Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.

Activation and inactivation of nuclear factor of kappa light chain gene enhancer in B cells (NFKB) is tightly regulated to ensure effective onset and cessation of defensive inflammatory signaling. However, mutations within NFKB, or change in activation and inactivation molecules have been reported in a few cancers. Although oral squamous cell carcinoma is one of the most prevalent forms of cancer in India, with a development associated with malignant transformation of precancerous lesions, the genetic status of NFKB and relative rates of change in oral precancerous lesions remain unknown. Hence in the present study we investigated all twenty four exons of NFKB gene in two precancerous lesions, namely oral submucous fibrosis (OSMF) and oral leukoplakia (OL) to understand its occurrence, incidence and assess its possible contribution to malignant transformation.', 'Chromosomal DNA isolated from twenty five each of OSMF and OL tissue biopsy samples were subjected to PCR amplification with intronic primers flanking twenty four exons of the NFKB gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status.', 'Sequence analysis identified a novel heterozygous mutation, c.419T>A causing substitution of leucine with glutamine at codon 140 (L140Q) in an OL sample.
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Matrix Metalloproteinase-26 (MMP-26) is the smallest member of matrix metalloproteinase (MMP) family that functions mainly in the extracellular milieu to cleave the extracellular matrix proteins. It is expressed in various cell types of placenta, but its function in placentation has been poorly understood. Considering the existence of a unique cysteine switch sequence in MMP-26 protein sequence, as well as the evidence in cancer cells indicating the digestion of the NH2-terminal domain of ERβ by MMP-26, we hypothesize that MMP-26 may have specific intracellular activity in human placental trophoblast cells.', 'This study aimed to identify the intracellular binding partners of MMP-26 and investigate how MMP-26 is involved in placentation through the interactions with its partners.', 'Yeast two-hybrid system was employed to screen potential binding partners of MMP-26 in human placenta. Immunoprecipitation and immunofluorescence assays were conducted to verify the interactions between MMP-26 and the binding partners. HEK293T and HTR8/SVneo cell lines were used as in vitro models to investigate the roles of the interaction between MMP-26 and its binding partner on cell behaviors.', 'RESULTS of yeast two-hybrid assay, immunoprecipitation, and immunofluorescence assays revealed that MMP-26 could bind to growth differentiation factor 15 (GDF15) in the intracellular milieu. The binding of MMP-26 to GDF15 was responsible for the processing and maturation of pro-GDF15, and the process was dependent on the enzymatic activity of MMP-26. In human placental trophoblast cells, MMP-26 could facilitate the pro-apoptotic effect of GDF15.
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The chronic inflammation plays an important role in heart failure and complement components might be useful markers of the prognosis. We set out to evaluate their predictive value in the clinical outcomes of patients with cardiac resynchronization therapy (CRT).', 'We determined the complement levels C3, C3a, sC5b-9 and also the N-terminus of the prohormone brain natriuretic peptide (NT-proBNP) of 126 heart failure patients in a prospective, single-center observational study before and 6\xa0months after CRT implantation.', 'CRT reduced the C3a [212.5 (148.2-283.6) vs. 153 (119.8-218.3)\xa0ng/mL, p\xa0<\xa00.0001] and the sC5b-9 levels [296.9 (234.2-358.8) vs. 255.1 (210.1-319.0)\xa0ng/mL, p\xa0=\xa00.0006], but not the total C3 levels [1.43 (1.26-1.61) vs. 1.38 (1.23-1.57) g/L, p\xa0=\xa00.57]. C3a predicted the 5-year mortality of the patients [C3a\xa0>\xa0165\xa0ng/mL hazard ratio\xa0=\xa04.21 (1.65-10.72), p\xa0=\xa00.003] independent of the NT-proBNP and other factors. After reclassification, we observed a significant net reclassification improvement [NRI\xa0=\xa00.71 (0.43-0.98), p\xa0<\xa00.0001] and integrated discrimination improvement [IDI\xa0=\xa00.08 (0.03-0.12), p\xa0=\xa00.0002].

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