Miracle-dz/UniFAR-FTUs huggingface dataset:
The Long Noncoding RNA MdLNC499 Bridges MdWRKY1 and MdERF109 Function to Regulate Early-Stage Light-Induced Anthocyanin Accumulation in Apple Fruit.

Anthocyanin pigments contribute to plant coloration and are valuable sources of antioxidants in the human diet as components of fruits and vegetables. Their production is known to be induced by light in (Malus domestica) apple fruit; however, the underlying molecular mechanism responsible for early-stage light-induced anthocyanin biosynthesis remains unclear. Here, we identified an ERF (ethylene response factor) protein, ERF109, involved in light-induced anthocyanin biosynthesis and found that it promotes coloration by directly binding to anthocyanin-related gene promoters. Promoter::GUS (β-glucuronidase) reporter analysis and Hi-C sequencing showed that a long non-coding RNA (lncRNA), MdLNC499, located upstream from MdERF109, induces the expression of MdERF109. A W-box cis-element in the MdLNC499 promoter was found to be regulated by a transcription factor, MdWRKY1. Transient expression in apple fruit and stable transformation of apple calli allowed us to reconstruct a MdWRKY1-MdLNC499-MdERF109 transcriptional cascade in which MdWRKY1 is activated by light to increase the transcription of MdLNC499, which in turn induces MdERF109. The MdERF109 protein induces the expression of anthocyanin-related genes and the accumulation of anthocyanins in the early stages of apple coloration. Our results provide a platform for better understanding the various regulatory mechanisms involved in light-induced apple fruit coloration.
Minimum Long-Loop Feedback Vertex Set and Network Dismantling

Network dismantling aims at breaking a network into disconnected components and attacking vertices that intersect with many loops has proven to be a most efficient strategy. Yet existing loop-focusing methods do not distinguish the short loops within densely connected local clusters (e.g., cliques) from the long loops connecting different clusters, leading to lowered performance of these algorithms. Here we propose a new solution framework for network dismantling based on a two-scale bipartite factor-graph representation, in which long loops are maintained while local dense clusters are simplistically represented as individual factor nodes. A mean-field spin-glass theory is developed for the corresponding long-loop feedback vertex set problem. The framework allows for the advancement of various existing dismantling algorithms; we developed the new version of two benchmark algorithms BPD (which uses the message-passing equations of the spin-glass theory as the solver) and CoreHD (which is fastest among well-performing algorithms). New solvers outperform current state-of-the-art algorithms by a considerable margin on networks of various sorts. Further improvement in dismantling performance is achievable by opting flexibly the choice of local clusters.
Plasma modification of carbon nanowalls induces transition from superhydrophobic to superhydrophilic

Graphene-based materials play an essential role in a wide range of modern technologies due to their surface properties such as adsorption capacity and controllable wettability, which depend on the production methods. For practical applications, it is crucial to control the surface properties to achieve the desired wetting characteristics, which can be described with the contact angle (CA). Here, we experimentally investigate the wettability properties of the carbon nanowalls and show how to manage a wetting transition from superhydrophobic to superhydrophilic states. A CA of 170° was reached with direct plasma synthesis, while an angle smaller than 20° was achieved during the atmosphere plasma modification. Combining the formation of the surface groups due to the plasma treatment results and the macroscale wetting behavior in terms of the Cassie–Baxter model, we qualitatively explain how the observed wetting enhancement is induced by both controlled chemical and geometrical surface-heterogeneity.
Vocal learning and flexible rhythm pattern perception are linked: Evidence from songbirds

Significance We can recognize the cadence of a friend’s voice or the rhythm of a familiar song across a wide range of tempi. This shows that our perception of temporal patterns relies strongly on the relative timing of events rather than on specific absolute durations. This tendency is foundational to speech and music perception, but to what extent is it shared by other species? We hypothesize that animals that learn their vocalizations are more likely to share this tendency. Here, we show that a vocal learning songbird robustly recognizes a basic rhythmic pattern independent of rate. Our findings pave the way for neurobiological studies to identify how the brain represents and perceives the temporal structure of auditory sequences. Rhythm perception is fundamental to speech and music. Humans readily recognize a rhythmic pattern, such as that of a familiar song, independently of the tempo at which it occurs. This shows that our perception of auditory rhythms is flexible, relying on global relational patterns more than on the absolute durations of specific time intervals. Given that auditory rhythm perception in humans engages a complex auditory–motor cortical network even in the absence of movement and that the evolution of vocal learning is accompanied by strengthening of forebrain auditory–motor pathways, we hypothesize that vocal learning species share our perceptual facility for relational rhythm processing. We test this by asking whether the best-studied animal model for vocal learning, the zebra finch, can recognize a fundamental rhythmic pattern—equal timing between event onsets (isochrony)—based on temporal relations between intervals rather than on absolute durations. Prior work suggests that vocal nonlearners (pigeons and rats) are quite limited in this regard and are biased to attend to absolute durations when listening to rhythmic sequences. In contrast, using naturalistic sounds at multiple stimulus rates, we show that male zebra finches robustly recognize isochrony independent of absolute time intervals, even at rates distant from those used in training. Our findings highlight the importance of comparative studies of rhythmic processing and suggest that vocal learning species are promising animal models for key aspects of human rhythm perception. Such models are needed to understand the neural mechanisms behind the positive effect of rhythm on certain speech and movement disorders.
Non-invasive hemoglobin measurement devices require refinement to match diagnostic performance with their high level of usability and acceptability

Anemia remains an important global health problem. Inexpensive, accurate, and noninvasive solutions are needed to monitor and evaluate anemia in resource-limited settings. We evaluated the performance of multiple point-of-care hemoglobin devices, including a novel noninvasive smartphone application tested on Apple® and Android® cell phones, Masimo Pronto®, and HemoCue® Hb-301 and Hb-801, against a gold-standard hematology analyzer (reference hemoglobin) using venous blood. We examined correlations between hemoglobin devices and reference hemoglobin, device accuracy (average bias, Bland-Altman plots, clinical performance) and classification bias (sensitivity, specificity) among 299 refugees (10mo-65y) in Atlanta, GA. Semi-structured interviews (n = 19) with participants and staff assessed usability and acceptability. Mean reference hemoglobin was 13.7 g/dL (SD:1.8) with 12.5% anemia. Noninvasive hemoglobin devices were not well correlated with reference hemoglobin (Apple® R2 = 0.08, Android® R2 = 0.11, Masimo Pronto® R2 = 0.29), but stronger correlations were reported with HemoCue® Hb-301 (R2 = 0.87) and Hb-801 (R2 = 0.88). Bias (SD) varied across each device: Apple®: -1.6 g/dL (2.0), Android®: -0.7 g/dL (2.0), Masimo Pronto®: -0.4 g/dL (1.6), HemoCue® Hb-301: +0.4 g/dL (0.7) and HemoCue® Hb-801: +0.2 g/dL (0.6). Clinically acceptable performance (within ± 1 g/dL of reference hemoglobin) was higher for the invasive devices (HemoCue® Hb-301: 90.3%; HemoCue® Hb-801: 93.4%) compared to noninvasive devices (Apple®: 31.5%; Android®: 34.6%; Masimo Pronto®: 49.5%). Sensitivity and specificity were 63.9% and 48.2% for Apple®, 36.1% and 67.6% for Android®, 45.7% and 85.3% for Masimo Pronto®, 54.3% and 97.6% for HemoCue® Hb-301, and 66.7% and 97.6% for HemoCue® Hb-801. Noninvasive devices were considered easy to use and were the preferred method by participants. Among the only studies to compare multiple point-of-care approaches to hemoglobin testing, the diagnostic ability of HemoCue® was comparable to reference hemoglobin, while noninvasive devices had high user acceptability but considerable biases. Improvements in noninvasive device performance and further testing in anemic populations are recommended before broader use.
Prehabilitation to prevent complications after cardiac surgery - A retrospective study with propensity score analysis

Background The rising prevalence of modifiable lifestyle-related risk factors (e.g. overweight and physical inactivity) suggests the need for effective and safe preoperative interventions to improve outcomes after cardiac surgery. This retrospective study explored potential short-term postoperative benefits and unintended consequences of a multidisciplinary prehabilitation program regarding in-hospital complications. Methods Data on patients who underwent elective cardiac surgery between January 2014 and April 2017 were analyzed retrospectively. Pearson’s chi-squared tests were used to compare patients who followed prehabilitation (three times per week, at a minimum of three weeks) during the waiting period with patients who received no prehabilitation. Sensitivity analyses were performed using propensity-score matching, in which the propensity score was based on the baseline variables that affected the outcomes. Results Of 1201 patients referred for elective cardiac surgery, 880 patients met the inclusion criteria, of whom 91 followed prehabilitation (53.8% ≥ 65 years, 78.0% male, median Euroscore II 1.3, IQR, 0.9–2.7) and 789 received no prehabilitation (60.7% ≥ 65 years, 69.6% male, median Euroscore II 1.6, IQR, 1.0–2.8). The incidence of atrial fibrillation (AF) was significantly lower in the prehabilitation group compared to the unmatched and matched standard care group (resp. 14.3% vs. 23.8%, P = 0.040 and 14.3% vs. 25.3%, P = 0.030). For the other complications, no between-group differences were found. Conclusions Prehabilitation might be beneficial to prevent postoperative AF. Patients participated safely in prehabilitation and were not at higher risk for postoperative complications. However, well-powered randomized controlled trials are needed to confirm and deepen these results.
Histone demethylase KDM5A enhances cell proliferation, induces EMT in lung adenocarcinoma cells, and have a strong causal association with paclitaxel resistance.

Recent reports suggest that histone demethylase KDM5A emerges as a new player in the development of drug resistance and thus increases the challenges of chemotherapy. Here, we explore the role of KDM5A in cell proliferation, epithelial-mesenchymal transition (EMT)and its causal association with paclitaxel resistance in lung adenocarcinoma. Paclitaxel-resistant lung adenocarcinoma PTX-Calu-3 cells showed significantly higher IC50 value (7±0.176 µM) upon paclitaxel treatment than lung adenocarcinoma SK-LI-1 (3.6±0.005 nM), Calu-3 (4.3±0.015 nM), and A549 (4.5±0.106 nM) cells. We found that expression of KDM5A and P-glycoprotein (P-gp), which plays a critical role in the development of paclitaxel resistance, were significantly higher in PTX-Calu-3 cells compared to SK-LI-1, Calu-3, and A549 cells. We observed a significant increase in the expression of mesenchymal markers N-cadherin and vimentin, and a concomitant decrease in expression of E-cadherin and α-catenin in PTX-Calu-3 compared to SK-LI-1, Calu-3, and A549 lung cancer cell lines. Transwell Boyden chamber and wound healing assays further demonstrated that a significantly higher number of PTX-Calu-3 cells were invasive and motile compared to SK-LI-1, Calu-3, and A549 cells, thus supporting the role of KDM5A in metastasis-associated processes. Additionally, a significantly higher expression of KDM5A was observed in lung adenocarcinoma patients' samples compared with adjacent normal tissues as well as in PTX-Calu-3 cells compared toSK-LI-1, Calu-3, and A549 cells, as shown both with histochemistry and real time-polymerase chain reaction (RT-PCR). In summary, these results suggest that KDM5A plays a key role in lung adenocarcinoma by promoting proliferation, EMT, and drug resistance to paclitaxel treatment.
Sample size calculation for two‐arm trials with time‐to‐event endpoint for nonproportional hazards using the concept of Relative Time when inference is built on comparing Weibull distributions

Sample size calculations for two‐arm clinical trials with a time‐to‐event endpoint have traditionally used the assumption of proportional hazards (PH) or the assumption of exponentially distributed survival times. Available software provides methods for sample size calculation using a nonparametric logrank test, Schoenfeld's formula for Cox PH model, or parametric calculations specific to the exponential distribution. In cases where the PH assumption is not valid, the first‐choice method is to compute sample size assuming a piecewise linear survival curve (Lakatos approach) for both the control and treatment arms with judiciously chosen cut‐points. Recent advances in literature have used the assumption of Weibull distributed times for single‐arm trials, and, newer methods have emerged that allow sample size calculations for two‐arm trials using the assumption of proportional time (PT) while considering non‐PH. These methods, however, always assume an instantaneous effect of treatment relative to control requiring that the effect size be defined by a single number whose magnitude is preserved throughout the trial duration. Here, we consider the scenarios where the hypothesized benefit of treatment relative to control may not be constant giving rise to the notion of Relative Time (RT). By assuming that survival times for control and treatment arm come from two different Weibull distributions with different location and shape parameters, we develop the methodology for sample size calculation for specific cases of both non‐PH and non‐PT. Simulations are conducted to assess the operation characteristics of the proposed method and a practical example is discussed.
Simultaneous 3-Nitrophenylhydrazine Derivatization Strategy of Carbonyl, Carboxyl and Phosphoryl Submetabolome for LC-MS/MS-Based Targeted Metabolomics with Improved Sensitivity and Coverage.

Metabolomics is a powerful and essential technology for profiling metabolic phenotypes and exploring metabolic reprogramming, which enables the identification of biomarkers and provides mechanistic insights into physiology and disease. However, its applications are still limited by the technical challenges particularly in its detection sensitivity for the analysis of biological samples with limited amount, necessitating the development of highly sensitive approaches. Here, we developed a highly sensitive liquid chromatography tandem mass spectrometry method based on a 3-nitrophenylhydrazine (3-NPH) derivatization strategy that simultaneously targets carbonyl, carboxyl, and phosphoryl groups for targeted metabolomic analysis (HSDccp-TM) in biological samples. By testing 130 endogenous metabolites including organic acids, amino acids, carbohydrates, nucleotides, carnitines, and vitamins, we showed that the derivatization strategy resulted in significantly improved detection sensitivity and chromatographic separation capability. Metabolic profiling of merely 60 oocytes and 5000 hematopoietic stem cells primarily isolated from mice demonstrated that this method enabled routine metabolomic analysis in trace amounts of biospecimens. Moreover, the derivatization strategy bypassed the tediousness of inferring the MS fragmentation patterns and simplified the complexity of monitoring ion pairs of metabolites, which greatly facilitated the metabolic flux analysis (MFA) for glycolysis, the tricarboxylic acid (TCA) cycle, and pentose phosphate pathway (PPP) in cell cultures. In summary, the novel 3-NPH derivatization-based method with high sensitivity, good chromatographic separation, and broad coverage showed great potential in promoting metabolomics and MFA, especially in trace amounts of biospecimens.
Comparative in silico prediction of P‐glycoprotein‐mediated transport for 2010–2020 US FDA‐approved drugs using six Web‐tools

P‐glycoprotein (P‐gp) is an efflux pump implicated in pharmacokinetics and drug–drug interactions. The identification of its substrates is consequently an important issue, notably for drugs under development. For such a purpose, various in silico methods have been developed, but their relevance remains to be fully established. The present study was designed to get insight about this point, through determining the performance values of six freely accessible Web‐tools (ADMETlab, AdmetSAR2.0, PgpRules, pkCSM, SwissADME and vNN‐ADMET), computationally predicting P‐gp‐mediated transport. Using an external test set of 231 marketed drugs, approved over the 2010–2020 period by the US Food and Drug Administration and fully in vitro characterized for their P‐gp substrate status, various performance parameters (including sensitivity, specificity, accuracy, Matthews correlation coefficient and area under the receiver operating characteristics curve) were determined. They were found to rather poorly meet criteria commonly required for acceptable prediction, whatever the Web‐tools were used alone or in combination. Predictions of being P‐gp substrate or non‐substrate by these online in silico methods may therefore be considered with caution.
Reference Case Methods for Expert Elicitation in Health Care Decision Making

Background The evidence used to inform health care decision making (HCDM) is typically uncertain. In these situations, the experience of experts is essential to help decision makers reach a decision. Structured expert elicitation (referred to as elicitation) is a quantitative process to capture experts’ beliefs. There is heterogeneity in the existing elicitation methodology used in HCDM, and it is not clear if existing guidelines are appropriate for use in this context. In this article, we seek to establish reference case methods for elicitation to inform HCDM. Methods We collated the methods available for elicitation using reviews and critique. In addition, we conducted controlled experiments to test the accuracy of alternative methods. We determined the suitability of the methods choices for use in HCDM according to a predefined set of principles for elicitation in HCDM, which we have also generated. We determined reference case methods for elicitation in HCDM for health technology assessment (HTA). Results In almost all methods choices available for elicitation, we found a lack of empirical evidence supporting recommendations. Despite this, it is possible to define reference case methods for HTA. The reference methods include a focus on gathering experts with substantive knowledge of the quantities being elicited as opposed to those trained in probability and statistics, eliciting quantities that the expert might observe directly, and individual elicitation of beliefs, rather than solely consensus methods. It is likely that there are additional considerations for decision makers in health care outside of HTA. Conclusions The reference case developed here allows the use of different methods, depending on the decision-making setting. Further applied examples of elicitation methods would be useful. Experimental evidence comparing methods should be generated.
A meta‐analysis on the incidence of donor‐related depression after liver transplant

Living donor liver transplantation (LDLT) is increasing, yet gaps exist in the understanding of psychological wellbeing of donors after liver transplant. This meta‐analysis seeks to evaluate the incidence and risk factors for donor‐related depression after liver transplantation. A search was conducted on Medline and Embase database. Articles assessing incidence of depression in LDLT donors were included. Incidence was pooled after Freeman–Turkey double‐arcsine transformation. For risk factors, dichotomous variables were analyzed with generalized linear model, while a conventional meta regression with logit transformation was conducted for continuous variables. Of 1069 abstracts, 40 articles underwent full‐text review. Seventeen articles were included. The pooled incidence of depression among 1888 LT donors was 7.66% (CI: 4.47–12.80%). Depression rates were significantly higher in Asian compared to Western studies (RR: 1.73, CI: 1.19–2.52, P = 0.0039). Female gender (P < 0.001), Caucasian ethnicity (P = 0.047), employment status (P < 0.001) and lower education levels (P = 0.044) were significantly associated with depression. Donor relationship with recipients was not a significant risk factor. LDLT remains a core aspect of the treatment of end‐stage liver disease. However, the high depression rates after LT suggest that there remains room for improvement in the care of donors’ mental health post‐transplant.
An electrodiffusive neuron-extracellular-glia model for exploring the genesis of slow potentials in the brain

Within the computational neuroscience community, there has been a focus on simulating the electrical activity of neurons, while other components of brain tissue, such as glia cells and the extracellular space, are often neglected. Standard models of extracellular potentials are based on a combination of multicompartmental models describing neural electrodynamics and volume conductor theory. Such models cannot be used to simulate the slow components of extracellular potentials, which depend on ion concentration dynamics, and the effect that this has on extracellular diffusion potentials and glial buffering currents. We here present the electrodiffusive neuron-extracellular-glia (edNEG) model, which we believe is the first model to combine compartmental neuron modeling with an electrodiffusive framework for intra- and extracellular ion concentration dynamics in a local piece of neuro-glial brain tissue. The edNEG model (i) keeps track of all intraneuronal, intraglial, and extracellular ion concentrations and electrical potentials, (ii) accounts for action potentials and dendritic calcium spikes in neurons, (iii) contains a neuronal and glial homeostatic machinery that gives physiologically realistic ion concentration dynamics, (iv) accounts for electrodiffusive transmembrane, intracellular, and extracellular ionic movements, and (v) accounts for glial and neuronal swelling caused by osmotic transmembrane pressure gradients. The edNEG model accounts for the concentration-dependent effects on ECS potentials that the standard models neglect. Using the edNEG model, we analyze these effects by splitting the extracellular potential into three components: one due to neural sink/source configurations, one due to glial sink/source configurations, and one due to extracellular diffusive currents. Through a series of simulations, we analyze the roles played by the various components and how they interact in generating the total slow potential. We conclude that the three components are of comparable magnitude and that the stimulus conditions determine which of the components that dominate.