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INTRODUCTION Predicting the rate of cognitive decline and the likelihood of progression to dementia remains a critical unmet need in clinical settings. METHODS We assessed progression to mild cognitive impairment (MCI) and all‐cause dementia in 492 individuals from the TRIAD, ADNI, and HABS‐HD cohorts followed for an average of 2.49 years. Amyloid‐positive participants were staged according to the Alzheimer's Association biological staging framework (A+T2‐/A+T2MTL+/A+T2MOD+/A+T2HIGH+). RESULTS Cognitively unimpaired (CU) individuals in the A+T2MTL+, A+T2MOD+, and A+T2HIGH+ biological Alzheimer's disease (AD) stages were at significantly higher risk of clinical progression compared to non‐AD CU individuals. In individuals with MCI, advanced tau stage was associated with an 83% likelihood of developing dementia over 4 years. Biological AD staging demonstrated superior accuracy in predicting clinical progression compared to amyloid‐PET (positron emission tomography) status, tau‐PET status, and demographic information. All tau‐PET‐positive individuals showed a significantly faster rate of cognitive decline than non‐AD controls, with the A+T2HIGH+ stage showing the steepest rate of decline (p < 0.001). DISCUSSION Our results highlight the prognostic value of biological AD staging. Highlights Cognitively unimpaired (CU) individuals in all tau‐PET (positron emission tomography)–positive biological Alzheimer's disease (AD) stages were at significantly higher risk of clinical progression compared to individuals without AD. In individuals with mild cognitive impairment (MCI), only the A+T2HIGH+ stage reached a point where 50% of individuals had progressed to all‐cause dementia, after 2.36 years. Biological AD staging demonstrated superior accuracy in predicting clinical progression to dementia compared to other PET biomarkers and demographic information. All tau‐PET‐positive individuals showed a significantly faster rate of cognitive decline than individuals without AD, with the A+T2HIGH+ stage showing the steepest rate of decline.

Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to generate the first protein microarray for a multi-cellular pathogen. Using well-established Brazilian cohorts of putatively resistant (PR) and chronically infected (CI) individuals stratified by the intensity of their S. mansoni infection, we probed arrays for IgG subclass and IgE responses to these antigens to detect antibody signatures that were reflective of protective vs. non-protective immune responses. Moreover, probing for IgE responses allowed us to identify antigens that might induce potentially deleterious hypersensitivity responses if used as subunit vaccines in endemic populations. Using multi-dimensional cluster analysis we showed that PR individuals mounted a distinct and robust IgG1 response to a small set of newly discovered and well-characterized surface (tegument) antigens in contrast to CI individuals who mounted strong IgE and IgG4 responses to many antigens. Herein, we show the utility of a vaccinomics approach that profiles antibody responses of resistant individuals in a high-throughput multiplex approach for the identification of several potentially protective and safe schistosomiasis vaccine antigens.

Background Glial responses are involved in neurodegenerative processes, with tau pathology often associated with increased glial inflammatory responses in Alzheimer’s disease (AD). The apolipoprotein E ( APOE ) ε4 allele, the major genetic susceptibility gene for AD, might contribute to this process by modulating both tau pathology and inflammatory cascades in the brain. Methods We used data from the Translational Biomarkers of Alzheimer’s Disease (TRIAD) cohort ( n  = 137) to investigate the association between YKL-40, a marker of reactive astrogliosis, and tau burden measured with PET imaging, while also exploring the involvement of APOE ε4 carriership. Statistical analyses included correlation and regression models controlling for age and sex. Results Here we show that tau pathology is positively associated with YKL-40 levels, reflecting regional patterns of astrocyte activity in the brain. Furthermore, this association is more widespread in individuals carrying the APOE ε4 allele, suggesting a genotype-specific modulation of the glial neuroinflammatory response. Conclusions Our findings demonstrate a link between tau accumulation and astrocyte-mediated neuroinflammation in AD and highlight the modulatory role of APOE ε4 in this process. Taken together, our findings help inform the multifaceted role of tau-associated neuroinflammation in the progression of AD. Plain language summary Alzheimer’s disease is a brain disorder characterized by the accumulation of abnormal proteins, including tau, which contribute to memory loss and cognitive decline. Brain support cells called astrocytes respond to this protein build-up by becoming reactive, which can lead to inflammation in the brain. In this study, we used brain scans and cerebrospinal fluid samples from 137 participants to examine how astrocyte reactivity, measured by the protein YKL-40, relates to tau accumulation. We also investigated whether carrying a common genetic risk factor, APOE ε4, influences this relationship. We found that higher tau levels are associated with increased astrocyte reactivity, and this association is stronger in people carrying APOE ε4. These findings suggest that genetic risk may amplify inflammation in Alzheimer’s disease. Trudel et al. investigate the relationship between tau pathology and reactive astrogliosis in Alzheimer’s disease using PET imaging and CSF biomarkers. Their findings suggest that APOE ε4 amplifies tau-associated glial inflammation, offering insights into genotype-specific mechanisms driving AD-associated neuroinflammation.

Background Cytauxzoonosis is a disease of felids in North America caused by the tick-transmitted apicomplexan parasite Cytauxzoon felis . Cytauxzoonosis is particularly virulent for domestic cats, but no vaccine currently exists. The parasite cannot be cultivated in vitro, presenting a significant limitation for vaccine development. Methods Recent sequencing of the C. felis genome has identified over 4300 putative protein-encoding genes. From this pool we constructed a protein microarray containing 673 putative C. felis proteins. This microarray was probed with sera from C. felis -infected and naïve cats to identify differentially reactive antigens which were incorporated into two expression library vaccines, one polyvalent and one monovalent. We assessed the efficacy of these vaccines to prevent of infection and/or disease in a tick-challenge model. Results Probing of the protein microarray resulted in identification of 30 differentially reactive C. felis antigens that were incorporated into the two expression library vaccines. However, expression library immunization failed to prevent infection or disease in cats challenged with C. felis . Conclusions Protein microarray facilitated high-throughput identification of novel antigens, substantially increasing the pool of characterized C. felis antigens. These antigens should be considered for development of C. felis vaccines, diagnostics, and therapeutics.

Babesia microti , a tick-transmitted, intraerythrocytic protozoan parasite circulating mainly among small mammals, is the primary cause of human babesiosis. While most cases are transmitted by Ixodes ticks, the disease may also be transmitted through blood transfusion and perinatally. A comprehensive analysis of genome composition, genetic diversity, and gene expression profiling of seven B. microti isolates revealed that genetic variation in isolates from the Northeast United States is almost exclusively associated with genes encoding the surface proteome and secretome of the parasite. Furthermore, we found that polymorphism is restricted to a small number of genes, which are highly expressed during infection. In order to identify pathogen-encoded factors involved in host-parasite interactions, we screened a proteome array comprised of 174 B. microti proteins, including several predicted members of the parasite secretome. Using this immuno-proteomic approach we identified several novel antigens that trigger strong host immune responses during the onset of infection. The genomic and immunological data presented herein provide the first insights into the determinants of B. microti interaction with its mammalian hosts and their relevance for understanding the selective pressures acting on parasite evolution.

This paper presents an experience of collective narrative practice with young people with Asperger Syndrome (Aspergers) who have experienced bullying. In Hong Kong, it is common to hear about bullying of young people with Aspergers. This article first discusses some dominant discourses relating to Aspergers and bullying. It then documents the innovative methodologies of the 'Smartphone of Life', which connects young people and assists them to develop second stories with alternative identities. The narrative practices of externalising conversations, re-authoring conversations, outsider-witness conversations, and definitional ceremonies are used to richly describe the stories of the young people. In this work, the local knowledge and skills of young people in resisting the challenges of bullying are documented through co-creating collective postcards. The article concludes with some reflections about the collective practice and ethical considerations.

Acquisition of acute toxoplasmosis during the first trimester of pregnancy can have catastrophic consequences for the foetus. Diagnosis is routinely based on the detection of maternal Toxoplasma gondii – antibodies using whole parasite extracts as detection antigen. While such assays are sensitive, they show no specificity for the stage of infection. We hypothesized diagnosis might be improved using recombinant antigens for detection, particularly if antibodies to certain antigen(s) were associated with early or late stages of infection. To address this, protein microarrays comprising 1513 T. gondii exon products were probed with well-characterized sera from seronegative (‘N’) controls, and acute (‘A’), chronic/IgM-persisting (‘C/M’) and chronic (‘C’) toxoplasmosis cases from Turkey. Three reactive exon products recognized preferentially in A infections, and three recognized preferentially in C/M infections, were expressed in Escherichia coli and tested for discrimination in IgG ELISAs. The best discriminators were exon 1 of TGME49_086450 (GRA5) which detected C/M infections with 70·6% sensitivity and 81·8% specificity, and exon 6 of TGME49_095700 (ubiquitin transferase domain-containing protein) which detected A infections with 84·8% sensitivity and 82·4% specificity. Overall, the data support a recombinant protein approach for the development of improved serodiagnostic tests for toxoplasmosis.

The slowdown in economy and weak market demand have affected shipments of consumer electronic products such as PCs and smartphones in 2022-2023. Shipments of servers, datacenters, and network equipment have grown slightly due to industry policies and digital transformation needs in businesses. This report provides an overview of the development of the global economy and IT hardware industry, comprising of notebook PC, desktop PC, motherboard, server, smartphone, broadband CPE, Wi-Fi router, etc.; examines the influence of the U.S.-China conflict on the IT supply chains, including the production diversification strategy, global brands' deployment strategies in Taiwan, and how the supply chain can transform with digital tools and Net Zero targets in mind.

Global semiconductor equipment market is still dominated by U.S., Japanese, and European brands with their proprietary processes and technologies and has relatively high barriers to enter. Pressured by U.S. semiconductor export controls, the Chinese semiconductor industry will be significantly affected. This report provides an overview of timeline of the trade conflict between the U.S. and China since 2018, analyzes the impact on semiconductor industry in China, the U.S. and Taiwan, outlines China’s possible countermeasures against the conflict, and examines possible opportunities if the conflict continues.

TSMC expressed its willingness to build a 12-inch wafer fab in Arizona, the United States, on May 15, 2020. The plant is expected to be completed and start mass production in 2024 and produce semiconductor chips on a 5nm process. The initial monthly capacity plan is about 20,000 wafers. This report analyzes the potential impact of TSMC's establishment of a factory in the United States and examines risks and benefits behind this decision.