Machine Learning Streamlines the Morphometric Characterization and Multiclass Segmentation of Nuclei in Different Follicular Thyroid Lesions: Everything in a NUTSHELL.

The diagnostic assessment of thyroid nodules is hampered by the persistence of uncertainty in borderline cases and further complicated by the inclusion of noninvasive follicular tumor with papillary-like nuclear features (NIFTP) as a less aggressive alternative to papillary thyroid carcinoma (PTC). In this setting, computational methods might facilitate the diagnostic process by unmasking key nuclear characteristics of NIFTP. The main aims of this work were to (1) identify morphometric features of NIFTP and PTC that are interpretable for the human eye and (2) develop a deep learning model for multiclass segmentation as a support tool to reduce diagnostic variability. Our findings confirmed that nuclei in NIFTP and PTC share multiple characteristics, setting them apart from hyperplastic nodules (HP). The morphometric analysis identified 15 features that can be translated into nuclear alterations readily understandable by pathologists, such as a remarkable internuclear homogeneity for HP in contrast to a major complexity in the chromatin texture of NIFTP and to the peculiar pattern of nuclear texture variability of PTC. A few NIFTP cases with available next-generation sequencing data were also analyzed to initially explore the impact of RAS-related mutations on nuclear morphometry. Finally, a pixel-based deep learning model was trained and tested on whole-slide images of NIFTP, PTC, and HP cases. The model, named NUTSHELL (NUclei from Thyroid tumors Segmentation to Highlight Encapsulated Low-malignant Lesions), successfully detected and classified the majority of nuclei in all whole-slide image tiles, showing comparable results with already well-established pathology nuclear scores. NUTSHELL provides an immediate overview of NIFTP areas and can be used to detect microfoci of PTC within extensive glandular samples or identify lymph node metastases. NUTSHELL can be run inside WSInfer with an easy rendering in QuPath, thus facilitating the democratization of digital pathology.

Effect of Propofol on Heart Rate and Its Coupling to Cortical Slow Waves in Humans.

BACKGROUND: Propofol causes significant cardiovascular depression and a slowing of neurophysiological activity. However, literature on its effect on the heart rate remains mixed, and it is not known whether cortical slow waves are related to cardiac activity in propofol anesthesia. METHODS: The authors performed a secondary analysis of electrocardiographic and electroencephalographic data collected as part of a previously published study where n = 16 healthy volunteers underwent a slow infusion of propofol up to an estimated effect-site concentration of 4 µg/ml. Heart rate, heart rate variability, and individual slow electroencephalographic waves were extracted for each subject. Timing between slow-wave start and the preceding R-wave was tested against a uniform random surrogate. Heart rate data were further examined as a post hoc analysis in n = 96 members of an American Society of Anesthesiologists Physical Status II/III older clinical population collected as part of the AlphaMax trial. RESULTS: The slow propofol infusion increased the heart rate in a dose-dependent manner (mean ± SD, increase of +4.2 ± 1.5 beats/min/[µg ml-1]; P < 0.001). The effect was smaller but still significant in the older clinical population. In healthy volunteers, propofol decreased the electrocardiogram R-wave amplitude (median [25th to 75th percentile], decrease of -83 [-245 to -28] µV; P < 0.001). Heart rate variability showed a loss of high-frequency parasympathetic activity. Individual cortical slow waves were coupled to the heartbeat. Heartbeat incidence peaked about 450 ms before slow-wave onset, and mean slow-wave frequency correlated with mean heart rate. CONCLUSIONS: The authors observed a robust increase in heart rate with increasing propofol concentrations in healthy volunteers and patients. This was likely due to decreased parasympathetic cardioinhibition. Similar to non-rapid eye movement sleep, cortical slow waves are coupled to the cardiac rhythm, perhaps due to a common brainstem generator.

Ten quick tips for fuzzy logic modeling of biomedical systems.

Fuzzy logic is useful tool to describe and represent biological or medical scenarios, where often states and outcomes are not only completely true or completely false, but rather partially true or partially false. Despite its usefulness and spread, fuzzy logic modeling might easily be done in the wrong way, especially by beginners and unexperienced researchers, who might overlook some important aspects or might make common mistakes. Malpractices and pitfalls, in turn, can lead to wrong or overoptimistic, inflated results, with negative consequences to the biomedical research community trying to comprehend a particular phenomenon, or even to patients suffering from the investigated disease. To avoid common mistakes, we present here a list of quick tips for fuzzy logic modeling any biomedical scenario: some guidelines which should be taken into account by any fuzzy logic practitioner, including experts. We believe our best practices can have a strong impact in the scientific community, allowing researchers who follow them to obtain better, more reliable results and outcomes in biomedical contexts.

Dietary omega-3 fatty acids modulate the production of platelet-derived microvesicles in an in vivo inflammatory arthritis model.

PURPOSE: The aim of this study was to investigate the effects of different ω-3 polyunsaturated fatty acid (PUFA) enriched diets, including a novel renewable plant source of ω-3 fatty acids (Buglossoides arvensis), on the development and progression of rheumatoid arthritis (RA). METHODS: RA was induced in mice consuming experimental diets using the K/BxN model. The experimental diets consisted of either a western control diet (control), diets containing B. arvensis oil or fish oil. The effects of the diets on platelets, platelet microvesicles (PMVs), and inflammatory markers such as clinical index, ankle thickness and cytokine/chemokine release were measured. RESULTS: While ω-3 PUFA-enriched diets did not prevent the development of arthritis in the K/BxN model, a significant decrease in ankle swelling was observed compared to the control group. Platelets isolated from mice consuming either low content of B. arvensis oil or fish oil diets exhibited significantly decreased PMVs production compared to mice consuming the control diet. CONCLUSION: Our study provides insight into the contribution of ω-3 PUFA supplementation in modulating the pro-inflammatory phenotype of platelets in RA pathology. Furthermore, our study suggests that low concentrations of dietary B. arvensis oil may have similar anti-inflammatory potential seen with dietary fish oil supplementation.

Preliminary Validation of Measures of Experienced, Perceived, and Internalized Stigma Among Adults Who Are d/Deaf or Hard of Hearing in the United States and Ghana.

OBJECTIVES: In this article, we examine the psychometric performance of 3 scales measuring experienced, perceived, and internalized d/Deaf or hard of hearing (d/DHH) stigma among adult (18 and older) populations of individuals who are d/DHH, including those who have been d/DHH since before they developed language (lifelong) and those who became d/DHH after they developed language (acquired) in the United States and Ghana. DESIGN: The preliminary validation study took place in the Greater Accra and Eastern regions of Ghana and across the United States. In the United States, all data were collected online via self-administered surveys in English. In Ghana, trained interviewers who are d/DHH and fluent in Ghanaian Sign Language conducted interviews with participants who are lifelong d/DHH using a video survey. Ghanaian participants with acquired d/DHH status were surveyed by trained hearing interviewers. We calculated polychoric correlation matrices between the measures to remove redundant and unrelated items and used exploratory factor analysis to create the final scales. We also tested the association between the factor scores and a simple summing method for calculating the scale. RESULTS: The study sample included people who have been d/DHH since before they developed language (Ghana: n = 171, United States n = 100) and people who became d/DHH after they developed language (Ghana: n = 174, United States: n = 219). The final experienced, perceived, and internalized scales included six, seven, and five items, respectively. All three scales performed well as unidimensional measures across all four samples. Across the four samples, the experienced, perceived, and internalized stigma scales yielded ordinal αs ranging from 0.725 to 0.947, 0.856 to 0.935, and 0.856 to 0.935, respectively. It would be acceptable to operationalize all stigma scales as sum-of-item scores. CONCLUSIONS: The scales performed well and appear to provide a valid means of measuring different types of stigma among diverse groups of people who are d/DHH. Future work should refine and validate these scales in additional contexts.

A tandem activity-based sensing and labeling strategy enables imaging of transcellular hydrogen peroxide signaling.

Reactive oxygen species (ROS) like hydrogen peroxide (H2O2) are transient species that have broad actions in signaling and stress, but spatioanatomical understanding of their biology remains insufficient. Here, we report a tandem activity-based sensing and labeling strategy for H2O2 imaging that enables capture and permanent recording of localized H2O2 fluxes. Peroxy Green-1 Fluoromethyl (PG1-FM) is a diffusible small-molecule probe that senses H2O2 by a boronate oxidation reaction to trigger dual release and covalent labeling of a fluorescent product, thus preserving spatial information on local H2O2 changes. This unique reagent enables visualization of transcellular redox signaling in a microglia-neuron coculture cell model, where selective activation of microglia for ROS production increases H2O2 in nearby neurons. In addition to identifying ROS-mediated cell-to-cell communication, this work provides a starting point for the design of chemical probes that can achieve high spatial fidelity by combining activity-based sensing and labeling strategies.

Effect of preparation design on fracture strength of compromised molars restored with direct composite resin restorations: An in vitro and finite element analysis study.

STATEMENT OF PROBLEM: More data are needed on the influence of preparation design on the fracture strength, failure type, repairability, and polymerization-induced cracks of molar teeth restored with direct composite resin restorations. PURPOSE: This in vitro and finite element analysis study investigated the effect of different preparation designs on fracture strength, failure type, repairability, tooth deformation, and the formation of polymerization-induced cracks of compromised molars restored with direct composite resin restorations. MATERIAL AND METHODS: Human molars (n=64) were randomly assigned to 4 different preparation designs: undermined inlay (UI), extended inlay (EI), restricted overlay (RO), and extended overlay (EO). The teeth were restored using direct composite resin and subjected to artificial thermomechanical aging in a mastication simulator, followed by load-to-failure testing. Three-dimensional (3D) finite element analysis was conducted to assess tooth deformation. Polymerization-induced cracks were evaluated using optical microscopy and transillumination. The fracture strength data were analyzed using a Kruskal-Wallis test, while the failure mode, repairability, and polymerization cracks were analyzed using the Fisher exact test (α=.05). RESULTS: All specimens withstood thermomechanical aging, and no statistically significant difference in fracture strength was observed among the 4 preparation designs (P>.05). The finite element analysis showed differences in tooth deformation, but no correlation was observed with in vitro fracture resistance. The RO and EO groups presented significantly more destructive failures compared with the UI and EI groups (P<.01). The RO group had significantly fewer repairable failures than the UI and EI groups (P=.024). A correlation was found between higher frequencies of repairability and higher tooth deformation. A significant correlation between the increase in microfractures and preparation design was observed (P<.01), with the UI group exhibiting a higher increase in microfracture size compared with the EO group (P<.05). CONCLUSIONS: No influence of preparation design on the fracture strength of compromised molars restored with direct composite resin restorations was evident in this study, but the failure mode of cusp coverage restorations was more destructive and often less repairable. The finite element analysis showed more tooth deformation in inlay preparations, with lower stresses within the root, leading to more reparable fractures. Since cusp coverage direct composite resin restorations fractured in a more destructive manner, this study suggests that even a tooth with undermined cusps should be restored without cusp coverage.

Enhancement of EDDS-photo-Fenton process with plant-based coagulants for winery wastewater management.

To achieve an efficient remediation of a winery wastewater (WW), it was studied a physical-chemical process (coagulation-flocculation-decantation - CFD) involving plant-based coagulants (PBC) with advanced oxidation processes (AOPs), aiming to achieve the Portuguese legal limits. Initially, one invasive (Acacia dealbata) and three native species (Quercus ilex, Platanus x acerifólia and Tanacetum vulgare) were collected and used as plant-based coagulants (PBCs). The combination of Platanus acerifólia (P.a.) seeds with polyvinylpolypyrrolidone (PVPP) achieved high turbidity (97.3%) and chemical oxygen demand (COD = 48.2%) removals, from raw WW, with [PBC] = 0.1 g/L, [PVPP] = 5 mg/L, pH = 3.0, fast mix = 150 rpm/3 min, slow mix = 20 rpm/20 min, sedimentation time = 12 h. Different AOPs were studied to treat raw WW, with photo-Fenton process revealing the highest COD efficiency (88.0%). To enhance the capabilities of photo-Fenton, ethylenediamine-N,N'-disuccinic acid trisodium salt (EDDS) was assessed as a chelation agent, reducing iron precipitation. The pre-treatment of WW by PBCs followed by EDDS/photo-Fenton (pH = 6.0, [H2O2] = 175 mM, [Fe2+] = 5 mM, [EDDS] = 1 mM, T = 298 K, time = 240 min) increased the COD removal, whatever the radiation source applied (UV-C, UV-A and solar). Among the different processes, the combined P. a. seeds and UV-C/EDDS/Fenton allowed increase the WW biodegradability from 0.26 to 0.46, and achieved a COD removal of 95.7%, reaching the Portuguese legal limits. As final remark, the synergy of PBCs and EDDS/photo-Fenton is considered effective and sustainable process for raw WW remediation and water reuse.

Maxillary overdentures supported by four or six implants in the anterior region: 10-year randomized controlled trial results.

AIM: To evaluate bar-supported maxillary implant overdenture treatment when supported by either four or six implants after 10 years. MATERIALS AND METHODS: Edentulous subjects with maxillary denture complaints and ample bone volume to facilitate implants in the anterior region of the maxilla were planned for implant overdenture treatment, randomized to receive either four implants (n = 25) or six implants (n = 25) and subsequently evaluated after 10 years of function. Outcome variables included peri-implant bone-level changes, implant and overdenture survival, complications, presence of plaque, calculus and bleeding, degree of peri-implant inflammation, probing depth and patient satisfaction. Differences between the groups and between evaluation periods were tested with a Student's t-test. RESULTS: Fourteen patients with totally 72 implants were lost to follow-up. Two patients from the six-implant group experienced implant loss (four implants), resulting in 96.1% implant survival in this group versus 100% survival in the four-implant group. Clinical, radiographical and patient-reported outcome measures did not differ statistically significant between the two groups. Patients from both groups were generally quite satisfied with the result after 10 years. CONCLUSIONS: Similar and favourable outcomes are seen in bar-supported maxillary overdentures on either four or six anteriorly placed implants after a 10-year evaluation period.

Gastrointestinal symptoms in patients with isolated oligodontia and a Wnt gene mutation.

OBJECTIVE: Since Wnt signaling plays an important role in both tooth agenesis and altered intestine homeostasis, the aim was to compare gastrointestinal symptoms in patients with isolated oligodontia caused by a Wnt pathway gene mutation and controls. METHODS: A case-control study was designed to compare self-reported gastrointestinal symptoms among patients with isolated oligodontia, caused by a Wnt signaling gene mutation, and fully dentate controls. The Gastrointestinal Symptom Rating Scale (GSRS) was used to assess gastrointestinal symptoms. Prevalence and severity of gastrointestinal symptoms among patients and age- and gender-matched controls were evaluated. RESULTS: Twenty patients with isolated oligodontia and a pathogenic variant in the wnt pathway genes WNT10A, LRP6, or PAX9 participated. The prevalence of gastrointestinal symptoms was higher in the oligodontia patients compared to their controls (Χ2 (1) = 87.33, p = .008). Mean GSRS total scores (p = .011) and domain scores for "abdominal pain" (p = .022), "reflux" (p = .003) and constipation (p = .030) were higher for these oligodontia patients compared to their controls. CONCLUSION: Gastrointestinal symptoms are more prevalent and more severe in patients with isolated oligodontia and a deficiency in a Wnt pathway-related gene, when compared to controls without tooth agenesis.

Enhancing the Extinction Efficiency and Plasmonic Response of Bimetallic Nanoparticles of Au-Ag in Robust Thin Film Sensing Platforms.

The extinction efficiency of noble metal nanoparticles (NPs), namely gold (Au) and silver (Ag), are dependent on their size and surrounding dielectric. Exploiting the Localized Surface Plasmon Resonance (LSPR) phenomenon, the composition and structure of the NPs might be tailored to achieve a configuration that optimizes their response (sensitivity) to environmental changes. This can be done by preparing a bimetallic system, benefiting from the chemical stability of Au NPs and the higher scattering efficiency of Ag NPs. To enhance the LSPR sensing robustness, incorporating solid supports in the form of nanocomposite thin films is a suitable alternative. In this context, the NPs composed of gold (Au), silver (Ag), and their mixture in bimetallic Au-Ag NPs, were grown in a titanium dioxide (TiO2) matrix using reactive DC magnetron sputtering. Thermal treatment at different temperatures (up to 700 °C) tuned the LSPR response of the films and, consequently, their sensitivity. Notably, the bimetallic film with Au/Ag atomic ratio 1 exhibited the highest refractive index sensitivity (RIS), with a value of 181 nm/RIU, almost one order of magnitude higher than monometallic Au-TiO2. The nanostructural analysis revealed a wide NP size distribution of bimetallic NPs with an average size of 31 nm, covering about 20% of the overall surface area. These findings underscore the significant potential of bimetallic film systems, namely AuAg-TiO2, in LSPR sensing enhancement.

Combined organic coagulants and photocatalytic processes for winery wastewater treatment.

Due to the consumers demand for quality wines, washing and disinfection operations are necessary in wine productions, leading to the generation of large volumes of winery wastewater (WW) with a high organic content which has the potential to cause irreversible environmental impacts. The aim and novelty of this work is the production of natural organic coagulants (NOCs) to be applied in coagulation-flocculation-decantation (CFD) process. To complement this treatment process, it is also aimed the performed a photo-Fenton process, combining hydrogen peroxide (H2O2) and potassium persulfate (KPS). The Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) showed that NOCs are carbon-based materials with adsorption capacity. Under the best operational conditions, NOCs achieved a turbidity removal between 86.2 and 98.9%, a total suspended solids (TSS) removal ranging between 85.0 and 94.9% and a dissolved organic carbon (DOC) removal ranging between 14.1 and 44.9%. To degrade the DOC present in the WW, different advanced oxidation processes (AOPs) were tested. Results showed that KPS-photo-Fenton, under the best operational conditions [Fe2+] = 2.5 mM, [KPS] = 1.0 mM, pH = 3.0, radiation UV-C mercury lamp (254 nm), agitation 350 rpm, temperature 298 K, reaction time 240 min achieved a DOC removal of 91.2 and 96.8%, with a H2O2 consumption of 156.9 and 199.0 mM, respectively for red and white WW. With application of combined CFD-KPS-photo-Fenton process, it was observed an increase of DOC removal with lower H2O2 consumptions. The energy consumption of the photosystem was evaluated by application of electric energy per mass (EEM). The application of KPS-photo-Fenton process achieved an EEM of 0.308 and 0.0309 kWh/g/L DOC, with a cost of 2.05 and 2.59 €/g/L DOC respectively for red and white WW. The combination of CFD-KPS-photo-Fenton decreased significantly the costs of treatment and the treated wastewater achieved the Portuguese legal values for wastewater discharge. This work shows that NOCs are a promising technology that can be an alternative to traditional metal salts, the combination of sulfate radicals with hydroxyl radicals can achieve high DOC removal and the combination of CFD with KPS-photo-Fenton process can decrease the operational costs.

Clinical performance of direct composite resin versus indirect restorations on endodontically treated posterior teeth: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: High-level evidence concerning the restoration of endodontically treated posterior teeth by means of direct composite resin or indirect restorations is lacking. PURPOSE: The purpose of this systematic review and meta-analysis was to analyze the current literature on the direct and indirect restoration of endodontically treated posterior teeth. MATERIAL AND METHODS: Databases MEDLINE, CENTRAL, and EMBASE were screened. Risk of bias was assessed by using the ROB2 tool for RCTs and the ROBINS-I tool for prospective and retrospective clinical studies. Randomized clinical trials (RCTs) and prospective and retrospective studies comparing direct composite resin and indirect restorations on endodontically treated posterior teeth were included. Outcomes were tooth and restoration survival. A meta-analysis was conducted for tooth retention and restorative success. RESULTS: Twenty-two studies were included (2 RCTs, 3 prospective, and 17 retrospective). Over the short term (2.5 to 3 years), low-quality evidence suggested no difference in tooth survival. For the prospective and retrospective clinical trials, the overall risk of bias was serious to critical from the risk of confounding because of a difference in restorative indication: Direct restorations were fabricated when one marginal ridge remained or when tooth prognosis was unfavorable. For short-term restorative success, low-quality evidence suggested no difference between the direct and indirect restorations. CONCLUSIONS: For the short term (2.5 to 3 years), low-quality evidence suggests no difference in tooth survival or restoration quality. To assess the influence of the type of restoration on the survival and restorative success of endodontically treated posterior teeth, clinical trials that control for the amount of coronal tooth tissue and other baseline characteristics are needed.

A 32-month evaluation of lithium disilicate cantilever resin-bonded fixed dental prostheses to replace a missing maxillary incisor.

STATEMENT OF PROBLEM: The absence of a tooth in the esthetic zone can cause emotional and social distress. The use of minimally invasive and visually pleasing lithium disilicate resin-bonded fixed dental prostheses (RBFDPs) may be a suitable option for replacing a missing maxillary incisor. However, the available literature on lithium disilicate cantilever RBFDPs is limited. PURPOSE: This retrospective multicenter study assessed the survival and success rates of lithium disilicate anterior cantilever RBFDPs with an average follow-up period of 3 years up to 9 years. MATERIAL AND METHODS: RBFDPs delivered by 3 operators were clinically assessed for survival using a modified United States Public Health Service criteria list. The incidence density was determined for each criterion and operator. The standard error and 95% confidence interval were calculated for each incidence density difference (α=.05 for all analyses). RESULTS: A total of 108 RBFDPs were evaluated after a mean period of 32.45 months, ranging from 14 days to 111 months. None of the restorations exhibited failure, carious lesions, or fractures during the follow-up period. The primary reasons for reduced success rates were inflammation of the surrounding soft tissues and discoloration, with incidence densities of 0.074 and 0.057 per year, respectively. Significant differences were observed among RBFDPs from different operators for criteria that included adaptation, color match, marginal adaptation, polishability, surface staining, gingival health, and antagonist wear. CONCLUSIONS: Cantilever lithium disilicate RBFDPs appear to be suitable for short-term restoration. RBFDPs exhibited visible changes after short-term follow-up. However, these changes did not result in failure.

Organometallic S-arylation Reagents for Rapid PEGylation of Biomolecules.

Bioconjugation techniques for biomolecule-polymer conjugation are numerous; however, slow kinetics and steric challenges generally necessitate excess reagents or long reaction times. Organometallic transformations are known to circumvent these issues; yet, harsh reaction conditions, incompatibility in aqueous media, and substrate promiscuity often limit their use in a biological context. The work reported herein demonstrates a facile and benign organometallic Au(III) S-arylation approach that enables the synthesis of poly(ethylene glycol) monomethyl ether (mPEG)-protein conjugates with high efficiency. Isolable and bench-stable 2, 5, and 10 kDa mPEG-Au(III) reagents were synthesized via oxidative addition into terminal aryl iodide substituents installed on mPEG substrates with a (Me-DalPhos)Au(I)Cl precursor. Reaction of the isolable mPEG-Au(III) oxidative addition complexes with a cysteine thiol on a biomolecule resulted in facile and selective cysteine arylation chemistry, forging covalent S-aryl linkages and affording the mPEG-biomolecule conjugates. Notably, low polymer reagent loadings were used to achieve near quantitative conversion at room temperature in 1 min due to the rapid kinetics and high chemoselectivity of this Au-based bioconjugation approach. Therefore, this work represents an important addition to the protein-polymer conjugation chemical toolbox.

Instantaneous wave-free ratio-guided revascularization of nonculprit lesions in STEMI patients with multivessel coronary disease: The WAVE registry.

BACKGROUND: Complete revascularization (CR) of nonculprit lesions (NCL) is strongly recommended in patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD), but no definitive evidence is available regarding which diagnostic strategy should be preferred. Instantaneous wave-free ratio (iFR) has never been investigated in this setting. We aimed to describe clinical outcomes of a cohort of patients undergoing iFR-guided CR. METHODS: Following primary percutaneous coronary intervention (PCI), consecutive patients with STEMI and intermediate NCL were enrolled and destinated to an iFR-guided CR. NCL with iFR ≤ 0.89 underwent PCI while NCL with iFR > 0.89 were deferred. The primary endpoint was NC target lesion failure (NC-TLF) and the secondary endpoint was major adverse cardiovascular events (MACE), at 1-year follow-up. RESULTS: Overall, 209 patients were enrolled (ischemic iFR = 83; nonischemic iFR = 126). Patients with ischemic iFR showed a higher prevalence of traditional cardiovascular risk factors and angiographically determined three-vessel disease. In the entire cohort, NC-TLF and MACE occurred in 6.7% and 10.5% of patients, respectively. Compared to the deferred group, patients with ischemic iFR experienced significantly higher rates of both NC-TLF (3.2% vs. 12.1%; p = 0.021) and MACE (7.1% vs. 16.9%; p = 0.041). These results were mostly driven by increased rates of NC-TLF PCI and further revascularizations in this latter group, while no differences were evident in terms of nonfatal myocardial infarction or death. At multivariable analysis, the strongest predictor of MACE was symptom onset to balloon time (HR = 1.17 [95% CI: 1.04-1.31], p = 0.008). CONCLUSIONS: In our study enrolling STEMI patients with MVD, iFR assessment was feasible and safe. PCI-deferring according to iFR evaluation of NCL was associated with low rates of adverse events. Further randomized studies are needed to investigate the effectiveness of iFR-guided revascularization compared to current practice in this setting.

Brain Complexities and Anesthesia: Their Meaning and Measurement.

SUMMARY: A complex system is often associated with emergence of new phenomena from the interactions between the system's components. General anesthesia reduces brain complexity and so inhibits the emergence of consciousness. An understanding of complexity is necessary for the interpretation of brain monitoring algorithms. Complexity indices capture the "difficulty" of understanding brain activity over time and/or space. Complexity-entropy plots reveal the types of complexity indices and their balance of randomness and structure. Lempel-Ziv complexity is a common index of temporal complexity for single-channel electroencephalogram containing both power spectral and nonlinear effects, revealed by phase-randomized surrogate data. Computing spatial complexities involves forming a connectivity matrix and calculating the complexity of connectivity patterns. Spatiotemporal complexity can be estimated in multiple ways including temporal or spatial concatenation, estimation of state switching, or integrated information. This article illustrates the concept and application of various complexities by providing working examples; a website with interactive demonstrations has also been created.

FiCoS: A fine-grained and coarse-grained GPU-powered deterministic simulator for biochemical networks.

Mathematical models of biochemical networks can largely facilitate the comprehension of the mechanisms at the basis of cellular processes, as well as the formulation of hypotheses that can be tested by means of targeted laboratory experiments. However, two issues might hamper the achievement of fruitful outcomes. On the one hand, detailed mechanistic models can involve hundreds or thousands of molecular species and their intermediate complexes, as well as hundreds or thousands of chemical reactions, a situation generally occurring in rule-based modeling. On the other hand, the computational analysis of a model typically requires the execution of a large number of simulations for its calibration, or to test the effect of perturbations. As a consequence, the computational capabilities of modern Central Processing Units can be easily overtaken, possibly making the modeling of biochemical networks a worthless or ineffective effort. To the aim of overcoming the limitations of the current state-of-the-art simulation approaches, we present in this paper FiCoS, a novel "black-box" deterministic simulator that effectively realizes both a fine-grained and a coarse-grained parallelization on Graphics Processing Units. In particular, FiCoS exploits two different integration methods, namely, the Dormand-Prince and the Radau IIA, to efficiently solve both non-stiff and stiff systems of coupled Ordinary Differential Equations. We tested the performance of FiCoS against different deterministic simulators, by considering models of increasing size and by running analyses with increasing computational demands. FiCoS was able to dramatically speedup the computations up to 855×, showing to be a promising solution for the simulation and analysis of large-scale models of complex biological processes.

Maxillary bar overdentures on four or six posterior implants: 10-year results from a randomized clinical trial.

OBJECTIVE: To compare clinical and patient-reported outcomes when providing maxillary overdentures on four and six splinted implants placed in the posterior region during a 10-year follow-up period. MATERIALS AND METHODS: Sixty-six edentulous participants with functional maxillary denture complaints and insufficient bone volume to allow implant placement were scheduled for a bone augmentation procedure. After healing, participants were randomized to receive either four or six implants in the posterior maxilla. After 3 months of osseointegration, a bar overdenture was constructed. Implant survival, overdenture survival, clinical scores, peri-implant bone height changes, and patient satisfaction were assessed. RESULTS: Forty-six participants completed the 10-year follow-up. Implant survival was 100% in the 4-implant group and 96.7% in the 6-implant group. Seven new overdentures were made in the 4-implant group and 12 new overdentures were made in the 6-implant group due to excessive wear of the denture base and teeth. Clinical parameters did not differ significantly between groups. Mean marginal bone loss compared to baseline was 0.41 ± 0.37 mm in the 4-implant group and 0.70 ± 1.07 mm in the 6-implant group. Overall, patient satisfaction improved significantly, but did not differ between groups. CONCLUSION: From this 10-year follow-up trial, it was concluded that bar maxillary overdentures on four or six implants in the posterior region of an augmented maxilla resulted in a comparable treatment outcome with high implant survival, limited loss of peri-implant marginal bone, and high patients' satisfaction. (Clinical trial registration number: NTR9729).

Scratching your tête over language-switched idioms: Evidence from eye-movement measures of reading.

Idioms are semantically non-compositional multiword units whose meanings often go beyond literal interpretations of their component words (e.g., break the ice, kick the bucket, spill the beans). According to hybrid models of idiom processing, idioms are subject to both direct retrieval from the lexicon in early stages of processing, and word-by-word compositional reanalysis in later stages of comprehension. However, a less clear aspect is how disrupting an idiom's canonical form, and thus its direct retrieval, impacts the time course of comprehension. In this eye-tracking reading study, healthy English-French bilingual adults with English as their dominant language read sentences containing English idioms in their canonical form (e.g., break the ice), or in a switched form where the phrase-final noun was translated into French (e.g., break the glace). Thus, within this manipulation, momentary language switches modified the canonical form of idioms, while at the same time minimally altering the semantics of their component words, thus nudging readers towards a compositional processing route. Analyses of eye-movement data revealed switching costs in longer reading times at early (but not late) processing stages for idioms compared to matched literal phrases. Interestingly, the cost of language switching was attenuated by the availability of a translationally equivalent idiom in the non-target language (French, e.g., briser la glace). Taken together, these results suggest that direct retrieval is the preferential route in the comprehension of idioms' canonical forms, which acts as an effective repair strategy by the language-processing system when recovering the underlying form of modified idioms.