A Novel Gaussian Extrapolation Approach for 2D Gel Electrophoresis Saturated Protein Spots

Analysis of images obtained from two-dimensional gel electrophoresis (2D-GE) is a topic of utmost importance in bioinformatics research, since commercial and academic software available currently has proven to be neither completely effective nor fully automatic, often requiring manual revision and refinement of computer generated matches. In this work, we present an effective technique for the detection and the reconstruction of over-saturated protein spots. Firstly, the algorithm reveals overexposed areas, where spots may be truncated, and plateau regions caused by smeared and overlapping spots. Next, it reconstructs the correct distribution of pixel values in these overexposed areas and plateau regions, using a two-dimensional least-squares fitting based on a generalized Gaussian distribution. Pixel correction in saturated and smeared spots allows more accurate quantification, providing more reliable image analysis results. The method is validated for processing highly exposed 2D-GE images, comparing reconstructed spots with the corresponding non-saturated image, demonstrating that the algorithm enables correct spot quantification

Radical improvement of signs and symptoms in systemic lupus erythematosus when treated with hemodiafiltration with endogenous reinfusion dialysis

Lupus nephritis is one of the most serious complications of systemic lupus erythematosus (SLE). In the kidney immune complexes (ICs) and autoantibodies activate mesangial cells that secrete the cytokines that further amplify inflammatory processes. We present a case of a 42-year-old woman presented Lupus Nephritis, with periods of exacerbation of SLE, with necrotic-like skin lesions, psoriatic arthritis without skin psoriasis, purpura to lower limb, petechial rash, joint pain, fever, eyelid edema with bilateral conjunctival hyperemia and itching When she was subjected to Hemodiafiltration with Endogenous Reinfusion (HFR) dialysis treatment with super high flux membrane Synclear 02 (SUPRA treatment), fever and joint pain was reduced immediately, subsequently all of her skin damages are reduced and she gradually decreased quantity of prednisone and immunosuppressor per die until completely suspend. As well known that SUPRA treatment remove cytokine from blood ; moreover was used the High-performance liquid chromatography coupled with Quadrupole Time-of-flight Mass Spectrometer (HPLC-QTOF-MS) for identification of proteins captured by resin bed during a dialysis session of the patient. With this technique was identified several biomarker of kidney injuries, uremic toxins, fragments of Immunoglobulins, antigen involved in anti-phospholipid syndrome and a new marker (α-defensin) that correlate significantly with disease activity. The removal of these different proteins can explain the improvement in the patient’s symptoms and the normalization of her LES, confirming that SUPRA are a suitable technique for LN treatment

A Novel Gaussian Extrapolation Approach for 2D Gel Electrophoresis Saturated Protein Spots

Analysis of images obtained from two-dimensional gel electrophoresis (2D-GE) is a topic of utmost importance in bioinformatics research, since commercial and academic software available currently has proven to be neither completely effective nor fully automatic, often requiring manual revision and refinement of computer generated matches. In this work, we present an effective technique for the detection and the reconstruction of over-saturated protein spots. Firstly, the algorithm reveals overexposed areas, where spots may be truncated, and plateau regions caused by smeared and overlapping spots. Next, it reconstructs the correct distribution of pixel values in these overexposed areas and plateau regions, using a two-dimensional least-squares fitting based on a generalized Gaussian distribution. Pixel correction in saturated and smeared spots allows more accurate quantification, providing more reliable image analysis results. The method is validated for processing highly exposed 2D-GE images, comparing reconstructed spots with the corresponding non-saturated image, demonstrating that the algorithm enables correct spot quantificatio

Whole-body radioiodine effective half-life in patients with differentiated thyroid cancer

Background: Radioactive 131I (RAI) therapy is used in patients with differentiated thyroid cancer (DTC) after total thyroidectomy for remnant ablation, adjuvant treatment or treatment of persistent disease. 131I retention data, which are used to indicate the time at which a 131I treated DTC patient can be released from the hospital, may bring some insights regarding clinical factors that prolong the length of hospitalization. The aim of this study was to investigate the 131I whole-body retention in DTC patients during 131I therapy. Methods: We monitored 166 DTC patients to follow the 131I whole-body retention during 131I therapy with a radioactivity detector fixed on the ceiling of each protected room. A linear regression fit permitted us to estimate the whole-body 131I effective half-life in each patient, and a relationship was sought between patients’ clinical characteristics and whole-body effective 131I half-life. Results: The effective 131I half-life ranged from 4.08 to 56.4 h. At multivariable analysis, longer effective 131I half-life was related to older age and extensive extra-thyroid disease. Conclusions: 131I effective half-life during 131I treatment in DTC patients is highly variable among patients and is significantly longer in older and in patients with RAI uptake in large thyroid remnants or in extrathyroidal disease that significantly prolongs the whole-body retention of 131I

Ablation rate after radioactive iodine therapy in patients with differentiated thyroid cancer at intermediate or high risk of recurrence: a systematic review and a meta-analysis

Purpose We performed a systematic review and a meta-analysis to investigate the successful ablation rate after radioiodine (RAI) administration in patients with differentiated thyroid cancer (DTC) at intermediate-high risk of recurrence. Methods: A comprehensive literature search of the PubMed, Scopus, and Web of Science databases was conducted according to the PRISMA statement. Results: The final analysis included 9 studies accounting for 3103 patients at intermediate-high risk of recurrence. In these patients, the successful ablation rates ranged from 51 to 94% with a 71% pooled successful ablation and were higher in intermediate (72%) than in high (52%)-risk patients. Despite the rigorous inclusion standards, a significant heterogeneity among the evaluated studies was observed. Higher administered RAI activities are associated with a lower successful ablation rate in the whole population and in the subgroup of high-risk patients. Furthermore, pooled recurrence rate in intermediate-risk patients achieving successful ablation was only 2% during the subsequent 6.4-year follow-up while the pooled recurrence rate was 14% in patients who did not achieve a successful ablation. Conclusion: In a large sample of 3103 patients at intermediate-high risk of persistent/recurrent disease, 71% of patients achieved a successful ablation. In these intermediate-risk patients, the probability of subsequent recurrence is low and most recurrence occurred in those with already abnormal findings at the first control

Quantification of Coronary Artery Atherosclerotic Burden and Muscle Mass: Exploratory Comparison of Two Freely Available Software Programs

Abstract: Coronary artery calcification and sarcopenia may have a relevant prognostic impact in oncological and non‐oncological patients. The use of freeware software is promising for quantitative evaluation of these parameters after whole‐body positron emission tomography (PET)/computed tomography (CT) and might be useful for one‐stop shop risk stratification without additional radiation ionizing burden and further charges to health care costs. In this study, we compared two semiautomatic freeware software tools (Horos Medical Image software and LIFEx) for the assessment of coronary artery calcium (CAC) score and muscle mass in 40 patients undergoing whole‐body PET/CT. The muscle areas obtained by the two software programs were comparable, showing high correlation with Lin’s concordance coefficient (0.9997; 95% confidence intervals: 0.9995–0.9999) and very good agreement with Bland–Altman analysis (mean difference = 0.41 cm2, lower limit = −1.06 cm2, upper limit = 1.89) was also found. For CAC score, Lin’s concordance correlation coefficient was 0.9976 (95% confidence intervals: 0.9965–0.9984) and in a Bland–Altman analysis an increasing mean difference from 8 to 78 by the mean values (intercept = −0.050; slope = 0.054; p < 0.001) was observed, with a slight overestimation of Horos CAC score as compared to LIFEx, likely due to a different calculation method of the CAC score, with the ROI being equal for the two software programs. Our results demonstrated that off‐line analysis performed with freeware software may allow a comprehensive evaluation of the oncological patient, making available the evaluation of parameters, such as muscle mass and calcium score, that may be relevant for the staging and prognostic stratification of these patients, beside standard data obtained by PET/CT imaging. For this purpose, the Horos and LIFEx software seem to be interchangeable

Cefiderocol treatment for carbapenem-resistant Acinetobacter baumannii infection in the ICU during the COVID-19 pandemic: a multicentre cohort study

open16noFunding: This study was carried out as part of our routine work and supported by internal funding.Objectives: To analyse the impact of cefiderocol use on outcome in patients admitted to the ICU for severe COVID-19 and further diagnosed with carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection.Methods: Retrospective multicentre observational study was performed at four Italian hospitals, from January 2020 to April 2021. Adult patients admitted to ICU for severe COVID-19 and further diagnosed with CR-Ab infections were enrolled. Patients treated with cefiderocol, as compassionate use, for at least 72 h were compared with those receiving alternative regimens. Primary endpoint was all-cause 28 day mortality. The impact of cefiderocol on mortality was evaluated by multivariable Cox regression model.Results: In total, 107 patients were enrolled (76% male, median age 65 years). The median time from ICU admission to CR-Ab infection diagnosis was 14 (IQR 8-20) days, and the main types of CR-Ab infections were bloodstream infection (58%) and lower respiratory tract infection (41%). Cefiderocol was administered to 42 patients within a median of 2 (IQR 1-4) days after CR-Ab infection diagnosis and as monotherapy in all cases. The remaining patients received colistin, mostly (82%) administered as combination therapy. All-cause 28 day mortality rate was 57%, without differences between groups (cefiderocol 55% versus colistin 58% P = 0.70). In multivariable analysis, the independent risk factor for mortality was SOFA score (HR 1.24, 95% CI 1.15-1.38, P &lt; 0.001). Cefiderocol was associated with a non-significant lower mortality risk (HR 0.64, 95% CI 0.38-1.08, P = 0.10).Conclusions: Our study confirms the potential role of cefiderocol in the treatment of CR-Ab infection, but larger clinical studies are needed.openPascale, Renato; Pasquini, Zeno; Bartoletti, Michele; Caiazzo, Luca; Fornaro, Giacomo; Bussini, Linda; Volpato, Francesca; Marchionni, Elisa; Rinaldi, Matteo; Trapani, Filippo; Temperoni, Chiara; Gaibani, Paolo; Ambretti, Simone; Barchiesi, Francesco; Viale, Pierluigi; Giannella, MaddalenaPascale, Renato; Pasquini, Zeno; Bartoletti, Michele; Caiazzo, Luca; Fornaro, Giacomo; Bussini, Linda; Volpato, Francesca; Marchionni, Elisa; Rinaldi, Matteo; Trapani, Filippo; Temperoni, Chiara; Gaibani, Paolo; Ambretti, Simone; Barchiesi, Francesco; Viale, Pierluigi; Giannella, Maddalen

Blood transcriptomics of drug-na\uefve sporadic Parkinson's disease patients

BACKGROUND: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. METHODS: Changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls ("Discovery set") were analyzed by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. Data analysis was performed by applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays. Functional annotations were assigned using GO, DAVID, GSEA to unveil significant enriched biological processes in the differentially expressed genes. The expressions of selected genes were validated using RT-qPCR and samples from an independent cohort of 12 patients and controls ("Validation set"). RESULTS: Gene expression profiling of blood samples discriminates PD patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts as CBX5, TCF3, MAN1C1 and DOCK10 were validated by RT-qPCR. CONCLUSIONS: Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

A novel Gaussian fitting approach for 2D gel electrophoresis saturated protein spots

Analysis of 2D-GE images is a hot topic in bioinformatics research, since currently available commercial and academic software has proven to be not really effective and not completely automatic, often requiring manual revision of spots detection and refinement of computer generated matches. In this work, we present an effective technique for the detection and the reconstruction of over-saturated protein spots. Firstly, it reveals overexposed areas where spots may be truncated, and plateau regions caused by smeared and overlapped spots. As next, the correct distribution of pixel values in the overexposed areas and plateau regions is recovered by a two-dimensional fitting based on a generalized Gaussian distribution approximating the spots volume. Pixel correction according to the generalized Gaussian curve in saturated and smeared spots allows more accurate quantifications, providing more reliable image analysis results. As validation, we process highly exposed 2D-GE image, containing saturate spots, with respect to the corresponding non-saturated image, confirming that the method can effectively fix the saturated spots and enable correct spots quantification