Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of EGFR Mutations in Plasma Cell-Free Tumor DNA of TKI-Treated Advanced-NSCLC Patients by Three Methodologies: Scorpion-ARMS, PNAClamp, and Digital PCR

Analysis of circulating cell-free tumor DNA (cftDNA) has emerged as a specific and sensitive blood-based approach to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients. Still, there is some debate on what should be the preferential clinical method for plasma-derived cftDNA analysis. We tested 31 NSCLC patients treated with anti-EGFR tyrosine kinase inhibitors (TKIs), at baseline and serially during therapy, by comparing three methodologies in detecting EGFR mutations (L858R, exon 19 deletion, and T790M) from plasma: scorpions-amplification refractory mutation system (ARMS) methodology by using EGFR Plasma RGQ PCR Kit-QIAGEN, peptide nucleic acid (PNA) clamp and PANA RealTyper integration by using PNAClamp EGFR-PANAGENE, and digital real time PCR by using QuantStudio 3D Digital PCR System-Thermo Fisher Scientific. Specificity was 100% for all three mutations, independently from the platform used. The sensitivity for L858R (42.86%) and T790M (100%) did not change based on the method, while the sensitivity for Del 19 differed markedly (Scorpion-ARMS 45%, PNAClamp 75%, and Digital PCR 85%). The detection rate was also higher (94.23%) as measured by Digital PCR, and when we monitored the evolution of EGFR mutations over time, it evidenced the extreme inter-patient heterogeneity in terms of levels of circulating mutated copies. In our study, Digital PCR showed the best correlation with tissue biopsy and the highest sensitivity to attain the potential clinical utility of monitoring plasma levels of EGFR mutations.
NEK1 Phosphorylation of YAP Promotes Its Stabilization and Transcriptional Output

Simple Summary We earlier described the involvement of the TLK1>NEK1>ATR>Chk1 axis as a key determinant of cell cycle arrest in androgen-dependent prostate cancer (PCa) cells after androgen deprivation. We now report that the TLK1>NEK1 axis is also involved in stabilization of yes-associated protein 1 (YAP1), the transcriptional co-activator in the Hippo pathway, presumably facilitating reprogramming of the cells toward castration-resistant PCa (CRPC). NEK1 interacts with YAP1 physically resulting in its phosphorylation of 6 residues, which enhance its stability and activity. Analyses of cancer Protein Atlas and TCGA expression panels revealed a link between activated NEK1 and YAP1 expression and several YAP transcription targets. Abstract Most prostate cancer (PCa) deaths result from progressive failure in standard androgen deprivation therapy (ADT), leading to metastatic castration-resistant PCa (mCRPC); however, the mechanism and key players leading to this are not fully understood. While studying the role of tousled-like kinase 1 (TLK1) and never in mitosis gene A (NIMA)-related kinase 1 (NEK1) in a DNA damage response (DDR)-mediated cell cycle arrest in LNCaP cells treated with bicalutamide, we uncovered that overexpression of wt-NEK1 resulted in a rapid conversion to androgen-independent (AI) growth, analogous to what has been observed when YAP1 is overexpressed. We now report that overexpression of wt-NEK1 results in accumulation of YAP1, suggesting the existence of a TLK1>NEK1>YAP1 axis that leads to adaptation to AI growth. Further, YAP1 is co-immunoprecipitated with NEK1. Importantly, NEK1 was able to phosphorylate YAP1 on six residues in vitro, which we believe are important for stabilization of the protein, possibly by increasing its interaction with transcriptional partners. In fact, knockout (KO) of NEK1 in NT1 PCa cells resulted in a parallel decrease of YAP1 level and reduced expression of typical YAP-regulated target genes. In terms of cancer potential implications, the expression of NEK1 and YAP1 proteins was found to be increased and correlated in several cancers. These include PCa stages according to Gleason score, head and neck squamous cell carcinoma, and glioblastoma, suggesting that this co-regulation is imparted by increased YAP1 stability when NEK1 is overexpressed or activated by TLK1, and not through transcriptional co-expression. We propose that the TLK1>NEK1>YAP1 axis is a key determinant for cancer progression, particularly during the process of androgen-sensitive to -independent conversion during progression to mCRPC.
Chlorella vulgaris Ameliorates Oxidative Stress and Improves the Muscle Regenerative Capacity of Young and Old Sprague-Dawley Rats

Muscle atrophy in ageing is a multifactorial degenerative process impacted by cellular ageing biology, which includes oxidative stress. Chlorella vulgaris is a coccoid green eukaryotic microalga rich in antioxidants. The aim of this study was to determine the effect of C. vulgaris in ameliorating oxidative stress, thus elucidating its mechanism in improving muscle mass, strength and function in young and old rats. Fifty-six male Sprague-Dawley (SD) rats aged 3 months (young) and 21 months (old) were divided into three groups: Group 1 (control) was given distilled water; Group 2 was treated with 150 mg/kg body weight (BW) of C. vulgaris; and Group 3 was treated with 300 mg/kg BW of C. vulgaris for three months. Grip and muscle strength and muscle integrity were determined on days 0, 30, 60, and 90 of treatment. Urine and blood were collected on days 0 and 90 of treatment for oxidative stress marker determination, while the gastrocnemius muscles were collected for muscle oxidative stress analysis. Increased grip strength of the front and hind paws was observed in young C. vulgaris-treated rats on days 30, 60, and 90 compared to the untreated control on the same days (p < 0.05). There was a significant increase in lean bone mineral content (BMC) in young rats treated with 300 mg/kg BW C. vulgaris compared to untreated rats on days 30 and 60. The fat mass was significantly decreased in young and old C. vulgaris-treated rats on day 90 compared to the untreated control. The total path was significantly increased for old rats treated with 300 mg/kg BW C. vulgaris on days 60 and 90 compared to day 0. Young and old C. vulgaris-treated rats demonstrated a significant decrease in urinary isoprostane F2t and plasma creatine kinase-MM (CKMM) compared to the control on day 90. A significant decrease in malondialdehyde (MDA) and 4-hydroxyalkenal (HAE) levels were observed in young and old rats treated with C. vulgaris. C. vulgaris improved the muscle mass, strength, and function in young and old rats. This effect could be due to its potency in ameliorating oxidative stress in the skeletal muscle of young and old rats.
Elucidating mechanisms of quality‐of‐life disparities in Hispanic women with breast cancer: An examination of disease stage, coping, and affect

Compared to non‐Hispanic white (NHW) women, Hispanic women with breast cancer (BCa) are more likely to be diagnosed at later stages of disease and experience reduced quality of life (QOL) following diagnosis. We hypothesized that the demands of later‐stage disease results in a perceived inability to cope and greater distress for Hispanic women, resulting in decreased QOL.
Derivation and investigation of the first human cell-based model of Beckwith-Wiedemann syndrome

ABSTRACT Genomic imprinting is a rare form of gene expression in mammals in which a small number of genes are expressed in a parent-of-origin-specific manner. The aetiology of human imprinting disorders is diverse and includes chromosomal abnormalities, mutations, and epigenetic dysregulation of imprinted genes. The most common human imprinting disorder is Beckwith-Wiedemann syndrome (BWS), frequently caused by uniparental isodisomy and DNA methylation alterations. Because these lesions cannot be easily engineered, induced pluripotent stem cells (iPSC) are a compelling alternative. Here, we describe the first iPSC model derived from patients with BWS. Due to the mosaic nature of BWS patients, both BWS and non-BWS iPSC lines were derived from the same patient’s fibroblasts. Importantly, we determine that DNA methylation and gene expression patterns of the imprinted region in the iPSC lines reflect the parental cells and are stable over time. Additionally, we demonstrate that differential expression in insulin signalling, cell proliferation, and cell cycle pathways was seen in hepatocyte lineages derived from BWS lines compared to controls. Thus, this cell based-model can be used to investigate the role of imprinting in the pathogenesis of BWS in disease-relevant cell types.
Shared Decision Making Enhances Pneumococcal Vaccination Rates in Adult Patients in Outpatient Care

Insufficient vaccination rates against pneumococcal disease are a major problem in primary health care, especially in adult patients. Shared decision-making (SDM) may address major barriers to vaccination. The objective of this review was to assess the impact of SDM on pneumococcal vaccination rates in adult patients. We conducted a systematic literature search in MEDLINE, EMBASE, CENTRAL, PsycINFO, and ERIC. RCTs and cluster RCTs were included, if they aimed to enhance pneumococcal vaccination rates in adult patients and comprised a personal interaction between health care provider (HCP) and patient. Three further aspects of the SDM process (patient activation, bi-directional exchange of information and bi-directional deliberation) were assessed. A meta-analysis was conducted for the effects of interventions on vaccination rates. We identified eight studies meeting the inclusion criteria. The pooled effect size was OR (95% CI): 2.26 (1.60–3.18) comparing intervention and control groups. Our findings demonstrate the efficacy of interventions that enable a SDM process to enhance pneumococcal vaccination rates; although, the quality of evidence was low. In exploratory subgroup analyses, we concluded that an impersonal patient activation and an exchange of information facilitated by nurses are sufficient to increase vaccination rates against pneumococcal disease in adult patients. However, the deliberation of options between physicians and patients seemed to be more effective than deliberation of options between nurses and patients.
Risk Factors That Most Accurately Predict Coronary Artery Disease Based on the Duration of Follow-up　- NIPPON DATA80.

BACKGROUND This study assessed sex-specific time-associated changes in the impact of risk factors on coronary artery disease (CAD) mortality in a general population over long-term follow-up.Methods and Results:A prospective longitudinal cohort study was conducted on representative Japanese populations followed up for 29 years. Data from 8,396 participants (3,745 men, 4,651 women) were analyzed. The sex-specific multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of 4 risk factors (smoking, diabetes, serum total cholesterol [TC], and systolic blood pressure [SBP]) for CAD mortality were calculated at baseline and at 10, 15, 20, 25, and 29 years of follow-up. In men, smoking (HR 3.23; 95% CI 1.16-9.02) and a 1-SD increase in TC (HR 1.82; 95% CI 1.29-2.57) were strongly associated with a higher risk of CAD in the first 10 years, but this association decreased over time. Diabetes (HR 2.30; 95% CI 1.37-3.85) and a 1-SD increase in SBP (HR 1.23; 95% CI 1.00-1.50) were strongly correlated with a higher risk of CAD after 29 years). In women, diabetes was correlated with CAD after 20 years (HR 2.53; 95% CI 1.19-5.36) and this correlation persisted until after 29 years (HR 2.47; 95% CI 1.40-4.35). CONCLUSIONS The duration of follow-up needed for the accurate assessment of risk factors for CAD mortality varies according to risk factor and sex.
Carbon Dots as Sensing Layer for Printed Humidity and Temperature Sensors

This work presents an innovative application of carbon dots (Cdots) nanoparticles as sensing layer for relative humidity detection. The developed sensor is based on interdigitated capacitive electrodes screen printed on a flexible transparent polyethylene terephthalate (PET) film. Cdots are deposited on top of these electrodes. An exhaustive characterization of the nanoparticles has been conducted along with the fabrication of the sensor structure. The accompanied experiments give all the sensibility to the Cdots, showing its dependence with temperature and exciting frequency. To the best of our knowledge, this work paves the path to the use of these kind of nanoparticles in printed flexible capacitive sensors aimed to be employed in the continuously expanding Internet of Things ecosystem.
Transfer Learning for Wireless Fingerprinting Localization Based on Optimal Transport

Wireless fingerprinting localization (FL) systems identify locations by building radio fingerprint maps, aiming to provide satisfactory location solutions for the complex environment. However, the radio map is easy to change, and the cost of building a new one is high. One research focus is to transfer knowledge from the old radio maps to a new one. Feature-based transfer learning methods help by mapping the source fingerprint and the target fingerprint to a common hidden domain, then minimize the maximum mean difference (MMD) distance between the empirical distributions in the latent domain. In this paper, the optimal transport (OT)-based transfer learning is adopted to directly map the fingerprint from the source domain to the target domain by minimizing the Wasserstein distance so that the data distribution of the two domains can be better matched and the positioning performance in the target domain is improved. Two channel-models are used to simulate the transfer scenarios, and the public measured data test further verifies that the transfer learning based on OT has better accuracy and performance when the radio map changes in FL, indicating the importance of the method in this field.
Room-Temperature Sodium–Sulfur Batteries with Liquid-Phase Sodium Polysulfide Catholytes and Binder-Free Multiwall Carbon Nanotube Fabric Electrodes

Charge/discharge of a room-temperature sodium–sulfur (Na–S) battery involves redox processes of a series of long-chain soluble sodium polysulfides (Na2Sn, 4 ≤ n ≤ 8). By taking advantage of this, a room-temperature Na–S battery is developed with dissolved sodium polysulfide catholyte and a free-standing, binder-free multiwall carbon nanotube (MWCNT) fabric electrode. Use of liquid-phase sodium polysulfide as a cathode not only provides a facile dispersion and homogeneous distribution of the sulfur active material into the conductive matrix but also supplies a unique approach to mechanistically understand the ambient-temperature Na–S battery system. With the intermediate products (polysulfides) as the starting cathode, the electrochemical characteristics of the Na–S battery in the lower-voltage-plateau region can be readily studied without the impact from the transformation process of elemental sulfur into long-chain sodium polysulfides. The nanostructured, free-standing MWCNT fabric electrode in this batt.
Pharmacophore Modeling and 3D-QSAR Study of Indole and Isatin Derivatives as Antiamyloidogenic Agents Targeting Alzheimer’s Disease †

Thirty-six novel indole-containing compounds, mainly 3-(2-phenylhydrazono) isatins and structurally related 1H-indole-3-carbaldehyde derivatives, were synthesized and assayed as inhibitors of beta amyloid (Aβ) aggregation, a hallmark of pathophysiology of Alzheimer’s disease. The newly synthesized molecules spanned their IC50 values from sub- to two-digit micromolar range, bearing further information into structure-activity relationships. Some of the new compounds showed interesting multitarget activity, by inhibiting monoamine oxidases A and B. A cell-based assay in tau overexpressing bacterial cells disclosed a promising additional activity of some derivatives against tau aggregation. The accumulated data of either about ninety published and thirty-six newly synthesized molecules were used to generate a pharmacophore hypothesis of antiamyloidogenic activity exerted in a wide range of potencies, satisfactorily discriminating the ‘active’ compounds from the ‘inactive’ (poorly active) ones. An atom-based 3D-QSAR model was also derived for about 80% of ‘active’ compounds, i.e., those achieving finite IC50 values lower than 100 μM. The 3D-QSAR model (encompassing 4 PLS factors), featuring acceptable predictive statistics either in the training set (n = 45, q2 = 0.596) and in the external test set (n = 14, r2ext = 0.695), usefully complemented the pharmacophore model by identifying the physicochemical features mainly correlated with the Aβ anti-aggregating potency of the indole and isatin derivatives studied herein.
Functional biases in attentional templates from associative memory

In everyday life, attentional templates—which facilitate the perception of task-relevant sensory inputs—are often based on associations in long-term memory. We ask whether templates retrieved from memory are necessarily faithful reproductions of the encoded information or if associative-memory templates can be functionally adapted after retrieval in service of current task demands. Participants learned associations between four shapes and four colored gratings, each with a characteristic combination of color (green or pink) and orientation (left or right tilt). On each trial, observers saw one shape followed by a grating and indicated whether the pair matched the learned shape-grating association. Across experimental blocks, we manipulated the types of nonmatch (lure) gratings most often presented. In some blocks the lures were most likely to differ in color but not tilt, whereas in other blocks this was reversed. If participants functionally adapt the retrieved template such that the distinguishing information between lures and targets is prioritized, then they should overemphasize the most commonly diagnostic feature dimension within the template. We found evidence for this in the behavioral responses to the lures: participants were more accurate and faster when responding to common versus rare lures, as predicted by the functional—but not the strictly veridical—template hypothesis. This shows that templates retrieved from memory can be functionally biased to optimize task performance in a flexible, context-dependent, manner.
Predictors of Stroke Outcome Extracted from Multivariate Linear Discriminant Analysis or Neural Network Analysis

Aim: The prediction of functional outcome is essential in the management of acute ischemic stroke patients. We aimed to explore the various prognostic factors with multivariate linear discriminant analysis or neural network analysis and evaluate the associations between candidate factors, baseline characteristics, and outcome. Methods: Acute ischemic stroke patients ( n =1,916) with premorbid modified Rankin Scale (mRS) scores of 0–2 were analyzed. The prediction models with multivariate linear discriminant analysis (quantification theory type II) and neural network analysis (log-linearized Gaussian mixture network) were used to predict poor functional outcome (mRS 3–6 at 3 months) with various prognostic factors added to age, sex, and initial neurological severity at admission. Results: Both models revealed that several nutritional statuses and serum alkaline phosphatase (ALP) levels at admission improved the predictive ability. Of the 1,484 patients without missing data, 560 patients (37.7%) had poor outcomes. The patients with poor outcomes had higher ALP levels than those without (294.3±259.5 vs. 246.3±92.5 U/l, P ＜0.001). Multivariable logistic analyses revealed that higher ALP levels (1-SD increase) were independently associated with poor stroke outcomes after adjusting for several confounding factors, including the neurological severity, malnutrition status, and inflammation (odds ratio 1.21, 95% confidence interval 1.02–1.49). Several nutritional indicators extracted from prediction models were also associated with poor outcome. Conclusion: Both the multivariate linear discriminant and neural network analyses identified the same indicators, such as nutritional status and serum ALP levels. These indicators were independently associated with functional stroke outcome.
Dengue Seroprevalence and Seroconversion in Urban and Rural Populations in Northeastern Thailand and Southern Laos

Dengue is the most rapidly spreading mosquito-borne viral disease in the world. The detection of clinical cases enables us to measure the incidence of dengue infection, whereas serological surveys give insights into the prevalence of infection. This study aimed to determine dengue seroprevalence and seroconversion rates in northeastern Thailand and southern Laos and to assess any association of mosquito control methods and socioeconomic factors with dengue virus (DENV) infection. Cross-sectional seroprevalence surveys were performed in May and November 2019 on the same individuals. Blood samples were collected from one adult and one child, when possible, in each of 720 randomly selected households from two urban and two rural sites in both northeastern Thailand and southern Laos. IgG antibodies against DENV were detected in serum using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Overall, 1071 individuals participated in the study. The seroprevalence rate was high (91.5%) across all 8 study sites. Only age and province were associated with seroprevalence rates. There were 33 seroconversions during the period from May to November, of which seven reported fever. More than half of the seroconversions occurred in the rural areas and in Laos. Dengue seroconversion was significantly associated with young age (<15 years old), female gender, province, and duration of living in the current residence. No socioeconomic factors or mosquito control methods were found to be associated with seroprevalence or seroconversion. Notably, however, the province with most seroconversions had lower diurnal temperature ranges than elsewhere. In conclusion, our study has highlighted the homogeneity of dengue exposure across a wide range of settings and most notably those from rural and urban areas. Dengue can no longer be considered to be solely an urban disease nor necessarily one linked to poverty.
Fungal Degradation of Paddy Straw for Enhancing Biogas Production

Fungal mediated degradation of chopped and moist paddy straw (3-4cm) was investigated using Trichoderma reesei MTCC 164 and Coriolus versicolor MTCC 138 at different time intervals. The pre-treated paddy straw was in turn used for biogas production. Paddy straw pretreated with T. reesei MTCC 164 showed 20.8% enhanced biogas production and a maximum of 30% silica was removed after 25 days treatment. The paddy straw treated with C. versicolor MTCC 138 showed 26.2% enhanced biogas production with a maximum of 19.1 and 32.5% reduction in lignin and silica content respectively. Results regarding change in proximate and chemical composition of T. reesei MTCC 164 and C. versicolor MTCC 138 pretreated straw indicate that both these fungi might be the potential organisms for silica degradation.