Miracle-dz/UniFAR-FTUs huggingface dataset:
Transformer- and Generative Adversarial Network–Based Inpatient Traditional Chinese Medicine Prescription Recommendation: Development Study

Background Traditional Chinese medicine (TCM) practitioners usually follow a 4-step evaluation process during patient diagnosis: observation, auscultation, olfaction, inquiry, pulse feeling, and palpation. The information gathered in this process, along with laboratory test results and other measurements such as vital signs, is recorded in the patient’s electronic health record (EHR). In fact, all the information needed to make a treatment plan is contained in the EHR; however, only a seasoned TCM physician could use this information well to make a good treatment plan as the reasoning process is very complicated, and it takes years of practice for a medical graduate to master the reasoning skill. In this digital medicine era, with a deluge of medical data, ever-increasing computing power, and more advanced artificial neural network models, it is not only desirable but also readily possible for a computerized system to mimic the decision-making process of a TCM physician. Objective This study aims to develop an assistive tool that can predict prescriptions for inpatients in a hospital based on patients’ clinical EHRs. Methods Clinical health records containing medical histories, as well as current symptoms and diagnosis information, were used to train a transformer-based neural network model using the corresponding physician’s prescriptions as the target. This was accomplished by extracting relevant information, such as the patient’s current illness, medicines taken, nursing care given, vital signs, examinations, and laboratory results from the patient’s EHRs. The obtained information was then sorted chronologically to produce a sequence of data for the patient. These time sequence data were then used as input to a modified transformer network, which was chosen as a prescription prediction model. The output of the model was the prescription for the patient. The ultimate goal is for this tool to generate a prescription that matches what an expert TCM physician would prescribe. To alleviate the issue of overfitting, a generative adversarial network was used to augment the training sample data set by generating noise-added samples from the original training samples. Results In total, 21,295 copies of inpatient electronic medical records from Guang’anmen Hospital were used in this study. These records were generated between January 2017 and December 2018, covering 6352 types of medicines. These medicines were sorted into 819 types of first-category medicines based on their class relationships. As shown by the test results, the performance of a fully trained transformer model can have an average precision rate of 80.58% and an average recall rate of 68.49%. Conclusions As shown by the preliminary test results, the transformer-based TCM prescription recommendation model outperformed the existing conventional methods. The extra training samples generated by the generative adversarial network help to overcome the overfitting issue, leading to further improved recall and precision rates.
PHACT: Phylogeny-Aware Computing of Tolerance for Missense Mutations

Abstract Evolutionary conservation is a fundamental resource for predicting the substitutability of amino acids and the loss of function in proteins. The use of multiple sequence alignment alone—without considering the evolutionary relationships among sequences—results in the redundant counting of evolutionarily related alteration events, as if they were independent. Here, we propose a new method, PHACT, that predicts the pathogenicity of missense mutations directly from the phylogenetic tree of proteins. PHACT travels through the nodes of the phylogenetic tree and evaluates the deleteriousness of a substitution based on the probability differences of ancestral amino acids between neighboring nodes in the tree. Moreover, PHACT assigns weights to each node in the tree based on their distance to the query organism. For each potential amino acid substitution, the algorithm generates a score that is used to calculate the effect of substitution on protein function. To analyze the predictive performance of PHACT, we performed various experiments over the subsets of two datasets that include 3,023 proteins and 61,662 variants in total. The experiments demonstrated that our method outperformed the widely used pathogenicity prediction tools (i.e., SIFT and PolyPhen-2) and achieved a better predictive performance than other conventional statistical approaches presented in dbNSFP. The PHACT source code is available at https://github.com/CompGenomeLab/PHACT.
Mussel-inspired polyurethane coating for bio-surface functionalization to enhance substrate adhesion and cell biocompatibility

Abstract Considerable implant materials are prone to cause a severe inflammatory reaction due to poor histocompatibility, which leads to various complications and implant failure. Surface coating modification of these implant materials is one of the most important techniques to settle this problem. However, fabricating a coating with both adequate adhesiveness and excellent biocompatibility remains a challenge. Inspired by the adhesion mechanism of mussels, a series of mussel-inspired polyurethanes (PU-LDAs) were synthysized through a step growth polymerization based on hexamethylene diisocyanate as a hard segment, polytetra-methylene-ether-glycol as a soft segment, lysine–dopamine (LDA) and butanediol as chain extenders with different mole ratios.The coatings of PU-LDAs were applied to various substrates, such as stainless steel, glass and PP using a facile one-step coating process. The introduction of 3,4-dihydroxyphenylalanine (DOPA) groups can greatly improve the adhesion ability of the coatings to the substrates demonstrated by a 180° peel test. The peel strength of the PU-LDA100 coating containing high LDA content was 76.3, 48.5 and 67.5 N/m, which was 106.2%, 246.4% and 192.2% higher than that of the PU-LDA00 coating without LDA on the surface of stainless steel, glass and PP, respectively. Meanwhile, this PU coating has a lower immune inflammatory response which provides a universal method for surface modification of implant materials. Moreover, the DOPA groups in PU-LDAs could combine with the amino and thiol groups on cell membrane surface, leading to the improvement of cell adhesion and growth. Therefore, it has great potential application in the field of biomedical implant materials for the clinic.
OmicsNet 2.0: a web-based platform for multi-omics integration and network visual analytics

Abstract Researchers are increasingly seeking to interpret molecular data within a multi-omics context to gain a more comprehensive picture of their study system. OmicsNet (www.omicsnet.ca) is a web-based tool developed to allow users to easily build, visualize, and analyze multi-omics networks to study rich relationships among lists of ‘omics features of interest. Three major improvements have been introduced in OmicsNet 2.0, which include: (i) enhanced network visual analytics with eleven 2D graph layout options and a novel 3D module layout; (ii) support for three new ‘omics types: single nucleotide polymorphism (SNP) list from genetic variation studies; taxon list from microbiome profiling studies, as well as liquid chromatography–mass spectrometry (LC–MS) peaks from untargeted metabolomics; and (iii) measures to improve research reproducibility by coupling R command history with the release of the companion OmicsNetR package, and generation of persistent links to share interactive network views. We performed a case study using the multi-omics data obtained from a recent large-scale investigation on inflammatory bowel disease (IBD) and demonstrated that OmicsNet was able to quickly create meaningful multi-omics context to facilitate hypothesis generation and mechanistic insights.
Feasibility, safety, and patient-reported outcomes 90 days after same-day total knee arthroplasty: a matched cohort study.

BACKGROUND AND PURPOSE Despite increased attention to and acceptance of fast-track procedures, there is a lack of studies concerning discharge on the day of surgery (DOS) following total knee arthroplasty (SD-TKA). We evaluated the feasibility of SD-TKA, and compared safety and patient-reported outcomes (PROs) between patients undergoing SD-TKA and patients undergoing standard TKA. PATIENTS AND METHODS A SD-TKA group (n = 101) was matched 1:1 to a standard TKA group (n = 101) on age, sex, and ASA score. Feasibility (being discharged on DOS), safety (unplanned contacts and complications evaluated by telephone calls (2 weeks), outpatient visits (2 weeks), and readmission (90 days)) were assessed. Further, Oxford Knee Score (OKS) and Visual Analogue Scale (VAS) (pain at rest and activity) were reported (90 days). RESULTS 89 of 101 SD-TKA patients were discharged on DOS. The number of telephone calls (≤ 83) and outpatient visits (12) were similar in the 2 groups. The number of readmissions was ≤ 3 in both groups, and only 1 of the readmissions was related to TKA surgery. No differences were found at 90-day follow-up in terms of OKS (34 in both groups) or VAS (rest: SD-TKA = 7 and standard TKA = 8; activity: SD-TKA = 17 and standard TKA = 15). INTERPRETATION SD-TKA is feasible in a selected group of patients, and safety and PROs are comparable to patients undergoing standard TKA.
Exploring the molecular interaction of pheniramine with Enterococcus faecalis homoserine kinase: In‐silico studies

Infections caused by the bacteria Enterococcus faecalis (also known as E. faecalis) are common in hospitals. This bacterium is resistant to a wide range of medicines and causes a variety of nosocomial infections. An increase in the number of infections caused by multidrug‐resistant (MDR) bacteria is causing substantial economic and health issues around the world. Consequently, new therapeutic techniques to tackle the growing threat of E. faecalis infections must be developed as soon as possible. In this regard, we have targeted a protein that is regarded to be critical for the survival of bacteria in this experiment. Homoserine kinase (HSK) is a threonine metabolism enzyme that belongs to the GHMP kinase superfamily. It is a crucial enzyme in threonine metabolism. This enzyme is responsible for a critical step in the threonine biosynthesis pathway. Given the important function that E. faecalis Homoserine Kinase (ESK) plays in bacterial metabolism, we report here cloning, expression, purification and structural studies of E. faecalis HSK using homology modelling. In addition, we have reported on the model's molecular docking and Molecular Dynamic Stimulation (MD Stimulation) investigations to validate the results of the docking experiments. The results were promising. In silico investigations came up with the conclusion: pheniramine has good binding affinity for the E. faecalis HSK.
Packaging and thermal management for kw/cm2 rl microwave amplifiers

This research is to develop a practical and affordable technique of packaging for the emerging wide bandgap (SiC, GaN) microwave power amplifiers with a power density up to 1 kW/cm 2 . This high power density packaging system consists of a hybrid multichip power module and an integrated microchannel cooling heat sink. A hybrid assembly of AlN ceramic coating and the AlSiC sheet acts as the substrate and baseplate. The AlN coated AlSiC is then attached with a networking microchannel heat sink also made of AlSiC. Such heatsink has the capacity: (1) heat flux, 1kw/cm 2 ; (2) uniform junction temperature among the array within 2°C; (3) thermal resistance of package less than 0.10°C cm 2 /W (the junction temperature increase less than 100°C); and (4) robust and scalable structure. Such heatsink can be fabricated by a micromaching or EDM (Electrical Discharge Machining). A mathematical modeling and computer simulation using a FEA (Finite Element Analysis) is also presented.
Reader reaction to “Outcome‐adaptive lasso: Variable selection for causal inference” by Shortreed and Ertefaie (2017)

Shortreed and Ertefaie introduced a clever propensity score variable selection approach for estimating average causal effects, namely, the outcome adaptive lasso (OAL). OAL aims to select desirable covariates, confounders, and predictors of outcome, to build an unbiased and statistically efficient propensity score estimator. Due to its design, a potential limitation of OAL is how it handles the collinearity problem, which is often encountered in high‐dimensional data. As seen in Shortreed and Ertefaie, OAL's performance degraded with increased correlation between covariates. In this note, we propose the generalized OAL (GOAL) that combines the strengths of the adaptively weighted L1 penalty and the elastic net to better handle the selection of correlated covariates. Two different versions of GOAL, which differ in their procedure (algorithm), are proposed. We compared OAL and GOAL in simulation scenarios that mimic those examined by Shortreed and Ertefaie. Although all approaches performed equivalently with independent covariates, we found that both GOAL versions were more performant than OAL in low and high dimensions with correlated covariates.
Associations of serum n–3 and n–6 polyunsaturated fatty acids with prevalence and incidence of nonalcoholic fatty liver disease

ABSTRACT Background Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver diseases worldwide, and lifestyle and diet are significant factors in its development. Recent studies have suggested that dietary fat quality is associated with the development of NAFLD. Objectives Our purpose was to investigate the cross-sectional and longitudinal associations of serum n–3 (ω-3) and n–6 (ω-6) PUFAs with NAFLD among middle-aged and older men and women from eastern Finland. We also investigated the associations of estimated Δ5-desaturase and Δ6-desaturase activities, enzymes involved in PUFA metabolism, with NAFLD. Methods After exclusions, the cross-sectional analyses included 1533 men examined in 1984–1989 and 674 men and 870 women examined in 1998–2001 in the Kuopio Ischaemic Heart Disease Risk Factor Study. The longitudinal analyses included 520 men examined in 1991–1993 and 301 men and 466 women examined in 2005–2008. Fatty liver index (FLI) was used as a surrogate for NAFLD. Hepatic steatosis was defined as FLI >60. ANCOVA and logistic regression were used for analyses. Results In the longitudinal analyses, participants with higher serum concentrations of total n–6 PUFA and linoleic acid, the major n–6 PUFA, had markedly lower FLI and lower odds for hepatic steatosis (e.g., odds ratios for incident hepatic steatosis in the highest compared with lowest quartiles were ≤0.41), whereas serum γ-linolenic acid concentration was associated with a higher FLI and higher odds for hepatic steatosis. The associations with the other PUFAs were generally weaker and nonsignificant. In the cross-sectional analyses, also the long-chain n–3 PUFAs had inverse associations. In most analyses, high estimated Δ5-desaturase activity was associated with lower risk and high estimated Δ6-desaturase activity with higher risk for NAFLD. Conclusions In middle-aged and older Finnish adults, higher serum concentrations of total n–6 PUFAs and linoleic acid were associated with lower odds for future NAFLD.
Genome Assembly and Evolutionary Analysis of the Mandarin Duck Aix galericulata Reveal Strong Genome Conservation among Ducks

Abstract The mandarin duck, Aix galericulata, is popular in East Asian cultures and displays exaggerated sexual dimorphism, especially in feather traits during breeding seasons. We generated and annotated the first mandarin duck de novo assembly, which was 1.08 Gb in size and encoded 16,615 proteins. Using a phylogenomic approach calibrated with fossils and molecular divergences, we inferred that the last common ancestor of ducks occurred 13.3–26.7 Ma. The majority of the mandarin duck genome repetitive sequences belonged to the chicken repeat 1 (CR1) retroposon CR1-J2_Pass, which underwent a duck lineage-specific burst. Synteny analyses among ducks revealed infrequent chromosomal rearrangements in which breaks were enriched in LINE retrotransposons and DNA transposons. The calculation of the dN/dS ratio revealed that the majority of duck genes were under strong purifying selection. The expanded gene families in the mandarin duck are primarily involved in olfactory perception as well as the development and morphogenesis of feather and branching structures. This new reference genome will improve our understanding of the morphological and physiological characteristics of ducks and provide a valuable resource for functional genomics studies to investigate the feather traits of the mandarin duck.
The Role of Physical Activity in Long-term Weight Loss: 36-month Results From a Randomized Controlled Trial.

BACKGROUND Physical activity (PA) may promote long-term weight loss, but facilitating high levels of PA in behavioral weight loss programs is challenging. PURPOSE This study reports the 36-month follow-up of a behavioral weight loss trial that tested the efficacy of increasing the emphasis on PA during treatment and using traditional or acceptance-based therapy (ABT) for this purpose. We also examined the extent to which long-term weight loss differed by PA pattern and tested if individual differences in eating behavior moderated this relationship. METHODS Participants (N = 320) were randomized to (1) standard behavioral weight loss treatment (BT), (2) BT with a focus on PA, or (3) ABT with a focus on PA. Weight loss and PA were measured at 24- and 36-month follow-up. RESULTS There were no differences between conditions in weight loss or PA at 24 or 36 months. Participants consistently engaging in high PA experienced the greatest weight losses. The positive impact of PA on weight loss was more pronounced among those with low emotional eating and those who believed that exercise did not affect their appetite. CONCLUSIONS Findings emphasize the difficulty of improving long-term PA among adults with overweight/obesity beyond what standard behavioral weight loss treatment achieves. This study highlights the need to develop new PA treatment strategies, and suggests that ABT for weight loss may be more effective when applied to eating behavior versus PA. Results also demonstrate the importance of addressing problematic eating behavior and cognitions to fully realize the benefits of PA for weight loss. CLINICAL TRIAL INFORMATION ClinicalTrials.gov identifier: NCT02363010.
Deletion of cox7c Results in Pan-Azole Resistance in Aspergillus fumigatus

In Aspergillus fumigatus, the most prevalent resistance to azoles results from mutational modifications of the azole target protein Cyp51A, but there are non-cyp51A mutants resistant to azoles, and the mechanisms underlying the resistance of these strains remain to be explored. Here, we identified a novel cytochrome c oxidase, cox7c (W56*), nonsense mutation in the laboratory and found that it caused reduced colony growth and resistance to multiantifungal agents. ABSTRACT In Aspergillus fumigatus, the most prevalent resistance to azoles results from mutational modifications of the azole target protein Cyp51A, but there are non-cyp51A mutants resistant to azoles, and the mechanisms underlying the resistance of these strains remain to be explored. Here, we identified a novel cytochrome c oxidase, cox7c (W56*), nonsense mutation in the laboratory and found that it caused reduced colony growth and resistance to multiantifungal agents. Meanwhile, we revealed that cold storage is responsible for increased tolerance of conidia to itraconazole (ITC) stress, which further advances azole-resistant mutations (cryopreservation→ITC tolerance→azole resistance). The deletion or mutation of cox7c results explicitly in resistance to antifungal-targeting enzymes, including triazoles, polyenes, and allylamines, required for ergosterol synthesis, or resistance to fungal ergosterol. A high-performance liquid chromatography (HPLC) assay showed that the cox7c knockout strain decreased intracellular itraconazole concentration. In addition, the lack of Cox7c resulted in the accumulation of intracellular heme B. We validated that an endogenous increase in, or the exogenous addition of, heme B was capable of eliciting azole resistance, which was in good accordance with the phenotypic resistance analysis of cox7c mutants. Furthermore, RNA sequencing verified the elevated transcriptional expression levels of multidrug transport genes. Additionally, lower itraconazole-induced reactive oxygen species generation in mycelia of a cox7c-deletion strain suggested that this reduction may, in part, contribute to drug resistance. These findings increase our understanding of how A. fumigatus’s direct responses to azoles promote fungal survival in the environment and address genetic mutations that arise from patients or environments.
Engineering interactions between superconducting qubits and phononic nanostructures

Nanomechanical systems made from phononic crystals can act as highly coherent microwave-frequency circuits at cryogenic temperatures. However, generating sufficient coupling between these devices and microwave superconducting quantum circuits is challenging due to the vastly different length scales of acoustic and electrical excitations. Here we demonstrate a general recipe for calculating these interactions and show that large piezoelectric coupling rates between microwave superconducting circuits containing Josephson junctions and nanoscale phononic resonances are possible, suggesting a route to phononic crystal circuits and systems that are nonlinear at the single-phonon level.
Information concealment in palliative patients: Development and pilot study of a new scale for caregivers

Abstract Previous studies on palliative care have assessed the phenomenon of Information Concealment (IC), confirmed its relevance and emphasised the need to have a scale for its assessment. The aim of this study was to design and validate such an instrument. The sample comprised 150 palliative caregivers (23 men and 127 women). The dimensionality of the items of the Information Concealment Scale for Caregivers (ECOI) was assessed using Exploratory Factor Analysis and an optimal implementation of parallel analysis. Reliability and criterion validity were analysed using sample data. The ECOI comprises three factors: Concealment or dissimulation about the disease, misrepresentation of the real situation and control of the information. The scale has excellent reliability and shows criterion validity. Therefore, the ECOI is a reliable and valid instrument to objectively measure IC among Spanish caregivers in palliative care settings.