Compact and cGMP-compliant automated synthesis of [F]FSPG on the Trasis AllinOne™.

Background: (S)-4-(3-F-Fluoropropyl)-ʟ-glutamic acid ([F]FSPG) is a positron emission tomography radiotracer used to image system x, an antiporter that is upregulated in several cancers. Not only does imaging system x with [F]FSPG identify tumours, but it can also provide an early readout of response and resistance to therapy. Unfortunately, the clinical production of [F]FSPG has been hampered by a lack of robust, cGMP-compliant methods.

An Exploration of the Knowledge and Current Practices of Frontline Workers Regarding Elder Abuse.

Annually, approximately 16% of adults aged 60 and older are victims of abuse in community settings. A critical first step toward effectively intervening and reducing the prevalence of elder abuse is to better understand the current state of knowledge, beliefs, and practices. This qualitative descriptive study explored the perceptions of US frontline community workers regarding elder abuse through focus groups and interviews conducted in the spring and summer of 2021.

Ageist Attitudes Among Radiologic Science Professionals.

Purpose: To measure radiologic science professionals' current attitudes toward older adults.

Methods: The Geriatrics Attitude Scale (GAS) paper survey was distributed to radiology and radiation oncology personnel in a large, single teaching hospital system. The GAS provides a global measure of ageist attitudes using 14 questions and 4 subscales.

Symptomatic progression of frontotemporal dementia with the I383V variant.

We present a longitudinal description of a man with the I383V variant of frontotemporal dementia (FTD). His progressive changes in behavior and language resulted in a diagnosis of the right temporal variant of FTD, also called the semantic behavioral variant (sbvFTD). We also present data from a small series of patients with the I383V variant who were enrolled in a nationwide FTD research collaboration (ALLFTD).

Abundant transcriptomic alterations in the human cerebellum of patients with a C9orf72 repeat expansion.

The most prominent genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) is a repeat expansion in the gene C9orf72. Importantly, the transcriptomic consequences of the C9orf72 repeat expansion remain largely unclear. Here, we used short-read RNA sequencing (RNAseq) to profile the cerebellar transcriptome, detecting alterations in patients with a C9orf72 repeat expansion.

Generation and characterization of monoclonal antibodies against pathologically phosphorylated TDP-43.

Inclusions containing TAR DNA binding protein 43 (TDP-43) are a pathological hallmark of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). One of the disease-specific features of TDP-43 inclusions is the aberrant phosphorylation of TDP-43 at serines 409/410 (pS409/410). Here, we developed rabbit monoclonal antibodies (mAbs) that specifically detect pS409/410-TDP-43 in multiple model systems and FTD/ALS patient samples.

Chemoselective Synthesis and Anti-Kinetoplastidal Properties of 2,6-Diaryl-4-tetrahydro-thiopyran-4-one -Oxides: Their Interplay in a Cascade of Redox Reactions from Diarylideneacetones.

2,6-Diaryl-4-tetrahydro-thiopyran-4-ones and corresponding sulfoxide and sulfone derivatives were designed to lower the major toxicity of their parent anti-kinetoplatidal diarylideneacetones through a prodrug effect. Novel diastereoselective methodologies were developed and generalized from diarylideneacetones and 2,6-diaryl-4-tetrahydro-thiopyran-4-ones to allow the introduction of a wide substitution profile and to prepare the related -oxides. The in vitro biological activity and selectivity of diarylideneacetones, 2,6-diaryl-4-tetrahydro-thiopyran-4-ones, and their -sulfoxide and sulfone metabolites were evaluated against , , and various species in comparison with their cytotoxicity against human fibroblasts MRC-5.

Erratum: Neurofilament light chain and vaccination status associate with clinical outcomes in severe COVID-19.

[This corrects the article DOI: 10.1016/j.isci.

Cryptic exon inclusion is a molecular signature of LATE-NC in aging brains.

The aggregation, mislocalization, and phosphorylation of TDP-43 are pathologic hallmarks of several neurodegenerative diseases and provide a defining criterion for the neuropathologic diagnosis of Limbic-predominant Age-related TDP-43 Encephalopathy (LATE). LATE neuropathologic changes (LATE-NC) are often comorbid with other neurodegenerative pathologies including Alzheimer's disease neuropathologic changes (ADNC). We examined whether TDP-43 regulated cryptic exons accumulate in the hippocampus of neuropathologically confirmed LATE-NC cases.

Special Focus Facilities vs Special Focus Facility Candidates: What is the Difference?

Objectives: This study compares Special Focus Facilities (SFFs) and Special Focus Facility Candidate Facilities (SFFcs) on organizational traits and quality outcomes to evaluate the effectiveness of the SFF program as a quality improvement intervention and inform potential areas for program reform.

Design: This is a retrospective analysis.

Settings And Participants: Using data from the Centers for Medicare and Medicaid Services archives for 2020, this retrospective study analyzed 247 nursing facilities (50 SFFs and 197 SFFcs).

Immunological drivers of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS), a devastating motor neuron disease involving complex genetic and environmental factors, is associated with neuroinflammation. Preclinical and clinical studies support immune system involvement in ALS pathogenesis, thereby spurring investigations into potential pathogenic mechanisms, immune response biomarkers, and ALS therapeutics.

Smart Speaker and ICT Use in Relationship With Social Connectedness During the Pandemic: Loneliness and Social Isolation Found in Older Adults in Low-Income Housing.

Background And Objectives: Social well-being of older adults living in low-income housing was disproportionately affected by the coronavirus disease 2019 pandemic. We explored low-income residents' experiences of social isolation and loneliness and strategies to remain socially connected during the pandemic.

Research Design And Methods: As part of a larger, 3-phase user-centered design study, we conducted a qualitative study using focus groups to gain insights into social isolation experiences and the role of information and communication technologies (ICTs), including smart speakers, in social connectedness (N = 25, 76% African American).

Roadmap for C9ORF72 in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis: Report on the C9ORF72 FTD/ALS Summit.

A summit held March 2023 in Scottsdale, Arizona (USA) focused on the intronic hexanucleotide expansion in the C9ORF72 gene and its relevance in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS; C9ORF72-FTD/ALS). The goal of this summit was to connect basic scientists, clinical researchers, drug developers, and individuals affected by C9ORF72-FTD/ALS to evaluate how collaborative efforts across the FTD-ALS disease spectrum might break down existing disease silos. Presentations and discussions covered recent discoveries in C9ORF72-FTD/ALS disease mechanisms, availability of disease biomarkers and recent advances in therapeutic development, and clinical trial design for prevention and treatment for individuals affected by C9ORF72-FTD/ALS and asymptomatic pathological expansion carriers.

Cultivating Relationships as a Community-Based Recruitment Strategy in Transdisciplinary Aging Research: Lessons From an Academic-Community Partnership.

Participation of Black American older adults in community-engaged research remains challenging in health sciences. The objectives of this study were to describe the specific efforts, successes, and challenges in recruiting Black American older adults in research led by the Health and Wellness in Aging Across the Lifespan core, part of the Virginia Commonwealth University Institute for Inclusion, Inquiry, and Innovation (iCubed). We conducted a cross-case analysis of 6 community-engaged research projects using the community-engaged research continuum model.

Artificial microRNA suppresses C9ORF72 variants and decreases toxic dipeptide repeat proteins in vivo.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects motor neurons, causing progressive muscle weakness and respiratory failure. The presence of an expanded hexanucleotide repeat in chromosome 9 open reading frame 72 (C9ORF72) is the most frequent mutation causing familial ALS and frontotemporal dementia (FTD). To determine if suppressing expression of C9ORF72 gene products can reduce toxicity, we designed a set of artificial microRNAs (amiRNA) targeting the human C9ORF72 gene.