bluuebunny/crossref_metadata_2025_split huggingface dataset:
CompLement C5 Antibodies for decreasing brain injury after aneurysmal Subarachnoid Haemorrhage (CLASH): study protocol for a randomized controlled phase II clinical trial
Authors: Koopman Inez , Rinkel Gabriel J.E. , Vergouwen Mervyn D.I. 
Published: October 2020

Abstract
Background The inflammatory response after aneurysmal subarachnoid haemorrhage (aSAH) has been associated with early brain injury, delayed cerebral ischemia, poor functional outcome, and case-fatality. In experimental SAH studies, complement C5 antibodies administered shortly after SAH reduced brain injury with approximately 40%. Complement component C5 may be a new therapeutic target to reduce brain injury and hereby improve outcome after aSAH. We aim to investigate the pharmacodynamic efficacy and safety of eculizumab (complement C5 antibody) in patients with aSAH.

Methods A randomized, controlled, open-label, phase II clinical trial with blinded outcome assessment. Eculizumab (1200 mg) is administered intravenously <12 hours, on day 3 and on day 7 after ictus. Patients in the intervention group receive prophylactic antibiotics for 4 weeks, and those with a central line or an external ventricular shunt and a positive fungal or yeast culture also receive prophylactic antifungal therapy for 4 weeks. The primary outcome is C5a concentration in cerebrospinal fluid (CSF) on day 3 after ictus. Secondary outcomes include the occurrence of adverse events, inflammatory parameters in blood and CSF, cerebral infarction on magnetic resonance imaging, and clinical- and cognitive outcomes. We aim to evaluate 26 patients with CSF assessments, 13 in the intervention group and 13 in the comparator group. To compensate for early case-fatality and inability to obtain CSF, we will include 20 patients per group.

Discussion The CLASH trial is the first trial to investigate the pharmacodynamic efficacy and safety of eculizumab in the early phase after aSAH.

Trial registration Netherlands Trial Register: NTR6752, https://www.trialregister.nl/trial/6579. Registered on 27 October 2017. European Clinical Trials Database: EudraCT 2017-004307-51.
Molecular detection of Rickettsia in fleas from micromammals in Chile
Authors: Salas Lucila Moreno , Carniglia Mario Espinoza , Schmeisser Nicol Lizama , Fuentes Luis Gonzalo Torres , Fuente María Carolina Silva de la , Lareschi Marcela , Acuña Daniel González 
Published: October 2020

Abstract
Background: Rickettsial diseases are considered important in public health due to their dispersal capacity determined by the particular characteristics of their reservoirs and/or vectors. Among the latter, fleas play an important role, since the vast majority of species parasitize wild and invasive rodents, so their detection is relevant to be able to monitor potential emerging diseases. The aim of this study was to detect, characterize, and compare Rickettsia spp. from the fleas of micromammals in areas with different human population densities in Chile. Methods: The presence of Rickettsia spp. was evaluated by standard polymerase chain reaction (PCR) and sequencing in 1315 fleas collected from 1512 micromammals in 29 locations, with different human population densities in Chile. A generalized linear model (GLM) was used to identify the variables that may explain Rickettsia prevalence in fleas. Results: DNA of Rickettsia spp. was identified in 13.2% (174 of 1315) of fleas tested. Fifteen flea species were found to be Rickettsia-positive. The prevalence of Rickettsia spp. was higher in winter, semi-arid region and natural areas, and the infection levels in fleas varied between species of flea. The prevalence of Rickettsia among flea species ranged between 0–35.1%. Areas of lower human density showed the highest prevalence of Rickettsia. The phylogenetic tree showed two well-differentiated clades with Rickettsia bellii positioned as basal in one clade. The second clade was subdivided into two subclades of species related to Rickettsia of the spotted fever group. Conclusions: To our knowledge, this is the first report of the occurrence and molecular characterization of Rickettsia spp. in 15 flea species of micromammals in Chile. In this study, fleas were detected carrying Rickettsia DNA with zoonotic potential, mainly in villages and natural areas of Chile. Considering that there are differences in the prevalence of Rickettsia in fleas associated with different factors, more investigations are needed to further understand the ecology of Rickettsia in fleas and their implications for human health.
Exploring perspectives on antimicrobial stewardship: a qualitative study of health managers in Kenya
Authors: Mbugua Samuel Mungai , Njoroge George , Kijogi Caroline , Kamita Moses , Kimani Rachel , Mwaura Peter , Waiganjo-Aidi Bibianne Wanja , Gitaka Jesse 
Published: October 2020

Abstract
Background: Antimicrobial resistance is a significant public health concern with the establishment of antimicrobial stewardship in hospitals being increasingly obligatory. Perspectives and insights of health managers on antimicrobial stewardship (AMS), complementary health services and building blocks are imperative towards implementation of robust AMS programs. This study aimed to understand perspectives of hospital managers on AMS and identify areas of management engagement while addressing potential blockades to change.Methods: A cross-sectional, qualitative, multicenter study was conducted in three hospitals in Kenya. Key-informant interviews on perspectives on AMS were administered to hospital managers. Qualitative data was captured using audio tapes and field notes, transcribed and managed using NVivo 12 software. An iterative process was used to develop the thematic framework and updated in two rounds of iteration analysis. Analysis charts for each emergent theme were developed and categorized across all participants.Results: Perspectives on AMS are described in five thematic categories; Importance of antimicrobial stewardship and the role of medicines and therapeutics committee, availability of antimicrobial formulary and usage surveillance systems, laboratory competency and recommendations for infection prevention and management, educational resources and communications channels available, building blocks and low-lying fruits for Antimicrobial Stewardship Committees. The role of stewardship collaboration in diagnosis and antimicrobial prescription was alluded to with managers indicating a growing rise in occurrence of antimicrobial resistance. There lacked contextualized, hospital specific antimicrobial formulary and adequate laboratory competency. Staff training and communication channels were available in varying capacity across the three hospitals. Building blocks identified include medicines and therapeutics committee, education, and training platforms (Continuous Medical Education and Continuous Professional Development activities) and hospital leadership commitment.Conclusions: The practice of antimicrobial stewardship is not implemented and well developed as demonstrated by lack of core AMS complementary health services. However, the health managers are aware of the fundamental importance of antimicrobial stewardship programs and the vast benefits of implementation and institutionalization of AMS to hospitals and their clients. The findings underpin the importance of understanding and incorporating perspectives of health managers on existing contextual mechanisms that can be leveraged on to establish robust AMS programs in the fight against antimicrobial resistance.
Analyses of the Local Control of Pulmonary Oligometastases after Stereotactic Body Radiotherapy and the Impact of Local Control on Survival
Authors: Yamamoto Takaya , Niibe Yuzuru , Aoki Masahiko , Shintani Takashi , Yamada Kazunari , Kobayashi Mitsuru , Yamashita Hideomi , Ozaki Masatoki , Manabe Yoshihiko , Onishi Hiroshi , Yahara Katsuya , Nishikawa Atsushi , Katsui Kuniaki , Oh Ryoong-Jin , Terahara Atsuro , Jingu Keiichi 
Published: October 2020

Abstract
Background: Successful local therapy for oligometastases may lead to longer survival. The purpose of this multicentre retrospective study was to investigate factors affecting the local control (LC) of pulmonary oligometastases treated by stereotactic body radiotherapy (SBRT) and to investigate the impact of LC on survival.Methods: The inclusion criteria included 1 to 5 metastases, the primary lesion and other extrathoracic metastases were controlled before SBRT, and the biological effective dose (BED10) of the SBRT was 75 Gy or more. The Cox proportional hazards model was used for analyses.Results: Data of 1378 patients with 1547 tumours from 68 institutions were analysed. The median follow-up period was 24.2 months. The one-year, 3-year and 5-year LC rates were 92.1%, 81.3% and 78.6%, respectively, and the 1-year, 3-year and 5-year overall survival rates were 90.1%, 60.3% and 45.5%, respectively. Multivariate analysis for LC showed that increased maximum tumour diameter (p=0.011), type A dose calculation algorithm (p=0.005), shorter overall treatment time of SBRT (p=0.035) and colorectal primary origin (p<0.001 excluding oesophagus origin) were significantly associated with a lower LC rate. In the survival analysis, local failure (p<0.001), worse performance status (1 vs. 0, p=0.013; 2–3 vs. 0, p<0.001), oesophageal primary origin (vs. colorectal origin, p=0.038), squamous cell carcinoma (vs. adenocarcinoma, p=0.006) and increased maximum tumour diameter (p<0.001) showed significant relationships with shorter survival.Conclusions: Several factors of oligometastases and SBRT affected LC. LC of pulmonary oligometastases by SBRT showed a significant survival benefit compared to patients with local failure.
Measuring health equity in emergency care using routinely collected data: a systematic review
Authors: Morisod Kevin , Luta Xhyljeta , Marti Joachim , Spycher Jacques , Malebranche Mary , Bodenmann Patrick 
Published: October 2020

Abstract
Abstract
Background : Achieving equity in health care remains a challenge for health care systems worldwide and marked inequities in access and quality of care persist. The performance assessment of health care systems is often limited to quality and efficiency indicators. Identifying indicators of health care equity is an important first step in integrating the concept of equity into assessments of health care system performance. Because emergency care serves as the interface between ambulatory and inpatient care, it is arguably an opportune setting in which to begin this process.
Methods: We conducted a systematic review of administrative data-derived health care equity indicators and their association with socio-economic determinants of health (SEDH) in emergency care settings. Following PRISMA-Equity reporting guidelines, Ovid MEDLINE, EMBASE, PUBMED and Web of Science were searched for relevant studies. The outcomes of interest were indicators of health care equity and the associated SEDH they examine.
Results: Among 29 studies identified, 14 equity indicators were identified and grouped into four categories that reflect the patient emergency care pathway. Total emergency department (ED) visits and ambulatory care sensitive condition-related ED visits were the two most frequently used equity indicators. The studies analysed equity based on seven SEDH: social deprivation, income, education level, social class, insurance coverage, health literacy and financial and non-financial barriers. Despite some conflicting results, all identified SEDH are associated with inequalities in access to and use of emergency care.
Conclusion: The use of administrative data-derived indicators in combination with identified SEDH could improve the measurement of health care equity in emergency care settings across health care systems worldwide. Using a combination of indicators is likely to lead to a more comprehensive, well-rounded measurement of health care equity than using any one indicator in isolation. Though studies analysed focused on emergency care settings, it seems possible to extrapolate these indicators to measure equity in other areas of the health care system. Further studies elucidating root causes of health inequities in and outside the health care system are needed.
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Tolvaptan-induced hypernatremia related to low serum potassium level accompanying high blood pressure in patients with acute decompensated heart failure.
Authors: Fukuoka Hidetada , Yachibana Koichi , Shinoda Yukinori , Minamisaka Tomoko , Inui Hirooki , Ueno Keisuke , Inoue Soki , Mine Kentaro , Ueda Kumpei , Hoshida Shiro 
Published: October 2020

Abstract
Backgrounds: Tolvaptan significantly increases urine volume in acute decompensated heart failure (ADHF); serum sodium level increases due to aquaresis in almost all cases. We aimed to elucidate clinical factors associated with hypernatremia in ADHF patients treated with tolvaptan.Methods: We enrolled 117 ADHF patients treated with tolvaptan in addition to standard therapy. We examined differences in clinical factors at baseline between patients with and without hypernatremia in the initial three days of hospitalization. Results: Systolic (p=0.045) and diastolic (p=0.004) blood pressure, serum sodium level (p=0.002), and negative water balance (p=0.036) were significantly higher and serum potassium level (p=0.026) was significantly lower on admission day in patients with hypernatremia (n=22). In multivariate regression analysis, hypernatremia was associated with low serum potassium level (p=0.034). Among patients with serum potassium level ≤3.8 mEq/L, the cutoff value obtained using receiver operating characteristic curve analysis, those with hypernatremia related to tolvaptan treatment showed significantly higher diastolic blood pressure on admission day (p=0.004).Conclusion: In tolvaptan treatment combined with standard therapy in ADHF patients, serum potassium level ≤ 3.8mEq/L may be a determinant factor for hypernatremia development. Among hypokalemic patients, those with higher diastolic blood pressure on admission may be carefully managed to prevent hypernatremia.
Nutritional and Inflammatory Measures Predict Survival of Patients with Stage IV Colorectal Cancer
Authors: Takamizawa Yasuyuki , Shida Dai , Boku Narikazu , Nakamura Yuya , Ahiko Yuka , Yoshida Takefumi , Tanabe Taro , Takashima Atsuo , Kanemitsu Yukihide 
Published: October 2020

Abstract
Background: This study aimed to evaluate the prognostic impact of nutritional and inflammatory measures (controlling nutritional status (CONUT) score, prognostic nutritional index (PNI), and modified Glasgow prognostic score (mGPS)) on overall survival (OS) in patients with stage IV colorectal cancer (CRC).Methods: Subjects were 996 patients with stage IV CRC who were referred to the National Cancer Center Hospital between 2001 and 2015. We retrospectively investigated correlations between OS and CONUT score, PNI, and mGPS. Multivariate analyses were performed using Cox proportional hazards regression models.Results: After adjusting for known factors (age, gender, BMI, ECOG performance status, location of primary tumor, CEA levels, histological type, M category, and prior surgical treatment), all three measures were found to be independent prognostic factors for OS in patients with stage IV CRC (CONUT score, p<0.001; PNI, p<0.001; mGPS, p<0.001). Significant differences in OS were found between low CONUT score (0/1) (n=614; 61%) and intermediate CONUT score (2/3) (n=276; 28%) (hazard ratio (HR)=1.20, 95% confidence interval (CI): 1.02-1.42, p=0.032), and intermediate CONUT score and high CONUT score (≥4) (n=106; 11%) (HR=1.30, 95% CI: 1.01-1.67, p=0.045). Significant differences in OS were found between mGPS=0 (n=633; 64%) and mGPS=1 (n=234; 23%) (HR=1.84, 95% CI: 1.54-2.19, p<0.001), but not between mGPS=1 and mGPS=2 (n=129; 13%) (HR=1.12, 95% CI: 0.88-1.41, p=0.349). Patients with low PNI (<48.0) (n=443; 44%) showed a significantly lower OS rate than those with high PNI (≥48.0) (n=553; 56%) (HR=1.39, 95% CI: 1.19-1.62, p<0.001).Conclusions: CONUT score, PNI, and mGPS were found to be independent prognostic factors for OS in patients with stage IV CRC, suggesting that nutritional and inflammatory status is a useful host-related prognostic indicator in stage IV CRC.
Analysis of the expression and potential molecular mechanism of interleukin-1 receptor antagonist (IL1RN) in papillary thyroid cancer via bioinformatics methods
Authors: Xie Zhenyu , Li Xin , He Yuzhen , Wu Song , Wang Shiyue , Sun Jianjian , He Yuchen , Lun Yu , Xin Shijie , Zhang Jian 
Published: October 2020

Abstract
Background: Interleukin-1 receptor antagonist (IL1RN) has been reported as a biomarker of many cancers. However, the biological function of IL1RN in papillary thyroid carcinoma (PTC) remains undetermined.Methods: We obtained IL1RN expression data from The Cancer Genome Atlas (TCGA) database. Enrichment analysis of coexpressed genes and IL1RN methylation analysis were performed via LinkedOmics. The correlations between IL1RN and immune infiltrates were investigated via ESTIMATE, TIMER and TISIDB. We analyzed the association of IL1RN expression with pancancer overall survival (OS) via Gene Expression Profiling Interactive Analysis (GEPIA).Results: IL1RN showed higher expression levels and lower methylation levels in PTC tissues than in normal tissues. Higher IL1RN expression was significantly associated with shorter progression-free survival (PFS), advanced tumor stage, tumor metastasis, increased incidence of BRAF mutations, and decreased incidence of N-RAS and H-RAS mutations. Genes coexpressed with IL1RN participate primarily in immune-related pathways. IL1RN expression positively correlated with immune infiltration, tumor progression and poor OS for all cancers.Conclusions: IL1RN is a good prognostic and diagnostic biomarker for PTC. IL1RN may promote thyroid cancer progression through immune-related pathways. Methylation may act as an upstream regulator of IL1RN expression and biological function. Additionally, IL1RN was shown to have broad prognostic value in a pancancer cohort.
Neuregulin-1 inhibits CoCl2-induced upregulation of excitatory amino acid carrier 1 expression and oxidative stress in SH-SY5Y cells and the hippocampus of mice
Authors: Kim Han-Byeol , Yoo Ji-Young , Yoo Seung-Yeon , Lee Jun-Ho , Chang Wonseok , Kim Hye-Sun , Baik Tai-Kyoung , Woo Ran-Sook 
Published: October 2020

Abstract
Excitatory amino acid carrier 1 (EAAC1) is an important subtype of excitatory amino acid transporters (EAATs) and is the route for neuronal cysteine uptake. CoCl 2 is not only a hypoxia-mimetic reagent but also an oxidative stress inducer. Here, we found that CoCl 2 induced significant EAAC1 overexpression in SH-SY5Y cells and the hippocampus of mice. Transient transfection of EAAC1 reduced CoCl 2 -induced cytotoxicity in SH-SY5Y cells. Based on this result, upregulation of EAAC1 expression by CoCl 2 is thought to represent a compensatory response against oxidative stress in an acute hypoxic state. We further demonstrated that pretreatment with Neuregulin-1 (NRG1) rescued CoCl 2 -induced upregulation of EAAC1 and tau expression. NRG1 plays a protective role in the CoCl 2 -induced accumulation of reactive oxygen species (ROS) and reduction in antioxidative enzyme (SOD and GPx) activity. Moreover, NRG1 attenuated CoCl 2 -induced apoptosis and cell death. NRG1 inhibited the CoCl 2 -induced release of cleaved caspase-3 and reduction in Bcl-X L levels. Our novel finding suggests that NRG1 may play a protective role in hypoxia through the inhibition of oxidative stress and thereby maintain normal EAAC1 expression levels.
Understanding the effects of beetroot juice intake on CrossFit performance by assessing hormonal, metabolic and mechanical response: a randomized, double-blind, crossover design
Authors: Garnacho-Castaño Manuel V. , Palau-Salvà Guillem , Serra-Payá Noemí , Ruiz-Hermosel Mario , Berbell Marina , Viñals Xavier , Bataller Manuel Gomis , Carbonell Teresa , Vilches-Saez Sergio , Cobo Eulogio Pleguezuelos , Molina-Raya Lorena 
Published: October 2020

Abstract
Background: Acute beetroot juice (BJ) intake has shown to enhance aerobic and anaerobic performance. However, no studies have evaluated the effects of BJ intake on CrossFit (CF) performance by linking hormonal, metabolic, and mechanical responses. The purpose of this study was to determine the causal physiological association between hormonal, metabolic and mechanical responses, and CF workouts performance after acute BJ intake. Methods: Twelve well-trained male practitioners undertook a CF workout ﻿after drinking 140 mL of BJ (~ 12.8 mmol NO3−) or placebo. The two experimental conditions (BJ or placebo) were administered using a randomized, double-blind, crossover design. The CF workout consisted of repeating the same exercise routine twice: Wall ball (WB) shots plus full back squat (FBS) with 3-min rest (1st routine) or without rest (2nd routine) between the two exercises. A 3-min rest was established between the two exercise routines.Results: An interaction effect was observed in the number of repetitions performed (p = 0.04). The Bonferroni test determined a higher number of repetitions after BJ than placebo intake when a 3-min rest between WB and FBS (1st routine) was established (p = 0.007). An interaction effect was detected in cortisol response (p = 0.04). Cortisol showed a higher increase after BJ compared to placebo intake (76% vs. 36%, respectively). No interaction effect was observed in the testosterone and testosterone/cortisol ratio (p > 0.05). A significant interaction effect was found in oxygen saturation (p = 0.01). A greater oxygen saturation drop was observed in BJ compared to placebo (p < 0.05). An interaction effect was verified in muscular fatigue (p = 0.03) with a higher muscular fatigue being observed with BJ than placebo (p = 0.02). Conclusions: BJ intake improved anaerobic performance only after the recovery time between exercises. This increase in performance in the first routine probably generated greater hypoxia in the muscle mass involved, possibly conditioning post-exercise performance. This was observed with a fall in oxygen saturation and in muscle fatigue measured at the end of the CF workout. The greatest perceived changes in cortisol levels after BJ intake could be attributed to the nitrate-nitrite-nitric oxide pathway