A machine learning approach for single cell interphase cell cycle staging

The cell nucleus is a tightly regulated organelle and its architectural structure is dynamically orchestrated to maintain normal cell function. Indeed, fluctuations in nuclear size and shape are known to occur during the cell cycle and alterations in nuclear morphology are also hallmarks of many diseases including cancer. Regrettably, automated reliable tools for cell cycle staging at single cell level using in situ images are still limited. It is therefore urgent to establish accurate strategies combining bioimaging with high-content image analysis for a bona fide classification. In this study we developed a supervised machine learning method for interphase cell cycle staging of individual adherent cells using in situ fluorescence images of nuclei stained with DAPI. A Support Vector Machine (SVM) classifier operated over normalized nuclear features using more than 3500 DAPI stained nuclei. Molecular ground truth labels were obtained by automatic image processing using fluorescent ubiquitination-based cell cycle indicator (Fucci) technology. An average F1-Score of 87.7% was achieved with this framework. Furthermore, the method was validated on distinct cell types reaching recall values higher than 89%. Our method is a robust approach to identify cells in G1 or S/G2 at the individual level, with implications in research and clinical applications.This work was supported by FEDER funds through the Operational Programme for Competitiveness Factors (COMPETE 2020), Programa Operacional de Competitividade e Internacionalização (POCI), Programa Opera-cional Regional do Norte (Norte 2020) and by National Funds through the Portuguese Foundation for Science and Technology (FCT), under the projects PTDC/BBB-IMG/0283/2014, PTDC/BTM-SAL/30383/2017, LARSyS-UIDB/50009/2020, LARSyS-UID/EEA/50009/2019, NORTE-01-0145-FEDER-000029 and doctoral grant SFRH/ BD/114687/2016. The authors acknowledge the American Association of Patients with Hereditary Gastric Cancer “No Stomach for Cancer” for funding Seruca’s research and the support of the i3S Scientific Platform Advanced Light Microscopy, member of the PPBI (PPBI-POCI-01-0145-FEDER-022122)

Diffusion-weighted MR imaging findings in an isolated abscess of the clivus

We report the finding of restricted diffusion in an isolated abscess of the clivus and discuss the imaging differential diagnosis, with an emphasis on the usefulness of diffusion-weighted imaging

In vivo assessment of gastrotomy closure with over-the-scope clips in an experimental model for varicocelectomy

BACKGROUND: Gastrotomy closure remains the major limiting factor for human translation of transgastric surgery; the over-the-scope clip (OTSC) system was proposed as a possibility for this purpose. Transgastric access is good for a pelvic approach, making varicocelectomy a possible indication for natural orifice transluminal endoscopic surgery (NOTES). OBJECTIVE: To evaluate the reliability of the OTSC system in vivo after transgastric testicular vessel ligation (varicocelectomy model). DESIGN: There were 3 experimental groups (5 animals in each): groups 1 and 3, gastrotomy dilation up to 18 mm, surgery was performed with a double-channel endoscope; group 2, gastrotomy dilation up to 13 mm, surgery was performed with a single-channel endoscope. SETTING: Surgical Sciences Research Domain, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal. INTERVENTIONS: Bilateral testicular vessel ligation by transgastric access. Gastrotomy closed with the largest version of OTSC system (12 mm): a single clip in groups 1 and 2, and 2 clips in group 3. Animals were monitored for 2 weeks, killed, and submitted for necropsy. MAIN OUTCOME MEASUREMENTS: Adequacy of closure and healing after the use of the OTSC system. Statistical analysis. RESULTS: Vessel ligation was easily achieved in all groups. Although differences in the complication rate did not reach statistical significance (P = .099), there was a clear tendency for a better prognosis in groups 2 and 3 than group 1. In fact, only 2 animals from group 1 had complications related to incomplete gastrotomy closure. LIMITATIONS: Small number of animals per group; nonrandomized study. CONCLUSIONS: The OTSC system was shown to be easy and efficient for gastrotomy closure in a survival experimental model of varicocelectomy, when correctly matching the gastrotomy size with the clip size and/or number

Counterfactual thinking in cooperation dynamics

Counterfactual Thinking is a human cognitive ability studied in a wide variety of domains. It captures the process of reasoning about a past event that did not occur, namely what would have happened had this event occurred, or, otherwise, to reason about an event that did occur but what would ensue had it not. Given the wide cognitive empowerment of counterfactual reasoning in the human individual, the question arises of how the presence of individuals with this capability may improve cooperation in populations of self-regarding individuals. Here we propose a mathematical model, grounded on Evolutionary Game Theory, to examine the population dynamics emerging from the interplay between counterfactual thinking and social learning (i.e., individuals that learn from the actions and success of others) whenever the individuals in the population face a collective dilemma. Our results suggest that counterfactual reasoning fosters coordination in collective action problems occurring in large populations, and has a limited impact on cooperation dilemmas in which coordination is not required. Moreover, we show that a small prevalence of individuals resorting to counterfactual thinking is enough to nudge an entire population towards highly cooperative standards.Comment: 18 page

Third-generation cholecystectomy by natural orifices: transgastric and transvesical combined approach (with video)

BACKGROUND:An isolated transgastric port has some limitations in performing transluminal endoscopic cholecystectomy. However, transvesical access to the peritoneal cavity has recently been reported to be feasible and safe.OBJECTIVE:To assess the feasibility and the technical benefits of transgastric and transvesical combined approach to overcome the limitations of isolated transgastric ports.DESIGN:We created a transgastric and transvesical combined approach to perform cholecystectomy in 7 consecutive anesthetized female pigs. The transgastric access was achieved after perforation and dilation of the gastric wall with a needle knife and with a balloon, respectively. Under cystoscopic control, an ureteral catheter, a guidewire, and a dilator of the ureteral sheath were used to place a transvesical 5-mm overtube into the peritoneal cavity. By using a gastroscope positioned transgastrically and a ureteroscope positioned transvesically, we carried out cholecystectomy in all animals.RESULTS:Establishment of transvesical and transgastric accesses took place without complications. Under a carbon dioxide pneumoperitoneum controlled by the transvesical port, gallbladder identification, cystic duct, and artery exposure were easily achieved in all cases. Transvesical gallbladder grasping and manipulation proved to be particularly valuable to enhance gastroscope-guided dissection. With the exclusion of 2 cases where mild liver-surface hemorrhage and bile leak secondary to the sliding of cystic clips occurred, all remaining cholecystectomies were carried out without incidents.LIMITATIONS:Once closure of the gastric hole proved to be unreliable when using endoclips, the animals were euthanized; necropsy was performed immediately after the surgical procedure.CONCLUSIONS:A transgastric and transvesical combined approach is feasible, and it was particularly useful to perform a cholecystectomy through exclusive natural orifices

Smart firefighters PPE: Impact of phase change materials

Considering the high level of heat and flame exposure firefighters encounter while performing their work activities, personal protective equipment (PPE) is of the utmost importance to enhance their safety. Phase change materials (PCMs) are known as advanced materials able to absorb high amounts of thermal energy, with the potential to increase the thermal performance of protective clothing. In this work, a PCM-vest was developed for the first time, and its thermal performance was evaluated. A three-stage approach was followed: (1) at a small scale in the laboratory, the effect of different encapsulated PCMs on a multilayer assembly performance was evaluated; (2) in the laboratory, the essential requirements of heat and flame tests were assessed; and (3) in a simulated urban fire, the thermal performance of three different PCM-vests (different textiles and designs) was studied. As the main conclusions, the PCMs significantly affected the heating rate of the multilayer assembly, particularly when a PCM with higher latent heat was used. In some cases, the heat transfer index (HTI) doubled by comparison with the sample without PCMs. As a drawback and as expected, the cooling time was increased. The PCM-vest sample ensured the requirements of the heat and flame tests. Through this study, the positive impact of using PCMs to enhance the heat protection of conventional PPE can be highlighted

Horizontal patterns of water temperature and salinity in an estuarine tidal channel: Ria de Aveiro

This work presents results from two complementary and interconnected approaches to study water temperature and salinity patterns in an estuarine tidal channel. This channel is one of the four main branches of the Ria de Aveiro, a shallow lagoon located in the Northwest coast of the Iberian Peninsula. Longitudinal and cross-sectional fields of water temperature and salinity were determined by spatial interpolation of field measurements. A numerical model (Mohid) was used in a 2D depth-integrated mode in order to compute water temperature and salinity patterns. The main purpose of this work was to determine the horizontal patterns of water temperature and salinity in the study area, evaluating the effects of the main forcing factors. The field results were depth-integrated and compared to numerical model results. These results obtained using extreme tidal and river runoff forcing, are also presented. The field results reveal that, when the river flow is weak, the tidal intrusion is the main forcing mechanism, generating saline and thermal fronts which migrate with the neap/spring tidal cycle. When the river flow increases, the influence of the freshwater extends almost as far as the mouth of the lagoon and vertical stratification is established. Results of numerical modelling reveal that the implemented model reproduces quite well the observed horizontal patterns. The model was also used to study the hydrology of the study area under extreme forcing conditions. When the model is forced with a low river flow (1 m3 s−1) the results confirm that the hydrology is tidally dominated. When the model is forced with a high river flow (1,000 m3 s−1) the hydrology is dominated by freshwater, as would be expected in such an area

Mastocytosis presenting with mast cell-mediator release-associated symptoms elicited by cyclo oxygenase inhibitors: prevalence, clinical, and laboratory features

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently avoided in mastocytosis, because of a potential increased risk for drug hypersensitivity reactions (DHRs) due to inhibition of cyclo-oxygenase (COX), subsequent depletion of prostaglandin E2 and release of leukotrienes. Objectives: Here, we aimed at determining the prevalence of mast cell (MC) mediator release symptoms triggered by NSAIDs in mastocytosis patients and the associated clinical and laboratory features of the disease. Methods: Medical records from 418 adults to 223 pediatric mastocytosis patients were retrospectively reviewed. Patients were classified according to tolerance patterns to NSAIDs and other COX inhibitors (COXi) and compared for epidemiological, clinical and laboratory findings. Results: Overall, 87% of adults and 91% of pediatric patients tolerated NSAIDs and other COXi. Among adult and pediatric patients presenting DHRs, 5% and 0% reacted to multiple NSAIDs, 4% and 0.7% were single reactors, and 3% and 8% were single reactors with known tolerance to paracetamol but unknown tolerance to other COXi, respectively. Among adults, hypersensitivity to ≥2 drugs was more frequent among females (p = 0.009), patients with prior history of anaphylaxis to triggers other than NSAIDs or other COXi and Hymenoptera venom (p = 0.009), presence of baseline flushing (p = 0.02), baseline serum tryptase ≥48 ng/ml (p = 0.005) and multilineage KIT mutation (p = 0.02). In contrast, tolerance to NSAIDs and other COXi was more frequent among males (p = 0.02), in patients with anaphylaxis caused by Hymenoptera venom (p = 0.02), among individuals who had skin lesions due to mastocytosis (p = 0.01), and in cases that had no baseline pruritus (p = 0.006). Based on these parameters, a score model was designed to stratify mastocytosis patients who have never received NSAIDs or other COXi apart from paracetamol, according to their risk of DHR. Conclusions: Our results suggest that despite the frequency of MC mediator related symptoms elicited by NSAIDs and other COXi apart from paracetamol is increased among mastocytosis patients versus the general population, it is lower than previously estimated and associated with unique disease features. Patients that tolerated NSAIDs and other COXi following disease onset should keep using them. In turn, adults with unknown tolerance to such drugs and a positive score should be challenged with a preferential/selective COX-2 inhibitor, while the remaining may be challenged with ibuprofen. © 2022 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.Funding text 1: This work was supported by grants from the Carlos III Health Institute co‐financed by the European Regional Development Fund (PI19/01166) and CIBERONC CB16/12/00400, Ministerio de Ciencia e Innovación (Madrid, Spain), Asociación Española de Mastocitosis y Enfermedades Relacionadas (AEDM 2019), Fondos de Investigación para Enfermedades Raras del Ministerio de Sanidad, Servicios Sociales e Igualdad (Madrid, Spain). ; Funding text 2: This work was supported by grants from the Carlos III Health Institute co-financed by the European Regional Development Fund (PI19/01166) and CIBERONC CB16/12/00400, Ministerio de Ciencia e Innovación (Madrid, Spain), Asociación Española de Mastocitosis y Enfermedades Relacionadas (AEDM 2019), Fondos de Investigación para Enfermedades Raras del Ministerio de Sanidad, Servicios Sociales e Igualdad (Madrid, Spain)