Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanism and Applications of CRISPR/Cas-9-Mediated Genome Editing

Abstract Clustered regularly interspaced short palindromic repeat (CRISPR) and their associated protein (Cas-9) is the most effective, efficient, and accurate method of genome editing tool in all living cells and utilized in many applied disciplines. Guide RNA (gRNA) and CRISPR-associated (Cas-9) proteins are the two essential components in CRISPR/Cas-9 system. The mechanism of CRISPR/Cas-9 genome editing contains three steps, recognition, cleavage, and repair. The designed sgRNA recognizes the target sequence in the gene of interest through a complementary base pair. While the Cas-9 nuclease makes double-stranded breaks at a site 3 base pair upstream to protospacer adjacent motif, then the double-stranded break is repaired by either non-homologous end joining or homology-directed repair cellular mechanisms. The CRISPR/Cas-9 genome-editing tool has a wide number of applications in many areas including medicine, agriculture, and biotechnology. In agriculture, it could help in the design of new grains to improve their nutritional value. In medicine, it is being investigated for cancers, HIV, and gene therapy such as sickle cell disease, cystic fibrosis, and Duchenne muscular dystrophy. The technology is also being utilized in the regulation of specific genes through the advanced modification of Cas-9 protein. However, immunogenicity, effective delivery systems, off-target effect, and ethical issues have been the major barriers to extend the technology in clinical applications. Although CRISPR/Cas-9 becomes a new era in molecular biology and has countless roles ranging from basic molecular researches to clinical applications, there are still challenges to rub in the practical applications and various improvements are needed to overcome obstacles.
Biocompatible and Enzymatically Degradable Gels for 3D Cellular Encapsulation under Extreme Compressive Strain

Cell encapsulating scaffolds are necessary for the study of cellular mechanosensing of cultured cells. However, conventional scaffolds used for loading cells in bulk generally fail at low compressive strain, while hydrogels designed for high toughness and strain resistance are generally unsuitable for cell encapsulation. Here we describe an alginate/gelatin methacryloyl interpenetrating network with multiple crosslinking modes that is robust to compressive strains greater than 70%, highly biocompatible, enzymatically degradable and able to effectively transfer strain to encapsulated cells. In future studies, this gel formula may allow researchers to probe cellular mechanosensing in bulk at levels of compressive strain previously difficult to investigate.
Geriatric Conditions and Functional Disability among a National Community-Dwelling Sample of Older Adults in India in 2017–2018

This study aimed to determine the prevalence of geriatric conditions and their association with disability in older community-dwelling adults in India. The cross-sectional sample consisted of 31,477 individuals (≥60 years) from the Longitudinal Ageing Study in India (LASI) Wave 1 in 2017–2018. Geriatric conditions assessed included injurious falls, impaired cognition, underweight, dizziness, incontinence, impaired vision and impaired hearing. More than two in five participants (44.3%) had no geriatric condition, 32.7% had one, 15.9% two and 7.1% had three or more geriatric conditions; 26.9% were underweight, 14.5% dizziness, 13.7% had impaired vision, 9.6% impaired hearing, 9.3% impaired cognition, 8.2% major depressive disorder, 5.7% injurious falls, 4.0% incontinence, and 7.4% had Activity of Daily Living (ADL) dependencies. In logistic regression analysis, adjusted by sociodemographic factors and the number of chronic conditions, we found a higher number of geriatric conditions, and a higher number of chronic conditions were associated with ADL dependencies. In a model adjusted for sociodemographic factors and the type of chronic conditions, we found that a higher number of geriatric conditions and heart disease, stroke, and bone or joint disorder were positively associated with ADL dependencies. The odds of ADL dependencies increased with impaired cognition, impaired vision, impaired hearing, and major depressive disorder. Impaired cognition, incontinence, impaired vision and major depressive disorder were positively associated with dressing, bathing, eating, transferring, and toileting dependency. In addition, impaired hearing was associated with transferring and toileting dependency. More than half of older adults in India had at least one geriatric condition. The prevalence of geriatric conditions was as high as the prevalence of chronic conditions, which in some cases were associated with disability. Geriatric conditions should be included in health care management.
Outcomes of Living Kidney Donor Candidates and Living Kidney Recipient Candidates with JC Polyomavirus and BK Polyomavirus Viruria

Introduction Recent data have emerged about a protective association between JCV viruria and chronic kidney disease (CKD). Material and Methods. Single-center retrospective cohort study; 230 living kidney donors (LKD) candidates and 59 potential living kidney receptors (LKR) were enrolled. Plasma and urinary JCV and BKV viral loads were measured in all LKD candidates and in nonanuric LKR candidates. Twenty-six living kidney transplant surgeries were performed. LKR were followed in order to evaluate BKV and JCV viremia and urinary viral shedding after KT. Results In LKD candidates, JCV viruria was negatively associated with proteinuria of >200 mg/24 hours (JC viruric LKD: 12.5% vs JCV nonviruric LKD: 26.7%, p=0.021, OR:0.393; 95% CI: 0.181–0.854). In a multivariate analysis, LKD candidates with JCV viruria had a lower risk of proteinuria of >200 mg/24 hours (p=0.009, OR: 0.342, 95% CI: 0.153–0.764), in a model adjusted for age, gender, presence of hypertension, and eGFR <80 mL/min. Prevalence of JCV viruria was higher in LKD candidates when compared with LKR candidates (40.0% vs 1.7%, p < 0.001). Among the 26 LKR, 14 (53.8%) KT patients evolved with JCV viruria; 71.4% received a graft from a JCV viruric donor. Conclusion Our data corroborate the recent findings of an eventual protective association between JCV viruria and kidney disease, and we extrapolated this concept to a South European population.
Applications of Functionalized Hydrogels in the Regeneration of the Intervertebral Disc

Intervertebral disc degeneration (IDD) is caused by genetics, aging, and environmental factors and is one of the leading causes of low back pain. The treatment of IDD presents many challenges. Hydrogels are biomaterials that possess properties similar to those of the natural extracellular matrix and have significant potential in the field of regenerative medicine. Hydrogels with various functional qualities have recently been used to repair and regenerate diseased intervertebral discs. Here, we review the mechanisms of intervertebral disc homeostasis and degeneration and then discuss the applications of hydrogel-mediated repair and intervertebral disc regeneration. The classification of artificial hydrogels and natural hydrogels is then briefly introduced, followed by an update on the development of functional hydrogels, which include noncellular therapeutic hydrogels, cellular therapeutic hydrogel scaffolds, responsive hydrogels, and multifunctional hydrogels. The challenges faced and future developments of the hydrogels used in IDD are discussed as they further promote their clinical translation.
Kinematic Evaluation via Inertial Measurement Unit Associated with Upper Extremity Motor Function in Subacute Stroke: A Cross-Sectional Study

Kinematic evaluation via portable sensor system has been increasingly applied in neurological sciences and clinical practice. However, conventional kinematic evaluation rarely extends the context beyond the motor impairment level. In addition, kinematic tasks with numerous items could be complex and time consuming that pose a burden to test applications and data processing. The study aimed to explore the correlation of finger-to-nose task (FNT) kinematics via Inertial Measurement Unit with upper limb motor function in subacute stroke. In this study, six FNT kinematic variables were used to measure movement time, smoothness, and velocity in 37 participants with subacute stroke. Upper limb motor function was evaluated with the Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Action Research Arm Test (ARAT), and modified Barthel Index (MBI). As a result, mean velocity, peak velocity, and the number of movement units were associated with the clinical assessments. The multivariable linear regression models could estimate 55%, 51%, and 32% of variance in FMA-UE, ARAT, and MBI, respectively. In addition, age, gender, type of stroke, and paretic side had no significant effects on these associations. Results show that FNT kinematic variables measured via Inertial Measurement Unit are associated with upper extremity motor function in individuals with subacute stroke. The objective kinematic evaluation may be suitable for predicting clinical measures of motor impairment and capacity to understand upper extremity motor recovery and clinical decision making after stroke. This trial is registered with ChiCTR1900026656.
From Nano-Gels to Marine Snow: A Synthesis of Gel Formation Processes and Modeling Efforts Involved with Particle Flux in the Ocean

Marine gels (nano-, micro-, macro-) and marine snow play important roles in regulating global and basin-scale ocean biogeochemical cycling. Exopolymeric substances (EPS) including transparent exopolymer particles (TEP) that form from nano-gel precursors are abundant materials in the ocean, accounting for an estimated 700 Gt of carbon in seawater. This supports local microbial communities that play a critical role in the cycling of carbon and other macro- and micro-elements in the ocean. Recent studies have furthered our understanding of the formation and properties of these materials, but the relationship between the microbial polymers released into the ocean and marine snow remains unclear. Recent studies suggest developing a (relatively) simple model that is tractable and related to the available data will enable us to step forward into new research by following marine snow formation under different conditions. In this review, we synthesize the chemical and physical processes. We emphasize where these connections may lead to a predictive, mechanistic understanding of the role of gels in marine snow formation and the biogeochemical functioning of the ocean.
Early Diagnosis of Classic Homocystinuria in Kuwait through Newborn Screening: A 6-Year Experience

Kuwait is a small Arabian Gulf country with a high rate of consanguinity and where a national newborn screening program was expanded in October 2014 to include a wide range of endocrine and metabolic disorders. A retrospective study conducted between January 2015 and December 2020 revealed a total of 304,086 newborns have been screened in Kuwait. Six newborns were diagnosed with classic homocystinuria with an incidence of 1:50,000, which is not as high as in Qatar but higher than the global incidence. Molecular testing for five of them has revealed three previously reported pathogenic variants in the CBS gene, c.969G>A, p.(Trp323Ter); c.982G>A, p.(Asp328Asn); and the Qatari founder variant c.1006C>T, p.(Arg336Cys). This is the first study to review the screening of newborns in Kuwait for classic homocystinuria, starting with the detection of elevated blood methionine and providing a follow-up strategy for positive results, including plasma total homocysteine and amino acid analyses. Further, we have demonstrated an increase in the specificity of the current newborn screening test for classic homocystinuria by including the methionine to phenylalanine ratio along with the elevated methionine blood levels in first-tier testing. Here, we provide evidence that the newborn screening in Kuwait has led to the early detection of classic homocystinuria cases and enabled the affected individuals to lead active and productive lives.
Gait Analysis Accuracy Difference with Different Dimensions of Flexible Capacitance Sensors

Stroke causes neurological pathologies, including gait pathologies, which are diagnosed by gait analysis. However, existing gait analysis devices are difficult to use in situ or are disrupted by external conditions. To overcome these drawbacks, a flexible capacitance sensor was developed in this study. To date, a performance comparison of flexible sensors with different dimensions has not been carried out. The aim of this study was to provide optimized sensor dimension information for gait analysis. To accomplish this, sensors with seven different dimensions were fabricated. The dimensions of the sensors were based on the average body size and movement range of 20- to 59-year-old adults. The sensors were characterized by 100 oscillations. The minimum hysteresis error was 8%. After that, four subjects were equipped with the sensor and walked on a treadmill at a speed of 3.6 km/h. All walking processes were filmed at 50 fps and analyzed in Kinovea. The RMS error was calculated using the same frame rate of the video and the sampling rate of the signal from the sensor. The smallest RMS error between the sensor data and the ankle angle was 3.13° using the 49 × 8 mm sensor. In this study, we confirm the dimensions of the sensor with the highest gait analysis accuracy; therefore, the results can be used to make decisions regarding sensor dimensions.
Combining Multiple Assays Improves Detection and Serotyping of Foot-and-Mouth Disease Virus. A Practical Example with Field Samples from East Africa

Multiple serotypes and topotypes of foot-and-mouth disease virus (FMDV) circulate in endemic areas, posing considerable impacts locally. In addition, introductions into new areas are of great concern. Indeed, in recent years, multiple FMDV outbreaks, caused by topotypes that have escaped from their original areas, have been recorded in various parts of the world. In both cases, rapid and accurate diagnosis, including the identification of the serotype and topotype causing the given outbreaks, plays an important role in the implementation of the most effective and appropriate measures to control the spread of the disease. In the present study, we describe the performance of a range of diagnostic and typing tools for FMDV on a panel of vesicular samples collected in northern Tanzania (East Africa, EA) during 2012–2018. Specifically, we tested these samples with a real-time RT-PCR targeting 3D sequence for pan-FMDV detection; an FMDV monoclonal antibody-based antigen (Ag) detection and serotyping ELISA kit; virus isolation (VI) on LFBKαVβ6 cell line; and a panel of four topotype-specific real-time RT-PCRs, specifically tailored for circulating strains in EA. The 3D real-time RT-PCR showed the highest diagnostic sensitivity, but it lacked typing capacity. Ag-ELISA detected and typed FMDV in 71% of sample homogenates, while VI combined with Ag-ELISA for typing showed an efficiency of 82%. The panel of topotype-specific real-time RT-PCRs identified and typed FMDV in 93% of samples. However, the SAT1 real-time RT-PCR had the highest (20%) failure rate. Briefly, topotype-specific real-time RT-PCRs had the highest serotyping capacity for EA FMDVs, although four assays were required, while the Ag-ELISA, which was less sensitive, was the most user-friendly, hence suitable for any laboratory level. In conclusion, when the four compared tests were used in combination, both the diagnostic and serotyping performances approached 100%.
Nonprehensile Manipulation of Parts on a Horizontal Circularly Oscillating Platform with Dynamic Dry Friction Control

This paper presents a novel method for nonprehensile manipulation of parts on a circularly oscillating platform when the effective coefficient of dry friction between the part and the platform is being dynamically controlled. Theoretical and experimental analyses have been performed to validate the proposed method and to determine the control parameters that define the characteristics of the part’s motion. A mathematical model of the manipulation process with dynamic dry friction control was developed and solved. The modeling showed that by changing the phase shift between the function for dynamic dry friction control and the function defining the circular motion of the platform, the part can be moved in any direction as the angle of displacement can be controlled in a full range from 0 to 2π. The nature of the trajectory and the mean displacement velocity of the part mainly depend on the width of the rectangular function for dynamic dry friction control. To verify the theoretical findings, an experimental setup was developed, and experiments of manipulation were carried out. The experimental results qualitatively confirmed the theoretical findings. The presented analysis enriches the classical theories of nonprehensile manipulation on oscillating platforms, and the presented findings are relevant for mechatronics, robotics, mechanics, electronics, medical, and other industries.
Medicago ABI3 Splicing Isoforms Regulate the Expression of Different Gene Clusters to Orchestrate Seed Maturation

Seed maturation comprises important developmental processes, such as seed filling and the acquisition of seed germination capacity, desiccation tolerance, longevity, and dormancy. The molecular regulation of these processes is tightly controlled by the LAFL transcription factors, among which ABSCISIC ACID INSENSITIVE 3 (ABI3) was shown to be involved in most of these seed maturation processes. Here, we studied the ABI3 gene from Medicago truncatula, a model legume plant for seed studies. With the transcriptomes of two loss-of-function Medicago abi3 mutants, we were able to show that many gene classes were impacted by the abi3 mutation at different stages of early, middle, and late seed maturation. We also discovered three MtABI3 expression isoforms, which present contrasting expression patterns during seed development. Moreover, by ectopically expressing these isoforms in Medicago hairy roots generated from the abi3 mutant line background, we showed that each isoform regulated specific gene clusters, suggesting divergent molecular functions. Furthermore, we complemented the Arabidopsis abi3 mutant with each of the three MtABI3 isoforms and concluded that all isoforms were capable of restoring seed viability and desiccation tolerance phenotypes even if not all isoforms complemented the seed color phenotype. Taken together, our results allow a better understanding of the ABI3 network in Medicago during seed development, as well as the discovery of commonly regulated genes from the three MtABI3 isoforms, which can give us new insights into how desiccation tolerance and seed viability are regulated.
Selective Effects of Methylphenidate on Attention and Inhibition in 22q11.2 Deletion Syndrome: Results From a Clinical Trial

Abstract Background Attention deficit and/or hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder in children with 22q11.2 deletion syndrome (22q11DS) and frequently persists into adulthood. Although medication with stimulant has been demonstrated to be highly effective in idiopathic ADHD, evidence in 22q11DS is still scarce. Previous studies have shown safety and effectiveness of methylphenidate (MPH) on core symptoms of ADHD as well as improvement of associated cognitive deficits. However, only a limited number of cognitive domains have been explored. Methods Twenty-three participants with 22q11DS and attention difficulties, aged 8–24 years, entered a clinical trial aiming to specify the effects of MPH on clinical symptoms, cognition, and daily-life behavior. The effects of treatment were compared with/without medication in a within-subject design. The trial included both participants naïve to the molecule and chronic users. Results Benefit from the treatment was demonstrated through a decrease in core ADHD symptoms, specifically inattention symptoms, and improvement of cognitive measures of attention and inhibition. Conversely, no significant change was found for other executive functions (such as cognitive flexibility, working memory, initiation), learning, or memory. Moreover, no significant improvement on ecological measures of daily-life executive functioning was found, possibly because of the short treatment period. We replicated safety, and although very frequent, side effects were of mild intensity and comparable with previous findings. Conclusions This study extends the current knowledge on the effects of MPH in patients with 22q11DS. Treatment was found to be effective for core ADHD symptoms and cognitive measures of attention and inhibition.
Large-Scale International Validation of an Indirect ELISA Based on Recombinant Nucleocapsid Protein of Rift Valley Fever Virus for the Detection of IgG Antibody in Domestic Ruminants

Diagnostic performance of an indirect enzyme-linked immunosorbent assay (I-ELISA) based on a recombinant nucleocapsid protein (rNP) of the Rift Valley fever virus (RVFV) was validated for the detection of the IgG antibody in sheep (n = 3367), goat (n = 2632), and cattle (n = 3819) sera. Validation data sets were dichotomized according to the results of a virus neutralization test in sera obtained from RVF-endemic (Burkina Faso, Democratic Republic of Congo, Mozambique, Senegal, Uganda, and Yemen) and RVF-free countries (France, Poland, and the USA). Cut-off values were defined using the two-graph receiver operating characteristic analysis. Estimates of the diagnostic specificity of the RVFV rNP I-ELISA in animals from RVF-endemic countries ranged from 98.6% (cattle) to 99.5% (sheep) while in those originating from RVF-free countries, they ranged from 97.7% (sheep) to 98.1% (goats). Estimates of the diagnostic sensitivity in ruminants from RVF-endemic countries ranged from 90.7% (cattle) to 100% (goats). The results of this large-scale international validation study demonstrate the high diagnostic accuracy of the RVFV rNP I-ELISA. Standard incubation and inactivation procedures evaluated did not have an adverse effect on the detectable levels of the anti-RVFV IgG in ruminant sera and thus, together with recombinant antigen-based I-ELISA, provide a simple, safe, and robust diagnostic platform that can be automated and carried out outside expensive bio-containment facilities. These advantages are particularly important for less-resourced countries where there is a need to accelerate and improve RVF surveillance and research on epidemiology as well as to advance disease control measures.
Classification of Ataxic Gait

Gait disorders accompany a number of neurological and musculoskeletal disorders that significantly reduce the quality of life. Motion sensors enable high-quality modelling of gait stereotypes. However, they produce large volumes of data, the evaluation of which is a challenge. In this publication, we compare different data reduction methods and classification of reduced data for use in clinical practice. The best accuracy achieved between a group of healthy individuals and patients with ataxic gait extracted from the records of 43 participants (23 ataxic, 20 healthy), forming 418 segments of straight gait pattern, is 98% by random forest classifier preprocessed by t-distributed stochastic neighbour embedding.