Miracle-dz/UniFAR-FTUs huggingface dataset:
Toward Structurally Novel and Metabolically Stable HIV-1 Capsid-Targeting Small Molecules

HIV-1 capsid protein (CA) plays an important role in many steps of viral replication and represents an appealing antiviral target. Several CA-targeting small molecules of various chemotypes have been studied, but the peptidomimetic PF74 has drawn particular interest due to its potent antiviral activity, well-characterized binding mode, and unique mechanism of action. Importantly, PF74 competes against important host factors for binding, conferring highly desirable antiviral phenotypes. However, further development of PF74 is hindered by its prohibitively poor metabolic stability, which necessitates the search for structurally novel and metabolically stable chemotypes. We have conducted a pharmacophore-based shape similarity search for compounds mimicking PF74. We report herein the analog synthesis and structure-activity relationship (SAR) of two hits from the search, and a third hit designed via molecular hybridization. All analogs were characterized for their effect on CA hexamer stability, antiviral activity, and cytotoxicity. These assays identified three active compounds that moderately stabilize CA hexamer and inhibit HIV-1. The most potent analog (10) inhibited HIV-1 comparably to PF74 but demonstrated drastically improved metabolic stability in liver microsomes (31 min vs. 0.7 min t1/2). Collectively, the current studies identified a structurally novel and metabolically stable PF74-like chemotype for targeting HIV-1 CA.
Early rehabilitation in cardiology – heart failure: The ERIC-HF protocol, a novel intervention to decompensated heart failure patients rehabilitation

Background: Decompensated heart failure patients are characterised by functional dependence and low exercise tolerance. Aerobic exercise can improve symptoms, functional capacity and an increase in exercise tolerance. However, the benefits of early rehabilitation have not yet been validated. Objective: To evaluate the safety and feasibility of an aerobic exercise training programme in functional capacity of decompensated heart failure patients. Methodology: A single centre, parallel, randomised controlled, open label trial, with 100 patients. The training group (TG, n=50) performed the training protocol and the control group (CG, n=50) performed the usual rehabilitation procedures. The London chest activity of daily living (LCADL) scale, the Barthel index (BI) and the 6 minute walking test (6MWT) at discharge were used to evaluate the efficacy of the protocol. Safety was measured by the existence of adverse events. Results: The mean age of the patients was 70 years, 20% were New York Heart Association (NYHA) class IV and 80% NYHA class III at admission. The major heart failure aetiology was ischaemic (35 patients) and valvular disease (25 patients). There were no significant differences between groups at baseline in terms of sociodemographic or pathophysiological characteristics. There was a statistically significant difference of 54.2 meters for the training group (P=0.026) in the 6MWT and at LCADL 12 versus 16 (P=0.003), but the BI did not: 96 versus 92 (P=0.072). No major adverse events occurred. Conclusions: The training protocol demonstrated safety and efficacy, promoting functional capacity. This study elucidated about the benefits of a systematised implementation of physical exercise during the patient’s clinical stabilisation phase, which had not yet been demonstrated. Trial registration: Clinicaltrials.gov NCT03838003, URL: https://clinicaltrials.gov/ct2/show/NCT03838003.
Effectiveness of Motivational Interviewing in Regard to Activities of Daily Living and Motivation for Rehabilitation among Stroke Patients

Background: Stroke patients urgently need rehabilitation to enhance activities of daily living. This study aims to determine whether motivational interviewing (MI) improves the performance of activities of daily living and enhances motivation for rehabilitation among first-stroke patients. Methods: A quasi-experimental design was used in this study. The study recruited 65 patients between March and October 2016. Before the intervention, all patients received routine care. The experimental group (n = 33) received weekly sessions of MI for 6 weeks, whereas the control group (n = 32) received individual attention from a research nurse weekly for 6 weeks. Structured questionnaires were used to collect data, including demographic data, activities of daily living data (Barthel index {BI} and instrumental activities of daily living {IADLs} scale), and rehabilitation motivation data. Results: The BI and IADLs scores significantly improved with time in both the experimental and control groups. The generalized estimating equation approach showed that at 6 weeks and 3 months after the intervention, the rehabilitation motivation scores in the experimental group were respectively 3.10 and 2.54 points higher than those in the control group, with significant differences. Conclusions: MI could effectively enhance motivation for rehabilitation among stroke patients.
Genome-Wide Identification, Expression Analysis and Functional Study of CCT Gene Family in Medicago truncatula

The control of flowering time has an important impact on biomass and the environmental adaption of legumes. The CCT (CO, COL and TOC1) gene family was elucidated to participate in the molecular regulation of flowering in plants. We identified 36 CCT genes in the M. truncatula genome and they were classified into three distinct subfamilies, PRR (7), COL (11) and CMF (18). Synteny and phylogenetic analyses revealed that CCT genes occurred before the differentiation of monocot and dicot, and CCT orthologous genes might have diversified among plants. The diverse spatial-temporal expression profiles indicated that MtCCT genes could be key regulators in flowering time, as well as in the development of seeds and nodules in M. truncatula. Notably, 22 MtCCT genes with typical circadian rhythmic variations suggested their different responses to light. The response to various hormones of MtCCT genes demonstrated that they participate in plant growth and development via varied hormones dependent pathways. Moreover, six MtCCT genes were dramatically induced by salinity and dehydration treatments, illustrating their vital roles in the prevention of abiotic injury. Collectively, our study provides valuable information for the in-depth investigation of the molecular mechanism of flowering time in M. truncatula, and it also provides candidate genes for alfalfa molecular breeding with ideal flowering time.
Patient‐reported experience measures are essential to improving quality of care for chronic wounds: An international qualitative study

Traditional quality measures for chronic wounds have focused on objective outcomes that are challenging to risk adjust, lack patient input, and have limited ability to inform quality improvement interventions. Patient‐reported experience measures (PREMs) provide information from the patient perspective regarding health care quality and have potential to improve patient‐centredness, increase care efficiency, and generate actionable data for quality improvement. The purpose of this study was to understand patient experiences and health care processes that impact quality of care among patients with chronic wounds. Sixty patients at least 18 years of age with various wound aetiologies were recruited from Canada, Denmark, The Netherlands, and the United States as part of a larger phase 1 qualitative study to develop a patient‐reported outcome measure for chronic wounds (WOUND‐Q). All patients had a chronic wound for at least 3 months, were fluent in their native speaking language, and able to participate in a one‐on‐one semi‐structured interview. Interviews were digitally recorded and transcribed verbatim. Interpretive description was used to identify recurrent themes relating to patient experience and quality of care. We identified five domains (care coordination, establishing/obtaining care, information delivery, patient‐provider interaction, and treatment delivery) and 21 sub‐domains (access to patient information, interdisciplinary communication, encounter efficiency, provider availability, specialist referral, staff professionalism, travel/convenience, modality, reciprocity, understandability/consistency, accountability, continuity, credentials, rapport, appropriateness, complication management, continuity, environment/setting, equipment and supply needs, expectation, and patient‐centred) as potential opportunities to measure and improve quality of care in the chronic wound population. PREMs for chronic wounds represent an important opportunity to engage patients and longitudinally assess quality across clinical settings and providers. Future research should focus on developing PREMs to complement traditional objective and patient‐reported outcome measures for chronic wounds.
Relationship between Individual Social Capital and Functional Ability among Older People in Anhui Province, China

This study aimed to explore the relationship between individual social capital and functional ability, with a focus on whether there is an interactive relationship that exists among social capital related to functional ability among older people in Anhui province, China. We conducted a cross-sectional study with a multi-stage stratified cluster random sampling method from July to September 2017. Data were collected through questionnaire including demographic characteristics, individual social capital status, and functional capability status. Binary logistic regression analysis model and classification and regression tree model (CART) were utilized. Overall, this study included 1810 elderly people, 43% of whom had functional disability. After the adjustment, subjects with lower social participation (AOR = 1.60; 95% CI: 1.26–2.03) and lower social connection (AOR = 1.74; 95% CI: 1.34–2.25) had an increased risk of functional disability. However, social support (AOR = 0.73; 95% CI: 0.57–0.94) was inversely related to functional ability. We also observed interactive relationship of social capital associated with functional ability, which indicated that special attention and efforts should be paid to older adults with less educational attainment, with multimorbidity, with advanced age, and with lower level of social participation, cohesion for the purpose of maintaining sound functional ability. Our findings may be of salient relevance for devising more targeted and effective interventions to prevent the onset of functional limitations among community-dwelling older adults.
Dissipative particle dynamics aided design of drug delivery systems: a review.

Nanocarrier drug delivery system, effectively assisting improve the solubility, bioavailability, and targeting of drugs in the human body, is a crucial means for treating cancer and other diseases. However, drug carriers usually possess multiple components and complex microstructures, and the studies on the formation mechanism and internal structural details of nanocarriers are still incomplete by experimental methods. In order to overcome this adversity, the dissipative particle dynamics (DPD) simulation has been widely used owing to its unique simulation time-space scale and satisfying computing efficiency. In the past decades, more and more kinds of complex nanocarrier with various structures have been successfully characterized, and influencing factors in mounting numbers have also been parameterized. Not only emphasizing on the self-assembly structure of nanocarriers, but the application area of DPD simulation has also become a complete system covering from the synthesis and preparation to interaction with the biomembrane. This article reviews the application of DPD simulations in drug delivery systems. We have established the connection between existing studies and proposed some outlooks for the further combination between DPD simulation and the design of drug delivery system.
Spastin mutations impair coordination between lipid droplet dispersion and reticulum

Lipid droplets (LD) are affected in multiple human disorders. These highly dynamic organelles are involved in many cellular roles. While their intracellular dispersion is crucial to ensure their function and other organelles-contact, underlying mechanisms are still unclear. Here we show that Spastin, one of the major proteins involved in Hereditary Spastic Paraplegia (HSP), controls LD dispersion. Spastin depletion in zebrafish affects metabolic properties and organelle dynamics. These functions are ensured by a conserved complex set of splice variants. M1 isoforms determine LD dispersion in the cell by orchestrating endoplasmic reticulum (ER) shape along microtubules (MTs). To further impact LD fate, Spastin modulates transcripts levels and subcellular location of other HSP key players, notably Seipin and REEP1. In pathological conditions, mutations in human Spastin M1 disrupt this mechanism and impacts LD network. Spastin depletion influences not only other key proteins but also modulates specific neutral lipids and phospholipids, revealing an impact on membrane and organelle components. Altogether our results show that Spastin and its partners converge in a common machinery that coordinates LD dispersion and ER shape along MTs. Any alteration of this system results in HSP clinical features and impacts lipids profile, thus opening new avenues for novel biomarkers of HSP.
Pharmacodynamic Effects of Topical Omiganan in Patients With Mild to Moderate Atopic Dermatitis in a Randomized, Placebo‐Controlled, Phase II Trial

Omiganan is an indolicidin analog with antimicrobial properties that could be beneficial for patients with atopic dermatitis. In this randomized, double‐blind, placebo‐controlled, phase II trial we explored the efficacy, pharmacodynamics, and safety of topical omiganan once daily in 36 patients with mild to moderate atomic dermatitis. Patients were randomized to apply topical omiganan 1%, omiganan 2.5%, or vehicle gel to one target lesion once daily for 28 consecutive days. Small but significant improvements in local objective SCORing Atopic Dematitis index and morning itch were observed in the omiganan 2.5% group compared with the vehicle gel group (−18.5%; 95% confidence interval, −32.9 to −1.0; P = 0.04; and −8.2; 95% confidence interval, −16.3 to −0.2; P = 0.05, respectively). A shift from lesional to nonlesional skin microbiota was observed in both omiganan treatment groups, in contrast to the vehicle group. Thus, treatment with topical omiganan improved dysbiosis in patients with mild to moderate atopic dermatitis, and small but statistically significant improvements in clinical scores were detected. Our findings warrant further exploration in future clinical trials.
Autumn Royal and Egnatia Grape Extracts differently modulate Cell Proliferation in Human Colorectal Cancer Cells.

OBJECTIVE Polyphenols extracted by table grape have been demonstrated to decrease cell proliferation in vitro and to exert anti-atherosclerotic and antithrombotic activities, regulating cell functions. Grape polyphenolic profile is affected by climate as well as grape cultivar. This study was aimed to characterize the berry skin polyphenolic composition, antioxidant activity and antiproliferative properties of two black grape cultivars, Autumn Royal and Egnatia. METHODS The phenolic composition of grape skin extracts (GSEs) was determined by HPLC analyses. The antioxidant activity was determined using DPPH, ABTS and ORAC tests. Caco2, HT29 and SW480 human colon cancer cell lines were used to test the effects of GSEs in vitro. Cell proliferation and cell cycle were assessed with the MTT method and a Muse cell analyzer, respectively. qPCR and Western Blotting analysis were used to evaluate gene and protein expression, respectively. RESULTS The total polyphenolic content and the total antioxidant capacity were significantly higher in Autumn Royal than in Egnatia. However, table grape Egnatia showed greater ability to affect cell proliferation and apoptosis, as well as to exert a growth arrest in S phase of the cell cycle, particularly in Caco2 cell line. CONCLUSION These data suggest that the new grape variety Egnatia is an interesting source of phenolic compounds that could be of interest in the food and pharmaceutical industries.
Role of Receptor for Advanced Glycation End Products

Pulmonary disease after World Trade Center particulate matter (WTC-PM) exposure is associated with dyslipidemia and the receptor for advanced glycation end products (RAGE); however, the mechanisms are not well understood.We used amurinemodel and a multiomics assessment to understand the role of RAGE in the pulmonary long-term effects of a single high-intensity exposure to WTC-PM. After 1 month, WTC-PM–exposed wild-type (WT) mice had airway hyperreactivity, whereas RAGE-deficient (Ager) mice were protected. PM-exposed WT mice also had histologic evidence of airspace disease, whereas Ager mice remained unchanged. Inflammatory mediators such as G-CSF (granulocyte colony–stimulating factor), IP-10 (IFN-g–induced protein 10), and KC (keratinocyte chemoattractant) were differentially expressed after WTC-PM exposure. WTC-PM induced a-SMA, DIAPH1 (protein diaphanous homolog 1), RAGE, and significant lung collagen deposition inWT compared withAgermice. Compared with WT mice with PM exposure, relative expression of phosphorylated to total CREB (cAMP response element–binding protein) and JNK (c-Jun N-terminal kinase) was significantly increased in the lung of PM-exposed Ager mice, whereas Akt (protein kinase B) was decreased. Random forests of the refined lung metabolomic profile classified subjects with 92% accuracy; principal component analysis captured 86.7% of the variance in three components and demonstrated prominent subpathway involvement, including known mediators of lung disease such as vitamin B6 metabolites, sphingolipids, fatty acids, and phosphatidylcholines. Treatment with a partial RAGE antagonist, pioglitazone, yielded similar fold-change expression of metabolites (N6-carboxymethyllysine, 1-methylnicotinamide, N 1Nacetylspermidine, and succinylcarnitine [C4-DC]) between WT and Ager mice exposed to WTC-PM. RAGE can mediate WTC-PM–induced airway hyperreactivity and warrants further investigation.
The Study of Correlation between Serum Vitamin D3 Concentrations and HBV DNA Levels and Immune Response in Chronic Hepatitis Patients

Chronic hepatitis B (CHB) is a common chronic disease. Previous studies have shown a link between 25-hydroxyvitamin D3 (vitamin D3) concentration and liver disease. Hepatitis B virus (HBV) infection has been attributed to the inappropriate functioning of cell-mediated immunity. However, the effects of vitamin D3, immune cell, and HBeAg status on HBV viral load in CHB patients are still unclear. We investigated the relationship between the serum concentration of vitamin D3, percentage of immune cells in peripheral blood, and the HBV viral load of CHB patients. Sixty CHB patients were recruited, and their blood samples were collected and analyzed. Vitamin D level was measured using a chemiluminescence assay. A level of 30 ng/mL or above was defined as a vitamin D3 sufficiency. We assigned vitamin D3 status as either normal (≥30 ng/mL), insufficient (20–30 ng/mL), or deficient (<20 ng/mL). T-lymphocyte and B-lymphocyte surface markers in peripheral blood were detected using flow cytometry. The factors associated with HBV viral load were analyzed using univariate and multivariate-adjusted models. The mean serum vitamin D3 concentration in the subjects was 20.9 ± 5.6 ng/mL. Up to 88.3% of the patients were either deficient in or had insufficient vitamin D3. The gender, BMI, hepatitis B surface antigen levels, and ALT levels were significantly related to serum vitamin D3 levels. Serum vitamin D3 concentration, HBe status, HBs levels, ALT, and AST levels showed a statistically significant correlation with the HBV DNA levels. Serum vitamin D3 concentrations and hepatitis B surface antigen levels were strongly correlated with HBV DNA levels. Vitamin D3 levels were significantly associated with CD19 numbers (β:−6.2, 95% CI: −10.5). In multivariate analysis, vitamin D3 levels in the deficient and insufficient groups, and the CD8, HBeAg, and WBC counts were significantly associated with HBV DNA levels. In the immune tolerance phase of HBeAg-negative chronic HBV infection, vitamin D3 may be a modulator of immune function via CD8, CD19, and HBV DNA.
Performance evaluation of humpback whale-inspired shortboard surfing fins based on ocean wave fieldwork

We present field results revealing improved surfing performance when a novel approach (“Real Whale”, RW) is used for applying several of the humpback whale’s passive flow control mechanisms, including tubercles, to surfboard fins. It is also the first study presenting evidence of dynamic performance of tubercled designs rotating on all three axes. We evaluated low aspect ratio, thruster-style 3-fin configurations used in high-performance surfing. Fieldwork involved surfing almost 2,000 ocean waves from around the world, comparing standard commercial fins with straight leading edges to RW fins. We collected surfing data from instrumentation attached to surfboards, including GPS and 9-axis motion sensors. Eighteen turn performance values were measured and calculated, including novel, surfing-specific rotational power coefficients. ANOVA revealed surfers using RW fins showed significant improvements in power generation compared to when they used standard commercial fins. Turn rates using RW fins also improved, although not significantly. We found using RW fins allowed a skilled surfer to improve their surfing performance relative to a professionally ranked surfer.
Aptamers, the Nucleic Acid Antibodies, in Cancer Therapy

The arrival of the monoclonal antibody (mAb) technology in the 1970s brought with it the hope of conquering cancers to the medical community. However, mAbs, on the whole, did not achieve the expected wonder in cancer therapy although they do have demonstrated successfulness in the treatment of a few types of cancers. In 1990, another technology of making biomolecules capable of specific binding appeared. This technique, systematic evolution of ligands by exponential enrichment (SELEX), can make aptamers, single-stranded DNAs or RNAs that bind targets with high specificity and affinity. Aptamers have some advantages over mAbs in therapeutic uses particularly because they have little or no immunogenicity, which means the feasibility of repeated use and fewer side effects. In this review, the general properties of the aptamer, the advantages and limitations of aptamers, the principle and procedure of aptamer production with SELEX, particularly the undergoing studies in aptamers for cancer therapy, and selected anticancer aptamers that have entered clinical trials or are under active investigations are summarized.
Speech Emotion Recognition Based on Selective Interpolation Synthetic Minority Over-Sampling Technique in Small Sample Environment

Speech emotion recognition often encounters the problems of data imbalance and redundant features in different application scenarios. Researchers usually design different recognition models for different sample conditions. In this study, a speech emotion recognition model for a small sample environment is proposed. A data imbalance processing method based on selective interpolation synthetic minority over-sampling technique (SISMOTE) is proposed to reduce the impact of sample imbalance on emotion recognition results. In addition, feature selection method based on variance analysis and gradient boosting decision tree (GBDT) is introduced, which can exclude the redundant features that possess poor emotional representation. Results of experiments of speech emotion recognition on three databases (i.e., CASIA, Emo-DB, SAVEE) show that our method obtains average recognition accuracy of 90.28% (CASIA), 75.00% (SAVEE) and 85.82% (Emo-DB) for speaker-dependent speech emotion recognition which is superior to some state-of-the-arts works.