DeepCut: Unsupervised Segmentation using Graph Neural Networks Clustering

Image segmentation is a fundamental task in computer vision. Data annotation for training supervised methods can be labor-intensive, motivating unsupervised methods. Current approaches often rely on extracting deep features from pre-trained networks to construct a graph, and classical clustering methods like k-means and normalized-cuts are then applied as a post-processing step. However, this approach reduces the high-dimensional information encoded in the features to pair-wise scalar affinities. To address this limitation, this study introduces a lightweight Graph Neural Network (GNN) to replace classical clustering methods while optimizing for the same clustering objective function. Unlike existing methods, our GNN takes both the pair-wise affinities between local image features and the raw features as input. This direct connection between the raw features and the clustering objective enables us to implicitly perform classification of the clusters between different graphs, resulting in part semantic segmentation without the need for additional post-processing steps. We demonstrate how classical clustering objectives can be formulated as self-supervised loss functions for training an image segmentation GNN. Furthermore, we employ the Correlation-Clustering (CC) objective to perform clustering without defining the number of clusters, allowing for k-less clustering. We apply the proposed method for object localization, segmentation, and semantic part segmentation tasks, surpassing state-of-the-art performance on multiple benchmarks

Physiological and pathological aspects of Aβ in iron homeostasis via 5'UTR in the APP mRNA and the therapeutic use of iron-chelators

Many studies have highlighted the pathological involvement of iron accumulation and iron-related oxidative stress (OS) in Alzheimer's disease (AD). Iron was further demonstrated to modulate expression of the Alzheimer's amyloid precursor holo-protein (APP) by a mechanism similar to that of regulation of ferritin-L and -H mRNA translation through an iron-responsive element (IRE) in their 5' untranslated regions (UTRs). Here, we discuss two aspects of the link between iron and AD, in relation to the recently discovered IRE in the 5'UTR of APP mRNA. The first is the physiological aspect: a compensatory neuroprotective response of amyloid-β protein (Aβ) in reducing iron-induced neurotoxicity. Thus, given that Aβ possesses iron chelation sites, it is hypothesized that OS-induced intracellular iron may stimulate APP holo-protein translation (via the APP 5'UTR) and subsequently the generation of its cleavage product, Aβ, as a compensatory response that eventually reduces OS. The second is the pathological aspect: iron chelating compounds target the APP 5'UTR and possess the capacity to reduce APP translation, and subsequently Aβ levels, and thus represent molecules with high potential in the development of drugs for the treatment of AD

Multi-target iron-chelators improve memory loss in a rat model of sporadic Alzheimer's disease

AIM: Novel effective treatment is urgently needed for sporadic Alzheimer's disease (sAD). M30 ([5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline]) and HLA-20 (5-{4-propargylpiperazin-1-ylmethyl}-8-hydroxyquinoline) are brain permeable, iron chelating compounds with antioxidant activity, showing also neuroprotective activity in animal models of neurodegeneration.Weaimed to explore their therapeutic potential in non-transgenic (non-Tg) rat model of sAD developed by intracerebroventricular administration of streptozotocin (STZ-icv). ----- MAIN METHODS: Therapeutic effects of chronic oral M30 (2 and 10 mg/kg) and HLA20 (5 and 10 mg/kg) treatment on cognitive impairment in STZ-icv rat model were explored by Morris Water Maze (MWM) and Passive Avoidance (PA) tests in neuropreventive and neurorescue paradigms. Data were analysed by Kruskal–Wallis and Mann–Whitney U test (p b 0.05). ----- KEY FINDINGS: Five-day oral pre-treatment with M30 and HLA20 dose-dependently prevented development of spatial memory impairment (MWM probe trial-time +116%/M30; +60%/HLA20) in STZ-icv rat model (p b 0.05). Eleven-week oral treatment with M30 (3×/week), initiated 8 days after STZ-icv administration dosedependently ameliorated already developed cognitive deficits in MWM test (reduced number of mistakes 3 months after the STZ-icv treatment — 59%; p b 0.05) and fully restored them in PA test (+314%; p b 0.05). Chronic M30 treatment fully restored (−47%/PHF1;−65%/AT8; p b 0.05) STZ-induced hyperphosphorylation of tau protein and normalized decreased expression of insulin degrading enzyme (+37%; p b 0.05) in hippocampus. ----- SIGNIFICANCE: The results provide first evidence of therapeutic potential of M30 and HLA20 in STZ-icv rat model of sAD with underlying molecular mechanism, further supporting the important role of multi-target ironchelators in sAD treatment

ARIEL4: An International, Multicenter, Randomized Phase 3 Study of the PARP Inhibitor Rucaparib vs Chemotherapy in Germline or Somatic BRCA1- or BRCA2-Mutated, Relapsed, High-Grade Ovarian Carcinoma

Описание In high-grade ovarian cancer, including fallopian tube and primary peritoneal cancers, approximately 18% of patients have tumors with a germline BRCA1 or BRCA2 mutation and approximately 7% of patients have tumors with a somatic BRCA1 or BRCA2 mutation1• The poly (ADP-ribose) polymerase (PARP) inhibitor rucaparib has demonstrated efficacy in tumors with homologous recombination deficiency (HRD), including a BRCA1 or BRCA2 mutation2-5–In cells with HRD, PARP inhibition results in accumulation of double-strand ..

COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated

The evolving landscape of COVID‐19 and post‐COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer

The psychological science accelerator’s COVID-19 rapid-response dataset

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data