Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of ATP/GTP Binding Protein 1 Has Prognostic Value for the Clinical Outcomes in Non-Small Cell Lung Carcinoma

ATP/GTP binding protein 1 (AGTPBP1) encodes a crucial protein, cytosolic carboxypeptidase 1 (CCP1), which plays a role in modulating the polyglutamylation of tubulin and has been studied in degenerative diseases. However, the role of AGTPBP1 in malignancy has not been completely studied yet. In this study, we examined the role of AGTPBP1 in cancer progression, its association with patient survival, and related mechanisms in lung cancer, using the A549 cell line and lung cancer gene expression datasets. AGTPBP1 knockdown increased the proliferation, migration, sphere formation, and drug resistance of A549 cells. Lung cancer datasets revealed significantly lower mRNA and protein expression levels of AGTPBP1 in lung cancer tissues, as compared to those in normal tissues. Importantly, AGTPBP1 expression positively correlated with patient survival. Analysis of co-expressed genes revealed that AGTPBP1 expression positively correlated with immune infiltration in lung cancer. Our results conclusively suggested that AGTPBP1 expression was correlated with cancer progression and immune infiltration in lung cancer.
Topical and systemic retinoids for the treatment of cutaneous viral warts: A systematic review and meta‐analysis

Cutaneous viral warts (CVW), caused by human papillomavirus, often have a self‐limited course. However, some patients experience a recalcitrant disease despite treatment. Retinoids are considered the mainstay of therapy in many dermatologic diseases. Data on their use for viral warts are limited. To systematically review the published evidence on the efficacy and safety of retinoids for the treatment of CVW. A systematic review and meta‐analysis of topical or systemic retinoid treatment for CVW was performed in accordance with the PRISMA statement. The primary outcome was clinical response; secondary outcomes were recurrence rate and adverse events. Fourteen publications including 399 patients treated exclusively with retinoids (65% topical, 35% systemic) were evaluated. The complete response rate was 64% (95% CI, 46‐78%; I2=80%) for topical treatment and 61% (95% CI, 44‐76%; I2=69%) for systemic treatment. The most common side effects were irritant contact dermatitis and cheilitis, respectively. Relapse rates were 6% and 17%, respectively. The reviewed studies were considerably heterogenous and most lacked a control group. Both topical and systemic retinoids are effective and safe as monotherapy for CVW. Further studies are required to determine their exact role in this setting.
Identification of invasive key genes in breast cancer by bioinformatics analysis.

PURPOSE Of all breast cancers, triple-negative and HER-2 positive are the most aggressive breast cancer subtypes with a high risk of recurrence and worse prognosis. The study's purpose was to further assess the molecular mechanisms underlying aggression of breast cancer. METHODS The microarray gene expression datasets of GSE29431 and GSE53752 were obtained from the GEO (Gene Expression Omnibus) database, which include HER-2 positive breast cancer, triple-negative breast cancer (TNBC) and normal breast tissue samples. Differentially expressed genes (DEGs) were determined using the LIMMA package of R software and subsequently functional enrichment analysis were performed by the ClusterProfiler package in the R platform. The STRING database was used to construct a protein-protein interaction (PPI) network. The most significant module and key genes were identified by Cytoscape software. Utilizing the Kaplan-Meier plotter and UALCAN database, we defined the key genes associated with prognotic values and molecular subtypes as invasive genes. RESULTS In total, 428 common DEGs were identified, including 143 upregulated and 285 downregulated. GO and KEGG pathway enrichment analysis indicated that the upregulated genes were associated with mitotic nuclear division and cell cycle, whereas the downregulated genes were significantly associated with response to peptide and PPAR signaling pathway, respectively. A PPI network with 57 nodes and 335 edges was established, from which one most significant module was identified. Moreover, 12 key genes selected from the module with high degree centrality more than 21 were highly associated with high clinical aggressiveness and worse overall survival rate. CONCLUSIONS Our studies could enhance the understanding of the molecular mechanism of breast cancer aggressiveness, and the identification of invasive key genes promoted the individualized and comprehensive treatment.
Protocol for an implementation study of an evidence-based home cardiac rehabilitation programme for people with heart failure and their caregivers in Scotland (SCOT:REACH-HF)

Introduction Despite evidence that cardiac rehabilitation (CR) is an essential component of care for people with heart failure, uptake is low. A centre-based format is a known barrier, suggesting that home-based programmes might improve accessibility. The aim of SCOT: Rehabilitation EnAblement in CHronic Heart Failure (REACH-HF) is to assess the implementation of the REACH-HF home-based CR intervention in the context of the National Health Service (NHS) in Scotland. This paper presents the design and protocol for this observational implementation study. Specific objectives of SCOT:REACH-HF are to: (1) assess service-level facilitators and barriers to the implementation of REACH-HF; (2) compare real-world patient and caregiver outcomes to those seen in a prior clinical trial; and (3) estimate the economic (health and social) impact of implementing REACH-HF in Scotland. Methods and analysis The REACH-HF intervention will be delivered in partnership with four ‘Beacon sites’ across six NHS Scotland Health Boards, covering rural and urban areas. Health professionals from each site will be trained to facilitate delivery of the 12-week programme to 140 people with heart failure and their caregivers. Patient and caregiver outcomes will be assessed at baseline and 4-month follow-up. Assessments include the Minnesota Living with Heart Failure Questionnaire (MLHFQ), five-dimension EuroQol 5L, Hospital Anxiety and Depression Scale, and the Caregiver Burden Questionnaire. Qualitative interviews will be conducted with up to 20 health professionals involved in programme delivery (eg, cardiac nurses, physiotherapists). 65 facilitator-patient consultations will be audio recorded and assessed for fidelity. Integrative analysis will address key research questions on fidelity, context and CR participant-related outcomes. The SCOT:REACH-HF findings will inform the future potential roll-out of REACH-HF in Scotland. Ethics and dissemination The study has been given ethical approval by the West of Scotland Research Ethics Service (reference 20/WS/0038, approved 25 March 2020). Written informed consent will be obtained from all participants. The study is listed on the ISRCTN registry with study ID ISRCTN53784122. The research team will ensure that the study is conducted in accordance with both General Data Protection Regulations and the University of Glasgow’s Research Governance Framework. Findings will be reported to the funder and shared with Beacon Sites, to facilitate service evaluation, planning and good practice. To broaden interest in, and understanding of REACH-HF, we will seek to publish in peer-reviewed scientific journals and present at stakeholder events, national and international conferences.
Prophages and Past Prophage-Host Interactions Revealed by CRISPR Spacer Content in a Fish Pathogen

The role of prophages in the evolution, diversification, or virulence of the fish pathogen Flavobacterium columnare has not been studied thus far. Here, we describe a functional spontaneously inducing prophage fF4 from the F. columnare type strain ATCC 23463, which is not detectable with commonly used prophage search methods. We show that this prophage type has a global distribution and is present in strains isolated from Finland, Thailand, Japan, and North America. The virions of fF4 are myoviruses with contractile tails and infect only bacterial strains originating from Northern Finland. The fF4 resembles transposable phages by similar genome organization and several gene orthologs. Additional bioinformatic analyses reveal several species in the phylum Bacteroidetes that host a similar type of putative prophage, including bacteria that are important animal and human pathogens. Furthermore, a survey of F. columnare Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) spacers indicate a shared evolutionary history between F. columnare strains and the fF4 phage, and another putative prophage in the F. columnare strain ATCC 49512, named p49512. First, CRISPR spacer content from the two CRISPR loci (types II-C and VI-B) of the fF4 lysogen F. columnare ATCC 23463 revealed a phage terminase protein-matching spacer in the VI-B locus. This spacer is also present in two Chinese F. columnare strains. Second, CRISPR analysis revealed four F. columnare strains that contain unique spacers targeting different regions of the putative prophage p49512 in the F. columnare strain ATCC 49512, despite the geographical distance or genomovar of the different strains. This suggests a common ancestry for the F. columnare prophages and different host strains.
Body-Worn IMU Human Skeletal Pose Estimation Using a Factor Graph-Based Optimization Framework

Traditionally, inertial measurement units- (IMU) based human joint angle estimation requires a priori knowledge about sensor alignment or specific calibration motions. Furthermore, magnetometer measurements can become unreliable indoors. Without magnetometers, however, IMUs lack a heading reference, which leads to unobservability issues. This paper proposes a magnetometer-free estimation method, which provides desirable observability qualities under joint kinematics that sufficiently excite the lower body degrees of freedom. The proposed lower body model expands on the current self-calibrating human-IMU estimation literature and demonstrates a novel knee hinge model, the inclusion of segment length anthropometry, segment cross-leg length discrepancy, and the relationship between the knee axis and femur/tibia segment. The maximum a posteriori problem is formulated as a factor graph and inference is performed via post-hoc, on-manifold global optimization. The method is evaluated (N = 12) for a prescribed human motion profile task. Accuracy of derived knee flexion/extension angle (4.34∘ root mean square error (RMSE)) without magnetometers is similar to current state-of-the-art with magnetometer use. The developed framework can be expanded for modeling additional joints and constraints.
Endocrine-Disrupting Air Pollutants and Their Effects on the Hypothalamus-Pituitary-Gonadal Axis

Anthropogenic endocrine-disrupting chemicals (EDCs) can contaminate air, soil, and water. Human exposures to EDCs occur through inhalation, absorption, and ingestion. EDCs act by disrupting various pathways in the endocrine system. When the hypothalamic–pituitary–gonadal (HPG) axis is disrupted by EDCs, there can be effects on fertility in both men and women. Not only can fertility be indirectly affected by EDC disruptions of the HPG axis, but EDCs can also directly affect the menstrual cycle and sperm morphology. In this review, we will discuss the current findings on EDCs that can be inhaled. This review examines effects of exposure to prominent EDCs: brominated and organophosphate flame retardants, diesel exhaust, polycyclic aromatic hydrocarbons, cadmium and lead, TCDD, and polychlorinated biphenyls on fertility through alterations that disrupt the HPG axis and fertility through inhalation. Although the studies included herein include multiple exposure routes, all the studies indicate receptor interactions that can occur from inhalation and the associated effects of all compounds on the HPG axis and subsequent fertility.
Comparison Between eGFR by Schwartz Formula with Measured GFR by Radionuclide Diethylenetriamine Pentaacetic Acid Scan (Tc99 DTPA scan), in Patients Undergoing Chemotherapy with Nephrotoxic Drugs.

INTRODUCTION Children with malignancy who are under treatment with nephrotoxic drugs are at risk of renal dysfunction. Due to increased life expectancy, evaluation of drug toxicity is now of higher importance than before. The aim of this study is to compare two methods of GFR measurement. METHODS An analytical study on children with malignancy undergoing chemotherapy with nephrotoxic drugs (cisplatin, carboplatin, cyclophosphamide, ifosfamind, etoposide) during 2016 and 2017 in Mofid Children Hospital was done. Demographic information, anthropometric measurements, type of malignancy, type of chemotherapy medication and also lab tests including CBC and the biochemistry indices were recorded. The GFR of each patient was calculated using Schwartz formula and DTPA scanning. The rates were compared and the difference was analyzed statistically. RESULTS According to Schwartz formula, 24% of patients needed dose adjustment, while based on DTPA scanning, this rate was 6%. Comparing these two measures by paired T-test, showed a significant statistical difference (P < .05). Schwartz formula had 25.5% more positive results of predicting the need for dose adjustment. The two measured GFRs for each person were evaluated in terms of compatibility and correlation based on Kappa statistical method, which were incompatible and had significant difference (P < .05). CONCLUSION Using evaluative methods including Schwartz formula cannot demonstrate renal dysfunctions reliability in patients taking nephrotoxic chemotherapy drugs. Eventually if the GFR measurement method overestimates patients with renal dysfunction, the patients will not be able to make adequate use of the therapeutic effects of chemotherapy with the appropriate dosage.
Improving the Intelligibility of Speech for Simulated Electric and Acoustic Stimulation Using Fully Convolutional Neural Networks

Combined electric and acoustic stimulation (EAS) has demonstrated better speech recognition than conventional cochlear implant (CI) and yielded satisfactory performance under quiet conditions. However, when noise signals are involved, both the electric signal and the acoustic signal may be distorted, thereby resulting in poor recognition performance. To suppress noise effects, speech enhancement (SE) is a necessary unit in EAS devices. Recently, a time-domain speech enhancement algorithm based on the fully convolutional neural networks (FCN) with a short-time objective intelligibility (STOI)-based objective function (termed FCN(S) in short) has received increasing attention due to its simple structure and effectiveness of restoring clean speech signals from noisy counterparts. With evidence showing the benefits of FCN(S) for normal speech, this study sets out to assess its ability to improve the intelligibility of EAS simulated speech. Objective evaluations and listening tests were conducted to examine the performance of FCN(S) in improving the speech intelligibility of normal and vocoded speech in noisy environments. The experimental results show that, compared with the traditional minimum-mean square-error SE method and the deep denoising autoencoder SE method, FCN(S) can obtain better gain in the speech intelligibility for normal as well as vocoded speech. This study, being the first to evaluate deep learning SE approaches for EAS, confirms that FCN(S) is an effective SE approach that may potentially be integrated into an EAS processor to benefit users in noisy environments.
Distinct roles for prominin-1 and photoreceptor cadherin in outer segment disc morphogenesis in CRISPR-altered X. laevis

ABSTRACT Mutations in prominin-1 (prom1) and photoreceptor cadherin (cdhr1) are associated with inherited retinal degenerative disorders but their functions remain unknown. Here, we used CRISPR-Cas9 to generate prom1-null, cdhr1-null, and prom1 plus cdhr1 double-null Xenopus laevis and then documented the effects of these mutations on photoreceptor structure and function. Prom1-null mutations resulted in severely dysmorphic photoreceptors comprising overgrown and disorganized disc membranes. Cone outer segments were more severely affected than rods and had an impaired electroretinogram response. Cdhr1-null photoreceptors did not appear grossly dysmorphic, but ultrastructural analysis revealed that some disc membranes were overgrown or oriented vertically within the plasma membrane. Double-null mutants did not differ significantly from prom1-null mutants. Our results indicate that neither prom1 nor cdhr1 are necessary for outer segment disc membrane evagination or the fusion event that controls disc sealing. Rather, they are necessary for the higher-order organization of the outer segment. Prom1 may align and reinforce interactions between nascent disc leading edges, a function more critical in cones for structural support. Cdhr1 may secure discs in a horizontal orientation prior to fusion and regulate cone lamellae size. This article has an associated First Person interview with the first author of the paper. Highlighted Article: Prominin-1 aligns and reinforces the leading edges and photoreceptor cadherin maintains higher-order organization. Both prominin-1 and photoreceptor cadherin regulate nascent disc membrane size.
The surface lipoproteins of gram-negative bacteria: Protectors and foragers in harsh environments

Gram-negative pathogens are enveloped by an outer membrane that serves as a double-edged sword: On the one hand, it provides a layer of protection for the bacterium from environmental insults, including other bacteria and the host immune system. On the other hand, it restricts movement of vital nutrients into the cell and provides a plethora of antigens that can be detected by host immune systems. One strategy used to overcome these limitations is the decoration of the outer surface of gram-negative bacteria with proteins tethered to the outer membrane through a lipid anchor. These surface lipoproteins (SLPs) fulfill critical roles in immune evasion and nutrient acquisition, but as more bacterial genomes are sequenced, we are beginning to discover their prevalence and their different roles and mechanisms and importantly how we can exploit them as antimicrobial targets. This review will focus on representative SLPs that gram-negative bacteria use to overcome host innate immunity, specifically the areas of nutritional immunity and complement system evasion. We elaborate on the structures of some notable SLPs required for binding target molecules in hosts and how this information can be used alongside bioinformatics to understand mechanisms of binding and in the discovery of new SLPs. This information provides a foundation for the development of therapeutics and the design of vaccine antigens.
The endothelial dysfunction blocker CU06-1004 ameliorates choline-deficient L-amino acid diet-induced non-alcoholic steatohepatitis in mice

Non-alcoholic steatohepatitis (NASH) is a severe, advanced form of non-alcoholic fatty liver disease (NAFLD) that is associated with features of metabolic syndrome and characterized by hepatic steatosis, inflammation, and fibrosis. In addition, NASH is associated with endothelial dysfunction within the hepatic vasculature. Treatment with CU06-1004 (previously called Sac-1004) ameliorates endothelial dysfunction by inhibiting hyperpermeability and inflammation. In this study, we investigated the protective effects of CU06-1004 in a choline-deficient L-amino acid (CDAA)-induced mouse model of NASH for 3 or 6 weeks. Specifically, we evaluated the effects of CU06-1004 on lipid accumulation, inflammation, hepatic fibrosis, and liver sinusoidal endothelial cell (LSEC) capillarization through biochemical analysis, immunohistochemistry, and real-time PCR. We found that the administration of CU06-1004 to mice improved liver triglyceride (TG) and serum alanine aminotransferase (ALT) in this CDAA-induced model of NASH for 6 weeks. In groups of NASH induced mice for both 3 and 6 weeks, CU06-1004 significantly reduced the hepatic expression of genes related to lipogenesis, inflammation, and cell adhesion. However, expression of genes related to hepatic fibrosis and vascular endothelial changes were only decreased in animals with mild NASH. These results suggest that the administration of CU06-1004 suppresses hepatic steatosis, inflammation, fibrosis, and LSEC capillarization in a CDAA-induced mouse model of NASH. This suggests that CU06-1004 has therapeutic potential for the treatment of mild NASH.
Leucine Supplementation Decreases HDAC4 Expression and Nuclear Localization in Skeletal Muscle Fiber of Rats Submitted to Hindlimb Immobilization

In this study we surveyed a rat skeletal muscle RNA-Seq for genes that are induced by hindlimb immobilization and, in turn, become attenuated by leucine supplementation. This approach, in search of leucine-atrophy protection mediating genes, identified histone deacetylase 4 (HDAC4) as highly responsive to both hindlimb immobilization and leucine supplementation. We then examined the impact of leucine on HDAC4 expression, tissue localization, and target genes. A total of 76 male Wistar rats (~280 g) were submitted to hindlimb immobilization and/or leucine supplementation for 3, 7 and 12 days. These animals were euthanized, and soleus muscle was removed for further analysis. RNA-Seq analysis of hindlimb immobilized rats indicated a sharp induction (log2 = 3.4) of HDAC4 expression which was attenuated by leucine supplementation (~50%). Real-time PCR and protein expression analysis by Western blot confirmed increased HDAC4 mRNA after 7 days of hindlimb immobilization and mitigation of induction by leucine supplementation. Regarding the HDAC4 localization, the proportion of positive nuclei was higher in the immobilized group and decreased after leucine supplementation. Also, we found a marked decrease of myogenin and MAFbx-atrogin-1 mRNA levels upon leucine supplementation, while CAMKII and DACH2 mRNA levels were increased by leucine supplementation. Our data suggest that HDAC4 inhibition might be involved in the anti-atrophic effects of leucine.
Waist Circumference as a Preventive Tool of Atherogenic Dyslipidemia and Obesity-Associated Cardiovascular Risk in Young Adults Males: A Cross-Sectional Pilot Study

Although the correlation coefficient between body mass index (BMI) and poor lipid profile has been reported, representing a cardiovascular risk, the need to find new early detection markers is real. Waist circumference and markers of atherogenic dyslipidemia are not usually measured in medical review appointments. The present study aimed to investigate the relationship between central adiposity and cardiovascular risk. This was a cross-sectional pilot study of 57 young males (age: 35.9 ± 10.85, BMI: 32.4 ± 6.08) recruited from community settings and allocated to non-obese or obese attending to their waist circumference. Total cholesterol (TC), high-density lipoproteins (HDL-C), and low-density lipoproteins (LDL-C) cholesterol and triglycerides (TG) were measured from plasma samples. Patients with at least 100 cm of waist circumference had significantly increased TC, LDL-C, non-HDL-C, and triglycerides and lower levels of HDL-C. The three atherogenic ratios TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C were all optimal in non-obese patients. LDL-C/HDL-C and TG/HDL-C were significantly higher and over the limit when assessing for atherogenic dyslipidemia. The number of patients at risk for cardiovascular events increases 2.5 folds in obese compared to non-obese. Measurement of waist circumference could be adopted as a simpler valid alternative to BMI for health promotion, to alert those at risk of atherogenic dyslipidemia.