Miracle-dz/UniFAR-FTUs huggingface dataset:
Are Migraine Patients at Increased Risk for Symptomatic Coronavirus Disease 2019 Due to Shared Comorbidities?

The coronavirus disease 2019 (COVID‐19) pandemic has rapidly transformed the whole world and forced us to look through comorbid diseases and risk factors from a different perspective. COVID‐19 shows some inherent risk factors like cardiovascular comorbidities independent from age, gender, and geographic location. One of the most peculiar features of the COVID‐19 pandemic is that severe acute respiratory syndrome coronavirus 2 respiratory infections disproportionately impact patients with hypertension, diabetes, and other cardiovascular comorbidities rather than those with allergic respiratory diseases and immune‐compromised conditions. Migraine is a complex neuro‐vasculo‐inflammatory disorder that is also packed frequently with certain medical conditions including vascular disorders, hypertension, allergic diseases such as asthma and systemic inflammatory disorders. Accordingly, 2 different questions arise during the pandemic: (1) Do share comorbidities of cardiovascular diseases and hypertension increase the risk of symptomatic COVID‐19 for migraine patients? (2) Do comorbid allergic and atopic diseases, including asthma act as opposite influencers alongside with female gender? This paper focuses on the co‐existence of comorbidities of COVID‐19, in comparison with migraine, based on a wide clinical dataset and available reports. Discussed mechanisms include potential strategic roles of angiotensin‐converting enzyme 2, angiotensin‐II, and nucleotide oligomerization domain‐like receptor family, pyrin domain containing 3 inflammasome, playing remarkable parts in the pathogenesis of COVID‐19 and migraine. There are also some clues about the importance of endothelial and pericyte dysfunction and neuroinflammation in COVID‐19 infection, related to complications and survival of the patients. The large epidemiological studies as well as basic research, focusing on migraine patients with COVID‐19 will clarify these vital questions during the upcoming periods.
Chemical Composition and In Vitro Antiplasmodial Activity of the Ethanolic Extract of Cyperus articulatus var. nodosus Residue

Cyperus articulatus L. is popularly known as priprioca. Its rhizomes are used as a medicine in the treatment of malaria in traditional medicine. Since priprioca oil is extracted for commercial purpose, we evaluated if the components from the priprioca residue can be a source of antiplasmodial active molecules. This study aimed to determine the in vitro antiplasmodial and cytotoxicity activities of the ethanolic extract of C. articulatus as an in vitro antiplasmodial agent. From the solid residue of the plant rhizomes, 40 g samples were removed and subjected to hot extraction using a Soxhlet extractor. The in vitro antiplasmodial activity was determined using the W2 and 3D7 strains of P. falciparum. The phytochemical study identified the following main compounds: corymbolone (14.25%), cyclocolorenone (9.75%), and cadalene (8.36%). The extract exhibited moderate IC50 (inhibitory concentration) against the two strains of P. falciparum: 1.21 ± 0.01 against the W2 strain and 1.10 ± 0.06 µg/mL against the 3D7 strain. Our results show the therapeutic potential of priprioca residue as a low-cost antiplasmodial agent.
Recommended dose voxel size and statistical uncertainty parameters for precision of Monte Carlo dose calculation in stereotactic radiotherapy

Abstract Monte Carlo (MC)‐based treatment planning requires a choice of dose voxel size (DVS) and statistical uncertainty (SU). These parameters effect both the precision of displayed dose distribution and time taken to complete a calculation. For efficient, accurate, and precise treatment planning in a clinical setting, optimal values should be selected. In this investigation, 30 volumetric modulated arc therapy (VMAT) stereotactic radiotherapy (SRT) treatment plans, 10 brain, 10 lung, and 10 spine were calculated in the Monaco 5.11. 02 treatment planning system (TPS). Each plan was calculated with a DVS of 0.1 and 0.2 cm using SU values of 0.50%, 0.75%, 1.00%, 1.50%, and 2.00%, along with a ground truth calculation using a DVS of 0.1 cm and SU of 0.15%. The variance at each relative dose level was calculated for all SU settings to assess their relationship. The variation from the ground truth calculation for each DVS and SU combination was determined for a range of DVH metrics and plan quality indices along with the time taken to complete the calculations. Finally, the effect of defining the maximum dose using a volume of 0.035 cc was compared to 0.100 cc when considering DVS and SU settings. Changes in the DVS produced greater variations from the ground truth calculation than changes in SU across the values tested. Plan quality metrics and mean dose values showed less sensitivity to changes in SU than DVH metrics. From this study, it was concluded that while maintaining an average calculation time of <10 min, 75% of plans could be calculated with variations of <2.0% from their ground truth values when using an SU setting of 1.50% and a DVS of 0.1 cm in the case of brain or spine plans, and a 0.2 cm DVS in the case of lung plans.
Leukocyte telomere length and mycophenolate therapy in chronic hypersensitivity pneumonitis

Recent prospective clinical trials have shown antifibrotic therapies slow lung function decline in patients with idiopathic pulmonary fibrosis (IPF) [1, 2] and progressive fibrosing interstitial lung disease (ILD). Similar findings were demonstrated in scleroderma-associated ILD [3], despite use of the immunosuppressive therapy mycophenolate mofetil (MMF). Prospective data for the treatment of other forms of ILD, such as chronic hypersensitivity pneumonitis (CHP) are lacking. Our groups previously reported that the treatment of CHP with MMF was associated with a decreased incidence of adverse events, a reduction in prednisone dose, and improved lung function when compared to prednisone alone [4, 5], but prospective studies are needed to confirm these findings. Patients with chronic hypersensitivity pneumonitis and telomere lengths above the first quartile may have improved survival with mycophenolate therapy. https://bit.ly/3maRXih
Fear in dreams and in wakefulness: Evidence for day/night affective homeostasis

Recent neuroscientific theories have proposed that emotions experienced in dreams contribute to the resolution of emotional distress and preparation for future affective reactions. We addressed one emerging prediction, namely that experiencing fear in dreams is associated with more adapted responses to threatening signals during wakefulness. Using a stepwise approach across two studies, we identified brain regions activated when experiencing fear in dreams and showed that frightening dreams modulated the response of these same regions to threatening stimuli during wakefulness. Specifically, in Study 1, we performed serial awakenings in 18 participants recorded throughout the night with high-density EEG and asked them whether they experienced any fear in their dreams. Insula and midcingulate cortex activity increased for dreams containing fear. In Study 2, we tested 89 participants and found that those reporting higher incidence of fear in their dreams showed reduced emotional arousal and fMRI response to fear-eliciting stimuli in the insula, amygdala and midcingulate cortex, while awake. Consistent with better emotion regulation processes, the same participants displayed increased medial prefrontal cortex activity. These findings support that emotions in dreams and wakefulness engage similar neural substrates, and substantiate a link between emotional processes occurring during sleep and emotional brain functions during wakefulness. SIGNIFICANT STATEMENT Highly debated while pivotal to current theoretical models of dreaming, the relationship between emotion processing during wakefulness and in dreams remains elusive. In a first study, we used high-density EEG recordings and observed that regions involved in fear processing (i.e. the insula and midcingulate cortex) were activated during fear-related dreams. This first finding demonstrates that emotions in dreams engage similar neural circuits as during wakefulness. In a second study, using fMRI, we show that higher incidence of fear in dreams was associated with reduced emotional arousal and brain responses indicative of better emotion regulation during wakefulness. Together, these results strongly support the idea that experiencing fear in a secure environment, as in dreams, relates to more adapted responses to threatening events in real life.
Surface quality and endothelial cell viability after femtosecond laser-assisted donor lenticule preparation for endothelial keratoplasty - An in-vitro study

Purpose: To compare surface quality and endothelial cell viability of descemet stripping automated endothelial keratoplasty (DSAEK) donor lenticules prepared with femtosecond laser (FSL) or microkeratome (MK). Methods: Experimental ex-vivo evaluation of 15 DSAEK donor lenticules prepared from optical quality donor corneas using 200 KHz FSL (9 eyes) or MK (6 eyes). Surface quality and smoothness of the cut were assessed using atomic force microscopy and endothelial cell viability was assessed using transmission electron microscopy. Results: Mean lenticule thickness was 121.89 ± 17.13 μm in FSL group and 112.67 ± 5.89 μm in MK group (P = 0.33). Average roughness of stromal surface (RMSavg) [FSL- 30.51 ± 4.55 nm, MK-22.37 ± 1.83 nm; P = 0.02] and root mean square roughness (RMSrough) [FSL-31.39 ± 5.75 nm, MK-23.08 ± 0.40 nm; P = 0.012] was significantly more in FSL group. Increased granular and linear irregularities were observed in the FSL group. Endothelial cell disruption was more in FSL group (FSL- 29.49 ± 6.91% MK-13.28 ± 3.62%; P < 0.001) with decreased mean nucleus length (FSL-5.56 ± 0.17 μm, MK-7.52 ± 0.65 μm; P < 0.001). Conclusion: Automated MKs are still the standard of care for donor lenticule preparation and MK-assisted donor lenticules have smoother surface with less endothelial cell disruption than FSL. Further research is mandatory before FSL platforms can be considered a viable alternative to the MK.
Squeeze for Sneeze: Compact Neural Networks for Cold and Flu Recognition

In digital health applications, speech offers advantages over other physiological signals, in that it can be easily collected, transmitted, and stored using mobile and Internet of Things (IoT) technologies. However, to take full advantage of this positioning, speech-based machine learning models need to be deployed on devices that can have considerable memory and power constraints. These constraints are particularly apparent when attempting to deploy deep learning models, as they require substantial amounts of memory and data movement operations. Herein, we test the suitability of pruning and quan-tisation as two methods to compress the overall size of neural networks trained for a health-driven speech classiﬁcation task. Key results presented on the Upper Respiratory Tract Infection Corpus indicate that pruning, then quantising a network can reduce the number of operational weights by almost 90%. They also demonstrate the overall size of the network can be reduced by almost 95%, as measured in MB, without affecting overall recognition performance.
Antidepressant drug sertraline modulates AMPK-MTOR signaling-mediated autophagy via targeting mitochondrial VDAC1 protein

ABSTRACT Macroautophagy/autophagy (hereafter autophagy), the process of mass degradation of unnecessary elements within the cell, is often dysregulated in many diseases such as cancer, atherosclerosis, and neurodegenerative diseases. Hence, autophagy modulating agents have a great potential to be therapeutic agents for the autophagy-related diseases. Here we report that an anti-depressant drug sertraline (Sert) is an autophagy-inducing agent. Mechanistically, Sert potentially binds to and antagonizes the mitochondrial VDAC1 (voltage dependent anion channel 1), resulting in reduced cellular ATP (adenosine triphosphate) level, activation of AMP-activated protein kinase (AMPK) and inhibition of its downstream, MTOR (mechanistic target of rapamycin kinase)-RPS6KB1 (ribosomal protein S6 kinase B1) signaling pathway. Cells lacking VDAC1 expression completely abrogate the modulatory effect of Sert on AMPK-MTOR pathway and autophagy-inducing activity. We further show that Sert suppresses tauopathy by promoting the autophagic degradation of MAPT (microtubule associated protein tau) protein via inducing autophagy. Our study demonstrates the potential of Sert as a novel small molecule autophagy-inducing agent and provides a new drug candidate to treat autophagy related diseases by targeting VDAC1. Abbreviations: AMP: adenosine monophosphate; AMPK: AMP-activated protein kinase; ATP: adenosine triphosphate; Baf: bafilomycin A1; BiFC: biomolecular fluorescence complementation; CAMKK2/CAMKKB: calcium/calmodulin dependent protein kinase kinase 2; CC: compound C; DARTS: drug affinity responsive target stability; HUVECs: human umbilical vein endothelial cells; Inda: indatraline; STK11/LKB1: serine/threonine kinase 11; MAPT: microtubule associated protein tau; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; 3-MA: 3-methyladenine; MEFs: mouse embryonic fibroblasts; MTOR: mechanistic target of rapamycin kinase; PI3K: phosphoinositide 3-kinase; Rapa: rapamycin; Sert: sertraline; RPS6KB1: ribosomal protein S6 kinase B1; SQSTM1/p62: sequestosome 1; SLC6A4/SERT1: solute carrier family 6 member 4; TFEB: transcription factor EB; VDAC1: voltage dependent anion channel 1; WT: wild-type; WM: wortmannin.
Pitfalls Associated with Discriminating Mixed-Species Biofilms by Flow Cytometry

Since biofilms are ubiquitous in different settings and act as sources of disease for humans, reliable methods to characterize and quantify these microbial communities are required. Numerous techniques have been employed, but most of them are unidirectional, labor intensive and time consuming. Although flow cytometry (FCM) can be a reliable choice to quickly provide a multiparametric analysis, there are still few applications on biofilms, and even less on the study of inter-kingdom communities. This work aimed to give insights into the application of FCM in order to more comprehensively analyze mixed-species biofilms, formed by different Pseudomonas aeruginosa and Candida albicans strains, before and after exposure to antimicrobials. For comparison purposes, biofilm culturability was also assessed determining colony-forming units. The results showed that some aspects, namely the microbial strain used, the morphological state of the cells and the biofilm matrix, make the accurate analysis of FCM data difficult. These aspects were even more challenging when double-species biofilms were being inspected, as they could engender data misinterpretations. The outcomes draw our attention towards the need to always take into consideration the characteristics of the biofilm samples to be analyzed through FCM, and undoubtedly link to the need for optimization of the processes tailored for each particular case study.
Evaluation of autonomic modulation of lung function and heart rate in children with cystic fibrosis

The autonomic nervous system (ANS) plays an important role in modulating bronchial smooth muscle contractility, which is altered in cystic fibrosis (CF). A convenient approach to probe ANS regulation is the quantitative analysis of heart rate variability (HRV). The purpose of this study was to evaluate ANS regulation in children with CF and to investigate the influence of colonization by Pseudonomas aeruginosa via assessment of HRV in colonized CF (CCF) children and noncolonized CF (NCCF) children. Sixteen children with CF (7 CCF and 9 NCCF) and seven healthy age‐matched control children were enrolled in the study. Heart rate was recorded for 10 min at rest in the supine and standing positions and HRV analysis was carried out using autoregressive spectral analysis. The CCF group was characterized by lower forced expiratory volume than NCCF, indicating an impairment of respiratory function. The HRV parameters further confirmed the possible sympathetic overactivity in CCF. Children with CF exhibited hyperactivity of the sympathetic nervous system. In particular, the CCF group presented a greater impairment of ANS modulation. Both CCF and NCCF children showed lower supine vagal activation in the HRV indices related to sympathetic activation and reduction of indices indicating vagal activity with the postural change from supine to standing when compared to the NCCF group.
Do End-to-End Speech Recognition Models Care About Context?

The two most common paradigms for end-to-end speech recognition are connectionist temporal classification (CTC) and attention-based encoder-decoder (AED) models. It has been argued that the latter is better suited for learning an implicit language model. We test this hypothesis by measuring temporal context sensitivity and evaluate how the models perform when we constrain the amount of contextual information in the audio input. We find that the AED model is indeed more context sensitive, but that the gap can be closed by adding self-attention to the CTC model. Furthermore, the two models perform similarly when contextual information is constrained. Finally, in contrast to previous research, our results show that the CTC model is highly competitive on WSJ and LibriSpeech without the help of an external language model.
Stability of psilocybin and its four analogs in the biomass of the psychotropic mushroom Psilocybe cubensis.

Psilocybin, psilocin, baeocystin, norbaeocystin, and aeruginascin are tryptamines structurally similar to the neurotransmitter serotonin. Psilocybin and its pharmacologically active metabolite psilocin in particular are known for their psychoactive effects. These substances typically occur in most species of the genus Psilocybe (Fungi, Strophariaceae). Even the sclerotia of some of these fungi known as "magic truffles" are of growing interest in microdosing due to them improving cognitive function studies. In addition to microdosing studies, psilocybin has also been applied in clinical studies, but only its pure form has been administrated so far. Moreover, the determination of tryptamine alkaloids is used in forensic analysis. In this study, freshly cultivated fruit bodies of Psilocybe cubensis were used for monitoring stability (including storage and processing conditions of fruiting bodies). Furthermore, mycelium and the individual parts of the fruiting bodies (caps, stipes, and basidiospores) were also examined. The concentration of tryptamines in final extracts was analyzed using ultra-high-performance chromatography coupled with mass spectrometry. No tryptamines were detected in the basidiospores and only psilocin was present at 0.47 wt. % in the mycelium. The stipes contained approximately half the amount of tryptamine alkaloids (0.52 wt.%) than the caps (1.03 wt.%); however, these results were not statistically significant, as the concentration of tryptamines in individual fruiting bodies is highly variable. The storage conditions showed that the highest degradation of tryptamines was seen in fresh mushrooms stored at -80°C and the lowest decay was seen in dried biomass stored in the dark at room temperature.
Does identifying frailty from ICD-10 coded data on hospital admission improve prediction of adverse outcomes in older surgical patients? A population-based study.

BACKGROUND frailty is a major contributor to poor health outcomes in older people, separate from age, sex and comorbidities. This population-based validation study evaluated the performance of the International Classification of Diseases, 10th revision, coded Hospital Frailty Risk Score (HFRS) in the prediction of adverse outcomes in an older surgical population and compared its performance against the commonly used Charlson Comorbidity Index (CCI). METHODS hospitalisation and death data for all individuals aged ≥50 admitted for surgery to New South Wales hospitals (2013-17) were linked. HFRS and CCI scores were calculated using both 2- and 5-year lookback periods. To determine the influence of individual explanatory variables, several logistic regression models were fitted for each outcome of interest (30-day mortality, prolonged length of stay (LOS) and 28-day readmission). Area under the receiving operator curve (AUC) and Akaike information criterion (AIC) were assessed. RESULTS of the 487,197 patients, 6.8% were classified as high HFRS, and 18.3% as high CCI. Although all models performed better than base model (age and sex) for prediction of 30-day mortality, there was little difference between CCI and HFRS in model discrimination (AUC 0.76 versus 0.75), although CCI provided better model fit (AIC 79,020 versus 79,910). All models had poor ability to predict prolonged LOS (AUC range 0.62-0.63) or readmission (AUC range 0.62-0.65). Using a 5-year lookback period did not improve model discrimination over the 2-year period. CONCLUSIONS adjusting for HFRS did not improve prediction of 30-mortality over that achieved by the CCI. Neither HFRS nor CCI were useful for predicting prolonged LOS or 28-day unplanned readmission.
Selectin-Targeting Glycosaminoglycan-Peptide Conjugate Limits Neutrophil Mediated Cardiac Reperfusion Injury.

AIMS One of the hallmarks of myocardial infarction (MI) is excessive inflammation. During an inflammatory insult, damaged endothelial cells shed their glycocalyx, a carbohydrate-rich layer on the cell surface which provides a regulatory interface to immune cell adhesion. Selectin-mediated neutrophilia occurs as a result of endothelial injury and inflammation. We recently designed a novel selectin-targeting glycocalyx mimetic (termed DS-IkL) capable of binding inflamed endothelial cells. This study examines the capacity of DS-IkL to limit neutrophil binding and platelet activation on inflamed endothelial cells, as well as the cardio-protective effects of DS-IkL after acute myocardial infarction. METHODS AND RESULTS In vitro, DS-IkL diminished neutrophil interactions with both recombinant selectin and inflamed endothelial cells, and limited platelet activation on inflamed endothelial cells. Our data demonstrated that DS-IkL localized to regions of vascular inflammation in vivo after 45 minutes of left anterior descending coronary artery ligation induced MI. Further, findings from this study show DS-IkL treatment had short- and long-term cardioprotective effects after ischemia/reperfusion at the left anterior descending coronary artery. Mice treated with DS-IkL immediately after ischemia/reperfusion and 24 hours later exhibited reduced neutrophil extravasation, macrophage accumulation, fibroblast and endothelial cell proliferation, and fibrosis compared to saline controls. CONCLUSIONS Our findings suggest that DS-IkL has great therapeutic potential after MI by limiting reperfusion injury induced by the immune response. TRANSLATIONAL PERSPECTIVE Cardiovascular disease remains the leading cause of mortality worldwide. Acute inflammation from myocardial infarction (MI) results in damaged endothelial cells, leading to the loss of glycocalyx. Here, we designed a novel selectin-targeting glycocalyx mimetic (termed DS-IkL) capable of binding inflamed endothelial cells. DS-IkL limits neutrophil binding and platelet activation on inflamed endothelial cells. Treatment with DS-IkL in a preclinical model of MI reduces infarct size by preventing neutrophil extravasation, macrophage accumulation, fibroblast and endothelial cell proliferation, and fibrosis. Our findings suggest that DS-IkL has great therapeutic potential after MI by limiting reperfusion injury induced by the immune response.