Miracle-dz/UniFAR-FTUs huggingface dataset:
Aging and Neurodegenerative Disease: Is the Adaptive Immune System a Friend or Foe?

Neurodegenerative diseases of the central nervous system (CNS) are characterized by progressive neuronal death and neurological dysfunction, leading to increased disability and a loss of cognitive or motor functions. Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis have neurodegeneration as a primary feature. However, in other CNS diseases such as multiple sclerosis, stroke, traumatic brain injury, and spinal cord injury, neurodegeneration follows another insult, such as demyelination or ischaemia. Although there are different primary causes to these diseases, they all share a hallmark of neuroinflammation. Neuroinflammation can occur through the activation of resident immune cells such as microglia, cells of the innate and adaptive peripheral immune system, meningeal inflammation and autoantibodies directed toward components of the CNS. Despite chronic inflammation being pathogenic in these diseases, local inflammation after insult can also promote endogenous regenerative processes in the CNS, which are key to slowing disease progression. The normal aging process in the healthy brain is associated with a decline in physiological function, a steady increase in levels of neuroinflammation, brain shrinkage, and memory deficits. Likewise, aging is also a key contributor to the progression and exacerbation of neurodegenerative diseases. As there are associated co-morbidities within an aging population, pinpointing the precise relationship between aging and neurodegenerative disease progression can be a challenge. The CNS has historically been considered an isolated, “immune privileged” site, however, there is mounting evidence that adaptive immune cells are present in the CNS of both healthy individuals and diseased patients. Adaptive immune cells have also been implicated in both the degeneration and regeneration of the CNS. In this review, we will discuss the key role of the adaptive immune system in CNS degeneration and regeneration, with a focus on how aging influences this crosstalk.
The Emerging Role of Renal Tubular Epithelial Cells in the Immunological Pathophysiology of Lupus Nephritis

Systemic lupus erythematosus (SLE) is a systemic, autoimmune disease that can involve virtually any organ of the body. Lupus nephritis (LN), the clinical manifestation of this disease in the kidney, is one of the most common and severe outcomes of SLE. Although a key pathological hallmark of LN is glomerular inflammation and damage, tubulointerstitial lesions have been recognized as an important component in the pathology of LN. Renal tubular epithelial cells are resident cells in the tubulointerstitium that have been shown to play crucial roles in various acute and chronic kidney diseases. In this context, recent progress has been made in examining the functional role of tubular epithelial cells in LN pathogenesis. This review summarizes recent advances in our understanding of renal tubular epithelial cells in LN, the potential role of tubular epithelial cells as biomarkers in the diagnosis, prognosis, and treatment of LN, and the future therapeutic potential of targeting the tubulointerstitium for the treatment of patients with LN.
Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients

The Coronavirus Disease 2019 (COVID-19), caused by the novel SARS-CoV-2, continues to spread globally with significantly high morbidity and mortality rates. Immunological surrogate markers, in particular antigen-specific responses, are of unquestionable value for clinical management of patients with COVID-19. Here, we investigated the kinetics of IgM, IgG against the spike (S) and nucleoproteins (N) proteins and their neutralizing capabilities in hospitalized patients with RT-PCR confirmed COVID-19 infection. Our data show that SARS-CoV-2 specific IgG, IgM and neutralizing antibodies (nAbs) were readily detectable in almost all COVID-19 patients with various clinical presentations. Notably, anti-S and -N IgG, peaked 20-40 day after disease onset, and were still detectable for at least up to 70 days, with nAbs observed during the same time period. Moreover, nAbs titers were strongly correlated with IgG antibodies. Significantly higher levels of nAbs as well as anti-S1 and N IgG and IgM antibodies were found in patients with more severe clinical presentations, patients requiring admission to intensive care units (ICU) or those with fatal outcomes. Interestingly, lower levels of antibodies, particularly anti-N IgG and IgM in the first 15 days after symptoms onset, were found in survivors and those with mild clinical presentations. Collectively, these findings provide new insights into the characteristics and kinetics of antibody responses in COVID-19 patients with different disease severity.
Social Visual Perception Under the Eye of Bayesian Theories in Autism Spectrum Disorder Using Advanced Modeling of Spatial and Temporal Parameters

Social interaction in individuals with Autism Spectrum Disorder (ASD) is characterized by qualitative impairments that highly impact quality of life. Bayesian theories in ASD frame an understanding of underlying mechanisms suggesting atypicalities in the evaluation of probabilistic links within the perceptual environment of the affected individual. To address these theories, the present study explores the applicability of an innovative Bayesian framework on social visual perception in ASD and demonstrates the use of gaze transitions between different parts of social scenes. We applied advanced analyses with Bayesian Hidden Markov Modeling (BHMM) to track gaze movements while presenting real-life scenes to typically developing (TD) children and adolescents (N = 25) and participants with ASD and Attention-Deficit/Hyperactivity Disorder (ASD+ADHD, N = 15) and ASD without comorbidity (ASD, N = 12). Regions of interest (ROIs) were generated by BHMM based both on spatial and temporal gaze behavior. Social visual perception was compared between groups using transition and fixation variables for social (faces, bodies) and non-social ROIs. Transition variables between faces, namely gaze transitions between faces and likelihood of linking faces, were reduced in the ASD+ADHD compared to TD participants. Fixation count to faces was also reduced in this group. The ASD group showed similar performance to TD in the studied variables. There was no difference between groups for non-social ROIs. Our study provides an innovative, interpretable example of applying Bayesian theories of social visual perception in ASD. BHMM analyses and gaze transitions have the potential to reveal fundamental social perception components in ASD, contributing thus to amelioration of social-skill interventions.
A Systematic Framework for Olfactory Bulb Signal Transformations

We describe an integrated theory of olfactory systems operation that incorporates experimental findings across scales, stages, and methods of analysis into a common framework. In particular, we consider the multiple stages of olfactory signal processing as a collective system, in which each stage samples selectively from its antecedents. We propose that, following the signal conditioning operations of the nasal epithelium and glomerular-layer circuitry, the plastic external plexiform layer of the olfactory bulb effects a process of category learning—the basis for extracting meaningful, quasi-discrete odor representations from the metric space of undifferentiated olfactory quality. Moreover, this early categorization process also resolves the foundational problem of how odors of interest can be recognized in the presence of strong competitive interference from simultaneously encountered background odorants. This problem is fundamentally constraining on early-stage olfactory encoding strategies and must be resolved if these strategies and their underlying mechanisms are to be understood. Multiscale general theories of olfactory systems operation are essential in order to leverage the analytical advantages of engineered approaches together with our expanding capacity to interrogate biological systems.
Effects of Non-insulin Anti-hyperglycemic Agents on Gut Microbiota: A Systematic Review on Human and Animal Studies

Background: As growing evidence links gut microbiota with the therapeutic efficacy and side effects of anti-hyperglycemic drugs, this article aims to provide a systematic review of the reciprocal interactions between anti-hyperglycemic drugs and gut microbiota taxa, which underlie the effect of the gut microbiome on diabetic control via bug-host interactions. Method: We followed the PRISMA requirements to perform a systematic review on human vs. animal gut microbiota data in PubMed, SCOPUS, and EMBASE databases, and used Cochrane, ROBIN-I, and SYRCLE tools to assess potential bias risks. The outcomes of assessment were trends on gut microbiota taxa, diversity, and associations with metabolic control (e.g., glucose, lipid) following anti-hyperglycemic treatment. Results: Of 2,804 citations, 64 studies (17/humans; 47/mice) were included. In human studies, seven were randomized trials using metformin or acarbose in obese, pre-diabetes, and type 2 diabetes (T2D) patients. Treatment of pre-diabetes and newly diagnosed T2D patients with metformin or acarbose was associated with decreases in genus of Bacteroides, accompanied by increases in both Bifidobacterium and Lactobacillus. Additionally, T2D patients receiving metformin showed increases in various taxa of the order Enterobacteriales and the species Akkermansia muciniphila. Of seven studies with significant differences in beta-diversity, the incremental specific taxa were associated with the improvement of glucose and lipid profiles. In mice, the effects of metformin on A. muciniphila were similar, but an inverse association with Bacteroides was reported. Animal studies on other anti-hyperglycemic drugs, however, showed substantial variations in results. Conclusions: The changes in specific taxa and β-diversity of gut microbiota were associated with metformin and acarbose in humans while pertinent information for other anti-hyperglycemic drugs could only be obtained in rodent studies. Further human studies on anti-hyperglycemic drugs other than metformin and acarbose are needed to explore gut microbiota's role in their therapeutic efficacies and side effects.
Diagnostic Test Criteria for HLA Genotyping to Prevent Drug Hypersensitivity Reactions: A Systematic Review of Actionable HLA Recommendations in CPIC and DPWG Guidelines

Introduction Certain HLA variants are associated with an increased risk of hypersensitivity reactions to specific drugs. Both the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG) have issued actionable HLA gene – drug interaction guidelines but diagnostic test criteria remain largely unknown. We present an overview of the diagnostic test criteria of the actionable HLA – drug pairs. Methods A systematic literature search was conducted in PubMed, Embase, Web of Science and Cochrane Library. Original case-control and cohort studies were selected and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and number needed to genotype (NNG) were calculated for the actionable HLA-drug pairs. Results In general, the HLA tests show high specificity and NPV for predicting hypersensitivity reactions. The sensitivity of HLA tests shows a wide range, from 0-33% for HLA-B*1502 testing to predict lamotrigine induced SJS/TEN up to 100% for HLA-B*5701 to predict immunologically confirmed abacavir hypersensitivity syndrome (ABC-HSR). PPV is low for all tests except for HLA-B*5701 and ABC-HSR which is approximately 50%. HLA-B*5701 to predict ABC-HSR shows the lowest NNG followed by HLA-B*5801 for allopurinol induced severe cutaneous adverse drug reactions and HLA-B*1502 for carbamazepine induced SJS/TEN. Discussion This is the first overview of diagnostic test criteria for actionable HLA-drug pairs. Studies researching HLA genes and hypersensitivity are scarce for some of the HLA-drug pairs in some populations and patient numbers in studies are small. Therefore, more research is necessary to calculate the diagnostic test criteria more accurately.
Local Sleep and Alzheimer’s Disease Pathophysiology

Even prior to the onset of the prodromal stages of Alzheimer’s disease (AD), a constellation of sleep disturbances are apparent. A series of epidemiological studies indicate that multiple forms of these sleep disturbances are associated with increased risk for developing mild cognitive impairment (MCI) and AD, even triggering disease onset at an earlier age. Through the combination of causal manipulation studies in humans and rodents, as well as targeted examination of sleep disturbance with respect to AD biomarkers, mechanisms linking sleep disturbance to AD are beginning to emerge. In this review, we explore recent evidence linking local deficits in brain oscillatory function during sleep with local AD pathological burden and circuit-level dysfunction and degeneration. In short, three deficits in the local expression of sleep oscillations have been identified in relation to AD pathophysiology: (1) frequency-specific frontal deficits in slow wave expression during non-rapid eye movement (NREM) sleep, (2) deficits in parietal sleep spindle expression, and (3) deficits in the quality of electroencephalographic (EEG) desynchrony characteristic of REM sleep. These deficits are noteworthy since they differ from that seen in normal aging, indicating the potential presence of an abnormal aging process. How each of these are associated with β-amyloid (Aβ) and tau pathology, as well as neurodegeneration of circuits sensitive to AD pathophysiology, are examined in the present review, with a focus on the role of dysfunction within fronto-hippocampal and subcortical sleep-wake circuits. It is hypothesized that each of these local sleep deficits arise from distinct network-specific dysfunctions driven by regionally-specific accumulation of AD pathologies, as well as their associated neurodegeneration. Overall, the evolution of these local sleep deficits offer unique windows into the circuit-specific progression of distinct AD pathophysiological processes prior to AD onset, as well as their impact on brain function. This includes the potential erosion of sleep-dependent memory mechanisms, which may contribute to memory decline in AD. This review closes with a discussion of the remaining critical knowledge gaps and implications of this work for future mechanistic studies and studies implementing sleep-based treatment interventions.
Contrasting the brain imaging features of MOG-antibody disease, with AQP4-antibody NMOSD and multiple sclerosis

Background: Identifying magnetic resonance imaging (MRI) markers in myelin-oligodendrocytes-glycoprotein antibody-associated disease (MOGAD), neuromyelitis optica spectrum disorder-aquaporin-4 positive (NMOSD-AQP4) and multiple sclerosis (MS) is essential for establishing objective outcome measures. Objectives: To quantify imaging patterns of central nervous system (CNS) damage in MOGAD during the remission stage, and to compare it with NMOSD-AQP4 and MS. Methods: 20 MOGAD, 19 NMOSD-AQP4, 18 MS in remission with brain or spinal cord involvement and 18 healthy controls (HC) were recruited. Volumetrics, lesions and cortical lesions, diffusion-imaging measures, were analysed. Results: Deep grey matter volumes were lower in MOGAD (p = 0.02) and MS (p = 0.0001), compared to HC and were strongly correlated with current lesion volume (MOGAD R = −0.93, p < 0.001, MS R = −0.65, p = 0.0034). Cortical/juxtacortical lesions were seen in a minority of MOGAD, in a majority of MS and in none of NMOSD-AQP4. Non-lesional tissue fractional anisotropy (FA) was only reduced in MS (p = 0.01), although focal reductions were noted in NMOSD-AQP4, reflecting mainly optic nerve and corticospinal tract pathways. Conclusion: MOGAD patients are left with grey matter damage, and this may be related to persistent white matter lesions. NMOSD-AQP4 patients showed a relative sparing of deep grey matter volumes, but reduced non-lesional tissue FA. Observations from our study can be used to identify new markers of damage for future multicentre studies.
Influence of Shoe Mass on Performance and Running Economy in Trained Runners

Purpose The aim of this study was to assess the effects of adding shoe mass on running economy (RE), gait characteristics, neuromuscular variables and performance in a group of trained runners. Methods Eleven trained runners (6 men and 5 women) completed four evaluation sessions separated by at least 7 days. The first session consisted of a maximal incremental test where the second ventilatory threshold (VT2) and the speed associated to the VO2max (vVO2max) were calculated. In the next sessions, RE at 75, 85, and 95% of the VT2 and the time to exhaustion (TTE) at vVO2max were assessed in three different shoe mass conditions (control, +50 g and +100 g) in a randomized, counterbalanced crossover design. Biomechanical and neuromuscular variables, blood lactate and energy expenditure were measured during the TTE test. Results RE worsened with the increment of shoe mass (Control vs. 100 g) at 85% (7.40%, 4.409 ± 0.29 and 4.735 ± 0.27 kJ⋅kg−1⋅km−1, p = 0.021) and 95% (10.21%, 4.298 ± 0.24 and 4.737 ± 0.45 kJ⋅kg−1⋅km−1, p = 0.005) of VT2. HR significantly increased with the addition of mass (50 g) at 75% of VT2 (p = 0.01) and at 75, 85, and 95% of VT2 (p = 0.035, 0.03, and 0.03, respectively) with the addition of 100 g. TTE was significantly longer (∼22%, ∼42 s, p = 0.002, ES = 0.149) in the Control condition vs. 100 g condition, but not between Control vs. 50 g (∼24 s, p = 0.094, ES = 0.068). Conclusion Overall, our findings suggest that adding 100 g per shoe impairs running economy and performance in trained runners without changes in gait characteristics or neuromuscular variables. These findings further support the use of light footwear to optimize running performance.
Soccer-Related Concussions Among Swedish Elite Soccer Players: A Descriptive Study of 1,030 Players

Objective: There are growing concerns about the short- and long-term consequences of sports-related concussion, which account for about 5–9% of all sports injuries. We hypothesized there may be sex differences in concussion history and concussion-related symptoms, evaluated among elite soccer players in Sweden. Design: Retrospective survey study. Participants and Setting: Soccer players (n = 1,030) from 55 Swedish elite soccer teams. Questionnaires were completed prior to the start of the 2017 season. Assessment of Risk Factors: Player history of soccer-related concussion (SoRC), symptoms and management following a SoRC were evaluated. Main Outcome Measures: Before the start of the season the players completed a baseline questionnaire assessing previous concussions. The Sports Concussion Assessment Tool 3 was included with regard to symptom evaluation. Results: Out of 993 responding players 334 (34.6%) reported a previous SoRC and 103 players (10.4%) reported a SoRC during the past year. After sustaining a SoRC, 114 players (34.2%) reported that they continued their ongoing activity without a period of rest, more commonly female (44.9%) than male players (27.7%; P = 0.002). Symptom resolution time was 1 week or less for 61.3% of the players that reported having persisting symptoms. A positive correlation was observed between number of previous concussions and prevalence of three persisting symptoms: fatigue (P < 0.001), concentration/memory issues (P = 0.002) and headache (P = 0.047). Conclusion: About 35% of male and female elite soccer players in Sweden have experienced a previous SoRC, and about 10% experienced a SoRC during the last year. Female players continued to play after a SoRC, without a period of rest, more often than males. A higher risk of persisting symptoms was observed in players with a history of multiple concussions.
Immersive Virtual Reality to Restore Natural Long-Range Autocorrelations in Parkinson’s Disease Patients’ Gait During Treadmill Walking

Effects of treadmill walking on Parkinson’s disease (PD) patients’ spatiotemporal gait parameters and stride duration variability, in terms of magnitude [coefficient of variation (CV)] and temporal organization [long range autocorrelations (LRA)], are known. Conversely, effects on PD gait of adding an optic flow during treadmill walking using a virtual reality headset, to get closer to an ecological walk, is unknown. This pilot study aimed to compare PD gait during three conditions: Overground Walking (OW), Treadmill Walking (TW), and immersive Virtual Reality on Treadmill Walking (iVRTW). Ten PD patients completed the three conditions at a comfortable speed. iVRTW consisted in walking at the same speed as TW while wearing a virtual reality headset reproducing an optic flow. Gait parameters assessed were: speed, step length, cadence, magnitude (CV) and temporal organization (evenly spaced averaged Detrended Fluctuation Analysis, α exponent) of stride duration variability. Motion sickness was assessed after TW and iVRTW using the Simulator Sickness Questionnaire (SSQ). Step length was greater (p = 0.008) and cadence lower (p = 0.009) during iVRTW compared to TW while CV was similar (p = 0.177). α exponent was similar during OW (0.77 ± 0.07) and iVRTW (0.76 ± 0.09) (p = 0.553). During TW, α exponent (0.85 ± 0.07) was higher than during OW (p = 0.039) and iVRTW (p = 0.016). SSQ was similar between TW and iVRTW (p = 0.809). iVRTW is tolerable, could optimize TW effects on spatiotemporal parameters while not increasing CV in PD. Furthermore, iVRTW could help to capture the natural LRA of PD gait in laboratory settings and could potentially be a challenging second step in PD gait rehabilitation.