bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Specifically Designed Injector for Controlled Lube Oil Addition in View of Investigation of Pre-Ignition Phenomena in Dual–Fuel/Gas Engines
Authors: Süess Pascal , Schneider Bruno , Wüthrich Dario , Wüthrich Silas , Herrmann Kai 
Published: May 2021

Internal combustion engines will continue to play a role during a transitional phase, especially in heavy-duty or marine applications. In this context, lean-burn gas/dual-fuel combustion is an attractive concept to reduce CO2, combined with considerably lower particulate and NOX pollution, and with efficiencies comparable to diesel combustion. However, ignition processes still pose considerable challenges, with pre-ignition in particular being a major issue. The underlying mechanisms are probably based on self-ignition of lube oil in hot zones. In order to investigate fundamentals of such phenomena in optically accessible test rigs, a novel injector was specifically developed to induce pre-ignitions artificially. The so-called “PieZo-Droplet-Injector” (PZDI) enables dosing of minor amounts of lubricating oil or even the injection of single droplets with diameters in the range of 100–200 µm. The working principle relies on a needle actuated with a piezo stack, which pushes a certain amount of lube oil in a bore so that (even single) droplets can be ejected through an adjustable nozzle. To confirm the PZDI functionality and to investigate droplet characteristics based on adjustable operating parameters, tests were performed under ambient conditions as well as in a constant volume combustion chamber under reasonable pressure and temperature conditions. Overall, the PZDI showed an excellent behavior in terms of capabilities to inject small amounts or even single droplets of lube oil. At last, this specially developed injector allows selective lube oil addition in an optically accessible engine test facility for upcoming examination of pre-ignition phenomena under real operating conditions.
Effects of Normoxia, Hyperoxia, and Mild Hypoxia on Macro-Hemodynamics and the Skeletal Muscle Microcirculation in Anesthetised Rats
Authors: Damiani Elisa , Casarotta Erika , Orlando Fiorenza , Carsetti Andrea , Scorcella Claudia , Domizi Roberta , Adrario Erica , Ciucani Silvia , Provinciali Mauro , Donati Abele 
Published: May 2021

Objectives: Excessive oxygen (O2) administration may have a negative impact on tissue perfusion by inducing vasoconstriction and oxidative stress. We aimed to evaluate the effects of different inhaled oxygen fractions (FiO2) on macro-hemodynamics and microvascular perfusion in a rat model.Methods: Isoflurane-anesthetised spontaneously breathing male Wistar rats were equipped with arterial (carotid artery) and venous (jugular vein) catheters and tracheotomy, and randomized into three groups: normoxia (FiO2 21%, n = 6), hyperoxia (FiO2 100%, n = 6) and mild hypoxia (FiO2 15%, n = 6). Euvolemia was maintained by infusing Lactate Ringer solution at 10 ml/kg/h. At hourly intervals for 4 h we collected measurements of: mean arterial pressure (MAP); stroke volume index (SVI), heart rate (HR), respiratory rate (by means of echocardiography); arterial and venous blood gases; microvascular density, and flow quality (by means of sidestream dark field videomicroscopy on the hindlimb skeletal muscle).Results: MAP and systemic vascular resistance index increased with hyperoxia and decreased with mild hypoxia (p &lt; 0.001 in both cases, two-way analysis of variance). Hyperoxia induced a reduction in SVI, while this was increased in mild hypoxia (p = 0.002). The HR increased under hyperoxia (p &lt; 0.05 vs. normoxia at 3 h). Cardiax index, as well as systemic O2 delivery, did not significantly vary in the three groups (p = 0.546 and p = 0.691, respectively). At 4 h, microvascular vessel surface (i.e., the percentage of tissue surface occupied by vessels) decreased by 29 ± 4% in the hyperoxia group and increased by 19 ± 7 % in mild hypoxia group (p &lt; 0.001). Total vessel density and perfused vessel density showed similar tendencies (p = 0.003 and p = 0.005, respectively). Parameters of flow quality (microvascular flow index, percentage of perfused vessels, and flow heterogeneity index) remained stable and similar in the three groups.Conclusions: Hyperoxia induces vasoconstriction and reduction in skeletal muscle microvascular density, while mild hypoxia has an opposite effect.
Risk Score for Predicting Dysphagia in Patients After Neurosurgery: A Prospective Observational Trial
Authors: Zeng Li , Song Yu , Dong Yan , Wu Qian , Zhang Lu , Yu Lei , Gao Liang , Shi Yan 
Published: May 2021

Background: Acquired dysphagia is common in patients with tracheal intubation and neurological disease, leading to increased mortality. This study aimed to ascertain the risk factors and develop a prediction model for acquired dysphagia in patients after neurosurgery.Methods: A multicenter prospective observational study was performed on 293 patients who underwent neurosurgery. A standardized swallowing assessment was performed bedside within 24 h of extubation, and logistic regression analysis with a best subset selection strategy was performed to select predictors. A nomogram model was then established and verified.Results: The incidence of acquired dysphagia in our study was 23.2% (68/293). Among the variables, days of neurointensive care unit (NICU) stay [odds ratio (OR), 1.433; 95% confidence interval (CI), 1.141–1.882; P = 0.005], tracheal intubation duration (OR, 1.021; CI, 1.001–1.062; P = 0.175), use of a nasogastric feeding tube (OR, 9.131; CI, 1.364–62.289; P = 0.021), and Acute Physiology and Chronic Health Evaluation (APACHE)-II C score (OR, 1.709; CI, 1.421–2.148; P &lt; 0.001) were selected as risk predictors for dysphagia and included in the nomogram model. The area under the receiver operating characteristic curve was 0.980 (CI, 0.965–0.996) in the training set and 0.971 (0.937–1) in the validation set, with Brier scores of 0.045 and 0.056, respectively.Conclusion: Patients who stay longer in the NICU, have a longer duration of tracheal intubation, require a nasogastric feeding tube, and have higher APACHE-II C scores after neurosurgery are likely to develop dysphagia. This developed model is a convenient and efficient tool for predicting the development of dysphagia.
Benchmarking the Extent and Speed of Reperfusion: First Pass TICI 2c-3 Is a Preferred Endovascular Reperfusion Endpoint
Authors: Yoo Albert J. , Soomro Jazba , Andersson Tommy , Saver Jeffrey L. , Ribo Marc , Bozorgchami Hormozd , Dabus Guilherme , Liebeskind David S. , Jadhav Ashutosh , Mattle Heinrich , Zaidat Osama O. 
Published: May 2021

Background and Purpose: End-of-procedure substantial reperfusion [modified Treatment in Cerebral Ischemia (mTICI) 2b-3], the leading endpoint for thrombectomy studies, has several limitations including a ceiling effect, with recent achieved rates of ~90%. We aimed to identify a more optimal definition of angiographic success along two dimensions: (1) the extent of tissue reperfusion, and (2) the speed of revascularization.Methods: Core-lab adjudicated TICI scores for the first three passes of EmboTrap and the final all-procedures result were analyzed in the ARISE II multicenter study. The clinical impact of extent of reperfusion and speed of reperfusion (first-pass vs. later-pass) were evaluated. Clinical outcomes included 90-day functional independence [modified Rankin Scale (mRS) 0–2], 90-day freedom-from-disability (mRS 0–1), and dramatic early improvement [24-h National Institutes of Health Stroke Scale (NIHSS) improvement ≥ 8 points].Results: Among 161 ARISE II subjects with ICA or MCA M1 occlusions, reperfusion results at procedure end showed substantial reperfusion in 149 (92.5%), excellent reperfusion in 121 (75.2%), and complete reperfusion in 79 (49.1%). Reperfusion rates on first pass were substantial in 81 (50.3%), excellent reperfusion in 62 (38.5%), and complete reperfusion in 44 (27.3%). First-pass excellent reperfusion (first-pass TICI 2c-3) had the greatest nominal predictive value for 90-day mRS 0–2 (sensitivity 58.5%, specificity 68.6%). There was a progressive worsening of outcomes with each additional pass required to achieve TICI 2c-3.Conclusions: First-pass excellent reperfusion (TICI 2c-3), reflecting rapid achievement of extensive reperfusion, is the technical revascularization endpoint that best predicted functional independence in this international multicenter trial and is an attractive candidate for a lead angiographic endpoint for future trials.Clinical Trial Registration:http://www.clinicaltrials.gov, identifier NCT02488915.
Lactobacillus acidophilus ATCC 4356 Alleviates Renal Ischemia–Reperfusion Injury Through Antioxidant Stress and Anti-inflammatory Responses and Improves Intestinal Microbial Distribution
Authors: Zhang Peng , Han Xiuwu , Zhang Xin , Zhu Xuhui 
Published: May 2021

Background: Ischemia–reperfusion injury (IRI) is one of the main causes of acute kidney injury. Our previous results have shown that anti-oxidative stress decreased in the renal IRI model. This study aimed to investigate the effect of Lactobacillus acidophilus ATCC 4356 on oxidative stress, inflammation, and intestinal flora in renal IRI.Methods: The model of renal IRI was established by cross-clamping the renal pedicle with non-traumatic vascular forceps. H&amp;E staining was applied to observe the damage of kidney tissue in each group. The concentrations of serum blood urea nitrogen (BUN), creatinine (Cre), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) were detected by biochemical kit. ELISA measured the concentrations of interleukin (IL)-1β, IL-8, IL-4, and IL-10. qRT-PCR was performed to detect molecular expressions of ATCC 4356, oxidative stress-related factors [nuclear factor-related factor 2 (Nrf2), heme oxygenase 1 (HO-1)], inflammatory factors [tumor necrosis factor (TNF)-α, IL-1β, IL-8, interferon (IFN)-γ, IL-4, IL-10], and apoptosis-related factors [caspase 3, Bax, Bcl2, high-mobility group box protein 1 (HMGB1)]. Except for ATCC 4356, the protein expression of the above indicators was detected by Western blot. The apoptosis level of renal tissue cells was detected by TdT-mediated dUTP nick end labeling (TUNEL). 16S rDNA gene sequencing was used to detect the changes of microbial species in the contents of the duodenum and screen out the differentially expressed flora.Results: Both the glomeruli and renal tubules of ischemia/reperfusion (I/R) mice were severely damaged. H&amp;E result displayed that L. acidophilus ATCC 4356 attenuated the infiltration of inflammatory cells caused by I/R. ATCC 4356 reduced the high expression of BUN and Cre in I/R mice with a dose effect. It also reduced the high expression of MDA, TNF-α, IL-1β, IL-8, IFN-γ, caspase 3, Bax, and HMGB1 in I/R mice, while it increased the low expression of SOD, GSH, Nrf2, HO-1, IL-4, IL-10, and Bcl2 in I/R mice. ATCC 4356 inhibited the high level of apoptosis in the kidney tissue of I/R mice. In IRI mice, the top 3 different gut microbiota were Helicobacter, cultivated_bacterium, and k__Bacteria_ASV_3 compared with sham mice. Oral L. acidophilus ATCC 4356 reversed this change.Conclusion:L. acidophilus ATCC 4356 attenuated renal IRI through anti-oxidative stress and anti-inflammatory response and improved the intestinal microbial distribution.
Treatment-Related Serious Adverse Events of Immune Checkpoint Inhibitors in Clinical Trials: A Systematic Review
Authors: Ouyang Tao , Cao Yanyan , Kan Xuefeng , Chen Lei , Ren Yanqiao , Sun Tao , Yan Liangliang , Xiong Bin , Liang Bin , Zheng Chuansheng 
Published: May 2021

BackgroundImmune Checkpoint Inhibitors (ICI) have been progressively used in cancer treatment and produced unique toxicity profiles. This systematic review aims to comprehend the patterns and occurrence of treatment-related adverse events (trAEs) based on ICI.MethodsPICOS/PRISMA methods were used to identify published English-language on PubMed, Web of Science, and Scopus from 2015 to 2020. Published clinical trials on ICI monotherapy, combined ICIs, and ICI plus other treatment with tabulated data on grade≥3 trAEs were included. Odds ratio (OR), χ2 tests were used to analyze for effect size and associations.ResultsThis review included 145 clinical trials involving 21786 patients. Grade 3-5 trAEs were more common with ICI when they were plused with other treatments compared with ICI monotherapy(54.3% versus 17.7%, 46.1%, p&lt;0.05). Grade 3-5 trAEs were also more common with CTLA-4 mAbs compared with anti-PD-1 and anti-PD-L1 (34.2% versus 15.1%, 13.6%, p&lt;0.05). Hyperthyroidism (OR 3.8, 95%CI 1.7–8.6), nausea (OR 3.7, 95%CI 2.5–5.3), diarrhea (OR 2.7, 95%CI 2.2–3.2), colitis (OR 3.4, 95%CI 2.7–4.3), ALT increase (OR 4.9, 95%CI 3.9–6.1), AST increase (OR 3.8, 95%CI 3.0–4.9), pruritus (OR 2.4, 95%CI 1.5–3.9), rash (OR 2.8, 95%CI 2.1–3.8), fatigue (OR 2.8, 95%CI 2.2–3.7), decreased appetite (OR 2.4, 95%CI 1.5–3.8), and hypophysitis (OR 2.0, 95%CI 1.2–3.3) were more frequent with combined ICIs. Diarrhea (OR 8.1, 95%CI 6.4–10.3), colitis (OR 12.2, 95%CI 8.7–17.1), ALT increase (OR 5.1, 95%CI 3.5–7.4), AST increase (OR 4.2, 95%CI 2.8–6.3), pruritus (OR 4.1, 95%CI 2.0–8.4), rash (OR 4.4, 95%CI 2.9–6.8), hypophysitis (OR 12.1, 95%CI 6.3–23.4) were more common with CTLA-4 mAbs; whereas pneumonitis (OR 4.7, 95% CI 2.1–10.3) were more frequent with PD-1 mAbs.ConclusionsDifferent immune checkpoint inhibitors are associated with different treatment-related adverse events profiles. A comprehensive data in this systematic review will provide comprehensive information for clinicians.
Using Population-Based Cancer Registration Data and Period Analysis to Accurately Assess and Predict 5-Year Relative Survival for Lung Cancer Patients in Eastern China
Authors: Li Runhua , Zhang Min , Cheng Yongran , Jiang Xiyi , Tang Huijuan , Wang Liangyou , Chen Tianhui , Chen Bicheng 
Published: May 2021

BackgroundThe assessment of long-term survival of lung cancer patients based on data from population-based caner registries, using period analysis, was scarce in China. We aimed to accurately assess the long-term survival of lung cancer patients, and to predict the long-term survival in the future, using cancer registry data from Taizhou City, eastern China.MethodsFour cancer registries with high-quality data were selected. Patients diagnosed with lung cancer during 2004–2018 were included. The long-term survival was evaluated using period analysis, with further stratification by sex, age at diagnosis and region. Additionally, projected 5-year relative survival (RS) of lung cancer patients for 2019-2023 was evaluated, using model-based period analysis.ResultsThe 5-year RS of lung cancer patients diagnosed during 2014–2018 was 40.2% (31.5% for men and 56.2% for women). A moderate age gradient was observed for the period estimate, with the estimate decreasing from 50.5 to 26.5% in the age group of 15–44 years and ≥75 years, respectively. The 5-year RS of urban area was higher than that of rural area (52.3% vs. 38.9%). The overall projected 5-year RS of lung cancer patients was 52.7% for 2019–2023, with estimate of 43.0 and 73.2% for men and women, respectively. A moderate age gradient was also observed for the projected estimate. Moreover, estimate reached nearly 50% for rural and urban areas.ConclusionPeriod analysis tended to provide the up-to-date and precise survival estimates for lung cancer patients, which is worth further application, and provides important evidence for prevention and intervention of lung cancer.
Complete Remission of Advanced Adrenocortical Cancer Following Mitotane Monotherapy: A Case Report and Literature Review of Predictive Markers
Authors: Tőke Judit , Jakab Zsuzsanna , Stark Júlia , Huszty Gergely , Reismann Péter , Tóth Miklós 
Published: May 2021

Mitotane has been used for the treatment of adrenocortical cancer (ACC) for over 50 years. Despite its widespread use both in monotherapy and in combination with chemotherapeutics, our knowledge of its mechanism of action and therapeutic efficacy is scarce. The number of patients with advanced ACC who have achieved complete remission documented by detailed clinical data is below ten. We report a case of a 64-year-old woman with a non-functional ACC. Histological examination showed vascular invasion, Ki67 of 10% and a mitotic count of 3/10 high-power field. Immunohistochemistry revealed p53 positivity. Pathological TNM grade was reported as T2N0M0, ENSAT stage 2. Nine months after the initial diagnosis, re-staging CT revealed multiple peritoneal nodules, lymph node and kidney metastases confirmed by histologic examination. Mitotane monotherapy was started with a maintenance dose between 2.0 and 2.5 grams/day. Partial remission was established at six months. Subsequently, for another 12 months, each of the three-monthly CT scans confirmed complete remission. Nineteen months after the initiation of mitotane, an unexpected sudden death occurred. A detailed autopsy work-up, performed in the full awareness of oncological history, confirmed complete remission. The authors review the molecular biomarkers and clinical features reported as predictors of response to mitotane monotherapy.
The Clinical and Imaging Characteristics Associated With Neurological Sequelae of Pediatric Patients With Acute Necrotizing Encephalopathy
Authors: Zhu Hong-Min , Zhang Si-Min , Yao Cong , Luo Meng-Qing , Ma Hui-Jing , Lei Tao , Yuan Chun-Hui , Wu Ge-Fei , Hu Jia-Sheng , Cai Chun-Quan , Liu Zhi-Sheng 
Published: May 2021

Background: Acute necrotizing encephalopathy of childhood (ANE) is a rare but rapidly progressing encephalopathy. Importantly, the exact pathogenesis and evidence-based treatment is scarce. Thus, we aimed to identify the clinical, imaging, and therapeutic characteristics that associated with prognosis of pediatric ANE patients.Methods: A retrospective study was conducted on pediatric patients with ANE who were admitted to Wuhan Children's Hospital between January 2014 and September 2019. All cases met the diagnostic criteria for ANE proposed by Mizuguchi in 1997. The clinical information and follow-up data were collected. The prognostic factors were analyzed by trend chi-square test and Goodman–Kruskal gamma test.Results: A total of 41 ANE patients ranging in age from 8.9 to 142 months were included in this study. Seven cases (17%) died, and the other 34 survivors had different degrees of neurological sequelae. Factors tested to be significantly correlated with the severity of neurological sequelae were the intervals from prodromal infection to acute encephalopathy (G = −0.553), conscious disturbance (r = 0.58), endotracheal intubation (r = 0.423), elevation of alanine aminotransferase (r = 0.345), aspartate aminotransferase (r = 0.393), and cerebrospinal fluid protein (r = 0.490). In addition, dynamic magnetic resonance imaging (MRI) evaluation on follow-up revealed that the total numbers of brain lesion location (χ2 = 6.29, P &lt; 0.05), hemorrhage (r = 0.580), cavitation (r = 0.410), and atrophy (r = 0.602) status were significantly correlated with the severity of neurological sequelae, while early steroid therapy (r = −0.127 and 0.212, respectively) and intravenous immunoglobulin (IVIG) (r = 0.111 and −0.023, respectively) within 24 h or within 72 h after onset showed no association.Conclusions: Intervals from prodromal infection to acute encephalopathy (≤1 day), total numbers of brain lesion location (≥3), the recovery duration of hemorrhage and atrophy (&gt;3 months), and the presence of cavitation predict severe neurological sequelae in pediatric patients with ANE. Early treatments, including steroid therapy and IVIG, had no correlation with better outcomes. Further studies are needed to establish a consensus guideline for the management of ANE.
Derivation of a Human In Vivo Benchmark Dose for Perfluorooctanoic Acid From ToxCast In Vitro Concentration–Response Data Using a Computational Workflow for Probabilistic Quantitative In Vitro to In Vivo Extrapolation
Authors: Loizou George , McNally Kevin , Dorne Jean-Lou C. M. , Hogg Alex 
Published: May 2021

A computational workflow which integrates physiologically based kinetic (PBK) modeling, global sensitivity analysis (GSA), approximate Bayesian computation (ABC), and Markov Chain Monte Carlo (MCMC) simulation was developed to facilitate quantitative in vitro to in vivo extrapolation (QIVIVE). The workflow accounts for parameter and model uncertainty within a computationally efficient framework. The workflow was tested using a human PBK model for perfluorooctanoic acid (PFOA) and high throughput screening (HTS) in vitro concentration–response data, determined in a human liver cell line, from the ToxCast/Tox21 database. In vivo benchmark doses (BMDs) for PFOA intake (ng/kg BW/day) and drinking water exposure concentrations (µg/L) were calculated from the in vivo dose responses and compared to intake values derived by the European Food Safety Authority (EFSA). The intake benchmark dose lower confidence limit (BMDL5) of 0.82 was similar to 0.86 ng/kg BW/day for altered serum cholesterol levels derived by EFSA, whereas the intake BMDL5 of 6.88 was six-fold higher than the value of 1.14 ng/kg BW/day for altered antibody titer also derived by the EFSA. Application of a chemical-specific adjustment factor (CSAF) of 1.4, allowing for inter-individual variability in kinetics, based on biological half-life, gave an intake BMDL5 of 0.59 for serum cholesterol and 4.91 (ng/kg BW/day), for decreased antibody titer, which were 0.69 and 4.31 the EFSA-derived values, respectively. The corresponding BMDL5 for drinking water concentrations, for estrogen receptor binding activation associated with breast cancer, pregnane X receptor binding associated with altered serum cholesterol levels, thyroid hormone receptor α binding leading to thyroid disease, and decreased antibody titer (pro-inflammation from cytokines) were 0.883, 0.139, 0.086, and 0.295 ng/ml, respectively, with application of no uncertainty factors. These concentrations are 5.7-, 36-, 58.5-, and 16.9-fold lower than the median measured drinking water level for the general US population which is approximately, 5 ng/ml.