Miracle-dz/UniFAR-FTUs huggingface dataset:
A deep learning algorithm to translate and classify cardiac electrophysiology

The development of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has been a critical in vitro advance in the study of patient-specific physiology, pathophysiology, and pharmacology. We designed a new deep learning multitask network approach intended to address the low throughput, high variability, and immature phenotype of the iPSC-CM platform. The rationale for combining translation and classification tasks is because the most likely application of the deep learning technology we describe here is to translate iPSC-CMs following application of a perturbation. The deep learning network was trained using simulated action potential (AP) data and applied to classify cells into the drug-free and drugged categories and to predict the impact of electrophysiological perturbation across the continuum of aging from the immature iPSC-CMs to the adult ventricular myocytes. The phase of the AP extremely sensitive to perturbation due to a steep rise of the membrane resistance was found to contain the key information required for successful network multitasking. We also demonstrated successful translation of both experimental and simulated iPSC-CM AP data validating our network by prediction of experimental drug-induced effects on adult cardiomyocyte APs by the latter.
Grief, COVID-19, and the South: Considerations and Recommendations

Purpose COVID-19 has devastated the United States (U.S.). One of the more notably impacted areas is the South. Compared to the rest of the U.S., the South is characterized by increased rurality, lowered access to healthcare, older populations, and higher religiosity, all of which might predispose its residents to more detrimental effects of COVID-19, including COVID-related fatalities. As such, this paper provides important considerations for individuals engaging in work with Southern, rural Americans dealing with COVID-related grief and loss. Methods A review of the literature addressing the impact of Southern legislature, rurality, cross-country factors, and faith on COVID-related grief among Southerners was conducted, with applicable considerations expressed. Conclusions Care should be taken by providers working with rural, Southern residents to attend to tangible and intangible losses experienced as a result of COVID-19. These considerations can help inform work with rural Southerners dealing with grief during the pandemic.
Polyurethane foam functionalized with an AIE-active polymer using an ultrasonication-assisted method: preparation and application for the detection of explosives

PU foams modified with an AIE-active polymer (PSiTPE) with a Si–O and TPE backbone using an ultrasonication-assisted method have been prepared. The as-prepared foams show a high sensitive to PA solution and DNT vapor. Moreover, it could be re-used several times. It is a novel promising probe for the detection of explosives.
Mindfulness Promotes Online Prosocial Behavior via Cognitive Empathy

Mindfulness plays an important role in promoting prosocial behavior and well-being. With the spread of Internet usage, people’s online prosocial behavior (OPB) has garnered great attention. Based on the link between online and offline behaviors, we predict that mindfulness can also facilitate OPB. We examined the association of mindfulness and OPB and the mediating effect of empathy. A total of 674 Chinese undergraduate students completed self-report measures of these constructs. The results showed that different dimensions of mindfulness predicted empathy, which in turn predicted OPB. Perspective taking was the main mediator in the mindfulness-OPB link. Mindfulness improves receptiveness to others’ needs and feelings, thereby enhancing the willingness to help them, even in none-face-to-face situations.
Hemodynamic Heterogeneity of Reduced Cardiac Reserve Unmasked by Volumetric Exercise Echocardiography

Background: Two-dimensional volumetric exercise stress echocardiography (ESE) provides an integrated view of left ventricular (LV) preload reserve through end-diastolic volume (EDV) and LV contractile reserve (LVCR) through end-systolic volume (ESV) changes. Purpose: To assess the dependence of cardiac reserve upon LVCR, EDV, and heart rate (HR) during ESE. Methods: We prospectively performed semi-supine bicycle or treadmill ESE in 1344 patients (age 59.8 ± 11.4 years; ejection fraction = 63 ± 8%) referred for known or suspected coronary artery disease. All patients had negative ESE by wall motion criteria. EDV and ESV were measured by biplane Simpson rule with 2-dimensional echocardiography. Cardiac index reserve was identified by peak-rest value. LVCR was the stress-rest ratio of force (systolic blood pressure by cuff sphygmomanometer/ESV, abnormal values ≤2.0). Preload reserve was defined by an increase in EDV. Cardiac index was calculated as stroke volume index * HR (by EKG). HR reserve (stress/rest ratio) <1.85 identified chronotropic incompetence. Results: Of the 1344 patients, 448 were in the lowest tertile of cardiac index reserve with stress. Of them, 303 (67.6%) achieved HR reserve <1.85; 252 (56.3%) had an abnormal LVCR and 341 (76.1%) a reduction of preload reserve, with 446 patients (99.6%) showing ≥1 abnormality. At binary logistic regression analysis, reduced preload reserve (odds ratio [OR]: 5.610; 95% confidence intervals [CI]: 4.025 to 7.821), chronotropic incompetence (OR: 3.923, 95% CI: 2.915 to 5.279), and abnormal LVCR (OR: 1.579; 95% CI: 1.105 to 2.259) were independently associated with lowest tertile of cardiac index reserve at peak stress. Conclusions: Heart rate assessment and volumetric echocardiography during ESE identify the heterogeneity of hemodynamic phenotypes of impaired chronotropic, preload or LVCR underlying a reduced cardiac reserve.
Force Field Parameterization for the Description of the Interactions between Hydroxypropyl-β-Cyclodextrin and Proteins

Cyclodextrins are cyclic oligosaccharides, widely used as drug carriers, solubilizers, and excipients. Among cyclodextrins, the functionalized derivative known as hydroxypropyl-β-cyclodextrin (HPβCD) offers several advantages due to its unique structural features. Its optimal use in pharmaceutical and medical applications would benefit from a molecular-level understanding of its behavior, as can be offered by molecular dynamics simulations. Here, we propose a set of parameters for all-atom simulations of HPβCD, based on the ADD force field for sugars developed in our group, and compare it to the original CHARMM36 description. Using Kirkwood–Buff integrals of binary HPβCD–water mixtures as target experimental data, we show that the ADD-based description results in a considerably improved prediction of HPβCD self-association and interaction with water. We then use the new set of parameters to characterize the behavior of HPβCD toward the different amino acids. We observe pronounced interactions of HPβCD with both polar and nonpolar moieties, with a special preference for the aromatic rings of tyrosine, phenylalanine, and tryptophan. Interestingly, our simulations further highlight a preferential orientation of HPβCD’s hydrophobic cavity toward the backbone atoms of amino acids, which, coupled with a favorable interaction of HPβCD with the peptide backbone, suggest a propensity for HPβCD to denature proteins.
Evolution of the drug-target residence time model

ABSTRACT Introduction The pharmacological action of a drug is linked to its affinity for a specific molecular target as quantified by in vitro equilibrium measurements. However, it is clear that for many highly effective drugs, interactions with their molecular targets do not conform to simple, equilibrium conditions in vivo and this results in a temporal discordance between pharmacokinetics and pharmacodynamics. The drug-target residence time model was developed to provide a theoretical framework with which to understand cases in which very slow dissociation of the drug-target complex in vivo results in durable PD effects even after systemic concentrations of drug have waned. Area covered In this article, the author provides a brief description of the drug-target residence time model and focuses on the refinements that have been made to the original model to incorporate the influences of compound rebinding in cells and pharmacokinetic properties of drug molecules. Expert opinion There is now overwhelming evidence for the utility of the drug-target residence time model as a framework for understanding in vivo drug action. The in vitro measured residence time (τR) must be used in concert with equilibrium measures of drug-target affinity (e.g. IC50) and with in vivo measures of pharmacokinetic half-life, to afford the researcher a powerful approach to compound optimization for clinical effect. Despite the significant use and refinement of this model, continued studies are required to better understand the dynamic interplay between residence time, target pathobiology, drug distribution and drug pharmacokinetics.
Experimental and Computational Analysis of MnO2@V2C-MXene for Enhanced Energy Storage

Herein, we studied the novel and emerging group of 2D materials namely MXene along with its nanocomposites. This work entails detailed experimental as well as computational study of the electrochemical behavior of vanadium carbide (V2CTx) MXene and MnO2-V2C nanocomposite with varying percentages of MnO2. A specific capacitance of 551.8 F/g was achieved for MnO2-V2C nanocomposite in 1 M KOH electrolyte solution, which is more than two times higher than the gravimetric capacitance of 196.5 F/g obtained for V2C. The cyclic stability achieved for the MnO2-V2C nanocomposite resulted in a retentivity of 96.5% until 5000 cycles. The c-lattice parameter achieved for MXene is 22.6 Å, which was 13.01 Å for MAX phase. The nanocomposite resulted in a c-lattice parameter of 27.2 Å, which showed that the spatial distance between the MXene layers was efficiently obtained. The method of wet etching was used for the preparation of pristine MXene and the liquid phase precipitation method was opted for the synthesis of the MnO2-V2C nanocomposite. Density functional theory calculation was exercised so as to complement the experimental results and to understand the microscopic details, such as structure stability and electronic structure. The current report presents a comprehensive experimental and computational study on 2D MXenes for future energy storage applications.
Systematic Review with Meta-Analyses: Diagnostic Accuracy of FibroMeter Tests in Patients with Non-Alcoholic Fatty Liver Disease

Early detection of liver fibrosis is crucial to select the correct care path for patients with non-alcoholic fatty liver disease (NAFLD). Here, we systematically review the evidence on the performance of FibroMeter versions in detecting different levels of fibrosis in patients with NAFLD. We searched four databases (Medline, Embase, the Cochrane library, and Web of Science) to find studies that included adults with NAFLD and biopsy-confirmed fibrosis (F1 to F4), compared with any version of FibroMeter. Two independent researchers screened the references, collected the data, and assessed the methodological quality of the included studies. We used a bivariate logit-normal random effects model to produce meta-analyses. From 273 references, 12 studies were eligible for inclusion, encompassing data from 3425 patients. Meta-analyses of the accuracy in detecting advanced fibrosis (F ≥ 3) were conducted for FibroMeter Virus second generation (V2G), NAFLD, and vibration controlled transient elaFS3stography (VCTE). FibroMeter VCTE showed the best diagnostic accuracy in detecting advanced fibrosis (sensitivity: 83.5% (95%CI 0.58–0.94); specificity: 91.1% (95%CI 0.89–0.93)), followed by FibroMeter V2G (sensitivity: 83.1% (95%CI 0.73–0.90); specificity: 84.4% (95%CI 0.62–0.95)) and FibroMeter NAFLD (sensitivity: 71.7% (95%CI 0.63–0.79); specificity: 82.8% (95%CI 0.71–0.91)). No statistically significant differences were found between the different FibroMeter versions. FibroMeter tests showed acceptable sensitivity and specificity in detecting advanced fibrosis in patients with NAFLD, but an urge to conduct head-to-head comparison studies in patients with NAFLD of the different FibroMeter tests remains.
Effects of Construal Level on Responses to Ambiguous Health Information about Alcohol Consumption

ABSTRACT Information about the health effects of alcohol consumption can be ambiguous (i.e., lacking in reliability, credibility, or adequacy) and thus may promote maladaptive health behavior. Guided by Construal Level Theory and a conceptual taxonomy of uncertainty in health care, we tested the hypothesis that manipulating construal level would promote adaptive responses to ambiguous health information. We examined the effects of ambiguous health information about alcohol on health cognitions, message responses, and intentions, as well as whether manipulating construal moderated these effects. Alcohol users (n = 135, Mag e = 20.15, 68.9% female) were randomly assigned to either a high-level or low-level construal task and then to read either an ambiguous or unambiguous health communication about the health effects of alcohol. Participants responded similarly to ambiguous health information as they did to unambiguous health information and participants in a high-level construal did not generally report differences compared with those in a low-level construal. Findings suggest that ambiguous health information might not always lead to maladaptive effects. More research is needed to examine moderators of the relationship between ambiguous health information and health outcomes, as well as to understand how and when using construal manipulations are effective in different health contexts.
Lactose-Gated Mesoporous Silica Particles for Intestinal Controlled Delivery of Essential Oil Components: An In Vitro and In Vivo Study

Mesoporous silica microparticles functionalized with lactose for the specific release of essential oil components (EOCs) in the small intestine are presented. In vitro and in vivo intestinal models were applied to validate the microparticles (M41-EOC-L), in which the presence of lactase acts as the triggering stimulus for the controlled release of EOCs. Among the different microdevices prepared (containing thymol, eugenol and cinnamaldehyde), the one loaded with cinnamaldehyde showed the most significant Caco-2 cell viability reduction. On the other hand, interaction of the particles with enterocyte-like monolayers showed a reduction of EOCs permeability when protected into the designed microdevices. Then, a microdevice loaded with cinnamaldehyde was applied in the in vivo model of Wistar rat. The results showed a reduction in cinnamaldehyde plasma levels and an increase in its concentration in the lumen of the gastrointestinal tract (GIT). The absence of payload release in the stomach, the progressive release throughout the intestine and the prolonged stay of the payload in the GIT-lumen increased the bioavailability of the encapsulated compound at the site of the desired action. These innovative results, based on the specific intestinal controlled delivery, suggest that the M41-payload-L could be a potential hybrid microdevice for the protection and administration of bioactive molecules in the small intestine and colon.
Anti-inflammatory, antibacterial and immunomodulatory treatment in children with symptoms corresponding to the research condition PANS (Pediatric Acute-onset Neuropsychiatric Syndrome): A systematic review

Objective To assess effects of treatment against a hypothesized neuroinflammation in children with symptoms corresponding to the research condition Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) which is not included in current diagnostic systems. Methods Systematic literature searches were performed (1998 to June 2020) in PubMed, Embase, the Cochrane Library, CINAHL, PsycInfo, and HTA databases. Inclusion criteria: patients (P) were children (<18 years) with PANS; intervention (I)/comparison (C) was use of, versus no use of, anti-inflammatory, antibacterial or immunomodulating treatments; outcomes (O) were health-related quality of life (HRQL), level of functioning, symptom change, and complications. Results Four randomised controlled trials (RCTs) and three non-RCTs, including 23 to 98 patients, fulfilled the PICO. HRQL was not investigated in any study. Regarding level of functioning, two RCTs investigated antibiotics (penicillin V, azithromycin) and one RCT investigated immunomodulating treatments (intravenous immunoglobulins (IVIG), plasma exchange). Regarding symptoms, two non-RCTs investigated anti-inflammatory treatment (cyclooxygenase (COX) inhibitors, corticosteroids), two RCTs and one non-RCT investigated antibiotics (penicillin V, azithromycin), and two RCTs investigated immunomodulating treatments (IVIG, plasma exchange). Complications, reported in five studies, were consistent with those listed in the summary of products characteristics (SPC). All studies were assessed to have some or major problems regarding directness, the absence of an established diagnosis contributing to clinical diversity in the studied populations. All studies were assessed to have major risk of bias, including selection and detection biases. Due to clinical and methodological diversity, meta-analyses were not performed. Conclusion This systematic review reveals very low certainty of evidence of beneficial effects, and moderate certainty of evidence of adverse effects, of anti-inflammatory, antibacterial or immunomodulating treatments in patients with symptoms corresponding to the research condition PANS. Available evidence neither supports nor excludes potential beneficial effects, but supports that such treatment can result in adverse effects. Registration PROSPERO (CRD42020155714).
Comparison of Hepatitis E Virus Sequences from Humans and Swine, The Netherlands, 1998–2015

Pigs are suspected to be a major source of zoonotic hepatitis E virus (HEV) infection in industrialized countries, but the transmission route(s) from pigs to humans are ill-defined. Sequence comparison of HEV isolates from pigs with those from blood donors and patients in 372 samples collected in The Netherlands in 1998 and 1999 and between 2008 and 2015 showed that all sequences were genotype 3 except for six patients (with travel history). Subgenotype 3c (gt3c) was the most common subtype. While the proportion of gt3c increased significantly between 1998 and 2008, it remained constant between 2008 and 2015. Among the few circulating HEV subtypes, there was no difference observed between the human and the pig isolates. Hepatitis E viruses in humans are very likely to originate from pigs, but it is unclear why HEV gt3c has become the predominant subtype in The Netherlands.
Comprehensive Evaluation of Volatile and Nonvolatile Compounds in Oyster Cuts of Roasted Lamb at Different Processing Stages Using Traditional Nang Roasting

Nang roasting is a traditional lamb processing method in Xinjiang (China) with a history of thousands of years. This study comprehensively evaluated the volatile and nonvolatile compounds of oyster cuts of roasted lamb at different processing stages of Nang roasting using gas chromatography mass spectrometry and amino acid automatic analyzer, respectively. Results indicated that aldehydes were the dominant profiles of volatile compounds, and hexanal, nonanal, octanal, (E)-2-nonenal, (E, E)-2,4-decadienal, (E, E)-2,4-nonadienal and 1-octen-3-ol were the key volatile compounds or aroma contributors to roasted oyster cuts. Isoamylol and 3-hydroxy-2-butanone could differentiate fresh and marinated oyster cuts from roasted ones; (E)-2-nonenal, (E, E)-2,4-decadienal, 1-octen-3-ol, hexanal, octanal, nonanal and (E, E)-2,4-nonadienal could differentiate Nang roasted oyster cuts of 60 min from those of 15, 30 and 45 min. Umami amino acids and sweet amino acids are the dominant profiles of nonvolatile compounds; glutamic acid, alanine and 5′-IMP were the key free amino acids or taste contributors to roasted oyster cuts. Glutamic acid, alanine and 5′-IMP could differentiate fresh and marinated oyster cuts from roasted samples. This work provided theoretical support for the control of flavor attributes of roasted lamb with traditional Nang roasting.
Equation for Tooth Size Prediction from Mixed Dentition Analysis for Taiwanese Population: A Pilot Study

Background: In mixed dentition analysis, estimation of the mesiodistal width of unerupted permanent canines and premolars is essential for successful diagnosis and treatment planning. The present study aimed to develop a simple linear equation to predict permanent tooth sizes from mixed dentition analysis for Taiwanese people. Methods: The sample comprised 200 dental casts, derived from Taiwanese patients (100 males and 100 females; age, 12–35 years). Mesial distal tooth widths were measured in dental casts with a digital caliper. A student’s t-test was conducted to detect tooth size correlations with gender-specific differences, as well as intra-arch counterparts. Standard linear regression was conducted to develop a simple equation representing predictions of canine-premolar relationships. Results: All teeth were not significantly different between the left and right sides, regardless of gender and upper or lower arches. In terms of types of teeth, males had larger tooth dimensions in both arches than females. New regression equations for estimating the dimensions of the unerupted canines and premolars in the Taiwanese population were developed. Conclusions: Using a sample of Taiwanese people, new models derived for females and males separately were developed, which should provide highly accurate predictions for unerupted canines and premolars in the Taiwanese population.
Primary Metabolite Profile Changes in Coffea spp. Promoted by Single and Combined Exposure to Drought and Elevated CO2 Concentration

Climate change scenarios pose major threats to many crops worldwide, including coffee. We explored the primary metabolite responses in two Coffea genotypes, C. canephora cv. Conilon Clone 153 and C. arabica cv. Icatu, grown at normal (aCO2) or elevated (eCO2) CO2 concentrations of 380 or 700 ppm, respectively, under well-watered (WW), moderate (MWD), or severe (SWD) water deficit conditions, in order to assess coffee responses to drought and how eCO2 can influence such responses. Primary metabolites were analyzed with a gas chromatography time-of-flight mass spectrometry metabolomics platform (GC-TOF-MS). A total of 48 primary metabolites were identified in both genotypes (23 amino acids and derivatives, 10 organic acids, 11 sugars, and 4 other metabolites), with differences recorded in both genotypes. Increased metabolite levels were observed in CL153 plants under single and combined conditions of aCO2 and drought (MWD and SWD), as opposed to the observed decreased levels under eCO2 in both drought conditions. In contrast, Icatu showed minor differences under MWD, and increased levels (especially amino acids) only under SWD at both CO2 concentration conditions, although with a tendency towards greater increases under eCO2. Altogether, CL153 demonstrated large impact under MWD, and seemed not to benefit from eCO2 in either MWD and SWD, in contrast with Icatu.