CRISPR-Cas9 Genome Editing Allows Generation of the Mouse Lung in a Rat.

Rationale: Recent efforts in bioengineering and embryonic stem cell (ESC) technology allowed the generation of ESC-derived mouse lung tissues in transgenic mice that were missing critical morphogenetic genes. Epithelial cell lineages were efficiently generated from ESC, but other cell types were mosaic. A complete contribution of donor ESCs to lung tissue has never been achieved. The mouse lung has never been generated in a rat. Objective: We sought to generate the mouse lung in a rat. Methods: Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 genome editing was used to disrupt the Nkx2-1 gene in rat one-cell zygotes. Interspecies mouse-rat chimeras were produced by injection of wild-type mouse ESCs into Nkx2-1-deficient rat embryos with lung agenesis. The contribution of mouse ESCs to the lung tissue was examined by immunostaining, flow cytometry, and single-cell RNA sequencing. Measurements and Main Results: Peripheral pulmonary and thyroid tissues were absent in rat embryos after CRISPR-Cas9-mediated disruption of the Nkx2-1 gene. Complementation of rat Nkx2-1-/- blastocysts with mouse ESCs restored pulmonary and thyroid structures in mouse-rat chimeras, leading to a near-99% contribution of ESCs to all respiratory cell lineages. Epithelial, endothelial, hematopoietic, and stromal cells in ESC-derived lungs were highly differentiated and exhibited lineage-specific gene signatures similar to those of respiratory cells from the normal mouse lung. Analysis of receptor-ligand interactions revealed normal signaling networks between mouse ESC-derived respiratory cells differentiated in a rat. Conclusions: A combination of CRISPR-Cas9 genome editing and blastocyst complementation was used to produce mouse lungs in rats, making an important step toward future generations of human lungs using large animals as "bioreactors."

Kilohertz high-frequency electrical stimulation ameliorate hyperalgesia by modulating transient receptor potential vanilloid-1 and N-methyl-D-aspartate receptor-2B signaling pathways in chronic constriction injury of sciatic nerve mice.

The number of patients with neuropathic pain is increasing in recent years, but drug treatments for neuropathic pain have a low success rate and often come with significant side effects. Consequently, the development of innovative therapeutic strategies has become an urgent necessity. Kilohertz High Frequency Electrical Stimulation (KHES) offers pain relief without inducing paresthesia. However, the specific therapeutic effects of KHES on neuropathic pain and its underlying mechanisms remain ambiguous, warranting further investigation. In our previous study, we utilized the Gene Expression Omnibus (GEO) database to identify datasets related to neuropathic pain mice. The majority of the identified pathways were found to be associated with inflammatory responses. From these pathways, we selected the transient receptor potential vanilloid-1 (TRPV1) and N-methyl-D-aspartate receptor-2B (NMDAR2B) pathway for further exploration. Mice were randomly divided into four groups: a Sham group, a Sham/KHES group, a chronic constriction injury of the sciatic nerve (CCI) group, and a CCI/KHES stimulation group. KHES administered 30 min every day for 1 week. We evaluated the paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL). The expression of TRPV1 and NMDAR2B in the spinal cord were analyzed using quantitative reverse-transcriptase polymerase chain reaction, Western blot, and immunofluorescence assay. KHES significantly alleviated the mechanical and thermal allodynia in neuropathic pain mice. KHES effectively suppressed the expression of TRPV1 and NMDAR2B, consequently inhibiting the activation of glial fibrillary acidic protein (GFAP) and ionized calcium binding adapter molecule 1 (IBA1) in the spinal cord. The administration of the TRPV1 pathway activator partially reversed the antinociceptive effects of KHES, while the TRPV1 pathway inhibitor achieved analgesic effects similar to KHES. KHES inhibited the activation of spinal dorsal horn glial cells, especially astrocytes and microglia, by inhibiting the activation of the TRPV1/NMDAR2B signaling pathway, ultimately alleviating neuropathic pain.

Glycine Exhibits Neuroprotective Effects in Ischemic Stroke in Rats through the Inhibition of M1 Microglial Polarization via the NF-κB p65/Hif-1α Signaling Pathway.

Glycine is a simple nonessential amino acid known to have neuroprotective properties. Treatment with glycine results in reduced infarct volume of the brain, neurologic function scores, and neuronal and microglial death in ischemic stroke injury. Neuroinflammation has been considered a major contributor to cerebral ischemia-induced brain damage. However, the role of glycine in neuroinflammation following ischemic stroke is unclear. The present study aimed to determine whether neuroinflammation is involved in the neuroprotective effects of glycine in cerebral ischemia injury. Ischemic stroke promotes M1 microglial polarization. Interestingly, we found that the injection of glycine in rats after injury can inhibit ischemia-induced inflammation and promote M2 microglial polarization in vivo (Sprague-Dawley rats) and in vitro (cortical microglia and BV-2 cells). We show that glycine suppresses Hif-1α by inhibiting the upregulation of NF-κB p65 after ischemia-reperfusion injury, resulting in the inhibition of proinflammatory activity. The activation of AKT mediates the inhibition of NF-κB p65/Hif-1α signaling by glycine. Moreover, we confirm that glycine-regulated AKT activation is mediated by the inhibition of PTEN in a PTEN depletion cell line, U251 cells. Glycine modulates microglial polarization after ischemic stroke, which indirectly inhibits ischemia-induced neuronal death and functional recovery. Taken together, our findings provide a new understanding of glycine in neuroprotection by inhibiting M1 microglial polarization and promoting anti-inflammation by suppressing NF-κB p65/Hif-1α signaling.

TP53 R249S mutation detected in circulating tumour DNA is associated with Prognosis of hepatocellular carcinoma patients with or without hepatectomy.

BACKGROUND AND AIMS: Somatic mutation R249S in TP53 is highly common in hepatocellular carcinoma (HCC). We aim to investigate the effects of R249S in ctDNA on the prognosis of HCC. METHODS: We analysed three cohorts including 895 HCC patients. TP53 mutation spectrum was examined by direct sequencing of genomic DNA from tissue specimens in HCC patients with hepatectomy (Cohort 1, N = 260). R249S and other recurrent missense mutations were assessed for their biological functions and associations with overall survival (OS) and progression-free survival (PFS) of HCC patients in Cohort 1. R249S within circulating tumour DNA (ctDNA) was detected through droplet digital polymerase chain reaction (ddPCR) and its association with OS and PRS was analysed in HCC patients with (Cohort 2, N = 275) or without (Cohort 3, N = 360) hepatectomy. RESULTS: In Cohort 1, R249S occupied 60.28% of all TP53 mutations. Overexpression of R249S induced more serious malignant phenotypes than those of the other three identified TP53 recurrent missense mutations. Additionally, R249S, but not other missense mutations, was significantly associated with worse OS (P = .006) and PFS (P = .01) of HCC patients. Consistent with the results in Cohort 1, HCC patients in Cohorts 2 and 3 with R249S had worse OS (P = 8.291 × 10-7 and 2.608 × 10-7 in Cohorts 2 and 3, respectively) and PFS (P = 5.115 × 10-7 and 5.900 × 10-13 in Cohorts 2 and 3, respectively) compared to those without this mutation. CONCLUSIONS: TP53 R249S mutation in ctDNA may serve as a promising prognosis biomarker for HCC patients with or without hepatectomy.

Consumer health information needs in China - a case study of depression based on a Social Q&A community.

BACKGROUND: The social Q&A community quickly becomes a popular platform for consumers to find health information because of its convenience and interactivity. METHODS: Based on the 10,861 depression questions collected in the Zhihu, the largest Q&A platform in China, we divided the healthy information needs description into nine categories with Latent Dirichlet Allocation (LDA). We also divided the healthy information needs type into Physiological, affective and cognitive needs based on the Wilson model. RESULTS: The results show that the largest categories are depression symptom and social activities while the less concerned health information is prevention and medical insurance. More attention is paid to cognitive needs. We also find there is no strong correlation between attention and needs type. CONCLUSIONS: The purpose of this paper is to refine the consumer health information needs types to better understand the consumer health information characteristic in China.

Genetic variants in five novel loci including CFB and CD40 predispose to chronic hepatitis B.

UNLABELLED: Hepatitis B virus affects more than 2 billion people worldwide, 350 million of which have developed chronic hepatitis B (CHB). The genetic factors that confer CHB risk are still largely unknown. We sought to identify genetic variants for CHB susceptibility in the Chinese population. We undertook a genome-wide association study (GWAS) in 2,514 CHB cases and 1,130 normal controls from eastern China. We replicated 33 of the most promising signals and eight previously reported CHB risk loci through a two-stage validation totaling 6,600 CHB cases and 8,127 controls in four independent populations, of which two populations were recruited from eastern China, one from northern China and one from southern China. The joint analyses of 9,114 CHB cases and 9,257 controls revealed significant association of CHB risk with five novel loci. Four loci are located in the human leukocyte antigen (HLA) region at 6p21.3, including two nonsynonymous variants (rs12614 [R32W] in complement factor B [CFB], Pmeta =1.28 × 10(-34) ; and rs422951 [T320A] in NOTCH4, Pmeta = 5.33 × 10(-16) ); one synonymous variant (rs378352 in HLA-DOA corresponding to HLA-DOA*010101, Pmeta = 1.04 × 10(-23) ); and one noncoding variant (rs2853953 near HLA-C, Pmeta = 5.06 × 10(-20) ). Another locus is located at 20q13.1 (rs1883832 in the Kozak sequence of CD40, Pmeta = 2.95 × 10(-15) ). Additionally, we validated seven of eight previously reported CHB susceptibility loci (rs3130542 at HLA-C, rs1419881 at TCF19, rs652888 at EHMT2, rs2856718 at HLA-DQB1, rs7453920 at HLA-DQB2, rs3077 at HLA-DPA1, and rs9277535 at HLA-DPA2, which are all located in the HLA region, 9.84 × 10(-71) ≤ Pmeta ≤ 9.92 × 10(-7) ). CONCLUSION: Our GWAS identified five novel susceptibility loci for CHB. These findings improve the understanding of CHB etiology and may provide new targets for prevention and treatment of this disease.

MiR-608 rs4919510 is associated with prognosis of hepatocellular carcinoma.

Single nucleotide polymorphisms (SNPs) within microRNAs (miRNAs) are considered potential markers for risk and prognosis of various cancers. In the current study, we aimed to determine whether miR-608 rs4919510 affected hepatocellular carcinoma (HCC) prognosis. We genotyped rs4919510 using DNA from blood samples of 362 HCC patients receiving surgical resection of HCC tumor. Associations between rs4919510 and overall survival (OS) and demographic characteristics and clinical features were estimated using the Cox proportional hazards model. Results showed that HCC patients who carried the rs4919510 CC genotype had a significantly longer OS compared to those who carried the GG genotype (P = 0.013, hazard ratio [HR] = 0.600, 95 % confidence interval [CI] 0.402-0.897) and the CG + GG genotype (P = 0.033, HR = 0.681, 95 % CI 0.479-0.970) in univariate analysis. Similar results were obtained in multivariate analysis. Further stratification analysis indicated that rs4919510 was significantly associated with OS in patients who were satisfied with one of the following criteria: male gender, HbsAg-positive, α-fetoprotein (AFP)-positive, tumor size >5 cm, cirrhosis, solitary tumor, I + II pTNM stage, or no tumor capsule. Finally, a significantly higher frequency of rs4919510 CC genotype was observed in patients with cirrhosis (22.9 %, 55/240) than those without cirrhosis (14.0 %, 17/121) (P = 0.047). In conclusion, our results illustrated the potential role of miR-608 rs4919510 as a prognostic marker for HCC patients undergoing surgical resection of the tumor.

miR-492G>C polymorphism (rs2289030) is associated with overall survival of hepatocellular carcinoma patients.

Single-nucleotide polymorphisms (SNPs) of microRNAs (miRNAs) are considered potential markers of cancer risk and prognosis in various cancers. In the current study, the primary aim is to determine whether the miR-492G>C polymorphism (rs2289030) altered hepatocellular carcinoma (HCC) prognosis. The SNP rs2289030 of miR-492 was genotyped using DNA from blood samples of 362 HCC patients that had undergone surgical resection of a HCC tumor. The associations between overall survival and demographic characteristics, clinical features, and the SNP rs2289030 were estimated using the Cox proportional hazards model. Results showed that patients who carried the CG genotype (P = 0.015, hazard ratio [HR] = 0.704, 95 % confidence interval [CI] 0.530-0.934) and CG+GG genotype (P = 0.011, HR = 0.703, 95 % CI 0.536-0.924) had significantly decreased risk of death compared to those with the CC genotype. Similar results were found in the multivariate analysis adjusted by tumor size and venous invasion. Further stratification analysis indicated that the effect of rs2289030 had more prominence in patients ≤50 years old and that reported ever using alcohol, male gender, a family history of HCC, being HbsAg or alpha fetoprotein (AFP) positive, differentiation I + II, presence of venous invasion or cirrhosis, multiple tumors, and pTNM stage I + II. Results from this study illustrate the potential use of miR-492 rs2289030 as a prognostic marker for HCC patients that have undergone a surgical resection of the tumor.

[Family history of liver cancer increases the risk of liver cancer incidence: a 20-year prospective cohort study in Qidong, China].

OBJECTIVE: To evaluate whether first-degree family history of liver cancer plays a role in liver cancer incidence by prospective evaluation of a patient cohort in Qidong, China over a 20-year period. METHODS: In May 1992, 708 hepatitis B surface antigen (HBsAg) carriers and 730 HBsAg-negadve controls from Qidong city were enrolled for participation in a prospective cohort study ending in November 2012.Follow-up was carried out every 6 to 12 months, and evaluations included serum assays to measure concentrations of alpha fetoprotein (AFP), HBsAg and alanine aminotransferase (ALT), as well as abdominal ultrasound to assess liver disease.The relationship between baseline (study entry) information of patients with first-degree family history of liver cancer and liver cancer incidence during the two decades of study was statistically assessed. RESULTS: There were 172 newly diagnosed liver cancer cases in the cohort during 25 753 person-years (py) of follow-up, representing an incidence of 667.88/100 000 py.The incidence rates of liver cancer among participants with or without liver cancer family history were 1 244.36/100 000 py and 509.70/100 000 py respectively, and the between-group difference reached the threshold for statistical significance (P less than 0.01, Relative Risk (RR):2.44, 95% Confidence Interval (CI):1.80-3.31).The incidence rates of liver cancer among participants who had a sibling with liver cancer and participants who had a parent with liver cancer were not significantly different (P > 0.05), but the liver cancer incidence among participants who had a mother with liver cancer was significantly higher than that of participants who had a father with liver cancer (P < 0.05, RR:1.86, 95% CI:1.03-3.36). Among the participants with liver cancer family history, 56.52% (39/69) were diagnosed before 50 years old, and this rate was significantly higher than that of participants without a family history of liver cancer (40.78%, 42/103, P less than 0.05).The incidence rate of liver cancer among the participants who were family history-positive and HBsAg-positive was significantly higher than that of participants who were family history-negative but HBsAg-positive (P < 0.01, RR:1.75, 95% CI:1.29-2.38), and was 59.59 times higher than for participants who were family history-negative and HBsAgnegative.Subgroup analysis of liver cancer incidence among participants who were family history-positive but HBsAg-negative and participants who were family history-negative and HBsAg-negative produced anRR of 2.60, but there was no statistically significant difference between the two subgroups (P > 0.05).At the study's end, the incidence rates of liver cancer for the different subgroups were 32.21% for the family history-positive and HBsAgpositive participants, 19.80% for the family history-negative and HBsAg-positive participants, 1.71% for the family history-positive and HBsAg-negative participants, and 0.65% for the family history-negative and HBsAg-negative participants. CONCLUSION: First-degree family history of liver cancer is a risk factor of liver cancer in Chinese patients from Qidong, and exhibits synergism with HBsAg-positivity for incidence of liver cancer.

Estimating prevalence of rare genetic disease diagnoses using electronic health records in a children's hospital.

Rare genetic diseases (RGDs) affect a significant number of individuals, particularly in pediatric populations. This study investigates the efficacy of identifying RGD diagnoses through electronic health records (EHRs) and natural language processing (NLP) tools, and analyzes the prevalence of identified RGDs for potential underdiagnosis at Cincinnati Children's Hospital Medical Center (CCHMC). EHR data from 659,139 pediatric patients at CCHMC were utilized. Diagnoses corresponding to RGDs in Orphanet were identified using rule-based and machine learning-based NLP methods. Manual evaluation assessed the precision of the NLP strategies, with 100 diagnosis descriptions reviewed for each method. The rule-based method achieved a precision of 97.5% (95% CI: 91.5%, 99.4%), while the machine-learning-based method had a precision of 73.5% (95% CI: 63.6%, 81.6%). A manual chart review of 70 randomly selected patients with RGD diagnoses confirmed the diagnoses in 90.3% (95% CI: 82.0%, 95.2%) of cases. A total of 37,326 pediatric patients were identified with 977 RGD diagnoses based on the rule-based method, resulting in a prevalence of 5.66% in this population. While a majority of the disorders showed a higher prevalence at CCHMC compared with Orphanet, some diseases, such as 1p36 deletion syndrome, indicated potential underdiagnosis. Analyses further uncovered disparities in RGD prevalence and age of diagnosis across gender and racial groups. This study demonstrates the utility of employing EHR data with NLP tools to systematically investigate RGD diagnoses in large cohorts. The identified disparities underscore the need for enhanced approaches to guarantee timely and accurate diagnosis and management of pediatric RGDs.

In vivo CRISPR knockout screen identifies p47 as a suppressor of HER2+ breast cancer metastasis by regulating NEMO trafficking and autophagy flux.

Autophagy is a conserved cellular process, and its dysfunction is implicated in cancer and other diseases. Here, we employ an in vivo CRISPR screen targeting genes implicated in the regulation of autophagy to identify the Nsfl1c gene encoding p47 as a suppressor of human epidermal growth factor receptor 2 (HER2)+ breast cancer metastasis. p47 ablation specifically increases metastasis without promoting primary mammary tumor growth. Analysis of human breast cancer patient databases and tissue samples indicates a correlation of lower p47 expression levels with metastasis and decreased survival. Mechanistic studies show that p47 functions in the repair of lysosomal damage for autophagy flux and in the endosomal trafficking of nuclear factor κB essential modulator for lysosomal degradation to promote metastasis. Our results demonstrate a role and mechanisms of p47 in the regulation of breast cancer metastasis. They highlight the potential to exploit p47 as a suppressor of metastasis through multiple pathways in HER2+ breast cancer cells.

Dramatic reduction of liver cancer incidence in young adults: 28 year follow-up of etiological interventions in an endemic area of China.

Qidong City, China, has had high liver cancer incidence from endemic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin. Based on etiologic studies, we began interventions in 1980 to reduce dietary aflatoxin and initiate neonatal HBV vaccination. We studied trends in liver cancer incidence rates in the 1.1 million inhabitants of Qidong and examined trends in aflatoxin exposure, staple food consumption, HBV infection markers and annual income. Aflatoxin exposure declined greatly in association with economic reform, increased earnings and educational programs to shift staple food consumption in the total population from moldy corn to fresh rice. A controlled neonatal HBV vaccination trial began in 1983 and ended in November, 1990, when vaccination was expanded to all newborns. Liver cancer incidence fell dramatically in young adults. Compared with 1980-83, the age-specific liver cancer incidence rates in 2005-08 significantly decreased 14-fold at ages 20-24, 9-fold at ages 25-29, 4-fold at ages 30-34, 1.5-fold at ages 35-39, 1.2-fold at ages 40-44 and 1.4-fold at ages 45-49, but increased at older ages. The 14-fold reduction at ages 20-24 might reflect the combined effects of reduced aflatoxin exposure and partial neonatal HBV vaccination. Decrease incidence in age groups >25 years could mainly be attributable to rapid aflatoxin reduction. Compared with 1980-83, liver cancer incidence in 1990-93 significantly decreased 3.4-fold at ages 20-24, and 1.9-fold at ages 25-29 when the first vaccinees were <11 years old.

High-frequency electrical stimulation reduced hyperalgesia and the activation of the Myd88 and NFκB pathways in chronic constriction injury of sciatic nerve-induced neuropathic pain mice.

Neuropathic pain has become a global public problem and health burden. Pharmacological interventions are the primary treatment, but the drug cure rate is low with side effects. There is an urgent need to develop novel treatment approaches. High frequency electrical stimulation (KHES) has been widely applied in clinical analgesia. However, its mechanism is poorly understood. In this study, datasets related to neuropathic pain were obtained from the GEO database. The differentially expressed genes (DEGs) and key genes were analyzed through functional enrichment analysis, showing that most of the pathways involve the inflammation. The MyD88 and NFκB pathways were further studied. KHES significantly alleviated mechanical and thermal allodynia in chronic constriction injury of the sciatic nerve mice. KHES also inhibited the increase in Myd88 and p-NFκB expression. The administration of NFκB pathway activator partly reversed the antinociceptive effects of KHES, and NFκB pathway inhibitor achieved analgesic effects similar to those of KHES. Therefore, KHES might be a novel intervention for the treatment of neuropathic pain.

Surface Roughness-Induced Changes in Important Physical Features of CoFeSm Thin Films on Glass Substrates during Annealing.

Co60Fe20Sm20 thin films were deposited onto glass substrates in a high vacuum setting. The films varied in thickness from 10 to 50 nm and underwent annealing processes at different temperatures: room temperature (RT), 100, 200, and 300 °C. Our analysis encompassed structural, magnetic, electrical, nanomechanical, adhesive, and optical properties in relation to film thickness and annealing temperature. X-ray diffraction (XRD) analysis did not reveal characteristic peaks in Co60Fe20Sm20 thin films due to insufficient growth-driving forces. Electrical measurements indicated reduced resistivity and sheet resistance with increasing film thickness and higher annealing temperatures, owing to hindered current-carrier transport resulting from the amorphous structure. Atomic force microscope (AFM) analysis showed a decrease in surface roughness with increased thickness and annealing temperature. The low-frequency alternating current magnetic susceptibility (χac) values increased with film thickness and annealing temperature. Nanoindentation analysis demonstrated reduced film hardness and Young's modulus with thicker films. Contact angle measurements suggested a hydrophilic film. Surface energy increased with greater film thickness, particularly in annealed films, indicating a decrease in contact angle contributing to this increase. Transmittance measurements have revealed intensified absorption and reduced transmittance with thicker films. In summary, the surface roughness of CoFeSm films at different annealing temperatures significantly influenced their magnetic, electrical, adhesive, and optical properties. A smoother surface reduced the pinning effect on the domain walls, enhancing the χac value. Additionally, diminished surface roughness led to a lower contact angle and higher surface energy. Additionally, smoother surfaces exhibited higher carrier conductivity, resulting in reduced electrical resistance. The optical transparency decreased due to the smoother surface of Co60Fe20Sm20 films.

[Relationship between serum hepatitis B virus DNA load and hepatocellular carcinoma in Qidong, China: a cohort follow-up study of 14 years].

OBJECTIVE: To explore the relationship between serum HBV DNA load and hepatocellular carcinogenesis in Qidong HBsAg carriers. METHODS: In 1997, 477 HBsAg carriers and 477 age, gender and residence matched HBsAg negative controls were enrolled as a prospective cohort in Qidong city. The entry serum samples were detected for the levels of HBeAg and HBV DNA. The relationship between baseline HBV DNA load and hepatocellular carcinoma (HCC) during the follow-up period from June 1997 to June 2011 were analyzed. RESULTS: The total observed person-years (PY) were 12 200. Eighty-seven patients developed HCC with an incidence of 1498/100 000 PY in the HBsAg positive group versus 6 with an incidence of 94/100 000 PY (P = 0.000) in the HBsAg negative group. The relative risk (RR) was 15.96. N o significant difference existed between the incidences of other tumors in two groups (P = 0.161). Compared with the HBsAg negative group, the RR of HCC was 11.38 (95%CI 4.87 - 26.62, P < 0.01)in the HBsAg+/HBeAg- group and 29.08 (95%CI 12.37 - 68.37, P < 0.01) in the HBsAg+/HBeAg+ group; 5.80 (95%CI 2.29 - 14.70, P < 0.01) in the HBsAg+/HBV DNA- group and 27.75 (95%CI 12.07 - 63.81, P < 0.01) in the HBsAg+/HBV DNA+ group. In HBsAg positive subjects, while the HBV DNA load was classified into 5 levels namely 250 - 10(4), 10(4)-, 10(5)-, 10(6)- and ≥ 10(7) copies/ml, the relative risks for HCC at each level were 2.84 (95%CI 1.44 - 5.61, P < 0.01), 5.75 (95%CI 2.77 - 11.95, P < 0.01), 9.05 (95%CI 4.71 - 17.41, P < 0.01), 6.39 (95%CI 2.79 - 14.64, P < 0.01) and 4.35 (95%CI 2.21 - 8.56, P < 0.01) respectively versus the < 250 copies/ml group. CONCLUSION: HBV DNA is an important risk predictor of hepatocellular carcinoma. The HBsAg carriers with the serum loads of HBV DNA between 10(5) - 10(6) copies/ml are most likely to present with HCC.

Multidimensional study of cell division cycle-associated proteins with prognostic value in gastric carcinoma.

Gastric cancer (GC) represents a widespread malignancy with a poor prognosis. Hence, discovering reliable biomarkers is necessary. The cell division cycle-associated protein (CDCA) family, comprising CDCA1-8, plays a key role in tumor progression. However, whether CDCA expression has prognostic value in GC, especially stomach adenocarcinoma (STAD), has not been elucidated yet. Consequently, we conducted a multifaceted study using bioinformatic tools aimed at exploring CDCA expression levels and appraising their potential prognostic values in patients with STAD. All eight CDCAs were significantly upregulated in STAD tissues compared with healthy tissues. Elevated CDCA4/7/8 mRNA expression predicted a short overall survival, and increased CDCA7 transcriptional levels predicted a short disease-free survival. The most frequent alteration in patients with STAD was low mRNA expression. The functional enrichment analysis incorporating the gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways showed that the cell cycle, foxO signaling pathway, and Epstein-Barr virus were relevant to the main functions of CDCAs. Finally, the immune infiltration analysis revealed a significant correlation between CDCA expression and the infiltration extent of six immunocytes. Therefore, differentially expressed CDCAs may represent potential biomarkers for the prognosis of patients with STAD that can improve survival. Furthermore, this study might offer new ideas for the design and development of immunotherapeutic drugs.

A novel self-learning semi-supervised deep learning network to detect fake news on social media.

Social media has become a popular means for people to consume and share news. However, it also enables the extensive spread of fake news, that is, news that deliberately provides false information, which has a significant negative impact on society. Especially recently, the false information about the new coronavirus disease 2019 (COVID-19) has spread like a virus around the world. The state of the Internet is forcing the world's tech giants to take unprecedented action to protect the "information health" of the public. Despite many existing fake news datasets, comprehensive and effective algorithms for detecting fake news have become one of the major obstacles. In order to address this issue, we designed a self-learning semi-supervised deep learning network by adding a confidence network layer, which made it possible to automatically return and add correct results to help the neural network to accumulate positive sample cases, thus improving the accuracy of the neural network. Experimental results indicate that our network is more accurate than the existing mainstream machine learning methods and deep learning methods.

A Two-Stage Model for Predicting Mild Cognitive Impairment to Alzheimer's Disease Conversion.

Early detection of Alzheimer's disease (AD), such as predicting development from mild cognitive impairment (MCI) to AD, is critical for slowing disease progression and increasing quality of life. Although deep learning is a promising technique for structural MRI-based diagnosis, the paucity of training samples limits its power, especially for three-dimensional (3D) models. To this end, we propose a two-stage model combining both transfer learning and contrastive learning that can achieve high accuracy of MRI-based early AD diagnosis even when the sample numbers are restricted. Specifically, a 3D CNN model was pretrained using publicly available medical image data to learn common medical features, and contrastive learning was further utilized to learn more specific features of MCI images. The two-stage model outperformed each benchmark method. Compared with the previous studies, we show that our model achieves superior performance in progressive MCI patients with an accuracy of 0.82 and AUC of 0.84. We further enhance the interpretability of the model by using 3D Grad-CAM, which highlights brain regions with high-predictive weights. Brain regions, including the hippocampus, temporal, and precuneus, are associated with the classification of MCI, which is supported by the various types of literature. Our model provides a novel model to avoid overfitting because of a lack of medical data and enable the early detection of AD.

A Novel Approach of Feature Space Reconstruction with Three-Way Decisions for Long-Tailed Text Classification.

Text classification is widely studied by researchers in the natural language processing field. However, real-world text data often follow a long-tailed distribution as the frequency of each class is typically different. The performance of current mainstream learning algorithms in text classification suffers when the training data are highly imbalanced. The problem can get worse when the categories with fewer data are severely undersampled to the extent that the variation within each category is not fully captured by the given data. At present, there are a few studies on long-tailed text classification which put forward effective solutions. Encouraged by the progress of handling long-tailed data in the field of image, we try to integrate effective ideas into the field of long-tailed text classification and prove the effectiveness. In this paper, we come up with a novel approach of feature space reconstruction with the help of three-way decisions (3WDs) for long-tailed text classification. In detail, we verify the rationality of using a 3WD model for feature selection in long-tailed text data classification, propose a new feature space reconstruction method for long-tailed text data for the first time, and demonstrate how to effectively generate new samples for tail classes in reconstructed feature space. By adding new samples, we enrich the representing information of tail classes, to improve the classification results of long-tailed text classification. After some comparative experiments, we have verified that our model is an effective strategy to improve the performance of long-tailed text classification.

Effect of Yttrium Addition on Structure and Magnetic Properties of Co60Fe20Y20 Thin Films.

In this paper, a Co60Fe20Y20 film was sputtered onto Si (100) substrates with thicknesses ranging from 10 to 50 nm under four conditions to investigate the structure, magnetic properties, and surface energy. Under four conditions, the crystal structure of the CoFeY films was found to be amorphous by an X-ray diffraction analyzer (XRD), suggesting that yttrium (Y) added into CoFe films and can be refined in grain size and insufficient annealing temperatures do not induce enough thermal driving force to support grain growth. The saturation magnetization (MS) and low-frequency alternate-current magnetic susceptibility (χac) increased with the increase of the thicknesses and annealing temperatures, indicating the thickness effect and Y can be refined grain size and improved ferromagnetic spin exchange coupling. The highest Ms and χac values of the Co60Fe20Y20 films were 883 emu/cm3 and 0.26 when the annealed temperature was 300 °C and the thickness was 50 nm. The optimal resonance frequency (fres) was 50 Hz with the maximum χac value, indicating it could be used at a low frequency range. Moreover, the surface energy increased with the increase of the thickness and annealing temperature. The maximum surface energy of the annealed 300 °C film was 30.02 mJ/mm2 at 50 nm. Based on the magnetic and surface energy results, the optimal thickness was 50 nm annealed at 300 °C, which has the highest Ms, χac, and a strong adhesion, which can be as a free or pinned layer that could be combined with the magnetic tunneling layer and applied in magnetic fields.