic groups. However, for HAs, lower mutational frequencies in KRAS and STK11 genes were observed. In genetic ancestry level analyses, multiple studies suggest that African ancestry is associated with a higher frequency of EGFR mutations. Conversely, Latin ancestry is associated with TP53 mutations. At the genomic level, several novel predisposing variants associated with African ancestry and increased risk of NSCLC were discovered. Family history among all racial/ethnic groups was also considered a risk factor for NSCLC.Conclusion: Results from racially and ethnically diverse studies can elucidate driving factors that may increase susceptibility and subsequent lung cancer risk across different racial/ethnic groups. Identification of biomarkers that can be used as diagnostic, prognostic, and therapeutic tools may help improve lung cancer survival among high-risk populations.
Antagonizing FcαR1 (CD89) as treatment in IgA-mediated chronic inflammation and autoimmunity
Authors: van Delft Myrthe A. M. , Aleyd Esil , Mast Richard van der , de Jong Niels , Boon Louis , Simons Peter J. , van Egmond Marjolein 
Published: April 2023

IntroductionImmunoglobulin A (IgA) is mostly considered as a non-inflammatory regulator at mucosal areas. However, previous work of our group showed that IgA can also be involved in disease pathology, because it provides a potent stimulus to activate neutrophils after crosslinking of surface CD89 (FcaRI), resulting in chronic inflammation and tissue damage. IgA (auto)antibodies and neutrophils are key players in various diseases, including blistering skin diseases and rheumatoid arthritis. Therefore, we generated an array of anti-CD89 monoclonal antibodies (mAbs) for therapeutic targeting of CD89. The biological activity of newly developed anti-human CD89 mAbs and their potential therapeutic capacity were investigated.MethodsHuman neutrophils were isolated from heparinized healthy donor blood. The ability of anti-CD89 mAbs to bind human neutrophils was investigated by flow cytometry. Furthermore, the capacity of these anti-CD89 mAbs to inhibit IgA-mediated phagocytosis, neutrophil extracellular trap (NET) release and migration was studied. To this end, neutrophils were pre-incubated with/without anti-CD89 mAbs after which they were stimulated with IgA-coated beads. The amount of phagocytosed beads, NET release and migrated neutrophils were subsequently analysed. In parallel, chemoattractant leukotriene B4 and lactoferrin (as a measure for degranulation) release were determined. Finally, the therapeutic potential of our prototypic anti-CD89 mAb clone 10E7 was in vivo tested in anti-mouse collagen XVII human IgA-treated transgenic CD89 mice, a preclinical model for autoimmune linear IgA bullous disease (LABD).ResultsOur results show that all generated anti-CD89 mAbs bound surface CD89 on neutrophils. Although these anti-CD89 mAbs bind to different epitopes on EC1 of CD89, they all have the capacity to inhibit IgA-mediated phagocytosis, neutrophil extracellular trap (NET) release and neutrophil migration. Moreover, IgA mediated leukotriene B4 and lactoferrin release are decreased in supernatant from anti-CD89 mAbs-treated neutrophils. Finally, anti-CD89 mAb clone 10E7, that was selected based on its selective binding profile on tissue micro arrays, reduced anti-mouse collagen XVII hIgA-induced neutrophil influx in an in vivo linear IgA bullous disease (LABD) mice model.ConclusionThis study clearly indicates that our newly developed anti-CD89 mAbs inhibited IgA-induced neutrophil activation and reduced anti-autoantigen IgA-induced neutrophil influx in vivo, supporting further clinical development for the treatment of LABD.
Whole transcriptome analysis reveals that immune infiltration- lncRNAs are related to cellular apoptosis in liver transplantation
Authors: Wu Shile , Cheng Chao , Zhu Wenjun , Yang Jinyu , He Bei-bei , Li Song , Wang Xinsheng , Guo Hao , Chen Dong , Guo Ya-min 
Published: April 2023

IntroductionIn most instances, liver transplantation (LT) is the only available treatment for end‐stage liver diseases. However, LT could also induce serious liver diseases or injury, and the underlying mechanisms of LT-induced complications remain largely unknown, especially the mechanisms of the dysfunction of the immune system mediated by long noncoding RNAs (lncRNAs).MethodsIn this study, we globally analyzed the proportion of immune cells by using the transcriptome sequencing data (RNA-seq) of needle-core liver biopsies from pre- and post-transplantation recipients. Dysregulated lncRNAs were found to be correlated with the altered fractions of immune cells. We finally explored the potential targets of dysregulated lncRNAs and analyzed their functions in LT.ResultsWe found that in the samples, some immune cells changed significantly after LT, including CD4 T cells, NK cells and mast cells. The proportion of macrophages in different polarization states also changed significantly, with M0 macrophages increasing and M2 macrophages decreasing. Through weighted gene co-expression network analysis (WGCNA), 7 gene expression modules related to LT were identified. These modules were related to changes in the proportion of different immune cells. The functions of these modules represent the response modes of different functional genes after LT. Among these modules, MEtan and MEyellow modules were primarily enriched in apoptosis and inflammatory pathways. Twelve immunity-related lncRNAs were identified for the first time, and the regulatory network co-changing with immune cells was also identified. The co-expressed genes of these lncRNAs were highly enriched in apoptosis-related pathways. Many apoptosis-related genes were found to be up-regulated after LT.DiscussionIn summary, we speculated that the expression and regulation of these apoptotic genes may be related to the changes in the proportion of immune cells. Some of these lncRNAs and apoptosis-related genes have been reported to be related to cell proliferation and apoptosis. They are also potential biomarkers or therapeutic targets.
Abundance and distribution of microplastics in tropical estuarine mangrove areas around Penang, Malaysia
Authors: Tan Evonne , Mohd Zanuri Norlaila Binti 
Published: April 2023

IntroductionThis study reports the abundance and distribution of microplastics in tropical estuarine mangrove areas in Penang, Malaysia.MethodsSamples were collected by using a neuston net and Ponar grab at four study sites (Seberang Perai, Kuala Muda, Penaga and Balik Pulau).Results and DiscussionA total of 8775 pieces were collected from the four sites, with abundance in coastal surface water, coastal bottom sediment, and estuarine sediment ranging between 201 ± 21.214 - 1407 ± 124.265 pcs/L, 255 ± 22.368 - 350 ± 25.892 pcs/kg, and 430 ± 7.234 - 4000 ± 29.174 pcs/kg respectively. Seberang Perai was found with the highest microplastics abundance in all compartments while fragment is the dominant morphology throughout all study sites. Stereomicroscopic analysis showed that microplastics are of numerous colours and irregular in shape while Field Emission Scanning Electron Microscope (FESEM) observed severe surficial weathering. Polyethylene is the most common identified polymer type via Fourier Transform Infrared Spectroscopy (FTIR) analysis and inorganic chemical compounds such as dimethylmercury were detected which pose a threat to organisms and the environment. The overall outcome suggests that human activities play a significant role in microplastic input into the estuarine environment and that the dominant polymer type in respective study site are closely related to the nature of human activities. This baseline study presents fundamental knowledge on microplastic pollution in the estuarine environment of Penang and encourages similar research to be conducted in the future for pollution control and management.
Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization: A clinical analysis
Authors: Baek Moon Seong , Kim Seungil , Kim Won-Young , Kweon Mi-Na , Huh Jin Won 
Published: April 2023

BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. Risk factors for CRE acquisition include broad-spectrum antibiotic use and microbiota dysbiosis in critically ill patients. Therefore, we evaluated the alteration of the intestinal microbiota associated with CRE colonization in critically ill patients.MethodsFecal samples of 41 patients who were diagnosed with septic shock or respiratory failure were collected after their admission to the intensive care unit (ICU). The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. The analysis of bacterial metabolic abundance to identify an association between CRE acquisition and metabolic pathway was performed.ResultsCRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. The alpha-diversity indices were significantly decreased in CRE carriers, and beta-diversity analysis demonstrated that the two groups were clustered significantly apart. Among short-chain fatty acids, the levels of isobutyric acid and valeric acid were significantly decreased in CRE carriers. Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups.ConclusionCritically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. Further studies are needed to determine whether amino acids supplementation improves microbiota dysbiosis in patients with CRE.
Biomarker discovery in galactosemia: Metabolomics with UPLC/HRMS in dried blood spots
Authors: Alodaib Ahmad N. , Nimer Refat M. , Alhumaidy Rowan , Alhenaky Alaa , Abdel Jabar Mai , AlMalki Reem H. , Abdel Rahman Anas M. 
Published: April 2023

Introduction:Galactosemia (GAL) is a genetic disorder that results in disturbances in galactose metabolism and can lead to life-threatening complications. However, the underlying pathophysiology of long-term complications in GAL remains poorly understood.Methods: In this study, a metabolomics approach using ultra-performance liquid chromatography coupled with high-resolution mass spectrometry was used to investigate metabolomic changes in dried blood spots of 15 patients with GAL and 39 healthy individuals.Results: The study found that 2,819 metabolites underwent significant changes in patients with GAL compared to the control group. 480 human endogenous metabolites were identified, of which 209 and 271 were upregulated and downregulated, respectively. PA (8:0/LTE4) and ganglioside GT1c (d18:0/20:0) metabolites showed the most significant difference between GAL and the healthy group, with an area under the curve of 1 and 0.995, respectively. Additionally, the study identified potential biomarkers for GAL, such as 17-alpha-estradiol-3-glucuronide and 16-alpha-hydroxy DHEA 3-sulfatediphosphate.Conclusion: This metabolomics study deepened the understanding of the pathophysiology of GAL and presented potential biomarkers that might serve as prognostic biomarkers to monitor the progression or support the clinical diagnosis of GAL.
A novel compound heterozygous mutation of COL6A3 in Chinese patients with isolated cervical dystonia
Authors: Wu Rui , Dou Weikang , Zhou Huimin , Shi Ming 
Published: April 2023

BackgroundThe etiology and pathogenesis of idiopathic dystonia remain obscure. Recent studies revealed that compound heterozygous mutations in collagen type VI alpha-3 gene COL6A3 may cause recessive isolated dystonia (DYT)-27. However, whether COL6A3 mutations are associated with Chinese patients with isolated dystonia is not yet reported.MethodsIn this study, 45 Chinese patients with isolated cervical dystonia were recruited, and their blood DNA samples were subjected to whole-exome sequencing. The potential causal variants of COL6A3 were identified based on the criteria of the American College of Medical Genetics and Genomics and by prediction software.ResultsAmong 45 isolated cervical dystonia patients, 18 patients (10 female patients and eight male patients) were found to have seven potential causal variants in the COL6A3 gene. Among these variants, a compound heterozygous mutation was found in one patient. One allele had a c.1264G&gt;A mutation in exon 4 that resulted in an amino acid substitution of methionine for valine at codon 422 (p.Val422Met) and the other a c.8965+9G&gt;A mutation involving a splicing change in exon 40. In addition, other five missense variants, including c.958G&gt;A (p.Ala320Thr), c.1478T&gt;C (p.Val493Ala), c.1597C&gt;T (p.Arg533Cys), c.1762G&gt;A (p.Asp588Asn), and c.4912G&gt;A (p.Ala1638Thr), were identified as well.ConclusionWe identified a novel deleterious compound heterozygous mutation as well as five missense variants in the COL6A3 gene of Chinese patients with cervical dystonia. These findings may expand the spectrum of the COL6A3 genotype in isolated dystonia.
Trajectories of interleukin 10 and heart fatty acid-binding protein levels in traumatic brain injury patients with or without extracranial injuries
Authors: Niiranen Toni J. U. , Chiollaz Anne-Cécile , Takala Riikka S. K. , Voutilainen Miko , Tenovuo Olli , Newcombe Virginia F. J. , Maanpää Henna-Riikka , Tallus Jussi , Mohammadian Mehrbod , Hossain Iftakher , van Gils Mark , Menon David K. , Hutchinson Peter J. , Sanchez Jean-Charles , Posti Jussi P. 
Published: April 2023

BackgroundInterleukin 10 (IL-10) and heart fatty acid-binding protein (H-FABP) have gained interest as diagnostic biomarkers of traumatic brain injury (TBI), but factors affecting their blood levels in patients with moderate-to-severe TBI are largely unknown.ObjectiveTo investigate the trajectories of IL-10 and H-FABP between TBI patients with and without extracranial injuries (ECI); to investigate if there is a correlation between the levels of IL-10 and H-FABP with the levels of inflammation/infection markers C-reactive protein (CRP) and leukocytes; and to investigate if there is a correlation between the admission level of H-FABP with admission levels of cardiac injury markers, troponin (TnT), creatine kinase (CK), and creatine kinase MB isoenzyme mass (CK-MBm).Materials and methodsThe admission levels of IL-10, H-FABP, CRP, and leukocytes were measured within 24 h post-TBI and on days 1, 2, 3, and 7 after TBI. The admission levels of TnT, CK, and CK-MBm were measured within 24 h post-TBI.ResultsThere was a significant difference in the concentration of H-FABP between TBI patients with and without ECI on day 0 (48.2 ± 20.5 and 12.4 ± 14.7 ng/ml, p = 0.02, respectively). There was no significant difference in the levels of IL-10 between these groups at any timepoints. There was a statistically significant positive correlation between IL-10 and CRP on days 2 (R = 0.43, p &lt; 0.01) and 7 (R = 0.46, p = 0.03) after injury, and a negative correlation between H-FABP and CRP on day 0 (R = -0.45, p = 0.01). The levels of IL-10 or H-FABP did not correlate with leukocyte counts at any timepoint. The admission levels of H-FABP correlated with CK (R = 0.70, p &lt; 0.001) and CK-MBm (R = 0.61, p &lt; 0.001), but not with TnT.ConclusionInflammatory reactions during the early days after a TBI do not significantly confound the use of IL-10 and H-FABP as TBI biomarkers. Extracranial injuries and cardiac sources may influence the levels of H-FABP in patients with moderate-to-severe TBI.
Phytochemical composition and antioxidant activities of some wild edible plants locally consumed by rural communities in northern Uganda
Authors: Nyero Alfred , Anywar Godwin Upoki , Achaye Innocent , Malinga Geoffrey Maxwell 
Published: April 2023

BackgroundAcalypha rhomboidea, Asystacia gangetica, Crassocephalum sacrobasis, Crotalaria ochroleuca, Heterosis rotundifolia, Hibiscus cannabinus, Hibiscus sp., Hibiscus surratensis, Ipomoea eriocarpa, Maerua angolensis, Senna obtusifolia and Vigna membranacea are among the common wild edible plants in the Acholi sub-region, northern Uganda. This study evaluated the phytochemical constituents and antioxidant potential of the plants.MethodsFresh leaves collected from each plant species were air-dried under shade. The phytochemical contents of the ethanol and petroleum ether extracts were determined using standard protocols. The antioxidant content of the methanolic extracts was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay.ResultsPreliminary phytochemical analyses indicated the presence of tannins, reducing compounds, alkaloids, flavonoids, flavons aglycones, flavanosides, anthracenosides, anthocyanosides, volatile oils, coumarins, steroid glycosides, sterols and triterpenes. However, the extracts did not contain any emodols and saponins. The results of the quantitative phytochemical analysis showed that the contents of different phytochemicals detected varied significantly (p &lt; 0.05) among the selected plants. The amount of tannins in mg/g (gallic acid equivalent) of dry weight varied from 3.90 ± 0.16 in C. ochroleuca to 10.41 ± 0.78 in I. eriocarpa, total flavonoids in RE, mg/g dry matter from 4.07 ± 0.11 in I. eriocarpa to 14.94 ± 0.08 in S. obtusifolia. Total alkaloids in mg/100 g ranged from 1.59 ± 0.30 in I. eriocarpa to 6.37 ± 0.24 in Hibiscus sp. Total phenolic content in GAE, mg/g dry matter ranged from 13.39 ± 0.26 in A. rhomboidea to 64.25 ± 0.54 in I. eriocarpa. The in vitro antioxidant assays revealed substantial free radical scavenging activity in all the plants. Antioxidant activity expressed as IC50 (ppm) ranged from 13.39 for A. rhomboidea to 64.84 for I. eriocarpa, compared to 12.82 for ascorbic acid standard. The total phenolic compounds and total tannins had significant and positive correlations with DPPH free radical scavenging activity.ConclusionThe findings of this study provide evidence that the species are good natural sources of phytochemicals and antioxidants, whose regular consumption could provide human health benefits by protecting against oxidative stress related diseases. Further research is needed on the structural characterization of the phytochemicals, profiling the plant extracts with high antioxidant activity and determining the antimicrobial activities.
Severe cutaneous adverse reactions to drugs: A real-world pharmacovigilance study using the FDA Adverse Event Reporting System database
Authors: Li Dongxuan , Gou Jinghui , Zhu Jun , Zhang Tongyan , Liu Feng , Zhang Daojun , Dai Liyang , Li Wenjun , Liu Qinglong , Qin Chunmeng , Du Qian , Liu Songqing 
Published: April 2023

Background: Sound drug safety information is important to optimize patient management, but the widely recognized comprehensive landscape of culprit-drugs that cause severe cutaneous adverse reactions (SCARs) is currently lacking.Objective: The main aim of the study is to provide a comprehensive landscape of culprit-drugs for SCARs to guide clinical practice.Methods: We analyzed reports associated with SCARs in the FDA Adverse Event Reporting System database between 1 January 2004 and 31 December 2021 and compiled a list of drugs with potentially serious skin toxicity. According to this list, we summarized the reporting proportions of different drugs and drug classes and conducted disproportionality analysis for all the drugs. In addition, the risk characteristic of SCARs due to different drugs and drug classes was summarized by the positive–negative distribution based on the results of the disproportionality analysis.Results: A total of 77,789 reports in the FDA Adverse Event Reporting System database were considered SCAR-related, of which lamotrigine (6.2%) was the most reported single drug followed by acetaminophen (5.8%) and allopurinol (5.8%) and antibacterials (20.6%) was the most reported drug class followed by antiepileptics (16.7%) and antineoplastics (11.3%). A total of 1,219 drugs were reported as culprit-drugs causing SCARs in those reports, and the largest number of drugs belonged to antineoplastics. In disproportionality analysis, 776 drugs showed at least one positive pharmacovigilance signal. Drugs with the most positive signals were lamotrigine, acetaminophen, furosemide, and sulfamethoxazole/trimethoprim.Conclusion: Our study provided a real-world overview of SCARs to drugs, and the investigation of SCAR positive–negative distribution across different drugs revealed its risk characteristics, which may help optimize patient management.