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: Treatment-resistant depression (TRD) is a pervasive and difficult to treat condition for which deep brain stimulation (DBS) of the subcallosal cingulate white matter (SCCwm) is an emerging therapeutic option. However, neuropsychological safety data for this novel treatment have only been published for a small number of subjects. Moreover, little is known regarding the neuropsychological profile present in TRD patients at baseline, prior to initiation of DBS therapy. This report describes the neuropsychological effects of TRD and acute and chronic DBS of the SCCwm in patients with unipolar and bipolar TRD.', 'Patients with TRD (N = 17) were compared to a healthy control group (N = 15) on subtests from the Cambridge Neuropsychological Test Automated Battery and the Stroop Task. Patients were then tested again at subsequent time points of 1 and 6 months following the initiation of chronic DBS of the SCCwm.', 'Patients with TRD showed similar levels of performance to healthy controls on most neuropsychological measures, with the exception that the TRD group had slower processing speed. Patients with bipolar TRD, relative to those with unipolar TRD, obtained lower scores on measures of executive function and memory only at baseline. With acute and chronic SCCwm DBS, neuropsychological function improved in multiple domains including processing speed and executive function (planning, set shifting, response inhibition), and memory remained stable.\Question: Do neuropsychological function before and after subcallosal cingulate deep brain stimulation in patients with treatment-resistant depression?
Patients with TRD show slowed processing speed but otherwise largely preserved neuropsychological functioning. DBS of the SCCwm does not result in worsening of any aspect of neuropsychological function and may improve certain domains. Future research is warranted to better understand the effects of TRD and DBS on neuropsychological function.

Context: Characteristic clinical heterogeneity and mostly slow-growing behavior of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) cause problems in finding appropriate treatments. Thus, current therapy options are not satisfactory. PKI-587 is a highly potent novel dual inhibitor of PI3K and mTORC1/C2.', 'We assessed the effects of PKI-587 in different GEP-NEN tumor models, including poorly differentiated cell line LCC-18, compared with the established mTORC1 inhibitor everolimus.', 'We treated the cell lines BON, QGP1, KRJ-I and LCC-18 with increasing concentrations of the inhibitor PKI-587, and compared with everolimus and DMSO. We assessed the impact of treatments on viability (WST-1 assay), on apoptotic processes (Caspase 3/7 assay, JC-1) and on cell cycle regulation (flow cytometry). We determined alterations of signaling mediators by phosphor-specific western blot analysis and conducted multiplexed gene expression analysis (nCounter® technology).', 'In all cell lines, PKI-587 dose-dependently inhibited proliferation whereas everolimus was less effective. Treatment with PKI-587 led to cell cycle arrest, induction of apoptosis and successfully suppressed activity of direct mTORC1 target 4E-BP1, a crucial factor for tumor genesis only partially inhibited by everolimus. Gene expression analyses revealed relevant changes of RAS, MAPK, STAT and PI3K pathway genes after treatment. Treatment dependent and cell line characteristic effects on AKT/RB/E2F signaling regarding cell cycle control and apoptosis are extensively discussed in this article.\Question: Is inhibition of mTORs Catalytic Site by PKI-587 a Promising Therapeutic Option for Gastroenteropancreatic Neuroendocrine Tumor Disease?
PI3K/mTOR dual targeting is a promising new therapeutic approach in neuroendocrine tumor disease that should be evaluated in further clinical trials.

Context: Muscle density is a risk factor for fractures in older adults; however, its association with falls is not well described. After adjusting for biologically relevant confounding factors, a unit decrease in muscle density was associated with a 17\xa0% increase in odds of reporting a fall, independent of functional mobility.', 'Falls are the leading cause of injury, disability, and fractures in older adults. Low muscle density (i.e., caused by muscle adiposity) and functional mobility have been identified as risk factors for incident disability and fractures in older adults; however, it is not known if these are also independently associated with falls. The purpose of this study was to explore the associations of muscle density and functional mobility with fall status.', 'Cross-sectional observational study of 183 men and women aged 60-98\xa0years. Descriptive data, including a 12-month fall recall, Timed Up and Go (TUG) test performance, lower leg muscle area, and density. Odds ratio (OR) of being a faller were calculated, adjusted for age, sex, body mass index, general health status, diabetes, and comorbidities.', 'Every mg/cm(3) increase in muscle density (mean 70.2, SD 2.6\xa0mg/cm(3)) independently reduced the odds of being a faller by 19\xa0% (OR 0.81 [95\xa0% CI 0.67 to 0.97]), and every 1\xa0s longer TUG test time (mean 9.8, SD 2.6\xa0s) independently increased the odds by 17\xa0% (OR 1.17 [95\xa0% CI 1.01 to 1.37]). When both muscle density and TUG test time were included in the same model, only age (OR 0.93 [95\xa0% CI 0.87 to 0.99]) and muscle density (OR 0.83 [95\xa0% CI 0.69 to 0.99]) were independently associated with fall status.\Question: Is lower leg muscle density independently associated with fall status in community-dwelling older adults?

Muscle density was associated with fall status, independent of functional mobility. Muscle density may compliment functional mobility tests as a biometric outcome for assessing fall risk in well-functioning older adults.