Case Series of Right-Hemisphere Nonfluent Variant of Primary Progressive Aphasia.

Background And Purpose: Nonfluent variant primary progressive aphasia (nfvPPA) is a neurodegenerative disorder characterized by the progressive deterioration of language functions that typically appears with atrophy predominating in the left peri-insular region (left-nfvPPA) on imaging. While both left-dominant and right-dominant presentations have been reported in semantic variant primary progressive aphasia, the other language presentation of frontotemporal dementia, no case series of nfvPPA with predominantly right-sided atrophy of the peri-insular region (right-nfvPPA) have been reported previously. This study explored whether such entities exist and what their clinical features might be.

Superior antitumor immune response achieved with proton over photon immunoradiotherapy is amplified by the nanoradioenhancer NBTXR3.

Recent findings suggest that immunoradiotherapy (IRT), combining photon radiotherapy (XRT) or proton radiotherapy (PRT) with immune checkpoint blockade, can enhance systemic tumor control. However, the comparative efficacy of XRT and PRT in IRT remains understudied. To address this, we compared outcomes between XRT + αPD1 and PRT + αPD1 in murine αPD1-resistant lung cancer (344SQR).

Novel engineered IL-2 Nemvaleukin alfa combined with PD1 checkpoint blockade enhances the systemic anti-tumor responses of radiation therapy.

Background: Combining interleukin-2 (IL-2) with radiotherapy (RT) and immune checkpoint blockade (ICB) has emerged as a promising approach to address ICB resistance. However, conventional IL-2 cytokine therapy faces constraints owing to its brief half-life and adverse effects. RDB 1462, the mouse ortholog of Nemvaleukin alfa, is an engineered IL-2 with an intermediate affinity that selectively stimulates antitumor CD8 T and NK cells while limiting regulatory T cell expansion.

Inhibition of MER proto-oncogene tyrosine kinase by an antisense oligonucleotide enhances treatment efficacy of immunoradiotherapy.

Background: The combination of radiotherapy and immunotherapy (immunoradiotherapy) has been increasingly used for treating a wide range of cancers. However, some tumors are resistant to immunoradiotherapy. We have previously shown that MER proto-oncogene tyrosine kinase (MerTK) expressed on macrophages mediates resistance to immunoradiotherapy.

Clinical and cortical trajectories in non-fluent primary progressive aphasia and Alzheimer's disease: A role for emotion processing.

Objectives: To examine the clinical trajectories and neural correlates of cognitive and emotion processing changes in the non-fluent/agrammatic (nfvPPA) and the logopenic (lvPPA) variants of primary progressive aphasia (PPA).

Design: Observational case-control longitudinal cohort study.

Setting: Research clinic of frontotemporal dementia.

Nanoparticle-enhanced proton beam immunoradiotherapy drives immune activation and durable tumor rejection.

The combination of radiation therapy (RT) and immunotherapy has emerged as a promising treatment option in oncology. Historically, x-ray radiation (XRT) has been the most commonly used form of RT. However, proton beam therapy (PBT) is gaining recognition as a viable alternative, as it has been shown to produce similar outcomes to XRT while minimizing off-target effects.

Do age and language impairment affect speed of recognition for words with high and low closeness centrality within the phonological network?

Purpose: Speed and accuracy of lexical access change with healthy ageing and neurodegeneration. While a word's immediate phonological neighbourhood density (i.e.

NBTXR3 improves the efficacy of immunoradiotherapy combining nonfucosylated anti-CTLA4 in an anti-PD1 resistant lung cancer model.

The efficacy of immunoradiotherapy consisting of radiation therapy and immune checkpoint blockade relies on effectively promoting the systemic antitumor immune response's activation while simultaneously reducing local factors favoring immune suppression. We previously demonstrated that NBTXR3, a nanoparticle radioenhancer, significantly improved immune responses in a murine anti-PD1-resistant metastatic lung cancer model. We hypothesize that radioactivated-NBTXR3 addition to anti-PD1 and a second-generation anti-CTLA4 could improve treatment effectiveness.

Combining a nanoparticle-mediated immunoradiotherapy with dual blockade of LAG3 and TIGIT improves the treatment efficacy in anti-PD1 resistant lung cancer.

Background: While improvements in immunoradiotherapy have significantly improved outcomes for cancer patients, this treatment approach has nevertheless proven ineffective at controlling the majority of malignancies. One of the mechanisms of resistance to immunoradiotherapy is that immune cells may be suppressed via the myriad of different immune checkpoint receptors. Therefore, simultaneous blockade of multiple immune checkpoint receptors may enhance the treatment efficacy of immunoradiotherapy.

Social, political, and economic determinants of access to biologics: A scoping review of structural determinants in the clinical disparities literature.

Background: The number of biologics among new medication approvals is increasing. Social, political, and economic factors influence access to these expensive medications. Disparities in access to new medications can exacerbate health disparities.

Utility of the Addenbrooke's Cognitive Examination III online calculator to differentiate the primary progressive aphasia variants.

The Addenbrooke's Cognitive Examination III is a brief cognitive screening tool that is widely used for the detection and monitoring of dementia. Recent findings suggest that the three variants of primary progressive aphasia can be distinguished based on their distinct profiles on the five subdomain scores of this test. Here, we investigated the utility of the Addenbrooke's Cognitive Examination III to differentiate the primary progressive aphasia variants based on their item-by-item performance profiles on this test.

Examining the presence and nature of delusions in Alzheimer's disease and frontotemporal dementia syndromes.

Objectives: Abnormal beliefs and delusions have been reported in some people with dementia, however, the prevalence of delusions, and their neurocognitive basis has been underexplored. This study aimed to examine the presence, severity, content and neural correlates of delusions in a large, well-characterised cohort of dementia patients using a transdiagnostic, cross-sectional approach.

Methods: Four-hundred and eighty-seven people with dementia were recruited: 102 Alzheimer's disease, 136 behavioural-variant frontotemporal dementia, 154 primary progressive aphasia, 29 motor neurone disease, 46 corticobasal syndrome, 20 progressive supranuclear palsy.

Cognitive and Neural Mechanisms of Social Communication Dysfunction in Primary Progressive Aphasia.

Mounting evidence suggests that, in parallel with well-defined changes in language, primary progressive aphasia (PPA) syndromes display co-occurring social cognitive impairments. Here, we explored multidimensional profiles of carer-rated social communication using the La Trobe Communication Questionnaire (LCQ) in 11 semantic dementia (SD), 12 logopenic progressive aphasia (LPA) and 9 progressive non-fluent aphasia (PNFA) cases and contrasted their performance with 19 Alzheimer's disease (AD) cases, 26 behavioural variant frontotemporal dementia (bvFTD) cases and 31 healthy older controls. Relative to the controls, the majority of patient groups displayed significant overall social communication difficulties, with common and unique profiles of impairment evident on the LCQ subscales.

Brain changes underlying progression of speech motor programming impairment.

Aquired apraxia of speech is a disorder that impairs speech production, despite intact peripheral neuromotor function. Its pathomechanism remains to be established. Neurodegenerative lesion models provide an unequalled opportunity to explore the neural correlates of apraxia of speech, which is present in a subset of patients diagnosed with non-semantic variants of primary progressive aphasia.

What to make of equivocal amyloid imaging results.

Introduction: Six patients with equivocal amyloid-PET results are discussed.

Methods: Patients underwent clinical/neuropsychological assessment, MRI, and amyloid-PET. Equivocal amyloid-PET was defined as cortical ligand binding with SUVR < 1.

Systematic Review of Evidence-Based Guidelines for Prehospital Care.

: Multiple national organizations have identified a need to incorporate more evidence-based medicine in emergency medical services (EMS) through the creation of evidence-based guidelines (EBGs). Tools like the Appraisal of Guidelines for Research and Evaluation (AGREE) II and criteria outlined by the National Academy of Medicine (NAM) have established concrete recommendations for the development of high-quality guidelines. While many guidelines have been created that address topics within EMS medicine, neither the quantity nor quality of prehospital EBGs have been previously reported.

Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer's disease.

Background: The Centiloid scale was developed to standardise the results of beta-amyloid (Aβ) PET. We aimed to determine the Centiloid unit (CL) thresholds for CERAD sparse and moderate-density neuritic plaques, Alzheimer's disease neuropathologic change (ADNC) score of intermediate or high probability of Alzheimer's Disease (AD), final clinicopathological diagnosis of AD, and expert visual read of a positive Aβ PET scan.

Methods: Aβ PET results in CL for 49 subjects were compared with post-mortem findings, visual read, and final clinicopathological diagnosis.

Correlates of anomia in non-semantic variants of primary progressive aphasia converge over time.

To track neural correlates of naming performance with disease progression, we estimated key areas affected in nonfluent/agrammatic (nfvPPA) and logopenic (lvPPA) primary progressive aphasia variants over time and changes in naming correlates over time. Twenty-nine non-semantic PPA participants (17 nfvPPA and 12 lvPPA) were selected based upon current diagnostic criteria and PiB-PET status and conducted a confrontation-naming task and a structural MRI. Linear mixed-effect models implemented in FreeSurfer were used for tracking cortical thickness and epicenters of atrophy over time.

Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia.

Objective: To estimate the prevalence of amyloid positivity, defined by positron emission tomography (PET)/cerebrospinal fluid (CSF) biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants.

Methods: We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n = 443], nonfluent [nfvPPA, n = 333], semantic [svPPA, n = 401], and mixed/unclassifiable [n = 74] variants of PPA) from 36 centers, with a measure of amyloid-β pathology (CSF [n = 600], PET [n = 366], and/or autopsy [n = 378]) available. The estimated prevalence of amyloid positivity according to PPA variant, age, and apolipoprotein E (ApoE) ε4 status was determined using generalized estimating equation models.