Clinical, Neuroimaging, and Genetic Markers in Cerebral Amyloid Angiopathy-Related Inflammation: A Systematic Review and Meta-Analysis

Background: There are limited data regarding the prevalence of distinct clinical, neuroimaging and genetic markers among patients diagnosed with cerebral amyloid angiopathy-related inflammation (CAA-ri). We sought to determine the prevalence of clinical, radiological, genetic and cerebrospinal fluid biomarker findings in patients with CAA-ri. Methods: A systematic review and meta-analysis of published studies including patients with CAA-ri was conducted to determine the prevalence of clinical, neuroimaging, genetic and cerebrospinal fluid biomarker findings. Subgroup analyses were performed based on (1) prospective or retrospective study design and (2) CAA-ri diagnosis with or without available biopsy. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using Cochran-Q and I2-statistics. Results: We identified 4 prospective and 17 retrospective cohort studies comprising 378 patients with CAA-ri (mean age, 71.5 years; women, 52%). The pooled prevalence rates were as follows: cognitive decline at presentation 70% ([95% CI, 54%-84%]; I2=82%), focal neurological deficits 55% ([95% CI, 40%-70%]; I2=82%), encephalopathy 54% ([95% CI, 39%-68%]; I2=43%), seizures 37% ([95% CI, 27%-49%]; I2=65%), headache 31% ([95% CI, 22%-42%]; I2=58%), T2/fluid-attenuated inversion recovery-hyperintense white matter lesions 98% ([95% CI, 93%-100%]; I2=44%), lobar cerebral microbleeds 96% ([95% CI, 92%-99%]; I2=25%), gadolinium enhancing lesions 54% ([95% CI, 42%-66%]; I2=62%), cortical superficial siderosis 51% ([95% CI, 34%-68%]; I2=77%) and lobar macrohemorrhage 40% ([95% CI, 11%-73%]; I2=88%). The prevalence rate of the ApoE (Apolipoprotein E) ϵ4/ϵ4 genotype was 34% ([95% CI, 17%-53%]; I2=76%). Subgroup analyses demonstrated no differences in these prevalence rates based on study design and diagnostic strategy. Conclusions: Cognitive decline was the most common clinical feature. Hyperintense T2/fluid-attenuated inversion recovery white matter lesions and lobar cerebral microbleeds were by far the most prevalent neuroimaging findings. Thirty-four percent of patients with CAA-ri have homozygous ApoE ϵ4/ϵ4 genotype and scarce data exist regarding the cerebrospinal fluid biomarkers and its significance in these patients

Sternalis muscle: an underestimated anterior chest wall anatomical variant

Over the recent years, an increased alertness for thorough knowledge of anatomical variants with clinical significance has been recorded in order to minimize the risks of surgical complications. We report a rare case of bilateral strap-like sternalis muscle of the anterior chest wall in a female cadaver. Its presence may evoke alterations in the electrocardiogram or confuse a routine mammography. The incidental finding of a sternalis muscle in mammography, CT, and MRI studies must be documented in a patient's medical records as it can be used as a pedicle flap or flap microvascular anastomosis during reconstructive surgery of the anterior chest wall, head and neck, and breast. Moreover, its presence may be misdiagnosed as a wide range of benign and malignant anterior chest wall lesions and tumors

Disease-Related Changes in the Cerebrospinal Fluid Metabolome in Amyotrophic Lateral Sclerosis Detected by GC/TOFMS

The changes in the cerebrospinal fluid (CSF) metabolome associated with the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are poorly understood and earlier smaller studies have shown conflicting results. The metabolomic methodology is suitable for screening large cohorts of samples. Global metabolomics can be used for detecting changes of metabolite concentrations in samples of fluids such as CSF.Using gas chromatography coupled to mass spectrometry (GC/TOFMS) and multivariate statistical modeling, we simultaneously studied the metabolome signature of ∼120 small metabolites in the CSF of patients with ALS, stratified according to hereditary disposition and clinical subtypes of ALS in relation to controls.The study is the first to report data validated over two sub-sets of ALS vs. control patients for a large set of metabolites analyzed by GC/TOFMS. We find that patients with sporadic amyotrophic lateral sclerosis (SALS) have a heterogeneous metabolite signature in the cerebrospinal fluid, in some patients being almost identical to controls. However, familial amyotrophic lateral sclerosis (FALS) without superoxide dismutase-1 gene (SOD1) mutation is less heterogeneous than SALS. The metabolome of the cerebrospinal fluid of 17 ALS patients with a SOD1 gene mutation was found to form a separate homogeneous group. Analysis of metabolites revealed that glutamate and glutamine were reduced, in particular in patients with a familial predisposition. There are significant differences in the metabolite profile and composition among patients with FALS, SALS and patients carrying a mutation in the SOD1 gene suggesting that the neurodegenerative process in different subtypes of ALS may be partially dissimilar.Patients with a genetic predisposition to amyotrophic lateral sclerosis have a more distinct and homogeneous signature than patients with a sporadic disease

1H-NMR-Based Metabolomic Profiling of CSF in Early Amyotrophic Lateral Sclerosis

Background: Pathophysiological mechanisms involved in amyotrophic lateral sclerosis (ALS) are complex and none has identified reliable markers useful in routine patient evaluation. The aim of this study was to analyze the CSF of patients with ALS by 1 H NMR (Nuclear Magnetic Resonance) spectroscopy in order to identify biomarkers in the early stages of the disease, and to evaluate the biochemical factors involved in ALS. Methodology: CSF samples were collected from patients with ALS at the time of diagnosis and from patients without neurodegenerative diseases. One and two-dimensional 1 H NMR analyses were performed and metabolites were quantified by the ERETIC method. We compared the concentrations of CSF metabolites between both groups. Finally, we performed principal component (PCA) and discriminant analyses. Principal Findings: Fifty CSF samples from ALS patients and 44 from controls were analyzed. We quantified 17 metabolites including amino-acids, organic acids, and ketone bodies. Quantitative analysis revealed significantly lower acetate concentrations (p = 0.0002) in ALS patients compared to controls. Concentration of acetone trended higher (p = 0.015), and those of pyruvate (p = 0.002) and ascorbate (p = 0.003) were higher in the ALS group. PCA demonstrated that the pattern of analyzed metabolites discriminated between groups. Discriminant analysis using an algorithm of 17 metabolites reveale

The impact of automated hippocampal volumetry on diagnostic confidence in patients with suspected Alzheimer's disease: an EADC study

INTRODUCTION: Hippocampal volume is a core biomarker of Alzheimer's disease (AD). However, its contribution over the standard diagnostic workup is unclear. METHODS: Three hundred fifty-six patients, under clinical evaluation for cognitive impairment, with suspected AD and Mini–Mental State Examination ≥20, were recruited across 17 European memory clinics. After the traditional diagnostic workup, diagnostic confidence of AD pathology (DCAD) was estimated by the physicians in charge. The latter were provided with the results of automated hippocampal volumetry in standardized format and DCAD was reassessed. RESULTS: An increment of one interquartile range in hippocampal volume was associated with a mean change of DCAD of −8.0% (95% credible interval: [−11.5, −5.0]). Automated hippocampal volumetry showed a statistically significant impact on DCAD beyond the contributions of neuropsychology, 18F-fluorodeoxyglucose positron emission tomography/single-photon emission computed tomography, and cerebrospinal fluid markers (−8.5, CrI: [−11.5, −5.6]; −14.1, CrI: [−19.3, −8.8]; −10.6, CrI: [−14.6, −6.1], respectively). DISCUSSION: There is a measurable effect of hippocampal volume on DCAD even when used on top of the traditional diagnostic workup

Measurement of the Higgs boson production via vector boson fusion and its decay into bottom quarks in proton-proton collisions at s \sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2308.01253v2 [hep-ex], https://arxiv.org/abs/2308.01253v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/HIG-22-009 (CMS Public Pages). Report number: CMS-HIG-22-009, CERN-EP-2023-110.A measurement of the Higgs boson (H) production via vector boson fusion (VBF) and its decay into a bottom quark-antiquark pair (bb¯) is presented using proton-proton collision data recorded by the CMS experiment at s√ = 13 TeV and corresponding to an integrated luminosity of 90.8 fb−1. Treating the gluon-gluon fusion process as a background and constraining its rate to the value expected in the standard model (SM) within uncertainties, the signal strength of the VBF process, defined as the ratio of the observed signal rate to that predicted by the SM, is measured to be μqqHHbb¯ = 1.01 +0.55−0.46. The VBF signal is observed with a significance of 2.4 standard deviations relative to the background prediction, while the expected significance is 2.7 standard deviations. Considering inclusive Higgs boson production and decay into bottom quarks, the signal strength is measured to be μincl.Hbb¯ = 0.99 +0.48−0.41, corresponding to an observed (expected) significance of 2.6 (2.9) standard deviations.SCOAP3, STFC; Marie-Curie program and the European Research Council and Horizon 2020 Gran

Search for new Higgs bosons via same-sign top quark pair production in association with a jet in proton-proton collisions at √s = 13 TeV

Data availability: Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in “CMS data preservation, re-use and open access policy” available online at: https://cms-docdb.cern.ch/cgi-bin/PublicDocDB/RetrieveFile?docid=6032&filename=CMSDataPolicyV1.2.pdf&version=2 .A preprint of this article is available online at arXiv:2311.03261v2 [hep-ex] https://arxiv.org/abs/2311.03261v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/TOP-22-010 (CMS Public Pages)A search is presented for new Higgs bosons in proton-proton (pp) collision events in which a same-sign top quark pair is produced in association with a jet, via the pp → tH/A → tt¯c and pp → tH/A → tt¯u processes. Here, H and A represent the extra scalar and pseudoscalar boson, respectively, of the second Higgs doublet in the generalized two-Higgs-doublet model (g2HDM). The search is based on pp collision data collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC, corresponding to an integrated luminosity of 138 fb−1. Final states with a same-sign lepton pair in association with jets and missing transverse momentum are considered. New Higgs bosons in the 200-1000 GeV mass range and new Yukawa couplings between 0.1 and 1.0 are targeted in the search, for scenarios in which either H or A appear alone, or in which they coexist and interfere. No significant excess above the standard model prediction is observed. Exclusion limits are derived in the context of the g2HDM.SCOAP3

Search for direct production of GeV-scale resonances decaying to a pair of muons in proton-proton collisions at s\sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2309.16003v2 [hep-ex], https://arxiv.org/abs/2309.16003v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables, including additional supplementary figures, can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/EXO-21-005 (CMS Public Pages). Report number: CMS-EXO-21-005, CERN-EP-2023-165.A search for direct production of low-mass dimuon resonances is performed using s√ = 13 TeV proton-proton collision data collected by the CMS experiment during the 2017-2018 operation of the CERN LHC with an integrated luminosity of 96.6 fb−1. The search exploits a dedicated high-rate trigger stream that records events with two muons with transverse momenta as low as 3 GeV but does not include the full event information. The search is performed by looking for narrow peaks in the dimuon mass spectrum in the ranges of 1.1-2.6 GeV and 4.2-7.9 GeV. No significant excess of events above the expectation from the standard model background is observed. Model-independent limits on production rates of dimuon resonances within the experimental fiducial acceptance are set. Competitive or world's best limits are set at 90% confidence level for a minimal dark photon model and for a scenario with two Higgs doublets and an extra complex scalar singlet (2HDM+S). Values of the squared kinetic mixing coefficient ε2 in the dark photon model above 10−6 are excluded over most of the mass range of the search. In the 2HDM+S, values of the mixing angle sin(θH) above 0.08 are excluded over most of the mass range of the search with a fixed ratio of the Higgs doublets vacuum expectation tanβ = 0.5.SCOAP3

Search for W′ bosons decaying to a top and a bottom quark in leptonic final states in proton-proton collisions at s \sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2310.19893v1 [hep-ex], https://arxiv.org/abs/2310.19893v1 . Comments: Submitted to the Journal of High Energy Physics. All figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/B2G-20-012 (CMS Public Pages). Report number: CMS-B2G-20-012, CERN-EP-2023-213.A search for W' bosons decaying to a top and a bottom quark in final states including an electron or a muon is performed with the CMS detector at the LHC. The analyzed data correspond to an integrated luminosity of 138 fb^{-1} of proton-proton collisions at a center-of-mass energy of 13 Tev. Good agreement with the standard model expectation is observed and no evidence for the existence of the W' boson is found over the mass range examined. The largest observed deviation from the standard model expectation is found for a W' boson mass (mW′) hypothesis of 3.8 TeV with a relative decay width of 1%, with a local (global) significance of 2.6 (2.0) standard deviations. Upper limits on the production cross sections of W' bosons decaying to a top and a bottom quark are set. Left- and right-handed W' bosons with mW′ below 3.9 and 4.3 TeV, respectively, are excluded at the 95% confidence level, under the assumption that the new particle has a narrow decay width. Limits are also set for relative decay widths up to 30%. These are the most stringent limits to date on this W' boson decay channel.SCOAP3

Search for long-lived heavy neutral leptons with lepton flavour conserving or violating decays to a jet and a charged lepton

A preprint version of the article is available at arXiv:2312.07484v3 [hep-ex], https://arxiv.org/abs/2312.07484 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/EXO-21-013 (CMS Public Pages)A search for long-lived heavy neutral leptons (HNLs) is presented, which considers the hadronic final state and coupling scenarios involving all three lepton generations in the 2-20 GeV HNL mass range for the first time. Events comprising two leptons (electrons or muons) and jets are analyzed in a data sample of proton-proton collisions, recorded with the CMS experiment at the CERN LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 138 fb−1. A novel jet tagger, based on a deep neural network, has been developed to identify jets from an HNL decay using various features of the jet and its constituent particles. The network output can be used as a powerful discriminating tool to probe a broad range of HNL lifetimes and masses. Contributions from background processes are determined from data. No excess of events in data over the expected background is observed. Upper limits on the HNL production cross section are derived as functions of the HNL mass and the three coupling strengths VℓN to each lepton generation ℓ and presented as exclusion limits in the coupling-mass plane, as lower limits on the HNL lifetime, and on the HNL mass. In this search, the most stringent limit on the coupling strength is obtained for pure muon coupling scenarios; values of |VμN|2 > 5 (4) × 10−7 are excluded for Dirac (Majorana) HNLs with a mass of 10 GeV at a confidence level of 95% that correspond to proper decay lengths of 17 (10) mm.SCOAP3