julilili42/papers huggingface dataset:
Treatment of infants with craniofacial malformations
2020-05-14

Infants with craniofacial malformations (CFMs) are at increased risk of various clinical problems, including respiratory and feeding disorders, the result of which may be long-lasting. An improvement in clinical care can be achieved by prenatal diagnosis and interdisciplinary birth preparation. Feeding problems may particularly be stressful for the family and require a team approach involving nursing staff, speech therapists and nutritional specialists to anticipate, avoid and treat sequelae such as failure to thrive or recurrent aspirations. Special techniques (eg, optimisation of breast feeding, alternative feeding methods or manual orofacial therapy) may be used individually to improve feeding competence; supplemental nutrition via a nasogastric or gastrostomy tube may be temporarily necessary to ensure adequate weight gain. The high prevalence of respiratory disorders in infants with craniofacial abnormalities requires anticipation and screening to prevent growth failure and neurological deficits. Treatment of upper airway obstruction varies widely, strategies can be divided into non-surgical and surgical, and in those aimed at widening the pharyngeal space (eg, prone position, palatal plates, craniofacial surgery) and those bridging the narrow upper airway (eg, nasopharyngeal airway, modified palatal plate, pneumatic airway stenting, tracheostomy). The complex management of an infant with CFM should be performed by a multidisciplinary team to offer specialised support and care for affected families.
Time Reading in Middle and Secondary School Students: The Influence of Basic-Numerical Abilities
2020-05-14

Time reading skills are central for the management of personal and professional life. However, little is known about the differential influence of basic numerical abilities on analog and digital time reading in general and in middle and secondary school students in particular. The present study investigated the influence of basic numerical skills separately for analog and digital time reading in <i>N</i> = 709 students from 5th to 8th grade. The present findings suggest that the development of time reading skills is not completed by the end of primary school. Results indicated that aspects of <i>magnitude manipulation</i> and <i>arithmetic fact knowledge</i> predicted analog time reading significantly over and above the influence of age. Furthermore, results showed that <i>spatial representations of number magnitude, magnitude manipulation</i>, <i>arithmetic fact knowledge</i>, and <i>conceptual knowledge</i> were significant predictors of digital time reading beyond general cognitive ability and sex. To the best of our knowledge, the present study is the first to show differential effects of basic numerical abilities on analog and digital time reading skills in middle and secondary school students. As time readings skills are crucial for everyday life, these results are highly relevant to better understand basic numerical processes underlying time reading.
An evaluation of avelumab for the treatment of genitourinary tumors
2020-05-14

Avelumab has shown promising antitumor activity and a manageable safety profile in patients with mRCC and mUC as mono- and combination therapy. The approach of an avelumab maintenance therapy in mUC is promising and could become part of future clinical practice. Results of ICI used in the neoadjuvant or adjuvant setting are eagerly awaited. Avelumab's uniqueness is its capacity to enhance antibody-dependent cell-mediated cytotoxicity. Because of this, currently ongoing clinical trials investigate the combination of avelumab with other immune modulating agents like IL-12 and IL-15. Thereby, it can be assumed that avelumab will have an ongoing role in the treatment of patients with genitourinary tumors.
Determining a novel feature-space for SARS-CoV-2 sequence data
2020-05-14

The pandemicity &amp;amp; the ability of the SARS-COV-2 to reinfect a cured subject, among other damaging characteristics of it, took everybody by surprise. A global collaborative scientific effort was direly required to bring learned people from different niches of medicine &amp;amp; data science together. Such a platform was provided by COVID19 Virtual BioHackathon, organized from the 5th to the 11th of April, 2020, to ponder on the related pressing issues varying in their diversity from text mining to genomics. Under the "Machine learning" track, we determined optimal k-mer length for feature extraction, constructed continuous distributed representations for protein sequences to create phylogenetic trees in an alignment-free manner, and clustered predicted MHC class I and II binding affinity to aid in vaccine design. All the related work in available in a Github repository under an MIT license for future research.
Global analysis of human SARS-CoV-2 infection and host-virus interaction
2020-05-14

As part of the virtual BioHackathon 2020, we formed a working group that focused on the analysis of gene expression in the context of COVID-19. More specifically, we performed transcriptome analyses on published datasets in order to better understand the interaction between the human host and the SARS-CoV-2 virus.The ideas proposed during this hackathon were divided into five projects. Projects 1 and 2 aimed to identify human genes that are important in the process of viral infection of human cells. Projects 3 and 4 aimed to take the candidate genes identified in projects 1 and 2, as well as by independent studies, and relate them to clinical information and to possible therapeutic interventions. Finally, Project 5 aimed to package and containerize software and workflows used and generated here in a reusable manner, ultimately providing scalable and reproducible workflows.
Optimality Principles in Human Point-to-Manifold Reaching Accounting for Muscle Dynamics
2020-05-15

Human arm movements are highly stereotypical under a large variety of experimental conditions. This is striking due to the high redundancy of the human musculoskeletal system, which in principle allows many possible trajectories toward a goal. Many researchers hypothesize that through evolution, learning, and adaption, the human system has developed optimal control strategies to select between these possibilities. Various optimality principles were proposed in the literature that reproduce human-like trajectories in certain conditions. However, these studies often focus on a single cost function and use simple torque-driven models of motion generation, which are not consistent with human muscle-actuated motion. The underlying structure of our human system, with the use of muscle dynamics in interaction with the control principles, might have a significant influence on what optimality principles best model human motion. To investigate this hypothesis, we consider a point-to-manifold reaching task that leaves the target underdetermined. Given hypothesized motion objectives, the control input is generated using Bayesian optimization, which is a machine learning based method that trades-off exploitation and exploration. Using numerical simulations with Hill-type muscles, we show that a combination of optimality principles best predicts human point-to-manifold reaching when accounting for the muscle dynamics.
Depth relationships and measures of tissue thickness in dorsal midbrain
2020-05-15

ABSTRACT Dorsal human midbrain contains two nuclei with clear laminar organization, the superior and inferior colliculi. These nuclei extend in depth between the superficial dorsal surface of midbrain and a deep midbrain nucleus, the periaqueductal gray matter (PAG). The PAG, in turn, surrounds the cerebral aqueduct (CA). This study examined the use of two depth metrics to characterize depth and thickness relationships within dorsal midbrain using the superficial surface of midbrain and CA as references. The first utilized nearest-neighbor Euclidean distance from one reference surface, while the second used a level-set approach that combines signed distance from both reference surfaces. Both depth methods provided similar functional depth profiles generated by saccadic eye movements in a functional MRI task, confirming their efficacy for superficial functional activity. Next, the boundaries of the PAG were estimated using Euclidean distance together with elliptical fitting, indicating that the PAG can be readily characterized by a smooth surface surrounding PAG. Finally, we used the level-set approach to measure tissue depth between the superficial surface and the PAG, thus characterizing the variable thickness of the colliculi. Overall, this study demonstrates depth-mapping schemes for human midbrain that enables accurate segmentation of the PAG and consistent depth and thickness estimates of the superior and inferior colliculi.
In situ detection of protein interactions for recombinant therapeutic enzymes
2020-05-15

Despite their therapeutic potential, many protein drugs remain inaccessible to patients since they are difficult to secrete. Each recombinant protein has unique physicochemical properties and requires different machinery for proper folding, assembly, and post-translational modifications (PTMs). Here we aimed to identify the machinery supporting recombinant protein secretion by measuring the protein-protein interaction (PPI) networks of four different recombinant proteins (SERPINA1, SERPINC1, SERPING1 and SeAP) with various PTMs and structural motifs using the proximity-dependent biotin identification (BioID) method. We identified PPIs associated with specific features of the secreted proteins using a Bayesian statistical model, and found proteins involved in protein folding, disulfide bond formation and N-glycosylation were positively correlated with the corresponding features of the four model proteins. Among others, oxidative folding enzymes showed the strongest association with disulfide bond formation, supporting their critical roles in proper folding and maintaining the ER stability. Knock down of ERP44, a measured interactor with the highest fold change, led to the decreased secretion of SERPINC1, which relies on its extensive disulfide bonds. Proximity-dependent labeling successfully identified the transient interactions supporting synthesis of secreted recombinant proteins and refined our understanding of key molecular mechanisms of the secretory pathway during recombinant protein production.
When Academic Achievement (Also) Reflects Personality: Using the Personality-Achievement Saturation Hypothesis (PASH) to Explain Differential Associations Between Achievement Measures and Personality Traits
2020-05-15

Students’ academic achievement is a key predictor of various life outcomes. The two most prominent measures of academic achievement are grades and standardized test scores. Both measures are commonly used during selection processes as well as for educational monitoring and accountability. Research has suggested that grades and test scores are strongly related to students’ characteristics (e.g., cognitive abilities) but might differentially reflect personality. In order to better explain differential personality-achievement associations, it is important to move beyond the dichotomy of grades versus test scores. To this end, we propose the personality-achievement saturation hypothesis (PASH), which suggests that associations between personality and achievement vary, depending on four main features of the achievement measure used: level of standardization, relevance for the student, curricular validity, and instructional sensitivity. The PASH suggests that conscientiousness should typically be more strongly associated with grade point average, followed by course grades and final examination grades, whereas openness should be more strongly associated with test scores. We used data from three large-scale studies (total N = 14,953) and aggregated our findings. In line with the PASH, conscientiousness was most strongly related to grades, which have lower standardization, moderate to high relevance, high curricular-validity, and high instructional sensitivity, whereas it had substantially weaker associations with more highly standardized, less curriculum-valid, and less instructionally sensitive measures. In addition, openness was most strongly related to highly standardized, less relevant, less curriculum-valid, and less instructionally sensitive measures in English. Implications for the ways in which achievement measures can be used are discussed.
Synthesis of Symmetrical Dodeco‐6,7‐diuloses
2020-05-16

Dodeco‐6,7‐diuloses represent a rare class of sugars and can be considered as anomerically linked di‐hexoses with two hemiacetal functions in the middle. Herein, the synthesis of three symmetrical dodeco‐6,7‐diuloses ( gluco ‐ gluco, galacto ‐ galacto, manno ‐ manno ) is described. For their preparation four synthetic strategies were pursued, whose mutual key step, the connection of the anomeric centers, is particularly emphasized. Specifically, C–C bond forming methods are employed, such as a Grubbs metathesis, a stannyl glycal homocoupling reaction, a coupling of a sulfinyl glycal with a sugar lactone and a Ramberg–Bäcklund rearrangement. Since the ring closure via hemiacetal formation of the target compounds cannot be predicted, intensive NMR spectroscopic structure elucidation of the diuloses was performed.
Evaluation of cerebellar function scores in relation to cerebellar axonal loss in multiple sclerosis
2020-05-16

Abstract Background Cerebellar damage is common in people with multiple sclerosis (pwMS) and is associated with worse progression and relapse recovery. Studies into the importance of the cerebellum in pwMS are hampered by limited understanding of cerebellar damage and its relation to cerebellar function in pwMS. Objective Examine axonal loss, as a primary driver of progressive neurological decline, in the cerebellum using advanced diffusion MRI and compare axonal loss with cerebellar dysfunction in pwMS Methods We recruited 55 pwMS and 14 healthy controls. Clinical assessments included scale for the assessment and rating of ataxia (SARA), and Bain tremor ratings. Subjects underwent FLAIR, T1-weighted and diffusion MRI. Cerebellar grey and white matter and lesion volume were calculated. Cerebellar axonal loss was examined with fibre-specific markers. Fibre density and cross-section (FDC) accounts for microscopic and macroscopic changes in a fibre bundle. Results Loss of cerebellar FDC was associated with increased SARA (r=-0.42, p&lt;0.01) and tremor severity (rho=-0.35, p=0.01). Cerebellar lesion volume correlated with SARA (r=0.49, p&lt;0.01) and tremor severity (rho=0.41, p=0.01). Conclusion Fibre-specific measures of cerebellar pathology could provide a functionally relevant marker of cerebellar damage in MS. Future trials using fibre-specific markers are needed to further characterize cerebellar pathology in pwMS and understand its significance in disease progression.
On the polymorphemic genesis of some Proto-Quechuan roots
2020-05-17

Abstract In the Proto-Quechuan lexicon, many two-segment phonetic substrings recur in semantically related roots, even though they are not independent morphemes. Such elements may have been morphemes before the Proto-Quechuan stage (i.e., in Pre-Proto-Quechuan). On the other hand, this may simply be due to chance, or to phonesthesia. In this paper, we introduce the Crosslinguistic Colexification Network Clustering (CCNC) algorithm, as well as an accompanying test statistic, which allow us to evaluate our claims against a neutral standard of semantic relatedness (the CLICS 2 database; List et al. 2018 ). We obtain very strong statistical evidence that there are hitherto unexplained recurrent elements within Proto-Quechuan roots, but not within roots reconstructed for Proto-Aymaran, the proto-language of a neighboring language family whose members are otherwise structurally very similar to Proto-Quechuan, and which has therefore long been considered an obvious candidate for deep shared ancestry. Some of these elements are explainable as phonesthemes, but most appear to reflect archaic Quechuan morphology. These findings are consistent with an emerging picture of the early Quechuan-Aymaran contact relationship in which Quechuan structure was reformatted on the Aymaran template.
Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses
2020-05-18

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype<sup>1-3</sup>. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10<sup>-8</sup>), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.
Online Mapping With the Deep Brain Stimulation Lead: A Novel Targeting Tool in Parkinson's Disease
2020-05-18

Abstract Background Beta‐frequency oscillations (13–30 Hz) are a subthalamic hallmark in patients with Parkinson's disease, and there is increased interest in their utility as an intraoperative marker. Objectives The objectives of this study were to assess whether beta activity measured directly from macrocontacts of deep brain stimulation leads could be used (a) as an intraoperative electrophysiological approach for guiding lead placements and (b) for physiologically informed stimulation delivery. Methods Every millimeter along the surgical trajectory, local field‐potential data were collected from each macrocontact, and power spectral densities were calculated and visualized (n = 39 patients). This was done for online intraoperative functional mapping and post hoc statistical analyses using 2 methods: generating distributions of spectral activity along surgical trajectories and direct delineation (presence versus lack) of beta peaks. In a subset of patients, this approach was corroborated by microelectrode recordings. Furthermore, the match rate between beta peaks at the final target position and the clinically determined best stimulation site were assessed. Results Subthalamic recording sites were delineated by both methods of reconstructing functional topographies of spectral activity along surgical trajectories at the group level ( P &lt; 0.0001). Beta peaks were detected when any portion of the 1.5 mm macrocontact was within the microelectrode‐defined subthalamic border. The highest beta peak at the final implantation site corresponded to the site of active stimulation in 73.3% of hemispheres ( P &lt; 0.0001). In 93.3% of hemispheres, active stimulation corresponded to the first‐highest or second‐highest beta peak. Conclusions Online measures of beta activity with the deep brain stimulation macroelectrode can be used to inform surgical lead placement and contribute to optimization of stimulation programming procedures. © 2020 International Parkinson and Movement Disorder Society
Gaseous dynamical friction under radiative feedback: do intermediate-mass black holes speed up or down?
2020-05-18

ABSTRACT Coalescence of intermediate-mass black holes (IMBHs) as a result of the migration toward galactic centres via dynamical friction may contribute to the formation of supermassive BHs. Here we reinvestigate the gaseous dynamical friction, which was claimed to be inefficient with radiative feedback from BHs in literature, by performing 3D radiation-hydrodynamics simulations that solve the flow structure in the vicinity of BHs. We consider a 104-M⊙ BH moving at the velocity vflow through the homogeneous medium with metallicity Z in the range of 0–0.1 Z⊙ and density n∞. We show that, if n∞ ≲ 106 cm−3 and vflow ≲ 60 km s−1, the BH is accelerated forward because of the gravitational pull from a dense shell ahead of an ionized bubble around the BH, regardless of the value of Z. If n∞ ≳ 106 cm−3, however, our simulation shows the opposite result. The ionized bubble and associating shell temporarily appear, but immediately go downstream with significant ram pressure of the flow. They eventually converge into a massive downstream wake, which gravitationally drags the BH backward. The BH decelerates over the time-scale of ∼0.01 Myr, much shorter than the dynamical time-scale in galactic discs. Our results suggest that IMBHs that encounter the dense clouds rapidly migrate toward galactic centres, where they possibly coalescence with others.
C-Fiber Loss as a Possible Cause of Neuropathic Pain in Schwannomatosis
2020-05-18

Schwannomatosis is the third form of neurofibromatosis and characterized by the occurrence of multiple schwannomas. The most prominent symptom is chronic pain. We aimed to test whether pain in schwannomatosis might be caused by small-fiber neuropathy. Twenty patients with schwannomatosis underwent neurological examination and nerve conduction studies. Levels of pain perception as well as anxiety and depression were assessed by established questionnaires. Quantitative sensory testing (QST) and laser-evoked potentials (LEP) were performed on patients and controls. Whole-body magnetic resonance imaging (wbMRI) and magnetic resonance neurography (MRN) were performed to quantify tumors and fascicular nerve lesions; skin biopsies were performed to determine intra-epidermal nerve fiber density (IENFD). All patients suffered from chronic pain without further neurological deficits. The questionnaires indicated neuropathic symptoms with significant impact on quality of life. Peripheral nerve tumors were detected in all patients by wbMRI. MRN showed additional multiple fascicular nerve lesions in 16/18 patients. LEP showed significant faster latencies compared to normal controls. Finally, IENFD was significantly reduced in 13/14 patients. Our study therefore indicates the presence of small-fiber neuropathy, predominantly of unmyelinated C-fibers. Fascicular nerve lesions are characteristic disease features that are associated with faster LEP latencies and decreased IENFD. Together these methods may facilitate differential diagnosis of schwannomatosis.