Molecular-Based Score inspired on metabolic signature improves prognostic stratification for myelodysplastic syndrome

Deregulated cellular energetics is formally incorporated as an emerging hallmark of cancer, however little is known about its processes in myelodysplastic syndromes (MDS). Using transcriptomic data of CD34+ cells from 159 MDS patients and 17 healthy donors, we selected 37 genes involved in cellular energetics and interrogated about its clinical and prognostic functions. Based on the low expression of ACLY, ANPEP, and PANK1, as well as high expression of PKM and SLC25A5, we constructed our Molecular-Based Score (MBS), that efficiently discriminated patients at three risks groups: favourable risk (n = 28; 3-year overall survival (OS): 100%); intermediate (n = 60; 76% [62–93%]) and adverse (n = 71; 35% [17–61%]). Adverse MBS risk was independently associated with inferior OS (HR = 10.1 [95% CI 1.26–81]; P = 0.029) in multivariable analysis using age, gender and the revised international prognostic score system as confounders. Transcriptional signature revealed that Favourable- and intermediate-risk patients presented enriched molecular programs related to mature myeloid progenitors, cell cycle progression, and oxidative phosphorylation, indicating that this cells differs in their origin, metabolic state, and cell cycle regulation, in comparison to the adverse-risk. Our study provides the first evidence that cellular energetics is transcriptionally deregulated in MDS CD34+ cells and establishes a new useful prognostic score based on the expression of five genes.

Generic characterization of diagnosis and prognosis for complex heterogeneous systems

Maintenance efficiency of complex industrial systems is an important economical and business issue. Main difficulties come from the choice of maintenance actions. A wrong choice can lead to maintenance costs that are not acceptable. In this paper, we propose a generic health monitoring system that integrates some diagnostic and prognostic capabilities to determine the current and future state of a large and complex system such as an aircraft. The diagnostic function aims at identifying faulty components that may cause global system failures. The prognostic function estimates the remaining time until the next global system failure. A formal and generic modeling framework for a complex system encapsulating the knowledge required to get the consistent coordination of the diagnostic and prognostic functions is presented. We propose in this framework to take into account component redundancies which is common in systems like aircrafts. Moreover, an original coupling of diagnosis and prognosis is established based on the characterization of the system operational modes and on a decentralized architecture of the monitoring system.

Biomarkers of sepsis: Time for a Reappraisal

Introduction : Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In the present review, we evaluate the progress in the research of sepsis biomarkers. Methods: Using the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms “Biomarker” AND “Sepsis”. There were no restrictions by age or language and all studies, clinical and experimental, were included. Results: We retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or C-reactive protein CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis. Conclusions : The number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular the clinical role of these biomarkers needs to be better evaluated.

Fluid Biomarkers for Predicting the Prognosis of Liver Cirrhosis

Liver cirrhosis is the terminal stage of most chronic liver conditions, with a high risk of mortality. Careful evaluation of the prognosis of cirrhotic patients and providing precise management are crucial to reduce the risk of mortality. Although the liver biopsy and hepatic venous pressure gradient (HVPG) can efficiently evaluate the prognosis of cirrhotic patients, their application is limited due to the invasion procedures. Child-Pugh score and the model for end-stage liver disease (MELD) score had been widely used in the assessment of cirrhotic prognosis, but the defects of subjective variable application in Child-Pugh score and unsuitability to all phases of liver cirrhosis in MELD score limit their prognostic values. In recent years, continuous efforts have been made to investigate the prognostic value of body fluid biomarkers for cirrhotic patients, and promising results have been reported. Since the collection of fluid specimens is easy, noninvasive, and repeatable, fluid biomarkers can be ideal indicators to predict the prognosis of cirrhosis. Here, we reviewed noninvasive fluid biomarkers in different prognostic functions, including the prediction of survival and complication development.

Biomarkers of Sepsis: Time for a Reappraisal

Introduction: Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In the present review, we evaluate the progress in the research of sepsis biomarkers.Methods: Using the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms “Biomarker” AND “Sepsis”. There were no restrictions by age or language and all studies, clinical and experimental, were included.Results: We retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or C-reactive protein CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis.Conclusions: The number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular the clinical role of these biomarkers needs to be better evaluated.

Retarded Mental Development in the Practice of Comprehensive Psychological and Psychiatric Expertise of Juvenile Offenders

The article is devoted to the problem of retarded mental development of juvenile offenders in forensic practice. The findings of male juvenile offenders (n = 30) who underwent a complex psychological and psychiatric expertise were analyzed. As a result of the study, a criminal-relevant pathopsychological symptom complex was identified in juvenile offenders with retarded mental development on organically imperfect soil. Violations manifest themselves in cognitive, emotional-volitional and personal spheres. They lead to a significant decrease in the level of arbitrary regulation, disrupting critical and prognostic functions, and deprive the minor during the time of the tort the ability to recognize and control the actual nature and public danger of his actions. In addition, partial retardation of mental development characteristic of juvenile defendants with personal immaturity without mental disorder is defined.

Interdisciplinary transforming of the functions of pedagogical comparativistics

The article presents a classification of interdisciplinary transformations of the functions of comparative pedagogy in the information age. The problem of transforming comparative pedagogy into pedagogical comparativistics was studied. The key functions of pedagogical comparativistics are revealed. Classification is considered in the evolutionary key. In the classification of the transformation of key functions, four types of evolutionary transformations were defined: 1) divergent, 2) parallel, 3) co-evolutionary, 4) convergent. Thus, the authors pointed to hybrid transformations under the influence of other sciences: cognitive neuroscience, mathematics, psychology, statistics, evaluation of results in social sciences, informatics and others. The main function was recognized as a comparative function that combines together analytical, representative, instrumental, evaluation and prognostic functions into a single whole.

Prognostic and Predictive Values of Subcellular Localisation of RET in Renal Clear-Cell Carcinoma

Metastatic renal cell carcinoma (RCC) presents a poor prognosis and an unpredictable course. To date, no validated biomarkers can predict the outcome of RCC. Ongoing efforts are conducted to identify the molecular markers of RCC progression, as well as the targets for novel therapeutic approaches. RET is a tyrosine kinase receptor which has been investigated as a possible target in other cancers because it is involved in oncogenic activation. To evaluate the predictive and prognostic functions of RET in ccRCC, a tissue microarray study was conducted on 273 ccRCC patients. Results showed that both RET cytoplasmic and nuclear expression were independently associated with PFS and OS, and the combined RET cytoplasmic and nuclear statuses demonstrated that the ratio of high nuclear RET and cytoplasmic RET was the strongest predictor of both PFS and OS. The high cytoplasmic RET expression retained its independent poor prognostic value in targeted drug treated patients. The RET nuclear expression was associated with distant metastasis. Moreover, the RET nuclear expression was an independent predictor of ccRCC postoperative metastasis. In conclusion, RET may be useful in prognostication and can be used at initial diagnosis to identify patients with high potential to develop metastasis.

Predictive and prognostic functions of microtubule-associated protein-tau and topoisomerase IIα protein in early breast cancer

e22169 Background: Topoisomerase IIα protein(topo II) is the molecular target of topo II inhibitors such as anthracyclines and Microtubule-Associated Protein(MAP)-tau protein is associated with taxane sensitivity. Anthracyclins and taxanes are major cytotoxic agents of breast cancer in the adjuvant setting. The aim of this study was to evaluate the predictive and prognostic functions of MAP-tau and topo II in early breast cancers. Methods: Representative breast tumor sections were constructed from paraffin embedded specimens from 78 node positive breast cancer patients. MAP-tau and topo II protein were assessed by immunochemistry using antibody clone 4F1(Affinity BioReagents,USA) and clone Ki-S1 antibody(Dakocytomation,USA). MAP-tau staining of tumor cells was semiquantatively scored as 0, 1+, 2+, 3+ and cases with 0 or 1+ staining intensity were considered MAP-tau negative. Topo II protein over- expression was defined as the detection of nuclear staining in more than median value of evaluated cells. Results: Thirty- four cases (43.6%) of 78 samples showed topo II overexpression and 35 cases(44.9%) showed MAP-tau overexpression in node positive breast cancers. HER2 overexpression was noted in 28 samples (35.9%) and 56 cases (71.8%) were compatible with the luminal type. In 43 patients (55.1%), anthracyclin and taxane were used as adjuvant therapy and in this group, both MAP-tau and topo II overexpression showed lower disease-free survival (DFS) than the others, but statistically not significant. In luminal type, MAP-tau overexpression was poor prognostic factor on DFS in Cox regression.(HR 5.644, 95% CI 1.14–28.07, p=0.034) Conclusions: Topo II overexpression and MAP-tau overexpression in node positive breast cancers were not significant predictive factors for anthracyclin and taxane therapies. As several investigators reported, MAP-tau is associated endocrine therapy sensitivity in patients without chemotherapy, but higher MAP-tau in luminal type was a strong poor prognostic factor in patients who were given chemotherapy and hormonal therapy. No significant financial relationships to disclose.