Miracle-dz/UniFAR-FTUs huggingface dataset:
Screening and Discovery of New Potential Biomarkers and Small Molecule Drugs for Cervical Cancer: A Bioinformatics Analysis

Background: Cervical cancer (CC) is the second most common type of malignant tumor survival rate is low in advanced stage, metastatic, and recurrent CC patients. This study aimed at identifying potential genes and drugs for CC diagnosis and targeting therapies. Methods: Three GEO mRNA microarray datasets of CC tissues and non-cancerous tissues were analyzed for differentially expressed genes (DEGs) by limma package. GO (Gene Ontologies) and KEGG (Kyoto Encyclopedia of Genes and Genomes) were used to explore the relationships between the DEGs. Protein-protein interaction (PPI) of these genes was established by the STRING database. MCODE was used for screening significant modules in the PPI networks to select hub genes. Biochemical mechanisms of the hub genes were investigated with Metascape. GEPIA database was used for validating the core genes. According to these DEGs, molecular candidates for CC were recognized from the CMAP database. Results: We identified 309 overlapping DEGs in the 2 tissue-types. Pathway analysis revealed that the DEGs were involved in cell cycle, DNA replication, and p53 signaling. PPI networks between overlapping DEGs showed 68 high-connectivity DEGs that were chosen as hub genes. The GEPIA database showed that the expression levels of RRM2, CDC45, GINS2, HELLS, KNTC1, MCM2, MYBL2, PCNA, RAD54 L, RFC4, RFC5, TK1, TOP2A, and TYMS in CC tissues were significantly different from those in the healthy tissues and were significantly relevant to the OS of CC. We found 10 small molecules from the CMAP database that could change the trend of gene expression in CC tissues, including piperlongumine and chrysin. Conclusions: The 14 DEGs identified in this study could serve as novel prognosis biomarkers for the detection and forecasting of CC. Small molecule drugs like piperlongumine and chrysin could be potential therapeutic drugs for CC treatment.
A Signal-Enhancement Algorithm for the Quantification of NMR Data in the Time Domain

Abstract A new enhancement algorithm is presented for cleaning up NMR data before estimating signal parameters using a subspace-based method. The proposed algorithm is based on the minimum variance estimation method, which starts from a very rectangular (instead of a square) Hankel structured data matrix in order to make the corresponding signal-only data matrix orthogonal to the noise, then computes an estimate of the signal-only data matrix, and finally restores the Hankel structure of the computed estimate. This algorithm has remarkable practical advantages over Cadzow′s and nonenhanced algorithms in both resolution performance and computational efficiency that make it well suited to the quantitative time-domain analysis of NMR measurement data. The convergence of the enhancement procedure is found to be redundant when followed by an SVD-based estimator such as HTLS, offering drastic reduction in the computational cost. Extensive computer simulations on NMR signals with overlapping peaks have been carried out to evaluate the new algorithm after one iteration, its convergence, and its combination with Cadzow′s method. The enhancement algorithms are applied to the parameter estimation of real-world NMR measurement data as well. In particular, the newly proposed algorithm is recommended for estimating the parameters of overlapping peaks when the signal-to-noise ratio is low and prior knowledge is hardly available.
Coronavirus disease 2019 (COVID-19), human erythrocytes and the PKC-alpha/-beta inhibitor chelerythrine –possible therapeutic implication

ABSTRACT The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. Until now, diverse drugs have been used for the treatment of COVID-19. These drugs are associated with severe side effects, e.g. induction of erythrocyte death, named eryptosis. This massively affects the oxygen (O2) supply of the organism. Therefore, three elementary aspects should be considered simultaneously: (1) a potential drug should directly attack the virus, (2) eliminate virus-infected host cells and (3) preserve erythrocyte survival and functionality. It is known that PKC-α inhibition enhances the vitality of human erythrocytes, while it dose-dependently activates the apoptosis machinery in nucleated cells. Thus, the use of chelerythrine as a specific PKC-alpha and -beta (PKC-α/-β) inhibitor should be a promising approach to treat people infected with SARS-CoV-2.
Factorial Validity and Variance of the Maslach Burnout Inventory between Demographic and Workload Groups among Dentists of Lithuania

There is a lack of evidence about burnout syndrome among Lithuanian dentists; as a reliable instrument to examine the syndrome in this professional group has not yet been tested. The study aimed to investigate the performance of the items and the subscales of the Maslach burnout inventory (MBI) by validating its factorial structure and analyzing its variance between demographic and workload groups of dental professionals in Lithuania. The survey was conducted among practicing dentists online or during the scientific conferences for dentists using an anonymous questionnaire. To evaluate the level of burnout the MBI was chosen. Reports of a total of 380 respondents were examined. Three-factor structure of the MBI with cross-loading of two items suggested a good fit to data (χ2/df = 1.67; CFI = 0.93; TLI = 0.93; IFI = 0.93; and RMSEA = 0.059) and was invariant across demographic and workload groups of dentists. Multigroup factorial analysis revealed that females as compared to males had higher average emotional exhaustion; and the respondents up to 30 years as compared to respondents over 30 years of age had higher averages of the emotional exhaustion and depersonalization components. Highly specialized dentists (oral surgeons, prosthodontists, orthodontists, endodontists and poedodontists) were particularly less prone to burnout syndrome than dentists of general practice. It was concluded that the MBI offers factorial validity and demonstrates its invariant structure and variance of burnout dimensions across demographic and workload groups. These findings are informative for burnout prevention and intervention programs among dentists in Lithuania. Such information may contribute to lessen professional burnout among dentists in Lithuania.
Review of Hearing Loss Among Racial/Ethnic Minorities in the United States

The purpose of this study is to synthesize the literature on hearing loss among racial/ethnic minorities in the United States. A scoping review of primary source articles from 1950 to 2019 was conducted across four databases—CINAHL, PsycINFO, PubMed, and Scopus—to identify peer-reviewed studies. Twenty-two research studies were included. Of the 22 studies, 19 were descriptive, and 3 were interventions. Among the 19 descriptive studies, five themes related to hearing loss were identified: hearing loss prevalence, accuracy of hearing loss assessment, hearing loss risk factors, access to hearing care, and attitudes toward hearing loss. The three interventional studies focused on measuring hearing loss prevalence and promoting access to hearing care. Findings from this scoping review highlight that hearing loss is prevalent in racial/ethnic minorities. More research is needed on how economic, cultural, and age-related factors may influence hearing outcomes for racial/ethnic minorities.
Dissecting protein domain variability in the core RNA interference machinery of five insect orders

ABSTRACT RNA interference (RNAi)-mediated gene silencing can be used to control specific insect pest populations. Unfortunately, the variable efficiency in the knockdown levels of target genes has narrowed the applicability of this technology to a few species. Here, we examine the current state of knowledge regarding the miRNA (micro RNA) and siRNA (small interfering RNA) pathways in insects and investigate the structural variability at key protein domains of the RNAi machinery. Our goal was to correlate domain variability with mechanisms affecting the gene silencing efficiency. To this end, the protein domains of 168 insect species, encompassing the orders Coleoptera, Diptera, Hemiptera, Hymenoptera, and Lepidoptera, were analysed using our pipeline, which takes advantage of meticulous structure-based sequence alignments. We used phylogenetic inference and the evolutionary rate coefficient (K) to outline the variability across domain regions and surfaces. Our results show that four domains, namely dsrm, Helicase, PAZ and Ribonuclease III, are the main contributors of protein variability in the RNAi machinery across different insect orders. We discuss the potential roles of these domains in regulating RNAi-mediated gene silencing and the role of loop regions in fine-tuning RNAi efficiency. Additionally, we identified several order-specific singularities which indicate that lepidopterans have evolved differently from other insect orders, possibly due to constant coevolution with plants and viruses. In conclusion, our results highlight several variability hotspots that deserve further investigation in order to improve the application of RNAi technology in the control of insect pests.
Effectiveness of a video-based education on fertility awareness: a randomized controlled trial with partnered women

Abstract Fertility awareness (FA) among young people is low. Fertility awareness interventions have been found to contribute to increase FA in the short-term. The long-term effectiveness of FA interventions on childless and presumed fertile people, committed in a heterosexual relationship and wishing to have children in the near future is not known. In a double-blind parallel randomized controlled trial conducted between 2016 and 2018, 652 childless partnered women were randomized to either watch a 5-min video about fertility (IG: ‘Intervention Group’) or to not receive any intervention (CG: ‘Control Group’). Participants filled out an online questionnaire at the start of the study (and in the IG group immediately before intervention). They then completed the questionnaire after 1 month, 6 months and 1 year. The questionnaire assessed FA and intentions to adopt fertility-protective behaviours. In the IG, FA levels were found to increase at 1 month post-intervention. However, significant interaction effects between group and time were only found for four out of the seven FA variables at the 6-month and 1-year follow-up. No effects were found for: (i) intentions to adopt fertility-protective behaviours; or (ii) desired timing of pregnancy. These results suggest that the fertility video intervention seems to partially increase FA in the long term. Future studies should investigate the effectiveness of different intervention formats with a focus on overcoming high attrition rates.
Spectroscopic Studies of Photoexcitations in Regioregular and Regiorandom Polythiophene Films

Using a variety of optical probe techniques we studied the steady state and transient dynamics of charged and neutral photoexcitations in thin films of poly-3-alkyl thiophene with regioregular order, which forms self-assembled lamellae structures with increased interchain interaction, as well as regiorandom order that keeps a chain-like morphology. In regiorandom polythiophene films we found that intrachain excitons with correlated photoinduced absorption and stimulated emission bands are the primary photoexcitations; they give rise to a moderately strong photoluminescence band, and long-lived triplet excitons and intrachain charged polarons. In regioregular polythiophene films, on the contrary we found that the primary photoexcitations are excitons with much larger interchain component; this results in lack of stimulated emission, vanishing intersystem crossing, and a very weak photoluminescence band. The long-lived photoexcitations in regioregular polythiophene films are interchain excitons and delocalized polarons (DP) within the lamellae, with very small relaxation energy. The characteristic properties of the DP species are thoroughly investigated as a function of the alkyl side group of the polymer backbone, film deposition conditions and solvents used, as well as at high hydrostatic pressure. The quantum interference between the low energy absorption band of the DP species and a series of photoinduced infrared active vibrations, which give rise to antiresonances that are superimposed on the electronic absorption band is studied and explained by a Fano-type interference mechanism, using the amplitude mode model.
VE1 immunohistochemistry is an adjunct tool for detection of BRAF V600E mutation: Validation in thyroid cancer patients

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy among other endocrine tumors, and BRAFV600E is a frequent genetic mutation occurring in the disease. Although different molecular techniques, most importantly sequencing has been widely recognized as a gold standard but molecular diagnosis remains an expensive, laborious, and time‐intensive process. Recently, immunohistochemistry (IHC) with anti‐BRAF V600E (VE1) antibody has increased practical utility and implemented clinically for the detection of BRAFV600E mutation. Therefore, the study aimed to evaluate diagnostic accuracy of VE1 IHC for detecting the BRAFV600E mutation frequency and clinical implementation in diagnostic laboratories. In this study, 72 formalin fixed paraffin‐embedded tissues (FFPE) were used to determine the BRAFV600E mutation status using IHC and Sanger sequencing. The mutation was found in 29% and 28% cases using IHC and Sanger sequencing, respectively. Furthermore, the results showed 100% sensitivity, 98.07% specificity, 95.2% positive predictive value, and 100% negative predictive value. Notably, significant associations were found between BRAFV600E status and tumor stage, tumor focality, and extrathyroidal extensions, respectively. VE1 IHC was found to be a highly sensitive, specific, and diagnostically accurate method in this cohort. Therefore, BRAFV600E detection through IHC has been considered as the best tailored technique for routine pathology laboratories.
A cell competition–based small molecule screen identifies a novel compound that induces dual c-Myc depletion and p53 activation

Breakpoint Cluster Region-Abelson kinase (BCR–Abl) is a driver oncogene that causes chronic myeloid leukemia and a subset of acute lymphoid leukemias. Although tyrosine kinase inhibitors provide an effective treatment for these diseases, they generally do not kill leukemic stem cells (LSCs), the cancer-initiating cells that compete with normal hematopoietic stem cells for the bone marrow niche. New strategies to target cancers driven by BCR–Abl are therefore urgently needed. We performed a small molecule screen based on competition between isogenic untransformed cells and BCR–Abl-transformed cells and identified several compounds that selectively impair the fitness of BCR–Abl-transformed cells. Interestingly, systems-level analysis of one of these novel compounds, DJ34, revealed that it induced depletion of c-Myc and activation of p53. DJ34-mediated c-Myc depletion occurred in a wide range of tumor cell types, including lymphoma, lung, glioblastoma, breast cancer, and several forms of leukemia, with primary LSCs being particularly sensitive to DJ34. Further analyses revealed that DJ34 interferes with c-Myc synthesis at the level of transcription, and we provide data showing that DJ34 is a DNA intercalator and topoisomerase II inhibitor. Physiologically, DJ34 induced apoptosis, cell cycle arrest, and cell differentiation. Taken together, we have identified a novel compound that dually targets c-Myc and p53 in a wide variety of cancers, and with particularly strong activity against LSCs.
New Design Method for Fabricating Multilayer Membranes Using CO2-Assisted Polymer Compression Process

It was verified that deep learning can be used in creating multilayer membranes with multiple porosities using the CO2-assisted polymer compression (CAPC) method. To perform training while reducing the number of experimental data as much as possible, the experimental data of the compression behavior of two layers were expanded to three layers for training, but sufficient accuracy could not be obtained. However, the accuracy was dramatically improved by adding the experimental data of the three layers. The possibility of only simulating process results without the necessity for a model is a merit unique to deep learning. Overall, in this study, the results show that by devising learning data, deep learning is extremely effective in designing multilayer membranes using the CAPC method.
Efficacy of Pomegranate Seed Powder on Glucose and Lipid Metabolism in Patients with Type 2 Diabetes: A Prospective Randomized Double-Blind Placebo-Controlled Clinical Trial

Introduction: Pomegranate is known as a functional food which has multiple health-promoting activities. It has been assessed for patients with metabolic syndrome. Specifically, an antidiabetic activity of its juice and plausible mechanisms for its action have been shown in multitudinous studies. The aim of this study was assessing the effects of complementary treatment with pomegranate seed powder (PSP) oral supplementation on patients with type 2 diabetes mellitus (T2DM). Methods: Sixty patients were treated for 8 weeks by 5 g PSP or placebo, twice daily. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol, and triglyceride (TG) were recorded as the outcome measures at the beginning and after the intervention. The findings were analyzed using the independent t test and Mann-Whitney U test. Results: After 8 weeks, the mean differences of FBG, HbA1c, cholesterol, and TG were significantly decreased in the PSP group when compared with the placebo group (p value <0.05). In addition, post-intervention values of FBG and HbA1c were significantly lower in patients treated with PSP compared to the placebo group (p values = 0.02 and 0.01, respectively). However, the latter comparison regarding cholesterol and TG showed no significant differences (p values = 0.51 and 0.26, respectively). Conclusion: It seems that complementary treatment with PSP may have beneficial effects on FBG and HbA1c of patients with T2DM. However, its effect on TG and cholesterol was equivocal.
Effect of Sequential Rounds of Cervical Cancer Screening on Management of HPV-positive Women: A 15-year Population-based Cohort Study from China

The study highlights the sustained effectiveness of mainstream HPV triage methods, such as cytology and genotyping, after sequential rounds of cervical screening. It also suggests that use of HPV persistence across rounds can improve management of HPV-positive women in cervical cancer screening. Women are anticipated to go through more than two rounds of cervical screening in their lifetime. Human papillomavirus (HPV) testing is increasingly used as the primary cervical cancer screening test. However, triage strategies for HPV-positive women were usually evaluated at baseline screening. We assessed the effect of sequential rounds of cervical screening on several algorithms for HPV triage. A total of 1,997 women ages 35–45 years were enrolled in 1999 in Shanxi, P.R. China and followed up three times at approximately 5-year intervals. Cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) prevalence by prior HPV results and performance of 12 triage algorithms with cytology, genotyping, and prior HPV were examined among 229 HPV-positive women at the fourth round. CIN2+ prevalence varied from 56.5% (95% confidence interval, 36.8%–74.4%) following 15 years HPV persistence to 3.5% (1.2%–9.9%) with an incident HPV within 15 years. Triage with cytology (with threshold of atypical squamous cells of undetermined significance) yielded positive predictive value (PPV) of 21.4% (13.8%–29.0%), entailing immediate colposcopic referral, and negative predictive value (NPV) of 97.4% (94.6%–100%), permitting retesting at short intervals. Triage with genotyping (16/18/31/33/45/52/58) or prior HPV results showed comparable performance with cytology. Among 11 triage algorithms with similar NPV to cytology, triage with prior HPV results and reflex genotyping (16/18) achieved highest PPV of 28.9% (18.8%–39.1%) and lowest colposcopy referral of 33.2% (27.4%–39.5%). HPV persistence across rounds is an effective risk stratifier in HPV-positive women. Mainstream cytology and genotyping, with or without consideration of prior HPV results, remain effective for HPV triage at fourth round. Prevention Relevance: The study highlights the sustained effectiveness of mainstream HPV triage methods, such as cytology and genotyping, after sequential rounds of cervical screening. It also suggests that use of HPV persistence across rounds can improve management of HPV-positive women in cervical cancer screening.
The integrated stress response mediates necrosis in murine Mycobacterium tuberculosis granulomas.

The mechanism by which only some individuals infected with M. tuberculosis (Mtb) develop necrotic granulomas with progressive disease while others form controlled granulomas that contain the infection remains poorly defined. Mice carrying the sst1-suscepible (sst1S) genotype develop necrotic inflammatory lung lesions, similar to human TB granulomas, which are linked to macrophage dysfunction while their congenic counterparts (B6) mice do not. In this study we report that (i) sst1S macrophages developed aberrant, biphasic responses to TNF characterized by super-induction of stress and type I interferon pathways after prolonged TNF stimulation; (ii) the late-stage TNF response was driven via a JNK - IFNβ - PKR circuit; and (iii) induced the integrated stress response (ISR) via PKR-mediated eIF2α phosphorylation and the subsequent hyper-induction of ATF3 and ISR-target genes Chac1, Trib3, Ddit4. The administration of ISRIB, a small molecule inhibitor of the ISR, blocked the development of necrosis in lung granulomas of Mtb-infected sst1S mice and concomitantly reduced the bacterial burden. Hence induction of the ISR and the locked-in state of escalating stress driven by type I IFN pathway in sst1S macrophages plays a causal role in the development of necrosis in TB granulomas. Interruption of the aberrant stress response with inhibitors such as ISRIB may offer novel host-directed therapy strategies.
RYGB increases postprandial gastric nesfatin-1 and rapid relieves NAFLD via gastric nerve detachment

Background Roux-en-Y gastric bypass (RYGB) could reduce nonalcoholic fatty liver disease (NAFLD) ahead of the weight-loss effects. But the detailed mechanisms remain unclear. Material and methods A high-fat diet (HFD) was fed to induce obesity. RYGB was then performed. Gastric nesfatin-1 was measured by enzyme-linked immunosorbent assay (ELISA) in portal vein and polymerase chain reaction (PCR) in gastric tissues. Modified surgeries including vagus-preserved bypass and vagectomy were performed and postprandial gastric nesfatin-1 were analyzed. The effects of nesfatin-1 on hepatocytes were studied by PCR and immunohistochemistry. Both intraperitoneal and intracerebroventricular injection (ICV) were performed to analyze the in vivo effects on liver lipid metabolism. Results Increased postprandial portal vein nesfatin-1 was observed in RYGB but not in control groups. This increase is mainly due to induction of gastric nesfatin-1. A modified RYGB in which the gastric vagus is preserved is conducted and, in this case, this nesfatin-1 induction effect is diminished. Mere vagectomy could also induce a similar nesfatin-1 increase pattern. The infusion of nesfatin-1 in the brain could inhibit the expression of gastric nesfatin-1, and the effects are diminished after gastric vagectomy. In vivo and in vitro nesfatin-1 stimulation in the liver resulted in improvements in lipid metabolism. Conclusions Severing the gastric vagus during RYGB could cut off the negative control from the central nervous system (CNS) and result in increased postprandial gastric nesfatin-1 post surgery, which in turn, improves NAFLD.