julilili42/papers huggingface dataset:
Subcortical shape alterations in major depressive disorder: Findings from the ENIGMA major depressive disorder working group
2020-03-21

Abstract Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD‐related differences in subcortical regions using shape analysis. In this meta‐analysis of subcortical shape from the ENIGMA‐MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta‐analysis. Relative to CTL, patients with adolescent‐onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = −0.164 to −0.180). Relative to first‐episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = − 0.173 to −0.184). Our results suggest that previously reported MDD‐associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.
Comparison of meniscal allograft transplantation techniques using a preclinical canine model
2020-03-21

Abstract Meniscal allograft transplantation (MAT) can be a safe, effective treatment for meniscal deficiency resulting in knee dysfunction, leading to osteoarthritis (OA) without proper treatment with 5‐year functional success rates (75%‐90%). While different grafts and techniques have generally proven safe and effective, complications include shrinkage, extrusion, progression of joint pathology, and failure. The objective of this study was to assess the functional outcomes after MAT using three different clinically‐relevant methods in a preclinical canine model. The study was designed to test the hypothesis that fresh meniscal‐osteochondral allograft transplantation would be associated with significantly better function and joint health compared with fresh‐viable or fresh‐frozen meniscus‐only allograft transplantations. Three months after meniscal release to induce meniscus‐deficient medial compartment disease, research hounds (n = 12) underwent MAT using meniscus allografts harvested from matched dogs. Three MAT conditions (n = 4 each) were compared: frozen meniscus–fresh‐frozen meniscal allograft with menisco‐capsular suture repair; fresh meniscus–fresh viable meniscal allograft (Missouri Osteochondral Preservation System (MOPS)‐preservation for 30 days) with menisco‐tibial ligament repair; fresh menisco‐tibial–fresh, viable meniscal‐tibial‐osteochondral allografts (MOPS‐preservation for 30 days) with menisco‐tibial ligament preservation and autogenous bone marrow aspirate concentrate on OCA bone. Assessment was performed up to 6 months after MAT. Pain, comfortable range of motion, imaging, and arthroscopic scores as well histological and cell viability findings were superior ( P &lt; .05) for the fresh menisco‐tibial group compared with the two other groups. Novel meniscal preservation and implantation techniques with fresh, MOPS‐preserved, viable meniscal‐osteochondral allografts with menisco‐tibial ligament preservation appears to be safe and effective for restoring knee function and joint health in this preclinical model. This has the potential to significantly improve outcomes after MAT.
The Lack of Evidence for an Association between Cancer Biomarker Conversion Patterns and CTC-Status in Patients with Metastatic Breast Cancer
2020-03-21

Circulating tumor cell (CTC) detection is a prognostic factor in the metastatic breast cancer (MBC) setting. Discrepancies in primary (PT) and metastatic tumor (MT) genetic profiles are also of prognostic importance. Our study aimed to compare the CTC statuses and prognoses between those with subtype stable MBCs and MBCs with specific biomarker conversions. The study enrolled 261 MBC patients, treated at the National Center for Tumor Diseases, Heidelberg, Germany in a five-year period. All underwent PT and MT biopsies and subsequent CTC enumeration before the initiation of systemic therapy. ER and HER2 statuses of the PTs and MTs were determined and progression free survivals (PFSs) and overall survivals (OSs) were recorded. We compared CTC statuses, CTC counts, PFSs and OSs between subgroups of patients with different receptor change patterns. Patients who had tumors that converted to triple negative MTs had the shortest median OSs, while HER2 expression was not associated with a shorter median OS. No significant differences in PFSs and OSs have been demonstrated by Kaplan-Meier curve comparisons in any of the subgroup analyses. CTC counts were similar in all subgroups. CTCs were comparably less frequently detected in patients with a stable HER2 expression. Similar proportions of CTC positives were observed in all other subtype change pattern subgroups, barring the aforementioned HER2 stable subgroup. The detection of CTCs was of no appreciable prognostic value in different receptor change pattern subgroups in our cohort.
Fibronectin Adsorption on Electrospun Synthetic Vascular Grafts Attracts Endothelial Progenitor Cells and Promotes Endothelialization in Dynamic In Vitro Culture
2020-03-23

Appropriate mechanical properties and fast endothelialization of synthetic grafts are key to ensure long-term functionality of implants. We used a newly developed biostable polyurethane elastomer (TPCU) to engineer electrospun vascular scaffolds with promising mechanical properties (E-modulus: 4.8 ± 0.6 MPa, burst pressure: 3326 ± 78 mmHg), which were biofunctionalized with fibronectin (FN) and decorin (DCN). Neither uncoated nor biofunctionalized TPCU scaffolds induced major adverse immune responses except for minor signs of polymorph nuclear cell activation. The in vivo endothelial progenitor cell homing potential of the biofunctionalized scaffolds was simulated in vitro by attracting endothelial colony-forming cells (ECFCs). Although DCN coating did attract ECFCs in combination with FN (FN + DCN), DCN-coated TPCU scaffolds showed a cell-repellent effect in the absence of FN. In a tissue-engineering approach, the electrospun and biofunctionalized tubular grafts were cultured with primary-isolated vascular endothelial cells in a custom-made bioreactor under dynamic conditions with the aim to engineer an advanced therapy medicinal product. Both FN and FN + DCN functionalization supported the formation of a confluent and functional endothelial layer.
Polystyrene microplastics do not affect juvenile brown trout (Salmo trutta f. fario) or modulate effects of the pesticide methiocarb
2020-03-23

Abstract Background There has been a rising interest within the scientific community and the public about the environmental risk related to the abundance of microplastics in aquatic environments. Up to now, however, scientific knowledge in this context has been scarce and insufficient for a reliable risk assessment. To remedy this scarcity of data, we investigated possible adverse effects of polystyrene particles (10 4 particles/L) and the pesticide methiocarb (1 mg/L) in juvenile brown trout ( Salmo trutta f. fario ) both by themselves as well as in combination after a 96 h laboratory exposure. PS beads (density 1.05 g/mL) were cryogenically milled and fractionated resulting in irregular-shaped particles (&lt; 50 μm). Besides body weight of the animals, biomarkers for proteotoxicity (stress protein family Hsp70), oxidative stress (superoxide dismutase, lipid peroxidation), and neurotoxicity (acetylcholinesterase, carboxylesterases) were analyzed. As an indicator of overall health, histopathological effects were studied in liver and gills of exposed fish. Results Polystyrene particles by themselves did not influence any of the investigated biomarkers. In contrast, the exposure to methiocarb led to a significant reduction of the activity of acetylcholinesterase and the two carboxylesterases. Moreover, the tissue integrity of liver and gills was impaired by the pesticide. Body weight, the oxidative stress and the stress protein levels were not influenced by methiocarb. Effects caused by co-exposure of polystyrene microplastics and methiocarb were the same as those caused by methiocarb alone. Conclusions Overall, methiocarb led to negative effects in juvenile brown trout. In contrast, polystyrene microplastics in the tested concentration did not affect the health of juvenile brown trout and did not modulate the toxicity of methiocarb in this fish species.
Light affects tissue patterning of the hypocotyl in the shade-avoidance response
2020-03-23

Plants have evolved strategies to avoid shade and optimize the capture of sunlight. While some species are tolerant to shade, plants such as Arabidopsis thaliana are shade-intolerant and induce elongation of their hypocotyl to outcompete neighboring plants. We report the identification of a developmental module acting downstream of shade perception controlling vascular patterning. We show that Arabidopsis plants react to shade by increasing the number and types of water-conducting tracheary elements in the vascular cylinder to maintain vascular density constant. Mutations in genes affecting vascular patterning impair the production of additional xylem and also show defects in the shade-induced hypocotyl elongation response. Comparative analysis of the shade-induced transcriptomes revealed differences between wild type and vascular patterning mutants and it appears that the latter mutants fail to induce sets of genes encoding biosynthetic and cell wall modifying enzymes. Our results thus set the stage for a deeper understanding of how growth and patterning are coordinated in a dynamic environment.
Probing and predicting ganglion cell responses to smooth electrical stimulation in healthy and blind mouse retina
2020-03-23

Abstract Retinal implants are used to replace lost photoreceptors in blind patients suffering from retinopathies such as retinitis pigmentosa. Patients wearing implants regain some rudimentary visual function. However, it is severely limited compared to normal vision because non-physiological stimulation strategies fail to selectively activate different retinal pathways at sufficient spatial and temporal resolution. The development of improved stimulation strategies is rendered difficult by the large space of potential stimuli. Here we systematically explore a subspace of potential stimuli by electrically stimulating healthy and blind mouse retina in epiretinal configuration using smooth Gaussian white noise delivered by a high-density CMOS-based microelectrode array. We identify linear filters of retinal ganglion cells (RGCs) by fitting a linear-nonlinear-Poisson (LNP) model. Our stimulus evokes spatially and temporally confined spiking responses in RGC which are accurately predicted by the LNP model. Furthermore, we find diverse shapes of linear filters in the linear stage of the model, suggesting diverse preferred electrical stimuli of RGCs. The linear filter base identified by our approach could provide a starting point of a model-guided search for improved stimuli for retinal prosthetics.
Queue Layouts of Planar 3-Trees
2020-03-23

Abstract A queue layout of a graph G consists of a linear order of the vertices of G and a partition of the edges of G into queues , so that no two independent edges of the same queue are nested. The queue number of graph G is defined as the minimum number of queues required by any queue layout of G . In this paper, we continue the study of the queue number of planar 3-trees, which form a well-studied subclass of planar graphs. Prior to this work, it was known that the queue number of planar 3-trees is at most seven. In this work, we improve this upper bound to five. We also show that there exist planar 3-trees whose queue number is at least four. Notably, this is the first example of a planar graph with queue number greater than three.
Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease
2020-03-23

Machado-Joseph disease (MJD/SCA3) is the most common form of dominantly inherited ataxia worldwide. The disorder is caused by an expanded CAG repeat in the <i>ATXN3</i> gene. Past studies have revealed that the length of the expansion partly explains the disease age at onset (AO) variability of MJD, which is confirmed in this study (Pearson's correlation coefficient R<sup>2</sup> = 0.62). Using a total of 786 MJD patients from five different geographical origins, a genome-wide association study (GWAS) was conducted to identify additional AO modifying factors that could explain some of the residual AO variability. We identified nine suggestively associated loci (<i>P</i> < 1 × 10<sup>-5</sup>). These loci were enriched for genes involved in vesicle transport, olfactory signaling, and synaptic pathways. Furthermore, associations between AO and the <i>TRIM29</i> and <i>RAG</i> genes suggests that DNA repair mechanisms might be implicated in MJD pathogenesis. Our study demonstrates the existence of several additional genetic factors, along with CAG expansion, that may lead to a better understanding of the genotype-phenotype correlation in MJD.
The Sound Settler
2020-03-23

The Sound Settler is a utopian project which combines engineering&#13;\\nand the arts. The utopian vision is to deploy an interactive music&#13;\\nsystem on Mars before the first humans arrive. Two real robotic&#13;\\narms are controlled in a gravity compensated master-slave mode&#13;\\nresembling the human part on Earth, and the robotic art piece&#13;\\nwhich is envisioned to be located on Mars. The movements generate&#13;\\nelectronic music by charging physical capacitors and on screen a&#13;\\nsimulated third arm is deployed, visualizing the movements on the&#13;\\nred planet. This report presents the artistic design, the implemented&#13;\\ninfrastructure and first subjective insights about human interactions&#13;\\nwith the art piece in public spaces. It motivates a more formal&#13;\\nanalysis and opens several research avenues for the future.
Extended Texture Analysis of Non-Enhanced Whole-Body MRI Image Data for Response Assessment in Multiple Myeloma Patients Undergoing Systemic Therapy
2020-03-24

Identifying MRI-based radiomics features capable to assess response to systemic treatment in multiple myeloma (MM) patients. Retrospective analysis of whole-body MR-image data in 67 consecutive stage III MM patients (40 men; mean age, 60.4 years). Bone marrow involvement was evaluated using a standardized MR-imaging protocol consisting of T1w-, short-tau inversion recovery- (STIR-) and diffusion-weighted-imaging (DWI) sequences. Ninety-two radiomics features were evaluated, both in focally and diffusely involved bone marrow. Volumes of interest (VOI) were used. Response to treatment was classified according to International Myeloma Working Group (IMWG) criteria in complete response (CR), very-good and/or partial response (VGPR + PR), and non-response (stable disease (SD) and progressive disease (PD)). According to the IMWG-criteria, response categories were CR (n = 35), VGPR + PR (n = 19), and non-responders (n = 13). On apparent diffusion coefficient (ADC)-maps, gray-level small size matrix small area emphasis (Gray Level Size Zone (GLSZM) small area emphasis (SAE)) significantly correlated with CR (p &lt; 0.001), whereas GLSZM non-uniformity normalized (NUN) significantly (p &lt; 0.008) with VGPR/PR in focal medullary lesions (FL), whereas in diffuse involvement, 1st order root mean squared significantly (p &lt; 0.001) correlated with CR, whereas for VGPR/PR Log (gray-level run-length matrix (GLRLM) Short Run High Gray Level Emphasis) proved significant (p &lt; 0.003). On T1w, GLRLM NUN significantly (p &lt; 0.002) correlated with CR in FL, whereas gray-level co-occurrence matric (GLCM) informational measure of correlation (Imc1) significantly (p &lt; 0.04) correlated with VGPR/PR. For diffuse myeloma involvement, neighboring gray-tone difference matrix (NGTDM) contrast and 1st order skewness were significantly associated with CR and VGPR/PR (p &lt; 0.001 for both). On STIR-images, CR correlated with gray-level co-occurrence matrix (GLCM) Informational Measure of Correlation (IMC) 1 (p &lt; 0.001) in FL and 1st order mean absolute deviation in diffusely involved bone marrow (p &lt; 0.001). VGPR/PR correlated at best in FL with GSZLM size zone NUN (p &lt; 0.019) and in all other involved medullary areas with GLSZM large area low gray level emphasis (p &lt; 0.001). GLSZM large area low gray level emphasis also significantly correlated with the degree of bone marrow infiltration assessed histologically (p = 0.006). GLCM IMC 1 proved significant throughout T1w/STIR sequences, whereas GLSZM NUN in STIR and ADC. MRI-based texture features proved significant to assess clinical and hematological response (CR, VPGR, and PR) in multiple myeloma patients undergoing systemic treatment.
Leveraging Open Hardware to Alleviate the Burden of COVID-19 on Global Health Systems
2020-03-24

With the current rapid spread of COVID-19, global health systems are increasingly overburdened by the sheer number of people that need diagnosis, isolation and treatment. Shortcomings are evident across the board, from staffing, facilities for rapid and reliable testing to availability of hospital beds and key medical-grade equipment. The scale and breadth of the problem calls for an equally substantive response not only from frontline workers such as medical staff and scientists, but from skilled members of the public who have the time, facilities and knowledge to meaningfully contribute to a consolidated global response. Here, we summarise community-driven approaches based on Free and Open Source scientific and medical Hardware (FOSH) currently being developed and deployed to bolster access to personal protective equipment (PPE), patient treatment and diagnostics.
Interference With Complex IV as a Model of Age-Related Decline in Synaptic Connectivity
2020-03-24

Age-related impairment of mitochondrial function may negatively impact energy-demanding processes such as synaptic transmission thereby triggering cognitive decline and processes of neurodegeneration. Here, we present a novel model for age-related mitochondrial impairment based on partial inhibition of cytochrome c oxidase subunit 4 (Cox4) of complex IV of the respiratory chain. miRNA-mediated knockdown of Cox4 correlated with a marked reduction in excitatory and inhibitory synaptic marker densities <i>in vitro</i> and <i>in vivo</i> as well as an impairment of neuronal network activity in primary neuronal cultures. Transcriptome analysis identified the deregulation of gene clusters, which link induced mitochondrial perturbation to impaired synaptic function and plasticity as well as processes of aging. In conclusion, the model of Cox4 deficiency reflects aspects of age-related dementia and might, therefore, serve as a novel test system for drug development.
A Finger-Based Numerical Training Failed to Improve Arithmetic Skills in Kindergarten Children Beyond Effects of an Active Non-numerical Control Training
2020-03-24

It is widely accepted that finger and number representations are associated: many correlations (including longitudinal ones) between finger gnosis/counting and numerical/arithmetical abilities have been reported. However, such correlations do not necessarily imply causal influence of early finger-number training; even in longitudinal designs, mediating variables may be underlying such correlations. Therefore, we investigated whether there may be a causal relation by means of an extensive experimental intervention in which the impact of finger-number training on initial arithmetic skills was tested in kindergarteners to see whether they benefit from the intervention even before they start formal schooling. The experimental group received 50 training sessions altogether for 10 weeks on a daily basis. A control group received phonology training of a similar duration and intensity. All children improved in the arithmetic tasks. To our surprise and contrary to most accounts in the literature, the improvement shown by the experimental training group was not superior to that of the active control group. We discuss conceptual and methodological reasons why the finger-number training employed in this study did not increase the initial arithmetic skills beyond the unspecific effects of the control intervention.
Fetal profile in fetuses with open spina bifida
2020-03-24

Abstract Objective To determine whether the frontomaxillary facial (FMF) angle and the prefrontal space ratio (PFSR) are helpful in screening for open spinal defects by ultrasound in the second and third trimesters of pregnancy. Methods The FMF angle and the PFSR were measured in fetuses with spina bifida according to standardized protocols. The normal range of the PFSR was previously published by our group. To determine the normal values for the FMF angle in the second and third trimesters of pregnancy, we used the same stored images from the above-mentioned study. Results 71 affected and 279 normal fetuses were included in this study. Median gestational ages in the two groups were 21.1 weeks and 21.6 weeks, respectively. In fetuses with spina bifida, the FMF angle was significantly smaller than in the normal population (72.9° versus 79.6°). However, the measurement was below the fifth centile in only 22.5% of the affected fetuses. The PFSR was similar in both groups. Conclusions The FMF angle is smaller in second and third trimester fetuses with open spina bifida. However, the difference is not large enough to implement this marker in current screening programs.
Onset features and time to diagnosis in Friedreich's Ataxia
2020-03-24

Abstract Background: In rare disorders diagnosis may be delayed due to limited awareness and unspecific presenting symptoms. Herein, we address the issue of diagnostic delay in Friedreich ́s Ataxia (FRDA), a genetic disorder caused by homozygous GAA-repeat expansions.Methods: 611 genetically confirmed FRDA patients were recruited within a multicentric natural history study conducted by the EFACTS (European FRDA Consortium for Translational Studies, ClinicalTrials.gov-Identifier NCT02069509). Age and symptoms at onset as well as age at suspicion of FRDA were collected retrospectively at the baseline visit.Results: In 554 of cases (90.7%), disease presented with gait or coordination disturbances. In the others (n=57, 9.3%), non-neurological features such as scoliosis or cardiomyopathy predated ataxia. Before the discovery of the causal mutation in 1996, median time to diagnosis was 4(IQR=2-9) years and it improved significantly after the introduction of genetic testing (2(IQR=1-5) years, p &lt;0.001). Still after 1996, time to diagnosis was longer in patients with a) non-neurological presentation (mean 6.7, 95%CI[5.5,7.9] vs 4.5, [4.2,5] years, p =0.001) as well as in b) patients with late-onset (3(IQR=1-7) vs 2(IQR=1-5) years compared to early onset &lt;25 years of age, p =0.03). Age at onset significantly correlated with GAA-repeat length in case of neurological onset (r=-0,6; p &lt;0,0001), but not in patients with non-neurological presentation (r=-0,1; p =0,4). Across 54 siblings’ pairs, differences in age at onset did not correlate with differences in GAA-repeat length (r=-0,14, p =0,3).Conclusions: In the genetic era, presentation with non-neurological features or in the adulthood still leads to a significant diagnostic delay in FRDA. Well-known correlations between GAA and disease milestones are not valid in case of atypical presentations or positive family history.