bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel ALK Fusion Gene (NSF-ALK) Identified in a Patient With Recurrent Spindle Cell Sarcoma Respond to Crizotinib: A Case Report
Authors: Jin Shuiling , Weng Lanling , Zhong Qian , Cui Chi , Tang Wenxue , Zong Hong , Ma Wang , Li Zhi 
Published: August 2020

Abstract
Background: Spindle cell sarcoma (SCS) is a rare malignant tumor which relapses quickly and has poor prognosis.Case presentation: We report a case of SCS deriving from the left side of chestpossessed a novel unreported ALK fusion gene named NSF-ALK found by Next Generation Sequencing (NGS) technology. Despite receiving three surgical resections, local recurrence occurred rapidly and distant brain metastasis was eventually observed in this patient. The subsequent administration of crizotinib1, an oral anaplastic lymphoma kinase inhibitor, resulted in dramatic tumor shrinkage and the patient entered a remission period that has been ongoing for more than 10 months.Conclusions: In summary, this study is the first to describe a novel NSF-ALK fusion in spindle cell sarcoma which has promising efficacy by crizotinib treatment. More importantly, the case also shows that next generation sequencing provids more information of mutation to guide treatment in clinical decisions by presenting molecular changes.
Value of Serum Macrophage Migration Inhibitory Factor (Mif), Adiponectin, and Other Adipokines as Markers of Proteinuria and Renal Dysfunctionin Lupus Nephritis: A Cross-sectional Study.
Authors: Gamez-Nava Jorge Ivan , Diaz-Rizo Valeria , Perez-Guerrero Edsaul Emilio , Muñoz-Valle Jose Francisco , Saldaña-Cruz Ana Miriam , Fajardo-Robledo Nicte Selene , Jacobo-Cuevas Heriberto , Nava-Valdivia Cesar Arturo , Alcaraz-Lopez Miriam Fabiola , Trujillo Xochitl , Huerta Miguel , Cardona-Muñoz Ernesto German , Gonzalez-Lopez Laura 
Published: August 2020

Abstract
BackgroundTo date, there is controverted the association between serum macrophage migration inhibitory factor (MIF) and serum adipokines with Lupus Nephrites.ObjectiveTo investigate the value of serum MIF, leptin, adiponectin and resistin levels as markers of proteinuria and renal dysfunction in lupus nephritisMethodsDesign: cross-sectional. We included 196 Systemic Lupus Erythematosus (SLE) and 52 controls (HC). In SLE, disease activity was assessed by SLEDAI. Renal involvement was investigated by Renal-SLEDAI: a) Renal-SLE involvement (n=43) and b) Non-Renal-SLE (n=153). MIF, adiponectin, leptin and resistin levels were quantified by ELISA. We assessed correlations of MIF, adipokines and renal involvement parameters [proteinuria (g/day), serum creatinine and other]. Multivariable linear regression was used for investigating factors associated with the intensity of proteinuria. ResultsSLE patients had higher MIF (p=0.02) and adiponectin levels (p<0.001) than HC. In renal-SLE involvement there were higher adiponectin levels (19.0 vs 13.3 µg/mL, p=0.002) and resistin levels (10.7 vs 8.9 ng/mL, p=0.01), compared with non-Renal-SLE. Proteinuria correlated with high adiponectin (rs=0.19, p<0.009) and resistin levels (rs=26, p<0.001). MIF (rs=0.27, p=0.04) and resistin (rs= 0.18; p=0.02) correlated with increased creatinine. High Renal activity correlated with adiponectin (rs=0.21, p=0.004). Multiple linear regression identified that elevated adiponectin (p=0.02), younger age (p=0.04) and low MIF (p=0.02) were associated with intensity of proteinuria. Low MIF and high adiponectin levels have interaction for intensity of proteinuria (R2=0.41). ConclusionsHigh adiponectin combined with low MIF concentrations interacts for increase proteinuria in renal-SLE, and MIF and resistin levels are associated with renal dysfunction. These findings highlight the relevance of including the assessment of MIF and adipokines as clinical markers in the evaluation of LN.
Multi-tiered External Facilitation: The Role of Feedback Loops and Tailored Interventions in Supporting Change in a Stepped-Wedge Implementation Trial
Authors: Penney Lauren S , Damush Teresa M. , Rattray Nicholas A. , Miech Edward J. , Baird Sean A. , Homoya Barbara J. , Myers Laura J. , Bravata Dawn M. 
Published: August 2020

Abstract
Background Facilitation is a complex, relational implementation strategy that guides change processes. Facilitators engage in multiple activities and tailor efforts to local contexts. The contextual factors that prompt facilitators to tailor activities have not been well-described. Methods We conducted a mixed methods evaluation of a trial to improve the quality of transient ischemic attack care. Six sites in the Veterans Health Administration received external facilitation (EF) before and during a 1-year active implementation period. We examined how EF was employed, perceived, and activated. Data analysis included prospective logs of facilitator correspondence with sites (160 site-directed episodes), stakeholder interviews (n=78), and collaborative call debriefs (n=22). Logs were descriptively analyzed across facilitators, sites, time periods, and activity types. Interview transcripts were coded for content related to EF and themes were identified. Debriefs were reviewed to identify instances of and utilization of EF during site critical junctures. Results Multi-tiered EF was supported by two groups (site-facing quality improvement [QI] facilitators and the implementation support team) that were connected by feedback loops. Each site received an average of 24 episodes of site-directed EF; most of the EF was delivered by the QI nurse. For each site, site-directed EF frequently involved networking (45%), preparation and planning (44%), process monitoring (44%), and/or education (36%). EF less commonly involved audit and feedback (20%), brainstorming solutions (16%), and/or stakeholder engagement (5%). However, site-directed EF varied widely across sites and time periods in terms of these facilitation types. Site participants recognized the responsiveness of the QI nurse, and valued her problem-solving, feedback, and accountability support. External facilitators used monitoring and dialogue to intervene by facilitating redirection during challenging periods of uncertainty about project direction and feasibility for sites. External facilitators, in collaboration with the implementation support team, successfully used strategies tailored to diverse local contexts, including networking, providing data, and brainstorming solutions. Conclusions Multi-tiered facilitation capitalizing on feedback loops allowed for tailored, site-directed facilitation that aligned with the types of supports that local participants valued. Critical juncture cases illustrate the complexity of EF and the need to often try multiple strategies in combination to facilitate implementation progress.
Nanoparticles in 472 Human Cerebrospinal Fluid: Changes in Extracellular Vesicle Concentration and miR-21 Expression as a Biomarker for Leptomeningeal metastasis
Authors: Lee Kyue-Yim , Im Ji Hye , Lin Weiwei , Gwak Ho-Shin , Kim Jong Heon , Yoo Byong Chul , Kim Tae Hoon , Park Jong Bae , Park Hyeon Jin , Kim Ho-Jin , Kwon Ji-Woong , Shin Sang Hoon , Yoo Heon , Lee Changjin 
Published: August 2020

Abstract
Background: Leptomeningeal metastasis (LM) has a poor prognosis and is difficult to diagnose and predict the response of treatment. In this study, we suggest that the monitoring of changes in the concentration of extracellular vesicles in cerebrospinal fluid could help to diagnose or predict outcomes for LM.Methods: We measured nanoparticles in 472 human CSF from controls and patients including LM with both Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA) after two-step centrifugations.Results: NTA revealed nanoparticles distributed at a median 193 nm in size, and 1.74 × 108 /ml in concentration, and those were significantly higher in LM compared to other groups (211 nm vs. 188 nm, p < 0.001 and 2.80 × 108 /ml vs. 1.49 × 108 /ml, p < 0.01, respectively). Changes in NTA-measured nanoparticles (EV from here) concentration after intra-CSF chemotherapy were further examined in non-small cell lung cancer patients with LM (n=33). Overall survival was longer for patients with increased EV than the others (442 vs. 165 days, p < 0.001). Exosome surface markers (CD9/CD63/CD81) significantly decreased in the EV-decreased group (ratio 0.64, p<0.0001). MicroRNA-21 expression decreased in this favorable prognostic group, whereas increased in the EV-decreased group (p = 0.003). Conclusions: The elevated concentration of extracellular vesicles in cerebrospinal fluid in patients with LM can be a diagnostic marker. Moreover, EV changes combined with microRNA-21 might be a biomarker for monitoring intracranial chemotherapy of LM.
Association between plasma complement factor H concentration and clinical outcomes in patients with sepsis
Authors: Shimizu Junji , Fujino Kazunori , Sawai Toshihiro , Tsujita Yasuyuki , Tabata Takahisa , Eguchi Yutaka 
Published: August 2020

Abstract
Background The complement system is important for defending against pathogens; however, excessive complement activation is associated with a poor prognosis and organ dysfunction in sepsis. Complement factor H (CFH) acts to prevent excessive complement activation and damage to the self through the regulation of the complement alternative pathway.This study aimed to investigate the association between plasma CFH levels on admission to the ICU and 90-day mortality and organ dysfunction, in patients with sepsis. Methods This is a single-center prospective observational study conducted from July 2016 to March 2019. Logistic regression analysis and correlation analysis were performed to assess the relationship between the plasma CFH on admission to the ICU and 90-day mortality, and organ dysfunction. Results This analysis included 62 patients. The plasma CFH levels were significantly lower in 90 day non survivors than those in survivors (70.0 μg/ml [interquartile range (IQR) 51.2 - 97.6] vs 104.8 μg/ml [IQR 66.8 - 124.2] , P=0.006) . The plasma CFH levels were associated with 90 day mortality (OR 0.977 95% CI 0.957 – 0.994, p = 0.01). Correlation analysis showed that the plasma CFH levels were negatively correlated with the Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score and Simplified Acute Physiology Score 2 (SAPS 2) (r= -0.35, P=0.005; r=-0.28, P=0.026; r=-0.30, P=0.019, respectively). Regarding the SOFA scores for each organ, those for the coagulation and neurological components were negatively correlated with the CFH concentration (r=-0.33, P=0.010; r=-0.25, P=0.046, respectively).Conclusion Lower plasma levels of CFH were associated with sepsis severity and mortality and were correlated with the coagulation and neurological components of the SOFA score in patients with sepsis on admission to the ICU.
A key role of gut microbiota-vagus nerve axis and gut microbiota-spleen axis in sleep deprivation-mediated aggravation of systemic inflammation after LPS administration
Authors: Zhang Yujing , Xie Bing , Lv Zheng , Qi Hong , Zhang Jiancheng , Yuan Shiying 
Published: August 2020

Abstract
Background: Sleep deprivation (SD) is shown to be correlated with exacerbated systemic inflammation after sepsis. However, the underlying mechanisms remain unclear. Methods: In this study, mice were intraperitoneally injected with lipopolysaccharide (LPS) followed by 3 consecutive days of SD. The subdiaphragmatic vagotomy (SDV) was performed 2 weeks before LPS injection. The pseudo germ-free mouse model was created by administering antibiotics for 14 consecutive days, and then fecal microbiota transplant (FMT) was performed by gavaging supernatant from fecal suspension of septic mice with or without SD into pseudo germ-free mice with or without SDV or splenectomy. Splenectomy was performed 14 days prior to antibiotics administration.Results: We found that SD after LPS administration increased the plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), reduced IL-10 plasma leve, increased spleen weight, and promoted pathological injury and IL-6 expression in lung, liver and kidney. Post-septic sleep deprivation had no effects on the diversity of gut microbiota. However, the relative abundance of Proteobacteria and its subgroups were increased in septic mice received SD. Pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD developed splenomegaly, systemic inflammation, organ inflammation and damage as their donors do. Intriguingly, SDV abolished the aggravated effects of SD on splenomegaly and inflammatory organ injury in septic mice received SD or in pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD. Furthermore, Splenectomy also abrogated the increase in IL-6 and TNF-α plasma levels and the decrease in IL-10 plasma level in pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD. Conclusions: Taken together, our results suggest that gut microbiota-vagus nerve axis and gut microbiota-spleen axis could play key roles in modulating systemic inflammation induced by SD after LPS administration.
Prevalence, Risk Factors and Outcomes of Platelet Transfusion Refractoriness in Critically Ill Patients: A Retrospective Cohort Study
Authors: Arabi Saeed , Almahayni Abdullah O , Alomair Abdulrahman , Masuadi Emad M , Damlaj Moussab , Al-Dorzi Hasan 
Published: August 2020

Abstract
Background: Refractoriness to platelet transfusion is an understudied phenomenon in critically ill patients. Our objective was to evaluate the prevalence, risk factors and clinical outcomes of platelet refractoriness among patients in a tertiary-care intensive care unit (ICU).Methods: A retrospective cohort study included all patients (age >14 years) who were admitted to a tertiary-care medical-surgical ICU between 2011 and 2016 and received ≥2 platelet transfusions during their ICU stay. We calculated platelet increment (PI) and corrected count increment (CCI). Results: A total of 267 patients were enrolled in the study, collectively receiving 1357 transfusions with a median of 3 (interquartile range: 2-6) transfusions per patient. The median pretransfusion platelet count was 31.0 x109/L (interquartile range: 16.0, 50.0) with a median PI of 6 x109/L (interquartile range: -5, 24). The prevalence of platelet transfusion refractoriness was 54.8% based on PI and 57.0% based on CCI. The two methods had excellent concordance in diagnosing refractoriness (kappa coefficient: 0.939). Refractoriness was more common in patients admitted by Hepatology, Liver Transplant, and Hematology services (69.7%, 69.2%, and 55.6%, respectively). On multivariable logistic regression, younger age was the only significant predictor of refractoriness (odds ratio per year increment: 0.975, 95% CI: 0.951-0.999). Finally, refractoriness was associated with increased length of stay in the ICU (p=0.02), but not with mortality.Conclusions: We demonstrated excellent concordance between PI and CCI for the diagnosis of platelet transfusion refractoriness. Platelet transfusion refractoriness was highly (>50%) prevalent in critically ill patients. However, it was not associated with increased mortality.
Argatroban anticoagulation for adult Extracorporeal Membrane Oxygenation: A systematic review
Authors: Geli Janos , Capoccia Massimo , Maybauer Dirk M , Maybauer Marc O 
Published: August 2020

Abstract
Background: Extracorporeal Membrane Oxygenation (ECMO) is an established method of circulatory support in critically ill patients. Heparin is the widely used anti-coagulation treatment for patients on ECMO in view of its features. Nevertheless, heparin-induced thrombocytopenia (HIT) and acquired anti-thrombin III (AT-III) deficiency may lead to sub-therapeutic anticoagulation with potentially serious consequences. Direct thrombin inhibitors are being proposed as potential alternatives with argatroban and bivalirudin as main agents. We aimed to review the evidence supporting the effectiveness and safety of argatroban as a potential definitive alternative to heparin in the adult patient population undergoing ECMO support. Methods: A web based systematic literature search was performed in Medline (PubMed) and Embase from inception until June 18th 2020. Results: The search identified 13 publications relevant to the target (4 cohort studies and 9 case series). Case reports and case series with less than 3 cases were not included in the qualitative synthesis. The aggregate number of argatroban treated patients on Extra Corporeal Life Support (ECLS) was n = 317. In the majority of studies argatroban was used as a continuous infusion without loading dose. Starting doses on ECMO varied between 0.05 and 2 μg/kg/min and were titrated to achieve the chosen therapeutic target range. The activated partial thormboplastin time (aPTT) was the anticoagulation parameter used for monitoring purposes in most studies, whereas some utilized the activated clotting time (ACT). Optimal therapeutic targets varied between 43-70 to 60-100 seconds for aPTT and 150-210 to 180-230 seconds for ACT. Bleeding and thromboembolic complication rates were comparable to patients treated with unfractionated heparin (UFH). Conclusions: Argatroban infusion rates and anticoagulation target ranges showed substantial variations. The rational for divergent dosing and monitoring approaches are discussed in this paper. Argatroban appears to be a safe and viable alternative to UFH in patients requiring ECLS. To establish an ideal dosing strategy, larger prospective studies on well-defined patient populations are warranted.
An SDF-1α Gene-activated Collagen Scaffold Restores Pro-angiogenic Wound Healing Features in Human Diabetic Adipose-derived Stem Cells
Authors: Laiva Ashang Luwang , O’Brien Fergal J. , Keogh Michael B. 
Published: August 2020

Abstract
Background: Diabetic foot ulcer is one of the leading causes of leg amputation and mortality in diabetic patients. Autologous stem cell therapy holds some potential to be a solution to this problem, however diabetic stem cells are relatively dysfunctional and restrictive in their wound healing abilities. This study sought to explore if a novel collagen-chondroitin sulfate (coll-CS) scaffold functionalized with polyplex nanoparticles carrying the gene encoding for stromal-derived factor-1 alpha (SDF-1α gene-activated scaffold) can enhance the regenerative functionality of human diabetic adipose-derived stem cells (ADSCs). Methods: Gene-activated scaffolds were first prepared by soak-loading polyethyleneimine nanoparticles carrying the plasmid encoding for SDF-1α gene into a freeze-dried coll-CS scaffold. ADSCs from healthy and diabetic donors were then seeded on the gene-activated scaffold. The response of the ADSCs in the gene-activated scaffold was then compared against those of the healthy ADSCs cultured on the gene-free scaffold over 2 weeks period. Functional response in the ADSCs such as the activation of SDF-1α mediated signaling, production of bioactive factors, pro-angiogenic bioactivity of secreted factors, matrix deposition and remodeling was determined using proteome profiling, Matrigel assay, qRT-PCR and immunofluorescence.Results: Overall, we found that SDF-1α gene-activated scaffold could restore pro-angiogenic regenerative response in the human diabetic ADSCs similar to the healthy ADSCs on the gene-free scaffold. Gene and protein expression analysis revealed that the SDF-1α gene-activated scaffold induced the overexpression of SDF-1α in diabetic ADSCs and engaged the receptor CXCR7, causing downstream signaling of β-arrestin as effectively as the transfected healthy ADSCs. The transfected diabetic ADSCs also effectively stimulated angiogenesis in endothelial cells while undergoing matrix remodeling characterized by reduction in deposition of fibronectin matrix and increase in the expression of basement membrane protein collagen IV. The SDF-1α gene-activated scaffold also induced a controlled pro- healing response in the healthy ADSCs by disabling the signaling of early developmental factors while promoting the expression of tissue remodeling components.Conclusion: We show that the SDF-1α gene-activated scaffold can overcome the deficiencies associated with diabetic ADSCs paving the way for autologous patient stem cell therapies in combination with novel biomaterials to treat diabetic foot ulcers.
Changes in Left Ventricular Electromechanical Relations During Targeted Hypothermia
Authors: Wisløff-Aase Kristin , Kerans Viesturs , Haugaa Kristina , Halvorsen Per Steinar , Skulstad Helge , Espinoza Andreas 
Published: August 2020

Abstract
Background: Targeted hypothermia, as used after cardiac arrest, increases electrical and mechanical systolic duration. Differences in duration of mechanical and electrical systole are correlated to ventricular arrhythmias. The electromechanical window (EMW) becomes negative when electrical systole outlasts the mechanical systole. Prolonged electrical systole is also associated with electrical and mechanical dispersion, both predisposing for arrhythmias. The electromechanical relations during targeted hypothermia are unknown, but treatment after cardiac arrest has not demonstrated increased incidence of ventricular arrhythmic events.We wanted to explore the electromechanical relations during hypothermia at 33 °C. We hypothesized that targeted hypothermia would increase electrical and mechanical systolic duration without an increase in electromechanical negativity, nor an increase in electrical and mechanical dispersion. Methods: In a porcine model (n = 14) we registered electrocardiogram (ECG) and echocardiographic recordings during 38 °C and 33 °C, at spontaneous and atrial paced heart rate 100 beats/min. EMW was calculated by subtracting electrical systole, QT interval, from the corresponding mechanical systole, recorded from onset QRS to aortic valve closure. Electrical dispersion was measured as time from peak to end of the ECG T wave. Mechanical dispersion was calculated by strain echocardiography as standard deviation of time to peak strain. Results:Electrical systole increased during hypothermia at spontaneous heart rate (p < 0.001) and heart rate 100 beats/min (p = 0.005). Mechanical systolic duration was prolonged and outlasted electrical systole independently of heart rate (p < 0.001). EMW changed from negative to positive value (-20 ± 19 to 27 ± 34 ms, p = 0.001). The positivity was even more pronounced at heart rate 100 beats/min (-25 ± 26 to 41 ± 18 ms, p < 0.001). Electrical dispersion decreased (p = 0.027 and p = 0.003), while mechanical dispersion did not differ (p = 0.078 and p = 0.297).Conclusion: Targeted hypothermia increased electrical and mechanical systolic duration, the electromechanical window became positive, electrical dispersion was reduced and mechanical dispersion was unchanged. These alterations may have clinical importance. Further clinical studies are required to clarify whether corresponding electromechanical alterations are accommodating in humans.