Miracle-dz/UniFAR-FTUs huggingface dataset:
Construction of a Nine-MicroRNA-Based Signature to Predict the Overall Survival of Esophageal Cancer Patients

Background Esophageal cancer (EC) is a common malignant tumor. MicroRNAs (miRNAs) play a key role in the occurrence and metastasis and are closely related to the prognosis of EC. Therefore, it will provide a powerful tool to predict the overall survival (OS) of EC patients based on miRNAs expression in EC tissues and blood samples. Methods Five independent databases, TCGA, GSE106817, GSE113486, GSE122497, and GSE112264, were used to construct nine-miRna signature and nomograms for prognosis. The bioinformatics analysis was used to predict the enrichment pathways of targets. Results A total of 132 overexpressed miRNAs and 23 suppressed miRNAs showed significant differential expression in both EC serum and tissue samples compared with normal samples. We also showed that nine miRNAs were related to the prognosis of EC. Higher levels of miR-15a-5p, miR-92a-3p, miR-92a-1-5p, miR-590-5p, miR-324-5p, miR-25-3p, miR-181b-5p, miR-421, and miR-93-5p were correlated to the shorter survival time in patients with EC. In addition, we constructed a risk prediction model based on the levels of nine differentially expressed miRNAs (DEMs) and found that the OS time of EC patients with high-risk score was shorter than that of EC patients with low-risk score. Furthermore, our results showed that the risk prediction scores of EC samples were higher than those of normal samples. Finally, the area under the curve (AUC) was used to analyze the risk characteristics of EC and normal controls. By calculating the AUC and the calibration curve, the RNA signature showed a good performance. Bioinformatics analysis showed that nine DEMs were associated with several crucial signaling, including p53, FoxO, PI3K-Akt, HIF-1, and TORC1 signaling. Finally, 14 messenger RNAs (mRNAs) were identified as hub targets of nine miRNAs, including BTRC, SIAH1, RNF138, CDC27, NEDD4L, MKRN1, RLIM, FBXO11, RNF34, MYLIP, FBXW7, RNF4, UBE3C, and RNF111. TCGA dataset validation showed that these hub targets were significantly differently expressed in EC tissues compared with normal samples. Conclusion We have constructed maps and nomograms of nine-miRna risk signals associated with EC prognosis. Bioinformatics analysis revealed that nine DEMs were associated with several crucial signaling, including p53, FoxO, PI3K-Akt, HIF-1, and TORC1 signaling, in EC. We think that this study will provide clinicians with an effective decision-making tool.
Wild Food Harvest, Food Security, and Biodiversity Conservation in Jamaica: A Case Study of the Millbank Farming Region

Harvesting wild food is an important coping strategy to deal with food insecurity in farming households across the Caribbean. The practice is tightly connected to the region's unique agrarian history, food heritage, traditional cuisine, and local knowledge of wild or semidomesticated plants. In Jamaica, small-scale farmers are the chief stewards of agrobiodiversity, and their food security and well-being are often dependent on wild food harvest. Yet, there is a paucity of empirical research on the relationship between wild food use, food security, and biodiversity conservation. In this paper, we use the knowledge and lived experience of rural farmers in a remote community (Millbank) at the edge of the Blue and John Crow Mountains National Park (BJMNP) to explore the relationship between wild food harvest and food insecurity within the context of protected area management. Specifically, we seek to (1) characterize different patterns of wild food harvest; (2) examine the relationship between food insecurity and wild food harvest, and (3) explore the implications of forest conservation measures for wild food harvest. Detailed interviews were conducted with 43 farmers to capture data on food insecurity, wild food collection, livelihood satisfaction, household characteristics, farming activities, livelihood strategies, and forest resource interaction. The Food Insecurity Experience Scale (FIES) was used to characterize food insecurity, while participatory techniques were used to develop indicators to assess the well-being of farmers. The results show strong evidence of a relationship between wild food harvest and food insecurity (p < 0.001). Overall, the findings support the importance of wild foods to the well-being of rural households and provide empirical evidence for its inclusion in food security, poverty, and biodiversity conservation policies.
Impaired Vitamin D Signaling in T Cells From a Family With Hereditary Vitamin D Resistant Rickets

The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), mediates its immunomodulatory effects by binding to the vitamin D receptor (VDR). Here, we describe a new point mutation in the DNA-binding domain of the VDR and its consequences for 1,25(OH)2D3 signaling in T cells from heterozygous and homozygous carriers of the mutation. The mutation did not affect the overall structure or the ability of the VDR to bind 1,25(OH)2D3 and the retinoid X receptor. However, the subcellular localization of the VDR was strongly affected and the transcriptional activity was abolished by the mutation. In heterozygous carriers of the mutation, 1,25(OH)2D3-induced gene regulation was reduced by ~ 50% indicating that the expression level of wild-type VDR determines 1,25(OH)2D3 responsiveness in T cells. We show that vitamin D-mediated suppression of vitamin A-induced gene regulation depends on an intact ability of the VDR to bind DNA. Furthermore, we demonstrate that vitamin A inhibits 1,25(OH)2D3-induced translocation of the VDR to the nucleus and 1,25(OH)2D3-induced up-regulation of CYP24A1. Taken together, this study unravels novel aspects of vitamin D signaling and function of the VDR in human T cells.
Oolemma Receptors in Mammalian Molecular Fertilization: Function and New Methods of Study

Fertilization is a key process in biology to the extent that a new individual will be born from the fusion of two cells, one of which leaves the organism in which it was produced to exert its function within a different organism. The structure and function of gametes, and main aspects of fertilization are well known. However, we have limited knowledge about the specific molecules participating in each of the steps of the fertilization process due to the transient nature of gamete interaction. Moreover, if we specifically focus in the fusion of both gametes’ membrane, we might say our molecular knowledge is practically null, despite that molecular mechanisms of cell-to-cell adhesion are well studied in somatic cells. Moreover, between both gametes, the molecular knowledge in the egg is even scarcer than in the spermatozoon for different reasons addressed in this review. Sperm-specific protein IZUMO1 and its oocyte partner, JUNO, are the first cell surface receptor pair essential for sperm–egg plasma membrane binding. Recently, thanks to gene editing tools and the development and validation of in vitro models, new oocyte molecules are being suggested in gamete fusion such as phosphatidylserine recognition receptors. Undoubtedly, we are in a new era for widening our comprehension on molecular fertilization. In this work, we comprehensively address the proposed molecules involved in gamete binding and fusion, from the oocyte perspective, and the new methods that are providing a better understanding of these crucial molecules.
Individual Pride and Collective Pride: Differences Between Chinese and American Corpora

This study investigated cross-cultural differences in individual pride and collective pride between Chinese and Americans using data from text corpora. We found higher absolute frequencies of pride items in the American corpus than in the Chinese corpus. Cross-cultural differences were found for relative frequencies of different types of pride, and some of them depended on the genre of the text corpora. For both blogs and news genres, Americans showed higher frequencies of individual pride items and lower frequencies of relational pride items than did their Chinese counterparts. Cross-cultural differences in national pride, however, depended on the genre: Chinese news genre included more national pride items than its American counterpart, but the opposite was true for the blog genre. We discuss the implications of these results in relation to the existing literature (based on surveys and laboratory-based experiments) on cultural differences in individual pride and collective pride.
Life Cycle and Genetic Identification of Argas persicus Infesting Domestic Fowl in Khyber Pakhtunkhwa, Pakistan

Ticks transmit numerous pathogens to animals including humans; therefore, they are parasites of health concern. Soft ticks infesting domestic fowl in Pakistan are carriers of viruses and bacteria and cause unestimated economic losses in the poultry sector. The current study was intended to identify soft ticks infesting domestic fowl and understand their spatiotemporal distribution along 1 year. A sum of 7,219 soft ticks were collected from 608 domestic fowl in 58 infested shelters; 938 (12.9%) ticks were found on the host and 6,281 (87%) in the shelters. The collected ticks comprised 3,503 (48.52%) adults including 1,547 (21.42%) males and 1,956 (27.09%) females, 3,238 (44.85%) nymphs, and 478 (6.62%) larvae. The most prevalent life stages were adults, followed by nymphs and larvae. Overall tick prevalence considering all visited shelters was 38.66% (58/150). The highest tick prevalence was found in district Lakki Marwat (50.03%) followed by Peshawar (31.08%) and Chitral (18.88%) districts. All ticks were morpho-taxonomically identified as Argas persicus. To determine their life cycle, adult A. persicus were reared in the laboratory infesting domestic fowl (Gallus gallus domesticus). The life cycle was completed in 113–132 days (egg to egg) with a mean temperature of 33 ± 3°C and relative humidity of 65 ± 5%. Individual ticks were used for DNA extraction and subjected to polymerase chain reaction (PCR) using specific primers for the amplification of a partial fragment of mitochondrial cytochrome oxidase subunit I (cox1) and 16S ribosomal RNA (16S rRNA) genes. Obtained amplicons were compared using basic local alignment search tool (BLAST) to scan for homologous sequences. Phylogenetic trees showed A. persicus from Pakistan clustering with conspecific sequences reported from Australia, Chile, China, Kenya, and the United States. This is the first study aiming to reproduce the life cycle of A. persicus and genetically identify this tick in the region. Further studies are encouraged to investigate the pathogens associated with this soft tick species in Pakistan.
Effects of the Brain Wave Modulation Technique Administered Online on Stress, Anxiety, Global Distress, and Affect During the First Wave of the COVID-19 Pandemic: A Randomized Clinical Trial

This study aims to evaluate the effects of an innovative mind-body practice named the brain wave modulation technique (BWM-T) on stress, anxiety, global distress, and affect. The technique was administered online through a web-based video conferencing platform. The intervention started on week four of the first quarantine in Italy (week commencing 30th March 2020), for a duration of 4 weeks and ended before lockdown measures were loosened. 310 people participated in the study, mean age 28.73 years old (SD = 9.16), 77.8% women. Of these, about half were randomly assigned to the experimental group and the other half served as controls. Participants completed online psychological tests before and after the intervention. 266 people (144 experimental, 122 controls) completed the post-intervention tests. Consistent with our hypothesis, the study’s findings indicate a reduction in the levels of stress, anxiety, global distress, and negative affect in the experimental group, compared to the control group. Moreover, the experimental group also showed higher levels of positive affect, compared to controls after the intervention. The present findings add to the current literature in suggesting that the BWM-T reduced stress not only when administered face-to face but also when administered online during the COVID-19 pandemic. Moreover, we also noted that the BWM-T has an effect on anxiety, global distress, and affect, which we had not investigated in previous studies.
Precision Medicine in Neonates: A Tailored Approach to Neonatal Brain Injury

Despite advances in neonatal care to prevent neonatal brain injury and neurodevelopmental impairment, predicting long-term outcome in neonates at risk for brain injury remains difficult. Early prognosis is currently based on cranial ultrasound (CUS), MRI, EEG, NIRS, and/or general movements assessed at specific ages, and predicting outcome in an individual (precision medicine) is not yet possible. New algorithms based on large databases and machine learning applied to clinical, neuromonitoring, and neuroimaging data and genetic analysis and assays measuring multiple biomarkers (omics) can fulfill the needs of modern neonatology. A synergy of all these techniques and the use of automatic quantitative analysis might give clinicians the possibility to provide patient-targeted decision-making for individualized diagnosis, therapy, and outcome prediction. This review will first focus on common neonatal neurological diseases, associated risk factors, and most common treatments. After that, we will discuss how precision medicine and machine learning (ML) approaches could change the future of prediction and prognosis in this field.
Multiomics Analysis Reveals Molecular Abnormalities in Granulosa Cells of Women With Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common complex endocrine and metabolic disease in women of reproductive age. It is characterized by anovulatory infertility, hormone disorders, and polycystic ovarian morphology. Regarding the importance of granulosa cells (GCs) in the pathogenesis of PCOS, few studies have investigated the etiology at a single “omics” level, such as with an mRNA expression array or methylation profiling assay, but this can provide only limited insights into the biological mechanisms. Here, genome-wide DNA methylation together with lncRNA-miRNA-mRNA profiles were simultaneously detected in GCs of PCOS cases and controls. A total of 3579 lncRNAs, 49 miRNAs, 669 mRNAs, and 890 differentially methylated regions (DMR)-associated genes were differentially expressed between PCOS cases and controls. Pathway analysis indicated that these differentially expressed genes were commonly associated with steroid biosynthesis and metabolism-related signaling, such as glycolysis/gluconeogenesis. In addition, we constructed ceRNA networks and identified some known ceRNA axes, such as lncRNAs-miR-628-5p-CYP11A1/HSD17B7. We also identified many new ceRNA axes, such as lncRNAs-miR-483-5p-GOT2. Interestingly, most ceRNA axes were also closely related to steroid biosynthesis and metabolic pathways. These findings suggest that it is important to systematically consider the role of reproductive and metabolic genes in the pathogenesis of PCOS.
Enhancing the Screening Efficiency of Breast Cancer by Combining Conventional Medical Imaging Examinations With Circulating Tumor Cells

Purpose Ultrasound (US) and mammogram (MMG) are the two most common breast cancer (BC) screening tools. This study aimed to assess how the combination of circulating tumor cells (CTC) with US and MMG would improve the diagnostic performance. Methods CTC detection and imaging examinations, US and MMG, were performed in 238 treatment-naive BC patients, 217 patients with benign breast diseases (BBD), and 20 healthy females. Correlations of CTC, US and MMG with patients’ clinicopathological characteristics were evaluated. Diagnostic performances of CTC, US and MMG were estimated by the receiver operating characteristic curves. Results CTC, US and MMG could all distinguish BC patients from the control (p < 0.0001). Area under curve (AUC) of CTC, US and MMG are 0.855, 0.861 and 0.759, respectively. While US has the highest sensitivity of 0.79, CTC and MMG have the same specificity of 0.92. Notably, CTC has the highest accuracy of 0.83. Combination with CTC increases the AUC of US and MMG to 0.922 and 0.899, respectively. Combining MMG with CTC or US increases the sensitivity of MMG to 0.87, however “CTC + MMG” has a higher specificity of 0.85. “CTC + US” performs the best in BC diagnosis, followed by “CTC + MMG” and then “US + MMG”. Conclusion CTC can be used as a diagnostic aid for BC screening. Combination with CTC increases the diagnostic potency of conventional BC screening imaging examinations, US and MMG, in BC diagnosis, especially for MMG.
Synthesis of Thiol-Modified Hemicellulose, Its Biocompatibility, Studies, and Appraisal as a Sustained Release Carrier of Ticagrelor

Background: Nature has always been considered as the primary source of pharmaceutical ingredients. A variety of hemicelluloses, as well as their modified forms, have been under investigation. Herein, a study was designed to explore the biocompatibility of hemicellulose and its modified form (thiolated hemicellulose) as well as its potential as a pharmaceutical excipient. Method: For thiol modification thiourea was used as the thiol donor, HCl as the catalytic reagent, and methanol was used for washing purposes. Modified polymers were characterized for physicochemical characteristics, including surface morphology, the amorphous or crystalline nature of the particles, modification of polymer by FTIR, and biocompatibilities. For acute oral toxicity study, a single dose of 2 g/kg was administered to albino rats of 200 g average weight (n = 3). Polymers were evaluated as pharmaceutical excipients by preparing compressed tablets of antiplatelet drug (Ticagrelor), followed by various quality control tests, such as swelling index, thickness and diameter, disintegration, and in-vitro drug release. Results: From the results, it was observed that thiol modification has been successfully accomplished as characteristic peaks belonging to –SH group appeared at 2667.7691 cm−1 in FTIR scan. The modified polymer was found safe in the use concentration range, confirming their safe use for in vivo analysis. No significant effect has been observed in the behavior, biological fluid (blood), or on vital organs. Thiolated hemicellulose was found to be an excellent drug retarding polymer as 8 h of dissolution studies showed that 67.08% of the drug has been released. Conclusion: Conclusively, incorporation of thiol moiety made the polymer more mucoadhesive with, and a worthy carrier of, the drug with good biocompatibilities.
Alteration of Autonomic Nervous System Is Associated With Severity and Outcomes in Patients With COVID-19

Background Previous studies suggest that coronavirus disease 2019 (COVID-19) is a systemic infection involving multiple systems, and may cause autonomic dysfunction. Objective To assess autonomic function and relate the findings to the severity and outcomes in COVID-19 patients. Methods We included consecutive patients with COVID-19 admitted to the 21st COVID-19 Department of the east campus of Renmin Hospital of Wuhan University from February 6 to March 7, 2020. Clinical data were collected. Heart rate variability (HRV), N-terminal pro-B-type natriuretic peptide (NT-proBNP), D-dimer, and lymphocytes and subsets counts were analysed at two time points: nucleic-acid test positive and negative. Psychological symptoms were assessed after discharge. Results All patients were divided into a mild group (13) and a severe group (21). The latter was further divided into two categories according to the trend of HRV. Severe patients had a significantly lower standard deviation of the RR intervals (SDNN) (P < 0.001), standard deviation of the averages of NN intervals (SDANN) (P < 0.001), and a higher ratio of low- to high-frequency power (LF/HF) (P = 0.016). Linear correlations were shown among SDNN, SDANN, LF/HF, and laboratory indices (P < 0.05). Immune function, D-dimer, and NT-proBNP showed a consistent trend with HRV in severe patients (P < 0.05), and severe patients without improved HRV parameters needed a longer time to clear the virus and recover (P < 0.05). Conclusion HRV was associated with the severity of COVID-19. The changing trend of HRV was related to the prognosis, indicating that HRV measurements can be used as a non-invasive predictor for clinical outcome.
Modeling the Energy Landscape of Side Reactions in the Cytochrome bc1 Complex

Much of the metabolic molecular machinery responsible for energy transduction processes in living organisms revolves around a series of electron and proton transfer processes. The highly redox active enzymes can, however, also pose a risk of unwanted side reactions leading to reactive oxygen species, which are harmful to cells and are a factor in aging and age-related diseases. Using extensive quantum and classical computational modeling, we here show evidence of a particular superoxide production mechanism through stray reactions between molecular oxygen and a semiquinone reaction intermediate bound in the mitochondrial complex III of the electron transport chain, also known as the cytochrome b c 1 complex. Free energy calculations indicate a favorable electron transfer from semiquinone occurring at low rates under normal circumstances. Furthermore, simulations of the product state reveal that superoxide formed at the Q o -site exclusively leaves the b c 1 complex at the positive side of the membrane and escapes into the intermembrane space of mitochondria, providing a critical clue in further studies of the harmful effects of mitochondrial superoxide production.
Canonical Secretomes, Innate Immune Caspase-1-, 4/11-Gasdermin D Non-Canonical Secretomes and Exosomes May Contribute to Maintain Treg-Ness for Treg Immunosuppression, Tissue Repair and Modulate Anti-Tumor Immunity via ROS Pathways

We performed a transcriptomic analyses using the strategies we pioneered and made the following findings: 1) Normal lymphoid Tregs, diseased kidney Tregs, splenic Tregs from mice with injured muscle have 3, 17 and 3 specific (S-) pathways, respectively; 2) Tumor splenic Tregs share 12 pathways with tumor Tregs; tumor splenic Tregs and tumor Tregs have 11 and 8 S-pathways, respectively; 3) Normal and non-tumor disease Tregs upregulate some of novel 2641 canonical secretomic genes (SGs) with 24 pathways, and tumor Tregs upregulate canonical secretomes with 17 pathways; 4) Normal and non-tumor disease tissue Tregs upregulate some of novel 6560 exosome SGs with 56 exosome SG pathways (ESP), tumor Treg ESP are more focused than other Tregs; 5) Normal, non-tumor diseased Treg and tumor Tregs upregulate some of novel 961 innate immune caspase-1 SGs and 1223 innate immune caspase-4 SGs to fulfill their tissue/SG-specific and shared functions; 6) Most tissue Treg transcriptomes are controlled by Foxp3; and Tumor Tregs had increased Foxp3 non-collaboration genes with ROS and 17 other pathways; 7) Immune checkpoint receptor PD-1 does, but CTLA-4 does not, play significant roles in promoting Treg upregulated genes in normal and non-tumor disease tissue Tregs; and tumor splenic and tumor Tregs have certain CTLA-4-, and PD-1-, non-collaboration transcriptomic changes with innate immune dominant pathways; 8) Tumor Tregs downregulate more immunometabolic and innate immune memory (trained immunity) genes than Tregs from other groups; and 11) ROS significantly regulate Treg transcriptomes; and ROS-suppressed genes are downregulated more in tumor Tregs than Tregs from other groups. Our results have provided novel insights on the roles of Tregs in normal, injuries, regeneration, tumor conditions and some of canonical and innate immune non-canonical secretomes via ROS-regulatory mechanisms and new therapeutic targets for immunosuppression, tissue repair, cardiovascular diseases, chronic kidney disease, autoimmune diseases, transplantation, and cancers.