Miracle-dz/UniFAR-FTUs huggingface dataset:
Combined Supra- and Sub-Lesional Epidural Electrical Stimulation for Restoration of the Motor Functions after Spinal Cord Injury in Mini Pigs

This study evaluates the effect of combined epidural electrical stimulation (EES) applied above (C5) and below (L2) the spinal cord injury (SCI) at T8–9 combined with motor training on the restoration of sensorimotor function in mini pigs. The motor evoked potentials (MEP) induced by EES applied at C5 and L2 levels were recorded in soleus muscles before and two weeks after SCI. EES treatment started two weeks after SCI and continued for 6 weeks led to improvement in multiple metrics, including behavioral, electrophysiological, and joint kinematics outcomes. In control animals after SCI a multiphasic M-response was observed during M/H-response testing, while animals received EES-enable training demonstrated the restoration of the M-response and H-reflex, although at a lower amplitude. The joint kinematic and assessment with Porcine Thoracic Injury Behavior scale (PTIBS) motor recovery scale demonstrated improvement in animals that received EES-enable training compared to animals with no treatment. The positive effect of two-level (cervical and lumbar) epidural electrical stimulation on functional restoration in mini pigs following spinal cord contusion injury in mini pigs could be related with facilitation of spinal circuitry at both levels and activation of multisegmental coordination. This approach can be taken as a basis for the future development of neuromodulation and neurorehabilitation therapy for patients with spinal cord injury.
The impact of including babies on the effectiveness of dialectical behaviour therapy skills groups in a community perinatal service

Abstract Background: Perinatal mental illnesses are a major public health issue, which untreated can have devastating impacts on women and their families. Problems with emotion regulation are a common feature across perinatal mental illnesses. Aims: This study sought to evaluate the impacts of dialectical behaviour therapy (DBT) skills groups for mothers and babies in a community perinatal service. We hypothesised that community perinatal DBT skills groups that included babies would reduce distress and improve emotional regulation. Method: A mixed-methods within-subjects design was utilised with outcome measures collected pre- and post-intervention. Qualitative interviews exploring mothers’ experiences of bringing their baby to group were also conducted. Results: Results indicated that DBT skills groups significantly improved levels of psychological distress and emotional regulation. Conclusions: Community perinatal DBT skills groups are effective when babies are present. Moreover, benefits of including babies were identified, under the themes of Self as Mother, Shared Experience, and Impact of Babies.
People who overvalue appearance selectively attend to descriptors of the attractiveness ideal: Findings from an emotional Stroop task.

OBJECTIVE Attentional biases to stimuli related to stigmatized appearance are theorized to stem from appearance overvaluation, but little research has examined this link. As well, little research has examined whether appearance overvaluation is associated with biases toward stimuli that describe the attractiveness ideal. We addressed these gaps in the literature using the emotional Stroop task and tested whether appearance overvaluation is associated with an attentional bias for words that describe stigmatized appearance (e.g., fat, ugly, shabby), the attractiveness ideal (e.g., thin, beautiful, fashionable), or both. METHOD AND RESULTS In Study 1, a community sample of people (N = 86) completed measures of appearance overvaluation, body dissatisfaction, and body mass index (BMI) followed by an emotional Stroop task. Appearance overvaluation was associated with an attentional bias for attractiveness ideal words-not stigmatized appearance words. Results remained significant when controlling for participants' body dissatisfaction, BMI, and gender. Study 2 (N = 316) replicated these findings. Finally, an integrative data analysis that pooled the data of Studies 1 and 2 (N = 402) provided additional support for our general hypothesis that people who overvalue appearance display an attentional bias to stimuli related to the attractiveness ideal. DISCUSSION The results show a robust association between appearance overvaluation and selective attention for attractiveness ideal stimuli. Results are discussed in reference to theory and research on information processing in eating disorders. We also call for research to examine information processing of stimuli related to the attractiveness ideal among people with eating disorders and who place high importance on appearance for self-definition.
Synthesis, In Silico and In Vitro Assessment of New Quinazolinones as Anticancer Agents via Potential AKT Inhibition

A series of novel quinazolinone derivatives (2–13) was synthesized and examined for their cytotoxicity to HepG2, MCF-7, and Caco-2 in an MTT assay. Among these derivatives, compounds 4 and 9 exhibited significant cytotoxic activity against Caco-2, HepG2, and MCF-7 cancer cells. Compound 4 had more significant inhibitory effects than compound 9 on Caco-2, HepG2, and MCF-7 cell lines, with IC50 values of 23.31 ± 0.09, 53.29 ± 0.25, and 72.22 ± 0. 14µM, respectively. The AKT pathway is one of human cancer’s most often deregulated signals. AKT is also overexpressed in human cancers such as glioma, lung, breast, ovarian, gastric, and pancreas. A molecular docking study was performed to analyze the inhibitory action of newly synthetic quinazolinone derivatives against Homo sapiens AKT1 protein. Molecular docking simulations were found to be in accordance with in vitro studies, and hence supported the biological activity. The results suggested that compounds 4 and 9 could be used as drug candidates for cancer therapy via its potential inhibition of AKT1 as described by docking study.
The Mismatch Repair System (MMR) in Head and Neck Carcinogenesis and Its Role in Modulating the Response to Immunotherapy: A Critical Review

Simple Summary The dysfunction of the mismatch repair system, an important mechanism for the detection and correction of DNA replication mistakes, may often lead to instability in the length of specific genetic sequences, known as microsatellites, and to the accumulation of mutations. Microsatellite instability is a well-known risk factor for the development of colorectal cancers and other types of tumors but is also considered a positive predictor of the immunotherapy response. Malignancies harboring such a specific genomic instability are very immunogenic because of the great number of aberrant antigens they produce. Therapies based on the blockade of specific immune checkpoints have shown to induce an effective immune response against microsatellite-unstable cancer. Many studies proved that microsatellite instability has a decisive role in the carcinogenesis and the malignant progression of head and neck cancer and, in the near future, it may become a useful tool in tailoring immunotherapy also in this field of precision oncology. Abstract The mismatch repair (MMR) system has a major role in the detection and correction of DNA replication errors, resulting from DNA polymerase slippage or nucleotides misincorporation. Specific inherited/acquired alterations or epigenetic inactivation of MMR genes are associated with microsatellite instability (MSI): the loss of crucial function in repairing DNA alterations can promote carcinogenesis by favoring the accumulation of thousands of mutations in a broad spectrum of different anatomic sites such as colon, stomach, prostate, esophagus, endometrium, lung and head and neck. Recent extensive data suggest that tumor mutational burden strongly correlates with a clinical response to immunotherapy using checkpoint inhibitors and this response is influenced by MMR deficiency in a wide range of human solid cancers. In this context, few data about this crucial point are available for head and neck cancer (HNC). In this review, we discuss the role of MMR alterations and the resulting MSI in HNC pathogenesis. Furthermore, by summarizing the clinical available data on how they influence the progression of precancerous lesions and the risk of recurrence or second primary tumors, we want to define the current role of MSI in the management of HNC. Finally, we analyze the complex interaction between cancer cells and the immune system addressing the data now available about a potential correlation between microsatellite instability and immunotherapy response in HNC.
An Adaptive Network Coding Scheme for Multipath Transmission in Cellular-Based Vehicular Networks

With the emergence of vehicular Internet-of-Things (IoT) applications, it is a significant challenge for vehicular IoT systems to obtain higher throughput in vehicle-to-cloud multipath transmission. Network Coding (NC) has been recognized as a promising paradigm for improving vehicular wireless network throughput by reducing packet loss in transmission. However, existing researches on NC do not consider the influence of the rapid quality change of wireless links on NC schemes, which poses a great challenge to dynamically adjust the coding rate according to the variation of link quality in vehicle-to-cloud multipath transmission in order to avoid consuming unnecessary bandwidth resources and to increase network throughput. Therefore, we propose an Adaptive Network Coding (ANC) scheme brought by the novel integration of the Hidden Markov Model (HMM) into the NC scheme to efficiently adjust the coding rate according to the estimated packet loss rate (PLR). The ANC scheme conquers the rapid change of wireless link quality to obtain the utmost throughput and reduce the packet loss in transmission. In terms of the throughput performance, the simulations and real experiment results show that the ANC scheme outperforms state-of-the-art NC schemes for vehicular wireless multipath transmission in vehicular IoT systems.
Exogenous Application of Proteoglycan to the Cell Surface Microenvironment Facilitates to Chondrogenic Differentiation and Maintenance

Osteoarthritis (OA), a disease that greatly impacts quality of life, has increasing worldwide prevalence as the population ages. However, its pathogenic mechanisms have not been fully elucidated and current therapeutic treatment strategies are inadequate. In recent years, abnormal endochondral ossification in articular cartilage has received attention as a pathophysiological mechanism in OA. Cartilage is composed of abundant extracellular matrix components, which are involved in tissue maintenance and regeneration, but how these factors affect endochondral ossification is not clear. Here, we show that the application of aggrecan-type proteoglycan from salmon nasal cartilage (sPG) exhibited marked proliferative capacity through receptor tyrosine kinases in chondroprogenitor cells, and also exhibited differentiation and three-dimensional structure formation via phosphorylation of Insulin-like Growth Factor-1 Receptor and Growth Differentiation Factor 5 expression. Furthermore, sPG inhibited calcification via expression of Runx2 and Col10 (factors related to induction of calcification), while increasing Mgp, a mineralization inhibitory factor. As a result of analyzing the localization of sPG applied to the cells, it was localized on the surface of the cell membrane. In this study, we found that sPG, as a biomaterial, could regulate cell proliferation, differentiation and calcification inhibition by acting on the cell surface microenvironment. Therefore, sPG may be the foundation for a novel therapeutic approach for cartilage maintenance and for improved symptoms in OA.
Advancement in female sports medicine and preventive medicine

Sport plays a major role in maintaining and improving physical function and health of women from adolescence to sexual maturity, through to menopause and old age, and it also plays a key role in social productivity and medicine from the perspective of preventive medicine. However, in routine clinical practice, there are many gynecological problems that affect the condition and performance of female athletes due to a lack of appropriate medical intervention, such as neglect of amenorrhea and menstruation‐related symptoms. In addition, the number of athletes aiming to return to competition post‐partum has been increasing in recent years, but there is little medical data on the well‐being of female athletes during pregnancy and the post‐partum period. I previously conducted clinical research on three separate topics, with the aim of clarifying the current issues unique to female athletes, mainly in terms of conditioning and injury prevention. The goal was that clinical research was to examine the situation of athletes with and without disabilities and provide feedback from the survey results to athletes and coaches. This paper divides the clinical studies conducted to date into three topics that will be explored herein: (i) research on the female athlete triad (Triad); (ii) research on oral contraceptives/low‐dose estrogen‐progestin; and (iii) research on pregnancy and post‐partum period.
On the connection between real-world circumstances and online player behaviour: The case of EVE Online

Games involving virtual worlds are popular in several segments of the population and societies. The online environment facilitates that players from different countries interact in a common virtual world. Virtual worlds involving social and economic interactions are particularly useful to test social and economic theories. Using data from EVE Online, a massive online multi-player game simulating a fantasy galaxy, we analyse the relation between the real-world context in which players live and their in-game behaviour at the country level. We find that in-game aggressiveness to non-player characters is positively related to real-world levels of aggressiveness as measured by the Global Peace Index and the Global Terrorist Index at the country level. The opposite is true for in-game aggressiveness towards other players, which seems to work as a safety valve for real-world player aggressiveness. The ability to make in-game friends is also positively related to real-world levels of aggressiveness in much the same way. In-game trading behaviour is dependent on the macro-economic environment where players live. The unemployment rate and exchange rate make players trade more efficiently and cautiously in-game. Overall, we find evidence that the real-world environment affects in-game behaviour, suggesting that virtual worlds can be used to experiment and test social and economic theories, and to infer real-world behaviour at the country level.
Disentangling the effects of reproductive behaviours and fertility preferences on child growth in India

We analysed population data from the 2015–16 National Family Health Survey to disentangle the intricate underlying effects of reproductive behaviours and fertility preferences on child growth. We expected birth interval length to be more strongly associated with stunting than sibsize and these effects to be moderated by whether the child was wanted or unintended (mistimed/unwanted). Regression analyses showed strong and equal effects of short birth interval and sibsize on stunting, when adjusted for potential confounders and unobserved between-mother heterogeneity. There were no statistical associations between stunting and mistiming/unwantedness of index children, suggesting the absence of discrimination against such children. We conclude that while fertility preferences have no effect, reproductive behaviours exert significant influence on child growth. Sibsize has been falling for many years in India but birth interval lengths have remained largely unchanged. The results underscore the need for strengthening uptake of reversible contraceptives to enable longer birth intervals.
Ultra-High Energy Density Hybrid Supercapacitors Using MnO2/Reduced Graphene Oxide Hybrid Nanoscrolls

Manganese oxide (MnO2) is a promising material for supercapacitor applications, with a theoretical ultra-high energy density of 308 Wh/kg. However, such ultra-high energy density has not been achieved experimentally in MnO2-based supercapacitors because of several practical issues, such as low electrical conductivity of MnO2, incomplete utilization of MnO2, and dissolution of MnO2. The present study investigates the potential of MnO2/reduced graphene oxide (rGO) hybrid nanoscroll (GMS) structures as electrode material for overcoming the difficulties and for developing ultra-high-energy storage systems. A hybrid supercapacitor, comprising MnO2/rGO nanoscrolls as anode material and activated carbon (AC) as a cathode, is fabricated. The GMS/AC hybrid supercapacitor exhibited enhanced energy density, superior rate performance, and promising Li storage capability that bridged the energy–density gap between conventional Li-ion batteries (LIBs) and supercapacitors. The fabricated GMS/AC hybrid supercapacitor demonstrates an ultra-high lithium discharge capacity of 2040 mAh/g. The GMS/AC cell delivered a maximum energy density of 105.3 Wh/kg and a corresponding power density of 308.1 W/kg. It also delivered an energy density of 42.77 Wh/kg at a power density as high as 30,800 W/kg. Our GMS/AC cell’s energy density values are very high compared with those of other reported values of graphene-based hybrid structures. The GMS structures offer significant potential as an electrode material for energy-storage systems and can also enhance the performance of the other electrode materials for LIBs and hybrid supercapacitors.
Fertility restoration of Chinese wild rice-type cytoplasmic male sterility by CRISPR/Cas9-mediated genome editing of nuclear-encoded RETROGRADE-REGULATED MALE STERILITY.

Cytoplasmic male sterility (CMS) is a trait that produces nonfunctional pollen caused by the interaction between mitochondrial and nuclear genes. In Chinese-wild (CW) type CMS, CWA, in rice (Oryza sativa L.), its mitochondria enhance the expression of the nuclear gene RETROGRADE-REGULATED MALE STERILITY (RMS), which causes pollen abortion. Fertility is recovered when its expression decreases in a restorer line, CWR. The expression of RMS is controlled by the single nucleotide polymorphism (SNP) located in the promoter region 2,286 bp upstream of the start codon of RMS. However, another gene, PPR2, which encodes pentatricopeptide repeat-domain containing protein, is predicted in the reverse strand of this region and a premature stop codon is created in CWR by the SNP. To prove RMS is directly involved in restoring fertility of CW-CMS, we introduced mutations into RMS and PPR2 using CRISPR/Cas9. Fertility was recovered in the genome-edited CMS plants with reduced expression of RMS and unaltered expression of PPR2, when the mutation was introduced in the promoter regions of RMS within or outside the coding sequence (CDS) of PPR2. Fertility restoration was not obtained when the mutation was introduced within the CDS of RMS. Our results demonstrated that PPR2 is not responsible for fertility restoration, and fertility was recovered by reduced expression of RMS, providing us with a new artificial fertility restorer line for agronomical use.
Purification of small-size acidic proteoglycan-like domain of carbonic anhydrase IX fused with thioredoxine expressed in Escherichia coli for structural characterization

Abstract Proteoglycan-like (PG) domain of carbonic anhydrase IX (CA IX) is a small-sized acidic domain (8.3 kDa; pI ∼ 3.5) with a very unusual amino acid composition. More than one third of its sequence consists of acidic amino acids and it contains no aromatic residues. It has been revealed that it holds one of the key roles in oncogenetic mechanisms, in which CA IX participates. However, it has not been structurally characterized yet. With these prospects, we developed an expression system of recombinant PG domain production in the form of a fusion protein using thioredoxine (Trx) as the fusion partner in Escherichia coli. We performed three steps during purification process utilizing affinity chromatography, anion-exchange chromatography and gel filtration; and the highest purity we reached was 93.7% with protein concentration 23.3 mg/L. Hypothetical yield of the recombinant protein would be 0.581 mg/L of culture. The applicability of the fusion protein Trx-PG for further structural studies was confirmed by in silico structure prediction tool and ELISA.
Metastatic sites as predictors in advanced NSCLC treated with PD-1 inhibitors: a systematic review and meta-analysis

ABSTRACT Background Programmed cell death protein 1 (PD-1) inhibitors are the first-line treatment for advanced non-small-cell lung cancer (NSCLC) patients. However, their efficacy in metastatic NSCLC patients remains controversial. Aim of the study The aim of our study was to evaluate the prognosis of advanced metastatic NSCLC patients treated with PD-1 inhibitors, and discuss the predictive effect of metastatic site on the long-term outcome. Methods The Embase, Ovid Medline, Cochrane Central Register of Controlled Trials, and PubMed databases were systematically screened up to February 10, 2020. Twenty-five eligible studies, involving 8,067 patients that assessed the impact of metastatic sites on survival outcome were incorporated in our study. Overall survival (OS) and progression-free survival (PFS) were described as hazard ratio (HR) with 95% confidence interval (CI). Results Among the advanced NSCLC patients, the median proportion of brain, liver, bone, and adrenal gland metastases were 21%, 17%, 35%, and 21%, respectively. Patients with metastases to the brain, liver, and bone had worse OS compared to patients without these metastases when treated with PD-1 inhibitors. Similarly, patients with metastasis to the brain and liver were more likely to progress when treated with PD-1 inhibitors. Besides, patients with multiple metastatic sites had worse PFS compared to patients with one metastatic site, while no significant difference was found in terms of OS. Conclusions Based on the findings of our systematic review and meta-analysis, metastatic sites were independent predictors of the survival outcome for advanced NSCLC patients treated with PD-1 inhibitors.
Temporal dynamics of QTL effects on vegetative growth in Arabidopsis thaliana

We assessed early vegetative growth in a population of 382 accessions of Arabidopsis thaliana using automated non-invasive high-throughput phenotyping. All accessions were imaged daily from seven to 18 days after sowing in three independent experiments and genotyped using the Affymetrix 250k SNP array. Projected leaf area (PLA) was derived from image analysis and used to calculate relative growth rates (RGR). In addition, initial seed size was determined. The generated data sets were used jointly for a genome-wide association study that identified 238 marker-trait associations (MTAs) individually explaining up to 8 % of the total phenotypic variation. Co-localisation of MTAs occurred at 33 genomic positions. At 21 of these positions, sequential co-localisation of MTAs for two to nine consecutive days was observed. The detected MTAs for PLA and RGR could be grouped according to their temporal expression patterns, emphasising that temporal variation of MTA action can be observed even during the vegetative growth phase, a period of continuous formation and enlargement of seemingly similar rosette leaves. This indicates that causal genes may be differentially expressed in successive periods. Analyses of the temporal dynamics of biological processes are needed to gain important insight into the molecular mechanisms of growth-controlling processes in plants. Highlight A genome-wide association study including the factor time highlighted that early plant growth in Arabidopsis is governed by several medium and many small effect loci, most of which act only during short phases of two to nine days.