Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Blood Product Transfusions on the Risk of ICU-Acquired Infections in Septic Shock*

Supplemental Digital Content is available in the text. OBJECTIVES: Transfusions of blood products are common in critically ill patients and have a potential for immunomodulation. The aim of this study is to address the impact of transfusion of blood products on the susceptibility to ICU-acquired infections in the high-risk patients with septic shock. DESIGN: A single-center retrospective study over a 10-year period (2008–2017). SETTING: A medical ICU of a tertiary-care center. PATIENTS: All consecutive patients diagnosed for septic shock within the first 48 hours of ICU admission were included. Patients who were discharged or died within the first 48 hours were excluded. INTERVENTIONS: RBC, platelet, and fresh frozen plasma transfusions collected up to 24 hours prior to the onset of ICU-acquired infection. MEASUREMENTS AND MAIN RESULTS: During the study period, 1,152 patients were admitted for septic shock, with 893 patients remaining alive in the ICU after 48 hours of management. A first episode of ICU-acquired infection occurred in 28.3% of the 48-hour survivors, with a predominance of pulmonary infections (57%). Patients with ICU-acquired infections were more likely to have received RBC, platelet, and fresh frozen plasma transfusions. In a multivariate Cox cause-specific analysis, transfusions of platelets (cause-specific hazard ratio = 1.55 [1.09–2.20]; p = 0.01) and fresh frozen plasma (cause-specific hazard ratio = 1.38 [0.98–1.92]; p = 0.05) were independently associated with the further occurrence of ICU-acquired infections. CONCLUSIONS: Transfusions of platelets and fresh frozen plasma account for risk factors of ICU-acquired infections in patients recovering from septic shock. The occurrence of ICU-acquired infections should be considered as a relevant endpoint in future studies addressing the indications of transfusions in critically ill patients.
The lymphocyte-C-reactive protein ratio as the optimal inflammation-based score in patients with hepatocellular carcinoma underwent TACE

The lymphocyte-C-reactive protein ratio (LCR) is a recently described inflammation-based score, and it remains unclear which is the optimal inflammation-based score among patients with hepatocellular carcinoma (HCC) who underwent transarterial chemoembolization (TACE). A large cohort of HCC patients (n=1625) who underwent TACE as the initial treatment were enrolled in the present study. Inflammation-based scores, including the Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), high-sensitivity modified Glasgow Prognostic Score (Hs-mGPS), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and LCR, were all related to the survival of HCC patients, but only the LCR score was a significant and independent predictor in multivariate analysis (hazard ratio: 1.45; 95% confidence interval: 1.27-1.65; P<0.001). Further analysis showed that the LCR score stably and consistently differentiated subgroup patients with distinct prognoses. The predictive accuracies of the LCR score (0.70, 0.68, and 0.68 for 1-, 3-, and 5-year C-index, respectively) were superior to the other inflammatory-based scores (0.60-0.64, 0.58-0.62, and 0.58-0.62 for 1-, 3-, and 5-year C-index, respectively). The LCR score was an independent prognostic indicator for HCC patients who underwent TACE, and it was superior to the other inflammation-based scores in prognostic ability.
A Fusion Transcription Factor–Driven Cancer Progresses to a Fusion-Independent Relapse via Constitutive Activation of a Downstream Transcriptional Target

In a model of cancer initiated by a fusion transcription factor, constitutive activation of a downstream transcriptional target leads to fusion oncoprotein-independent recurrences, thereby highlighting a novel progression mechanism and therapeutic target. Targeted monotherapies usually fail due to development of resistance by a subgroup of cells that evolve into recurrent tumors. Alveolar rhabdomyosarcoma is an aggressive myogenic soft-tissue cancer that is associated with a characteristic PAX3-FOXO1 gene fusion encoding a novel fusion transcription factor. In our myoblast model of PAX3-FOXO1–induced rhabdomyosarcoma, deinduction of PAX3-FOXO1 simulates a targeted therapy that antagonizes the fusion oncoprotein. This simulated therapy results initially in regression of the primary tumors, but PAX3-FOXO1–independent recurrent tumors eventually form after a delay. We report here that upregulation of FGF8, a direct transcriptional target of PAX3-FOXO1, is a mechanism responsible for PAX3-FOXO1–independent tumor recurrence. As a transcriptional target of PAX3-FOXO1, FGF8 promoted oncogenic activity in PAX3-FOXO1–expressing primary tumors that developed in the myoblast system. In the recurrent tumors forming after PAX3-FOXO1 deinduction, FGF8 expression was necessary and sufficient to induce PAX3-FOXO1–independent tumor growth through an autocrine mechanism. FGF8 was also expressed in human PAX3-FOXO1–expressing rhabdomyosarcoma cell lines and contributed to proliferation and transformation. In a human rhabdomyosarcoma cell line with reduced PAX3-FOXO1 expression, FGF8 upregulation rescued oncogenicity and simulated recurrence after PAX3-FOXO1–targeted therapy. We propose that deregulated expression of a PAX3-FOXO1 transcriptional target can generate resistance to therapy directed against this oncogenic transcription factor and postulate that this resistance mechanism may ultimately be countered by therapeutic approaches that antagonize the corresponding downstream pathways. Significance: In a model of cancer initiated by a fusion transcription factor, constitutive activation of a downstream transcriptional target leads to fusion oncoprotein-independent recurrences, thereby highlighting a novel progression mechanism and therapeutic target.
Molecular Orientation of E7 Liquid Crystal in POLICRYPS Holographic Gratings: A Micro-Raman Spectroscopic Analysis

Micro-Raman Spectroscopy was used to determine the orientation of the E7 nematic liquid crystal molecules inside the POLICRYPS (POlymer LIquid CRYstal Polymer Slices) holographic gratings. The POLICRYPS grating was analyzed after defining the Raman features of each single component of the system: i.e the random aligned nematic liquid crystal E7 and Norland Optical Adhesive (NOA-61). Among the Raman bands of the liquid crystal molecules, a specific one was selected, which exhibits strong anisotropy of the Raman tensor. The modulation of its intensity, depending on the sample orientation with respect to the laser polarization, provided the experimental evidence about the orientation of the E7 molecules, which occurred to be perpendicular to the polymeric slices.
The Effect of Laser Bio‐modulation on Dysplastic Lesions, an Animal Study

Potentially malignant disorders are one of the clinical challenges. Dysplasia in these lesions can be a predictor of more potential for malignant changes. Photo‐bio‐modulation in benign lesions has advantages, but there is doubt on its safety in potentially malignant lesions. This study aims to assess if low‐level laser can promote dysplastic changes while the method can play an important role in management of dysplastic lesions. Dysplasia was induced on anterior wall of the buccal pouch of 80 young Syrian male hamsters. Then, hamsters were divided to four groups to receive 4 and 12 sessions irradiation of 660 and 810 nanometers low‐level lasers. For histopathologic study of the tissue, we used light microscopes. Using SPSS, data were analyzed via Wilcoxon signed rank test and Mann–Whitney U‐test. In all of our four groups, the severity of dysplasia had no statistical difference in study sides comparing with their own controls. Wavelength and numbers of laser irradiation sessions had no statistically meaningful effect on the severity of dysplasia either. Low‐level lasers appear to show no relevant or significant effect over the aggravation of the dysplasia's severity. Neither the wavelength nor the number of sessions appear to have any impact in the results.
Essential oils from Artemisia species inhibit biofilm formation and the virulence of Escherichia coli EPEC 2348/69

Abstract Enteropathogenic Escherichia coli E2346/69 (EPEC) has caused foodborne outbreaks worldwide and the bacterium forms antimicrobial-tolerant biofilms. The anti-biofilm formation of various components of essential oils extracted from selected medicinal plants were investigated and tested on EPEC and wild strains of E. coli. Oils extracted from the family Asteraceae and their major common constituents at 0.031 and 0.062% (V/v) were found to significantly inhibit biofilm formation without affecting the growth of planktonic cells. In addition, three plants belonging to this family (Artemisia herba alba, Artemisia campestris and Artemisia absinthium) played important roles in the antimicrobial activity. Interestingly, their essential oils reduced the ability of E. coli (the EPEC and K12 strains) to form a biofilm. The crystal violet reduction assay showed that the plant extracts tested reduced biofilm formation with the inhibition of bacterial attachment up to 45% for EPEC and 70% for E. coli K-12 after 24 h treatment at 0.62 mg ml−1, demonstrating that Artemisia oils had a high anti-biofilm activity on the bacteria tested. The results indicate that the locus of enterocyte effacement (LEE) acquired by horizontal transfer promotes the formation of the attaching and effacing (A/E) lesion and increases the capacity of the photogen strain (EPEC) to form a biofilm. The chemical composition of the volatile compounds was obtained by gas chromatography-mass spectrometry analysis, which showed that the essential oils consisted of thirty-four compounds. Chamazulene (39.21%), β-pinene (32.07%), and α-thujone (29.39%) were the main constituents of the essential oils of A. herba alba, A. absinthium and A. campestris, respectively.
Cell Cycle–Dependent Regulation and Function of ARGONAUTE1 in Plants[OPEN]

Cell cycle–dependent accumulation of small RNAs associated with ARGONAUTE1 and their targets. Regulated gene expression is key to the orchestrated progression of the cell cycle. Many genes are expressed at specific points in the cell cycle, including important cell cycle regulators, plus factors involved in signal transduction, hormonal regulation, and metabolic control. We demonstrate that post-embryonic depletion of Arabidopsis (Arabidopsis thaliana) ARGONAUTE1 (AGO1), the main effector of plant microRNAs (miRNAs), impairs cell division in the root meristem. We utilized the highly synchronizable tobacco (Nicotiana tabacum) Bright yellow 2 (BY2) cell suspension to analyze mRNA, small RNAs, and mRNA cleavage products of synchronized BY2 cells at S, G2, M, and G1 phases of the cell cycle. This revealed that in plants, only a few miRNAs show differential accumulation during the cell cycle, and miRNA-target pairs were only identified for a small proportion of the more than 13,000 differentially expressed genes during the cell cycle. However, this unique set of miRNA-target pairs could be key to attenuate the expression of several transcription factors and disease resistance genes. We also demonstrate that AGO1 binds to a set of 19-nucleotide, tRNA-derived fragments during the cell cycle progression.
METTL3-mediated m6A methylation negatively modulates autophagy to support porcine blastocyst development‡

Abstract N6-methyladenosine (m6A) catalyzed by METTL3 regulates the maternal-to-zygotic transition in zebrafish and mice. However, the role and mechanism of METTL3-mediated m6A methylation in blastocyst development remains unclear. Here, we show that METTL3-mediated m6A methylation sustains porcine blastocyst development via negatively modulating autophagy. We found that reduced m6A levels triggered by METTL3 knockdown caused embryonic arrest during morula-blastocyst transition and developmental defects in trophectoderm cells. Intriguingly, overexpression of METTL3 in early embryos resulted in increased m6A levels and these embryos phenocopied METTL3 knockdown embryos. Mechanistically, METTL3 knockdown or overexpression resulted in a significant increase or decrease in expression of ATG5 (a key regulator of autophagy) and LC3 (an autophagy marker) in blastocysts, respectively. m6A modification of ATG5 mRNA mainly occurs at 3'UTR, and METTL3 knockdown enhanced ATG5 mRNA stability, suggesting that METTL3 negatively regulated autophagy in an m6A dependent manner. Furthermore, single-cell qPCR revealed that METTL3 knockdown only increased expression of LC3 and ATG5 in trophectoderm cells, indicating preferential inhibitory effects of METTL3 on autophagy activity in the trophectoderm lineage. Importantly, autophagy restoration by 3MA (an autophagy inhibitor) treatment partially rescued developmental defects of METTL3 knockdown blastocysts. Taken together, these results demonstrate that METTL3-mediated m6A methylation negatively modulates autophagy to support blastocyst development. Summary sentence METTL3 sustains porcine blastocyst development via inhibiting autophagy.
Combining the Copenhagen Adduction Exercise and Nordic Hamstring Exercise Improves Dynamic Balance Among Male Athletes: A Randomized Controlled Trial

Background: Copenhagen adduction exercise (CAE) and Nordic hamstring exercise (NHE) reduce the incidence of groin and hamstring injuries. Efficient dynamic balance can improve motor performance and reduce the risk of injuries in athletes. However, the effects of these exercises on dynamic balance have not been investigated. Hypothesis: CAE and NHE, as well as a combination of both exercises, would improve dynamic balance among amateur male athletes. Study Design: Randomized controlled trial. Level of Evidence: Level 1. Methods: A total of 200 male athletes aged 21.9 ± 2.4 years were included in the study and randomly assigned to 4 groups: CAE group (n = 50), NHE group (n = 50), CAE and NHE group (n = 50), and a control group (n = 50). A total of 177 male athletes completed the study. The primary outcome measure was the limit of stability (LoS), which was measured using the Biodex Stability System to assess the performance of the dynamic balance. The LoS of the athletes’ performance was measured pre- and postintervention after 6 weeks. Results: The LoS significantly improved in all treatment groups, including CAE (44.5% ± 5.3%), NHE (43.2% ± 5.3%), and CAE + NHE (48.4% ± 5.1%) groups when compared with the control group (28.3% ± 4.8%) after 6 weeks (all Ps < 0.01). The improvement of LoS was significantly greater in the CAE + NHE group compared with other groups (CAE, NHE, and control groups). Conclusion: There was a significant increase in dynamic balance performance postintervention among male athletes. CAE and NHE may improve injury prevention programs. Clinical Relevance: The results of this study provide evidence for athlete trainers and coaches to consider including the CAE and NHE as components of injury prevention programs to improve balance capacity and performance in athletes. Such improvements in balance may prevent injury risk and decrease absenteeism and injury-related financial burdens.
von Willebrand Factor Multimer Formation Contributes to Immunothrombosis in Coronavirus Disease 2019

Supplemental Digital Content is available in the text. OBJECTIVES: Prevention and therapy of immunothrombosis remain crucial challenges in the management of coronavirus disease 2019, since the underlying mechanisms are incompletely understood. We hypothesized that endothelial damage may lead to substantially increased concentrations of von Willebrand factor with subsequent relative deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). DESIGN: Prospective controlled cross-over trial. SETTING: Blood samples of patients with confirmed coronavirus disease 2019 and healthy controls were obtained in three German hospitals and analyzed in a German hemostaseologic laboratory. PATIENTS: Seventy-five patients with confirmed coronavirus disease 2019 of mild to critical severity and 30 healthy controls. MEASUREMENTS AND MAIN RESULTS: von Willebrand factor antigen, ADAMTS13, and von Willebrand factor multimer formation were analyzed. von Willebrand factor antigen was 4.1 times higher in COVID-19 patients compared with healthy controls (p < 0.0001), whereas ADAMTS13 activities were not significantly different (p = 0.18). The ADAMTS13/von Willebrand factor antigen ratio was significantly lower in COVID-19 than in the control group (24.4 ± 20.5 vs 82.0 ± 30.7; p < 0.0001). Fourteen patients (18.7%) undercut a critical ratio of 10 as described in thrombotic thrombocytopenic purpura. Gel analysis of multimers resembled a thrombotic thrombocytopenic purpura pattern with loss of the largest multimers in 75% and a smeary triplet pattern in 39% of the patients. The ADAMTS13/von Willebrand factor antigen ratio decreased continuously from mild to critical disease (analysis of variance p = 0.026). Furthermore, it differed significantly between surviving patients and those who died from COVID-19 (p = 0.001) yielding an area under the curve of 0.232 in receiver operating characteristic curve curve analysis. Conclusion: COVID-19 is associated with a substantial increase in von Willebrand factor levels, which can exceed the ADAMTS13 processing capacity resulting in the formation of large von Willebrand factor multimers indistinguishable from thrombotic thrombocytopenic purpura. The ADAMTS13/von Willebrand factor antigen ratio is an independent predictor of severity of disease and mortality. These findings provide a rationale to consider plasma exchange as a therapeutic option in COVID-19 and to include von Willebrand factor and ADAMTS13 in the diagnostic workup.
OMEGA—open-source emission tomography software

In this paper we present OMEGA, an open-source software, for efficient and fast image reconstruction in positron emission tomography (PET). OMEGA uses the scripting language of MATLAB and GNU Octave allowing reconstruction of PET data with a MATLAB or GNU Octave interface. The goal of OMEGA is to allow easy and fast reconstruction of any PET data, and to provide a computationally efficient, easy-access platform for development of new PET algorithms with built-in forward and backward projection operations available to the user as a MATLAB/Octave class. OMEGA also includes direct support for GATE simulated data, facilitating easy evaluation of the new algorithms using Monte Carlo simulated PET data. OMEGA supports parallel computing by utilizing OpenMP for CPU implementations and OpenCL for GPU allowing any hardware to be used. OMEGA includes built-in function for the computation of normalization correction and allows several other corrections to be applied such as attenuation, randoms or scatter. OMEGA includes several different maximum-likelihood and maximum a posteriori (MAP) algorithms with several different priors. The user can also input their own priors to the built-in MAP functions. The image reconstruction in OMEGA can be computed either by using an explicitly computed system matrix or with a matrix-free formalism, where the latter can be accelerated with OpenCL. We provide an overview on the software and present some examples utilizing the different features of the software.
Inference of symbiotic adaptations in nature using experimental evolution

Microbes must adapt to the presence of other species, but it can be difficult to recreate the natural context for these interactions in the laboratory. We describe a method for inferring the existence of symbiotic adaptations by experimentally evolving microbes that would normally interact in an artificial environment without access to other species. By looking for changes in the fitness effects microbes adapted to isolation have on their partners, we can infer the existence of ancestral adaptations that were lost during experimental evolution. The direction and magnitude of trait changes can offer useful insight as to whether the microbes have historically been selected to help or harm one another in nature. We apply our method to the complex symbiosis between the social amoeba Dictyostelium discoideum and two intracellular bacterial endosymbionts, Paraburkholderia agricolaris and Paraburkholderia hayleyella. Our results suggest P. hayleyella—but not P. agricolaris—has generally been selected to attenuate its virulence in nature, and that D. discoideum has evolved to antagonistically limit the growth of Paraburkholderia. The approach demonstrated here can be a powerful tool for studying adaptations in microbes, particularly when the specific natural context in which the adaptations evolved is unknown or hard to reproduce.
Outcomes of Pediatric Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis

Supplemental Digital Content is available in the text. OBJECTIVE: The goal of this work is to provide insight into survival and neurologic outcomes of pediatric patients supported with extracorporeal cardiopulmonary resuscitation. DATA SOURCES: A systematic search of Embase, PubMed, Cochrane, Scopus, Google Scholar, and Web of Science was performed from January 1990 to May 2020. STUDY SELECTION: A comprehensive list of nonregistry studies with pediatric patients managed with extracorporeal cardiopulmonary resuscitation was included. DATA EXTRACTION: Study characteristics and outcome estimates were extracted from each article. DATA SYNTHESIS: Estimates were pooled using random-effects meta-analysis. Differences were estimated using subgroup meta-analysis and meta-regression. The Meta-analyses Of Observational Studies in Epidemiology guideline was followed and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation system. Twenty-eight studies (1,348 patients) were included. There was a steady increase in extracorporeal cardiopulmonary resuscitation occurrence rate from the 1990s until 2020. There were 32, 338, and 1,094 patients’ articles published between 1990 and 2000, 2001 and 2010, and 2010 and 2020, respectively. More than 70% were cannulated for a primary cardiac arrest. Pediatric extracorporeal cardiopulmonary resuscitation patients had a 46% (CI 95% = 43–48%; p < 0.01) overall survival rate. The rate of survival with favorable neurologic outcome was 30% (CI 95% = 27–33%; p < 0.01). CONCLUSIONS: The use of extracorporeal cardiopulmonary resuscitation is rapidly expanding, particularly for children with underlying cardiac disease. An overall survival of 46% and favorable neurologic outcomes add credence to this emerging therapy.