Can Class-Priors Help Single-Positive Multi-Label Learning?

Single-positive multi-label learning (SPMLL) is a typical weakly supervised multi-label learning problem, where each training example is annotated with only one positive label. Existing SPMLL methods typically assign pseudo-labels to unannotated labels with the assumption that prior probabilities of all classes are identical. However, the class-prior of each category may differ significantly in real-world scenarios, which makes the predictive model not perform as well as expected due to the unrealistic assumption on real-world application. To alleviate this issue, a novel framework named {\proposed}, i.e., Class-pRiors Induced Single-Positive multi-label learning, is proposed. Specifically, a class-priors estimator is introduced, which could estimate the class-priors that are theoretically guaranteed to converge to the ground-truth class-priors. In addition, based on the estimated class-priors, an unbiased risk estimator for classification is derived, and the corresponding risk minimizer could be guaranteed to approximately converge to the optimal risk minimizer on fully supervised data. Experimental results on ten MLL benchmark datasets demonstrate the effectiveness and superiority of our method over existing SPMLL approaches

Utilizing systematic Mendelian randomization to identify potential therapeutic targets for mania

BackgroundMania has caused incalculable economic losses for patients, their families, and even society, but there is currently no effective treatment plan for this disease without side effects.MethodsUsing bioinformatics and Mendelian randomization methods, potential drug target genes and key substances associated with mania were explored at the mRNA level. We used the chip expression profile from the GEO database to screen differential genes and used the eQTL and mania GWAS data from the IEU database for two-sample Mendelian randomization (MR) to determine core genes by colocalization. Next, we utilized bioinformatics analysis to identify key substances involved in the mechanism of action and determined related gene targets as drug targets.ResultsAfter differential expression analysis and MR, a causal relationship between the expression of 46 genes and mania was found. Colocalization analysis yielded six core genes. Five key substances were identified via enrichment analysis, immune-related analysis, and single-gene GSVA analysis of the core genes. MR revealed phenylalanine to be the only key substance that has a unidirectional causal relationship with mania. In the end, SBNO2, PBX2, RAMP3, and QPCT, which are significantly associated with the phenylalanine metabolism pathway, were identified as drug target genes.ConclusionSBNO2, PBX2, RAMP3, and QPCT could serve as potential target genes for mania treatment and deserve further basic and clinical research. Medicinal target genes regulate the phenylalanine metabolism pathway to achieve the treatment of mania. Phenylalanine is an important intermediate substance in the treatment of mania that is regulated by drug target genes

Analysis of the Clinical Characteristics of Malignant Tumor Patients with Rheumatic Symptoms and Rheumatic Disease Combined with Malignant Tumor Patients

Objective: We study the relationship between rheumatic immune disease and malignant tumor to provide the basis for clinical diagnosis and treatment. Methods: We selected 53 patients who were hospitalized in our department from January 2013 to February 2020, including 26 patients with rheumatic immune disease combined with malignant tumor and 27 patients with malignant tumor with rheumatic symptoms. We retrospectively analyzed the relationship between gender, age, main clinical manifestations, tumor system distribution, metastasis rate, rheumatic immune disease type and tumor type. Results: Among the patients with rheumatic immune disease complicated with tumor, 26.1% were male and 66.7% were female. Among the tumor patients with rheumatic symptoms, 73.9% were male and 33.3% were female. There was a significant difference in gender composition between the two groups. Among the patients with rheumatic immune disease complicated with tumor, respiratory system tumor was the highest. Among the tumor patients with rheumatic symptoms, the incidence of hematological tumors was the highest. The distribution of tumor system was different between the two groups. The proportion of metastatic tumor in patients with rheumatic symptoms is higher than that in patients with rheumatic immune disease combined with malignant tumor. The percentage of concurrent tumor in three diseases in the same period was 0.363% for rheumatoid arthritis, 2.02% for polymyositis/ dermatomyositis and 0.24% for Sjogren's syndrome. This study shows that patients with polymyositis/ dermatomyositis are more likely to develop malignant tumors. Conclusion: There were significant differences in gender composition, distribution of tumor system and the proportion of metastatic tumor between patients with rheumatic immune disease complicated with malignant tumor and patients with rheumatic symptoms, and malignant tumor was more common in patients with polymyositis/ dermatomyositis

PITX2C loss-of-function mutations responsible for idiopathic atrial fibrillation

OBJECTIVE: This study aimed to identify novel PITX2c mutations responsible for idiopathic atrial fibrillation. METHODS: A cohort of 210 unrelated patients with idiopathic atrial fibrillation and 200 unrelated, ethnically matched healthy individuals used as controls were recruited. The whole coding exons and splice junctions of the PITX2c gene, which encodes a paired-like homeobox transcription factor required for normal cardiovascular morphogenesis, were sequenced in 210 patients and 200 control subjects. The causative potentials of the identified mutations were automatically predicted by MutationTaster and PolyPhen-2. The functional characteristics of the PITX2c mutations were explored using a dual-luciferase reporter assay system. RESULTS: Two novel heterozygous PITX2c mutations (p.Q105L and p.R122C) were identified in 2 of the 210 unrelated patients with idiopathic atrial fibrillation. These missense mutations were absent in the 400 control chromosomes and were both predicted to be pathogenic. Multiple alignments of PITX2c protein sequences across various species showed that the altered amino acids were highly evolutionarily conserved. A functional analysis demonstrated that the mutant PITX2c proteins were both associated with significantly reduced transcriptional activity compared with their wild-type counterparts. CONCLUSION: The findings of this study associate PITX2c loss-of-function mutations with atrial fibrillation, supporting the hypothesis that dysfunctional PITX2c confers enhanced susceptibility to atrial fibrillation and suggesting potential implications for early prophylaxis and allele-specific therapy for this common arrhythmia

Effects of ACE inhibition on endothelial progenitor cell mobilization and prognosis after acute myocardial infarction in type 2 diabetic patients

OBJECTIVE: We aimed to assess the chemotactic response of endothelial progenitor cells to angiotensin-converting enzyme inhibitors in T2DM patients after acute myocardial infarction, as well as the associated prognosis. METHODS: Sixty-eight T2DM patients with acute myocardial infarction were randomized to either receive or not receive daily oral perindopril 4 mg, and 36 non-diabetic patients with acute myocardial infarction were enrolled as controls. The numbers of circulating CD45−/low+CD34+CD133+KDR+ endothelial progenitor cells, as well as the stromal cell-derived factor-α and high-sensitivity C reactive protein levels, were measured before acute percutaneous coronary intervention and on days 1, 3, 5, 7, 14, and 28 after percutaneous coronary intervention. Patients were followed up for 6 months. Chinese Clinical Trial Registry: ChiCTR-TRC-12002599. RESULTS: T2DM patients had lower circulating endothelial progenitor cell counts, decreased plasma vascular endothelial growth factor and α levels, and higher plasma high-sensitivity C reactive protein levels compared with non-diabetic controls. After receiving perindopril, the number of circulating endothelial progenitor cells increased from day 3 to 7, as did the plasma levels of vascular endothelial growth factor and stromal cell-derived factor-α, compared with the levels in T2DM controls. Plasma high-sensitivity C reactive protein levels in the treated group decreased to the same levels as those in non-diabetic controls. Furthermore, compared with T2DM controls, the perindopril-treated T2DM patients had lower cardiovascular mortality and occurrence of heart failure symptoms (