bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Characteristics of Bloodstream Infection in Immunosuppressed Patients: A 5-Year Retrospective Cohort Study
Authors: Lin Hongxia , Yang Lili , Fang Jie , Gao Yulian , Zhu Haixing , Zhang Shengxiong , Summah Hanssa Dwarka , Shi Guochao , Sun Jingyong , Ni Lei , Feng Yun 
Published: April 2022

IntroductionImmunosuppressed patients with bloodstream infection are at risk of mortality. Our objective was to assess the independent risk factors of bloodstream infection with mortality in immunosuppressive states.MethodsThe medical data of a total of 896 patients who were hospitalized in our hospital were collected from January 2015 to December 2019. Evaluation of the independent risk factors of mortality was done by univariate and multivariate logistic regression analyses.ResultsOf the 896 immunosuppressed patients with bloodstream infection, 698 had over 60-day survivals and 198 had 60-day mortality. In our study, PCT (mean ±; standard: 11.40 ±; 31.89 µg/l vs. 62.45 ±; 17.10 µg/l, p = 0.007) and presence of age &gt;60 years (40% vs. 14.19%, p = 0.001) were significantly different between situations with and without 60-day survivals in both univariate and multivariate logistic regression analyses. Age &gt;60 years and PCT could be used as indicators for bloodstream infection with 60-day death in immunosuppressive states; the OR (95% CI) were 1.532 (1.099–2.135) and 2.063 (1.413–3.013), respectively. In different subgroups, PCT and age were also independent risk factors of blood system diseases, Klebsiella pneumoniae infection, diabetes, and ICU-stay subgroups.ConclusionsAge and PCT were independently associated with mortality in immunosuppressive states, which may help to identify the highly risky situation of bloodstream infection in immunosuppressive states.
Gut Microbiome and Metabolome Changes in Mice With Acute Vestibular Deficit
Authors: Li Feitian , Feng Yisi , Liu Hongyan , Kong Dedi , Hsueh Chi-Yao , Shi Xunbei , Wu Qianru , Li Wei , Wang Jing , Zhang Yibo , Dai Chunfu 
Published: April 2022

Vestibular deficit is a very common disorder in clinical practice and is characterized by vertigo, spontaneous nystagmus, and autonomic nervous symptoms, including nausea, vomiting, and sweating. In addition, the comorbidity of vestibular deficit and anxiety has long been an integral component of the medical literature. Previous studies have suggested that the mechanisms underlying this comorbidity involved overlap of vestibular and cerebellar networks. Emerging evidence has shown that the microbiota–gut–brain axis plays a key role in the regulation of affective disorders. Thus, we hypothesized that the gut microbiota may be involved in the comorbidity of vestibular deficit and anxiety. To verify this, we constructed a unilateral labyrinthectomy mouse model to simulate vestibular deficit. Then, 16S rRNA gene sequencing and liquid chromatography–mass spectrometry (LC-MS) were used to analyze the microbiome and metabolome of the cecal samples collected from mice in the unilateral labyrinthectomy, sham surgery, and control groups. Notably, unilateral labyrinthectomy shaped the composition of the mouse gut microbiome, resulting in increased abundance of Lachnospiraceae NK4A136 group, Odoribacter and Roseburia and decreased abundance of Prevotella and Parasutterella at the genus level. Tax4Fun functional prediction indicated a decrease in tryptophan metabolism in mice in the unilateral labyrinthectomy group. Moreover, functional correlation of changes in gut microbes and metabolites between different groups showed that the oleamide level was negatively correlated with Odoribacter abundance (r = -0.89, p = 0.0002). The butyric acid level was positively correlated with Parasutterella abundance (r = 0.85, p = 0.0010). The propanoate level was negatively correlated with Prevotella abundance (r = -0.81, p = 0.0020). The 20-HETE level was positively correlated with Parasutterella abundance (r = 0.84, p = 0.0013). The altered microbes and metabolites were closely related to the pathogenesis of affective disorders. Our results not only offer novel insights into the vestibular deficit comorbid with anxiety but also build an important basis for future research on this etiology.
Association Between Obesity and Lower Short- and Long-Term Mortality in Coronary Care Unit Patients: A Cohort Study of the MIMIC-III Database
Authors: Yan Junlue , Li Xinyuan , Long Wenjie , Yuan Tianhui , Xian Shaoxiang 
Published: April 2022

IntroductionObesity has long been considered an independent risk factor for cardiovascular diseases (CVD), even in the COVID-19 pandemic. However, recent studies have found that a certain degree of obesity may be beneficial for patients who have already suffered from CVD, which is called the “obesity paradox”. Our objective was to investigate whether the obesity paradox existed in coronary care unit (CCU) patients and the relationship between body mass index (BMI) and short- and long-term mortality.MethodsWe performed a cohort analysis of 3,502 adult CCU patients from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The patients were divided into four groups according to the WHO BMI categories. Both multivariable logistic regression and Cox regression were used to reveal the relation between BMI and mortality. Subgroup analyses were performed based on Simplified Acute Physiology Score (SAPS) and age.ResultsAfter adjusting for confounders, obese patients had 33% and 30% lower mortality risk at 30-day and 1-year (OR 0.67, 95% CI 0.51 to 0.89; HR 0.70, 95% CI 0.59 to 0.83; respectively) compared with normal-weight patients, while the underweight group were opposite, with 141% and 81% higher in short- and long-term (OR 2.41, 95% CI 1.37 to 4.12; HR 1.81, 95% CI 1.34 to 2.46; respectively). Overweight patients did not have a significant survival advantage at 30-day (OR 0.91, 95% CI 0.70 to 1.17), but did have a 22% lower mortality risk at 1-year (HR 0.78; 95% CI 0.67 to 0.91). The results were consistent after being stratified by SAPS and age.ConclusionOur study supports that obesity improved survival at both 30-day and 1-year after CCU admission, and the obesity paradox existed in CCU patients.
Higher Dementia Risk in People With Gastroesophageal Reflux Disease: A Real-World Evidence
Authors: Gau Shuo-Yan , Lai Jung-Nien , Yip Hei-Tung , Wu Meng-Che , Wei James Cheng-Chung 
Published: April 2022

BackgroundWhether or not patients with gastroesophageal reflux disease (GERD) have a higher risk of developing subsequent dementia remains unknown, and no observational evidence from population-based data is available. This study was to determine whether patients with GERD have a higher future risk of developing dementia.MethodsFor the period 2000–2012, datasets from the Longitudinal Health Insurance Database (LHID, subset of National Health Insurance Research Database in Taiwan) were analyzed. Definition of GERD was based on ICD-9-CM codes 530.11 and 530.81 and prescriptions for PPIs. After matching gender, age, index year, and comorbidities, each GERD patient was matched with four control patients without GERD. Future risk of dementia was evaluated, and sensitivity analysis of subgroups was conducted to clarify the potential association.ResultsIn the present study, 13,570 patients were included in the GERD cohort and 54,280 patients were included in the control cohort. Patients with GERD showed higher risk developing dementia than control group, with an aHR of 1.34 (95% C.I., 1.07, 1.67). In GERD patients between above 70 years old, the risk of developing dementia was higher than that of the control groups (aHR = 1.34; 95% C.I., 1.01, 1.77).ConclusionPatients with GERD showed higher incidence of dementia, and elder patients had the highest risk of developing dementia. Clinicians should be concern of the association between GERD and dementia and should develop strategies to prevent dementia while managing patients with GERD.
Transcutaneous Auricular Vagus Nerve Stimulation Promotes White Matter Repair and Improves Dysphagia Symptoms in Cerebral Ischemia Model Rats
Authors: Long Lu , Zang Qianwen , Jia Gongwei , Fan Meng , Zhang Liping , Qi Yingqiang , Liu Yilin , Yu Lehua , Wang Sanrong 
Published: April 2022

BackgroundClinical and animal studies have shown that transcutaneous auricular vagus nerve stimulation (ta-VNS) exerts neuroprotection following cerebral ischemia. Studies have revealed that white matter damage after ischemia is related to swallowing defects, and the degree of white matter damage is related to the severity of dysphagia. However, the effect of ta-VNS on dysphagia symptoms and white matter damage in dysphagic animals after an ischemic stroke has not been investigated.MethodsMiddle cerebral artery occlusion (MCAO) rats were randomly divided into the sham, control and vagus nerve stimulation (VNS) group, which subsequently received ta-VNS for 3 weeks. The swallowing reflex was measured once weekly by electromyography (EMG). White matter remyelination, volume, angiogenesis and the inflammatory response in the white matter were assessed by electron microscopy, immunohistochemistry, stereology, enzyme-linked immunosorbent assay (ELISA) and Western blotting.Resultsta-VNS significantly increased the number of swallows within 20 s and reduced the onset latency to the first swallow. ta-VNS significantly improved remyelination but did not alleviate white matter shrinkage after MCAO. Stereology revealed that ta-VNS significantly increased the density of capillaries and increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2) expression in the white matter. ta-VNS significantly alleviated the increase inTLR4, MyD88, phosphorylated MAPK and NF-κB protein levels and suppressed the expression of the proinflammatory factors IL-1β and TNF-α.ConclusionThese results indicated ta-VNS slightly improved dysphagia symptoms after ischemic stroke, possibly by increasing remyelination, inducing angiogenesis, and inhibiting the inflammatory response in the white matter of cerebral ischaemia model rats, implying that ta-VNS may be an effective therapeutic strategy for the treatment of dysphagia after ischemic stroke.
High Expression of CSF-1R Predicts Poor Prognosis and CSF-1Rhigh Tumor-Associated Macrophages Inhibit Anti-Tumor Immunity in Colon Adenocarcinoma
Authors: Wang Xingchao , Zhang Jianfeng , Hu Baoying , Qian Fei 
Published: April 2022

BackgroundColony stimulating factor 1 receptor (CSF-1R) is a single channel III transmembrane receptor tyrosine kinase (RTK) and plays an important role in immune regulation and the development of various cancer types. The expression of CSF-1R in colon adenocarcinoma (COAD) and its prognostic value remain incompletely understood. Therefore, we aim to explore the prognostic value of CSF-1R in COAD and its relationship with tumor immunity.MethodsCSF-1R expression in a COAD cohort containing 103 patients was examined using immunohistochemistry (IHC). The relationship between CSF-1R expression and clinicopathological parameters and prognosis was evaluated. Dual immunofluorescence staining was conducted to determine the localization of CSF-1R in COAD tissues. Univariate and multivariate Cox regression analysis were performed to evaluate independent prognostic factors. Transcriptomic profiles of CSF-1Rhigh and CSF-1Rlow tumor-associated macrophages (TAMs) were investigated. Gene enrichment analysis was used to explore the signal pathways related to CSF-1R. In addition, the relationship between CSF-1R in tumor microenvironment (TME) and tumor immunity was also studied.ResultsIHC analysis showed that CSF-1R was overexpressed in COAD, and higher expression was associated with shorter overall survival (OS). Immunofluorescence staining showed that CSF-1R was co-localized with macrophage marker CD68. Univariate and multivariate Cox regression analysis showed that CSF-1R was an independent prognostic factor for COAD. The results of gene enrichment analysis showed that CSF-1R was involved in tumor immune response and regulation of TME. In addition, CSF-1R was significantly correlated with TME, immune cell infiltration, TMB, MSI, Neoantigen, and immune checkpoint molecules.ConclusionCSF-1R can serve as an independent prognostic factor of COAD and promising immunotherapeutic target of COAD.
Immunogenic Cell Death-Relevant Damage-Associated Molecular Patterns and Sensing Receptors in Triple-Negative Breast Cancer Molecular Subtypes and Implications for Immunotherapy
Authors: Xu Ming , Lu Jin-hua , Zhong Ya-zhen , Jiang Jing , Shen Yue-zhong , Su Jing-yang , Lin Sheng-you 
Published: April 2022

ObjectivesTriple-negative breast cancer (TNBC) is defined as a highly aggressive type of breast cancer which lacks specific biomarkers and drug targets. Damage-associated molecular pattern (DAMP)-induced immunogenic cell death (ICD) may influence the outcome of immunotherapy for TNBC patients. This study aims to develop a DAMPs gene signature to classify TNBC patients and to further predict their prognosis and immunotherapy outcome.MethodsWe identified the DAMPs-associated subtypes of 330 TNBCs using K-means analysis. Differences in immune status, genomic alterations, and predicted immunotherapy outcome were compared among each subtype.ResultsA total of 330 TNBCs were divided into three subtypes according to DAMPs gene expression: the nuclear DAMPs subtype, featuring the upregulation of nuclear DAMPs; the inflammatory DAMPs subtype, characterized by the gene set enrichment of the adaptive immune system and cytokine signaling in the immune system; and the DAMPs-suppressed subtype, having the lowest level of ICD-associated DAMPs. Among them, the inflammatory subtype patients had the most favorable survival, while the DAMPs-suppressed subtype was associated with the worst prognosis. The DAMPs subtyping system was successfully validated in the TCGA cohort. Furthermore, we systemically revealed the genomic alterations among the three DAMPs subtypes. The inflammatory DAMPs subtype was predicted to have the highest response rate to immunotherapy, suggesting that the constructed DAMPs clustering had potential for immunotherapy efficacy prediction.ConclusionWe established a novel ICD-associated DAMPs subtyping system in TNBC, and DAMPs expression might be a valuable biomarker for immunotherapy strategies. Our work could be helpful to the development of new immunomodulators and may contribute to the development of precision immunotherapy for TNBC.
Music-Induced Analgesia in Healthy Participants Is Associated With Expected Pain Levels but Not Opioid or Dopamine-Dependent Mechanisms
Authors: Lunde Sigrid Juhl , Vuust Peter , Garza-Villarreal Eduardo A. , Kirsch Irving , Møller Arne , Vase Lene 
Published: April 2022

Music interventions accommodate the profound need for non-pharmacological pain treatment. The analgesic effect of listening to music has been widely demonstrated across studies. Yet, the specific mechanisms of action have still to be elucidated. Although the endogenous opioid and dopamine systems have been suggested to play an important role, a direct link has not been established. In addition, the involvement of placebo mechanisms is likely while largely unexplored. We examined the analgesic effect of music in healthy participants (n = 48) using a 3 × 3 within-subjects design with pharmacological manipulations and a matched, auditory control for music. Participants were exposed to thermal pain stimuli while listening to three auditory excerpts: music (active condition), nature sound (matched, auditory contextual condition), and noise (neutral control condition). The participants rated their expected and perceived pain levels in relation to each of the auditory excerpts. To investigate the involvement of the endogenous opioid and dopamine systems, the test session was performed three times on separate days featuring a double-blind randomized oral administration of naltrexone (opioid antagonist), haloperidol (dopamine antagonist), and an inactive agent (control). Our results support an analgesic effect of music. Contrary to current hypotheses, neither of the antagonists attenuated the effect of music. Yet, the participants' expectations for pain relief predicted their perceived pain levels during the auditory excerpts—even when controlling for a gradual learning effect. In conclusion, we demonstrate that the analgesic effect of music is at least partially mediated by expectations of an analgesic effect—a core mechanism in placebo effects—but not by opioid and dopamine-dependent mechanisms.Clinical Trial Registrationwww.clinicaltrials.gov, identifier: NCT03410563.
Chorioamnionitis Causes Kidney Inflammation, Podocyte Damage, and Pro-fibrotic Changes in Fetal Lambs
Authors: Hoogenboom Lieke A. , Lely A. Titia , Kemp Matthew W. , Saito Masatoshi , Jobe Alan H. , Wolfs Tim G. A. M. , Schreuder Michiel F. 
Published: April 2022

BackgroundPerinatal complications, such as prematurity and intrauterine growth restriction, are associated with increased risk of chronic kidney disease. Although often associated with reduced nephron endowment, there is also evidence of increased susceptibility for sclerotic changes and podocyte alterations. Preterm birth is frequently associated with chorioamnionitis, though studies regarding the effect of chorioamnionitis on the kidney are scarce. In this study, we aim to unravel the consequences of premature birth and/or perinatal inflammation on kidney development using an ovine model.MethodsIn a preterm sheep model, chorioamnionitis was induced by intra-amniotic injection of lipopolysaccharide (LPS) at either 2, 8, or 15 days prior to delivery. Control animals received intra-amniotic injections of sterile saline. All lambs were surgically delivered at 125 days’ gestation (full term is 150 days) and immediately euthanized for necropsy. Kidneys were harvested and processed for staining with myeloperoxidase (MPO), Wilms tumor-1 (WT1) and alpha-smooth muscle actine (aSMA). mRNA expression of tumor necrosis factor alpha (TNFA), Interleukin 10 (IL10), desmin (DES), Platelet derived growth factor beta (PDGFB), Platelet derived growth factor receptor beta (PDGFRB), synaptopodin (SYNPO), and transforming growth factor beta (TGFB) was measured using quantitative PCR.ResultsAnimals with extended (but not acute) LPS exposure had an inflammatory response in the kidney. MPO staining was significantly increased after 8 and 15 days (p = 0.003 and p = 0.008, respectively). Expression of TNFA (p = 0.016) and IL10 (p = 0.026) transcripts was increased, peaking on day 8 after LPS exposure. Glomerular aSMA and expression of TGFB was increased on day 8, suggesting pro-fibrotic mesangial activation, however, this was not confirmed with PDFGB or PDGFRB. The number of WT1 positive nuclei in the glomerulus, as well as expression of synaptopodin, decreased, indicating podocyte injury.ConclusionWe report that, in an ovine model of prematurity, LPS-induced chorioamnionitis leads to inflammation of the immature kidney. In addition, this process was associated with podocyte injury and there are markers to support pro-fibrotic changes to the glomerular mesangium. These data suggest a potential important role for antenatal inflammation in the development of preterm-associated kidney disease, which is frequent.
Stratification by Non-invasive Biomarkers of Non-alcoholic Fatty Liver Disease in Children
Authors: Kwon Yiyoung , Kim Eun Sil , Choe Yon Ho , Kim Mi Jin 
Published: April 2022

BackgroundThe spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from isolated hepatic steatosis to non-alcoholic steatohepatitis to fibrosis. We aimed to introduce useful biomarkers released during liver inflammation and fibrogenesis that are easy to use in outpatient clinic and adjust to children to evaluate each NAFLD stage without biopsy.MethodsThis prospective study included 60 patients aged under 19 years whose alanine aminotransferase (ALT) levels were elevated from March 2021. All patients were proven to have NAFLD by ultrasonography and laboratory work-up to exclude other causes of hepatitis. Fibroscan and additional laboratory tests for biomarkers [procollagen type1 amino-terminal propeptide (P1NP), osteocalcin, interleukin-6 (IL-6), and Mac-2 binding protein glycosylated isomer (M2BPGi)] were performed. Fibroscan-AST (FAST) score was used for the comparison of steatohepatitis and liver stiffness measurement (kPa) was used for the comparison of advanced fibrosis.ResultsThe biomarker that showed a significant difference between the FAST-positive and negative groups was the P1NP/osteocalcin ratio with a p-value of 0.008. The area under receiver operating characteristic (AUROC) of P1NP/osteocalcin ratio*ALT values (values obtained through multivariate analysis) was 0.939 with the cut-off value of 305.38. The biomarkers that showed a significant difference between the LSM-positive and negative groups were IL-6 and M2BPGi with a p-values of 0.005 and &lt;0.001. AUROC of IL-6 *AST values (values obtained through multivariate analysis) was 0.821 with the cut-off value of 228.15. M2BPGi showed a significant linear relationship with LSM in Pearson correlation analysis (Pearson correlation coefficient = 0.382; p = 0.003). The diagnostic capability of M2BPGi to evaluate advanced fibrosis showed an acceptable result (AUROC = 0.742; p = 0.022).ConclusionsNon-invasive biomarkers can be used to predict each stage of NAFLD in children. The measurements of P1NP, IL-6 or M2BPGi along with the basic chemistry tests would help determine the stage of NAFLD they correspond to at the time of initial diagnosis and predict responsiveness after the treatment.
In vitro Anticancer Activity of the Polar Fraction From the Lophocereus schottii Ethanolic Extract
Authors: Orozco-Barocio Arturo , Robles-Rodríguez Blanca Susana , Camacho-Corona María del Rayo , Méndez-López Luis Fernando , Godínez-Rubí Marisol , Peregrina-Sandoval Jorge , Rivera Gildardo , Rojas Mayorquín Argelia E. , Ortuno-Sahagun Daniel 
Published: April 2022

Cancer is an increasingly common disease and is considered one of the main causes of death in the world. Lophocereus schottii (L. schottii) is a cactus used in Mexico in traditional medicine for cancer treatment. This study aimed to determine the effect of the ethanolic extract and the polar and nonpolar fractions of L. schottii in murine L5178Y lymphoma cells in vitro, analyzing their effect on the proliferative activity of splenocytes, and establishing the effective concentration 50 (EC50) of the polar fraction. In addition, the secondary metabolites present in the extracts were determined by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The study establishes that the three extracts of L. schottii have a cytotoxic effect on L5178Y cells and on the splenocytes stimulated with ConA. Additionally, the polar fraction has a significantly greater effect being three times more effective than cyclophosphamide on inhibiting the viability of L5178Y cells. Secondary metabolites present are mainly flavonoids and alkaloids, but there are also some terpenoids and sterols. Ultimately, polar fraction can be considered an anticancer substance, since its EC50 of 15 μg/mL is within the parameters established by the National Cancer Institute.