bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiological Emergence of Amyloid-β During the Acute Cerebral Stress of Mechanical Ventilation Reduces Peri-Hippocampal and Cortical Blood-Brain Barrier Permeability and Neuronal Injury
Authors: Gezalian Michael M , Rajput Padmesh , Sparrow Nicklaus , Mangiacotti Luigi , Koronyo Yosef , Koronyo-Hamaoui Maya , Lahiri Shouri 
Published: August 2020

Abstract
Background: Prior published data show that short-term mechanical ventilation contributes to pathological hallmarks of Alzheimer’s Disease (AD) by increasing cerebral accumulation of the amyloid-β1-40 (Aβ1-40) peptide and neuroinflammation while unexpectedly decreasing blood-brain barrier permeability. In this study, we hypothesized that the acute cerebral immunochallenge of mechanical ventilation promotes physiological emergence of Aβ1-40 to regions of acute vascular disruption, resulting in reduced neuronal injury.Methods: Immunohistology was used to assess the regional relationship between cerebral Aβ1-40 accumulation, acute vascular disruption, and neuronal inflammation and apoptosis as measured by cleaved caspase-3 (CC3) expression from mechanically ventilated double transgenic AD-model (ADtg) mice and compared to mechanically ventilated wild-type (WT) controls.Results: There was significantly decreased expression of CC3 in regions of cortical and hippocampal Aβ1-40 accumulation in mechanically ventilated ADtg animals (p=0.0224). In contrast, CC3 expression was significantly increased in cortical and hippocampal regions of mechanically ventilated WT controls (p=0.0260). Aβ1-40 accumulation occurred in regions of acute vascular disruption in a characteristic banding pattern and reduced blood-brain barrier permeability. The banding pattern was significantly increased in ADtg mice subjected to mechanical ventilation compared to non-mechanically ventilated ADtg mice (p=0.0002). Additionally, no evidence of irreversible neurological injury is seen in mechanically ventilated ADtg and WT mice, as demonstrated by the absence of TUNEL positive staining. Conclusions: This study provides first evidence that acute short-term mechanical ventilation-induced cerebral immunochallenge promotes physiological emergence of Aβ1-40 to reduce blood-brain barrier permeability and neuronal injury. While it is expected that sustained or long-term activation of this normally protective pathway leads to dysregulated Aβ1-40 accumulation, neurodegeneration, and cognitive impairment, these data suggest that a window of opportunity may exist within which implementation of timely interventions may limit cognition-relevant cerebral injury.
Plasma thiol redox status as indicator of acute kidney injury
Authors: Boekhoud Lisanne , Koeze Jacqueline , Slikke Elisabeth C. van der , Bourgonje Arno R. , Moser Jill , Zijlstra Jan G , Kobold Anneke C. Muller , Bulthuis Marian L.C. , Meurs Matijs van , Goor Harry van , Bouma Hjalmar R. 
Published: August 2020

Abstract
Introduction: Acute kidney injury (AKI) is associated with the abrupt loss of kidney function resulting in increased morbidity and mortality. Oxidative stress plays an important role in the pathophysiology of AKI. Free thiols (R-SH, sulfhydryl groups) are crucial components of the extracellular antioxidant machinery and reliably reflect systemic oxidative stress. Lower levels of thiols represent higher levels of oxidative stress. In this study, we hypothesized that plasma free thiols are associated with AKI upon admission to the intensive care unit (ICU). Methods: In this study, 301 critically ill patients were included for analysis. Plasma samples were taken upon admission. Plasma levels of albumin-adjusted plasma free thiols were determined and correlated with AKI stage upon ICU admission. Results: Albumin-adjusted plasma free thiols were significantly lower in patients with AKI (n=43, median [interquartile range] 7.28 µmol/g [3.52,8.95]) compared to patients without AKI (8.50 µmol/g [5.82, 11.28]; p < 0.05) upon admission to the ICU. Higher age (B = -0.72, p < 0.001), higher levels of neutrophil gelatinase-associated lipocalin (B = -0.002, p < 0.05), creatinine (B = -0.01, p < 0.05) and lower serum albumin (B = 0.47, p < 0.001) were associated with lower free thiol levels. Further, albumin-adjusted free thiol levels were significantly reduced in patients with sepsis (8.30 [5.52-10.64] µmol/g) compared to patients without sepsis (6.95 [3.72-8.92] µmol/g; p < 0.05). Conclusion: Albumin-adjusted plasma free thiols were significantly reduced in patients with AKI and patients with sepsis compared with patients without AKI and sepsis. Together, these data suggest that free thiol levels are mainly reduced in sepsis-associated AKI.
Corticosteroid use in COVID-19 patients: A systematic review and meta-analysis on clinical outcomes
Authors: Hoekstra Eva M. , Neumann Katinka M.I. , Boot Pauline C. , Paassen Judith van , Arbous Sesmu M. 
Published: August 2020

Abstract
Background In the current SARS-CoV-2 pandemic, there has been worldwide debate on the use of corticosteroids in COVID-19. In a recent RCT (RECOVERY trial), a reduced 28-day mortality in patients requiring oxygen therapy or mechanical ventilation evaluating the effect of dexamethasone was shown. Their results have led to considering amendments in guidelines or actually already recommending corticosteroid use in COVID-19. However, the supposed effect of corticosteroids on mortality and viral clearance remains unclear and a clear evidence-based therapeutic strategy is still lacking.Objectives The aim of this systematic review and meta-analysis was to evaluate the effect of corticosteroids on mortality, viral clearance and secondary outcomes in COVID-19 patients.Data source, study eligibility, participants, interventionsA systematic literature search was performed across Medline/PubMed, Embase, and Web of Science from 1st of December 2019 until 10th of July 2020, according to the PRISMA guidelines. RCTs and cohort studies reporting in English, on ≥15 adult COVID-19 patients, treated with any type of corticosteroid therapy were included. Studies on pregnant women, reviews and with a NOS (Newcastle Ottawa Scale for validity assessment of observational studies) score of ≤4 were excluded.Results Twenty-two articles were included, covering 9,760 patients. In eight studies, the effect of corticosteroid use was quantified. The pooled estimate of the observational studies supported the positive effect on mortality of corticosteroid therapy in COVID-19 as reported in the RECOVERY trial, in respiratory compromised COVID-19 patients, i.e. oxygen or mechanical ventilation dependent or with ARDS. The overall pooled estimate (observational studies and the RCT) showed reduced mortality in the corticosteroid group (relative risk 0.55 [95% CI 0.27-0.83]). Furthermore, mechanical ventilation rate seemed lower in corticosteroid treated COVID-19 patients, though no definite conclusions could be drawn because of a low number of studies. With regard to potential side effects of corticosteroids, the effect on viral clearance duration was ambiguous, i.e. prolonged in 4 of 9 and without effect in 5 of 9 studies.Conclusions It appears safe with respect to viral clearance to administer corticosteroids in respiratory compromised COVID-19 patients with possible improvement in mortality and conflicting effects on viral clearance.
Systematic Construction and Validation of an RNA Binding Proteins-Based Signature for Prognostic Prediction in Gastric Cancer
Authors: Zhang Yi , Wang Yuzhi , Li Chengwen , Jiang Tianhua 
Published: August 2020

Abstract
Background: Gastric cancer (GC) is one of the most common cancers with high incidence and mortality worldwide. Recently, RNA-binding proteins (RBPs) have drawn more and more attention for its role in cancer pathophysiology. In this study, we aim to explore the function and clinical implication of RBPs in GC. Methods: RNA sequencing data along with the corresponding clinical information of GC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed RNA-binding proteins (DERBPs) between tumor and normal tissues were identified by ‘limma’ package. Functional enrichment analysis and the protein-protein interaction (PPI) network were harnessed to explore the function and interaction of DERBPs. Next, Univariate and multiple Cox regression were applied to screen prognosis-related hub RBPs and to construct a signature for BC. Meanwhile, a nomogram was built based on the same RBPs. Results: A total of 296 DERBPs were found, and most of them mainly related to post-transcriptional regulation of RNA and ribonucleoprotein. A PPI network of DERBPs was constructed, consisting of 262 nodes and 2567 edges. A prognostic signature was built depended on seven prognosis-related hub RBPs that could divide GC patients into high- and low-risk groups. Survival analysis showed that the high-risk group had a worse prognosis compared to the low-risk group and the time-dependent receiver operating characteristic (ROC) curves suggested that the signature existed moderate predictive capacities of survival for GC patients. Similar results were obtained from another independent set GSE84437, confirming the robustness of signature. Calibration plots reported good consistency between overall survival (OS) prediction by nomogram and actual observation. Conclusion: The findings of this study would provide evidence of the effect of RBPs on GC as well as offering novel potential biomarkers in prognosis prediction and clinical decision for GC patients.
Montelukast in Hospitalized Patients Diagnosed with COVID-19
Authors: Khan Ahsan , Misdary Christian , Yegya-Raman Nikhil , Kim Sinae , Narayanan Navaneeth , Siddiqui Sheraz , Salgame Padmini , Radbel Jared , De Groote Frank , Michel Carl , Mehnert Janice , Hernandez Caleb , Braciale Thomas , Malhotra Jyoti , Gentile Michael A. , Jabbour Salma K. 
Published: August 2020

Abstract
Background Several therapeutic agents have been assessed for the treatment of COVID-19, but few approaches have been proven efficacious. Because leukotriene receptor antagonists such as montelukast have been shown to reduce both cytokine release and lung inflammation in preclinical models of viral influenza and acute respiratory distress syndrome, we hypothesized that therapy with montelukast would reduce clinical deterioration as measured by the COVID-19 Ordinal Scale.Methods We performed a retrospective analysis of COVID-19 confirmed hospitalized patients treated with or without montelukast. We used “clinical deterioration” as the primary endpoint, a binary outcome defined as any increase in the Ordinal Scale value from Day 1 to Day 3 of hospital stay, as these data were uniformly available for all admitted patients before hospital discharge. Rates of clinical deterioration between the montelukast and non-montelukast groups were compared using the Fisher’s exact test. Univariate logistic regression was also used to assess the association between montelukast use and clinical deterioration.Results A total of 92 patients were analyzed, 30 received montelukast at the discretion of the treating physician and 62 patients who did not receive montelukast. Patients receiving montelukast experienced significantly fewer events of clinical deterioration compared to patients not receiving montelukast (10% vs 32%, p = 0.022). Sensitivity analysis among those without asthma showed a trend toward fewer clinical deterioration events in the montelukast group than non-montelukast groups (11% vs 33%, p = 0.077). Sensitivity analysis among those who did not receive azithromycin showed fewer clinical deterioration events in the montelukast group vs. non-montelukast groups (8% vs 32%, p = 0.030).Conclusions Our findings suggest that montelukast associates with a reduction in clinical deterioration for COVID-19 confirmed patients as measured on the COVID-19 Ordinal Scale. Montelukast may have activity in COVID-19 infection, and future efforts should evaluate this potential therapy.
The proteomic characteristics of airway mucus from critical ill COVID-19 patients
Authors: Zhang Zili , Wang Tao , Liu Fei , Zhu Airu , Gu Guoping , Luo Jieping , Xu Jingyi , Zhao Jincun , Li Yiming , Liu Xiaoqing , Zhong Nanshan , Lu Wenju 
Published: August 2020

Abstract
Background: The pandemic of the coronavirus disease 2019 (COVID-19) has brought a global public health crisis. However, the pathogenesis underlying COVID-19 are barely understood. Methods: In this study, we performed proteomic analyses of airway mucus obtained by bronchoscopy from severe COVID-19 patients. In total, 2351 and 2073 proteins were identified and quantified in COVID-19 patients and healthy controls, respectively. Results: Among them, 92 differentiated expressed proteins (DEPs) (46 up-regulated and 46 down-regulated) were found with a fold change > 1.5 or < 0.67 and a p-value < 0.05, and 375 proteins were uniquely present in airway mucus from COVID-19 patients. Pathway and network enrichment analyses revealed that the 92 DEPs were mostly associated with metabolic, complement and coagulation cascades, lysosome, and cholesterol metabolism pathways, and the 375 COVID-19 only proteins were mainly enriched in amino acid degradation (Valine, Leucine and Isoleucine degradation), amino acid metabolism (beta-Alanine, Tryptophan, Cysteine and Methionine metabolism), oxidative phosphorylation, phagosome, and cholesterol metabolism pathways. Conclusions: This study aims to provide fundamental data for elucidating proteomic changes of COVID-19, which may implicate further investigation of molecular targets directing at specific therapy.
Alteration of Gut Microbiota in type 2 Diabetes Complicated with Cholelithiasis Patients
Authors: Chen Jiajia , Yan Linlin , Ma Xingfan , Yuan Ping , Zhao Fan , Han Zihan , Liu Jingshan , Wang Wenbo , Zhou Donghai , Zhao Hongyu , Feng Nan , Huang Dandan , Hu Shoukui , Gu Jin 
Published: August 2020

Abstract
Background: Epidemiological studies showed that diabetes patients are more prone to developing cholelithiasis. Although composition of gut microbiota in type 2 diabetes or cholelithiasis have been studied respectively, the underlying role of gut microbiota in developing from diabetes to cholelithiasis remains unclear. By 16S rRNA gene sequencing, the gut microbial composition of 33 healthy subjects, 53 type 2 diabetes, 31 cholelithiasis and 32 type 2 diabetes complicated with cholelithiasis patients were studied. Results: Microbial diversity significantly decreased in type 2 diabetes complicated with cholelithiasis patients. In type 2 diabetes patients, phylum Proteobacteria class Gammaproteobacteria and order Lactobacillales were significantly increased. In cholelithiasis patients, phylum Bacteroidetes, class Bacteroidia order Bacteroidales family Bacteroidaceae and genus Bacteroides were significantly increased. There were also significant increases of phylum Proteobacteria, class Gammaproteobacteria order Lactobacillales family Lactobacillaceae and genus Lactobacillus in type 2 diabetes complicated with cholelithiasis patients accompanied by elevated serum triglyceride and total bile acids. Conclusions: The results show similar but more intricate gut microbiota dysbiosis in type 2 diabetes complicated with cholelithiasis compared with type 2 diabetes, which might partially explain the mechanism of type 2 diabetes as the risk factor of cholelithiasis from the perspective of gut microbiota.
Effects of Securigera Securidaca Seed Extract, Alone and in combination with Glibenclamide, on Circulating Levels of Pro-Angiogenic/Anti-Angiogenic Biomarkers in Hyperglycemic Rats
Authors: Alizadeh-Fanalou Shahin , Babaei Mohammad , Bahreini Elham 
Published: August 2020

Abstract
Background: Many diabetic patients use herbal medicines in addition to their mainstream treatments. Plants contain a well-known and unknown set of compounds that may exacerbate or improve diabetes complications. Thus, the side effects of these herbs should be known before prescribing. The aim of the study is to investigate the effects of hydroalcoholic extract of Securigera securidaca (L.) Degen & Dorfl (S. securidaca) seed (HESS) on angiogenesis/anti-angiogenesis balance in Streptozotocin (STZ)-induced diabetic rats, alone and in combination with glibenclamide. Methods: The groups involved in this animal study included diabetic and healthy control groups, groups treated with three doses of HESS, group treated with glibenclamide, and groups received combination therapy. Serum samples were taken and analyzed for the levels of angiogenic/ anti-angiogenic biomarkers.Results: Induction of diabetes increased serum levels of angiogenic agents and decreased circulating anti-angiogenic factors. The herbal extract, even with the highest dose, had little effects on the blood levels of the tested biomarkers except with TGF-β. Glibenclamide was more effective than the highest dose of HESS in preventing the increase in serum levels of angiogenic factors and in inhibiting the decrease in anti-angiogenic agents in diabetic rats. Combination therapy with the highest dose of HESS partly enhanced the glibenclamide effects.Conclusions: Although glibenclamide was more effective than the highest dose of HESS used in this study in preventing changes in serum concentrations of angiogenic/ anti-angiogenic biomarkers in the diabetic animals, this study show that S. securidaca has no side effects on diabetes complications caused by vascular disorders and neovascularization, and still it can be used as a herbal supplement with the standard drug.
Phase II Study of Definitive Chemoradiation Therapy Using S-1 for Esophageal Squamous Cell Carcinoma Patients --- the ESO-Shanghai 7 Trial Protocol
Authors: Tseng Ihsuan , Chen Yun , Zhu Zhengfei , Zhao Weixin , Liu Qi , Zhang Junhua , Deng Jiaying , Ai Dashan , Lu Saiquan , Jia Huixun , Zhao Kuaile 
Published: August 2020

Abstract
Background: Concurrent chemoradiotherapy (CCRT) is a standard treatment for inoperable locally advanced esophageal carcinoma. However, there exists a group of patients who are intolerable to intravenous chemotherapy for the old age or with serious comorbidities. S-1 is an oral fluorouracil derivative with well tolerance than 5-fluorouracil. The ESO-Shanghai 7 trial aimed to access the safety and efficacy of S-1 combined with radiotherapy for esophageal squamous cell carcinoma (ESCC) patients who are elderly or with serious comorbidities.Methods: 105 ESCC patients with old age or serious comorbidities will be enrolled in this prospective, single-arm phase 2 clinical trial. Patients will receive S-1 orally at a dose of 40 mg (BSA ≤ 1.6 m2) or 50 mg (BSA >1.6 m2) twice daily for 28 days. The concurrent radiotherapy dose is 61.2 Gy delivered in 34 fractions. The primary endpoints are 3-yr local control and number and grade of participants with adverse events, and the secondary endpoint is overall survival. Discussion: The aim of this phase 2 trial is to determine the tolerance and efficacy of S-1 concurrent with radiotherapy for ESCC patients with old age or serious comorbidities. A very promising 3-yr local control should beat least 60% from the clinical point of view.Trial registration: ClinicalTrials.gov, NCT01831531. Registered 29 March 2013, https://clinicaltrials.gov/ct2/show/NCT01831531?term=NCT01831531&draw=2&rank=1
Advantages of Surgical Implantation Impella 5.5 SmartAssist in the Management of Acute Post-Infarction Ventricular Septal Defect with Cardiogenic Shock
Authors: Madjarov Jeko , Katz Michael G , Madzharov Svetozar , Fazal Shahood , Robicsek francis 
Published: August 2020

Abstract
ABSTRACT Background: Despite advances in surgical techniques and aggressive therapy of post-infarction ventricular septal defect (VSD) with cardiogenic shock, the overall morbidity and mortality is frustratingly high. The Impella 5.5 SmartAssist (Abiomed, Danvers, MA) is a surgically implanted temporary device, recently approved by the FDA for treatment of patients in cardiogenic shock, and may fill a technological gap for perioperative patients who require acute circulatory support. Case presentation: We report our initial experience with trans-aortic implantation of the Impella 5.5 SmartAssist for two patients with post myocardial infarction VSD in the setting of cardiogenic shock. First patient had a posterior VSD with a left to right shunt (Qp/Qs ratio of 3.3), right ventricle dysfunction, severe pulmonary arterial hypertension, and severe mitral valve regurgitation. Second patient was admitted for massive MI with large anterior VSD (Qp/Qs ratio of 2.8). Under cardiopulmonary bypass with cardioplegic arrest both patients underwent urgent VSD closure with trans-aortic implantation of the Impella. Minimal postoperative support was required. Patients were discharged on postoperative day 10 and 14 and remained well three months later. Follow-up echocardiogram showed no residual shunt. Conclusions: Early surgical implantation of Impella 5.5 SmartAssist can prevent multiorgan dysfunction and stabilize the patients in cardiogenic shock with post-myocardial infarction VSD.
Clinicopathology and Outcomes of Small Bowel Metastases: A Retrospective Study of 31 Consecutive Cases
Authors: Liao Yu-Tso , Lin Been-Ren , Lai I-Rue , Chen Chiung-Nien , Liang Jin-Tung , Lin Ming-Tsan 
Published: August 2020

Abstract
BACKGROUND

The small bowel (SB) is a rare site for distant metastasis. Few recent studies have systematically reported on the clinicopathology and outcomes of SB metastasis. This study aimed to describe the clinicopathology and outcomes of SB metastasis.
METHODS

A retrospective study involving patients diagnosed with SB metastasis at a single medical center between January 2009 and December 2019 was conducted. Patients with secondary SB cancer with direct invasion or peritoneal carcinomatosis by a primary tumor were excluded. The demographic characteristics of the patients, clinical patterns of primary cancer and SB metastasis, and outcomes were analyzed.
RESULTS

During the 10-year period, we identified 31 patients eligible for analysis. The female:male ratio was 8:24, and the median patient age was 63.5 years. Metastasis of lung cancer to the SB was noted most frequently. Most patients presented with abdominal pain, gastrointestinal bleeding, or abnormal imaging findings. The interval between primary cancer and SB metastasis was 19.2 months. Sole SB metastasis was noted in 20 patients (64.5%). Twenty-two (70.1%) patients underwent surgical intervention. The median survival was 6.6 months.
Conclusions

Distant metastasis of other primary cancers to the SB is noted extremely rarely. The presence of SB metastasis indicated extremely poor prognosis. Surgery plays an important role in ameliorating critical symptoms However, surgery does not confer survival benefits.