A new possibilistic-based clustering method for probability density functions and its application to detecting abnormal elements.

Cluster analysis can also detect abnormalities besides building a basis for identifying elements into clusters. Detecting abnormalities is a highly developed feature in the field of unsupervised learning. However, existing studies have mainly focused on discrete data, not probability density functions. This paper enables a possibilistic approach to solving the clustering for probability density functions dealing with abnormal elements. First, the data are extracted using the density function. Then, they are passed through the proposed algorithm to produce a possibilistic partition. Finally, a decision rule is established to recognize which function is abnormal. We compare the proposed algorithm with baseline algorithms in clustering PDFs, such as k-means, FCF, and Self-Updated Clustering. The results of three numerical examples applied to the image are typical for this new method. Furthermore, The proposed algorithm reaches accuracy at 100% over simulated benchmark data and outperforms baseline methods. Additionally, two last examples apply to image data reaching G-mean up from 96 to 100% (Sensitivity: 92-100% and Specificity: 100%). The proposed method can be researched and used to understand the internal structures of big data in the digital age through the probability density functions.

Antimicrobial and therapeutic potentials of the blackberry extracts against Escherichia coli infection in male albino rats.

BACKGROUND: Blackberries have garnered attention recently due to their high concentration of bioactive components like anthocyanin and their health advantages. Therefore, this study aims to determine the bioactive profile, antioxidant and antibacterial effects of blackberry extracts (BBEs). Then, evaluate the protective effect of BBEs (20%, 30% and 40%) in a rat model of 2 mL of 4-8 × 106 Escherichia coli ATTC 25922 strain colony-forming unit mL-1 oral infection on the seventh day of the experiment. RESULTS: Rats were divided into six groups: G1: control (C-: normal or negative group), G2: (C+: infected or positive group), G3: infected-treated group by 20% BBE, G4: infected-treated group by 30% BBE, G5: infected-treated group by 40% of BBE and G6: infected-treated group by Gentamicin. The results showed that BBE had a high content of total phenolic compounds, flavonoid, anthocyanin contents, and different vitamins (vitamins A, E and C), reaching 450, 186, 58.83 mg 100 g-1, 2.68, 2.14 and 107.46 mg 100g-1 fresh weight, respectively, which showed great antioxidant and antibacterial effects. Therefore, liver enzymes, kidney function and lipid profiles were significantly higher in the infected group than in the control or infected-treated groups. Furthermore, BBE ameliorated inflammation of the intestine and hepatocyte damage compared to the infected control group. CONCLUSION: These results suggest that consistent intake of BBE might alleviate hepatic inflammation and the gut microbiota in ways that could significantly impact human health. © 2024 Society of Chemical Industry.

Exploring the Potential of a Tailored Executive Functioning Training Program for Children with Congenital Heart Disease: A Brief Report.

The aim of this pilot study was to explore whether executive functioning (EF) problems of children with severe congenital heart disease (CHD) could be improved through a personalized EF-training program. Eleven preschool-aged children (mean age = 62 months, SD = 6) received a standardized test battery. Eight children were eligible for training and six children participated in the training and posttest. Due to the small sample size, only effect sizes were analyzed. Clinically relevant improvements were found with large effect sizes. Findings indicate that a personalized EF-training program could be effective in improving EF of children with severe CHD. Further research is needed.

Bright light therapy-induced improvements of mood, cognitive functions and cerebellar functional connectivity in subthreshold depression: A randomized controlled trial.

Background: The efficacy of bright light therapy (BLT) in ameliorating depression has been validated. The present study is to investigate the changes of depressive symptoms, cognitive function and cerebellar functional connectivity (FC) following BLT in individuals with subthreshold depression (StD). Method: Participants were randomly assigned to BLT group (N = 47) or placebo (N = 41) in this randomized controlled trial between March 2020 and June 2022. Depression severity and cognitive function were assessed, as well as resting-state functional MRI scan was conducted before and after 8-weeks treatment. Seed-based whole-brain static FC (sFC) and dynamic FC (dFC) analyses of the bilateral cerebellar subfields were conducted. Besides, a multivariate regression model examined whether baseline brain FC was associated with changes of depression severity and cognitive function during BLT treatment. Results: After 8-week BLT treatment, individuals with StD showed improved depressive symptoms and attention/vigilance cognitive function. BLT also increased sFC between the right cerebellar lobule IX and left temporal pole, and decreased sFC within the cerebellum, and dFC between the right cerebellar lobule IX and left medial prefrontal cortex. Moreover, the fusion of sFC and dFC at baseline could predict the improvement of attention/vigilance in response to BLT. Conclusions: The current study identified that BLT improved depressive symptoms and attention/vigilance, as well as changed cerebellum-DMN connectivity, especially in the cerebellar-frontotemporal and cerebellar internal FC. In addition, the fusion features of sFC and dFC at pre-treatment could serve as an imaging biomarker for the improvement of attention/vigilance cognitive function after BLT in StD.

On the analysis of two-time correlation functions: equilibrium versus non-equilibrium systems.

X-ray photon correlation spectroscopy (XPCS) is a powerful tool for the investigation of dynamics covering a broad range of timescales and length scales. The two-time correlation function (TTC) is commonly used to track non-equilibrium dynamical evolution in XPCS measurements, with subsequent extraction of one-time correlations. While the theoretical foundation for the quantitative analysis of TTCs is primarily established for equilibrium systems, where key parameters such as the diffusion coefficient remain constant, non-equilibrium systems pose a unique challenge. In such systems, different projections ('cuts') of the TTC may lead to divergent results if the underlying fundamental parameters themselves are subject to temporal variations. This article explores widely used approaches for TTC calculations and common methods for extracting relevant information from correlation functions, particularly in the light of comparing dynamics in equilibrium and non-equilibrium systems.

Independent-channels models of temporal-order judgment revisited: A model comparison.

The perception of temporal order or simultaneity of stimuli is almost always explained in terms of independent-channels models, such as perceptual-moment, triggered-moment, and attention-switching models. Independent-channels models generally posit that stimuli are processed in separate peripheral channels and that their arrival-time difference at a central location is translated into an internal state of order (simultaneity) if it reaches (misses) a certain threshold. Non-monotonic and non-parallel psychometric functions in a ternary-response task provided critical evidence against a wide range of independent-channels models. However, two independent-channels models have been introduced in the last decades that can account for such shapes by considering misreports of internal states (response-error model) or by assuming that simultaneity and order judgments rely on distinct sensory and decisional processes (two-stage model). Based on previous ideas, we also consider a two-threshold model, according to which the same arrival-time difference may need to reach a higher threshold for order detection than for successiveness detection. All three models were fitted to various data sets collected over a period of more than a century. The two-threshold model provided the best balance between goodness of fit and parsimony. This preference for the two-threshold model over the two-stage model and the response-error model aligns well with several lines of evidence from cognitive modeling, psychophysics, mental chronometry, and psychophysiology. We conclude that the seemingly deviant shapes of psychometric functions can be explained within the framework of independent-channels models in a simpler way than previously assumed.

The role of executive functions in long-term memory: case report.

The role of executive functions in long-term memory has been studied. We describe a single-case study, consisting of a 45-year-old male patient, hospitalized for right frontal stroke. After the stroke, the patient had memory alterations in everyday activities. However, performance in short-term memory tests was not significantly altered. Long-term memory assessments included pre- and post-stroke episodic, semantic, and procedural memories. Specific skills involved in the acquisition of new learning (auditory-verbal and visual reproduction) were also evaluated, as well as executive functions. The results evidence that short-term memory was not affected. Regarding long-term memory, significant differences were observed between pre- and post-stroke knowledge, the former being better preserved, which reveals anterograde amnesia. Pre-stroke long-term memory was also affected, but only with respect to episodic knowledge, with semantic and procedural memories preserved (episodic retrograde amnesia). Executive functions were altered as well, which could have been a factor affecting the acquisition and consolidation of new learning, despite the fact that short-term memory was not significantly altered. Therefore, executive functions might be a determinant factor in the acquisition of new learning, regardless of short-term memory processes, at least partially. According to the results of the present study, alterations in these functions might lead to anterograde amnesia. This entails the need to evaluate executive functions as an intrinsic part of memory evaluation.

Exosomal CircRNAs: A Future Star in Colorectal Cancer.

Colorectal cancer (CRC) is currently the third most common malignancy world-wide, with an increasing mortality rate and treatment resistance. Due to the lack of effective biomarkers and therapeutic targets, the early diagnosis and treatment of colorectal cancer re-main suboptimal. Circular RNAs (circRNAs) are a novel class of non-coding RNAs with co-valent closed-loop structures that are well stabilized and conserved and are involved in multi-ple pathological conditions in humans. CircRNAs have been identified to be enriched and sta-ble in exosomes. In addition, there is growing proof that exosomal circRNAs that have been identified as oncogenes or tumor suppressors regulate CRC growth, migration, and sensitivity to radiotherapy and chemotherapy. Exosomal circRNAs represent promising candidates as di-agnostic biomarkers and anti-tumor targets. In this article, we explore recent studies on exo-somal circRNAs in CRC and describe their biological functions in colorectal cancer develop-ment, illustrating their potential as biomarkers and targeted therapeutic capabilities.

Helicobacter pylori Outer Membrane Vesicles: Biogenesis, Composition, and Biological Functions.

Helicobacter pylori has been recognized not only as a causative agent of a spectrum of gastroduodenal diseases including chronic gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer, but also as the culprit in several extra-gastric diseases. However, the association of H. pylori infection with extra-gastric diseases remains elusive, prompting a reevaluation of the role of H. pylori-derived outer membrane vesicles (OMVs). Like other gram-negative bacteria, H. pylori constitutively sheds biologically active OMVs for long-distance delivery of bacterial virulence factors in a concentrated and protected form, averting the need of direct bacterial contact with distant host cells to induce extra-gastric diseases associated with this gastric pathogen. Additionally, H. pylori-derived OMVs contribute to bacterial survival and chronic gastric pathogenesis. Moreover, the immunogenic activity, non-replicable nature, and anti-bacterial adhesion effect of H. pylori OMVs make them a desirable vaccine candidate against infection. The immunogenic potency and safety concerns of the OMV contents are challenges in the development of H. pylori OMV-based vaccines. In this review, we discuss recent advances regarding H. pylori OMVs, focusing on new insights into their biogenesis mechanisms and biological functions.

Co-production of the 'EPIC' multidimensional tool-kit to support neurodivergent children and young people at home and school: a feasibility and pilot study.

BACKGROUND: Interventions focused on cognitive function in neurodivergent children typically focus on single functions, e.g. working memory training. They are often focused on 'deficit' models and lack an emphasis on understanding areas of individual strengths and difficulties as a prerequisite to appropriate support. The multidimensional nature and phenotypic variability of cognitive profiles in these children indicate a need for a multicomponent-tailored intervention programme focused on understanding and supporting an individual child's cognitive functioning. AIMS: The 'EPIC' intervention (Edinburgh Psychoeducation Intervention for Children and Young People) is focused on improving cognition, learning and behaviour in neurodivergent children such as those with attention deficit hyperactivity disorder (ADHD) or who are autistic. Building on our previous co-production work, this study aimed to use a participatory methods approach to develop EPIC practices and materials in relation to our key principles which include psychoeducation, multicomponent, individualised approach, strengths and difficulties profiling and pairing of a child's individual strengths and difficulties with internal and external strategies. We also set out to assess the feasibility and acceptability of EPIC, and pilot this novel tool-kit intervention with neurodivergent children and their parents and teachers. METHODS: The intervention practices, materials and strategies of EPIC were co-produced with neurodivergent children, their parents, teachers and clinicians taking a strengths and difficulties approach. Identification of psychoeducation activities and strategy practices (e.g. mind-maps, chunking), testing of feasibility and collection of pilot data were conducted over a bi-weekly 8-week programme. Eleven neurodivergent children aged 7 to 12 completed the 16-session individualised programme. Acceptability and feasibility were ascertained via qualitative reports elicited within child and teacher interviews and child ratings of enjoyment. Pilot evaluation data was collected pre- and post-intervention participation, and across cognitive assessments (CANTAB, BRIEF), educational attainment (WIAT) and parent and teacher questionnaires measuring clinical symptoms and behaviour (Conners, AQ, SDQ, self-perception). Data was compared with a matched neurodivergent treatment-as-usual control group (N = 9). RESULTS: The co-produced EPIC intervention was both feasible to deliver and acceptable to children, parents and their teachers. Pilot data identified that the 8-week intervention improved cognition (short-term and working memory) and literacy (receptive vocabulary, oral word fluency, listening comprehension). Improvements in the intervention group were also found for parent-reported child behavioural difficulties and aggression, and teacher-reported scholastic competence. Effect sizes generated (Cohen's d) ranged from 0.65 to 2.83. Parents reported continuing to use EPIC strategies when interviewed over a year after participating in the programme. CONCLUSION: The current study met our objectives fully. 'EPIC' (Edinburgh Psychoeducation Intervention for Children and Young People) is feasible in home and school contexts and improves a range of aspects of cognition, learning and behaviour in neurodivergent children. Our findings show EPIC is suitable to be assessed within a full-scale trial.

Plasmodium sporozoite shows distinct motility patterns in responses to three-dimensional environments.

During malaria infection, Plasmodium sporozoites, the fast-moving stage of the parasite, are injected by a mosquito into the skin of the mammalian host. In the skin, sporozoites need to migrate through the dermal tissue to enter the blood vessel. Sporozoite motility is critical for infection but not well understood. Here, we used collagen hydrogels with tunable fiber structures, as an in vitro model for the skin. After injecting sporozoites into the hydrogel, we analyzed their motility in three-dimension (3D). We found that sporozoites demonstrated chiral motility, in that they mostly follow right-handed helical trajectories. In high-concentration collagen gel, sporozoites have lower instantaneous speed, but exhibit straighter tracks compared to low-concentration collagen gel, which leads to longer net displacement and faster dissemination. Taken together, our study indicates an inner mechanism for sporozoites to adapt to the environment, which could help with their successful exit from the skin tissue.

Cognitive Alterations Associated with Remission and Alcohol Dependence Severity in Ethnically Diverse Patients of Siberia.

Background: Impaired cognition in individuals with alcohol dependence may be associated with increased relapse risk. It has been recorded in more than half of patients during six months after treatment. In certain ethnic groups, for example, Tuvinians, the indigenous people of Siberia, relapses occur in extremely short periods of one to three months after treatment. An approach currently used to alcohol dependence treatment may be less effective for these patients. Objective: The study aimed to investigate cognitive sequelae in indigenous Tuvinian patients with alcohol dependence. Methods: The sample included 166 patients, 74 of indigenous ethnicity (Tuvinians) and 92 non-indigenous white patients. Data on inhibitory control, cognitive flexibility, attention, and working memory were collected from all the patients and processed using cluster analysis. The clustering data were then complemented by indicators of disorder dynamics, impulsivity, and emotion regulation. Results: The clustering procedure revealed groups with severe cognitive sequelae. More than four-fold attention decrease was found in 43.5% of non-indigenous patients, and more impaired cognitive flexibility was revealed among 60.8% of indigenous patients. Groups with severe cognitive sequelae had higher impulsivity, maladaptive emotion regulation, more hospitalizations, faster disease progression, and shorter remissions. The latter was significantly reduced to 90 days on average in the severe group of indigenous patients versus 135 days of remission in the non-indigenous severe group. Conclusion: Results obtained may advance tailored intervention in alcohol-dependent patients of the indigenous Tuvinian ethnicity. While little is still known about the alcohol dependence course and consequences in the indigenous Tuvinians of Siberia, this study contributes to the global mental health data on alcohol abuse and dependence in indigenous communities.

Assessment of Cognitive Functions Among Remitted Patients of Schizophrenia and Bipolar Disorder: A Comparative Study.

Introduction Bipolar disorder and schizophrenia exhibit different patterns of cognitive impairment, with schizophrenia demonstrating more profound deficiencies in verbal memory and bipolar disorder in social cognition. Understanding these patterns may guide the development of interventions to enhance cognition in these disorders. Aim This study aims to assess and compare the cognitive abilities of persons diagnosed with bipolar illness and schizophrenia. Methodology A facility-based cross-sectional study was done from December 2016 to June 2017 among 30 schizophrenia and 30 bipolar disorder patients aged 18-45 years, in remission selected after screening through Hamilton Depression Rating Scale (HDRS), Young Mania Rating Scale (YMRS), or Positive and Negative Syndrome Scale (PANSS). Exclusions included schizoaffective disorder, systemic illness, brain/neurological conditions, and substance abuse. After collecting the baseline demographic and clinical profile of the selected patients, the cognitive domains were assessed such as attention (digit span), verbal memory (Rey's Auditory Verbal Learning Test (RAVLT)), visual memory (Rey Complex Figure), verbal fluency (Animal Naming), and executive functions (Stroop and Trail Making). The data was analyzed using the IBM SPSS Statistics for Windows, Version 16 (Released 2007; IBM Corp., Armonk, New York, United States) using standard descriptive and inferential statistics. Results Sociodemographic and clinical characteristics were largely similar between groups. Schizophrenia patients showed poorer attention, working memory, and visual attention/task-switching compared to bipolar patients. Bipolar patients demonstrated relatively preserved abilities in these domains but exhibited more impairments in visual and verbal memory. Distinct patterns highlight unique neurobiological underpinnings, showing association of more generalized cognitive deficits in schizophrenia and more localized impairments in memory functions in bipolar disorder. Conclusion The study findings explain these disorders' unique neurobiological mechanisms and may help develop targeted cognitive remediation and pharmacological interventions to improve functional outcomes and quality of life.

Reprogramming of glucose metabolism: The hallmark of malignant transformation and target for advanced diagnostics and treatments.

Reprogramming of cancer metabolism has become increasingly concerned over the last decade, particularly the reprogramming of glucose metabolism, also known as the "Warburg effect". The reprogramming of glucose metabolism is considered a novel hallmark of human cancers. A growing number of studies have shown that reprogramming of glucose metabolism can regulate many biological processes of cancers, including carcinogenesis, progression, metastasis, and drug resistance. In this review, we summarize the major biological functions, clinical significance, potential targets and signaling pathways of glucose metabolic reprogramming in human cancers. Moreover, the applications of natural products and small molecule inhibitors targeting glucose metabolic reprogramming are analyzed, some clinical agents targeting glucose metabolic reprogramming and trial statuses are summarized, as well as the pros and cons of targeting glucose metabolic reprogramming for cancer therapy are analyzed. Overall, the reprogramming of glucose metabolism plays an important role in the prediction, prevention, diagnosis and treatment of human cancers. Glucose metabolic reprogramming-related targets have great potential to serve as biomarkers for improving individual outcomes and prognosis in cancer patients. The clinical innovations related to targeting the reprogramming of glucose metabolism will be a hotspot for cancer therapy research in the future. We suggest that more high-quality clinical trials with more abundant drug formulations and toxicology experiments would be beneficial for the development and clinical application of drugs targeting reprogramming of glucose metabolism.This review will provide the researchers with the broader perspective and comprehensive understanding about the important significance of glucose metabolic reprogramming in human cancers.

Effect of mutation of phaC on carbon supply, extracellular polysaccharide production, and pathogenicity of Xanthomonas oryzae pv. oryzae.

Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight in rice. Polyhydroxyalkanoates (PHAs) consitute a diverse group of biopolyesters synthesized by bacteria under nutrient-limited conditions. The phaC gene is important for PHA polymerization. We investigated the effects of phaC gene mutagensis in Xoo strain PXO99A. The phaC gene knock-out mutant exhibited reduced swarming ability relative to that of the wild-type. Under conditions where glucose was the sole sugar source, extracellular polysaccharide (EPS) production by ΔphaC declined by 44.8%. ΔphaC showed weak hypersensitive response (HR) induction in the leaves of non-host Nicotiana tabacum, concomitant with downregulation of hpa1 gene expression. When inoculated in rice leaves by the leaf-clipping method, ΔphaC displayed reduced virulence in terms of lesion length compared with the wild-type strain. The complemented strain showed no significant difference from the wild-type strain, suggesting that the deletion of phaC in Xoo induces significant alterations in various physiological and biological processes. These include bacterial swarming ability, EPS production, transcription of hrp genes, and glucose metabolism. These changes are intricately linked to the energy utilization and virulence of Xoo during plant infection. These findings revealed involvement of phaC in Xoo is in the maintaining carbon metabolism by functioning in the PHA metabolic pathway.

Innovation Efficiency, Productive Performance and Undesirable Outputs across European Regions: Are there any missing links?

We introduce an analytical methodological framework that links knowledge generation efficiency with economic efficiency and the corresponding environmental impact for 199 European Regions during 2000-2018, using a benchmarking approach and especially a chain network DEA technique. A clear trade-off between knowledge generation efficiency and productive performance emerges. European regions which exhibit high innovation efficiency enjoy higher overall performance compared to their counterparts. In a second stage, we investigate the convergence patterns of the examined regions with respect to all the three facets of the estimated efficiency where the coexistence of multi-type convergence clubs is revealed.

The effects of language learning on cognitive functioning and psychosocial well-being in cognitively healthy older adults: A semi-blind randomized controlled trial.

This study investigated the impact of language learning in comparison to other complex learning activities on cognitive functioning and psychosocial well-being in cognitively healthy, community-dwelling older adults. In a randomized controlled trial, 43 Dutch functionally monolinguals aged 65-78 completed a three-month English course (n = 15), music training (n = 13), or a lecture series (n = 15). Cognitive functioning (global cognition, cognitive flexibility, episodic memory, working memory, verbal fluency, and attention) and psychosocial well-being were assessed before and immediately after the intervention, and at a four-month follow-up. The language learners significantly improved on episodic memory and cognitive flexibility. However, the magnitude of cognitive change did not significantly differ between the language learning and music training conditions, except for a larger positive change in cognitive flexibility for the language learners from pretest to follow-up. Our results suggest that language learning in later life can improve some cognitive functions and fluency in the additional language, but that its unique effects seem limited.

Functional Insights into the Sphingolipids C1P, S1P, and SPC in Human Fibroblast-like Synoviocytes by Proteomic Analysis.

The (patho)physiological function of the sphingolipids ceramide-1-phosphate (C1P), sphingosine-1-phosphate (S1P), and sphingosylphosphorylcholine (SPC) in articular joints during osteoarthritis (OA) is largely unknown. Therefore, we investigated the influence of these lipids on protein expression by fibroblast-like synoviocytes (FLSs) from OA knees. Cultured human FLSs (n = 7) were treated with 1 of 3 lipid species-C1P, S1P, or SPC-IL-1ß, or with vehicle. The expression of individual proteins was determined by tandem mass tag peptide labeling followed by high-resolution electrospray ionization (ESI) mass spectrometry after liquid chromatographic separation (LC-MS/MS/MS). The mRNA levels of selected proteins were analyzed using RT-PCR. The 3sphingolipids were quantified in the SF of 18 OA patients using LC-MS/MS. A total of 4930 proteins were determined using multiplex MS, of which 136, 9, 1, and 0 were regulated both reproducibly and significantly by IL-1ß, C1P, S1P, and SPC, respectively. In the presence of IL-1ß, all 3 sphingolipids exerted ancillary effects. Only low SF levels of C1P and SPC were found. In conclusion, the 3 lipid species regulated proteins that have not been described in OA. Our results indicate that charged multivesicular body protein 1b, metal cation symporter ZIP14, glutamine-fructose-6-P transaminase, metallothionein-1F and -2A, ferritin, and prosaposin are particularly interesting proteins due to their potential to affect inflammatory, anabolic, catabolic, and apoptotic mechanisms.

Conceptualization and characterization of "primary" and "secondary" cognitive impairment in schizophrenia.

Cognitive impairment represents one of the core features of schizophrenia, involves both neurocognition and social cognition domains, and has a significant negative impact on real-world functioning. The present review provides a framework for the conceptualization and characterization of "primary" and "secondary" cognitive impairment in schizophrenia. In this conceptualization, primary cognitive impairment can be defined as a consequence of the neurobiological alterations that underlie psychopathological manifestations of the disorder, while secondary cognitive impairment can be defined as the results of a source issue that has a negative impact on cognitive performance. Sources of secondary cognitive impairment are frequent in people with schizophrenia and include several different factors, such as positive and negative symptoms, depressive symptoms, autistic symptoms, pharmacotherapy, substance abuse, metabolic syndrome, social deprivation, and sleep disorders. It can be hypothesized that secondary cognitive impairment may be improved by effectively resolving the source issue, while primary cognitive impairment may benefit from dedicated treatment. Further research is required to confirm this hypothesis, to better characterize the distinction between primary and secondary cognitive impairment in a clinical and in a neurobiological perspective, and to evaluate the impact of systematically assessing and treating secondary cognitive impairment.

Are we ready to cure post-stroke cognitive impairment? Many key prerequisites can be achieved quickly and easily.

PURPOSE: Post-stroke (PS) cognitive impairment (CI) is frequent and its devastating functional and vital consequences are well known. Despite recent guidelines, they are still largely neglected. A large number of recent studies have re-examined the epidemiology, diagnosis, imaging determinants and management of PSCI. The aim of this update is to determine whether these new data answer the questions that are essential to reducing PSCI, the unmet needs, and steps still to be taken. METHODS: Literature review of stroke unit-era studies examining key steps in the management of PSCI: epidemiology and risk factors, diagnosis (cognitive profile and assessments), imaging determinants (quantitative measures, voxelwise localization, the disconnectome and associated Alzheimer's disease [AD]) and treatment (secondary prevention, symptomatic drugs, rehabilitation and noninvasive brain stimulation) of PSCI. FINDINGS: (1) the prevalence of PSCI of approximately 50% is probably underestimated; (2) the sensitivity of screening tests should be improved to detect mild PSCI; (3) comprehensive assessment is now well-defined and should include apathy; (4) easily available factors can identify patients at high risk of PSCI; (5) key imaging determinants are the location and volume of the lesion and the resulting disconnection, associated AD and brain atrophy; WMH, ePVS, microhemorrhages, hemosiderosis, and cortical microinfarcts may contribute to cognitive impairment but are more likely to be markers of brain vulnerability or associated AD that reduce PS recovery; (6) remote and online assessment is a promising approach for selected patients; (7) secondary stroke prevention has not been proven to prevent PSCI; (8) symptomatic drugs are ineffective in treating PSCI and apathy; (9) in addition to cognitive rehabilitation, the benefits of training platforms and computerized training are yet to be documented; (10) the results and the magnitude of improvement of noninvasive brain stimulation, while very promising, need to be substantiated by large, high-quality, sham-controlled RCTs. DISCUSSION AND CONCLUSION: These major advances pave the way for the reduction of PSCI. They include (1) the development of more sensitive screening tests applicable to all patients and (2) online remote assessment; crossvalidation of (3) clinical and (4) imaging factors to (5) identify patients at risk, as well as (6) factors that prompt a search for associated AD; (7) the inclusion of cognitive outcome as a secondary endpoint in acute and secondary stroke prevention trials; and (8) the validation of the benefit of noninvasive brain stimulation through high-quality, randomized, sham-controlled trials. Many of these objectives can be rapidly and easily attained.