Hospital burden of pneumococcal disease in Spain (2016-2022): A retrospective study.

Pneumococcal disease is a leading cause of morbidity and mortality worldwide. From 2016 to 2022, 358,603 hospitalized patients were identified as having pneumococcal disease. The overall annual hospitalization rate was 108.

Biomarkers.

Background: About 20-30% of clinically diagnosed AD dementia patients do not meet pathologic criteria for AD and this proportion is even higher in amnestic MCI. Among tau-negative amnestic patients, limbic-predominant age-related TDP-43 encephalopathy (LATE) has been described as a principal diagnostic alternative, especially at advanced age. LATE is characterized by a specific temporo-limbic hypometabolic signature on FDG-PET that may aid in differential diagnosis.

Biomarkers.

Background: The preclinical stage of Alzheimer's disease (AD) has gained attention for the window of opportunity it opens for early detection and intervention. Given the high invasiveness of PET and CSF markers, electrophysiology and plasma biomarkers are being studied as alternate biomarkers for early detection and disease tracking. The aim of this study is twofold.

Biomarkers.

Background: Alzheimer's disease (AD) blood biomarkers alone can detect amyloid-β (Aβ) pathology in cognitively unimpaired (CU) individuals. We assessed whether combining different plasma biomarkers improves the detection of Aβ-positivity and identifies rapid amyloid deposition in CU individuals.

Method: CU participants from the ALFA+ cohort were included.

Biomarkers.

Background: Brain, cerebrospinal fluid (CSF), and plasma metabolomics have been informative in identifying disrupted metabolism pathways in Alzheimer's disease (AD). However, many AD-focused metabolomics studies profiled a relatively small number of individuals and metabolites, especially for CSF. In addition, past studies were limited to one or two tissues.

Biomarkers.

Background: Alzheimer disease (AD) plasma biomarkers change in the preclinical stage of AD. However, the robustness of the discrimination performance of these biomarkers, as well as their association with longitudinal primary pathology (amyloid and tau) changes, is less understood. We aimed to determine the ability of baseline and longitudinal plasma amyloid-β (Aβ)42/40, p-tau181, GFAP and NfL to detect primary pathology in CU individuals at risk of AD.

Biomarkers.

Background: Accumulating evidence indicates that biological sex may influence clinical manifestation within the spectrum of frontotemporal lobar degeneration (FTLD), implying differences in cognitive reserve. Nonetheless, investigations into the impact of biological sex during the preclinical and minimally symptomatic stages of FTLD are lacking.

Method: We included 275 mutation carriers (158 females; 127 with C9orf72, 68 with GRN, and 80 with MAPT mutations) and 161 non-carrier familial controls (97 females) from the ALLFTD Consortium (Staffaroni et al.

Biomarkers.

Background: Sleep disturbances have been identified as a risk factor for developing dementia. The hypothalamus is involved in sleep regulation and may be affected early by neurodegeneration. Our aim was to investigate the relationship between subjective sleep and hypothalamic structure in adults at higher risk of developing dementia.

Biomarkers.

Background: The brain undergoes structural changes during aging, such as gray matter loss, enlarged ventricles, and sulcal widening. However, previous studies have primarily investigated these changes in isolation, without describing the complex spatial relationships between overall brain shape and regions. Here, we tested how gradients of expansion and compression of the global shape of the brain as well as between homologous brain regions across hemispheres are affected by age, and whether these changes further contribute to clinical impairment and cognitive deficits in older adults.

Biomarkers.

Background: Dementia with Lewy bodies (DLB) is a an α-synucleinopathy characterized by dementia and a combination of parkinsonism, visual hallucinations, fluctuating cognition or REM sleep behaviour disorder. Specific biomarkers for DLB are lacking. DLB-related pattern (DLBRP) is a metabolic network imaging biomarker which expression can be quantified on a single patient basis.

Low-coordinate bis-phosphine and monophosphine Ni(0) complexes: synthesis and reactivity in C-S cross-coupling.

Preformed Ni(0) complexes are rarely used as precatalysts in cross-coupling reactions, although they can incorporate catalytically active nickel directly into the reaction. In this work, we focus on the preparation and the catalytic application of low-coordinate Ni(0) complexes supported by bulky monophosphine ligands in C-S cross-coupling reactions. We have prepared two families of Ni(0) complexes, bis-phosphine aducts of the type [Ni(PRAr')] (Ar' = -terphenyl group) and monophosphine derivatives of the type [Ni(PRAr')(DVDS)] (DVDS = divinyltetramethyldisiloxane).

Ultrasensitive Detection and Monitoring of Circulating Tumor DNA using Structural Variants in Early-Stage Breast Cancer.

Purpose: The detection of circulating tumor DNA (ctDNA) after curative-intent therapy in early breast cancer (EBC) is highly prognostic of disease recurrence. Current ctDNA assays, mainly targeting single nucleotide variants (SNVs), vary in sensitivity and specificity. While increasing the number of SNVs in tumor-informed assays improves sensitivity, structural variants (SVs) may achieve similar or better sensitivity without compromising specificity.

Biomarkers.

Background: Bilingualism can stimulate brain plasticity (Jafari et al. Ann N Y Acad Sci. 2021;1505(1):8-22) and is also associated with better executive function (Grundy.

Large, recursive membrane platforms are associated to Trop-1, Trop-2 and protein kinase signaling for cell growth.

The transmembrane glycoproteins Trop-1/EpCAM and Trop-2 independently trigger Ca and kinase signals for cell growth and tumor progression. Our findings indicated that Trop-1 and Trop-2 tightly colocalize at macroscopic, ruffle-like protrusions (RLP), that elevate from the cell perimeter, and locally recur over hundreds of seconds. These previously unrecognized elevated membrane regions ≥20 µm-long, up to 1.

Biomarkers.

Background: Different patterns of atrophy exist in the dementia stage of AD. However, little is known about the heterogeneity of atrophy patterns and the mechanisms that drive subsequent propagation of the disease in the preclinical stages.

Method: From the AMYPAD-PNHS cohort, we included a total of 1323 non-demented individuals, including 1094 amyloid-negative, and 229 amyloid-positive participants (Table 1).

Biomarkers.

Background: Neuropsychiatric symptoms (NPS), including depression and circadian rhythm disruptions, are early non-cognitive markers along the Alzheimer's Disease (AD) continuum. These pathological states are thought to resemble AD pathogenesis, both of which are characterized by a marked decline in adult hippocampal neurogenesis.

Method: 96 elderly participants divided into three groups based on the global depression scale, neuropsychiatric inventory, clinical dementia rating, and mini-mental status examination.

Biomarkers.

Background: Fluid biomarkers provide a convenient way to predict AD pathophysiology. However, few studies have focused on determining associations with tau neurofibrillary tangle pathology in the early preclinical AD continuum, relevant to prevention strategies.

Methods: Ninety-nine cognitively unimpaired individuals from the ALFA+ cohort with valid F-RO-948 and F-flutemetamol PET, T1-weighted MRI, cognition, CSF, and plasma biomarkers were included.

Biomarkers.

Background: Familial Alzheimer's disease research necessitates innovative methodologies to disentangle the intricate relationships between genetic factors and neuroimaging measures. Traditional frequentist approaches, often hampered by small sample sizes in this population and challenges in incorporating prior knowledge transparently, may limit the robustness of findings.

Methods: We analyzed neuroimaging data of preclinical PSNE1 single mutation carriers, utilizing the software JASP to test effects of carrier status on measures of basal forebrain functional connectivity using both frequentist and Bayesian approach.

Biomarkers.

Background: The amygdala is a hotspot for neuropathologies; however, it is unclear 1) which neuropathologies lead to amygdala neurodegeneration, 2) what specific amygdala subnuclei are affected, and 3) if the neuropathologies related to amygdala volume are local (inside the amygdala), or distal (in other regions). We investigate the relationships between different neuropathologies (tau, amyloid-β [Aβ], α-synuclein [α-syn], and transactive response DNA-binding protein 43 [TDP-43]) and amygdala volumes.

Method: We analyzed postmortem data from 73 individuals with and without neurodegenerative diseases (age: 77±11 [45-101] years; 26 [36%] females; 51 [70%] cognitively impaired).

Biomarkers.

Background: Alzheimer's disease (AD) plasma biomarkers related to amyloid (A), tau (T), and neurodegeneration (N) can potentially be used to identify these pathological features of the disease, as shown in recent studies. Our objective was to compare the clinical and analytical performance of plasma AD biomarkers measured using the single-molecule array (Simoa) and Lumipulse platforms.

Method: We quantified ATN and AT plasma biomarkers in 127 patients with mild cognitive impairment (MCI) (n = 81), AD (n = 30), and non-AD dementia (n = 16) using a Simoa HD-1/HD-X analyser (Quanterix) and a Lumipulse G600II automated platform (Fujirebio Europe NV).

Biomarkers.

Large neuroimaging datasets play a crucial role in longitudinal modelling and prediction of neurodegenerative diseases, as they provide the opportunity to study biomarker trajectories over time. Noteworthy, the availability of these large datasets coexists with a paradigm shift in the theoretical understanding of these diseases: while classical studies aimed at defining disease signatures as group patterns obtained with static cross-sectional analyses, novel approaches focus on providing individual predictions in the context of phenotypical and temporal heterogeneity. This scenario is often aggravated by the fact that datasets are not homogeneous and suffer from missing points and noisy data.

Biomarkers.

Background: Arterial spin labelling (ASL) is a non-invasive MRI technique for quantifying cerebral blood flow (CBF), used for monitoring changes over the course of a disease or treatment. A crucial parameter in ASL is the post-labelling delay (PLD), determined by the time it takes for blood to travel from the labeling location to the tissue under investigation. Time-encoded ASL (te-ASL) utilizes multiple PLDs for more accurate quantification.

Biomarkers.

Background: Tau-PET imaging allows in-vivo detection of neurofibrillary tangles. One tau-PET tracer (i.e.

Biomarkers.

Background: Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a neurodegenerative disease that is often comorbid with Alzheimer's disease (AD) and for which there are no reliable specific chemical or PET biomarkers available. Recent progress in disease-modifying treatments for AD elevates the need for reliable in vivo detection of LATE and other comorbid neurodegenerative diseases. The promise of postmortem and antemortem MRI studies in LATE is that they will lead to the discovery of patterns of neurodegeneration associated with TDP-43 pathology that could be reliably detected in vivo and used as a biomarker of LATE.