Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Modifiers and Phenotype of Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis

The transforming growth factor beta (TGFβ) pathway could modulate the Duchenne muscular dystrophy (DMD) phenotype. This meta-analysis aims to estimate the association of genetic variants involved in the TGFβ pathway, including the latent transforming growth factor beta binding protein 4 (LTBP4) and secreted phosphoprotein 1 (SPP1) genes, among others, with age of loss of ambulation (LoA) and cardiac function in patients with DMD. Meta-analyses were conducted for the hazard ratio (HR) of LoA for each genetic variant. A subgroup analysis was performed in patients treated exclusively with glucocorticoids. Eight studies were included in the systematic review and four in the meta-analyses. The systematic review suggests a protective effect of LTBP4 haplotype IAAM (recessive model) for LoA. It is also suggested that the SPP1 rs28357094 genotype G (dominant model) is associated with early LoA in glucocorticoids-treated patients. The meta-analysis of the LTBP4 haplotype IAAM showed a protective association with LoA, with an HR = 0.78 (95% CI: 0.67–0.90). No association with LoA was observed for the SPP1 rs28357094. The LTBP4 haplotype IAAM is associated with a later LoA, especially in the Caucasian population, while the SPP1 rs28357094 genotype G could be associated with a poor response to glucocorticoids. Future research is suggested for SPP1 rs11730582, LTBP4 rs710160, and THBS1 rs2725797.
Thermal Stability and Decomposition Mechanism of PLA Nanocomposites with Kraft Lignin and Tannin

Packaging applications cover approximately 40% of the total plastics production, whereas food packaging possesses a high proportion within this context. Due to several environmental concerns, petroleum-based polymers have been shifted to their biobased counterparts. Poly(lactic acid) (PLA) has been proved the most dynamic biobased candidate as a substitute of the conventional polymers. Despite its numerous merits, PLA exhibits some limitations, and thus reinforcing agents are commonly investigated as fillers to ameliorate several characteristics. In the present study, two series of PLA-based nanocomposites filled with biobased kraft-lignin (KL) and tannin (T) in different contents were prepared. A melt–extrusion method was pursued for nanocomposites preparation. The thermal stability of the prepared nanocomposites was examined by Thermogravimetric Analysis, while thermal degradation kinetics was applied to deepen this process. Pyrolysis–Gas Chromatography/Mass Spectrometry was employed to provide more details of the degradation process of PLA filled with the two polyphenolic fillers. It was found that the PLA/lignin nanocomposites show better thermostability than neat PLA, while tannin filler has a small catalytic effect that can reduce the thermal stability of PLA. The calculated Eα value of PLA-T nanocomposite was lower than that of PLA-KL resulting in a substantially higher decomposition rate constant, which accelerate the thermal degradation.
External Load and Muscle Activation Monitoring of NCAA Division I Basketball Team Using Smart Compression Shorts

There is scarce research into the use of Strive Sense3 smart compression shorts to measure external load with accelerometry and muscle load (i.e., muscle activations) with surface electromyography in basketball. Sixteen external load and muscle load variables were measured from 15 National Collegiate Athletic Association Division I men’s basketball players with 1137 session records. The data were analyzed for player positions of Centers (n = 4), Forwards (n = 4), and Guards (n = 7). Nonparametric bootstrapping was used to find significant differences between training and game sessions. Significant differences were found in all variables except Number of Jumps and all muscle load variables for Guards, and all variables except Muscle Load for Forwards. For Centers, the Average Speed, Average Max Speed, and Total Hamstring, Glute, Left, and Right Muscle variables were significantly different (p < 0.05). Principal component analysis was conducted on the external load variables. Most of the variance was explained within two principal components (70.4% in the worst case). Variable loadings of principal components for each position were similar during training but differed during games, especially for the Forward position. Measuring muscle activation provides additional information in which the demands of each playing position can be differentiated during training and competition.
Sex Disparities in Efficacy in COVID-19 Vaccines: A Systematic Review and Meta-Analysis

Sex differences in adaptive and innate immune responses have been shown to occur and anecdotal reports suggest that vaccine efficacy and safety may be sex-dependent. We investigated the influence of sex on the efficacy of COVID-19 vaccines through a systematic review and meta-analysis of clinical trials on COVID-19 vaccines. The safety profile of COVID-19 vaccines was also investigated. A systematic review included eligible articles published in three databases and three websites. A meta-analysis of available data, stratified by sex, was conducted. Statistical analysis was performed using the Hartung–Knapp–Sidik–Jonkman method, as well as influence and heterogeneity analysis. Pooled analysis showed significantly higher efficacy, measured as the rate of new COVID-19 cases, in men compared to women in the vaccine group (OR = 0.67, 95% CI 0.48–0.94). No sex differences were found in the rate of new cases in the control group (OR = 0.92, 95% CI 0.78–1.09). Safety profiles derived from pharmacovigilance reports appear to indicate increased toxicity in women. In conclusion, evidence of a potential role of sex in COVID-19 vaccine efficacy was described. It strengthens the need to include sex as a core variable in the clinical trial design of COVID-19 vaccines.
Chemogenetic Activation of Cortical Parvalbumin-Positive Interneurons Reverses Noise-Induced Impairments in Gap Detection

Exposure to loud noises not only leads to trauma and loss of output from the ear but also alters downstream central auditory circuits. A perceptual consequence of noise-induced central auditory disruption is impairment in gap-induced prepulse inhibition, also known as gap detection. Recent studies have implicated cortical parvalbumin (PV)-positive inhibitory interneurons in gap detection and prepulse inhibition. Here, we show that exposure to loud noises specifically reduces the density of cortical PV but not somatostatin (SOM)-positive interneurons in the primary auditory cortex in mice (C57BL/6) of both sexes. Optogenetic activation of PV neurons produced less cortical inhibition in noise-exposed than sham-exposed animals, indicative of reduced PV neuron function. Activation of SOM neurons resulted in similar levels of cortical inhibition in noise- and sham-exposed groups. Furthermore, chemogenetic activation of PV neurons with the hM3-based designer receptor exclusively activated by designer drugs completely reversed the impairments in gap detection for noise-exposed animals. These results support the notions that cortical PV neurons encode gap in sound and that PV neuron dysfunction contributes to noise-induced impairment in gap detection. SIGNIFICANCE STATEMENT Noise-induced hearing loss contributes to a range of central auditory processing deficits (CAPDs). The mechanisms underlying noise-induced CAPDs are still poorly understood. Here we show that exposure to loud noises results in dysfunction of PV-positive but not somatostatin-positive inhibitory interneurons in the primary auditory cortex. In addition, cortical PV inhibitory neurons in noise-exposed animals had reduced expression of glutamic acid decarboxylases and weakened inhibition on cortical activity. Noise exposure resulted in impaired gap detection, indicative of disrupted temporal sound processing and possibly tinnitus. We found that chemogenetic activation of cortical PV inhibitory interneurons alleviated the deficits in gap detection. These results implicate PV neuron dysfunction as a mechanism for noise-induced CAPDs.
Free Amino Acid Alterations in Patients with Gynecological and Breast Cancer: A Review

Gynecological and breast cancers still remain a significant health problem worldwide. Diagnostic methods are not sensitive and specific enough to detect the disease at an early stage. During carcinogenesis and tumor progression, the cellular need for DNA and protein synthesis increases leading to changes in the levels of amino acids. An important role of amino acids in many biological pathways, including biosynthesis of proteins, nucleic acids, enzymes, etc., which serve as an energy source and maintain redox balance, has been highlighted in many research articles. The aim of this review is a detailed analysis of the literature on metabolomic studies of gynecology and breast cancers with particular emphasis on alterations in free amino acid profiles. The work includes a brief overview of the metabolomic methodology and types of biological samples used in the studies. Special attention was paid to the possible role of selected amino acids in the carcinogenesis, especially proline and amino acids related to its metabolism. There is a clear need for further research and multiple external validation studies to establish the role of amino acid profiling in diagnosing gynecological and breast cancers.
Vehicle Trajectory Prediction Using Hierarchical Graph Neural Network for Considering Interaction among Multimodal Maneuvers

Predicting the trajectories of surrounding vehicles by considering their interactions is an essential ability for the functioning of autonomous vehicles. The subsequent movement of a vehicle is decided based on the multiple maneuvers of surrounding vehicles. Therefore, to predict the trajectories of surrounding vehicles, interactions among multiple maneuvers should be considered. Recent research has taken into account interactions that are difficult to express mathematically using data-driven deep learning methods. However, previous studies have only considered the interactions among observed trajectories due to subsequent maneuvers that are unobservable and numerous maneuver combinations. Thus, to consider the interaction among multiple maneuvers, this paper proposes a hierarchical graph neural network. The proposed hierarchical model approximately predicts the multiple maneuvers of vehicles and considers the interaction among the maneuvers by representing their relationships in a graph structure. The proposed method was evaluated using a publicly available dataset and a real driving dataset. Compared with previous methods, the results of the proposed method exhibited better prediction performance in highly interactive situations.
Surface Roughness Effects on Self-Interacting and Mutually Interacting Rayleigh Waves

Rayleigh waves are very useful for ultrasonic nondestructive evaluation of structural and mechanical components. Nonlinear Rayleigh waves have unique sensitivity to the early stages of material degradation because material nonlinearity causes distortion of the waveforms. The self-interaction of a sinusoidal waveform causes second harmonic generation, while the mutual interaction of waves creates disturbances at the sum and difference frequencies that can potentially be detected with minimal interaction with the nonlinearities in the sensing system. While the effect of surface roughness on attenuation and dispersion is well documented, its effects on the nonlinear aspects of Rayleigh wave propagation have not been investigated. Therefore, Rayleigh waves are sent along aluminum surfaces having small, but different, surface roughness values. The relative nonlinearity parameter increased significantly with surface roughness (average asperity heights 0.027–3.992 μm and Rayleigh wavelengths 0.29–1.9 mm). The relative nonlinearity parameter should be decreased by the presence of attenuation, but here it actually increased with roughness (which increases the attenuation). Thus, an attenuation-based correction was unsuccessful. Since the distortion from material nonlinearity and surface roughness occur over the same surface, it is necessary to make material nonlinearity measurements over surfaces having the same roughness or in the future develop a quantitative understanding of the roughness effect on wave distortion.
Importance of smoking cessation for cardiovascular risk reduction.

Nearly 60 years ago, the Framingham Heart Study first reported on the association between smoking and coronary heart disease on a population-based level. Since then, innumerable data have confirmed a strong, graded relationship of smoking, smoking duration, and number of cigarettes smoked per day with cardiovascular and non-cardiovascular morbidity and mortality risks. Although smoking prevalence has globally decreased by 25% from 1980 to 2012, at least 25% of the world’s male and 5% of the world’s female population are still actively smoking. Moreover, the smoking prevalence trends have in many places been shown to differ among young and old and rich and poor, which raises concerns for an expansion of the already unfavourable social gradients that exist in cardiovascular health. In particular, it is notable that although tobacco use among young people appears to be declining in many places in the Western world, disturbingly increases have been observed in some countries with a lower human development index, secondary to cigarettes becoming more affordable. In 2015, smoking was estimated to cause >11% of the world’s deaths, and >27% and 12% of all ischaemic heart disease-related mortalities in 2017 among men and women, respectively. Although the population-attributable fractions of ischaemic heart disease mortality associated with smoking on a global level declined by a modest 33% Graphical Abstract The mapped data are from the Global Burden of Disease Study 2019, accessed July 19, 2021 at http://ghdx.healthdata. org/ gbd-2019.
Microvesicles Transfer Mitochondria and Increase Mitochondrial Function in Brain Endothelial Cells

We have demonstrated, for the first time that microvesicles, a sub-type of extracellular vesicles (EVs) derived from hCMEC/D3: a human brain endothelial cell (BEC) line transfer polarized mitochondria to recipient BECs in culture and to neurons in mice acute brain cortical and hippocampal slices. This mitochondrial transfer increased ATP levels by 100 to 200-fold (relative to untreated cells) in the recipient BECs exposed to oxygen-glucose deprivation, an in vitro model of cerebral ischemia. We have also demonstrated that transfer of microvesicles, the larger EV fraction, but not exosomes resulted in increased mitochondrial function in hypoxic endothelial cultures. Gene ontology and pathway enrichment analysis of EVs revealed a very high association to glycolysis-related processes. In comparison to heterotypic macrophage- derived EVs, BEC-derived EVs demonstrated a greater selectivity to transfer mitochondria and increase endothelial cell survival under ischemic conditions. Highlights Microvesicles transfer mitochondria to endothelial cells and brain slice neurons Mitochondrial transfer increased ATP in ischemic brain endothelial cells (BECs) Transfer of microvesicles increased mitochondrial function in hypoxic BECs Transfer of exosomes did not affect mitochondrial function in hypoxic BECs Homotypic BEC-derived EVs result in greater ATP levels in the recipient BECs
Using Multi-Level Precueing to Improve Performance in Path-Following Tasks in Virtual Reality

Work on VR and AR task interaction and visualization paradigms has typically focused on providing information about the current step (a cue) immediately before or during its performance. Some research has also shown benefits to simultaneously providing information about the next step (a precue). We explore whether it would be possible to improve efficiency by precueing information about multiple upcoming steps before completing the current step. To accomplish this, we developed a remote VR user study comparing task completion time and subjective metrics for different levels and styles of precueing in a path-following task. Our visualizations vary the precueing level (number of steps precued in advance) and style (whether the path to a target is communicated through a line to the target, and whether the place of a target is communicated through graphics at the target). Participants in our study performed best when given two to three precues for visualizations using lines to show the path to targets. However, performance degraded when four precues were used. On the other hand, participants performed best with only one precue for visualizations without lines, showing only the places of targets, and performance degraded when a second precue was given. In addition, participants performed better using visualizations with lines than ones without line
Micropatterned Fibrous Scaffold Produced by Using Template-Assisted Electrospinning Technique for Wound Healing Application

This paper describes the fabrication of a structural scaffold consisting of both randomly oriented nanofibers and triangular prism patterns on the scaffold surface using a combination technique of electrospinning and collector templates. The polycaprolactone (PCL) nanofibers were electrospun over a triangular prism pattern mold, which acted as a template. The deposited scaffold was removed from the template to produce a standalone structural scaffold of three-dimensional micropatterned nanofibers. The fabricated structural scaffold was compared with flat randomly oriented nanofibers based on in vitro and in vivo studies. The in vitro study indicated that the structural scaffold demonstrated higher fibroblast cell proliferation, cell elongation with a 13.48 ± 2.73 aspect ratio and 70% fibroblast cell orientation compared with flat random nanofibers. Among the treatment groups, the structural scaffold escalated the wound closure to 92.17% on day 14. Histological staining of the healed wound area demonstrated that the structural scaffold exhibited advanced epithelization of the epidermal layer accompanied by mild inflammation. The proliferated fibroblast cells and collagen fibers in the structural scaffold appeared denser and arranged more horizontally. These results determined the potential of micropatterned scaffolds for stimulating cell behavior and their application for wound healing.
The HSV1 Tail-Anchored Membrane Protein pUL34 Contains a Basic Motif That Supports Active Transport to the Inner Nuclear Membrane Prior to Formation of the Nuclear Egress Complex

Herpes simplex virus type 1 nucleocapsids are released from the host nucleus by a budding process through the nuclear envelope called nuclear egress. Two viral proteins, the integral membrane proteins pUL34 and pUL31, form the nuclear egress complex at the inner nuclear membrane, which is critical for this process. The nuclear import of both proteins ensues separately from each other: pUL31 is actively imported through the central pore channel, while pUL34 is transported along the peripheral pore membrane. With this study, we identified a functional bipartite NLS between residues 178 and 194 of pUL34. pUL34 lacking its NLS is mislocalized to the TGN but retargeted to the ER upon insertion of the authentic NLS or a mimic NLS, independent of the insertion site. If co-expressed with pUL31, either of the pUL34-NLS variants is efficiently, although not completely, targeted to the nuclear rim where co-localization with pUL31 and membrane budding seem to occur, comparable to the wild-type. The viral mutant HSV1(17+)Lox-UL34-NLS mt is modestly attenuated but viable and associated with localization of pUL34-NLS mt to both the nuclear periphery and cytoplasm. We propose that targeting of pUL34 to the INM is facilitated by, but not dependent on, the presence of an NLS, thereby supporting NEC formation and viral replication.
HIV in the Brain: Identifying Viral Reservoirs and Addressing the Challenges of an HIV Cure

Advances in antiretroviral therapy have prolonged the life of people living with HIV and diminished the level of virus in these individuals. Yet, HIV quickly rebounds after disruption and/or cessation of treatment due to significant cellular and anatomical reservoirs for HIV, which underscores the challenge for HIV cure strategies. The central nervous system (CNS), in particular, is seeded with HIV within 1–2 weeks of infection and is a reservoir for HIV. In this review, we address the paradigm of HIV reservoirs in the CNS and the relevant cell types, including astrocytes and microglia, that have been shown to harbor viral infection even with antiretroviral treatment. In particular, we focus on developmental aspects of astrocytes and microglia that lead to their susceptibility to infection, and how HIV infection propagates among these cells. We also address challenges of measuring the HIV latent reservoir, advances in viral detection assays, and how curative strategies have evolved in regard to the CNS reservoir. Current curative strategies still require optimization to reduce or eliminate the HIV CNS reservoir, and may also contribute to levels of neuroinflammation that lead to cognitive decline. With this in mind, the latent HIV reservoir in the brain should remain a prominent focus when assessing treatment options and overall viral burden in the clinic, especially in the context of HIV-associated neurocognitive disorders (HAND).
The Role of Phylogenetics in Unravelling Patterns of HIV Transmission towards Epidemic Control: The Quebec Experience (2002–2020)

Phylogenetics has been advanced as a structural framework to infer evolving trends in the regional spread of HIV-1 and guide public health interventions. In Quebec, molecular network analyses tracked HIV transmission dynamics from 2002–2020 using MEGA10-Neighbour-joining, HIV-TRACE, and MicrobeTrace methodologies. Phylogenetics revealed three patterns of viral spread among Men having Sex with Men (MSM, n = 5024) and heterosexuals (HET, n = 1345) harbouring subtype B epidemics as well as B and non-B subtype epidemics (n = 1848) introduced through migration. Notably, half of new subtype B infections amongst MSM and HET segregating as solitary transmissions or small cluster networks (2–5 members) declined by 70% from 2006–2020, concomitant to advances in treatment-as-prevention. Nonetheless, subtype B epidemic control amongst MSM was thwarted by the ongoing genesis and expansion of super-spreader large cluster variants leading to micro-epidemics, averaging 49 members/cluster at the end of 2020. The growth of large clusters was related to forward transmission cascades of untreated early-stage infections, younger at-risk populations, more transmissible/replicative-competent strains, and changing demographics. Subtype B and non-B subtype infections introduced through recent migration now surpass the domestic epidemic amongst MSM. Phylodynamics can assist in predicting and responding to active, recurrent, and newly emergent large cluster networks, as well as the cryptic spread of HIV introduced through migration.