Empowering precision medicine through high performance computing clusters

The role of High Performance Computing (HPC) in Medicine is greatly increase in these last years, moving from basic research to the clinics. With the advent of Next Generation Sequencing (NGS) technologies, diverse areas of human health have been investigated through different omics techniques. The extensive use of these NGS platforms to high throughput profile human health issues in a cost-efficient manner, is generating huge amount of sequencing data pushing " (https://www.facebook.com/pages/Oatext/1439466783004774) # $ % (https://www.youtube.com/user/users/oatext) ○ ○ ○ Article Article Info Author Info Figures & Data bioinformatic research in the big-data field. Speed, accuracy and reproducibility of massively sequencing analysis have allowed to transfer molecular biology knowledge into precision medicine. Furthermore, Molecular Dynamics (MD) earned a great importance in aiding genome research. Sequencing studies of cancer have allowed to detect and characterize mutated genes that drive tumorigenesis. As a complementary approach, from a biophysical perspective, MD simulations, executed on HPC architectures, have permitted to investigate the role played by pathological mutations on the molecular mechanism of activation

Uniform sampling of steady states in metabolic networks: heterogeneous scales and rounding

The uniform sampling of convex polytopes is an interesting computational problem with many applications in inference from linear constraints, but the performances of sampling algorithms can be affected by ill-conditioning. This is the case of inferring the feasible steady states in models of metabolic networks, since they can show heterogeneous time scales . In this work we focus on rounding procedures based on building an ellipsoid that closely matches the sampling space, that can be used to define an efficient hit-and-run (HR) Markov Chain Monte Carlo. In this way the uniformity of the sampling of the convex space of interest is rigorously guaranteed, at odds with non markovian methods. We analyze and compare three rounding methods in order to sample the feasible steady states of metabolic networks of three models of growing size up to genomic scale. The first is based on principal component analysis (PCA), the second on linear programming (LP) and finally we employ the lovasz ellipsoid method (LEM). Our results show that a rounding procedure is mandatory for the application of the HR in these inference problem and suggest that a combination of LEM or LP with a subsequent PCA perform the best. We finally compare the distributions of the HR with that of two heuristics based on the Artificially Centered hit-and-run (ACHR), gpSampler and optGpSampler. They show a good agreement with the results of the HR for the small network, while on genome scale models present inconsistencies.Comment: Replacement with major revision

Are health literacy and lifestyle of undergraduates related to the educational field? An italian survey

Background: Health literacy (HL) is a fundamental ability to successfully deal with health and illness issues. This study aimed to assess HL among undergraduates from healthcare and non-healthcare degree courses of two Italian universities and the association between their HL, lifestyles, and BMI assumed as health outcome. Methods: The Health Literacy Assessment Tool (HLAT-8) and the Newest Vital Sign (NVS) were used to assess health literacy dimensions. Demographic and anthropometric data, adherence to Mediterranean diet (MD), physical activity levels, and smoking habits were assessed in the enrolled sample to highlight possible associations. Results: A total sample of 806 undergraduates (46% males, mean age 21.01 ± 1.78 years) was recruited. Higher HL scores were found among healthcare rather than non-healthcare students (28.7 ± 4.5 vs. 26.7 ± 4.2 for HLAT-8 and 4.9 ± 1.5 vs. 3.9 ± 1.8 for NVS, p < 0.01). However, healthcare undergraduates were more likely to report unhealthy behaviors. Body Mass Index (BMI) was associated with literacy and numeracy skills only in non-healthcare undergraduates. Significant associations were found between HL scores and adherence to MD in both groups. In the regression analysis, educational field and MD were shown to be predictors of HL scores. Conclusions: Attending a healthcare related degree course was associated with higher HL scores but not with healthy behaviors. This issue should be addressed considering the role that healthcare professionals may have in educating patients towards a healthy lifestyle. Adherence to MD seems to be related to higher HL scores

Macular Microcysts in Mitochondrial Optic Neuropathies: Prevalence and Retinal Layer Thickness Measurements.

PurposeTo investigate the thickness of the retinal layers and to assess the prevalence of macular microcysts (MM) in the inner nuclear layer (INL) of patients with mitochondrial optic neuropathies (MON).MethodsAll patients with molecularly confirmed MON, i.e. Leber's Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), referred between 2010 and 2012 were enrolled. Eight patients with MM were compared with two control groups: MON patients without MM matched by age, peripapillary retinal nerve fiber layer (RNFL) thickness, and visual acuity, as well as age-matched controls. Retinal segmentation was performed using specific Optical coherence tomography (OCT) software (Carl Zeiss Meditec). Macular segmentation thickness values of the three groups were compared by one-way analysis of variance with Bonferroni post hoc corrections.ResultsMM were identified in 5/90 (5.6%) patients with LHON and 3/58 (5.2%) with DOA. The INL was thicker in patients with MON compared to controls regardless of the presence of MM [133.1±7μm vs 122.3±9μm in MM patients (p<0.01) and 128.5±8μm vs. 122.3±9μm in no-MM patients (p<0.05)], however the outer nuclear layer (ONL) was thicker in patients with MM (101.4±1mμ) compared to patients without MM [77.5±8mμ (p<0.001)] and controls [78.4±7mμ (p<0.001)]. ONL thickness did not significantly differ between patients without MM and controls.ConclusionThe prevalence of MM in MON is low (5-6%), but associated with ONL thickening. We speculate that in MON patients with MM, vitreo-retinal traction contributes to the thickening of ONL as well as to the production of cystic spaces

Functional Changes of Retinal Ganglion Cells and Visual Pathways in Patients with Chronic Leber's Hereditary Optic Neuropathy during One Year of Follow-up.

Purpose: To assess changes of retinal ganglion cells (RGCs) and visual pathways' function in patients with Leber's hereditary optic neuropathy (LHON) during 12 months of follow-up of the chronic phase. Design: Retrospective case series. Participants: Twenty-two patients with LHON (mean age, 36.3±9.3 years) in the "chronic phase" of the disease, providing 42 eyes (LHON group) with different pathogenic mitochondrial DNA mutations (group 11778: 21 eyes; group 3460: 4 eyes; group 14484: 13 eyes; and group 14568: 4 eyes) were enrolled. Twenty-five age-similar healthy participants, providing 25 eyes, served as controls. Methods: Pattern electroretinogram (PERG) and visual evoked potentials (VEP), in response to 60ʹ and 15ʹ checks visual stimuli, were recorded at baseline in all subjects and after 6 and 12 months of follow-up in patients with LHON. At baseline, in all LHON eyes for each PERG and VEP parameter (amplitude and implicit time), the 95% confidence limit (CL) of test–retest variability was calculated. The PERG and VEP mean values observed in LHON eyes were compared (1-way analysis of variance [ANOVA]) with those of controls. During the follow-up, the PERG and VEP differences observed with respect to baseline were evaluated by ANOVA. Main Outcome Measures: Changes of individual and mean absolute values of 60ʹ and 15ʹ PERG amplitude and VEP amplitude and implicit time at each time point compared with baseline values in the LHON group. Results: At baseline, mean values of PERG and VEP parameters detected in the LHON group were significantly (P 0.01) different from baseline values. Conclusions: In our untreated patients with chronic LHON, with different specific pathogenic mutations, RGCs and visual pathways function were not significantly modified during 12 months of follow-up. This should be considered in the disease natural history when attempts for treatments are proposed in chronic LHON

Sedentary behaviors and physical activity of Italian undergraduate students during lockdown at the time of COVID−19 pandemic

Background: From March to May 2020, lockdown measures were adopted in Italy to contain the epidemic of the novel Coronavirus. People were forced to restrict their movement and social contacts, therefore having a higher risk of inactivity. This study, carried out among Italian undergraduates, explored their sedentary and physical activities (PA) during the lockdown with respect to their previous habits. Methods: An electronic questionnaire was administered once to students attending three Italian universities after the end of lockdown. Results: A total of 1430 students (mean age 22.9 ± 3.5 years, 65.5% females) completed the questionnaire. All the sedentary behaviors increased significantly, and all the physical activities decreased significantly during the lockdown. Time spent using electronic devices showed the highest increase (+52.4 min/day), and walking the greatest decrease (−365.5 min/week). Being younger than 22 years old, female, and previously active, attending the universities of Naples and Rome and having at least one graduate parent were associated with the achievement of recommended levels of PA even during the lockdown. Conclusions: This study highlights the reduction of PA among Italian undergraduates in the course of home-confinement due to the CoViD-19 pandemic. The practice of adequate PA during the lockdown was mainly associated with the previous adoption of an active lifestyle. Promoting active lifestyles during the non-pandemic period may have had positive effects also in case of lockdown

Stereotactic body radiotherapy vs conventionally fractionated chemoradiation in locally advanced pancreatic cancer: A multicenter case‐control study (PAULA‐1)

The aim of this study was to compare two cohorts of LAPC patients treated with SBRT ± CHT vs CRT ± CHT in terms of local control (LC), distant metastases- free survival (DMFS), progression-free survival (PFS), overall survival (OS), and toxicity. Eighty patients were included. Patients in the two cohorts were matched ac- cording to: age ≤/>65 years, tumor diameter (two cut-offs

Prospective validation of the CLIP score: a new prognostic system for patient with cirrhosis and hepatocellular carcinoma

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage, As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with RCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection