bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colonization With Extensively Drug-Resistant Acinetobacter baumannii and Prognosis in Critically Ill Patients: An Observational Cohort Study
Authors: Zheng Yue , Xu Nana , Pang Jiaojiao , Han Hui , Yang Hongna , Qin Weidong , Zhang Hui , Li Wei , Wang Hao , Chen Yuguo 
Published: April 2021

Background:Acinetobacter baumannii is one of the most frequently isolated opportunistic pathogens in intensive care units (ICUs). Extensively drug-resistant A. baumannii (XDR-AB) strains lack susceptibility to almost all antibiotics and pose a heavy burden on healthcare institutions. In this study, we evaluated the impact of XDR-AB colonization on both the short-term and long-term survival of critically ill patients.Methods: We prospectively enrolled patients from two adult ICUs in Qilu Hospital of Shandong University from March 2018 through December 2018. Using nasopharyngeal and perirectal swabs, we evaluated the presence of XDR-AB colonization. Participants were followed up for 6 months. The primary endpoints were 28-day and 6-month mortality after ICU admission. The overall survival rate was estimated by the Kaplan-Meier method. We identified risk factors associated with 28-day and 6-month mortality using the logistic regression model and a time-dependent Cox regression model, respectively.Results: Out of 431 patients, 77 were colonized with XDR-AB. Based on the Kaplan-Meier curve results, the overall survival before 28 days did not differ by colonization status; however, a significantly lower overall survival rate was obtained at 6 months in colonized patients. Univariate and multivariate analysis results confirmed that XDR-AB colonization was not associated with 28-day mortality, but was an independent risk factor of lower overall survival at 6 months (HR = 1.749, 95% CI = 1.174–2.608).Conclusions: XDR-AB colonization has no effect on short-term overall survival, but is associated with lower long-term overall survival in critically ill patients.
A Multimodal Imaging Approach Demonstrates Reduced Midbrain Functional Network Connectivity Is Associated With Freezing of Gait in Parkinson's Disease
Authors: Droby Amgad , Pelosin Elisa , Putzolu Martina , Bommarito Giulia , Marchese Roberta , Mazzella Luca , Avanzino Laura , Inglese Matilde 
Published: April 2021

Background: The pathophysiological mechanisms underlying freezing of gait (FOG) are poorly defined. MRI studies in FOG showed a distinct pattern of cortical atrophy and decreased functional connectivity (FC) within motor and cognitive networks. Furthermore, reduced rs-FC within midbrain, frontal, and temporal areas has been also described. This study investigated the patterns of whole-brain FC alterations within midbrain inter-connected regions in PD-FOG patients, and whether these patterns are linked to midbrain structural damage using a multi-modal imaging approach, combing structural and functional imaging techniques.Methods: Thirty three PD patients (16 PD-FOG, 17 PD noFOG), and 21 sex- and age-matched healthy controls (HCs) were prospectively enrolled. All subjects underwent MRI scan at 1.5T, whereas only PD patients underwent clinical and cognitive assessment. Grey matter (GM) integrity was measured using voxel-based morphometry (VBM). VBM findings served as basis to localize midbrain damage, and were further used as a seed region for investigating whole-brain FC alterations using rs-fMRI.Results: In rs-fMRI, patients with PD and FOG demonstrated significant decrease of midbrain-cortical FC levels in the R PCG, right postcentral, and supramarginal gyri compared to controls and the middle cingulate compared to noFOG group. Based on the regression analysis, MOCA, UPDRS-III total score, and FOG severity scores were associated with FC levels in several frontal, parietal and temporal regions.Discussion: The present results suggest that midbrain structural damage as well as decreased FC within the brainstem functional network might contribute to FOG occurrence in PD patients.
Heat Treatment of Milk: A Rapid Review of the Impacts on Postprandial Protein and Lipid Kinetics in Human Adults
Authors: Fatih Mona , Barnett Matthew P. G. , Gillies Nicola A. , Milan Amber M. 
Published: April 2021

Background: Most milk consumed by humans undergoes heat treatment to ensure microbiological safety and extend shelf life. Although heat treatment impacts the structure and physiochemical properties of milk, effects on nutrient absorption in humans are unclear. Therefore, a rapid review was performed to identify studies conducted on healthy human adult subjects that have assessed the impacts of heat treatment of milk on protein and fat digestion and metabolism in the postprandial period (up to 24 h).Methods: Relevant databases (Medline, EMBASE, Cochrane, Scopus) were systematically screened for intervention studies on healthy adult men and women that assessed the impact of consuming heat-treated milk on the postprandial kinetics or appearance in peripheral circulation or urine of ingested proteins and/or lipids. The risk-of-bias assessment tool 2 was used for quality assessment.Results: Of 511 unique database records, 4 studies were included encompassing 6 study treatments (n = 57 participants, 20–68 years). Three studies evaluated pasteurization, two evaluated ultra-high temperature (UHT) treatment, and one evaluated oven-heated milk. Protein and lipid appearances in peripheral blood were reported in two sets of two studies. None of the studies used the same heat treatments and outcome measures, limiting generalization of effects. Protein appearance (ng/mL or area under the curve) (as plasma amino acids - lysine) was reduced when milk was oven-heated for 5 h in one study (n = 7 participants), while the other study reported a reduced retention of dietary N with UHT milk (n = 25 participants). Overall plasma triacylglycerol responses were unaffected by milk heat treatments reported, but plasma fatty acid composition differed. The studies observed higher plasma myristic and palmitic acid abundance with successive heat treatment at 2 h (n = 11 participants; pasteurized) and 4 h (n = 14 participants; UHT) after ingestion; other differences were inconsistent. All studies had moderate-high risk of bias, which should be taken into consideration when interpreting findings.Discussion: This review identified few studies reporting the effects of milk heat treatment on postprandial nutrient responses in adults. Although the findings suggest that milk heat treatment likely affects postprandial protein and lipid dynamics, generalization of the findings is limited as treatments, outcomes, and methods differed across studies. Because of the study variability, and the acute post-prandial nature of the studies, it is also difficult to draw conclusions regarding potential long-term health outcomes. However, the possibility that altered digestive kinetics may influence postprandial protein retention and anabolic use of dietary N suggests heat treatment of milk may impact outcomes such as long-term maintenance of muscle mass.
Radiation Recall Pneumonitis After Treatment With Checkpoint Blockade Immunotherapy: A Case Series and Review of Literature
Authors: Riviere Paul , Sumner Whitney , Cornell Mariel , Sandhu Ajay , Murphy James D. , Hattangadi-Gluth Jona , Bruggeman Andrew , Kim Sangwoo S. , Randall J. Michael , Sharabi Andrew B. 
Published: April 2021

BackgroundRadiation recall pneumonitis (RRP) is a poorly understood clinical syndrome in which patients develop radiation pneumonitis triggered by a systemic agent, often years after the completion of radiation therapy. Immune checkpoint blockade agents have only recently been posited as a trigger for RRP. Here, we present three cases of immunotherapy-induced RRP.Case PresentationOur first patient was diagnosed with primary lung adenocarcinoma, and 4.5 years after completing radiation therapy developed symptomatic RRP immediately following a second dose of nivolumab-containing immunotherapy regimen. Our second patient was diagnosed with primary bladder cancer metastatic to the mediastinum, which was treated twice with radiation therapy. He developed RRP in the days following his second course of ipilimumab-pembrolizumab which was months after his second course of radiation that he received. Our final patient was diagnosed with metastatic small cell lung cancer and received local consolidative radiation therapy in addition to whole-brain radiation. He developed RRP on the 11th day after concluding his 4th cycle of nivolumab-ipilimumab, approximately 7 months after having had completed chest radiation therapy.ConclusionsImmunotherapy-induced RRP is a rare diagnosis which can present more focally than traditional immunotherapy pneumonitis and which must be clinically differentiated from other local processes such as pneumonia. Further research should explore the mechanisms underlying these radiation recall reactions as many patients receive radiation and immunotherapy during the course of their cancer treatment.
Monitoring Treatment Efficacy of Antiangiogenic Therapy Combined With Hypoxia-Activated Prodrugs Online Using Functional MRI
Authors: Ma Mengjie , Liang Jianye , Zhang Dong , Xu Xi , Cheng Qingqing , Xiao Zeyu , Shi Changzheng , Luo Liangping 
Published: April 2021

ObjectiveThis study aimed to investigate the effectiveness of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) and blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in monitoring tumor responses to antiangiogenic therapy combined with hypoxia-activated prodrugs (HAPs).Materials and methodsEstablishing colon cancer xenograft model by subcutaneously injecting the HCT116 cell line into BALB/C nude mice. Twenty-four tumor-bearing mice were randomly divided into four groups and injected with bevacizumab combined with TH-302 (A), bevacizumab (B), TH-302 (C), or saline (D) on days 1, 4, 7, 10 and 13. Functional MRI was performed before and at 3, 6, 9, 12 and 15 days after treatment. Pathologic examinations, including HE staining, HIF-1α and CD31 immunohistochemical staining, and TUNEL and Ki-67 immunofluorescent staining, were performed after the last scan.ResultsAt the end of the study, Group A showed the lowest tumor volume, followed by Groups B, C, and D (F=120.652, P&lt;0.001). For pathologic examinations, Group A showed the lowest percentage of CD31 staining (F=73.211, P&lt;0.001) and Ki-67 staining (F=231.170, P&lt;0.001), as well as the highest percentage of TUNEL staining (F=74.012, P&lt;0.001). Moreover, the D* and f values exhibited positive correlations with CD31 (r=0.868, P&lt;0.001, and r=0.698, P=0.012, respectively). R2* values was positively correlated with HIF-1α (r=0.776, P=0.003). D values were positively correlated with TUNEL (r=0.737, P=0.006) and negatively correlated with Ki-67 (r=0.912, P&lt;0.001). The standard ADC values were positive correlated with TUNEL (r=0.672, P=0.017) and negative correlated with Ki-67 (r=0.873, P&lt;0.001).ConclusionAnti-angiogenic agents combined with HAP can inhibit tumor growth effectively. In addition, IVIM-DWI and BOLD-MRI can be used to monitor the tumor microenvironment, including perfusion, hypoxia, cell apoptosis and proliferation, in a noninvasive manner.
Investigation Into the Current Situation and Analysis of the Factors Influencing Extrauterine Growth Retardation in Preterm Infants
Authors: Zhao Ting , Feng Hui-Ming , Caicike Bayier , Zhu Yan-Ping 
Published: April 2021

Objective: This study aims to explore the occurrence of extrauterine growth retardation (EUGR) in preterm infants with a gestational age of &lt;34 weeks, at discharge, and the factors influencing the occurrence of EUGR.Method: A retrospective analysis of 691 preterm infants with a gestational age of less than 34 weeks, born in our hospital over the past 3 years. At discharge, the growth indicators head circumference, weight, and length were used to divide the infants into an EUGR group (n = 255) and the non-EUGR group (n = 436). The occurrence of EUGR and its influencing factors were then analyzed.Results: Of the 691 preterm infants evaluated for inclusion in the study, 255 cases (36.9%) met the requirements of EUGR at discharge. The different growth indicators used, i.e., weight, length, and head circumference, classified the infants differently. The incidence of EUGR using these measures was 30.2% (209), 27.9% (193), and 23.2% (161), respectively. The results of a univariate analysis showed that gestational age, birth weight, intrauterine growth retardation (IUGR), maternal gestational hypertension, age at which the infant commenced feeding, duration of the application of an invasive ventilator, length of hospital stay, nosocomial infection, respiratory and gastrointestinal diseases, symptomatic patent ductus arteriosus, and the early onset of neonatal sepsis were correlated with the occurrence of EUGR. Further logistic multivariate regression analysis revealed that low gestational age, low birth weight, complicated IUGR, respiratory distress syndrome, and necrotizing enterocolitis were independent risk factors for EUGR in preterm infants with a gestational age &lt;34 weeks.Conclusion: In preterm infants with a gestational age &lt;34 weeks in our hospital, there is a high incidence of EUGR, which is affected by factors such as the gestational age, birth weight, IUGR, respiratory distress syndrome, necrotizing enterocolitis, and other factors.
Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation–A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU): Study Protocol and Analysis Plan
Authors: Schlapbach Luregn J. , Gibbons Kristen , Ridolfi Roberta , Harley Amanda , Cree Michele , Long Debbie , Buckley David , Erickson Simon , Festa Marino , George Shane , King Megan , Singh Puneet , Raman Sainath , Bellomo Rinaldo ,   The RESPOND PICU study investigators and the Australian New Zealand Intensive Care Society Paediatric Study Group (ANZICS PSG)
Published: April 2021

Introduction: Septic shock remains amongst the leading causes of childhood mortality. Therapeutic options to support children with septic shock refractory to initial resuscitation with fluids and inotropes are limited. Recently, the combination of intravenous hydrocortisone with high dose ascorbic acid and thiamine (HAT therapy), postulated to reduce sepsis-related organ dysfunction, has been proposed as a safe approach with potential for mortality benefit, but randomized trials in paediatric patients are lacking. We hypothesize that protocolised early use of HAT therapy (“metabolic resuscitation”) in children with septic shock is feasible and will lead to earlier resolution of organ dysfunction. Here, we describe the protocol of the Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation–A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU).Methods and Analysis: The RESPOND PICU study is an open label randomized-controlled, two-sided multicentre pilot study conducted in paediatric intensive care units (PICUs) in Australia and New Zealand. Sixty children aged between 28 days and 18 years treated with inotropes for presumed septic shock will be randomized in a 1:1 ratio to either metabolic resuscitation (1 mg/kg hydrocortisone q6h, 30 mg/kg ascorbic acid q6h, 4 mg/kg thiamine q12h) or standard septic shock management. Main outcomes include feasibility of the study protocol and survival free of organ dysfunction censored at 28 days. The study cohort will be followed up at 28-days and 6-months post enrolment to assess neurodevelopment, quality of life and functional status. Biobanking will allow ancillary studies on sepsis biomarkers.Ethics and Dissemination: The study received ethical clearance from Children's Health Queensland Human Research Ethics Committee (HREC/18/QCHQ/49168) and commenced enrolment on June 12th, 2019. The primary study findings will be submitted for publication in a peer-reviewed journal.Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12619000829112). Protocol Version: V1.8 22/7/20.
Effects of Three Different Doses of Dexmedetomidine and Ropivacaine on Analgesia and the Stress Response in Hypospadias Surgery: A Randomized Trial
Authors: Wang Yuan , Jia Ying-Ping , Zhao Li-Yuan , He Qiu-Juan , Qi Jin-Lian , Zhou Rui , Yang Ting , Zhao Zeng-Xiao , Wei Hao-Quan 
Published: April 2021

Objective: This study was designed to investigate the effects of three different doses of dexmedetomidine in caudal blocks on postoperative stress and pain after pediatric urethroplasty.Methods: A total of 160 children who underwent elective urethroplasty were enrolled in this study. They were randomly divided into four groups: groups D1, D2, and D3, in which the patients were injected respectively with a mixed solution of 1, 1.5, or 2 μg kg−1 of dexmedetomidine and 0.25% ropivacaine into the sacral canal; and group R, in which the patients were injected with 0.25% ropivacaine into the sacral canal. Cortisol and interleukin-6 (IL-6) levels within 24 h, the incidence of adverse events in the circulatory system during surgery, onset time of the caudal block, duration of postoperative analgesia, the incidence of agitation during recovery, and other anesthetic adverse reactions were observed and recorded.Results: Compared with group R, cortisol and IL-6 levels in groups D1, D2, and D3 decreased within 24 h after the operation (T2–T6). The incidence of intraoperative hypertension, tachycardia, and shivering during the recovery period decreased, the onset time of the caudal block decreased, and the duration of postoperative analgesia increased (p &lt; 0.01). Compared with group D1, the duration of postoperative analgesia increased in groups D2 and D3 (p &lt; 0.01). Compared with groups D1 and D2, the incidence of excessive sedation and bradycardia in group D3 increased (p &lt; 0.05).Conclusion: The administration of 1.5 μg kg−1 of dexmedetomidine appears to be most feasible in accelerating the onset of the caudal block, reducing stress and inflammation, stabilizing the circulation, increasing the duration of postoperative analgesia, and reducing anesthesia- and operation-associated adverse events.
How Aconiti Radix Cocta can Treat Gouty Arthritis Based on Systematic Pharmacology and UPLC-QTOF-MS/MS
Authors: Ye Xietao , Wu Jianxiong , Zhang Dayong , Lan Zelun , Yang Songhong , Zhu Jing , Yang Ming , Gong Qianfeng , Zhong Lingyun 
Published: April 2021

Background: Gouty arthritis (GA) is a common metabolic disease caused by a long-term disorder of purine metabolism and increased serum levels of uric acid. The processed product of dried root of Aconitum carmichaeli Debeaux (Aconiti Radix cocta, ARC) is used often in traditional Chinese medicine (TCM) to treat GA, but its specific active components and mechanism of action are not clear.Methods: First, we used ultra-performance liquid chromatography-quadrupole/time-of-flight tandem mass spectrometry to identify the chemical spectrum of ARC. Based on this result, we explored the active components of ARC in GA treatment and their potential targets and pathways. Simultaneously, we used computer simulations, in vitro cell experiments and animal experiments to verify the prediction results of systems pharmacology. In vitro, we used aurantiamide acetate (AA) to treat monosodium urate (MSU)-stimulated THP-1 cells and demonstrated the reliability of the prediction by western blotting and real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). ELISAs kit were used to measure changes in levels of proinflammatory factors in rats with GA induced by MSU to demonstrate the efficacy of ARC in GA treatment.Results: Forty-three chemical constituents in ARC were identified. ARC could regulate 65 targets through 29 active components, and then treat GA, which involved 1427 Gene Ontology (GO) terms and 146 signaling pathways. Signaling pathways such as proteoglycans in cancer, C-type lectin receptor signaling pathway, and TNF signaling pathway may have an important role in GA treatment with ARC. In silico results showed that the active components songoramine and ignavine had high binding to mitogen-activated protein kinase p38 alpha (MAPK14) and matrix metallopeptidase (MMP)9, indicating that ARC treatment of GA was through multiple components and multiple targets. In vitro experiments showed that AA in ARC could effectively reduce expression of MAPK14, MMP9, and cyclooxygenase2 (PTGS2) in THP-1 cells stimulated by MSU, whereas it could significantly inhibit the mRNA expression of Caspase-1, spleen tyrosine kinase (SYK), and PTGS2. Animal experiments showed that a ARC aqueous extract could significantly reduce expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and intereleukin (IL)-18 in the serum of GA rats stimulated by MSU. Hence, ARC may inhibit inflammation by regulating the proteoglycans in cancer-associated signaling pathways.Conclusion: ARC treatment of GA may have the following mechanisms, ARC can reduce MSU crystal-induced joint swelling, reduce synovial tissue damage, and reduce the expression of inflammatory factors in serum. AA in ARC may inhibit inflammation by regulating the protein expression of MAPK14, MMP9, and PTGS2 and the mRNA expression of caspase-1, SYK, and PTGS2.
Endoplasmic Reticulum Adaptation and Autophagic Competence Shape Response to Fluid Shear Stress in T24 Bladder Cancer Cells
Authors: Del Favero Giorgia , Zeugswetter Michael , Kiss Endre , Marko Doris 
Published: April 2021

Accumulation of xenobiotics and waste metabolites in the urinary bladder is constantly accompanied by shear stress originating from the movement of the luminal fluids. Hence, both chemical and physical cues constantly modulate the cellular response in health and disease. In line, bladder cells have to maintain elevated mechanosensory competence together with chemical stress response adaptation potential. However, much of the molecular mechanisms sustaining this plasticity is currently unknown. Taking this as a starting point, we investigated the response of T24 urinary bladder cancer cells to shear stress comparing morphology to functional performance. T24 cells responded to the shear stress protocol (flow speed of 0.03 ml/min, 3 h) by significantly increasing their surface area. When exposed to deoxynivalenol-3-sulfate (DON-3-Sulf), bladder cells increased this response in a concentration-dependent manner (0.1–1 µM). DON-3-Sulf is a urinary metabolite of a very common food contaminant mycotoxin (deoxynivalenol, DON) and was already described to enhance proliferation of cancer cells. Incubation with DON-3-Sulf also caused the enlargement of the endoplasmic reticulum (ER), decreased the lysosomal movement, and increased the formation of actin stress fibers. Similar remodeling of the endoplasmic reticulum and area spread after shear stress were observed upon incubation with the autophagy activator rapamycin (1–100 nM). Performance of experiments in the presence of chloroquine (chloroquine, 30 μM) further contributed to shed light on the mechanistic link between adaptation to the biomechanical stimulation and ER stress response. At the molecular level, we observed that ER reshaping was linked to actin organization, with the two components mutually regulating each other. Indeed, we identified in the ER stress–cytoskeletal rearrangement an important axis defining the physical/chemical response potential of bladder cells and created a workflow for further investigation of urinary metabolites, food constituents, and contaminants, as well as for pharmacological profiling.