Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolomics of Cerebrospinal Fluid from Healthy Subjects Reveal Metabolites Associated with Ageing

To increase our understanding of age-related diseases affecting the central nervous system (CNS) it is important to understand the molecular processes of biological ageing. Metabolomics of cerebrospinal fluid (CSF) is a promising methodology to increase our understanding of naturally occurring processes of ageing of the brain and CNS that could be reflected in CSF. In the present study the CSF metabolomes of healthy subjects aged 30–74 years (n = 23) were studied using liquid chromatography high-resolution mass spectrometry (LC-HRMS), and investigated in relation to age. Ten metabolites were identified with high confidence as significantly associated with ageing, eight with increasing levels with ageing: isoleucine, acetylcarnitine, pipecolate, methionine, glutarylcarnitine, 5-hydroxytryptophan, ketoleucine, and hippurate; and two decreasing with ageing: methylthioadenosine and 3-methyladenine. To our knowledge, this is the first time the CSF metabolomes of healthy subjects are assessed in relation to ageing. The present study contributes to the field of ageing metabolomics by presenting a number of metabolites present in CSF with potential relevance for ageing and the results motivate further studies.
Fine-Tuning the Biological Profile of Multitarget Mitochondriotropic Antioxidants for Neurodegenerative Diseases

Neurotransmitter depletion and mitochondrial dysfunction are among the multiple pathological events that lead to neurodegeneration. Following our previous studies related with the development of multitarget mitochondriotropic antioxidants, this study aims to evaluate whether the π-system extension on the chemical scaffolds of AntiOXCIN2 and AntiOXCIN3 affects their bioactivity and safety profiles. After the synthesis of four triphenylphosphonium (TPP+) conjugates (compounds 2–5), we evaluated their antioxidant properties and their effect on neurotransmitter-metabolizing enzymes. All compounds were potent equine butyrylcholinesterase (eqBChE) and moderate electric eel acetylcholinesterase (eeAChE) inhibitors, with catechols 4 and 5 presenting lower IC50 values than AntiOXCIN2 and AntiOXCIN3, respectively. However, differences in the inhibition potency and selectivity of compounds 2–5 towards non-human and human cholinesterases (ChEs) were observed. Co-crystallization studies with compounds 2–5 in complex with human ChEs (hChEs) showed that these compounds exhibit different binging modes to hAChE and hBChE. Unlike AntiOXCINs, compounds 2–5 displayed moderate human monoamine oxidase (hMAO) inhibitory activity. Moreover, compounds 4 and 5 presented higher ORAC-FL indexes and lower oxidation potential values than the corresponding AntiOXCINs. Catechols 4 and 5 exhibited broader safety windows in differentiated neuroblastoma cells than benzodioxole derivatives 2 and 3. Compound 4 is highlighted as a safe mitochondria-targeted antioxidant with dual ChE/MAO inhibitory activity. Overall, this work is a contribution for the development of dual therapeutic agents addressing both mitochondrial oxidative stress and neurotransmitter depletion.
Multirate Processing with Selective Subbands and Machine Learning for Efficient Arrhythmia Classification †

The usage of wearable gadgets is growing in the cloud-based health monitoring systems. The signal compression, computational and power efficiencies play an imperative part in this scenario. In this context, we propose an efficient method for the diagnosis of cardiovascular diseases based on electrocardiogram (ECG) signals. The method combines multirate processing, wavelet decomposition and frequency content-based subband coefficient selection and machine learning techniques. Multirate processing and features selection is used to reduce the amount of information processed thus reducing the computational complexity of the proposed system relative to the equivalent fixed-rate solutions. Frequency content-dependent subband coefficient selection enhances the compression gain and reduces the transmission activity and computational cost of the post cloud-based classification. We have used MIT-BIH dataset for our experiments. To avoid overfitting and biasness, the performance of considered classifiers is studied by using five-fold cross validation (5CV) and a novel proposed partial blind protocol. The designed method achieves more than 12-fold computational gain while assuring an appropriate signal reconstruction. The compression gain is 13 times compared to fixed-rate counterparts and the highest classification accuracies are 97.06% and 92.08% for the 5CV and partial blind cases, respectively. Results suggest the feasibility of detecting cardiac arrhythmias using the proposed approach.
Pavement Overrides the Effects of Tree Species on Soil Bacterial Communities

Human disturbance and vegetation are known to affect soil microorganisms. However, the interacting effects of pavement and plant species on soil bacterial communities have received far less attention. In this study, we collected soil samples from pine (Pinus tabuliformis Carr.), ash (Fraxinus chinensis), and maple (Acer truncatum Bunge) stands that grew in impervious, pervious, and no pavement blocks to investigate the way pavement, tree species, and their interaction influence soil bacterial communities by modifying soil physicochemical properties. Soil bacterial community composition and diversity were evaluated by bacterial 16S amplicon sequencing. The results demonstrated that soil bacterial community composition and diversity did differ significantly across pavements, but not with tree species. The difference in soil bacterial community composition across pavements was greater in pine stands than ash and maple stands. Soil bacterial diversity and richness indices decreased beneath impervious pavement in pine stands, and only bacterial richness indices decreased markedly in ash stands, but neither showed a significant difference across pavements in maple stands. In addition, bacterial diversity did not differ dramatically between pervious pavement and no pavement soil. Taken together, these results suggest that pavement overwhelmed the effects of tree species on soil bacterial communities, and had a greater effect on soil bacterial communities in pine stands, followed by ash and maple stands. This study highlights the importance of anthropogenic disturbance, such as pavement, which affects soil microbial communities.
Magnetically Counting Hand Movements: Validation of a Calibration-Free Algorithm and Application to Testing the Threshold Hypothesis of Real-World Hand Use after Stroke

There are few wearable sensors suitable for daily monitoring of wrist and finger movements for hand-related healthcare applications. Here, we describe the development and validation of a novel algorithm for magnetically counting hand movements. We implemented the algorithm on a wristband that senses magnetic field changes produced by movement of a magnetic ring worn on the finger (the “Manumeter”). The “HAND” (Hand Activity estimated by Nonlinear Detection) algorithm assigns a “HAND count” by thresholding the real-time change in magnetic field created by wrist and/or finger movement. We optimized thresholds to achieve a HAND count accuracy of ~85% without requiring subject-specific calibration. Then, we validated the algorithm in a dexterity-impaired population by showing that HAND counts strongly correlate with clinical assessments of upper extremity (UE) function after stroke. Finally, we used HAND counts to test a recent hypothesis in stroke rehabilitation that real-world UE hand use increases only for stroke survivors who achieve a threshold level of UE functional capability. For 29 stroke survivors, HAND counts measured at home did not increase until the participants’ Box and Blocks Test scores exceeded ~50% normal. These results show that a threshold-based magnetometry approach can non-obtrusively quantify hand movements without calibration and also verify a key concept of real-world hand use after stroke.
The Sex Determination Cascade in the Silkworm

In insects, sex determination pathways involve three levels of master regulators: primary signals, which determine the sex; executors, which control sex-specific differentiation of tissues and organs; and transducers, which link the primary signals to the executors. The primary signals differ widely among insect species. In Diptera alone, several unrelated primary sex determiners have been identified. However, the doublesex (dsx) gene is highly conserved as the executor component across multiple insect orders. The transducer level shows an intermediate level of conservation. In many, but not all examined insects, a key transducer role is performed by transformer (tra), which controls sex-specific splicing of dsx. In Lepidoptera, studies of sex determination have focused on the lepidopteran model species Bombyx mori (the silkworm). In B. mori, the primary signal of sex determination cascade starts from Fem, a female-specific PIWI-interacting RNA, and its targeting gene Masc, which is apparently specific to and conserved among Lepidoptera. Tra has not been found in Lepidoptera. Instead, the B. mori PSI protein binds directly to dsx pre-mRNA and regulates its alternative splicing to produce male- and female-specific transcripts. Despite this basic understanding of the molecular mechanisms underlying sex determination, the links among the primary signals, transducers and executors remain largely unknown in Lepidoptera. In this review, we focus on the latest findings regarding the functions and working mechanisms of genes involved in feminization and masculinization in Lepidoptera and discuss directions for future research of sex determination in the silkworm.
A Neurodevelopment Approach for a Transitional Model of Early Onset Schizophrenia

In the last decades, the conceptualization of schizophrenia has dramatically changed, moving from a neurodegenerative process occurring in early adult life to a neurodevelopmental disorder starting be-fore birth, showing a variety of premorbid and prodromal symptoms and, in relatively few cases, evolving in the full-blown psychotic syndrome. High rates of co-occurring different neurodevelopmental disorders such as Autism spectrum disorder and ADHD, predating the onset of SCZ, and neurobio-logical underpinning with significant similarities, support the notion of a pan-developmental disturbance consisting of impairments in neuromotor, receptive language, social and cognitive development. Con-sidering that many SCZ risk factors may be similar to symptoms of other neurodevelopmental psychi-atric disorders, transition processes from child & adolescent to adult systems of care should include both high risk people as well as subject with other neurodevelopmental psychiatric disorders with different levels of severity. This descriptive mini-review discuss the need of innovative clinical approaches, re-considering specific diagnostic categories, stimulating a careful analysis of risk factors and promoting the appropriate use of new and safer medications.
Respiratory Burst and TNF-α Receptor Expression of Neutrophils after Sepsis and Severe Injury-Induced Inflammation in Children

Systemic inflammatory response syndrome (SIRS) is defined as the systemic host response to infection or a non-infectious factor. The purpose of this study was to evaluate the involvement of reactive oxygen species (ROS) in severe inflammation and to assess the discrimination strength of the neutrophil BURSTTEST assay regarding its etiology in three groups of patients (sepsis, burns, and bone fractures) who met the SIRS criteria. The neutrophil activation (respiratory burst of granulocytes as well as p55 and p75 tumor necrosis factor (TNF-α) receptor expression) was evaluated twice using flow cytometry, and the results were compared with healthy controls and among SIRS subjects. A decreased oxygen metabolism in neutrophils after E. coli stimulation and increased TNF-α receptor expression were found in septic and burned patients on admission, while ROS production augmented and TNF-α receptor expression diminished with the applied therapy. The significant differences in neutrophil respiratory burst intensity among septic and burned patients and those with sepsis and bone fractures were found (however, there were not any such differences between patients with thermal and mechanical injuries). This study indicates that the neutrophil BURSTTEST evaluation might be a clinically reliable marker for differentiating the SIRS etiology.
Anti-TNF Alpha Antibody Humira with pH-dependent Binding Characteristics: A constant-pH Molecular Dynamics, Gaussian Accelerated Molecular Dynamics, and In Vitro Study

Humira is a monoclonal antibody that binds to TNF alpha, inactivates TNF alpha receptors, and inhibits inflammation. Neonatal Fc receptors can mediate the transcytosis of Humira–TNF alpha complex structures and process them toward degradation pathways, which reduces the therapeutic effect of Humira. Allowing the Humira–TNF alpha complex structures to dissociate to Humira and soluble TNF alpha in the early endosome to enable Humira recycling is crucial. We used the cytoplasmic pH (7.4), the early endosomal pH (6.0), and pKa of histidine side chains (6.0–6.4) to mutate the residues of complementarity-determining regions with histidine. Our engineered Humira (W1-Humira) can bind to TNF alpha in plasma at neutral pH and dissociate from the TNF alpha in the endosome at acidic pH. We used the constant-pH molecular dynamics, Gaussian accelerated molecular dynamics, two-dimensional potential mean force profiles, and in vitro methods to investigate the characteristics of W1-Humira. Our results revealed that the proposed Humira can bind TNF alpha with pH-dependent affinity in vitro. The W1-Humira was weaker than wild-type Humira at neutral pH in vitro, and our prediction results were close to the in vitro results. Furthermore, our approach displayed a high accuracy in antibody pH-dependent binding characteristics prediction, which may facilitate antibody drug design. Advancements in computational methods and computing power may further aid in addressing the challenges in antibody drug design.
Phosphor-Free, Color-Tunable Monolithic InGaN Light-Emitting Diodes

We have demonstrated phosphor-free color-tunable monolithic GaN-based light-emitting diodes (LEDs) by inserting an ultrathin 1-nm-thick InGaN shallow quantum well (QW) between deep InGaN QWs and GaN barriers. Without using any phosphors, this monolithic LED chip can be tuned to realize wide-range multicolor emissions from red to yellow under different injection currents. In partical, when the injection current reaches an upper level above 100 mA, the LEDs will achieve white emission with a very high color rending index (CRI) of 85.6. This color-tunable characteristic is attributed to the carrier redistribution in the shallow/deep QWs and the energy band filling effect as well.
Host Defence RNases as Antiviral Agents against Enveloped Single Stranded RNA Viruses

ABSTRACT Owing to the recent outbreak of Coronavirus Disease of 2019 (COVID-19), it is urgent to develop effective and safe drugs to treat the present pandemic and prevent other viral infections that might come in the future. Proteins from our own innate immune system can serve as ideal sources of novel drug candidates thanks to their safety and immune regulation versatility. Some host defense RNases equipped with antiviral activity have been reported over time. Here, we try to summarize the currently available information on human RNases that can target viral pathogens, with special focus on enveloped single-stranded RNA (ssRNA) viruses. Overall, host RNases can fight viruses by a combined multifaceted strategy, including the enzymatic target of the viral genome, recognition of virus unique patterns, immune modulation, control of stress granule formation, and induction of autophagy/apoptosis pathways. The review also includes a detailed description of representative enveloped ssRNA viruses and their strategies to interact with the host and evade immune recognition. For comparative purposes, we also provide an exhaustive revision of the currently approved or experimental antiviral drugs. Finally, we sum up the current perspectives of drug development to achieve successful eradication of viral infections.
Urinary vanin-1 for predicting acute pyelonephritis in young children with urinary tract infection: a pilot study

Abstract Background Vanin-1, an epithelial glycosylphosphatidylolinositol (GPI)-anchored pantetheinase, is a valuable marker of renal injury. Purpose The aim of this study was to assess the predictive value of vanin-1 in acute pyelonephritis (APN) in comparison to the conventional serum inflammatory markers in children aged 1–24 months with the first episode of urinary tract infection (UTI). Material and methods Urinary vanin-1, vanin-1/Cr ratio, WBC, CRP, PCT were analysed in 58 children with febrile UTI and in 18 children with non-febrile UTI. Febrile UTI group was divided into APN subgroup (n = 29) and non-APN subgroup (n = 29), based on the results of Tc-99m-ethylenedicysteine scan. Results The mean vanin-1 level was higher in the APN group compared to the non-febrile UTI group (p = 0.02) and did not differ between APN and non-APN subgroup. In univariate analysis, vanin-1 (p = 0.042), CRP (p < 0.001), PCT (p < 0.001), and WBC (p = 0.022), were associated with APN, but only vanin-1 (p = 0.048) and CRP (p = 0.002) were independent markers of APN. In ROC analysis, vanin-1, with its best cut-off value of 16.53 ng/mL, had worse diagnostic profile (AUC 0.629, sensitivity 58,6%, specificity 63.8%) than CRP, PCT and WBC (AUC: 0.937; 0.880; 0.667, respectively). Conclusions Vanin-1 is not useful for predicting APN, since its diagnostic value is inferior to other conventional serum inflammatory markers.
Does Carotid Artery Tortuosity Play a Role in Stroke?

Purpose: To explore the association between carotid artery length and tortuosity, and the occurrence of stroke. Material and Methods: In this retrospective study, IRB approved, 411 consecutive patients (males: 245; median age: 56 ± 12 years, age range: 21-93 years) with anterior circulation ischemic stroke were included. Only patients that underwent CTA within 7 days were considered and stroke caused by cardiac embolism and thoracic aorta embolism were excluded. For each patient, both carotid arteries were considered, and the ICA, CCA-ICA length and tortuosity were calculated. Inter-observer analysis was quantified with the Bland-Altman test. Mann-Whitney test and logistic regression analysis were also calculated to test the association between length and tortuosity with the occurrence of stroke. Results: In the final analysis, 166 patients (males: 72; median age: 54 ± 12 years, age range: 24-89 years) with anterior circulation ischemic stroke that were admitted to our hospital between February 2008 and December 2013 were included. The results showed a good concordance for the length of the vessels with a mean variation of 0.7% and 0.5% for CCA-ICA and ICA length respectively an for the tortuosity with a mean variation of 0.2% and -0.4% for CCA-ICA and ICA respectively. The analysis shows a statistically significant association between the tortuosity index of the ICA and CCA-ICA sides with stroke (P value = 0.0001 in both cases) and these findings were confirmed also with the logistic regression analysis. Conclusion: Results of this study suggest that tortuosity index is associated with the presence of stroke whereas the length of the carotid arteries does not play a significant role.
Transmission mode of watermelon silver mottle virus by Thrips palmi

Thrips and thrips-transmitted tospoviruses cause significant losses in crop yields worldwide. The melon thrips (Thrips palmi) is not only a pest of cucurbit crops, but also a vector that transmits tospoviruses, such as the watermelon silver mottle virus (WSMoV). Vector transmission of tospoviruses has been well studied in the tomato spotted wilt virus (TSWV)–Frankliniella occidentalis model system; however, until now the transmission mode of WSMoV by T. palmi has not been sufficiently examined. The results of the transmission assays suggest that T. palmi transmits WSMoV in a persistent manner, and that the virus is mainly transmitted by adults, having been ingested at the first-instar larval stage. Complementary RNAs corresponding to the NSm and NSs genes of WSMoV were detected in viruliferous thrips by reverse transcription-polymerase chain reaction; NSs protein was also detected in viruliferous thrips by western blotting, verifying the replication of WSMoV in T. palmi. Furthermore, we demonstrated that in thrips infected with WSMoV at the first-instar larval stage, the virus eventually infected various tissues of the adult thrips, including the primary salivary glands. Taken together, these results suggest that T. palmi transmits WSMoV in a persistent-propagative mode. The results of this study make a significant contribution to the understanding of the transmission biology of tospoviruses in general.
Hip Arthroscopy Versus Physical Therapy for the Treatment of Symptomatic Acetabular Labral Tears in Patients Older Than 40 Years: A Randomized Controlled Trial

Background: Previous observational studies have suggested poor results of arthroscopic surgery for the treatment of acetabular labral tears in patients older than 40 years. Purpose: To compare hip arthroscopy versus nonoperative management for symptomatic labral tears in patients older than 40 years who have limited radiographic osteoarthritis. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: In this single-surgeon, parallel randomized controlled trial, patients older than 40 years who had symptomatic, MRI-confirmed labral tears and limited radiographic osteoarthritis (Tönnis grades 0-2) were randomized 1:1 to arthroscopic surgery with postoperative physical therapy (SPT) or physical therapy alone (PTA) using an electronic randomization program. PTA patients who achieved unsatisfactory improvement were permitted to cross over to SPT after completing ≥14 weeks of physical therapy. The primary outcomes were International Hip Outcome Tool (iHOT-33) and modified Harris Hip Score (mHHS) at 12 months after randomization, and secondary outcomes included other patient-reported outcome measures and the visual analog scale. Outcomes were assessed at baseline and at 3, 6, and 12 months after randomization. Primary analysis was performed on an intention-to-treat basis using linear mixed-effect models. Sensitivity analyses included modified as-treated analysis and treatment-failure analysis. Due to infeasibility, patients and health care providers were both unblinded. Results: The study enrolled 90 patients (46 [51.1%] SPT; 44 [48.9%] PTA); of these, 81 patients (42 [51.9%] SPT; 39 (48.1%) PTA) completed 12-month follow-up. A total of 28 of the 44 PTA patients crossed over to SPT within the study period (63.6% crossover). Intention-to-treat analysis revealed significantly greater iHOT-33 scores (+12.11; P = .007) and mHHS scores (+6.99 points; P = .04) in the SPT group than the PTA group at 12 months. Modified as-treated analysis revealed that these differences exceeded the minimal clinically important difference of 10.0 points (SPT-PTA iHOT-33, +11.95) and 8.0 points (SPT-PTA mHHS, +9.76), respectively. Conclusion: In patients older than 40 years with limited osteoarthritis, arthroscopic acetabular labral repair with postoperative physical therapy led to better outcomes than physical therapy alone. Thus, age over 40 years should not be considered a contraindication to arthroscopic acetabular labral repair. Registration: NCT03909178 (ClinicalTrials.gov identifier)