Thermal refugia reinforce macroalgal resilience against climate change in the southeastern Bay of Biscay.

Rising global temperatures present unprecedented challenges to marine ecosystems, demanding a profound understanding of their ecological dynamics for effective conservation strategies. Over a comprehensive macroalgal assessment spanning three decades, we investigated the spatiotemporal evolution of shallow-water benthic communities in the southern Bay of Biscay, uncovering climate-resilient areas amidst the ongoing phase shift in the region. Our investigation identified seven locations serving as potential climate refugia, where cold-affinity, canopy-forming macroalgal species persisted and community structure was similar to that observed in 1991. We unveiled a clear association between the emergence of these refugia, sea surface temperature (SST), and the Community Temperature Index, positioning SST as a significant driver of the observed phase shift in the region. Warming processes, defined as tropicalization (increase of warm-affinity species) and deborealization (decrease of cold-affinity species), were prominent outside refugia. In contrast, cooling processes, defined as borealization (increase of cold-affinity species) and detropicalization (decrease of warm-affinity species), prevailed inside refugia. Refugia exhibited approximately 35% lower warming processes compared to non-refuge areas. This resulted in a dominance of warm-affinity species outside refugia, contrasting with the stability observed within refugia. The persistence of canopy-forming species in refuge areas significantly contributed to maintaining ecosystem diversity and stability. These findings underscored the pivotal role of climate refugia in mitigating climate-driven impacts. Prioritizing the protection and restoration of these refugia can foster resilience and ensure the preservation of biodiversity for future generations. Our study illustrates the importance of refining our understanding of how marine ecosystems respond to climate change, offering actionable insights essential for informed conservation strategies and sustainable environmental management.

Paradoxical interatrial conduction recovery after cavotricuspid isthmus ablation: A case report.

We present a case of a patient with advanced interatrial block who was admitted for cavotricuspid isthmus ablation as treatment of typical atrial flutter. A baseline advanced interatrial block pattern turned into partial interatrial block pattern and prolonged PR interval after the procedure. We discuss the mechanism underlying that change.

Evaluation of Malware Classification Models for Heterogeneous Data.

Machine learning (ML) has found widespread application in various domains. Additionally, ML-based techniques have been employed to address security issues in technology, with numerous studies showcasing their potential and effectiveness in tackling security problems. Over the years, ML methods for identifying malicious software have been developed across various security domains. However, recent research has highlighted the susceptibility of ML models to small input perturbations, known as adversarial examples, which can significantly alter model predictions. While prior studies on adversarial examples primarily focused on ML models for image processing, they have progressively extended to other applications, including security. Interestingly, adversarial attacks have proven to be particularly effective in the realm of malware classification. This study aims to explore the transparency of malware classification and develop an explanation method for malware classifiers. The challenge at hand is more complex than those associated with explainable AI for homogeneous data due to the intricate data structure of malware compared to traditional image datasets. The research revealed that existing explanations fall short in interpreting heterogeneous data. Our employed methods demonstrated that current malware detectors, despite high classification accuracy, may provide a misleading sense of security and measuring classification accuracy is insufficient for validating detectors.

Electrophysiological characteristics of epicardial to endocardial breakthrough in intractable cavotricuspid isthmus-dependent atrial flutter.

BACKGROUND: Epicardial to endocardial breakthrough (EEB) exists widely in atrial arrhythmia and is a cause for intractable cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL). This study aimed to investigate the electrophysiological features of EEB in EEB-related CTI dependent AFL. METHODS: Six patients with EEB-related CTI-dependent AFL were identified among 142 consecutive patients who underwent CTI-dependent AFL catheter ablation with an ultra-high-density, high-resolution mapping system in three institutions. Activation maps and ablation procedure were analyzed. RESULTS: A total of seven EEBs were found in six patients. Four EEBs (including three at the right atrial septum and one in paraseptal isthmus) were recorded in three patients during tachycardia. The other three EEBs were identified at the inferolateral right atrium (RA) during pacing from the coronary sinus. The conduction characteristics through the EEB-mediated structures were evaluated in three patients. Two patients only showed unidirectional conduction. Activation maps indicated that CTI-dependent AFL with EEB at the atrial septum was actually bi-atrial macro-reentrant atrial tachycardia (BiAT). Intensive ablation at the central isthmus could block CTI bidirectionally in four cases. However, ablation targeted at the inferolateral RA EEB was required in two cases. Meanwhile, local potentials at the EEB location gradually split into two components with a change in activation sequence. CONCLUSIONS: EEB is an underlying cause for intractable CTI-dependent AFL. EEB-mediated structure might show unidirectional conduction. CTI-dependent AFL with EEB at the atrial septum may represent BiAT. Intensive ablation targeting the central isthmus or EEB at the inferolateral RA could block the CTI bidirectionally.

Comparison of Five Conductivity Tensor Models and Image Reconstruction Methods Using MRI.

Imaging of the electrical conductivity distribution inside the human body has been investigated for numerous clinical applications. The conductivity tensors of biological tissue have been obtained from water diffusion tensors by applying several models, which may not cover the entire phenomenon. Recently, a new conductivity tensor imaging (CTI) method was developed through a combination of B1 mapping, and multi-b diffusion weighted imaging. In this study, we compared the most recent CTI method with the four existing models of conductivity tensors reconstruction. Two conductivity phantoms were designed to evaluate the accuracy of the models. Applied to five human brains, the conductivity tensors using the four existing models and CTI were imaged and compared with the values from the literature. The conductivity image of the phantoms by the CTI method showed relative errors between 1.10% and 5.26%. The images by the four models using DTI could not measure the effects of different ion concentrations subsequently due to prior information of the mean conductivity values. The conductivity tensor images obtained from five human brains through the CTI method were comparable to previously reported literature values. The images by the four methods using DTI were highly correlated with the diffusion tensor images, showing a coefficient of determination (R2) value of 0.65 to 1.00. However, the images by the CTI method were less correlated with the diffusion tensor images and exhibited an averaged R2 value of 0.51. The CTI method could handle the effects of different ion concentrations as well as mobilities and extracellular volume fractions by collecting and processing additional B1 map data. It is necessary to select an application-specific model taking into account the pros and cons of each model. Future studies are essential to confirm the usefulness of these conductivity tensor imaging methods in clinical applications, such as tumor characterization, EEG source imaging, and treatment planning for electrical stimulation.

Application of Maxillary Sinus Effusion Detection in Diagnosis of Drowning.

ABSTRACT: Objective To study the imaging characteristics of maxillary sinus effusion in drowned bodies, to explore its morphological characteristics and value in the diagnosis of the cause of death, and to provide objective evidence to support the study of virtual anatomy of drowning. Methods The 154 postmortem CT examination cases （31 cases of drowning, 123 cases of non-drowning） of Beijing Public Security Bureau Forensic Center in 2019 were collected. The bodies of all cases were scanned by multi-layer spiral CT before double-blind reading by clinical imaging experts. Maxillary sinus of corpses with maxillary sinus effusion in imaging findings was punctured. The detection rate of maxillary sinus effusion was calculated. The CT value and volume of maxillary sinus effusion were measured on 3D DICOM workstation. Results The detection rate of maxillary sinus effusion in the drowning was 100%, the shape was horizontal liquid level, the volume was 1.2-11.2 mL, the CT value was 6.08-19.02 Hu, with an average value of 12.85 Hu. The detection rate of maxillary sinus effusion in non-drowning was 19.51% （24/123）, the shape was wavy or irregular, and there were bubbles inside, the volume was 0.4-13.4 mL, the CT value was 23.68-77.75 Hu, with an average value of 42.08 Hu. The differences in CT value between the two groups had statistical significance. Conclusion The postmortem CT examination method can be used to observe the shape and measure the CT value of the maxillary sinus effusion in the bodies in water, which can be an auxiliary examination method for identification of drowning.

Functional analysis of Cti6 core domain responsible for recruitment of epigenetic regulators Sin3, Cyc8 and Tup1.

Mapping of effective protein domains is a demanding stride to disclose the functional relationship between regulatory complexes. Domain analysis of protein interactions is requisite for understanding the pleiotropic responses of the respective partners. Cti6 is a multifunctional regulator for which we could show recruitment of co-repressors Sin3, Cyc8 and Tup1. However, the responsible core domain tethering Cti6 to these co-repressors is poorly understood. Here, we report the pivotal domain of Cti6 that is indispensable for co-repressor recruitment. We substantiated that amino acids 450-506 of Cti6 bind PAH2 of Sin3. To analyse this Cti6-Sin3 Interaction Domain (CSID) in more detail, selected amino acids within CSID were replaced by alanine. It is revealed that hydrophobic amino acids V467, L481 and L491 L492 L493 are important for Cti6-Sin3 binding. In addition to PAH2 of Sin3, CSID also binds to tetratricopeptide repeats (TPR) of Cyc8. Indeed, we could demonstrate Cti6 recruitment to promoters of genes, such as RNR3 and SMF3, containing iron-responsive elements (IRE). Importantly, Sin3 is also recruited to these promoters but only in the presence of functional Cti6. Our findings provide novel insights toward the critical interaction domain in the co-regulator Cti6, which is a component of regulatory complexes that are closely related to chromatin architecture and the epigenetic status of genes that are regulated by pleiotropic co-repressors.

Validation of conductivity tensor imaging using giant vesicle suspensions with different ion mobilities.

BACKGROUND: Electrical conductivity of a biological tissue at low frequencies can be approximately expressed as a tensor. Noting that cross-sectional imaging of a low-frequency conductivity tensor distribution inside the human body has wide clinical applications of many bioelectromagnetic phenomena, a new conductivity tensor imaging (CTI) technique has been lately developed using an MRI scanner. Since the technique is based on a few assumptions between mobility and diffusivity of ions and water molecules, experimental validations are needed before applying it to clinical studies. METHODS: We designed two conductivity phantoms each with three compartments. The compartments were filled with electrolytes and/or giant vesicle suspensions. The giant vesicles were cell-like materials with thin insulating membranes. We controlled viscosity of the electrolytes and the giant vesicle suspensions to change ion mobility and therefore conductivity values. The conductivity values of the electrolytes and giant vesicle suspensions were measured using an impedance analyzer before CTI experiments. A 9.4-T research MRI scanner was used to reconstruct conductivity tensor images of the phantoms. RESULTS: The CTI technique successfully reconstructed conductivity tensor images of the phantoms with a voxel size of [Formula: see text]. The relative [Formula: see text] errors between the conductivity values measured by the impedance analyzer and those reconstructed by the MRI scanner was between 1.1 and 11.5. CONCLUSIONS: The accuracy of the new CTI technique was estimated to be high enough for most clinical applications. Future studies of animal models and human subjects should be pursued to show the clinical efficacy of the CTI technique.

Interactions of U24 from Roseolovirus with WW domains: canonical vs noncanonical.

U24 is a C-terminal membrane-anchored protein found in both human herpes virus type 6 and 7 (HHV-6 and HHV-7), with an N-terminal segment that is rich in prolines (PPxY motif in both HHV-6A and 7; PxxP motif in HHV-6A). Previous work has shown that U24 interacts strongly with Nedd4 WW domains, in particular, hNedd4L-WW3*. It was also shown that this interaction depends strongly on the nature of the amino acids that are upstream from the PY motif in U24. In this contribution, data was obtained from pull-downs, isothermal titration calorimetry, and NMR to further determine what modulates U24:WW domain interactions. Specifically, 3 non-canonical WW domains from human Smad ubiquitination regulatory factor (Smurf), namely hSmurf2-WW2, hSmurf2-WW3, and a tandem construct hSmurf2-WW2 + 3, were studied. Overall, the interactions between U24 and these Smurf WW domains were found to be weaker than those in U24:Nedd4 WW domain pairs, suggesting that U24 function is tightly linked to specific E3 ubiqitin ligases.

The Impact of Criminal Justice Involvement and Housing Outcomes Among Homeless Persons with Co-occurring Disorders.

The relationship between criminal justice involvement and housing among homeless persons with co-occurring disorders was examined. Program participants assisted in moving to stable housing were interviewed at baseline, six months, and discharge. Those who remained homeless at follow-up and discharge had significantly more time in jail in the past month than those who were housed. However, criminal justice involvement was not significantly related to housing status at the six month follow-up or discharge. Findings suggest that housing people with complex behavioral health issues reduces the likelihood of further criminal justice involvement.

Platelets do not express the oxidized or reduced forms of tissue factor.

BACKGROUND: Expression of tissue factor (TF) antigen and activity in platelets is controversial and dependent upon the laboratory and reagents used. Two forms of TF were described: an oxidized functional form and a reduced nonfunctional form that is converted to the active form through the formation of an allosteric disulfide. This study tests the hypothesis that the discrepancies regarding platelet TF expression are due to differential expression of the two forms. METHODS: Specific reagents that recognize both oxidized and reduced TF were used in flow cytometry of unactivated and activated platelets and western blotting of whole platelet lysates. TF-dependent activity measurements were used to confirm the results. RESULTS: Western blotting analyses of placental TF demonstrated that, in contrast to anti-TF#5, which is directed against the oxidized form of TF, a sheep anti-human TF polyclonal antibody recognizes both the reduced and oxidized forms. Flow cytometric analyses demonstrated that the sheep antibody did not react with the surface of unactivated platelets or platelets activated with thrombin receptor agonist peptide, PAR-1. This observation was confirmed using biotinylated active site-blocked factor (F)VIIa: no binding was observed. Likewise, neither form of TF was detected by western blotting of whole platelet lysates with sheep anti-hTF. Consistent with these observations, no FXa or FIXa generation by FVIIa was detected at the surface of these platelets. Similarly, no TF-related activity was observed in whole blood using thromboelastography. CONCLUSION AND SIGNIFICANCE: Platelets from healthy donors do not express either oxidized (functional) or reduced (nonfunctional) forms of TF.

Factor VIII assay mimicking in vivo coagulation conditions.

Under certain circumstances, the determination of coagulation factor VIII (FVIII) is hampered by assay discrepancies between clotting and chromogenic approaches. These are observed in certain patients' plasma as well as in certain concentrates. We intended to develop a novel assay for the quantification of coagulation FVIII which reflects the physiological situation better than the established assays. It is based on plasma without chelation of divalent cations and simultaneously minimizes the generation of activated factors which could function as uncontrolled triggers of coagulation. FVIII deficient plasma is prepared with the aid of biotinylated antibodies against FVIII from normal plasma in presence of inhibitors of contact activation. To start the assay only tiny amounts of activated FIX serve as trigger. The FVIII determination is performed in a kinetic experiment and is based on the cleavage of a fluorogenic substrate for activated FX. FVIII concentrations between 0.01 and 1 IU mL(-1) are easily determined. Plasma-derived and recombinant FVIII concentrates were compared. All plasma-derived concentrates were found to contain FVIII activities within the specification of the manufacturer. Recombinant concentrates yielded only 35-50% of the claimed potency. The novel in vivo-like assay avoids the undue advantage or disadvantage of certain product characteristics by eliminating unphysiological assay conditions. Its usefulness could turn out in future experiments with plasma from haemophilia A patients.

Factor XII-independent activation of the bradykinin-forming cascade: Implications for the pathogenesis of hereditary angioedema types I and II.

BACKGROUND: We have previously reported that prekallikrein expresses an active site when it is bound to high-molecular-weight kininogen (HK) and can digest HK to produce bradykinin. The reaction is stoichiometric and inhibited by C1 inhibitor (C1-INH) or corn trypsin inhibitor. Addition of heat shock protein 90 leads to conversion of prekallikrein to kallikrein in a zinc-dependent reaction. OBJECTIVE: Our goal was to determine whether these reactions are demonstrable in plasma and distinguish them from activation through factor XII. METHODS: Plasma was incubated in polystyrene plates and assayed for kallikrein formation. C1-INH was removed from factor XII-deficient plasma by means of immunoadsorption. RESULTS: We demonstrate that prekallikrein-HK will activate to kallikrein in phosphate-containing buffers and that the rate is further accelerated on addition of heat shock protein 90. Prolonged incubation of plasma deficient in both factor XII and C1-INH led to conversion of prekallikrein to kallikrein and cleavage of HK, as was seen in plasma from patients with hereditary angioedema but not plasma from healthy subjects. CONCLUSIONS: These results indicate that C1-INH stabilizes the prekallikrein-HK complex to prevent HK cleavage either by prekallikrein or by prekallikrein-HK autoactivation to generate kallikrein. In patients with hereditary angioedema, kallikrein and bradykinin formation can occur without invoking factor XII activation, although the kallikrein formed can rapidly activate factor XII if it is surface bound.

Systemic inflammation and insulin resistance-related indicator predicts poor outcome in patients with cancer cachexia.

BACKGROUND: The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia. METHODS: In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses. RESULTS: The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13-1.33), 34% (internal test cohort, 95%CI = 1.11-1.62), and 35% (external validation cohort, 95%CI = 1.14-1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22-1.71; internal test cohort, HR = 1.62, 95%CI = 1.12-2.36; external validation cohort, HR = 1.61, 95%CI = 1.15-2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05-4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42-3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52-4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24-2.55] in patients with cancer cachexia. CONCLUSION: The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice.

The thermal journey of macroalgae: Four decades of temperature-induced changes in the southeastern Bay of Biscay.

Global warming is triggering significant shifts in temperate macroalgal communities worldwide, favoring small, warm-affinity species over large canopy-forming, cold-affinity species. The Cantabrian Sea, a region acutely impacted by climate change, is also witnessing this shift. This study delved into the impacts of increasing sea surface temperature on the subtidal macroalgal communities in the southeastern Bay of Biscay over the last four decades, by using data from the years 1982, 2007, 2014, and 2020. We found that temperature has shaped the community structure, with warm-affinity species steadily displacing their cold-affinity counterparts. Notably, new communities exhibited a profusion of smaller algal species, explaining the observed increased biodiversity within the area. In the last period investigated (2014-2020), we observed a partial recovery of the communities, coinciding with cooler sea surface temperatures. Shallow algal communities were more reactive to temperature variations than deeper communities, possibly associated with higher exposure to increased temperatures. Our study offered insights into the intricate relationship between the changes in ocean temperature and algal species in the southeastern Bay of Biscay, shedding light on the ongoing ecological shifts in this region.

Intracardiac Echocardiography Guidance Improves Procedural Outcomes in Patients Undergoing Cavotricuspidal Isthmus Ablation for Typical Atrial Flutter.

Atrial flutter (AFL) represents a prevalent variant of supraventricular tachycardia, distinguished by a macro-reentrant pathway encompassing the cavotricuspid isthmus (CTI). Radiofrequency (RF) catheter ablation stands as the favored therapeutic modality for managing recurring CTI-dependent AFL. Intracardiac echocardiography (ICE) has been proposed as a method to reduce radiation exposure during CTI ablation. This study aims to comprehensively compare procedural parameters between ICE-guided CTI ablation and fluoroscopy-only procedures. A total of 370 consecutive patients were enrolled in our single-center retrospective study. In 151 patients, procedures were performed using fluoroscopy guidance only, while 219 patients underwent ICE-guided CTI ablation. ICE guidance significantly reduced fluoroscopy time (73 (36; 175) s vs. 900 (566; 1179) s; p < 0.001), fluoroscopy dose (2.45 (0.6; 5.1) mGy vs. 40.5 (25.7; 62.9) mGy; p < 0.001), and total procedure time (70 (52; 90) min vs. 87.5 (60; 102.5) min; p < 0.001). Total ablation time (657 (412; 981) s vs. 910 (616; 1367) s; p < 0.001) and the time from the first to last ablation (20 (11; 36) min vs. 40 (25; 55) min; p < 0.01) were also significantly shorter in the ICE-guided group. Acute success rate was 100% in both groups, and no major complications occurred in either group. ICE-guided CTI ablation in patients with AFL resulted in shorter procedure times, reduced fluoroscopy exposure, and decreased ablation times, compared to the standard fluoroscopy-only approach.

Ablation of CTI-dependent flutter using different ablation technologies: acute and long-term outcome from the LEONARDO study.

BACKGROUND: A novel ablation catheter has been released to map and ablate the cavo-tricuspid isthmus (CTI) in patients with atrial flutter (AFL), improving ablation efficiency. METHODS: We evaluated the acute and long-term outcome of CTI ablation aiming at bidirectional conduction block (BDB) in a prospective, multicenter cohort study enrolling 500 patients indicated for typical AFL ablation. Patients were grouped on the basis of the AFL ablation method (linear anatomical approach, Conv group n = 425, or maximum voltage guided, MVG group, n = 75) and ablation catheter (mini-electrodes technology, MiFi group, n = 254, or a standard 8-mm ablation catheter, BLZ group, n = 246). RESULTS: Complete BDB according to both validation criteria (sequential detailed activation mapping or mapping only the ablation site) was achieved in 443 patients (88.6%). The number of RF applications needed to achieve BDB was lower in the MiFi MVG group vs both the MiFi Conv group and the BLZ Conv group (3.2 ± 2 vs 5.2 ± 4 vs 9.3 ± 5, p < 0.0001 for all comparisons). Fluoroscopy time was similar among groups, whereas we observed a reduction in the procedure duration from the BLZ Conv group (61.9 ± 26min) to the MiFi MVG group (50.6 ± 17min, p = 0.048). During a mean follow-up of 548 ± 304 days, 32 (6.2%) patients suffered an AFL recurrence. No differences were found according to BDB achieved by both validation criteria. CONCLUSIONS: Ablation was highly effective in achieving acute CTI BDB and long-term arrhythmia freedom irrespective of the ablation strategy or the validation criteria for CTI chosen by the operator. The use of an ablation catheter equipped with mini-electrodes technology seems to improve ablation efficiency. CLINICAL TRIAL REGISTRATION: Atrial Flutter Ablation in a Real World Population. (LEONARDO). CLINICALTRIALS: gov Identifier: NCT02591875.

Short-term response of macroalgal communities to ocean warming in the Southern Bay of Biscay.

Climate change is causing significant shifts in biological communities worldwide, including the degradation of marine communities. Previous research has predicted that southern Bay of Biscay canopy-forming subtidal macroalgal communities will shift into turf-forming Mediterranean-like communities by the end of the century. These predictions were based on a community-environment relationship model that used macroalgal abundance data and IPCC environmental projections. We have tested the short-term accuracy of that model by resampling the same communities and locations four years later and found the short-term predictions to be consistent with the observed communities. Changes in sea surface temperature were positively correlated with changes in the Community Temperature Index, suggesting that macroalgal communities had responded quickly to global warming. The changes over four years were significant, but canopy-forming macroalgae were more resilient in local sites with favourable temperature conditions. Our study demonstrated that updating predictive models with new data has the potential to yield reliable predictions and inform effective conservation strategies.