Miracle-dz/UniFAR-FTUs huggingface dataset:
Harnessing the Potential of Human Pluripotent Stem Cell-Derived Motor Neurons for Drug Discovery in Amyotrophic Lateral Sclerosis: From the Clinic to the Laboratory and Back to the Patient

Amyotrophic Lateral Sclerosis (ALS) is a motor neurodegenerative disorder whose cellular hallmarks are the progressive death of motor neurons (MNs) located in the anterior horn of the spinal cord, brainstem and motor cortex, and the formation of intracellular protein aggregates. Over the course of the disease, progressive paralysis takes place, leading to patient death within 3–5 years after the diagnosis. Despite decades of intensive research, only a few therapeutic options exist, with a limited benefit on the disease progression. Preclinical animal models have been very useful to decipher some aspects of the mechanisms underlying ALS. However, discoveries made using transgenic animal models have failed to translate into clinically meaningful therapeutic strategies. Thus, there is an urgent need to find solutions to discover drugs that could impact on the course of the disease, with the ultimate goal to extend the life of patients and improve their quality of life. Induced pluripotent stem cells (iPSCs), similarly to embryonic stem cells (ESCs), have the capacity to differentiate into all three embryonic germ layers, which offers the unprecedented opportunity to access patient-specific central nervous system cells in an inexhaustible manner. Human MNs generated from ALS patient iPSCs are an exciting tool for disease modelling and drug discovery projects, since they display ALS-specific phenotypes. Here, we attempted to review almost 2 decades of research in the field, first highlighting the steps required to efficiently generate MNs from human ESCs and iPSCs. Then, we address relevant ALS studies which employed human ESCs and iPSC-derived MNs that led to the identification of compounds currently being tested in clinical trials for ALS. Finally, we discuss the potential and caveats of using patient iPSC-derived MNs as a platform for drug screening, and anticipate ongoing and future challenges in ALS drug discovery.
Platelet Phenotype Analysis of COVID-19 Patients Reveals Progressive Changes in the Activation of Integrin αIIbβ3, F13A1, the SARS-CoV-2 Target EIF4A1 and Annexin A5

Background: The fatal consequences of an infection with severe acute respiratory syndrome coronavirus 2 are not only caused by severe pneumonia, but also by thrombosis. Platelets are important regulators of thrombosis, but their involvement in the pathogenesis of COVID-19 is largely unknown. The aim of this study was to determine their functional and biochemical profile in patients with COVID-19 in dependence of mortality within 5-days after hospitalization. Methods: The COVID-19-related platelet phenotype was examined by analyzing their basal activation state via integrin αIIbβ3 activation using flow cytometry and the proteome by unbiased two-dimensional differential in-gel fluorescence electrophoresis. In total we monitored 98 surviving and 12 non-surviving COVID-19 patients over 5 days of hospital stay and compared them to healthy controls (n = 12). Results: Over the observation period the level of basal αIIbβ3 activation on platelets from non-surviving COVID-19 patients decreased compared to survivors. In line with this finding, proteomic analysis revealed a decrease in the total amount of integrin αIIb (ITGA2B), a subunit of αIIbβ3, in COVID-19 patients compared to healthy controls; the decline was even more pronounced for the non-survivors. Consumption of the fibrin-stabilizing factor coagulation factor XIIIA (F13A1) was higher in platelets from COVID-19 patients and tended to be higher in non-survivors; plasma concentrations of the latter also differed significantly. Depending on COVID-19 disease status and mortality, increased amounts of annexin A5 (ANXA5), eukaryotic initiation factor 4A-I (EIF4A1), and transaldolase (TALDO1) were found in the platelet proteome and also correlated with the nasopharyngeal viral load. Dysregulation of these proteins may play a role for virus replication. ANXA5 has also been identified as an autoantigen of the antiphospholipid syndrome, which is common in COVID-19 patients. Finally, the levels of two different protein disulfide isomerases, P4HB and PDIA6, which support thrombosis, were increased in the platelets of COVID-19 patients. Conclusion: Platelets from COVID-19 patients showed significant changes in the activation phenotype, in the processing of the final coagulation factor F13A1 and the phospholipid-binding protein ANXA5 compared to healthy subjects. Additionally, these results demonstrate specific alterations in platelets during COVID-19, which are significantly linked to fatal outcome. Graphical Abstract
Sex Differences in Hemostatic Factors in Patients With Ischemic Stroke and the Relation With Migraine—A Systematic Review

Background: Women are more affected by stroke than men. This might, in part, be explained by sex differences in stroke pathophysiology. The hemostasis system is influenced by sex hormones and associated with female risk factors for stroke, such as migraine. Aim: To systematically review possible sex differences in hemostatic related factors in patients with ischemic stroke in general, and the influence of migraine on these factors in women with ischemic stroke. Results: We included 24 studies with data on sex differences of hemostatic factors in 7247 patients with ischemic stroke (mean age 57–72 years, 27–57% women) and 25 hemostatic related factors. Levels of several factors were higher in women compared with men; FVII:C (116% ± 30% vs. 104% ± 30%), FXI (0.14 UI/mL higher in women), PAI-1 (125.35 ± 49.37 vs. 96.67 ± 38.90 ng/mL), D-dimer (1.25 ± 0.31 vs. 0.95 ± 0.24 μg/mL), and aPS (18.7% vs. 12.0% positive). In contrast, protein-S (86.2% ± 23.0% vs. 104.7% ± 19.8% antigen) and P-selectin (48.9 ± 14.4 vs. 79.1 ± 66.7 pg/mL) were higher in men. Most factors were investigated in single studies, at different time points after stroke, and in different stroke subtypes. Only one small study reported data on migraine and hemostatic factors in women with ischemic stroke. No differences in fibrinogen, D-dimer, t-PA, and PAI-1 levels were found between women with and without migraine. Conclusion: Our systematic review suggests that sex differences exist in the activation of the hemostatic system in ischemic stroke. Women seem to lean more toward increased levels of procoagulant factors whereas men exhibit increased levels of coagulation inhibitors. To obtain better insight in sex-related differences in hemostatic factors, additional studies are needed to confirm these findings with special attention for different stroke phases, stroke subtypes, and not in the least women specific risk factors, such as migraine.
Resistance to Antibiotics in Thermophilic Campylobacters

Campylobacter jejuni (C. jejuni) is one of the most frequent causes of bacterial enterocolitis globally. The disease in human is usually self-limiting, but when complications arise antibiotic therapy is required at a time when resistance to antibiotics is increasing worldwide. Mechanisms of antibiotic resistance in bacteria are diverse depending on antibiotic type and usage and include: enzymatic destruction or drug inactivation; alteration of the target enzyme; alteration of cell membrane permeability; alteration of ribosome structure and alteration of the metabolic pathway(s). Resistance of Campylobacter spp. to antibiotics, especially fluoroquinolones is now a major public health problem in developed and developing countries. In this review the mechanisms of resistance to fluoroquinolones, macrolides, tetracycline, aminoglycoside and the role of integrons in resistance of Campylobacter (especially at the molecular level) are discussed, as well as the mechanisms of resistance to β-lactam antibiotics, sulphonamides and trimethoprim. Multiple drug resistance is an increasing problem for treatment of campylobacter infections and emergence of resistant strains and resistance are important One Health issues.
Response: Commentary: Is So-Called “Split Alpha” in EEG Spectral Analysis a Result of Methodological and Interpretation Errors?

My comment is short because it is written just to communicate that the Commentary of Olejarczyk and Sobieszek (2021) does not refer to the content of my article Zalewska (2020), but repeats their own erroneous statements from their original article (Olejarczyk et al., 2017). This clearly proves that the Authors did not consider my explanation of their errors and have not used any of what I have presented in publication Zalewska (2020). In this context, both my name and the title of my article Zalewska (2020) are used in an unauthorized manner. The Authors attribute me statements which I have not made, and which is in fact contrary to what I have described in Zalewska (2020). In what follows, I only shortly point out the inadequate citation of my article by Olejarczyk and Sobieszek (2021) in the Commentary in question.
Implementation of a Healthcare of Elderly Course With Multi-Professional Teachers for Undergraduate Medical Students in a Public University in Malaysia—A Quasi-Experimental Pre and Post Study

Clinical practise in the ageing population is changing from organ-specific specialty care to holistic care. This is done through comprehensive geriatric assessment and multi-disciplinary team management. Hence, we adopted an approach consisting of multi-professional teachers teaching a Healthcare of Elderly Course (HEC), in a public university in Malaysia. We aimed to analyze the students' attitude, self-perceived competency and interest in geriatric medicine as a career before and after the course. We also investigated variables that might influence this interest among these students. All 96 students in the course were invited to participate in the survey. Sixty-eight (70.8%) completed both pre and post-course questionnaires. Although most students (93%) have a positive attitude (University of California at Los Angeles Geriatric Attitude Scale >3) toward older adults at baseline, it did not significantly increase post-course. We found that the mean scores for self-perceived competency increased from 3.62 (±0.76) to 3.81 (±0.56) post-course (p < 0.01). However, the students remained neutral with no significant change in the mean interest in pursuing a geriatric medicine career after the course. Students with higher self-perceived competency post-course were found to be more interested in geriatric medicine (β = 0.56, p < 0.001). In conclusion, the HEC in our centre could sustain a positive attitude and increase self-perceived competency in students. It is important to increase the preparedness of our graduates in managing older adults with frailty and multimorbidity. Future studies may involve inter-professional education of students from multiple disciplines undergoing the same course to nurture real-life collaborations in managing the ageing population.
Realizing the Application of EEG Modeling in BCI Classification: Based on a Conditional GAN Converter

Electroencephalogram (EEG) modeling in brain-computer interface (BCI) provides a theoretical foundation for its development. However, limited by the lack of guidelines in model parameter selection and the inability to obtain personal tissue information in practice, EEG modeling in BCI is mainly focused on the theoretical qualitative level which shows a gap between the theory and its application. Based on such problems, this work combined the surface EEG simulation with a converter based on the generative adversarial network (GAN), to establish the connection from simulated EEG to its application in BCI classification. For the scalp EEGs modeling, a mathematical model was built according to the physics of surface EEG, which consisted of the parallel 3-population neural mass model, the equivalent dipole, and the forward computation. For application, a converter based on the conditional GAN was designed, to transfer the simulated theoretical-only EEG to its practical version, in the lack of individual bio-information. To verify the feasibility, based on the latest microexpression-assisted BCI paradigm proposed by our group, the converted simulated EEGs were used in the training of BCI classifiers. The results indicated that, compared with training with insufficient real data, by adding the simulated EEGs, the overall performance showed a significant improvement (P = 0.04 < 0.05), and the test performance can be improved by 2.17% ± 4.23, in which the largest increase was up to 12.60% ± 1.81. Through this work, the link from theoretical EEG simulation to BCI classification has been initially established, providing an enhanced novel solution for the application of EEG modeling in BCI.
Very Early Cognitive Screening and Self-Reported Feeling of Fatigue Three Months After Stroke

Stroke is a major cause of disability and the second leading cause of death worldwide. Post-stroke fatigue has been reported as one of the most limiting symptoms after a stroke. Early identification of risk factors for developing post-stroke fatigue is important for providing timely rehabilitation. A correlation has been found between fatigue and cognitive impairment after stroke, but 2 months after stroke at the earliest. In the present study, we examined whether cognitive function screening using the Montreal Cognitive Assessment (MoCA) very early after stroke could explain fatigue 3 months after stroke. A total of 311 stroke patients admitted to a comprehensive stroke unit in Sweden between 2011 and 2016 were included in this longitudinal study. Cognition was screened within 2 days after admission to the stroke unit. Data on self-reported feeling of fatigue were retrieved from Riksstroke’s 3-month follow-up form. The data were analyzed using binary logistic regression. We found that the cognitive function in an acute phase after stroke could not explain self-reported feeling of fatigue in a later stage. The correlation between cognitive impairment and fatigue that has been reported may be detectable no earlier than the subacute phase of stroke. As previous studies have shown that functional outcome, severity of stroke, and sex also correlate with fatigue after stroke, we controlled for these variables in our analysis. In line with previous studies, we found that female patients had higher odds of experiencing fatigue. This is something that health care professionals should be aware of when working with stroke patients.
Shared Genetic Liability and Causal Associations Between Major Depressive Disorder and Cardiovascular Diseases

Major depressive disorder (MDD) is phenotypically associated with cardiovascular diseases (CVD). We aim to investigate mechanisms underlying relationships between MDD and CVD in the context of shared genetic variations. Polygenic overlap analysis was used to test genetic correlation and to analyze shared genetic variations between MDD and seven cardiovascular outcomes (coronary artery disease (CAD), heart failure, atrial fibrillation, stroke, systolic blood pressure, diastolic blood pressure, and pulse pressure measurement). Mendelian randomization analysis was used to uncover causal relationships between MDD and cardiovascular traits. By cross-trait meta-analysis, we identified a set of genomic loci shared between the traits of MDD and stroke. Putative causal genes for MDD and stroke were prioritized by fine-mapping of transcriptome-wide associations. Polygenic overlap analysis pointed toward substantial genetic variation overlap between MDD and CVD. Mendelian randomization analysis indicated that genetic liability to MDD has a causal effect on CAD and stroke. Comparison of genome-wide genes shared by MDD and CVD suggests 20q12 as a pleiotropic region conferring risk for both MDD and CVD. Cross-trait meta-analyses and fine-mapping of transcriptome-wide association signals identified novel risk genes for MDD and stroke, including RPL31P12, BORSC7, PNPT11, and PGF. Many genetic variations associated with MDD and CVD outcomes are shared, thus, pointing that genetic liability to MDD may also confer risk for stroke and CAD. Presented results shed light on mechanistic connections between MDD and CVD phenotypes.
Individual Variation in Dietary Wariness Is Predicted by Head Color in a Specialist Feeder, the Gouldian Finch

Shifts in resource availability due to environmental change are increasingly confronting animals with unfamiliar food types. Species that can rapidly accept new food types may be better adapted to ecological change. Intuitively, dietary generalists are expected to accept new food types when resources change, while dietary specialists would be more averse to adopting novel food. However, most studies investigating changes in dietary breadth focus on generalist species and do not delve into potential individual predictors of dietary wariness and the social factors modulating these responses. We investigated dietary wariness in the Gouldian finch, a dietary specialist, that is expected to avoid novel food. This species occurs in two main head colors (red, black), which signal personality in other contexts. We measured their initial neophobic responses (approach attempts before first feed and latency to first feed) and willingness to incorporate novel food into their diet (frequency of feeding on novel food after first feed). Birds were tested in same-sex pairs in same and different head color pairings balanced across experiments 1 and 2. Familiar and novel food (familiar food dyed) were presented simultaneously across 5 days for 3 h, each. Gouldian finches fed on the familiar food first demonstrating food neophobia, and these latencies were repeatable. Birds made more approach attempts before feeding on novel than familiar food, particularly red-headed birds in experiment 1 and when partnered with a black-headed bird. Individuals consistently differed in their rate of incorporation of novel food, with clear differences between head colors; red-headed birds increased their feeding visits to novel food across experimentation equaling their familiar food intake by day five, while black-headed birds continually favored familiar food. Results suggest consistent among individual differences in response to novel food with red-headed birds being adventurous consumers and black-headed birds dietary conservatives. The differences in food acceptance aligned with responses to novel environments on the individual level (found in an earlier study) providing individuals with an adaptive combination of novelty responses across contexts in line with potential differences in movement patterns. Taken together, these novelty responses could aid in population persistence when faced with environmental changes.
Exposure to 10 Hz Pulsed Magnetic Fields Do Not Induce Cellular Senescence in Human Fetal Lung Fibroblasts

Rapid population aging has led to a global burden of late-life diseases. As the largest risk factor for a multitude of age-related diseases, aging is not only the result of genotype but also closely related to external factors. With the rapid expansion in the usage of electromagnetic fields (EMFs), the effect of EMFs on aging has also attracted attention. Cells are the basic unit of organs and body tissues, and cellular senescence plays an important role in the aging process. The effect of EMFs on cellular senescence has been investigated in a few studies, but the information is limited, and the results are inconsistent; thus, further investigation is required. In this study, we investigated the effect of 10 Hz pulsed magnetic fields (MFs) on cellular senescence in a 2BS cell line, isolated from human fetal lung fibroblasts, and found that intermittent (1 d on/1 d off) exposure to 10 Hz pulsed MFs at 1.0 mT for 2 weeks induced DNA damage, but no other significant phenotype of cellular senescence in 2BS cells.
Case Report: Prominent Brainstem Involvement in Two Patients With Anti-CASPR2 Antibody-Associated Autoimmune Encephalitis

Anti-contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is commonly characterized by limbic encephalitis with clinical symptoms of mental and behavior disorders, cognitive impairment, deterioration of memory, and epilepsy. The classical lesions reported are located at the medial temporal lobe or hippocampus, whereas prominent brainstem lesions have not been addressed to date. Herein, we reported two patients mimicking progressive brainstem infarction with severe neurological manifestations. On brain magnetic resonance imaging (MRI), prominent brainstem lesions were noted, although multifocal lesions were also shown in the juxtacortical and subcortical white matters, basal ganglia, hippocampus, and cerebellar hemisphere. Unexpectedly and interestingly, both cases had detectable CASPR2 antibodies in sera, and an exclusive IgG1 subclass was documented in the further analysis. They were treated effectively with aggressive immunosuppressive therapies including corticosteroids, intravenous immunoglobulin G, and rituximab, with the first case achieving a rapid remission and the other undergoing a slow but gradual improvement. To the best of our knowledge, this is the first report on prominent brainstem involvement with definite MRI lesions in anti-CASPR2 antibody-associated autoimmune encephalitis, which helps to expand the clinical spectrum of this rare autoimmune disease and update the lesion patterns in the CNS.