Miracle-dz/UniFAR-FTUs huggingface dataset:
Metal-dependent programmed cell death-related lncRNA prognostic signatures and natural drug sensitivity prediction for gastric cancer

Background: Gastric cancer is one of the most important malignancies with poor prognosis. Ferroptosis and cuproptosis are newly discovered metal-dependent types of programmed cell death, which may directly affect the outcome of gastric cancer. Long noncoding RNAs (lncRNAs) can affect the prognosis of cancer with stable structures, which could be potential prognostic prediction factors for gastric cancer. Methods: Differentially expressed metal-dependent programmed cell death (PCD)-related lncRNAs were identified with DESeq2 and Pearson’s correlation analysis. Through GO and KEGG analyses and GSEA , we identified the potential effects of metal-dependent PCD-related lncRNAs on prognosis. Using Cox regression analysis with the LASSO method, we constructed a 12-lncRNA prognostic signature model. Also, we evaluated the prognostic efficiency with Kaplan–Meier (K-M) survival curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) methods. The sensitivities for antitumor drugs were then predicted with the pRRophetic method. Also, we discuss Chinese patent medicines and plant extracts that could induce metal-dependent programmed cell death. Results: We constructed a metal-dependent PCD-related lncRNA-gene co-expression network. Also, a metal-dependent PCD-related gastric cancer prognostic signature model including 12 lncRNAs was constructed. The K-M survival curve revealed a poor prognosis in the high-risk group. ROC curve analysis shows that the AUC of our model is 0.766, which is better than that of other published models. Moreover, the half-maximum inhibitory concentration (IC50) for dasatinib, lapatinib, sunitinib, cytarabine, saracatinib, and vinorelbine was much lower among the high-risk group. Conclusion: Our 12 metal-dependent PCD-related lncRNA prognostic signature model may improve the OS prediction for gastric cancer. The antitumor drug sensitivity analysis results may also be helpful for individualized chemotherapy regimen design.
A review of non-invasive sensors and artificial intelligence models for diabetic foot monitoring

Diabetic foot complications have multiple adverse effects in a person’s quality of life. Yet, efficient monitoring schemes can mitigate or postpone any disorders, mainly by early detecting regions of interest. Nowadays, optical sensors and artificial intelligence (AI) tools can contribute efficiently to such monitoring processes. In this work, we provide information on the adopted imaging schemes and related optical sensors on this topic. The analysis considers both the physiology of the patients and the characteristics of the sensors. Currently, there are multiple approaches considering both visible and infrared bands (multiple ranges), most of them coupled with various AI tools. The source of the data (sensor type) can support different monitoring strategies and imposes restrictions on the AI tools that should be used with. This review provides a comprehensive literature review of AI-assisted DFU monitoring methods. The paper presents the outcomes of a large number of recently published scholarly articles. Furthermore, the paper discusses the highlights of these methods and the challenges for transferring these methods into a practical and trustworthy framework for sufficient remote management of the patients.
Prevention and treatment of ventilator-associated pneumonia in COVID-19

Ventilator-associated pneumonia (VAP) is the most common acquired infection in the intensive care unit. Recent studies showed that the critical COVID-19 patients with invasive mechanical ventilation have a high risk of developing VAP, which result in a worse outcome and an increasing economic burden. With the development of critical care medicine, the morbidity and mortality of VAP remains high. Especially since the outbreak of COVID-19, the healthcare system is facing unprecedented challenges. Therefore, many efforts have been made in effective prevention, early diagnosis, and early treatment of VAP. This review focuses on the treatment and prevention drugs of VAP in COVID-19 patients. In general, prevention is more important than treatment for VAP. Prevention of VAP is based on minimizing exposure to mechanical ventilation and encouraging early release. There is little difference in drug prophylaxis from non-COVID-19. In term of treatment of VAP, empirical antibiotics is the main treatment, special attention should be paid to the antimicrobial spectrum and duration of antibiotics because of the existence of drug-resistant bacteria. Further studies with well-designed and large sample size were needed to demonstrate the prevention and treatment of ventilator-associated pneumonia in COVID-19 based on the specificity of COVID-19.
Structural consequences of sequence variation in mammalian prion β2α2 loop segments

Sequence variation in the β2α2 loop, residues 165-175 of the mammalian prion protein (PrP), influences its structure. To better understand the consequences of sequence variation in this region of the protein, we biochemically and biophysically interrogate natural and artificial sequence variants of the β2α2 loop of mammalian PrP. Using microcrystal electron diffraction (MicroED), we determine atomic resolution structures of segments encompassing residues 168-176 from the β2α2 loop of PrP with sequences corresponding to human, mouse/cow, bank vole/hamster, rabbit/pig/guinea pig, and naked mole rat (elk-T174S) β2α2 loops, as well as synthetic β2α2 loop sequences. This collection of structures presents two dominant amyloid packing polymorphisms. In the first polymorph, denoted “clasped”, side chains within a sheet form polar clasps by facing each other on the same strand, exemplified by the mouse/cow, human, and bank vole/hamster sequences. Because its stability is derived from within a strand and through polar ladders within a sheet, the sequence requirements for the mating strand are less restrictive. A second polymorph, denoted “interdigitated,” has sidechains interdigitate across mating sheets, exemplified by the elk, naked mole rat (elk T174S), and rabbit sequences. The two types of packing present distinct networks of stabilizing hydrogen bonds. The identity of residue 174 appears to strongly influence the packing adopted in these peptides, but consideration of the overall sequence of a given segment is needed to understand the stability of its assemblies. Incorporation of these β2α2 loop sequences into an 85 residue recombinant segment encoding wild-type bank vole PrP94–178 demonstrates that even single residue substitutions could impact fibril morphology as evaluated by negative stain electron microscopy. This is in line with recent findings supporting the accessibility of different structural geometries by varied mammalian prion sequences, and indicates that sequence-specific polymorphisms may be influenced by residues in the β2α2 loop.
Unraveling the mechanism of furfural tolerance in engineered Pseudomonas putida by genomics

As a dehydration product of pentoses in hemicellulose sugar streams derived from lignocellulosic biomass, furfural is a prevalent inhibitor in the efficient microbial conversion process. To solve this obstacle, exploiting a biorefinery strain with remarkable furfural tolerance capability is essential. Pseudomonas putida KT2440 (P. putida) has served as a valuable bacterial chassis for biomass biorefinery. Here, a high-concentration furfural-tolerant P. putida strain was developed via adaptive laboratory evolution (ALE). The ALE resulted in a previously engineered P. putida strain with substantially increased furfural tolerance as compared to wild-type. Whole-genome sequencing of the adapted strains and reverse engineering validation of key targets revealed for the first time that several genes and their mutations, especially for PP_RS19785 and PP_RS18130 [encoding ATP-binding cassette (ABC) transporters] as well as PP_RS20740 (encoding a hypothetical protein), play pivotal roles in the furfural tolerance and conversion of this bacterium. Finally, strains overexpressing these three striking mutations grew well in highly toxic lignocellulosic hydrolysate, with cell biomass around 9-, 3.6-, and two-fold improvement over the control strain, respectively. To our knowledge, this study first unravels the furan aldehydes tolerance mechanism of industrial workhorse P. putida, which provides a new foundation for engineering strains to enhance furfural tolerance and further facilitate the valorization of lignocellulosic biomass.
Identification and validation of a novel tumor driver gene signature for diagnosis and prognosis of head and neck squamous cell carcinoma

Objective: Head and neck squamous cell carcinoma (HNSCC) is a common heterogeneous cancer with complex carcinogenic factors. However, the current TNM staging criteria to judge its severity to formulate treatment plans and evaluate the prognosis are particularly weak. Therefore, a robust diagnostic model capable of accurately diagnosing and predicting HNSCC should be established. Methods: Gene expression and clinical data were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. Key prognostic genes associated with HNSCC were screened with the weighted gene co-expression network analysis and least absolute shrinkage and selection operator (LASSO) Cox regression model analysis. We used the timeROC and survival R packages to conduct time-dependent receiver operating characteristic curve analyses and calculated the area under the curve at different time points of model prediction. Patients in the training and validation groups were divided into high- and low-risk subgroups, and Kaplan-Meier (K-M) survival curves were plotted for all subgroups. Subsequently, LASSO and support vector machine algorithms were used to screen genes to construct diagnostic model. Furthermore, we used the Wilcoxon signed-rank test to compare the half-maximal inhibitory concentrations of common chemotherapy drugs among patients in different risk groups. Finally, the expression levels of eight genes were measured using quantitative real-time polymerase chain reaction and immunohistochemistry. Results: Ten genes (SSB, PFKP, NAT10, PCDH9, SHANK2, PAX8, CELSR3, DCLRE1C, MAP2K7, and ODF4) with prognostic potential were identified, and a risk score was derived accordingly. Patients were divided into high- and low-risk groups based on the median risk score. The K-M survival curves confirmed that patients with high scores had significantly worse overall survival. Receiver operating characteristic curves proved that the prognostic signature had good sensitivity and specificity for predicting the prognosis of patients with HNSCC. Univariate and multivariate Cox regression analyses confirmed that the gene signature was an independent prognostic risk factor for HNSCC. Diagnostic model was built by identifying eight genes (SSB, PFKP, NAT10, PCDH9, CELSR3, DCLRE1C, MAP2K7, and ODF4). The high-risk group showed higher sensitivity to various common chemotherapeutic drugs. DCLRE1C expression was higher in normal tissues than in HNSCC tissues. Conclusion: Our study identified the important role of tumor-driver genes in HNSCC and their potential clinical diagnostic and prognostic values to facilitate individualized management of patients with HNSCC.
Engineered 5-HT producing gut probiotic improves gastrointestinal motility and behavior disorder

Slow transit constipation is an intractable constipation with unknown aetiology and uncertain pathogenesis. The gut microbiota maintains a symbiotic relationship with the host and has an impact on host metabolism. Previous studies have reported that some gut microbes have the ability to produce 5-hydroxytryptamine (5-HT), an important neurotransmitter. However, there are scarce data exploiting the effects of gut microbiota-derived 5-HT in constipation-related disease. We genetically engineered the probiotic Escherichia coli Nissle 1917 (EcN-5-HT) for synthesizing 5-HT in situ. The ability of EcN-5-HT to secrete 5-HT in vitro and in vivo was confirmed. Then, we examined the effects of EcN-5-HT on intestinal motility in a loperamide-induced constipation mouse model. After two weeks of EcN-5-HT oral gavage, the constipation-related symptoms were relieved and gastrointestinal motility were enhanced. Meanwhile, administration of EcN-5-HT alleviated the constipation related depressive-like behaviors. We also observed improved microbiota composition during EcN-5-HT treatment. This work suggests that gut microbiota-derived 5-HT might promise a potential therapeutic strategy for constipation and related behavioral disorders.
Noncoding RNAs as a novel approach to target retinopathy of prematurity

Retinopathy of prematurity (ROP), a vascular disease characterized by abnormal vessel development in the retina, has become a primary cause of blindness in children around the world. ROP can be developed during two different phases: vessel loss and vessel proliferation. Once preterm infants with immature retinal vessel growth are exposed to high level of oxygen inside the incubator, vessel loss can occur. When infants are exposed to room air, they may experience the proliferation of vessels in the retina. Although multiple factors are reported to be involved in the pathogenesis of ROP, including vaso-endothelial growth factors (VEGFs) and hypoxia-inducible factors, the pathogenesis of ROP is not completely understood. Although laser therapy and pharmacologic agents, such as anti-VEGF agents, have been commonly used to treat ROP, the incidence of ROP is rapidly rising. Given that current therapies can be invasive and long-term effects are not fully known, the search for novel therapeutic targets with less destructive properties needs to be considered. Within the last decade, the field of noncoding RNA therapy has shown potential as next-generation therapy to treat diverse diseases. In this review, we introduce various noncoding RNAs regulating ROP and discuss their role as potential therapeutic targets in ROP.
Delving into the relationship between teacher emotion regulation, self-efficacy, engagement, and anger: A focus on English as a foreign language teachers

Due to the potent role of teachers’ emotion regulation in effective teaching, it seems essential to see how emotion regulation can contribute to other relevant teaching constructs. In this regard, the present study is intended to probe into the causal relationship among teacher emotion regulation, self-efficacy beliefs, engagement, and anger. In so doing, the Language Teacher Emotion Regulation Inventory (LTERI), The Teacher Sense of Efficacy Scale (TSES), The Engaged Teacher Scale (ETS), and The Teacher Anger Scale (TAS) were administered to 581 English as a Foreign Language (EFL) teachers in Iran. To gauge the causal relationships among the variables, confirmatory factor analysis (CFA) and structural equation modeling (SEM) using LISREL 8.80 were conducted. The results indicated that language teacher emotion regulation could positively and significantly predict teachers’ self-efficacy beliefs and engagement at work. Moreover, the influence of language teacher emotion regulation on the teacher’s anger is significantly negative. That is, the stronger emotion regulation is implemented the better teachers can manage their anger. The implications of this study may uncover new prospects for effective teaching, especially during the COVID-19 pandemic.
Tissue concentration of vascular endothelial growth factor is not related to the depth of trophoblastic invasion in ampullary pregnancies—A pilot study

Introduction: The factors that modulate trophoblastic invasion into the tubal wall remain uncertain. Moreover, it is known that the concentration of vascular endothelial growth factor (VEGF) is increased in cases of deeper trophoblastic invasion in the fallopian tubes. Objective: This study aimed to assess if there is a correlation between VEGF tissue expression and the depth of trophoblastic infiltration into the tubal wall in patients with ampullary pregnancy. Methods: A cross-sectional study was conducted in patients with a diagnosis of tubal pregnancy in the ampullary region who underwent salpingectomy. Inclusion criteria were spontaneously conceived singleton pregnancies, diagnosis of tubal pregnancy in the ampullary region, and radical surgical treatment. A lack of agreement regarding the location of the tubal pregnancy and impossibility of either anatomopathological or tissue VEGF analysis were the exclusion criteria. Histologically, trophoblastic invasion into the tubal wall was classified as grade I when limited to the tubal mucosa, grade II when it reached the muscle layer, and grade III when it comprised the full thickness of the tubal wall. A total of 42 patients fulfilled the inclusion criteria and were selected to participate in the study. Eight patients were excluded. After surgery, tissue VEGF expression was measured by immunohistochemistry and the point counting technique. Results: Histological analysis revealed that eight patients had stage I tubal infiltration, seven had stage II, and 19 had stage III. The difference between the percentage of VEGF expression in the trophoblastic tissue was not significant in relation to the degree of trophoblastic invasion (p = 0.621) (ANOVA). Trophoblastic tissue VEGF showed no statistical difference for prediction of both degrees of trophoblastic invasion (univariate multinomial regression). Conclusion: The depth of trophoblastic penetration into the tubal wall in ampullary pregnancies is not associated with tissue VEGF expression.
Development of multiplex cross displacement amplification combined with lateral flow biosensor assay for detection of virulent shigella sonnei

Shigella sonnei is the most common Shigella spp. in developed areas and the second most common in undeveloped regions. In this study, a multiple cross displacement amplification (MCDA) assay was used in combination with a lateral flow biosensor (LFB) assay to detect virulent S. sonnei strains containing the ipaH and wbgX genes. The multiplex MCDA-LFB assay detected wbgX at ≥1 pg/μL and ipaH at ≥10 fg/μL within 30 min in pure cultures maintained at 63°C. This assay was sensitive for ~37 CFU of virulent S. sonnei and ~3.7 CFU of Shigella spp. and enteroinvasive E. coli in stimulated fecal samples and had 100% specificity among 59 reference strains. The MCDA-LFB assay was also able to differentiate between virulent S. sonnei and other Shigella spp. and enteroinvasive E. coli among 99 clinical isolates. In summary, a multiplex MCDA-LFB assay was developed for rapid, convenient, point-of-care, and accurate identification of virulent S. sonnei within 30 min and at a constant temperature without the need for expensive lab equipment.
A novel prognostic model based on urea cycle-related gene signature for colorectal cancer

Background Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the world. This study aimed to develop a urea cycle (UC)-related gene signature that provides a theoretical foundation for the prognosis and treatment of patients with CRC. Methods Differentially expressed UC-related genes in CRC were confirmed using differential analysis and Venn diagrams. Univariate Cox and least absolute shrinkage and selection operator regression analyses were performed to identify UC-related prognostic genes. A UC-related signature was created and confirmed using distinct datasets. Independent prognostic predictors were authenticated using Cox analysis. The Cell-type Identification by Estimating Relative Subsets of RNA Transcripts algorithm and Spearman method were applied to probe the linkage between UC-related prognostic genes and tumor immune-infiltrating cells. The Human Protein Atlas database was used to determine the protein expression levels of prognostic genes in CRC and normal tissues. Verification of the expression levels of UC-related prognostic genes in clinical tissue samples was performed using real-time quantitative polymerase chain reaction (qPCR). Results A total of 49 DEUCRGs in CRC were mined. Eight prognostic genes (TIMP1, FABP4, MMP3, MMP1, CD177, CA2, S100P, and SPP1) were identified to construct a UC-related gene signature. The signature was then affirmed using an external validation set. The risk score was demonstrated to be a credible independent prognostic predictor using Cox regression analysis. Functional enrichment analysis revealed that focal adhesion, ECM-receptor interaction, IL-17 signaling pathway, and nitrogen metabolism were associated with the UC-related gene signature. Immune infiltration and correlation analyses revealed a significant correlation between UC-related prognostic genes and differential immune cells between the two risk subgroups. Finally, the qPCR results of clinical samples further confirmed the results of the public database. Conclusion Taken together, this study authenticated UC-related prognostic genes and developed a gene signature for the prognosis of CRC, which will be of great significance in the identification of prognostic molecular biomarkers, clinical prognosis prediction, and development of treatment strategies for patients with CRC.
Maintaining social capital in offenders with schizophrenia spectrum disorder—An explorative analysis of influential factors

The importance of “social capital” in offender rehabilitation has been well established: Stable family and community relationships offer practical assistance in the resettlement process after being released from custody and can serve as motivation for building a new sense of self off the criminal past, thus reducing the risk of re-offending. This also applies to offenders with severe mental disorders. The aim of this study was to identify factors that promote or hinder the establishment or maintenance of social relationships upon release from a court-ordered inpatient treatment using a modern statistical method—machine learning (ML)—on a dataset of 369 offenders with schizophrenia spectrum disorder (SSD). With an AUC of 0.73, support vector machines (SVM) outperformed all the other ML algorithms. The following factors were identified as most important for the outcome in respect of a successful re-integration into society: Social integration and living situation prior to the hospitalization, a low risk of re-offending at time of discharge from the institution, insight in the wrongfulness of the offense as well as into the underlying psychiatric illness and need for treatment, addressing future perspectives in psychotherapy, the improvement of antisocial behavior during treatment as well as a detention period of less than 1 year emerged as the most predictive out of over 500 variables in distinguishing patients who had a social network after discharge from those who did not. Surprisingly, neither severity and type of offense nor severity of the psychiatric illness proved to affect whether the patient had social contacts upon discharge or not. The fact that the majority of determinants which promote the maintenance of social contacts can be influenced by therapeutic interventions emphasizes the importance of the rehabilitative approach in forensic-psychiatric therapy.