bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory Dendritic Cells, T Cell Tolerance, and Dendritic Cell Therapy for Immunologic Disease
Authors: Ness Sara , Lin Shiming , Gordon John R. 
Published: March 2021

Dendritic cells (DC) are antigen-presenting cells that can communicate with T cells both directly and indirectly, regulating our adaptive immune responses against environmental and self-antigens. Under some microenvironmental conditions DC develop into anti-inflammatory cells which can induce immunologic tolerance. A substantial body of literature has confirmed that in such settings regulatory DC (DCreg) induce T cell tolerance by suppression of effector T cells as well as by induction of regulatory T cells (Treg). Many in vitro studies have been undertaken with human DCreg which, as a surrogate marker of antigen-specific tolerogenic potential, only poorly activate allogeneic T cell responses. Fewer studies have addressed the abilities of, or mechanisms by which these human DCreg suppress autologous effector T cell responses and induce infectious tolerance-promoting Treg responses. Moreover, the agents and properties that render DC as tolerogenic are many and varied, as are the cells’ relative regulatory activities and mechanisms of action. Herein we review the most current human and, where gaps exist, murine DCreg literature that addresses the cellular and molecular biology of these cells. We also address the clinical relevance of human DCreg, highlighting the outcomes of pre-clinical mouse and non-human primate studies and early phase clinical trials that have been undertaken, as well as the impact of innate immune receptors and symbiotic microbial signaling on the immunobiology of DCreg.
The Effects of Corticosteroids on the Respiratory Microbiome: A Systematic Review
Authors: Hartmann Julia E. , Albrich Werner C. , Dmitrijeva Marija , Kahlert Christian R. 
Published: March 2021

Background: Since its discovery, the respiratory microbiome has been implicated in the pathogenesis of multiple pulmonary diseases. Even though corticosteroid treatments are widely prescribed for pulmonary diseases, their effects on the respiratory microbiome are still poorly understood. This systematic review summarizes the current understanding of the effects of corticosteroids on the microbiome of the airways.Research Question: How does treatment with corticosteroids impact the respiratory microbiome?Study Design and Methods: According to the PRISMA guidelines, Embase, Medline, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were systematically searched for all observational or randomized-controlled studies comparing the microbiome parameters of patients receiving corticosteroids to those of controls. The primary outcomes of interest were changes in the diversity, composition and total burden of the respiratory microbiome as assessed by culture-independent molecular methods.Results: Out of 1,943 identified reports, five studies could be included: two on patients with asthma, two on patients with chronic obstructive pulmonary disease and one on patients with chronic rhinosinusitis. The studies were highly heterogeneous with regards to the methods used and the populations investigated. Microbiome diversity increased with corticosteroids at least transiently in three studies and decreased in one study. The effects of corticosteroids on the composition of the respiratory microbiome were significant but without a clear shared direction. A significant increase in microbial burden after corticosteroids was seen in one study.Interpretation: Data on the effect of corticosteroids on the respiratory microbiome are still limited, with considerable heterogeneity between studies. However, available data suggest that corticosteroid treatment may have significant effects on the composition and possibly the diversity of the respiratory microbiome. Further research is needed to better understand the influence of corticosteroids on the respiratory microbiome and thus better target its widespread therapeutic use.
Dynamic Chronological Changes in Serum Triglycerides Are Associated With the Time Point for Non-alcoholic Fatty Liver Disease Development in the Nationwide Korean Population Cohort
Authors: Rim John Hoon , Youk Taemi , Gee Heon Yung , Cho Jooyoung , Yoo Jongha 
Published: March 2021

Background: We investigated the effects of anthropometric, laboratory, and lifestyle factors on the development of non-alcoholic fatty liver disease (NAFLD) in a nationwide, population-based, 4-year retrospective cohort.Methods: The propensity score-matched study and control groups contained 1,474 subjects who had data in the Korean National Health Insurance Service-National Sample Cohort in 2009, 2011, and 2013. NAFLD was defined using medical records of a diagnosis confirmed by primary clinicians and meeting two previously validated fatty liver prediction models. Chronological changes in anthropometric variables, laboratory results, and lifestyle factors during two periods were compared between patient and control groups in order to find out parameters with consistent dynamics in pre-NAFLD stage which was defined as period just before the NAFLD development.Results: Among the 5 anthropometric, 10 laboratory, and 3 lifestyle factors, prominent chronological decremental changes in serum triglycerides were consistently observed during the pre-NAFLD stage, although the degrees of changes were more predominant in men (−9.46 mg/dL) than women (−5.98 mg/dL). Furthermore, weight and waist circumference changes during the pre-NAFLD stage were noticeable only in women (+0.36 kg and +0.9 cm for weight and waist circumference, respectively), which suggest gender difference in NAFLD.Conclusion: Early screening strategies for people with abrupt chronological changes in serum triglycerides to predict NAFLD development before the progression is recommended.
Gait Assessment Using Three-Dimensional Acceleration of the Trunk in Idiopathic Normal Pressure Hydrocephalus
Authors: Yamada Shigeki , Aoyagi Yukihiko , Ishikawa Masatsune , Yamaguchi Makoto , Yamamoto Kazuo , Nozaki Kazuhiko 
Published: March 2021

Background: The subjective evaluation of pathological gait exhibits a low inter-rater reliability. Therefore, we developed a three-dimensional acceleration of the trunk during walking to assess the pathological gait quantitatively.Methods: We evaluated 97 patients who underwent the cerebrospinal tap test and were diagnosed with idiopathic normal pressure hydrocephalus (iNPH) and 68 healthy elderlies. The gait features of all patients were evaluated and classified as one of the following: freezing of gait, wide-based gait, short-stepped gait, shuffling gait, instability, gait festination, difficulty in changing direction, and balance disorder in standing up. All gait features of 68 healthy elderlies were treated as normal. Trunk acceleration was recorded automatically by a smartphone placed on the umbilicus during a 15-foot walking test. Two novel indices were created. The first index was a trunk acceleration index, which was defined as (forward acceleration fluctuation) + (vertical acceleration fluctuation) – (lateral acceleration fluctuation) based on the multivariate logistics regression model, and the second index was created by multiplying the forward acceleration with the vertical acceleration. Additionally, 95% confidence ellipsoid volume of the three-dimensional accelerations was assessed.Results: Forward and vertical acceleration fluctuations were significantly associated with the probability of an iNPH-specific pathological gait. The trunk acceleration index demonstrated the strongest association with the probability of an iNPH-specific pathological gait. The areas under the receiver-operating characteristic curves for detecting 100% probability of an iNPH-specific pathological gait were 86.9% for forward acceleration fluctuation, 88.0% for vertical acceleration fluctuation, 82.8% for lateral acceleration fluctuation, 89.0% for trunk acceleration index, 88.8% for forward × vertical acceleration fluctuation, and 87.8% for 95% confidence ellipsoid volume of the three-dimensional accelerations.Conclusions: The probability of a pathological gait specific to iNPH is high at the trunk acceleration fluctuation, reduced in the forward and vertical directions, and increased in the lateral direction.
Dietary Fibers (Gum Arabic) Supplementation Modulates Hepatic and Renal Profile Among Rheumatoid Arthritis Patients, Phase II Trial
Authors: Kamal Ebtihal , Kaddam Lamis AbdelGadir , Alagib Alnour , Saeed Amal 
Published: March 2021

Background: Rheumatoid arthritis (RA) is an autoimmune disease that mainly affects the synovial joints with systemic manifestations. RA has a major impact on liver and kidney functions as part of the disease pathogenesis or as a sequel of disease medications or, mostly, both of them. The kidney and liver involvement increases the RA morbidity and mortality. Nowadays, dietary interventions are proposed as potential modifiers for disease severity. Gum Arabic (GA) is acacia senegal exudates; it is soluble fiber with prebiotic properties. GA has been discovered to be protective against experimental nephrotoxicity and hepatotoxicity, with comparable findings in human studies. This article addresses the effect of GA on hepatic and renal profile among RA patients.Methods: Forty patients aged 18–70 received GA daily for 12 weeks as a single dose of 30 g. The liver enzymes, total protein level, serum albumin, serum globulin level, urea, creatinine, and serum electrolytes have been measured as a baseline after 4 weeks and by the end of the study. Cobas C311 (Roche, Germany) automated chemistry analyzer directly determined the values for total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and creatinine. The study ethically has been approved by the Ethical Committee of the National Medicines and Poisons Board. Trial Registration Identifier: NCT02804581.Results: Regarding the liver enzymes, GA has significantly decreased the liver enzymes apart from alkaline phosphatase, which showed no significant change. In contrast, GA has increased the serum albumin level with a minor impact on the serum globulin level. Furthermore, GA has also significantly decreased the level of urea (P = 0.0001) and level of Sodium (P = 0.002) with nonsignificant change on creatinine and potassium concentrations.Conclusion: GA presents hepatic and renal protective effects among RA patients, evidenced by the significant reduction of urea and liver enzymes. Thus, it can be recommended as a dietary supplement for RA patients. Nonetheless, we recommend further investigation to support our findings.
Cause-Specific Mortality Among Survivors From T1N0M0 Renal Cell Carcinoma: A Registry-Based Cohort Study
Authors: Wang Zhixian , Wang Jing , Zhu Yunpeng , Liu Chang , Li Xing , Zeng Xiaoyong 
Published: March 2021

ObjectiveMore T1N0M0 renal cell carcinoma (RCC) is detected and the prognosis has improved, but, the current focus on non-RCC-related mortality is superficial. We investigated cause-specific mortality and its temporal patterns after an RCC diagnosis.MethodsIn the Surveillance, Epidemiology, and End Results-18 database, patients with T1N0M0 RCC treated with partial nephrectomy (PN) or radical nephrectomy (RN) during 2000–15 were identified. Standardized mortality ratios (SMRs) for cause of death were calculated. Risk predictors for each cause-specific mortality were investigated using the Fine and Gray sub-distribution model.ResultsIn all, 68,612 eligible patients were pooled. A total of 14,047 (20.5%) patients had died (cardiovascular disease [CVD], 28.3%; other non-cancer-related diseases, 20.3%; RCC, 18.7%; other cancer types, 16.3%; non-disease events, 16.1%) during follow-up. Heart disease, diabetes mellitus, and cerebrovascular disease were the primary causes of non-RCC-related mortality within 1 year after the diagnosis. The greatest proportion of death (39.0%) occurred within 1–5 years after the diagnosis, mostly due to RCC itself, followed by heart disease. However, &gt;5 years after the diagnosis, heart disease became the leading cause of death. Compared with the general US population, a 21% (SMR, 1.21; 95%CI 1.19–1.23) increased risk of all-mortality was observed; RCC patients had a higher risk of heart disease-related death within 5–10 years (SMR, 1.10; 95%CI 1.04–1.17) and &gt;10 years (1.12; 1.02–1.22) after the diagnosis. Older age and RN increased the death risk of CVD and RCC-specific mortality. Although a larger tumor diameter increased the risk of RCC-specific death, this was not a significant predictor for CVD. Moreover, for T1N0M0 RCC tumors of diameter &gt;4 cm, there was no significant difference in CVD incidence for RN vs. PN.ConclusionsRCC-specific mortality is a common challenge for the prognosis. Importantly, a large proportion and higher SMRs of other non-RCC-related diseases (especially CVD) should not be disregarded for the better holistic management of survivors of local RCC. Targeted prevention strategies for non-RCC-related death could lead to significant reductions in mortality for RCC survivors.
Prediction of Post-hepatectomy Liver Failure in Patients With Hepatocellular Carcinoma Based on Radiomics Using Gd-EOB-DTPA-Enhanced MRI: The Liver Failure Model
Authors: Chen Yuyan , Liu Zelong , Mo Yunxian , Li Bin , Zhou Qian , Peng Sui , Li Shaoqiang , Kuang Ming 
Published: March 2021

Objectives: Preoperative prediction of post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) is significant for developing appropriate treatment strategies. We aimed to establish a radiomics-based clinical model for preoperative prediction of PHLF in HCC patients using gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI).Methods: A total of 144 HCC patients from two medical centers were included, with 111 patients as the training cohort and 33 patients as the test cohort, respectively. Radiomics features and clinical variables were selected to construct a radiomics model and a clinical model, respectively. A combined logistic regression model, the liver failure (LF) model that incorporated the developed radiomics signature and clinical risk factors was then constructed. The performance of these models was evaluated and compared by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC) with 95% confidence interval (CI).Results: The radiomics model showed a higher AUC than the clinical model in the training cohort and the test cohort for predicting PHLF in HCC patients. Moreover, the LF model had the highest AUCs in both cohorts [0.956 (95% CI: 0.955–0.962) and 0.844 (95% CI: 0.833–0.886), respectively], compared with the radiomics model and the clinical model.Conclusions: We evaluated quantitative radiomics features from MRI images and presented an externally validated radiomics-based clinical model, the LF model for the prediction of PHLF in HCC patients, which could assist clinicians in making treatment strategies before surgery.
Early Robotic-Assisted Laparoscopic Pyeloplasty for Infants Under 3 Months With Severe Ureteropelvic Junction Obstruction
Authors: Li Pin , Zhou Huixia , Cao Hualin , Guo Tao , Zhu Weiwei , Zhao Yang , Tao Tian , Zhou Xiaoguang , Ma Lifei , Yang Yunjie , Feng Zhichun 
Published: March 2021

Objective: To present our primary experience of robotic-assisted laparoscopic pyeloplasty (RALP) for severe ureteropelvis junction obstruction (UPJO) infants under 3 months.Methods: We performed a retrospective study of 9 infants under 3 months who underwent RALP for severe UPJO between April 2017 and March 2019 in our center. The severe UPJO was defined as infants with severe hydronephrosis (Society of Fetal Urology grades III or IV, anteroposterior diameter &gt;3 cm or split renal function &lt;40% or T 1/2 &gt;20 min) involving bilateral, solitary kidney, or contralateral renal hypoplasia UPJO at the same time. All clinical, perioperative, and postoperative information was collected.Results: There were four bilateral UPJO cases, two solitary kidney UPJO cases and three unilateral UPJO with contralateral renal hypoplasia cases included. One single surgeon performed RALP on all of the infants. The mean age of the infants was 1.62 ± 0.54 months. The mean operative time was 109.55 ± 10.47 min. The mean estimated blood loss was 19.29 ± 3.19 ml, and the mean length of hospital stay was 5.57 ± 0.73 days. According to the ultrasonography results, all patients had a significant recovery of renal function at 12 months after the operation.Conclusions: To maximize the protection of renal function, early RALP is a safe and feasible option for the treatment of severe UPJO in infants under 3 months.
Evaluation of a Multidisciplinary Antimicrobial Stewardship Program in a Saudi Critical Care Unit: A Quasi-Experimental Study
Authors: Haseeb Abdul , Faidah Hani Saleh , Al-Gethamy Manal , Iqbal Muhammad Shahid , Barnawi Abrar Mohammed , Elahe Shuruq S. , Bukhari Duha Nabeel , Noor Al-Sulaimani Turki Mohammad , Fadaaq Mohammad , Alghamdi Saad , Almalki Waleed Hassan , Saleem Zikria , Elrggal Mahmoud Essam , Khan Amer Hayat , Algarni Mohammed A , Ashgar Sami S. , Hassali Mohamed Azmi 
Published: March 2021

Background: Antimicrobial stewardship programs (ASPs) are collaborative efforts to optimize antimicrobial use in healthcare institutions through evidence-based quality improvement strategies. With regard to critically ill patients, appropriate antimicrobial usage is of significance, and any delay in therapy increases their risk of mortality. Therefore, the implementation of structured multidisciplinary ASPs in critical care settings is of the utmost importance to promote the judicious use of antimicrobials.Methods: This quasi-experimental study evaluating a multidisciplinary ASP in a 20-bed critical care setting was conducted from January 1, 2016 to July 31, 2017. Outcomes were compared nine months before and after ASP implementation. The national antimicrobial stewardship toolkit by Ministry of health was reviewed and the hospital antibiotic prescribing policy was accordingly modified. The antimicrobial stewardship algorithm (Start Smart and Then Focus) and an ASP toolkit were distributed to all intensive care unit staff. Prospective audit and feedback, in addition to prescribing forms for common infectious diseases and education, were the primary antimicrobial strategies.Results: We found that the mean total monthly antimicrobial consumption measured as defined daily dose per 100 bed days was reduced by 25% (742.86 vs. 555.33; p = 0.110) compared to 7% in the control condition (tracer medications) (35.35 vs. 38.10; p = 0.735). Interestingly, there was a negative impact on cost in the post-intervention phase. Interestingly, the use of intravenous ceftriaxone measured as defined daily dose per 100 bed days was decreased by 82% (94.32 vs. 16.68; p = 0.008), whereas oral levofloxacin use was increased by 84% (26.75 vs. 172.29; p = 0.008) in the intensive care unit.Conclusion: Overall, involvement of higher administration in multidisciplinary ASP committees, daily audit and feedback by clinical pharmacists and physicians with infectious disease training, continuous educational activities about antimicrobial use and resistance, use of local antimicrobial prescribing guidelines based on up-to-date antibiogram, and support from the intensive care team can optimize antibiotic use in Saudi healthcare institutions.
The Bioequivalence of Emulsified Isoflurane With a New Formulation of Emulsion: A Single-Center, Single-Dose, Double-Blinded, Randomized, Two-Period Crossover Study
Authors: Yang Hui , Yin Qinqin , Huang Luying , Zhang Min , Zhang Xinxin , Sun Qirong , Liu Xuewei , Wang Qi , Yang Xi , Tan Lingcan , Ye Mao , Liu Jin 
Published: March 2021

Background: Emulsified isoflurane is a novel intravenous general anesthetic obtained by encapsulating isoflurane molecules into emulsion. The formulation of emulsion has been improved according to the latest regulations of the China Food and Drug Administration. This study was designed to compare the bioequivalence of the new and previous formulation emulsion of isoflurane.Methods: In a single-center, single-dose, double-blinded, randomized, two-period crossover study, healthy volunteers received intravenous injection of 30 mg/kg of isoflurane with either previous formulation of emulsion isoflurane (PFEI) or new formulation of emulsion isoflurane (NFEI). Arterial and venous blood samples were obtained for geometric mean test/reference ratios of Cmax, AUC0-t, and AUC0-∞, as well as their 90% confidence interval (CI90) as the primary outcome. The secondary outcomes were safety measurements such as vital signs, 12-lead electrocardiography, adverse effects, and laboratory tests; and anesthesia efficacy was assessed by Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score, bispectral index (BIS), and loss/recovery of eyelash reflex.Results: 24 subjects were eligible, of which 21 completed the whole experiment (NFEI n = 21, PFEI n = 23). Arterial geometric mean test/reference ratios of Cmax, AUC0-t, and AUC0-∞ were 104.50% (CI90 92.81%–117.65%), 108.23% (94.51%–123.96%), and 106.53% (93.94%∼120.80%), respectively. The most commonly seen adverse effects for NFEI and PFEI were injection pain (38.1% vs. 34.8%), hypotension (19.0% vs. 13.0%), apnea (14.3% vs. 17.4%), and upper airway obstruction (14.3% vs. 13.0%). No severe adverse effect was observed. The effectiveness of general anesthesia was similar between the two formulations.Conclusion: The CI90 of Cmax, AUC0-t, AUC0-∞, NFEI, and PFEI were within the range of 80%–125%, suggesting bioequivalence between NFEI and PFEI. The safety and anesthesia effectiveness were also similar.
Simultaneous Two-Photon Fluorescence Microscopy of NADH and FAD Using Pixel-to-Pixel Wavelength-Switching
Authors: Qin Yifan , Xia Yuanqin 
Published: March 2021

Two-photon fluorescence (TPF) microscopy of intrinsic fluorophores provides physiological and pathological information from biological tissues. Reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are two endogenous fluorescent coenzymes existing on the intracellular scale. Autofluorescence images of NADH and FAD have been applied to noninvasively record changes during metabolism, according to their distributions and concentrations. However, the widely used sequential (non-simultaneous) excitation scheme results in artifacts caused by sample motion or laser power fluctuation. The single-wavelength illumination scheme suffers from low excitation efficiency and spectral bleed-through. In this paper, we demonstrate a new imaging system simultaneously capturing autofluorescence images from NADH and FAD, with high excitation efficiency and negligible spectral bleed-through. Two temporally multiplexed and spatially overlapped excitation beams were achieved with fast-switching light paths based on an electro-optic modulator. The switching beams were centered at 750 and 860 nm, enabling independent excitations of NADH and FAD. Autofluorescence images of NADH and FAD were acquired at the wavelength ranges of 415–455 nm and 500–550 nm, respectively. The electro-optic modulator was synchronized with the pixel clock from the microscope, achieving pixel-to-pixel wavelength-switching. The capability of the system was demonstrated by performing TPF imaging of freshly excised mouse colon tissues. The microenvironment of the colon wall was depicted by the distributions of colonocytes, goblet cells, and crypts of Lieberkühn, and the relative concentrations of NADH and FAD were estimated. The experimental results show that the system can effectively perform simultaneous imaging of NADH and FAD, and is considered a promising tool for investigations into metabolism-associated processes and diseases.