Sleep apnea-hypopnea quantification by cardiovascular data analysis

Sleep apnea is the most common sleep disturbance and it is an important risk factor for cardiovascular disorders. Its detection relies on a polysomnography, a combination of diverse exams. In order to detect changes due to sleep disturbances such as sleep apnea occurrences, without the need of combined recordings, we mainly analyze systolic blood pressure signals (maximal blood pressure value of each beat to beat interval). Nonstationarities in the data are uncovered by a segmentation procedure, which provides local quantities that are correlated to apnea-hypopnea events. Those quantities are the average length and average variance of stationary patches. By comparing them to an apnea score previously obtained by polysomnographic exams, we propose an apnea quantifier based on blood pressure signal. This furnishes an alternative procedure for the detection of apnea based on a single time series, with an accuracy of 82%

Be nice if you have to — the neurobiological roots of strategic fairness

Social norms, such as treating others fairly regardless of kin relations, are essential for the functioning of human societies. Their existence may explain why humans, among all species, show unique patterns of prosocial behaviour. The maintenance of social norms often depends on external enforcement, as in the absence of credible sanctioning mechanisms prosocial behaviour deteriorates quickly. This sanction-dependent prosocial behaviour suggests that humans strategically adapt their behaviour and act selfishly if possible but control selfish impulses if necessary. Recent studies point at the role of the dorsolateral prefrontal cortex (DLPFC) in controlling selfish impulses. We test whether the DLPFC is indeed involved in the control of selfish impulses as well as the strategic acquisition of this control mechanism. Using repetitive transcranial magnetic stimulation, we provide evidence for the causal role of the right DLPFC in strategic fairness. Because the DLPFC is phylogenetically one of the latest developed neocortical regions, this could explain why complex norm systems exist in humans but not in other social animals

Comparison of three commercial decision support platforms for matching of next-generation sequencing results with therapies in patients with cancer

Objective Precision oncology depends on translating molecular data into therapy recommendations. However, with the growing complexity of next-generation sequencing-based tests, clinical interpretation of somatic genomic mutations has evolved into a formidable task. Here, we compared the performance of three commercial clinical decision support tools, that is, NAVIFY Mutation Profiler (NAVIFY; Roche), QIAGEN Clinical Insight (QCI) Interpret (QIAGEN) and CureMatch Bionov (CureMatch). Methods In order to obtain the current status of the respective tumour genome, we analysed cell-free DNA from patients with metastatic breast, colorectal or non-small cell lung cancer. We evaluated somatic copy number alterations and in parallel applied a 77-gene panel (AVENIO ctDNA Expanded Panel). We then assessed the concordance of tier classification approaches between NAVIFY and QCI and compared the strategies to determine actionability among all three platforms. Finally, we quantified the alignment of treatment suggestions across all decision tools. Results Each platform varied in its mode of variant classification and strategy for identifying druggable targets and clinical trials, which resulted in major discrepancies. Even the frequency of concordant actionable events for tier I-A or tier I-B classifications was only 4.3%, 9.5% and 28.4% when comparing NAVIFY with QCI, NAVIFY with CureMatch and CureMatch with QCI, respectively, and the obtained treatment recommendations differed drastically. Conclusions Treatment decisions based on molecular markers appear at present to be arbitrary and dependent on the chosen strategy. As a consequence, tumours with identical molecular profiles would be differently treated, which challenges the promising concepts of genome-informed medicine

MUG Mel3 Cell Lines Reflect Heterogeneity in Melanoma and Represent a Robust Model for Melanoma in Pregnancy

Melanomas are aggressive tumors with a high metastatic potential and an increasing incidence rate. They are known for their heterogeneity and propensity to easily develop therapy-resistance. Nowadays they are one of the most common cancers diagnosed during pregnancy. Due to the difficulty in balancing maternal needs and foetal safety, melanoma is challenging to treat. The aim of this study was to provide a potential model system for the study of melanoma in pregnancy and to illustrate melanoma heterogeneity. For this purpose, a pigmented and a non-pigmented section of a lymph node metastasis from a pregnant patient were cultured under different conditions and characterized in detail. All four culture conditions exhibited different phenotypic, genotypic as well as tumorigenic properties, and resulted in four newly established melanoma cell lines. To address treatment issues, especially in pregnant patients, the effect of synthetic human lactoferricin-derived peptides was tested successfully. These new BRAF-mutated MUG Mel3 cell lines represent a valuable model in melanoma heterogeneity and melanoma pregnancy research. Furthermore, treatment with anti-tumor peptides offers an alternative to conventionally used therapeutic options—especially during pregnancy

Diminished heart beat non-stationarities in congestive heart failure

Studies on heart rate variability (HRV) have become popular and the possibility of diagnosis based on non-invasive techniques compels us to overcome the difficulties originated on the environmental changes that can affect the signal. We perform a non-parametric segmentation which consists of locating the points where the signal can be split into stationary segments. By finding stationary segments we are able to analyze the size of these segments and evaluate how the signal changes from one segment to another, looking at the statistical moments given in each patch, for example, mean and variance. We analyze HRV data for 15 patients with congestive heart failure (CHF; 11 males, 4 females, age 56±11 years), 18 elderly healthy subjects (EH; 11 males, 7 females, age 50±7 years), and 15 young healthy subjects (YH; 11 females, 4 males, age 31±6 years). Our results confirm higher variance for YH, and EH, while CHF displays diminished variance with p-values <0.01, when compared to the healthy groups, presenting higher HRV in healthy subjects. Moreover, it is possible to distinguish between YH and EH with p < 0.05 through the segmentation outcomes. We found high correlations between the results of segmentation and standard measures of HRV analysis and a connection to results of detrended fluctuation analysis (DFA). The segmentation applied to HRV studies detects aging and pathological conditions effects on the non-stationary behavior of the analyzed groups, promising to contribute in complexity analysis and providing risk stratification measures

Effect of L- to D-Amino Acid Substitution on Stability and Activity of Antitumor Peptide RDP215 against Human Melanoma and Glioblastoma

The study investigates the antitumor effect of two cationic peptides, R-DIM-P-LF11-215 (RDP215) and the D-amino acid variant 9D-R-DIM-P-LF11-215 (9D-RDP215), targeting the negatively charged lipid phosphatidylserine (PS) exposed by cancer cells, such as of melanoma and glioblastoma. Model studies mimicking cancer and non-cancer membranes revealed the specificity for the cancer-mimic PS by both peptides with a slightly stronger impact by the D-peptide. Accordingly, membrane effects studied by DSC, leakage and quenching experiments were solely induced by the peptides when the cancer mimic PS was present. Circular dichroism revealed a sole increase in β-sheet conformation in the presence of the cancer mimic for both peptides; only 9D-RDP215 showed increased structure already in the buffer. Ex vitro stability studies by SDS-PAGE as well as in vitro with melanoma A375 revealed a stabilizing effect of D-amino acids in the presence of serum, which was also confirmed in 2D and 3D in vitro experiments on glioblastoma LN-229. 9D-RDP215 was additionally able to pass a BBB model, whereupon it induced significant levels of cell death in LN-229 spheroids. Summarized, the study encourages the introduction of D-amino acids in the design of antitumor peptides for the improvement of their stable antitumor activity

Diminished heart beat non-stationarities in congestive heart failure

Studies on heart rate variability (HRV) have become popular and the possibility of diagnosis based on non-invasive techniques compels us to overcome the difficulties originated on the environmental changes that canaffect the signal. We perform a nonparametric segmentation which consists of locating the points where the sig-nal can be split into stationary segments. By finding stationary segments we are able to analyze the size of thesesegments and evaluate how the signal changes from one segment to another, looking at the statistical momentsgiven in each patch, for example, mean and variance. We analyze HRV data for 15 patients with congestive heartfailure (CHF; 11 males, 4 females, age 56 &#177; 11 years), 18 elderly healthy subjects (EH; 11 males, 7 females, age50 &#177; 7 years), and 15 young healthy subjects (YH; 11 females, 4 males, age 31 &#177; 6 years). Our results confirmhigher variance for YH, and EH, while CHF displays diminished variance with p-values &lt; 0.01, when comparedto the healthy groups, presenting higher HRV in healthy subjects. Moreover, it is possible to distinguish betweenYH and EH with p &lt; 0.05 through the segmentation outcomes. We found high correlations between the resultsof segmentation and standard measures of HRV analysis and a connection to results of detrended fluctuationanalysis. The segmentation applied to HRV studies detects aging and pathological conditions effects on thenonstationary behavior of the analyzed groups, promising to contribute in complexity analysis and providingrisk stratification measures

Killing of melanoma cells and their metastases by human lactoferricin derivatives requires interaction with the cancer marker phosphatidylserine

Despite favorable advancements in therapy cancer is still not curative in many cases, which is often due to inadequate specificity for tumor cells. In this study derivatives of a short cationic peptide derived from the human host defense peptide lactoferricin were optimized in their selective toxicity towards cancer cells. We proved that the target of these peptides is the negatively charged membrane lipid phosphatidylserine (PS), specifically exposed on the surface of cancer cells. We have studied the membrane interaction of three peptides namely LF11-322, its N-Acyl derivative 6-methyloctanoyl-LF11-322 and its retro repeat derivative R(etro)-DIM-P-LF11-322 with liposomes mimicking cancerous and non-cancerous cell membranes composed of PS and phosphatidylcholine (PC), respectively. Calorimetric and permeability studies showed that N-Acylation and even more the repeat derivative of LF11-322 leads to strongly improved interaction with the cancer mimic PS, whereas only the N-Acyl derivative also slightly affects PC. Tryptophan fluorescence of selective peptide R-DIM-P-LF11-322 revealed specific peptide penetration into the PS membrane interface and circular dichroism showed change of its secondary structure by increase of proportion of b-sheets just in the presence of the cancer mimic. Data correlated with in vitro studies with cell lines of human melanomas, their metastases and melanocytes, revealing R-DIM-P-LF11-322 to exhibit strongly increased specificity for cancer cells. This indicates the need of high affinity to the target PS, a minimum length and net positive charge, an adequate but moderate hydrophobicity, and capability of adoption of a defined structure exclusively in presence of the target membrane for high antitumor activity