instruction:
In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
question:
Context: In humans, glucocorticoid-induced osteoporosis is the most common cause of medication-induced osteoporosis. Recent clinical data suggest that glucocorticoid therapy increases the risk of vertebral fractures within a short treatment period. Therefore, this study aimed at investigating vertebral bone in a rat model of glucocorticoid-induced postmenopausal osteoporosis.', 'Fifty Sprague-Dawley rats were randomly assigned into three groups: 1) untreated controls, 2) Sham-operated group, and 3) ovariectomized rats treated with glucocorticoid (dexamethasone) for 3 months (3M) after recovery from bilateral ovariectomy. Osteoporotic bone status was determined by means of the gold standard dual energy X-ray absorptiometry (DEXA) scan. Vertebral bodies were examined using µCT, histological analysis, mRNA expression analysis, and biomechanical compression testing. Further systemic effects were studied biochemically using serum marker analysis.', 'Dexamethasone treatment showed at 3M a significantly lower bone mineral density in ovariectomized rats compared to Sham-operated control (p < 0.0001) as analyzed in vivo by DEXA. Furthermore, Z scores reached levels of -5.7 in the spine indicating sever osteoporotic bone status. Biomechanical testing of compression stability indicated a lower functional competence (p < 0.0001) in the spine of treated rats. µCT analysis showed significant reduction of bone volume density (BV/TV%; p < 0.0001), significantly enhanced trabecular spacing (Tb.Sp; p < 0.0001) with less trabecular number (Tb.N; p < 0.001) and complete loss of trabecular structures in glucocorticoid-treated ovariectomized rats. Histological analysis by osteoblast and osteoclast activities reflected a higher bone catabolism reflected by osteoclast counts by TRAP (p < 0.019) and lower bone catabolism indicated by ALP-stained area (p < 0.035).Serum analysis showed a significant increase in osteocalcin (p < 0.0001), osteopontin (p < 0.01) and insulin (p < 0.001) at 3M. Expression analysis of molecular markers in the vertebral body revealed lower expression in tenascin C in the OVX-steroid animals at 3M.\Question: Does short-term glucocorticoid treatment cause spinal osteoporosis in ovariectomized rats?
answer:
Short-term glucocorticoid treatment of ovariectomized rats indicates according to DEXA standards a severe osteoporotic bone status in vertebral bone. Nonetheless, dysfunctional bone anabolism and enhanced bone catabolism are observed. Alterations of bone extracellular matrix proteins that correlate to inferior mechanical stability and affected microstructure were noticed and suggest further investigation. Treatment with dexamethasone was also seen to affect insulin and osteopontin levels and thus osteoblast function and maturation. This described animal model presents a recapitulation of clinically obtained data from early phase glucocorticoid-induced osteoporosis observed in patients.


question:
Context: Prognosis and treatment of patients with breast carcinoma of no special type (NST) is dependent on a few established parameters, such as tumor size, histological grade, lymph node stage, expression of estrogen receptor, progesterone receptor, and HER-2/neu, and proliferation index. The original Nottingham Prognostic Index (NPI) employs a three-tiered classification system that stratifies patients with breast cancer into good, moderate, and poor prognostic groups. The aim of our study was to use robust immunohistochemical methodology for determination of ER, PR, HER-2/neu, Ki-67, p53, and Bcl-2, and to observe differences in the expression of these markers when patients are stratified according to the original, three-tiered Nottingham Prognostic Index.', 'Paraffin blocks from 120 patients diagnosed with breast carcinoma, NST, were retrieved from our archive. Cases included in the study were female patients previously treated with modified radical mastectomy and axillary dissection.', 'Our study demonstrates that expression of markers of good prognosis, such as ER, PR, and Bcl-2, is seen with higher frequency in good and moderate NPI groups. In contrast, overexpression of HER-2/neu, a marker of adverse prognosis, is more frequent in moderate and poor NPI groups. High proliferation index, as measured by Ki-67, is seen in moderate and poor NPI groups, whereas low proliferation index is seen in good NPI groups.\Question: Does classification of patients with breast cancer according to Nottingham prognostic index highlight significant differences in immunohistochemical marker expression?
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These data confirm that the original, three-tiered NPI statistically correlates with the expression of prognostic immunohistochemical markers in breast carcinoma NST.


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Context: This work aimed to identify altered pathways in congenital heart defects (CHD) in Down syndrome (DS) by systematically tracking the dysregulated modules of reweighted protein-protein interaction (PPI) networks.', 'We performed systematic identification and comparison of modules across normal and disease conditions by integrating PPI and gene-expression data. Based on Pearson correlation coefficient (PCC), normal and disease PPI networks were inferred and reweighted. Then, modules in the PPI network were explored by clique-merging algorithm; altered modules were identified via maximum weight bipartite matching and ranked in non-increasing order. Finally, pathways enrichment analysis of genes in altered modules was carried out based on Database for Annotation, Visualization, and Integrated Discovery (DAVID) to study the biological pathways in CHD in DS.', 'Our analyses revealed that 348 altered modules were identified by comparing modules in normal and disease PPI networks. Pathway functional enrichment analysis of disrupted module genes showed that the 4 most significantly altered pathways were: ECM-receptor interaction, purine metabolism, focal adhesion, and dilated cardiomyopathy.\Question: Does systematic Tracking of Disrupted Modules identify Altered Pathways Associated with Congenital Heart Defects in Down Syndrome?
answer:

We successfully identified 4 altered pathways and we predicted that these pathways would be good indicators for CHD in DS.