Miracle-dz/UniFAR-FTUs huggingface dataset:
Compartmentalized Replication of SARS-Cov-2 in Upper vs. Lower Respiratory Tract Assessed by Whole Genome Quasispecies Analysis

We report whole-genome and intra-host variability of SARS-Cov-2 assessed by next generation sequencing (NGS) in upper (URT) and lower respiratory tract (LRT) from COVID-19 patients. The aim was to identify possible tissue-specific patterns and signatures of variant selection for each respiratory compartment. Six patients, admitted to the Intensive Care Unit, were included in the study. Thirteen URT and LRT were analyzed by NGS amplicon-based approach on Ion Torrent Platform. Bioinformatic analysis was performed using both realized in-house and supplied by ThermoFisher programs. Phylogenesis showed clade V clustering of the first patients diagnosed in Italy, and clade G for later strains. The presence of quasispecies was observed, with variants uniformly distributed along the genome and frequency of minority variants spanning from 1% to ~30%. For each patient, the patterns of variants in URT and LRT were profoundly different, indicating compartmentalized virus replication. No clear variant signature and no significant difference in nucleotide diversity between LRT and URT were observed. SARS-CoV-2 presents genetic heterogeneity and quasispecies compartmentalization in URT and LRT. Intra-patient diversity was low. The pattern of minority variants was highly heterogeneous and no specific district signature could be identified, nevertheless, analysis of samples, longitudinally collected in patients, supported quasispecies evolution.
Do the P1 and P2 hairpins of the Guanidine-II riboswitch interact?

Abstract Riboswitches regulate genes by adopting different structures in responds to metabolite binding. The guanidine-II riboswitch is the smallest representative of the ykkC class with the mechanism of its function being centred on the idea that its two stem loops P1 and P2 form a kissing hairpin interaction upon binding of guanidinium (Gdm+). This mechanism is based on in-line probing experiments with the full-length riboswitch and crystal structures of the truncated stem loops P1 and P2. However, the crystal structures reveal only the formation of the homodimers P1 | P1 and P2 | P2 but not of the proposed heterodimer P1 | P2. Here, site-directed spin labeling (SDSL) in combination with Pulsed Electron–Electron Double Resonance (PELDOR or DEER) is used to study their structures in solution and how they change upon binding of Gdm+. It is found that both hairpins adopt different structures in solution and that binding of Gdm+ does indeed lead to the formation of the heterodimer but alongside the homodimers in a statistical 1:2:1 fashion. These results do thus support the proposed switching mechanism.
The Maintenance of Mitochondrial DNA Integrity and Dynamics by Mitochondrial Membranes

Mitochondria are complex organelles that harbour their own genome. Mitochondrial DNA (mtDNA) exists in the form of a circular double-stranded DNA molecule that must be replicated, segregated and distributed around the mitochondrial network. Human cells typically possess between a few hundred and several thousand copies of the mitochondrial genome, located within the mitochondrial matrix in close association with the cristae ultrastructure. The organisation of mtDNA around the mitochondrial network requires mitochondria to be dynamic and undergo both fission and fusion events in coordination with the modulation of cristae architecture. The dysregulation of these processes has profound effects upon mtDNA replication, manifesting as a loss of mtDNA integrity and copy number, and upon the subsequent distribution of mtDNA around the mitochondrial network. Mutations within genes involved in mitochondrial dynamics or cristae modulation cause a wide range of neurological disorders frequently associated with defects in mtDNA maintenance. This review aims to provide an understanding of the biological mechanisms that link mitochondrial dynamics and mtDNA integrity, as well as examine the interplay that occurs between mtDNA, mitochondrial dynamics and cristae structure.
Wearable Tendon Kinetics

This study introduces a noninvasive wearable system for investigating tendon loading patterns during outdoor locomotion on variable terrain. The system leverages shear wave tensiometry, which is a new approach for assessing tendon load by tracking wave speed within the tissue. Our wearable tensiometry system uses a battery-operated piezoelectric actuator to induce micron-scale shear waves in a tendon. A data logger monitors wave propagation by recording from two miniature accelerometers mounted on the skin above the tendon. Wave speed is determined from the wave travel time between accelerometers. The wearable system was used to record Achilles tendon wave speed at 100 Hz during 1-km outdoor walking trials in nine young adults. Inertial measurement units (IMUs) simultaneously monitored participant position, walking speed, and ground incline. An analysis of 5108 walking strides revealed the coupled biomechanical effects of terrain slope and walking speed on tendon loading. Uphill slopes increased the tendon wave speed during push-off, whereas downhill slopes increased tendon wave speeds during early stance braking. Walking speed significantly modulated peak tendon wave speed on uphill slopes but had less influence on downhill slopes. Walking speed consistently induced greater early stance wave speeds for all slopes. These observations demonstrate that wearable shear wave tensiometry holds promise for evaluating tendon tissue kinetics in natural environments and uncontrolled movements. There are numerous practical applications of wearable tensiometry spanning orthopedics, athletics, rehabilitation, and ergonomics.
Nanostructure of Unconventional Liquid Crystals Investigated by Synchrotron Radiation

The macroscopic properties of novel liquid crystal (LC) systems—LCs with unconventional molecular structure as well as conventional LCs in unconventional geometries—directly descend from their mesoscopic structural organization. While X-ray diffraction (XRD) is an obvious choice to investigate their nanoscale structure, conventional diffractometry is often hampered by experimental difficulties: the low scattering power and short-range positional order of the materials, resulting in weak and diffuse diffraction features; the need to perform measurements in challenging conditions, e.g., under magnetic and/or electric fields, on thin films, or at high temperatures; and the necessity to probe micron-sized volumes to tell the local structural properties from their macroscopic average. Synchrotron XRD allows these problems to be circumvented thanks to the superior diffraction capabilities (brilliance, q-range, energy and space resolution) and advanced sample environment available at synchrotron beamlines. Here, we highlight the potentiality of synchrotron XRD in the field of LCs by reviewing a selection of experiments on three unconventional LC systems: the potentially biaxial and polar nematic phase of bent-core mesogens; the very high-temperature nematic phase of all-aromatic LCs; and polymer-dispersed liquid crystals. In all these cases, synchrotron XRD unveils subtle nanostructural features that are reflected into macroscopic properties of great interest from both fundamental and technological points of view.
Fourier Series Estimation of Ground Skink Population Density

Scincella lateralis is a small ground-dwelling lizard that is among the more commonly seen reptiles within its range in the southern United States (Conant and Collins, 1991). Conventional censusing methods, such as pitfall trapping, are poorly suited for S. lateralis as recaptures are rare for adult animals (C. K Dodd Jr., pers. comm.) and even radioactively tagged skinks are seldomly relocated (Fitch and von Achen, 1977). My initial attempts to determine population density of Scincella using randomized quadrats (Jaeger and Inger, 1994) underestimated population density because few of the lizards observed were found in quadrats. Skinks often eluded hand capture by darting into litter. Although I saw many S. lateralis in the study area between quadrats, only lizards captured within a quadrat were included in the census. This suggested that observance might be more appropriate for estimating population density in this species. The line transect method (Burnham et al., 1980; Buckland et al., 1996) uses sightings of animals, rather than captures, to estimate population density. Scincella appears suited to distance sampling methods because it is conspicuous and individual positions can be determined readily. The accuracy of the distance sampling estimate of population density rests in meeting the following four assumptions: (1) animals directly on the transect line are not missed; (2) animals are counted only once during a line survey (i.e., the position of the initial sighting is fixed); (3) the distance between a sighting position and the transect line is measured exactly; and (4) all observations are independent. Careful survey design is required to match these assumptions and to make distance sampling effective.
Diagnosis of Osteoarthritis (OA) Progression using Image Processing

: Knee Osteoarthritis is a kind of joint inflammation, which often occurs in one or both the knee joints. Osteoarthritis is often called as 'wear and tear' process of joint that results in dynamic disintegration of articular cartilage. Cartilage is smooth substantial layer that ensures movement to occur effortlessly. In Osteoarthritis, cartilage is inclined towards the destruction as it loses elasticity and becomes brittle. Our project deals with the detection of Osteoarthritis (OA) progression of any age group of people. According to the centers for Disease Control and Prevention (CDC), OA affects 27 million people. We have proposed a new algorithm to detect OA using machine learning techniques in image processing, which is more accurate for finding the severity of the knee OA than the existing methods in which the accuracy level was not sufficient enough for OA analysis.
Parvalbumin and Somatostatin Interneurons Contribute to the Generation of Hippocampal Gamma Oscillations

γ-frequency oscillations (30-120 Hz) in cortical networks influence neuronal encoding and information transfer, and are disrupted in multiple brain disorders. While synaptic inhibition is important for synchronization across the γ-frequency range, the role of distinct interneuronal subtypes in slow (<60 Hz) and fast γ states remains unclear. Here, we used optogenetics to examine the involvement of parvalbumin-expressing (PV+) and somatostatin-expressing (SST+) interneurons in γ oscillations in the mouse hippocampal CA3 ex vivo, using animals of either sex. Disrupting either PV+ or SST+ interneuron activity, via either photoinhibition or photoexcitation, led to a decrease in the power of cholinergically induced slow γ oscillations. Furthermore, photoexcitation of SST+ interneurons induced fast γ oscillations, which depended on both synaptic excitation and inhibition. Our findings support a critical role for both PV+ and SST+ interneurons in slow hippocampal γ oscillations, and further suggest that intense activation of SST+ interneurons can enable the CA3 circuit to generate fast γ oscillations. SIGNIFICANCE STATEMENT The generation of hippocampal γ oscillations depends on synchronized inhibition provided by GABAergic interneurons. Parvalbumin-expressing (PV+) interneurons are thought to play the key role in coordinating the spike timing of excitatory pyramidal neurons, but the role distinct inhibitory circuits in network synchronization remains unresolved. Here, we show, for the first time, that causal disruption of either PV+ or somatostatin-expressing (SST+) interneuron activity impairs the generation of slow γ oscillations in the ventral hippocampus ex vivo. We further show that SST+ interneuron activation along with general network excitation is sufficient to generate high-frequency γ oscillations in the same preparation. These results affirm a crucial role for both PV+ and SST+ interneurons in hippocampal γ oscillation generation.
Neural Control of Robot Manipulators With Trajectory Tracking Constraints and Input Saturation

This article presents a control scheme for the robot manipulator’s trajectory tracking task considering output error constraints and control input saturation. We provide an alternative way to remove the feasibility condition that most BLF-based controllers should meet and design a control scheme on the premise that constraint violation possibly happens due to the control input saturation. A bounded barrier Lyapunov function is proposed and adopted to handle the output error constraints. Besides, to suppress the input saturation effect, an auxiliary system is designed and emerged into the control scheme. Moreover, a simplified RBFNN structure is adopted to approximate the lumped uncertainties. Simulation and experimental results demonstrate the effectiveness of the proposed control scheme.
Lymphocyte Infiltration Determines the Hypoxia-Dependent Response to Definitive Chemoradiation in Head-and-Neck Cancer: Results from a Prospective Imaging Trial

Tumor hypoxia in head-and-neck squamous cell carcinoma (HNSCC) leads to an immunosuppressive microenvironment and reduces the response to radiotherapy. In this prospective imaging trial, we investigated potential interactions between functional hypoxia imaging and infiltrating lymphocyte levels as a potential predictor for treatment response in HNSCC patients. Methods: In total, 49 patients receiving definitive chemoradiation for locally advanced HNSCCs underwent pretherapeutic biopsies and peritherapeutic hypoxia imaging using 18F-misonidazole PET at weeks 0, 2, and 5 during chemoradiation. Hematoxylin–eosin and immunohistochemical stainings for tumor-infiltrating lymphocytes, tissue-based hypoxia, and microvascular markers were analyzed and correlated with the longitudinal hypoxia dynamics and patient outcomes. Results: High levels of tumor-infiltrating total lymphocytes correlated with superior locoregional control (LRC) (hazard ratio [HR], 0.279; P = 0.011) and progression-free survival (PFS) (HR, 0.276; P = 0.006). Similarly, early resolution of 18F-misonidazole PET–detected tumor hypoxia quantified by 18F-misonidazole dynamics between weeks 0 and 2 of chemoradiation was associated with improved LRC (HR, 0.321; P = 0.015) and PFS (HR, 0.402; P = 0.043). Outcomes in the favorable early hypoxia resolution subgroup significantly depended on infiltrating lymphocyte counts, with patients who showed both an early hypoxia response and high lymphocyte infiltration levels exhibiting significantly improved LRC (HR, 0.259; P = 0.036) and PFS (HR, 0.242; P = 0.017) compared with patients with an early hypoxia response but low lymphocyte counts. These patients exhibited oncologic results comparable to those of patients with no hypoxia response within the first 2 wk of chemoradiation. Conclusion: This analysis established a clinical hypoxia-immune score that predicted treatment responses and outcomes in HNSCC patients undergoing chemoradiation and may help to devise novel concepts for biology-driven personalization of chemoradiation.
Effectiveness of Health-Led Cognitive Behavioral-Based Group Therapy on Pain, Functional Disability and Psychological Outcomes among Knee Osteoarthritis Patients in Malaysia

Background: Psychosocial interventions for patients with osteoarthritis (OA) of the knee to reduce pain and improve physical and psychological functioning are still lacking in Malaysia. Methods: A parallel-group unblinded randomized controlled trial involving 300 patients was conducted in two hospital orthopedics clinics in Malaysia. Patients were randomly assigned to receive cognitive behavioral-based group therapy (n = 150) or no further intervention (n = 150). The primary outcome was the change from baseline in knee pain as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS) at 6 months. The data collected were analyzed by covariate-adjusted mixed design repeated measures analysis of variance. All analyses were performed under the terms of intention-to-treat. Results: At 6 months, mean change from baseline in the KOOS knee pain score was 0.6 points (95% CI −1.73 to 2.94) in the control group and 8.9 points (95% CI 6.62 to 11.23) (denoting less knee pain intensity) in the intervention group (significant treatment effect p < 0.0001). Patients treated with such an approach also experienced significant improvement in functional ability when performing activities of daily living and had improved ability to cope with depression, anxiety and pain catastrophizing. Conclusion: The intervention module delivered by healthcare professionals had a sustained effect on knee OA pain and functionality over 6 months, thereby leading to an overall improvement in psychological well-being, thus benefitting most of the Malaysian knee OA patients.
Role of Momordica charantia in preventing the natural aging process of skin and sexual organs in mice

Although various methods for improving the natural aging of skin have been examined, an effective method is currently unavailable. Therefore, in this study, we investigated the effects of Momordica charantia on the natural aging of skin of mice and how sex differences influenced these effects. To this end, we bred female and male hairless mice without ultraviolet ray irradiation and physical stress for 2 years. During the study period, mice were orally administered 50 mg/kg/day Momordica charantia fruit extract, three times per week. The characteristics of naturally aging skin, in terms of moisture retention, hydration, thickness, and reduced wrinkle score, improved after Momordica charantia treatment in both male and female mice. Furthermore, reduced cell apoptosis was observed in the female ovaries and male testes, and the levels of testosterone and 17β‐estradiol in blood were maintained. After treatment with Momordica charantia, the expression of matrix metalloprotease (MMP)‐1 and hyaluronidase (HAYL)2 decreased in the skin of female mice, whereas the serum levels of interleukin (IL)‐33 increased in the male mice. These results indicated that the natural aging of the skin was decelerated by Momordica charantia via regulation of the 17β‐estradiol/mast cell/MMP‐1/HAYL2 and testosterone/mast cell/IL‐33 signaling pathways in female and male mice, respectively.
The Long and Winding Road for Breast Cancer Biomarkers to Reach Clinical Utility

Tumor data from the ABCSG 5 trial of chemotherapy versus endocrine therapy for premenopausal ER+ breast cancer supports molecular subtyping by Ki-67 IHC as a prognostic marker. But while this tissue was handled uniformly, Ki-67 testing overall is unstandardized, complicating clinical utility. Increasing potential biomarkers herald more challenges in biomarker validation. See related article by Bago-Horvath et al., p. 5682
Diffraction and Polarization Properties of Electrically–Tunable Nematic Liquid Crystal Grating

This work demonstrates an electrically-tunable nematic liquid crystal (NLC) diffraction grating with a periodic electrode structure, and discusses the polarization properties of its diffraction. The efficiency of the first-order diffraction can be gradually controlled by applying external electric fields cross the NLC, and the maximum diffraction efficiency of the first-order diffraction that can be obtained is around 12.5% under the applied voltage of 5.0 V. In addition to the applied electric field, the efficiency of the first-order diffraction can also vary by changing the polarized state of the incident beam. Antisymmetric polarization states with symmetrical intensities in the diffractions corresponding to the +1 and −1 order diffraction signals are also demonstrated.
Approximate Target Pre-Cueing Reduces Programming Quiet Eye and Movement Preparation Time: Evidence for Parameter Pre-Programming?

ABSTRACT Purpose: We examined the effect of target pre-cues on quiet eye duration (QED). If quiet eye (QE) represents the initial and only period for the programming of movement parameters, then the precision of target pre-cues should not affect QED. In contrast, shorter QED after pre-cueing of targets implies some initial programming process to have occurred before QE. Method: Sixteen participants threw darts at targets projected onto a soft screen. We manipulated the precision of target pre-cues by highlighting an area within which the target would appear. These pre-cued areas were either the full screen (i.e., no cue), any half, quarter, or sixteenth of the screen. Participants threw eight times in each condition. Dependent measures included QED (programming and online segments), movement preparation time (MPT; from target presentation to initiation of movement), and radial error (cm). Results: Analysis revealed that programming QE was shorter when the target was pre-cued in the most precise sixteenth condition, compared to the no cue condition. Also, MPT was shorter when pre-cued in the sixteenth condition than in either the no cue or half screen conditions. Target pre-cueing conditions did not affect the other dependent variables. Conclusions: Shorter PQE following the most precise target pre-cueing implies that some pre-programming occurred before QE, perhaps through inhibition, but only when the pre-cue was specific enough to make pre-programming possible.
First-in-Human Evaluation of 18F-SynVesT-1, a Radioligand for PET Imaging of Synaptic Vesicle Glycoprotein 2A

Visual Abstract The use of synaptic vesicle glycoprotein 2A radiotracers with PET imaging could provide a way to measure synaptic density quantitatively in living humans. 11C-UCB-J ((R)-1-((3-(11C-methyl-11C)pyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one), previously developed and assessed in nonhuman primates and humans, showed excellent kinetic properties as a PET radioligand. However, it is labeled with the short half-life isotope 11C. We developed a new tracer, an 18F-labeled difluoro-analog of UCB-J (18F-SynVesT-1, also known as 18F-SDM-8), which displayed favorable properties in monkeys. The purpose of this first-in-human study was to assess the kinetic and binding properties of 18F-SynVesT-1 and compare with 11C-UCB-J. Methods: Eight healthy volunteers participated in a baseline study of 18F-SynVesT-1. Four of these subjects were also scanned after a blocking dose of the antiepileptic drug levetiracetam (20 mg/kg). Metabolite-corrected arterial input functions were measured. Regional time–activity curves were analyzed using 1-tissue-compartment (1TC) and 2-tissue-compartment (2TC) models and multilinear analysis 1 to compute total distribution volume (VT) and binding potential (BPND). The centrum semiovale was used as a reference region. The Lassen plot was applied to compute levetiracetam occupancy and nondisplaceable distribution volume. SUV ratio-1 (SUVR-1) over several time windows was compared with BPND. Results: Regional time–activity curves were fitted better with the 2TC model than the 1TC model, but 2TC VT estimates were unstable. The 1TC VT values matched well with those from the 2TC model (excluding the unstable values). Thus, 1TC was judged as the most useful model for quantitative analysis of 18F-SynVesT-1 imaging data. The minimum scan time for stable VT measurement was 60 min. The rank order of VT and BPND was similar between 18F-SynVesT-1 and 11C-UCB-J. Regional VT was slightly higher for 11C-UCB-J, but BPND was higher for 18F-SynVesT-1, though these differences were not significant. Levetiracetam reduced the uptake of 18F-SynVesT-1 in all regions and produced occupancy of 85.7%. The SUVR-1 of 18F-SynVesT-1 from 60 to 90 min matched best with 1TC BPND. Conclusion: The novel synaptic vesicle glycoprotein 2A tracer, 18F-SynVesT-1, displays excellent kinetic and in vivo binding properties in humans and holds great potential for the imaging and quantification of synaptic density in neuropsychiatric disorders.