Analysis of mutations in precision oncology using the automated, accurate, and user-friendly web tool PredictONCO.

Next-generation sequencing technology has created many new opportunities for clinical diagnostics, but it faces the challenge of functional annotation of identified mutations. Various algorithms have been developed to predict the impact of missense variants that influence oncogenic drivers. However, computational pipelines that handle biological data must integrate multiple software tools, which can add complexity and hinder non-specialist users from accessing the pipeline.

A computational workflow for analysis of missense mutations in precision oncology.

Every year, more than 19 million cancer cases are diagnosed, and this number continues to increase annually. Since standard treatment options have varying success rates for different types of cancer, understanding the biology of an individual's tumour becomes crucial, especially for cases that are difficult to treat. Personalised high-throughput profiling, using next-generation sequencing, allows for a comprehensive examination of biopsy specimens.

EEG alpha band functional brain network correlates of cognitive performance in children after perinatal stroke.

Mechanisms underlying cognitive impairment after perinatal stroke could be explained through brain network alterations. With aim to explore this connection, we conducted a matched test-control study to find a correlation between functional brain network properties and cognitive functions in children after perinatal stroke. First, we analyzed resting-state functional connectomes in the alpha frequency band from a 64-channel resting state EEG in 24 children with a history of perinatal stroke (12 with neonatal arterial ischemic stroke and 12 with neonatal hemorrhagic stroke) and compared them to the functional connectomes of 24 healthy controls.

Beyond the Preventive Measures: A Delphi Method-Based Study of the Impact of the COVID-19 Pandemic on the Mental Health of Different Age Groups.

The coronavirus disease 2019 (COVID-19) preventive measures affected various aspects of people's lives, while also representing an important risk factor for people's mental health. In the present study, we examined the negative psychological consequences of the preventive measures on people's mental health and the protective factors that strengthened their mental health and well-being during the pandemic. A study, using a combination of qualitative and quantitative methods based on a Delphi protocol, was conducted with a sample of Slovenian professionals who worked with people from different demographic groups (i.

Protein sialylation affects the pH-dependent binding of ferric ion to human serum transferrin.

Physiological or pathophysiological changes lead to posttranslational changes in the sialic acid content of human serum transferrin (hTf), an essential mediator of iron transport in the human body, resulting in a significantly increased concentration of desialylated hTf. The intrinsic fluorescence quenching upon binding of iron to hTf was successfully modeled using the binding polynomial for two iron-binding sites, allowing measurements in a high-throughput format. Removal of sialic acid residues resulted in a 3-fold increase in iron binding affinity for both sites of hTf at pH 7.

AggreProt: a web server for predicting and engineering aggregation prone regions in proteins.

Recombinant proteins play pivotal roles in numerous applications including industrial biocatalysts or therapeutics. Despite the recent progress in computational protein structure prediction, protein solubility and reduced aggregation propensity remain challenging attributes to design. Identification of aggregation-prone regions is essential for understanding misfolding diseases or designing efficient protein-based technologies, and as such has a great socio-economic impact.

Longitudinal study of immunity to SARS-CoV2 in ocrelizumab-treated MS patients up to 2 years after COVID-19 vaccination.

Objectives: (1) To plot the trajectory of humoral and cellular immune responses to the primary (two-dose) COVID-19 mRNA series and the third/booster dose in B-cell-depleted multiple sclerosis (MS) patients up to 2 years post-vaccination; (2) to identify predictors of immune responses to vaccination; and (3) to assess the impact of intercurrent COVID-19 infections on SARS CoV-2-specific immunity.

Methods: Sixty ocrelizumab-treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre-vaccination, and then 4, 12, 24, and 48 weeks post-primary series, and 4, 12, 24, and 48 weeks post-booster.

Mortality and its predictors among human immunodeficiency virus-infected children younger than 15 years receiving antiretroviral therapy in Ethiopia: a systematic review and meta-analysis.

Background: Despite antiretroviral treatment (ART), the human immunodeficiency virus (HIV) continues to pose a considerable health burden in resource-poor countries. This systematic review and meta-analysis aimed to determine the pooled incidence density of mortality and identify potential predictors among HIV-infected children receiving ART, from studies conducted in various parts of Ethiopia.

Methods: A comprehensive database search was made in Excerpta Medica, PubMed, Web of Science, African Journals Online, Google Scholar, and Scopus.

Diversity, equity, and inclusion (DEI) in medical education: DEI at the bedside.

Background: The ability to recognize and address bias is an important communication skill not typically addressed during training. We describe the design of an educational curriculum that aims to identify and change behavior related to diversity, equity, and inclusion (DEI). "DEI at the Bedside" uses the existing infrastructure of bedside teaching and provides a tool to normalize DEI discussions and develop skills to address bias during a neurology inpatient rotation.

Sexual dimorphism in subterranean amphipod crustaceans covaries with subterranean habitat type.

Sexual dimorphism can evolve in response to sex-specific selection pressures that vary across habitats. We studied sexual differences in subterranean amphipods Niphargus living in shallow subterranean habitats (close to the surface), cave streams (intermediate), and cave lakes (deepest and most isolated). These three habitats differ because at greater depths there is lower food availability, reduced predation, and weaker seasonality.

Out of sight: chronic kidney diseases among diabetic patients attending care and follow up. Findings from pastoralist health facilities of Southern Ethiopia.

Background: In Ethiopia, the prevalence of chronic kidney disease (CKD) among the adult population ranges to 19.1%. The disease's impact has increased in low-resource settings due to a lack of knowledge about the condition and its risk factors.

Groundwater is a hidden global keystone ecosystem.

Groundwater is a vital ecosystem of the global water cycle, hosting unique biodiversity and providing essential services to societies. Despite being the largest unfrozen freshwater resource, in a period of depletion by extraction and pollution, groundwater environments have been repeatedly overlooked in global biodiversity conservation agendas. Disregarding the importance of groundwater as an ecosystem ignores its critical role in preserving surface biomes.

Successful Autologous Hematopoietic Stem Cell Transplant in Glycine Receptor Antibody-Positive Stiff Person Syndrome: A Case Report.

Background And Objectives: To describe a case of glycine receptor (GlyR) antibody-positive stiff person syndrome (SPS) treated with autologous hematopoietic stem cell transplant (aHSCT).

Methods: This was a multicenter collaboration for the treatment of a single patient who underwent aHSCT as part of a clinical trial (NCT00716066). To objectively assess the response to transplantation, several clinical outcome measures were evaluated pretransplant and up to 18 months post-transplant, including modified Rankin Score (mRS), stiffness index, Hauser Ambulation Score (HAS), hypersensitivity index, timed 25-foot walk, and Montreal Cognitive Assessment.

PredictONCO: a web tool supporting decision-making in precision oncology by extending the bioinformatics predictions with advanced computing and machine learning.

PredictONCO 1.0 is a unique web server that analyzes effects of mutations on proteins frequently altered in various cancer types. The server can assess the impact of mutations on the protein sequential and structural properties and apply a virtual screening to identify potential inhibitors that could be used as a highly individualized therapeutic approach, possibly based on the drug repurposing.

Determinants of mortality among pediatric patients admitted to Wolaita Sodo University Comprehensive Specialized Hospital with acute bacterial meningitis, Southern Ethiopia: an unmatched case-control study.

Background: People of all ages suffer from acute bacterial meningitis, but children are the most vulnerable, accounting for over 50% of all cases and deaths in children under the age of five. It is the leading cause of morbidity, mortality, and long-term suffering worldwide. Children are at great risk of disease and mortality due to a lack of specific immunity associated with their young age.

FireProt 2.0: web-based platform for the fully automated design of thermostable proteins.

Thermostable proteins find their use in numerous biomedical and biotechnological applications. However, the computational design of stable proteins often results in single-point mutations with a limited effect on protein stability. However, the construction of stable multiple-point mutants can prove difficult due to the possibility of antagonistic effects between individual mutations.

Temperature variation in caves and its significance for subterranean ecosystems.

Climate change affects all ecosystems, but subterranean ecosystems are repeatedly neglected from political and public agendas. Cave habitats are home to unknown and endangered species, with low trait variability and intrinsic vulnerability to recover from human-induced disturbances. We studied the annual variability and cyclicity of temperatures in caves vis-à-vis surface in different climatic areas.

Preparation and characterization of iron(III) nitrilotriacetate complex in aqueous solutions for quantitative protein binding experiments.

Various preparations of iron(III) nitrilotriacetate (FeNTA) solution reported in the literature lack a comprehensive method for accurate determination of FeNTA concentration and often result in unstable solutions. A detailed procedure for the preparation of FeNTA solution is presented that includes the standardization of both components of the chelate. The standardization of the components allowed the accurate determination of the molar absorption coefficients for the calculation of the FeNTA concentration in two different buffers at pH 5.

Neutralizing Activity of SARS-CoV-2 Antibodies in Patients with COVID-19 and Vaccinated Individuals.

Background: Serological diagnosis of COVID-19 is complex due to the emergence of different SARS-CoV-2 variants.

Methods: 164 serum samples from (I) patients who recovered from COVID-19 ( = 62) as well as (II) vaccinated individuals ( = 52) and (III) vaccinated individuals who were infected with different SARS-CoV-2 variants after vaccination ( = 50) were included. All samples were tested using EIA (binding antibodies) and a virus neutralization test (VNT) using the Wuhan strain (NT antibodies).

SARS-CoV-2 mRNA vaccination induces an antigen-specific T cell response correlating with plasma interferon-gamma in B cell depleted patients.

Emerging evidence is encouraging and suggests that a substantial proportion of patients without antibody responses (due to anti-CD20 therapy or other etiologies) to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines develop T cell responses. However, antigen-specific T cellular responses are notoriously difficult to assess clinically, given the lack of such assays under satisfactory CAP/CLIA regulation, and the laborious nature of the flow cytometric assessment. To evaluate the ability to apply a clinically feasible assay to measure T cellular responses to SARS-CoV-2 mRNA vaccination, we compared flow cytometric and enzyme-linked immunosorbent assay (ELISA) based assays in 24 participants treated with anti-CD20 therapy.

Potential Clinically Relevant Effects of Sialylation on Human Serum AAG-Drug Interactions Assessed by Isothermal Titration Calorimetry: Insight into Pharmacoglycomics?

Human serum alpha-1 acid glycoprotein is an acute-phase plasma protein involved in the binding and transport of many drugs, especially basic and lipophilic substances. It has been reported that the sialic acid groups that terminate the N-glycan chains of alpha-1 acid glycoprotein change in response to certain health conditions and may have a major impact on drug binding to alpha-1 acid glycoprotein. The interaction between native or desialylated alpha-1 acid glycoprotein and four representative drugs-clindamycin, diltiazem, lidocaine, and warfarin-was quantitatively evaluated using isothermal titration calorimetry.