Miracle-dz/UniFAR-FTUs huggingface dataset:
Preliminary Validation of a Two-Point Estimation Task for the Measurement of Sensory Dissociation in Patients with Chronic Low Back Pain.

Objectives Sensory dissociation (SEDI), the discrepancy between perception and actual size or shape of a painful body part, is a frequently observed finding in patients with chronic low back pain. However, the current methods of evaluating SEDI have several limitations, such as a qualitative nature and weak evidence supporting their reliability. In the current study, the reliability of two versions (manual and verbal) of a novel test, a two-point estimation task (TPE), was investigated. Methods To perform the manual version of the task, patients estimated the distance between two tactile stimuli delivered to their back using callipers, whereas in the verbal version they verbally reported the estimated distance. Results The manual version of TPE showed greater interexaminer reliability than the verbal version, and the mean of the two repeated measurements was sufficient for reaching excellent reliability for the pain-free (intraclass correlation coefficient [ICC] = 0.91, 95% confidence interval [CI] = 0.77-0.97) and painful (ICC = 0.86, 95% CI = 0.65-0.94) sides. Intra-examiner reliability was moderate to excellent (ICC = 0.66-0.96) for the manual version performed at the pain-free and painful sides. Distribution, duration, and intensity of pain significantly predicted SEDI and accounted for 42% of the total variance (corrected R2 = 0.42, P < 0.01). Conclusions TPE showed higher reliability coefficients compared with tools previously suggested in the literature and can therefore be used clinically and experimentally by one or more examiners. Further research is required to investigate the validity of this new test.
Genetic risk score modifies the effect of APOE on risk and age onset of Alzheimer's disease

Single nucleotide polymorphism (SNP)‐based genetic risk score (GRS) and APOE genotype are both important in risk prediction of Alzheimer's disease (AD); however, the interaction between GRS and APOE has not been extensively investigated. Our objective was to determine whether GRS modifies the APOE effect on AD risk and age at onset (AAO). The study included 774 AD cases and 767 controls of European descent. Population standardized GRS was calculated based on 17 previously implicated AD risk‐associated SNPs. Association was analyzed using logistic regression, Cox proportional hazards model and Kaplan‐Meier curve. We found that GRS was significantly associated with AD risk and the association was stronger among APOE ε4 carriers. Compared to ε4 non‐carriers, the Odds Ratio (OR) for AD was 8.09 (95% Confidence Interval [CI]: 4.98‐13.63) for ε4 carriers with high‐GRS (≥1.5). In contrast, the OR was 2.55 (95% CI: 1.46‐4.49) for ε4 carriers with low‐GRS (<0.6). In conclusion, these results suggest SNP‐based GRS may supplement APOE for better assessment of inherited risk and age of onset of AD.
A genetic screen pinpoints ribonucleotide reductase residues that sustain dNTP homeostasis and specifies a highly mutagenic type of dNTP imbalance

Abstract The balance and the overall concentration of intracellular deoxyribonucleoside triphosphates (dNTPs) are important determinants of faithful DNA replication. Despite the established fact that changes in dNTP pools negatively influence DNA replication fidelity, it is not clear why certain dNTP pool alterations are more mutagenic than others. As intracellular dNTP pools are mainly controlled by ribonucleotide reductase (RNR), and given the limited number of eukaryotic RNR mutations characterized so far, we screened for RNR1 mutations causing mutator phenotypes in Saccharomyces cerevisiae. We identified 24 rnr1 mutant alleles resulting in diverse mutator phenotypes linked in most cases to imbalanced dNTPs. Among the identified rnr1 alleles the strongest mutators presented a dNTP imbalance in which three out of the four dNTPs were elevated (dCTP, dTTP and dGTP), particularly if dGTP levels were highly increased. These rnr1 alleles caused growth defects/lethality in DNA replication fidelity-compromised backgrounds, and caused strong mutator phenotypes even in the presence of functional DNA polymerases and mismatch repair. In summary, this study pinpoints key residues that contribute to allosteric regulation of RNR’s overall activity or substrate specificity. We propose a model that distinguishes between different dNTP pool alterations and provides a mechanistic explanation why certain dNTP imbalances are particularly detrimental.
Kanamycin induces free radicals formation in melanocytes: An important factor for aminoglycosides ototoxicity

Ototoxicity is well‐documented but not fully understood undesirable side effect of aminoglycoside antibiotic, kanamycin. Kanamycin is capable of binding to melanin biopolymers—natural pigments of the skin, hair, and eyes. Melanin‐producing cells, melanocytes, are also present in the inner ear and are known to be necessary for normal hearing. It was considered that melanin content in the inner ear may influence aminoglycoside‐induced ototoxic effect. The impact of kanamycin on melanocytes homeostasis may thus play role in the antibiotic‐induced ototoxic effect. Previously, we demonstrated that kanamycin disturbs homeostasis in light‐pigmented melanocytes. To investigate if/how melanization contributes to this phenomenon, the study using in vitro model of dark‐pigmented melanocytes is required. Spectrophotometric measurements and electron paramagnetic resonance (EPR) spectroscopy analysis were performed. Kanamycin induced a concentration‐dependent loss in HEMn‐DP melanocytes viability. The value of IC 50 was estimated to be 5.0 mM. Modulation of the activity of analyzed antioxidant enzymes and increased production of free radicals as well as the decrease of the melanin content were observed. Our results confirmed that kanamycin generates oxidative stress in melanocytes. The increased level of free radicals caused by kanamycin may be responsible for the imbalance of antioxidant defense and the reduction of melanin content in melanocytes. The role of melanin in the mechanism of kanamycin‐induced hearing impairment was discussed and the obtained results were compared with the previously demonstrated data concerning light‐pigmented melanocytes.
Dynamic graph-based multi-cell scheduling for femtocell networks

This paper proposes a dynamic semi-centralized resource partitioning algorithm to mitigate the problem of co-tier interference in dense femtocell deployments. This algorithm incorporates graph-colouring and network utility concepts to address inter-cell interference in femtocell networks. The aforementioned scheme acts as a multi-cell coordination mechanism on top of intra-cell scheduling by applying a low complexity graph-based algorithm. The objective of the coordination mechanism is the efficient management of resource conflicts due to interference in a multi-cell environment consisting of femtocells. This coordination mechanism defines a novel category of graph-based ICIC algorithms that uses bipartite graph colouring to avoid resource conflicts by randomizing them in time domain.
Hyperspectral and LiDAR Fusion Using Deep Three-Stream Convolutional Neural Networks

Recently, convolutional neural networks (CNN) have been intensively investigated for the classification of remote sensing data by extracting invariant and abstract features suitable for classification. In this paper, a novel framework is proposed for the fusion of hyperspectral images and LiDAR-derived elevation data based on CNN and composite kernels. First, extinction profiles are applied to both data sources in order to extract spatial and elevation features from hyperspectral and LiDAR-derived data, respectively. Second, a three-stream CNN is designed to extract informative spectral, spatial, and elevation features individually from both available sources. The combination of extinction profiles and CNN features enables us to jointly benefit from low-level and high-level features to improve classification performance. To fuse the heterogeneous spectral, spatial, and elevation features extracted by CNN, instead of a simple stacking strategy, a multi-sensor composite kernels (MCK) scheme is designed. This scheme helps us to achieve higher spectral, spatial, and elevation separability of the extracted features and effectively perform multi-sensor data fusion in kernel space. In this context, a support vector machine and extreme learning machine with their composite kernels version are employed to produce the final classification result. The proposed framework is carried out on two widely used data sets with different characteristics: an urban data set captured over Houston, USA, and a rural data set captured over Trento, Italy. The proposed framework yields the highest OA of 92 . 57 % and 97 . 91 % for Houston and Trento data sets. Experimental results confirm that the proposed fusion framework can produce competitive results in both urban and rural areas in terms of classification accuracy, and significantly mitigate the salt and pepper noise in classification maps.
Learning Representations of Natural Language Texts with Generative Adversarial Networks at Document, Sentence, and Aspect Level

The ability to learn robust, resizable feature representations from unlabeled data has potential applications in a wide variety of machine learning tasks. One way to create such representations is to train deep generative models that can learn to capture the complex distribution of real-world data. Generative adversarial network (GAN) approaches have shown impressive results in producing generative models of images, but relatively little work has been done on evaluating the performance of these methods for the learning representation of natural language, both in supervised and unsupervised settings at the document, sentence, and aspect level. Extensive research validation experiments were performed by leveraging the 20 Newsgroups corpus, the Movie Review (MR) Dataset, and the Finegrained Sentiment Dataset (FSD). Our experimental analysis suggests that GANs can successfully learn representations of natural language texts at all three aforementioned levels.
MASP-1 and MASP-2 Serum Levels Are Associated With Worse Prognostic in Cervical Cancer Progression

Background: MBL-associated serine proteases (MASP-1, MASP-2, MASP-3, MAp-44, and MAp-19) are key factors in the activation of the lectin pathway of complement. Serum levels of these components have been associated with recurrence and poor survival of some types of cancer, such as colorectal and ovarian cancer. In this investigation, we determined the serum levels of MASP-1, MASP-2, MASP-3, MAp-44, and MAp-19 in patients with cervical cancer and cervical intraepithelial neoplasia (CIN). Methods:A total of 351 women who underwent screening for cervical cancer or treatment at the Erasto Gaertner Cancer Hospital in Curitiba-Brazil, were enrolled in the study. Based on their latest cervical colposcopy-guided biopsy results, they were divided into four groups: CIN-I: n = 52; CIN-II: n = 73; CIN-III: n = 141; and invasive cancer: n = 78. All the serum protein levels were determined by time-resolved immunofluorometric assay (TRIFMA). Results:Patients with invasive cancer presented significantly higher MASP-2, MASP-1, and MAp-19 serum levels than other groups (p < 0.0001; p = 0.012; p = 0.025 respectively). No statistically significant differences in MASP-3 and MAp-44 serum levels were found between the four studied groups. In addition, high MASP-2, MASP-1, and MAp-19 serum levels were significantly associated with poor survival in patients with invasive cancer and relapse (p = 0.002, p = 0.0035 and p = 0.025, respectively). Conclusion:High MASP-2, MASP-1, and MAp-19 serum levels were associated with cervical cancer progression and worse disease prognosis. These novel findings demonstrate the involvement of the serine proteases of the lectin pathway in the pathogenesis of cervical cancer and future investigations should clarify their role in the disease process.
Drug Use-Related Normative Misperceptions and Behaviors Among Persons Seeking Heroin Withdrawal Management.

OBJECTIVE Normative perceptions about substance use are well-established predictors of substance use risk behaviors, yet no research to date has examined how people who use heroin perceive the drug use behaviors and their association with personal behaviors. In a sample of persons seeking heroin withdrawal, we compared normative beliefs (descriptive norms) about others' drug use behaviors, and examined the association between normative beliefs and behaviors. METHOD Participants (n = 241) were patients undergoing short-term inpatient heroin withdrawal management in Massachusetts. t-Tests were used to compare participants' perceptions about various substance use behaviors among both US adults and persons seeking heroin withdrawal at the same site. We also examined associations between participants' normative beliefs and personal substance use behaviors. RESULTS Participants significantly overestimated drug-related risk behaviors of adults nationally; overall, participants estimated that 44.7% had tried heroin, 37.6% had injected drugs in the past year, and 63.2% had smoked marijuana in the past month when actual national rates are 2.0%, 0.3%, and 5.5%, respectively. Participants also held significant misperceptions about contemporaneous patients in the heroin withdrawal program; behaviors about sharing works, diverting buprenorphine or methadone, and exchanging sex for drugs or money were most substantially overestimated. Normative perceptions were associated with a range of personal drug-using behaviors (eg, injection drug use, exchanging sex for drugs or money). CONCLUSIONS Consistent with existing substance use norms research, participants in the current sample tended to overestimate others' engagement in risky substance use, and these normative perceptions were associated with increased personal risk. Leveraging norms in heroin harm reduction interventions may hold substantial promise.
COXPRESdb v7: a gene coexpression database for 11 animal species supported by 23 coexpression platforms for technical evaluation and evolutionary inference

Abstract The advent of RNA-sequencing and microarray technologies has led to rapid growth of transcriptome data generated for a wide range of organisms, under various cellular, organ and individual conditions. Since the number of possible combinations of intercellular and extracellular conditions is almost unlimited, cataloging all transcriptome conditions would be an immeasurable challenge. Gene coexpression refers to the similarity of gene expression patterns under various conditions, such as disease states, tissue types, and developmental stages. Since the quality of gene coexpression data depends on the quality and quantity of transcriptome data, timely usage of the growing data is key to promoting individual research in molecular biology. COXPRESdb (http://coxpresdb.jp) is a database providing coexpression information for 11 animal species. One characteristic feature of COXPRESdb is its ability to compare multiple coexpression data derived from different transcriptomics technologies and different species, which strongly reduces false positive relationships in individual gene coexpression data. Here, we summarized the current version of this database, including 23 coexpression platforms with the highest-level quality till date. Using various functionalities in COXPRESdb, the new coexpression data would support a broader area of research from molecular biology to medical sciences.
Drug delivery to tumours using a novel 5-FU derivative encapsulated into lipid nanocapsules

Abstract In this work, a novel lipophilic 5-fluorouracil (5-FU) derivative was synthesised and encapsulated into lipid nanocapsules (LNC). 5-FU was modified with lauric acid to give a lipophilic mono-lauroyl-derivative (5-FU-C12, MW of about 342 g/mol, yield of reaction 70%). 5-FU-C12 obtained was efficiently encapsulated into LNC (encapsulation efficiency above 90%) without altering the physico-chemical characteristics of LNC. The encapsulation of 5-FU-C12 led to an increased stability of the drug when in contact with plasma being the drug detectable until 3 h following incubation. Cytotoxicity assay carried out using MTS on 2D cell culture showed that 5-FU-C12-loaded LNC had an enhanced cytotoxic effect on glioma (9L) and human colorectal (HTC-116) cancer cell line in comparison with 5-FU or 5-FU-C12. Then, HCT-116 tumour spheroids were cultivated and the reduction of spheroid volume was measured following treatment with drug-loaded LNC and drugs alone. Similar reduction on spheroids volume was observed following the treatment with drug-loaded LNC, 5-FU-C12 and 5-FU alone, while blank LNC displayed a reduction in cell viability only at high concentration. Globally, our data suggest that the encapsulation increased the activity of the 5-FU-C12. However, in-depth evaluations of LNC permeability into spheroids are needed to disclose the potential of these nanosystems for cancer treatment.
Low glycaemic index diets as an intervention for obesity: a systematic review and meta‐analysis

Low glycaemic index (GI) diets may aid in weight loss by reducing postprandial blood glucose excursions, leading to more stable blood glucose concentrations and therefore a reduction in hunger. To test this hypothesis, we conducted a systematic review and meta‐analysis of randomized controlled trials comparing low GI diets with other diet types.
Characterization of CRISPR Mutants Targeting Genes Modulating Pectin Degradation in Ripening Tomato1[OPEN]

Comparative analysis of tomato cell wall mutants indicates only pectate lyase has a major impact on fruit softening, but other enzymes play an important role in coordinating cell wall disassembly. Tomato (Solanum lycopersicum) is a globally important crop with an economic value in the tens of billions of dollars, and a significant supplier of essential vitamins, minerals, and phytochemicals in the human diet. Shelf life is a key quality trait related to alterations in cuticle properties and remodeling of the fruit cell walls. Studies with transgenic tomato plants undertaken over the last 20 years have indicated that a range of pectin-degrading enzymes are involved in cell wall remodeling. These studies usually involved silencing of only a single gene and it has proved difficult to compare the effects of silencing these genes across the different experimental systems. Here we report the generation of CRISPR-based mutants in the ripening-related genes encoding the pectin-degrading enzymes pectate lyase (PL), polygalacturonase 2a (PG2a), and β-galactanase (TBG4). Comparison of the physiochemical properties of the fruits from a range of PL, PG2a, and TBG4 CRISPR lines demonstrated that only mutations in PL resulted in firmer fruits, although mutations in PG2a and TBG4 influenced fruit color and weight. Pectin localization, distribution, and solubility in the pericarp cells of the CRISPR mutant fruits were investigated using the monoclonal antibody probes LM19 to deesterified homogalacturonan, INRA-RU1 to rhamnogalacturonan I, LM5 to β-1,4-galactan, and LM6 to arabinan epitopes, respectively. The data indicate that PL, PG2a, and TBG4 act on separate cell wall domains and the importance of cellulose microfibril-associated pectin is reflected in its increased occurrence in the different mutant lines.
Elementary Grade Intervention Approaches to Treat Specific Learning Disabilities, Including Dyslexia.

Purpose The purpose of this narrative review of the literature is to provide a description of intensive interventions for elementary grade students with dyslexia, students with learning disabilities, and students with intensive reading and writing needs. Method First, we provide a brief overview of response to intervention. Second, we explain our theoretical framework for the review. Third, we describe evidence-based interventions, which are divided into predominantly reading or writing interventions. Fourth, we explain data-based individualization for these programs based on a taxonomy of intensity, and we provide an illustrative case study. Conclusion We conclude by describing a set of links to websites and technical assistance resources that may be helpful for speech-language pathologists, teachers, and other interventionists to stay current with this research base and to lead professional learning communities.
Novel exploration of customized 3D printed shoulder prosthesis in revision of total shoulder arthroplasty

Rationale: This paper describes the application of individual customized 3-dimensional (3D) printed macro-porous Ti6Al4 V shoulder prosthesis in the revision of total shoulder arthroplasty (TSA) for the patient with severe bone defects. Patient concerns: A 47-year-old male had been under proximal humeral resection and TSA due to shoulder chondrosarcoma 6 years ago, but a second surgery to insert a new prosthesis was then performed because the prosthesis became loose 2 months ago leaving severe bone defects which conventional prosthesis was not suitable for revision of TSA. American Shoulder and Elbow Surgeons’ Form (ASES), Neer and Constant-Murley score were 36, 39, and 39, respectively. Diagnoses: The patient was diagnosed with shoulder bone defects and restriction of the shoulder movement. Interventions: 3D printed shoulder model and computer-aided design (CAD) were used for prosthesis design and surgical simulation. The novel 3D printed titanium alloy shoulder prosthesis was customized subsequently to be used in the revision of TSA. The patient was followed up regularly after surgery. The ASES, Neer Shoulder score and Constant-Murley Shoulder score were evaluated during pre-operation, post-operation, and follow-up. Outcomes: Prosthesis was successfully implanted to complete anatomic reconstruction intraoperatively. The scores of ASES, Neer, and Constant-Murley were gradually increased after the operation. According to the X-ray, the bone healed satisfactorily without change of prosthetic position at 3rd and 12th months after the operation. The function of shoulder could meet the requirements of daily activities. Lessons: The application of customized 3D printed titanium alloy shoulder prosthesis in the revision of TSA achieves satisfactory results. It provides a novel method for the similar revision surgery with severe bone defects.