Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationship between neurochemical concentrations and neurofunctional measures in late-onset GM2 gangliosidosis

Magnetic resonance spectroscopy (MRS) and functional MRI (fMRI), related through common biophysical bases, provide complementary information about brain function. The link between MRS and fMRI measures is of interest, especially in the ultra-rare, metabolic disease late-onset GM2 gangliosidosis (LOGG). Imaging studies on LOGG have been few and far between, with cerebellar atrophy and neurochemical impairments being the most prominent findings. However, it remains unknown as to how these neurochemical aberrations relate to neurofunctional characteristics. The goal of this study (7 LOGG, 7 age/sex matched controls) was to assess the relationship between MRS concentrations and fMRI measures derived from the same MRS ROI (cerebellum, thalamus, precuneus) in LOGG. To quantify the communication between MRS regions and rest of the brain, we employed graph measures estimated from resting-state fMRI functional connectivity. We found that one such measure, local efficiency, which quantifies the aggregate relationship between a MRS region and rest of the brain, was significantly associated with N-acetylaspartate (NAA) in the cerebellum and thalamus (p<0.05, FDR corrected). Poorer neuronal health, neuronal loss (NAA), and neuroinflammation (myo-inositol) were related to poorer cerebellum-brain communication. Likewise, reduced thalamus-brain communication was also associated with poorer neuronal health and longer disease duration (p=0.002). These findings hint at a model of impaired neurochemical concentrations in these regions, leading to aberrant communication between them and rest of the brain, which may exacerbate disease progression. Future research must replicate these findings in larger cohorts, and further investigate such abnormalities in the cerebellum, thalamus and precuneus in this ultra-rare neurological disease.
The landscape of functional brain network impairments in late-onset GM2 gangliosidosis

Late-onset GM2 gangliosidosis (LOGG) is an ultra-rare neurological disease with motor, cognitive and psychiatric manifestations. It is caused by mutations in the HEXA or HEXB genes. Although cerebellar structural and metabolic impairments have been established, global brain functional impairments in this disease remain unknown. In this first functional MRI (fMRI) report on LOGG (N=14), we took an exploratory, multi-pronged approach by assessing impairments in several resting-state fMRI signal characteristics: fMRI signal strength, neurovascular coupling, static and time-varying functional connectivity, and network topology. Contrary to the predominance of cerebellar aberrations in prior non-functional studies, we found more widespread cortical aberrations (p<0.05, FDR-corrected) mainly in cognitive control networks but also in the default mode and somatomotor networks. There was reduced fMRI signal strength, enhanced neurovascular coupling, pathological hyper-connectivity, and altered temporal variability of connectivity in the LOGG cohort. We also observed an imbalance between functional segregation and integration as seen in other psychiatric/neurological disorders, with heightened segregation and suppressed integration (i.e., inefficient brain-wide communication). Some of these imaging markers were significantly associated with clinical measures, as well as with HEXA and HEXB gene expression. These aberrations might contribute to psychiatric symptoms (psychosis, mood disturbances), cognitive impairments (memory, attention, executive function), and oculomotor disturbances commonly seen in LOGG. Future LOGG imaging studies should probe brain function in addition to structure/metabolism while looking for mechanistic insights beyond the cerebellum.
Econometric Theory and Methods: International Edition

Econometric Theory and Methods International Edition provides a unified treatment of modern econometric theory and practical econometric methods. The geometrical approach to least squares is emphasized, as is the method of moments, which is used to motivate a wide variety of estimators and tests. Simulation methods, including the bootstrap, are introduced early and used extensively. The book deals with a large number of modern topics. In addition to bootstrap and Monte Carlo tests, these include sandwich covariance matrix estimators, artificial regressions, estimating functions and the generalized method of moments, indirect inference, and kernel estimation. Every chapter incorporates numerous exercises, some theoretical, some empirical, and many involving simulation.
Independence Conditions for Nets of Local Algebras as Sheaf Conditions

We apply constructions from topos-theoretic approaches to quantum theory to algebraic quantum field theory. Thus a net of operator algebras is reformulated as a functor that maps regions of spacetime into a category of ringed topoi. We ask whether this functor is a sheaf, a question which is related to the net satisfying certain kinematical independence conditions. In addition, we consider a C*-algebraic version of Nuiten’s recent sheaf condition, and demonstrate how it relates to C*-independence of the underlying net of operator algebras.
Hyperplastic melanocytes with chromosomal aberrations in surrounding skin of subungual melanoma: fluorescence in situ hybridisation analysis using whole‐slide digital imaging

Subungual melanoma (SUM) is increasingly being treated with conservative surgery. Consequently, the evaluation of the resection margins has increased in importance. However, in several cases it is difficult to distinguish the in‐situ lesion of SUM from hyperplastic melanocytes in the surrounding skin. We examined whether PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry and fluorescence in situ hybridisation (FISH) labelling of CCND1 (11q13), RREB1 (6p25), MYB (6q23), and centromere 6 (CEP6) genes differentiated SUM from hyperplastic melanocytes.
FluentSigners-50: A signer independent benchmark dataset for sign language processing

This paper presents a new large-scale signer independent dataset for Kazakh-Russian Sign Language (KRSL) for the purposes of Sign Language Processing. We envision it to serve as a new benchmark dataset for performance evaluations of Continuous Sign Language Recognition (CSLR) and Translation (CSLT) tasks. The proposed FluentSigners-50 dataset consists of 173 sentences performed by 50 KRSL signers resulting in 43,250 video samples. Dataset contributors recorded videos in real-life settings on a wide variety of backgrounds using various devices such as smartphones and web cameras. Therefore, distance to the camera, camera angles and aspect ratio, video quality, and frame rates varied for each dataset contributor. Additionally, the proposed dataset contains a high degree of linguistic and inter-signer variability and thus is a better training set for recognizing a real-life sign language. FluentSigners-50 baseline is established using two state-of-the-art methods, Stochastic CSLR and TSPNet. To this end, we carefully prepared three benchmark train-test splits for models’ evaluations in terms of: signer independence, age independence, and unseen sentences. FluentSigners-50 is publicly available at https://krslproject.github. io/FluentSigners-50/
MRI of Cerebrovascular Injury Associated With COVID-19 and Non-COVID-19 Acute Respiratory Distress Syndrome: A Matched Case-Control Study

OBJECTIVES: Cerebrovascular injury associated with COVID-19 has been recognized, but the mechanisms remain uncertain. Acute respiratory distress syndrome (ARDS) is a severe pulmonary injury, which is associated with both ischemic and hemorrhagic stroke. It remains unclear if cerebrovascular injuries associated with severe COVID-19 are unique to COVID-19 or a consequence of severe respiratory disease or its treatment. The frequency and patterns of cerebrovascular injury on brain MRI were compared among patients with COVID-19 ARDS and non-COVID-19 ARDS. DESIGN: A case-control study. SETTING: A tertiary academic hospital system PATIENTS: Adult patients (>18 yr) with COVID-19 ARDS (March 2020 to July 2021) and non-COVID-19 ARDS (January 2010-October 2018) who underwent brain MRI during their index hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cerebrovascular injury on MRI included cerebral ischemia (ischemic infarct or hypoxic ischemic brain injury) and intracranial hemorrhage (intraparenchymal, subarachnoid, or subdural, and cerebral microbleed [CMB]). Twenty-six patients with COVID-19 ARDS and sixty-six patients with non-COVID ARDS underwent brain MRI during the index hospitalization, resulting in 23 age- and sex-matched pairs. The frequency of overall cerebrovascular injury (57% vs 61%), cerebral ischemia (35% vs 43%), intracranial hemorrhage (43% vs 48%), and CMB (52% vs 41%) between COVID-19 ARDS and non-COVID-19 ARDS patients was similar (all p values >0.05). However, four of 26 patients (15%) with COVID-19 and no patients with non-COVID-19 ARDS had disseminated leukoencephalopathy with underlying CMBs, an imaging pattern that has previously been reported in patients with COVID-19. CONCLUSIONS: In a case-control study of selected ARDS patients with brain MRI, the frequencies of ischemic and hemorrhagic cerebrovascular injuries were similar between COVID-19 versus non-COVID-19 ARDS patients. However, the MRI pattern of disseminated hemorrhagic leukoencephalopathy was unique to the COVID-19 ARDS patients in this cohort.
Association between epidemiological and clinico-pathological features of breast cancer with prognosis, family history, Ki-67 proliferation index and survival in Tunisian breast cancer patients

Breast cancer has different epidemio-clinical characteristics in Middle East and North-African populations compared to those reported in the Western countries. The aim of this study is to analyze the epidemiological and clinico-pathological features of breast cancer in Tunisia and to determine prognostic factors with special interest to family history, Ki-67 proliferation index and comorbidity. We retrospectively reviewed epidemiological and clinico-pathological data from patients’ medical records, treated in the Medical Oncology Department at Abderrahmane Mami Hospital, in the period 2011–2015. Data has been collected on 602 breast cancer patients and analyzed using SPSS software V.23. 0. Our study showed high fractions of young breast cancer patients and cases with dense breasts. The most prevalent comorbidities observed in the studied cohort were cardiovascular diseases and diabetes. Familial breast cancer was found in 23.3% of cases and was associated with younger age at diagnosis (p<0.001) and advanced stage (p = 0.015). Ki-67 index >20% was significantly associated with early age at diagnosis, lymph node involvement (p = 0.002), advanced tumor grade (p<0.001) and high risk of relapse (p = 0.007). Ki-67 cut-off 30% predicted survival in luminal cases. Survival was worse in patients with triple negative breast cancer compared to non-triple negative breast cancer, inflammatory breast cancer compared to non-inflammatory breast cancer, moderately to poorly differentiated tumors compared to well-differentiated tumors and with positive lymph nodes compared to pN0 (p<0.05). Our study showed new insights into epidemiological and clinico-pathological characteristics of breast cancer that are not well explored in Tunisian population. Considering our findings along with the implementation of electronic health record system may improve patient health care quality and disease management.
Classical resonance interactions and Josephson junction in macroscopic quantum dynamics

It is shown that the classical dynamics of 1:1 resonance interaction between two identical linearly coupled Duffing oscillators is equivalent to the symmetric (non-biased) case of `macroscopic' quantum dynamics of two weakly coupled Bose-Einstein condensates. The analogy develops through the boson Josephson junction equations, however, reduced to a single conservative energy partition (EP) oscillator. The derived oscillator is solvable in quadratures, furthermore it admits asymptotic solution in terms of elementary functions after transition to the action-angle variables. Energy partition and coherency indexes are introduced to provide a complete characterization of the system dynamic states through the state variables of the EP oscillator. In particular, nonlinear normal and local mode dynamics of the original system associate with equilibrium points of such oscillator. Additional equilibrium points - the local modes - may occur on high energy level as a result of the symmetry breaking bifurcation, which is equivalent to the macroscopic quantum self-trapping effect in boson Josephson junction. Finally, since the Hamiltonian of EP oscillator is always quadratic with respect its linear momentum, the idea of second quantization can be explored without usual transition to the rigid pendulum approximation.
Do Placebos Primarily Affect Subjective as Opposed to Objective Measures? A Meta-Analysis of Placebo Responses in Insomnia RCTs

ABSTRACT Introduction: Little is known about the relative magnitude of placebo responses on objective and subjective measures of sleep continuity. To address this issue, the pre-post effects of placebos on objective and subjective measures (i.e., polysomnography [PSG] and sleep diaries) were evaluated meta-analytically. The guiding hypothesis was that large responses would be observed on sleep diary measures and small responses would be observed on PSG measures. Methods: PubMed searches, 1967–2016, yielded 329 possible articles, 17 of which met the inclusion and exclusion criteria for the present analysis (including 879 subjects with PSG data, 1,209 subjects with diary data, and six studies with both PSG and sleep diary data). Average change and weighted effect sizes (ESs) were computed via modeling for sleep latency (SL), wake after sleep onset (WASO) and total sleep time (TST). Results: Pre-to-post change on PSG measures were: SL −13.7 min., ES = −0.37; WASO −14.3 min., ES = −0.36; and TST 29.8 min., ES = 0.50. Pre-to-post change on sleep diary measures were: SL −13.5 min., ES = −0.36; WASO −13.3 min., ES = −0.20; and TST 25.5 min., ES = 0.36. The modeled average objective subjective difference per sleep continuity measure was less than 5 minutes. The modeled average objective subjective difference per sleep continuity measure (in effect sizes) was less than 0.17. Discussion: The observed outcomes of this analysis suggest that placebos produce comparable effects on objective and subjective measures of sleep continuity. Thus, objective measures do not appear to protect against placebo responses. This being the case and given the importance of the subjective experience of illness severity and recovery, such data suggests that prospectively sampled sleep continuity data (sleep diaries) may be the optimal data for clinical trials, particularly when only one measure is possible.
A recurrent prosthetic joint infection caused by Erysipelothrix rhusiopathiae: case report and literature review.

Prosthetic knee joint infection caused by Erysipelothrix rhusiopathiae is uncommon and only one case of recurrent infection has previously been described. Here, we describe the case of a 77-year-old male patient who was admitted to the teaching hospital of Rennes (France) with bilateral and nocturnal gonalgia evolving for 1 month. He had bilateral knee prosthesis 10 years ago, and a history of large B-cell lymphoma in remission. A diagnosis of infective endocarditis, with prosthetic knee infection, was made, with positive cultures of synovial fluids and blood; colonies of E. rhusiopathiae were identified by MALDI-TOF MS. Initial treatment involved debridement, implant retention surgery and intravenous amoxicillin (12 g day-1) for 6 weeks with gentamicin 3 mg kg-1 day-1 added for the first 4 days. One year later, a second episode of E. rhusiopathiae infection occurred, suggesting a recurrence or reinfection due to the same bacterial species. The patient was finally cured after a two-stage exchange with a cemented articulated spacer and a 3 month course of amoxicillin (12 g day-1, iv). Different characteristics of E. rhusiopathiae infection were discussed, with a review of all cases of prosthetic joint infections caused by Erysipelothrix species. This case highlights the need for a long-term survey of patients, and a good knowledge of their environment to avoid any risk of reinfection.
Electroacupuncture modulates gut microbiota in mice: A potential target in postoperative cognitive dysfunction

The detailed mechanism of inflammation in postoperative cognitive dysfunction (POCD) is unclear. This study aimed to determine whether electroacupuncture (EA) ameliorates POCD by modulating gut microbial dysbiosis. Compared to the control group, mice in the EA group were treated at the acupoints Zusanli (ST36), Quchi (L111), Baihui (GV20), and Dazhui (GV14) 1 week before appendectomy. Novel object recognition and the Morris water maze tests were used to assess learning and spatial reference memory deficits, whereas hippocampus samples and stool samples were collected for central inflammatory tests and 16S‐rRNA sequencing of intestinal flora, respectively. In amyloid precursor protein/presenilin 1 (APP/PS1) mice, EA enhanced spatial memory and learning deficits. The fecal microbial community was altered in APP/PS1 mice in the absence of EA following surgery. Among them, Coprococcus and Bacteroidetes were more abundant in the EA groups than in the control groups; however, Actinobacteriota, Helicobacteraceae, and Escherichia/shigella constitute the minor bacterial colonization in the EA groups. Furthermore, we found a significant negative correlation between Firmicutes and escape latency (Pearson correlation coefficient − 0.551, p < 0.01) and positive correlation between Proteobacteria and escape latency (Pearson correlation coefficient 0.462, p < 0.05). Electron microscopy revealed signs of blood–brain barrier (BBB) impairments and immunofluorescence images showed glial cells activated in the hippocampus of APP/PS mice without EA, and serum diamine oxidase levels were increased in these mice; whereas EA treatment significantly relieved the above pathological changes. Our findings implied that EA decreases hippocampal inflammation of APP/PS1 by upregulating benificial gut microbiota, reducing BBB and intestinal barrier dysfunction, thus alleviates postoperative cognitive dysfunction. This may provide a novel target in POCD management.
Role of autoantibody levels as biomarkers in the management of patients with myasthenia gravis: A systematic review and expert appraisal

Although myasthenia gravis (MG) is recognized as an immunoglobulin G autoantibody‐mediated disease, the relationship between autoantibody levels and disease activity in MG is unclear. We sought to evaluate this landscape through systematically assessing the evidence, testing the impact of predefined variables on any relationship, and augmenting with expert opinion.
Variance in translational fidelity of different bacterial species is affected by pseudouridines in the tRNA anticodon stem-loop

ABSTRACT Delicate variances in the translational machinery affect how efficiently different organisms approach protein synthesis. Determining the scale of this effect, however, requires knowledge on the differences of mistranslation levels. Here, we used a dual-luciferase reporter assay cloned into a broad host range plasmid to reveal the translational fidelity profiles of Pseudomonas putida, Pseudomonas aeruginosa and Escherichia coli. We observed that these profiles are surprisingly different, whereas species more prone to translational frameshifting are not necessarily more prone to stop codon readthrough. As tRNA modifications are among the factors that have been implicated to affect translation accuracy, we also show that translational fidelity is context-specifically influenced by pseudouridines in the anticodon stem-loop of tRNA, but the effect is not uniform between species.
Design and in silico analysis of mRNA vaccine construct against Salmonella

Abstract Salmonella infections are continuously growing. Causative serovars have gained enhanced drug resistance and virulence. Current vaccines have fallen short of providing sufficient protection. mRNA vaccines have come up with huge success against SARS-CoV-2; Pfizer-BioNTech and Moderna vaccines have resulted in >90% efficacy with efficient translocation, expression, and presentation of antigen to the host immune system. Herein, based on the same approach a mRNA vaccine construct has been designed and analyzed against Salmonella by joining regions of genes of outer membrane proteins C and F of S. Typhi through a flexible linker. Construct was flanked by regulatory regions that have previously shown better expression and translocation of encoded protein. GC content of the construct was improved to attain structural and thermodynamic stability and smooth translation. Sites of strong binding miRNAs were removed through codon optimization. Protein encoded by this construct is structurally plausible, highly antigenic, non-allergen to humans, and does not cross-react to the human proteome. It is enriched in potent, highly antigenic, and conserved linear and conformational epitopes. Most conserved conformational epitopes of core protein lie on extended beta hairpins exposed to the cellular exterior. Stability and thermodynamic attributes of the final construct were found highly comparable to the Pfizer-BioNTech vaccine construct. Both contain a stable stem-loop structure downstream of the start codon and do not offer destabilizing secondary structures upstream of the start codon. Given structural and thermodynamic stability, effective immune response, and epitope composition the construct is expected to provide broad-spectrum protection against clinically important Salmonella serovars. Communicated by Ramaswamy H. Sarma
THE EXACT SOLUTIONS TO THE GRAVITATIONAL CONTRACTION IN COMOVING COORDINATE SYSTEM

The gravitational collapse of a star is a warmly discussed but still puzzling problem, which not only involves the dynamics of the gases, but also the subtle coordinate transformation. In this letter, we give some more detailed investigation on this problem, and reach the results: (I). The comoving coordinate system for the stellar system is only compatible with the zero-pressure free falling particles. (II). For the free falling dust, there are three kind of solutions respectively corresponding to the oscillating, the critical and the open trajectories. The solution of Oppenheimer and Snyder is the critical case. (III). All solutions are exactly derived. There is a new kind singularity in the solution, but its origin is unclear.
Blobby accretion in magnetic cataclysmic variables

The processes of accretion of the gaseous blobs with different masses and densities onto strongly magnetized white dwarfs in the systems of polars have been modeled. We have proved that shot noise in blue wavelengths represents accretion of the smaller and denser blobs than in redder wavelengths. Using combined "smooth particle hydrodynamics - drag force" model, we have predicted a shape of the accretion stream and active regions on the white dwarf surface.