Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

[EX Q]: Context: Nociceptin/orphanin FQ (N/OFQ) receptor (NOP) agonists produce anxiolytic-like effects in rodents while antagonists promote antidepressant-like effects. The aim of this study was to investigate the effect on anxiety and depression of NOP receptor partial agonists such as the peptides [F/G]N/OFQ(1-13)NH2 and UFP-113 and the non-peptide AT-090.', 'In\xa0vitro AT-090, UFP-113, and [F/G]N/OFQ(1-13)NH2 were tested for their ability to promote NOP/G-protein and NOP/β-arrestin 2 interaction, using a bioluminescence resonance energy transfer assay. In\xa0vivo, they were tested in mice in the elevated plus maze (EPM) and in the forced swim (FST) tests. NOP partial agonists effects were systematically compared to those of full agonists (N/OFQ and Ro 65-6570) and antagonists (UFP-101 and SB-612111).', 'In\xa0vitro, AT-090, UFP-113, and [F/G]N/OFQ(1-13)NH2 promoted NOP/G protein interaction, with maximal effects lower than those evoked by N/OFQ and Ro 65-6570. AT-090 behaved as a NOP partial agonist also in inducing β-arrestin 2 recruitment, while UFP-113 and [F/G]N/OFQ(1-13)NH2 were inactive in this assay. In\xa0vivo, AT-090 induced anxiolytic-like effects in the EPM but was inactive in the FST. Opposite results were obtained with UFP-113 and [F/G]N/OFQ(1-13)NH2.
Answer: NOP ligands producing similar effects on NOP/G protein interaction (partial agonism) but showing different effects on β-arrestin 2 recruitment (partial agonism vs antagonism) elicited different actions on anxiety and mood. These results suggest that the action of a NOP ligand on emotional states is better predicted based on its β-arrestin 2 rather than G-protein efficacy.
[EX A]: Does beta-arrestin 2 rather than G protein efficacy determine the anxiolytic-versus antidepressant-like effects of nociceptin/orphanin FQ receptor ligands?

[EX Q]: Context: We hypothesised that abnormal global longitudinal strain (GLS) would predict outcome in hypertrophic cardiomyopathy (HCM) better than current echocardiographic measures.', 'Retrospective analysis of risk markers in relation to outcomes in 472 patients with HCM at a single tertiary institution (2006-2012). Exclusion criteria were left ventricular (LV) hypertrophy of other origin, patients in atrial fibrillation, lost to follow-up and insufficient image quality to perform strain analysis. Standardised echocardiogram recordings were reviewed and standard variables and LV GLS were measured. The primary end-point included all cardiac deaths, appropriate defibrillator shocks and heart failure (HF) admissions. The secondary end-point was death by HF and admissions related to HF.', "Mean age was 50.0±15.0\u2005years; 322 (68%) were men. At a median of 4.3\u2005years (IQR 0.1-7.8) follow-up, 21 (4.4%) patients experienced cardiovascular death: 6 (1.3%) died from HF, 13 (2.7%) had sudden cardiac death and 2 (0.4%) died secondary to stroke. Four (0.8%) patients experienced appropriate defibrillator shock, and 13 (2.7%) were admitted for HF. On multivariate Fine-Gray proportional hazard analyses, GLS was significantly associated with the primary end-point (HR=0.90, 95% CI 0.83 to 0.98, p=0.018) independently of age, maximal provoked LV outflow-tract gradient and LV end-systolic volume. Moreover, GLS was particularly associated with the secondary end-point (HR=0.82, 95% CI 0.75 to 0.90, p<0.0001) independently of age, previous atrial fibrillation, New York Heart Association (NYHA) class III-IV, LV end-systolic volume, E/E', and outflow-tract gradient. Survival curves confirmed that GLS was associated with HF events (GLS <15.6%, p=0.0035).
Answer: In patients with HCM, reduced GLS is an independent factor associated with poor cardiac outcomes, and particularly HF outcomes.
[EX A]: Is global longitudinal strain associated with heart failure outcomes in hypertrophic cardiomyopathy?

[EX Q]: Context: Excessive anticipatory reactions to potential future adversity are observed across a range of anxiety disorders, but the neurogenetic mechanisms driving interindividual differences are largely unknown. We aimed to discover and validate a gene-brain-behavior pathway by linking presumed genetic risk for anxiety-related psychopathology, key neural activity involved in anxious anticipation, and resulting aversive emotional states.', "The functional neuroanatomy of aversive anticipation was probed through functional magnetic resonance imaging in two independent samples of healthy subjects (n = 99 and n = 69), and we studied the influence of genetic variance in the serotonin transporter linked polymorphic region (5-HTTLPR). Skin conductance and startle data served as objective psychophysiological indices of the intensity of individuals' anticipatory responses to potential threat.", 'Threat cues signaling risk of future electrical shock activated the dorsomedial prefrontal cortex (dmPFC), anterior insula, bed nucleus of the stria terminalis, thalamus, and midbrain consistently across both samples. Threat-related dmPFC activation was enhanced in 5-HTTLPR short allele carriers in sample 1 and this effect was validated in sample 2. Critically, we show that this region mediates the increase in anticipatory psychophysiological reactions in short allele carriers indexed by skin conductance (experiment 1) and startle reactions (experiment 2).
Answer: The converging results from these experiments demonstrate that innate 5-HTTLPR linked variation in dmPFC activity predicts psychophysiological responsivity to pending threats. Our results reveal a neurogenetic pathway mediating interindividual variability in anticipatory responses to threat and yield a novel mechanistic account for previously reported associations between genetic variability in serotonin transporter function and stress-related psychopathology.
[EX A]:
Does dorsomedial Prefrontal Cortex mediate the Impact of Serotonin Transporter Linked Polymorphic Region Genotype on Anticipatory Threat Reactions?