pinecone/core-2020-05-10-deduplication huggingface dataset:
Deep gray matter volume loss drives disability worsening in multiple sclerosis

Gray matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS. We analyzed 3,604 brain high‐resolution T1‐weighted magnetic resonance imaging scans from 1,417 participants: 1,214 MS patients (253 clinically isolated syndrome [CIS], 708 relapsing‐remitting [RRMS], 128 secondary‐progressive [SPMS], and 125 primary‐progressive [PPMS]), over an average follow‐up of 2.41 years (standard deviation [SD] = 1.97), and 203 healthy controls (HCs; average follow‐up = 1.83 year; SD = 1.77), attending seven European centers. Disability was assessed with the Expanded Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem, and cerebral white matter. Hierarchical mixed models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time‐to‐EDSS progression. SPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time‐to‐EDSS progression (hazard ratio = 0.73; 95% confidence interval, 0.65, 0.82; p < 0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow‐up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (–1.45%), PPMS (–1.66%), and RRMS (–1.34%) than CIS (–0.88%) and HCs (–0.94%; p < 0.01). The rate of temporal GM atrophy in SPMS (–1.21%) was significantly faster than RRMS (–0.76%), CIS (–0.75%), and HCs (–0.51%). Similarly, the rate of parietal GM atrophy in SPMS (–1.24‐%) was faster than CIS (–0.63%) and HCs (–0.23%; all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta = 0.04; p < 0.001). This large, multicenter and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions. Ann Neurol 2018;83:210–22
Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies.

In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the "central vein sign") improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as central nervous system (CNS) inflammatory vasculopathies, is lacking. In a multicenter study, we assessed the frequency of perivenular lesions in MS versus systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS).
In 31 patients with inflammatory CNS vasculopathies and 52 with relapsing-remitting MS, 3-dimensional T2*-weighted and T2-fluid-attenuated inversion recovery images were obtained during a single MRI acquisition after gadolinium injection. For each lesion, the central vein sign was evaluated according to consensus guidelines. For each patient, lesion count, volume, and brain location, as well as fulfillment of dissemination in space MRI criteria, were assessed.
MS showed higher frequency of perivenular lesions (median = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies, Behçet disease showed the highest median frequency of perivenular lesions (34%), followed by PACNS (14%), antiphospholipid syndromes (12%), Sjögren syndrome (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular lesions was applied, central vein sign discriminated MS from inflammatory vasculopathies with a diagnostic accuracy of 100%.
The central vein sign differentiates inflammatory CNS vasculopathies from MS at standard clinical magnetic field strengths. Ann Neurol 2018;83:283-294
Predicting clinical diagnosis in Huntington's disease: An imaging polymarker

Objective Huntington's disease (HD) gene carriers can be identified before clinical diagnosis; however, statistical models for predicting when overt motor symptoms will manifest are too imprecise to be useful at the level of the individual. Perfecting this prediction is integral to the search for disease modifying therapies. This study aimed to identify an imaging marker capable of reliably predicting real‐life clinical diagnosis in HD. Method A multivariate machine learning approach was applied to resting‐state and structural magnetic resonance imaging scans from 19 premanifest HD gene carriers (preHD, 8 of whom developed clinical disease in the 5 years postscanning) and 21 healthy controls. A classification model was developed using cross‐group comparisons between preHD and controls, and within the preHD group in relation to “estimated” and “actual” proximity to disease onset. Imaging measures were modeled individually, and combined, and permutation modeling robustly tested classification accuracy. Results Classification performance for preHDs versus controls was greatest when all measures were combined. The resulting polymarker predicted converters with high accuracy, including those who were not expected to manifest in that time scale based on the currently adopted statistical models. Interpretation We propose that a holistic multivariate machine learning treatment of brain abnormalities in the premanifest phase can be used to accurately identify those patients within 5 years of developing motor features of HD, with implications for prognostication and preclinical trials
Focal conduction block in the dorsal root ganglion in experimental allergic neuritis

Acute experimental allergic neuritis was induced in Lewis rats by inoculation with bovine intradural root myelin and adjuvants. In terminal experiments, sensory conduction was assessed in rats with hindlimb ataxia and weakness by stimulating the exposed sciatic nerve and recording directly from the exposed L-4 spinal nerve, dorsal root ganglion, dorsal root, and dorsal root entry zone. Focal conduction block was present in a high proportion of large-diameter fibers in the dorsal root ganglion. In contrast, nerve conduction in the peripheral nerve and spinal nerve was essentially normal apart from probable conduction block in some fibers in the proximal spinal nerve in a minority of rats. The afferent volley arriving at the dorsal root entry zone of the spinal cord was greatly reduced, as a consequence of the conduction block in the dorsal root ganglion and probable conduction block in the dorsal root. The M wave recorded from the fourth dorsal interosseus muscle of the hindfoot was normal in amplitude but slightly prolonged in latency and the H reflex was absent. These electrophysiological findings correlated well with the histological findings of inflammation and prominent demyelination in the dorsal root ganglia and dorsal roots with minimal involvement of the proximal spinal nerve and no involvement of the sciatic nerve. It is concluded that the hindlimb ataxia in rats with this form of acute experimental allergic neuritis is due to demyelination-induced nerve conduction block in the dorsal root ganglia and probably in the dorsal roots
Cortically evoked motor responses in patients with Xp22.3-linked Kallmann's syndrome and in female gene carriers

Patients with Kallmann's syndrome show hypothalamic hypogonadism, hyposmia, and congenital mirror movements. As a correlate, a defect of gonadotropic neuron migration into the brain was recently detected. Considering abnormal outgrowth of neurons also as a possible substrate underlying mirror movements, we studied 3 patients and 2 asymptomatic female gene carriers from a kindred with proven linkage to Xp22.3, using focal transcranial magnetic stimulation of motor cortex hand areas with a figure-eight coil. In all 3 affected brothers, bilateral responses could be evoked almost simultaneously in their thenar muscles (slight latency differences were statistically insignificant). In contrast, the mother and the maternal aunt showed only unilateral, normal thenar responses, even with maximum tolerable stimulator output and high signal amplification. Correspondingly, mirror movements were present in the patients, but not in the gene carriers. Bilaterality of cortically evoked hand muscle responses and mirror movements, therefore, behaved as X-chromosomal recessive traits. A likely cause might be a disorder of neuronal outgrowth in the motor system, particularly of inhibitory callosal fibers. For normal anatomical development of the motor system, one intact Xp22.3 gene seems necessary.
The apolipoprotein E ε2 allele is associated with an increased risk of early-onset Alzheimer's disease and a reduced survival

It was suggested that in contrast to the E4 allele, the E2 allele of the apolipoprotein E gene (APOE *2) has a protective effect for late-onset Alzheimer's disease and early-onset Alzheimer's disease (EOAD). We studied the role of the APOE*2 allele in the pathogenesis of EOAD in a Dutch population-based study of 175 probable EOAD patients with onset age at or before 65 years and 532 age-matched controls. In our population, there was no evidence for a protective effect of the APOE*2 allele on the risk of EOAD. However, our data show that among EOAD patients, survival for APOE*2 carriers was significantly reduced. When restricting the analysis to patients ascertained early after diagnosis at a stage of disease when mortality is low, our data suggest an increased risk of EOAD for subjects with APOE2E2, APOE2E3, APOE3E4, and APOE4E4 genotypes
Benzodiazepine receptor binding in cerebellar degenerations studied with positron emission tomography

We used positron emission tomography with [ 11 C]flumazenil to study gamma‐aminobutyric acid type A/benzodiazepine receptor binding quantitatively in the cerebral hemispheres, basal ganglia, thalamus, cerebellum, and brainstem of 72 subjects, including 14 with multiple system atrophy of the ataxic (olivopontocerebellar atrophy) type, 5 with multiple system atrophy of the extrapyramidal/autonomic (Shy‐Drager syndrome) type, 18 with sporadic olivoponto‐cerebellar atrophy, 15 with dominantly inherited olivopontocerebellar atrophy, and 20 normal control subjects with similar age and sex distributions. In comparison with data obtained from the normal control subjects, we found significantly Decemberreased ligand influx in the cerebellum and brainstem of multiple system atrophy patients of the olivopontocerebellar atrophy type and in patients with sporadic olivopontocerebellar atrophy, but not in patients with multiple system atrophy of the Shy‐Drager syndrome type. Despite these differences in ligand influx, benzodiazepine binding was largely preserved in the cerebral hemispheres, basal ganglia, thalamus, cerebellum, and brainstem in patients with multiple system atrophy of both types as well as those with sporadic or dominantly inhierited olivoponto‐cerebellar atrophy as compared with normal control subjects. The finding of relative preservation of benzodiazepine receptors indicates that these sites are available for pharmacological therapy in these disorders
A case-control study of apolipoprotein E genotypes in Alzheimer's disease associated with Down syndrome.

The prevalence of clinical signs and neuropathological findings of Alzheimer's disease (AD) is high in Down's syndrome (DS). In the general population, the apolipoprotein E (ApoE) epsilon 4 isoform is an important risk for AD. We studied the allelic frequencies of ApoE in 26 DS cases fulfilling clinical diagnostic criteria for AD and in 26 DS controls matched for age, sex, and premorbid level of mental retardation. A meta-analysis of data available in the literature was used for comparison with allele frequencies in other AD and control populations. ApoE type 2, 3, or 4 allele frequencies were not significantly different in AD-DS cases and DS controls. The ApoE epsilon 4 frequency in DS cases with AD (0.14; CI, 0.06-0.26) was significantly lower than in any other AD population studied so far and it is within the range of nondemented controls from the general population. These findings suggest that ApoE epsilon 4 does not significantly affect the pathogenesis of AD in DS patients
Genotype-phenotype correlation in adult-onset acid maltase deficiency

We performed a clinical, biochemical, and genetic study in 16 patients from 11 families with adult‐onset acid maltase deficiency. All patients were compound heterozygotes and carried the IVS1(– 13T→G) transversion on one allele; the second allele harbored either a deletion of a T at position 525 in exon 2 (7 probands, 64%) or a deletion of exon 18 (1 proband, 9%). Detrioration of handicap was related to age, and decrease in vital capacity to duration of the symptomatic stage. Respiratory insufficiency was never the first manifestation. The levels of activity of serum creatine kinase and of β‐glucosidase in peripheral blood cells or muscle were helpful for the diagnosis, but did not have prognostic value. The adult form of acid maltase deficiency appears to be both clinically and genetically rather homogeneous; decrease of β‐glucosidase activity is the final common pathway leading to destruction of muscle fibers and progression of muscle weakness over a period of years. Copyrigh
Apolipoprotein E genotype in patients with Alzheimer's disease: Implications for the risk of dementia among relatives

Numerous studies have shown that the risk of Alzheimer's disease (AD) is associated with the dose of the ϵ4 allele of apolipoprotein E (ApoE). However, more than one third of AD patients lack ϵ4 and many persons having ϵ4 survive cognitively intact to old age. We evaluated the lifetime risk of disease in 3,999 first‐degree relatives of 549 probands who met the criteria for probable or definite AD and whose ApoE genotypes were known. ApoE genotypes for relatives were not determined. After age 65 the risk among relatives was proportional, as much as 7 to 10% at age 85, to the number of ϵ4 alleles present in the proband. Risks to relatives of ApoE 2/2 and 2/3 probands were nearly identical at all ages to risks for relatives of ApoE 3/3 probands. The expected proportion of relatives having at least one ϵ4 allele was calculated for each genotype group based on the distribution of parents, sibs, and offspring in the sample. Among relatives in the ApoE 3/3 group, the lifetime risk for AD by age 90 was three times greater than the expected proportion of ϵ4 carriers, suggesting that factors other than ApoE contribute to AD susceptibility. Furthermore, the 44% risk of AD by age 93 among relatives of ApoE 4/4 probands indicates that as many as 50% of people having at least one ϵ4 allele do not develop AD. We also found that among male relatives, risk of AD in the ApoE 3/4 group was similar to that for the ApoE 3/3 group but significantly less than the risk for the ApoE 4/4 group. In contrast, among female relatives the risk for the ApoE 3/4 group was nearly twice that for the ApoE 3/3 group and identical to the risk for the ApoE 4/4 group. These findings are consistent with a sex‐modification effect of the E4 isoform on disease susceptibility. Copyrigh
Increased Circulating Antiganglioside Antibodies in Primary and Secondary Progressive Multiple Sclerosis

Plasma samples from 70 patients with multiple sclerosis (MS), 41 patients with other neurological diseases (OND), and 38 healthy subjects were examined for antibodies against gangliosides GM1, GM3, GDla, GD1b, and GD3 using enzyme-linked immunosorbent assays. The percentages of subjects with increased anti-GM3 responses were significantly higher in the primary progressive MS (56.3%) and secondary progressive MS (42.9%) groups than in the relapsing-remitting MS (2.9%), healthy subject (2.6%), and OND (14.6%) groups. Elevated antiganglioside antibodies may be secondary to axonal damage or may be a cause of axonal damage and accumulating disability in progressive MS. In either case, they may serve as a marker of axonal damage in MS
An advanced variant of an interpolatory graphical display algorithm

In this paper an advanced interpolatory graphical display algorithm based on cardinal B-spline functions is provided. It is well-known that B-spline functions are a flexible tool to design various scale rapresentations of a signal. The proposed method allows to display without recursion a function at any desiderable resolution so that only initial data and opportune vectors weight are involved. In this way the structure of the algorithm is independent across the scale and a computational efficiency is reached. In this paper mono and bi-dimensional vectors weight generated by means of centered cubic cardinal B-spline functions have been supplied
Modified moments and orthogonal rational functions

In a series of articles about the numerical computation of orthogonal polynomials on a subset of the real line, Gautschi shows that computing orthogonal polynomials starting from the moments µ_k = ∫ x^k dµ(x) of the measure is generally an ill-conditioned problem. However, in one of these papers an alternative approach is presented, based on so-called modified moments, which works better in certain situations. In this paper we generalize these results to the computation of orthogonal rational functions and provide a new modified moment algorithm, based on the connection between modified moments and interpolatory quadrature.status: publishe
Electrons in a Strong Magnetic Field on a Disk

The problem of interacting electrons moving under the influence of a strong
magnetic field in two dimensions on a finite disk is reconsidered. First, the
results of exact diagonalizations for up to $N=9$ electrons for Coulomb as well
as for a short--range interaction are used in the search for a peculiar ground
state corresponding to filling factor $1/3$. Not for the Coulomb, but only for
the short--range interaction, can the $1/3$--state be safely identified amongst
the spectra of various filling factors close to $1/3$. Second, the propositions
of the concept of quasiparticles, as used in the hierarchical theory, are
examined in view of the exact results for the disk geometry. Whereas the theory
for the quasiholes is in complete accordance with the spectra, for the
quasielectrons, finite size corrections make an analysis difficult. For the
quasielectron energy, an extrapolation to $N \rightarrow \infty$ is given and
compared with the corresponding extrapolations of three different proposals for
trial wave functions. While the limiting value for the best trial wave function
is very close to the limit of the exact results, the behavior of the finite
size corrections of the exact energies and of the trial wave functions,
respectively, is qualitatively rather different.Comment: 24 pages, 6 figures available upon request from W. Apel, LaTe
Towards a theory of the integer quantum Hall transition: from the
  nonlinear sigma model to superspin chains

A careful study of the supersymmetric version of Pruisken's nonlinear sigma
model for the integer quantum Hall effect is presented. The lattice regularized
model is cast in Hamiltonian form by taking the anisotropic limit and
interpreting the topological density as an alternating sum of Wess-Zumino
terms. It is argued that the relevant large-scale physics of the model is
preserved by projection of the quantum Hamiltonian on its sector of degenerate
strong-coupling ground states. For values of the Hall conductivity close to
e^2/2h (mod e^2/h), where a delocalization transition occurs, this yields the
Hamiltonian of a quantum superspin chain which is closely related to an
anisotropic version of the Chalker-Coddington model. The relation implies that
the ratio of magnetic length over potential correlation length is an irrelevant
parameter at the transition. The superspin chain resembles a 1d isotropic
antiferromagnet with spin 1/2. It has an alternating structure which however
permits an invariance under translation by one site. The conductance
coefficients of a quantum Hall system with N small contacts translate into
N-superspin correlation functions which are governed by conformal invariance.
The superspin formalism provides a framework for studying the crossover from
classical to quantum percolation. It does not however encompass the
frequency-dependent correlations of wave amplitudes at criticality.Comment: 64 pages, plain TEX, with 8 figures appended as uuencoded postscript
  files, to appear in Annalen der Physik (Germany
Simulations of Single Polymer Chains in the Dense Limit

We present simulation results for single a-thermal chain polymers in finite
volumes. For this we use a recently proposed recursive implementation of the
enrichment method. In 3 dimensions it allows the simulation of extremely long
chains (up to $N=300,000$). It is much less efficient for $d=2$, but we can
also there extend considerably the previously accessible range of chain lengths
and densities. We verify all tested scaling laws except one, and we point out
similarities with complex optimization problems.Comment: LATEX, 19 page
Ferromagnetism in the Hubbard model: instability of the Nagaoka state on
  the triangular, honeycomb and kagome lattices

In order to analyse the lattice dependence of ferromagnetism in the
two-dimensional Hubbard model we investigate the instability of the fully
polarized ferromagnetic ground state (Nagaoka state) on the triangular,
honeycomb and kagome lattices. We mainly focus on the local instability,
applying single spin flip variational wave functions which include majority
spin correlation effects. The question of global instability and phase
separation is addressed in the framework of Hartree-Fock theory. We find a
strong tendency towards Nagaoka ferromagnetism on the non-bipartite lattices
(triangular, kagome) for more than half filling. For the triangular lattice we
find the Nagaoka state to be unstable above a critical density of $n=1.887$ at
$U=\infty$, thereby significantly improving former variational results. For the
kagome lattice the region where ferromagnetism prevails in the phase diagram
widely exceeds the flat band regime. Our results even allow the stability of
the Nagaoka state in a small region below half filling. In the case of the
bipartite honeycomb lattice several disconnected regions are left for a
possible Nagaoka ground state.Comment: 31 pages + 11 figures, submitted as uuencoded compressed ps-file, to
  be published in Annalen der Physi
Transition from SU(2)_L x SU(2)_R x U(1)_(B-L) Representation to SU(2)_L
  x U(1)_Y by q-Deformation and the Corresponding Classical Breaking Term of
  Chiral U(2)

The minimal Standard Model exhibits a nontrivial chiral U(2) symmetry if the
vev and the hypercharge splitting (Delta) of right-handed leptons (quarks) in a
family vanish and Q=T_0 + Y independently in each helicity sector. As a
generalization, we start with SU(2)_L x SU(2)_R x U(1)_{(B-L)} and introduce
Delta as a continuous parameter which is a measure of explicit symmetry
breakdown. Values of Delta between zero and 1/2 take the neutral generator of
the isospin-1/2 representation to the singlet representation, i.e. `deformes'
the LR representation into the minimal Standard one. The corresponding
classical O(3)-breaking term is a magnetic field perpendicular to the x_3-axis.
A simple mapping on the fundamental Drinfeld-Jimbo q-deformed SU(2)
representation is given.Comment: DESY 94-129, 12 page