γ-Linolenic acid in maternal milk drives cardiac metabolic maturation.

Birth presents a metabolic challenge to cardiomyocytes as they reshape fuel preference from glucose to fatty acids for postnatal energy production1,2. This adaptation is triggered in part by post-partum environmental changes3, but the molecules orchestrating cardiomyocyte maturation remain unknown. Here we show that this transition is coordinated by maternally supplied γ-linolenic acid (GLA), an 18:3 omega-6 fatty acid enriched in the maternal milk. GLA binds and activates retinoid X receptors4 (RXRs), ligand-regulated transcription factors that are expressed in cardiomyocytes from embryonic stages. Multifaceted genome-wide analysis revealed that the lack of RXR in embryonic cardiomyocytes caused an aberrant chromatin landscape that prevented the induction of an RXR-dependent gene expression signature controlling mitochondrial fatty acid homeostasis. The ensuing defective metabolic transition featured blunted mitochondrial lipid-derived energy production and enhanced glucose consumption, leading to perinatal cardiac dysfunction and death. Finally, GLA supplementation induced RXR-dependent expression of the mitochondrial fatty acid homeostasis signature in cardiomyocytes, both in vitro and in vivo. Thus, our study identifies the GLA-RXR axis as a key transcriptional regulatory mechanism underlying the maternal control of perinatal cardiac metabolism.

Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis.

BACKGROUND: Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited. METHODS: At 18 centers, we randomly assigned patients who presented with acute pancreatitis to receive goal-directed aggressive or moderate resuscitation with lactated Ringer's solution. Aggressive fluid resuscitation consisted of a bolus of 20 ml per kilogram of body weight, followed by 3 ml per kilogram per hour. Moderate fluid resuscitation consisted of a bolus of 10 ml per kilogram in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 ml per kilogram per hour in all patients in this group. Patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to the patient's clinical status. The primary outcome was the development of moderately severe or severe pancreatitis during the hospitalization. The main safety outcome was fluid overload. The planned sample size was 744, with a first planned interim analysis after the enrollment of 248 patients. RESULTS: A total of 249 patients were included in the interim analysis. The trial was halted owing to between-group differences in the safety outcomes without a significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; adjusted relative risk, 1.30; 95% confidence interval [CI], 0.78 to 2.18; P = 0.32). Fluid overload developed in 20.5% of the patients who received aggressive resuscitation and in 6.3% of those who received moderate resuscitation (adjusted relative risk, 2.85; 95% CI, 1.36 to 5.94, P = 0.004). The median duration of hospitalization was 6 days (interquartile range, 4 to 8) in the aggressive-resuscitation group and 5 days (interquartile range, 3 to 7) in the moderate-resuscitation group. CONCLUSIONS: In this randomized trial involving patients with acute pancreatitis, early aggressive fluid resuscitation resulted in a higher incidence of fluid overload without improvement in clinical outcomes. (Funded by Instituto de Salud Carlos III and others; WATERFALL ClinicalTrials.gov number, NCT04381169.).

Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homeostasis.

Hematopoietic stem cells (HSCs) balance self-renewal and differentiation to maintain hematopoietic fitness throughout life. In steady-state conditions, HSC exhaustion is prevented by the maintenance of most HSCs in a quiescent state, with cells entering the cell cycle only occasionally. HSC quiescence is regulated by retinoid and fatty-acid ligands of transcriptional factors of the nuclear retinoid X receptor (RXR) family. Herein, we show that dual deficiency for hematopoietic RXRα and RXRß induces HSC exhaustion, myeloid cell/megakaryocyte differentiation, and myeloproliferative-like disease. RXRα and RXRß maintain HSC quiescence, survival, and chromatin compaction; moreover, transcriptome changes in RXRα;RXRß-deficient HSCs include premature acquisition of an aging-like HSC signature, MYC pathway upregulation, and RNA intron retention. Fitness loss and associated RNA transcriptome and splicing alterations in RXRα;RXRß-deficient HSCs are prevented by Myc haploinsufficiency. Our study reveals the critical importance of RXRs for the maintenance of HSC fitness and their protection from premature aging.

The Peptidoglycan Recognition Protein 1 confers immune evasive properties on pancreatic cancer stem cells.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant 'stem-like' cells, known as cancer stem cells (CSCs), are implicated in PDAC aggressiveness. Thus, comprehending how this subset of cells evades the immune system is crucial for advancing novel therapies. DESIGN: We used the KPC mouse model (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre) and primary tumour cell lines to investigate putative CSC populations. Transcriptomic analyses were conducted to pinpoint new genes involved in immune evasion. Overexpressing and knockout cell lines were established with lentiviral vectors. Subsequent in vitro coculture assays, in vivo mouse and zebrafish tumorigenesis studies, and in silico database approaches were performed. RESULTS: Using the KPC mouse model, we functionally confirmed a population of cells marked by EpCAM, Sca-1 and CD133 as authentic CSCs and investigated their transcriptional profile. Immune evasion signatures/genes, notably the gene peptidoglycan recognition protein 1 (PGLYRP1), were significantly overexpressed in these CSCs. Modulating PGLYRP1 impacted CSC immune evasion, affecting their resistance to macrophage-mediated and T-cell-mediated killing and their tumourigenesis in immunocompetent mice. Mechanistically, tumour necrosis factor alpha (TNFα)-regulated PGLYRP1 expression interferes with the immune tumour microenvironment (TME) landscape, promoting myeloid cell-derived immunosuppression and activated T-cell death. Importantly, these findings were not only replicated in human models, but clinically, secreted PGLYRP1 levels were significantly elevated in patients with PDAC. CONCLUSIONS: This study establishes PGLYRP1 as a novel CSC-associated marker crucial for immune evasion, particularly against macrophage phagocytosis and T-cell killing, presenting it as a promising target for PDAC immunotherapy.

Plastic pigtail vs lumen-apposing metal stents for drainage of walled-off necrosis (PROMETHEUS study): an open-label, multicenter randomized trial.

BACKGROUND: Lumen-apposing metal stents (LAMS) have displaced double-pigtail plastic stents (DPS) as the standard treatment for walled-off necrosis (WON),ß but evidence for exclusively using LAMS is limited. We aimed to assess whether the theoretical benefit of LAMS was superior to DPS. METHODS: This multicenter, open-label, randomized trial was carried out in 9 tertiary hospitals. Between June 2017, and Oct 2020, we screened 99 patients with symptomatic WON, of whom 64 were enrolled and randomly assigned to the DPS group (n = 31) or the LAMS group (n = 33). The primary outcome was short-term (4-weeks) clinical success determined by the reduction of collection. Secondary endpoints included long-term clinical success, hospitalization, procedure duration, recurrence, safety, and costs. Analyses were by intention-to-treat. CLINICALTRIALS: gov, NCT03100578. RESULTS: A similar clinical success rate in the short term (RR, 1.41; 95% CI 0.88-2.25; p = 0.218) and in the long term (RR, 1.2; 95% CI 0.92-1.58; p = 0.291) was observed between both groups. Procedure duration was significantly shorter in the LAMS group (35 vs. 45-min, p = 0.003). The hospital admission after the index procedure (median difference, - 10 [95% CI - 17.5, - 1]; p = 0.077) and global hospitalization (median difference - 4 [95% CI - 33, 25.51]; p = 0.82) were similar between both groups. Reported stent-related adverse events were similar for the two groups (36 vs.45% in LAMS vs. DPS), except for de novo fever, which was significantly 26% lower in LAMS (RR, 0.26 [0.08-0.83], p = 0.015). CONCLUSIONS: The clinical superiority of LAMS over DPS for WON therapy was not proved, with similar clinical success, hospital stay and similar safety profile between both groups, yet a significant reduction in procedure time was observed. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03100578.

Pancreatic cancer screening in high-risk individuals.

The incidence of pancreatic cancer is increasing, although globally it represents less than 3% of all cancers. Despite advances in medical and surgical management, survival rates have not significantly improved in recent years. Consequently, pancreatic cancer, though relatively uncommon, is the third leading cause of cancer-related deaths. This is primarily due to the disease´s late detection. Symptoms appear late and are nonspecific, and over 80% of cases are diagnosed at an advanced stage and unsuitable for curative surgery, resulting in a five-year survival rate below 10%. However, the exceptional cases that are diagnosed early show five-year survival rates exceeding 80%. Therefore, one of the keys to improving pancreatic cancer prognosis lies in early detection, making screening in high-risk individuals a potentially crucial strategy.

User Experience Design for Social Robots: A Case Study in Integrating Embodiment.

Social robotics is an emerging field with a high level of innovation. For many years, it was a concept framed in the literature and theoretical approaches. Scientific and technological advances have made it possible for robots to progressively make their way into different areas of our society, and now, they are ready to make the leap out of the industry and extend their presence into our daily lives. In this sense, user experience plays a fundamental role in achieving a smooth and natural interaction between robots and humans. This research focused on the user experience approach in terms of the embodiment of a robot, centring on its movements, gestures, and dialogues. The aim was to investigate how the interaction between robotic platforms and humans takes place and what differential aspects should be considered when designing the robot tasks. To achieve this objective, a qualitative and quantitative study was conducted based on a real interview between several human users and the robotic platform. The data were gathered by recording the session and having each user complete a form. The results showed that participants generally enjoyed interacting with the robot and found it engaging, which led to greater trust and satisfaction. However, delays and errors in the robot's responses caused frustration and disconnection. The study found that incorporating embodiment into the design of the robot improved the user experience, and the robot's personality and behaviour were significant factors. It was concluded that robotic platforms and their appearance, movements, and way of communicating have a decisive influence on the user's opinion and the way they interact.

Over-the-scope-clip (OTSC®) as a rescue treatment for gastrointestinal bleeding secondary to peptic ulcer disease.

BACKGROUND AND AIMS: over-the-scope-clips (OTSC®) have been proposed as a rescue treatment for bleeding peptic ulcers. However, their effectiveness has not been evaluated in Spain. METHODS: this retrospective and single-center study (January 2018-December 2021) assessed the technical success, clinical success and safety of the device within 30 days. All patients with upper gastrointestinal bleeding due to a peptic ulcer and treated with the OTSC® clip (OVESCO) as a rescue therapy were included in the study. RESULTS: a total of eleven patients were included in the study, nine due to rebleeding and two due to persistent bleeding. Technical success was 81.9 % (9/11, confidence interval [CI] 95 %: 52-95 %). The per-protocol and intention-to-treat clinical success were 88.9 % (8/9, CI 95 %: 57-98 %) and 72.7 % (8/11, CI 95 %: 43-90 %), respectively. No device-related adverse effects were recorded. CONCLUSION: the OTSC® clip was an effective and safe rescue therapy for bleeding peptic ulcers.

Endoscopy-Related Bleeding and Thromboembolic Events in Patients on Direct Oral Anticoagulants or Vitamin K Antagonists.

BACKGROUND & AIMS: Few prospective studies have assessed the safety of direct oral anticoagulants (DOACs) in elective endoscopy. Our primary aim was to compare the risks of endoscopy-related gastrointestinal bleeding and thromboembolic events in patients on DOACs or vitamin K antagonists (VKAs) in this setting. Secondarily, we examined the impact of the timing of anticoagulant resumption on the risk of delayed bleeding in high-risk therapeutic procedures. METHODS: We conducted a multicenter, prospective, observational study from January 2018 to March 2020 of 1602 patients on oral anticoagulants (1004 on VKAs and 598 on DOACs) undergoing 1874 elective endoscopic procedures. Our primary outcomes were 90-day thromboembolic events and 30-day endoscopy-related gastrointestinal bleeding. The inverse probability of treatment weighting propensity score method was used for baseline covariate adjustment. RESULTS: The 2 groups had similar risks of endoscopy-related gastrointestinal bleeding (VKAs vs DOACs, 6.2% vs 6.7%; adjusted odds ratio [OR], 1.05; 95% CI, 0.67-1.65) and thromboembolic events (VKAs vs DOACs, 1.3% vs 1.5%; adjusted OR, 0.90; 95% CI, 0.34-2.38). In high bleeding risk procedures (n = 747), delayed anticoagulant resumption (> 48 hours or 24-48 hours vs < 24 hours) did not reduce the risk of postprocedural bleeding (10.3%, 9%, and 5.8%, respectively; adjusted P = .43). Hot and cold snare polypectomy were the most frequent high-risk interventions (41.8% and 39.8%, respectively). CONCLUSION: In a prospective study of patients on DOACs or VKAs undergoing elective endoscopy, endoscopy-related bleeding and thromboembolic events showed similar risk. Our study suggests that early anticoagulant resumption is safe in most patients, but more data are needed for advanced high-risk therapeutic procedures.

Polypharmacy in Patients With Inflammatory Bowel Disease: Prevalence and Outcomes in a Single-center Series.

BACKGROUND: Polypharmacy can complicate the course and management of chronic diseases, and has been little explored in patients with inflammatory bowel disease (IBD) to date. AIM: The aim of this study was to determine the prevalence of polypharmacy in a series of IBD patients, describing associated factors and its correlation with poor disease outcomes. MATERIALS AND METHODS: Retrospective study of a single-center series. Polypharmacy was defined as the simultaneous use of 5 or more drugs. Disease outcomes, IBD treatment nonadherence and undertreatment were evaluated at 1 year. RESULTS: A total of 407 patients were included [56% males, median age: 48 y (interquartile range, 18 to 92 y)], of whom 60.2% had Crohn's disease; Chronic comorbidity and multiple comorbidities were present in 54% and 27% of patients, respectively. Median number of prescriptions per patient was 3 (range: 0 to 15). Polypharmacy was identified in 18.4% of cases, inappropriate medication in 10.5% and use of high-risk drugs in 6.1% (mainly opioids). In multivariate analysis, polypharmacy was associated with chronic comorbidity [odds ratio (OR)=10.1, 95% confidence interval (CI): 2.14-47.56; P˂0.003], multiple comorbidities (OR=3.53, 95% CI: 1.46-8.51; P=0.005) and age above 62 years (OR=3.54, 95% CI: 1.67-7.51; P=0.001). No association with poor disease outcomes was found at 12 months. However, polypharmacy was the only factor associated with IBD treatment nonadherence (OR=2.24, 95% CI: 1.13-4.54, P=0.02). CONCLUSIONS: Polypharmacy occurs in around 1 in 5 patients with IBD, mainly in older adults and those with comorbidity. This situation could interfere with adherence to IBD treatment and therapeutic success.

Colorectal Cancer and Polyp Detection Using a New Preparation-Free, Colon-Scan Capsule: A Pilot Study of Safety and Patient Satisfaction.

BACKGROUND: Current strategies to prevent colorectal cancer (CRC) vary considerably regarding safety, invasiveness, and patient satisfaction. A known deterrent for patients is the required bowel cleansing for colonoscopy. A new colon-scan capsule system is a unique preparation-free approach that provides structural information on colonic mucosa intended for detection of colorectal polyps and masses. AIMS: The aim of this study was to determine safety and patient satisfaction with the colon-scan capsule. METHODS: Prospective single-arm pilot study conducted at two tertiary care centers. Patients with a pre-scheduled colonoscopy for CRC screening or surveillance were included. Patients participating in this study underwent the colon-scan capsule and colonoscopy. Safety was defined by the occurrence of procedure or device-related adverse events. Satisfaction was based on survey questionnaires using a scoring system 1 (strongly disagree) to 5 (strongly agree). Patient satisfaction with the colon-scan capsule was compared to colonoscopy. RESULTS: Forty patients were included (52.9 [5.7] years; 64.1% females). There were no serious adverse events and no occurrences of capsule retention. The most common (12.5%) complaint was self-limiting abdominal cramping. Satisfaction questionnaires were completed by more than 87% of patients, with patients likely to recommend the capsule (score 4.1 [1.03]) compared to colonoscopy (score 2.8 [1.2]), p = 0.001. CONCLUSIONS: The new prepless colon-scan capsule system is an innovative, minimally invasive technology with demonstrated safety and high patient satisfaction. A multicenter pivotal study is planned to validate the performance, safety, and accuracy of polyp detection using the capsule system in comparison with colonoscopy.

Changes of physico-chemical properties of nano-biomaterials by digestion fluids affect the physiological properties of epithelial intestinal cells and barrier models.

BACKGROUND: The widespread use of nano-biomaterials (NBMs) has increased the chance of human exposure. Although ingestion is one of the major routes of exposure to NBMs, it is not thoroughly studied to date. NBMs are expected to be dramatically modified following the transit into the oral-gastric-intestinal (OGI) tract. How these transformations affect their interaction with intestinal cells is still poorly understood. NBMs of different chemical nature-lipid-surfactant nanoparticles (LSNPs), carbon nanoparticles (CNPs), surface modified Fe3O4 nanoparticles (FNPs) and hydroxyapatite nanoparticles (HNPs)-were treated in a simulated human digestive system (SHDS) and then characterised. The biological effects of SHDS-treated and untreated NBMs were evaluated on primary (HCoEpiC) and immortalised (Caco-2, HCT116) epithelial intestinal cells and on an intestinal barrier model. RESULTS: The application of the in vitro SDHS modified the biocompatibility of NBMs on gastrointestinal cells. The differences between SHDS-treated and untreated NBMs could be attributed to the irreversible modification of the NBMs in the SHDS. Aggregation was detected for all NBMs regardless of their chemical nature, while pH- or enzyme-mediated partial degradation was detected for hydroxyapatite or polymer-coated iron oxide nanoparticles and lipid nanoparticles, respectively. The formation of a bio-corona, which contains proteases, was also demonstrated on all the analysed NBMs. In viability assays, undifferentiated primary cells were more sensitive than immortalised cells to digested NBMs, but neither pristine nor treated NBMs affected the intestinal barrier viability and permeability. SHDS-treated NBMs up-regulated the tight junction genes (claudin 3 and 5, occludin, zonula occludens 1) in intestinal barrier, with different patterns between each NBM, and increase the expression of both pro- and anti-inflammatory cytokines (IL-1ß, TNF-α, IL-22, IL-10). Notably, none of these NBMs showed any significant genotoxic effect. CONCLUSIONS: Overall, the results add a piece of evidence on the importance of applying validated in vitro SHDS models for the assessment of NBM intestinal toxicity/biocompatibility. We propose the association of chemical and microscopic characterization, SHDS and in vitro tests on both immortalised and primary cells as a robust screening pipeline useful to monitor the changes in the physico-chemical properties of ingested NBMs and their effects on intestinal cells.

CfrA, a Novel Carbon Flow Regulator, Adapts Carbon Metabolism to Nitrogen Deficiency in Cyanobacteria.

Cyanobacteria unable to fix atmospheric nitrogen have evolved sophisticated adaptations to survive to long periods of nitrogen starvation. These genetic programs are still largely unknown-as evidenced by the many proteins whose expression is regulated in response to nitrogen availability, but which belong to unknown or hypothetical categories. In Synechocystis sp. PCC 6803, the global nitrogen regulator NtcA activates the expression of the sll0944 gene upon nitrogen deprivation. This gene encodes a protein that is highly conserved in cyanobacteria, but of unknown function. Based on the results described herein, we named the product of sll0944 carbon flow regulator A (CfrA). We analyzed the phenotypes of strains containing different levels of CfrA, including a knock-out strain (ΔcfrA), and two strains overexpressing CfrA from either the constitutive P trc promoter (Ptrc-cfrA) or the arsenite-inducible promoter P arsB (Pars-cfrA). Our results show that the amount of CfrA determines the accumulation of glycogen, and affects the synthesis of protein and photosynthetic pigments as well as amino acid pools. Strains with high levels of CfrA present high levels of glycogen and a decrease in photosynthetic pigments and protein content when nitrogen is available. Possible interactions between CfrA and the pyruvate dehydrogenase complex or PII protein have been revealed. The phenotype associated with CfrA overexpression is also observed in PII-deficient strains; however, it is lethal in this genetic background. Taken together, our results indicate a role for CfrA in the adaptation of carbon flux during acclimation to nitrogen deficiency.

Unique perspective of Muslim patients on gender preference for GI endoscopists: a multicenter survey.

BACKGROUND AND AIMS: Patient preference for a healthcare professional is mediated by physician gender. The primary aim of this study was to assess gender preference for an endoscopist in a cohort of Muslim patients. The secondary aim was to identify factors that influence gender preference. METHODS: This was a multicenter cross-sectional study conducted at 3 tertiary care hospitals in Pakistan. Consecutive patients scheduled for elective outpatient upper endoscopy or colonoscopy were asked to complete a questionnaire immediately before and after the procedure. Data collected included patient demographics, occupation, education level, procedure type, gender preference, and reason for preference. RESULTS: A total of 1078 patients completed the questionnaire (age 43.5 ± 15.8 years; 53.2% men). Upper endoscopy was the most frequent procedure, performed in 84% of patients. Gender preference was expressed by 707 patients (65.6%), of which 511 (72.3%) were willing to wait for an average of 7 days for an endoscopist of the preferred gender. Male patients' preferences (45.1% male endoscopist, 17.1% female endoscopist, 37.8% no preference) differed from female participants' (16.9% male endoscopist, 52.6% female endoscopist, and 30.5% no preference; P < .00001). No education was associated with having a gender preference (odds ratio, .55; 95% confidence interval, .37-.81; P = .003). Reasons for gender preference included religious values and family pressure, which were more frequently expressed by women (P < .0001). CONCLUSIONS: Most Muslims in Pakistan expressed a gender preference, and both female and male patients showed a preference for a same-gender endoscopist. No education was associated with having a gender preference.

Safety and efficacy of sucroferric oxyhydroxide in pediatric patients with chronic kidney disease.

BACKGROUND: Pediatric patients with advanced chronic kidney disease (CKD) are often prescribed oral phosphate binders (PBs) for the management of hyperphosphatemia. However, available PBs have limitations, including unfavorable tolerability and safety. METHODS: This phase 3, multicenter, randomized, open-label study investigated safety and efficacy of sucroferric oxyhydroxide (SFOH) in pediatric and adolescent subjects with CKD and hyperphosphatemia. Subjects were randomized to SFOH or calcium acetate (CaAc) for a 10-week dose titration (stage 1), followed by a 24-week safety extension (stage 2). Primary efficacy endpoint was change in serum phosphorus from baseline to the end of stage 1 in the SFOH group. Safety endpoints included treatment-emergent adverse events (TEAEs). RESULTS: Eighty-five subjects (2-18 years) were randomized and treated (SFOH, n = 66; CaAc, n = 19). Serum phosphorus reduction from baseline to the end of stage 1 in the overall SFOH group (least squares [LS] mean ± standard error [SE]) was - 0.488 ± 0.186 mg/dL; p = 0.011 (post hoc analysis). Significant reductions in serum phosphorus were observed in subjects aged ≥ 12 to ≤ 18 years (LS mean ± SE - 0.460 ± 0.195 mg/dL; p = 0.024) and subjects with serum phosphorus above age-related normal ranges at baseline (LS mean ± SE - 0.942 ± 0.246 mg/dL; p = 0.005). Similar proportions of subjects reported ≥ 1 TEAE in the SFOH (75.8%) and CaAc (73.7%) groups. Withdrawal due to TEAEs was more common with CaAc (31.6%) than with SFOH (18.2%). CONCLUSIONS: SFOH effectively managed serum phosphorus in pediatric patients with a low pill burden and a safety profile consistent with that reported in adult patients.

Recurrent computations for visual pattern completion.

Making inferences from partial information constitutes a critical aspect of cognition. During visual perception, pattern completion enables recognition of poorly visible or occluded objects. We combined psychophysics, physiology, and computational models to test the hypothesis that pattern completion is implemented by recurrent computations and present three pieces of evidence that are consistent with this hypothesis. First, subjects robustly recognized objects even when they were rendered <15% visible, but recognition was largely impaired when processing was interrupted by backward masking. Second, invasive physiological responses along the human ventral cortex exhibited visually selective responses to partially visible objects that were delayed compared with whole objects, suggesting the need for additional computations. These physiological delays were correlated with the effects of backward masking. Third, state-of-the-art feed-forward computational architectures were not robust to partial visibility. However, recognition performance was recovered when the model was augmented with attractor-based recurrent connectivity. The recurrent model was able to predict which images of heavily occluded objects were easier or harder for humans to recognize, could capture the effect of introducing a backward mask on recognition behavior, and was consistent with the physiological delays along the human ventral visual stream. These results provide a strong argument of plausibility for the role of recurrent computations in making visual inferences from partial information.

Waymarking in Social Robots: Environment Signaling Using Human-Robot Interaction.

Travellers use the term waymarking to define the action of posting signs, or waymarks, along a route. These marks are intended to be points of reference during navigation for the environment. In this research, we will define waymarking as the skill of a robot to signal the environment or generate information to facilitate localization and navigation, both for its own use and for other robots as well. We present an automated environment signaling system using human-robot interaction and radio frequency identification (RFID) technology. The goal is for the robot, through human-robot interaction, to obtain information from the environment and use this information to carry out the signaling or waymarking process. HRI will play a key role in the signaling process since this type of communication makes it possible to exchange more specific and enriching information. The robot uses common phrases such as "Where am I?" and "Where can I go?", just as we humans do when we ask other people for information about the environment. It is also possible to guide the robot and "show" it the environment to carry out the task of writing the signs. The robot will use the information received to create, update, or improve the navigation data in the RFID signals. In this paper, the signaling process will be described, how the robot acquires the information for signals, writing and updating process and finally, the implementation and integration in a real social robot in a real indoor environment.

Untangling the Cooperative Role of Nuclear Receptors in Cardiovascular Physiology and Disease.

The heart is the first organ to acquire its physiological function during development, enabling it to supply the organism with oxygen and nutrients. Given this early commitment, cardiomyocytes were traditionally considered transcriptionally stable cells fully committed to contractile function. However, growing evidence suggests that the maintenance of cardiac function in health and disease depends on transcriptional and epigenetic regulation. Several studies have revealed that the complex transcriptional alterations underlying cardiovascular disease (CVD) manifestations such as myocardial infarction and hypertrophy is mediated by cardiac retinoid X receptors (RXR) and their partners. RXRs are members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors and drive essential biological processes such as ion handling, mitochondrial biogenesis, and glucose and lipid metabolism. RXRs are thus attractive molecular targets for the development of effective pharmacological strategies for CVD treatment and prevention. In this review, we summarize current knowledge of RXR partnership biology in cardiac homeostasis and disease, providing an up-to-date view of the molecular mechanisms and cellular pathways that sustain cardiomyocyte physiology.

Current clinical and research fluid biomarkers to aid risk stratification of pancreatic cystic lesions.

Pancreatic cystic lesions (PCL) are composed of a heterogeneous group of entities that are increasingly diagnosed, generally as incidental findings in asymptomatic patients. In conjunction with this growing incidence, the potential for malignant transformation of mucin-producing cysts makes PCL a challenging clinical conundrum for the clinician, patient, and healthcare system. Cyst characterization based on morphology is often difficult and inaccurate. Therefore, several intracystic fluid biomarkers have been evaluated as ancillary testing to enhance the difficult balance between sparing a patient from an unnecessary high-risk pancreatic surgery and missing the opportunity to prevent or diagnose pancreatic adenocarcinoma at an early disease stage. There are two questions that are key to guide the care of patients with PCL: 1) is it a non-mucinous cyst that does not require any follow-up? and 2) if mucinous, does the cyst harbor advanced neoplasia (high-grade dysplasia or invasive carcinoma) that requires surgical resection, or is it a low-risk lesion that will benefit from a surveillance program? The purpose of this review is to give a general and practical overview of the different cyst fluid biomarkers that have been studied to address these specific questions, from classic biochemical markers such as carcinoembryonic antigen to novel genetic and epigenetic markers such as microRNA or intracystic bacterial DNA.