Emotions in motion: affective valence can influence compatibility effects with graspable objects.

Previous studies showed that affective valence (positive, negative) influences Stimulus-Response Compatibility (SRC) effects elicited by both relevant and irrelevant spatial dimensions. We tested whether valence influences SRC effects when the irrelevant spatial dimension rather than being conveyed by the entire stimulus location is conveyed by the location of the stimulus' graspable part, i.e., the Handle-Response (H-R) compatibility effect. Participants saw objects with either a flower, a spider or nothing on their handle and categorized them as kitchen utensils or garage tools through button presses. In Experiment 1, a random presentation of valenced stimuli was used, whereas in Experiment 2 differently valenced stimuli were arranged in different blocks. Furthermore, participants in Experiment 2 could be spider-fearful or not. In Experiment 1, an H-R compatibility effect occurred for response latencies, regardless of whether stimuli presented a negative, positive or no element on their handle. In Experiment 2 the effect occurred only when a positive element was shown on the object's handle. In addition, spider-fearful individuals showed significantly slower responses when the element appearing on the object's handle had a negative valence. These results suggest that the SRC effect observed with pictures of graspable objects may be sensitive to the affective characteristics of stimuli and that approach/avoidance response tendencies may also depend on individual differences (being spider-fearful or not).

Novelty and learning in cognitive control: evidence from the Simon task.

While information that is associated with inappropriate responses can interfere with an ongoing task and be detrimental to performance, cognitive control mechanisms and specific contextual conditions can alleviate interference from unwanted information. In the spatial correspondence (Simon) task, interference has been consistently shown to be reduced by spatial non-correspondence in the previous trial (i.e., correspondence sequence effect, CSE); however the mechanisms supporting this sequential effect are not well understood. Here we investigated the role of novelty and trial-to-trial changes in stimulus and response features in a Simon task, observing similar modulation of CSE for novel and non-novel stimulus changes. However, changing the response modality from trial to trial dampened CSE, and this dampening was more pronounced when the probability of switch trials was higher, suggesting a role for long-term learning. The results are consistent with recent accounts, which indicate that spatial interference can be prevented by cognitive control mechanisms triggered by learned bindings.

A Novel Assay in Whole Blood Demonstrates Restoration of Mitochondrial Activity in Phagocytes After Successful HSCT in Hyperinflamed X-Linked Chronic Granulomatous Disease.

X-linked chronic granulomatous disease is a rare disease caused by mutations in the CYBB gene. While more extensive knowledge is available on genetics, pathogenesis, and possible therapeutic options, mitochondrial activity and its implications on patient monitoring are still not well-characterized. We have developed a novel protocol to study mitochondrial activity on whole blood of XCGD patients before and after transplantation, as well as on XCGD carriers. Here we present results of these analyses and of the restoration of mitochondrial activity in hyperinflamed X-linked Chronic Granulomatous Disease after hematopoietic stem cell transplantation. Moreover, we show a strong direct correlation between mitochondrial activity, chimerism, and DHR monitored before and after transplantation and in XCGD carriers. In conclusion, based on these findings, we suggest testing this new ready-to-use marker to better characterize patients before and after treatment and to investigate disease expression in carriers.

Practice effects vs. transfer effects in the Simon task.

The Simon effect refers to the fact that, even though stimulus position is task-irrelevant, responses to a task-relevant stimulus dimension are faster and more accurate when the stimulus and response spatially correspond than when they do not. Although the Simon effect is a very robust phenomenon, it is modulated by practice or transfer from previous tasks. Practice refers to the modulation of the Simon effect as a function of number of trials. Transfer refers to the modulation of the Simon effect as a function of preceding tasks. The aim of the present study is to disentangle the role of practice and transfer in modulating the Simon effect and to investigate whether such modulation can be extended to a different response modality. Three experiments were conducted, which included three sessions: the Baseline session, the Inducer session and the Diagnostic session. The task performed in the Baseline and the Diagnostic sessions were comprised of location-irrelevant trials (i.e., they were Simon tasks). The task performed in the Inducer session required performing location-relevant trials (i.e., it was a spatial compatibility task with a compatible or an incompatible stimulus-response mapping). In the first and third experiments, participants were required to respond manually in all sessions. In the second experiment, the task performed in the Inducer session required manual response, while in the Baseline and Diagnostic sessions the tasks required ocular response. Results showed a reduced-Diagnostic Simon effect after both compatible and incompatible mapping in the Inducer session, regardless of whether response modality was the same or different. These results support the notion that the practice effect prevails over the transfer effect.

Pulmonary Vascular Thrombosis in COVID-19 Pneumonia.

OBJECTIVES: During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, dramatic endothelial cell damage with pulmonary microvascular thrombosis have been was hypothesized to occur. The aim was to assess whether pulmonary vascular thrombosis (PVT) is due to recurrent thromboembolism from peripheral deep vein thrombosis or to local inflammatory endothelial damage, with a superimposed thrombotic late complication. DESIGN: Observational study. SETTING: Medical and intensive care unit wards of a teaching hospital. PARTICIPANTS: The authors report a subset of patients included in a prospective institutional study (CovidBiob study) with clinical suspicion of pulmonary vascular thromboembolism. INTERVENTIONS: Computed tomography pulmonary angiography and evaluation of laboratory markers and coagulation profile. MEASUREMENTS AND MAIN RESULTS: Twenty-eight of 55 (50.9%) patients showed PVT, with a median time interval from symptom onset of 17.5 days. Simultaneous multiple PVTs were identified in 22 patients, with bilateral involvement in 16, mostly affecting segmental/subsegmental pulmonary artery branches (67.8% and 96.4%). Patients with PVT had significantly higher ground glass opacity areas (31.7% [22.9-41] v 17.8% [10.8-22.1], p < 0.001) compared with those without PVT. Remarkably, in all 28 patients, ground glass opacities areas and PVT had an almost perfect spatial overlap. D-dimer level at hospital admission was predictive of PVT. CONCLUSIONS: The findings identified a specific radiologic pattern of coronavirus disease 2019 (COVID-19) pneumonia with a unique spatial distribution of PVT overlapping areas of ground-glass opacities. These findings supported the hypothesis of a pathogenetic relationship between COVID-19 lung inflammation and PVT and challenged the previous definition of pulmonary embolism associated with COVID-19 pneumonia.

Correspondence effect driven by salient visual asymmetries in integral object stimuli.

The handle-to-hand correspondence effect consists of faster and more accurate responses when the responding hand is aligned with the handle side of an object tool, compared to when they lay on opposite sides. This effect has been attributed to the activation of affordances. Recent studies, however, claimed that it may depend on the spatial coding of the object on the basis of its visual asymmetry (location-coding account). Affordances are namely direct and meaningful relations between recognized objects and the observers' action system. Therefore, any manipulation that disrupts the body structure of object tools could potentially affect their identification and prevent the activation of affordances. The present study investigated the nature of the handle-to-hand correspondence effects by manipulating structural asymmetry and visual salience of object tools, while preserving their integrity that is, leaving unaltered the original possibilities to activate grasping affordances. Three experiments were run. Results were consistent with the location-coding account and claim for accurate control of visual asymmetries in object stimuli during investigation of affordance effects.

Assessing orienting of attention to understand the time course of mental calculation.

Number processing induces spatial attention shifts to the left or right side for small or large numbers, respectively. This spatial-numerical association (SNA) extends to mental calculation, such that subtractions and additions induce left or right biases, respectively. However, the time course of activating SNAs during mental calculation is unclear. Here, we addressed this issue by measuring visual position discrimination during auditory calculation. Thirty-four healthy adults listened in each trial to five successive elements of arithmetic facts (first operand, operator, second operand, equal and result) and verbally classified their correctness. After each element (except for the result), a fixation dot moved equally often to either the left or right side and participants pressed left or right buttons to discriminate its movement direction (four times per trial). First and second operand magnitude (small/large), operation (addition/subtraction), result correctness (right/wrong) and movement direction (left/right) were balanced across 128 trials. Manual reaction times of dot movement discriminations were considered in relation to previous arithmetic elements. We found no evidence of early attentional shifts after first operand and operator presentation. Discrimination performance was modulated consistent with SNAs after the second operand, suggesting that attentional shifts occur once there is access to all elements necessary to complete an arithmetic operation. Such late-occurring attention shifts may reflect a combination of multiple element-specific biases and confirm their functional role in mental calculation.

The unimanual handle-to-hand correspondence effect: evidence for a location coding account.

The handle-to-hand correspondence effect refers to faster and more accurate responses when the responding hand is aligned with the graspable part of an object tool, compared to when they lay on opposite sides. We performed four behavioral experiments to investigate whether this effect depends on the activation of grasping affordances (affordance activation account) or is to be traced back to a Simon effect, resulting from the spatial coding of stimuli and responses and from their dimensional overlap (location coding account). We manipulated the availability of a response alternative by requiring participants to perform either a unimanual go/no-go task (absence of a response alternative) or a joint go/no-go task (available response alternative) and the type of response required (button-press or grasping response). We found no handle-to-hand correspondence effect in the individual go/no-go task either when a button-press (Experiment 1A) or a grasping (Experiment 2A) response was required, whereas a significant effect emerged in the joint go/no-go task, irrespective of response modality (Experiments1B and 2B). These results do not support the idea that complex motor affordances are activated for meaningful objects, but are rather consistent with the more parsimonious location coding account.

Gastric cancer: texture analysis from multidetector computed tomography as a potential preoperative prognostic biomarker.

OBJECTIVES: To investigate the association between preoperative texture analysis from multidetector computed tomography (MDCT) and overall survival in patients with gastric cancer. METHODS: Institutional review board approval and informed consent were obtained. Fifty-six patients with biopsy-proved gastric cancer were examined by MDCT and treated with surgery. Image features from texture analysis were quantified, with and without filters for fine to coarse textures. The association with survival time was assessed using Kaplan-Meier and Cox analysis. RESULTS: The following parameters were significantly associated with a negative prognosis, according to different thresholds: energy [no filter] - Logarithm of relative risk (Log RR): 3.25; p = 0.046; entropy [no filter] (Log RR: 5.96; p = 0.002); entropy [filter 1.5] (Log RR: 3.54; p = 0.027); maximum Hounsfield unit value [filter 1.5] (Log RR: 3.44; p = 0.027); skewness [filter 2] (Log RR: 5.83; p = 0.004); root mean square [filter 1] (Log RR: - 2.66; p = 0.024) and mean absolute deviation [filter 2] (Log RR: - 4.22; p = 0.007). CONCLUSIONS: Texture analysis could increase the performance of a multivariate prognostic model for risk stratification in gastric cancer. Further evaluations are warranted to clarify the clinical role of texture analysis from MDCT. KEY POINTS: • Textural analysis from computed tomography can be applied in gastric cancer. • Preoperative non-invasive texture features are related to prognosis in gastric cancer. • Texture analysis could help to evaluate the aggressiveness of this tumour.

Phase 1B trial of Nab-paclitaxel plus gemcitabine, capecitabine, and cisplatin (PAXG regimen) in patients with unresectable or borderline resectable pancreatic adenocarcinoma.

BACKGROUND: Nab-paclitaxel-gemcitabine combination significantly improved overall survival over gemcitabine in metastatic pancreatic adenocarcinoma. A phase 1b trial was performed (ClinicalTrials.gov number, NCT01730222) to determine the recommended phase 2 dose (RP2D) of nab-paclitaxel in combination with cisplatin, capecitabine, and gemcitabine at fixed dose (800, 30, and 1250 mg m(-2) every 2 weeks, respectively; PAXG regimen). METHODS: Nab-paclitaxel doses were escalated from 100 (level one) to 125 (level two) and 150 mg m(-2) (level three) every 2 weeks in cohorts of 3-6 patients with pathologically confirmed unresectable or borderline resectable pancreatic adenocarcinoma. RESULTS: Between Dec 2012 and Apr 2014, 24 patients were enroled (3 at level one, 5 at level two, 16 at level three) and received 117 cycles of PAXG. No dose-limiting toxicity occurred and level three was the RP2D. At this dose, nab-paclitaxel dose-intensity was 91%. Worse per patient grade 3/4 toxicity were neutropenia 25/31%; fatigue 19%; anaemia and hand-foot syndrome 12%, nausea 6%, and febrile neutropenia 6%. A partial response (PR) was observed in 16 (67%) and stable disease (SD) in 8 patients (33%). Among 21 patients with a baseline positive positron emission tomography (PET) scan, a complete metabolic response was observed in 9 (43%), PR in 10 (48%), SD in 2. CA19-9 decreased by ⩾49% in all the 19 patients with elevated basal value. Six patients were resected after chemotherapy. Progression-free survival at 6 months (PFS-6) was 96%. CONCLUSIONS: The RP2D of nab-paclitaxel in the PAXG regimen was 150 mg m(-2) every 2 weeks. The preliminary results are promising and warrant further exploration.

Preoperative locoregional staging of gastric cancer: is there a place for magnetic resonance imaging? Prospective comparison with EUS and multidetector computed tomography.

BACKGROUND: The aim of this study was to prospectively compare the diagnostic performance of magnetic resonance imaging (MRI), multidetector computed tomography (MDCT) and endoscopic ultrasonography (EUS) in the preoperative locoregional staging of gastric cancer. METHODS: This study had Institutional Review Board approval, and informed consent was obtained from all patients. Fifty-two patients with biopsy-proven gastric cancer underwent preoperative 1.5-T MRI, 64-channel MDCT and EUS. All images were analysed blind, and the results were compared with histopathological findings according to the seventh edition of the TNM classification. After the population had been divided on the basis of the local invasion (T1-3 vs T4a-b) and nodal involvement (N0 vs N+), sensitivity, specificity, positive and negative predictive value, and accuracy were calculated and diagnostic performance measures were assessed using the McNemar test. RESULTS: For T staging, EUS showed higher sensitivity (94%) than MDCT and MRI (65 and 76%; p = 0.02 and p = 0.08). MDCT and MRI had significantly higher specificity (91 and 89%) than EUS (60%) (p = 0.0009 and p = 0.003). Adding MRI to MDCT or EUS did not result in significant differences for sensitivity. For N staging, EUS showed higher sensitivity (92%) than MRI and MDCT (69 and 73%; p = 0.01 and p = 0.02). MDCT showed better specificity (81%) than EUS and MRI (58 and 73%; p = 0.03 and p = 0.15). CONCLUSIONS: Our prospective study confirmed the leading role of EUS and MDCT in the staging of gastric cancer and did not prove, at present, the value of the clinical use of MRI.

Clinical and immunologic responses in melanoma patients vaccinated with MAGE-A3-genetically modified lymphocytes.

Cancer vaccines have recently been shown to induce some clinical benefits. The relationship between clinical activity and anti-vaccine T cell responses is somewhat controversial. Indeed, in many trials it has been documented that the induction of vaccine-specific T cells exceeds the clinical responses observed. Here, we evaluate immunological and clinical responses in 23 MAGE-A3(+) melanoma patients treated with autologous lymphocytes genetically engineered to express the tumor antigen MAGE-A3 and the viral gene product thymidine kinase of the herpes simplex virus (HSV-TK). HSV-TK was used as safety system in case of adverse events and as tracer antigen to monitor the immune competence of treated patients. The increase of anti-TK and anti-MAGE-A3 T-cells after vaccination was observed in 90 and 27% of patients, respectively. Among 19 patients with measurable disease, we observed a disease control rate of 26.3%, with one objective clinical response, and four durable, stable diseases. Three patients out of five with no evidence of disease (NED) at the time of vaccination remained NED after 73+, 70+ and 50+ months. Notably, we report that only patients experiencing MAGE-A3-specific immune responses showed a clinical benefit. Additionally, we report that responder and non-responder patients activate and expand T cells against the tracer antigen TK in a similar way, suggesting that local rather than systemic immune suppression might be involved in limiting clinically relevant antitumor immune responses.

Perceiving object dangerousness: an escape from pain?

A variety of studies showed that participants are facilitated when responding to graspable objects, while it has not been fully investigated what happens during interactions with graspable objects that are potentially dangerous. The present study focuses on the mechanisms underlying the processing of dangerous objects. In two experiments, we adopted a paradigm that has never been employed in this context, a bisection task. The line was flanked by objects belonging to different categories. We explored the sensitivity to the distinction between neutral and dangerous objects, by measuring whether the performance was biased toward a specific object category. In Experiment 1 both teenagers and adults bisected lines flanked by dangerous and neutral graspable objects, and they misperceived the line midpoint toward the neutral graspable object or, stated differently, on the opposite side of the dangerous graspable object. In Experiment 2 adults bisected lines flanked by dangerous and neutral objects matched on graspability (both graspable and ungraspable, Experiment 2a), or by graspable and ungraspable objects matched on dangerousness (both neutral and dangerous, Experiment 2b). Results confirmed the finding of Experiment 1, but also indicated that participants misperceived the line midpoint toward the ungraspable object when it was presented, being it dangerous or not. This evidence demonstrated sensitivity to object dangerousness maintained across lifespan. The emergence of aversive affordances evoked by dangerous graspable objects strenghtens the importance to consider graspability in the investigation of dangerous objects. Possible neural mechanisms involved in the processing of dangerous graspable objects are discussed.

Compatibility effects with destination and origin of motion.

Previous studies highlighted spatial compatibility effects other than those strictly arising from stimulus-response locations. In particular, the so-called Destination Compatibility (DC) effect refers to faster responses for dynamic (i.e., moving) stimuli the end point of which is spatially compatible with the response key. Four experiments examined whether the DC effect also occurs with static visual stimuli symbolically representing either motion destination alone (Experiment 1a), or both motion origin and destination (Experiments 1b, 2a, and 2b). Overall, our results are consistent in showing a DC effect; most importantly, the present findings reveal a predominance of the effect of destination of motion over that of origin, even when both the starting and ending positions of the stimulus are symbolically represented and participants are instructed to respond according to motion origin. This finding suggests that the DC effect is independent from other stimulus-response compatibility (SRC) effects.

Delayed ocular disengagement from arousing scenes.

Visual exploration of the world is supported by eye movements which can be speeded up or delayed depending on bottom-up stimulation, top-down goals, and prior associations. Previous studies observed faster initiation of saccades toward emotional than neutral natural scenes; however, less is known concerning saccades which originate from emotional, compared with neutral, scenes. Here, we addressed this issue by examining a task in which participants continuously moved their gaze from and toward pictures (natural scenes), which could be emotional or neutral, and changed position in every trial. Saccades were initiated later when the starting picture was emotional compared to neutral, and this slowing was associated with the arousal value of the picture, suggesting that ocular disengagement does not vary with stimulus valence but is affected by engaging picture contents such as erotica and threat/injuries.

Feasibility and safety of EUS-guided cryothermal ablation in patients with locally advanced pancreatic cancer.

BACKGROUND: New therapies are needed for pancreatic cancer. OBJECTIVE: To determine the feasibility and safety of a new endoscopic treatment. Secondary endpoints were to determine effects on tumor growth measured with CT scan and to find the overall survival. DESIGN: A cohort study of patients with local progression of advanced pancreatic adenocarcinoma after neoadjuvant therapy. The cryotherm probe (CTP), a flexible bipolar device that combines radiofrequency with cryogenic cooling, was used under EUS guidance. SETTING: San Raffaele Hospital, Milan, Italy; University Medical Center, Hamburg-Eppendorf, Germany. PATIENTS: A total of 22 patients (male/female 11/11; mean age 61.9 years) were enrolled from September 2009 to May 2011. INTERVENTION: Radiofrequency heating: 18 W; pressure for cooling: 650 psi (Pounds per Square Inch); application time: depending on tumor size. MAIN OUTCOME MEASUREMENTS: Feasibility was evaluated during the procedure. A clinical and radiologic follow-up was planned. RESULTS: The CTP was successfully applied in 16 patients (72.8%); in 6 it was not possible because of stiffness of the GI wall and of the tumor. Amylase arose in 3 of 16 patients; none had clinical signs of pancreatitis. Late complications arose in 4 cases: 3 were mostly related to tumor progression. Median postablation survival time was 6 months. A CT scan was performed in all patients, but only in 6 of 16 was it possible to clearly define the tumor margins after ablation. In these patients, the tumor appeared smaller compared with the initial mass (P = .07). LIMITATIONS: Small sample of patients, difficulty of objectifying the size of the ablated zone by CT scan. CONCLUSION: EUS-guided CTP ablation is feasible and safe. Further investigations are needed to demonstrate progression-free survival and local control.

Is access to the body structural description sensitive to a body part's significance for action and cognition? A study of the sidedness effect using feet.

There is evidence suggesting that viewing hands triggers automatic access to the Body Structural Description, a visual-spatial representation of human body parts configuration. Hands, however, have a special representational status within the brain because of their significance for action and cognition. We tested whether feet, less important in gestural and object-directed action, would similarly show automatic access to the Body Structural Description. Positive evidence of that would be finding a Sidedness effect (Ottoboni et al. J Exp Psychol Hum Percept Perform 31:778-789, 2005), a Simon-like paradigm previously used to study automatic hand recognition. This effect demonstrates that processing hands generates spatial codes corresponding to the side of the body on which the hand would be located within the Body Structural Description map. Feet were shown with toes pointing upwards (Experiment 1), without any connection to the ankle and the leg (Experiment 2) and with toes pointing downwards (Experiment 3). Results revealed a Sidedness effect in both Experiments 1 and 3: spatial compatibility occurred according to the side of the body that each foot would assume within the Body Structural Description. In Experiment 2, as already found in stimuli similarly featured, no effect emerged, due to the lack of the necessary anatomical links connecting the foot to a body. Results suggest that body parts with variable degrees of significance for action and cognition can access automatically the Body Structural Description hence reinforcing the hypothesis of its pure visuo-spatial nature.

Grasping the pain: motor resonance with dangerous affordances.

Two experiments, one on school-aged children and one on adults, explored the mechanisms underlying responses to an image prime (hand vs. control object) followed by graspable objects that were, in certain cases, dangerous. Participants were presented with different primes (a male, a female and a robotic grasping-hand; a male and a female static-hand; a control stimulus) and objects representing two risk levels (neutral and dangerous). The task required that a natural/artifact categorization task be performed by pressing different keys. In both adults and children graspable objects activated a facilitating motor response, while dangerous objects evoked aversive affordances, generating an interference-effect. Both children and adults were sensitive to the distinction between biological and non-biological hands, however detailed resonant mechanisms related to the hand-prime gender emerged only in adults. Implications for how the concept of "dangerous object" develops and the relationship between resonant mechanisms and perception of danger are discussed.

Self, others, objects: how this triadic interaction modulates our behavior.

Two experiments investigated whether the triadic interaction between objects, ourselves and other persons modulates motor system activation during language comprehension. Participants were faced with sentences formed by a descriptive part referring to a positive or negative emotively connoted object and an action part composed of an imperative verb implying a motion toward the self or toward other persons (e.g., "The object is attractive/ugly. Bring it toward you/Give it to another person/Give it to a friend"). Participants judged whether each sentence was sensible or not by moving the mouse toward or away from their body. Findings showed that the simulation of a social context influenced both (1) the motor system and (2) the coding of stimulus valence. Implications of the results for theories of embodied and social cognition are discussed.

Gaze direction and facial expressions exert combined but different effects on attentional resources.

Gaze direction and facial expressions are critical components of face processing and have been shown to influence attention deployment. We investigated whether gaze direction (direct vs. averted) combined with a neutral or angry expression modulates the deployment of attentional resources over time. In a rapid serial visual presentation (RSVP) paradigm participants had to decide the gender of a neutral or an angry target face with direct or averted gaze (T1) and then to judge the orientation of a target picture of a landscape (T2), following the face at different time intervals. Results showed no attentional blink effect (i.e., no deterioration in T2 accuracy) when T1 was an angry face with direct gaze, whereas it was present for angry faces with averted gaze or neutral faces with either averted or direct gaze. These findings are consistent with appraisal theories and are discussed against the background of automatic processing of threat stimuli.