Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein model quality assessment using 3D oriented convolutional neural networks

Protein model quality assessment (QA) is a crucial and yet open problem in structural bioinformatics. The current best methods for single-model QA typically combine results from different approaches, each based on different input features constructed by experts in the field. Then, the prediction model is trained using a machine-learning algorithm. Recently, with the development of convolutional neural networks (CNN), the training paradigm has changed. In computer vision, the expert-developed features have been significantly overpassed by automatically trained convolutional filters. This motivated us to apply a three-dimensional (3D) CNN to the problem of protein model QA. We developed a novel method for single-model QA called Ornate. Ornate (Oriented Routed Neural network with Automatic Typing) is a residue-wise scoring function that takes as input 3D density maps. It predicts the local (residue-wise) and the global model quality through a deep 3D CNN. Specifically, Ornate aligns the input density map, corresponding to each residue and its neighborhood, with the backbone topology of this residue. This circumvents the problem of ambiguous orientations of the initial models. Also, Ornate includes automatic identification of atom types and dynamic routing of the data in the network. Established benchmarks (CASP 11 and CASP 12) demonstrate the state-of-the-art performance of our approach among singlemodel QA methods. The method is available at https://team.inria. fr/nanod/software/Ornate/. It consists of a C++ executable that transforms molecular structures into volumetric density maps, and a Python code based on the TensorFlow framework for applying the Ornate model to these maps.
Asenapine maleate-loaded nanostructured lipid carriers: optimization and in vitro, ex vivo and in vivo evaluations.

AIM To prepare nanostructured lipid carriers (NLCs) loaded with asenapine maleate (ASPM) to increase its oral bioavailability by intestinal lymphatic uptake. MATERIALS & METHODS ASPM-NLCs were prepared by ultrasound dispersion technique, by adopting Design of Experiment approach, and characterized. RESULTS The optimized formulation exhibited good physicochemical parameters. Differential scanning calorimetry and x-ray diffraction studies indicated the amorphized nature of ASPM in lipid matrix. In vitro drug release study indicated the sustained release of drug from NLCs. ASPM-NLCs showed greater permeability across Caco2 cells and everted rat ileum. ASPM-NLCs showed greater cellular uptake, superior preclinical oral bioavailability and higher efficacy in reducing the L-DOPA-carbidopa-induced locomotor count compared with plain drug. CONCLUSION ASPM-NLCs were successfully developed that showed enhanced performance both in vitro and in vivo.
Friend or Foe: A Cancer Suppressor MicroRNA-34 Potentially Plays an Adverse Role in Vascular Diseases by Regulating Cell Apoptosis and Extracellular Matrix Degradation

Background MicroRNAs (miRNAs) have emerged as central regulators of many processes. MiRNA-34 (miR-34) functions as a well-known tumor suppressor. The aim of this study was to investigate the mechanisms underlying how miR-34 participates in vascular disorders. Material/Methods Three miR-34 family members (miR-34a, miR-34b, and miR-34c) were overexpressed or silenced in human vascular smooth muscle cells (VSMCs) and umbilical vein endothelial cells (UVECs), respectively, before the proliferation and apoptosis of cells were detected by using Cell Counting Kit-8 assay and Annexin V- fluorescein isothiocyanate/propidium iodide flow cytometry. The protein expression of apoptosis biomarkers was detected by western blot. Dual-luciferase reporter assay was performed to determine the candidate target of miR-34, and enzyme-linked immune sorbent assay was used to evaluate the effect of miR-34 on the expression of the target gene. Results Overexpression of miR-34 family members repressed proliferation and promoted apoptosis of VSMCs and UVECs, whereas miR-34 knockdown led to the opposite results. In addition, miR-34a inhibited the expression of alpha-1 antitrypsin (AAT), a serine protease inhibitor that suppresses the degradation of extracellular matrix, through a miR-34-binding site within the 3′-UTR of AAT. Conclusions MiR-34 promoted apoptosis of VSMC and UVEC cells by inhibiting AAT expression. This finding provides an update on the understanding of the clinical value of miR-34, which might assist to uncover novel and effective therapeutic strategies for the treatment of vascular diseases.
Connectome-based individualized prediction of loneliness

Abstract Loneliness is an increasingly prevalent condition linking with enhanced morbidity and premature mortality. Despite recent proposal on medicalization of loneliness, so far no effort has been made to establish a model capable of predicting loneliness at the individual level. Here, we applied a machine-learning approach to decode loneliness from whole-brain resting-state functional connectivity (RSFC). The relationship between whole-brain RSFC and loneliness was examined in a linear predictive model. The results revealed that individual loneliness could be predicted by within- and between-network connectivity of prefrontal, limbic and temporal systems, which are involved in cognitive control, emotional processing and social perceptions and communications, respectively. Key nodes that contributed to the prediction model comprised regions previously implicated in loneliness, including the dorsolateral prefrontal cortex, lateral orbital frontal cortex, ventromedial prefrontal cortex, caudate, amygdala and temporal regions. Our findings also demonstrated that both loneliness and associated neural substrates are modulated by levels of neuroticism and extraversion. The current data-driven approach provides the first evidence on the predictive brain features of loneliness based on organizations of intrinsic brain networks. Our work represents initial efforts in the direction of making individualized prediction of loneliness that could be useful for diagnosis, prognosis and treatment.
Why Women Are Not Talking About It: Reasons for Nondisclosure of Sexual Victimization and Associated Symptoms of Posttraumatic Stress Disorder and Depression

Disclosure of traumatic experiences is typically encouraged and associated with positive outcomes. However, there is limited research on nondisclosure of sexual trauma and consequent symptomology. This online study of undergraduate females examines reasons for nondisclosure and associated symptoms of posttraumatic stress disorder (PTSD) and depression. Of 221 participants who reported sexual victimization, 25% had not previously disclosed it. Four reasons for nondisclosure were identified: shame, minimization of experience, fear of consequences, and privacy. Nondisclosers who minimized the experience and nondisclosers low on shame reported fewer PTSD symptoms than disclosers. These findings suggest that reasons for nondisclosure are associated with symptomology.
The discovery and development of topical medicines for wound healing

ABSTRACT Introduction: Chronic, nonhealing skin wounds claim >3% of the health-care budget in industrialized countries, and the incidence is rising. Currently, two parallel trends influence innovations within the field of wound healing: the need to reduce spread of antibiotic resistance and the emerging use of health economy and value-based models. Areas covered: This review focuses on the discovery of drug candidates and development of treatments aiming to enhance wound healing in the heterogeneous group of patients with nonhealing wounds. Expert opinion: Nonhealing wounds are multifaceted and recognized as difficult indications. The majority of products currently in use are medical device dressings, or concepts of negative pressure or hyperbaric oxygen treatment. Global best practice guidelines for the treatment of diabetic foot ulcers recommend debridement, redressing, as well as infection control, and are critical to the lack of coherent clinical evidence for many approved products in active wound care. To accelerate wound healing, there is an emerging trend toward biologics, gene therapy, and novel concepts for drug delivery in research and in the pipeline for clinical trials. Scientific delineation of the therapeutic mechanism of action is, in our opinion, vital for clinical trial success and for an increased fraction of medical products in the pharmaceutical pipeline.
RETRACTED ARTICLE: The biological function of long noncoding RNA FAL1 in oesophageal carcinoma cells

Abstract We, the Editors and Publisher of the journal Artificial Cells, Nanomedicine, and Biotechnology, have retracted the following article: Zhiguo Yang, Dongyan Liu, Dan Wu, Fang Liu & Cuiping Liu (2019) The biological function of long noncoding RNA FAL1 in oesophageal carcinoma cells. Artificial Cells, Nanomedicine, and Biotechnology, 47:1, 896–903, DOI: 10.1080/21691401.2019. 1573738 It has come to our attention that the full authorship list and affiliations for this manuscript, including the study site and ethics committee, were changed after the article was submitted. We have contacted the corresponding author for an explanation, but we have not received a satisfactory explanation. As determining authorship and the location of where the research was conducted is core to the integrity of published work, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.
Serum Concentration of Genistein, Luteolin and Colorectal Cancer Prognosis

Although flavonoid phytoestrogens have been suggested to be associated with reduced risk of colorectal cancer (CRC), their influence on CRC prognosis remains uncertain. A population-based cohort of 2051 patients diagnosed with stage I–III CRC in southwest Germany in 2003–2010 were followed for five years. Post-diagnostic serum concentration of genistein and luteolin were measured using Ultra-Performance Liquid Chromatography with mass spectrometry. Multivariable Cox regression analysis was conducted to calculate the Hazard Ratios (HRs) and 95% confidence interval (CI) for the association between flavonoids concentration and overall morality, CRC-specific mortality, CRC recurrence, and disease-free survival (DFS). Median (interquartile range) serum concentration of genistein and luteolin was 11.90 ng/µL (10.08–14.13) and 7.20 ng/µL (6.40–8.16), respectively. Neither serum genistein nor luteolin was associated with CRC prognosis. There was no clear evidence of departure from linearity. However, the association might be differential by adjuvant chemotherapy. Associations pointed towards lower risk in patients who received chemotherapy and higher risk in those without chemotherapy for overall mortality regarding serum genistein (P-interaction = 0.02) and correspondingly for CRC recurrence (P-interaction: 0.03) and DFS (P-interaction: 0.01) with respect to luteolin. Our study provides little evidence that serum genistein and luteolin are associated with colorectal cancer prognosis. Future studies are warranted to evaluate the potential interaction with adjuvant chemotherapy.
Inorganic nitrate, hypoxia, and the regulation of cardiac mitochondrial respiration—probing the role of PPARα

Dietary inorganic nitrate prevents aspects of cardiac mitochondrial dysfunction induced by hypoxia, although the mechanism is not completely understood. In both heart and skeletal muscle, nitrate increases fatty acid oxidation capacity, and in the latter case, this involves up‐regulation of peroxisome proliferator‐activated receptor (PPAR)α expression. Here, we investigated whether dietary nitrate modifies mitochondrial function in the hypoxic heart in a PPARα‐dependent manner. Wild‐type (WT) mice and mice without PPARα (Ppara−/−) were given water containing 0.7 mM NaCl (control) or 0.7 mM NaNO3 for 35 d. After 7 d, mice were exposed to normoxia or hypoxia (10% O2) for the remainder of the study. Mitochondrial respiratory function and metabolism were assessed in saponin‐permeabilized cardiac muscle fibers. Environmental hypoxia suppressed mass‐specific mitochondrial respiration and additionally lowered the proportion of respiration supported by fatty acid oxidation by 18% (P < 0.001). This switch away from fatty acid oxidation was reversed by nitrate treatment in hypoxic WT but not Ppara−/− mice, indicating a PPARα‐dependent effect. Hypoxia increased hexokinase activity by 33% in all mice, whereas lactate dehydrogenase activity increased by 71% in hypoxic WT but not Ppara−/− mice. Our findings indicate that PPARα plays a key role in mediating cardiac metabolic remodeling in response to both hypoxia and dietary nitrate supplementation. —Horscroft, J. A. , O'Brien, K. A. , Clark, A. D. , Lindsay, R. T. , Steel, A. S. , Procter, N. E. K. , Devaux, J., Frenneaux, M. , Harridge, S. D. R. , Murray, A. J. Inorganic nitrate, hypoxia, and the regulation of cardiac mitochondrial respiration—probing the role of PPARα. FASEB J. 33, 7563–7577 (2019). www.fasebj. org
Effects of Video Encoding on Camera-Based Heart Rate Estimation

Objective: Public databases are important for evaluating and comparing different methods and algorithms for camera-based heart rate estimation. Because uncompressed video requires huge file sizes, a need for compression algorithms exists to store and share video data. Due to the optimization of modern video codecs for human perception, video compression can influence heart rate estimation negatively by reducing or eliminating small color changes of the skin (PPG) that are needed for camera based heart rate estimation. In this paper, we contribute a comprehensive analysis to answer the question of how to compress video without compromising PPG information. Methods: To analyze the influence of video compression, we compare the effect of several encoding parameters: two modern encoders (H264, H265), compression rate, resolution changes using different scaling algorithms, color subsampling, and file size on two publicly available datasets. Results: We show that increasing the compression rate decreases the accuracy of heart rate estimation, but that resolution can be reduced (up to a cutoff point) and color subsampling can be applied for reducing file size without a big impact on heart rate estimation. Conclusions: From the results, we derive and propose guidelines for the recording and encoding of video data for camera-based heart rate estimation. Significance: The paper can sensitize the research community toward the problems of video encoding, and the proposed recommended practices can help with conducting future experiments and creating valuable datasets that can be shared publicly. Such datasets would improve comparability and reproducibility in the research field.
Irregular eating patterns associate with hypomanic symptoms in bipolar disorders

ABSTRACT Objective: We present novel dimensional methods to describe the timing of eating in psychopathology. We focused on the relationship between current mood in bipolar disorder (BD) and the stability of the temporal pattern of daily eating events. Methods: Consenting BD patients (n = 69) from an outpatient, tertiary care clinic completed hourly charts of mood and eating for two weeks. Mood was also evaluated with Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS). Results: Illustrative displays, or eatograms, enabling visualization of all recorded eating events were used to guide assessment of the temporal structure of eating across the two week assessment period. We computed indices to quantify irregularities in timing of eating, namely IFRQ, ITIM and IINT for the variability of frequency, timing, and interval of eating events, respectively. In this cohort, irregular temporal pattern of eating correlated with hypomanic symptoms (YMRS with IFRQ, Spearman rank order rh = 0.28, p = .019, with ITIM, rh = 0.44, p < .001, and with IINT rh = 0.38, p = .001), but not depressive symptoms or anthropometric measures. Conclusions: Our data suggest a link between the instability of the temporal order of daily eating and mood. The dimensional measures for eating pattern introduced here enable future investigations of correlations with psychopathology. GRAPHICAL ABSTRACT
High‐Sensitivity Cardiac Troponin After Cardiac Stress Test: A Systematic Review and Meta‐Analysis

Background The recent introduction of high‐sensitivity cardiac troponin (hs‐cTn) assays has allowed clinicians to measure hs‐cTn before and after cardiac stress testing, but the hs‐cTn release pattern and potential utility in identifying inducible myocardial ischemia are unclear. We thus conducted a systematic review and meta‐analysis to improve our understanding of hs‐cTn release associated with exercise and pharmacological stress testing. Methods and Results Studies published between January 2008 and July 2016 that reported hs‐cTn change values (high‐sensitivity cardiac troponin T [hs‐cTnT] or high‐sensitivity cardiac troponin I [hs‐cTnI]) in relation to cardiac stress testing were searched and reviewed by 2 independent screeners. Primary outcomes were pooled estimates of absolute and relative hs‐cTn changes after cardiac stress test, stratified by the presence of inducible myocardial ischemia. This meta‐analysis included 11 studies (n=2432 patients). After exercise stress testing, hs‐cTnT increased by 0.5 ng/L or 11% (6 studies, n=406) and hs‐cTnI by 2.4 ng/L or 41% (4 studies, n=365) in patients with inducible myocardial ischemia versus hs‐cTnT by 1.1 ng/L or 18% (8 studies, n=629; P=0.29) and hs‐cTnI by 1.8 ng/L or 72% (4 studies, n=831; P=0.61) in patients who did not develop inducible myocardial ischemia. After pharmacological stress test, hs‐cTnT changed by −0.1 ng/L or −0.4% (6 studies, n=251) and hs‐cTnI by 2.4 ng/L or 32% (2 studies, n=108) in patients with inducible myocardial ischemia versus hs‐cTnT by 0.7 ng/L or 11% (5 studies, n=443, P=0.44) and hs‐cTnI by 1.7 ng/L or 38% (2 studies, n=116; P=0.62) in patients who did not develop inducible myocardial ischemia. Conclusions hs‐cTn rising patterns after exercise and pharmacological stress testing appear inconsistent and comparably small, and do not appear to be correlated with inducible myocardial ischemia.
Lemon: a framework for rapidly mining structural information from the Protein Data Bank

Abstract Motivation The Protein Data Bank (PDB) currently holds over 140 000 biomolecular structures and continues to release new structures on a weekly basis. The PDB is an essential resource to the structural bioinformatics community to develop software that mine, use, categorize and analyze such data. New computational biology methods are evaluated using custom benchmarking sets derived as subsets of 3D experimentally determined structures and structural features from the PDB. Currently, such benchmarking features are manually curated with custom scripts in a non-standardized manner that results in slow distribution and updates with new experimental structures. Finally, there is a scarcity of standardized tools to rapidly query 3D descriptors of the entire PDB. Results Our solution is the Lemon framework, a C++11 library with Python bindings, which provides a consistent workflow methodology for selecting biomolecular interactions based on user criterion and computing desired 3D structural features. This framework can parse and characterize the entire PDB in <10 min on modern, multithreaded hardware. The speed in parsing is obtained by using the recently developed MacroMolecule Transmission Format to reduce the computational cost of reading text-based PDB files. The use of C++ lambda functions and Python bindings provide extensive flexibility for analysis and categorization of the PDB by allowing the user to write custom functions to suite their objective. We think Lemon will become a one-stop-shop to quickly mine the entire PDB to generate desired structural biology features. Availability and implementation The Lemon software is available as a C++ header library along with a PyPI package and example functions at https://github.com/chopralab/lemon. Supplementary information Supplementary data are available at Bioinformatics online.
To What Degree Are the 13 Entrustable Professional Activities Already Incorporated Into Physicians’ Performance Schemas for Medical Students?

Abstract Phenomenon: There is an abundance of literature on Entrustable Professional Activities (EPAs) in theory, but there are few studies on the EPAs in practice for undergraduate clinical education. In addition, little is known about the degree to which the EPAs are or are not aligned with physician assessors’ performance schemas of the clerkship student. Investigating the degree to which physician assessors’ performance schemas are already aligned with the activities described by the EPAs is critical for effective workplace assessment design. Approach: We sampled 1,032 areas of strength (strength) and areas for improvement (improvement) written evaluation comments by 423 physician assessors for clerkship students’ performance in academic years 2014–15 and 2015–16 at the University of Utah School of Medicine. Two researchers independently categorized each comment by EPA and/or coded by non-EPA topic. The proportion of comment types was compared between strength comments and improvement comments with the Wilcoxon Signed-Rank Test. Findings: The most frequently mentioned EPAs in comments were about history gathering/physical exam, differential diagnosis, documentation, presentation, and interprofessional collaboration; few mentioned diagnostic tests, patient handovers, recognition of urgent patient care, and patient safety, and none mentioned orders/prescriptions and informed consent. The most frequent non-EPA topics were about medical knowledge, need to read more, learning attitude, work ethic, professionalism/maturity, and receptiveness to feedback. The proportion of comments aligned with an EPA only, a non-EPA topic only, or both an EPA and non-EPA topic was significantly different for clerkship students’ strength compared to improvement. Insights: Physician assessors’ performance schemas for clerkship students were aligned with EPAs to varying degrees depending on the specific EPA and whether describing strength or improvement. Of interest, the frequently mentioned non-EPA comments represented some of the competencies that contribute to effectively performing particular EPAs and are Accreditation Council for Graduate Medical Education (ACGME) core competencies (e.g., medical knowledge, professionalism), used in residency programs. Because physician assessors for undergraduate medical education often also participate in graduate medical education, the frequency of non-EPA topics aligned to ACGME competencies may suggest influence of graduate medical education evaluative frameworks on performance schemas for clerkship students; this could be important when considering implementation of EPAs in undergraduate medical education.