Diagnostic Accuracy of Magnetic Resonance Imaging Features and Tumor-to-Nipple Distance for the Nipple-Areolar Complex Involvement of Breast Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis evaluated the accuracy of preoperative breast magnetic resonance imaging (MRI) features and tumor-to-nipple distance (TND) for diagnosing occult nipple-areolar complex (NAC) involvement in breast cancer. MATERIALS AND METHODS: The MEDLINE, Embase, and Cochrane databases were searched for articles published until March 20, 2022, excluding studies of patients with clinically evident NAC involvement or those treated with neoadjuvant chemotherapy. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Two reviewers independently evaluated studies that reported the diagnostic performance of MRI imaging features such as continuity to the NAC, unilateral NAC enhancement, non-mass enhancement (NME) type, mass size (> 20 mm), and TND. Summary estimates of the sensitivity and specificity curves and the summary receiver operating characteristic (SROC) curve of the MRI features for NAC involvement were calculated using random-effects models. We also calculated the TND cutoffs required to achieve predetermined specificity values. RESULTS: Fifteen studies (n = 4002 breast lesions) were analyzed. The pooled sensitivity and specificity (with 95% confidence intervals) for NAC involvement diagnosis were 71% (58-81) and 94% (91-96), respectively, for continuity to the NAC; 58% (45-70) and 97% (95-99), respectively, for unilateral NAC enhancement; 55% (46-64) and 83% (75-88), respectively, for NME type; and 88% (68-96) and 58% (40-75), respectively, for mass size (> 20 mm). TND had an area under the SROC curve of 0.799 for NAC involvement. A TND of 11.5 mm achieved a predetermined specificity of 85% with a sensitivity of 64%, and a TND of 12.3 mm yielded a predetermined specificity of 83% with a sensitivity of 65%. CONCLUSION: Continuity to the NAC and unilateral NAC enhancement may help predict occult NAC involvement in breast cancer. To achieve the desired diagnostic performance with TND, a suitable cutoff value should be considered.

Chromosomal abnormalities of 19,000 couples with recurrent spontaneous abortions: a multicenter study.

OBJECTIVE: To investigate the demographic data and karyotypes of 19,000 couples who experienced recurrent spontaneous abortion (RSA). DESIGN: A cross-sectional study of 19,000 couples. SETTING: Five hospitals. PATIENT(S): A total of 19,000 couples experiencing RSA. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Cytogenetic analysis of blood lymphocytes. RESULT(S): A total of 844 couples (4.44%) showed chromosomal aberrations in either partner. Females were more likely to have chromosomal aberrations. The mean age of females and males with chromosomal aberrations was younger than that of females and males without chromosomal aberrations. Interestingly, sex and age distribution varied significantly depending on the subtypes of chromosomal aberrations. We detected 324 balanced translocations, including 223 novel ones. They were distributed across all chromosomes; the frequency of balanced translocations decreased according to the numerical order of autosomes (strong negative correlation; r = -0.84). Individuals with balanced translocations were younger than other groups. All 58 inversions, including 25 novel ones, were detected in autosomes; the negative correlation also existed. Thirteen Robertsonian translocations, 5 deletions, and 3 duplications were detected. Six types of Turner variants, triple X mosaicism, and mosaic Down syndrome were detected in females; Klinefelter variants and mosaic XYY syndrome were detected in males. Marker chromosomes at various mosaic levels and 7 different complex chromosomal rearrangements were also observed. CONCLUSION(S): Patients who experienced RSA induced by chromosomal aberrations experienced miscarriages at a younger age. Significant correlations existed between the patients' age or sex and the subtypes of chromosomal aberrations. This study detected several chromosomal abnormalities associated with RSA, including various novel aberrations.

Mutation spectrum and genotype-phenotype correlations in 157 Korean CADASIL patients: a multicenter study.

CADASIL is an inherited disease caused by mutations in the NOTCH3 gene. We aimed to investigate the mutation and clinical spectrum, and genotype-phenotype correlations of Korean CADASIL patients. Samples from 492 clinically suspicious patients were collected from four hospitals. Sanger sequencing was performed to screen exons 2 to 25 of the NOTCH3 gene and variants of unknown significance (VUS) were analyzed using the ACMG guidelines. The medical records and MRI data were received from each hospital, for comprehensive analysis of genotype-phenotype correlations. Previously reported NOTCH3 variants were most commonly detected in exon 11 whereas exon 4 was the most common in European studies. The variants were detected equally between the EGFr domains 1-6 and 7-34, which was different from EGFr 1-6 predominant European studies. The average age-of-onset of patients with EGFr 1-6 variants were 4.81 ± 1.95 years younger than patients with EGFr 7-34 variants. Overall, it took Korean patients 51.2 ± 10 years longer to develop CADASIL in comparison to European patients. The most common mutation was p.R544C, which was associated with a later onset of stroke and a significant time-to-event curve difference. We verified four atypical phenotypes of p.R544C that had been reported in previous studies. Eight novel variants in 15 patients were detected but remained a VUS based on the ACMG criteria. This study reported a different EGFr distribution of Korean patients in comparison to European patients and its correlation with a later age-of-onset. An association between a later onset of stroke/TIA and p.R544C was observed.

Identification of a novel HLA-B*54 allele, HLA-B*54:01:08, in a Korean individual.

HLA-B*54:01:08 differs from B*54:01:01 by a synonymous mutation at codon 228 in exon 4.

Proteomic analysis of liver in miniature pigs according to developmental stages using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

Due to the shortage of human organ donors for transplant, various studies of xenotransplantation, or the use of animal organs instead of human organs, have been carried out. The organs of porcine are thought to be safer and of a more suitable size for xenotransplantationthan those of nonhuman primates. Understanding the levels of expression of proteins, and their post-translational regulation, would be very practical between different species and among developing stages, though the molecular profiling for xenotransplantation has been rarely studied for porcine, while that of human and rodent is well known. Here, in this present study, we report protein regulation of the developing stages of liver (4-day old neonate, 19-day old piglet and 14-month old adult miniature pigs) using 2-DE and MALDI-TOF. From images of the three different stages, a total of 8 spotswhich were differently regulated were identified, and 5 spots were identified with MALDI-TOF MS. The data presented within this study provides critical direction relating to the development of livers of miniature pigs, which will assist future proteome analysis of the liver, and advance our understanding of the hurdles facing xenotransplantaion.

Protection of cardiomyocytes from ischemic/hypoxic cell death via Drbp1 and pMe2GlyDH in cardio-specific ARC transgenic mice.

The ischemic death of cardiomyocytes is associated in heart disease and heart failure. However, the molecular mechanism underlying ischemic cell death is not well defined. To examine the function of apoptosis repressor with a caspase recruitment domain (ARC) in the ischemic/hypoxic damage of cardiomyocytes, we generated cardio-specific ARC transgenic mice using a mouse alpha-myosin heavy chain promoter. Compared with the control, the hearts of ARC transgenic mice showed a 3-fold overexpression of ARC. Langendoff preparation showed that the hearts isolated from ARC transgenic mice exhibited improved recovery of contractile performance during reperfusion. The cardiomyocytes cultured from neonatal ARC transgenic mice were significantly resistant to hypoxic cell death. Furthermore, the ARC C-terminal calcium-binding domain was as potent to protect cardiomyocytes from hypoxic cell death as ARC. Genome-wide RNA expression profiling uncovered a list of genes whose expression was changed (>2-fold) in ARC transgenic mice. Among them, expressional regulation of developmentally regulated RNA-binding protein 1 (Drbp1) or the dimethylglycine dehydrogenase precursor (pMe(2)GlyDH) affected hypoxic death of cardiomyocytes. These results suggest that ARC may protect cardiomyocytes from hypoxic cell death by regulating its downstream, Drbp1 and pMe(2)GlyDH, shedding new insights into the protection of heart from hypoxic damages.

A positive role of the PI3-K/Akt signaling pathway in PC12 cell differentiation.

Activation of phosphatidylinositol 3-kinase (PI3-K) is considered to be a key event upon stimulation of cells with growth factors. Akt is known to be a downstream target of PI3-K when it is activated by nerve growth factor (NGF). NGF induces cell differentiation of PC12 cells as indicated by neurite outgrowth. In order to investigate the role of PI3-K/Akt in NGF-induced differentiation of PC12 cells, we generated cells ectopically expressing constitutively activated (CA), wild type (WT) and dominant negative (DN) forms of Akt. NGF-induced neurite outgrowth was greatly accelerated in the cells expressing CA-Akt, and dramatically inhibited in those expressing DN-Akt. Pre-treatment with an Akt inhibitor, ML-9 [1-(5-chloronaphthalene-1-sulfonyl)-1H- hexahydro-1,4-diazepine], inhibited NGF-induced Akt phosphorylation as well as neurite outgrowth but did not markedly affect the activities of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). The PI3-K inhibitors wortmannin and LY294002 blocked NGF-induced Akt phosphorylation as well as neurite outgrowth. These results indicate that PI3-K/Akt is a positive regulator of NGF-induced neuronal differentiation in PC12 cells.