Miracle-dz/UniFAR-FTUs huggingface dataset:
Detecting and Characterizing A-To-I microRNA Editing in Cancer

Simple Summary Adenosine to inosine (A-to-I) editing is a type of RNA editing where individual adenosines are enzymatically converted into inosines. A-to-I RNA editing plays an important role in cancer biology. Several studies have demonstrated that A-to-I editing of microRNAs (miRNAs) very often affect miRNA function as oncosuppressors or oncogenes, hence showing clinical relevance. Hence, A-to-I miRNA editing has been suggested as a potential diagnostic and prognostic tool in the monitoring of cancer patients. Nevertheless, the process of identifying and characterizing miRNA editing events in tumor samples still presents several challenges. In this review, we outline molecular aspects linked to miRNA A-to-I editing and retrace methods and approaches dedicated to detection of editing sites and functional characterization of edited miRNAs in cancer. Abstract Adenosine to inosine (A-to-I) editing consists of an RNA modification where single adenosines along the RNA sequence are converted into inosines. Such a biochemical transformation is catalyzed by enzymes belonging to the family of adenosine deaminases acting on RNA (ADARs) and occurs either co- or post-transcriptionally. The employment of powerful, high-throughput detection methods has recently revealed that A-to-I editing widely occurs in non-coding RNAs, including microRNAs (miRNAs). MiRNAs are a class of small regulatory non-coding RNAs (ncRNAs) acting as translation inhibitors, known to exert relevant roles in controlling cell cycle, proliferation, and cancer development. Indeed, a growing number of recent researches have evidenced the importance of miRNA editing in cancer biology by exploiting various detection and validation methods. Herein, we briefly overview early and currently available A-to-I miRNA editing detection and validation methods and discuss the significance of A-to-I miRNA editing in human cancer.
Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

Simple Summary This review provides a critical overview of the state of the art of the characterization of the immunological profile of a rare component of the tumors, denominated cancer stem cells (CSCs) or cancer initiating cells (CICs). These cells are endowed with the ability to form and propagate tumors and resistance to therapies, including the most innovative approaches. These investigations contribute to understanding the mechanisms regulating the interaction of CSCs/CICs with the immune system and identifying novel therapeutic approaches to render these cells visible and susceptible to immune responses. Abstract Cancer cells endowed with stemness properties and representing a rare population of cells within malignant lesions have been isolated from tumors with different histological origins. These cells, denominated as cancer stem cells (CSCs) or cancer initiating cells (CICs), are responsible for tumor initiation, progression and resistance to therapies, including immunotherapy. The dynamic crosstalk of CSCs/CICs with the tumor microenvironment orchestrates their fate and plasticity as well as their immunogenicity. CSCs/CICs, as observed in multiple studies, display either the aberrant expression of immunomodulatory molecules or suboptimal levels of molecules involved in antigen processing and presentation, leading to immune evasion. MicroRNAs (miRNAs) that can regulate either stemness properties or their immunological profile, with in some cases dual functions, can provide insights into these mechanisms and possible interventions to develop novel therapeutic strategies targeting CSCs/CICs and reverting their immunogenicity. In this review, we provide an overview of the immunoregulatory features of CSCs/CICs including miRNA profiles involved in the regulation of the interplay between stemness and immunological properties.
Radiometric Calibration for a Multispectral Sensor Onboard RISESAT Microsatellite Based on Lunar Observations

Radiometric calibration utilizing the Moon as a reference source is termed as lunar calibration. It is a useful method for evaluating the performance of optical sensors onboard satellites orbiting the Earth. Lunar calibration provides sufficient radiometric calibration opportunities without requiring any special equipment, and is suitable for nano/microsatellites. This study applies lunar calibration to a multispectral sensor, Ocean Observation Camera (OOC), on board a microsatellite named Rapid International Scientific Experiment Satellite. Simulating the brightness of the Moon based on the RObotic Lunar Observatory and SELENE/Spectrum Profiler models, sensitivity degradation was proven to be negligible in any of the four spectral bands of the OOC with the sensor temperature correction. A bluing trend in the OOC’s sensor sensitivity was revealed, indicating a shorter observation wavelength shows larger irradiance. Comparing the top-of-atmosphere reflectance of Railroad Valley Playa with the Radiometric Calibration Network dataset revealed that the derived calibration parameter from the lunar calibration was valid for correcting the bluing trend in the visible range. Although the lunar and vicarious calibration parameters for the infrared band were unexpectedly inconsistent, lunar calibration could potentially contribute toward estimating the contaminated background radiance in the Earth observation images.
Relationship between Orexigenic Peptide Ghrelin Signal, Gender Difference and Disease

Growth hormone secretagogue receptor 1a (GHS-R1a), which is one of the G protein-coupled receptors (GPCRs), is involved in various physiological actions such as energy consumption, growth hormone secretion promoting action, and cardiovascular protective action. The ligand was searched for as an orphan receptor for a while, but the ligand was found to be acylated ghrelin (ghrelin) discovered by Kangawa and Kojima et al. in 1999. Recently, it has also been reported that dysregulation of GHS-R1a mediates reduced feeding in various diseases. On the other hand, since the physiological effects of ghrelin have been studied exclusively in male mice, few studies have been conducted on gender differences in ghrelin reactivity. In this review, we describe (1) the characteristics of GHS-R1a, (2) the role of ghrelin in hypophagia due to stress or anticancer drugs, and (3) the gender differences in the physiological effects of GHS-R1a and the influence of stress on it.
Health-Related Quality of Life among Cancer Survivors Depending on the Occupational Status

The study aimed to identify and compare the factors affecting health-related quality of life (HRQoL) depending on the occupational status of cancer survivors. This study was a secondary data analysis from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2014 to 2018. Hierarchical multivariate linear regression was used to investigate the factors affecting the HRQoL of each group. Non-working cancer survivors had significantly lower HRQoL than working cancer survivors (p < 0.001). A hierarchical multiple regression model showed that demographic, health-related, and psychological characteristics explained 62.0% of non-working cancer survivors’ HRQoL (F = 4.29, p < 0.001). Among the input variables, health-related characteristics were the most influential factors (ΔR2 = 0.274, F = 9.84, p < 0.001). For working cancer survivors, health-related characteristics were the only variable that was statistically associated with HRQoL (F = 5.556, p < 0.001). It is important to enhance physical activities and manage the chronic disease to improve the HRQoL of working cancer survivors. Further, managing health-related characteristics, including depressive symptoms and suicidal ideation, is necessary for non-working cancer survivors. Regarding working survivors, psychological factors such as depressive symptoms and suicidal tendencies did not affect HRQoL. Therefore, an early and effective return to work program should be developed for the improvement of their HRQoL.
The Yin and Yang of Discoidin Domain Receptors (DDRs): Implications in Tumor Growth and Metastasis Development

Simple Summary The tumor microenvironment plays an important role in tumor development and metastasis. Collagens are major components of the extracellular matrix and can influence tumor development and metastasis by activating discoidin domain receptors (DDRs). This work shows the different roles of DDRs in various cancers and highlights the complexity of anti-DDR therapies in cancer treatment. Abstract The tumor microenvironment is a complex structure composed of the extracellular matrix (ECM) and nontumoral cells (notably cancer-associated fibroblasts (CAFs) and immune cells). Collagens are the main components of the ECM and they are extensively remodeled during tumor progression. Some collagens are ligands for the discoidin domain receptor tyrosine kinases, DDR1 and DDR2. DDRs are involved in different stages of tumor development and metastasis formation. In this review, we present the different roles of DDRs in these processes and discuss controversial findings. We conclude by describing emerging DDR inhibitory strategies, which could be used as new alternatives for the treatment of patients.
Virtual Reality in Neurorehabilitation: An Umbrella Review of Meta-Analyses

Neurological disorders are a leading cause of death and disability worldwide. Can virtual reality (VR) based intervention, a novel technology-driven change of paradigm in rehabilitation, reduce impairments, activity limitations, and participation restrictions? This question is directly addressed here for the first time using an umbrella review that assessed the effectiveness and quality of evidence of VR interventions in the physical and cognitive rehabilitation of patients with stroke, traumatic brain injury and cerebral palsy, identified factors that can enhance rehabilitation outcomes and addressed safety concerns. Forty-one meta-analyses were included. The data synthesis found mostly low- or very low-quality evidence that supports the effectiveness of VR interventions. Only a limited number of comparisons were rated as having moderate and high quality of evidence, but overall, results highlight potential benefits of VR for improving the ambulation function of children with cerebral palsy, mobility, balance, upper limb function, and body structure/function and activity of people with stroke, and upper limb function of people with acquired brain injury. Customization of VR systems is one important factor linked with improved outcomes. Most studies do not address safety concerns, as only nine reviews reported adverse effects. The results provide critical recommendations for the design and implementation of future VR programs, trials and systematic reviews, including the need for high quality randomized controlled trials to test principles and mechanisms, in primary studies and in meta-analyses, in order to formulate evidence-based guidelines for designing VR-based rehabilitation interventions.
Predictive Factors for RAI-Refractory Disease and Short Overall Survival in PDTC

Simple Summary Poorly differentiated thyroid cancer is a rare subtype of thyroid cancer. The course of this disease can vary substantially. Treatment options consist of surgery and radioactive iodine therapy, if possible, and in tyrosine kinase inhibitors for patients where this is not possible. The aim of this study was to identify risk factors for the development of disease that does not respond to radioactive iodine therapy and for premature death, in order to better identify patients in need of more extensive tumor staging and treatment. We identified primary tumor size and infiltration of the tissue surrounding the thyroid gland as risk factors for the development of disease that does not respond to radioactive iodine therapy and tumor volume as a risk factor for early death. Abstract Background: The clinical phenotype of poorly differentiated thyroid cancer (PDTC) can vary substantially. We aim to evaluate risk factors for radioiodine refractory (RAI-R) disease and reduced overall survival (OS). Methods: We retrospectively screened our institutional database for PDTC patients. For the assessment of RAI-R disease, we included patients who underwent dual imaging with 18F-FDG-PET and 124I-PET/131I scintigraphy that met the internal standard of care. We tested primary size, extrathyroidal extension (ETE), and age >55 years as risk factors for RAI-R disease at initial diagnosis and during the disease course using uni- and multivariate analyses. We tested metabolic tumor volume (MTV), total lesion glycolysis (TLG) on 18F-FDG-PET, and the progression of stimulated thyroglobulin within 4–6 months of initial radioiodine therapy as prognostic markers for OS. Results: Size of primary >40 mm and ETE were significant predictors of RAI-R disease in the course of disease in univariate (81% vs. 27%, p = 0.001; 89% vs. 33%, p < 0.001) and multivariate analyses. Primary tumor size was an excellent predictor of RAI-R disease (AUC = 0.90). TLG/MTV > upper quartile and early thyroglobulin progression were significantly associated with shorter median OS (29.0 months vs. 56.9 months, p < 0.05; 57.8 months vs. not reached p < 0.005, respectively). Discussion: PDTC patients, especially those with additional risk factors, should be assessed for RAI-R disease at initial diagnosis and in the course of disease, allowing for early implementation of multimodal treatment. Primary tumor size >40 mm, ETE, and age >55 are significant risk factors for RAI-R disease. High MTV/TLG is a significant risk factor for premature death and can help identify patients requiring intervention.
Acute Moderate Hypoxia Reduces One-Legged Cycling Performance Despite Compensatory Increase in Peak Cardiac Output: A Pilot Study

In severe hypoxia, single-leg peak oxygen uptake (VO2peak) is reduced mainly due to the inability to increase cardiac output (CO). Whether moderate altitude allows CO to increase during single-leg cycling, thereby restoring VO2peak, has not been extensively investigated. Five healthy subjects performed an incremental, maximal, two-legged cycle ergometer test, and on separate days a maximal incremental one-leg cycling test in normoxia and in moderate hypoxia (fraction of inspired oxygen (FiO2) = 15%). Oxygen uptake, heart rate, blood pressure responses, power output, and CO (PhysioFlow) were measured during all tests. Moderate hypoxia lowered single-leg peak power output (154 ± 31 vs. 128 ± 26 watts, p = 0.03) and oxygen uptake (VO2) (36.8 ± 6.6 vs. 33.9 ± 6.9 mL/min/kg, p = 0.04), despite higher peak CO (16.83 ± 3.10 vs. 18.96 ± 3.59 L/min, p = 0.04) and systemic oxygen (O2) delivery (3.37 ± 0.84 vs. 3.47 ± 0.89 L/min, p = 0.04) in hypoxia compared to normoxia. Arterial–venous O2 difference (a–vDO2) was lower in hypoxia (137 ± 21 vs. 112 ± 19 mL/l, p = 0.03). The increases in peak CO from normoxia to hypoxia were negatively correlated with changes in mean arterial pressure (MABP) (p < 0.05). These preliminary data indicate that the rise in CO was not sufficient to prevent single-leg performance loss at moderate altitude and that enhanced baroreceptor activity might limit CO increases in acute hypoxia, likely by reducing sympathetic activation. Since the systemic O2 delivery was enhanced and the calculated a–vDO2 reduced in moderate hypoxia, a potential diffusion limitation cannot be excluded.
Reduced Claudin-12 Expression Predicts Poor Prognosis in Cervical Cancer

Background: Within the claudin (CLDN) family, CLDN12 mRNA expression is altered in various types of cancer, but its clinicopathological relevance has yet to be established due to the absence of specific antibodies (Abs) with broad applications. Methods: We generated a monoclonal Ab (mAb) against human/mouse CLDN12 and verified its specificity. By performing immunohistochemical staining and semiquantification, we evaluated the relationship between CLDN12 expression and clinicopathological parameters in tissues from 138 cases of cervical cancer. Results: Western blot and immunohistochemical analyses revealed that the established mAb selectively recognized the CLDN12 protein. Twenty six of the 138 cases (18.8%) showed low CLDN12 expression, and the disease-specific survival (DSS) and recurrence-free survival rates were significantly decreased compared with those in the high CLDN12 expression group. We also demonstrated, via univariable and multivariable analyses, that the low CLDN12 expression represents a significant prognostic factor for the DSS of cervical cancer patients (HR 3.412, p = 0.002 and HR 2.615, p = 0.029, respectively). Conclusions: It can be concluded that a reduced CLDN12 expression predicts a poor outcome for cervical cancer. The novel anti-CLDN12 mAb could be a valuable tool to evaluate the biological relevance of the CLDN12 expression in diverse cancer types and other diseases.
The Role of Parent/Caregiver with Children Affected by Rare Diseases: Navigating between Love and Fear

In this paper, we propose a vision of the role of parent/caregiver with children affected by a rare disease. This vision is rooted in data obtained from our own research; however, our analysis and interpretation of this data have been subsequently checked against existing theoretical models. The research aims to explore how parents who look after children with a rare disease experience their role as caregivers and how they assimilate their role identity in this task. Semi-structured interviews were performed with parents of 10 children, and a qualitative data analysis was conducted using grounded theory. We have identified ten main categories using a grounded theory approach: stress, disorientation, insecurity, isolation, faith, trust, attention, communication with professionals, private proactivity and public proactivity. Our results also show that when parents perceive a greater burden due to looking after a child with a rare disease, the result is a change in the usual parental role. In our contribution, we offer a general outline of how parents build a role identity centred on caring for a child with a rare disease. We posit that this role identity is the outcome of the parents’ success or failure in gradually overcoming fear through love. We have conceptualized this process as navigating between love and fear.
Involvement of Neuropeptide Galanin Receptors 2 and 3 in Learning, Memory and Anxiety in Aging Mice

The neuropeptide galanin (GAL), which is expressed in limbic brain structures, has a strong impact on the regulation of mood and behavior. GAL exerts its effects via three G protein-coupled receptors (GAL1–3-R). Little is known about the effects of aging and loss of GAL-Rs on hippocampal-mediated processes connected to neurogenesis, such as learning, memory recall and anxiety, and cell proliferation and survival in the dorsal dentate gyrus (dDG) in mice. Our results demonstrate that loss of GAL3-R, but not GAL2-R, slowed learning and induced anxiety in older (12–14-month-old) mice. Lack of GAL2-R increased cell survival (BrdU incorporation) in the dDG of young mice. However, normal neurogenesis was observed in vitro using neural stem and precursor cells obtained from GAL2-R and GAL3-R knockouts upon GAL treatment. Interestingly, we found sub-strain differences between C57BL/6J and C57BL/6N mice, the latter showing faster learning, less anxiety and lower cell survival in the dDG. We conclude that GAL-R signaling is involved in cognitive functions and can modulate the survival of cells in the neurogenic niche, which might lead to new therapeutic applications. Furthermore, we observed that the mouse sub-strain had a profound impact on the behavioral parameters analyzed and should therefore be carefully considered in future studies.
MRI-Based Radiomics and Radiogenomics in the Management of Low-Grade Gliomas: Evaluating the Evidence for a Paradigm Shift

Low-grade gliomas (LGGs) are tumors that affect mostly adults. These neoplasms are comprised mainly of oligodendrogliomas and diffuse astrocytomas. LGGs remain vexing to current management and therapeutic modalities although they exhibit more favorable survival rates compared with high-grade gliomas (HGGs). The specific genetic subtypes that these tumors exhibit result in variable clinical courses and the need to involve multidisciplinary teams of neurologists, epileptologists, neurooncologists and neurosurgeons. Currently, the diagnosis of an LGG pivots mainly around the preliminary radiological findings and the subsequent definitive surgical diagnosis (via surgical sampling). The introduction of radiomics as a high throughput quantitative imaging technique that allows for improved diagnostic, prognostic and predictive indices has created more interest for such techniques in cancer research and especially in neurooncology (MRI-based classification of LGGs, predicting Isocitrate dehydrogenase (IDH) and Telomerase reverse transcriptase (TERT) promoter mutations and predicting LGG associated seizures). Radiogenomics refers to the linkage of imaging findings with the tumor/tissue genomics. Numerous applications of radiomics and radiogenomics have been described in the clinical context and management of LGGs. In this review, we describe the recently published studies discussing the potential application of radiomics and radiogenomics in LGGs. We also highlight the potential pitfalls of the above-mentioned high throughput computerized techniques and, most excitingly, explore the use of machine learning artificial intelligence technologies as standalone and adjunct imaging tools en route to enhance a personalized MRI-based tumor diagnosis and management plan design.
Synergizing Off-Target Predictions for In Silico Insights of CENH3 Knockout in Cannabis through CRISPR/Cas

The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-mediated genome editing system has recently been used for haploid production in plants. Haploid induction using the CRISPR/Cas system represents an attractive approach in cannabis, an economically important industrial, recreational, and medicinal plant. However, the CRISPR system requires the design of precise (on-target) single-guide RNA (sgRNA). Therefore, it is essential to predict off-target activity of the designed sgRNAs to avoid unexpected outcomes. The current study is aimed to assess the predictive ability of three machine learning (ML) algorithms (radial basis function (RBF), support vector machine (SVM), and random forest (RF)) alongside the ensemble-bagging (E-B) strategy by synergizing MIT and cutting frequency determination (CFD) scores to predict sgRNA off-target activity through in silico targeting a histone H3-like centromeric protein, HTR12, in cannabis. The RF algorithm exhibited the highest precision, recall, and F-measure compared to all the tested individual algorithms with values of 0.61, 0.64, and 0.62, respectively. We then used the RF algorithm as a meta-classifier for the E-B method, which led to an increased precision with an F-measure of 0.62 and 0.66, respectively. The E-B algorithm had the highest area under the precision recall curves (AUC-PRC; 0.74) and area under the receiver operating characteristic (ROC) curves (AUC-ROC; 0.71), displaying the success of using E-B as one of the common ensemble strategies. This study constitutes a foundational resource of utilizing ML models to predict gRNA off-target activities in cannabis.