Publications

16 May 2022

Structural MRI-Based Schizophrenia Classification Using Autoencoders and 3D Convolutional Neural Networks in Combination with Various Pre-Processing Techniques

Schizophrenia is a severe neuropsychiatric disease whose diagnosis, unfortunately, lacks an objective diagnostic tool supporting a thorough psychiatric examination of the patient. We took advantage of today’s computational abilities, structural magnetic resonance imaging, and modern machine learning methods, such as stacked autoencoders (SAE) and 3D convolutional neural networks (3D CNN), to teach them to classify 52 patients with schizophrenia and 52 healthy controls. The main aim of this study was to explore whether complex feature extraction methods can help improve the accuracy of deep learning-based classifiers compared to minimally preprocessed data. Our experiments employed three commonly used preprocessing steps to extract three different feature types.

16 May 2022

Computer-aided engineering of staphylokinase toward enhanced affinity and selectivity for plasmin

Cardio- and cerebrovascular diseases are leading causes of death and disability, resulting in one of the highest socio-economic burdens of any disease type. The discovery of bacterial and human plasminogen activators and their use as thrombolytic drugs have revolutionized treatment of these pathologies. Fibrin-specific agents have an advantage over non-specific factors because of lower rates of deleterious side effects. Specifically, staphylokinase (SAK) is a pharmacologically attractive indirect plasminogen activator protein of bacterial origin that forms stoichiometric noncovalent complexes with plasmin, promoting the conversion of plasminogen into plasmin. Here we report a computer-assisted re-design of the molecular surface of SAK to increase its affinity for plasmin.

16 May 2022

Contribution of the multi-echo approach in accelerated functional magnetic resonance imaging multiband acquisition

We wanted to verify the effect of combining multi-echo (ME) functional magnetic resonance imaging (fMRI) with slice acceleration in simultaneous multi-slice acquisition. The aim was to shed light on the benefits of multiple echoes for various acquisition settings, especially for levels of slice acceleration and flip angle. Whole-brain ME fMRI data were obtained from 26 healthy volunteers (using three echoes; seven runs with slice acceleration 1, 4, 6, and 8; and two different flip angles for each of the first three acceleration factors) and processed as single-echo (SE) data and ME data based on optimal combinations weighted by the contrast-to-noise ratio. Global metrics (temporal signal-to-noise ratio, signal-to-noise separation, number of active voxels, etc.) and local characteristics in regions of interest were used to evaluate SE and ME data.

16 May 2022

Prenatal stress and its association with amygdala-related structural covariance patterns in youth

Background: Prenatal stress influences brain development and mood disorder vulnerability. Brain structural covariance network (SCN) properties based on inter-regional volumetric correlations may reflect developmentally-mediated shared plasticity among regions. Childhood trauma is associated with amygdala-centric SCN reorganization patterns, however, the impact of prenatal stress on SCN properties remains unknown.

Methods: The study included participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) with archival prenatal stress data and structural MRI acquired in young adulthood (age 23-24). SCNs were constructed based on Freesurfer-extracted volumes of 7 subcortical and 34 cortical regions. 

16 May 2022

Is pregnancy in MS patients safe and what is its impact on MS course? Real World evidence of 1533 pregnancies in Czech Republic

Background: A special care of MS women planning a pregnancy is highly demanding especially in the terms of disease modifying treatment (DMD) decisions and counselling regarding periods of conception, pregnancy and postpartum period.

Objective: To provide data about impact of pregnancy, delivery or miscarriage/artificial abortion on MS disease course in Czech women with MS based on analysis of retrospective data from the Czech national registry ReMuS.

Methods: The analysis focused on women with MS with at least one record of pregnancy in the registry. Clinical data (EDSS, relapses) were collected prior to conception, during pregnancy and after delivery or miscarriage/artificial abortion. 

16 May 2022

A New Framework for Investigating the Biological Basis of Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 5]: Mechanical Stress, Vulnerability and Time

Study design: Literature Review (Narrative).

Objective: To propose a new framework, to support the investigation and understanding of the pathobiology of DCM, AO Spine RECODE-DCM research priority number 5.

Methods: Degenerative cervical myelopathy is a common and disabling spinal cord disorder. In this perspective, we review key knowledge gaps between the clinical phenotype and our biological models. We then propose a reappraisal of the key driving forces behind DCM and an individual's susceptibility, including the proposal of a new framework.

16 May 2022

Degenerative Cervical Myelopathy: Development and Natural History [AO Spine RECODE-DCM Research Priority Number 2]

Study design: Narrative review.

Objectives: To discuss the current understanding of the natural history of degenerative cervical myelopathy (DCM).

Methods: Literature review summarizing current evidence pertaining to the natural history and risk factors of DCM.

Results: DCM is a common condition in which progressive arthritic disease of the cervical spine leads to spinal cord compression resulting in a constellation of neurological symptoms, in particular upper extremity dysfunction and gait impairment. Anatomical factors including cord-canal mismatch, congenitally fused vertebrae and genetic factors may increase individuals' risk for DCM development. 

9 May 2022

EXPRESS: Association of statin pretreatment with baseline stroke severity and outcome in patients with acute ischemic stroke: an observational study

ABSTRACTBackground:Statins have an important role in stroke prevention, especially in high-risk populations and may also affect the initial stroke severity and outcomes in patients taking them before an ischemic stroke.

Aims: Our aim was to evaluate the association of statin pretreatment with the severity in acute ischemic stroke (AIS).

Methods: We analyzed SITS International Thrombolysis and Thrombectomy Registry data from January 2011 to December 2017. We identified patients with statin information at baseline. The primary outcome was baseline NIH stroke scale (NIHSS) score. Secondary outcomes were NIHSS score at 24 hours, symptomatic intracerebral hemorrhage (SICH) and functional outcome at 90 days after acute intervention. 

9 May 2022

Rationale and study design of a trial to assess r TMS add - on v alue for the amelioration of negative symptoms of schizophrenia (RADOVAN)

Background: Schizophrenia is a severe and often difficult to treat psychiatric illness. In many patients, negative symptoms dominate the clinical picture. Meta-analysis has suggested moderate, but significant effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on these symptoms. For treatment of depression a much shorter protocol - intermittent theta burst stimulation (iTBS) - has shown to be non-inferior to conventional high-frequency rTMS. This randomized, sham-controlled, rater-blinded clinical trial assesses the effects of conventional HF-rTMS as well as of iTBS of the left dorsolateral prefrontal cortex in comparison with sham.

Methods: The study will be conducted at two psychiatric university hospitals in Germany and at two in the Czech Republic. 

9 May 2022

Intensive Circuit Class Therapy in Patients with Relapsing-Remitting Multiple Sclerosis

Objective: Long-term physiotherapy is of considerable benefit to patients with multiple sclerosis (MS) who have motor dysfunction or gait impairment. The aim of this study was to determine the effectiveness of a 12-week intensive circuit class therapy for patients with MS, with a wider focus on fatigue and gait ability.

Methods: A total of 46 patients with relapsing-remitting MS were divided randomly into 2 groups: 23 patients (mean Expanded Disability Status Scale (EDSS) 2.33 ± 0.74) participated in an intensive 12-week course of intensive circuit class therapy, and 23 patients (mean EDSS 2.04 ± 0.63) served as a control group. The EDSS, Timed Up and Go (TUG) test and Four-Stage Balance Test (FSBT) made up the physical testing part, supplemented by questionnaires such as the Modified Fatigue Impact Scale (MFIS), 12-Item Multiple Sclerosis Walking Scale (MSWS-12), Beck Depression Inventory (BDI) and 36-Item Short Form Survey (SF-36).

22 Apr 2022

Bridging structural and functional biomarkers in functional movement disorder using network mapping

Background: There are gaps in our neurobiological understanding of functional movement disorder (FMD).

Objectives: We investigated gray matter volumetric profiles in FMD, and related findings to resting-state functional connectivity (rsFC) profiles using Human Connectome Project data.

Methods: Volumetric differences between 53 FMD patients and 50 controls were examined, as well as relationships between individual differences in FMD symptom severity and volumetric profiles. Atrophy network mapping was also used to probe whether FMD-related structural alterations preferentially impacted brain areas with dense rsFC.

Results: Compared to controls without neurological comorbidities (albeit with mild depression and anxiety as a group), the FMD cohort did not show any volumetric differences.

22 Apr 2022

LuminoCell: a versatile and affordable platform for real-time monitoring of luciferase-based reporters

Luciferase reporter assays represent a simple and sensitive experimental system in cell and molecular biology to study multiple biological processes. However, the application of these assays is often limited by the costs of conventional luminometer instruments and the versatility of their use in different experimental conditions. Therefore, we aimed to develop a small, affordable luminometer allowing continuous measurement of luciferase activity, designed for inclusion into various kinds of tissue culture incubators. Here, we introduce LuminoCell-an open-source platform for the construction of an affordable, sensitive, and portable luminometer capable of real-time monitoring in-cell luciferase activity. The LuminoCell costs $40, requires less than 1 h to assemble, and it is capable of performing real-time sensitive detection of both magnitude and duration of the activity of major signalling pathways in cell cultures, including receptor tyrosine kinases (EGF and FGF), WNT/β-catenin, and NF-κB.

14 Apr 2022

The blood-brain barrier and the neurovascular unit in subarachnoid hemorrhage: molecular events and potential treatments

he response of the blood-brain barrier (BBB) following a stroke, including subarachnoid hemorrhage (SAH), has been studied extensively. The main components of this reaction are endothelial cells, pericytes, and astrocytes that affect microglia, neurons, and vascular smooth muscle cells. SAH induces alterations in individual BBB cells, leading to brain homeostasis disruption. Recent experiments have uncovered many pathophysiological cascades affecting the BBB following SAH. Targeting some of these pathways is important for restoring brain function following SAH. BBB injury occurs immediately after SAH and has long-lasting consequences, but most changes in the pathophysiological cascades occur in the first few days following SAH. These changes determine the development of early brain injury as well as delayed cerebral ischemia. SAH-induced neuroprotection also plays an important role and weakens the negative impact of SAH.

4 Apr 2022

Functional Abilities of an International Post-Stroke Population: Standard Assessment of Global Everyday Activities (SAGEA) Scale

Background and objectives: Function is an important outcome after stroke; traditional assessments may not capture functional deficits important to patients. We examined the validity of the Standard Assessment of Global Everyday Activities (SAGEA), a patient-reported outcome that assesses activities important to patients and for use in international clinical trials.

Methods: The NAVIGATE-ESUS trial evaluated rivaroxaban compared to aspirin in preventing recurrent stroke in 7213 participants. The Modified Rankin Scale (mRS), the National Institutes of Health Stroke Scale (NIHSS), and the SAGEA were collected at entry. Chi square tests were used to compare proportions and Spearman rank correlations were used to compare between measures. SAGEA was compared to the Modified Frailty Index (MFI) and the occurrence of infarct to examine criterion validity RESULTS: 

17 Mar 2022

HLA-E and HLA-F Are Overexpressed in Glioblastoma and HLA-E Increased After Exposure to Ionizing Radiation

Background/aim: Glioblastoma (GBM) is one of the deadliest human cancers responding very poorly to therapy. Although the central nervous system has been traditionally considered an immunologically privileged site with an enhanced immune response, GBM appears to benefit from this immunosuppressive milieu. Immunomodulatory molecules play an important role in immune tumor-host interactions. Non-classical human leukocyte antigens (HLA) class Ib molecules HLA-E, HLA-F, and HLA-G have been previously described to be involved in protecting semi-allogeneic fetal allografts from the maternal immune response and in transplant tolerance as well as tumoral immune escape. Unfortunately, their role in GBM remains poorly understood. Our study, therefore, aimed to characterize the relationship between the expression of these molecules in GBM on the transcriptional level and clinicopathological and molecular features of GBM as well as the effect of ionizing radiation.

17 Mar 2022

Evaluating Rates of Recurrent Ischemic Stroke Among Young Adults With Embolic Stroke of Undetermined Source: The Young ESUS Longitudinal Cohort Study

Importance: Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain. Objective: To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults. Design, setting, and participants: This multicenter longitudinal cohort study with enrollment from October 2017 to October 2019 and a mean follow-up period of 12 months ending in October 2020 included 41 stroke research centers in 13 countries. 

17 Mar 2022

Clozapine Reverses Dysfunction of Glutamatergic Neurons Derived From Clozapine-Responsive Schizophrenia Patients

The cellular pathology of schizophrenia and the potential of antipsychotics to target underlying neuronal dysfunctions are still largely unknown. We employed glutamatergic neurons derived from induced pluripotent stem cells (iPSC) obtained from schizophrenia patients with known histories of response to clozapine and healthy controls to decipher the mechanisms of action of clozapine, spanning from molecular (transcriptomic profiling) and cellular (electrophysiology) levels to observed clinical effects in living patients. Glutamatergic neurons derived from schizophrenia patients exhibited deficits in intrinsic electrophysiological properties, synaptic function and network activity. Deficits in K⁺ and Na⁺ currents, network behavior, and glutamatergic synaptic signaling were restored by clozapine treatment, but only in neurons from clozapine-responsive patients.

24 Feb 2022

Intensive circuit class therapy in patients with relapsing-remitting multiple sclerosis

Long-term physiotherapy is of considerable benefit to patients with motor dysfunction or gait impairment in patients with multiple sclerosis (MS). The aim of this study was to determine the effectiveness of 12-week intensive circuit class therapy (ICT) for patients with MS, with a wider focus on fatigue and gait ability. Methods: A total of 46 relapsing-remitting MS patients were divided randomly: Twenty-three of them (mean Expanded Disability Status Scale (EDSS) 2.33±0.74) took part in an intensive 12-week course of ICT and 23 (mean EDSS 2.04±0.63) served as a control group. The EDSS, Timed Up and Go (TUG) test and Four-Stage Balance Test (FSBT) made up the physical testing part, supplemented by questionnaires such as the Modified Fatigue Impact Scale (MFIS), 12-Item Multiple Sclerosis Walking Scale (MSWS-12), Beck Depression Inventory (BDI) and 36-Item Short Form Survey (SF-36).