bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness Analysis of Caspofungin and Fluconazole for Primary Treatment of Invasive Candidiasis and Candidemia in Ethiopia
Authors: Gebretekle Gebremedhin Beedemariam , Fentie Atalay Mulu , Gebremariam Girma Tekle , Ali Eskinder Eshetu , Erku Daniel Asfaw , Alemayehu Tinsae , Abebe Workeabeba , Sander Beate 
Published: January 2022

Abstract
Background: Caspofungin was shown to be more effective than fluconazole in treating patients with invasive candidiasis and/or candidaemia (IC/C). However, cost-effectiveness of caspofungin for treating IC/C in Ethiopia remains unknown. We aimed to assess the cost-effectiveness of caspofungin compared to fluconazole as primary treatment of IC/C in Ethiopia.Methods: A Markov cohort model was developed to compare the cost-utility of caspofungin versus fluconazole antifungal agents as first-line treatment for adult inpatients with IC/C from the Ethiopian health system perspective. Treatment outcome was categorized as either a clinical success or failure, with clinical failure being switched to a different antifungal medication. Liposomal amphotericin B (L-AmB) was used as a rescue agent for patients who had failed caspofungin treatment, while caspofungin or L-AmB were used for patients who had failed fluconazole treatment. Primary outcomes were expected quality-adjusted life years (QALYs), costs (US$2021), and the incremental cost-effectiveness ratio (ICER). QALYs and costs were discounted at 3% annually. Cost data was obtained from Addis Ababa hospitals while locally unavailable data were derived from the literature. Cost-effectiveness was assessed against the recommended threshold of 50% of Ethiopia’s gross domestic product/capita. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the findings.Results: In the base-case analysis, treatment of IC/C with caspofungin as first-line treatment resulted in better health outcomes (12.86 QALYs) but higher costs (US$7,714) compared to fluconazole-initiated treatment followed by caspofungin (12.30 QALYs; US$3,217) or L-AmB (10.92 QALYs; US$2,781) as second-line treatment. Caspofungin as primary treatment for IC/C was not cost-effective when compared to fluconazole-initiated therapies. Fluconazole-initiated treatment followed by caspofungin was cost-effective for the treatment of IC/C compared to fluconazole with L-AmB as second-line treatment, at US$316/QALY gained. Our findings were sensitive to medication costs, drug effectiveness, infection recurrence, and infection-related mortality rates. Probabilistic sensitivity analysis confirmed the stability of our findings.Conclusions: Our study showed that the use of caspofungin as primary treatment for IC/C in Ethiopia was not cost-effective when compared with fluconazole-initiated treatment alternatives. The findings supported the use of fluconazole-initiated therapy with caspofungin as a second-line treatment to treat IC/C in Ethiopia and other low-income countries.
The Impact of Heart Rate Circadian Rhythm on In-hospital Mortality in Stroke and Critically Ill Patients: Insights from the eICU Collaborative Research Database
Authors: Yang Zhengning , Li Zhe , He Xu , Yao Zhen , Xie XiaoXia , Zhang Sha , Shen Yan , Li Shaowei , Qiao Shuzhen , Hui Zhenliang , Gao Chao , Chen Jun 
Published: January 2022

Abstract
Background: The dysregulation of the heart rate circadian rhythm has been documented to be an independent risk factor in multiple diseases. However, data showing the impact of dysregulated heart rate circadian rhythm in stroke and critically ill patients are scarce.Methods: Stroke and critically ill patients in the ICU between 2014 and 2015 from the recorded eICU Collaborative Research Database were included in the current analyses. The impact of circadian rhythm of heart rate on in-hospital mortality was analyzed. Three variables, Mesor (rhythm-adjusted mean of heart rate), Amplitude (distance from the highest point of circadian rhythm of heart rate to Mesor), and Peak time (time when the circadian rhythm of heart rate reaches the highest point) were used to evaluate the heart rate circadian rhythm. The incremental value of circadian rhythm variables in addition to Acute Physiology and Chronic Health Evaluation (APACHE) IV score to predict in-hospital mortality was also explored.Results: A total of 6,201 eligible patients were included. The in-hospital mortality was 16.2% (1,002/6,201). The circadian rhythm variables of heart rate, Mesor, Amplitude, and Peak time, were identified to be independent risk factors of in-hospital mortality. After adjustments, Mesor per 10 beats per min (bpm) increase was associated with a 1.17-fold (95%CI: 1.11, 1.24, P<0.001) and Amplitude per 5 bpm was associated with a 1.14-fold (95%CI: 1.06, 1.24, P<0.001) increase in the risk of in-hospital mortality, respectively. The risk of in-hospital mortality was lower in patients who had Peak time reached between 18:00-24:00 or 00:00-06:00; whereas the risk was highest in patients who had Peak time reached between 12:00-18:00 (OR: 1.33, 95%CI: 1.05, 1.68, P=0.017). Compared with APACHE IV score only (c-index=0.757), combining APACHE IV score and circadian rhythm variables of heart rate (c-index=0.766) was associated with increased discriminative ability (P=0.003).Conclusion: Circadian rhythm of heart rate is an independent risk factor of the in-hospital mortality in stroke and critically ill patients. Including circadian rhythm variables regarding heart rate might increase the discriminative ability of the risk score to predict the short-term prognosis of patients.
Lnc027912 Reduces Lipid Accumulation Through Akt/MTOR/SREBP1C Axis in Hepatic Cells
Authors: Chu Kaifei , Zhao Niannian , Feng Rong , Zhang Li , Hu Xudong , Liu Li , Li Wei , Liu Lin 
Published: January 2022

Abstract
Background: Various metabolism diseases are closely related to lipid metabolism disorder, but long noncoding-RNAs (lncRNA) involve in regulating function of lipid was limited elucidated. Previous our work have found that lnc027912 involve in cholesterol metabolism. Here, we further explore the role of lipid metabolism-associated lncRNA-lnc027912 in oleic acid- (OA) and palmitic acid (PA)-induced hepatic cells. Methods: The overexpression of lnc027912 cell model was constructed by using virus particles transfection, and the level of lnc027912 in AML12 cells were detected by RT-qPCR. High fat cell model was established by treating AML12 cells with OA and PA, and the level of lipid drops was detected by Oil red O staining and triglyceride analyze Kit. The lipid metabolism related-genes, such as SREBP1C, FAS, PPARγ, MTTP, ApoE and ApoC3 level, was detected using RT-qPCR and Western blot. The role of SREBP1C in lipid metabolism was further analyzed using double luciferase reporter gene assay and Immunofluorescence. The Akt/mTOR signal pathway related genes was detected by Western blot. Results: We found that TG level was inhibited in overexpression of lnc027912 cell. Upregulated lnc027912 of AML12 cells treated with OA and PA showed a significant decrease in lipid accumulation and TG levels. Furthermore, overexpression of lnc027912, the lipid biosynthesis genes of SREBP1C, FAS and PPARγ was significantly decreased and a significant increase in expression of MTTP and ApoE. Interestingly, lnc027912 inhibited Akt/mTOR signaling axis and decreased SREBP1C transit into nucleus and the promoter activity of SREBP1C and regulated expression of its targets. Conclusions: Our study revealed a new insights into the molecular function of lnc027912 in lipid metabolism by Akt/mTOR/SREBP1C signaling axis and highlights the potential of lnc027912 as a new therapeutic target for lipid disorder diseases (such as, NAFLD).
Perioperative Application of Diltiazem in Patients Undergoing On-Pump Coronary Artery Bypass Grafting
Authors: Zhang Xiaopeng , Hu Yirui , Friscia Michael , Wu Xianren , Zhang Li , Casale Alfred 
Published: January 2022

Abstract
Diltiazem is frequently applied during the perioperative period of coronary artery bypass grafting with cardiopulmonary bypass (on-pump CABG) to prevent arterial graft spasm; however, the short- and long-term outcome effects are unclear. In this retrospective cohort study, from October 2008 to October 2018, adult patients who underwent isolated CABG with cardiopulmonary bypass (CPB) were identified. Patients in the perioperative diltiazem (DILT) and non-intervention (non-DILT) cohorts were matched based on propensity scores. Logistic regression was fitted to evaluate the impact on short-term outcomes. Long-term outcome was investigated by survival analyses. Total of 1004 patients were included. There were no statistically significant differences between the cohorts in perioperative outcomes, although at 24 hours postoperatively, patients in DILT were more likely to be on hemodynamic support from inotropic and/or vasoactive agents. The overall long-term survival was similar between the cohorts; however, in the subgroup of patients who received more than one arterial graft, perioperative diltiazem may be associated with higher long-term all-cause mortality. Based on these data, the perioperative and long-term outcome benefits of continuous iv infusion of diltiazem in patients who underwent on-pump CABG.
In silico evaluation of the impact of the Omicron variant on the sensitivity of RT-qPCR assays for SARS-CoV-2 detection using whole genome sequencing
Authors: Sharma Divya , Ye Chengjin , Lippi Giusppe , Torrelles Jordi B. , Martinez-Sobrido Luis , Gromiha M. Michael , Henry Brandon Michael 
Published: January 2022

Abstract
Background

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VoC) Omicron (B.1.1.529) has rapidly spread around the world presenting a new threat to global public human health. Due to the large number of mutations possessed by Omicron, concerns have emerged over potentially reduced diagnostic accuracy of reverse transcription polymerase chain reaction (RT-qPCR), the gold standard diagnostic test for SARS-CoV-2. Here, we aimed to assess the impact of Omicron on the integrity and sensitivity of RT-qPCR assays used for coronavirus disease-2019 (COVID-19) diagnosis via in silico analysis employing whole genome sequencing data and evaluated the potential for false negatives or test failure due to mismatches between primers/probes and viral genome.
Methods

In silico sensitivity of 12 RT-qPCR tests (containing 30 primers and probe sets) developed for detection of SARS-CoV-2 reported by the World Health Organization (WHO) or available in the literature, was assessed for use in detecting SARS-CoV-2 Omicron BA.1 and BA.2 sublineages, obtained after removing redundancy from publicly available genomes from National Center for Biotechnology Information (NCBI) and Global Initiative on Sharing Avian Influenza Data (GISAID) databases. The mismatches between the amplicon regions of the SARS-CoV-2 Omicron VoC and primers and probe sets were evaluated, and the clustering analysis of the corresponding amplicon sequences was carried out.
Results

From the 232 representative SARS-CoV-2 BA.1 Omicron sublineage genomes analyzed, 229 showed substitutions at the forward primer annealing site for assay China-CDC N, 226 showed mismatches in the reverse primer annealing site for assay Thai N, and all 232 had substitution at the 3’ end of the reverse primer annealing site for assay HKUniv RdRp/Hel. Therefore, the lowest sensitivity was observed for assay ChinaCDC N, Thai N and HKUniv RdRp/Hel for SARS-CoV-2 BA.1 sublineage genomes. For 5 SARS-CoV-2 BA.2 Omicron sublineage genomes, false negative results were observed for assays ChinaCDC N, Thai N, HKUniv RdRp/Hel, SigmAldr S5, SigmAldr S6 and HKUniv S.
Conclusion

In this study, we observed three (25%) assays (ChinaCDC N, Thai N, and HKUniv RdRp/Hel) demonstrated potential for false negatives for the SARS-CoV-2 Omicron BA.1 sublineage, while four (33.3%) assays (ChinaCDC N, Thai N, HKUniv RdRp/Hel, HKUniv S, SigmAldr S5 and SigmAldr S6) demonstrated potential false negative results for the for SARS-CoV-2 Omicron BA.2 sublineage, which also has the potential for Spike (S) gene dropout despite lacking 69-70 deletion in the S gene. Further, amplicon clustering and additional substitutions analysis along with the sensitivity analysis could be used for modification and development of RT-qPCR assays for detection of SARS-CoV-2 Omicron VoC lineages.
Risks and Association of Impaired Cerebral Autoregulation With Outcomes in Aortic Arch Surgery: A Single-center, Retrospective Cohort Study
Authors: Peng Ling , Guo Dan , Shi Yinhui , Yang Jiapei , Wei Wei 
Published: January 2022

Abstract
BackgroundImpairment of cerebral autoregulation (CA) has been observed in patients undergoing cardiopulmonary bypass (CPB), but little is known about its risks and associations with outcomes. The objective of this study was to analyze the risks of impaired CA, based on cerebral oximetry index (COx), in patients undergoing total aortic arch replacement with CPB and moderate hypothermic circulatory arrest (MHCA). We also evaluated the association between impaired CA and patient outcomes.MethodsOne hundred fifteen four adult patients who underwent total aortic arch replacement with stented elephant trunk implantation under CPB and MHCA at our hospital were retrospectively analyzed. Patients were defined as having new-onset impaired CA if post-CPB COx > 0.3, calculated based on a moving linear correlation coefficient between regional cerebral oxygen saturation (rScO2) and mean blood pressure (MAP). Pre- and intraoperative factors were tested for independent association with impaired CA. Postoperative outcomes were compared between patients with normal and impaired CA.ResultsIn our 154 patients, 46(29.9%) developed new-onset impaired CA after CPB with MHCA. Multivariate analysis revealed a prolonged low rScO2 (rScO2 <55%) independently associated with onset of impaired CA, and receiver operating charactoristic curve showed a cutoff value at 40 min (sensitivity, 89.5%; specificity, 68.0%). Compared with normal CA patients, those with impaired CA showed a significantly higher rates of in-hospital mortality and postoperative complications.ConclusionProlonged low rScO2 (rScO2 <55%) during aortic arch surgery was closely related to onset of impaired CA. Impaired CA remained associated with the increased rates of postoperative complications and in-hospital mortality.Trial registration: ChiCTR1800014545 with registered date 20/01/2018.
Nomogram for Predicting Persistent Organ Failure with Acute Pancreatitis in Pregnancy
Authors: Sheng Chengcheng , Xu Zongxu , Wang Jun 
Published: January 2022

Abstract
Background: Acute pancreatitis in pregnancy (APIP) with persistent organ failure (POF) poses a high risk of death for mother and fetus. This study sought to create a nomogram model for early prediction of POF with APIP patients.Methods: We conducted a cross-sectional study on APIP patients with organ failure (OF) between January 2012 and March 2021 in a university hospital. 131 patients were collected. Their clinical courses and pregnancy outcomes were obtained. Risk factors for POF were identified by univariate and multivariate logistic regression analysis. Prediction models with POF were built and nomogram was plotted. The performance of the nomogram was evaluated by using a bootstrapped-concordance index and calibration plots.Results: Hypertriglyceridemia was the most common etiology in this group of APIP patients, which accounted for 50% of transient organ failure (TOF) and 72.3% of POF. All in-hospital maternal death was in the POF group (P<0.05), which also had a significantly higher perinatal mortality rate than the TOF group (P<0.05). Univariate and multivariate logistic regression analysis determined that lactate dehydrogenase, triglycerides, serum creatinine, and procalcitonin were independent risk factors for predicting POF in APIP. A nomogram for POF was created by using the four indicators. The area under the curve was 0.875 (95% confidence interval 0.80–0.95). The nomogram had a bootstrapped-concordance index of 0.85 and was well-calibrated.Conclusions: Hypertriglyceridemia was the leading cause of organ failure-related APIP. Lactate dehydrogenase, triglycerides, serum creatinine, and procalcitonin were the independent risk factors of POF in APIP. Our nomogram model showed an effective prediction of POF with the four indicators in APIP patients.
Effects of Anxiety, Depression, and Stress on Sleep Disorder and Night Eating Syndrome in Adolescents: Results of an Internet Survey
Authors: Gundogdu Ummugulsum 
Published: January 2022

Abstract
PurposeThe current study examined how sleep quality is related to night eating syndrome (NES) via the indirect effects of anxiety, depression, and stress to determine the mechanism of its development. MethodsThis cross-sectional web-based study included 171 adolescents aged 12-18 years (55.0% girls). Participants completed the self-report Night Eating Questionnaire (NEQ), Scales for Outcomes in Parkinson’s disease (SCOPA) Sleep Scale, and Depression, Anxiety and Stress Scale–21 items (DASS-21). ResultsThe results showed that anxiety, depression, and stress directly influenced the NEQ. AMOS path analysis was used to examine whether these also had an indirect influence on the NEQ. Moreover, for the anxiety, depression, and stress subscales, only the anxiety subscale influenced nighttime eating problems due to increased sleep problems, which in turn increased the difficulty of morning sleepiness and falling asleep at night. ConclusionConsequently, depression and stress directly increased nighttime eating problems. Anxiety exacerbates eating problems, both directly and indirectly, through sleep. Behavioral and psychological interventions to reduce anxiety, depression, and stress may be helpful strategies for the treatment of night eating syndrome.Level of evidence: Level IV
Sublethal exposure to an emulsion based on Pogostemon cablin (Lamiaceae) essential oil impairs digestibility, feeding, fecundity, and mobility of the coffee berry borer, Hypothenemus hampei
Authors: Santos Abraão Almeida , Farder-Gomes Cliver F. , Ribeiro Arthur V. , Costa Thiago L. , França Josélia Carvalho Oliveira , Bacci Leandro , Demuner Antônio Jacinto , Serrão José Eduardo , Picanço Marcelo Coutinho 
Published: January 2022

Abstract
The global search for eco-friendly and human-safe pesticides has intensified, and research on essential oils (EOs) has expanded due to their remarkable insecticidal activities and apparent human-safe. Despite this, most of the literature focuses on short-term and simplified efforts to understand lethal effects, with only a few comprehensive studies addressing sublethal exposures. To fill this shortcoming, we explore the lethal and sublethal effects of Pogostemon cablin (Lamiaceae) EO and an EO-based emulsion (18%) using the coffee berry borer Hypothenemus hampei Ferrari (Coleoptera: Curculionidae: Scolytinae) as a model. First, we determine the toxicity of EO and EO-based emulsion using dose-mortality curves and lethal times. Second, we subjected adult females of H. hampei to sublethal doses to assess whether they affected their behavior, reproductive output, and histological features. Our findings reveal that patchoulol (43.05%), α-Guaiene (16.06%), and α-Bulnesene (13.69%) were the main components of the EO. Furthermore, the EO and its emulsion had similar toxicity, with dose-mortality curves and lethal times overlapping 95% confidence intervals. We also observed that sublethal exposure of females of H. hampei reduces reproduction and feeding, increases walking activity, and causes histopathological changes in the midgut. This study advances the knowledge of sublethal effects of an eco-friendly substance on insects.
Prediction of pan-solid tumor pembrolizumab benefit by integrating tumor mutation and gene expression profiling
Authors: Khazanov Nickolay , Shreve Melissa , Lamb Laura , Hovelson Daniel , Matrana Marc , Burkard Mark , Yang Eddy , Edenfield William , Dees Claire , Onitilo Adedayo , Thompson Michael , Buchschacher Gary , Miller Alan , Menter Alexander , Parsons Benjamin , Wassenaar Timothy , Hwang Leon , Suga J. , Siegel Robert , Irvin William , Nair Suresh , Slim Jennifer , Kwiatkowski Kat , Mitchell Khalis , Hu-Seliger Tina , Drewery Stephanie , Fischer Andrew , Hipp Jennifer , Reeder Travis , Vakil Hana , Johnson Bryan , Rhodes Daniel , Tomlins Scott 
Published: January 2022

Abstract
Pembrolizumab is approved in many advanced solid tumor types, however predictive biomarkers and the proportion of pembrolizumab-benefiting patients vary. Biomarkers beyond PD-L1 immunohistochemistry, microsatellite instability (MSI) status, and tumor mutation burden (TMB) may improve benefit prediction. Here, leveraging treatment data (time to next treatment [TTNT]) and comprehensive genomic and quantitative transcriptomic profiling on routine tumor tissue from 708 patients (24 tumor types) collected in an ongoing observational trial (NCT03061305), we report a multivariate, integrative predictor of pan-solid tumor pembrolizumab benefit. The Immune Response Score (IRS) model, which includes TMB and quantitative PD-1, PD-L2, ADAM12 and CD4 RNA expression, was confirmed as predictive through comparison of pembrolizumab TTNT with previous chemotherapy TTNT in a subset of 166 patients treated with both. Applying IRS to the entire NCT03061305 cohort (n=25,770 patients), 13.2-30.7% of patients (2.2-9.6% of patients outside of pembrolizumab approved tumor types [including TMB-High and MSI-High]) are predicted to benefit substantially from pembrolizumab. Hence, if prospectively validated, the IRS model may improve pembrolizumab benefit prediction across approved tumor types including patients outside of currently approved indications.
Age- and sex-specific pediatric LMS-Percentiles for Laboratory Parameters enabled by Data mining
Authors: Hundhausen Thomas , Madsen Andre 
Published: January 2022

Abstract
Background:Various laboratory parameters routinely measured in pediatric practice covariate with sex and age. Conventional reference intervals are not suitable to account for this variation. Here we demonstrate construction of continuous LMS percentile curves from routine laboratory data. This allows adequate adjustment for both sex- and age-dependent covariation in childhood.Material and Methods:Anonymized routine blood test results requested by primary health care physicians were collected, outliers excluded and LMS-models generated in R.Results:Percentiles for several biomarkers derived from a regional population were established in the 'LMS' framework and provided here for comparison with etablished reference ranges, discussion and, potentially, clinical use.Conclusion: The reference framework 'LMS' is well-known from pediatric growth charts and can also be used in laboratory medicine.