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CitationGPTRetr1000

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: CSF biomarkers of neuroinflammation in distinct forms and subtypes of neurodegenerative dementia. Abstract of the paper: BACKGROUND In neurodegenerative dementias (NDs) such as prion disease, Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD), protein misfolding leads to the tissue deposition of protein aggregates which, in turn, trigger neuroinflammation and neurodegeneration. Cerebrospinal fluid (CSF) biomarkers have the potential to reflect different aspects of these phenomena across distinct clinicopathological subtypes and disease stages. METHODS We investigated CSF glial markers, namely chitotriosidase 1 (CHIT1), chitinase-3-like protein 1 (YKL-40) and glial fibrillary acidic protein (GFAP) in prion disease subtypes (n = 101), AD (n = 40), clinicopathological subgroups of FTLD (n = 72), and controls (n = 40) using validated, commercially available ELISA assays. We explored glial biomarker levels' associations with disease variables and neurodegenerative CSF biomarkers and evaluated their diagnostic accuracy. The genotype of the CHIT1 rs3831317 polymorphic site was also analyzed. RESULTS Each ND group showed increased levels of CHIT1, YKL-40, and GFAP compared to controls with a difference between prion disease and AD or FTLD limited to YKL-40, which showed higher values in the former group. CHIT1 levels were reduced in both heterozygotes and homozygotes for the CHIT1 24-bp duplication (rs3831317) in FTLD and controls, but this effect was less significant in AD and prion disease. After stratification according to molecular subgroups, we demonstrated (i) an upregulation of all glial markers in Creutzfeldt-Jakob disease VV2 compared to other disease subtypes, (ii) a difference in CHIT1 levels between FTLD with TAU and TDP43 pathology, and (iii) a marked increase of YKL-40 in FTLD with amyotrophic lateral sclerosis (ALS) in comparison with FTLD without ALS. In prion disease, glial markers correlated with disease stage and were already elevated in one pre-symptomatic case of Gerstmann-Sträussler-Scheinker disease. Regarding the diagnostic value, YKL-40 was the only glial marker that showed a moderate accuracy in the distinction between controls and NDs. CONCLUSIONS NDs share a CSF profile characterized by increased levels of CSF CHIT1, YKL-40, and GFAP, which likely reflects a common neuroinflammatory response to protein misfolding and aggregation. CSF glial markers of neuroinflammation demonstrate limited diagnostic value but have some potential for monitoring the clinical and, possibly, preclinical phases of NDs.

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CitationGPTRetr1001

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: Increased Levels of Chitotriosidase and YKL-40 in Cerebrospinal Fluid from Patients with Alzheimer's Disease. Abstract of the paper: BACKGROUND The cerebrospinal fluid (CSF) biomarkers total tau, abnormally phosphorylated tau and amyloid β 1-42 are strongly associated with Alzheimer's disease (AD). Apart from the pathologic hallmarks that these biomarkers represent, other processes such as inflammation and microglial activation are present in the brains of patients with AD. New biomarkers related to these processes could be valuable for the diagnosis and follow-up of AD patients and for the evaluation of inflammation-related pathologies. AIM The aim of this study was to evaluate the association of inflammatory CSF biomarkers with AD. METHODS Twenty-five AD patients and 25 controls who had a pathological and normal CSF profile of the core AD biomarkers, respectively, were included in this study. CSF levels of chitotriosidase, YKL-40 (also known as chitinase-3-like protein 1) and monocyte chemoattractant protein-1 (MCP-1) were quantified and the levels compared between the groups. RESULTS AD patients had increased CSF levels of chitotriosidase and YKL-40 (both approximately twice higher than in controls), while the levels of MCP-1 were similar in the AD and control groups. CONCLUSION The results indicate that chitotriosidase and YKL-40 may be helpful for the evaluation of cerebral inflammatory activity in AD patients.

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CitationGPTRetr1002

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression. Abstract of the paper: OBJECTIVE There is a clear need to develop biomarkers for Parkinson disease (PD) diagnosis, differential diagnosis of Parkinsonian disorders, and monitoring disease progression. We and others have demonstrated that a decrease in DJ-1 and/or α-synuclein in the cerebrospinal fluid (CSF) is a potential index for Parkinson disease diagnosis, but not for PD severity. METHODS Using highly sensitive and quantitative Luminex assays, we measured total tau, phosphorylated tau, amyloid beta peptide 1-42 (Aβ(1-42)), Flt3 ligand, and fractalkine levels in CSF in a large cohort of PD patients at different stages as well as healthy and diseased controls. The utility of these 5 markers was evaluated for disease diagnosis and severity/progression correlation alone, as well as in combination with DJ-1 and α-synuclein. The major results were further validated in an independent cohort of cross-sectional PD patients as well as in PD cases with CSF samples collected longitudinally. RESULTS The results demonstrated that combinations of these biomarkers could differentiate PD patients not only from normal controls but also from patients with Alzheimer disease (AD) and multiple system atrophy. Particularly, with CSF Flt3 ligand, PD could be clearly differentiated from multiple system atrophy, a disease that overlaps with PD clinically, with excellent sensitivity (99%) and specificity (95%). In addition, we identified CSF fractalkine/Aβ(1-42) that positively correlated with PD severity in cross-sectional samples as well as with PD progression in longitudinal samples. INTERPRETATION We have demonstrated that this panel of 7 CSF proteins could aid in Parkinson disease diagnosis, differential diagnosis, and correlation with disease severity and progression.

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CitationGPTRetr1003

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: CSF multianalyte profile distinguishes Alzheimer and Parkinson diseases. Abstract of the paper: The therapeutic imperative for Alzheimer disease (AD) and Parkinson disease (PD) calls for discovery and validation of biomarkers. Increased cerebrospinal fluid (CSF) tau and decreased amyloid (A) beta42 have been validated as biomarkers of AD. In contrast, there is no validated CSF biomarker for PD. We validated our proteomics-discovered multianalyte profile (MAP) in CSF from 95 control subjects, 48 patients with probable AD, and 40 patients with probable PD. An optimal 8-member MAP agreed with expert diagnosis for 90 control subjects (95%), 36 patients with probable AD (75%), and 38 patients with probable PD (95%). This MAP consisted of the following (in decreasing order of contribution): tau, brain-derived neurotrophic factor, interleukin 8, Abeta42, beta2-microglobulin, vitamin D binding protein, apolipoprotein (apo) AII, and apoE. This first large-scale validation of a proteomic-discovered MAP suggests a panel of 8 CSF proteins that are highly effective at identifying PD and moderately effective at identifying AD.

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CitationGPTRetr1004

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: New fluid biomarkers tracking non-amyloid-β and non-tau pathology in Alzheimer's disease. Abstract of the paper: Cerebrospinal fluid (CSF) biomarkers based on the core pathological proteins associated with Alzheimer's disease (AD), i.e., amyloid-β (Aβ) and tau protein, are widely regarded as useful diagnostic biomarkers. However, a lack of biomarkers for monitoring the treatment response and indexing clinical severity has proven to be problematic in drug trials targeting Aβ. Therefore, new biomarkers are needed to track non-Aβ and non-tau pathology. Many proteins involved in the pathophysiological progression of AD have shown promise as new biomarkers. Neurodegeneration- and synapse-related biomarkers in CSF (e.g., neurofilament light polypeptide [NFL], neurogranin, and visinin-like protein 1) and blood (e.g., NFL) aid prediction of AD progress, as well as early diagnosis. Neuroinflammation, lipid dysmetabolism, and impaired protein clearance are considered important components of AD pathophysiology. Inflammation-related proteins in the CSF, such as progranulin, intercellular adhesion molecule 1, and chitinase-3-like protein 1 (YKL-40), are useful for the early detection of AD and can represent clinical severity. Several lipid metabolism-associated biomarkers and protein clearance-linked markers have also been suggested as candidate AD biomarkers. Combinations of subsets of new biomarkers enhance their utility in terms of broadly characterizing AD-associated pathological changes, thereby facilitating precise selection of susceptible patients and comprehensive monitoring of the treatment response. This approach could facilitate the development of effective treatments for AD.

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CitationGPTRetr1005

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias. Abstract of the paper: BACKGROUND YKL-40 (also known as Chitinase 3-like 1) is a glycoprotein produced by inflammatory, cancer and stem cells. Its physiological role is not completely understood but YKL-40 is elevated in the brain and cerebrospinal fluid (CSF) in several neurological and neurodegenerative diseases associated with inflammatory processes. Yet the precise characterization of YKL-40 in dementia cases is missing. METHODS In the present study, we comparatively analysed YKL-40 levels in the brain and CSF samples from neurodegenerative dementias of different aetiologies characterized by the presence of cortical pathology and disease-specific neuroinflammatory signatures. RESULTS YKL-40 was normally expressed in fibrillar astrocytes in the white matter. Additionally YKL-40 was highly and widely expressed in reactive protoplasmic cortical and perivascular astrocytes, and fibrillar astrocytes in sporadic Creutzfeldt-Jakob disease (sCJD). Elevated YKL-40 levels were also detected in Alzheimer's disease (AD) but not in dementia with Lewy bodies (DLB). In AD, YKL-40-positive astrocytes were commonly found in clusters, often around β-amyloid plaques, and surrounding vessels with β-amyloid angiopathy; they were also distributed randomly in the cerebral cortex and white matter. YKL-40 overexpression appeared as a pre-clinical event as demonstrated in experimental models of prion diseases and AD pathology. CSF YKL-40 levels were measured in a cohort of 288 individuals, including neurological controls (NC) and patients diagnosed with different types of dementia. Compared to NC, increased YKL-40 levels were detected in sCJD (p < 0.001, AUC = 0.92) and AD (p < 0.001, AUC = 0.77) but not in vascular dementia (VaD) (p > 0.05, AUC = 0.71) or in DLB/Parkinson's disease dementia (PDD) (p > 0.05, AUC = 0.70). Further, two independent patient cohorts were used to validate the increased CSF YKL-40 levels in sCJD. Additionally, increased YKL-40 levels were found in genetic prion diseases associated with the PRNP-D178N (Fatal Familial Insomnia) and PRNP-E200K mutations. CONCLUSIONS Our results unequivocally demonstrate that in neurodegenerative dementias, YKL-40 is a disease-specific marker of neuroinflammation showing its highest levels in prion diseases. Therefore, YKL-40 quantification might have a potential for application in the evaluation of therapeutic intervention in dementias with a neuroinflammatory component.

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CitationGPTRetr1006

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: CSF biomarkers in different phenotypes of Parkinson disease. Abstract of the paper: CSF biomarker studies were performed in 6 patients each with tremor-dominant (TD) and non-tremor-dominant (NT) Parkinson disease (PD) patients, 27 Alzheimer disease (AD) and 17 age-matched controls. In both NT-PD and AD patients total tau levels and the cortex tau/Aβ-42 were significantly increased compared to both TD-PD patients and controls (p < 0.01). These data in a small cohort confirm previous studies, corroborating the opinion that CSF levels of tau protein and the index total-tau/Aβ-42 may be potential markers of the severity of neurodegeneration in PD.

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CitationGPTRetr1007

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: Identification of longitudinally dynamic biomarkers in Alzheimer's disease cerebrospinal fluid by targeted proteomics. Abstract of the paper: BACKGROUND Alzheimer's disease (AD) is the leading cause of dementia affecting greater than 26 million people worldwide. Although cerebrospinal fluid (CSF) levels of Aβ42, tau, and p-tau181 are well established as diagnostic biomarkers of AD, there is a need for additional CSF biomarkers of neuronal function that continue to change during disease progression and could be used as pharmacodynamic measures in clinical trials. Multiple proteomic discovery experiments have reported a range of CSF biomarkers that differ between AD and control subjects. These potential biomarkers represent multiple aspects of the disease pathology. The performance of these markers has not been compared with each other, and their performance has not been evaluated longitudinally. RESULTS We developed a targeted-proteomic, multiple reaction monitoring (MRM) assay for the absolute quantitation of 39 peptides corresponding to 30 proteins. We evaluated the candidate biomarkers in longitudinal CSF samples collected from aged, cognitively-normal control (n = 10), MCI (n = 5), and AD (n = 45) individuals (age > 60 years). We evaluated each biomarker for diagnostic sensitivity, longitudinal consistency, and compared with CSF Aβ42, tau, and p-tau181. Four of 28 quantifiable CSF proteins were significantly different between aged, cognitively-normal controls and AD subjects including chitinase-3-like protein 1, reproducing published results. Four CSF markers demonstrated significant longitudinal change in AD: Amyloid precursor protein, Neuronal pentraxin receptor, NrCAM and Chromogranin A. Robust correlations were observed within some subgroups of proteins including the potential disease progression markers. CONCLUSION Using a targeted proteomics approach, we confirmed previous findings for a subset of markers, defined longitudinal performance of our panel of markers, and established a flexible proteomics method for robust multiplexed analyses.

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CitationGPTRetr1008

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Abstract of the paper: BACKGROUND Alzheimer's disease biomarkers are important for early diagnosis in routine clinical practice and research. Three core CSF biomarkers for the diagnosis of Alzheimer's disease (Aβ42, T-tau, and P-tau) have been assessed in numerous studies, and several other Alzheimer's disease markers are emerging in the literature. However, there have been no comprehensive meta-analyses of their diagnostic performance. We systematically reviewed the literature for 15 biomarkers in both CSF and blood to assess which of these were most altered in Alzheimer's disease. METHODS In this systematic review and meta-analysis, we screened PubMed and Web of Science for articles published between July 1, 1984, and June 30, 2014, about CSF and blood biomarkers reflecting neurodegeneration (T-tau, NFL, NSE, VLP-1, and HFABP), APP metabolism (Aβ42, Aβ40, Aβ38, sAPPα, and sAPPβ), tangle pathology (P-tau), blood-brain-barrier function (albumin ratio), and glial activation (YKL-40, MCP-1, and GFAP). Data were taken from cross-sectional cohort studies as well as from baseline measurements in longitudinal studies with clinical follow-up. Articles were excluded if they did not contain a cohort with Alzheimer's disease and a control cohort, or a cohort with mild cognitive impairment due to Alzheimer's disease and a stable mild cognitive impairment cohort. Data were extracted by ten authors and checked by two for accuracy. For quality assessment, modified QUADAS criteria were used. Biomarker performance was rated by random-effects meta-analysis based on the ratio between biomarker concentration in patients with Alzheimer's disease and controls (fold change) or the ratio between biomarker concentration in those with mild cognitive impariment due to Alzheimer's disease and those with stable mild cognitive impairment who had a follow-up time of at least 2 years and no further cognitive decline. FINDINGS Of 4521 records identified from PubMed and 624 from Web of Science, 231 articles comprising 15 699 patients with Alzheimer's disease and 13 018 controls were included in this analysis. The core biomarkers differentiated Alzheimer's disease from controls with good performance: CSF T-tau (average ratio 2·54, 95% CI 2·44-2·64, p<0·0001), P-tau (1·88, 1·79-1·97, p<0·0001), and Aβ42 (0·56, 0·55-0·58, p<0·0001). Differentiation between cohorts with mild cognitive impairment due to Alzheimer's disease and those with stable mild cognitive impairment was also strong (average ratio 0·67 for CSF Aβ42, 1·72 for P-tau, and 1·76 for T-tau). Furthermore, CSF NFL (2·35, 1·90-2·91, p<0·0001) and plasma T-tau (1·95, 1·12-3·38, p=0·02) had large effect sizes when differentiating between controls and patients with Alzheimer's disease, whereas those of CSF NSE, VLP-1, HFABP, and YKL-40 were moderate (average ratios 1·28-1·47). Other assessed biomarkers had only marginal effect sizes or did not differentiate between control and patient samples. INTERPRETATION The core CSF biomarkers of neurodegeneration (T-tau, P-tau, and Aβ42), CSF NFL, and plasma T-tau were strongly associated with Alzheimer's disease and the core biomarkers were strongly associated with mild cognitive impairment due to Alzheimer's disease. Emerging CSF biomarkers NSE, VLP-1, HFABP, and YKL-40 were moderately associated with Alzheimer's disease, whereas plasma Aβ42 and Aβ40 were not. Due to their consistency, T-tau, P-tau, Aβ42, and NFL in CSF should be used in clinical practice and clinical research. FUNDING Swedish Research Council, Swedish State Support for Clinical Research, Alzheimer's Association, Knut and Alice Wallenberg Foundation, Torsten Söderberg Foundation, Alzheimer Foundation (Sweden), European Research Council, and Biomedical Research Forum.

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CitationGPTRetr1009

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: From Cerebrospinal Fluid to Blood: The Third Wave of Fluid Biomarkers for Alzheimer's Disease. Abstract of the paper: The past five years have seen an enormous development in the field of fluid biomarkers for Alzheimer's disease (AD) and related disorders. The proteins that constitute the foundation for the cerebrospinal fluid (CSF) tests for the classical AD pathologies are now being explored as potential blood-based biomarkers, thanks to the recent implementation of ultrasensitive measurement technologies in academic and clinical laboratories worldwide. The current blood-derived data are still less clear than those obtained using CSF as the sample type, but independent research suggests that there are biomarker signals in blood that relate to plaque and tangle pathologies in AD, which are relevant to explore further. Additionally, neurofilament light has emerged as the first robust blood-based biomarker for neurodegeneration in a broad range of central nervous system disorders, as well as for acute brain injuries. Here, we briefly recapitulate the first and second waves of fluid biomarker analysis in AD, i.e., the development and validation of established and novel CSF biomarkers for the disorder, followed by a focused discussion on blood-based biomarkers for AD, which we describe as the third wave of fluid biomarker analysis that hopefully will gain further momentum during the coming five years.

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CitationGPTRetr1010

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: Cerebrospinal Fluid Biomarkers of Alzheimer's Disease: Current Evidence and Future Perspectives. Abstract of the paper: Alzheimer's disease is a progressive, clinically heterogeneous, and particularly complex neurodegenerative disease characterized by a decline in cognition. Over the last two decades, there has been significant growth in the investigation of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease. This review presents current evidence from many clinical neurochemical studies, with findings that attest to the efficacy of existing core CSF biomarkers such as total tau, phosphorylated tau, and amyloid-β (Aβ42), which diagnose Alzheimer's disease in the early and dementia stages of the disorder. The heterogeneity of the pathophysiology of the late-onset disease warrants the growth of the Alzheimer's disease CSF biomarker toolbox; more biomarkers showing other aspects of the disease mechanism are needed. This review focuses on new biomarkers that track Alzheimer's disease pathology, such as those that assess neuronal injury (VILIP-1 and neurofilament light), neuroinflammation (sTREM2, YKL-40, osteopontin, GFAP, progranulin, and MCP-1), synaptic dysfunction (SNAP-25 and GAP-43), vascular dysregulation (hFABP), as well as CSF α-synuclein levels and TDP-43 pathology. Some of these biomarkers are promising candidates as they are specific and predict future rates of cognitive decline. Findings from the combinations of subclasses of new Alzheimer's disease biomarkers that improve their diagnostic efficacy in detecting associated pathological changes are also presented.

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CitationGPTRetr1011

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study. Abstract of the paper: INTRODUCTION Within-person trajectories of cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD) are not well defined. METHODS We included 467 subjects from the BIOMARKAPD study with at least two serial CSF samples. Diagnoses were subjective cognitive decline (n = 75), mild cognitive impairment (n = 128), and AD dementia (n = 110), and a group of cognitively unimpaired subjects (n = 154) were also included. We measured baseline and follow-up CSF levels of total tau (t-tau), phosphorylated tau (p-tau), YKL-40, and neurofilament light (NfL). Median CSF sampling interval was 2.1 years. RESULTS CSF levels of t-tau, p-tau, NfL, and YKL-40 were 2% higher per each year of baseline age in controls (P <.001). In AD, t-tau levels were 1% lower (P <.001) and p-tau levels did not change per each year of baseline age. Longitudinally, only NfL (P <.001) and YKL-40 (P <.02) increased during the study period. DISCUSSION All four CSF biomarkers increase with age, but this effect deviates in AD for t-tau and p-tau.

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CitationGPTRetr1012

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: CSF biomarkers in neurodegenerative and vascular dementias. Abstract of the paper: Neurodegenerative diseases with abnormal protein aggregates such as Alzheimer's disease, tauopathies, synucleinopathies, and prionopathies, together with vascular encephalopathies, are cause of cognitive impairment and dementia. Identification of reliable biomarkers in biological fluids, particularly in the cerebrospinal fluid (CSF), is of extreme importance in optimizing the precise early clinical diagnosis of distinct entities and predicting the outcome in particular settings. In addition, the study of CSF biomarkers is useful to identify and monitor the underlying pathological processes developing in the central nervous system of affected individuals. Evidence suggests that levels of key CSF molecules correlate, in some circumstances, with prediction, disease progression, and severity of cognitive decline. Correlation of CSF markers and underlying pathological molecular substrates in brain is an exciting field for further study. However, while some dementias such as Creutzfeldt-Jakob disease have accurate CSF biomarkers, other disease types such as dementia with Lewy bodies, vascular dementia, and frontotemporal dementia lack reliable biomarkers for their specific clinical diagnosis.

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CitationGPTRetr1013

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: Cerebrospinal Fluid Biomarkers for Target Engagement and Efficacy in Clinical Trials for Alzheimer's and Parkinson's Diseases. Abstract of the paper: BACKGROUND Cerebrospinal fluid (CSF) is increasingly being used to detect biochemical changes that occur in different neurological conditions. In Alzheimer's disease (AD), three CSF biomarkers (Aβ42, total tau, and phosphorylated tau) are used in clinical practice to support the diagnosis in the prodromal stages of the disease. In Parkinson's disease (PD), the investigation is following the pathway of AD research and some promising markers have been identified, with the main aim to favor an early diagnosis, i.e. in the premotor phase. Some of these CSF markers have also been incorporated in AD and PD clinical trials to demonstrate target engagement of the drug and/or to enrich the patient populations. In this chapter, we will review the main CSF biomarkers for AD and PD and their potential application to clinical trials. SUMMARY In clinical trials assessing the efficacy of disease-modifying agents for AD, CSF biomarkers are currently used both as a diagnostic criterion for inclusion and for monitoring the biochemical impact of the drug on the upstream neurodegenerative mechanisms. Accordingly, recent trials devoted to PD are following such a procedure, although in this neurodegenerative disorder CSF biomarkers are not ready yet for routine clinical use. KEY MESSAGES AD and PD are neurodegenerative disorders that share a long asymptomatic/prodromal phase in which neurodegenerative phenomena already take place in the brain. Clinical trials assessing the efficacy of disease-modifying agents should include the CSF measurement of related biomarkers as biochemical proof of the underlying pathology as well as of the impact of the drug on these pathogenic mechanisms.

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CitationGPTRetr1014

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: Plasma and CSF NfL are differentially associated with biomarker evidence of neurodegeneration in a community-based sample of 70-year-olds. Abstract of the paper: Neurofilament light protein (NfL) in cerebrospinal fluid (CSF) and plasma (P) are suggested to be interchangeable markers of neurodegeneration. However, evidence is scarce from community-based samples. NfL was examined in a small-scale sample of 287 individuals from the Gothenburg H70 Birth cohort 1944 study, using linear models in relation to CSF and magnetic resonance imaging (MRI) biomarker evidence of neurodegeneration. CSF-NfL and P-NfL present distinct associations with biomarker evidence of Alzheimer's disease (AD) pathology and neurodegeneration. P-NfL was associated with several markers that are characteristic of AD, including smaller hippocampal volumes, amyloid beta (Aβ)42, Aβ42/40, and Aβ42/t-tau (total tau). CSF-NfL demonstrated associations with measures of synaptic and neurodegeneration, including t-tau, phosphorylated tau (p-tau), and neurogranin. Our findings suggest that P-NfL and CSF-NfL may exert different effects on markers of neurodegeneration in a small-scale community-based sample of 70-year-olds.

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CitationGPTRetr1015

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: High Correlation among Brain-Derived Major Protein Levels in Cerebrospinal Fluid: Implication for Amyloid-Beta and Tau Protein Changes in Alzheimer's Disease. Abstract of the paper: The cerebrospinal fluid (CSF) plays an important role in homeostasis of the brain. We previously demonstrated that major CSF proteins such as lipocalin-type prostaglandin D2 synthase (L-PGDS) and transferrin (Tf) that are biosynthesized in the brain could be biomarkers of altered CSF production. Here we report that the levels of these brain-derived CSF proteins correlated well with each other across various neurodegenerative diseases, including Alzheimer's disease (AD). In addition, protein levels tended to be increased in the CSF samples of AD patients compared with the other diseases. Patients at memory clinics were classified into three categories, consisting of AD (n = 61), mild cognitive impairment (MCI) (n = 42), and cognitively normal (CN) (n = 23), with MMSE scores of 20.4 ± 4.2, 26.9 ± 1.7, and 29.0 ± 1.6, respectively. In each category, CSF protein levels were highly correlated with each other. In CN subjects, increased CSF protein levels correlated well with those of AD markers, including amyloid-β and tau protein, whereas in MCI and AD subjects, correlations declined with AD markers except p-tau. Future follow-up on each clinical subject may provide a clue that the CSF proteins would be AD-related biomarkers.

False

CitationGPTRetr1016

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: CSF Biomarkers of Alzheimer Disease in Patients With Concomitant α-Synuclein Pathology. Abstract of the paper: BACKGROUND AND OBJECTIVES Cerebrospinal fluid (CSF) biomarkers amyloid-β42 (Aβ42), phosphorylated tau (p-tau181), total tau (t-tau) and neurogranin (Ng) can diagnose Alzheimer's disease (AD) in life. However, it is unknown if CSF concentrations, and thus their accuracies, are affected by concomitant pathologies common in AD, such as α-synuclein (αSyn). Our primary goal was to test if biomarkers in patients with AD are altered by concomitant αSyn. We compared CSF Aβ42, p-tau181, t-tau and Ng levels across autopsy-confirmed AD and concomitant AD and αSyn (AD+αSyn). Antemortem CSF levels were related to postmortem accumulations of αSyn. Finally, we tested how concommitant AD+αSyn affected diagnostic accuracy of two CSF-based strategies: the ATN framework and the t-tau/Aβ42 ratio. METHODS Inclusion criteria were neuropathologic diagnoses of AD, mixed AD+αSyn, and αSyn. A convenience sample of non-impaired controls were selected with available CSF and a mini mental state exam (MMSE)≥27. αSyn without AD and controls were included as reference groups. Analyses of covariance (ANCOVAs) tested planned comparisons were CSF Aβ42, p-tau181, t-tau, and Ng differences across AD and AD+αSyn. Linear models tested how biomarkers were altered by αSyn accumulation in AD, accounting for pathologic amyloid-β and tau. Receiver operating characteristic and area under the curve (AUC), including 95% confidence intervals (CI), evaluated diagnostic accuracy. RESULTS Participants were 61 AD, 39 mixed AD+αSyn, 20 αSyn, and 61 Controls. AD had similar median age (73 [IQR=12]), MMSE (23 [IQR=9]), and sex distribution (Male=49%) compared to AD+αSyn age (70 [IQR=13]; p=0.3), MMSE (25 [IQR=9.5]; p=0.19), and sex distribution (Male=69%; p=0.077). ANCOVAs showed AD+αSyn had lower p-tau181 (F(1,94)=17, p=0), t-tau (F(1,93)=11, p=0.0004), and Ng levels (F(1,50)=12, p=0.0004) than AD; there was no difference in Aβ42 (p=0.44). Models showed increasing αSyn related to lower p-tau181 (β=-0.26, SE=0.092, p=0.0065), t-tau (β=-0.19, SE=0.092, p=0.041), and Ng levels (β=-0.2, SE=0.066, p=0.0046); αSyn was not a significant factor for Aβ42 (p=1). T-tau/Aβ42 had the highest accuracy when detecting AD, including mixed AD+αSyn cases (AUC=0.95; CI=0.92 to 0.98). DISCUSSION Findings demonstrate that concomitant αSyn pathology in AD is associated with lower CSF p-tau181, t-tau, and Ng levels, and can affect diagnositic accuracy in AD patients.

False

CitationGPTRetr1017

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: CSF biomarkers associated with disease heterogeneity in early Parkinson's disease: the Parkinson's Progression Markers Initiative study. Abstract of the paper: The development of biomarkers to predict the progression of Parkinson's disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson's Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1-42 (Aβ1-42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1-42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1-42, or highest t-tau/Aβ1-42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1-42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance.

False

CitationGPTRetr1018

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: Cerebrospinal fluid neurogranin and YKL-40 as biomarkers of Alzheimer's disease. Abstract of the paper: OBJECTIVE Widespread implementation of cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) in clinical settings requires improved accuracy for diagnosis of prodromal disease and for distinguishing AD from non-AD dementias. Novel and promising CSF biomarkers include neurogranin, a marker of synaptic degeneration, and YKL-40, a marker of neuroinflammation. METHODS CSF neurogranin and YKL-40 were measured in a cohort of 338 individuals including cognitively healthy controls and patients with stable mild cognitive impairment (sMCI), MCI who later developed AD (MCI-AD), AD dementia, Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), vascular dementia (VaD), and frontotemporal dementia (FTD). The diagnostic accuracy of neurogranin and YKL-40 were compared with the core AD biomarkers, β-amyloid (Aβ42 and Aβ40) and tau. RESULTS Neurogranin levels were increased in AD and decreased in non-AD dementia compared with healthy controls. As a result, AD patients showed considerably higher CSF levels of neurogranin than DLB/PDD, VaD and FTD patients. CSF YKL-40 levels were increased in AD compared with DLB/PDD but not with VaD or FTD. Neither CSF neurogranin nor YKL-40 levels differed significantly between sMCI patients and MCI-AD patients. Both biomarkers correlated positively with CSF Aβ40 and tau. CSF neurogranin and YKL-40 could separate AD dementia from non-AD dementias (neurogranin, area under the curve [AUC] = 0.761; YKL-40, AUC = 0.604; Aβ42/neurogranin, AUC = 0.849; Aβ42/YKL-40, AUC = 0.785), but the diagnostic accuracy was not better compared to CSF Aβ and tau (Aβ42, AUC = 0.755; tau AUC = 0.858; Aβ42/tau, AUC = 0.895; Aβ42/Aβ40, AUC = 0.881). Similar results were obtained when separating sMCI from MCI-AD cases. INTERPRETATION CSF neurogranin and YKL-40 do not improve the diagnostic accuracy of either prodromal AD or AD dementia when compared to the core CSF AD biomarkers. Nevertheless, the CSF level of neurogranin is selectively increased in AD dementia, whereas YKL-40 is increased in both AD and FTD suggesting that synaptic degeneration and glial activation may be important in these neurodegenerative conditions.

False

CitationGPTRetr1019

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: a panel of additional csf biomarkers had been analyzed in a subset of the cohort for previous studies and was here reevaluated in the context of rpad with consideration of disease stage as a potential influencing factor nfl 29 total prionprotein tprp 30 chitinase3like protein 1 ykl40 31 lipocalin 2 lcn2 32 and αsynuclein Title of the paper: Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum. Abstract of the paper: INTRODUCTION The biological pathways involved in the preclinical stage of the Alzheimer's continuum are not well understood. METHODS We used NeuroToolKit and Elecsys® immunoassays to measure cerebrospinal fluid (CSF) amyloid-β (Aβ)42, Aβ40, phosphorylated tau (p-tau), total tau (t-tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100, and α-synuclein in cognitively unimpaired participants of the ALFA+ study, many within the Alzheimer's continuum. RESULTS CSF t-tau, p-tau, and neurogranin increase throughout aging only in Aβ-positive individuals, whereas NfL and glial biomarkers increase with aging regardless of Aβ status. We modelled biomarker changes as a function of CSF Aβ42/40, p-tau and p-tau/Aβ42 as proxies of disease progression. The first change observed in the Alzheimer's continuum was a decrease in the CSF Aβ42/40 ratio. This is followed by a steep increase in CSF p-tau; t-tau; neurogranin; and, to a lesser extent, in NfL and glial biomarkers. DISCUSSION Multiple biological pathways are altered and could be targeted very early in the Alzheimer's continuum.

False

CitationGPTRetr1020

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: MicroRNA regulation of Alzheimer's Amyloid precursor protein expression. Abstract of the paper: Gene dosage effects of Amyloid precursor protein (APP) can cause familial AD. Recent evidence suggest that microRNA (miRNA) pathways, implicated in gene transcriptional control, could be involved in the development of sporadic Alzheimer's disease (AD). We therefore investigated whether miRNAs could participate in the regulation of APP gene expression. We show that miRNAs belonging to the miR-20a family (that is, miR-20a, miR-17-5p and miR-106b) could regulate APP expression in vitro and at the endogenous level in neuronal cell lines. A tight correlation between these miRNAs and APP was found during brain development and in differentiating neurons. We thus identify miRNAs as novel endogenous regulators of APP expression, suggesting that variations in miRNA expression could contribute to changes in APP expression in the brain during development and disease. This possibility is further corroborated by the observation that a statistically significant decrease in miR-106b expression was found in sporadic AD patients.

True

CitationGPTRetr1021

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: In vivo regulation of amyloid precursor protein neuronal splicing by microRNAs. Abstract of the paper: The β-amyloid peptide that accumulate in Alzheimer's disease (AD) brain derive from proteolytic processing of the amyloid precursor protein (APP). Recent evidence suggest that microRNAs (miRNAs) participate in the post-transcriptional regulation of APP expression. Because gene dosage effects of the APP gene can cause genetic AD, dysregulation of the miRNA network could contribute significantly to disease. Here, we present evidence that, besides APP expression regulation, miRNAs are equally involved in the regulation of neuronal APP mRNA alternative splicing. Lack of miRNAs in post-mitotic neurons in vivo is associated with APP exons 7 and 8 inclusion, while ectopic expression of miR-124, an abundant neuronal-specific miRNA, reversed these effects in cultured neurons. Similar results were obtained by depletion of endogenous polypyrimidine tract binding protein 1 (PTBP1) in cells, a recognized miR-124 target gene. Furthermore, PTBP1 levels correlate with the presence of APP exons 7 and 8, while PTBP2 levels correlate with the skipping of these exons during neuronal differentiation. Finally, we show that miR-124 is down-regulated in AD brain. In sum, our results suggest that specific miRNAs are involved in the fine-tuning of APP alternative splicing in neurons. Since abnormal neuronal splicing of APP affects β-amyloid peptide production, these results could contribute to the understanding of the implication of miRNAs in brain health and disease.

True

CitationGPTRetr1022

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: Mammalian microRNAs predominantly act to decrease target mRNA levels. Abstract of the paper: MicroRNAs (miRNAs) are endogenous approximately 22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (>/=84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.

False

CitationGPTRetr1023

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: Current drug targets for modulating Alzheimer's amyloid precursor protein: role of specific micro-RNA species. Abstract of the paper: Alzheimer's disease (AD) is the most common form of dementia in the United States and is increasing in prevalence every year throughout the world. Recent clinical trial failures highlight the need for further insights into the molecular events that underlie the neurobiology of AD. Pathological aberrations in AD are believed to result, in part, from excess accumulation of amyloid-beta peptide (Aβ), a product of Aβ precursor protein (APP). Targeting APP levels would then be expected to reduce Aβ production in all forms of AD. Therefore, clarifying the regulatory network that governs APP expression is likely to reveal molecular players that could serve as novel drug targets. This review highlights recent work demonstrating the involvement of microRNA (miRNA) in this regulatory network. MiRNA are small, non-coding RNA that interact with target mRNA at sites of imperfect complementarity and mediate translational inhibition or transcript destabilization. We first review the neurobiology of AD and describe current therapeutic strategies. We then review transcriptional and post-transcriptional mechanisms utilized by cells to control APP expression. We conclude by highlighting recent work, including our own, which suggests miRNA are integral components of this regulatory framework and potential targets for future AD therapeutics.

False

CitationGPTRetr1024

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: MicroRNA-153 physiologically inhibits expression of amyloid-β precursor protein in cultured human fetal brain cells and is dysregulated in a subset of Alzheimer disease patients. Abstract of the paper: Regulation of amyloid-β (Aβ) precursor protein (APP) expression is complex. MicroRNAs (miRNAs) are expected to participate in the molecular network that controls this process. The composition of this network is, however, still undefined. Elucidating the complement of miRNAs that regulate APP expression should reveal novel drug targets capable of modulating Aβ production in AD. Here, we investigated the contribution of miR-153 to this regulatory network. A miR-153 target site within the APP 3'-untranslated region (3'-UTR) was predicted by several bioinformatic algorithms. We found that miR-153 significantly reduced reporter expression when co-transfected with an APP 3'-UTR reporter construct. Mutation of the predicted miR-153 target site eliminated this reporter response. miR-153 delivery in both HeLa cells and primary human fetal brain cultures significantly reduced APP expression. Delivery of a miR-153 antisense inhibitor to human fetal brain cultures significantly elevated APP expression. miR-153 delivery also reduced expression of the APP paralog APLP2. High functional redundancy between APP and APLP2 suggests that miR-153 may target biological pathways in which they both function. Interestingly, in a subset of human AD brain specimens with moderate AD pathology, miR-153 levels were reduced. This same subset also exhibited elevated APP levels relative to control specimens. Therefore, endogenous miR-153 inhibits expression of APP in human neurons by specifically interacting with the APP 3'-UTR. This regulatory interaction may have relevance to AD etiology, where low miR-153 levels may drive increased APP expression in a subset of AD patients.

True

CitationGPTRetr1025

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: The impact of microRNAs on protein output. Abstract of the paper: MicroRNAs are endogenous approximately 23-nucleotide RNAs that can pair to sites in the messenger RNAs of protein-coding genes to downregulate the expression from these messages. MicroRNAs are known to influence the evolution and stability of many mRNAs, but their global impact on protein output had not been examined. Here we use quantitative mass spectrometry to measure the response of thousands of proteins after introducing microRNAs into cultured cells and after deleting mir-223 in mouse neutrophils. The identities of the responsive proteins indicate that targeting is primarily through seed-matched sites located within favourable predicted contexts in 3' untranslated regions. Hundreds of genes were directly repressed, albeit each to a modest degree, by individual microRNAs. Although some targets were repressed without detectable changes in mRNA levels, those translationally repressed by more than a third also displayed detectable mRNA destabilization, and, for the more highly repressed targets, mRNA destabilization usually comprised the major component of repression. The impact of microRNAs on the proteome indicated that for most interactions microRNAs act as rheostats to make fine-scale adjustments to protein output.

False

CitationGPTRetr1026

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: Genome-wide analysis of miRNA signature in the APPswe/PS1ΔE9 mouse model of alzheimer's disease. Abstract of the paper: Alzheimer's disease (AD) is the most common cause of dementia. One of the pathological hallmarks of AD is amyloid β (Aβ) deposition. MicroRNAs (miRNAs) are small non-coding RNAs whose expression levels change significantly during neuronal pathogenesis and may be used as diagnostic markers. Some miRNAs are important in AD development by targeting genes responsible for Aβ metabolism. However, a systematic assessment of the miRNA expression profile induced by Aβ-mediated neuronal pathogenesis is still lacking. In the present study, we examined miRNA expression profile by using the APPswe/PS1ΔE9 mouse model of AD. Two sibling pairs of mice were examined, showing 30 and 24 miRNAs with significantly altered expression levels from each paired control, respectively. Nine known miRNAs were common in both groups. Prediction of putative target genes and functional annotation implied that these altered miRNAs affect many target genes mainly involved in PI3K/Akt signaling pathway. This study provides a general profile of miRNAs regulated by Aβ-associated signal pathways, which is helpful to understand the mechanism of Aβ-induced neuronal dysfunction in AD development.

False

CitationGPTRetr1027

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: MicroRNAs can regulate human APP levels. Abstract of the paper: A number of studies have shown that increased APP levels, resulting from either a genomic locus duplication or alteration in APP regulatory sequences, can lead to development of early-onset dementias, including Alzheimer's disease (AD). Therefore, understanding how APP levels are regulated could provide valuable insight into the genetic basis of AD and illuminate novel therapeutic avenues for AD. Here we test the hypothesis that APP protein levels can be regulated by miRNAs, evolutionarily conserved small noncoding RNA molecules that play an important role in regulating gene expression. Utilizing human cell lines, we demonstrate that miRNAs hsa-mir-106a and hsa-mir-520c bind to their predicted target sequences in the APP 3'UTR and negatively regulate reporter gene expression. Over-expression of these miRNAs, but not control miRNAs, results in translational repression of APP mRNA and significantly reduces APP protein levels. These results are the first to demonstrate that levels of human APP can be regulated by miRNAs.

False

CitationGPTRetr1028

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: The multiMiR R package and database: integration of microRNA-target interactions along with their disease and drug associations. Abstract of the paper: microRNAs (miRNAs) regulate expression by promoting degradation or repressing translation of target transcripts. miRNA target sites have been catalogued in databases based on experimental validation and computational prediction using various algorithms. Several online resources provide collections of multiple databases but need to be imported into other software, such as R, for processing, tabulation, graphing and computation. Currently available miRNA target site packages in R are limited in the number of databases, types of databases and flexibility. We present multiMiR, a new miRNA-target interaction R package and database, which includes several novel features not available in existing R packages: (i) compilation of nearly 50 million records in human and mouse from 14 different databases, more than any other collection; (ii) expansion of databases to those based on disease annotation and drug microRNAresponse, in addition to many experimental and computational databases; and (iii) user-defined cutoffs for predicted binding strength to provide the most confident selection. Case studies are reported on various biomedical applications including mouse models of alcohol consumption, studies of chronic obstructive pulmonary disease in human subjects, and human cell line models of bladder cancer metastasis. We also demonstrate how multiMiR was used to generate testable hypotheses that were pursued experimentally.

False

CitationGPTRetr1029

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: MicroRNA networks surrounding APP and amyloid-β metabolism--implications for Alzheimer's disease. Abstract of the paper: MicroRNAs (miRNAs) are small non-coding RNA regulators of protein synthesis that function as "fine-tuning" tools of gene expression in development and tissue homeostasis. Their profiles are significantly altered in neurodegenerative diseases such as Alzheimer's disease (AD) that is characterized by both amyloid-β (Aβ) and tau deposition in brain. A key challenge remains in determining how changes in miRNA profiles translate into biological function in a physiological and pathological context. The key lies in identifying specific target genes for deregulated miRNAs and understanding which pathogenic factors trigger their deregulation. Here we review the literature about the intricate network of miRNAs surrounding the regulation of the amyloid precursor protein (APP) from which Aβ is derived by proteolytic cleavage. Normal brain function is highly sensitive to any changes in APP metabolism and miRNAs function at several steps to ensure that the correct APP end product is produced and in the right form and abundance. Disruptions in this miRNA regulatory network may therefore alter Aβ production, which in turn can affect miRNA expression.

False

CitationGPTRetr1030

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: MicroRNA-101 downregulates Alzheimer's amyloid-β precursor protein levels in human cell cultures and is differentially expressed. Abstract of the paper: The full repertoire of regulatory interactions utilized by human cells to control expression of amyloid-β precursor protein (APP) is still undefined. We investigated here the contribution of microRNA (miRNA) to this regulatory network. Several bioinformatic algorithms predicted miR-101 target sites within the APP 3'-untranslated region (3'-UTR). Using reporter assays, we confirmed that, in human cell cultures, miR-101 significantly reduced the expression of a reporter under control of APP 3'-UTR. Mutation of predicted site 1, but not site 2, eliminated this reporter response. Delivery of miR-101 directly to human HeLa cells significantly reduced APP levels and this effect was eliminated by co-transfection with a miR-101 antisense inhibitor. Delivery of a specific target protector designed to blockade the interaction between miR-101 and its functional target site within APP 3'-UTR enhanced APP levels in HeLa. Therefore, endogenous miR-101 regulates expression of APP in human cells via a specific site located within its 3'-UTR. Finally, we demonstrate that, across a series of human cell lines, highest expression of miR-101 levels was observed in model NT2 neurons.

False

CitationGPTRetr1031

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: Most mammalian mRNAs are conserved targets of microRNAs. Abstract of the paper: MicroRNAs (miRNAs) are small endogenous RNAs that pair to sites in mRNAs to direct post-transcriptional repression. Many sites that match the miRNA seed (nucleotides 2-7), particularly those in 3' untranslated regions (3'UTRs), are preferentially conserved. Here, we overhauled our tool for finding preferential conservation of sequence motifs and applied it to the analysis of human 3'UTRs, increasing by nearly threefold the detected number of preferentially conserved miRNA target sites. The new tool more efficiently incorporates new genomes and more completely controls for background conservation by accounting for mutational biases, dinucleotide conservation rates, and the conservation rates of individual UTRs. The improved background model enabled preferential conservation of a new site type, the "offset 6mer," to be detected. In total, >45,000 miRNA target sites within human 3'UTRs are conserved above background levels, and >60% of human protein-coding genes have been under selective pressure to maintain pairing to miRNAs. Mammalian-specific miRNAs have far fewer conserved targets than do the more broadly conserved miRNAs, even when considering only more recently emerged targets. Although pairing to the 3' end of miRNAs can compensate for seed mismatches, this class of sites constitutes less than 2% of all preferentially conserved sites detected. The new tool enables statistically powerful analysis of individual miRNA target sites, with the probability of preferentially conserved targeting (P(CT)) correlating with experimental measurements of repression. Our expanded set of target predictions (including conserved 3'-compensatory sites), are available at the TargetScan website, which displays the P(CT) for each site and each predicted target.

False

CitationGPTRetr1032

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: Identification of real microRNA precursors with a pseudo structure status composition approach. Abstract of the paper: Containing about 22 nucleotides, a micro RNA (abbreviated miRNA) is a small non-coding RNA molecule, functioning in transcriptional and post-transcriptional regulation of gene expression. The human genome may encode over 1000 miRNAs. Albeit poorly characterized, miRNAs are widely deemed as important regulators of biological processes. Aberrant expression of miRNAs has been observed in many cancers and other disease states, indicating they are deeply implicated with these diseases, particularly in carcinogenesis. Therefore, it is important for both basic research and miRNA-based therapy to discriminate the real pre-miRNAs from the false ones (such as hairpin sequences with similar stem-loops). Particularly, with the avalanche of RNA sequences generated in the postgenomic age, it is highly desired to develop computational sequence-based methods in this regard. Here two new predictors, called "iMcRNA-PseSSC" and "iMcRNA-ExPseSSC", were proposed for identifying the human pre-microRNAs by incorporating the global or long-range structure-order information using a way quite similar to the pseudo amino acid composition approach. Rigorous cross-validations on a much larger and more stringent newly constructed benchmark dataset showed that the two new predictors (accessible at http://bioinformatics.hitsz.edu.cn/iMcRNA/) outperformed or were highly comparable with the best existing predictors in this area.

False

CitationGPTRetr1033

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: Exosome isolation for proteomic analyses and RNA profiling. Abstract of the paper: While the existence of exosomes has been known for over three decades, they have garnered recent interest due to their potential diagnostic and therapeutic relevance. The expression and release of specific tumor-derived proteins into the peripheral circulation has served as the centerpiece of cancer screening and diagnosis. Recently, tissue-associated microRNA (miRNA) has been shown to be characteristic of tumor type and developmental origin, as well as exhibit diagnostic potential. Tumors actively release exosomes, exhibiting proteins and RNAs derived from the originating cell, into the peripheral circulation and other biologic fluids. Recently, we have demonstrated the presence of miRNAs within the RNA fraction of circulating tumor-derived exosomes. Currently, in over 75 investigations compiled in ExoCarta, over 2,300 proteins and 270 miRNAs have been linked with exosomes derived from biologic fluids. Our previous work has indicated that these circulating exosomal proteins and miRNAs can serve as surrogates for the tumor cell-associated counterparts, extending their diagnostic potential to asymptomatic individuals. In this chapter, we compare currently utilized methods for purifying exosomes for postisolation analyses. The exosomes derived from these approaches were assessed for quantity and quality of specific RNA populations and specific marker proteins. These results suggest that, while each method purifies exosomal material, circulating exosomes isolated by ExoQuick precipitation produces exosomal RNA and protein with greater purity and quantity than chromatography, ultracentrifugation, and DynaBeads. While this precipitation approach isolates exosomes in general and does not exhibit specificity for the originating cell, the increased quantity and quality of exosomal proteins and RNA should enhance the sensitivity and accuracy of down-stream analyses, such as qRT-PCR profiling of miRNA and mass spectrometric and electrophoretic analyses of exosomal proteins.

False

CitationGPTRetr1034

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: Studying micro RNA Function and Dysfunction in Alzheimer's Disease. Abstract of the paper: Alzheimer's disease (AD) is a tragic, progressive, age-related neurological dysfunction, representing one of the most prevalent neurodegenerative disorders in industrialized societies. Globally, 5 million new cases of AD are diagnosed annually, with one new AD case being reported every 7 s. Most recently there has been a surge in the study of the regulatory mechanisms of the AD process, and the particular significance of small non-coding ∼22 ribonucleotide RNAs called micro RNAs (miRNAs). Abundant data have profiled miRNA patterns in healthy, aging brain, in mild cognitive impairment (MCI), and in the moderate- and late-stages of AD. The major mode of action of miRNA is to interact, via base-pair complementarity, with ribonucleotides located within the 3' untranslated region (3'-UTR) of multiple target messenger RNAs (mRNAs), and in doing so decrease the capability of that specific mRNA to be expressed. Many miRNAs are highly cell- and tissue-specific. The human brain appears to use only a highly specific fraction of all known human miRNAs, whose speciation and complexity are defined as a discrete subset of all known small non-coding RNAs (sncRNAs) in the brain. In general, in contrast to normally, aging human brain, in AD a family of pathogenically up-regulated miRNAs appear to be down-regulating the expression certain brain-essential mRNA targets, including key regulatory genes involved interactively in neuroinflammation, synaptogenesis, neurotrophic functions, and amyloidogenesis. These up-regulated, NF-kB-sensitive miRNAs, involved in the innate immune and inflammatory response and synaptic, neurotrophic, and amyloidogenic functions include miRNA-9, miRNA-125b, miRNA-146a, and miRNA-155. Other miRNAs of the miRNA-15/107 family, miRNA-153 and miRNA-190, and others, will be discussed. Overall, this manuscript will review the known contribution of miRNAs to aging brain function and the role they appear to play in the incidence and progression of AD.

False

CitationGPTRetr1035

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: Target gene repression mediated by miRNAs miR-181c and miR-9 both of which are down-regulated by amyloid-β. Abstract of the paper: MicroRNAs (miRNAs) are small non-coding RNA regulators of protein synthesis that are essential for normal brain development and function. Their profiles are significantly altered in neurodegenerative diseases such as Alzheimer's disease (AD) that is characterized by amyloid-β (Aβ) and tau deposition in brain. How deregulated miRNAs contribute to AD is not understood, as their dysfunction could be both a cause and a consequence of disease. To address this question we had previously profiled miRNAs in models of AD. This identified miR-9 and -181c as being down-regulated by Aβ in hippocampal cultures. Interestingly, there was a remarkable overlap with those miRNAs that are deregulated in Aβ-depositing APP23 transgenic mice and in human AD tissue. While the Aβ precursor protein APP itself is a target of miRNA regulation, the challenge resides in identifying further targets. Here, we expand the repertoire of miRNA target genes by identifying the 3' untranslated regions (3' UTRs) of TGFBI, TRIM2, SIRT1 and BTBD3 as being repressed by miR-9 and -181c, either alone or in combination. Taken together, our study identifies putative target genes of miRNAs miR-9 and 181c, which may function in brain homeostasis and disease pathogenesis.

False

CitationGPTRetr1036

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: Imperfect centered miRNA binding sites are common and can mediate repression of target mRNAs. Abstract of the paper: BACKGROUND MicroRNAs (miRNAs) bind to mRNAs and target them for translational inhibition or transcriptional degradation. It is thought that most miRNA-mRNA interactions involve the seed region at the 5' end of the miRNA. The importance of seed sites is supported by experimental evidence, although there is growing interest in interactions mediated by the central region of the miRNA, termed centered sites. To investigate the prevalence of these interactions, we apply a biotin pull-down method to determine the direct targets of ten human miRNAs, including four isomiRs that share centered sites, but not seeds, with their canonical partner miRNAs. RESULTS We confirm that miRNAs and their isomiRs can interact with hundreds of mRNAs, and that imperfect centered sites are common mediators of miRNA-mRNA interactions. We experimentally demonstrate that these sites can repress mRNA activity, typically through translational repression, and are enriched in regions of the transcriptome bound by AGO. Finally, we show that the identification of imperfect centered sites is unlikely to be an artifact of our protocol caused by the biotinylation of the miRNA. However, the fact that there was a slight bias against seed sites in our protocol may have inflated the apparent prevalence of centered site-mediated interactions. CONCLUSIONS Our results suggest that centered site-mediated interactions are much more frequent than previously thought. This may explain the evolutionary conservation of the central region of miRNAs, and has significant implications for decoding miRNA-regulated genetic networks, and for predicting the functional effect of variants that do not alter protein sequence.

False

CitationGPTRetr1037

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: Integrative analysis reveals disrupted pathways regulated by microRNAs in cancer. Abstract of the paper: MicroRNAs (miRNAs) are small endogenous regulatory molecules that modulate gene expression post-transcriptionally. Although differential expression of miRNAs have been implicated in many diseases (including cancers), the underlying mechanisms of action remain unclear. Because each miRNA can target multiple genes, miRNAs may potentially have functional implications for the overall behavior of entire pathways. Here, we investigate the functional consequences of miRNA dysregulation through an integrative analysis of miRNA and mRNA expression data using a novel approach that incorporates pathway information a priori. By searching for miRNA-pathway associations that differ between healthy and tumor tissue, we identify specific relationships at the systems level which are disrupted in cancer. Our approach is motivated by the hypothesis that if an miRNA and pathway are associated, then the expression of the miRNA and the collective behavior of the genes in a pathway will be correlated. As such, we first obtain an expression-based summary of pathway activity using Isomap, a dimension reduction method which can articulate non-linear structure in high-dimensional data. We then search for miRNAs that exhibit differential correlations with the pathway summary between phenotypes as a means of finding aberrant miRNA-pathway coregulation in tumors. We apply our method to cancer data using gene and miRNA expression datasets from The Cancer Genome Atlas and compare ∼105 miRNA-pathway relationships between healthy and tumor samples from four tissues (breast, prostate, lung and liver). Many of the flagged pairs we identify have a biological basis for disruption in cancer.

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CitationGPTRetr1038

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: MicroRNA: Biogenesis, Function and Role in Cancer. Abstract of the paper: MicroRNAs are small, highly conserved non-coding RNA molecules involved in the regulation of gene expression. MicroRNAs are transcribed by RNA polymerases II and III, generating precursors that undergo a series of cleavage events to form mature microRNA. The conventional biogenesis pathway consists of two cleavage events, one nuclear and one cytoplasmic. However, alternative biogenesis pathways exist that differ in the number of cleavage events and enzymes responsible. How microRNA precursors are sorted to the different pathways is unclear but appears to be determined by the site of origin of the microRNA, its sequence and thermodynamic stability. The regulatory functions of microRNAs are accomplished through the RNA-induced silencing complex (RISC). MicroRNA assembles into RISC, activating the complex to target messenger RNA (mRNA) specified by the microRNA. Various RISC assembly models have been proposed and research continues to explore the mechanism(s) of RISC loading and activation. The degree and nature of the complementarity between the microRNA and target determine the gene silencing mechanism, slicer-dependent mRNA degradation or slicer-independent translation inhibition. Recent evidence indicates that P-bodies are essential for microRNA-mediated gene silencing and that RISC assembly and silencing occurs primarily within P-bodies. The P-body model outlines microRNA sorting and shuttling between specialized P-body compartments that house enzymes required for slicer -dependent and -independent silencing, addressing the reversibility of these silencing mechanisms. Detailed knowledge of the microRNA pathways is essential for understanding their physiological role and the implications associated with dysfunction and dysregulation.

False

CitationGPTRetr1039

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: for example mir175p mir20a and mir106b repressed the expression of app 56 as listed in table 1 mir153 57 and mir193b 58 also inhibited the level of app as listed in table 1 mir124 was involved in the splicing of app mrna 59 see table 1 mir144 and mir451 were reported as inhibitors of adam10 as listed in table 1 Title of the paper: Mouse let-7 miRNA populations exhibit RNA editing that is constrained in the 5'-seed/ cleavage/anchor regions and stabilize predicted mmu-let-7a:mRNA duplexes. Abstract of the paper: Massively parallel sequencing of millions of < 30-nt RNAs expressed in mouse ovary, embryonic pancreas (E14.5), and insulin-secreting beta-cells (betaTC-3) reveals that approximately 50% of the mature miRNAs representing mostly the mmu-let-7 family display internal insertion/deletions and substitutions when compared to precursor miRNA and the mouse genome reference sequences. Approximately, 12%-20% of species associated with mmu-let-7 populations exhibit sequence discrepancies that are dramatically reduced in nucleotides 3-7 (5'-seed) and 10-15 (cleavage and anchor sites). This observation is inconsistent with sequencing error and leads us to propose that the changes arise predominantly from post-transcriptional RNA-editing activity operating on miRNA:target mRNA complexes. Internal nucleotide modifications are most enriched at the ninth nucleotide position. A common ninth base edit of U-to-G results in a significant increase in stability of down-regulated let-7a targets in inhibin-deficient mice (Inha-/-). An excess of U-insertions (14.8%) over U-deletions (1.5%) and the presence of cleaved intermediates suggest that a mammalian TUTase (terminal uridylyl transferase) mediated dUTP-dependent U-insertion/U-deletion cycle may be a possible mechanism. We speculate that mRNA target site-directed editing of mmu-let-7a duplex-bulges stabilizes "loose" miRNA:mRNA target associations and functions to expand the target repertoire and/or enhance mRNA decay over translational repression. Our results also demonstrate that the systematic study of sequence variation within specific RNA classes in a given cell type from millions of sequences generated by next-generation sequencing (NGS) technologies ("intranomics") can be used broadly to infer functional constraints on specific parts of completely uncharacterized RNAs.

False

CitationGPTRetr1040

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Disturbances of sleep quality, timing and structure and their relationship with other neuropsychiatric symptoms in Alzheimer's disease and schizophrenia: Insights from studies in patient populations and animal models. Abstract of the paper: The high prevalence of sleep disturbance in neurodegenerative and psychiatric conditions is often interpreted as evidence for both sleep's sensitivity to and causal involvement in brain pathology. Nevertheless, how and which aspects of sleep contribute to brain function remains largely unknown. This review provides a critical evaluation of clinical and animal literature describing sleep and circadian disturbances in two distinct conditions and animal models thereof: Alzheimer's disease (AD) and schizophrenia. Its goal is to identify commonalities and distinctiveness of specific aspects of sleep disturbance and their relationship to symptoms across conditions. Despite limited standardisation, data imply that reductions in sleep continuity and alterations in sleep timing are common to AD and schizophrenia, whereas reductions in REM sleep and sleep spindle activity appear more specific to AD and schizophrenia, respectively. Putative mechanisms underlying these alterations are discussed. A standardised neuroscience based quantification of sleep and disease-independent assessment of symptoms in patients and animal models holds promise for furthering the understanding of mechanistic links between sleep and brain function in health and disease.

False

CitationGPTRetr1041

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Sleep and its regulation: An emerging pathogenic and treatment frontier in Alzheimer's disease. Abstract of the paper: A majority of patients with Alzheimer's disease (AD) experience some form of sleep disruption, including nocturnal sleep fragmentation, increased daytime napping, decreased slow-wave sleep (SWS, stage N3), and decreased rapid-eye-movement sleep (REM). Clinical studies are investigating whether such sleep disturbances are a consequence of the underlying disease, and whether they also contribute to the clinical and pathological manifestations of AD. Emerging research has provided a direct link between several of these sleep disruptions and AD pathophysiology, suggesting that treating sleep disorders in this population may target basic mechanisms of the disease. Here, we provide a comprehensive review of sleep disturbances associated with the spectrum of AD, ranging from the preclinical stages through dementia. We discuss how sleep interacts with AD pathophysiology and, critically, whether sleep impairments can be targeted to modify the disease course in a subgroup of affected AD patients. Ultimately, larger studies that fully utilize new diagnostic and experimental tools will be required to better define the most relevant sleep disturbance to target in AD, the interventions that best modulate this target symptom, and whether successful early intervention can modify AD risk and prevent dementia.

False

CitationGPTRetr1042

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: EEG alterations during wake and sleep in mild cognitive impairment and Alzheimer's disease. Abstract of the paper: Patients with Alzheimer's disease (AD) undergo a slowing of waking electroencephalographic (EEG) rhythms since prodromal stages, which could be ascribed to poor sleep quality. We examined the relationship between wake and sleep alterations by assessing EEG activity during sleep and (pre-sleep/post-sleep) wakefulness in AD, mild cognitive impairment (MCI) and healthy controls. AD and MCI show high sleep latency and less slow-wave sleep. Reduced sigma activity characterizes non-rapid eye movement (NREM) sleep, reflecting sleep spindles loss. The EEG slowing characterizes REM sleep and wakefulness of AD and MCI, with strong correlations among the two phenomena suggesting common neuropathological mechanisms. Evening-to-morning variations in waking EEG revealed the gradual disappearance in MCI and AD of overnight changes in delta activity, indicating a progressive decay of sleep restorative functions on diurnal activity that correlates with the impairment of sleep high-frequency activity in AD. Our findings support a linkage between wake and sleep alterations, and the importance of sleep-related processes in Alzheimer's disease progression.

False

CitationGPTRetr1043

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Alzheimer's disease and sleep disturbances: a review. Abstract of the paper: The association between Alzheimer's disease (AD) and sleep disturbances has received increasing scientific attention in the last decades. However, little is known about the impact of sleep and its disturbances on the development of preclinical AD stages, such as mild cognitive impairment. This review describes the evolution of knowledge about the potential bidirectional relationships between AD and sleep disturbances exploring recent large prospective studies and meta-analyses and studies of the possible mechanisms through which sleep and the neurodegenerative process could be associated. The review also makes a comprehensive exploration of the sleep characteristics of older people, ranging from cognitively normal individuals, through patients with mild cognitive impairment, up to the those with dementia with AD.

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CitationGPTRetr1044

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Symposium: Cognitive processes and sleep disturbances: Sleep/wake patterns in Alzheimer's disease: relationships with cognition and function. Abstract of the paper: Alzheimer's disease (AD), the most common dementing disorder of aging, is a progressive neurodegenerative disease of unknown etiology. Two of the common clinical features of AD are progressive cognitive and functional impairment, and disturbed sleep/wake patterns. We examined sleep/wake patterns and cognitive and functional status measures in a large sample of AD subjects ranging from mild to moderate-severe in impairment. All subjects survived at least 2 years after initial diagnosis. Regression analyses revealed that sleep/wake variables were highly correlated with and explained significant variance in cognitive and functional measures. More wakefulness during the night and longer REM latencies were associated with impaired cognition and function while more REM and slow-wave sleep were associated with preserved cognition and function. These results indicate that with advancing severity of the disease, sleep/wake patterns are disrupted in parallel with the disturbances in cognition and function that are the hallmarks of AD. Further, they suggest that the neural substrates underlying each process degenerate at somewhat comparable rates.

False

CitationGPTRetr1045

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Interactions between sleep disturbances and Alzheimer's disease on brain function: a preliminary study combining the static and dynamic functional MRI. Abstract of the paper: Though sleep disturbance constitutes the risk factor for Alzheimer's disease (AD), the underlying mechanism is still unclear. This study aims to explore the interaction between sleep disturbances and AD on brain function. We included 192 normal controls, 111 mild cognitive impairment (MCI), and 30 AD patients, with either poor or normal sleep (PS, NS, respectively). To explore the strength and stability of brain activity, we used static amplitude of low-frequency fluctuation (sALFF) and dynamic ALFF (dALFF) variance. Further, we examined white matter hyperintensities (WMH) and amyloid PET deposition, representing the vascular risk factor and AD-related hallmark, respectively. We observed that sleep disturbance significantly interacted with disease severity, exposing distinct effects on sALFF and dALFF variance. Interestingly, PS groups showed the dALFF variance trajectory of initially increased, then decreased and finally increased along the AD spectrum, while showing the opposite trajectory of sALFF. Further correlation analysis showed that the WMH burden correlates with dALFF variance in PS groups. Conclusively, our study suggested that sleep disturbance interacts with AD severity, expressing as effects of compensatory in MCI and de-compensatory in AD, respectively. Further, vascular impairment might act as important pathogenesis underlying the interaction effect between sleep and AD.

False

CitationGPTRetr1046

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Alzheimer's disease pathogenesis: The role of disturbed sleep in attenuated brain plasticity and neurodegenerative processes. Abstract of the paper: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairments. The classical symptoms of the disease include gradual deterioration of memory and language. Epidemiological studies indicate that around 25-40% of AD patients have sleep-wake cycle disturbances. Importantly, a series of studies suggested that the relationship between AD and sleep disturbance may be complex and bidirectional. Indeed, accumulation of the extracellular neuronal protein amyloid-beta (Aβ) leads to altered sleep-wake behavior in both mice and humans. At the same time, disturbances of the normal sleep-wake cycle may facilitate AD pathogenesis. This paper will review the mechanisms underlying this potential interrelated connection including locus coeruleus damage, reductions in orexin neurotransmission, alterations in melatonin levels, and elevated cytokine levels. In addition, we will also highlight how both the development of AD and sleep disturbances lead to changes in intracellular signaling pathways involved in regulating neuronal plasticity and connectivity, particularly extremes in cofilin phosphorylation. Finally, current pharmacological and nonpharmacological therapeutic approaches will be discussed.

False

CitationGPTRetr1047

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Is Sleep Disruption a Cause or Consequence of Alzheimer's Disease? Reviewing Its Possible Role as a Biomarker. Abstract of the paper: In recent years, the idea that sleep is critical for cognitive processing has gained strength. Alzheimer's disease (AD) is the most common form of dementia worldwide and presents a high prevalence of sleep disturbances. However, it is difficult to establish causal relations, since a vicious circle emerges between different aspects of the disease. Nowadays, we know that sleep is crucial to consolidate memory and to remove the excess of beta-amyloid and hyperphosphorilated tau accumulated in AD patients' brains. In this review, we discuss how sleep disturbances often precede in years some pathological traits, as well as cognitive decline, in AD. We describe the relevance of sleep to memory consolidation, focusing on changes in sleep patterns in AD in contrast to normal aging. We also analyze whether sleep alterations could be useful biomarkers to predict the risk of developing AD and we compile some sleep-related proposed biomarkers. The relevance of the analysis of the sleep microstructure is highlighted to detect specific oscillatory patterns that could be useful as AD biomarkers.

False

CitationGPTRetr1048

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Neural Correlates of Sleep Disturbance in Alzheimer's Disease: Role of the Precuneus in Sleep Disturbance. Abstract of the paper: BACKGROUND Sleep disturbance may affect the development of Alzheimer's disease (AD), but the neural correlates of sleep disturbance in AD have not been fully clarified. OBJECTIVE To examine the factors associated with sleep disturbance in AD. METHODS A retrospective study was performed in 63 patients with AD. None of the patients had been prescribed antidementia or psychoactive drugs, and all underwent brain magnetic resonance imaging (MRI) before medication. Sleep disturbance was defined as a score of at least 1 point on the sleep disturbance subscale of the Neuropsychiatric Inventory (NPI). Whole brain image analysis was performed using SPM8 and VBM8. A two-sample t-test was used to compare patients with AD with (n = 19) and without (n = 44) sleep disturbance, with age and gender included as covariates. The statistical thresholds were set to an uncorrected p-value of 0.001 at the voxel level and a corrected p-value of 0.05 at the cluster level. In addition, pineal gland volume (PGV) measured using MRI, and white matter hyperintensity (WMH) assessed with the modified Fazekas scale were compared between patients with AD with and without sleep disturbance using independent group t-tests. RESULTS In whole brain analysis, the precuneus volume in patients with AD with sleep disturbance was significantly smaller than those without sleep disturbance. There were no significant differences in PGV and WMH between the two groups. CONCLUSION Sleep disturbance in AD was associated with reduction of precuneus volume. This suggests that the precuneus might be an important region in sleep disturbance in AD.

False

CitationGPTRetr1049

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Role of Sleep Disturbance in the Trajectory of Alzheimer's Disease. Abstract of the paper: Sleep disturbances such as insomnia, hypersomnia, and circadian rhythm disturbance are common in normal elderly and Alzheimer's disease (AD) patients. To date, special attention has been paid to sleep disturbance in the clinical course of AD insofar as the interaction of sleep disturbance with the pathogenesis of AD may impact the clinical course and cognitive function of AD patients. This review covers the bidirectional relationship between sleep disturbance and AD pathogenesis; the associations between sleep disturbance and AD-specific neurotransmitters, brain structure, and aspects of sleep disturbance in each phase of AD; and the effects of sleep disturbance on the cognitive functions of patients in each phase of AD. We consider several factors required to exactly interpret the results and suggest a direction for future studies on the role of sleep disturbance in AD.

False

CitationGPTRetr1050

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: The Synergistic Relationship between Alzheimer's Disease and Sleep Disorders: An Update. Abstract of the paper: Sleep disorders are frequently reported in Alzheimer's disease (AD), with a significant impact on patients and caregivers and a major risk factor for early institutionalization. Although changes in sleep organization are a hallmark of the normal aging processes, sleep macro- and micro-architectural alterations are more evident in patients affected by AD. Degeneration of neural pathways regulating sleep-wake patterns and sleep architecture may contribute to sleep alterations. In return, several recent studies suggested that common sleep disorders may precede clinical symptoms of dementia and represent risk factors for cognitive decline, through impairment of sleep-dependent memory consolidation processes. Thus, a close relationship between sleep disorders and AD has been largely hypothesized. Here, sleep alterations in AD and its pre-dementia stage, mild cognitive impairment, and their complex interactions are reviewed.

False

CitationGPTRetr1051

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Altered intrinsic brain activity in mild Alzheimer's disease patients with sleep disturbances. Abstract of the paper: Sleep disturbances are one of the preventive factors to delay the onset and progression of Alzheimer's disease. Early identification of Alzheimer's disease patients prone to develop sleep disturbances to offer early medical intervention is important. Resting-state functional MRI is a widely used method to investigate the neural mechanisms and find neuroimaging biomarkers in neuropsychiatric diseases. In this study, we applied percent amplitude of fluctuation (PerAF) and mPerAF (divided by global mean PerAF) to test the strength of intrinsic brain activity in 38 mild Alzheimer's disease patients with sleep disturbances (ADSD) and 21 mild Alzheimer's disease patients without sleep disturbances (ADNSD). Compared with ADNSD, we found decreased intrinsic brain activity in the calcarine gyrus, the lingual gyrus, the fusiform gyrus extending to the parahippocampal gyrus, the precentral gyrus, the postcentral gyrus (all in the left hemisphere) and the left brainstem. Conclusively, ADSD exhibited reduced neural activity in specific brain regions related to the sensorimotor network and the visual network, which indicated the contribution of sleep disturbances to the progression of Alzheimer's disease. Especially, the ventral visual pathway to the hippocampus might serve for the memory impaired by sleep disturbances in Alzheimer's disease, and the brainstem might be critical in the initiation of sleep disturbances in Alzheimer's disease. These findings further elucidate the interactions between Alzheimer's disease and sleep disturbances and could help with the early recognition of Alzheimer's disease patients who tend to develop sleep disturbances.

False

CitationGPTRetr1052

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Brain Functional and Structural Changes in Alzheimer's Disease With Sleep Disorders: A Systematic Review. Abstract of the paper: Introduction: Sleep disorders (SLD) are supposed to be associated with increased risk and development of Alzheimer's disease (AD), and patients with AD are more likely to show SLD. However, neurobiological performance of patients with both AD and SLD in previous studies is inconsistent, and identifying specific patterns of the brain functional network and structural characteristics in this kind of comorbidity is warranted for understanding how AD and SLD symptoms interact with each other as well as finding effective clinical intervention. Thus, the aims of this systematic review were to summarize the relevant findings and their limitations and provide future research directions. Methods: A systematic search on brain functional and structural changes in patients with both AD and SLD was conducted from PubMed, Web of Science, and EMBASE databases. Results: Nine original articles published between 2009 and 2021 were included with a total of 328 patients with comorbid AD and SLD, 367 patients with only AD, and 294 healthy controls. One single-photon emission computed tomography study and one multislice spiral computed tomography perfusion imaging study investigated changes of cerebral blood flow; four structural magnetic resonance imaging (MRI) studies investigated brain structural changes, two of them used whole brain analysis, and another two used regions of interest; two resting-state functional MRI studies investigated brain functional changes, and one 2-deoxy-2-(18F)fluoro-d-glucose positron emission tomography (18F-FDG-PET) investigated 18F-FDG-PET uptake in patients with comorbid AD and SLD. Findings were inconsistent, ranging from default mode network to sensorimotor cortex, hippocampus, brain stem, and pineal gland, which may be due to different imaging techniques, measurements of sleep disorder and subtypes of AD and SLD. Conclusions: Our review provides a systematic summary and promising implication of specific neuroimaging dysfunction underlying co-occurrence of AD and SLD. However, limited and inconsistent findings still restrict its neurobiological explanation. Further studies should use unified standards and comprehensive brain indices to investigate the pathophysiological basis of interaction between AD and SLD symptoms in the development of the disease spectrums.

False

CitationGPTRetr1053

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Integrating Sleep and Alzheimer's Disease Pathophysiology: Hints for Sleep Disorders Management. Abstract of the paper: Sleep represents an active phenomenon regulated by a highly integrated network of cortical and subcortical structures. This complex model results in disruptions at various levels during physiological aging and more deeply during neurodegenerative disorders, thus leading to different sleep alterations. In Alzheimer's disease (AD), sleep-wake abnormalities were described to occur even in the preclinical phase, thus suggesting they could be a possible AD biomarker. On the other hand, they also favor the progression of the disease. In this paper, we review current theories regarding sleep regulations and functions to highlight the pathophysiological mechanisms at the basis of the bidirectional relationship between sleep and AD. A better understanding of these complex interactions might also be useful to target both sleep disorder management and AD-related symptoms.

False

CitationGPTRetr1054

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Sleep Disorders Associated With Alzheimer's Disease: A Perspective. Abstract of the paper: Sleep disturbances, as well as sleep-wake rhythm disturbances, are typical symptoms of Alzheimer's disease (AD) that may precede the other clinical signs of this neurodegenerative disease. Here, we describe clinical features of sleep disorders in AD and the relation between sleep disorders and both cognitive impairment and poor prognosis of the disease. There are difficulties of the diagnosis of sleep disorders based on sleep questionnaires, polysomnography or actigraphy in the AD patients. Typical disturbances of the neurophysiological sleep architecture in the course of the AD include deep sleep and paradoxical sleep deprivation. Among sleep disorders occurring in patients with AD, the most frequent disorders are sleep breathing disorders and restless legs syndrome. Sleep disorders may influence circadian fluctuations of the concentrations of amyloid-β in the interstitial brain fluid and in the cerebrovascular fluid related to the glymphatic brain system and production of the amyloid-β. There is accumulating evidence suggesting that disordered sleep contributes to cognitive decline and the development of AD pathology. In this mini-review, we highlight and discuss the association between sleep disorders and AD.

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CitationGPTRetr1055

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Altered functional connectivity in early Alzheimer's disease: a resting-state fMRI study. Abstract of the paper: Previous studies have led to the proposal that patients with Alzheimer's disease (AD) may have disturbed functional connectivity between different brain regions. Furthermore, recent resting-state functional magnetic resonance imaging (fMRI) studies have also shown that low-frequency (<0.08 Hz) fluctuations (LFF) of the blood oxygenation level-dependent signals were abnormal in several brain areas of AD patients. However, few studies have investigated disturbed LFF connectivity in AD patients. By using resting-state fMRI, this study sought to investigate the abnormal functional connectivities throughout the entire brain of early AD patients, and analyze the global distribution of these abnormalities. For this purpose, the authors divided the whole brain into 116 regions and identified abnormal connectivities by comparing the correlation coefficients of each pair. Compared with healthy controls, AD patients had decreased positive correlations between the prefrontal and parietal lobes, but increased positive correlations within the prefrontal lobe, parietal lobe, and occipital lobe. The AD patients also had decreased negative correlations (closer to zero) between two intrinsically anti-correlated networks that had previously been found in the resting brain. By using resting-state fMRI, our results supported previous studies that have reported an anterior-posterior disconnection phenomenon and increased within-lobe functional connectivity in AD patients. In addition, the results also suggest that AD may disturb the correlation/anti-correlation effect in the two intrinsically anti-correlated networks.

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CitationGPTRetr1056

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Resting-state network dysfunction in Alzheimer's disease: A systematic review and meta-analysis. Abstract of the paper: INTRODUCTION We performed a systematic review and meta-analysis of the Alzheimer's disease (AD) literature to examine consistency of functional connectivity alterations in AD dementia and mild cognitive impairment, using resting-state functional magnetic resonance imaging. METHODS Studies were screened using a standardized procedure. Multiresolution statistics were performed to assess the spatial consistency of findings across studies. RESULTS Thirty-four studies were included (1363 participants, average 40 per study). Consistent alterations in connectivity were found in the default mode, salience, and limbic networks in patients with AD dementia, mild cognitive impairment, or in both groups. We also identified a strong tendency in the literature toward specific examination of the default mode network. DISCUSSION Convergent evidence across the literature supports the use of resting-state connectivity as a biomarker of AD. The locations of consistent alterations suggest that highly connected hub regions in the brain might be an early target of AD.

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CitationGPTRetr1057

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Sleep disturbance and Alzheimer's disease: relationship to behavioral problems. Abstract of the paper: We studied the sleep characteristics of 108 outpatients with probable Alzheimer's disease and found that sleep disturbance was significantly related to daytime behavioral disturbance but not to cognitive impairment. Possible treatment strategies and neuropathological and neurochemical mechanisms are discussed.

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CitationGPTRetr1058

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Sleep in Alzheimer's disease and the sundown syndrome. Abstract of the paper: Approximately 10% of the elderly population have a dementing illness that manifests itself clinically by significant cognitive deficits. Half of these individuals have Alzheimer's disease (AD), a progressive degeneration of cortical and subcortical neurons. Disturbances of sleep and the sleep-wake rhythm are a common clinical observation in AD, as is "sundowning," the onset or exacerbation of delirium during the evening or night. Here we describe the neurologic basis for the disturbed sleep of patients with AD, the phenomenology of that disturbance, and its implications. Further, we describe the prevalence, possible causes, and treatment of sundowning.

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CitationGPTRetr1059

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: aberrations in restingstate neural activity in patients on the alzheimers disease spectrum have been extensively explored in the literature and more recent studies have begun to show similar restingstate alterations related to sleep disturbances however the interaction of alzheimers disease pathology and sleep disturbances on neural oscillatory activity has not been studied Title of the paper: Sleep in Alzheimer's Disease - Beyond Amyloid. Abstract of the paper: Sleep disorders are prevalent in Alzheimer's disease (AD) and a major cause of institutionalization. Like AD pathology, sleep abnormalities can appear years before cognitive decline and may be predictive of dementia. A bidirectional relationship between sleep and amyloid β (Aβ) has been well established with disturbed sleep and increased wakefulness leading to increased Aβ production and decreased Aβ clearance; whereas Aβ deposition is associated with increased wakefulness and sleep disturbances. Aβ fluctuates with the sleep wake cycle and is higher during wakefulness and lower during sleep. This fluctuation is lost with Aβ deposition, likely due to its sequestration into amyloid plaques. As such, Aβ is believed to play a significant role in the development of sleep disturbances in the preclinical and clinical phase of AD. In addition to Aβ, the influence of tau AD pathology is likely important to the sleep disturbances observed in AD. Abnormal tau is the earliest observable AD-like pathology in the brain with abnormal tau phosphorylation in many sleep regulating regions such as the locus coeruleus, dorsal raphe, tuberomammillary nucleus, parabrachial nucleus, and basal forebrain prior to the appearance of amyloid or cortical tau pathology. Furthermore, human tau mouse models exhibit AD-like sleep disturbances and sleep changes are very common in other tauopathies including frontotemporal dementia and progressive supranuclear palsy. Together these observations suggest that tau pathology can induce sleep disturbances and may play a large role in the sleep disruption seen in AD. To elucidate the relationship between sleep and AD it will be necessary to not only understand the role of amyloid but also tau and how these two pathologies, together with comorbid pathology such as alpha-synuclein, interact and affect sleep regulation in the brain.

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CitationGPTRetr1060

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Phage-displayed peptide libraries. Abstract of the paper: Over the past year, significant advances have been achieved through the use of phage-displayed peptide libraries. A wide variety of bioactive molecules, including antibodies, receptors and enzymes, have selected high-affinity and/or highly-specific peptide ligands from a number of different types of peptide library. The demonstrated therapeutic potential of some of these peptides, as well as new insights into protein structure and function that peptide ligands have provided, highlight the progress made within this rapidly-expanding field.

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CitationGPTRetr1061

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Drugs derived from phage display: from candidate identification to clinical practice. Abstract of the paper: Phage display, one of today’s fundamental drug discovery technologies, allows identification of a broad range of biological drugs, including peptides, antibodies and other proteins, with the ability to tailor critical characteristics such as potency, specificity and cross-species binding. Further, unlike in vivo technologies, generating phage display-derived antibodies is not restricted by immunological tolerance. Although more than 20 phage display-derived antibody and peptides are currently in late-stage clinical trials or approved, there is little literature addressing the specific challenges and successes in the clinical development of phage-derived drugs. This review uses case studies, from candidate identification through clinical development, to illustrate the utility of phage display as a drug discovery tool, and offers a perspective for future developments of phage display technology.

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CitationGPTRetr1062

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Phage display of combinatorial antibody libraries. Abstract of the paper: The selection of antibodies from combinatorial libraries displayed on the surface of filamentous phage has become an important methodology for the generation of reagent, diagnostic, and therapeutic molecules and for the study of natural immune responses. Using this technique, antibody genes have been cloned from multiple species or expressed directly from large man-made repertoires of antibody-encoding genes. Recent studies demonstrate that the technique allows for the in vitro evolution of antibodies to create molecules whose affinity for antigen exceeds that observed in nature.

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CitationGPTRetr1063

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Antibody phage display technology and its applications. Abstract of the paper: In recent years, the use of display vectors and in vitro selection technologies has transformed the way in which we generate ligands, such as antibodies and peptides, for a given target. Using this technology, we are now able to design repertoires of ligands from scratch and use the power of phage selection to select those ligands having the desired (biological) properties. With phage display, tailor-made antibodies may be synthesized and selected to acquire the desired affinity of binding and specificity for in vitro and in vivo diagnosis, or for immunotherapy of human disease. This review addresses recent progress in the construction of, and selection from phage antibody libraries, together with novel approaches for screening phage antibodies. As the quality of large naïve and synthetic antibody repertoires improves and libraries becomes more generally available, new and exciting applications are pioneered such as the identification of novel antigens using differential selection and the generation of receptor a(nta)gonists. A combination of the design and generation of millions to billions of different ligands, together with phage display for the isolation of binding ligands and with functional assays for identifying (and possibly selecting) bio-active ligands, will open even more challenging applications of this inspiring technology, and provide a powerful tool for drug and target discovery well into the next decade.

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CitationGPTRetr1064

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Phage display-derived peptides as therapeutic alternatives to antibodies. Abstract of the paper: Peptide-based drugs are now viable alternatives to biopharmaceuticals, such as antibodies. Most of the past limitations of peptides have been removed by new technologies, so that peptides now face similar hurdles to antibodies. Phage-display technology provides novel peptides that bind protein targets with high affinity and specificity. Most marketed peptide-based drugs are receptor agonists derived from natural peptides. To address the need for antagonists, novel strategies have been developed for inhibiting receptor-ligand interactions. We review results from phage display in finding peptide drug candidates and conclude with some business benefits of developing peptides.

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CitationGPTRetr1065

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Peptide phage display as a tool for drug discovery: targeting membrane receptors. Abstract of the paper: Ligands selected from phage-displayed random peptide libraries tend to be directed to biologically relevant sites on the surface of the target protein. Consequently, peptides derived from library screenings often modulate the target protein's activity in vitro and in vivo and can be used as lead compounds in drug design and as alternatives to antibodies for target validation in both genomics and drug discovery. This review discusses the use of phage display to identify membrane receptor modulators with agonistic or antagonistic activities. Because isolating or producing recombinant membrane proteins for use as target molecules in library screening is often impossible, innovative selection strategies such as panning against whole cells or tissues, recombinant receptor ectodomains, or neutralizing antibodies to endogenous binding partners were devised. Prominent examples from a two-decade history of peptide phage display will be presented, focusing on the design of affinity selection experiments, methods for improving the initial hits, and applications of the identified peptides.

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CitationGPTRetr1066

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Mirror image phage display--a method to generate D-peptide ligands for use in diagnostic or therapeutical applications. Abstract of the paper: Mirror image phage display is a straightforward approach to identify new potentially therapeutically active D-enantiomeric peptides. Such D-peptides are more resistant to proteolytic degradation compared to L-peptides. In this review, several examples of mirror image phage display derived D-peptides with therapeutical potential are introduced and discussed.

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CitationGPTRetr1067

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Selecting peptides for use in nanoscale materials using phage-displayed combinatorial peptide libraries. Abstract of the paper: Materials that combine inorganic components and biological molecules provide a new paradigm for synthesizing nanoscale and larger structures with tailored physical properties. These synthesis techniques utilize the molecular recognition properties of many biological molecules to nucleate and control growth of the nanoscale structure. Phage-displayed peptide libraries are a powerful tool to identify peptides that selectively recognize and bind to a variety of inorganic surfaces that are utilized in electronic and photonic devices. These libraries have been used extensively to study the peptide-mediated nucleation and growth of some metallic and semiconducting materials, and the application to designed nanostructures has been demonstrated.

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CitationGPTRetr1068

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Efficient construction of a large collection of phage-displayed combinatorial peptide libraries. Abstract of the paper: Selections from phage-displayed combinatorial peptide libraries are an effective strategy for identifying peptide ligands to target proteins. Existing protocols for constructing phage-displayed libraries utilize either ligation into double-stranded phage DNA or Kunkel mutagenesis with single-stranded phagemid DNA. Although the Kunkel approach rapidly provides library sizes of up to 10(11), as many as 20% of the phagemids may be non-recombinant. With several modifications to current Kunkel protocols, we have generated peptide libraries with sizes of up to 10(11) clones and recombination frequencies approaching 100%. The production of phage libraries, as opposed to phagemid libraries, simplifies selection experiments by eliminating the need for helper phage. Our approach relies upon the presence of an amber stop codon in the coding region of gene III of bacteriophage M13. Oligonucleotides containing randomized stretches of DNA are annealed to the phage genome such that the randomized region forms a heteroduplex with the stop codon. The oligonucleotide is then enzymatically extended to generate covalently-closed, circular DNA, which is electroporated into a non-suppressor strain of Escherichia coli. If the amber stop codon is present in the DNA molecule, protein III is not synthesized and the phage cannot propagate itself. This method is customizable for the display of either random or focused peptide libraries. To date, we have constructed 22 different libraries ranging from 8-20 amino acids in length, utilizing complete or reduced codon sets.

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CitationGPTRetr1069

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Phage Display Technique as a Tool for Diagnosis and Antibody Selection for Coronaviruses. Abstract of the paper: Phage display is one of the important and effective molecular biology techniques and has remained indispensable for research community since its discovery in the year 1985. As a large number of nucleotide fragments may be cloned into the phage genome, a phage library may harbour millions or sometimes billions of unique and distinctive displayed peptide ligands. The ligand-receptor interactions forming the basis of phage display have been well utilized in epitope mapping and antigen presentation on the surface of bacteriophages for screening novel vaccine candidates by using affinity selection-based strategy called biopanning. This versatile technique has been modified tremendously over last three decades, leading to generation of different platforms for combinatorial peptide display. The translation of new diagnostic tools thus developed has been used in situations arising due to pathogenic microbes, including bacteria and deadly viruses, such as Zika, Ebola, Hendra, Nipah, Hanta, MERS and SARS. In the current situation of pandemic of Coronavirus disease (COVID-19), a search for neutralizing antibodies is motivating the researchers to find therapeutic candidates against novel SARS-CoV-2. As phage display is an important technique for antibody selection, this review presents a concise summary of the very recent applications of phage display technique with a special reference to progress in diagnostics and therapeutics for coronavirus diseases. Hopefully, this technique can complement studies on host-pathogen interactions and assist novel strategies of drug discovery for coronaviruses.

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CitationGPTRetr1070

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Phage display: selecting straws instead of a needle from a haystack. Abstract of the paper: An increasing number of peptides with specific binding affinity to various protein and even non-protein targets are being discovered from phage display libraries. The power of this method lies in its ability to efficiently and rapidly identify ligands with a desired target property from a large population of phage clones displaying diverse surface peptides. However, the search for the needle in the haystack does not always end successfully. False positive results may appear. Thus instead of specific binders phage with no actual affinity toward the target are recovered due to their propagation advantages or binding to other components of the screening system, such as the solid phase, capturing reagents, contaminants in the target sample or blocking agents, rather than the target. Biopanning experiments on different targets performed in our laboratory revealed some previously identified and many new target-unrelated peptide sequences, which have already been frequently described and published, but not yet recognized as target-unrelated. Distinguishing true binders from false positives is an important step toward phage display selections of greater integrity. This article thoroughly reviews and discusses already identified and new target-unrelated peptides and suggests strategies to avoid their isolation.

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CitationGPTRetr1071

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Next-generation sequencing of phage-displayed peptide libraries. Abstract of the paper: Genetically encoded peptide libraries enabled the discovery of ligands for clinically relevant targets and functional materials. Next-generation sequencing (NGS) of these libraries improved the selection of ligands by detecting low abundant clones and quantifying changes in copy numbers of clones without many rounds of selection. Although NGS platforms have been widely used in genome assembly, quantification of gene expression (RNA-seq), and metagenomic analyses, few examples in the literature describe sequencing phage libraries. This chapter aims to provide a detailed method for sequencing a Ph.D.-7 phage display library by Ion Torrent. The main techniques covered in this chapter include (1) preparation of a phage library for sequencing, (2) sequencing, and (3) analysis of the sequencing data by a custom Matlab script.

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CitationGPTRetr1072

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Phage display screening of therapeutic peptide for cancer targeting and therapy. Abstract of the paper: Recently, phage display technology has been announced as the recipient of Nobel Prize in Chemistry 2018. Phage display technique allows high affinity target-binding peptides to be selected from a complex mixture pool of billions of displayed peptides on phage in a combinatorial library and could be further enriched through the biopanning process; proving to be a powerful technique in the screening of peptide with high affinity and selectivity. In this review, we will first discuss the modifications in phage display techniques used to isolate various cancer-specific ligands by in situ, in vitro, in vivo, and ex vivo screening methods. We will then discuss prominent examples of solid tumor targeting-peptides; namely peptide targeting tumor vasculature, tumor microenvironment (TME) and over-expressed receptors on cancer cells identified through phage display screening. We will also discuss the current challenges and future outlook for targeting peptide-based therapeutics in the clinics.

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CitationGPTRetr1073

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Mirror image phage display--generating stable therapeutically and diagnostically active peptides with biotechnological means. Abstract of the paper: Peptides are attracting increasing attention as therapeutics. D-enantiomeric peptides are remarkably resistant to in vivo proteolysis and elicit low immunogenic responses when compared with the respective L-peptides. Therefore, D-peptides can serve as therapeutic and early diagnosis agents for drug development. Here we discuss the application of mirror image phage display in pharmaceutical biotechnology aiming to identify protease resistant D-peptides with biotechnological approaches.

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CitationGPTRetr1074

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Mapping of vascular ZIP codes by phage display. Abstract of the paper: Each organ and pathology has a unique vascular ZIP code that can be targeted with affinity ligands. In vivo peptide phage display can be used for unbiased mapping of the vascular diversity. Remarkably, some of the peptides identified by such screens not only bind to target vessels but also elicit biological responses. Recently identified tissue-penetrating CendR peptides trigger vascular exit and parenchymal spread of a wide range of conjugated and coadministered payloads. This review is designed to serve as a practical guide for researchers interested in setting up ex vivo and in vivo phage display technology. We focus on T7 coliphage platform that our lab prefers to use due to its versatility, physical resemblance of phage particles to clinical nanoparticles, and ease of manipulation.

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CitationGPTRetr1075

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Engineered affinity proteins--generation and applications. Abstract of the paper: The use of combinatorial protein engineering to design proteins with novel binding specificities and desired properties has evolved into a powerful technology, resulting in the recent advances in protein library selection strategies and the emerge of a variety of new engineered affinity proteins. The need for different protein library selection methods is due to that each target protein pose different challenges in terms of its availability and inherent properties. At present, alternative engineered affinity proteins are starting to complement and even challenge the classical immunoglobulins in different applications in biotechnology and potentially also for in vivo use as imaging agents or as biotherapeutics. This review article covers the generation and use of affinity proteins generated through combinatorial protein engineering. The most commonly used selection techniques for isolation of desired variants from large protein libraries are described. Different antibody derivatives, as well as a variety of the most validated engineered protein scaffolds, are discussed. In addition, we provide an overview of some of the major present and future applications for these engineered affinity proteins in biotechnology and medicine.

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CitationGPTRetr1076

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Abstract of the paper: Foreign DNA fragments can be inserted into filamentous phage gene III to create a fusion protein with the foreign sequence in the middle. The fusion protein is incorporated into the virion, which retains infectivity and displays the foreign amino acids in immunologically accessible form. These "fusion phage" can be enriched more than 1000-fold over ordinary phage by affinity for antibody directed against the foreign sequence. Fusion phage may provide a simple way of cloning a gene when an antibody against the product of that gene is available.

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CitationGPTRetr1077

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Identifying the cellular targets of natural products using T7 phage display. Abstract of the paper: Covering: up to the end of 2015While Nature continues to deliver a myriad of potent and structurally diverse biologically active small molecules, the cellular targets and modes of action of these natural products are rarely identified, significantly hindering their development as new chemotherapeutic agents. This article provides an introductory tutorial on the use of T7 phage display as a tool to rapidly identify the cellular targets of natural products and is aimed specifically at natural products chemists who may have only limited experience in molecular biology. A brief overview of T7 phage display is provided, including its strengths, weaknesses, and the type of problems that can and cannot be tackled with this technology. Affinity probe construction is reviewed, including linker design and natural product derivatisation strategies. A detailed description of the T7 phage biopanning procedure is provided, with valuable tips for optimising each step in the process, as well as advice for identifying and avoiding the most commonly encountered challenges and pitfalls along the way. Finally, a brief discussion is provided on techniques for validating the cellular targets identified using T7 phage display.

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CitationGPTRetr1078

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Library-based display technologies: where do we stand? Abstract of the paper: Over the past two decades, library-based display technologies have been staggeringly optimized since their appearance in order to mimic the process of natural molecular evolution. Display technologies are essential for the isolation of specific high-affinity binding molecules (proteins, polypeptides, nucleic acids and others) for diagnostic and therapeutic applications in cancer, infectious diseases, autoimmune, neurodegenerative, inflammatory pathologies etc. Applications extend to other fields such as antibody and enzyme engineering, cell-free protein synthesis and the discovery of protein-protein interactions. Phage display technology is the most established of these methods but more recent fully in vitro alternatives, such as ribosome display, mRNA display, cis-activity based (CIS) display and covalent antibody display (CAD), as well as aptamer display and in vitro compartmentalization, offer advantages over phage in library size, speed and the display of unnatural amino acids and nucleotides. Altogether, they have produced several molecules currently approved or in diverse stages of clinical or preclinical testing and have provided researchers with tools to address some of the disadvantages of peptides and nucleotides such as their low affinity, low stability, high immunogenicity and difficulty to cross membranes. In this review we assess the fundamental technological features and point out some recent advances and applications of display technologies.

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CitationGPTRetr1079

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: the seven different scfvs utilized table i 11 12 30 50 61 were each expressed on the surface on bacteriophage as described Title of the paper: Assembly of bacteriophage into functional materials. Abstract of the paper: For the last decade, the fabrication of ordered structures of phage has been of great interest as a means of utilizing the outstanding biochemical properties of phage in developing useful materials. Combined with other organic/inorganic substances, it has been demonstrated that phage is a superior building block for fabricating various functional devices, such as the electrode in lithium-ion batteries, photovoltaic cells, sensors, and cell-culture supports. Although previous research has expanded the utility of phage when combined with genetic engineering, most improvements in device functionality have relied upon increases in efficiency owing to the compact, more densely packable unit size of phage rather than on the unique properties of the ordered nanostructures themselves. Recently, self-templating methods, which control both thermodynamic and kinetic factors during the deposition process, have opened up new routes to exploiting the ordered structural properties of hierarchically organized phage architectures. In addition, ordered phage films have exhibited unexpected functional properties, such as structural color and optical filtering. Structural colors or optical filtering from phage films can be used for optical phage-based sensors, which combine the structural properties of phage with target-specific binding motifs on the phage-coat proteins. This self-templating method may contribute not only to practical applications, but also provide insight into the fundamental study of biomacromolecule assembly in in vivo systems under complicated and dynamic conditions.

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CitationGPTRetr1080

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Salience Network Atrophy Links Neuron Type-Specific Pathobiology to Loss of Empathy in Frontotemporal Dementia. Abstract of the paper: Each neurodegenerative syndrome reflects a stereotyped pattern of cellular, regional, and large-scale brain network degeneration. In behavioral variant of frontotemporal dementia (bvFTD), a disorder of social-emotional function, von Economo neurons (VENs), and fork cells are among the initial neuronal targets. These large layer 5 projection neurons are concentrated in the anterior cingulate and frontoinsular (FI) cortices, regions that anchor the salience network, a large-scale system linked to social-emotional function. Here, we studied patients with bvFTD, amyotrophic lateral sclerosis (ALS), or both, given that these syndromes share common pathobiological and genetic factors. Our goal was to determine how neuron type-specific TAR DNA-binding protein of 43 kDa (TDP-43) pathobiology relates to atrophy in specific brain structures and to loss of emotional empathy, a cardinal feature of bvFTD. We combined questionnaire-based empathy assessments, in vivo structural MR imaging, and quantitative histopathological data from 16 patients across the bvFTD/ALS spectrum. We show that TDP-43 pathobiology within right FI VENs and fork cells is associated with salience network atrophy spanning insular, medial frontal, and thalamic regions. Gray matter degeneration within these structures mediated loss of emotional empathy, suggesting a chain of influence linking the cellular, regional/network, and behavioral levels in producing signature bvFTD clinical features.

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CitationGPTRetr1081

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Distinct network topology in Alzheimer's disease and behavioral variant frontotemporal dementia. Abstract of the paper: BACKGROUND Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) cause distinct atrophy and functional disruptions within two major intrinsic brain networks, namely the default network and the salience network, respectively. It remains unclear if inter-network relationships and whole-brain network topology are also altered and underpin cognitive and social-emotional functional deficits. METHODS In total, 111 participants (50 AD, 14 bvFTD, and 47 age- and gender-matched healthy controls) underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessments. Functional connectivity was derived among 144 brain regions of interest. Graph theoretical analysis was applied to characterize network integration, segregation, and module distinctiveness (degree centrality, nodal efficiency, within-module degree, and participation coefficient) in AD, bvFTD, and healthy participants. Group differences in graph theoretical measures and empirically derived network community structures, as well as the associations between these indices and cognitive performance and neuropsychiatric symptoms, were subject to general linear models, with age, gender, education, motion, and scanner type controlled. RESULTS Our results suggested that AD had lower integration in the default and control networks, while bvFTD exhibited disrupted integration in the salience network. Interestingly, AD and bvFTD had the highest and lowest degree of integration in the thalamus, respectively. Such divergence in topological aberration was recapitulated in network segregation and module distinctiveness loss, with AD showing poorer modular structure between the default and control networks, and bvFTD having more fragmented modules in the salience network and subcortical regions. Importantly, aberrations in network topology were related to worse attention deficits and greater severity in neuropsychiatric symptoms across syndromes. CONCLUSIONS Our findings underscore the reciprocal relationships between the default, control, and salience networks that may account for the cognitive decline and neuropsychiatric symptoms in dementia.

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CitationGPTRetr1082

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Functional network connectivity in the behavioral variant of frontotemporal dementia. Abstract of the paper: INTRODUCTION The aim of this study was to investigate, using resting state (RS) functional magnetic resonance imaging (fMRI), the functional connectivity within and among brain networks in patients with the behavioral variant of frontotemporal dementia (bvFTD), compared with healthy controls and patients with probable Alzheimer's disease (pAD). METHODS Twelve bvFTD patients were compared with 30 controls and 18 pAD patients. Functional connectivity within the salience, default mode (DMN), executive (EXN), attention/working memory (ATT/WM), and dorsal attentional networks was assessed using independent component analysis. The temporal associations among RS networks (RSNs) were explored using the functional network connectivity toolbox. RESULTS A decreased dorsal salience network (DSN) connectivity, mainly involving the anterior cingulum, was observed in bvFTD versus controls and pAD. BvFTD was also characterized by a decreased ventral salience network connectivity in the basal ganglia, and divergent connectivity effects versus controls in the dorsolateral prefrontal cortex (decreased) and precuneus (enhanced) within the right ATT/WM network. The dorsal attentional network had a decreased connectivity with the DMN and EXN in bvFTD versus controls, and a decreased connectivity with the DSN versus pAD. CONCLUSIONS RSN functional abnormalities occur in bvFTD, involving not only the salience network, but also the DMN and fronto-parietal network associated with ATT and WM modulation. The pattern of functional changes differs from that seen in pAD. The altered interactions among RSN observed in bvFTD and pAD may provide a new venue to explore the functional correlates of cognitive abnormalities in neurodegenerative and psychiatric disorders.

False

CitationGPTRetr1083

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: The behavioral variant of Alzheimer's disease does not show a selective loss of Von Economo and phylogenetically related neurons in the anterior cingulate cortex. Abstract of the paper: BACKGROUND The neurobiological origins of the early and predominant behavioral changes seen in the behavioral variant of Alzheimer's disease (bvAD) remain unclear. A selective loss of Von Economo neurons (VENs) and phylogenetically related neurons have been observed in behavioral variant frontotemporal dementia (bvFTD) and several psychiatric diseases. Here, we assessed whether these specific neuronal populations show a selective loss in bvAD. METHODS VENs and GABA receptor subunit theta (GABRQ)-immunoreactive pyramidal neurons of the anterior cingulate cortex (ACC) were quantified in post-mortem tissue of patients with bvAD (n = 9) and compared to typical AD (tAD, n = 6), bvFTD due to frontotemporal lobar degeneration based on TDP-43 pathology (FTLD, n = 18) and controls (n = 13) using ANCOVAs adjusted for age and Bonferroni corrected. In addition, ratios of VENs and GABRQ-immunoreactive (GABRQ-ir) pyramidal neurons over all Layer 5 neurons were compared between groups to correct for overall Layer 5 neuronal loss. RESULTS The number of VENs or GABRQ-ir neurons did not differ significantly between bvAD (VENs: 26.0 ± 15.3, GABRQ-ir pyramidal: 260.4 ± 87.1) and tAD (VENs: 32.0 ± 18.1, p = 1.00, GABRQ-ir pyramidal: 349.8 ± 109.6, p = 0.38) and controls (VENs: 33.5 ± 20.3, p = 1.00, GABRQ-ir pyramidal: 339.4 ± 95.9, p = 0.37). Compared to bvFTD, patients with bvAD showed significantly more GABRQ-ir pyramidal neurons (bvFTD: 140.5 ± 82.658, p = 0.01) and no significant differences in number of VENs (bvFTD: 10.9 ± 13.8, p = 0.13). Results were similar when assessing the number of VENs and GABRQ-ir relative to all neurons of Layer 5. DISCUSSION VENs and phylogenetically related neurons did not show a selective loss in the ACC in patients with bvAD. Our results suggest that, unlike in bvFTD, the clinical presentation in bvAD may not be related to the loss of VENs and related neurons in the ACC.

True

CitationGPTRetr1084

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease. Abstract of the paper: BACKGROUND We previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer's disease (bvAD), with relative sparing of frontal regions. Here, we aimed to understand the clinico-anatomical dissociation in bvAD based on alternative neuroimaging markers. METHODS We retrospectively included 150 participants, including 29 bvAD, 28 "typical" amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other diagnostic groups on glucose metabolism and metabolic connectivity measured by [18F]FDG-PET, and on subcortical gray matter and white matter hyperintensity (WMH) volumes measured by MRI. A receiver-operating-characteristic-analysis was performed to determine the neuroimaging measures with highest diagnostic accuracy. RESULTS bvAD and tAD showed predominant temporoparietal hypometabolism compared to controls, and did not differ in direct contrasts. However, overlaying statistical maps from contrasts between patients and controls revealed broader frontoinsular hypometabolism in bvAD than tAD, partially overlapping with bvFTD. bvAD showed greater anterior default mode network (DMN) involvement than tAD, mimicking bvFTD, and reduced connectivity of the posterior cingulate cortex with prefrontal regions. Analyses of WMH and subcortical volume showed closer resemblance of bvAD to tAD than to bvFTD, and larger amygdalar volumes in bvAD than tAD respectively. The top-3 discriminators for bvAD vs. bvFTD were FDG posterior-DMN-ratios (bvAD<bvFTD), MRI posterior-DMN-ratios (bvAD<bvFTD), MRI salience-network-ratios (bvAD>bvFTD, area under the curve [AUC] range 0.85-0.91, all p < 0.001). The top-3 for bvAD vs. tAD were amygdalar volume (bvAD>tAD), MRI anterior-DMN-ratios (bvAD<tAD), FDG anterior-DMN-ratios (bvAD<tAD, AUC range 0.71-0.84, all p < 0.05). CONCLUSIONS Subtle frontoinsular hypometabolism and anterior DMN involvement may underlie the prominent behavioral phenotype in bvAD.

False

CitationGPTRetr1085

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Resting state functional connectivity differences between behavioral variant frontotemporal dementia and Alzheimer's disease. Abstract of the paper: INTRODUCTION Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. Early differentiation between both types of dementia may be challenging due to heterogeneity and overlap of symptoms. Here, we apply resting state functional magnetic resonance imaging (fMRI) to study functional brain connectivity differences between AD and bvFTD. METHODS We used resting state fMRI data of 31 AD patients, 25 bvFTD patients, and 29 controls from two centers specialized in dementia. We studied functional connectivity throughout the entire brain, applying two different analysis techniques, studying network-to-region and region-to-region connectivity. A general linear model approach was used to study group differences, while controlling for physiological noise, age, gender, study center, and regional gray matter volume. RESULTS Given gray matter differences, we observed decreased network-to-region connectivity in bvFTD between (a) lateral visual cortical network and lateral occipital and cuneal cortex, and (b) auditory system network and angular gyrus. In AD, we found decreased network-to-region connectivity between the dorsal visual stream network and lateral occipital and parietal opercular cortex. Region-to-region connectivity was decreased in bvFTD between superior temporal gyrus and cuneal, supracalcarine, intracalcarine cortex, and lingual gyrus. CONCLUSION We showed that the pathophysiology of functional brain connectivity is different between AD and bvFTD. Our findings support the hypothesis that resting state fMRI shows disease-specific functional connectivity differences and is useful to elucidate the pathophysiology of AD and bvFTD. However, the group differences in functional connectivity are less abundant than has been shown in previous studies.

False

CitationGPTRetr1086

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Divergent social functioning in behavioral variant frontotemporal dementia and Alzheimer disease: reciprocal networks and neuronal evolution. Abstract of the paper: Behavioral variant frontotemporal dementia (bvFTD) disrupts our most human social and emotional functions. Early in the disease, patients show focal anterior cingulate cortex (ACC) and orbital frontoinsula (FI) degeneration, accentuated in the right hemisphere. The ACC and FI, though sometimes considered ancient in phylogeny, feature a large bipolar projection neuron, the von Economo neuron (VEN), which is found only in humans, apes, and selected whales-all large-brained mammals with complex social structures. In contrast to bvFTD, Alzheimer disease (AD) often spares social functioning, and the ACC and FI, until late in its course, damaging instead a posterior hippocampal-cingulo-temporal-parietal network involved in episodic memory retrieval. These divergent patterns of functional and regional impairment remain mysterious despite extensive molecular-level characterization of bvFTD and AD. In this report, we further develop the hypothesis that VENs drive the regional vulnerability pattern seen in bvFTD, citing recent evidence from functional imaging in healthy humans, and also structural imaging and quantitative neuropathology data from bvFTD and AD. Our most recent findings suggest that bvFTD and AD target distinct, anticorrelated intrinsic connectivity networks and that bvFTD-related VEN injury occurs throughout the ACC-FI network. We suggest that the regional and neuronal vulnerability patterns seen in bvFTD and AD underlie the divergent impact of these disorders on recently evolved social-emotional functions.

False

CitationGPTRetr1087

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Primary empathy deficits in frontotemporal dementia. Abstract of the paper: Loss of empathy is an early central symptom and diagnostic criterion of the behavioral variant frontotemporal dementia (bvFTD). Although changes in empathy are evident and strongly affect the social functioning of bvFTD patients, few studies have directly investigated this issue by means of experimental paradigms. The current study assessed multiple components of empathy (affective, cognitive and moral) in bvFTD patients. We also explored whether the loss of empathy constitutes a primary deficit of bvFTD or whether it is explained by impairments in executive functions (EF) or other social cognition domains. Thirty-seven bvFTD patients with early/mild stages of the disease and 30 healthy control participants were assessed with a task that involves the perception of intentional and accidental harm. Participants were also evaluated on emotion recognition, theory of mind (ToM), social norms knowledge and several EF domains. BvFTD patients presented deficits in affective, cognitive and moral aspects of empathy. However, empathic concern was the only aspect primarily affected in bvFTD that was neither related nor explained by deficits in EF or other social cognition domains. Deficits in the cognitive and moral aspects of empathy seem to depend on EF, emotion recognition and ToM. Our findings highlight the importance of using tasks depicting real-life social scenarios because of their greater sensitivity in the assessment of bvFTD. Moreover, our results contribute to the understanding of primary and intrinsic empathy deficits of bvFTD and have important theoretical and clinical implications.

False

CitationGPTRetr1088

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Brain network modulation in Alzheimer's and frontotemporal dementia with transcranial electrical stimulation. Abstract of the paper: The default mode (DMN) and the salience (SN) networks show functional hypo-connectivity in Alzheimer's disease (AD) and the behavioral variant of frontotemporal dementia (bvFTD), respectively, along with patterns of hyper-connectivity. We tested the clinical and neurobiological effects of noninvasive stimulation over these networks in 45 patients (AD and bvFTD) who received either anodal (target network: DMN in AD, SN in bvFTD) or cathodal stimulation (target network: SN in AD, DMN in bvFTD). We evaluated changes in clinical, cognitive, functional and structural connectivity, and perfusion measures. In both patient groups, cathodal stimulation was followed by behavioral improvement, whereas anodal stimulation led to cognitive improvement. Neither functional connectivity nor perfusion showed significant effects. A significant interaction between DMN and SN functional connectivity changes and stimulation protocol was reported in AD. These results suggest a protocol-dependent response, whereby the protocols studied show divergent effects on cognitive and clinical measures, along with a divergent modulatory pattern of connectivity in AD.

False

CitationGPTRetr1089

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Social Cognition and Emotional Assessment (SEA) is a marker of medial and orbital frontal functions: a voxel-based morphometry study in behavioral variant of frontotemporal degeneration. Abstract of the paper: The aim of this study was to explore the cerebral correlates of functional deficits that occur in behavioral variant frontotemporal dementia (bvFTD). A specific neuropsychological battery, the Social cognition & Emotional Assessment (SEA; Funkiewiez et al., 2012), was used to assess impaired social and emotional functions in 20 bvFTD patients who also underwent structural MRI scanning. The SEA subscores of theory of mind, reversal-learning tests, facial emotion identification, and apathy evaluation were entered as covariates in a voxel-based morphometry analysis. The results revealed that the gray matter volume in the rostral part of the medial prefrontal cortex [mPFC, Brodmann area (BA) 10] was associated with scores on the theory of mind subtest, while gray matter volume within the orbitofrontal (OFC) and ventral mPFC (BA 11 and 47) was related to the scores observed in the reversal-learning subtest. Gray matter volume within BA 9 in the mPFC was correlated with scores on the emotion recognition subtest, and the severity of apathetic symptoms in the Apathy scale covaried with gray matter volume in the lateral PFC (BA 44/45). Among these regions, the mPFC and OFC cortices have been shown to be atrophied in the early stages of bvFTD. In addition, SEA and its abbreviated version (mini-SEA) have been demonstrated to be sensitive to early impairments in bvFTD (Bertoux et al., 2012). Taken together, these results suggest a differential involvement of orbital and medial prefrontal subregions in SEA subscores and support the use of the SEA to evaluate the integrity of these regions in the early stages of bvFTD.

False

CitationGPTRetr1090

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Affective mentalizing and brain activity at rest in the behavioral variant of frontotemporal dementia. Abstract of the paper: BACKGROUND bvFTD patients display an impairment in the attribution of cognitive and affective states to others, reflecting GM atrophy in brain regions associated with social cognition, such as amygdala, superior temporal cortex and posterior insula. Distinctive patterns of abnormal brain functioning at rest have been reported in bvFTD, but their relationship with defective attribution of affective states has not been investigated. OBJECTIVE To investigate the relationship among resting-state brain activity, gray matter (GM) atrophy and the attribution of mental states in the behavioral variant of fronto-temporal degeneration (bvFTD). METHODS We compared 12 bvFTD patients with 30 age- and education-matched healthy controls on a) performance in a task requiring the attribution of affective vs. cognitive mental states; b) metrics of resting-state activity in known functional networks; and c) the relationship between task-performances and resting-state metrics. In addition, we assessed a connection between abnormal resting-state metrics and GM atrophy. RESULTS Compared with controls, bvFTD patients showed a reduction of intra-network coherent activity in several components, as well as decreased strength of activation in networks related to attentional processing. Anomalous resting-state activity involved networks which also displayed a significant reduction of GM density. In patients, compared with controls, higher affective mentalizing performance correlated with stronger functional connectivity between medial prefrontal sectors of the default-mode and attentional/performance monitoring networks, as well as with increased coherent activity in components of the executive, sensorimotor and fronto-limbic networks. CONCLUSIONS Some of the observed effects may reflect specific compensatory mechanisms for the atrophic changes involving regions in charge of affective mentalizing. The analysis of specific resting-state networks thus highlights an intermediate level of analysis between abnormal brain structure and impaired behavioral performance in bvFTD, reflecting both dysfunction and compensation mechanisms.

False

CitationGPTRetr1091

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Dominant hemisphere lateralization of cortical parasympathetic control as revealed by frontotemporal dementia. Abstract of the paper: The brain continuously influences and perceives the physiological condition of the body. Related cortical representations have been proposed to shape emotional experience and guide behavior. Although previous studies have identified brain regions recruited during autonomic processing, neurological lesion studies have yet to delineate the regions critical for maintaining autonomic outflow. Even greater controversy surrounds hemispheric lateralization along the parasympathetic-sympathetic axis. The behavioral variant of frontotemporal dementia (bvFTD), featuring progressive and often asymmetric degeneration that includes the frontoinsular and cingulate cortices, provides a unique lesion model for elucidating brain structures that control autonomic tone. Here, we show that bvFTD is associated with reduced baseline cardiac vagal tone and that this reduction correlates with left-lateralized functional and structural frontoinsular and cingulate cortex deficits and with reduced agreeableness. Our results suggest that networked brain regions in the dominant hemisphere are critical for maintaining an adaptive level of baseline parasympathetic outflow.

False

CitationGPTRetr1092

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Frontal paralimbic network atrophy in very mild behavioral variant frontotemporal dementia. Abstract of the paper: BACKGROUND Behavioral variant frontotemporal dementia (bvFTD) strikes hardest at the frontal lobes, but the sites of earliest injury remain unclear. OBJECTIVE To determine atrophy patterns in distinct clinical stages of bvFTD, testing the hypothesis that the mildest stage is restricted to frontal paralimbic cortex. DESIGN A bvFTD cohort study. SETTING University hospital dementia clinic. PARTICIPANTS Patients with bvFTD with Clinical Dementia Rating (CDR) scale scores of 0.5 (n = 15), 1 (n = 15), or 2 to 3 (n = 15) age and sex matched to each other and to 45 healthy controls. MAIN OUTCOME MEASURES Magnetic resonance voxel-based morphometry estimated gray matter and white matter atrophy at each disease stage compared with controls. RESULTS Patients with a CDR score of 0.5 had gray matter loss in frontal paralimbic cortices, but atrophy also involved a network of anterior cortical and subcortical regions. A CDR score of 1 showed more extensive frontal gray matter atrophy and white matter losses in corpus callosum and brainstem. A CDR score of 2 to 3 showed additional posterior insula, hippocampus, and parietal involvement, with white matter atrophy in presumed frontal projection fibers. CONCLUSIONS Very mild bvFTD targets a specific subset of frontal and insular regions. More advanced disease affects white matter and posterior gray matter structures densely interconnected with the sites of earliest injury.

False

CitationGPTRetr1093

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Abnormal salience network in normal aging and in amnestic mild cognitive impairment and Alzheimer's disease. Abstract of the paper: The salience network (SN) serves to identify salient stimuli and to switch between the central executive network (CEN) and the default-mode network (DMN), both of which are impaired in Alzheimer's disease (AD)/amnestic mild cognitive impairment (aMCI). We hypothesized that both the structural and functional organization of the SN and functional interactions between the SN and CEN/DMN are altered in normal aging and in AD/aMCI. Gray matter volume (GMV) and resting-state functional connectivity (FC) were analyzed from healthy younger (HYC) to older controls (HOC) and from HOC to aMCI and AD patients. All the SN components showed significant differences in the GMV, intranetwork FC, and internetwork FC between the HYC and HOC. Most of the SN components showed differences in the GMV between the HOC and AD and between the aMCI and AD. Compared with the HOC, AD patients exhibited significant differences in intra- and internetwork FCs of the SN, whereas aMCI patients demonstrated differences in internetwork FC of the SN. Most of the GMVs and internetwork FCs of the SN and part of the intranetwork FC of the SN were correlated with cognitive differences in older subjects. Our findings suggested that structural and functional impairments of the SN may occur as early as in normal aging and that functional disconnection between the SN and CEN/ DMN may also be associated with both normal aging and disease progression.

False

CitationGPTRetr1094

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Clinical utility of short social cognitive tests in early differentiation of behavioral variant frontotemporal dementia from Alzheimer's disease. Abstract of the paper: BACKGROUND Traditional cognitive tests used in clinical practice may not be sensitive enough for the early differentiation of behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD). A growing body of literature has shown that deficits in various aspects of social cognition can be found in bvFTD. AIM The objective of this study is to investigate whether short and easily administered tests of social cognition are useful in providing clinical information which might aid in the differentiation of bvFTD from AD in the early stages of bvFTD. METHODS 11 patients diagnosed with bvFTD and 10 patients diagnosed with AD completed a neuropsychological assessment comprising global, executive and social cognitive tasks. RESULTS Measures of global cognitive function showed no significant difference between the two groups, whereas even the short social cognitive measures (the Reading the Mind in the Eyes Test and the Emotion Hexagon) showed significant group differences, reflecting a poorer performance by the bvFTD group. CONCLUSION Our results suggest that it may indeed be relevant to include short and easily administered measures of social cognition in the differential diagnosis of early bvFTD and AD.

False

CitationGPTRetr1095

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Different functional connectivity and network topology in behavioral variant of frontotemporal dementia and Alzheimer's disease: an EEG study. Abstract of the paper: We investigated whether the functional connectivity and network topology in 69 Alzheimer's disease (AD), 48 behavioral variant of frontotemporal dementia (bvFTD) patients, and 64 individuals with subjective cognitive decline are different using resting-state electroencephalography recordings. Functional connectivity between all pairs of electroencephalography channels was assessed using the phase lag index (PLI). We subsequently calculated PLI-weighted networks, from which minimum spanning trees (MSTs) were constructed. Finally, we investigated the hierarchical clustering organization of the MSTs. Functional connectivity analysis showed frequency-dependent results: in the delta band, bvFTD showed highest whole-brain PLI; in the theta band, the whole-brain PLI in AD was higher than that in bvFTD; in the alpha band, AD showed lower whole-brain PLI compared with bvFTD and subjective cognitive decline. The MST results indicate that frontal networks appear to be selectively involved in bvFTD against the background of preserved global efficiency, whereas parietal and occipital loss of network organization in AD is accompanied by global efficiency loss. Our findings suggest different pathophysiological mechanisms in these 2 separate neurodegenerative disorders.

False

CitationGPTRetr1096

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: The pathogenesis of cingulate atrophy in behavioral variant frontotemporal dementia and Alzheimer's disease. Abstract of the paper: BACKGROUND Early atrophy of the cingulate cortex is a feature of both behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD), with degeneration of the anterior cingulate region increasingly recognized as a strong predictor of bvFTD. The total number of neurons in this region, rather than the density of neurons, is associated with mood disturbance in other dementias, although there are no data on the extent and magnitude of neuronal loss in patients with bvFTD. While the density of small populations of neurons in this region has been assessed, it is unlikely that the degree of atrophy of the cingulate cortex seen in bvFTD can be explained by the loss of these subpopulations. This suggests that there is more generalized degeneration of neurons in this region in bvFTD.The present study assesses total neuronal number, as well as characteristic pathologies, in the anterior and posterior cingulate cortices of pathologically confirmed bvFTD (N = 11) and AD (N = 9) patients compared with age-matched controls (N = 14). The bvFTD cohort comprised 5 cases with tau pathology (Pick's disease), and 6 with TDP-43 pathology. RESULTS At postmortem, atrophy was detected in the anterior and posterior cingulate cortices of bvFTD cases, but only in the posterior cingulate cortex of AD cases. As predicted, there was a significant reduction in both the density and total number of neurons in the anterior but not the posterior cingulate cortex of bvFTD cases with the opposite observed for the AD cases. Importantly, neuronal loss in the anterior cingulate cortex was only observed in cases with tau pathology. CONCLUSIONS This study confirms significant neuronal loss in the posterior but not anterior cingulate cortex in AD, and demonstrates that significant neuron loss in bvFTD occurs only in the anterior cingulate cortex but only in cases with tau pathology compared with cases with TDP pathology. We propose that significant neurodegeneration in the anterior cingulate cortex may be useful in differentiating the pathological subtypes in vivo.

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CitationGPTRetr1097

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Comparative cognitive neuropsychological studies of frontal lobe function: implications for therapeutic strategies in frontal variant frontotemporal dementia. Abstract of the paper: Patients with mild frontal variant frontotemporal dementia (fvFTD) who attend the clinic are usually unaware of the pervasive changes in their personality and behaviour, despite the fact it is these changes which have prompted the referral from the patient's spouse or carer. Comparative studies across various species offer unique insights into the heterogeneous structure and functions of the prefrontal cortex, and can allow a novel approach to the precise identification of the neuropsychological deficits present in these patients. We have found that they may show marked deficits on tests sensitive to ventromedial prefrontal or orbitofrontal function, in the relative absence of impairments on tests sensitive to dorsolateral prefrontal function. We highlight important differences in the neurocognitive profile of these patients with that of patients with other neurodegenerative conditions, including basal ganglia diseases and dementia of the Alzheimer type. The specific nature of these neuropsychological deficits, together with converging evidence from clinical and neuropathological studies, may provide useful clues about the predominant locus of dysfunction in the early stages of fvFTD and possible underlying neurotransmitter abnormalities. This is important for the successful development of therapeutic intervention strategies for both cognitive and behavioural symptoms in fvFTD. Finally, we evaluate critically the rationales for therapeutic modulation of noradrenergic, serotonergic and dopaminergic neurotransmitter systems at various stages of disease.

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CitationGPTRetr1098

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Network dysfunction in Alzheimer's disease and frontotemporal dementia: implications for psychiatry. Abstract of the paper: Structural and functional connectivity methods are changing how researchers conceptualize and explore neuropsychiatric disease. Here, we summarize emerging evidence of large-scale network dysfunction in Alzheimer's disease and behavioral variant frontotemporal dementia, focusing on the divergent impact these disorders have on the default mode network and the salience network. We update a working model for understanding the functions of these networks within a broader anatomical context and highlight the relevance of this model for understanding psychiatric illness. Finally, we look ahead to persistent challenges in the application of network-based imaging methods to patients with Alzheimer's disease, behavioral variant frontotemporal dementia, and other neuropsychiatric conditions. Recent advances and persistent needs are discussed, with an eye toward anticipating the hurdles that must be overcome for a network-based framework to clarify the biology of psychiatric illness and aid in the drug discovery process.

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CitationGPTRetr1099

Predict the citation correlation between the following sentence and a biomedical paper represented by the provided title and abstract. Sentence: compared with bvftd bvad participants showed less involvement of the salience network which is one of the networks that regulate socioemotional processing and social cognition alongside the semantic appraisal network and components of the default mode network moreover neuropathological small samples of patients with bvad suggested that they may not show a selective loss of von economo neurons in the anterior cingulate cortex which are specialized neurons located within key regions of the salience network that serve social functioning in humans and highly intelligent mammals therefore traditional regions implicated in social cognition in bvftd may not underlie social cognition deficits in bvad Title of the paper: Longitudinal Memory Profiles in Behavioral-Variant Frontotemporal Dementia and Alzheimer's Disease. Abstract of the paper: BACKGROUND Alzheimer's disease (AD) and behavioral-variant of frontotemporal dementia (bvFTD) can present with an overlapping neuropsychological profile, which often hinders their clinical differentiation. OBJECTIVE To compare changes over time in memory, general cognition tasks, and functional scales between bvFTD and AD. METHODS Consecutive cases diagnosed with probable bvFTD (n = 22) and typical AD (n = 31) with at least two clinical visits were selected. Of these, 13 (9 AD, 4 bvFTD) underwent Pittsburgh compound B PET scan, which supported the clinical diagnosis in all cases. Mixed-model regressions were used to estimate the differential rate of decline on selected tasks between cohorts. RESULTS Analyses demonstrated that, despite equivalent baseline performance, bvFTD patients experienced a more rapid functional deterioration and a steeper decline in global cognition than AD patients. At baseline, both groups were impaired on executive function and memory tasks compared to controls, but these deficits were more marked in the bvFTD group. In addition, performance on these domains continued to decline more rapidly in this group. CONCLUSIONS Neither the initial neuropsychological assessment nor projected performances can reliably distinguish the totality of bvFTD and AD individuals. Nevertheless, annual rates of progression on cognitive tasks provide valuable information and will potentially help establish the impact of future therapeutic treatments in these dementia syndromes.

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