Miracle-dz/UniFAR-FTUs huggingface dataset:
Whole chromosome loss is promoted by telomere dysfunction in primary cells

Errors in chromosome segregation during mitosis result in aneuploidy, which in humans may play a role in the onset of neoplasia by changing gene dosage. Nearly all solid tumors exhibit genomic instability at the chromosomal level, showing both structural and numerical chromosome abnormalities. Chromosomal instability occurs early in the development of cancer and may represent an important step in the initiation and/or progression of the disease. Telomere integrity appears to be a critical element in the genesis of structural chromosome imbalances, but it is still not clear whether it can also generate numerical chromosome aberrations. We investigated the possible relationship between telomere shortening and aneuploidy formation in human mammary epithelial cells using the cytokinesis‐block micronucleus assay combined with fluorescent DNA probes. In this cell system, uncapped chromosomes fuse with each other resulting in dicentric chromosomes, which are known to be a source of new structural chromosome rearrangements. Here, we show that in primary epithelial cells, the chromosomes with short telomeres are more frequently involved in missegregation events than chromosomes of normal telomere length. Whole chromosome aneuploidy occurs through both nondisjunction and anaphase lagging of dicentric chromatids, which suggests that pulling anaphase bridges toward opposite poles can generate the necessary force for detaching a chromosome from the microtubules of one or both spindle poles. Therefore, telomere‐driven instability can promote not only the appearance of chromosomal rearrangements but also the appearance of numerical chromosome aberrations that could favor cell immortalization and the acquisition of a tumor phenotype. © 2010 Wiley‐Liss, Inc.
Sulfatase 1 and sulfatase 2 in hepatocellular carcinoma: Associated signaling pathways, tumor phenotypes, and survival

The heparin‐degrading endosulfatases sulfatase 1 (SULF1) and sulfatase 2 (SULF2) have opposing effects in hepatocarcinogenesis despite structural similarity. Using mRNA expression arrays, we analyzed the correlations of SULF expression with signaling networks in human hepatocellular carcinomas (HCCs) and the associations of SULF expression with tumor phenotype and patient survival. Data from two mRNA microarray analyses of 139 and 36 HCCs and adjacent tissues were used as training and validation sets. Partek and Metacore software were used to identify SULF correlated genes and their associated signaling pathways. Associations between SULF expression, the hepatoblast subtype of HCC, and survival were examined. Both SULF1 and 2 had strong positive correlations with periostin, IQGAP1, TGFB1, and vimentin and inverse correlations with HNF4A and IQGAP2. Genes correlated with both SULFs were highly associated with the cell adhesion, cytoskeletal remodeling, blood coagulation, TGFB, and Wnt/β‐catenin and epithelial mesenchymal transition signaling pathways. Genes uniquely correlated with SULF2 were more associated with neoplastic processes than genes uniquely correlated with SULF1. High SULF expression was associated with the hepatoblast subtype of HCC. There was a bimodal effect of SULF1 expression on prognosis, with patients in the lowest or highest tertile having a worse prognosis than those in the middle tertile. SULFs have complex effects on HCC signaling and patient survival. There are functionally similar associations with cell adhesion, ECM remodeling, TGFB, and WNT pathways, but also unique associations of SULF1 and SULF2. The roles and targeting of the SULFs in cancer require further investigation. © 2010 Wiley‐Liss, Inc.
Serum amyloid A and atherosclerosis

Purpose of review Atherosclerosis is a chronic inflammation associated with increased expression of the acute phase isoforms of serum amyloid A (SAA) and in humans is a plasma biomarker for future cardiovascular events. However, whether SAA is only a biomarker or participates in the development of cardiovascular disease is not well characterized. The purpose of this review is to summarize putative functions of SAA relevant to atherogenesis and in-vivo murine studies that directly examine the effect of SAA on atherosclerosis. Recent findings Modulation of the expression of SAA1 and/or SAA2 in murine models of atherosclerosis suggests that SAA promotes early atherogenesis. SAA secreted from bone-marrow-derived cells contributes to this antiatherogenic phenotype. SAA also promotes angiotensin-induced abdominal aneurysm in atherogenic mouse models. The reduction in atherosclerosis may be due, at least in part, to remodeling of the acute phase HDL to reduce its capacity to promote cholesterol efflux and reduce its anti-inflammatory ability. Summary SAA is more than a marker of cardiovascular disease and is a participant in the early atherogenic process.
Acoustic wave therapy for cellulite, body shaping and fat reduction

ABSTRACT Background: Cellulite is a common aesthetic condition that affects almost every woman. Objective: To evaluate the efficacy of acoustic wave therapy (AWT) for cellulite and body shaping. Methods: In this open-label, single-centre trial, 30 women presenting moderate or severe cellulite underwent 12 sessions of AWT on the gluteus and back of the thighs, over six weeks. The following assessments were performed at baseline, and up to 12 weeks after treatment: Cellulite Severity Scale (CSS), body circumference measurements, subcutaneous fat thickness by magnetic resonance imaging (MRI), quality of life related by Celluqol® and a satisfaction questionnaire. Results: The treatment reduced cellulite severity from baseline up to 12 weeks after the last treatment session (subjects presenting severe cellulite: 60% to 38%). The mean CSS shifted from 11.1 to 9.5 (p < 0.001). Hips circumferences reduced from 99.7 and 103.2 cm to 96.2 and 100.3 cm (respectively, p < 0.001). The average thickness of the subcutaneous fat tissue also decreased (28.3 ± 6.5 mm to 26.7 ± 6.1mm; p < 0.001). The treatment also improved quality of life. More than 90% of the subjects would undergo the treatment again and 89% were satisfied with the results. No serious adverse events were reported. Conclusions: AWT is a safe treatment to improve cellulite appearance and reduce body circumferences.
Evaluation of myofibroblasts in oral epithelial dysplasia and squamous cell carcinoma.

BACKGROUND Carcinogenesis is accompanied by a number of changes in the adjacent stroma including the appearance of myofibroblasts. The purpose of this study was to evaluate and compare the presence of myofibroblasts in normal mucosa, oral epithelial dysplasia, and different grades of oral squamous cell carcinoma. METHODS The study sample consisted of three groups, including 40 oral squamous cell carcinomas, 15 dysplasias, and 15 sections of normal oral epithelium. Vimentin, desmin, and alpha-smooth muscle actin were used to identify myofibroblasts. RESULTS The percentage and intensity of alpha-smooth muscle actin were examined, and positive immunostaining was observed in the myofibroblasts of all squamous cell carcinomas; however these cells did not stain in the dysplasias or normal epithelium specimens. The presence of myofibroblasts was significantly higher in oral squamous cell carcinomas compared to both, dysplasias and normal mucosa cases (P < 0.001). A significant difference was not observed between the different grades of oral squamous cell carcinoma (P = 0.2). CONCLUSIONS These findings show the presence of myofibroblasts in the stroma of oral squamous cell carcinoma but not dysplasia and normal mucosa, suggesting further investigation to clarify the role of myofibroblasts in the carcinogenesis of this tumor.
Cryolipolysis for submental fat reduction in Asians

ABSTRACT Background: Cryolipolysis is a noninvasive method for the selective reduction of fat, especially proven to be safe and effective in body contouring. There is a demand for reduction in submental fat, which is related not only with a favorable appearance but also with signs of aging. Objective: This study evaluated the efficacy and safety of cryolipolysis for subcutaneous fat reduction in the submental area in Asians. Materials and methods: Ten healthy Koreans were treated using a cryolipolysis contact device (CoolMini applicator, Zeltiq Aesthetics). The device was applied on the participant’s neck twice via two lateral approaches. Patient’s body weight was measured, and photographs were taken at baseline and during the follow-up visit after 8 weeks. Participants were examined with ultrasound and the depth of the subcutaneous fat layer was measured. Results: The subjective reduction of submental fat was noted in most of the participants. Reduction of the subcutaneous fat layer depth was confirmed by ultrasound after 8 weeks of treatment. Conclusion: The results of this study indicate that submental fat can be safely and effectively reduced with use of a cryolipolysis applicator. The present study shows that cryolipolysis can be an option for nonsurgical facial contouring.
Editorial [The Upper Airway Resistance Syndrome: Fact or Fiction?]

Daytime fatigue and sleepiness caused by inspiratory flow limitation throughout NREM sleep (with associated arousals), in the absence of the clinical and polysomnographic features of obstructive sleep apnea hypoapnea syndrome (OSA/HS) has been described as the upper airway resistance syndrome (UARS) [1]. Some authors had tried to assign uniqueness to this relatively “young” syndrome, including polysomnographic features (increased alpha frequency during NREM sleep in patients with UARS) and palatal sensory function (intact in patients with UARS) [1,2]. Recent studies have shown that patients with UARS are more somnolent than patients with OSA/H, leading to the hypothesis of a cause-and-effect relationship between airway collapse and physiologic hyperarousals [3]. In one such study, pharyngeal critical pressure (Pcrit) was used as the index of upper airway collapsibility (the airway pressure at the flow-limiting site below which the flow-limiting site collapses). Patients with UARS have been characterized to have lower values of Pcrit when compared with patients with OSA/HS, and just mildly increased when compared to normal individuals [3].
Clinical significance of apolipoprotein A5

Purpose of review We have examined the evidence from recent human studies examining the role of apolipoprotein A-V in triglyceride-rich lipoprotein metabolism and cardiovascular disease risk. Special emphasis was placed on the evidence emerging from the association between genetic variability at the apolipoprotein A5 locus, lipid phenotypes and disease outcomes. Moreover, we address recent reports evaluating apolipoprotein A5 gene–environment interactions in relation to cardiovascular disease and its common risk factors. Recent findings Several genetic association studies have continued to strengthen the position of APOA5 as a major gene that is involved in triglyceride metabolism and modulated by dietary factors and pharmacological therapies. Moreover, genetic variants at this locus have been significantly associated with both coronary disease and stroke risks. Summary Apolipoprotein A-V has an important role in lipid metabolism, specifically for triglyceride-rich lipoproteins. However, its mechanism of action is still poorly understood. Clinical significance at present comes largely from genetic studies showing a consistent association with plasma triglyceride concentrations. Moreover, the effects of common genetic variants on triglyceride concentrations and disease risk are further modulated by other factors such as diet, pharmacological interventions and BMI. Therefore, these genetic variants could be potentially used to predict cardiovascular disease risk and individualize therapeutic options to decrease cardiovascular disease risk.
Association between genomic alterations and metastatic behavior of colorectal cancer identified by array‐based comparative genomic hybridization

Colorectal cancers (CRCs) exhibit multiple genetic alterations, including allelic imbalances (copy number alterations, CNAs) at various chromosomal loci. In addition to genetic aberrations, DNA methylation also plays important roles in the development of CRC. To better understand the clinical relevance of these genetic and epigenetic abnormalities in CRC, we performed an integrative analysis of copy number changes on a genome‐wide scale and assessed mutations of TP53, KRAS, BRAF, and PIK3CA and DNA methylation of six marker genes in single glands isolated from 39 primary tumors. Array‐based comparative genomic hybridization (array‐CGH) analysis revealed that genomic losses commonly occurred at 3q26.1, 4q13.2, 6q21.32, 7q34, 8p12‐23.3, 15qcen and 18, while gains were commonly found at 1q21.3‐23.1, 7p22.3‐q34, 13q12.11‐14.11, and 20. The total numbers and lengths of the CNAs were significantly associated with the aberrant DNA methylation and Dukes' stages. Moreover, hierarchical clustering analysis of the array‐CGH data suggested that tumors could be categorized into four subgroups. Tumors with frequent DNA methylation were most strongly enriched in subgroups with infrequent CNAs. Importantly, Dukes' D tumors were enriched in the subgroup showing the greatest genomic losses, whereas Dukes' C tumors were enriched in the subgroup with the greatest genomic gains. Our data suggest an inverse relationship between chromosomal instability and aberrant methylation and a positive association between genomic losses and distant metastasis and between genomic gains and lymph node metastasis in CRC. Therefore, DNA copy number profiles may be predictive of the metastatic behavior of CRCs. © 2012 Wiley Periodicals, Inc.
A matter of insulin: Developmental programming of body weight regulation

Alterations of the intrauterine and early postnatal nutritional, metabolic and hormonal environment may cause a predisposition for disorders and diseases throughout later life. Studies in offspring of diabetic mothers (ODM) have decisively contributed to this perception and our understanding of causal mechanisms. Hormones in particular are environment-dependent organizers of the developing organism. When they are present in non-physiological concentrations during critical periods of early development, they can dose-dependently lead to a permanent malprogramming of fundamental regulatory systems. Worthy of note, fetal and neonatal hyperinsulinism is the pathognomic feature in ODM. Epidemiological, clinical, as well as experimental data obtained by our group during the past two decades indicate that insulin itself, when occurring in elevated concentrations during perinatal life, may program the development of obesity and diabetes. Similarly, this may occur due to general increase of fetal food supply, e.g., in overweight pregnant women and neonatal overfeeding. From a clinical point of view, universal screening and therapy for all types of diabetes during pregnancy as well as avoidance of early postnatal overfeeding, especially by promoting breast feeding, are, therefore, recommended. These measures might serve as causal approaches to a genuine primary prevention.
Toll-like receptor signaling links dietary fatty acids to the metabolic syndrome

Purpose of review Dietary saturated fatty acids (SFAs) have been implicated in promoting the metabolic syndrome and atherosclerotic cardiovascular disease. Recent evidence suggests that SFAs promote the metabolic syndrome by activating Toll-like receptor 4 (TLR4). Here we examine emerging molecular evidence that SFAs directly engage pathways of innate immunity, thereby promoting inflammatory aspects of the metabolic syndrome. Recent findings Accumulation of SFA in the body is tightly regulated by stearoyl-CoA desaturase 1, an enzyme that converts endogenous SFA to monounsaturated fatty acids. Recent studies have demonstrated that the accumulation of SFA seen with genetic deletion or inhibition of stearoyl-CoA desaturase 1 promotes inflammation, TLR4 hypersensitivity, and accelerated atherosclerosis. Therefore, stearoyl-CoA desaturase 1 may play an unexpected role in suppressing inflammation by preventing excessive accumulation of endogenous SFA-derived TLR4 agonists. In parallel, several independent laboratories have demonstrated that TLR4 is necessary for dietary SFAs to induce obesity, insulin resistance, and vascular inflammation in rodent models. Summary The metabolic syndrome and atherosclerotic cardiovascular disease have long been linked to dietary SFA intake and inflammation. Recent mechanistic insights into how SFAs and downstream metabolites can potentiate inflammation-driven metabolic disease are discussed here.
New Strategies for Prevention of Neonatal Respiratory Distress Syndrome: Acceleration of Fetal Lung Maturation and Exogenous Surfactant Replacement

The pioneering observations of Avery and Mead, 1 that the surface activity of pulmonary sur­ factant of infants dying of hyaline membrane dis­ ease (HMD) was decreased and Adams' 2 finding that airway secretions from infants with HMD were deficient in surface active phospholipids, began a cascade of laboratory and clinical studies into the mechanism, prevention, and treatment of neonatal respiratory distress syndrome (RDS). One such treatment mechanism for the restoration of surfac­ tant sufficiency is the antenatal administration of drugs and hormones. Liggins and Howie 3 demonstrated accelerated surfactant production in the lungs of corti-costeroid-treated fetal lambs (118 to 123 days) com­ pared with their untreated twins. Multiple clinical trials and further laboratory investigation explor­ ing the potential beneficial effect of antenatal cor­ ticosteroids have been undertaken. 4-13 Although steroids are the most extensively studied of the an­ tenatal protagonists for pulmonary maturation, the potential lung accelerating effect of a variety of hormones
VI. Intensity of oestrous behaviour and errors in diagnosis of oestrus

Abstract During the 1970 season, 90 members of the Taranaki Livestock Improvement Association used a simple scoring system to record the intensity of oestrous behaviour observed in each cow at the morning milking before insemination. The maximum score of 5 was for cows that stood when ridden by other cows. Among the 8094 cows scored before their first insemination, only 7.4% scored 3 or less. The conception rate for these cows with lower scores was 52.6% compared with 66.7% for cows receiving scores of 4 or 5, and 65.7% for all cows. Some of the cows which received these higher scores would not have been in oestrus. Six hundred and eighty-seven cows received a score of 4 or 5 before their first insemination but returned to service 20 or 21 days later. The conception rate to second insemination for this group, which would have included very few cows incorrectly diagnosed in oestrus, was 78.9%. The results suggest that most errors in diagnosis occurred because herd owners liberally interpreted behavioural s.
Beware imposters: MA‐1, a novel MALT lymphoma cell line, is misidentified and corresponds to Pfeiffer, a diffuse large B‐cell lymphoma cell line—A reply: Despite the same 8‐code STR, MA‐1 and Pfeiffer are cytogenetically diverse

Dear Editors: We appreciate the comments of Capes-Davis et al. (2013a) on our article, entitled “Establishment of a novel MALT lymphoma cell Line, Ma-1, from a patient with t(14;18)(q32;q21)-positive Helicobacter pylori-independent gastric MALT lymphoma” (Kuo et al., 2011). In the correspondence, CapesDavis et al. compared and demonstrated the similarity of the 8-codes short tandem repeat (STR) profiling between our MA-1 cells and Pfeiffer, a diffuse large B-cell lymphoma cell line (Gabay et al., 1999), and suggested our MA-1 cell line was crosscontaminated by Pfeiffer and cannot be used as a model for MALT lymphoma (Capes-Davis et al., 2013a). In our original article, we described that fluorescence in situ hybridization (FISH) analyses of MA1 cells disclosed the existence of three sub-clones, characterized by t(14;18)(q32;q21)/IGH-BCL2, t(14;18)(q32;q21)/IGH-MALT1, and co-existence of the two translocations in the same cell, respectively (Kuo et al., 2011). To dissect more specifically the biological role of the t(14;18)(q32;q21)/ IGH-MALT1 translocation in B-cell lymphoma, we have worked on and successfully established three single cell-derived subclones of MA-1 cells: the MA-1.2, MA-1.46, and MA-1.72 subclones after our initial publication. All the three subclones proliferate as single-cell suspensions without clump formation, and have been grown in continuous culture in RPMI1640 for more than 24 months. In order to respond to the critics, we re-checked the STRs of the Pfeiffer, MA-1, MA-1.46, and the original frozen diagnostic gastric biopsy sample from the donor. Our results confirmed the same 8-core STR loci among the MA-1, MA-1.46, and Pfeiffer cells, which were different from the original donor’s materials (Table 1). FISH analysis using a commercial probe (Vysis LSI/Abbott, IGH/MALT1 dual color, dual fusion translocation probe) confirmed the presence of a t(14;18)(q32;q21)/IGH-MALT1 in MA-1 and MA-1.46, but not in Pfeiffer cells (Fig. 1) (Ye et al., 2005). Furthermore, the unique IGH/MALT1 fusion was more readily detected in MA-1.46 than in the parental MA-1 cells, suggesting that MA1.46 is a more homogenous t(14;18) (q32;q21)/ IGH-MALT1-containing cell line. In summary, despite sharing the same STR as Pfeiffer, we provided further evidence not only to demonstrate that MA-1 and its MA-1.46 subclones are cytogenetically different from Pfeiffer cells (Capes-Davis et al., 2013b) but also to reinforce our argument to the comment of Flossbach et al. (2013) (Kuo et al., 2013). We thus believe MA-1 and its MA-1.46 subclone can be useful in dissecting the molecular pathogenesis of t(14;18)(q32;q21)/IGH-MALT1containing B-cell lymphoma.
Expanding the clinical phenotype of hereditary BAP1 cancer predisposition syndrome, reporting three new cases

The clinical phenotype of BAP1 hereditary cancer predisposition syndrome (MIM 614327) includes uveal melanoma (UM), cutaneous melanoma (CM), renal cell carcinoma (RCC), and mesothelioma. However, the frequency of the syndrome in patients with UM and the association with other cancers are still not clear. In this study, we screened 46 previously untested, unrelated UM patients with high risk for hereditary cancer for germline mutation in BAP1. We also studied four additional patients with a personal or family history suggestive of BAP1 hereditary cancer syndrome. We identified three patients with germline pathogenic mutations (c.2050 C>T, pGln684*; c.1182C>G, p.Tyr394*, and c.1882_1885delTCAC, p. Ser628Profs*8) in BAP1. Two of these three patients presented with UM and the third with a metastatic adenocarcinoma likely from a hepatic cholangiocarcinoma. Reported family histories included UM, mesothelioma, RCC, CM, and several other internal malignancies. The results of this study confirm the association between germline BAP1 mutation and predisposition to UM, mesothelioma, CM and RCC. However, other cancers, such as cholangiocarcinoma and breast carcinoma may be part of the phenotype of this hereditary cancer predisposition syndrome. In addition, the results support the existence of other candidate genes in addition to BAP1 contributing to hereditary predisposition to UM. © 2013 Wiley Periodicals, Inc.