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.

Context: The current standard of care for glioblastoma (GBM) involves a combination of surgery, radiotherapy, and temozolomide chemotherapy, but this regimen fails to achieve long-term tumor control. Resistance to temozolomide is largely mediated by expression of the DNA repair enzyme MGMT; however, emerging evidence suggests that inactivation of MSH6 and other mismatch repair proteins plays an important role in temozolomide resistance. Here, we investigate endogenous MSH6 mutations in GBM, anaplastic oligodendroglial tumor tissue, and corresponding brain tumor-initiating cell lines (BTIC).', 'MSH6 sequence and MGMT promoter methylation were determined in human tumor samples and BTICs. Sensitivity to temozolomide was evaluated in vitro using BTICs in the absence and presence of O(6)-benzylguanine to deplete MGMT. The influence of MGMT and MSH6 status on in vivo sensitivity to temozolomide was evaluated using intracranial BTIC xenografts.', 'We identified 11 previously unreported mutations in MSH6 in nine different glioma samples and six paired BTIC lines from adult patients. In addition, MSH6 mutations were documented in three oligodendrogliomas and two treatment-naïve gliomas, both previously unreported findings. These mutations were found to influence the sensitivity of BTICs to temozolomide both in vitro and in vivo, independent of MGMT promoter methylation status.\Question: Do novel MSH6 mutations in treatment-naïve glioblastoma and anaplastic oligodendroglioma contribute to temozolomide resistance independently of MGMT promoter methylation?
These data demonstrate that endogenous MSH6 mutations may be present before alkylator therapy and occur in at least two histologic subtypes of adult glial neoplasms, with this report serving as the first to note these mutations in oligodendroglioma. These findings broaden our understanding of the clinical response to temozolomide in gliomas.

Context: The observation of intact non-covalent complexes by electrospray ionization mass spectrometry (ESI-MS) hinges on the ability to minimize in-source activation processes that take place during analyte desolvation. We explored the merits of replacing the sampling cone of a standard Z-spray source with a heated capillary that makes the desolvation process slower and more gradual. We employed well-characterized protein-RNA, RNA-RNA, and DNA-DNA assemblies to compare the alternative configurations.', 'Mass analysis evaluated the integrity of the complexes, whereas traveling wave ion mobility experiments assessed the stability of biomolecular structure. Analyses were performed back-to-back on the same samples on a Synapt G2 HDMS equipped with either the standard sampling cone or the heated-capillary apparatus. In each configuration, the source/capillary temperature was varied in controlled fashion, while keeping all other desolvation parameters constant to monitor the in-source dissociation of selected DNA duplexes. Ion mobility data were obtained from the same precursor by using the alternative configurations under the same settings.', 'Monitoring the percentage of associated complex demonstrated that the heated capillary provided softer desolvation that was more conducive to the detection of intact non-covalent interactions. This configuration failed to produce complete dissociation of 14\u2009bp and 24\u2009bp duplexes, even when the source/capillary temperature was increased well above their solution melting points. Analyzed by IMS-MS, a selected construct displayed just one conformation with the heated capillary, but two with the standard sampling cone.\Question: Does a simple heated-capillary modification improve the analysis of non-covalent complexes by Z-spray electrospray ionization?
The heated capillary minimizes in-source activation processes that can lead to unintended dissociation of complexes and perturbation of biomolecular structure, which rely on the integrity of non-covalent interactions. This effect can be attributed to the attenuation of the supersonic expansion typical of the Z-spray geometry and the greater ability to control the energy imparted to the system. This hardware modification will be expected to benefit the analysis of biomolecular structure performed on this particular instrumental platform.

Context: Transrectal ultrasound guided prostate needle biopsy (TRUS) is the standard procedure to diagnose or exclude prostate cancer. This procedure can be associated with significant discomfort, both on insertion of the ultrasound probe as well as on taking the biopsy. We evaluated a new technique for pain relief during TRUS biopsy.', 'In Group 1 (n = 60), the biopsies were taken without any analgesia. In Group 2 (n = 60), 11 ml of Instillagel (2% lignocaine) was administered rectally prior to probe insertion and 5 ml of 1% lignocaine periprostatic injection was administered before taking the biopsy. The discomfort encountered during the procedure was graded by the patient on a scale ranging from no discomfort to mild, moderate and severe pain.', 'In Group 2, there was a marked reduction in the pain experienced during the procedure. The Chi-squared test for trend showed a significant association between the rectal administration of local anaesthetic gel and reduction in pain on probe insertion (P = 0.0001). There was also a significant association between the use of periprostatic lignocaine injection and reduction in pain on taking the biopsy (P < 0.0001).\Question: Does the rectal administration of lignocaine gel and periprostatic lignocaine infiltration during transrectal ultrasound-guided prostate biopsy provide effective analgesia?

The use of lignocaine gel prior to probe insertion and periprostatic infiltration of lignocaine before taking the needle biopsy significantly reduces the pain experienced by the patient during TRUS-guided prostate biopsy.