bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monosodium Glutamate-Induced Mouse Model With Unique Diabetic Retinal Neuropathy Features and Artificial Intelligence Techniques for Quantitative Evaluation
Authors: Liu Yanfei , Huang Hui , Sun Yu , Li Yiwen , Luo Binyu , Cui Jing , Zhu Mengmeng , Bi Fukun , Chen Keji , Liu Yue 
Published: April 2022

ObjectiveTo establish an artificial intelligence-based method to quantitatively evaluate subtle pathological changes in retinal nerve cells and synapses in monosodium glutamate (MSG) mice and provide an effective animal model and technique for quantitative evaluation of retinal neurocytopathies.MethodsICR mice were subcutaneously injected with MSG to establish a model of metabolic syndrome. We then established a mouse model of type 1 diabetes, type 2 diabetes, and KKAy mouse model as control. The HE sections of the retina were visualized using an optical microscope. AI technology was used for quantitative evaluation of the retinal lesions in each group of rats. The surface area custom parameters of the retinal nerve fiber layer (RNFL), inner plexiform layer (IPL), inner nuclear layer (INL), and outer plexiform layer (OPL) were defined as SR, SIPL, SINL, and SOPL, respectively. Their heights were defined as HR, HIPL, HINL, and HOPL, and the number of ganglion cells was defined as A. Then, the attention-augmented fully convolutional Unet network was used to segment the retinal HE images, and AI technology to identify retinal neurocytopathies quantitatively.ResultsThe attention-augmented fully convolutional Unet network increased PA and IOU parameters for INL, OPL, RNFL, and ganglion cells and was superior in recognizing fine structures. A quantitative AI identification of the height of each layer of the retina showed that the heights of the IPL and INL of the MSG model were significantly less than those of the control groups; the retinas of the other diabetic models did not exhibit this pathological feature. The RNFLs of type 2 diabetes were thinner, and the characteristics of retinopathy were not obvious in the other animal models. The pathological changes seen on HE images were consistent with the results of the quantitative AI evaluation. Immunohistochemistry results showed that NMDAR2A, GluR2, and NRG1 were significantly downregulated in the retina of MSG mice.ConclusionsThe MSG retinopathy model is closely associated with neurotransmitter abnormalities and exhibits important characteristics of retinal neurodegeneration, making it suitable for studying retinal neurocytopathies. The AI recognition technology for retinal images established in the present study can be used for the quantitative and objective evaluation of drug efficacy.
Inhibition of CCCTC Binding Factor-Programmed Cell Death Ligand 1 Axis Suppresses Emergence of Chemoresistance Induced by Gastric Cancer-Derived Mesenchymal Stem Cells
Authors: Wang Qianqian , Huang Chao , Ding Ying , Wen Shaodi , Wang Xin , Guo Shuwei , Gao Qiuzhi , Chen Zhihong , Zhao Yuanyuan , Wang Mei , Shen Bo , Zhu Wei 
Published: April 2022

BackgroundGastric cancer (GC) is the third leading cause of cancer-associated deaths worldwide. Stromal cells, especially mesenchymal stem cells (MSCs), play significant roles in the development of therapy resistance depending on their paracrine function. The PD-1/PD-L1 crosstalk between cancer and immune cells has been well studied. Emerging evidence suggests that PD-L1 also contributes to tumor resistance to therapy.MethodsCell survival and apoptosis were assessed using CCK-8, colony formation, and flow cytometry assays. Protein alterations were analyzed via Western blot. Gene knockdown and overexpression were achieved with siRNA/shRNA and lentiviral infection, respectively. Drug effects on tumors in vivo were assessed with xenografts in nude mice. In addition, GC patient samples after chemotherapy treatment were collected to observe the relationship between chemotherapy effect and CTCF or PD-L1.ResultsIn response to 5-fluorouracil or paclitaxel treatment, GCMSC-CM enhanced the cell viability and decreased the apoptosis rate. Furthermore, blocking PD-L1 or CTCF in GC cells prevented GCMSC-induced drug resistance accompanied by a decline in cell stemness. Consistent with these in vitro observations, mice treated with GCMSC-CM showed a lower sensitivity to 5-fluorouracil. In addition, high expression of CTCF and PD-L1 was associated with poor chemotherapy progression in the clinic.ConclusionStudy results demonstrate a mechanism where GCMSC-CM promotes GC chemoresistance by upregulating CTCF-PD-L1 and provide strong evidence in support of targeting CTCF-PD-L1 signaling as a strategy to prevent resistance in the clinic.
Effect of Polypropylene Grafted Maleic Anhydride (PP-G-MAH) on the Properties of Asphalt and its Mixture Modified With Recycled Polyethylene/Recycled Polypropylene (RPE/RPP) Blends
Authors: Zhang Wencai , Hao Xiaogang , Fan Changxin , Zhang Shuai , Ma Dechong , Yu Xiaofang , Fu Zhaohua , Feng Gongji 
Published: April 2022

In this study, a ternary blend modifier (TBM) was prepared with RPE, RPP, and various dosages of PP-g-MAH (i.e., 0%, 1%, 3%, 5%, 7%, and 9% by weight of RPE and RPP) by a twin-screw extruder. The performance of TBM (4% by weight of asphalt) modified asphalt was studied, with the increase of PP-g-MAH content, the penetration decreases gradually, but softening point and viscosity increases and ductility exists minimum value at 7% content, with the increasing of PP-g-MAH percentage, the dynamic rheological properties show that |G*| increases, while the δ and |G*|cosδ decrease, and the fatigue performance (|G*|sinδ) of TBM modified asphalt is worse than virgin asphalt. Dynamic stability test shows that TBM shows the prominent high-temperature properties of a modified (asphalt mixture. BBR test indicates that the m-value of asphalt modified with TBM does not fulfill the requirements (m-value&gt;0.3) except at 5% and 7%, but the S meets the standard requirements (S &lt; 300 MPa), and increases from 0% to 7%, then decreases slightly. In order to illuminate possible reasons, a chemical reaction (ester compounds generated) and physical twines of concerned polymer molecules were put forward, and the results were confirmed by infrared analysis.
Effect of Different Environmental Conditions on Durabilities of Polyester- and Vinylester-Based Glass-Fiber-Reinforced Polymer Pultruded Profiles
Authors: Yang Shulan , Chu Mingkun , Chen Fangyi , Fu Miaorui , Lv Yiwen , Xiao Ziyi , Feng Ningning , Song Yang , Li Jiannan 
Published: April 2022

This paper presents the results of experimental investigations on the durability of glass-fiber-reinforced polymer (GFRP) pultruded profiles made of unsaturated polyester (UP) and vinylester (VE) resins commonly used in civil engineering. The water absorption, tensile properties, and microstructures of GFRP profiles exposed to several typical accelerated aging environments (e.g., deionized water, salt water, salt fog, and combined hygrothermal cycles) for 12 months were investigated. Moreover, a sustained loading factor was included in the test to reflect the behavior of the GFRP profiles in real structures. A normalization approach based on the controlled specimens was used to assess the effectiveness and relevance of the accelerated exposure. The results indicated that the maximum moisture absorption of both UP and VE GFRP profiles was immersed in deionized water, where the masses increased by 1.03 and 0.53%, respectively, leading to the maximum degradation of tensile strength (24.03%) of UP GFRP profile immersion in deionized water after 360 days of aging. However, the tensile modulus was more sensitive to high temperatures and has the maximum degradation (47.03%) after hygrothermal cycles. Moreover, VE GFRP profiles show superior humidity and temperature endurance. Furthermore, the sustained loading exacerbated the degradation of tensile properties slightly under the same conditions. Finally, by incorporating the cumulative damage caused by the sustained loading and a time-dependent factor into a residual strength model, a revised model was proposed to describe the tensile strength loss of pultruded UP GFRP profiles.
Reducing Changeover Time Between Surgeries Through Lean Thinking: An Action Research Project
Authors: Amati Mirjam , Valnegri Alan , Bressan Alessandro , La Regina Davide , Tassone Claudio , Lo Piccolo Antonio , Mongelli Francesco , Saporito Andrea 
Published: April 2022

BackgroundMaximizing the utilization of the operating room suite by safely and efficiently changing over patients is an opportunity to deliver more value to patients and be more efficient in the operating suite. Lean Thinking is a concept that focuses on the waste inadvertently generated during organization and development of an activity, which should maximize customer value while minimizing waste. It has been widely applied to increase process efficiency and foster continuous improvement in healthcare and in the operating room environment. The objective of this paper is to provide insight on how healthcare professionals can be engaged in continuous improvement by embracing Lean Thinking and ultimately reducing changeover time between surgeries.MethodsUsing an action research approach, Lean methodology such as Gemba walks, Process Mapping, Root-Cause-Analysis, and the Single Minute Exchange of Dies (SMED) system was applied to understand the causes of variability and wastes concerning changeovers and improve processes in the context of gynecological- and general surgery. Data were collected and analyzed through observations and video recordings. Problem and issue have been raised to management team attention and included in the annual balanced scorecard of the hospital. This initiative has been also made relevant to the team working in the operating suite and related processes before and after the entry of the patient in the operating suite.ResultsImproved patient flow and inter-professional collaboration through standardized and safer work enabled effective parallel processing and allowed the hospital to reduce changeover time between operations by 25% on average, without changes in terms of infrastructure, technology or resources.ConclusionLean thinking allowed the team to re-evaluate how the whole operating suite performs as a system, by starting from a sub-process as changeover. It is fundamental in order to improve further and obtain sustainable results over time, to act on a system level by defining a common goal between all stakeholders supported by a management and leading system such as visual/weekly management, optimizing planning, implementing standard-works to be followed by every associate and guaranteeing the role of the surgeon as process driver who pull performances.
Case Report: Use of Amniotic Membrane for Tectonic Repair of Peripheral Ulcerative Keratitis With Corneal Perforation
Authors: Eslami Maryam , Benito-Pascual Blanca , Goolam Saadiah , Trinh Tanya , Moloney Greg 
Published: April 2022

PurposeTo provide a perspective and surgical video demonstration of peripheral corneal ulceration and perforation managed with multilayered amniotic membrane transplantation.Case ReportsCase 1 describes a 48-year-old female with progressive redness and pain, and an inferonasal corneal thinning and perforation in the left eye from peripheral ulcerative keratitis. She underwent conjunctival recession with amniotic membrane inlay and onlay (Sandwich technique) transplantation. The amniotic membrane integrated well, and her Snellen visual acuity improved from 6/21 preoperatively to 6/9 at 3 months post op. Case 2 describes a 78-year-old male with redness and pain with temporal corneal thinning bilaterally and perforation in the right eye from peripheral ulcerative keratitis. Both eyes underwent similar surgical intervention with smooth integration of the amniotic membrane in the cornea and improvement in the visual acuity. Both patients were also started on systemic immunosuppression in collaboration with the rheumatology team.ConclusionWe report successful use of multilayered amniotic membrane transplantation for the treatment of corneal ulceration and perforation. The authors believe the simplicity of the surgical technique, easier access to amniotic membrane tissue, and lower induced post-operative astigmatism all provide advantages over alternative treatment modalities.
A Novel Neutrophil-Based Biomarker to Monitor Disease Activity and Predict Response to Infliximab Therapy in Patients With Ulcerative Colitis
Authors: Zhou Zhou , Zhang Yinghui , Pan Yan , Yang Xue , Li Liangping , Gao Caiping , He Chong 
Published: April 2022

BackgroundUlcerative colitis (UC) is characterized by refractory and recurrent mucosal inflammation, leading to a substantial healthcare burden. Diagnostic biomarkers predicting disease activity and treatment response remain elusive. To evaluate the application value of a novel neutrophil-based index (the neutrophil-to-albumin ratio, NAR) as a novel diagnostic biomarker in patients with UC and a predictive marker for disease activity and response to infliximab (IFX) therapy.MethodsClinical characteristics and laboratory parameters of enrolled subjects (patients with UC and healthy controls) were retrieved from the electronic medical record database of our hospital. Serum cytokine and fecal calprotectin levels were measured by enzyme-linked immunosorbent assay (ELISA). Mucosal expression levels of inflammatory agents were measured by quantitative RT-PCR (qRT-PCR).ResultsWe found that NAR, which had not yet been explored in UC, was significantly increased in patients with UC (n = 146) compared to that in controls (n = 133) (1.95 ± 0.41 vs. 1.41 ± 0.23, p &lt; 0.0001). NAR showed a positive association with the disease activity and inflammatory load in patients with UC. Pre-treatment NAR was significantly lower in IFX responders than that in non-responders (2.18 ± 0.29 vs. 2.44 ± 0.21, p = 0.0118), showing a significant ability to discriminate initial responders from primary non-responders to IFX induction therapy (AUC = 0.7866, p = 0.0076). Moreover, pre-treatment NAR predicted postinduction serum IFX trough level.ConclusionOur study provides evidences to utilize NAR in the diagnosis, activity monitoring, and IFX response prediction in patients with UC.
Association Between Different DVT Prevention Methods and Outcomes of Septic Shock Caused by Intestinal Perforation in China: A Cross-Sectional Study
Authors: Wang Lu , Ma Xudong , He Huaiwu , Su Longxiang , Guo Yanhong , Shan Guangliang , Wang Ye , Zhou Xiang , Liu Dawei , Long Yun 
Published: April 2022

IntroductionSeptic shock, largely caused by intestinal perforation, is the most common critical illness in intensive care unit (ICU). As an important quality control strategy in ICU, deep vein thrombosis (DVT) prevention is routinely used in the treatment of septic shock. Nevertheless, the effects of DVT prevention on septic shock are not fully revealed. This study was thus designed to investigate the effects of DVT prevention on septic shock caused by intestinal perforation in China.MethodsA total of 463 hospitals were enrolled in a survey, led by the China National Critical Care Quality Control Center (China NCCQC) from January 1, 2018 to December 31, 2018. The association between DVT prevention, including pharmacological prophylaxis and mechanical prophylaxis, and outcomes, such as prognosis, complications, hospital stays, and hospitalization costs, was determined in the present study.Main ResultsNotably, the increased rates of DVT prevention were not associated with the onset of complications in patients with septic shock caused by intestinal perforation (p &gt; 0.05). In addition, even though increased DVT prevention did not affect hospital stays, it significantly decreased the discharge rates without doctor's order in patients with septic shock caused by intestinal perforation (p &lt; 0.05). Nevertheless, it should be noted that the rates of pharmacological prophylaxis but not mechanical prophylaxis were significantly associated with the costs of septic shock caused by intestinal perforation (p &lt; 0.05). Although increased total rates of DVT prevention and the rates of mechanical prophylaxis did not reduce the mortality in patients with septic shock caused by intestinal perforation, the higher frequent intervention using pharmacological prophylaxis indicated the lower mortality of these patients (p &lt; 0.05).ConclusionsDVT prevention by any means is a safe therapeutic strategy for treating septic shock caused by intestinal perforation, and pharmacological prophylaxis reduced the mortality of patients with septic shock caused by intestinal perforation.
The German Quality Network Sepsis: Evaluation of a Quality Collaborative on Decreasing Sepsis-Related Mortality in a Controlled Interrupted Time Series Analysis
Authors: Schwarzkopf Daniel , Rüddel Hendrik , Brinkmann Alexander , Fleischmann-Struzek Carolin , Friedrich Marcus E. , Glas Michael , Gogoll Christian , Gründling Matthias , Meybohm Patrick , Pletz Mathias W. , Schreiber Torsten , Thomas-Rüddel Daniel O. , Reinhart Konrad 
Published: April 2022

BackgroundSepsis is one of the leading causes of preventable deaths in hospitals. This study presents the evaluation of a quality collaborative, which aimed to decrease sepsis-related hospital mortality.MethodsThe German Quality Network Sepsis (GQNS) offers quality reporting based on claims data, peer reviews, and support for establishing continuous quality management and staff education. This study evaluates the effects of participating in the GQNS during the intervention period (April 2016–June 2018) in comparison to a retrospective baseline (January 2014–March 2016). The primary outcome was all-cause risk-adjusted hospital mortality among cases with sepsis. Sepsis was identified by International Classification of Diseases (ICD) codes in claims data. A controlled time series analysis was conducted to analyze changes from the baseline to the intervention period comparing GQNS hospitals with the population of all German hospitals assessed via the national diagnosis-related groups (DRGs)-statistics. Tests were conducted using piecewise hierarchical models. Implementation processes and barriers were assessed by surveys of local leaders of quality improvement teams.ResultsSeventy-four hospitals participated, of which 17 were university hospitals and 18 were tertiary care facilities. Observed mortality was 43.5% during baseline period and 42.7% during intervention period. Interrupted time-series analyses did not show effects on course or level of risk-adjusted mortality of cases with sepsis compared to the national DRG-statistics after the beginning of the intervention period (p = 0.632 and p = 0.512, respectively). There was no significant mortality decrease in the subgroups of patients with septic shock or ventilation &gt;24 h or predefined subgroups of hospitals. A standardized survey among 49 local quality improvement leaders in autumn of 2018 revealed that most hospitals did not succeed in implementing a continuous quality management program or relevant measures to improve early recognition and treatment of sepsis. Barriers perceived most commonly were lack of time (77.6%), staff shortage (59.2%), and lack of participation of relevant departments (38.8%).ConclusionAs long as hospital-wide sepsis quality improvement efforts will not become a high priority for the hospital leadership by assuring adequate resources and involvement of all pertinent stakeholders, voluntary initiatives to improve the quality of sepsis care will remain prone to failure.
The Host CYP1A1-Microbiota Metabolic Axis Promotes Gut Barrier Disruption in Methicillin-Resistant Staphylococcus aureus-Induced Abdominal Sepsis
Authors: Ma Xiaoyuan , Jin Huaijian , Chu Xiang , Dai Weihong , Tang Wanqi , Zhu Junyu , Wang Fangjie , Yang Xue , Li Wei , Liu Guodong , Yang Xia , Liang Huaping 
Published: April 2022

BackgroundHost-microbiota crosstalk has been implicated in multiple host metabolic pathway axes that regulate intestinal barrier function. Although constitutive cytochrome P4501A1 (CYP1A1) expression perturbs the microbiome-derived autoregulatory loop following enteric infection, little is known about the role of host CYP1A1 in modulating gut microbiome-mediated signaling during methicillin-resistant Staphylococcus aureus (MRSA)-induced abdominal sepsis and its effects on intestinal barrier integrity.MethodsAbdominal sepsis was induced by the intraperitoneal injection of MRSA in mice. The effect of CYP1A1 deficiency on gut barrier integrity was investigated using RNA sequencing, microbiome analyses, and targeted metabolomics. The microbiota-produced metabolites were validated in patients with sepsis and persistent MRSA infection.ResultsMice lacking CYP1A1 exhibited an altered gut microbiome, a reduced metabolic shift from lysine to cadaverine in the caecal contents and antimicrobial molecule production (Retnlb, Gbp7, and Gbp3), and they were protected against gut barrier disruption when subjected to MRSA challenge. These beneficial effects were validated in aryl hydrocarbon receptor (AHR) knockout (KO) mice by cohousing with CYP1A1 KO mice and abrogated after supplementation with cadaverine or Enterococcus faecalis, the primary microbiota genus for cadaverine synthesis. Antibiotic-driven gut dysbacteriosis impaired the survival benefit and disrupted the intestinal barrier integrity in CYP1A1 KO mice after MRSA infection. Furthermore, increased cadaverine levels in feces and serum were detected in critically ill patients with gut leakiness during persistent MRSA infection, whereas cadaverine was not detected in healthy controls. Additionally, microbiota-derived cadaverine induced enterocyte junction disruption by activating the histamine H4 receptor/nuclear factor-κB/myosin light-chain kinase signaling pathway.ConclusionThis study revealed the unexpected function of host CYP1A1 in microbiota-mediated cadaverine metabolism, with crucial consequences for dysbacteriosis following MRSA-induced abdominal sepsis, indicating that inhibiting CYP1A1 or blocking cadaverine-histamine H4 receptor signaling could be a potential therapeutic target against abdominal sepsis.Clinical Trial Registration[http://www.chictr.org.cn/index.aspx], identifier [ChiCTR1800018646].
Immune Checkpoint Molecules Expressed on CD4+ T Cell Subsets in Chronic Asymptomatic Hepatitis B Virus Carriers With Hepatitis B e Antigen-Negative
Authors: Cui Dawei , Jiang Daixi , Yan Cuilin , Liu Xia , Lv Yan , Xie Jue , Chen Yu 
Published: April 2022

BackgroundChronic hepatitis B virus (HBV) infection remains a major public health problem worldwide. Immune checkpoint molecules expressed on CD4+ T cells play critical roles in chronic HBV infection. However, their roles in chronic asymptomatic HBV carriers (ASCs) with hepatitis B e antigen (HBeAg)-negative remain unclear. In this study, we explored the role of immune checkpoint molecules expressed on CD4+ T cell subsets in chronic ASCs with HBeAg-negative.MethodsHuman peripheral blood mononuclear cells (PBMCs) from the ASCs with HBeAg-negative and healthy controls (HC) were isolated, and immune checkpoint molecules expressed on CD4+ T cell subsets and serum cytokines were detected by flow cytometry. Moreover, the mRNA expressions of immune checkpoint molecules were analyzed by a real-time quantitative PCR assay.ResultsIn comparison with HC, CD4+ T cells highly expressed LAG-3, TIM-3, and PD-1 in PBMCs from chronic ASCs with HBeAg-negative. Interestingly, the expressions of TIM-3 and PD-1 on circulating follicular helper T (Tfh) cells in ASCs were significantly high. Moreover, high expressions of LAG-3, TIM-3, and PD-1 were different among Treg, Th1, Th2, and Th17 cells. In addition, the expressions of TIM-3 and CTLA-4 mRNA in PBMCs from ASCs were significantly elevated. However, the frequency of CTLA-4+CD4+ T cell subsets in PBMCs from ASCs was not different from HC. The levels of six cytokines in serum from ASCs were not clearly different from HC.ConclusionImmune checkpoint molecules highly expressed on CD4+ T cell subsets indicated an important role in chronic ASCs with HBeAg-negative, which provided potential therapeutic targets in the pathogenesis of chronic HBV infection.