Optimal multiparametric set-up modelled for best survival outcomes in palliative treatment of liver malignancies: unsupervised machine learning and 3 PM recommendations.

Over the last decade, a rapid rise in deaths due to liver disease has been observed especially amongst young people. Nowadays liver disease accounts for approximately 2 million deaths per year worldwide: 1 million due to complications of cirrhosis and 1 million due to viral hepatitis and hepatocellular carcinoma. Besides primary liver malignancies, almost all solid tumours are capable to spread metastases to the liver, in particular, gastrointestinal cancers, breast and genitourinary cancers, lung cancer, melanomas and sarcomas. A big portion of liver malignancies undergo palliative care. To this end, the paradigm of the palliative care in the liver cancer management is evolving from "just end of the life" care to careful evaluation of all aspects relevant for the survivorship. In the presented study, an evidence-based approach has been taken to target molecular pathways and subcellular components for modelling most optimal conditions with the longest survival rates for patients diagnosed with advanced liver malignancies who underwent palliative treatments. We developed an unsupervised machine learning (UML) approach to robustly identify patient subgroups based on estimated survival curves for each individual patient and each individual potential biomarker. UML using consensus hierarchical clustering of biomarker derived risk profiles resulted into 3 stable patient subgroups. There were no significant differences in age, gender, therapy, diagnosis or comorbidities across clusters. Survival times across clusters differed significantly. Furthermore, several of the biomarkers demonstrated highly significant pairwise differences between clusters after correction for multiple testing, namely, "comet assay" patterns of classes I, III, IV and expression rates of calgranulin A (S100), SOD2 and profilin-all measured ex vivo in circulating leucocytes. Considering worst, intermediate and best survival curves with regard to identified clusters and corresponding patterns of parameters measured, clear differences were found for "comet assay" and S100 expression patterns. In conclusion, multi-faceted cancer control within the palliative care of liver malignancies is crucial for improved disease outcomes including individualised patient profiling, predictive models and implementation of corresponding cost-effective risks mitigating measures detailed in the paper. The "proof-of-principle" model is presented.

Liquid biopsy and multiparametric analysis in management of liver malignancies: new concepts of the patient stratification and prognostic approach.

BACKGROUND: The annually recorded incidence of primary hepatic carcinomas has significantly increased over the past two decades accounting for over 800 thousand of annual deaths caused by hepatocellular carcinoma (HCC) alone globally. Further, secondary liver malignancies are much more widespread compared to primary hepatic carcinomas: almost all solid malignancies are able to metastasise into the liver. The primary tumours most frequently metastasising to the liver are breast followed by colorectal carcinomas. Given the increased incidence of both primary and metastatic liver cancers, a new, revised approach is needed to advance medical care based on predictive diagnostics, innovative screening programmes, targeted preventive measures, and patient stratification for treatment algorithms tailored to individualised patient profile. ADVANTAGES OF THE APPROACH TAKEN: The current pilot study took advantage of systemic alterations characteristic for liver malignancies, utilising liquid biopsy (blood samples) and specific biomarker patterns detected. Key molecular pathways relevant for pathomechanisms of liver cancers have been considered opening a perspective for both-individualised diagnostics and targeted treatment. Systemic alterations have been analysed prior to the therapy application avoiding molecular biological effects potentially diminishing predictive power of the biomarker-panel proposed. Multi-omics at DNA and protein (both expression and activity) levels has been applied. An established biomarker panel is considered as a powerful tool for individualised patient profiling and improved multi-level diagnostics-both predictive and prognostic ones. RESULTS AND CONCLUSIONS: Biomarker panels have been created for the patient stratification, prediction of a more optimal therapy and prognosis of survival based on the individualised patient profiling. Although there are some limitations of the pilot study performed, the results are encouraging, as it may be possible, through further research along these lines, to find a clinically and cost-effective means of stratifying liver cancer patients for personalised care and therapy. The benefits to the patient and society of accurate treatment stratification cannot be overemphasised.

Premenopausal breast cancer: potential clinical utility of a multi-omics based machine learning approach for patient stratification.

BACKGROUND: The breast cancer (BC) epidemic is a multifactorial disease attributed to the early twenty-first century: about two million of new cases and half a million deaths are registered annually worldwide. New trends are emerging now: on the one hand, with respect to the geographical BC prevalence and, on the other hand, with respect to the age distribution. Recent statistics demonstrate that young populations are getting more and more affected by BC in both Eastern and Western countries. Therefore, the old rule "the older the age, the higher the BC risk" is getting relativised now. Accumulated evidence shows that young premenopausal women deal with particularly unpredictable subtypes of BC such as triple-negative BC, have lower survival rates and respond less to conventional chemotherapy compared to the majority of postmenopausal BC. WORKING HYPOTHESIS: Here we hypothesised that a multi-level diagnostic approach may lead to the identification of a molecular signature highly specific for the premenopausal BC. A multi-omic approach using machine learning was considered as a potent tool for stratifying patients with benign breast alterations into well-defined risk groups, namely individuals at high versus low risk for breast cancer development. RESULTS AND CONCLUSIONS: The study resulted in identifying multi-omic signature specific for the premenopausal BC that can be used for stratifying patients with benign breast alterations. Our predictive model is capable of discriminating individually between high and low BC-risk with high confidence (>90%) and considered of potential clinical utility. Novel risk assessment approaches and advanced screening programmes-as the long-term target of this project-are of particular importance for predictive, preventive and personalised medicine as the medicine of the future, due to the expected health benefits for young subpopulations and the healthcare system as a whole.

Multi-omic approach decodes paradoxes of the triple-negative breast cancer: lessons for predictive, preventive and personalised medicine.

Breast cancer epidemic in the early twenty-first century results in around two million new cases and half-a-million of the disease-related deaths registered annually worldwide. A particularly dramatic situation is attributed to some specific patient subgroups such as the triple-negative breast cancer (TNBC). TNBC is a particularly aggressive type of breast cancer lacking clear diagnostic approach and targeted therapies. Consequently, more than 50% of the TNBC patients die of the metastatic BC within the first 6 months of the diagnosis. In the current study we have hypothesised that multi-omic approach utilising blood samples may lead to discovery of a unique molecular signature of the TNBC subtype. The results achieved demonstrate, indeed, multi-omics as highly promising approach that could be of great clinical utility for development of predictive diagnosis, targeted prevention and treatments tailored to the person-overall advancing the management of the TNBC.

Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine.

Whereas the physiologic wound healing (WH) successfully proceeds through the clearly defined sequence of the individual phases of wound healing, chronic non-healing wounds/ulcers fail to complete the individual stages and the entire healing process. There are many risk factors both modifiable (such as stress, smoking, inappropriate alcohol consumption, malnutrition, obesity, diabetes, cardio-vascular disease, etc.) and non-modifiable (such as genetic diseases and ageing) strongly contributing to the impaired WH. Current statistics demonstrate that both categories are increasingly presented in the populations, which causes dramatic socio-economic burden to the healthcare sector and society at large. Consequently, innovative concepts by predictive, preventive and personalised medicine are crucial to be implemented in the area. Individual risk factors, causality, functional interrelationships, molecular signature, predictive diagnosis, and primary and secondary prevention are thoroughly analysed followed by the expert recommendations in this paper.

Breast cancer risk assessment: a non-invasive multiparametric approach to stratify patients by MMP-9 serum activity and RhoA expression patterns in circulating leucocytes.

Breast cancer is a multifactorial disease classified by several sub-types which differ from each other by risk factors, specific molecular promoters and severity of outcomes. Tumour aggressiveness and metastatic disease are the key determinants of breast cancer outcomes. Tumour cell ability to degrade the extracellular matrix and to be motile is the hallmark of invasion and essential step in a development of breast cancer metastatic disease. Therefore, a coordinated action between cell motility and ability to degrade the extracellular matrix is currently under extensive investigation focused on molecular targets for both diagnostic and therapeutic purposes. Contextually, our current study was dedicated to patient stratification utilising MMP-9 serum activity levels and RhoA expression patterns measured in circulating leucocytes. Biomarker patterns were "masked" in non-stratified patient groups. In contrast, the multiparametric stratification approach led to highly improved clinical utility of biomarker patterns. Presented stratification system is recommended for population screening as a cost-effective non-invasive approach to facilitate predictive diagnostics of breast cancer predisposition, pre-lesions and early stages, when the pathology can be effectively prevented or cured. Proposed approach might be particularly useful for early and predictive breast cancer diagnostics applied to certain phenotypes such as premenopausal rather than postmenopausal women, women with dense breast tissue, where highly increased RhoA/MMPs activities are utilised for effective proteolysis of the matrix and cancer cell migration into dense matrices, as well as for breast cancer of unclear origin such as particularly aggressive triple-negative sub-type.

Breast cancer epidemic in the early twenty-first century: evaluation of risk factors, cumulative questionnaires and recommendations for preventive measures.

Rapidly increasing incidence of breast cancer is a new social challenge resulting from a spectrum of internal and external risk factors which appear to be well accepted as an attribute of the early twenty-first century, being, however, new for female sub-populations compared to the past. These include altered socio-economical conditions such as occupational exposure, rotating shift work, specific environmental factors (increased pollution and environmental toxicity, altered dietary habits, quality and composition of meal) as well as consequently shifted and/or adapted physiologic factors such as lower age at menarche, late age of first full-term pregnancy, if any, shorter periods of breastfeeding and later menopause. Consolidated expert statements suggest that over 50 % of all breast cancer cases may be potentially prevented by risk reduction strategy such as regulation of modifiable risk factors. Currently available risk assessment models may estimate potential breast cancer predisposition, in general; however, they are not able to predict the disease manifestation individually. Further, current deficits in risk assessment and effective breast cancer prevention have been recently investigated and summarised as follows: gaps in risk estimation, preventive therapy, lifestyle prevention, understanding of the biology of breast cancer risk and implementation of known preventive measures. This paper overviews the most relevant risk factors, provides recommendations for improved risk assessment and proposes an extended questionnaire for effective preventive measures.

Patients with hepatic breast cancer metastases demonstrate highly specific profiles of matrix metalloproteinases MMP-2 and MMP-9 after SIRT treatment as compared to other primary and secondary liver tumours.

BACKGROUND: Patients with primary and metastatic liver malignancies represent a highly heterogeneous patient pool characterised by some of the shortest life expectancies amongst oncology patients. Investigation and better understanding of liver malignancies is an emerging field which requires high-quality multidisciplinary research and collaboration. METHODS: A study of 158 patients with primary hepatic carcinomas and secondary liver metastases, altogether 15 cancer types of different origin, who underwent selective internal radiation therapy (SIRT) with Yttrium(90) or transarterial chemoembolisation, was undertaken in an effort to detect distinguishing features with respect to activity profiles of both blood matrix metalloproteinase (MMP-2 and MMP-9). RESULTS: Noteworthy, stratification of all hepatic cancer groups with respect to MMP-2 and MMP-9 activities revealed characteristic patterns specifically in patients with hepatic breast cancer metastases who had undergone SIRT. In contrast to all other groups, these patients demonstrated well-consolidated profiles of both MMPs, reflecting a common feature, namely an immediate and durable increase of their activity after the SIRT treatment. Although the total number of patients in the breast cancer group is relatively small (15 patients), since increased activities of MMP-2 and MMP-9 are well known prognostic factors for poor outcomes of oncologic patients, the significance and clear group-specificity (from 15 ones investigated here) of this previously unanticipated finding requires particular attention and further investigations. Particularly important is to determine, whether this increase of the metalloproteinase activity was provoked by SIRT, as well as whether special selection criteria are required for patients with breast cancer metastases to the liver who are being considered for SIRT. CONCLUSIONS: It is recommended that a more focused, multidisciplinary and large-scaled investigations of the possible adverse effects of SIRT in patients with advanced metastatic disease of breast cancer be undertaken, with an appropriate patients' stratification, set-up of the relevant patient profiles and disease modelling.

Selective internal radiation therapy in treatment of hepatocellular carcinoma: new concepts of personalization.

Hepatocellular carcinoma (HCC) is a global health problem, with more than half a million new cases diagnosed annually and mortality rates at similar level. The majority of HCC is diagnosed at intermediate-advanced stages being, therefore, an issue for palliative rather than curative care. Selective internal radiation therapy (SIRT) is one of the best appropriate palliative treatment modalities in HCC management. Although delivering satisfactory results, SIRT application comes along with frequent complications and tumor recurrence. Recent studies suggest treatment algorithm tailored to the person as improving individual outcomes and reducing treatment-related complications. This review provides insights to implicate innovative concepts of predictive, preventive and personalized medicine in SIRT application to HCC cohorts.

Potential biomarker panels in overall breast cancer management: advancements by multilevel diagnostics.

Breast cancer (BC) prevalence has reached an epidemic scale with half a million deaths annually. Current deficits in BC management include predictive and preventive approaches, optimized screening programs, individualized patient profiling, highly sensitive detection technologies for more precise diagnostics and therapy monitoring, individualized prediction and effective treatment of BC metastatic disease. To advance BC management, paradigm shift from delayed to predictive, preventive and personalized medical services is essential. Corresponding step forwards requires innovative multilevel diagnostics procuring specific panels of validated biomarkers. Here, we discuss current instrumental advancements including genomics, proteomics, epigenetics, miRNA, metabolomics, circulating tumor cells and cancer stem cells with a focus on biomarker discovery and multilevel diagnostic panels. A list of the recommended biomarker candidates is provided.

'Suspect molecular signature' in blood as the indicator of undiagnosed breast cancer, cancer risk and targeted prevention.

BACKGROUND: Breast cancer is a multifactorial disease with the highest incidence rates amongst all cancer types. Further, high levels of circulating tumour cells are a characteristic of breast cancer patients demonstrating a particular predisposition to the development of breast cancer metastatic disease. Actual diagnostic approaches are frequently unable to recognise early stages of tumour development which impairs individual outcomes. In contrast, predictive and preventive risk assessment and early diagnosis may lead to full recovery after surgical resection. Recently, the authors have reported about the construction of diagnostic windows, which could influence the molecular diagnostics of breast cancer. MATERIAL AND METHODS: In a previous study, diagnostic windows for breast cancer risk assessment were analysed. Women with non-malignant breast diseases demonstrating molecular profiles similar to those of breast cancer patients were enrolled into this follow-up study. In the interviews, for patients identified as predisposed to cancer, a specialised questionnaire has been set up to characterise individual risk factors and estimate their potential impacts on cancer onset and progression. RESULTS AND CONCLUSIONS: By utilising the technological tool of diagnostic windows, 13 individuals have been identified demonstrating molecular profiles typical for patients diagnosed with breast cancer. The current paper summarises the analytical results and makes statements to the application of the pathology-specific molecular profiles recognised as the technological tool for improved diagnostic approach, breast cancer risk assessment and preventive health care management. The necessity to create individual patient profiles and analyse the evolution of the molecular signature is justified for advanced medical services. Expert recommendations are provided to promote further developments in the field of advanced breast cancer management.

Differences in gene expression in lymphocytes of patients with high-tension, PEX, and normal-tension glaucoma and in healthy subjects.

PURPOSE: Purpose Differences in the gene expression of leukocytes between patients with normal-tension glaucoma (NTG) and controls have been described. This study was performed in order to detect the differences in gene expression in peripheral lymphocytes in patients with primary open-angle glaucoma (POAG), patients with pseudoexfoliation glaucoma (PEX), and patients with NTG, and in healthy subjects. METHODS: Ten patients with POAG, 11 patients with PEX, 10 patients with NTG, and 42 sex- and age-matched healthy persons were recruited. All study subjects were Caucasian. Twenty-two preselected genes were chosen and their expression in blood lymphocytes was quantified by real-time PCR. First, a univariate comparison among all groups was performed using the nonparametric Friedman test. Second, an L1 penalized logistic regression was performed. RESULTS: Using the Friedman test to compare the 4 groups, 9 genes showed a different expression (p<0.05). Comparing the controls vs patients with POAG, 8 genes were differently expressed (p<0.05). Comparing patients with PEX vs controls, 9 genes were significantly different (p≤0.05). The statistical analysis of patients with NTG vs controls showed a difference in gene expression of 7 genes (p≤0.05). All these genes were upregulated in the glaucoma groups compared with the controls. The genes RhoGDI and RAR showed the most significant statistical difference in the L1-penalized logistic regression. The genes overexpressed in POAG/PEX differed from the ones in NTG. CONCLUSIONS: In this masked study among the preselected 22 genes, several genes are overexpressed in the blood lymphocytes of Caucasian patients with glaucoma compared with the controls. The genes upregulated in POAG/PEX differed from the ones in NTG.

Risk assessment, disease prevention and personalised treatments in breast cancer: is clinically qualified integrative approach in the horizon?

Breast cancer is a multifactorial disease. A spectrum of internal and external factors contributes to the disease promotion such as a genetic predisposition, chronic inflammatory processes, exposure to toxic compounds, abundant stress factors, a shift-worker job, etc. The cumulative effects lead to high incidence of breast cancer in populations worldwide. Breast cancer in the USA is currently registered with the highest incidence rates amongst all cancer related patient cohorts. Currently applied diagnostic approaches are frequently unable to recognise early stages in tumour development that impairs individual outcomes. Early diagnosis has been demonstrated to be highly beneficial for significantly enhanced therapy efficacy and possibly full recovery. Actual paper shows that the elaboration of an integrative diagnostic approach combining several levels of examinations creates a robust platform for the reliable risk assessment, targeted preventive measures and more effective treatments tailored to the person in the overall task of breast cancer management. The levels of examinations are proposed, and innovative technological approaches are described in the paper. The absolute necessity to create individual patient profiles and extended medical records is justified for the utilising by routine medical services. Expert recommendations are provided to promote further developments in the field.

Opinion controversy to chromium picolinate therapy's safety and efficacy: ignoring 'anecdotes' of case reports or recognising individual risks and new guidelines urgency to introduce innovation by predictive diagnostics?

Due to the important physiologic function of trivalent chromium in glucose/insulin homeostasis, some commercial organisations promote Cr3+ supplements in maintaining proper carbohydrate and lipid metabolism; regulation of reducing carbohydrate carvings and appetite; prevention of insulin resistance and glucose intolerance; regulation of body composition, including reducing fat mass and increasing lean body mass; optimal body building for athletes; losing weight; treatment of atypical depression as an antidepressant; and prevention of obesity and type 2 diabetes mellitus. On one hand, case reports are commented as 'nonevidence-based anecdotes'. On the other hand, a number of independent studies warn against adverse health outcomes assigned to chromium picolinate (CrPic) dietary application. This review analyses opinion controversies, demonstrates highly individual reactions towards CrPic dietary supplements and highlights risks when the dietary supplements are used freely as therapeutic agents, without application of advanced diagnostic tools to predict individual outcomes.

Chromium-picolinate therapy in diabetes care: individual outcomes require new guidelines and navigation by predictive diagnostics.

AIMS: Nephropathy is the leading secondary complication of metabolic syndrome. Nutritional supplement by chromium-picolinate is assumed to have renoprotective effects. However, potential toxic effects reported increase the concerns about the safety of chromium-picolinate. The experimental design aimed at determining, whether the treatment with clinically relevant doses of chromium-picolinate can harm individual oucomes through DNA damage and extensive alterations in central detoxification / cell-cycle regulating pathways in treatment of diabetes. METHODS: The study was performed in a double-blind manner. Well-acknowledged animal model of db/db-mice and clinically relevant doses of chromium- picolinate were used. As an index of DNA-damage, measurement of DNA-breaks was performed using "Comet Assay"-analysis. Individual and group-specific expression patterns of SOD-1 and P53 were evaluated to get insights into central detoxification and cell-cycle regulating pathways under the treatment conditions. RESULTS: Experimental data revealed highly individual reaction towards the treatment conditions. The highest variability of DNA-damage was monitored under the prolonged treatment with high dosage of CrPic. Expression patterns demonstrated a correlation with the subcellular imaging and dosage-dependent suppression under the chromium-picolinate treatment. INTERPRETATION AND RECOMMENDATIONS: Population at-risk for diabetes is huge and increasing in pandemic scale. One of the reasons might be the failed attempt to prevent the disease by application of artificial supplements and drugs with hardly recognised individual risks. Consequently, a multimodal approach of integrative medicine by predictive diagnostics, targeted prevention and individually created treatment algorithms is highly desirable.

Chromium-picolinate therapy in diabetes care: molecular and subcellular profiling revealed a necessity for individual outcome prediction, personalised treatment algorithms and new guidelines.

AIMS: Global figures clearly demonstrate inadequacy of current diabetes care: every 10 seconds one patient dies of diabetes-related pathologies. Nephropathy is the leading secondary complication of the disease. Nutritional supplement by chromium-picolinate is assumed to have beneficial therapeutic effects. However, potential toxic effects reported increase concerns about safety of chromium-picolinate. The experimental design aimed at determining, whether the treatment with clinically relevant doses of chromium-picolinate can harm through DNA damage and extensive alterations in central detoxification / cell-cycle regulating pathways in treatment of diabetes. METHODS: Well-acknowledged animal model of db/db-mice and clinically relevant doses of chromium-picolinate were used. As an index of DNA-damage, measurement of DNA-breaks was performed using "Comet Assay"-analysis. Individual and group-specific expression patterns of SOD-1 and P53 were evaluated to give a clue about central detoxification and cell-cycle regulating pathways under treatment conditions. The study was performed in a double-blind manner. RESULTS: Experimental data revealed highly individual reaction under treatment conditions. However, group-specific patterns were monitored: highest amount of damaged DNA--under the longest treatment with high doses, in contrast to groups with low doses of chromium-picolinate. Comet patterns were intermediate between untreated diabetised and control animals. Expression patterns demonstrated a correlation with subcellular imaging and dosage-dependent suppression under chromium-picolinate treatment. CONCLUSIONS: This article highlights possible risks for individual long-term effects, when chromium-picolinate is used freely as a therapeutic nutritional modality agent without application of advanced diagnostic tools to predict risks and individual outcomes. Targeted measures require a creation of new guidelines for advanced Diabetes care.

Degenerative valve disease and bioprostheses: risk assessment, predictive diagnosis, personalised treatments.

Aortic stenosis (AS) is the most frequent valvular heart disease. Severe AS results in concentric left ventricular hypertrophy, and ultimately, the heart dilates and fails. During a long period of time patients remain asymptomatic. In this period a pathology progression should be monitored and effectively thwarted by targeted measures. A cascade of cellular and molecular events leads to chronic degeneration of aortic valves. There are some molecular attributes characteristic for the process of valvular degeneration with clear functional link between shifted cell-cycle control, calcification and tissue remodelling of aortic valves. Bioactivity of implanted bioprosthesis is assumed to result in its dysfunction. Age, gender (females), smoking, Diabetes mellitus, and high cholesterol level dramatically shorten the re-operation time. Therefore, predictive and preventive measures would be highly beneficial, in particular for young female diabetes-predisposed patients. Molecular signature of valvular degeneration is reviewed here with emphases on clinical meaning, risk-assessment, predictive diagnosis, individualised treatments.

Birth asphyxia as the major complication in newborns: moving towards improved individual outcomes by prediction, targeted prevention and tailored medical care.

Perinatal Asphyxia-oxygen deficit at delivery-can lead to severe hypoxic ischaemic organ damage in newborns followed by a fatal outcome or severe life-long pathologies. The severe insults often cause neurodegenerative diseases, mental retardation and epilepsies. The mild insults lead to so-called "minimal brain-damage disorders" such as attention deficits and hyperactivity, but can also be associated with the development of schizophrenia and life-long functional psychotic syndromes. Asphyxia followed by re-oxygenation can potentially lead to development of several neurodegenerative pathologies, diabetes type 2 and cancer. The task of individual prediction, targeted prevention and personalised treatments before a manifestation of the life-long chronic pathologies usually developed by newborns with asphyxic deficits, should be given the extraordinary priority in neonatology and paediatrics. Socio-economical impacts of educational measures and advanced strategies in development of robust diagnostic approaches targeted at effected molecular pathways, biomarker-candidates and potential drug-targets for tailored treatments are reviewed in the paper.

Noninvasive subcellular imaging in breast cancer risk assessment: construction of diagnostic windows.

AIM: Breast cancer is the most common cause of cancer-related death among women. Delayed diagnosis leads to development of metastasis and impairs the outcome. This study was designed to utilize subcellular DNA imaging by 'comet assay' and determine pathology-specific comet patterns as the robust biomarker to distinguish between high and low risk for breast cancer development among predisposed individuals with benign breast alterations. MATERIALS & METHODS: A total of 161 patients were grouped as follows: benignancy, premenopause (n = 59); benignancy, postmenopause (n = 20); breast cancer, premenopause (n = 19); breast cancer, postmenopause (n = 63). On average, 800-1000 comets were evaluated per patient. RESULTS & CONCLUSION: The qualitative comet assay is an innovative approach for breast cancer risk assessment that can be utilized for the screening of highly predisposed individuals among patients with benign breast alterations. Pathology-specific comet patterns have been identified as the robust biomarker for breast cancer risk. Mathematic model-based diagnostic windows have been constructed for their clinical application.

Inadequate diabetic care: global figures cry for preventive measures and personalized treatment.

Diabetes mellitus (DM) is a lifelong progressive disease. Currently there are more than 285 million DM-affected people worldwide. Globally the prevalence of diabetes continues to rise and is more pronounced in countries with large populations such as China, India and USA. Driving forces behind the epidemic are obesity, aging of the population and longer life expency. Prospective, the majority of diabetic population will be in their six to eight decades of life with the implication of more females than males. Severe micro- and macrovascular complications associated with diabetes lead to a highly increased morbidity and mortality. Therefore, DM is projected to be one of the leading health problems of 21st centuary. Urgent measures are required to reduce the diabetic burden. Thus advanced predictive diagnostic tools and personalized treatment strategies in (pre)diabetic care are critical and should exert beneficial impact on public health.