On the Fractal Nature of Nervous Cell System

In a detailed study entitled “Morphological development of thick – tufted layer V pyramidal cells in the rat somatosensory cortex, ” an international team of scientists (Romand et al., 2011) reported a series of results pertaining to an analytical investigation of the morphological development of thick-tufted layer V pyramidal cells (also called the principal cells) in the rat somatosensory cortex. At the end of the Introduction Section, the Authors stated “all compartments of a TTL5 cell undergo different developmental changes, supporting the notion that multiple functional compartments receive different inputs an

When Eye-Tracking Meets Machine Learning: A Systematic Review on Applications in Medical Image Analysis

Eye-gaze tracking research offers significant promise in enhancing various healthcare-related tasks, above all in medical image analysis and interpretation. Eye tracking, a technology that monitors and records the movement of the eyes, provides valuable insights into human visual attention patterns. This technology can transform how healthcare professionals and medical specialists engage with and analyze diagnostic images, offering a more insightful and efficient approach to medical diagnostics. Hence, extracting meaningful features and insights from medical images by leveraging eye-gaze data improves our understanding of how radiologists and other medical experts monitor, interpret, and understand images for diagnostic purposes. Eye-tracking data, with intricate human visual attention patterns embedded, provides a bridge to integrating artificial intelligence (AI) development and human cognition. This integration allows novel methods to incorporate domain knowledge into machine learning (ML) and deep learning (DL) approaches to enhance their alignment with human-like perception and decision-making. Moreover, extensive collections of eye-tracking data have also enabled novel ML/DL methods to analyze human visual patterns, paving the way to a better understanding of human vision, attention, and cognition. This systematic review investigates eye-gaze tracking applications and methodologies for enhancing ML/DL algorithms for medical image analysis in depth

Statin therapy blunts inflammatory activation and improves prognosis and left ventricular performance assessed by Tissue Doppler Imaging in subjects with chronic ischemic heart failure: results from the Daunia Heart Failure Registry

BACKGROUND: A limited number of studies have used Tissue Doppler Imaging (TDI) to evaluate the effect of statin therapy on left ventricular dysfunction in patients with chronic heart failure. In this work, we aimed to determine whether statin administration influenced prognosis, inflammatory activation and myocardial performance evaluated by Tissue Doppler Imaging in subjects enrolled in the Daunia Heart Failure Registry, a local registry of patients with chronic heart failure. METHODS: This study retrospectively analyzed 353 consecutive outpatients with chronic heart failure (mean follow-up 384 days), based on whether statin therapy was used. In all patients, several Tissue Doppler Imaging parameters were measured; circulating levels of interleukin (IL)-6, IL-10 and C-reactive protein were also assayed. RESULTS: Statin administration in 128 subjects with ischemic heart disease was associated with a lower incidence of adverse events (rehospitalization for HF 15% vs. 46%, p<0.001; ventricular arrhythmias 5% vs. 21%, p<0.01; cardiac death 1% vs. 8%, p<0.05), lower circulating levels of IL-6 (p<0.05) and IL-10 (p<0.01), lower rates of chronic heart failure (p<0.001) and better Tissue Doppler Imaging performance (E/E' ratio 12.82 + 5.42 vs. 19.85 + 9.14, p<0.001; ET: 260.62+ 44.16 vs. 227.11 +37.58 ms, p<0.05; TP: 176.79 + 49.93 vs. 136.7 + 37.78 ms, p<0.05 and St: 352.35 + 43.17 vs. 310.67 + 66.46 + 37.78 ms, p<0.05). CONCLUSIONS: Chronic ischemic heart failure outpatients undergoing statin treatment had fewer readmissions for adverse events, blunted inflammatory activation and improved left ventricular performance assessed by Tissue Doppler Imaging

Spatial and time domain analysis of eye-tracking data during screening of brain magnetic resonance images

Introduction: Eye-tracking research has been widely used in radiology applications. Prior studies exclusively analysed either temporal or spatial eye-tracking features, both of which alone do not completely characterise the spatiotemporal dynamics of radiologists’ gaze features. Purpose: Our research aims to quantify human visual search dynamics in both domains during brain stimuli screening to explore the relationship between reader characteristics and stimuli complexity. The methodology can be used to discover strategies to aid trainee radiologists in identifying pathology, and to select regions of interest for machine vision applications. Method: The study was performed using eye-tracking data 5 seconds in duration from 57 readers (15 Brain-experts, 11 Other-experts, 5 Registrars and 26 Naïves) for 40 neuroradiological images as stimuli (i.e., 20 normal and 20 pathological brain MRIs). The visual scanning patterns were analysed by calculating the fractal dimension (FD) and Hurst exponent (HE) using re-scaled range (R/S) and detrended fluctuation analysis (DFA) methods. The FD was used to measure the spatial geometrical complexity of the gaze patterns, and the HE analysis was used to measure participants’ focusing skill. The focusing skill is referred to persistence/anti-persistence of the participants’ gaze on the stimulus over time. Pathological and normal stimuli were analysed separately both at the “First Second” and full “Five Seconds” viewing duration. Results: All experts were more focused and a had higher visual search complexity compared to Registrars and Naïves. This was seen in both the pathological and normal stimuli in the first and five second analyses. The Brain-experts subgroup was shown to achieve better focusing skill than Other-experts due to their domain specific expertise. Indeed, the FDs found when viewing pathological stimuli were higher than those in normal ones. Viewing normal stimuli resulted in an increase of FD found in five second data, unlike pathological stimuli, which did not change. In contrast to the FDs, the scanpath HEs of pathological and normal stimuli were similar. However, participants’ gaze was more focused for “Five Seconds” than “First Second” data. Conclusions: The HE analysis of the scanpaths belonging to all experts showed that they have greater focus than Registrars and Naïves. This may be related to their higher visual search complexity than non-experts due to their training and expertise

Cancer initiation and progression: an unsimplifiable complexity

BACKGROUND: Cancer remains one of the most complex diseases affecting humans and, despite the impressive advances that have been made in molecular and cell biology, how cancer cells progress through carcinogenesis and acquire their metastatic ability is still widely debated. CONCLUSION: There is no doubt that human carcinogenesis is a dynamic process that depends on a large number of variables and is regulated at multiple spatial and temporal scales. Viewing cancer as a system that is dynamically complex in time and space will, however, probably reveal more about its underlying behavioural characteristics. It is encouraging that mathematicians, biologists and clinicians continue to contribute together towards a common quantitative understanding of cancer complexity. This way of thinking may further help to clarify concepts, interpret new and old experimental data, indicate alternative experiments and categorize the acquired knowledge on the basis of the similarities and/or shared behaviours of very different tumours

Sperm protein 17 is expressed in human nervous system tumours

BACKGROUND: Human sperm protein 17 (Sp17) is a highly conserved protein that was originally isolated from a rabbit epididymal sperm membrane and testis membrane pellet. It has recently been included in the cancer/testis (CT) antigen family, and shown to be expressed in multiple myeloma and ovarian cancer. We investigated its immunolocalisation in specimens of nervous system (NS) malignancies, in order to establish its usefulness as a target for tumour-vaccine strategies. METHODS: The expression of Sp17 was assessed by means of a standardised immunohistochemical procedure [(mAb/antigen) MF1/Sp17] in formalin-fixed and paraffin embedded surgical specimens of NS malignancies, including 28 neuroectodermal primary tumours (6 astrocytomas, 16 glioblastoma multiforme, 5 oligodendrogliomas, and 1 ependymoma), 25 meningeal tumours, and five peripheral nerve sheath tumours (4 schwannomas, and 1 neurofibroma),. RESULTS: A number of neuroectodermal (21%) and meningeal tumours (4%) were found heterogeneously immunopositive for Sp17. None of the peripheral nerve sheath tumours was immunopositive for Sp17. The expression pattern was heterogeneous in all of the positive samples, and did not correlate with the degree of malignancy. CONCLUSION: The frequency of expression and non-uniform cell distribution of Sp17 suggest that it cannot be used as a unique immunotherapeutic target in NS cancer. However, our results do show the immunolocalisation of Sp17 in a proportion of NS tumour cells, but not in their non-pathological counterparts. The emerging complex function of Sp17 makes further studies necessary to clarify the link between it and immunopositive cells

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)