Miracle-dz/UniFAR-FTUs huggingface dataset:
Residual mitral regurgitation following isolated aortic valve replacement

To the Editor, Therapeutic strategy for those with severe aortic stenosis and functional mitral regurgitation remains controversial. Voisine et al. demonstrated that mitral regurgitation improved in 60% of patients following the isolated aortic valve replacement. Improvement in mitral regurgitation was associated with baseline greater left ventricular dimension and better long‐term survival. Several concerns have been raised. The authors assessed the improvement in mitral regurgitation using the latest available echocardiograms following the aortic valve replacements. Detailed timing of the echocardiographic assessments would be informative. Improvement in mitral regurgitation is achieved soon after the procedure or can be achieved even after several years? The authors found several baseline echocardiographic characteristics associating with the postprocedural improvement in mitral regurgitation. Expansion of this analysis to other clinical parameters including age, laboratory data, and hemodynamics would be helpful for clinicians to consider therapeutic strategy and risk stratification. The existence of postprocedural perivalvular leakage might hinder postprocedural improvement in mitral regurgitation. The authors found that those without improvement in mitral regurgitation had worse survival. Did the authors perform any specific interventions to the persistent mitral regurgitation, including percutaneous mitral valve repair? Even though mitral regurgitation does not improve following the isolated aortic valve replacement, such an additional intervention might eventually improve clinical outcomes.
Problem Solving Training for Veterans with Complex Comorbidities: Treatment Delivery Adaptations during COVID-19

ABSTRACT Objectives To summarize adaptations due to COVID-19 for VA Problem Solving Training (PST) for clinicians serving medically complex patients and to compare patient mental health outcomes in the year before (2019) and during COVID-19 (2020). Methods Clinicians attended a multi-day workshop and up to 6 months of small-group consultation for two training cases. In 2019 and 2020, 122 Veteran patients completed baseline and posttreatment measures of depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7 item), and negative problem-solving beliefs (Negative Problem Orientation Questionnaire). Qualitative data were collected on clinician’s pandemic-related treatment implementation challenges. Results Program adaptations during COVID-19 addressed challenges due to delivering treatment by telephone, video, or in person; Veteran patient recruitment barriers; and privacy issues for telephone and video. Veterans in both pre-pandemic and COVID-19 cohorts had significant improvements in depression, anxiety, and negative problem-solving beliefs, with no significant differences in the amount of improvement between the two cohorts. Conclusions Flexibilities afforded to clinicians delivering the PST training program during the pandemic addressed key obstacles and barriers to recruitment, and implementation did not diminish the effectiveness of the intervention. Clinical implications Findings support continued implementation of the PST training program with added flexibility to treatment delivery beyond the pandemic.
Insights into the structure and RNA-binding specificity of Caenorhabditis elegans Dicer-related helicase 3 (DRH-3)

Abstract DRH-3 is critically involved in germline development and RNA interference (RNAi) facilitated chromosome segregation via the 22G-siRNA pathway in Caenorhabditis elegans. DRH-3 has similar domain architecture to RIG-I-like receptors (RLRs) and belongs to the RIG-I-like RNA helicase family. The molecular understanding of DRH-3 and its function in endogenous RNAi pathways remains elusive. In this study, we solved the crystal structures of the DRH-3 N-terminal domain (NTD) and the C-terminal domains (CTDs) in complex with 5′-triphosphorylated RNAs. The NTD of DRH-3 adopts a distinct fold of tandem caspase activation and recruitment domains (CARDs) structurally similar to the CARDs of RIG-I and MDA5, suggesting a signaling function in the endogenous RNAi biogenesis. The CTD preferentially recognizes 5′-triphosphorylated double-stranded RNAs bearing the typical features of secondary siRNA transcripts. The full-length DRH-3 displays unique structural dynamics upon binding to RNA duplexes that differ from RIG-I or MDA5. These features of DRH-3 showcase the evolutionary divergence of the Dicer and RLR family of helicases.
Expanding the chemical functionality of DNA nanomaterials generated by rolling circle amplification

Abstract Rolling circle amplification (RCA) is a powerful tool for the construction of DNA nanomaterials such as hydrogels, high-performance scaffolds and DNA nanoflowers (DNFs), hybrid materials formed of DNA and magnesium pyrophosphate. Such DNA nanomaterials have great potential in therapeutics, imaging, protein immobilisation, and drug delivery, yet limited chemistry is available to expand their functionality. Here, we present orthogonal strategies to produce densely modified RCA products and DNFs. We provide methods to selectively modify the DNA component and/or the protein cargo of these materials, thereby greatly expanding the range of chemical functionalities available to these systems. We have used our methodology to construct DNFs bearing multiple surface aptamers and peptides capable of binding to cancer cells that overexpress the HER2 oncobiomarker, demonstrating their potential for diagnostic and therapeutic applications.
Transplantation of 3D bio-printed cardiac mesh improves cardiac function and vessel formation via ANGPT1/Tie2 pathway in rats with acute myocardial infarction

A novel tissue engineering strategy using 3D bio-print technology has become a promising therapeutic method for acute myocardial infarction (AMI) in an animal model. However, the application of 3D bio-printed tissue remains limited due to poor graft survival. Therefore, it is a scientific priority to enhance graft survival by precisely adjusting the 3D environment of encapsulated cells. In this study, novel transplantable 3D cardiac mesh (cMesh) tissue with a porous mesh structure was presented using human cardiomyocytes, human cardiac fibroblasts, and gelatin-methacryloyl–collagen hydrogel. Cardiomyocytes and cardiac fibroblasts were well spreaded. The cardiomyocytes were connected with a gap junction channel in bio-printed cMesh and a 3D cardiac patch with an aggregated structure. Porous cMesh demonstrated structural advantages by increased phosphorylation of mTOR, AKT, and ERK signals associated with cell survival. Transplanted cMesh in rats with AMI improved long-term graft survival, vessel formation, and stabilization, reduced fibrosis, increased left ventricle thickness, and enhanced cardiac function. Our results suggest that porous cMesh provides structural advantages and a positive therapeutic effect in an AMI animal model.
Oxidative damage in the liver and brain of the rats exposed to frequency-dependent radiofrequency electromagnetic exposure: biochemical and histopathological evidence

Abstract The study aimed to discover a link between the liver and brain's functional status due to frequency dependent-radiofrequency electromagnetic radiation (RF-EMR). Forty Wistar rats were randomly classified as control (sham-exposed) and EMR exposed groups. Animals were exposed to 900, 1800, and 2100 MHz with the specific absorption rate (SAR) 0.434 (W/Kg), 0.433 (W/Kg), and 0.453 (W/Kg) respectively. Animal exposure was limited at 1 h/day, 5 days/week for 1 month with a restricted power density (900 MHz- 11.638 µW/m2, 1800- 11.438 µW/m2 and 2100 MHz frequency- 8.237 µW/m2). Exposure at various frequencies showed a frequency-dependent change in the body weight and hematologic parameters (RBCs, WBCs, platelets, hemoglobin, and hematocrit) as compared with the control group (p ≤ 0.01) (p ≤ 0.001). A significant elevation in serum transaminases and bilirubin, urea, uric acid, and creatinine was noted, whereas albumin significantly decreased after EMR exposure (p ≤ 0.01) (p ≤ 0.001). The blood glucose, lipid peroxidation, triglycerides, and cholesterol were elevated while adenosine triphosphatases, acetylcholinesterase, and tissue antioxidants such as glutathione, superoxide dismutase, catalase, glutathione reductase, glutathione Peroxidase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenases were decreased significantly (p ≤ 0.001). Histopathological observations of the liver showed centrilobular mononuclear cell infiltration and swelling in sinusoidal spaces, while in the brain degenerated pyramidal and Purkinje neurons were seen. Furthermore, Substantial evidence was found that the brain is more susceptible to oxidative mutilation compare to the liver of exposed animals. In conclusion, RF-EMR exposure showed oxidative damage to the liver, increasing the incidence of brain damage in a frequency-dependent manner. Highlights EMR exposure showed frequency-dependent toxicity. Alterations in blood profile and modifications in the serological markers. Increasing lipid peroxidation indicating membrane damage. Inhibition of acetylcholinesterase activity affecting cholinergic neurotransmission. EMR exposure resulted in the loss of cellular energy and production of excess amounts of ROS thereby altering several antioxidant enzymes. Histopathological evidence of severe degenerative changes in the liver and brain.
Seeing is believing: tools to study the role of Rho GTPases during cytokinesis

ABSTRACT Cytokinesis is required to cleave the daughter cells at the end of mitosis and relies on the spatiotemporal control of RhoA GTPase. Cytokinesis failure can lead to changes in cell fate or aneuploidy, which can be detrimental during development and/or can lead to cancer. However, our knowledge of the pathways that regulate RhoA during cytokinesis is limited, and the role of other Rho family GTPases is not clear. This is largely because the study of Rho GTPases presents unique challenges using traditional cell biological and biochemical methods, and they have pleiotropic functions making genetic studies difficult to interpret. The recent generation of optogenetic tools and biosensors that control and detect active Rho has overcome some of these challenges and is helping to elucidate the role of RhoA in cytokinesis. However, improvements are needed to reveal the role of other Rho GTPases in cytokinesis, and to identify the molecular mechanisms that control Rho activity. This review examines some of the outstanding questions in cytokinesis, and explores tools for the imaging and control of Rho GTPases.
Viperin has species-specific roles in response to herpes simplex virus infection

Viperin is a gene with a broad spectrum of antiviral functions and various mechanisms of action. The role of viperin in herpes simplex virus type 1 (HSV-1) infection is unclear, with conflicting data in the literature that is derived from a single human cell type. We have addressed this gap by investigating viperin during HSV-1 infection in several cell types, spanning species and including immortalized, non-immortalized and primary cells. We demonstrate that viperin upregulation by HSV-1 infection is cell-type-specific, with mouse cells typically showing greater increases compared with those of human origin. Further, overexpression and knockout of mouse, but not human viperin significantly impedes and increases HSV-1 replication, respectively. In primary mouse fibroblasts, viperin upregulation by infection requires viral gene transcription and occurs in a predominantly IFN-independent manner. Further we identify the N-terminal domain of viperin as being required for the anti-HSV-1 activity. Interestingly, this is the region of viperin that differs most between mouse and human, which may explain the apparent species-specific activity against HSV-1. Finally, we show that HSV-1 virion host shutoff (vhs) protein is a key viral factor that antagonises viperin in mouse cells. We conclude that viperin can be upregulated by HSV-1 in mouse and human cells, and that mouse viperin has anti-HSV-1 activity.
Age-Related Changes in Voice Emotion Recognition by Postlingually Deafened Listeners With Cochlear Implants

Objectives: Identification of emotional prosody in speech declines with age in normally hearing (NH) adults. Cochlear implant (CI) users have deficits in the perception of prosody, but the effects of age on vocal emotion recognition by adult postlingually deaf CI users are not known. The objective of the present study was to examine age-related changes in CI users’ and NH listeners’ emotion recognition. Design: Participants included 18 CI users (29.6 to 74.5 years) and 43 NH adults (25.8 to 74.8 years). Participants listened to emotion-neutral sentences spoken by a male and female talker in five emotions (happy, sad, scared, angry, neutral). NH adults heard them in four conditions: unprocessed (full spectrum) speech, 16-channel, 8-channel, and 4-channel noise-band vocoded speech. The adult CI users only listened to unprocessed (full spectrum) speech. Sensitivity (d’) to emotions and Reaction Times were obtained using a single-interval, five-alternative, forced-choice paradigm. Results: For NH participants, results indicated age-related declines in Accuracy and d’, and age-related increases in Reaction Time in all conditions. Results indicated an overall deficit, as well as age-related declines in overall d’ for CI users, but Reaction Times were elevated compared with NH listeners and did not show age-related changes. Analysis of Accuracy scores (hit rates) were generally consistent with d’ data. Conclusions: Both CI users and NH listeners showed age-related deficits in emotion identification. The CI users’ overall deficit in emotion perception, and their slower response times, suggest impaired social communication which may in turn impact overall well-being, particularly so for older CI users, as lower vocal emotion recognition scores have been associated with poorer subjective quality of life in CI patients.
Survey of Adverse Events After The First Dose of The ChAdOx1 nCoV-19 Vaccine: A Single-Center Experience in Korea

Vaccination is an important strategy for controlling the coronavirus disease 2019 (COVID-19) pandemic. We conducted a web-based cross-sectional survey based on Google Forms to collect data on adverse events (AEs) after the first dose of the ChAdOx1 nCoV-19 vaccine for healthcare workers (HCWs). Among the 1,676 vaccinated HCWs, 59.5% (998/1,676) responded to the survey. In total, 809 (81.1%) respondents reported experiencing AEs. There were no serious AEs, such as anaphylaxis. The most common AE was pain at the injection site (76.2%), followed by fatigue (75.9%), myalgia (74.9%), and fever (58.4%). HCWs in the younger age group experienced significantly more AEs than in the older age group.
Menstrual regularity and bleeding is associated with sleep duration, sleep quality and fatigue in a community sample

Female menstrual health and its relationship with sleep is an understudied subject. The aim of this investigation was to determine the association between the two in a community sample. Data were obtained from n = 579 menstruating females who participated in the Sleep and Health Activity, Diet, Environment, and Socialization (SHADES) study, a community‐based sample of adults aged 22–60 years. Participants were asked, “How regular is your period? ”, with response choices of “very regular”, “mostly regular”, “fairly regular” and “not regular”. They were also asked, “How much bleeding do you usually experience during your period? ” Response choices were: “very heavy”, “heavy”, “medium”, “light” or “very light”. These were evaluated as ordinal outcomes. Sleep‐related predictors included sleep duration (in hr; ≤ 6 [short], 7–9 [normal] and ≥ 9 [long]), Insomnia Severity Index score, Pittsburgh Sleep Quality Index score, Epworth Sleepiness Scale score and Fatigue Severity Scale score. Covariates included age, education, income, race/ethnicity and body mass index. Short sleep duration was associated with heavier bleeding (odds ratio = 1.46, p = 0.026) and greater cycle irregularity (odds ratio = 1.44, p = 0.031) as compared with normal sleep. Higher Pittsburgh Sleep Quality Index score was associated with greater cycle irregularity (odds ratio = 1.05, p = 0.022). Higher Fatigue Severity Scale score was associated with heavier bleeding (odds ratio = 1.02, p = 0.003) and greater cycle irregularity (odds ratio = 1.02, p = 0.008). Long sleep, Insomnia Severity Index and Epworth Sleepiness Scale were not associated with either outcome. These results demonstrate an association between short sleep duration, poor sleep quality, fatigue, stress and depression with heavier bleeding and menstrual cycle irregularity, highlighting the need for further studies to improve treatment options.
Sigma-1R Protects Retinal Ganglion Cells in Optic Nerve Crush Model for Glaucoma

Purpose The purpose of this study was to determine the effects of the Sigma-1R (σ-1r) on retinal ganglion cell (RGC) survival following optic nerve crush (ONC) and the signaling mechanism involved in the σ-1r protection. Methods The overall strategy was to induce injury by ONC and mitigate RGC death by increasing σ-1r expression and/or activate σ-1r activity in σ-1r K/O mice and wild type (WT) mice. AAV2-σ-1r vector was used to increase σ-1r expression and σ-1r agonist used to activate the σ-1r and RGCs were counted. Immunohistochemical and Western blot analysis determined phosphorylated (p)-c-Jun, c-Jun, and Caspase-3. Pattern electroretinography (PERG) determined RGC activity. Results RGC counts and function were similar in pentazocine-treated WT mice when compared to untreated mice and in WT mice when compared with σ-1r K/O mice. Pentazocine-induced effects and the effects of σ-1r K/O were only observable after ONC. ONC resulted in decreased RGC counts and activity in both WT and σ-1r K/O mice, with σ-1r K/O mice experiencing significant decreases compared with WT mice. The σ-1r transgenic expression resulted in increased RGC counts and activity following ONC. In WT mice, treatment with σ-1r agonist pentazocine resulted in increased RGC counts and increased activity when compared with untreated WT mice. There were time-dependent increases in c-jun, p-c-jun, and caspase-3 expression in ONC mice that were mitigated with pentazocine-treatment. Conclusions These findings suggest that the apoptotic pathway is involved in RGC losses seen in an ONC model. The σ-1r offers neuroprotection, as activation and/or transgenic expression of σ-1r attenuated the apoptotic pathway and restored RGCs number and function following ONC.
Preparing Silver Linings for a Cloudy Day: The Consequences of Preemptive Benefit Finding

Waiting for important news is stressful. In four studies, we assess the utility of preemptive benefit finding, a coping strategy in which people seek silver linings in bad news before receiving news, for emotional well-being across several waiting periods (waiting for bar exam results, the outcome of political elections, and results of a fictitious health risk assessment). Our findings support the effectiveness of preemptive benefit finding while waiting, such that identifying benefits in bad news while waiting predicts more positive emotions during the wait (Studies 3 and 4) and buffers people against the emotional consequences of bad news by boosting post-news positive emotions (Studies 2–4). Importantly, engaging in preemptive benefit finding does not backfire if a person ultimately receives good news (Studies 1, 3, and 4). We discuss results from a mini meta-analysis and consider implications of our findings for interventions to improve well-being while waiting and after news arrives.
Toward a machine learning model for a primary diagnosis of Guillain-Barré syndrome subtypes

Guillain-Barré Syndrome (GBS) is a neurological disorder affecting people of any age and sex, mainly damaging the peripheral nervous system. GBS is divided into several subtypes, in which only four are the most common, demanding different treatments. Identifying the subtype is an expensive and time-consuming task. Early GBS detection is crucial to save the patient’s life and not aggravate the disease. This work aims to provide a primary screening tool for GBS subtypes fast and efficiently without complementary invasive methods, based only on clinical variables prospected in consultation, taken from clinical history, and based on risk factors. We conducted experiments with four classifiers with different approaches, five different filters for feature selection, six wrappers, and One versus All (OvA) classification. For the experiments, we used a data set that includes 129 records of Mexican patients and 26 clinical representative variables. Random Forest filter obtained the best results in each classifier for the diagnosis of the four subtypes, in the same way, this filter with the SVM classifier achieved the best result (0.6840). OvA with SVM classifier reached a balanced accuracy of 0.8884 for the Miller-Fisher (MF) subtype.
Effect of heat acclimation on metabolic adaptations induced by endurance training in soleus rat muscle

Aerobic training leads to well‐known systemic metabolic and muscular alterations. Heat acclimation may also increase mitochondrial muscle mass. We studied the effects of heat acclimation combined with endurance training on metabolic adaptations of skeletal muscle. Thirty‐two rats were divided into four groups: control (C), trained (T), heat‐acclimated (H), and trained with heat acclimation (H+T) for 6 weeks. Soleus muscle metabolism was studied, notably by the in situ measurement of mitochondrial respiration with pyruvate (Pyr) or palmitoyl‐coenzyme A (PCoA), under phosphorylating conditions ( V˙max ) or not ( V˙0 ). Aerobic performance increased, and retroperitoneal fat mass decreased with training, independently of heat exposure (p < 0.001 and p < 0.001, respectively). Citrate synthase and hydroxyl‐acyl‐dehydrogenase activity increased with endurance training (p < 0.001 and p < 0.01, respectively), without any effect of heat acclimation. Training induced an increase of the V˙0 and V˙max for PCoA (p < .001 and p < .01, respectively), without interference with heat acclimation. The training‐induced increase of V˙0 (p < 0.01) for pyruvate oxidation was limited when combined with heat acclimation (−23%, p < 0.01). Training and heat acclimation independently increased the V˙max for pyruvate (+60% p < 0.001 and +50% p = 0.01, respectively), without an additive effect of the combination. Heat acclimation doubled the training effect on muscle glycogen storage (p < 0.001). Heat acclimation did not improve mitochondrial adaptations induced by endurance training in the soleus muscle, possibly limiting the alteration of carbohydrate oxidation while not facilitating fatty‐acid utilization. Furthermore, the increase in glycogen storage observed after HA combined with endurance training, without the improvement of pyruvate oxidation, appears to be a hypoxic metabolic phenotype.