Miracle-dz/UniFAR-FTUs huggingface dataset:
Nrf2/HO-1 Axis Regulates the Angiogenesis of Gastric Cancer via Targeting VEGF

Purpose Gastric cancer (GC) is one of the most fatal digestive tumors worldwide. Abnormal activation or accumulation of the nuclear factor-erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) axis is a malignant event in numerous solid tumors. However, its involvement in angiogenesis of GC remains unknown. This study investigated the role of the Nrf2/HO-1 axis in angiogenesis of GC. Methods The expression of Nrf2, HO-1, and vascular endothelial growth factor (VEGF) in BGC-823 cells under hypoxia was analyzed using immunocytochemistry, immunofluorescence, Western blotting, and quantitative polymerase chain reaction. The effects of brusatol (Nrf2 inhibitor) and tert-butylhydroquinone (Nrf2 inducer) on these factors and angiogenesis were examined using immunofluorescence, Western blotting, quantitative polymerase chain reaction, and tube formation assay. Moreover, immunohistochemistry and Western blotting were used to determine these factors and microvessel density in tumor and normal tissues of tumor-bearing and tumor-free mice, respectively. Immunohistochemistry and Western blotting were employed to examine these factors and microvessel density in human paracancerous tissues, well-differentiated GC, and poorly differentiated GC. The correlations between Nrf2, HO-1, and VEGF gene expression in 375 patients with GC from The Cancer Genome Atlas cohort were analyzed. Results The expression of Nrf2, HO-1, and VEGF was increased in hypoxic BGC-823 cells (P<0.05). Although brusatol decreased their expression and angiogenesis (P<0.05), tert-butylhydroquinone had the opposite effect (P<0.05). Moreover, the expression of Nrf2, HO-1, and VEGF, and microvessel density in tumor tissues was higher than that recorded in normal tissues of nude mice (P<0.05). Similarly, these parameters were low in paracancerous tissues, but high in GC tissues (P<0.05). Also, they were weak in well-differentiated GC, but strong in poorly differentiated GC (P<0.05). In addition, there was a significant correlation between Nrf2, HO-1, and VEGF (P<0.05). Conclusion The Nrf2/HO-1 axis may regulate the angiogenesis of GC via targeting VEGF. These findings provide a promising biomarker and potential treatment target for GC.
The complete chloroplast genome of pioneering plant Cyperus iria L. (Cyperaceae) in ecological restoration

Abstract Cyperus iria L. is an annual weed of the family Cyperaceae, which plays an important role in the environmental remediation of uranium contaminate. Here, the complete chloroplast (cp) genome of Cyperus iria has been reconstructed from the complete genome Illumina sequencing data. The complete cp genome was 185,697 bp in length, containing a large single copy region (LSC) of 99,360 bp and a small single copy region (SSC) of 10,267 bp, which were separated by a pair of 38,035 bp inverted repeat regions (IRs). The cp genome contained 135 genes, including 89 protein-coding genes (PCGs), eight rRNA genes, and 38 tRNA genes. The cp genome has a GC content of 33.16%. Further, the phylogenetic analysis showed a strong sister relationship with Cyperus rotundus.
Use of Preoperative Magnetic Resonance Imaging to Predict Clinical Outcomes After Core Muscle Injury Repair

Background: Core muscle injury (CMI), often referred to as a sports hernia or athletic pubalgia, is a common cause of groin pain in athletes. Imaging modalities used to assist in the diagnosis of CMI include ultrasound (US) and magnetic resonance imaging (MRI). Purpose: To determine if preoperative MRI findings predict clinical outcomes after surgery for CMI. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective cohort study was performed on a consecutive series of patients who were operatively treated for CMI by a single surgeon. CMI was diagnosed based on history, physical examination, and a positive US. In addition, all patients underwent a preoperative MRI. Patients were divided into 2 groups based on whether the MRI was interpreted as positive or negative for CMI. All patients underwent mini-open CMI repair. Patient-reported outcomes (PROs) were collected both pre- and postoperatively and included a visual analog scale (VAS) for pain, the University of California, Los Angeles (UCLA) activity score, and the modified Harris Hip Score. Results: A total of 39 hips were included in this study, of which 17 had a positive MRI interpretation for CMI (44%) and 22 had a negative MRI interpretation (56%). Mean age at the time of surgery was 35 years (range, 17-56 years), and mean follow-up was 21 months (range, 12-35 months). No significant difference was found between groups in mean age or time to follow-up. Patients in both groups demonstrated significant improvement from preoperative to most recent follow-up in terms of the UCLA activity score (P < .05). VAS scores significantly improved for patients with a positive MRI interpretation (P = .001) but not for those with a negative MRI interpretation (P = .094). No significant difference on any PROs was found between groups at the most recent follow-up. Conclusion: Successful clinical outcomes can be expected in patients undergoing surgery for CMI diagnosed based on history, physical examination, and US. Patients with a preoperative MRI consistent with CMI may experience greater improvement in pain postoperatively, although MRI does not predict postoperative activity level in these patients.
High-yield purification of exceptional-quality, single-molecule DNA substrates

Single-molecule studies involving DNA or RNA, require homogeneous preparations of nucleic acid substrates of exceptional quality. Over the past several years, a variety of methods have been published describing different purification methods but these are frustratingly inconsistent with variable yields even in the hands of experienced bench scientists. To address these issues, we present an optimized and straightforward, column-based approach that is reproducible and produces high yields of substrates or substrate components of exceptional quality. Central to the success of the method presented is the use of a non-porous anion exchange resin. In addition to the use of this resin, we encourage the optimization of each step in the construction of substrates. The fully optimized method produces high yields of a hairpin DNA substrate of exceptional quality. While this substrate is suitable for single-molecule, magnetic tweezer experiments, the described method is readily adaptable to the production of DNA substrates for the majority of single-molecule studies involving nucleic acids ranging in size from 70–15000 bp.
Statement on additional scientific evidence in relation to the essential composition of total diet replacement for weight control

Abstract Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to revise the Opinion on the essential composition of total diet replacements for weight control (TDRs) regarding the minimum content of linoleic acid (LA) and alpha‐linolenic acid (ALA) and the maximum content of magnesium (Mg). Through a comprehensive literature search, human studies were retrieved reporting on LA and ALA concentrations in adipose tissue (AT), on weight loss and gallstone formation following TDR consumption and on diarrhoea after supplemental Mg intake. The distribution of the amount of LA and ALA release from AT during weight loss when consuming TDRs was estimated using statistical simulations. Using the fifth percentile, the coverage of the adequate intake (AI) for both FA was estimated. For the risk of developing diarrhoea when consuming TDRs with an Mg content of 350 mg/day, four cross‐over studies using 360–368 mg Mg/day were reviewed. The Panel concludes that (1) there is no need to add LA to TDRs, as the amount released from AT during weight loss when consuming TDRs is sufficient to cover the AI for LA; (2) a minimum of 0.8 g/day ALA is needed in TDRs in order to meet the AI for ALA; (3) the minimum fat content of TDRs of 20 g/day as derived in the Panel's previous opinion is proposed to be maintained until the availability of further evidence, given the considerable uncertainty as to the amount of fat required for reducing the risk of gallstone formation; and (4) the likelihood that Mg‐induced diarrhoea occurs at a severity that may be considered of concern for overweight and obese individuals consuming TDRs is low when the total maximum Mg content in TDRs is 350 mg/day.
3D Culture of Circulating Tumor Cells for Evaluating Early Recurrence and Metastasis in Patients with Hepatocellular Carcinoma

Purpose Circulating tumor cells (CTCs) are considered to be a key factor involved in tumor metastasis. However, the isolation and culture of CTCs in vitro remains challenging, and their clinical application for predicting prognosis and survival is still limited. The development of accurate evaluating system for CTCs will benefit for clinical assessment of HCC. Methods Density gradient centrifugation and magnetic separation based on CD45 antibody were used to isolate CTCs. 3D culture was used to maintain and amplify CTCs and HCC cells. Cellular immunofluorescence was used to identify CTCs and spheroids. The cutoff value of CTC spheroid was calculated using X-tile software. The relationship between clinicopathological variables and CTC spheroids in HCC patients is analyzed. In vivo models were used to evaluate tumor growth and metastasis of CTC spheroids. Results Patient-derived CTCs/HCC cells were isolated and expanded to form spheroids using 3D culture. CTC spheroids could be used to predict short-term recurrence of CTCs compared with conventional CTC enumeration. Different cell lines exhibited different formation rates and grew to different sizes. Identification of CTC spheroids revealed that EpCAM and β-catenin were expressed in spheroids derived from HCC cells and in the HCC/CTCs. EpCAM-positive HCC cells exhibited improved spheroid formation in 3D culture and were more tumorigenic and likely to metastasize to the lung in vivo. Abnormal activation of the Wnt/β-catenin signaling pathway was observed in EpCAM positive cells. Conclusion CTC spheroids could predict prognosis of HCC more precisely compared with conventional CTC enumeration. EpCAM may participate in the formation and survival of CTC spheroids which dependent on Wnt/β-catenin signaling pathway.
The Challenges of Intersectionality in the Lives of Older Adults Living in Rural Areas with Limited Financial Resources

The objective of this study was to use intersectionality to better understand the challenges of having the combined statuses of being an older adult, living in a rural area and having limited financial resources. Eight focus groups and 38 individual interviews were conducted in southern Georgia. Participants included program participants and staff, community members, and community leaders. Thematic analysis was done using verbatim transcripts from focus groups and interviews. Results demonstrate that the multiplicative and intersecting statuses of the study population create challenges in the areas of transportation, health care, food, and housing. The challenges of these intersectional statuses limit access to services in ways that each individual status did not, thereby compounding challenges. While previous literature describes the challenges of one or two of these statuses, this work explores the multiplicative effects of the combination of the three statuses using intersectionality. Programmatic and policy recommendations and implications are discussed.
Anxiety and Depression in Patients with Pulmonary Hypertension and its Impact on Health-Related Quality of Life

Background: Pulmonary Hypertension (PH) is a chronic progressive disease which affects quality of life. The prevalence of mood disorders in PH patients in Saudi Arabia is not known. Objectives: This is a prospective observational study to investigate the prevalence of anxiety and depression in patients with pulmonary hypertension and its effect on health-related quality of life (HRQoL). Methods: Forty-two PH patients were evaluated for mood disorders by using Hospital Anxiety and Depression Scale (HADS) and health related quality of life was assessed with The Short Form 36 (SF-36) Health Survey questionnaire. Results: Mean age for the cohort was 42.8 (13.3) years and 31(73%) were female. Mean pulmonary artery pressure was 46.4 (15) mm Hg and 25 (60%) patients had severe PH (mPAP >45 mmHg). Thirty-eight (90%) patients were in World Health Organization Functional Class (WHO-FC) II/III and 5 (10%) class IV. HADS anxiety and depression score was positive (11-21) in 4 (10%) and 6 (14%) patients respectively. Presence of anxiety and/or depression affected HRQoL. Conclusion: Prevalence of anxiety and depression in PH patients in Saudi Arabia is low (10% and 14% respectively) compared to published studies. The low prevalence may be explained by cultural and social differences and strong family support.
Modelling to inform the COVID-19 response in Bangladesh

Background: Non-pharmaceutical interventions (NPIs) used to limit SARS-CoV-2 transmission vary in their feasibility, appropriateness and effectiveness in different contexts. In Bangladesh a national lockdown implemented after the first detected case in early March 2020 rapidly exacerbated poverty and was considered untenable long-term, whilst surging cases in 2021 warrant renewed NPIs. We examine potential outcomes and costs of NPIs considered appropriate and feasible to deploy in Dhaka over the course of the pandemic including challenges of compliance and scale up. Methods: We developed an SEIR model for application to Dhaka District, parameterised from literature values and calibrated to death data from Bangladesh. We discussed scenarios and parameterizations with policymakers using an interactive app, to guide modelling of lockdown and post-lockdown measures considered feasible to deliver; symptoms-based household quarantining and compulsory mask-wearing. We examined how testing capacity affects case detection and compared deaths, hospitalisations relative to capacity, working days lost from illness and NPI compliance, and cost-effectiveness. Results: Lockdowns alone were predicted to delay the first epidemic peak but were unable to prevent overwhelming of the health service and were extremely costly. Predicted impacts of post-lockdown interventions depended on their reach within communities and levels of compliance: symptoms-based household quarantining alone was unable to prevent hospitalisations exceeding capacity whilst mask-wearing could prevent overwhelming health services and be cost-effective given masks of high filtration efficiency. The modelled combination of these measures was most effective at preventing excess hospitalizations for both medium and high filtration efficiency masks. Even at maximum testing capacity, confirmed cases far underestimate total cases, with saturation limiting reliability for assessing trends. Recalibration to surging cases in 2021 suggests limited immunity from previous infections and the need to re-sensitize communities to increase mask wearing. Conclusions: Masks and symptoms-based household quarantining act synergistically to prevent transmission, and are cost-effective in mitigating impacts. Our interactive app was valuable in supporting decision-making in Bangladesh, where mask-wearing was mandated early, and community teams have been deployed to support household quarantining across Dhaka. This combination of measures likely contributed to averting the worst impacts of a public health disaster as predicted under an unmitigated epidemic, but delivering an effective response at scale has been challenging. Moreover, lack of protection to the B.1. 351 variant means messaging to improve mask-wearing is urgently needed in response to surging cases.
A normative model representing autistic individuals amidst Autism Spectrum Disorders phenotypic heterogeneity

Approaches to deal and understand Autism Spectrum Disorder (ASD) phenotypic heterogeneity, quantitatively and multidimensionally, are in need. Being able to access a specific individual relative to a normative reference ASD sample would provide a severity estimate that takes into account the spectrum variance. We propose such an approach analyzing the principal components of variance observable in a clinical reference sample. Using phenotypic data available in a comprehensive reference sample, the Simons Simplex Collection (n=2744 individuals), we performed Principal Component Analysis (PCA). The PCA considered ASD core-symptoms (accessed by ADI-R), important clinical features (accessed by VABS and CBCL) and IQ. PCA-projected dimensions supported a normative modeling where a multivariate normal distribution was used to calculate percentiles. An additional phenotypically homogeneous sample (ASD, IQ<75, 6-7yr, n=60) is presented as a case study to illustrate the phenotypic heterogeneity assessment and individual placement under the normative modeling approach. Three PCs embedded 72% of the normative sample variance, interpreted based on correlations (>0.50) with clinical features as: Social Functionality (39%), Behavioral Disturbance (18%) and Communication Problems (15%). A Multidimensional Severity Score (MSS) to evaluate new prospective single subjects was developed based on percentiles. Additionally, the disequilibrium among PCA-projected dimensions gave rise to an individualized Imbalance Score (ImS). The approach, named TEAplot, is implemented in user-friendly free software and was illustrated in a homogenous independent sample. Our approach proposes a basis for patient monitoring in clinical practice, guides research sample selection and pushes the field towards personalized precision medicine.
A Decoder-Free Variational Deep Embedding for Unsupervised Clustering

In deep clustering frameworks, autoencoder (AE)- or variational AE-based clustering approaches are the most popular and competitive ones that encourage the model to obtain suitable representations and avoid the tendency for degenerate solutions simultaneously. However, for the clustering task, the decoder for reconstructing the original input is usually useless when the model is finished training. The encoder–decoder architecture limits the depth of the encoder so that the learning capacity is reduced severely. In this article, we propose a decoder-free variational deep embedding for unsupervised clustering (DFVC). It is well known that minimizing reconstruction error amounts to maximizing a lower bound on the mutual information (MI) between the input and its representation. That provides a theoretical guarantee for us to discard the bloated decoder. Inspired by contrastive self-supervised learning, we can directly calculate or estimate the MI of the continuous variables. Specifically, we investigate unsupervised representation learning by simultaneously considering the MI estimation of continuous representations and the MI computation of categorical representations. By introducing the data augmentation technique, we incorporate the original input, the augmented input, and their high-level representations into the MI estimation framework to learn more discriminative representations. Instead of matching to a simple standard normal distribution adversarially, we use end-to-end learning to constrain the latent space to be cluster-friendly by applying the Gaussian mixture distribution as the prior. Extensive experiments on challenging data sets show that our model achieves higher performance over a wide range of state-of-the-art clustering approaches.
APLN: A potential novel biomarker for cervical cancer

Apelin (APLN) is recently demonstrated a direct association with many malignant diseases. However, its effects on cervical cancer remain unclear. This study therefore aims to evaluate the association between APLN expression and cervical cancer using publicly available data from The Cancer Genome Atlas (TCGA). The Pearson χ2 test and Fish exact test, as well as logistic regression, were used to evaluate the relationship between clinicopathological factors in cervical cancer and the expression of APLN. Additionally, the Cox regression and Kaplan-Meier methods were conducted to analyze the Overall Survival (OS) of cervical cancer patients in TCGA. Finally, gene set enrichment analysis (GSEA) was performed to establish its biological functions. High expression of APLN in cervical cancer was significantly associated with a more advanced clinical stage (OR = 1.91 (1.21–3.05) for Stage II, Stage III, and Stage IV vs Stage I, p = 0.006). Additionally, it was associated with poor outcome after primary therapy (OR = 2.14 (1.03–4.59) for Progressive Disease (PD), Stable Disease (SD), and Partial Response (PR) vs Complete Remission (CR), p = 0.045) and high histologic grade (OR = 1.67 (1.03–2.72) for G3 and G4 vs G1 and G2, p = 0.037). Moreover, multivariate analysis showed that high expression of APLN was associated with a shorter OS. GSEA demonstrated that six KEGG pathways, including PPAR signaling, ECM-receptor interaction, focal adhesion, MAPK signaling, TGF-beta signaling, and Gap junction pathways were differentially enriched in the high expression APLN phenotype. The recent study suggests that APLN plays an important role in the progression of cervical cancer and might be a promising prognostic biomarker of the disease.
Deformable microparticles for shuttling nanoparticles to the vascular wall

Hydrogel microparticle carriers delivered more nanoparticles to the vascular wall in vivo than ones freely injected. Vascular-targeted drug carriers must localize to the wall (i.e., marginate) and adhere to a diseased endothelium to achieve clinical utility. The particle size has been reported as a critical physical property prescribing particle margination in vitro and in vivo blood flows. Different transport process steps yield conflicting requirements—microparticles are optimal for margination, but nanoparticles are better for intracellular or tissue delivery. Here, we evaluate deformable hydrogel microparticles as carriers for transporting nanoparticles to a diseased vascular wall. Depending on microparticle modulus, nanoparticle-loaded poly(ethylene glycol)–based hydrogel microparticles delivered significantly more 50-nm nanoparticles to the vessel wall than freely injected nanoparticles alone, resulting in >3000% delivery increase. This work demonstrates the benefit of optimizing microparticles’ efficient margination to enhance nanocarriers’ transport to the vascular wall.