Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells

Cockayne Syndrome (CS) is an autosomal recessive neurodegenerative premature aging disorder associated with defects in nucleotide excision repair (NER). Cells from CS patients, with mutations in CSA or CSB genes, present elevated levels of reactive oxygen species (ROS) and are defective in the repair of a variety of oxidatively generated DNA lesions. In this study, six purine lesions were ascertained in wild type (wt) CSA, defective CSA, wtCSB and defective CSB-transformed fibroblasts under different oxygen tensions (hyperoxic 21%, physioxic 5% and hypoxic 1%). In particular, the four 5′,8-cyclopurine (cPu) and the two 8-oxo-purine (8-oxo-Pu) lesions were accurately quantified by LC-MS/MS analysis using isotopomeric internal standards after an enzymatic digestion procedure. cPu levels were found comparable to 8-oxo-Pu in all cases (3–6 lesions/106 nucleotides), slightly increasing on going from hyperoxia to physioxia to hypoxia. Moreover, higher levels of four cPu were observed under hypoxia in both CSA and CSB-defective cells as compared to normal counterparts, along with a significant enhancement of 8-oxo-Pu. These findings revealed that exposure to different oxygen tensions induced oxidative DNA damage in CS cells, repairable by NER or base excision repair (BER) pathways. In NER-defective CS patients, these results support the hypothesis that the clinical neurological features might be connected to the accumulation of cPu. Moreover, the elimination of dysfunctional mitochondria in CS cells is associated with a reduction in the oxidative DNA damage.
Improved nearest-neighbor parameters for the stability of RNA/DNA hybrids under a physiological condition

Abstract The stability of Watson–Crick paired RNA/DNA hybrids is important for designing optimal oligonucleotides for ASO (Antisense Oligonucleotide) and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)–Cas9 techniques. Previous nearest-neighbour (NN) parameters for predicting hybrid stability in a 1 M NaCl solution, however, may not be applicable for predicting stability at salt concentrations closer to physiological condition (e.g. ∼100 mM Na+ or K+ in the presence or absence of Mg2+). Herein, we report measured thermodynamic parameters of 38 RNA/DNA hybrids at 100 mM NaCl and derive new NN parameters to predict duplex stability. Predicted ΔG°37 and Tm values based on the established NN parameters agreed well with the measured values with 2.9% and 1.1°C deviations, respectively. The new results can also be used to make precise predictions for duplexes formed in 100 mM KCl or 100 mM NaCl in the presence of 1 mM Mg2+, which can mimic an intracellular and extracellular salt condition, respectively. Comparisons of the predicted thermodynamic parameters with published data using ASO and CRISPR–Cas9 may allow designing shorter oligonucleotides for these techniques that will diminish the probability of non-specific binding and also improve the efficiency of target gene regulation.
Impact of evening alcohol consumption on nocturnal autonomic and cardiovascular function in adult men and women: A dose-response laboratory investigation.

STUDY OBJECTIVES To investigate the dose-dependent impact of moderate alcohol intake on sleep-related cardiovascular (CV) function, in adult men and women. METHODS Twenty-six healthy adults (30-60y; 11 women) underwent three nights of laboratory polysomnographic (PSG) recordings in which different doses of alcohol (low: 1 standard drink for women and 2 drinks for men; high: 3 standard drinks for women and 4 drinks for men; placebo: no-alcohol) were administered in counterbalanced order before bedtime. These led to bedtime average breath alcohol levels of up to 0.02% for the low doses and around 0.05% for the high doses. Autonomic and CV function were evaluated using electrocardiography, impedance cardiography, and beat-to-beat blood pressure monitoring. RESULTS Pre-sleep alcohol ingestion resulted in an overall increase in nocturnal heart rate (HR), suppressed total and high-frequency (vagal) HR variability, reduced baroreflex sensitivity, and increased sympathetic activity, with effects pronounced after high-dose alcohol ingestion (p's<0.05); these changes followed different dose- and measure-dependent nocturnal patterns in men and women. Systolic blood pressure showed greater increases during the morning hours of the high-alcohol dose night compared to the low-alcohol dose night and placebo, in women only (p's<0.05). CONCLUSIONS Acute evening alcohol consumption, even at moderate doses, has marked dose- and time-dependent effects on sleep CV regulation in adult men and women. Further studies are needed to evaluate the potential CV risk of repeated alcohol-related alterations in night-time CV restoration in healthy individuals and in those at high risk for CV diseases, considering sex and alcohol dose and time effects.
Evaluation of Vertical Ground Reaction Forces Pattern Visualization in Neurodegenerative Diseases Identification Using Deep Learning and Recurrence Plot Image Feature Extraction

To diagnose neurodegenerative diseases (NDDs), physicians have been clinically evaluating symptoms. However, these symptoms are not very dependable—particularly in the early stages of the diseases. This study has therefore proposed a novel classification algorithm that uses a deep learning approach to classify NDDs based on the recurrence plot of gait vertical ground reaction force (vGRF) data. The irregular gait patterns of NDDs exhibited by vGRF data can indicate different variations of force patterns compared with healthy controls (HC). The classification algorithm in this study comprises three processes: a preprocessing, feature transformation and classification. In the preprocessing process, the 5-min vGRF data divided into 10-s successive time windows. In the feature transformation process, the time-domain vGRF data are modified into an image using a recurrence plot. The total recurrence plots are 1312 plots for HC (16 subjects), 1066 plots for ALS (13 patients), 1230 plots for PD (15 patients) and 1640 plots for HD (20 subjects). The principal component analysis (PCA) is used in this stage for feature enhancement. Lastly, the convolutional neural network (CNN), as a deep learning classifier, is employed in the classification process and evaluated using the leave-one-out cross-validation (LOOCV). Gait data from HC subjects and patients with amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD) and Parkinson’s disease (PD) obtained from the PhysioNet Gait Dynamics in Neurodegenerative disease were used to validate the proposed algorithm. The experimental results included two-class and multiclass classifications. In the two-class classification, the results included classification of the NDD and the HC groups and classification among the NDDs. The classification accuracy for (HC vs. ALS), (HC vs. HD), (HC vs. PD), (ALS vs. PD), (ALS vs. HD), (PD vs. HD) and (NDDs vs. HC) were 100%, 98.41%, 100%, 95.95%, 100%, 97.25% and 98.91%, respectively. In the multiclass classification, a four-class gait classification among HC, ALS, PD and HD was conducted and the classification accuracy of HC, ALS, PD and HD were 98.99%, 98.32%, 97.41% and 96.74%, respectively. The proposed method can achieve high accuracy compare to the existing results, but with shorter length of input signal (Input of existing literature using the same database is 5-min gait signal, but the proposed method only needs 10-s gait signal).
Patient-Ventilator Asynchronies: Clinical Implications and Practical Solutions

Mechanical ventilation is a supportive treatment commonly applied in critically ill patients. Whenever the patient is spontaneously breathing, the pressure applied to the respiratory system depends on the sum of the pressure generated by the respiratory muscles and the pressure generated by the ventilator. Mechanical ventilation is a supportive treatment commonly applied in critically ill patients. Whenever the patient is spontaneously breathing, the pressure applied to the respiratory system depends on the sum of the pressure generated by the respiratory muscles and the pressure generated by the ventilator. Patient-ventilator interaction is of utmost importance in spontaneously breathing patients, and thus the ventilator should be able to adapt to patient’s changes in ventilatory demand and respiratory mechanics. Nevertheless, a lack of coordination between patient and ventilator due to a mismatch between neural and ventilator timing throughout the respiratory cycle may make weaning difficult and lead to prolonged mechanical ventilation. Therefore, appropriate monitoring of asynchronies is mandatory to improve the applied strategies and thus improve patient-ventilator interaction. We conducted a literature review regarding patient-ventilator interaction with a focus on the different kinds of inspiratory and expiratory asynchronies, their monitoring, clinical implications, possible prevention, and treatment. We believe that monitoring patient-ventilator interaction is mandatory in spontaneously breathing patients to understand, by using the available technologies, the type of asynchrony and consequently improve the adaptation of the ventilator to the patient’s needs. Asynchronies are relatively frequent during mechanical ventilation in critically ill patients, and they are associated with poor outcomes. This review summarizes the different types of asynchronies and their mechanisms, consequences, and potential management. The development and understanding of monitoring tools are necessary to allow a better appraisal of this area, which may lead to better outcomes for patients.
Promoting breastfeeding in Chinese women undergoing cesarean section based on the health belief model

Abstract Background: The high rate of cesarean section is an important factor affecting breastfeeding in China. To improve the nation's current situation of breastfeeding, promoting breastfeeding in women undergoing cesarean section is essential. Objective: To explore the effects of health belief model-based interventions on breastfeeding knowledge, breastfeeding behaviors, and breastfeeding satisfaction of Chinese cesarean women. Methods: A total of 346 cesarean section women were enrolled in the randomized controlled trial conducted at a center in Chengdu, China, between July 1, 2018 and August 31, 2018. While the control group (n = 173) received conventional breastfeeding guidance only, the intervention group (n = 173) received additional interventions based on the health belief model. Questionnaires were distributed to assess breastfeeding knowledge, breastfeeding behavior, and breastfeeding satisfaction at discharge, 42 days postpartum, and 4 months postpartum, respectively. Results: At discharge from hospital, the breastfeeding knowledge score of the intervention group was higher than that of the control group (Z = −11.753, P < .001). The exclusive breastfeeding rates in the intervention group at the time of discharge, 42 days postpartum, and 4 months postpartum were 67.3%, 60.7%, and 52.9%, respectively, while those of the control group were 41.2%, 41.6%, and 40.4%, respectively. The differences were statistically significant (χ2 = 23.353, P < .001; χ2 = 11.853, P < .001; χ2 = 4.805, P = .03). The breastfeeding satisfaction of the intervention group was also higher than the control group at the time of discharge, 42 days postpartum and 4 months postpartum (t = 4.955, P < .001; t = 3.051, P = .002; Z = −3.801, P < .001). Conclusion: The health belief model-based interventions can effectively increase breastfeeding knowledge for Chinese cesarean women and improve their breastfeeding behaviors and breastfeeding satisfaction within 4 months after delivery. Clinical Trial Registration: ChiCTR1900026006
The Synthetic Small Molecule FL3 Combats Intestinal Tumorigenesis via Axin1-Mediated Inhibition of Wnt/β-Catenin Signaling

Targeting of PHB1 by FL3 provides a novel mechanism to combat Wnt-driven cancers, with limited intestinal toxicity. Colorectal cancer exhibits aberrant activation of Wnt/β-catenin signaling. Many inhibitors of the Wnt/β-catenin pathway have been tested for Wnt-dependent cancers including colorectal cancer, but are unsuccessful due to severe adverse reactions. FL3 is a synthetic derivative of natural products called flavaglines, which exhibit anti-inflammatory and cytoprotective properties in intestinal epithelial cells, but has not been previously tested in cell or preclinical models of intestinal tumorigenesis. In vitro studies suggest that flavaglines target prohibitin 1 (PHB1) as a ligand, but this has not been established in the intestine. PHB1 is a highly conserved protein with diverse functions that depend on its posttranslational modifications and subcellular localization. Here, we demonstrate that FL3 combats intestinal tumorigenesis in the azoxymethane-dextran sodium sulfate and ApcMin/+ mouse models and in human colorectal cancer tumor organoids (tumoroids) by inhibiting Wnt/β-catenin signaling via induction of Axin1 expression. FL3 exhibited no change in cell viability in normal intestinal epithelial cells or human matched-normal colonoids. FL3 response was diminished in colorectal cancer cell lines and human colorectal cancer tumoroids harboring a mutation at S45 of β-catenin. PHB1 deficiency in mice or in human colorectal cancer tumoroids abolished FL3-induced expression of Axin1 and drove tumoroid death. In colorectal cancer cells, FL3 treatment blocked phosphorylation of PHB1 at Thr258, resulting in its nuclear translocation and binding to the Axin1 promoter. These results suggest that FL3 inhibits Wnt/β-catenin signaling via PHB1-dependent activation of Axin1. FL3, therefore, represents a novel compound that combats Wnt pathway–dependent cancers, such as colorectal cancer. Significance: Targeting of PHB1 by FL3 provides a novel mechanism to combat Wnt-driven cancers, with limited intestinal toxicity. Graphical Abstract: http://cancerres.aacrjournals. org/content/canres/80/17/3519/F1.large. jpg. Graphical Abstract
Update Alert 2: Epidemiology of and Risk Factors for Coronavirus Infection in Health Care Workers

Supplement Table 1. Burden of SARS-CoV-2, SARS-CoV-1, and MERS-CoV Supplement Table 2. Mental health and sleep outcomes associated with SARS-CoV-2 Supplement Table 3. Results of individual studies, risk factors for SARS-CoV-2 infection in HCWs Supplement Table 4. Results of individual studies, risk factors for SARS-CoV-1 infection in HCWs (unchanged from prior Update Alert) Supplement Table 5. Results of individual studies, risk factors for MERS-CoV infection in HCWs (unchanged from prior Update Alert) Supplement Table 6. Demographic characteristics and HCW role or position and risk for infection with SARS-CoV-2, SARS-CoV-1, or MERS-CoV in HCWs Supplement Table 7. Exposure history and risk for infection with SARS-CoV-2, SARS-CoV-1, or MERS-CoV in HCWs Supplement Table 8. Education or training, environmental and physical factors, and infection control policies and risk for infection with SARS-CoV-2, SARS-CoV-1, or MERS-CoV in HCWs Supplement Table 9. Mask use and risk for infection with SARS-CoV-2, SARS-CoV-1, or MERS-CoV in HCWs Supplement Table 10. Infection Prevention and Control Factors (Other Than Masks) and Risk for Infection With SARS-CoV-2, SARS-CoV-1, or MERS-CoV in HCWs Supplement Table 11. Results of individual studies, household transmission of SARS-CoV-1 from health care workers (unchanged from prior Update Alert)
Randomized trials of invasive cardiovascular interventions that include a placebo control: a systematic review and meta-analysis.

AIMS The difference in the benefit of invasive cardiovascular interventions compared with placebo controls has not been analysed systematically. METHODS AND RESULTS MEDLINE and Web of Science were searched through 29 March 2020. Randomized, placebo-controlled trials of invasive cardiovascular interventions (including catheter-based interventions and pacemaker-like devices) investigating predefined primary outcomes were included. Standardized mean differences (SMD) and odds ratios were calculated for continuous and dichotomous outcomes, respectively. Meta-regression analyses were performed to assess whether estimates of treatment effects were associated with methodological characteristics of trials. Thirty trials, including 4102 patients, were analysed. The overall risk of bias was judged to be low in only 43% of the trials. Ten trials (33%) demonstrated statistically significant superiority of invasive interventions over placebo controls for the respective predefined primary outcomes. In almost half of the 16 trials investigating continuous predefined primary outcomes, the SMD between the active and placebo procedure indicated a small (n = 4) to moderate (n = 3) treatment effect of active treatment over placebo. In contrast, one trial indicated a small treatment effect in favour of the placebo procedure. In the remaining trials, there was no relevant treatment effect of active treatment over placebo. In trials with a protocol-mandated stable and symmetrical use of co-interventions, the superiority of active procedures vs. invasive placebo procedures was significantly larger as compared with trials with frequent or unbalanced changes in co-interventions (P for interaction 0.027). CONCLUSIONS The additional treatment effect of invasive cardiovascular interventions compared with placebo controls was small in most trials.
Examining the Factor Structure and Measurement Invariance of the Trauma Symptom Checklist for Children in a Diverse Sample of Trauma-Exposed Adolescents

The Trauma Symptom Checklist for Children (TSCC) is a widely used youth assessment of broad, transdiagnostic symptomatology following trauma. However, its factor structure has not been thoroughly tested in diverse samples. Youth (N = 738) exposed to interpersonal violence, including physical and sexual abuse, completed the TSCC. Confirmatory factor analysis was used to test one-, six-, and eight-factor models of the TSCC clinical scales, based on previous literature and the TSCC manual. We examined measurement invariance across boys and girls and Black and non-Black participants, as well as convergent and discriminant validity. An eight-factor structure, consisting of posttraumatic stress, anxiety, depression, anger, overt dissociation, fantasy dissociation, sexual preoccupation, and sexual distress, demonstrated the best fit, with two items removed. Invariance tests supported configural and metric (but not scalar) invariance. This research highlights the need for further testing before differences between gender and racial groups can be accurately compared.
Simultaneous Coercivity and Size Determination of Magnetic Nanoparticles

Magnetic nanoparticles are increasingly employed in biomedical applications such as disease detection and tumor treatment. To ensure a safe and efficient operation of these applications, a noninvasive and accurate characterization of the particles is required. In this work, a magnetic characterization technique is presented in which the particles are excited by specific pulsed time-varying magnetic fields. This way, we can selectively excite nanoparticles of a given size so that the resulting measurement gives direct information on the size distribution without the need for any a priori assumptions or complex postprocessing procedures to decompose the measurement signal. This contrasts state-of-the-art magnetic characterization techniques. The possibility to selectively excite certain particle types opens up perspectives in “multicolor” particle imaging, where different particle types need to be imaged independently within one sample. Moreover, the presented methodology allows one to simultaneously determine the size-dependent coercivity of the particles. This is not only a valuable structure–property relation from a fundamental point of view, it is also practically relevant to optimize applications like magnetic particle hyperthermia. We numerically demonstrate that the novel characterization technique can accurately reconstruct several particle size distributions and is able to retrieve the coercivity–size relation of the particles. The developed technique advances current magnetic nanoparticle characterization possibilities and opens up exciting pathways for biomedical applications and particle imaging procedures.
Survivor-Centered Practice and Survivor Empowerment: Evidence From A Research–Practitioner Partnership

In the domestic violence field, a survivor-centered approach to services is a shared ideal, but there is little empirical work demonstrating its importance. This study filled that gap, focusing on a key outcome—safety-related empowerment. We gathered data from 177 intimate partner violence (IPV) survivors seeking community-based services, and after one session with an advocate, results revealed a significant change in two of three subscales of the Measure of Victim Empowerment Related to Safety (MOVERS) measure: Internal Tools and Expectations of Support. There was no change in Trade-Offs (pursuing safety causing new problems). More survivor-defined practice predicted greater changes in empowerment, over and above severity of violence, post-traumatic stress disorder (PTSD), and demographics.
Structures reveal gatekeeping of the mitochondrial Ca2+ uniporter by MICU1-MICU2

The mitochondrial calcium uniporter is a Ca2+-gated ion channel complex that controls mitochondrial Ca2+ entry and regulates cell metabolism. MCU and EMRE form the channel while Ca2+-dependent regulation is conferred by MICU1 and MICU2 through an enigmatic process. We present a cryo-EM structure of an MCU-EMRE-MICU1-MICU2 holocomplex comprising MCU and EMRE subunits from the beetle Tribolium castaneum in complex with a human MICU1-MICU2 heterodimer at 3.3 Å resolution. With analogy to how neuronal channels are blocked by protein toxins, a uniporter interaction domain on MICU1 binds to a channel receptor site comprising MCU and EMRE subunits to inhibit ion flow under resting Ca2+ conditions. A Ca2+-bound structure of MICU1-MICU2 at 3.1 Å resolution indicates how Ca2+-dependent changes enable dynamic response to cytosolic Ca2+ signals.
Regulatory B Cells and Their Cytokine Profile in HCV-Related Hepatocellular Carcinoma: Association with Regulatory T Cells and Disease Progression

Although regulatory B cells (Bregs) have been proven to play a suppressive role in autoimmune diseases, infections and different tumors, little is known regarding hepatocellular carcinoma (HCC), especially in hepatitis C-related settings. Herein, we analyzed the frequency of circulating Bregs, serum levels of IL-10, IL-35 and B-cell activating factor (BAFF) and investigated their association with regulatory T cells (Tregs) and disease progression in HCV-related HCC. For comparative purposes, four groups were enrolled; chronic HCV (CHC group, n = 35), HCV-related liver cirrhosis (HCV-LC group, n = 35), HCV-related HCC (HCV-HCC group, n = 60) and an apparently healthy control (Control-group, n = 20). HCC diagnosis and staging were in concordance with the Barcelona Clinic Liver Cancer (BCLC) staging system. Analysis of the percentage of Breg cells and peripheral lymphocyte subsets (Treg) was performed by flow cytometry. Serum cytokine levels of IL-10, IL-35 and B-cell activating factor (BAFF) were measured by ELISA. The frequency of Bregs was significantly higher in the HCV-HCC group compared to the other groups and controls. A significant increase was noted in late-HCC versus those in the early stages. The frequency of Bregs was positively correlated with Tregs, serum IL-10, IL-35 and BAFF. In conclusion, Peripheral Bregs were positively correlated with the frequency of Tregs, IL-10, IL-35 and BAFF, and may be associated with HCV-related HCC progression.