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During meiosis, crossover recombination connects homologous chromosomes to direct their accurate segregation1. Defective crossing over causes infertility, miscarriage and congenital disease. Each pair of chromosomes attains at least one crossover via the formation and biased resolution of recombination intermediates known as double Holliday junctions2,3. A central principle of crossover resolution is that the two Holliday junctions are resolved in opposite planes by targeting nuclease incisions to specific DNA strands4. The endonuclease activity of the MutLγ complex has been implicated in the resolution of crossovers5-10, but the mechanisms that activate and direct strand-specific cleavage remain unknown. Here we show that the sliding clamp PCNA is important for crossover-biased resolution. In vitro assays with human enzymes show that PCNA and its loader RFC are sufficient to activate the MutLγ endonuclease. MutLγ is further stimulated by a co-dependent activity of the pro-crossover factors EXO1 and MutSγ, the latter of which binds Holliday junctions11. MutLγ also binds various branched DNAs, including Holliday junctions, but does not show canonical resolvase activity, implying that the endonuclease incises adjacent to junction branch points to achieve resolution. In vivo, RFC facilitates MutLγ-dependent crossing over in budding yeast. Furthermore, PCNA localizes to prospective crossover sites along synapsed chromosomes. These data highlight similarities between crossover resolution and the initiation steps of DNA mismatch repair12,13 and evoke a novel model for crossover-specific resolution of double Holliday junctions during meiosis.

Compared with sun-exposed melanomas, less is known regarding the pathogenesis of sun-protected melanomas. Sun-protected melanomas share many epidemiologic factors, but their genetic heterogeneity is not well studied. We investigated the genomic profile of acral, mucosal, and vulvovaginal melanomas. We hypothesize that mucosal melanomas, recognized for their uniquely aggressive clinical behavior, have distinct genomic features. We performed whole transcriptome messenger RNA and DNA (1711 genes) sequencing, messenger RNA expression profiling, tumor mutational burden, ultraviolet signature, and copy number variants analysis on 29 volar/digital acral, 7 mucosal, and 6 vulvovaginal melanomas. There was significant genetic heterogeneity, particularly in acral melanomas, with 36% having BRAF alterations, whereas other melanomas had none (P =.0159). Nonzero ultraviolet signatures were more frequent in acral melanomas, suggesting greater ultraviolet involvement. Mucosal melanomas formed a distinct group with increased expression of cell cycle and proliferation genes. Various targetable aberrations were identified, such as AURKA and ERBB2 , in mucosal and acral melanomas, respectively. The sample size was a small. There is significant genetic heterogeneity among sun-protected melanomas. Mucosal melanomas have upregulation in cell cycle and proliferation genes, which may explain their aggressive behavior. Ultraviolet radiation plays some role in a subset of acral but not other melanomas. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study is to find an accurate and fast method to diagnose the pathogen of bronchiectasis PATIENTS AND METHODS: Ten bronchiectasic patients diagnosed with Mucoid Pseudomonas Aeruginosa (MPA) in the past two years were analyzed. Accuracy and time were compared between microbiology rapid on-site evaluation (M-ROSE) and sputum bacterial culture. RESULTS: The accuracy rate of M-ROSE in the patients is 100% consistent with bacterial culture results. The average time of M-ROSE is about 4.3 min, which is over 1000 times shorter than that of sputum bacterial culture. CONCLUSIONS: M-ROSE may be a better method for etiological diagnosis of MPA. [ABSTRACT FROM AUTHOR]

Background: Atypical network encompasses several patterns. Few studies assess the sensitivity, specificity, and positive and negative predictive values of network subtypes.Objective: We assessed the diagnostic value of atypical network subtypes and their histopathologic correlates in cutaneous melanocytic lesions.Methods: A retrospective search (2014-2018) from a high-risk melanoma clinic for cases scored for atypical network with accompanying dermoscopic photographs yielded 120 lesions (15 melanoma; 30 severely, 38 moderately, and 32 mildly atypical nevi; 4 compound nevi; and 1 junctional nevus). A dermatopathologist blinded to diagnosis assessed dermoscopic and histologic features. Network abnormality correlates with histopathology and clinical diagnoses were assessed with sensitivity, specificity, positive and negative predictive values, and odds ratios.Results: A multivariable model with shiny white streaks (odds ratio 3.02) and inverse network (OR 4.46) was most predictive of melanoma or severe atypia. Positive predictive value for melanoma or severe atypia in decreasing order was inverse network (73.9%), shiny white streaks (71.4%), loss of network (46%), branched streaks (29.4%), and thick brown lines (28.4%).Limitations: Cases were retrospectively found from a pigmented lesion clinic and evaluated by a single dermatopathologist.Conclusion: Shiny white streaks and inverse network are most predictive of melanoma or severe atypia and warrant biopsy if found on dermoscopy. [ABSTRACT FROM AUTHOR]

Background Repigmentation at previous biopsy sites pose a significant diagnostic dilemma given clinical and histologic similarities between recurrent nevi and locally recurrent melanoma. Though common in melanoma, the role of TERT promoter mutations (TPMs) in recurrent nevi is unknown. Objective We investigated the role of TPMs in recurrent nevi and whether the presence of hotspot TPM distinguishes recurrent nevi from locally recurrent melanoma. We also characterized clinical and histologic features differentiating these lesions. Methods We analyzed 11 locally recurrent melanomas, 17 recurrent nevi, and melanoma and nevus controls to determine TPM status. We also assessed clinical and histologic features of the recurrent groups. Results Hotspot TPMs were more common in recurrent melanomas than recurrent nevi (P =.008). Recurrent melanomas were more likely to have solar elastosis (P =.0047), multilayering of melanocytes in the epidermis (P =.0221), adnexal involvement (P =.0069), and epidermal consumption (P =.0204). Recurrent nevi had intra-epidermal atypia limited to the area above the scar (P <.0001) and occurred earlier after the original biopsy (P <.0008). Solar elastosis, months to recurrence, and hotspot TPMs were independently associated with recurrent melanoma in multivariate analysis. Limitations This was a retrospective study. Conclusion Hotspot TPMs are significantly more frequent in recurrent melanomas and could serve as a diagnostic clue in histologically ambiguous cases. [ABSTRACT FROM AUTHOR]

Background: BRCA1-associated protein 1 (BAP1)-inactivated melanocytic tumors (BIMTs) are often the earliest sign of the BAP1 tumor predisposition syndrome. Identification of BIMTs and selection of patients for germline testing affect the lives of patients with germline BAP1 mutations.Objective: To describe the spectrum of histomorphologic findings in BAP1-inactivated melanocytic lesions to improve their recognition. We determined the frequency of sporadic versus germline cases in our cohort, assessing whether any features were statistically linked to germline status.Methods: Histomorphologic features of BAP1-inactivated melanocytic lesions were analyzed by comparing cases with germline mutations with those with unknown or negative status. Available clinical follow-up data were reported.Results: The histomorphologic spectrum of BAP1-inactivated melanocytic lesions is broad; it includes cases with spitzoid cytomorphology (69%), smaller epithelioid cells without spitzoid features (31%), and rhabdoid cytologic features (58%). BIMTs from patients with germline mutations were statistically more likely to have an extensive junctional component of BAP1-inactivated melanocytes (P = .0177). All 11 patients with suspected or confirmed germline mutations had a history of cutaneous melanoma or multiple BIMTs.Limitations: The unknown germline status of 77 patients.Conclusion: Approximately 12% of patients with BIMTs have germline mutations. Extensive junctional involvement in a BIMT and a personal history of melanoma or previous BIMT may be additional indications for germline testing. [ABSTRACT FROM AUTHOR]

Background: Shiny white streaks (SWSs) are best visualized with polarized dermoscopy and correlate with dermal fibroplasia histopathologically. SWSs have been described at higher frequencies in melanomas than in benign nevi.Objective: We assessed the diagnostic value of different patterns of SWSs and their histologic correlate in melanocytic lesions.Methods: Polarized dermoscopic images of 1507 histopathologically diagnosed melanocytic neoplasms were analyzed for presence and pattern of SWSs. Histology was also reviewed for correlation.Results: Among 1507 melanocytic neoplasms, SWSs were observed in 31 of 144 melanomas (22%) and 22 of 1363 benign neoplasms (1.6%) (P < .001). The sensitivity and specificity of SWSs for melanoma were 22% and 98%, respectively. Diffuse SWSs exhibited the greatest diagnostic value for melanoma, with sensitivity of 11.8% and specificity of 99.5%. Focal central and peripheral SWSs were comparable in diagnostic significance. The presence of SWSs was highly uncommon in dysplastic nevi, whereas in certain benign subgroups of nevi such as Spitz nevi and atypical genital special site nevi, SWSs were not uncommon. Diffuse SWSs correlated with greater breadth of deep fibroplasia than focal SWSs (P = .009), and SWSs correlated with greater Breslow depth among melanomas (P = .007).Limitations: This study was retrospective.Conclusion: Polarized dermoscopy is a valuable diagnostic tool in the identification of SWSs, a feature that is highly specific for melanoma. [ABSTRACT FROM AUTHOR]

The preparation of glass-ceramics with high contents of red mud ash using TiO2 and titanium slag as nucleation agents, respectively, is proposed. The effects of different formulations on physicochemical properties, microstructure and phase composition of glass-ceramics were investigated, followed by the analysis of the crystallisation behaviours. The results showed that the primary crystalline phase was Ca2(Al(AlSi)O7) in both cases, while the secondary crystalline phase was (CaFeO6Si2) and Ca(Al2Si2O8), respectively. Also, the crystallinity increased with increasing content of nucleation agent, and condensations were observed once the nucleation agent content exceeded a critical value. With the contents of TiO2 and titanium slag to be 1 and 6·6%, respectively, the overall content of industrial solid wastes achieved 93·9 and 95·3%, respectively. The performance of as-prepared glass-ceramics can satisfy the requirements of JC/T 872-2000 standard. Therefore, this study is of great significance for the recycling of industrial solid wastes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To elucidate the association of fat-mass and obesity-associated gene (FTO) rs9939609 polymorphism with obesity among children and adolescents. METHODS: A literature search was conducted in PubMed, MEDLINE, Springer, and Google scholar to identify eligible studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used for four models: co-dominant model (AA vs. TT, AT vs. TT), dominant model (AA + AT vs. TT), recessive model (AA vs. AT + TT), and allelic model (A vs. T). Subgroup analyses stratified by ethnicity (Caucasian, others) and participants (children, children and adolescents) were assessed under allelic model. The heterogeneity and publication bias were examined. RESULTS: This meta-analysis included 12 eligible studies consisting 5,000 cases and 9,853 controls. The results revealed that FTO rs9939609 polymorphism was significantly associated with the increased risk of obesity in co-dominant model (AA vs. TT: OR = 1.91, 95% CI: 1.47-2.48, p < 0.01; AT vs. TT: OR = 1.18, 95% CI: 1.02-1.38, p = 0.03), dominant model (AA + AT vs. TT: OR = 1.47, 95% CI: 1.35-1.59, p < 0.01), recessive model (AA vs. AT + TT: OR = 1.79, 95% CI: 1.47-2.17, p < 0.01), and allelic model (A vs.T: OR = 1.39, 95% CI: 1.221.58, p < 0.01). Similar results were obtained for the subgroup analyses stratified by ethnicity and participants under allelic model. CONCLUSIONS: FTO rs9939609 polymorphism is associated with the increased risk of obesity among children and adolescents, especially the homozygous carriers. [ABSTRACT FROM AUTHOR]

Abstract: The National Cancer Institute Enterprise Vocabulary Services (NCI EVS) uses a wide range of quality assurance (QA) techniques to maintain and extend NCI Thesaurus (NCIt). NCIt is a reference terminology and biomedical ontology used in a growing number of NCI and other systems that extend from translational and basic research through clinical care to public information and administrative activities. Both automated and manual QA techniques are employed throughout the editing and publication cycle, which includes inserting and editing NCIt in NCI Metathesaurus. NCI EVS conducts its own additional periodic and ongoing content QA. External reviews, and extensive evaluation by and interaction with EVS partners and other users, have also played an important part in the QA process. There have always been tensions and compromises between meeting the needs of dependent systems and providing consistent and well-structured content; external QA and feedback have been important in identifying and addressing such issues. Currently, NCI EVS is exploring new approaches to broaden external participation in the terminology development and QA process. [Copyright &y& Elsevier]