Miracle-dz/UniFAR-FTUs huggingface dataset:
Perinatal Arterial Ischemic Stroke Is Associated to Materno-Fetal Immune Activation and Intracranial Arteritis

The medium-size intra-cranial arteries arising from the carotid bifurcation are prone to perinatal arterial ischemic strokes (PAIS). PAIS’ physiopathology needs to be better understood to develop preventive and therapeutic interventions that are currently missing. We hypothesized that materno-fetal inflammation leads to a vasculitis affecting selectively the carotidian tree and promoting a focal thrombosis and subsequent stroke. Dams were injected with saline or lipopolysaccharide (LPS) from Escherichia coli. A prothrombotic stress was applied on LPS-exposed vs. saline (S)-exposed middle cerebral arteries (MCA). Immunolabeling detected the inflammatory markers of interest. In S-exposed newborn pups, a constitutive higher density of macrophages combined to higher expressions of tumor necrosis factor-α (TNF-α), and interleukin 1β (IL-1β) was observed within the wall of intra- vs. extra-cranial cervicocephalic arteries. LPS-induced maternal and placental inflammatory responses mediated by IL-1β, TNF-α and monocyte chemotactic protein 1 (MCP-1) were associated with: (i) increased density of pro-inflammatory macrophages (M1 phenotype); and (ii) pro-inflammatory orientation of the IL-1 system (IL-1β/IL-1 receptor antagonist (IL-1Ra) ratio) within the wall of LPS-, vs. S-exposed, intra-cranial arteries susceptible to PAIS. LPS plus photothrombosis, but not sole photothrombosis, triggered ischemic strokes and subsequent motor impairments. Based on these preclinical results, the combination of pro-thrombotic stress and selective intra-cranial arteritis arising from end gestational maternal immune activation seem to play a role in the pathophysiology of human PAIS.
Application of a Novel Neural Approach to 3D Gaze Tracking: Vergence Eye-Movements in Autostereograms

Vergence eye-movements occur not only in real environ- ments, but also in virtual 3D environments. Autostere- ograms can cover large visual angles without requiring vergence beyond natural parameters and are thus well- suited for the investigation of vergence movements in virtual 3D images. We developed an anaglyph-based 3D calibration procedure and used a parametrized self- organizing map (PSOM) to approximate the 3D gaze point from a subject's binocular eye-movement data. Besides analyzing the general pattern of vergence eye- movements in autostereogram images, the present study examined the in∞uence of image granularity on these movements. Unlike previous research on random-dot stereograms, we found substantially overshooting con- vergence eye-movements, especially for medium gran- ularities. Moreover, divergence movements were com- pleted more quickly for coarse than for One granularities. Results are discussed in the context of granularity eAEects on autostereogram perception and the dissociation be- tween convergence and divergence eye-movements.
Recessively inherited parkinsonism: effect of ATP13A2 mutations on the clinical and neuroimaging phenotype.

OBJECTIVE To determine clinical features and to identify changes in brain structure and function in compound heterozygous and heterozygous ATP13A2 mutation carriers. DESIGN Prospective multimodal clinical and neuroimaging study. SETTING University of Lübeck, Lübeck, Germany. PARTICIPANTS Eight family members of a large Chilean pedigree with Kufor-Rakeb syndrome (KRS). INTERVENTIONS Clinical characterization, dopamine transporter (DAT) imaging, voxel-based morphometry (VBM), and transcranial sonography (TCS). MAIN OUTCOME MEASURES Frequency of parkinsonian signs, brain structure, and functional alterations. RESULTS The only available patient with compound heterozygous KRS showed a markedly reduced striatal DAT density bilaterally. Magnetic resonance imaging revealed severe global brain atrophy as well as iron deposition in the basal ganglia. The heterozygous mother had definite parkinsonism with reduced DAT density in both putamina. While all asymptomatic heterozygous siblings displayed subtle extrapyramidal signs, DAT imaging revealed striatal tracer uptake within physiological levels. Voxel-based morphometry revealed an increase in gray matter volume in the right putamen and a decrease in the cerebellum of the heterozygous carriers. In all mutation carriers, the substantia nigra had a normal appearance on TCS. CONCLUSIONS Single ATP13A2 heterozygous mutations may be associated with clinical signs of parkinsonism and contribute to structural and functional brain changes. Lack of hyperechogenicity in the substantia nigra may be a distinctive feature of this form of genetic parkinsonism. This, along with the finding of iron in the basal ganglia in our patient with KRS, implies a different underlying pathophysiology compared with other monogenic forms of parkinsonism and idiopathic PD and may place KRS among the syndromes of neurodegeneration with brain iron accumulation (NBIA).
Random Keys on ICE: Marginal Product Factorized Probability Distributions in Permutation Optimization

In this paper, we discuss multivariately factorized probability distributions for permutation random variables and a greedy approach to estimating these probability distributions from data. We use the representation known as random keys for permutations. The major benefit of using random keys is that no infeasible solution can be generated if crossover is applied in an evolutionary algorithm (EA). The estimated multivariately factorized probability distribution can be used to construct a linkage friendly crossover operator with which new offspring can be generated. We call the EA that uses this technique to construct a crossover operator, ICE. This technical report specifically presents the details of estimating multivariately factorized probability distributions for permutations using the random keys representation. As such, this paper is a extension of an earlier publication in which experiments with an EA that follows this approach have been reported as well [7].
Magnetic Resonance Imaging and Computed Tomography Characteristics of Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusion

Purpose To characterize Xp11.2 translocation renal cell carcinoma (RCC) using magnetic resonance imaging (MRI) and computed tomography (CT). Methods This study retrospectively collected the MRI and CT data of twelve patients with Xp11.2 translocation RCC confirmed by pathology. Nine cases underwent dynamic contrast-enhanced MRI (DCE-MRI) and 6 cases underwent CT, of which 3 cases underwent MRI and CT simultaneously. The MRI and CT findings were analyzed in regard to tumor position, size, hemorrhagic, cystic or necrotic components, calcification, tumor density, signal intensity and enhancement features. Results The age of the 12 patients ranged from 13 to 46 years (mean age: 23 years). T2WI revealed heterogeneous intensity, hyper-intensity, and slight hypo-intensity in 6 cases, 2 cases, and 1 case, respectively. On DCE-MR images, mild, moderate, and marked rim enhancement of the tumor in the corticomedullary phase (CMP) were observed in 1, 6, and 2 cases, respectively. The tumor parenchyma showed iso-attenuation (n = 4) or slight hyper-attenuation (n = 1) compared to the normal renal cortex on non-contrast CT images. Imaging findings were suggestive of hemorrhage (n = 4) or necrosis (n = 8) in the tumors, and there was evidence of calcification in 8 cases by CT (n = 3) and pathology (n = 8). On dynamic contrast-enhanced CT images, 3 cases and 1 case manifested moderate and strong CMP enhancement, respectively. Nine tumors by MRI and 4 tumors by CT showed prolonged enhancement. Three neoplasms presented at stage I, 2 at stage II, 3 at stage III, and 4 at stage IV according the 2010 AJCC staging criteria. Conclusions XP11.2 translocation RCC should be considered when a child or young adult patient presents with a renal tumor with heterogeneous features such as hemorrhage, necrosis, cystic changes, and calcification on CT and MRI and/or is accompanied by metastatic evidence.
Phages of Listeria offer novel tools for diagnostics and biocontrol

Historically, bacteriophages infecting their hosts have perhaps been best known and even notorious for being a nuisance in dairy-fermentation processes. However, with the rapid progress in molecular microbiology and microbial ecology, a new dawn has risen for phages. This review will provide an overview on possible uses and applications of Listeria phages, including phage-typing, reporter phage for bacterial diagnostics, and use of phage as biocontrol agents for food safety. The use of phage-encoded enzymes such as endolysins for the detection and as antimicrobial agent will also be addressed. Desirable properties of candidate phages for biocontrol will be discussed. While emphasizing the enormous future potential for applications, we will also consider some of the intrinsic limitations dictated by both phage and bacterial ecology.
Regulation of Neurogenesis in Adult Mouse Hippocampus by cAMP and the cAMP Response Element-Binding Protein

The cAMP cascade, including the cAMP response element-binding protein (CREB), is known to play an important role in neuronal survival and plasticity. Here the influence of this cascade on neurogenesis in adult hippocampus was determined. Activation of the cAMP cascade by administration of rolipram, an inhibitor of cAMP breakdown, increased the proliferation of newborn cells in adult mouse hippocampus. In addition, rolipram induction of cell proliferation resulted in mature granule cells that express neuronal-specific markers. Increased cell proliferation is accompanied by activation of CREB phosphorylation in dentate gyrus granule cells, suggesting a role for this transcription factor. This possibility is supported by studies demonstrating that cell proliferation is decreased in conditional transgenic mice that express a dominant negative mutant of CREB in hippocampus. The results suggest that the cAMP–CREB cascade could contribute to the actions of neurotransmitters and neurotrophic factors on adult neurogenesis.
Intersegmental Coordination of Cockroach Locomotion: Adaptive Control of Centrally Coupled Pattern Generator Circuits

Animals’ ability to demonstrate both stereotyped and adaptive locomotor behavior is largely dependent on the interplay between centrally generated motor patterns and the sensory inputs that shape them. We utilized a combined experimental and theoretical approach to investigate the relative importance of CPG interconnections vs. intersegmental afferents in the cockroach: an animal that is renowned for rapid and stable locomotion. We simultaneously recorded coxal levator and depressor motor neurons (MN) in the thoracic ganglia of Periplaneta americana, while sensory feedback was completely blocked or allowed only from one intact stepping leg. In the absence of sensory feedback, we observed a coordination pattern with consistent phase relationship that shares similarities with a double-tripod gait, suggesting central, feedforward control. This intersegmental coordination pattern was then reinforced in the presence of sensory feedback from a single stepping leg. Specifically, we report on transient stabilization of phase differences between activity recorded in the middle and hind thoracic MN following individual front-leg steps, suggesting a role for afferent phasic information in the coordination of motor circuits at the different hemiganglia. Data were further analyzed using stochastic models of coupled oscillators and maximum likelihood techniques to estimate underlying physiological parameters, such as uncoupled endogenous frequencies of hemisegmental oscillators and coupling strengths and directions. We found that descending ipsilateral coupling is stronger than ascending coupling, while left–right coupling in both the meso- and meta-thoracic ganglia appear to be symmetrical. We discuss these results in comparison with recent findings in stick insects that share similar neural and body architectures, and argue that the two species may exemplify opposite extremes of a fast–slow locomotion continuum, mediated through different intersegment coordination strategies.
Neurochemical and Behavioral Effects Related to 5-HT1B/1D Receptors

Abstract The lack of selective agonists and antagonists for serotonin 5-HT1B/1D receptors has made it difficult to determine the neurochemical, behavioral, and clinical effects controlled by 5-HT1B/1D receptors. However, by combining data from various compounds with different receptor affinity profiles, it is possible to tentatively determine those effects that result from interactions at the 5-HT1B/1D receptors. This discussion contains a review of the in vitro and in vivo neuropharmacology of the 5-HT1B/1D group of receptor subtypes, and attempts to identify their possible functions and potential implications in central nervous system disorders.
Hip Arthroplasty for Salvage of Failed Treatment of Intertrochanteric Hip Fractures

Background: Failed treatment of an intertrochanteric fracture typically leads to profound functional disability and pain. Treatment with repeated attempts to gain union and to preserve the host femoral head usually is preferred for young patients, but salvage treatment with hip arthroplasty may be considered for selected older patients with poor bone quality, bone loss, or articular cartilage damage. The purpose of the present study was to evaluate the results and complications of hip arthroplasty performed as a salvage procedure after the failed treatment of an intertrochanteric hip fracture. Methods: Between 1985 and 1997, sixty patients (forty-nine women and eleven men) with a mean age of seventy-eight years were treated at our institution with hip arthroplasty after the failed treatment of an intertrochanteric fracture. Thirty-two patients had a total hip arthroplasty with a cemented cup (twenty-four patients) or an uncemented cup (eight patients), twenty-seven had a bipolar hemiarthroplasty, and one had a unipolar hemiarthroplasty. A calcar-replacement design, extended-neck stem, or long-stem implant was used in fifty-one of the sixty hips. Results: Ten patients died within two years (all with the implant intact), and six were lost to follow-up. The remaining forty-four patients were followed for a mean of five years (range, two to fifteen years). At the time of the last follow-up, thirty-nine patients had no or mild pain and five had moderate or severe pain; in all of these patients, the pain was in the region of the greater trochanter. Forty patients were able to walk, twenty-six with one-arm support or less. Twelve patients had a total of thirteen medical complications postoperatively. A total of five reoperations were performed: two patients had a revision, one had a rewiring procedure because of trochanteric avulsion, one had late removal of trochanteric hardware, and one had débridement of fat necrosis. One patient had two dislocations, both of which were treated with closed reduction. Kaplan-Meier survivorship analysis with revision of the implant for any reason as the end point revealed a survival rate of 100% at seven years and 87.5% (95% confidence interval, 67.3% to 100%) at ten years. Conclusions: Hip arthroplasty is an effective salvage procedure after the failed treatment of an intertrochanteric fracture in an older patient. Most patients have good pain relief and functional improvement. Calcar-replacement and long-stem implants often are required. Despite the operative challenges, surprisingly few serious orthopaedic complications were associated with this procedure in the present study. Level of Evidence: Therapeutic study, Level IV (case series [no, or historical, control group]). See Instructions to Authors for a complete description of levels of evidence.
Effect of Cultivation Methods on Wood Static Bending Properties in Alnus Glutinosa

This study was carried out to determine radial variation of wood density, modulus of elasticity (MOE), modulus of rupture (MOR) and stress at elastic limit in plantation and natural alder (Alnus glutinosa) forests in north of Iran. Testing samples were taken at breast height of the stem and at three radial positions (10, 50 and 90 % of radius) for both cultivation methods (natural and plantation forests) to determine wood mechanical strength properties according to the ASTM standard. Analysis of variance indicated that cultivation methods (natural and plantation forest), radial position and interaction between planting position and radial direction had no significant effects on the modulus of elasticity (MOE), modulus of rupture (MOR) and stress at elastic limit in alder wood. Only the radial position had a significant effect on the wood density. Wood density was increased along radial direction from the pith to the periphery for both planting conditions. Overall, the mechanical strength properties in plantation forest were slightly higher than in natural forest. The relationship between wood density and mechanical properties were analyzed by linear regression. A positive relationship was found between wood density and mechanical properties for both planting conditions. These relationships were stronger in plantation forest than in natural forest.
Biology of Human Tumors Kidney Cancer Is Characterized by Aberrant Methylation of Tissue-Speci fi c Enhancers That Are Prognostic for Overall Survival

Purpose: Even though recent studies have shown that genetic changes at enhancers can influence carcinogenesis, most methylomic studies have focused on changes at promoters. We used renal cell carcinoma (RCC), an incurable malignancy associated with mutations in epigenetic regulators, as a model to study genome-wide patterns of DNA methylation at a high resolution. Experimental Design: Analysis of cytosine methylation status of 1.3 million CpGs was determined by the HELP assay in RCC and healthy microdissected renal tubular controls. Results: We observed that the RCC samples were characterized by widespread hypermethylation that preferentially affected gene bodies. Aberrant methylation was particularly enriched in kidney-specific enhancer regions associated with H3K4Me1 marks. Various important underexpressed genes, such as SMAD6, were associated with aberrantly methylated, intronic enhancers, and these changes were validated in an independent cohort. MOTIF analysis of aberrantly hypermethylated regions revealed enrichment for binding sites of AP2a, AHR, HAIRY, ARNT, and HIF1 transcription factors, reflecting contributions of dysregulated hypoxia signaling pathways in RCC. The functional importance of this aberrant hypermethylation was demonstrated by selective sensitivity of RCC cells to low levels of decitabine. Most importantly, methylationof enhancerswas predictive of adverse prognosis in 405 cases of RCC inmultivariate analysis. In addition, parallel copy-number analysis from MspI representations demonstrated novel copy-number variations that were validated in an independent cohort of patients. Conclusions:Our study is the first high-resolutionmethylome analysis of RCC, demonstrates thatmany kidney-specific enhancers are targeted by aberrant hypermethylation, and reveals the prognostic importance of these epigenetic changes in an independent cohort. Clin Cancer Res; 20(16); 4349–60. 2014 AACR.
Anomalistic Psychology: Exploring Paranormal Belief and Experience

Ever since records began, in every known society, a substantial proportion of the population has reported unusual experiences many of which we would today label as “paranormal”. Opinion polls show that the majority of the general public accepts that paranormal phenomena do occur. Such widespread experience of and belief in the paranormal can only mean one of two things. Either the paranormal is real, in which case this should be accepted by the wider scientific community which currently rejects such claims; or else belief in and experience of ostensibly paranormal phenomena can be fully explained in terms of psychological factors. This presentation will provide an introduction to the sub-discipline of anomalistic psychology, which may be defined as the study of extraordinary phenomena of behaviour and experience, in an attempt to provide nonparanormal explanations in terms of known psychological and physical factors. This approach will be illustrated with examples relating to a range of ostensibly paranormal phenomena.
Serial MR imaging of experimental autoimmune encephalomyelitis induced by human white matter or by chimeric myelin-basic and proteolipid protein in the common marmoset.

BACKGROUND AND PURPOSE Experimental autoimmune encephalomyelitis (EAE) in the marmoset was monitored by serial MR imaging to determine correlates to the natural-history MR studies in multiple sclerosis (MS). The relationships of MR-revealed lesions to clinical status and histopathologic findings were also explored. METHODS We induced EAE by subcutaneous inoculation in two marmosets by human white matter (HWM) and in seven marmosets by MP4 (a chimeric recombinant fusion protein of myelin-basic and proteolipid protein) in adjuvant along with intravenous inactivated pertussis vaccine to facilitate the disease process. The HWM-inoculated animals were induced with Freund's adjuvant as the established model of marmoset EAE. The MP4-inoculated animals were induced with either Freund's incomplete adjuvant or TiterMax as part of a preclinical treatment trial. MR imaging was performed at 1.5 T at baseline, and repeated at 1- to 2-week intervals for a period of up to 16 weeks in six EAE-induced marmosets, and intermittently for up to 70 weeks in three EAE-induced and two control marmosets. Proton density- (PD-) and T2-weighted, pre- and postgadopentetate dimeglumine enhancement, T1-weighted, and magnetization transfer (MT) images were obtained. The brains were prepared for histologic evaluation of lesion distribution and counts, characterization of lesions as demyelinating or inflammatory, and histopathologic scoring. The clinical, MR, and pathologic scoring were done on grading systems, and correlated for evaluation. RESULTS White matter (WM) changes after EAE induction were observed first at 9 days in the HWM-induced animals and at 2.5 weeks in the MP4-induced animals, with subsequent week-to-week fluctuations on PD- and T2-weighted images. Contrast-enhancing lesions were not observed in all animals. MR-revealed WM lesions correlated to histopathologic analysis of EAE lesions, measuring from 0.5 mm to 1.5 mm. The lesion count and extent of demyelination was greater in the HWM-induced animals than in the MP4-induced animals. Some MR-revealed lesions correlated directly to clinical symptoms, but the majority of lesions were clinically silent. CONCLUSION On MR images, lesions in the EAE marmoset model were confined to the WM, and their development, resolution, distribution, and enhancing characteristics fluctuated over the duration of the study. The dynamic presentation of MR-revealed lesions confirms the parallels between EAE in the marmoset and relapsing-remitting MS. Clinical symptoms alone were not representative of ongoing pathologic brain lesions. Therefore, serial MR imaging serves as a very important adjunct to clinical and histologic surveillance of the development of new and the persistence of existing brain lesions in this animal model of MS.