Miracle-dz/UniFAR-FTUs huggingface dataset:
Systematic investigation on the chemical base of anti-NAFLD Qushi Huayu Fang. Part1: metabolic profiles in vivo and in vitro by high-performance liquid chromatography quadrupole time-of-flight mass spectrometry.

Qushi Huayu Fang (QHF) is a clinic-empirical prescription for treating nonalcoholic fatty liver disease (NAFLD) in China, composed of five herbs. However, the bioactive constituents responsible for the efficacy of QHF are still indistinct to date. Thus, a high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF) method was established and adopted to identify the constituents of QHF, and profile its metabolism in vivo and in vitro. Among the 66 constituents in QHF, only 14 compounds of six structural types were absorbed into rats, and 34 metabolites were generated through eight metabolic pathways. A total of 20 metabolites were first reported, including four organic acids, one iridoid, two flavones, five naphthols, three anthraquinones, and five stilbenes. Glucuronidation and sulfation were the main metabolic pathways, and the intestinal metabolism played an important role in the biotransformation of QHF. Many compounds, especially those detected in the liver, the target organ of QHF, were reported to display the anti-NAFLD activity. This is the first time to explore the constituents of QHF and its metabolism in vivo and in vitro, which realize the first step to clarify the chemical basis of QHF qualitatively, and lay the foundation for further research on the anti-NAFLD mechanism of QHF.
Expressure: Detect Expressions Related to Emotional and Cognitive Activities Using Forehead Textile Pressure Mechanomyography

We investigate how pressure-sensitive smart textiles, in the form of a headband, can detect changes in facial expressions that are indicative of emotions and cognitive activities. Specifically, we present the Expressure system that performs surface pressure mechanomyography on the forehead using an array of textile pressure sensors that is not dependent on specific placement or attachment to the skin. Our approach is evaluated in systematic psychological experiments. First, through a mimicking expression experiment with 20 participants, we demonstrate the system’s ability to detect well-defined facial expressions. We achieved accuracies of 0.824 to classify among three eyebrow movements (0.333 chance-level) and 0.381 among seven full-face expressions (0.143 chance-level). A second experiment was conducted with 20 participants to induce cognitive loads with N-back tasks. Statistical analysis has shown significant correlations between the Expressure features on a fine time granularity and the cognitive activity. The results have also shown significant correlations between the Expressure features and the N-back score. From the 10 most facially expressive participants, our approach can predict whether the N-back score is above or below the average with 0.767 accuracy.
Unique subsite specificity and potential natural function of a chitosan deacetylase from the human pathogen Cryptococcus neoformans

Significance The opportunistic fungal pathogen Cryptococcus neoformans is a major threat to immunocompromised patients. Most fungal cell walls expose chitin, which is recognized by the human immune system, but C. neoformans is one of the few species that instead exposes chitosan, the deacetylated form of chitin. Chitosan is produced by chitin synthases and chitin deacetylases, the latter acting on chitin as a substrate. Here we describe the detailed functional analysis of CnCda4, a chitin deacetylase with unusual subsite specificity resulting in a preference for chitosan rather than chitin. By testing the effect of CnCda4 deacetylation products on human peripheral blood-derived macrophages, we show that the enzyme probably helps the pathogen to evade the host immune system by further deacetylating exposed chitosans. Cryptococcus neoformans is an opportunistic fungal pathogen that infects ∼280,000 people every year, causing >180,000 deaths. The human immune system recognizes chitin as one of the major cell-wall components of invading fungi, but C. neoformans can circumvent this immunosurveillance mechanism by instead exposing chitosan, the partly or fully deacetylated form of chitin. The natural production of chitosans involves the sequential action of chitin synthases (CHSs) and chitin deacetylases (CDAs). C. neoformans expresses four putative CDAs, three of which have been confirmed as functional enzymes that act on chitin in the cell wall. The fourth (CnCda4/Fpd1) is a secreted enzyme with exceptional specificity for d-glucosamine at its −1 subsite, thus preferring chitosan over chitin as a substrate. We used site-specific mutagenesis to reduce the subsite specificity of CnCda4 by converting an atypical isoleucine residue in a flexible loop region to the bulkier or charged residues tyrosine, histidine, and glutamic acid. We also investigated the effect of CnCda4 deacetylation products on human peripheral blood-derived macrophages, leading to a model explaining the function of CnCda4 during infection. We propose that CnCda4 is used for the further deacetylation of chitosans already exposed on the C. neoformans cell wall (originally produced by CnChs3 and CnCda1 to 3) or released from the cell wall as elicitors by human chitinases, thus making the fungus less susceptible to host immunosurveillance. The absence of CnCda4 during infection could therefore promote the faster recognition and elimination of this pathogen.
Determinants of Oral Bisphosphonate Use Beyond 5 Years

BACKGROUND: Few studies have examined factors that determine bisphosphonate (BP) continuation beyond 5 years in clinical practice. OBJECTIVE: To investigate factors associated with BP continuation among women who completed 5 years of BP therapy. METHODS: Women who received 5 consecutive years of oral BP treatment entered the cohort during 2002-2014 and were followed up to 5 additional years. Multivariable logistic regression was used to evaluate the association of demographic and clinical factors with adherent treatment continuation. RESULTS: The cohort included 19,091 women with a median age of 72 years. Baseline and time-varying factors associated with increased odds of BP continuation after 5 years were (a) most recent bone mineral density (BMD) T-score -2 to -2.4 (OR = 1.31, 95% CI = 1.25-1.38), T-score -2.5 to -2.9 (OR = 1.48, 95% CI = 1.39-1.57), and T-score ≤ -3.0 (OR = 1.57, 95% CI = 1.47-1.68) versus T-scores above -2.0; (b) index date before 2008 (OR =1.35, 95% CI = 1.29-1.41); and (c) diabetes mellitus (OR = 1.08, 95% CI = 1.01-1.16). In contrast, factors associated with decreased odds of BP continuation were (a) recent hip (OR = 0.61, 95% CI = 0.52-0.71) or humerus (OR = 0.79, 95% CI = 0.66-0.94) fracture or fracture other than hip, wrist, spine, or humerus (OR = 0.90, 95% CI = 0.84-0.97); (b) Charlson Comorbidity Index score > 2 (OR = 0.91, 95% CI = 0.84-0.98); (c) history of rheumatoid arthritis (OR = 0.89, 95% CI = 0.80-0.99); (d) Hispanic (OR = 0.89, 95% CI=0.85-0.94) or Asian (OR = 0.90, 95% CI = 0.85-0.94) race/ethnicity; and (e) use of proton pump inhibitors (OR = 0.65, 95% CI = 0.59-0.71). Patient age and fracture before BP initiation were not associated with treatment continuation. CONCLUSIONS: Clinical factors predicting continued BP treatment beyond 5 years include low BMD T-score, absence of recent fracture, and earlier era of treatment. Use of proton pump inhibitors was associated with lower likelihood of BP continuation. Other clinical and demographic factors were also noted to have variable effects on BP treatment continuation.
Brn3/POU‐IV‐type POU homeobox genes—Paradigmatic regulators of neuronal identity across phylogeny

One approach to understand the construction of complex systems is to investigate whether there are simple design principles that are commonly used in building such a system. In the context of nervous system development, one may ask whether the generation of its highly diverse sets of constituents, that is, distinct neuronal cell types, relies on genetic mechanisms that share specific common features. Specifically, are there common patterns in the function of regulatory genes across different neuron types and are those regulatory mechanisms not only used in different parts of one nervous system, but are they conserved across animal phylogeny? We address these questions here by focusing on one specific, highly conserved and well‐studied regulatory factor, the POU homeodomain transcription factor UNC‐86. Work over the last 30 years has revealed a common and paradigmatic theme of unc‐86 function throughout most of the neuron types in which Caenorhabditis elegans unc‐86 is expressed. Apart from its role in preventing lineage reiterations during development, UNC‐86 operates in combination with distinct partner proteins to initiate and maintain terminal differentiation programs, by coregulating a vast array of functionally distinct identity determinants of specific neuron types. Mouse orthologs of unc‐86, the Brn3 genes, have been shown to fulfill a similar function in initiating and maintaining neuronal identity in specific parts of the mouse brain and similar functions appear to be carried out by the sole Drosophila ortholog, Acj6. The terminal selector function of UNC‐86 in many different neuron types provides a paradigm for neuronal identity regulation across phylogeny.
A Retrospective Study to Compare the Efficacy of Preoperative Halo-Gravity Traction and Postoperative Halo-Femoral Traction After Posterior Spinal Release in Corrective Surgery for Severe Kyphoscoliosis

Background This retrospective clinical study aimed to compare the efficacy of preoperative halo-gravity traction with postoperative halo-femoral traction after posterior spinal release in corrective surgery for patients with severe kyphoscoliosis. Material/Methods A retrospective clinical study included patients who underwent elective corrective surgery for severe kyphoscoliosis (N=60) between 2013 and 2015. Two patient groups were compared, the postoperative halo-femoral traction after posterior spinal release (R-HF) group (N=30) and the preoperative halo-gravity traction (HGT) group (N=30). Demographic and clinicopathological data included age, gender, Cobb angle, degree of spinal curvature, history of osteotomy, and etiological factors. Patients in the two study groups were matched. Postoperative surgical outcome was evaluated by the radiographic coronal Cobb angle, global kyphosis, coronal balance, and the sagittal vertical axis (SVA). Clinical outcome was assessed using the Scoliosis Research Society Outcomes Questionnaire (SRS-22). Results The preoperative Cobb angle was similar between the R+HF group and the HGT group (123.5±12.7° vs. 123.1±14.1°; P=0.909). Following postoperative traction, a significantly higher correction rate was found in the R+HF group than the HGT group (31.8±7.8% vs. 19.3±12.9%; P=0.001). The postoperative correction rate in the R+HF group was significantly higher than the HGT group (44.7±7.8% vs. 39.0±12.8%; P=0.042). In both study groups, the postoperative SRS-22 scores were significantly improved with no statistical difference between the two groups, and no neurological complications occurred. Conclusions Patients with severe kyphoscoliosis who underwent postoperative halo-femoral traction after posterior spinal release achieved satisfactory radiographic correction.
GINS complex subunit 4, a prognostic biomarker and reversely mediated by Krüppel‐like factor 4, promotes the growth of colorectal cancer

GINS complex subunit 4 (GINS4) is essential for DNA replication initiation and elongation in the G1/S phase cell cycle in eukaryotes, however, its functional roles and molecular mechanisms remain unclear in many aspects. Our study was designed to investigate the clinical significance, biological function, and molecular mechanism of GINS4 in colorectal cancer (CRC). First, we confirmed that GINS4 expression was significantly overexpressed in CRC cells and tissues. The immunohistochemical results in tissue microarray from 106 CRC patients showed that a high level of GINS4 expression was positively correlated with advanced T stage, higher tumor TNM stage, and poor differentiation. The results from univariate and multivariate survival analysis models based on 106 CRC patients revealed that GINS4 might serve as an independent prognostic indicator for overall survival and disease‐free survival of CRC patients. Moreover, downregulated GINS4 can inhibit growth and the cell cycle and accelerate cell apoptosis progression in vitro as well as inhibit tumorigenesis in vivo. Besides, our results also indicated that Krüppel‐like factor 4 (KLF4) can negatively regulate GINS4 expression at the transcriptional level and the KLF/GINS4 pathway might play a vital role in the growth and prognosis of CRC.
Adherence to DASH dietary pattern is inversely associated with osteoarthritis in Americans

Abstract Osteoarthritis (OA) is one of the most common diseases that cause disability among older adults. The objective of this study was to assess the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) and OA in American adults. This study included adults (≥ aged 20 years) who participated in the National Health and Examination Survey (NHANES) 2007–2016 in the United States. Adherence to the DASH score was calculated from 8 food groups. Higher scores indicate better adherence to the DASH dietary pattern. Among the 21,901 participants included in this study, 10.26% reported having OA. Results of our multivariable logistic regression indicated a statistically significant inverse association between DASH score tertiles and OA. The adjusted ORs (95% CI) were 1.00 (ref), 0.89 (0.72; 1.10), and 0.78 (0.60; 1.00) across increasing DASH score tertiles (P for trend = 0.045). In this representative sample of American adults, greater adherence to the DASH dietary pattern was associated with lower likelihood of having OA. Graphical Abstract
The New Genomics Era: Integration of genomics into mainstream oncology and implications for psycho‐oncological care

There is increasing attention to the transformation of healthcare using genomics. Oncology, in particular, increasingly has genomic technologies incorporated into everyday practice. This can be attributed to the dual effect of faster, more affordable genetic/genomic testing, coupled with the capacity for genomic data to inform precision screening, diagnostics and personalised treatment, and management plans. The term “mainstreaming” refers to routine integration of genomics into every clinic and speciality across the health service. Alongside technological advances, it is paramount that healthcare professionals and the public are adequately aware of, and prepared for, routine use of genomics in health management. Attention to psychosocial considerations has always been a central tenet of genetic counselling. An acute increase in distress and anxiety can occur around the time of testing and can usually be managed within the genetic counselling process, with a smaller number of patients requiring referral for ongoing psychological support. The purpose of this commentary is to provide an overview of genomic testing in oncology to review what has changed and why, implementation in practice, how oncology clinicians need to evolve alongside this transformation, and to consider behavioural, psychological, and communication challenges in order to optimise patient management. This commentary has largely drawn on the current status of genomic testing in the United Kingdom, but relevant information pertaining to other countries is also discussed.
7-MEOTA and 2-aminobenzothiazole heterodimers: structure-mechanism relationship of amyloid inhibitors based on rational design.

The formation and accumulation of amyloid aggregates are the accompanying phenomena of amyloidoses, which are currently untreatable and include Alzheimer's and Parkinson's diseases, diabetes mellitus, non-neuropathic lysozyme systemic amyloidosis and others. One of the very promising therapeutic approaches seems to be inhibition of amyloid formation and/or clearance of amyloid aggregates. Small molecules have a great potential to interfere with amyloid fibrillation of poly/peptides, which can be improved by connection of cyclic structures into single multicyclic molecule and their dimerization. In our study, we focused on heterodimers consisting of 7-MEOTA and 2-aminobenzothiazole (BTZ) parent molecules connected by an aliphatic linker. Using in vitro and in silico methods, we investigated the ability of studied compounds to inhibit the amyloid aggregation of hen egg white lysozyme (HEWL). Heterodimerization led to significant improvement of inhibitory activity compared to parent molecules. Moreover, the efficiency of heterodimers varied; the most effective inhibitor contained the longest, eight carbon long linker. We suggest that binding of heterodimer to lysozyme blocks the interaction between β-domain and C-helix region essential for formation of amyloid cross-β structure. Prolongation of the linker ultimately enhances compounds ability to prevent this interaction by allowing the BTZ part of the heterodimer to bind more effectively, increasing compounds binding affinity, and also by greater steric obstruction. This study represents an important contribution for the recent rational design of potential lead small molecules with anti-amyloid properties and studied heterodimers are perspective candidates for the treatment of systemic lysozyme amyloidosis and other amyloid-related diseases.
Long non-coding RNA AFAP1-AS1 promotes proliferation and migration of gastric cancer by downregulating KLF2.

OBJECTIVE To clarify the function of actin filament associated protein 1-antisense RNA1 (AFAP1-AS1) to promote the proliferation and migration of gastric cancer (GC) cells by downregulating Krüppel-like factor 2 (KLF2). MATERIALS AND METHODS Expression level of AFAP1-AS1 in GC tissues and matched paracancerous tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Besides, its level in GC either with lymphatic metastasis or not, and those in different tumor stages were determined as well. Regulatory roles of AFAP1-AS1 in cellular behaviors of GC cells were evaluated by functional experiments. The ability of AFAP1-AS1 to recruit EZH2 was evaluated through chromatin immunoprecipitation (ChIP) assay. The expression level of KLF2 in GC cells influenced by AFAP1-AS1 and EZH2 was detected by Western blot. Finally, a series of rescue experiments were conducted to clarify the role of AFAP-AS1/KLF2 in GC cell performances. RESULTS AFAP1-AS1 was upregulated in GC tissues, and its expression in lymph node metastasis and progressive gastric cancer tissues were much higher. Knockdown of AFAP1-AS1 reduced the viability, proliferative and migratory abilities, but induced apoptosis of GC cells. AFAP1-AS1 was verified to bind to EZH2. After knockdown of AFAP1-AS1, the ability of AFAP1-AS1 to recruit EZH2 was remarkably attenuated. Knockdown of AFAP1-AS1 or EZH2 upregulated KLF2 expression in GC cells. Notably, knockdown of KLF2 partially reversed the effect of AFAP1-AS1 on GC cell performances. CONCLUSIONS LncRNA AFAP1-AS1 accelerates the proliferative and migratory abilities of GC cells by downregulating the expression of KLF2, thus promoting the progression of GC.
Tumor necrosis factor receptor family costimulation increases regulatory T‐cell activation and function via NF‐κB

Several drugs targeting members of the TNF superfamily or TNF receptor superfamily (TNFRSF) are widely used in medicine or are currently being tested in therapeutic trials. However, their mechanism of action remains poorly understood. Here, we explored the effects of TNFRSF co‐stimulation on murine Foxp3+ regulatory T cell (Treg) biology, as they are pivotal modulators of immune responses. We show that engagement of TNFR2, 4‐1BB, GITR, and DR3, but not OX40, increases Treg proliferation and survival. Triggering these TNFRSF in Tregs induces similar changes in gene expression patterns, suggesting that they engage common signal transduction pathways. Among them, we identified a major role of canonical NF‐κB. Importantly, TNFRSF co‐stimulation improves the ability of Tregs to suppress colitis. Our data demonstrate that stimulation of discrete TNFRSF members enhances Treg activation and function through a shared mechanism. Consequently, therapeutic effects of drugs targeting TNFRSF or their ligands may be mediated by their effect on Tregs.
Protection reveals density-dependent dynamics in fish populations: A case study in the central Mediterranean

Casting light on how the interaction between protection and density dependence affects fish population dynamics is critical for understanding the effectiveness of marine protected areas (MPAs). We developed a framework based on nonparametric statistics, model selection and multi-model inference to contrast alternative hypotheses about the effect of density dependence on demographic dynamics under protected and unprotected conditions. We trialed it using a 12-year long time series of white seabream (Diplodus sargus sargus) population density within the no-take zone of Torre Guaceto MPA (Italy) and at two nearby unprotected locations. Then, we showed how the demographic models obtained can be used to assess the consequences of protection on population viability. Population dynamics were significantly influenced by fish density within the MPA and at one of the unprotected locations, where demography is possibly driven by directional recruitment subsidy from the MPA. The comparison of population growth rates within and outside the MPA suggests that in unprotected conditions the fishery may remove a fraction between 40 and 70% of the population each year. The population viability analysis pointed out that, while the probability that the population becomes depleted (i.e. undergoes a local, temporary quasi-extinction) is high in unprotected locations, it is negligible within the no-take zone of the MPA.
Diet quality, nutrient intakes and biochemical status of New Zealand women of childbearing age according to alcohol consumption patterns

Abstract Objective: To investigate associations between alcohol consumption patterns and diet quality, nutrient intakes and biochemical profile of women of childbearing age. Design: Nutrient intake data from 24 h diet recalls, alcohol consumption data and diet quality from the Dietary Habits Questionnaire, and biochemical analyses from the cross-sectional 2008/09 Adult Nutrition Survey in New Zealand. Setting: New Zealand households. Participants: New Zealand women aged 18–45 years (n 1124). Results: All analyses were completed using Stata and survey weights were used to allow for the complex survey design to produce population estimates. Multinomial logistic regression models were used to examine the associations between drinking patterns and the variables of interest, with ‘infrequent moderate/light’ drinkers being the reference category. The findings indicate that alcohol-consuming women of childbearing age tend to replace food energy with alcohol energy (P = 0·022). ‘More frequent heavy’ and ‘more frequent moderate/light’ drinkers had higher intakes of total, mono- and polyunsaturated fats with the latter group also consuming higher levels of saturated fats (P < 0·05). Women who were ‘infrequent moderate/light’ drinkers had relatively better diet quality, nutrient intakes and adequate biochemical status in comparison to other drinkers and abstainers. ‘Infrequent heavy’ drinkers, who were predominantly younger in age, had lower serum vitamin B12 levels (P = 0·01) with a higher proportion of women in this category having below-recommended levels of serum folate (P < 0·05). Conclusions: Alcohol consumption, especially heavy drinking patterns, may compromise nutritional status of women of childbearing age.