Post-translational processing leads to conformational changes in protein structure that modulate molecular functions and change the signature of metabolic transformations and immune responses. Some ...post-translational modifications (PTMs), such as phosphorylation and acetylation, are strongly related to oncogenic processes and malignancy. This study investigated a PTM pattern in patients with gender-specific ovarian or breast cancer. Proteomic profiling and analysis of cancer-specific PTM patterns were performed using high-resolution UPLC-MS/MS. Structural analysis, topology, and stability of PTMs associated with sex-specific cancers were analyzed using molecular dynamics modeling. We identified highly specific PTMs, of which 12 modified peptides from eight distinct proteins derived from patients with ovarian cancer and 6 peptides of three proteins favored patients from the group with breast cancer. We found that all defined PTMs were localized in the compact and stable structural motifs exposed outside the solvent environment. PTMs increase the solvent-accessible surface area of the modified moiety and its active environment. The observed conformational fluctuations are still inadequate to activate the structural degradation and enhance protein elimination/clearance; however, it is sufficient for the significant modulation of protein activity.
Patients with end-stage kidney disease receiving maintenance hemodialysis (HD) are at increased risk for mortality after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ...compared with the general population. However, it is currently unknown whether the long-term SARS-CoV-2 humoral and cellular immune responses in patients receiving HD are comparable to individuals with normal kidney function.
The prospective cohort study included 24 patients treated with maintenance HD and 27 non-renal controls with confirmed history of coronavirus disease (COVID-19). In all participants the levels of specific IgG were quantified at three timepoints: 10, 18, and 26 weeks from disease onset. In a subgroup of patients, specific T-cell responses were evaluated.
The seropositivity rate declined in controls over time and was 85% and 70.4% at weeks 18 and 26, respectively. All HD patients remained seropositive over the study period. Seropositivity rate at week 26 was greater among patients receiving HD: RR = 1.4 95%CI: 1.17-1.94 (reciprocal of RR = 0.7 95% CI: 0.52-0.86),
= 0.0064. In both groups, IgG levels decreased from week 10 to week 26, but antibodies vanished more rapidly in controls than in HD group (ANOVA
= 0.0012). The magnitude of T-cell response was significantly lower in controls than in HD patients at weeks 10 (
= 0.019) and 26 (
= 0.0098) after COVID-19 diagnosis, but not at week 18.
Compared with non-renal adults, patients receiving HD maintain significant long-term humoral and cellular immune responses following natural COVID-19.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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•Systematic approach realizes common features between related and unrelated diseases.•Neural network can use both meaningful and unassigned mass spectrometry-based data.•Convolutional ...neural network discriminates closely related phenotypes.•Neural network suggests comorbidity between schizophrenia and oncophenotypes.
The association between cancer risk and schizophrenia is widely debated. Despite many epidemiological studies, there is still no strong evidence regarding the molecular basis for the comorbidity between these two pathological conditions. The vast majority of assays have been performed using clinical records of schizophrenic patients or those undergoing cancer treatment and monitored for sufficient time to find shared features between the considered conditions. We performed mass spectrometry-based proteomic and metabolomic investigations of patients with different cancer phenotypes (breast, ovarian, renal, and prostate) and patients with schizophrenia. The resulting vast quantity of proteomic and metabolomic data were then processed using systems biology and one-dimensional (1D) convolutional neural network (1DCNN) machine learning approaches. Traditional systematic approaches permit the segregation of schizophrenia and cancer phenotypes on the level of biological processes, while 1DCNN recognized “signatures” that could segregate distinct cancer phenotypes and schizophrenia at the comorbidity level. The designed network efficiently discriminated unrelated pathologies with a model accuracy of 0.90 and different subtypes of oncophenotypes with an accuracy of 0.94. The proposed strategy integrates systematic analysis of identified compounds and application of 1DCNN model for unidentified ones to reveal the similarity between distinct phenotypes.
Background
The aim of the study was to assess the prevalence of seropositive status for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-IgA, -IgM, and -IgG; its dynamics in connection ...with restrictive measures during the coronavirus disease (COVID-19) pandemic; and the quantitative dynamics of antibody levels in the population of St. Petersburg, Russia.
Methods
From May to November 2020, a retrospective analysis of Saint Petersburg State University Hospital laboratory database was performed. The database included 158,283 test results of 87,067 patients for SARS-CoV-2 detection by polymerase chain reaction (PCR) and antibody detection of SARS-CoV-2-IgA, -IgM, and -IgG. The dynamics of antibody level was assessed using R v.3.6.3.
Results
The introduction of a universal lockdown was effective in containing the spread of COVID-19. The proportion of seropositive patients gradually decreased; approximately 50% of these patients remained seropositive for IgM after 3–4 weeks; for IgG, by follow-up week 22; and for IgA, by week 12. The maximum decrease in IgG and IgA was observed 3–4 months and 2 months after the detection of the seropositive status, respectively.
Conclusions
The epidemiological study of post-infection immunity to COVID-19 demonstrates significant differences in the dynamics of IgA, IgM, and IgG seropositivity and in PCR test results over time, which is linked to the introduction of restrictive measures. Both the proportion of seropositive patients and the level of all antibodies decreased in terms of the dynamics, and only approximately half of these patients remained IgG-positive 6 months post-infection.
Background: Despite the obvious advantages of transradial access and its widespread use, there are technical problems that force interventional surgeons to improve the methods of endovascular ...interventions. Aims: to analyze the effectiveness and safety of distal and traditional radial access for endovascular interventions. Methods: The study included 282 patients who underwent an endovascular intervention with distal radial access (DRA, 139 patients) or traditional radial access (TRA, 143 patients). The study is registered at www.clinicaltrials.gov, NCT04211584. Results: The median diameter of the radial artery in its proximal part, i.e. at the site of TRA, was 2.5 mm Q1; Q3: 2.27; 2.8, in the DRA group the median was 2.28 mm Q1; Q3: 2.06; 3.56, p 0.0001. We noted statistically significant differences in the duration of puncture (p=0.0215), but not in the duration of the introducer insertion, catheterization of the coronary artery, fluoroscopy, the total time of intervention, the dose of ionizing radiation. In total, 28 complications developed (9.9% of 282): 14 in each of the groups in one year after the intervention. Two (0.7% of 282) patients developed bleeding 1 (0.7% of 139) DRA, 1 (0.7% of 143) TRA, 5 (1.8% of 282) radial artery dissection 2 (1.4% of 139) DRA, 3 (2.1% of 143) TRA, 9 (3.2% of 282) puncture failure 7 (5% of 139) DRA, 2 (1.4% of 143) TRA, 4 (1.4% of 282) radial artery perforation 2 (1.4% of 139) DRA, 2 (1.4% of 143) TRA, 7 (2.5% of 282) hematoma more than 5 cm 2 (1.4% of 139) DRA, 5 (3.5% of 143) TRA, 1 (0.4% of 282) radial artery thrombosis (0.7% of 143) TRA. The risk of complications did not depend on the type of access. Conclusions: Distal and traditional radial access do not differ in their efficiency and safety. At the same time, we noted a certain tendency to a longer puncture of the radial artery with distal radial access compared to the traditional one, which is due to the smaller diameter of the radial artery.
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