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CitationGPTv2_test

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CitationGPTRetr100

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: Cryo-EM structures of tau filaments from Alzheimer's disease with PET ligand APN-1607. Abstract of the paper: Tau and Aβ assemblies of Alzheimer's disease (AD) can be visualized in living subjects using positron emission tomography (PET). Tau assemblies comprise paired helical and straight filaments (PHFs and SFs). APN-1607 (PM-PBB3) is a recently described PET ligand for AD and other tau proteinopathies. Since it is not known where in the tau folds PET ligands bind, we used electron cryo-microscopy (cryo-EM) to determine the binding sites of APN-1607 in the Alzheimer fold. We identified two major sites in the β-helix of PHFs and SFs and a third major site in the C-shaped cavity of SFs. In addition, we report that tau filaments from posterior cortical atrophy (PCA) and primary age-related tauopathy (PART) are identical to those from AD. In support, fluorescence labelling showed binding of APN-1607 to intraneuronal inclusions in AD, PART and PCA. Knowledge of the binding modes of APN-1607 to tau filaments may lead to the development of new ligands with increased specificity and binding activity. We show that cryo-EM can be used to identify the binding sites of small molecules in amyloid filaments.

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CitationGPTRetr101

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: Helical structure, stability, and dynamics in human apolipoprotein E3 and E4 by hydrogen exchange and mass spectrometry. Abstract of the paper: Apolipoprotein E (apoE) plays a critical role in cholesterol transport in both peripheral circulation and brain. Human apoE is a polymorphic 299-residue protein in which the less common E4 isoform differs from the major E3 isoform only by a C112R substitution. ApoE4 interacts with lipoprotein particles and with the amyloid-β peptide, and it is associated with increased incidence of cardiovascular and Alzheimer's disease. To understand the structural basis for the differences between apoE3 and E4 functionality, we used hydrogen-deuterium exchange coupled with a fragment separation method and mass spectrometric analysis to compare their secondary structures at near amino acid resolution. We determined the positions, dynamics, and stabilities of the helical segments in these two proteins, in their normal tetrameric state and in mutation-induced monomeric mutants. Consistent with prior X-ray crystallography and NMR results, the N-terminal domain contains four α-helices, 20 to 30 amino acids long. The C-terminal domain is relatively unstructured in the monomeric state but forms an α-helix ∼70 residues long in the self-associated tetrameric state. Helix stabilities are relatively low, 4 kcal/mol to 5 kcal/mol, consistent with flexibility and facile reversible unfolding. Secondary structure in the tetrameric apoE3 and E4 isoforms is similar except that some helical segments in apoE4 spanning residues 12 to 20 and 204 to 210 are unfolded. These conformational differences result from the C112R substitution in the N-terminal helix bundle and likely relate to a reduced ability of apoE4 to form tetramers, thereby increasing the concentration of functional apoE4 monomers, which gives rise to its higher lipid binding compared with apoE3.

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CitationGPTRetr102

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Abstract of the paper: Comparative protein modeling is increasingly gaining interest since it is of great assistance during the rational design of mutagenesis experiments. The availability of this method, and the resulting models, has however been restricted by the availability of expensive computer hardware and software. To overcome these limitations, we have developed an environment for comparative protein modeling that consists of SWISS-MODEL, a server for automated comparative protein modeling and of the SWISS-PdbViewer, a sequence to structure workbench. The Swiss-PdbViewer not only acts as a client for SWISS-MODEL, but also provides a large selection of structure analysis and display tools. In addition, we provide the SWISS-MODEL Repository, a database containing more than 3500 automatically generated protein models. By making such tools freely available to the scientific community, we hope to increase the use of protein structures and models in the process of experiment design.

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CitationGPTRetr103

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: Interaction of the N-terminal domain of apolipoprotein E4 with heparin. Abstract of the paper: Apolipoprotein E (apoE) is an important lipid-transport protein in human plasma and brain. It has three common isoforms (apoE2, apoE3, and apoE4). ApoE is a major genetic risk factor in heart disease and in neurodegenerative disease, including Alzheimer's disease. The interaction of apoE with heparan sulfate proteoglycans plays an important role in lipoprotein remnant uptake and likely in atherogenesis and Alzheimer's disease. Here we report our studies of the interaction of the N-terminal domain of apoE4 (residues 1-191), which contains the major heparin-binding site, with an enzymatically prepared heparin oligosaccharide. Identified by its high affinity for the N-terminal domain of apoE4, this oligosaccharide was determined to be an octasaccharide of the structure DeltaUAp2S(1-->[4)-alpha-D-GlcNpS6S(1-->4)-alpha-L-IdoAp2S(1-->](3)4)-alpha-D-GlcNpS6S by nuclear magnetic resonance spectroscopy, capillary electrophoresis, and polyacrylamide gel electrophoresis. Kinetic analysis of the interaction between the N-terminal apoE4 fragment and immobilized heparin by surface plasmon resonance yielded a K(d) of 150 nM. A similar binding constant (K(d) = 140 nM) was observed for the interaction between immobilized N-terminal apoE4 and the octasaccharide. Isothermal titration calorimetry revealed a K(d) of 75 nM for the interaction of the N-terminal apoE fragment and the octasaccharide with a binding stoichiometry of approximately 1:1. Using previous studies and molecular modeling, we propose a binding site for this octasaccharide in a basic residue-rich region of helix 4 of the N-terminal fragment. From the X-ray crystal structure of the N-terminal apoE4, we predicted that binding of the octasaccharide at this site would result in a change in intrinsic fluorescence. This prediction was confirmed experimentally by an observed increase in fluorescence intensity with octasaccharide binding corresponding to a K(d) of approximately 1 microM.

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CitationGPTRetr104

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: Chemical cross-linking/mass spectrometry maps the amyloid β peptide binding region on both apolipoprotein E domains. Abstract of the paper: Apolipoprotein E (apoE) binds the amyloid β peptide (Aβ), one of the major culprits in Alzheimer's disease development. The formation of apoE:Aβ complexes is implicated in both Aβ clearance and fibrillization. However, the binding interface between apoE and Aβ is poorly defined despite substantial previous research efforts, and the exact role of apoE in the pathology of Alzheimer's disease remains largely elusive. Here, we compared the three main isoforms of apoE (E2, E3, and E4) for their interaction with Aβ1-42 in an early stage of aggregation and at near physiological conditions. Using electron microscopy and Western blots, we showed that all three isoforms are able to prevent Aβ fibrillization and form a noncovalent complex, with one molecule of Aβ bound per apoE. Using chemical cross-linking coupled to mass spectrometry, we further examined the interface of interaction between apoE2/3/4 and Aβ. Multiple high-confidence intermolecular apoE2/3/4:Aβ cross-links confirmed that Lys16 is located in the region of Aβ binding to apoE2/3/4. Further, we demonstrated that both N- and C-terminal domains of apoE2/3/4 are interacting with Aβ. The cross-linked sites were mapped onto and evaluated in light of a recent structure of apoE. Our results support binding of the hydrophobic Aβ at the apoE domain-domain interaction interface, which would explain how apoE is able to stabilize Aβ and thereby prevent its subsequent aggregation.

False

CitationGPTRetr105

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: Role of the N- and C-terminal domains in binding of apolipoprotein E isoforms to heparan sulfate and dermatan sulfate: a surface plasmon resonance study. Abstract of the paper: The ability of apolipoprotein E (apoE) to bind to cell-surface glycosaminoglycans (GAGs) is important for lipoprotein remnant catabolism. Using surface plasmon resonance, we previously showed that the binding of apoE to heparin is a two-step process; the initial binding involves fast electrostatic interaction, followed by a slower hydrophobic interaction. Here we examined the contributions of the N- and C-terminal domains to each step of the binding of apoE isoforms to heparan sulfate (HS) and dermatan sulfate (DS). ApoE3 bound to less sulfated HS and DS with a decreased favorable free energy of binding in the first step compared to heparin, indicating that the degree of sulfation has a major effect on the electrostatic interaction of GAGs with apoE. Mutation of a key Lys residue in the N-terminal heparin binding site of apoE significantly affected this electrostatic interaction. Progressive truncation of the C-terminal alpha-helical regions which favors the monomeric form of apoE3 greatly weakened the ability of apoE3 to bind to HS, with a much reduced favorable free energy of binding of the first step, suggesting that the C-terminal domain contributes to the GAG binding of apoE by the oligomerization effect. In agreement with this, dimerization of the apoE3 N-terminal fragment via disulfide linkage restored the electrostatic interaction of apoE with HS. Significantly, apoE4 exhibited much stronger binding to HS and DS than apoE2 or apoE3 in both lipid-free and lipidated states, perhaps resulting from enhanced electrostatic interaction through the N-terminal domain. This isoform difference in GAG binding of apoE may be physiologically significant such as in the retention of apoE-containing lipoproteins in the arterial wall.

False

CitationGPTRetr106

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: Helix orientation of the functional domains in apolipoprotein e in discoidal high density lipoprotein particles. Abstract of the paper: Human apolipoprotein E (apoE) mediates high affinity binding to the low density lipoprotein receptor when present on a lipidated complex. In the absence of lipid, however, apoE does not bind the receptor. Whereas the x-ray structure of lipid-free apoE3 N-terminal (NT) domain is known, the structural organization of its lipid-associated, receptor-active conformation is poorly understood. To study the organization of apoE amphipathic alpha-helices in a lipid-associated state, single tryptophan-containing apoE3 variants were employed in fluorescence quenching studies. The relative positions of the Trp residues with respect to the phospholipid component of apoE/lipid particles were established from the degree of quenching by phospholipids bearing nitroxide groups at various positions along their fatty acyl chains. Four apoE3-NT variants bearing Trp reporter groups at positions 141, 148, 155, or 162 within helix 4 and two apoE3 variants containing single Trp at positions 257 or 264 in the C-terminal (CT) domain, were reconstituted into phospholipid-containing discoidal complexes. Parallax analysis revealed that each engineered Trp residue in helix 4 of apoE3-NT, as well as those in the CT domain of apoE, localized approximately 5 A from the center of the bilayer. Circular dichroism studies revealed that lipid association induces additional helix formation in apoE. Protease protection assays suggest the flexible loop segment between the NT and CT domains may transition from unstructured to helix upon lipid association. Taken together, these data support a model wherein the alpha-helices in the receptor-binding region and the CT domain of apoE align perpendicular to the fatty acyl chains of the phospholipid bilayer. In this alignment, the residues of helix 4 are arrayed in a positively charged, curved helical segment for optimal receptor interaction.

False

CitationGPTRetr107

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: PDBe-KB: a community-driven resource for structural and functional annotations. Abstract of the paper: The Protein Data Bank in Europe-Knowledge Base (PDBe-KB, https://pdbe-kb.org) is a community-driven, collaborative resource for literature-derived, manually curated and computationally predicted structural and functional annotations of macromolecular structure data, contained in the Protein Data Bank (PDB). The goal of PDBe-KB is two-fold: (i) to increase the visibility and reduce the fragmentation of annotations contributed by specialist data resources, and to make these data more findable, accessible, interoperable and reusable (FAIR) and (ii) to place macromolecular structure data in their biological context, thus facilitating their use by the broader scientific community in fundamental and applied research. Here, we describe the guidelines of this collaborative effort, the current status of contributed data, and the PDBe-KB infrastructure, which includes the data exchange format, the deposition system for added value annotations, the distributable database containing the assembled data, and programmatic access endpoints. We also describe a series of novel web-pages-the PDBe-KB aggregated views of structure data-which combine information on macromolecular structures from many PDB entries. We have recently released the first set of pages in this series, which provide an overview of available structural and functional information for a protein of interest, referenced by a UniProtKB accession.

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CitationGPTRetr108

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: Carboxyl-terminal domain of human apolipoprotein E: expression, purification, and crystallization. Abstract of the paper: Thioredoxin fusion expression vectors for two carboxyl-terminal fragments of human apolipoprotein (apo) E (residues 223-272 and 223-299) were generated from an apoE cDNA with the objective of obtaining structural information on this functionally important region of apoE by X-ray crystallography. A thrombin cleavage recognition site was positioned at the fusion junction to release the apoE fragments from the fusion protein. The fusion proteins were expressed in Escherichia coli, isolated from cell lysates by nickel-affinity column chromatography, and cleaved with thrombin. After gel filtration and ion exchange chromatography, yields of each fragment were approximately 14 mg/L. Both fragments bind to the phospholipid dimyristoylphosphatidylcholine in a manner similar to that of the 216-299 fragment of apoE isolated from plasma, which represents the major lipid-binding region of the protein. Orthorhombic crystals of the apoE 223-272 fragment that diffracted to 1.8 A were obtained in a mixture of 0.1 M imidazole (pH 6.0) and 0.4 M NaOAc (pH 7.0-7.5), containing 30% glycerol. The space group is C222 with cell dimensions of a = 35.17 A, b = 38.95 A, and c = 133.27 A.

False

CitationGPTRetr109

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: The X-ray structure of an antiparallel dimer of the human amyloid precursor protein E2 domain. Abstract of the paper: Amyloid beta-peptide, which forms neuronal and vascular amyloid deposits in Alzheimer's disease, is derived from an integral membrane protein precursor. The biological function of the precursor is currently unclear. Here we describe the X-ray structure of E2, the largest of the three conserved domains of the precursor. The structure of E2 consists of two coiled-coil substructures connected through a continuous helix and bears an unexpected resemblance to the spectrin family of protein structures. E2 can reversibly dimerize in the solution, and the dimerization occurs along the longest dimension of the molecule in an antiparallel orientation, which enables the N-terminal substructure of one monomer to pack against the C-terminal substructure of a second monomer. Heparan sulfate proteoglycans, the putative ligand for the precursor present in extracellular matrix, bind to E2 at a conserved and positively charged site near the dimer interface.

False

CitationGPTRetr110

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: Characterization of the high affinity heparin binding site of the Alzheimer's disease beta A4 amyloid precursor protein (APP) and its enhancement by zinc(II). Abstract of the paper: The Alzheimer's disease beta A4 amyloid precursor protein (APP) has been shown to be involved in a diverse set of biological activities including regulation of cell growth, neurite outgrowth and adhesiveness. The APP and amyloid protein precursor-like proteins (APLP1 and APLP2) belong to a superfamily of proteins that are probably functionally related. In order to characterize the cell adhesion properties of APP the brain specific isoform APP695 was purified and used to assess the binding to heparin, a structural and functional analogue of the glycosaminoglycan heparan sulfate. We show that APP binds in a time dependent and saturable manner to heparin. The salt concentration of 620 mM at which APP elutes from heparin Sepharose is greater than physiological. The apparent equilibrium constant for dissociation was determined to be 300 pM for APP binding to heparin Sepharose. A high affinity heparin binding site was identified within a region conserved in rodent and human APP, APLP1 and APLP2. This binding site was located between residues 316-337 of APP695 which is within the carbohydrate domain of APP. We also demonstrate an interaction between this heparin binding site and the zinc(II) binding site which is conserved in all members of the APP superfamily. We show by using an automated surface plasmon resonance biosensor (BIAcore, Pharmacia) that the affinity for heparin is increased two- to four-fold in the presence of micromolar zinc(II). The identification of zinc-enhanced binding of APP to heparan sulfate side chains of proteoglycans offers a molecular link between zinc(II), as a putative environmental toxin for Alzheimer's disease, and aggregation of amyloid beta A4 protein.

False

CitationGPTRetr111

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: Cryo-EM structures of τ filaments from human brain. Abstract of the paper: Electron cryo-microscopy (cryo-EM) has made it possible to determine near-atomic structures of τ filaments from human brain. Previous work had shown that the cores of paired helical and straight filaments of Alzheimer's disease are made of two identical, but differently arranged C-shaped protofilaments. In recent years, cryo-EM has shown that the Alzheimer τ fold is 79 amino acids long. Five of the eight β-strands give rise to two antiparallel β-sheets, with the other three forming a β-helix. High-affinity binding sites of positron emission tomography ligand APN-1607 (PM-PBB3) are in the β-helix region. The Alzheimer fold contrasts with the 94 amino acid-long Pick fold, which is J-shaped and comprises nine β-strands that give rise to four antiparallel β-sheets, in the absence of a β-helix. Chronic traumatic encephalopathy τ fold is similar to the Alzheimer fold, but differs in the β-helix region, which is larger and contains a non-proteinaceous density that is probably hydrophobic. These folds are mostly two-layered. By contrast, the 107 amino acid τ fold of the 4R tauopathy corticobasal degeneration is four-layered and comprises 11 β-strands. It contains an internal, probably hydrophilic, density that is surrounded by τ. The τ folds described here share the presence of microtubule-binding repeats 3 and 4, as well as 10-13 amino acids after repeat 4.

False

CitationGPTRetr112

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: RCSB Protein Data bank: Tools for visualizing and understanding biological macromolecules in 3D. Abstract of the paper: Now in its 52nd year of continuous operations, the Protein Data Bank (PDB) is the premiere open-access global archive housing three-dimensional (3D) biomolecular structure data. It is jointly managed by the Worldwide Protein Data Bank (wwPDB) partnership. The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) is funded by the National Science Foundation, National Institutes of Health, and US Department of Energy and serves as the US data center for the wwPDB. RCSB PDB is also responsible for the security of PDB data in its role as wwPDB-designated Archive Keeper. Every year, RCSB PDB serves tens of thousands of depositors of 3D macromolecular structure data (coming from macromolecular crystallography, nuclear magnetic resonance spectroscopy, electron microscopy, and micro-electron diffraction). The RCSB PDB research-focused web portal (RCSB.org) makes PDB data available at no charge and without usage restrictions to many millions of PDB data consumers around the world. The RCSB PDB training, outreach, and education web portal (PDB101.RCSB.org) serves nearly 700 K educators, students, and members of the public worldwide. This invited Tools Issue contribution describes how RCSB PDB (i) is organized; (ii) works with wwPDB partners to process new depositions; (iii) serves as the wwPDB-designated Archive Keeper; (iv) enables exploration and 3D visualization of PDB data via RCSB.org; and (v) supports training, outreach, and education via PDB101.RCSB.org. New tools and features at RCSB.org are presented using examples drawn from high-resolution structural studies of proteins relevant to treatment of human cancers by targeting immune checkpoints.

False

CitationGPTRetr113

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: High-affinity multivalent interactions between apolipoprotein E and the oligomers of amyloid-β. Abstract of the paper: Although the interaction of apoE isoforms with amyloid-β (Aβ) peptides plays a critical role in the progression of Alzheimer's disease, how they interact with each other remains poorly understood. Here, we investigate the molecular mechanism of apoE-Aβ interactions by comparing the effects of the different domains of apoE on Aβ. The kinetics of aggregation of Aβ1-42 are delayed dramatically in the presence of substoichiometric, nanomolar concentrations of N-terminal fragment (NTF), C-terminal fragment (CTF) and full-length apoE both in lipid-free and in lipidated forms. However, interactions between apoE and Aβ as measured by intermolecular Förster resonance energy transfer (FRET) analysis were found to be minimal at t = 0 but to increase in a time-dependent manner. Thus, apoE must interact with one or more 'intermediates' rather than the monomers of Aβ. Kinetics of FRET between full-length apoE4 labelled with EDANS at position 62 or 139 or 210 or 247 or 276, and tetramethylrhodamine-labelled Aβ (TMR-Aβ), further support an involvement of all the three domains of apoE in the interactions. However, the above-mentioned residues do not appear to form a single pocket in the 3-dimensional structure of apoE. A competitive binding assay examining the effects of unlabelled fragments or full-length apoE on the FRET between EDANS-apoE and TMR-Aβ show that binding affinity of the full-length apoE to Aβ is much higher than that of the fragments. Furthermore, apoE4 is found to interact more strongly than apoE3. We hypothesize that high affinity of the apoE-Aβ interaction is attained due to multivalent binding mediated by multiple interactions between oligomeric Aβ and full-length apoE.

False

CitationGPTRetr114

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: cDNA cloning and chromosome mapping of the human Fe65 gene: interaction of the conserved cytoplasmic domains of the human beta-amyloid precursor protein and its homologues with the mouse Fe65 protein. Abstract of the paper: Using the yeast two hybrid system, a mouse embryo cDNA library was screened for proteins that interact with the C-terminus of the human beta-amyloid precursor protein (beta PP). A fusion protein was identified that interacts specifically with the cytoplasmic domain of beta PP and does not interact with the beta-amyloid region. The protein encoded by this partial mouse cDNA is identical to the C-terminus of the rat Fe65 protein. This mouse protein also interacts with the homologous C-terminal domains of the mouse amyloid precursor-like proteins, APLP1 and APLP2. These conserved cytoplasmic regions contain a common amino acid motif, Asn-Pro-Thr-Tyr, which has previously been shown to influence both the secretion and internalization of beta PP. Fe65 has been implicated in regulatory and cell signaling mechanisms because it contains two different motifs involved in protein binding, a WW domain (a variant of Src homology 3 domains) and a phosphotyrosine interaction domain (PID). Interestingly, the PID domain binds to the same motif present in the conserved cytoplasmic domains of the beta PP and beta PP-like proteins. RNA analyses reveal that Fe65 is predominantly expressed in brain and in the regions most affected by Alzheimer's disease (AD)-associated neuropathology. The human Fe65 mRNA was cloned from a fetal brain cDNA library. The message encodes a protein of 735 amino acids that is 95% identical to the rat Fe65 protein. The human Fe65 gene was mapped on human metaphase chromosomes to band 11p15 using fluorescence in situ hybridization.

False

CitationGPTRetr115

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: Structural variation in human apolipoprotein E3 and E4: secondary structure, tertiary structure, and size distribution. Abstract of the paper: Human apolipoprotein E (apoE) is a 299-amino-acid protein with a molecular weight of 34 kDa. The difference between the apoE3 and apoE4 isoforms is a single residue substitution involving a Cys-Arg replacement at residue 112. ApoE4 is positively associated with atherosclerosis and late-onset and sporadic Alzheimer's disease (AD). ApoE4 and its C-terminal truncated fragments have been found in the senile plaques and neurofibrillary tangles in the brain of AD patients. However, detail structural information regarding isoform and domain interaction remains poorly understood. We prepared full-length, N-, and C-terminal truncated apoE3 and apoE4 proteins and studied their structural variation. Sedimentation velocity and continuous size distribution analysis using analytical ultracentrifugation revealed apoE3(72-299) as consisting of a major species with a sedimentation coefficient of 5.9. ApoE4(72-299) showed a wider and more complicated species distribution. Both apoE3 and E4 N-terminal domain (1-191) existed with monomers as the major component together with some tetramer. The oligomerization and aggregation of apoE protein increased when the C-terminal domain (192-271) was incorporated. The structural influence of the C-terminal domain on apoE is to assist self-association with no significant isoform preference. Circular dichroism and fluorescence studies demonstrated that apoE4(72-299) possessed a more alpha-helical structure with more hydrophobic residue exposure. The structural variation of the N-terminal truncated apoE3 and apoE4 protein provides useful information that helps to explain the greater aggregation of the apoE4 isoform and thus has implication for the involvement of apoE4 in AD.

False

CitationGPTRetr116

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: ModBase, a database of annotated comparative protein structure models and associated resources. Abstract of the paper: ModBase (http://salilab.org/modbase) is a database of annotated comparative protein structure models. The models are calculated by ModPipe, an automated modeling pipeline that relies primarily on Modeller for fold assignment, sequence-structure alignment, model building and model assessment (http://salilab.org/modeller/). ModBase currently contains almost 30 million reliable models for domains in 4.7 million unique protein sequences. ModBase allows users to compute or update comparative models on demand, through an interface to the ModWeb modeling server (http://salilab.org/modweb). ModBase models are also available through the Protein Model Portal (http://www.proteinmodelportal.org/). Recently developed associated resources include the AllosMod server for modeling ligand-induced protein dynamics (http://salilab.org/allosmod), the AllosMod-FoXS server for predicting a structural ensemble that fits an SAXS profile (http://salilab.org/allosmod-foxs), the FoXSDock server for protein-protein docking filtered by an SAXS profile (http://salilab.org/foxsdock), the SAXS Merge server for automatic merging of SAXS profiles (http://salilab.org/saxsmerge) and the Pose & Rank server for scoring protein-ligand complexes (http://salilab.org/poseandrank). In this update, we also highlight two applications of ModBase: a PSI:Biology initiative to maximize the structural coverage of the human alpha-helical transmembrane proteome and a determination of structural determinants of human immunodeficiency virus-1 protease specificity.

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CitationGPTRetr117

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: RCSB Protein Data Bank: biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy. Abstract of the paper: The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB, rcsb.org), the US data center for the global PDB archive, serves thousands of Data Depositors in the Americas and Oceania and makes 3D macromolecular structure data available at no charge and without usage restrictions to more than 1 million rcsb.org Users worldwide and 600 000 pdb101.rcsb.org education-focused Users around the globe. PDB Data Depositors include structural biologists using macromolecular crystallography, nuclear magnetic resonance spectroscopy and 3D electron microscopy. PDB Data Consumers include researchers, educators and students studying Fundamental Biology, Biomedicine, Biotechnology and Energy. Recent reorganization of RCSB PDB activities into four integrated, interdependent services is described in detail, together with tools and resources added over the past 2 years to RCSB PDB web portals in support of a 'Structural View of Biology.'

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CitationGPTRetr118

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: Domain structure and lipid interaction in human apolipoproteins A-I and E, a general model. Abstract of the paper: Detailed structural information on human exchangeable apolipoproteins (apo) is required to understand their functions in lipid transport. Using a series of deletion mutants that progressively lacked different regions along the molecule, we probed the structural organization of lipid-free human apoA-I and the role of different domains in lipid binding, making comparisons to apoE, which is a member of the same gene family and known to have two structural domains. Measurements of alpha-helix content by CD in conjunction with tryptophan and 8-anilino-1-naphthalenesulfonic acid fluorescence data demonstrated that deletion of the amino-terminal or central regions disrupts the tertiary organization, whereas deletion of the carboxyl terminus has no effect on stability and induces a more cooperative structure. These data are consistent with the lipid-free apoA-I molecule being organized into two structural domains similar to apoE; the amino-terminal and central parts form a helix bundle, whereas the carboxyl-terminal alpha-helices form a separate, less organized structure. The binding of the apoA-I variants to lipid emulsions is modulated by reorganization of the helix bundle structure, because the rate of release of heat on binding is inversely correlated with the stability of the helix bundle. Based on these observations, we propose that there is a two-step mechanism for lipid binding of apoA-I: apoA-I initially binds to a lipid surface through amphipathic alpha-helices in the carboxyl-terminal domain, followed by opening of the helix bundle in the amino-terminal domain. Because apoE behaves similarly, this mechanism is probably a general feature for lipid interaction of other exchangeable apolipoproteins, such as apoA-IV.

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CitationGPTRetr119

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for each of the four proteins reference structures were selected and fetched from the pdb using the corresponding chains from the entries with entry id 7d8x chain b for psn1 46 7fcr for apoe 47 4pqd chain a and 1tkn model 1 for app695 4849 and 5ud8 chain b and 5eli chain a for trem2 Title of the paper: Cryo-EM structures of the ABCA4 importer reveal mechanisms underlying substrate binding and Stargardt disease. Abstract of the paper: ABCA4 is an ATP-binding cassette (ABC) transporter that flips N-retinylidene-phosphatidylethanolamine (N-Ret-PE) from the lumen to the cytoplasmic leaflet of photoreceptor membranes. Loss-of-function mutations cause Stargardt disease (STGD1), a macular dystrophy associated with severe vision loss. To define the mechanisms underlying substrate binding and STGD1, we determine the cryo-EM structure of ABCA4 in its substrate-free and bound states. The two structures are similar and delineate an elongated protein with the two transmembrane domains (TMD) forming an outward facing conformation, extended and twisted exocytoplasmic domains (ECD), and closely opposed nucleotide binding domains. N-Ret-PE is wedged between the two TMDs and a loop from ECD1 within the lumen leaflet consistent with a lateral access mechanism and is stabilized through hydrophobic and ionic interactions with residues from the TMDs and ECDs. Our studies provide a framework for further elucidating the molecular mechanism associated with lipid transport and disease and developing promising disease interventions.

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CitationGPTRetr120

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Benzodiazepines may have protective effects against Alzheimer disease. Abstract of the paper: In this study, we examined the association between benzodiazepine use and the occurrence of Alzheimer disease and vascular dementia. The study was based on longitudinal data from a case-control study of 668 individuals aged 75 and older. The elderly were examined extensively by physicians, and family interviews were assessed. Dementia diagnosis was made by using DSM-III-R criteria. Individuals with a history of continuous use of benzodiazepines (BDZ+) were compared with nonusers (BDZ-), with respect to the incidence of Alzheimer disease or vascular dementia at follow-up 3 years later. It was found that there was a significantly lower incidence of Alzheimer disease in the BDZ+ group than in the BDZ- group. This negative association remained significant when controlling for age, gender, level of education, use of nonsteriodal antiinflammatory drugs, and estrogens. These results suggest that benzodiazepines may have protective effects against the disease.

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CitationGPTRetr121

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Risk of Dementia in Long-Term Benzodiazepine Users: Evidence from a Meta-Analysis of Observational Studies. Abstract of the paper: BACKGROUND AND PURPOSE There is conflicting evidence in the literature on the association between benzodiazepines (BDZs) and the risk of dementia. This meta-analysis aimed to determine the relationship between the long-term usage of BDZs and the risk of dementia. METHODS The PubMed and Embase databases were systematically searched for relevant publications up to September 2017. The literature search focused on observational studies that analyzed the relationship between the long-term use of BDZs and the risk of dementia. Pooled rate ratios (RRs) with 95% confidence interval (CI) were assessed using a random-effects model. The robustness of the results was checked by performing subgroup and sensitivity analyses. RESULTS Ten studies were included: six case-control and four cohort studies. The pooled RR for developing dementia was 1.51 (95% CI=1.17-1.95, p=0.002) in patients taking BDZ. The risk of dementia was higher in patients taking BDZs with a longer half-life (RR=1.16, 95% CI=0.95-1.41, p=0.150) and for a longer time (RR=1.21, 95% CI=1.04-1.40, p=0.016). CONCLUSIONS This meta-analysis that pooled ten studies has shown that BDZ significantly increases the risk of dementia in the elderly population. The risk is higher in patients taking BDZ with a longer half-life (>20 hours) and for a longer duration (>3 years).

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CitationGPTRetr122

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Benzodiazepines and Related Drugs as a Risk Factor in Alzheimer's Disease Dementia. Abstract of the paper: Benzodiazepines (BZDs) and Z-drugs are compounds widely prescribed in medical practice due to their anxiolytic, hypnotic, and muscle relaxant properties. Yet, their chronic use is associated with cases of abuse, dependence, and relapse in many patients. Furthermore, elderly people are susceptible to alterations in pharmacodynamics, pharmacokinetics as well as to drug interaction due to polypharmacy. These situations increase the risk for the appearance of cognitive affectations and the development of pathologies like Alzheimer's disease (AD). In the present work, there is a summary of some clinical studies that have evaluated the effect of BZDs and Z-drugs in the adult population with and without AD, focusing on the relationship between their use and the loss of cognitive function. Additionally, there is an assessment of preclinical studies focused on finding molecular proof on the pathways by which these drugs could be involved in AD pathogenesis. Moreover, available data (1990-2019) on BZD and Z-drug use among elderly patients, with and without AD, was compiled in this work. Finally, the relationship between the use of BZD and Z-drugs for the treatment of insomnia and the appearance of AD biomarkers was analyzed. Results pointed to a vicious circle that would worsen the condition of patients over time. Likewise, it put into relevance the need for close monitoring of those patients using BZDs that also suffer from AD. Consequently, future studies should focus on optimizing strategies for insomnia treatment in the elderly by using other substances like melatonin agonists, which is described to have a much more significant safety profile.

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CitationGPTRetr123

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Association between Development of Dementia and Use of Benzodiazepines: A Systematic Review and Meta-Analysis. Abstract of the paper: STUDY OBJECTIVE The use of benzodiazepines and the development of dementia is controversial, with studies indicating that benzodiazepines could be either a protective factor or a risk factor for dementia, or no association may exist between the two. Our objective was to identify whether such an association exists. DESIGN Systematic review and meta-analysis of 12 prospective and retrospective cohort studies and case-control studies. PARTICIPANTS A total of 981,133 (in the systematic review) and 980,860 (in the meta-analysis) adults or elderly individuals. MEASUREMENTS AND MAIN RESULTS A search of the PubMed, LILACS, and Cochrane Central Register of Controlled Trials databases, as well as a manual search of the reference lists of the included publications and reviews, was performed. We included studies that reported the incidence of dementia and in ever users of benzodiazepines. Data were analyzed by using a random effects model in R software. Quality of the evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) certainty ratings system. The results of the main meta-analysis suggest that benzodiazepines can be a risk factor for developing dementia (odds ratio 1.38, 95% confidence interval 1.07-1.77; I2 = 98%; 95% prediction interval 0.58-3.25; very low certainty). CONCLUSION Our results suggest an association between the use of benzodiazepines and the development of dementia. However, the current evidence lacks the power to infer differences between the effects of Alzheimer's disease and vascular dementias, long-acting and short-acting benzodiazepines, and various exposure loads (duration and dose). Future long-term prospective cohort studies are necessary, with adequate adjustments for confounding variables, strategies to minimize reverse causality, reporting of subgroups aimed at greater homogeneity of findings, adequate statistical power to identify high-magnitude effects, and defined daily dose analyses for dose-response gradient.

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CitationGPTRetr124

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: The Benzodiazepine-Dementia Disorders Link: Current State of Knowledge. Abstract of the paper: The short-term effects of benzodiazepines on memory are well established and are suspected in the long term. Eleven studies have been published so far concerning benzodiazepine use and the risk of dementia disorders; nine of these studies concluded these drugs have a deleterious effect, one found a protective effect, and one (the most recently published) observed no effect. The positive association found in some studies could be due to a reverse causation bias since the main indications for benzodiazepines (e.g. sleep disorders, anxiety) can also be prodromes of dementia disorders. This bias is less likely for treatments started more than 10 years before the diagnosis. Among others, three mechanisms could underlie the potential influence of benzodiazepines on the development of dementia disorders. First, benzodiazepines can decrease beta-site amyloid precursor protein-cleaving enzyme 1 (BACE-1) and γ-secretase activity and slow down the accumulation of Aβ oligomers in the brain. This potential positive effect has never been confirmed; the same is true for the prevention of excitotoxicity through benzodiazepine anti-glutamatergic action. Second, since astrocytes located in the area of amyloid plaques could have gamma-aminobutyric acid (GABA)-secreting activity, patients with pre-dementia lesions could be at increased risk of presenting with more pronounced deleterious cognitive effects of benzodiazepines. Finally, owing to the neural compensation and cognitive reserve concepts, some subjects could cope with initial lesions by using/developing alternative networks. By lowering the brain activation level, benzodiazepines could limit this capacity. In conclusion, it is essential that animal studies explore the mechanistic hypotheses of this association found by most of the pharmacoepidemiological studies conducted on this topic.

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CitationGPTRetr125

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Use of Benzodiazepines in Alzheimer's Disease: A Systematic Review of Literature. Abstract of the paper: BACKGROUND Benzodiazepines are frequently prescribed in patients with Alzheimer's disease. Unfortunately, studies evaluating their benefits and risks in these patients are limited. METHODS Clinical trials focusing on the effect of benzodiazepines on cognitive functions, disease progression, behavioral symptoms, sleep disturbances, and the general frequency of benzodiazepine use were included in this review. Published articles from January 1983 to January 2015 were identified using specific search terms in MEDLINE and PubMed Library according to the recommendations of The Strengthening the Reporting of Observational Studies in Epidemiology initiative. RESULTS Of the 657 articles found, 18 articles met predefined selection criteria and were included in this review (8 on frequency, 5 on cognitive functions, 5 on behavioral and sleep disturbances). The frequency of benzodiazepine use ranged from 8.5% to 20%. Five studies reported accelerated cognitive deterioration in association with benzodiazepine use. Two studies reported clinical efficacy for lorazepam and alprazolam to reduce agitation in Alzheimer's disease patients. No evidence was found for an improvement of sleep quality using benzodiazepines. CONCLUSION This systematic review shows a relatively high prevalence of benzodiazepine use but limited evidence for clinical efficacy in Alzheimer's disease patients. However, there is a paucity of methodologically high quality controlled clinical trials. Our results underscore a need for randomized controlled trials in this area.

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CitationGPTRetr126

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Association between Benzodiazepine Use and Dementia: A Meta-Analysis. Abstract of the paper: BACKGROUND The association between long-term benzodiazepine use and risk of dementia remains controversial. Therefore, current study aimed to quantify this association, and to explore a potential dose-response pattern. METHODS We searched PubMed, Embase and the Cochrane Library through August 17, 2014. We included nested case-control or prospective cohort studies that provided risk estimates on the association of benzodiazepine use with risk of dementia, and a clear definition of status of benzodiazepine use. Overall effect size was calculated using a random-effects model. FINDINGS Six studies were eligible for inclusion, involving 11,891 dementia cases and 45,391 participants. Compared with never users, pooled adjusted risk ratios (RRs) for dementia were 1.49 (95% confidence interval (CI) 1.30-1.72) for ever users, 1.55 (95% CI 1.31-1.83) for recent users, and 1.55 (95% CI 1.17-2.03) for past users. The risk of dementia increased by 22% for every additional 20 defined daily dose per year (RR, 1.22, 95%CI 1.18-1.25). When we restricted our meta-analyses to unadjusted RRs, all initial significant associations persisted. CONCLUSIONS Long-term benzodiazepine users have an increased risk of dementia compared with never users. However, findings from our study should be treated with caution due to limited studies and potential reverse causation. Large prospective cohort studies with long follow-up duration are warranted to confirm these findings.

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CitationGPTRetr127

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Neurocognitive Effects of Antiseizure Medications in Children and Adolescents with Epilepsy. Abstract of the paper: Impairments in cognition are common in epilepsy and may be caused or exacerbated by antiseizure medications (ASMs). Positive effects on cognition may also be seen with some ASMs. Cognitive outcomes are of particular concern in children who may be at an increased risk of cognitive adverse effects of treatment. A comprehensive literature search was conducted in PubMed in order to evaluate the evidence for cognitive changes associated with treatment with ASMs in paediatric epilepsy patients. The ASMs considered were those in the current edition of the British National Formulary (BNF). For most ASMs, remarkably few studies providing robust data on cognitive effects in paediatric patients were identified. The available evidence suggests cognitive impairments may be associated with treatment with phenobarbital. Topiramate and phenytoin are also associated with negative effects on cognition, in particular word-finding difficulties and other language deficits with topiramate, but there are few data available specifically on children. Lamotrigine, levetiracetam and fenfluramine are associated with improvements in some cognitive domains, although it is unclear whether these effects are directly attributable to the medications or are a result of improvements in seizures. Neutral effects on cognition (no substantial evidence of worsening) were suggested for carbamazepine, everolimus, lacosamide, oxcarbazepine, perampanel and valproate. There is limited data for cannabidiol, clobazam, eslicarbazepine acetate, ethosuximide, rufinamide, vigabatrin and zonisamide, although the available evidence suggests these drugs are not associated with severe cognitive impairment. There was too little information to reach conclusions about the effects of brivaracetam, felbamate, gabapentin, pregabalin, retigabine, stiripentol or tiagabine.

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CitationGPTRetr128

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Benzodiazepine Use Attenuates Cortical β-Amyloid and is Not Associated with Progressive Cognitive Decline in Nondemented Elderly Adults: A Pilot Study Using F18-Florbetapir Positron Emission Tomography. Abstract of the paper: OBJECTIVE It is inconclusive as to whether benzodiazepines (BZDs) are related to cognitive deterioration in the elderly populations. Animal studies suggest that γ-aminobutyric acid A receptor agonists, such as BZDs, may prevent Aβ-neurotoxicity and reduce β-amyloid (Aβ). However, no studies have investigated the effects of BZD use on Aβ in humans. METHODS This cross-sectional, prospective study using Alzheimer's Disease Neuroimaging Initiative sites in the United States and Canada on nondemented elderly adults between 55 and 90 years of age assessed cortical Aβ levels by positron emission tomography radiotracer F18-Florbetapir. Changes in global cognitive function and verbal memory performance over 2 years were assessed using scores on Montreal Cognitive Assessment and five domains of Rey Auditory Verbal Learning Test, respectively. RESULTS Previous BZD users (N = 15) had lower cortical Aβ levels in frontal (F(1, 26) = 8.82, p = 0.006), cingulate (F(1, 26) = 8.58, p = 0.007), parietal (F(1, 26) = 7.31, p = 0.012), and temporal (F(1, 26) = 7.67, p = 0.010) regions compared with matched BZD nonusers (N = 15), after controlling for history of psychiatric disorders and antidepressant use. Also, no differences were found in global cognitive function and changes in cortical Aβ over 2 years between continuous BZD users (N = 15) andthe matched nonuser group (N = 15). CONCLUSION Previous BZD use was associated with lower cortical Aβ levels in nondemented elderly control subjects. Future studies with larger samples are required to replicate our findings.

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CitationGPTRetr129

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Benzodiazepine, psychotropic medication, and dementia: A population-based cohort study. Abstract of the paper: INTRODUCTION Benzodiazepine use has been associated with increased risk of dementia. However, it remains unclear whether the risk relates to short or long half-life benzodiazepines and whether it extends to other psychotropic drugs. METHODS Prospective cohort study among 8240 individuals ≥65, interviewed on medication use. Incident dementia confirmed by an end point committee after a multistep procedure. RESULTS During a mean of 8 years of follow-up, 830 incident dementia cases were observed. Users of benzodiazepines at baseline had a 10% increased risk of dementia (adjusted hazard ratio [HR], 1.10; 95% confidence interval, 0.90-1.34). However, long half-life (>20 hours) benzodiazepine users had a marked increased risk of dementia (HR = 1.62; 1.11-2.37) compared with short half-life users (HR = 1.05; 0.85-1.30). Users of psychotropics had an increased risk of dementia (HR = 1.47; 1.16-1.86). DISCUSSION Results of this large, prospective study show increased risk of dementia for long half-life benzodiazepine and psychotropic use.

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CitationGPTRetr130

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Benzodiazepine use and risk of dementia: evidence from the Caerphilly Prospective Study (CaPS). Abstract of the paper: BACKGROUND Benzodiazepine use is widespread in older people, although its benefit is uncertain. AIM To investigate the long-term effect of benzodiazepine use upon dementia risk. METHODS A prospective cohort of men seen on five occasions over 22 years with full medication histories, repeat measures of cognitive function and a clinical diagnosis of dementia. RESULTS Of 1134 men with complete data, 103 (9.1%) had been taking benzodiazepines regularly at one or more phases. These men showed a marked increased incidence of dementia (OR=3.50, 95% CI 1.57 to 7.79, p=0.002), which persisted despite adjustment for psychological distress and other covariates. Men exposed in earlier phases showed a greater association than more recent exposure, counter to what one would expect if this was due to reverse causation, though we failed to demonstrate a dose-response effect with drug duration. CONCLUSION The taking of benzodiazepines is associated with an increased risk of dementia.

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CitationGPTRetr131

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Benzodiazepine Use and Risk of Dementia in the Elderly Population: A Systematic Review and Meta-Analysis. Abstract of the paper: BACKGROUND Benzodiazepines are a widely used medication in developed countries, particularly among elderly patients. However, benzodiazepines are known to affect memory and cognition and might thus enhance the risk of dementia. The objective of this review is to synthesize evidence from observational studies that evaluated the association between benzodiazepines use and dementia risk. SUMMARY We performed a systematic review and meta-analysis of controlled observational studies to evaluate the risk of benzodiazepines use on dementia outcome. All control observational studies that compared dementia outcome in patients with benzodiazepine use with a control group were included. We calculated pooled ORs using a random-effects model. Ten studies (of 3,696 studies identified) were included in the systematic review, of which 8 studies were included in random-effects meta-analysis and sensitivity analyses. Odds of dementia were 78% higher in those who used benzodiazepines compared with those who did not use benzodiazepines (OR 1.78; 95% CI 1.33-2.38). In subgroup analysis, the higher association was still found in the studies from Asia (OR 2.40; 95% CI 1.66-3.47) whereas a moderate association was observed in the studies from North America and Europe (OR 1.49; 95% CI 1.34-1.65 and OR 1.43; 95% CI 1.16-1.75). Also, diabetics, hypertension, cardiac disease, and statin drugs were associated with increased risk of dementia but negative association was observed in the case of body mass index. There was significant statistical and clinical heterogeneity among studies for the main analysis and most of the sensitivity analyses. There was significant statistical and clinical heterogeneity among the studies for the main analysis and most of the sensitivity analyses. Key Messages: Our results suggest that benzodiazepine use is significantly associated with dementia risk. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or the result of some unmeasured confounding variable. Therefore, more research is needed.

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CitationGPTRetr132

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Benzodiazepine use and risk of dementia: a nested case-control study. Abstract of the paper: The objective of this article was to examine the possible association between benzodiazepine use and the risk of dementia in the elderly. This was a nested case--control study set in community settings in Bordeaux area, France. The participants were a representative sample of 3,777 elderly persons (65 years of age and older) followed from 1989 to 1997. The main outcome measures were the use of benzodiazepines in incident cases of dementia versus nondemented controls. On the basis of medical and psychological data, 150 patients were diagnosed with dementia according to the criteria of the third revision of the Diagnostic and Statistical Manual of Mental Disorders. Information on benzodiazepine use was obtained by face-to-face interview and visual assessment of patient's medicine chest by a trained neuropsychologist. After controlling for age, gender, education level, living alone, wine consumption, psychiatric history, and depressive symptomatology, ever use of benzodiazepines was associated with a significantly increased risk of dementia [adjusted odds ratio (OR), 1.7; 95% confidence interval, 1.2-2.4]. Former use was associated with a significantly increased risk of dementia (adjusted OR, 2.3; 95% CI,1.2-4.5). No association was found between dementia and the current use of benzodiazepines (adjusted OR, 1.0; 95% CI, 0.6-1.6). Our finding suggest that former use of benzodiazepines could be a risk factor for dementia, but more detailed investigation are needed.

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CitationGPTRetr133

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Use of benzodiazepines and related drugs is associated with a risk of stroke among persons with Alzheimer's disease. Abstract of the paper: The aim of our study was to investigate the risk of any, ischemic, and hemorrhagic stroke associated with incident benzodiazepine and related drug (BZDR) use among community-dwelling individuals with Alzheimer's disease (AD). Data from the MEDALZ cohort including all community-dwelling persons newly diagnosed with AD between 2005 and 2011 in Finland were utilized. Incident BZDR users were identified with a 1-year washout period for previous use. Persons with a previous stroke were excluded, resulting in a final study sample of 45 050 individuals. Incident any, ischemic, and hemorrhagic strokes were identified from the Hospital Discharge and Causes of Death registers. The risk of stroke between time on BZDRs was compared with nonuse time with Cox proportional hazard models. During the follow-up, 21.9% (N=9879) of persons started BZDR use. Compared with nonuse, BZDR use was associated with an increased risk of any stroke [adjusted hazard ratio (aHR): 1.21; 95% confidence interval (CI): 1.04-1.40] and ischemic stroke (aHR: 1.21; 95% CI: 1.02-1.44), but the association between BZDR use and hemorrhagic stroke did not reach significance (aHR: 1.26; 95% CI: 0.91-1.74). Z-drug use was associated with a similar risk as benzodiazepine use. In conclusion, BZDR use was associated with an increased risk of stroke among older individuals with AD.

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CitationGPTRetr134

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: The risk of Alzheimer's disease associated with benzodiazepines and related drugs: a nested case-control study. Abstract of the paper: OBJECTIVE To assess the association between benzodiazepine and related drug (BZDR) use and risk of Alzheimer's disease (AD) with cumulative consumption and duration of use based models. METHOD A nationwide nested case-control study of all Finnish community-dwelling persons who received clinically verified AD diagnosis in 2005-2011 (N = 70 719) and their matched controls (N = 282 862). AD diagnosis was based on DSM-IV and NINCDS-ADRDA criteria. BZDR purchases were extracted from the Prescription Register since 1995. The association between BZDR use and AD was assessed using conditional logistic regression with 5-year lag time between exposure and outcome. RESULTS Benzodiazepine and related drug use was associated with modestly increased risk of AD (adjusted OR 1.06, 95% CI 1.04-1.08). A dose-response relationship was observed with both cumulative consumption and duration. Adjustment for other psychotropics removed the cumulative dose-response relationship by attenuating the ORs in the highest dose category. CONCLUSION Benzodiazepine and related drug use in general was associated with modestly increased risk of AD. No major differences were observed between different subcategories of BZDRs (i.e. benzodiazepines, Z drugs, short-/medium-acting or long-acting BZDRs). As dose-response relationship abolished after adjustment for other psychotropics, it is possible that the association may partially be due to antidepressants and/or antipsychotics, or concomitant use of these medications.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Benzodiazepine use and cognitive decline in the elderly. Abstract of the paper: PURPOSE Published evidence on the relationship between benzodiazepine exposure and altered cognition in the geriatric population is reviewed. SUMMARY Benzodiazepines constitute one of the most commonly prescribed medication classes and are used primarily for management of anxiety and insomnia. Despite strong recommendations based on high-quality evidence warning of the potential cognitive adverse effects of benzodiazepine use, particularly in patients 65 years of age or older, published literature suggests that a substantial proportion of the U.S. geriatric population use these medications in a chronic fashion. The body of evidence suggesting that benzodiazepine use may be a modifiable risk factor for dementia continues to grow. Evidence exists to suggest that benzodiazepine use in the elderly population is associated with cognitive decline, dementia, and Alzheimer's disease, although evidence regarding the correlation between benzodiazepine use and dementia is conflicting; the more recent studies in this area have focused on eliminating causation bias. Pharmacists in a variety of settings can educate patients and assist providers in selecting an appropriate medication regimen for anxiety or insomnia that is tailored to each elderly patient's needs and takes into account the immediate and long-term safety of the patient. CONCLUSION Investigations of the association between benzodiazepine therapy and cognitive decline in elderly patients have yielded mixed findings. Stronger links have emerged from studies examining longer- rather than shorter-acting benzodiazepines, longer rather than shorter durations of use, or earlier rather than later exposure. Questions remain about causality and the impact of confounders on study interpretation.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Benzodiazepine Use and Risk of Developing Alzheimer's Disease or Vascular Dementia: A Case-Control Analysis. Abstract of the paper: INTRODUCTION Previous observational studies have associated benzodiazepine use with an increased risk of dementia. However, limitations in the study methods leave questions unanswered regarding the interpretation of the findings. METHODS A case-control analysis was conducted using data from the UK-based Clinical Practice Research Datalink (CPRD). A total of 26,459 patients aged ≥65 years with newly diagnosed Alzheimer's disease (AD) or vascular dementia (VaD) between 1998 and 2013 were identified and matched 1:1 to dementia-free controls on age, sex, calendar time, general practice, and number of years of recorded history. Adjusted odds ratios (aORs) were calculated with 95% confidence intervals (CIs) of developing AD or VaD in relation to previous benzodiazepine use, stratified by duration and benzodiazepine type. RESULTS The aOR (95% CI) of developing AD for those who started benzodiazepines <1 year before diagnosis was 2.20 (1.91-2.53), and fell to the null for those who started between 2 and <3 years before [aOR 0.99 (0.84-1.17)]. The aOR (95% CI) of developing VaD for those who started benzodiazepines <1 year before diagnosis was 3.30 (2.78-3.92), and fell close to the null for those who started between 3 and <4 years before [aOR 1.16 (0.96-1.40)]. After accounting for benzodiazepine use initiated during this prodromal phase, long-term use of benzodiazepines was not associated with an increased risk of developing AD [aOR 0.69 (0.57-0.85)] or VaD [aOR 1.11 (0.85-1.45)]. CONCLUSION After taking a prodromal phase into consideration, benzodiazepine use was not associated with an increased risk of developing AD or VaD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: The association between dementia and long-term use of benzodiazepine in the elderly: nested case-control study using claims data. Abstract of the paper: OBJECTIVES The aim of this study was to examine the association between long-term benzodiazepines (BZDs) use and the risk of dementia. DESIGN Population-based nested case-control study of dementia. SETTING All subjects were aged 45 and older and enrolled in the National Health Insurance Research Database in Taiwan, 1997-2004. PARTICIPANTS Cases (N = 779) were patients who were identified with dementia at least two times in their outpatient claims. They were individually matched to six comparison subjects (N = 4,626) based on age and gender. MEASUREMENTS BZD usage (average dosage per year, average days per year, and cumulative dose and periods) and potential confounding comobidities, including cardiovascular and psychiatric diseases. RESULTS Subjects with dementia had higher cumulative dose, longer duration of BZDs exposure, and more likelihood to be long-term BZDs users. CONCLUSION Our findings suggest that long-term use of BZDs is associated with an increased risk for dementia, but the underlying mechanisms remain unclear, and further investigations are needed. Long-term use of BZDs should be avoided among the elderly, who may be at a higher risk for developing dementia, in addition to other health problems.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: History of Benzodiazepine Prescriptions and Risk of Dementia: Possible Bias Due to Prevalent Users and Covariate Measurement Timing in a Nested Case-Control Study. Abstract of the paper: Previous estimates of whether long-term exposure to benzodiazepines increases dementia risk are conflicting and are compromised by the difficulty of controlling for confounders and by reverse causation. We investigated how estimates for the association between benzodiazepine use and later dementia incidence varied based on study design choices, using a case-control study nested within the United Kingdom's Clinical Practice Research Datalink. A total of 40,770 dementia cases diagnosed between April 2006 and July 2015 were matched on age, sex, available data history, and deprivation to 283,933 control subjects. Benzodiazepines and Z-drug prescriptions were ascertained in a drug-exposure period 4-20 years before dementia diagnosis. Estimates varied with the inclusion of new or prevalent users, with the timing of covariate ascertainment, and with varying time between exposure and outcome. There was no association between any new prescription of benzodiazepines and dementia (adjusted odds ratio (OR) = 1.03, 95% confidence interval (CI): 1.00, 1.07), whereas an inverse association was observed among prevalent users (adjusted OR = 0.91, 95% CI: 0.87, 0.95), although this was likely induced by unintentional adjustment for colliders. By considering the choice of confounders and timing of exposure and covariate measurement, our findings overall are consistent with no causal effect of benzodiazepines or Z-drugs on dementia incidence.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: likewise phenobarbital pb benzodiazepines bdzs and tpm were associated with an increased risk of eliciting cognitive deficits so these asms should be forbidden for ad patients with or without seizures a similar conclusion can be drawn for zns the effects of which on cognitive function need to be clarified Title of the paper: Is benzodiazepine use a risk factor for cognitive decline and dementia? A literature review of epidemiological studies. Abstract of the paper: BACKGROUND A major public health issue is to determine whether long-term benzodiazepine use may induce cognitive deficits persisting after withdrawal. The aim of the present review was to examine findings from prospective studies carried out in general population samples exploring whether exposure to benzodiazepines is associated with an increased risk of incident cognitive decline. METHOD Using a MEDLINE search and a hand-search of related references in selected papers, we retrieved original studies published in peer-reviewed journals that explored in general population samples the association between benzodiazepine exposure and change in cognitive performance between baseline and follow-up assessment. RESULTS Six papers met the inclusion criteria. Two studies reported a lower risk of cognitive decline in former or ever users, two found no association whatever the category of user, and three found an increased risk of cognitive decline in benzodiazepine users. CONCLUSIONS The discrepant findings obtained by studies examining the link between benzodiazepine exposure and risk of cognitive decline may be due to methodological differences, especially regarding the definitions of exposure and cognitive outcome. As a large proportion of subjects are exposed to benzodiazepines, a small increase in the risk of cognitive decline may have marked deleterious consequences for the health of the general population. This issue needs to be explored further by pharmaco-epidemiological studies.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Microglia emerge as central players in brain disease. Abstract of the paper: There has been an explosion of new findings recently giving us insights into the involvement of microglia in central nervous system (CNS) disorders. A host of new molecular tools and mouse models of disease are increasingly implicating this enigmatic type of nervous system cell as a key player in conditions ranging from neurodevelopmental disorders such as autism to neurodegenerative disorders such as Alzheimer's disease and chronic pain. Contemporaneously, diverse roles are emerging for microglia in the healthy brain, from sculpting developing neuronal circuits to guiding learning-associated plasticity. Understanding the physiological functions of these cells is crucial to determining their roles in disease. Here we focus on recent developments in our rapidly expanding understanding of the function, as well as the dysfunction, of microglia in disorders of the CNS.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Microglia roles in synaptic plasticity and myelination in homeostatic conditions and neurodevelopmental disorders. Abstract of the paper: Microglia are the immune cells of the brain, involved in synapse formation, circuit sculpting, myelination, plasticity, and cognition. Being active players during early development as well as in adulthood, microglia affect other cells directly by their long processes and unique receptors and indirectly by secreting growth factors and cytokines. In this review, we discuss the roles of microglia in neurodevelopmental disorders, synaptic plasticity, myelination, and homeostatic conditions throughout human and mouse development. Within these processes, we specifically focus on the contribution of altered microglial interactions with neurons and oligodendrocytes, altered cytokine and growth factor activities, and alterations in the complement system. We conclude by highlighting future perspectives and providing an overview of future research on microglia.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Microglia and the Brain: Complementary Partners in Development and Disease. Abstract of the paper: An explosion of findings driven by powerful new technologies has expanded our understanding of microglia, the resident immune cells of the central nervous system (CNS). This wave of discoveries has fueled a growing interest in the roles that these cells play in the development of the CNS and in the neuropathology of a diverse array of disorders. In this review, we discuss the crucial roles that microglia play in shaping the brain-from their influence on neurons and glia within the developing CNS to their roles in synaptic maturation and brain wiring-as well as some of the obstacles to overcome when assessing their contributions to normal brain development. Furthermore, we examine how normal developmental functions of microglia are perturbed or remerge in neurodevelopmental and neurodegenerative disease.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Microglia: actively surveying and shaping neuronal circuit structure and function. Abstract of the paper: The traditional role of microglia has been in brain infection and disease, phagocytosing debris and secreting factors to modify disease progression. Recent evidence extends their role to healthy brain homeostasis, including the regulation of cell death, synapse elimination, neurogenesis, and neuronal surveillance. These actions contribute to the maturation and plasticity of neural circuits that ultimately shape behavior. Here we review microglial contributions to the development, plasticity, and maintenance of neural circuits with a focus on interactions with synapses. We introduce this topic by reviewing recent studies on the migration and proliferation of microglia within the brain, and conclude with the proposal that microglia dysfunction may adversely affect brain function, and thereby contribute to the development of psychiatric and neurological disorders.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Microglia Function in Central Nervous System Development and Plasticity. Abstract of the paper: The nervous system comprises a remarkably diverse and complex network of different cell types, which must communicate with one another with speed, reliability, and precision. Thus, the developmental patterning and maintenance of these cell populations and their connections with one another pose a rather formidable task. Emerging data implicate microglia, the resident myeloid-derived cells of the central nervous system (CNS), in the spatial patterning and synaptic wiring throughout the healthy, developing, and adult CNS. Importantly, new tools to specifically manipulate microglia function have revealed that these cellular functions translate, on a systems level, to effects on overall behavior. In this review, we give a historical perspective of work to identify microglia function in the healthy CNS and highlight exciting new work in the field that has identified roles for these cells in CNS development, maintenance, and plasticity.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Microglia across the lifespan: from origin to function in brain development, plasticity and cognition. Abstract of the paper: Microglia are the only immune cells that permanently reside in the central nervous system (CNS) alongside neurons and other types of glial cells. The past decade has witnessed a revolution in our understanding of their roles during normal physiological conditions. Cutting-edge techniques revealed that these resident immune cells are critical for proper brain development, actively maintain health in the mature brain, and rapidly adapt their function to physiological or pathophysiological needs. In this review, we highlight recent studies on microglial origin (from the embryonic yolk sac) and the factors regulating their differentiation and homeostasis upon brain invasion. Elegant experiments tracking microglia in the CNS allowed studies of their unique roles compared with other types of resident macrophages. Here we review the emerging roles of microglia in brain development, plasticity and cognition, and discuss the implications of the depletion or dysfunction of microglia for our understanding of disease pathogenesis. Immune activation, inflammation and various other conditions resulting in undesirable microglial activity at different stages of life could severely impair learning, memory and other essential cognitive functions. The diversity of microglial phenotypes across the lifespan, between compartments of the CNS, and sexes, as well as their crosstalk with the body and external environment, is also emphasised. Understanding what defines particular microglial phenotypes is of major importance for future development of innovative therapies controlling their effector functions, with consequences for cognition across chronic stress, ageing, neuropsychiatric and neurological diseases.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Microglia Function in the Central Nervous System During Health and Neurodegeneration. Abstract of the paper: Microglia are resident cells of the brain that regulate brain development, maintenance of neuronal networks, and injury repair. Microglia serve as brain macrophages but are distinct from other tissue macrophages owing to their unique homeostatic phenotype and tight regulation by the central nervous system (CNS) microenvironment. They are responsible for the elimination of microbes, dead cells, redundant synapses, protein aggregates, and other particulate and soluble antigens that may endanger the CNS. Furthermore, as the primary source of proinflammatory cytokines, microglia are pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses. Alterations in microglia functionality are implicated in brain development and aging, as well as in neurodegeneration. Recent observations about microglia ontogeny combined with extensive gene expression profiling and novel tools to study microglia biology have allowed us to characterize the spectrum of microglial phenotypes during development, homeostasis, and disease. In this article, we review recent advances in our understanding of the biology of microglia, their contribution to homeostasis, and their involvement in neurodegeneration. Moreover, we highlight the complexity of targeting microglia for therapeutic intervention in neurodegenerative diseases.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy. Abstract of the paper: Microglia are the resident macrophages of the central nervous system (CNS) acting as the first line of defense in the brain by phagocytosing harmful pathogens and cellular debris. Microglia emerge from early erythromyeloid progenitors of the yolk sac and enter the developing brain before the establishment of a fully mature blood-brain barrier. In physiological conditions, during brain development, microglia contribute to CNS homeostasis by supporting cell proliferation of neural precursors. In post-natal life, such cells contribute to preserving the integrity of neuronal circuits by sculpting synapses. After a CNS injury, microglia change their morphology and down-regulate those genes supporting homeostatic functions. However, it is still unclear whether such changes are accompanied by molecular and functional modifications that might contribute to the pathological process. While comprehensive transcriptome analyses at the single-cell level have identified specific gene perturbations occurring in the "pathological" microglia, still the precise protective/detrimental role of microglia in neurological disorders is far from being fully elucidated. In this review, the results so far obtained regarding the role of microglia in neurodegenerative disorders will be discussed. There is solid and sound evidence suggesting that regulating microglia functions during disease pathology might represent a strategy to develop future therapies aimed at counteracting brain degeneration in multiple sclerosis, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Microglia: Key players in neurodevelopment and neuronal plasticity. Abstract of the paper: Microglia are the primary innate immune cells in the CNS. Since their initial discovery and characterization, decades of research have revealed their unique roles not only in maintaining immune homeostasis, but also being indispensable to brain development and cognitive function. As such, microglia drive synaptogenesis, synaptic pruning, neurogenesis and neuronal activity. Microglia-specific mutations are implicated in several neurodevelopmental disorders, and dysregulation of microglial function is strongly linked to several pathologies, including cognitive decline and Alzheimer's disease. Importantly, developmental insults can lead to long-term changes in microglial function that may compromise the ability of the adult brain to fight infections and process cognitive information. Adult lifestyle or injury can also lastingly influence microglial morphology and function. Here we highlight key research on microglia's role in neuronal plasticity across the lifespan.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Microglia Plasticity During Health and Disease: An Immunological Perspective. Abstract of the paper: Microglia are macrophages of the central nervous system (CNS) that continuously scrutinize their environment for damage. They colonize the cephalic mesenchyme during embryogenesis and actively shape the developing neuronal network by immune-mediated mechanisms. Upon CNS maturation, microglia drastically change phenotype and function. During health, adult microglia contribute to homeostasis, but also the establishment and resolution of inflammatory conditions. Fulfillment of these distinct tasks requires these long-lived cells to accurately adjust to their changing environment. Deciphering microglia responsiveness to divergent stimuli is central to understanding this cell type and for eventual microglia manipulation to potentially reduce disease burden. Here we discuss new aspects of myeloid cell biology in general with special emphasis on the shifting role of microglia during establishment and protection of CNS integrity.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Investigating Microglia in Health and Disease: Challenges and Opportunities. Abstract of the paper: Microglia are tissue-resident macrophages implicated in central nervous system (CNS) development, homeostasis, and response to injury. Recent advances in transcriptomics, multiplex protein expression analysis, and experimental depletion of microglia have cemented their importance. However, it is still unclear which models are best suited to investigate microglia and explore their function in human disease. Here, we discuss issues regarding off-targeting during experimental manipulation, and differences and similarities between human and rodent microglia. With new developments in transgenic lines and human-rodent chimeras, we anticipate that in coming years, a clearer picture of microglia function in health and disease will emerge.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Microglia in CNS development: Shaping the brain for the future. Abstract of the paper: Microglial cells are the resident macrophages of the central nervous system (CNS) and are mainly known for their roles in neuropathologies. However, major recent developments have revealed that these immune cells actively interact with neurons in physiological conditions and can modulate the fate and functions of synapses. Originating from myeloid precursors born in the yolk sac, microglial cells invade the CNS during early embryonic development. As a consequence they can potentially influence neuronal proliferation, migration and differentiation as well as the formation and maturation of neuronal networks, thereby contributing to the entire shaping of the CNS. We review here recent evidence indicating that microglial cells are indeed involved in crucial steps of the CNS development, including neuronal survival and apoptosis, axonal growth, migration of neurons, pruning of supernumerary synapses and functional maturation of developing synapses. We also discuss current hypotheses proposing that diverting microglial cells of their physiological functions, by promoting the expression of an immune phenotype during development, may be central to neurodevelopmental disorders such as autism, schizophrenia and epilepsy.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: The "quad-partite" synapse: microglia-synapse interactions in the developing and mature CNS. Abstract of the paper: Microglia are the resident immune cells and phagocytes of our central nervous system (CNS). While most work has focused on the rapid and robust responses of microglia during CNS disease and injury, emerging evidence suggests that these mysterious cells have important roles at CNS synapses in the healthy, intact CNS. Groundbreaking live imaging studies in the anesthetized, adult mouse demonstrated that microglia processes dynamically survey their environment and interact with other brain cells including neurons and astrocytes. More recent imaging studies have revealed that microglia dynamically interact with synapses where they appear to serve as "synaptic sensors," responding to changes in neural activity and neurotransmitter release. In the following review, we discuss the most recent work demonstrating that microglia play active roles at developing and mature synapses. We first discuss the important imaging studies that have led us to better understand the physical relationship between microglia and synapses in the healthy brain. Following this discussion, we review known molecular mechanisms and functional consequences of microglia-synapse interactions in the developing and mature CNS. Our current knowledge sheds new light on the critical functions of these mysterious cells in synapse development and function in the healthy CNS, but has also incited several new and interesting questions that remain to be explored. We discuss these open questions, and how the most recent findings in the healthy CNS may be related to pathologies associated with abnormal and/or loss of neural circuits.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Physiology of microglia. Abstract of the paper: Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed "resting microglia." Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the "activated microglial cell." This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Microglia in health and disease. Abstract of the paper: Microglia, one of three glial cell types in the central nervous system (CNS), play an important role as resident immunocompetent and phagocytic cells in the CNS in the event of injury and disease. It was del Rio Hortega in 1927 who determined that microglia belong a distinct glial cell type apart from astrocytes and oligodendrocytes, and since 1970s there has been wide recognition that microglia are immune effectors in the CNS that respond to pathological conditions and participate in initiation and progression of neurological disorders including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and acquired immune deficiency syndrome dementia complex by releasing potentially cytotoxic molecules such as proinflammatory cytokines, reactive oxygen intermediates, proteinases and complement proteins. There is also evidence to suggest that microglia are capable of secreting neurotrophic or neuron survival factors upon activation via inflammation or injury. It is thus timely to review current status of knowledge on biology and immunology of microglia, and consider new directions of investigation on microglia in health and disease.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Physiology of Microglia. Abstract of the paper: Microglia constitute the major immune cells that permanently reside in the central nervous system (CNS) alongside neurons and other glial cells. These resident immune cells are critical for proper brain development, actively maintain brain health throughout the lifespan and rapidly adapt their function to the physiological or pathophysiological needs of the organism. Cutting-edge fate mapping and imaging techniques applied to animal models enabled a revolution in our understanding of their roles during normal physiological conditions. Here, we highlight studies that demonstrate the embryonic yolk sac origin of microglia and describe factors, including crosstalk with the periphery and external environment, that regulate their differentiation, homeostasis and function in the context of healthy CNS. The diversity of microglial phenotypes observed across the lifespan, between brain compartments and between sexes is also discussed. Understanding what defines specific microglial phenotypes is critical for the development of innovative therapies to modulate their effector functions and improve clinical outcomes.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Microglia: unique and common features with other tissue macrophages. Abstract of the paper: Microglia are highly specialized tissue macrophages of the brain with dedicated functions in neuronal development, homeostasis and recovery from pathology Despite their unique localization in the central nervous system (CNS), microglia are ontogenetically and functionally related to their peripheral counterparts of the mononuclear phagocytic system in the body, namely tissue macrophages and circulating myeloid cells. Recent developments provided new insights into the myeloid system in the body with microglia emerging as intriguing unique archetypes. Similar to other tissue macrophages, microglia develop early during embryogenesis from immature yolk sac progenitors. But in contrast to most of their tissue relatives microglia persist throughout the entire life of the organism without any significant input from circulating blood cells due to their longevity and their capacity of self-renewal. Notably, microglia share some features with short-lived blood monocytes to limit CNS tissue damage in pathologies, but only bone marrow-derived cells display the ability to become permanently integrated in the parenchyma. This emphasizes the therapeutic potential of bone marrow-derived microglia-like cells. Further understanding of both fate and function of microglia during CNS pathologies and considering their uniqueness among other tissue macrophages will be pivotal for potential manipulation of immune cell function in the CNS, thereby reducing disease burden. Here, we discuss new aspects of myeloid cell biology in general with special emphasis on the brain-resident macrophages and microglia.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Microglia - insights into immune system structure, function, and reactivity in the central nervous system. Abstract of the paper: Microglia are essential cellular components of a well-functioning central nervous system (CNS). The development and establishment of the microglial population differs from the other major cell populations in the CNS i.e. neurons and macroglia (astrocytes and oligodendrocytes). This different ontogeny gives microglia unique properties. In recent years detailed studies of the microglial population have been greatly facilitated by the use of bone marrow (BM) chimeric animals. Experimental BM transplants have provided the opportunity to trace and investigate how BM cells migrate into the CNS and settle to become microglia. Furthermore various functional properties of microglia in the normal and pathological CNS are now being revealed because of combinations of BM transplantations and experimental disease models. Here, we describe some of the latest findings in microglial biology and discuss the potential for using microglia in therapeutic interventions.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Isolation and Culture of Microglia. Abstract of the paper: Microglia represent 5-10% of cells in the central nervous system and contribute to the development, homeostasis, injury, and repair of neural tissues. As the tissue-resident macrophages of the central nervous system, microglia execute core innate immune functions such as detection of pathogens/damage, cytokine secretion, and phagocytosis. However, additional properties that are specific to microglia and their neural environment are beginning to be appreciated. This article describes approaches for purification of microglia by fluorescence-activated cell sorting using microglia-specific surface markers and for enrichment of microglia by magnetic sorting and immunopanning. Detailed information about culturing primary microglia at various developmental stages is also provided. Throughout, we focus on special considerations for handling microglia and compare the relative strengths or disadvantages of different protocols. © 2018 by John Wiley & Sons, Inc.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: intricate research projects utilizing various forms of microglial culture have helped identify their roles in synaptic plasticity 44 bloodbrain barrier permeability 4546 and synaptic pruning Title of the paper: Fine-tuning the central nervous system: microglial modelling of cells and synapses. Abstract of the paper: Microglia constitute as much as 10-15% of all cells in the mammalian central nervous system (CNS) and are the only glial cells that do not arise from the neuroectoderm. As the principal CNS immune cells, microglial cells represent the first line of defence in response to exogenous threats. Past studies have largely been dedicated to defining the complex immune functions of microglial cells. However, our understanding of the roles of microglia has expanded radically over the past years. It is now clear that microglia are critically involved in shaping neural circuits in both the developing and adult CNS, and in modulating synaptic transmission in the adult brain. Intriguingly, microglial cells appear to use the same sets of tools, including cytokine and chemokine release as well as phagocytosis, whether modulating neural function or mediating the brain's innate immune responses. This review will discuss recent developments that have broadened our views of neuro-glial signalling to include the contribution of microglial cells.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: A review of neuroimaging biomarkers of Alzheimer's disease. Abstract of the paper: Neuroimaging biomarkers have potential role in the early diagnosis as well as periodic follow-up of neurodegenerative diseases such as Alzheimer's disease (AD). Structural imaging biomarkers can be used to predict those who are at risk or in preclinical stages of AD. It could possibly be useful even in predicting the conversion of Mild Cognitive Impairment (MCI) an early stage of AD to AD. In addition there has been a lot of progress in molecular imaging in AD. This article presents a review of recent progress in selected imaging biomarkers for early diagnosis, classification, and progression, of AD. A comprehensive integrative strategy initiated early in the cognitive decline is perhaps the most effective method of controlling progression to Alzheimer's disease.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Quantitative evaluation of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) can be definitively diagnosed only by histopathologic examination of brain tissue; the identification and differential diagnosis of AD is especially challenging in its early stages. Neuroimaging is playing an increasingly relevant role in the identification and quantification of AD in vivo, especially in the preclinical stages, when therapeutic intervention could be more effective. Neuroimaging enables quantification of brain volume loss (structural imaging), detection of early cerebral dysfunction (functional imaging), probing into the finest cerebral structures (microstructural imaging), and investigation of amyloid plaque and neurofibrillary tangle build-up (amyloid imaging). Throughout the years, several imaging tools have been developed, ranging from simple visual rating scales to sophisticated computerized algorithms. As recently revised criteria for AD require quantitative evaluation of biomarkers mostly based on imaging, this paper provides an overview of the main neuroimaging tools which might be used presently or in the future in routine clinical practice for AD diagnosis.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Neuroimaging in Alzheimer's disease: current role in clinical practice and potential future applications. Abstract of the paper: 'Alzheimer's disease is the most common cause of dementia and its prevalence is expected to increase in the coming years. Therefore, accurate diagnosis is crucial for patients, clinicians and researchers. Neuroimaging techniques have provided invaluable information about Alzheimer's disease and, owing to recent advances, these methods will have an increasingly important role in research and clinical practice. The purpose of this article is to review recent neuroimaging studies of Alzheimer's disease that provide relevant information to clinical practice, including a new modality: in vivo amyloid imaging. Magnetic resonance imaging, single photon emission computed tomography and 18F-fluorodeoxyglucose-positron emission tomography are currently available for clinical use. Patients with suspected Alzheimer's disease are commonly investigated with magnetic resonance imaging because it provides detailed images of brain structure and allows the identification of supportive features for the diagnosis. Neurofunctional techniques such as single photon emission computed tomography and 18F-fluorodeoxyglucose-positron emission tomography can also be used to complement the diagnostic investigation in cases of uncertainty. Amyloid imaging is a non-invasive technique that uses positron emission tomography technology to investigate the accumulation of the β-amyloid peptide in the brain, which is a hallmark of Alzheimer's disease. This is a promising test but currently its use is restricted to very few specialized research centers in the world. Technological innovations will probably increase its availability and reliability, which are the necessary steps to achieve robust clinical applicability. Thus, in the future it is likely that amyloid imaging techniques will be used in the clinical evaluation of patients with Alzheimer's disease.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Neuroimaging in dementias. Abstract of the paper: PURPOSE OF REVIEW To critically review data on the use of neuroimaging tools in the clinical diagnostic investigation of dementias. RECENT FINDINGS For many years, the use of neuroimaging tools in the evaluation of dementias has been restricted to excluding neurosurgical lesions that may account for the cognitive decline. However, modern neuroimaging extends beyond this traditional role of excluding other conditions and has a key role in the clinical investigation of Alzheimer's disease and of other degenerative cortical dementias. MRI, PET with fluorodeoxyglucose, and single-photon emission computed tomography are topographic markers of neural damage and enable the identification of specific lesional patterns that characterize Alzheimer's disease and other cortical dementias. More recently, PET amyloid markers have enabled the in-vivo assessment of amyloid load, a key feature in the physiopathology of Alzheimer's disease. SUMMARY The combined use of neuroimaging examinations with clinical, neuropsychological, and cerebrospinal fluid markers can improve the specificity of the diagnosis of Alzheimer's disease, even at early stages of the disease. In the following years, progress in research will provide standardized and validated imaging markers of Alzheimer's disease and other dementias, which may increase their application in clinical settings.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Neuroimaging markers for the prediction and early diagnosis of Alzheimer's disease dementia. Abstract of the paper: Alzheimer's disease (AD) is a progressive age-related neurodegenerative disease. At the time of clinical manifestation of dementia, significant irreversible brain damage is already present, rendering the diagnosis of AD at early stages of the disease an urgent prerequisite for therapeutic treatment to halt, or at least slow, disease progression. In this review, we discuss various neuroimaging measures that are proving to have potential value as biomarkers of AD pathology for the detection and prediction of AD before the onset of dementia. Recent studies that have identified AD-like structural and functional brain changes in elderly people who are cognitively within the normal range or who have mild cognitive impairment (MCI) are discussed. A dynamic sequence model of changes that occur in neuroimaging markers during the different disease stages is presented and the predictive value of multimodal neuroimaging for AD dementia is considered.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: The role of neuroimaging in dementia. Abstract of the paper: Potential new therapies for the treatment of Alzheimer's disease demand early and accurate diagnosis. Although clinical evaluation is generally sufficient when the disease is well established, neuroimaging tools are helpful to detect the earliest changes of Alzheimer's disease or differentiate Alzheimer's disease from the other forms of dementia. This article reviews the basic concepts of brain imaging and clinical application. It concludes with a brief discussion of future directions in neuroimaging for the diagnosis and longitudinal follow-up of Alzheimer's disease.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Current neuroimaging techniques in Alzheimer's disease and applications in animal models. Abstract of the paper: With Alzheimer's disease (AD) quickly becoming the most costly disease to society, and with no disease-modifying treatment currently, prevention and early detection have become key points in AD research. Important features within this research focus on understanding disease pathology, as well as finding biomarkers that can act as early indicators and trackers of disease progression or potential treatment. With the advances in neuroimaging technology and the development of new imaging techniques, the search for cheap, noninvasive, sensitive biomarkers becomes more accessible. Modern neuroimaging techniques are able to cover most aspects of disease pathology, including visualization of senile plaques and neurofibrillary tangles, cortical atrophy, neuronal loss, vascular damage, and changes in brain biochemistry. These methods can provide complementary information, resulting in an overall picture of AD. Additionally, applying neuroimaging to animal models of AD could bring about greater understanding in disease etiology and experimental treatments whilst remaining in vivo. In this review, we present the current neuroimaging techniques used in AD research in both their human and animal applications, and discuss how this fits in to the overall goal of understanding AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Potential neuroimaging biomarkers of pathologic brain changes in Mild Cognitive Impairment and Alzheimer's disease: a systematic review. Abstract of the paper: BACKGROUND Neuroimaging-biomarkers of Mild Cognitive Impairment (MCI) allow an early diagnosis in preclinical stages of Alzheimer's disease (AD). The goal in this paper was to review of biomarkers for Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD), with emphasis on neuroimaging biomarkers. METHODS A systematic review was conducted from existing literature that draws on markers and evidence for new measurement techniques of neuroimaging in AD, MCI and non-demented subjects. Selection criteria included: 1) age ≥ 60 years; 2) diagnosis of AD according to NIAAA criteria, 3) diagnosis of MCI according to NIAAA criteria with a confirmed progression to AD assessed by clinical follow-up, and 4) acceptable clinical measures of cognitive impairment, disability, quality of life, and global clinical assessments. RESULTS Seventy-two articles were included in the review. With the development of new radioligands of neuroimaging, today it is possible to measure different aspects of AD neuropathology, early diagnosis of MCI and AD become probable from preclinical stage of AD to AD dementia and non-AD dementia. CONCLUSIONS The panel of noninvasive neuroimaging-biomarkers reviewed provides a set methods to measure brain structural and functional pathophysiological changes in vivo, which are closely associated with preclinical AD, MCI and non-AD dementia. The dynamic measures of these imaging biomarkers are used to predict the disease progression in the early stages and improve the assessment of therapeutic efficacy in these diseases in future clinical trials.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: The role of neuroimaging in mild cognitive impairment. Abstract of the paper: The main purposes of neuroimaging in Alzheimer's disease (AD) have been moved from diagnosis of advanced AD to diagnosis of very early AD at a prodromal stage of mild cognitive impairment, prediction of conversion from mild cognitive impairment (MCI) to AD, and differential diagnosis from other diseases causing dementia. Structural MRI studies and functional studies using F-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) and brain perfusion single-photon emission computed tomography (SPECT) are widely used in diagnosis of AD. Outstanding progress in diagnostic accuracy of these neuroimaging modalities has been obtained using statistical analysis on a voxel-by-voxel basis after spatial normalization of individual scans to a standardized brain-volume template instead of visual inspection or a conventional region of interest technique. In a very early stage of AD, this statistical approach revealed gray matter loss in the entorhinal and hippocampal areas and hypometabolism or hypoperfusion in the posterior cingulate cortex and precuneus. These two findings might be related in view of anatomical knowledge that the regions are linked through the circuit of Papez. This statistical approach also offers prediction of conversion from MCI to AD. Presence of hypometabolism or hypoperfusion in parietal association areas and entorhinal atrophy at the MCI stage has been reported to predict rapid conversion to AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Quantitative multimodal multiparametric imaging in Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is a progressive neurodegenerative disorder, causing changes in memory, thinking, and other dysfunction of brain functions. More and more people are suffering from the disease. Early neuroimaging techniques of AD are needed to develop. This review provides a preliminary summary of the various neuroimaging techniques that have been explored for in vivo imaging of AD. Recent advances in magnetic resonance (MR) techniques, such as functional MR imaging (fMRI) and diffusion MRI, give opportunities to display not only anatomy and atrophy of the medial temporal lobe, but also at microstructural alterations or perfusion disturbance within the AD lesions. Positron emission tomography (PET) imaging has become the subject of intense research for the diagnosis and facilitation of drug development of AD in both animal models and human trials due to its non-invasive and translational characteristic. Fluorodeoxyglucose (FDG) PET and amyloid PET are applied in clinics and research departments. Amyloid beta (Aβ) imaging using PET has been recognized as one of the most important methods for the early diagnosis of AD, and numerous candidate compounds have been tested for Aβ imaging. Besides in vivo imaging method, a lot of ex vivo modalities are being used in the AD researches. Multiphoton laser scanning microscopy, neuroimaging of metals, and several metal bioimaging methods are also mentioned here. More and more multimodality and multiparametric neuroimaging techniques should improve our understanding of brain function and open new insights into the pathophysiology of AD. We expect exciting results will emerge from new neuroimaging applications that will provide scientific and medical benefits.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Alzheimer's disease neuroimaging. Abstract of the paper: PURPOSE OF REVIEW The aim of this study was to discuss the contribution of neuroimaging studies to our understanding of Alzheimer's disease. We now have the capability of measuring both tau and beta-amyloid (Aβ) proteins in the brain, which together with more traditional neuroimaging modalities, has led the field to focus on using neuroimaging to better characterize disease mechanisms underlying Alzheimer's disease. RECENT FINDINGS Studies have utilized tau and Aβ PET, as well as [18F]fluorodeoxyglucose PET, and structural and functional MRI, to investigate the following topics: phenotypic variability in Alzheimer's disease , including how neuroimaging findings are related to clinical phenotype and age; multimodality analyses to investigate the relationships between different neuroimaging modalities and what that teaches us about disease mechanisms; disease staging by assessing neuroimaging changes in the very earliest phases of the disease in cognitively normal individuals and individuals carrying an autosomal dominant Alzheimer's disease mutation; and influence of other comorbidities and proteins to the disease process. SUMMARY The findings shed light on the role of tau and Aβ, as well as age and other comorbidities, in the neurodegenerative process in Alzheimer's disease. This knowledge will be crucial in the development of better disease biomarkers and targeted therapeutic approaches.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Neuroimaging biomarkers for clinical trials of disease-modifying therapies in Alzheimer's disease. Abstract of the paper: The pathophysiologic process leading to neurodegeneration in Alzheimer's disease (AD) is thought to begin long before clinical symptoms develop. Existing therapeutics for AD improve symptoms, but increasing efforts are being directed toward the development of therapies to impede the pathologic progression of the disease. Although these medications must ultimately demonstrate efficacy in slowing clinical decline, there is a critical need for biomarkers that will indicate whether a candidate disease-modifying therapeutic agent is actually altering the underlying degenerative process. A number of in vivo neuroimaging techniques, which can reliably and noninvasively assess aspects of neuroanatomy, chemistry, physiology, and pathology, hold promise as biomarkers. These neuroimaging measures appear to relate closely to neuropathological and clinical data, such as rate of cognitive decline and risk of future decline. As this work has matured, it has become clear that neuroimaging measures may serve a variety of potential roles in clinical trials of candidate neurotherapeutic agents for AD, depending in part on the question of interest and phase of drug development. In this article, we review data related to the range of neuroimaging biomarkers of Alzheimer's disease and consider potential applications of these techniques to clinical trials, particularly with respect to the monitoring of disease progression in trials of disease-modifying therapies.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Imaging Biomarkers in Alzheimer's Disease: A Practical Guide for Clinicians. Abstract of the paper: Although recent developments in imaging biomarkers have revolutionized the diagnosis of Alzheimer's disease at early stages, the utility of most of these techniques in clinical setting remains unclear. The aim of this review is to provide a clear stepwise algorithm on using multitier imaging biomarkers for the diagnosis of Alzheimer's disease to be used by clinicians and radiologists for day-to-day practice. We summarized the role of most common imaging techniques and their appropriate clinical use based on current consensus guidelines and recommendations with brief sections on acquisition and analysis techniques for each imaging modality. Structural imaging, preferably MRI or alternatively high resolution CT, is the essential first tier of imaging. It improves the accuracy of clinical diagnosis and excludes other potential pathologies. When the results of clinical examination and structural imaging, assessed by dementia expert, are still inconclusive, functional imaging can be used as a more advanced option. PET with ligands such as amyloid tracers and 18F-fluorodeoxyglucose can improve the sensitivity and specificity of diagnosis particularly at the early stages of the disease. There are, however, limitations in using these techniques in wider community due to a combination of lack of facilities and expertise to interpret the findings. The role of some of the more recent imaging techniques including tau imaging, functional MRI, or diffusion tensor imaging in clinical practice, remains to be established in the ongoing and future studies.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Alzheimer disease: new concepts on its neurobiology and the clinical role imaging will play. Abstract of the paper: Alzheimer disease (AD) is one of, if not the most, feared diseases associated with aging. The prevalence of AD increases exponentially with age after 60 years. Increasing life expectancy coupled with the absence of any approved disease-modifying therapies at present position AD as a dominant public health problem. Major advances have occurred in the development of disease biomarkers for AD in the past 2 decades. At present, the most well-developed AD biomarkers are the cerebrospinal fluid analytes amyloid-β 42 and tau and the brain imaging measures amyloid positron emission tomography (PET), fluorodeoxyglucose PET, and magnetic resonance imaging. CSF and imaging biomarkers are incorporated into revised diagnostic guidelines for AD, which have recently been updated for the first time since their original formulation in 1984. Results of recent studies suggest the possibility of an ordered evolution of AD biomarker abnormalities that can be used to stage the typical 20-30-year course of the disease. When compared with biomarkers in other areas of medicine, however, the absence of standardized quantitative metrics for AD imaging biomarkers constitutes a major deficiency. Failure to move toward a standardized system of quantitative metrics has substantially limited potential diagnostic usefulness of imaging in AD. This presents an important opportunity that, if widely embraced, could greatly expand the application of imaging to improve clinical diagnosis and the quality and efficiency of clinical trials.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Imaging biomarkers in Alzheimer's disease: added value in the clinical setting. Abstract of the paper: Over the last 20 years the availability of magnetic resonance imaging and positron-emission tomography technologies as well as of cerebrospinal fluid biomarkers has allowed research and clinical approach to Alzheimer's disease (AD) to move towards the earliest manifestations of the disease. This new approach resulted in an increasing knowledge about in-vivo biological and neuropathological processes of each phase of the AD-related damage from preclinical, to mild cognitive impairment, and finally to dementia due to AD. The present narrative review deals with the available data as well as with the unsolved issued related to the incorporation of AD biomarkers into the clinical practice. Ongoing research efforts aiming to better define and implement the use of imaging AD biomarkers in clinical practice according to a patient-centered approach and sustainability for clinical-care systems are also discussed.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Structural and functional neuroimaging in Alzheimer's disease: an update. Abstract of the paper: The field of neuroimaging has made several recent advances understanding Alzheimer's disease, a debilitating disease which affects approximately 4 million people in the United States [1]. Despite recent therapeutic advances, available treatments at present are aimed primarily at slowing progression of the disease rather than halting it completely or reversing its progression. Early detection of the disease has, therefore, been a major focus of a variety of neuroimaging techniques, including Positron Emission Tomography (PET), functional Magnetic Resonance Imaging (fMRI), and structural MRI. Recently, these techniques have also been found to be useful in monitoring cognitive and pathological progression of the disease, as well as monitoring response to clinical intervention treatment. A methodology review will be included here as well as a critical evaluation of the advantages and disadvantages of the various techniques.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: A focus on structural brain imaging in the Alzheimer's disease neuroimaging initiative. Abstract of the paper: In recent years, numerous laboratories and consortia have used neuroimaging to evaluate the risk for and progression of Alzheimer's disease (AD). The Alzheimer's Disease Neuroimaging Initiative is a longitudinal, multicenter study that is evaluating a range of biomarkers for use in diagnosis of AD, prediction of patient outcomes, and clinical trials. These biomarkers include brain metrics derived from magnetic resonance imaging (MRI) and positron emission tomography scans as well as metrics derived from blood and cerebrospinal fluid. We focus on Alzheimer's Disease Neuroimaging Initiative studies published between 2011 and March 2013 for which structural MRI was a major outcome measure. Our main goal was to review key articles offering insights into progression of AD and the relationships of structural MRI measures to cognition and to other biomarkers in AD. In Supplement 1, we also discuss genetic and environmental risk factors for AD and exciting new analysis tools for the efficient evaluation of large-scale structural MRI data sets such as the Alzheimer's Disease Neuroimaging Initiative data.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Advances in MRI biomarkers for the diagnosis of Alzheimer's disease. Abstract of the paper: With the prevalence of Alzheimer's disease (AD) predicted to increase substantially over the coming decades, the development of effective biomarkers for the early detection of the disease is paramount. In this short review, the main neuroimaging techniques which have shown potential as biomarkers for AD are introduced, with a focus on MRI. Structural MRI measures of the hippocampus and medial temporal lobe are still the most clinically validated biomarkers for AD, but newer techniques such as functional MRI and diffusion tensor imaging offer great scope in tracking changes in the brain, particularly in functional and structural connectivity, which may precede gray matter atrophy. These new advances in neuroimaging methods require further development and crucially, standardization; however, before they are used as biomarkers to aid in the diagnosis of AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Imaginem oblivionis: the prospects of neuroimaging for early detection of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by the gradual onset of dementia. The pathological hallmarks of the disease are A beta amyloid plaques, neurofibrillary tangles, and reactive gliosis. Current diagnosis of AD is made by clinical, neuropsychologic, and neuroimaging assessments. Routine structural neuroimaging evaluation is based on non-specific features such as atrophy, a late feature in the progression of the disease, hence the crucial importance of developing new approaches for early and specific recognition at the prodromal stages of AD. Functional neuroimaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) could prove to be valuable in the differential diagnosis of AD, as well as in assessing prognosis. With the advent of new therapeutic strategies aimed at reducing the A beta amyloid burden in the brain, there is increasing interest in the development of PET and SPECT radioligands that will permit the assessment of A beta amyloid burden in vivo. From this, the prospect of specific preclinical diagnosis arises, possibly in conjunction with other related A beta biomarkers in plasma and CSF.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: at a vastly different level of analysis the macroscopic level noninvasive neuroimaging has been used as a vector for diagnostic biomarkers of ad due to its excellent speed considerable spatial resolution and ability to record neuronal activity 101112 and it also plays a crucial role in the clinical identification of mci and ad Title of the paper: Neuroimaging of Alzheimer's disease: focus on amyloid and tau PET. Abstract of the paper: Although the diagnosis of dementia is still largely a clinical one, based on history and disease course, neuroimaging has dramatically increased our ability to accurately diagnose it. Neuroimaging modalities now play a wider role in dementia beyond their traditional role of excluding neurosurgical lesions and are recommended in most clinical guidelines for dementia. In addition, new neuroimaging methods facilitate the diagnosis of most neurodegenerative conditions after symptom onset and show diagnostic promise even in the very early or presymptomatic phases of some diseases. In the case of Alzheimer's disease (AD), extracellular amyloid-β (Aβ) aggregates and intracellular tau neurofibrillary tangles are the two neuropathological hallmarks of the disease. Recent molecular imaging techniques using amyloid and tau PET ligands have led to preclinical diagnosis and improved differential diagnosis as well as narrowed subject selection and treatment monitoring in clinical trials aimed at delaying or preventing the symptomatic phase of AD. This review discusses the recent progress in amyloid and tau PET imaging and the key findings achieved by the use of this molecular imaging modality related to the respective roles of Aβ and tau in AD, as well as its specific limitations.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Potential Ocular Biomarkers for Early Detection of Alzheimer's Disease and Their Roles in Artificial Intelligence Studies. Abstract of the paper: Alzheimer's disease (AD) is the leading cause of dementia worldwide. Early detection is believed to be essential to disease management because it enables physicians to initiate treatment in patients with early-stage AD (early AD), with the possibility of stopping the disease or slowing disease progression, preserving function and ultimately reducing disease burden. The purpose of this study was to review prior research on the use of eye biomarkers and artificial intelligence (AI) for detecting AD and early AD. The PubMed database was searched to identify studies for review. Ocular biomarkers in AD research and AI research on AD were reviewed and summarized. According to numerous studies, there is a high likelihood that ocular biomarkers can be used to detect early AD: tears, corneal nerves, retina, visual function and, in particular, eye movement tracking have been identified as ocular biomarkers with the potential to detect early AD. However, there is currently no ocular biomarker that can be used to definitely detect early AD. A few studies that used AI with ocular biomarkers to detect AD reported promising results, demonstrating that using AI with ocular biomarkers through multimodal imaging could improve the accuracy of identifying AD patients. This strategy may become a screening tool for detecting early AD in older patients prior to the onset of AD symptoms.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Use of ocular biomarkers as a potential tool for early diagnosis of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide which unfortunately has no known effective cure to date. Despite many clinical trials indicating the effectiveness of preclinical treatment, a sensitive tool for screening of AD is yet to be developed. Due to multiple similarities between ocular and the brain tissue, the eye is being explored by researchers for this purpose, with utmost attention focused on the retinal tissue. Besides visual functional impairment, neuronal degeneration and apoptosis, retinal nerve fiber degeneration, increase in the cup-to-disc ratio, and retinal vascular thinning and tortuosity are the changes observed in the retinal tissue which are related to AD. Studies have shown that targeting these changes in the retina is an effective way of reducing the degeneration of retinal neuronal tissue. Similar mechanisms of neurodegeneration have been demonstrated in the brain and the eyes of AD patients. Multiple studies are underway to investigate the potential of diagnosing AD and detection of amyloid-β (Aβ) levels in the retinal tissue. Since the tissues in the anterior segment of the eye are more accessible for in vivo imaging and examination, they have more potential as screening biomarkers. This article provides a concise review of available literature on the ocular biomarkers in anterior and posterior segments of the eye including the cornea, aqueous humour (AH), crystalline lens, and retina in AD. This review will also highlight the newer technological tools available for the detection of potential biomarkers in the eye for early diagnosis of AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Ophthalmic Biomarkers for Alzheimer's Disease: A Review. Abstract of the paper: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by neuronal loss, extracellular amyloid-β (Aβ) plaques, and intracellular neurofibrillary tau tangles. A diagnosis is currently made from the presenting symptoms, and the only definitive diagnosis can be done post-mortem. Over recent years, significant advances have been made in using ocular biomarkers to diagnose various neurodegenerative diseases, including AD. As the eye is an extension of the central nervous system (CNS), reviewing changes in the eye's biology could lead to developing a series of non-invasive, differential diagnostic tests for AD that could be further applied to other diseases. Significant changes have been identified in the retinal nerve fiber layer (RNFL), cornea, ocular vasculature, and retina. In the present paper, we review current research and assess some ocular biomarkers' accuracy and reliability that could potentially be used for diagnostic purposes. Additionally, we review the various imaging techniques used in the measurement of these biomarkers.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Ocular biomarkers for early detection of Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is the most common form of dementia and is clinically characterized by a progressive decline in memory, learning, and executive functions, and neuropathologically characterized by the presence of cerebral amyloid deposits. Despite a century of research, there is still no cure or conclusive premortem diagnosis for the disease. A number of symptom-modifying drugs for AD have been developed, but their efficacy is minimal and short-lived. AD cognitive symptoms arise only after significant, irreversible neural deterioration has occurred; hence there is an urgent need to detect AD early, before the onset of cognitive symptoms. An accurate, early diagnostic test for AD would enable current and future treatments to be more effective, as well as contribute to the development of new treatments. While most AD related pathology occurs in the brain, the disease has also been reported to affect the eye, which is more accessible for imaging than the brain. AD-related proteins exist in the normal human eye and may produce ocular pathology in AD. There is some homology between the retinal and cerebral vasculatures and the retina also contains nerve cells and fibers that form a sensory extension of the brain. The eye is the only place in the body where vasculature or neural tissue is available for non-invasive optical imaging. This article presents a review of current literature on ocular morphology in AD and discusses the potential for an ocular-based screening test for AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Protein and Imaging Biomarkers in the Eye for Early Detection of Alzheimer's Disease. Abstract of the paper: Alzheimer's disease (AD) is one of the most common causes of dementia worldwide. Although no formal curative therapy exists for the treatment of AD, considerable research has been performed to identify biomarkers for early detection of this disease, and thus improved subsequent management. Given that the eye can be examined and imaged non-invasively with relative ease, it has emerged as an exciting area of research for evidence of biomarkers and to aid in the early diagnosis of AD. This review explores the current understanding of both protein and retinal imaging biomarkers in the eye. Herein, primary findings in the literature regarding AD biomarkers associated with the lens, retina, and other ocular structures are reviewed.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: The Eye As a Biomarker for Alzheimer's Disease. Abstract of the paper: Alzheimer's disease (AD) is a progressive neurodegenerative disorder resulting in dementia and eventual death. It is the leading cause of dementia and the number of cases are projected to rise in the next few decades. Pathological hallmarks of AD include the presence of hyperphosphorylated tau and amyloid protein deposition. Currently, these pathological biomarkers are detected either through cerebrospinal fluid analysis, brain imaging or post-mortem. Though effective, these methods are not widely available due to issues such as the difficulty in acquiring samples, lack of infrastructure or high cost. Given that the eye possesses clear optics and shares many neural and vascular similarities to the brain, it offers a direct window to cerebral pathology. These unique characteristics lend itself to being a relatively inexpensive biomarker for AD which carries the potential for wide implementation. The development of ocular biomarkers can have far implications in the discovery of treatments which can improve the quality of lives of patients. In this review, we consider the current evidence for ocular biomarkers in AD and explore potential future avenues of research in this area.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Ocular Biomarkers of Alzheimer's Disease: The Role of Anterior Eye and Potential Future Directions. Abstract of the paper: Globally, Alzheimer's disease (AD) is a growing health and economic challenge that has no effective cure. Recent clinical trials indicate that preclinical treatment may be required but a routine screening tool for AD has been elusive. Hence, a simple, yet sensitive biomarker for preclinical AD, when the disease is most likely to be amenable to treatment, is lacking. Due to several features, the eye has been explored for this purpose and, among the ocular tissues, the retina has received the most attention. Currently, major works investigating the potential AD diagnosis by detecting amyloid-β (Aβ) signatures in the retinal tissue are underway, while the anterior eye is more accessible for in vivo imaging and examination. This report provides a concise review of current literature on the anterior eye components, including the crystalline lens, cornea, and aqueous humor, in AD. We also discuss the potential for assessment of the corneal nerve structure and regeneration as well as conjunctival tissue for AD-related alterations. The crystalline lens has received considerable attention, but further research is required to confirm whether Aβ accumulates in the lens and whether it mirrors brain neuropathologic changes, particularly in preclinical AD. The rich corneal neural network and conjunctival vasculature also merit exploration in future studies to shed light on their potential association with AD pathologic changes.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Emerging ocular biomarkers of Alzheimer disease. Abstract of the paper: Interest in reliable biomarkers of Alzheimer disease, the leading cause of dementia, has been fuelled by challenges in diagnosing the disease and monitoring disease progression as well as the response to therapy. A range of ocular manifestations of Alzheimer disease, including retinal and lens amyloid-beta accumulation, retinal nerve fiber layer loss, and retinal vascular changes, have been proposed as potential biomarkers of the disease. Herein, we examine the evidence regarding the potential value of these ocular biomarkers of Alzheimer disease.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Ocular Biomarkers for Alzheimer Disease Dementia: An Umbrella Review of Systematic Reviews and Meta-analyses. Abstract of the paper: Importance Several ocular biomarkers have been proposed for the early detection of Alzheimer disease (AD) and mild cognitive impairment (MCI), particularly fundus photography, optical coherence tomography (OCT), and OCT angiography (OCTA). Objective To perform an umbrella review of systematic reviews to assess the diagnostic accuracy of ocular biomarkers for early diagnosis of Alzheimer disease. Data Sources MEDLINE, Embase, and PsycINFO were searched from January 2000 to November 2021. The references of included reviews were also searched. Study Selection Systematic reviews investigating the diagnostic accuracy of ocular biomarkers to detect AD and MCI, in secondary care or memory clinics, against established clinical criteria or clinical judgment. Data Extraction and Synthesis The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline checklist was followed and the Risk Of Bias in Systematic reviews tool was used to assess review quality. Main Outcomes and Measures The prespecified outcome was the accuracy of ocular biomarkers for diagnosing AD and MCI. The area under the curve (AUC) was derived from standardized mean difference. Results From the 591 titles, 14 systematic reviews were included (median [range] number of studies in each review, 14 [5-126]). Only 4 reviews were at low risk of bias on all Risk of Bias in Systematic Reviews domains. The imaging-derived parameters with the most evidence for detecting AD compared with healthy controls were OCT peripapillary retinal nerve fiber layer thickness (38 studies including 1883 patients with AD and 2510 controls; AUC = 0.70; 95% CI, 0.53-0.79); OCTA foveal avascular zone (5 studies including 177 patients with AD and 371 controls; AUC = 0.73; 95% CI, 0.50-0.89); and saccadic eye movements prosaccade latency (30 studies including 651 patients with AD/MCI and 771 controls; AUC = 0.64; 95% CI, 0.58-0.69). Antisaccade error was investigated in fewer studies (12 studies including 424 patients with AD/MCI and 382 controls) and yielded the best accuracy (AUC = 0.79; 95% CI, 0.70-0.88). Conclusions and Relevance This umbrella review has highlighted limitations in design and reporting of the existing research on ocular biomarkers for diagnosing AD. Parameters with the best evidence showed poor to moderate diagnostic accuracy in cross-sectional studies. Future longitudinal studies should investigate whether changes in OCT and OCTA measurements over time can yield accurate predictions of AD onset.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Diagnostic and Prognostic Potential of Retinal Biomarkers in Early On-Set Alzheimer's Disease. Abstract of the paper: OBJECTIVE Accumulating evidence suggests that the eye can be used in the assessment of early on-set Alzheimer's disease (AD). The eye offers a natural window to the brain through the retina. The retina and brain share common developmental origins and patho-physiological origins and mechanisms, having been sequestered from it during early development, but retaining its connections with the brain via the optic nerve. Therefore, it is well understood that neurological abnormalities have a direct profound impact on the retina. Recent studies suggest an array of physiological and pathological changes in the retina in dementia and specifically in AD. There are also reports on imaging the two hallmark proteins of the disease, extracellular amyloid beta peptides and intracellular hyper phosphorylated tau protein, as a proxy to neuroimaging. RESULTS In this review, we summarise retinal structural, functional and vascular changes reported to be associated with AD. We also review techniques employed to image these two major hall mark proteins of AD and their relevance for early detection of AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Beta-amyloid sequelae in the eye: a critical review on its diagnostic significance and clinical relevance in Alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder. There is no test for its definitive diagnosis in routine clinical practice. Although phase III clinical trials have failed, only symptomatic treatment is currently available; a possible reason for these failed trials is that intervention commenced at an advanced stage of the disease. The hallmarks of an AD brain include plaques comprising of extracellular beta-amyloid (Aβ) protein aggregates and intracellular hyperphosphorylated neurofibrillary tangles of tau. Research into the preclinical diagnosis of AD has provided considerable evidence regarding early neuropathological changes using brain Aβ imaging and the cerebrospinal fluid biomarkers, Aβ and tau. Both these approaches have limitations that are expensive, invasive or time consuming and thus preclude them from screening at-risk population. Recent studies have demonstrated the presence of Aβ plaques in the eyes of AD subjects, which is positively associated with their brain Aβ burden. Thus ocular biomarkers point to a potential avenue for an earlier, relatively low-cost diagnosis in order for therapeutic interventions to be effective. Here we review the literature that spans the investigation for the presence of Aβ in aging eyes and the significance of its deposition in relation to AD pathology. We discuss clinical studies investigating in vivo imaging of Aβ in the eye and its association with brain Aβ burden and therapies that target ocular Aβ. Finally, we focus on the need to characterize AD-specific retinal Aβ to differentiate Aβ found in some eye diseases. Based on the current evidence, we conclude that integration of ocular biomarkers that can correctly predict brain Aβ burden would have an important role as a non-invasive, yet economical surrogate marker in the diagnostic process of AD.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Visual and Ocular Manifestations of Alzheimer's Disease and Their Use as Biomarkers for Diagnosis and Progression. Abstract of the paper: Alzheimer's disease (AD) is the most common form of dementia affecting the growing aging population today, with prevalence expected to rise over the next 35 years. Clinically, patients exhibit a progressive decline in cognition, memory, and social functioning due to deposition of amyloid β (Aβ) protein and intracellular hyperphosphorylated tau protein. These pathological hallmarks of AD are measured either through neuroimaging, cerebrospinal fluid analysis, or diagnosed post-mortem. Importantly, neuropathological progression occurs in the eye as well as the brain, and multiple visual changes have been noted in both human and animal models of AD. The eye offers itself as a transparent medium to cerebral pathology and has thus potentiated the development of ocular biomarkers for AD. The use of non-invasive screening, such as retinal imaging and visual testing, may enable earlier diagnosis in the clinical setting, minimizing invasive and expensive investigations. It also potentially improves disease management and quality of life for AD patients, as an earlier diagnosis allows initiation of medication and treatment. In this review, we explore the evidence surrounding ocular changes in AD and consider the biomarkers currently in development for early diagnosis.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Ocular indicators of Alzheimer's: exploring disease in the retina. Abstract of the paper: Although historically perceived as a disorder confined to the brain, our understanding of Alzheimer's disease (AD) has expanded to include extra-cerebral manifestation, with mounting evidence of abnormalities in the eye. Among ocular tissues, the retina, a developmental outgrowth of the brain, is marked by an array of pathologies in patients suffering from AD, including nerve fiber layer thinning, degeneration of retinal ganglion cells, and changes to vascular parameters. While the hallmark pathological signs of AD, amyloid β-protein (Aβ) plaques and neurofibrillary tangles (NFT) comprising hyperphosphorylated tau (pTau) protein, have long been described in the brain, identification of these characteristic biomarkers in the retina has only recently been reported. In particular, Aβ deposits were discovered in post-mortem retinas of advanced and early stage cases of AD, in stark contrast to non-AD controls. Subsequent studies have reported elevated Aβ42/40 peptides, morphologically diverse Aβ plaques, and pTau in the retina. In line with the above findings, animal model studies have reported retinal Aβ deposits and tauopathy, often correlated with local inflammation, retinal ganglion cell degeneration, and functional deficits. This review highlights the converging evidence that AD manifests in the eye, especially in the retina, which can be imaged directly and non-invasively. Visual dysfunction in AD patients, traditionally attributed to well-documented cerebral pathology, can now be reexamined as a direct outcome of retinal abnormalities. As we continue to study the disease in the brain, the emerging field of ocular AD warrants further investigation of how the retina may faithfully reflect the neurological disease. Indeed, detection of retinal AD pathology, particularly the early presenting amyloid biomarkers, using advanced high-resolution imaging techniques may allow large-scale screening and monitoring of at-risk populations.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Alzheimer's disease in the human eye. Clinical tests that identify ocular and visual information processing deficit as biomarkers. Abstract of the paper: Alzheimer's disease (AD) is the most common form of dementia with progressive deterioration of memory and cognition. Complaints related to vision are common among AD patients. Several changes in the retina, lens, and in the vasculature have been noted in the AD eye that may be the cause of visual symptoms experienced by the AD patient. Anatomical changes have been detected within the eye before signs of cognitive impairment and memory loss are apparent. Unlike the brain, the eye is a unique organ that can be visualized noninvasively at the cellular level because of its transparent nature, which allows for inexpensive testing of biomarkers in a clinical setting. In this review, we have searched for candidate biomarkers that could enable diagnosis of AD, covering ocular neurodegeneration associated with functional tests. We explore the evidence that suggests that inexpensive, noninvasive clinical tests could be used to detect AD ocular biomarkers.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Alzheimer's Disease Seen through the Eye: Ocular Alterations and Neurodegeneration. Abstract of the paper: Alzheimer's Disease (AD) is one of the main neurodegenerative diseases worldwide. Unfortunately, AD shares many similarities with other dementias at early stages, which impedes an accurate premortem diagnosis. Therefore, it is urgent to find biomarkers to allow for early diagnosis of the disease. There is increasing scientific evidence highlighting the similarities between the eye and other structures of the CNS, suggesting that knowledge acquired in eye research could be useful for research and diagnosis of AD. For example, the retina and optic nerve are considered part of the central nervous system, and their damage can result in retrograde and anterograde axon degeneration, as well as abnormal protein aggregation. In the anterior eye segment, the aqueous humor and tear film may be comparable to the cerebrospinal fluid. Both fluids are enriched with molecules that can be potential neurodegenerative biomarkers. Indeed, the pathophysiology of AD, characterized by cerebral deposits of amyloid-beta (Aβ) and tau protein, is also present in the eyes of AD patients, besides numerous structural and functional changes observed in the structure of the eyes. Therefore, all this evidence suggests that ocular changes have the potential to be used as either predictive values for AD assessment or as diagnostic tools.

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CitationGPTRetr195

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Retinal Biomarkers of Alzheimer Disease. Abstract of the paper: PURPOSE To address challenges associated with identifying retinal biomarkers for Alzheimer's disease (AD) and strategies for future investigation of novel ophthalmologic biomarkers. DESIGN Perspective. METHODS Summarization of the current understanding of retinal changes that have been identified using advances in imaging technology, analysis of current research into how these changes reflect neurodegenerative pathology, and recommendations for further research in this area that will allow for the identification of unique biomarkers for early AD. RESULTS Some retinal changes detectable using various imaging modalities may reflect neurodegeneration or other AD-related pathology on a cellular level. Structural changes in both the peripapillary and macular retina and changes in vascular parameters have been identified. Some imaging findings correlate with known histopathologic findings, and some are associated with cognitive decline. However, multiple challenges exist, such as identifying retinal biomarkers that are specific to biomarker-positive AD, clinical syndrome of AD, and/or pathologic AD brain, finding features that are highly sensitive and specific to AD in patients with other eye diseases, and validating potential biomarkers in population-based longitudinal cohorts. CONCLUSIONS Further research is needed to validate retinal biomarkers for AD, with accurate classification of patients according to diagnosis and cognitive symptoms. Advances in imaging technology, big data, and machine learning, as well as carefully designed studies, will help to identify and confirm potential biomarkers and may lead to novel treatment approaches.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: The Eye as a Diagnostic Tool for Alzheimer's Disease. Abstract of the paper: Alzheimer's disease (AD) is a progressive neurodegenerative disorder impacting cognition, function, and behavior in the elderly population. While there are currently no disease-modifying agents capable of curing AD, early diagnosis and management in the preclinical stage can significantly improve patient morbidity and life expectancy. Currently, the diagnosis of Alzheimer's disease is a clinical one, often supplemented by invasive and expensive biomarker testing. Over the last decade, significant advancements have been made in our understanding of AD and the role of ocular tissue as a potential biomarker. Ocular biomarkers hold the potential to provide noninvasive and easily accessible diagnostic and monitoring capabilities. This review summarizes current research for detecting biomarkers of Alzheimer's disease in ocular tissue.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Developing retinal biomarkers for the earliest stages of Alzheimer's disease: What we know, what we don't, and how to move forward. Abstract of the paper: The last decade has seen a substantial increase in research focused on the identification, development, and validation of diagnostic and prognostic retinal biomarkers for Alzheimer's disease (AD). Sensitive retinal biomarkers may be advantageous because they are cost and time efficient, non-invasive, and present a minimal degree of patient risk and a high degree of accessibility. Much of the work in this area thus far has focused on distinguishing between symptomatic AD and/or mild cognitive impairment (MCI) and cognitively normal older adults. Minimal work has been done on the detection of preclinical AD, the earliest stage of AD pathogenesis characterized by the accumulation of cerebral amyloid absent clinical symptoms of MCI or dementia. The following review examines retinal structural changes, proteinopathies, and vascular alterations that have been proposed as potential AD biomarkers, with a focus on studies examining the earliest stages of disease pathogenesis. In addition, we present recommendations for future research to move beyond the discovery phase and toward validation of AD risk biomarkers that could potentially be used as a first step in a multistep screening process for AD risk detection.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Biomarkers for Alzheimer's Disease Early Diagnosis. Abstract of the paper: Alzheimer's disease (AD) is the most common cause of dementia, affecting the central nervous system (CNS) through the accumulation of intraneuronal neurofibrillary tau tangles (NFTs) and β-amyloid plaques. By the time AD is clinically diagnosed, neuronal loss has already occurred in many brain and retinal regions. Therefore, the availability of early and reliable diagnosis markers of the disease would allow its detection and taking preventive measures to avoid neuronal loss. Current diagnostic tools in the brain, such as magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, and cerebrospinal fluid (CSF) biomarkers (Aβ and tau) detection are invasive and expensive. Brain-secreted extracellular vesicles (BEVs) isolated from peripheral blood have emerged as novel strategies in the study of AD, with enormous potential as a diagnostic evaluation of therapeutics and treatment tools. In addition; similar mechanisms of neurodegeneration have been demonstrated in the brain and the eyes of AD patients. Since the eyes are more accessible than the brain, several eye tests that detect cellular and vascular changes in the retina have also been proposed as potential screening biomarkers. The aim of this study is to summarize and discuss several potential markers in the brain, eye, blood, and other accessible biofluids like saliva and urine, and correlate them with earlier diagnosis and prognosis to identify individuals with mild symptoms prior to dementia.

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Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: in this section we discuss in detail ocular biomarkers according to their classification into structural biomarkers or functional biomarkersfig 2ocular biomarkers that can be used to detect alzheimers diseasetable 1ocular biomarkers for detecting alzheimers disease and early alzheimers diseaseocular biomarkersspecific descriptiondetecting adaearly adastructural biomarkerstearsproteomics components 14 18 19xelevated levels of ttau and aβ42 20microrna200b5p higher level of total microrna 25  corneal nervesreductions in corneal sensitivities xdifferent morphology of corneal nerve fibers in ccm Title of the paper: Retinal Dysfunction in Alzheimer's Disease and Implications for Biomarkers. Abstract of the paper: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that manifests as cognitive deficits and memory decline, especially in old age. Several biomarkers have been developed to monitor AD progression. Given that the retina and brain share some similarities including features related to anatomical composition and neurological functions, the retina is closely associated with the progression of AD. Herein, we review the evidence of retinal dysfunction in AD, particularly at the early stage, together with the underlying molecular mechanisms. Furthermore, we compared the retinal pathologies of AD and other ophthalmological diseases and summarized potential retinal biomarkers measurable by existing technologies for detecting AD, providing insights for the future development of diagnostic tools.

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