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Background DNA methylation in the SHOX2 locus was previously used to reliably detect lung cancer in a group of critical controls, including 'cytologically negative' samples with no visible tumor cell content, at a high specificity based on the analysis of bronchial lavage samples. This study aimed to investigate, if the methylation correlates with SHOX2 gene expression and/or copy number alterations. An amplification of the SHOX2 gene locus together with the observed tumor-specific hypermethylation might explain the good performance of this marker in bronchial lavage samples. Methods SHOX2 expression, gene copy number and DNA methylation were determined in lung tumor tissues and matched morphologically normal adjacent tissues (NAT) from 55 lung cancer patients. Quantitative HeavyMethyl (HM) real-time PCR was used to detect SHOX2 DNA methylation levels. SHOX2 expression was assayed with quantitative real-time PCR, and copy numbers alterations were measured with conventional real-time PCR and array CGH. Results A hypermethylation of the SHOX2 locus in tumor tissue as compared to the matched NAT from the same patient was detected in 96% of tumors from a group of 55 lung cancer patients. This correlated highly significantly with the frequent occurrence of copy number amplification (p < 0.0001), while the expression of the SHOX2 gene showed no difference. Conclusions Frequent gene amplification correlated with hypermethylation of the SHOX2 gene locus. This concerted effect qualifies SHOX2 DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples.

Interstitial deletions of chromosome band 10q22 are rare. We report on the characterization of three overlapping de novo 10q22 deletions by high-resolution array comparative genomic hybridization in three unrelated patients. Patient 1 had a 7.9 Mb deletion in 10q21.3–q22.2 and suffered from severe feeding problems, facial dysmorphisms and profound mental retardation. Patients 2 and 3 had nearly identical deletions of 3.2 and 3.6 Mb, the proximal breakpoints of which were located at an identical low-copy repeat. Both patients were mentally retarded; patient 3 also suffered from growth retardation and hypotonia. We also report on the results of breakpoint analysis by array painting in a mentally retarded patient with a balanced chromosome translocation 46,XY,t(10;13)(q22;p13)dn. The breakpoint in 10q22 was found to disrupt C10orf11 , a brain-expressed gene in the common deleted interval of patients 1–3. This finding suggests that haploinsufficiency of C10orf11 contributes to the cognitive defects in 10q22 deletion patients.

Autism and mental retardation (MR) are often associated, suggesting that these conditions are etiologically related. Recently, array‐based comparative genomic hybridization (array CGH) has identified submicroscopic deletions and duplications as a common cause of MR, prompting us to search for such genomic imbalances in autism. Here we describe a 1.5‐Mb duplication on chromosome 16p13.1 that was found by high‐resolution array CGH in four severe autistic male patients from three unrelated families. The same duplication was identified in several variably affected and unaffected relatives. A deletion of the same interval was detected in three unrelated patients with MR and other clinical abnormalities. In one patient we revealed a further rearrangement of the 16p13 imbalance that was not present in his unaffected mother. Duplications and deletions of this 1.5‐Mb interval have not been described as copy number variants in the Database of Genomic Variants and have not been identified in >600 individuals from other cohorts examined by high‐resolution array CGH in our laboratory. Thus we conclude that these aberrations represent recurrent genomic imbalances which predispose to autism and/or MR. Hum Mutat 28(7), 674–682, 2007. © 2007 Wiley‐Liss, Inc.

We report on three unrelated mentally disabled patients, each carrying a de novo balanced translocation that truncates the autism susceptibility candidate 2 (AUTS2) gene at 7q11.2. One of our patients shows relatively mild mental retardation; the other two display more profound disorders. One patient is also physically disabled, exhibiting urogenital and limb malformations in addition to severe mental retardation. The function of AUTS2 is presently unknown, but it has been shown to be disrupted in monozygotic twins with autism and mental retardation, both carrying a translocation t(7;20)(q11.2;p11.2) (de la Barra et al. in Rev Chil Pediatr 57:549-554, 1986; Sultana et al. in Genomics 80:129-134, 2002). Given the overlap of this autism/mental retardation (MR) phenotype and the MR-associated disorders in our patients, together with the fact that mapping of the additional autosomal breakpoints involved did not disclose obvious candidate disease genes, we ascertain with this study that AUTS2 mutations are clearly linked to autosomal dominant mental retardation.

Very little is known about the molecular basis of autosomal recessive MR (ARMR) because in developed countries, small family sizes preclude mapping and identification of the relevant gene defects. We therefore chose to investigate genetic causes of ARMR in large consanguineous Iranian families. This study reports on a family with six mentally retarded members. Array-based homozygosity mapping and high-resolution microarray-based comparative genomic hybridization (array CGH) revealed a deletion of approximately 150-200 kb, encompassing the promoter and the first six exons of the MCPH1 gene, one out of four genes that have been previously implicated in ARMR with microcephaly. Reexamination of affected individuals revealed a high proportion of prematurely condensed chromosomes, which is a hallmark of this condition, but in spite of the severity of the mutation, all patients showed only borderline to mild microcephaly. Therefore the phenotypic spectrum of MCPH1 mutations may be wider than previously assumed, with ARMR being the only consistent clinical finding.

Background: Intermediate-risk acute pulmonary embolism (PE) is clinically heterogeneous, and early deterioration may occur despite initial normotension. The Endothelial Activation and Stress Index (EASIX) is a readily available laboratory index reflecting endothelial activation, cellular injury, renal-perfusion stress, and platelet-related thromboinflammatory burden. We investigated whether admission EASIX and echocardiographic right ventricular-pulmonary arterial (RV-PA) coupling assessed by the TAPSE/PASP ratio identify intermediate-risk PE patients at increased risk for an early adverse clinical outcome (EACO). Methods: This retrospective cohort study included 900 consecutive intermediate-risk acute PE patients admitted between 1 January 2020 and 10 June 2025. EASIX was calculated as LDH (U/L) × creatinine (mg/dL)/platelet count (109/L). The primary endpoint was EACO within the first seven days after PE diagnosis during the index hospitalization, including hemodynamic decompensation, vasopressor/inotrope requirement, intensive care unit transfer, rescue reperfusion therapy, ventilatory support, cardiac arrest, or PE-related death. Hierarchical logistic regression, ROC analysis, calibration assessment, bootstrap internal validation, and 10-fold cross-validation were performed. Results: EACO occurred in 110 patients (12.2%). Patients with EACO had higher EASIX (2.28 [1.52–3.27] vs. 1.27 [0.86–2.00], p < 0.001) and lower TAPSE/PASP ratio (0.29 [0.23–0.36] vs. 0.42 [0.33–0.57], p < 0.001). log2-EASIX correlated inversely with TAPSE/PASP (Spearman rho = −0.30, p < 0.001). In the final combined model, log2-EASIX (OR 1.55 per doubling, 95% CI 1.14–2.10, p = 0.005) and TAPSE/PASP per 0.1-unit decrease (OR 1.36, 95% CI 1.10–1.68, p = 0.004) remained independently associated with EACO after adjustment for clinical variables, troponin, lactate, D-dimer, and C-reactive protein-to-albumin ratio. The final model showed higher discrimination than the clinical-laboratory model, although the absolute AUC increment was modest (AUC 0.920 vs. 0.904). Bootstrap optimism-corrected AUC was 0.910 and 10-fold cross-validated AUC was 0.904. Conclusions: Admission EASIX and impaired RV-PA coupling may provide complementary prognostic information for early risk stratification in intermediate-risk acute PE. Because this was a retrospective single-center study without external validation, these findings should be considered hypothesis-generating and should not be used as definitive treatment-escalation triggers before independent external validation.

The aim of this 2-group study was to investigate the following question: Are there significant differences between scaffolded design-based learning controlled using 7 forms and teacher-directed instruction methods for the toy crane project on grade 7 students’ posttest scores on the simple machines achievement test, attitude toward simple machines, and attitude toward creativity in simple machines after adjusting for their respective pretest scores and the prior semester science grades? The study group (N = 65) consisted of grade 7 students in public middle schools in Burdur, Turkey. There were significant treatment effects favoring the first method with large effect sizes on both achievement and creative attitude scores. Teaching topics about simple machines with the design-based method increased students’ achievement and creative attitude without disadvantaging their attitude toward the topic as they constructed new knowledge through each step of the precise process.

Objective Thyroid tuberculosis (TTB) is a very rare condition, even in countries with a high prevalence of tuberculosis. The aim of this article is to review and retrieve data about thyroid tuberculosis from the English‐language literature in order to gain a better understanding of the clinical characteristics of TTB. Study Design We performed Medline, PubMed, and library searches using the key words “thyroid tuberculosis,” “throid disease,” “tuberculosis and thyroid.” Reference lists of the articles obtained and previous reviews were also examined. Results We retrieved 76 cases matching our selection criteria from the search. Review of the cases with TTB revealed a slight female preponderance. The patients reported in the literature ranged in age from 9 to 83 years, with a median age of 40 ± 16 years for men and 44 ± 17 years for women. In the articles surveyed, TTB presented with a broad spectrum of manifestations, ranging from an isolated nodule to thyrotoxicosis. It seems that diagnosis of thyroid tuberculosis has recently been increasing, perhaps because of the growing incidence of tuberculosis and the diagnostic use of fine‐needle aspiration cytology in the diagnosis. Although, in the past, the diagnosis was genarally made by the examination of the specimens, at present, fine‐needle aspiration cytology seems to be a useful method in diagnosis tuberculous thyroiditis.The role of surgery is limited after the diagnosis. The choice of treatment should be medical antituberculous therapy. Conclusiıons Preoperative diagnosis of thyroid tuberculosis is important because of the availability of medical treatment and the limited role of surgery. This condition should be kept in mind in evaluating patients with a thyroid nodule, in communities where the prevalence of tuberculosis is high.