julilili42/papers huggingface dataset:
Phenotypic characterization of seven individuals with Marbach–Schaaf neurodevelopmental syndrome
2022-07-05

Abstract We present the phenotypes of seven previously unreported patients with Marbach–Schaaf neurodevelopmental syndrome, all carrying the same recurrent heterozygous missense variant c.1003C&gt;T (p.Arg335Trp) in PRKAR1B . Clinical features of this cohort include global developmental delay and reduced sensitivity to pain, as well as behavioral anomalies. Only one of the seven patients reported here was formally diagnosed with autism spectrum disorder (ASD), while ASD‐like features were described in others, overall indicating a lower prevalence of ASD in Marbach–Schaaf neurodevelopmental syndrome than previously assumed. The clinical spectrum of the current cohort is similar to that reported in the initial publication, delineating a complex developmental disorder with behavioral and neurologic features. PRKAR1B encodes the regulatory subunit R1β of the protein kinase A complex (PKA), and is expressed in the adult and embryonal central nervous system in humans. PKA is crucial to a plethora of cellular signaling pathways, and its composition of different regulatory and catalytic subunits is cell‐type specific. We discuss potential molecular disease mechanisms underlying the patients' phenotypes with respect to the different known functions of PKA in neurons, and the phenotypes of existing R1β‐deficient animal models.
BCImat: a Matlab-based framework for IntracorticalBrain-Computer Interfaces and their simulation with an artificialspiking neural network
2022-07-05

Ferrea et al., (2022). BCImat: a Matlab-based framework for Intracortical Brain-Computer Interfaces and their simulation with an artificial spiking neural network. Journal of Open Source Software, 7(75), 3956, https://doi.org/10.21105/joss.03956
Risk assessment in COVID‐19: Prognostic importance of cardiovascular parameters
2022-07-05

Abstract Background Cardiovascular risk factors and comorbidities are highly prevalent among COVID‐19 patients and are associated with worse outcomes. Hypothesis We therefore investigated if established cardiovascular risk assessment models could efficiently predict adverse outcomes in COVID‐19. Furthermore, we aimed to generate novel risk scores including various cardiovascular parameters for prediction of short‐ and midterm outcomes in COVID‐19. Methods We included 441 consecutive patients diagnosed with SARS‐CoV‐2 infection. Patients were followed‐up for 30 days after the hospital admission for all‐cause mortality (ACM), venous/arterial thromboembolism, and mechanical ventilation. We further followed up the patients for post‐COVID‐19 syndrome for 6 months and occurrence of myocarditis, heart failure, acute coronary syndrome (ACS), and rhythm events in a 12‐month follow‐up. Discrimination performance of DAPT, GRACE 2.0, PARIS‐CTE, PREDICT‐STABLE, CHA2‐DS2‐VASc, HAS‐BLED, PARIS‐MB, PRECISE‐DAPT scores for selected endpoints was evaluated by ROC‐analysis. Results Out of established risk assessment models, GRACE 2.0 score performed best in predicting combined endpoint and ACM. Risk assessment models including age, cardiovascular risk factors, echocardiographic parameters, and biomarkers, were generated and could successfully predict the combined endpoint, ACM, venous/arterial thromboembolism, need for mechanical ventilation, myocarditis, ACS, heart failure, and rhythm events. Prediction of post‐COVID‐19 syndrome was poor. Conclusion Risk assessment models including age, laboratory parameters, cardiovascular risk factors, and echocardiographic parameters showed good discrimination performance for adverse short‐ and midterm outcomes in COVID‐19 and outweighed discrimination performance of established cardiovascular risk assessment models.
Associations between abdominal adipose tissue, reproductive span, and brain characteristics in post-menopausal women
2022-07-05

The menopause transition involves changes in oestrogens and adipose tissue distribution, which may influence female brain health post-menopause. Although increased central fat accumulation is linked to risk of metabolic diseases, adipose tissue also serves as the primary biosynthesis site of oestrogens post-menopause. It is unclear whether different types of adipose tissue play diverging roles in female brain health post-menopause, and whether this depends on lifetime oestrogen exposure, which can have lasting effects on the brain and body even after menopause. Using the UK Biobank sample, we investigated associations between brain characteristics and visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT) in 10,251 post-menopausal females, and assessed whether the relationships varied depending on length of reproductive span (age at menarche to age at menopause). To parse the effects of common genetic variation, we computed polygenic scores for reproductive span. The results showed that higher VAT and ASAT were both associated with higher grey and white matter brain age, and greater white matter hyperintensity load. The associations varied positively with reproductive span, indicating more prominent associations between adipose tissue and brain measures in females with a longer reproductive span. The results could not be fully explained by genetic variation or relevant confounders. Our findings indicate that associations between abdominal adipose tissue and brain health post-menopause may partly depend on individual differences in cumulative oestrogen exposure during reproductive years, emphasising the complexity of neural and endocrine ageing processes in females.
Nonequilibrium Roughness Evolution of Small Molecule Mixed Films Reflecting Equilibrium Phase Behavior
2022-07-05

Understanding nonequilibrium phenomena, such as growth, and connecting them to equilibrium phase behavior is a major challenge, in particular for complex multicomponent materials. We use X-ray reflectivity to determine the surface roughness of binary mixtures of several prototypical organic compounds. By analyzing the roughness as a function of composition, we find a systematic behavior depending on the bulk phase behavior in terms of intermixing, co-crystallization, or phase separation. Supported by kinetic Monte Carlo simulations, we provide evidence that the growth behavior can be rationalized by a lowered step edge barrier in the mixed films which is induced by reduced in-plane crystallinity.
Holocene Evolution of Minor Mountain Lacustrine Basins in the Northern Apennines, Italy: The Lake Moo Case Study
2022-07-05

Sedimentary systems developed in small (&lt;1 km2) mountain lacustrine basins represent high-resolution geological archives, able to record subtle climatic and tectonic signatures over historical times. The studied example from the Mt. Ragola ophiolitic massif in the Northern Apennines (Italy) allowed us to better understand the role of the different (neo)tectonic and climatic events on the development and distribution of large landslides and lakes/peat bogs during the last 10 kyrs. Implementing a multidisciplinary approach that includes detailed acquisition of bedrock, geomorphological, topographic, and geophysical data, we detected and mapped ridge splitting, trenches, closed depressions, double ridges, and counterscarps. These morphostructures are interpreted as relevant factors influencing the distribution of sediments in historical times by shifting the position of the local equilibrium point (i.e., erosion vs. deposition) and have been correlated to a combination of climatic (i.e., increased flood events) and tectonic (i.e., spatial–temporal clustering of seismic shocks) forcing, starting from the demise of the Little Ice Age in the mid-19th century to the present-day situation. This approach allowed us to better describe the current changes in the hydrologic cycle, reaching beyond the limits of historical instrumental data. Furthermore, allowing the recognition and dating of recent tectonic vs. gravitational deformations, it also constitutes an integrative method for assessing the local geological hazard.
YgfB increases β-lactam resistance inPseudomonas aeruginosaby counteracting AlpA-mediatedampDh3expression
2022-07-05

Abstract YgfB-mediated β-lactam resistance was recently identified in multi drug resistant Pseudomonas aeruginosa. We show that YgfB upregulates expression of the β-lactamase AmpC by repressing the function of the regulator of the programmed cell death pathway AlpA. In response to DNA damage, the antiterminator AlpA induces expression of the alpBCDE autolysis genes and of the peptidoglycan amidase AmpDh3. YgfB interacts with AlpA and represses the ampDh3 expression. Thus, YgfB indirectly prevents AmpDh3 from reducing the levels of cell wall-derived 1,6-anhydro-N-acetylmuramyl-peptides, required to induce the transcriptional activator AmpR in promoting the ampC expression and β-lactam resistance. Ciprofloxacin-mediated DNA damage induces AlpA-dependent production of AmpDh3 as previously shown, which should reduce β-lactam resistance. YgfB, however, counteracts the β-lactam enhancing activity of ciprofloxacin by repressing ampDh3 expression and lowering the benefits of this drug combination. Altogether, YgfB represents a new player in the complex regulatory network of AmpC regulation.
dataset of the work entitled "The spatial distribution of rhizosphere microbial activities under drought: water availability is more important than root-hair controlled exudation"
2022-07-05

&lt;p&gt;This is the dataset of the enzyme kinetics, and other biochemical properties obtained from zymography, &lt;sup&gt;14&lt;/sup&gt;C images and water images of the work entitled &quot;The spatial distribution of rhizosphere microbial activities under drought: water availability is more important than root-hair controlled exudation&quot;.&nbsp;&lt;/p&gt;
Consensus nucleotide sequences for env and gag for paper: Insights to HIV-1 coreceptor usage by estimating HLA adaptation with Bayesian generalized linear mixed models
2022-07-05

This is the consensus sequence repository to the manuscript "Insights to HIV-1 coreceptor usage by estimating HLA adaptation with Bayesian generalized linear mixed models". It contains the 10% consensus nucleotide sequences of the env and gag (only p24) protein of HIV-1 used for the training and leftout data set. The NGS sequences are available under BioProject ID PRJNA810303 and the corresponding BioSample Accession IDs are SAMN26241863:26242168 and SAMN28728524:SAMN28728529 env_leftout.fasta A fasta file that contains the consensus nucleotide sequences for the env protein for the leftout data set env_nt_274.fasta A fasta file that contains the consensus nucleotide sequences for the env protein for the training data set gag_leftout.fasta A fasta file that contains the consensus nucleotide sequences for the gag protein for the leftout data set gag_nt_274.fasta A fasta file that contains the consensus nucleotide sequences for the gag protein for the training data set
dataset of the work entitled "The spatial distribution of rhizosphere microbial activities under drought: water availability is more important than root-hair controlled exudation"
2022-07-05

This is the dataset of the enzyme kinetics, and other biochemical properties obtained from zymography, <sup>14</sup>C images and water images of the work entitled "The spatial distribution of rhizosphere microbial activities under drought: water availability is more important than root-hair controlled exudation".
Minimal dataset for "Insights to HIV-1 coreceptor usage by estimating HLA adaptation with Bayesian generalized linear mixed models"
2022-07-05

&lt;p&gt;This repository contains a minimal data set to reproduce all results that don&#39;t compromise the privacy concerns for the manuscript &quot;Insights to HIV-1 coreceptor usage by estimating HLA adaptation with Bayesian generalized linear mixed models&quot;.&lt;br&gt; &lt;br&gt; The repository contains the following data:&lt;/p&gt; &lt;ul&gt; &lt;li&gt;adaptscore_acute.csv &lt;ul&gt; &lt;li&gt;A csv file that contains the estimated adaptation scores for the acute data set with HLA I model.&lt;/li&gt; &lt;/ul&gt; &lt;/li&gt; &lt;li&gt;adaptscore_leftout.csv &lt;ul&gt; &lt;li&gt;A csv file that contains the estimated adaptation scores for the leftout data set with the joint HLA I and HLA II model&lt;/li&gt; &lt;/ul&gt; &lt;/li&gt; &lt;li&gt;adaptscore_training.csv &lt;ul&gt; &lt;li&gt;A csv file that contains the estimated adaptation scores for the traininig data set with the joint HLA I and HLA II model&lt;/li&gt; &lt;/ul&gt; &lt;/li&gt; &lt;li&gt;adaptscore_training_hla1_without_clin.csv &lt;ul&gt; &lt;li&gt;A csv file that contains the estimated adaptation scores for the training data set with the HLA I model (via cross-validation)&lt;/li&gt; &lt;/ul&gt; &lt;/li&gt; &lt;li&gt;adaptscore_training_seed2.csv &lt;ul&gt; &lt;li&gt;A csv file that contains the estimated adaptation scores for the training data set with the joint HLA I and HLA II model via cross-validation with another seed&lt;/li&gt; &lt;/ul&gt; &lt;/li&gt; &lt;/ul&gt;
dataset of the work entitled "The spatial distribution of rhizosphere microbial activities under drought: water availability is more important than root-hair controlled exudation"
2022-07-05

This is the dataset of the enzyme kinetics, and other biochemical properties obtained from zymography, 14C images and water images of the work entitled &amp;quot;The spatial distribution of rhizosphere microbial activities under drought: water availability is more important than root-hair controlled exudation&amp;quot;.&amp;nbsp;
Reappraisal of the late Miocene elasmotheriine Parelasmotherium schansiense from Kutschwan (Shanxi Province, China) and its phylogenetic relationships
2022-07-05

Elasmotheres, such as the huge Siberian unicorn (<i>Elasmotherium sibiricum</i>), are amongst the most iconic large mammals ever to roam Eurasia. Several different elasmotheriine taxa are also known from the upper Miocene of Asia, including the large genus <i>Parelasmotherium</i>. Herein we present the re-examination of the holotype of its type species <i>Parelasmotherium schansiense</i>, using high resolution X-ray computed tomography. The μCT analysis reveals thus far unknown morphological features of the M1 and the unerupted P4 and M2, thereby adding to our knowledge about this species. This allows comparisons with other species that have been referred to <i>Parelasmotherium</i>, ‘<i>Parelasmotherium</i>’ <i>simplum</i> and ‘<i>Parelasmotherium</i>’ <i>linxiaense</i>, which, according to the results of the phylogenetic analysis, should not be included in the same genus as <i>P. schansiense</i>. Furthermore, based on comparisons to other Miocene elasmotheriines the diagnosis of <i>Parelasmotherium schansiense</i> was amended and its phylogenetic position was assessed. <i>Parelasmotherium schansiense</i> is placed in a monophyletic group of ‘derived elasmotheriines,’ which also includes the genera <i>Elasmotherium</i>, <i>Sinotherium</i>, and <i>Ninxiatherium</i>.
Early knapping techniques do not necessitate cultural transmission
2022-07-06

Early stone tool production, or knapping, techniques are claimed to be the earliest evidence for cultural transmission in the human lineage. Previous experimental studies have trained human participants to knap in conditions involving opportunities for cultural transmission. Subsequent knapping was then interpreted as evidence for a necessity of the provided cultural transmission opportunities for these techniques. However, a valid necessity claim requires showing that individual learning alone cannot lead to early knapping techniques. Here, we tested human participants ( N = 28) in cultural isolation for the individual learning of early knapping techniques by providing them with relevant raw materials and a puzzle task as motivation. Twenty-five participants were technique naïve according to posttest questionnaires, yet they individually learned early knapping techniques, therewith producing and using core and flake tools. Early knapping techniques thus do not necessitate cultural transmission of know-how and could likewise have been individually derived among premodern hominins.
Awake Mouse fMRI and Pupillary Recordings in the Ultra-High Magnetic Field
2022-07-06

Awake rodent fMRI is becoming a promising non-invasive brain imaging module when investigating large-scale brain function given behavioral tasks. Previous studies have either applied sedatives during scanning or pre-treatment of anesthetics, e.g., isoflurane, to reduce the motion of animals, which could confound the brain function of “awake” states in rodents. Here, we have established a long training awake mouse fMRI-pupillometry paradigm/setup without the initial use of anesthesia. To validate the awake mouse fMRI platform, evoked BOLD-fMRI was performed to identify brain activation in the visual cortex, dorsal lateral geniculate nuclei, and superior colliculus. Furthermore, pupil signal fluctuation was investigated during scanning, showing a less dilated pupil after 5–8 weeks of intermittent training. Thus, using the awake mouse fMRI with real-time pupillometry provides a longitudinal functional mapping tool to study fully conscious mice.
Reduction in Acquisition Time and Improvement in Image Quality in T2-Weighted MR Imaging of Musculoskeletal Tumors of the Extremities Using a Novel Deep Learning-Based Reconstruction Technique in a Turbo Spin Echo (TSE) Sequence
2022-07-06

Background: The aim of this study was to assess the technical feasibility and the impact on image quality and acquisition time of a deep learning-accelerated fat-saturated T2-weighted turbo spin echo sequence in musculoskeletal imaging of the extremities. Methods: Twenty-three patients who underwent MRI of the extremities were prospectively included. Standard T2w turbo inversion recovery magnitude (TIRMStd) imaging was compared to a deep learning-accelerated T2w TSE (TSEDL) sequence. Image analysis of 23 patients with a mean age of 60 years (range 30–86) was performed regarding image quality, noise, sharpness, contrast, artifacts, lesion detectability and diagnostic confidence. Pathological findings were documented measuring the maximum diameter. Results: The analysis showed a significant improvement for the T2 TSEDL with regard to image quality, noise, contrast, sharpness, lesion detectability, and diagnostic confidence, as compared to T2 TIRMStd (each p &lt; 0.001). There were no differences in the number of detected lesions. The time of acquisition (TA) could be reduced by 52–59%. Interrater agreement was almost perfect (κ = 0.886). Conclusion: Accelerated T2 TSEDL was technically feasible and superior to conventionally applied T2 TIRMStd. Concurrently, TA could be reduced by 52–59%. Therefore, deep learning-accelerated MR imaging is a promising and applicable method in musculoskeletal imaging.
Expanding PRDX3 disease: broad range of onset age and infratentorial MRI signal changes
2022-07-06

Variants in PRDX3 have recently been described to cause autosomal-recessive cerebellar ataxia.1 However, confirmation by an independent second report is still lacking and information on phenotypic variety (in particular, distribution of age of onset) and MRI findings is limited. Here we leverage an updated screening of >3500 ataxia exomes and genomes to identify two novel autosomal-recessive PRDX3 families. Our findings represent an independent confirmation of this novel ataxia gene, suggest a neurodevelopmental component of PRDX3 disease, and a broad range of striking MRI signal changes, which indicate damage also to non-cerebellar neuronal systems in PRDX3 disease. Whole-exome (WES) or whole genome (WGS) sequencing was performed in 3500 families diagnosed with cerebellar ataxia and >20 000 individuals with other, unrelated phenotypes. Sequencing data was analysed with bioinformatics tools provided by the GENESIS genomics platform (PMID: 26173844) and the IMGAG GSvar pipeline (https://github.com/imgag/ngs-bits/tree/master/doc/GSvar).2 Recessive missense variants were analysed using strict filters for allele frequency [minimum allele frequency (MAF)gnomAD < 0.01], high functional prediction [Combined Annotation Dependent Depletion (CADD) > 20] and conservation [Genomic Evolutionary Rate Profiling (GERP) > 3] scores; loss-of-function variants were analysed irrespective of functional and conservation scores. Beyond the previously identified PRDX3 patients,1 we identified two novel unrelated recessive families with novel PRDX3 loss-of-function variants: c.43C>T, p.Arg15Ter, homozygous in a Syrian patient from a consanguineous family with infantile onset cerebellar ataxia; and c.658C<T, Gln220Ter (Fig. 1A and B and Table 1), homozygous in a Turkish patient from a consanguineous family with mid-adult onset (35 years) cerebellar ataxia. PRDX3 variants and segregation analysis were confirmed by Sanger sequencing (Fig. 1A). Both variants are predicted to be ‘pathogenic’ according to the ACMG (American College of Medical Genetics) criteria, including the very strong PVS1 criterium for null variants and the strong PM2 criterium for extreme low allele frequency in population databases. No biallelic PRDX3 variants were observed in any of the other probands’ WES/WGS datasets with unrelated phenotypes, indicating the specificity of the finding of damaging PRDX3 variants to ataxia and thus further supporting their pathogenic relevance.
Key factors for effective mitotane therapy in children with adrenocortical carcinoma
2022-07-06

Adjuvant treatment with mitotane and chemotherapy is recommended for paediatric advanced and metastatic adrenocortical carcinoma (ACC). Yet, questions on the indication, dosage, and length of therapy are unanswered. Data from the German Paediatric Oncology Haematology-Malignant Endocrine Tumour studies were analysed retrospectively for patients receiving mitotane during first- and/or second-line therapy. Forty-three patients were identified (median age: 7.5 years (range: 0.2–17.8); 29 female) with median follow-up of 2.2 years (range: 0.04–12.71). Three-year overall (OS) and progression-free survival (PFS) were 44.9% and 28.5%, respectively. Eleven of 43 patients received mitotane as neoadjuvant treatment, and 4/11 tumours reached partial remission (PR). Twenty-seven of 43 patients received mitotane combined with chemotherapy in an adjuvant setting resulting in PR of measurable target lesions in 5/13 patients. Metastatic disease (hazard ratio (HR): 3.2; 95% CI: 1.2–18.6; P = 0.018), duration of mitotane treatment &lt;9 months (HR: 5.6; 95% CI: 1.9–16.9; P = 0.002), and not achieving drug target range (TR) (HR: 28.5; 95% CI: 5.4–150.3; P &lt; 0.001) significantly impacted as negative prognostic factors upon PFS and OS (metastatic disease: HR: 4.9; 95% CI: 1.6–15.5; P = 0.006; duration of mitotane treatment: HR: 7.0: 95% CI 1.9–26.0; P = 0.004; TR not reached: HR: 13.5; 95% CI 3.6–50.3; P &lt; 0.001). Cox regression determined the risk of event decreasing by 10.4% for each month of mitotane treatment ( P = 0.015). Re-treatment with mitotane after first-line treatment proved ineffective. The duration of mitotane treatment and reaching mitotane TR significantly impacted survival. Improving the efficacy of mitotane, including appropriate indications, needs to be evaluated in prospective randomized trials.