Fast response times signal social connection in conversation.

Clicking is one of the most robust metaphors for social connection. But how do we know when two people "click"? We asked pairs of friends and strangers to talk with each other and rate their felt connection. For both friends and strangers, speed in response was a robust predictor of feeling connected. Conversations with faster response times felt more connected than conversations with slower response times, and within conversations, connected moments had faster response times than less-connected moments. This effect was determined primarily by partner responsivity: People felt more connected to the degree that their partner responded quickly to them rather than by how quickly they responded to their partner. The temporal scale of these effects (<250 ms) precludes conscious control, thus providing an honest signal of connection. Using a round-robin design in each of six closed networks, we show that faster responders evoked greater feelings of connection across partners. Finally, we demonstrate that this signal is used by third-party listeners as a heuristic of how well people are connected: Conversations with faster response times were perceived as more connected than the same conversations with slower response times. Together, these findings suggest that response times comprise a robust and sufficient signal of whether two minds "click."

On-site accuracy evaluation of laser tracking attitude measurement system.

In this study, an on-site attitude accuracy evaluation method based on parallel mechanism model and indirect traceability from length to angle is proposed. Firstly, the mathematical model is established. Through orthogonal experimental design, quantitative analysis shows that the ranging accuracy and control layout have a significant impact on the accuracy of the evaluation system. On this basis, the layout of control field is optimized by genetic algorithm. Finally, the practicability of the evaluation method is verified by experiments. The results show that the yaw and pitch accuracy of the method are 0.008°and 0.007°respectively in the range of -25°to 25°within the working distance of 8 m. This method can accurately and effectively evaluate the attitude angle information of the measurement system and is adapted to various on-site environments. The research provides an innovative idea which can be used to ensure the strict requirements of attitude angle measurement in fields such as intelligent manufacturing and in situ processing.

Dioleoylphosphatidylglycerol Inhibits Heat Shock Protein B4 (HSPB4)-Induced Inflammatory Pathways In Vitro.

Our previous work shows that dioleoylphosphatidylglycerol (DOPG) accelerates corneal epithelial healing in vitro and in vivo by unknown mechanisms. Prior data demonstrate that DOPG inhibits toll-like receptor (TLR) activation and inflammation induced by microbial components (pathogen-associated molecular patterns, PAMPs) and by endogenous molecules upregulated in psoriatic skin, which act as danger-associated molecular patterns (DAMPs) to activate TLRs and promote inflammation. In the injured cornea, sterile inflammation can result from the release of the DAMP molecule, heat shock protein B4 (HSPB4), to contribute to delayed wound healing. Here, we show in vitro that DOPG inhibits TLR2 activation induced in response to HSPB4, as well as DAMPs that are elevated in diabetes, a disease that also slows corneal wound healing. Further, we show that the co-receptor, cluster of differentiation-14 (CD14), is necessary for PAMP/DAMP-induced activation of TLR2, as well as of TLR4. Finally, we simulated the high-glucose environment of diabetes to show that elevated glucose levels enhance TLR4 activation by a DAMP known to be upregulated in diabetes. Together, our results demonstrate the anti-inflammatory actions of DOPG and support further investigation into its development as a possible therapy for corneal injury, especially in diabetic patients at high risk of vision-threatening complications.

Effect sizes and test-retest reliability of the fMRI-based neurologic pain signature.

Identifying biomarkers that predict mental states with large effect sizes and high test-retest reliability is a growing priority for fMRI research. We examined a well-established multivariate brain measure that tracks pain induced by nociceptive input, the Neurologic Pain Signature (NPS). In N = 295 participants across eight studies, NPS responses showed a very large effect size in predicting within-person single-trial pain reports (d = 1.45) and medium effect size in predicting individual differences in pain reports (d = 0.49). The NPS showed excellent short-term (within-day) test-retest reliability (ICC = 0.84, with average 69.5 trials/person). Reliability scaled with the number of trials within-person, with ≥60 trials required for excellent test-retest reliability. Reliability was tested in two additional studies across 5-day (N = 29, ICC = 0.74, 30 trials/person) and 1-month (N = 40, ICC = 0.46, 5 trials/person) test-retest intervals. The combination of strong within-person correlations and only modest between-person correlations between the NPS and pain reports indicate that the two measures have different sources of between-person variance. The NPS is not a surrogate for individual differences in pain reports but can serve as a reliable measure of pain-related physiology and mechanistic target for interventions.

A Generalizable Multivariate Brain Pattern for Interpersonal Guilt.

Feeling guilty when we have wronged another is a crucial aspect of prosociality, but its neurobiological bases are elusive. Although multivariate patterns of brain activity show promise for developing brain measures linked to specific emotions, it is less clear whether brain activity can be trained to detect more complex social emotional states such as guilt. Here, we identified a distributed guilt-related brain signature (GRBS) across two independent neuroimaging datasets that used interpersonal interactions to evoke guilt. This signature discriminated conditions associated with interpersonal guilt from closely matched control conditions in a cross-validated training sample (N = 24; Chinese population) and in an independent test sample (N = 19; Swiss population). However, it did not respond to observed or experienced pain, or recalled guilt. Moreover, the GRBS only exhibited weak spatial similarity with other brain signatures of social-affective processes, further indicating the specificity of the brain state it represents. These findings provide a step toward developing biological markers of social emotions, which could serve as important tools to investigate guilt-related brain processes in both healthy and clinical populations.

Syphilitic retinitis presentations: punctate inner retinitis and posterior placoid chorioretinitis.

PURPOSE: To describe two distinct presentations of syphilitic fundus features in a series of patients with ocular syphilis. METHODS: This is a retrospective, interventional case series of 22 eyes from 16 serology confirmed cases. Clinical examination, fluorescein angiography, and optical coherence tomography were performed at presentation and following high-dose intravenous penicillin G. RESULTS: In our cohort, the mean age was 47.6 years (range 24-59 years) and 14 patients were male (87.5%), 11 patients were positive for human immunodeficiency virus (68.8%), and 6 had bilateral involvement (37.5%). Mean best-corrected visual acuity improved from 0.99 ± 0.79 logarithm of the minimal angle of resolution (LogMAR) at the time of presentation to 0.29 ± 0.36 LogMAR on final visit (P < 0.01). Posterior segment examinations in eyes with retinitis showed two distinct types (1) discrete, placoid lesions in the macula consistent with acute syphilitic posterior placoid chorioretinitis or (2) punctate inner retinitis with corresponding fluorescein pooling in a segmental pattern. These findings rapidly resolved after antibiotic therapy. CONCLUSION: In the era of resurgence, ocular syphilis may present with two phenotypes of discrete retinal lesions. Recognition of the characteristic ocular features may help make the diagnosis and monitor treatment response.

Intersubject representational similarity analysis reveals individual variations in affective experience when watching erotic movies.

We spend much of our lives pursuing or avoiding affective experiences. However, surprisingly little is known about how these experiences are represented in the brain and if they are shared across individuals. Here, we explored variations in the construction of an affective experience during a naturalistic viewing paradigm based on subjective preferences in sociosexual desire and self-control using intersubject representational similarity analysis (IS-RSA). We found that when watching erotic movies, intersubject variations in sociosexual desire preferences of 26 heterosexual males were associated with similarly structured fluctuations in the cortico-striatal reward, default mode, and mentalizing networks. In contrast, variations in the self-control preferences were associated with shared dynamics in the fronto-parietal executive control and cingulo-insular salience networks. Importantly, these results were specific to the affective experience, as we did not observe any relationship with variation in preferences when individuals watched neutral movies. Moreover, these results appear to require multivariate representations of preferences as we did not observe any significant associations using single scalar summary scores. Our findings indicate that multidimensional variations in individual preferences can be used to uncover unique dimensions of an affective experience, and that IS-RSA can provide new insights into the neural processes underlying psychological experiences elicited through naturalistic experimental designs.

Comparison of cumulative dispersed energy (CDE) in femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification.

PURPOSE: To compare the amount of phacoemulsification ultrasound energy used between eyes undergoing femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification. METHODS: One eye of consecutive patients undergoing routine non-complicated phacoemulsification from January 2014 to December of 2015 was included in the analysis. FLACS was performed using the Alcon LenSx. Linear regression was used for analysis with type of surgery (FLACS versus conventional phacoemulsification) as the exposure and cumulative dispersed energy (CDE) as the outcome variable. Age, surgeon, eye side, and eye sequence (first versus second eye) were covariates. RESULTS: A total of 1159 surgeries met inclusion criteria. The average age of the cohort was 70.6 (SD 8.6) years, 590 cases (51%) were performed by surgeon 1, and 582 cases (50%) were right eyes. Overall, FLACS resulted in significantly lower CDE as compared to conventional phacoemulsification (ß = 0.89, 95% CI 0.83, 0.95). When stratified by eye side and surgeon, FLACS performed on left eyes operated on by surgeon 1 resulted in lower CDE as compared to conventional phacoemulsification (ß = 0.76, 95% CI 0.66, 0.87), but not for right eyes operated on by surgeon 1 (ß = 0.92, 95% CI 0.79, 1.07) or for eyes operated on by surgeons 2 or 3. CONCLUSIONS: The use of FLACS on the Alcon LenSx platform results in a small decrease in phacoemulsification energy as compared to conventional phacoemulsification in certain cases. Further study assessing optimal laser settings and surgical technique is necessary.

Reduced Fear-Conditioned Pain Modulation in Experienced Meditators: A Preliminary Study.

OBJECTIVE: Mindfulness-based practice is a form of cognitive/affective training that may help reduce suffering by attenuating maladaptive anticipatory processes. This study's objective was to examine the pain modulating impact of classical fear learning in meditation practitioners. METHODS: The hyperalgesic effects of pain expectation and uncertainty were assessed outside formal meditation in 11 experienced meditators (>1000 hours) compared with meditation-naive controls during a Pavlovian classical fear-conditioning paradigm involving two visual stimuli (CS+/CS-), one of which (CS+) co-terminated with a noxious electrical stimulus (unconditioned stimulus) on 50% of trials. A Rescorla-Wagner/Pearce-Hall hybrid model was fitted onto the conditioned skin conductance responses using computational modeling to estimate two learning parameters: expected shock probability and associability (i.e., uncertainty). RESULTS: Using a scale ranging between 0 (no pain) and 100 (extremely painful), meditators reported less pain (M = 19.9, SE = 5.1 for meditators, M = 32.4, SE = 2.4 for controls) but had comparable spinal motor responses (nociceptive flexion reflex) to the unconditioned stimulus. Multilevel mediation analyses revealed that meditators also exhibited reduced hyperalgesic effects of fear learning on higher-order pain responses but comparable effects on the nociceptive flexion reflex. These results suggest that mindfulness affects higher-order perceptual processes to a greater extent than from descending inhibitory controls. Furthermore, meditators showed reduced hyperalgesic effects of fear conditioning with no significant group difference in conditioned learning as evidenced by discriminative anticipatory skin conductance responses and learning parameters derived from computational modeling. CONCLUSIONS: These results highlight potential mechanisms underlying mindfulness-related hypoalgesia, relevant to clinical conditions in which repeated pain exposure might reinforce hyperalgesic processes through fear conditioning.

A Sensitive and Specific Neural Signature for Picture-Induced Negative Affect.

Neuroimaging has identified many correlates of emotion but has not yet yielded brain representations predictive of the intensity of emotional experiences in individuals. We used machine learning to identify a sensitive and specific signature of emotional responses to aversive images. This signature predicted the intensity of negative emotion in individual participants in cross validation (n =121) and test (n = 61) samples (high-low emotion = 93.5% accuracy). It was unresponsive to physical pain (emotion-pain = 92% discriminative accuracy), demonstrating that it is not a representation of generalized arousal or salience. The signature was comprised of mesoscale patterns spanning multiple cortical and subcortical systems, with no single system necessary or sufficient for predicting experience. Furthermore, it was not reducible to activity in traditional "emotion-related" regions (e.g., amygdala, insula) or resting-state networks (e.g., "salience," "default mode"). Overall, this work identifies differentiable neural components of negative emotion and pain, providing a basis for new, brain-based taxonomies of affective processes.

Multivariate Brain Prediction of Heart Rate and Skin Conductance Responses to Social Threat.

Psychosocial stressors induce autonomic nervous system (ANS) responses in multiple body systems that are linked to health risks. Much work has focused on the common effects of stress, but ANS responses in different body systems are dissociable and may result from distinct patterns of cortical-subcortical interactions. Here, we used machine learning to develop multivariate patterns of fMRI activity predictive of heart rate (HR) and skin conductance level (SCL) responses during social threat in humans (N = 18). Overall, brain patterns predicted both HR and SCL in cross-validated analyses successfully (rHR = 0.54, rSCL = 0.58, both p < 0.0001). These patterns partly reflected central stress mechanisms common to both responses because each pattern predicted the other signal to some degree (rHR→SCL = 0.21 and rSCL→HR = 0.22, both p < 0.01), but they were largely physiological response specific. Both patterns included positive predictive weights in dorsal anterior cingulate and cerebellum and negative weights in ventromedial PFC and local pattern similarity analyses within these regions suggested that they encode common central stress mechanisms. However, the predictive maps and searchlight analysis suggested that the patterns predictive of HR and SCL were substantially different across most of the brain, including significant differences in ventromedial PFC, insula, lateral PFC, pre-SMA, and dmPFC. Overall, the results indicate that specific patterns of cerebral activity track threat-induced autonomic responses in specific body systems. Physiological measures of threat are not interchangeable, but rather reflect specific interactions among brain systems. SIGNIFICANCE STATEMENT: We show that threat-induced increases in heart rate and skin conductance share some common representations in the brain, located mainly in the vmPFC, temporal and parahippocampal cortices, thalamus, and brainstem. However, despite these similarities, the brain patterns that predict these two autonomic responses are largely distinct. This evidence for largely output-measure-specific regulation of autonomic responses argues against a common system hypothesis and provides evidence that different autonomic measures reflect distinct, measurable patterns of cortical-subcortical interactions.

Large-Scale Meta-Analysis of Human Medial Frontal Cortex Reveals Tripartite Functional Organization.

UNLABELLED: The functional organization of human medial frontal cortex (MFC) is a subject of intense study. Using fMRI, the MFC has been associated with diverse psychological processes, including motor function, cognitive control, affect, and social cognition. However, there have been few large-scale efforts to comprehensively map specific psychological functions to subregions of medial frontal anatomy. Here we applied a meta-analytic data-driven approach to nearly 10,000 fMRI studies to identify putatively separable regions of MFC and determine which psychological states preferentially recruit their activation. We identified regions at several spatial scales on the basis of meta-analytic coactivation, revealing three broad functional zones along a rostrocaudal axis composed of 2-4 smaller subregions each. Multivariate classification analyses aimed at identifying the psychological functions most strongly predictive of activity in each region revealed a tripartite division within MFC, with each zone displaying a relatively distinct functional signature. The posterior zone was associated preferentially with motor function, the middle zone with cognitive control, pain, and affect, and the anterior with reward, social processing, and episodic memory. Within each zone, the more fine-grained subregions showed distinct, but subtler, variations in psychological function. These results provide hypotheses about the functional organization of medial prefrontal cortex that can be tested explicitly in future studies. SIGNIFICANCE STATEMENT: Activation of medial frontal cortex in fMRI studies is associated with a wide range of psychological states ranging from cognitive control to pain. However, this high rate of activation makes it challenging to determine how these various processes are topologically organized across medial frontal anatomy. We conducted a meta-analysis across nearly 10,000 studies to comprehensively map psychological states to discrete subregions in medial frontal cortex using relatively unbiased data-driven methods. This approach revealed three distinct zones that differed substantially in function, each of which were further subdivided into 2-4 smaller subregions that showed additional functional variation. Each individual region was recruited by multiple psychological states, suggesting subregions of medial frontal cortex are functionally heterogeneous.

Does Psychosocial Stress Impact Cognitive Reappraisal? Behavioral and Neural Evidence.

Cognitive reappraisal (CR) is regarded as an effective emotion regulation strategy. Acute stress, however, is believed to impair the functioning of prefrontal-based neural systems, which could result in lessened effectiveness of CR under stress. This study tested the behavioral and neurobiological impact of acute stress on CR. While undergoing fMRI, adult participants ( n = 54) passively viewed or used CR to regulate their response to negative and neutral pictures and provided ratings of their negative affect in response to each picture. Half of the participants experienced an fMRI-adapted acute psychosocial stress manipulation similar to the Trier Social Stress Test, and a control group received parallel manipulations without the stressful components. Relative to the control group, the stress group exhibited heightened stress as indexed by self-report, heart rate, and salivary cortisol throughout the scan. Contrary to our hypothesis, we found that reappraisal success was equivalent in the control and stress groups, as was electrodermal response to the pictures. Heart rate deceleration, a physiological response typically evoked by aversive pictures, was blunted in response to negative pictures and heightened in response to neutral pictures in the stress group. In the brain, we found weak evidence of stress-induced increases of reappraisal-related activity in parts of the PFC and left amygdala, but these relationships were statistically fragile. Together, these findings suggest that both the self-reported and neural effects of CR may be robust to at least moderate levels of stress, informing theoretical models of stress effects on cognition and emotion.

Group-regularized individual prediction: theory and application to pain.

Multivariate pattern analysis (MVPA) has become an important tool for identifying brain representations of psychological processes and clinical outcomes using fMRI and related methods. Such methods can be used to predict or 'decode' psychological states in individual subjects. Single-subject MVPA approaches, however, are limited by the amount and quality of individual-subject data. In spite of higher spatial resolution, predictive accuracy from single-subject data often does not exceed what can be accomplished using coarser, group-level maps, because single-subject patterns are trained on limited amounts of often-noisy data. Here, we present a method that combines population-level priors, in the form of biomarker patterns developed on prior samples, with single-subject MVPA maps to improve single-subject prediction. Theoretical results and simulations motivate a weighting based on the relative variances of biomarker-based prediction-based on population-level predictive maps from prior groups-and individual-subject, cross-validated prediction. Empirical results predicting pain using brain activity on a trial-by-trial basis (single-trial prediction) across 6 studies (N=180 participants) confirm the theoretical predictions. Regularization based on a population-level biomarker-in this case, the Neurologic Pain Signature (NPS)-improved single-subject prediction accuracy compared with idiographic maps based on the individuals' data alone. The regularization scheme that we propose, which we term group-regularized individual prediction (GRIP), can be applied broadly to within-person MVPA-based prediction. We also show how GRIP can be used to evaluate data quality and provide benchmarks for the appropriateness of population-level maps like the NPS for a given individual or study.

Brain Mechanisms of the Placebo Effect: An Affective Appraisal Account.

Placebos are sham medical treatments. Nonetheless, they can have substantial effects on clinical outcomes. Placebos depend on a person's psychological and brain responses to the treatment context, which influence appraisals of future well-being. Appraisals are flexible cognitive evaluations of the personal meaning of events and situations that can directly impact symptoms and physiology. They also shape associative learning processes by guiding what is learned from experience. Appraisals are supported by a core network of brain regions associated with the default mode network involved in self-generated emotion, self-evaluation, thinking about the future, social cognition, and valuation of rewards and punishment. Placebo treatments for acute pain and a range of clinical conditions engage this same network of regions, suggesting that placebos affect behavior and physiology by changing how a person evaluates their future well-being and the personal significance of their symptoms.

Computational substrates of social value in interpersonal collaboration.

Decisions to engage in collaborative interactions require enduring considerable risk, yet provide the foundation for building and maintaining relationships. Here, we investigate the mechanisms underlying this process and test a computational model of social value to predict collaborative decision making. Twenty-six participants played an iterated trust game and chose to invest more frequently with their friends compared with a confederate or computer despite equal reinforcement rates. This behavior was predicted by our model, which posits that people receive a social value reward signal from reciprocation of collaborative decisions conditional on the closeness of the relationship. This social value signal was associated with increased activity in the ventral striatum and medial prefrontal cortex, which significantly predicted the reward parameters from the social value model. Therefore, we demonstrate that the computation of social value drives collaborative behavior in repeated interactions and provide a mechanistic account of reward circuit function instantiating this process.

Novel function discovery with GeneMANIA: a new integrated resource for gene function prediction in Escherichia coli.

MOTIVATION: The model bacterium Escherichia coli is among the best studied prokaryotes, yet nearly half of its proteins are still of unknown biological function. This is despite a wealth of available large-scale physical and genetic interaction data. To address this, we extended the GeneMANIA function prediction web application developed for model eukaryotes to support E.coli. RESULTS: We integrated 48 distinct E.coli functional interaction datasets and used the GeneMANIA algorithm to produce thousands of novel functional predictions and prioritize genes for further functional assays. Our analysis achieved cross-validation performance comparable to that reported for eukaryotic model organisms, and revealed new functions for previously uncharacterized genes in specific bioprocesses, including components required for cell adhesion, iron-sulphur complex assembly and ribosome biogenesis. The GeneMANIA approach for network-based function prediction provides an innovative new tool for probing mechanisms underlying bacterial bioprocesses. CONTACT: gary.bader@utoronto.ca; mohan.babu@uregina.ca SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

FGF2-mediated reciprocal tumor cell-endothelial cell interplay contributes to the growth of chemoresistant cells: a potential mechanism for superficial bladder cancer recurrence.

Patients with superficial bladder cancer can be definitively cured by one single transurethral resection (TUR) with additional intravesical chemotherapy; however, up to 75 % of cases display frequent and multiple recurrences. One of the major causes of recurrence is that chemotherapeutic drugs used in intravesical regimens may induce chemoresistance. However, the mechanisms by which these chemoresistant cells develop into recurrent tumors remain unclear. Recent clinical evidence revealed that the expression of pro-angiogenic factor FGF2 was associated with early local relapse in patients with superficial bladder cancer. In this study, we conducted a preliminary investigation of the mechanisms of chemoresistant cells mediated bladder cancer recurrence, focusing on FGF2-initiated tumor cell-endothelial cell interaction on chemoresistant cancer cell growth. We found that the expression of FGF2 was increased in chemoresistant bladder cell lines and in bladder tissues after intravesical chemotherapy. Although chemoresistant bladder cells grow slower than parental cells, chemoresistant bladder cancer cells had stronger ability than parental cells to stimulate endothelial cell migration, growth, and tube formation by producing FGF2. Inversely, endothelial cells significantly promoted chemoresistant bladder cancer growth in vitro and in vivo. Thus, targeting chemotherapy-induced FGF2 upregulation may provide a promising approach to manage the recurrence of superficial bladder cancer.

Kaempferol suppresses bladder cancer tumor growth by inhibiting cell proliferation and inducing apoptosis.

The effects of the flavonoid compound, kaempferol, which is an inhibitor of cancer cell proliferation and an inducer of cell apoptosis have been shown in various cancers, including lung, pancreatic, and ovarian, but its effect has never been studied in bladder cancer. Here, we investigated the effects of kaempferol on bladder cancer using multiple in vitro cell lines and in vivo mice studies. The MTT assay results on various bladder cancer cell lines showed that kaempferol enhanced bladder cancer cell cytotoxicity. In contrast, when analyzed by the flow cytometric analysis, DNA ladder experiment, and TUNEL assay, kaempferol significantly was shown to induce apoptosis and cell cycle arrest. These in vitro results were confirmed in in vivo mice studies using subcutaneous xenografted mouse models. Consistent with the in vitro results, we found that treating mice with kaempferol significant suppression in tumor growth compared to the control group mice. Tumor tissue staining results showed decreased expressions of the growth related markers, yet increased expressions in apoptosis markers in the kaempferol treated group mice tissues compared to the control group mice. In addition, our in vitro and in vivo data showed kaempferol can also inhibit bladder cancer invasion and metastasis. Further mechanism dissection studies showed that significant down-regulation of the c-Met/p38 signaling pathway is responsible for the kaempferol mediated cell proliferation inhibition. All these findings suggest kaempferol might be an effective and novel chemotherapeutic drug to apply for the future therapeutic agent to combat bladder cancer.

The challenges of forecasting resilience.

Developing prospective models of resilience using the translational and transdiagnostic framework proposed in the target article is a challenging endeavor and will require large-scale data sets with dense intraindividual temporal sampling and innovative analytic methods.