julilili42/papers huggingface dataset:
The Personalized Cancer Network Explorer (PeCaX) as a visual analytics tool to support molecular tumor boards
2021-06-25

Abstract Background Personalized oncology represents a shift in cancer treatment from conventional methods to target specific therapies where the decisions are made based on the patient specific tumor profile. Selection of the optimal therapy relies on a complex interdisciplinary analysis and interpretation of these variants by experts in molecular tumor boards. With up to hundreds of somatic variants identified in a tumor, this process requires visual analytics tools to guide and accelerate the annotation process. Results The Personal Cancer Network Explorer (PeCaX) is a visual analytics tool supporting the efficient annotation, navigation, and interpretation of somatic genomic variants through functional annotation, drug target annotation, and visual interpretation within the context of biological networks. Starting with somatic variants in a VCF file, PeCaX enables users to explore these variants through a web-based graphical user interface. The most protruding feature of PeCaX is the combination of clinical variant annotation and gene-drug networks with an interactive visualization. This reduces the time and effort the user needs to invest to get to a treatment suggestion and helps to generate new hypotheses. PeCaX is being provided as a platform-independent containerized software package for local or institution-wide deployment. PeCaX is available for download at https://github.com/KohlbacherLab/PeCaX-docker .
Activity of the Mouse Notch ligand DLL1 is Sensitive to C-terminal Tagging in Vivo
2021-06-25

Abstract Objective The mammalian Notch ligand DLL1 has essential functions during development. To visualise DLL1 in tissues, for sorting and enrichment of DLL1-expressing cells, and to efficiently purify DLL1 protein complexes we tagged DLL1 in mice with AcGFPHA or Strep/FLAG. Results We generated constructs to express DLL1 that carried C-terminal in-frame an AcGFPHA tag flanked by loxP sites followed by a Strep/FLAG (SF) tag out of frame. Cre-mediated recombination replaced AcGFP-HA by SF. The AcGFPHAstopSF cassette was added to DLL1 for tests in cultured cells and introduced into endogenous DLL1 in mice by homologous recombination. Tagged DLL1 protein was detected by antibodies against GFP and HA or Flag, respectively, both in CHO cells and embryo lysates. In CHO cells the AcGFP protein fused to DLL1 was functional. I n vivo AcGFP expression was below the level of detection by direct fluorescence. However, the SF tag allowed us to specifically purify DLL1 complexes from embryo lysates. Homozygous mice expressing AcGFPHA or SF-tagged DLL1 revealed a vertebral column phenotype reminiscent of disturbances in AP polarity during somitogenesis, a process most sensitive to reduced DLL1 function. Thus, even small C-terminal tags can impinge on sensitive developmental processes requiring DLL1 activity.
Structural and Trap‐State Density Enhancement in Flash Infrared Annealed Perovskite Layers
2021-06-26

Abstract Perovskite solar cells are well‐known for their high energy conversion efficiency, low‐temperature processing, and cost‐effective production. Flash infrared annealing (FIRA) of slot‐die cast perovskite precursors offers an attractive manufacturing route using high‐throughput roll‐to‐roll technology. Despite the recent progress in FIRA perovskite annealing, the optimal composition of the perovskite precursor is yet to be developed. Here, the effect of methylammonium chloride (MACl) on the perovskite structure and trap‐state density as a function of the FIRA annealing time is investigated. In situ real‐time grazing‐incidence wide‐angle X‐ray scattering (GIWAXS) is employed to monitor the perovskite layer formation during FIRA annealing with millisecond temporal resolution. In addition, the density of states in the bandgap is estimated using ex situ energy‐resolved electrochemical impedance spectroscopy. Evidence is found that adding 10% MACl into the perovskite precursor solution significantly improves the crystallographic orientation of the perovskite layers while reducing the trap‐state density by one order of magnitude. In addition, using time‐resolved GIWAXS, the most favorable time window for the FIRA processing of perovskite films with the lowest mosaicity and trap‐state density is identified. The results are of general importance for elucidating the appropriate temporal windows in complex and fast‐evolving crystallization processes.
Genetic Analyses and Genome-Wide Association Studies on Pathogen Resistance of Bos taurus and Bos indicus Cattle Breeds in Cameroon
2021-06-26

Autochthonous taurine and later introduced zebu cattle from Cameroon differ considerably in their resistance to endemic pathogens with little to no reports of the underlying genetic make-up. Breed history and habitat variations are reported to contribute significantly to this diversity worldwide, presumably in Cameroon as well, where locations diverge in climate, pasture, and prevalence of infectious agents. In order to investigate the genetic background, the genotypes of 685 individuals of different Cameroonian breeds were analysed by using the BovineSNP50v3 BeadChip. The variance components including heritability were estimated and genome-wide association studies (GWAS) were performed. Phenotypes were obtained by parasitological screening and categorised in Tick-borne pathogens (TBP), gastrointestinal nematodes (GIN), and onchocercosis (ONC). Estimated heritabilities were low for GIN and TBP (0.079 (se = 0.084) and 0.109 (se = 0.103) respectively) and moderate for ONC (0.216 (se = 0.094)). Further than revealing the quantitative nature of the traits, GWAS identified putative trait-associated genomic regions on five chromosomes, including the chromosomes 11 and 18 for GIN, 20 and 24 for TBP, and 12 for ONC. The results imply that breeding for resistant animals in the cattle population from Northern Cameroon might be possible for the studied pathogens; however, further research in this field using larger datasets will be required to improve the resistance towards pathogen infections, propose candidate genes or to infer biological pathways, as well as the genetic structures of African multi-breed populations.
Molecular mapping of the PDS70 system
2021-06-27

Context. Determining the chemical properties of the atmosphere of young forming gas giants might shed light on the location their formation occurred and the mechanisms involved. Aims. Our aim was to detect molecules in the atmosphere of the young forming companion PDS70 b by searching for atmospheric absorption features typical of substellar objects. Methods. We obtained medium-resolution ( R ≈ 5075) spectra of the PDS70 planetary system with the SINFONI integral field spectrograph at the Very Large Telescope. We applied molecular mapping, based on cross-correlation with synthetic spectra, to identify signatures of molecular species in the atmosphere of the planet. Results. Although the planet emission is clearly detected when resampling the data to lower resolution, no molecular species could be identified with the cross-correlation technique. We estimated upper limits on the abundances of H 2 O, CO, and CH 4 (log( X mol ) &lt; −4.0, − 4.1, and − 4.9, respectively) assuming a clear atmosphere, and we explored the impact of clouds, which increase the upper limits by a factor of up to 0.7 dex. Assuming that the observations directly probe the planet’s atmosphere, we found a lack of molecular species compared to other directly imaged companions or field objects. Under the assumption that the planet atmosphere presents similar characteristics to other directly imaged planets, we conclude that a dusty environment surrounds the planet, effectively obscuring any feature generated in its atmosphere. We quantify the extinction necessary to impede the detection ( A V ≈ 16−17 mag), pointing to the possibility of higher optical thickness than previously estimated from other studies. Finally, the non-detection of molecular species conflicts with atmospheric models previously proposed to describe the forming planet. Conclusions. To reveal how giant planets form a comprehensive approach that includes constraints from multiple techniques needs to be undertaken. Molecular mapping emerges as an alternative to more classical techniques like SED fitting. Specifically tuned atmospheric models are likely required to faithfully describe the atmospheres of forming protoplanets, and higher spectral resolution data may reveal molecular absorption lines despite the dusty environment enshrouding PDS70 b.
Social, Emotional, and Behavioral Skills: An Integrative Model of the Skills Associated With Success During Adolescence and Across the Life Span
2021-06-28

Social, emotional, and behavioral (SEB) skills encompass a wide range of competencies related to how individuals build and maintain relationships, understand and manage emotions, pursue goals, and learn from experience. Despite near-consensus on the importance of SEB skills for success in life, there are numerous frameworks that simultaneously converge and diverge in how they define and measure SEB skills. In this article, we discuss our integrative model encompassing five broad skill domains: Self-Management, Innovation, Social Engagement, Cooperation, and Emotional Resilience Skills (Soto et al., 2021a). Our model defines SEB skills as skills (i.e., what someone is capable of doing) and not traits (i.e., what someone tends to do). Using this definition and model as a foundation, we argue for the importance of investigating SEB skill development during adolescence, a period where SEB skills may be both particularly amenable to change and particularly predictive of life outcomes. In particular, we highlight how SEB skills allow adolescents to take advantage of the new opportunities afforded to them as they make major cognitive and social transitions.
Characterization of Pharmaceutical Tablets Using UV Hyperspectral Imaging as a Rapid In-Line Analysis Tool
2021-06-28

A laboratory prototype for hyperspectral imaging in ultra-violet (UV) region from 225 to 400 nm was developed and used to rapidly characterize active pharmaceutical ingredients (API) in tablets. The APIs are ibuprofen (IBU), acetylsalicylic acid (ASA) and paracetamol (PAR). Two sample sets were used for a comparison purpose. Sample set one comprises tablets of 100% API and sample set two consists of commercially available painkiller tablets. Reference measurements were performed on the pure APIs in liquid solutions (transmission) and in solid phase (reflection) using a commercial UV spectrometer. The spectroscopic part of the prototype is based on a pushbroom imager that contains a spectrograph and charge-coupled device (CCD) camera. The tablets were scanned on a conveyor belt that is positioned inside a tunnel made of polytetrafluoroethylene (PTFE) in order to increase the homogeneity of illumination at the sample position. Principal component analysis (PCA) was used to differentiate the hyperspectral data of the drug samples. The first two PCs are sufficient to completely separate all samples. The rugged design of the prototype opens new possibilities for further development of this technique towards real large-scale application.
ANXA7 Regulates Platelet Lipid Metabolism and Ca 2+ Release in Arterial Thrombosis
2021-06-28

Rationale: Platelet activation after contact to subendothelial collagen leads to acute arterial thrombosis. ANXA7 (Annexin A7) is a phospholipid-binding protein participating in the regulation of intracellular Ca 2+ and exocytosis. Objective: The present study aimed to determine the role of ANXA7 in platelet Ca 2+ signaling and lipid metabolism during platelet activation in arterial thrombosis using the ANXA7 inhibitor 6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine (ABO) and gene-targeted mice lacking Anxa7 ( Anxa7 −/− ). Methods and Results: ANXA7 is strongly expressed in platelets. Functionally, luminescence aggregometry revealed significantly abrogated aggregation and secretion of ABO-treated or Anxa7 −/− platelets when compared with untreated or Anxa7 +/+ platelets after activation with collagen or the GPVI (glycoprotein VI)-specific agonist collagen-related peptide. Furthermore, while both thrombus formation on collagen-coated surfaces under high arterial shear rates in ABO-treated or Anxa7 -deficient whole blood, and thrombotic vascular occlusion after FeCl 3 -induced injury in vivo in Anxa7 −/− bone marrow chimeric mice were significantly diminished, no prolongation of bleeding time was observed in ABO-treated or Anxa7 −/− mice. Fura-2-AM spectrofluorimetry unraveled a blunted [Ca 2+ ] i increase in ABO-treated or Anxa7 −/− platelets after GPVI stimulation. Due to an abolished phospholipase Cγ2 phosphorylation, Anxa7 −/− platelets displayed abrogated intracellular Ca 2+ mobilization following collagen-related peptide-dependent platelet activation. Quantitative lipidomics analysis further revealed that ANXA7 critically affects platelet oxylipin metabolism following GPVI-dependent platelet activation. Anxa7 −/− platelets showed a significantly reduced generation of several bioactive metabolites, particularly thromboxane A 2 and 12(S)-hydroxy-eicosatetraenoic acid. Finally, defective phospholipase Cγ2 phosphorylation and blunted [Ca 2+ ] i increase in Anxa7 −/− platelets could be rescued by exogenous addition of 12(S)-hydroxy-eicosatetraenoic acid, indicating that ANXA7 is a critical regulator of the platelet 12-lipoxygenase in GPVI-dependent platelet Ca 2+ signaling during arterial thrombosis. Conclusions: The present study unravels ANXA7 as a regulator of oxylipin metabolism and Ca 2+ -dependent platelet activation downstream of GPVI. ANXA7 plays an important role in platelet signaling during arterial thrombosis and thus may reflect a promising target for novel antiplatelet strategies.
Ovipositor of the braconid wasp Habrobracon hebetor: structural and functional aspects
2021-06-28

The Braconidae are a megadiverse and ecologically highly important group of insects. The vast majority of braconid wasps are parasitoids of other insects, usually attacking the egg or larval stages of their hosts. The ovipositor plays a crucial role in the assessment of the potential host and precise egg laying. We used light- and electron-microscopic techniques to investigate all inherent cuticular elements of the ovipositor (the female 9 th abdominal tergum, two pairs of valvifers, and three pairs of valvulae) of the braconid Habrobracon hebetor (Say, 1836) in detail with respect to their morphological structure and microsculpture. Based on serial sections, we reconstructed the terebra in 3D with all its inherent structures and the ligaments connecting it to the 2 nd valvifers. We examined the exact position of the paired valvilli, which are bilateral concave structures that protrude into the egg canal. In H. hebetor , these structures putatively divert the egg ventrally between the 1 st valvulae for oviposition. We discuss further mechanical and functional aspects of the ovipositor in order to increase the understanding of this putative key feature in the evolution of braconids and of parasitoid wasps in general.
Recognizing heat‐treated chert: A comparison between infrared spectroscopy and fracture surface analysis
2021-06-28

Abstract Heat treatment of lithic raw material is used for the first time in Europe in the Solutrean of the upper Paleolithic. The study of which heating technique was used by these groups requires analytical methods to understand and recognize the chemical and physical processes involved. Roughness measurements were tested as a tool for recognizing heat treatment and to compare them to infrared spectroscopy. We also measured the surface topography of geological samples to observe its evolution as a function of heating and then compare the results with those obtained on Solutrean artefacts. Near infrared analyses was carried out for comparing the effectiveness of surface roughness measurements. This work complements our knowledge about the heating environment used by Solutrean groups by confirming the use of controlled heating. In addition, our roughness measurements provide promising results for the recognition of heat treatment through the quantification of the surface luster.
Distinct Phyllosphere Microbiome of Wild Tomato Species in Central Peru Upon Dysbiosis
2021-06-28

<title>Abstract</title> Plants are colonized by myriads of microbes across kingdoms, which affect host development, fitness and reproduction. Hence, plant microbiomes have been explored across a broad range of host species, including model organisms, crops and trees under controlled and natural conditions. Tomato is one of the world’s most important vegetable crops, however little is known about the microbiota of wild tomato species. To obtain insights into the tomato microbiota occurring in natural environments, we sampled epiphytic microbes from leaves of four tomato species, Solanum habrochaites, S. corneliomulleri, S. peruvianum and S. pimpinellifolium, from two geographical locations within the Lima region of Peru over two consecutive years. Here, a high-throughput sequencing approach was applied to investigate microbial compositions including bacteria, fungi and eukaryotes across tomato species and geographical locations. The phyllosphere microbiome composition varies between hosts and location. Yet, we identified persistent microbes across tomato species that form the tomato microbial core community. In addition, we phenotypically defined healthy and dysbiotic samples and performed a downstream analysis to reveal the impact on microbial community structures. To do so, we compared microbial diversities, unique OTUs, relative abundances of core taxa and microbial hub taxa, as well as co-occurrence network characteristics in healthy and dysbiotic tomato leaves and found that dysbiosis affects the phyllosphere microbial composition in a host species-dependent manner Yet, overall, the present data suggests an enrichment of plant-promoting microbial taxa in healthy leaves, whereas numerous microbial taxa containing plant pathogens occurred in dysbiotic leaves. Concluding, we identify the core phyllosphere microbiome of wild tomato species, and show that the overall phyllosphere microbiome can be impacted by sampling time point, geographical location, host genotype and plant health. Future studies in these components will help understand the microbial contribution to plant health in natural systems and can be of use in cultivated tomatoes.
PAX6 is frequently expressed in ependymal tumours and associated with prognostic relevant subgroups
2021-06-28

Aims An ependymoma shows divergent morphological and molecular features depending on their location. The paired box 6 ( PAX6 ) transcription factor is a putative tumour suppressor and drives cancer cells towards a stem cell-like state. A transcriptome study reported high PAX6 expression in ependymal tumours, but data on protein expression are lacking. Methods We, therefore, analysed PAX6 expression by immunohistochemistry in 172 ependymoma samples and correlated its expression to histology, WHO grade, anatomical location and molecular subgroups. Results Mean PAX6 nuclear expression in ependymoma was 27.5% (95% CI 23.3 to 31.7). PAX6 expression in subependymoma (mean: 5%) was significantly lower compared with myxopapillary (30%), WHO grade II (26%) and anaplastic ependymoma (35%). Supratentorial ependymomas also displayed significant lower PAX6 levels (15%) compared with spinal cord tumours (30%). Expression levels in YAP1-fused ependymoma (41%) were higher compared with REL-associated protein (RELA)-fusion positive tumours (17%), while PAX6 expression was similar in posterior fossa group A (33%) and B (29%) ependymomas. Kaplan-Meier analysis in RELA-fusion positive ependymomas and posterior fossa group B showed a significant better outcome for PAX6 at or above the cut-off of 19.45% compared with tumours with PAX6 below the cut-off. Conclusions We demonstrate that PAX6 is frequently expressed in human ependymal tumours and immunohistochemistry may be helpful in determining prognostic relevant subgroups.
Machine Learning Identifies ICU Outcome Predictors in a Multicenter COVID-19 Cohort.
2021-06-28

Abstract Background. Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective &amp; prospective clinical data, to stratify patient risk and predict ICU survival and outcomes. Methods. A Germany-wide electronic registry was established to pseudonymously collect admission, therapeutic and discharge information of SARS-CoV-2 ICU patients retrospectively and prospectively. Machine learning approaches were evaluated for the accuracy and interpretability of predictions. The Explainable Boosting Machine approach was selected as the most suitable method. Individual, non-linear shape functions for predictive parameters and parameter interactions are reported. Results. 1,039 patients were included in the Explainable Boosting Machine model, 596 patients retrospectively collected, and 443 patients prospectively collected. The model for prediction of general ICU outcome was shown to be more reliable to predict “survival”. Age, inflammatory and thrombotic activity, and severity of ARDS at ICU admission were shown to be predictive of ICU survival. Patients’ age, pulmonary dysfunction and transfer from an external institution were predictors for ECMO therapy. The interaction of patient age with D-dimer levels on admission and creatinine levels with SOFA score without GCS were predictors for renal replacement therapy. Conclusions. Using Explainable Boosting Machine analysis, we confirmed and weighed previously reported and identified novel predictors for outcome in critically ill COVID-19 patients. Using this strategy, predictive modeling of COVID-19 ICU patient outcomes can be performed overcoming the limitations of linear regression models. Trial registration. “ClinicalTrials” (clinicaltrials.gov) under NCT04455451
Deficits in or preservation of basic number processing in Parkinson’s disease? A registered report
2021-06-28

Abstract Neurodegenerative diseases such as Parkinson's disease (PD) have a huge impact on patients, caregivers, and the health‐care system. To date, the diagnosis of mild cognitive impairments in PD has been established based on domain‐general functions such as executive functions, attention, or working memory. However, specific numerical deficits observed in clinical practice have not yet been systematically investigated. PD‐immanent deterioration of domain‐general functions and domain‐specific numerical areas suggests the mechanisms of both primary and secondary dyscalculia. The current study will systematically investigate basic number processing performance in PD patients for the first time, targeting domain‐specific cognitive representations of numerosity and the influence of domain‐general factors. The overall sample consists of patients with a diagnosis of PD, according to consensus guidelines, and healthy controls. PD patients will be stratified into patients with normal cognition or mild cognitive impairment (level I‐PD‐MCI based on cognitive screening). Basic number processing will be assessed using transcoding, number line estimation, and (non)symbolic number magnitude comparison tasks. Discriminant analysis will be employed to assess whether basic number processing tasks can differentiate between a healthy control group and both PD groups. All participants will be subjected to a comprehensive numerical and a neuropsychological test battery, as well as sociodemographic and clinical measures. Study results will give the first broad insight into the extent of basic numerical deficits in different PD patient groups and will help us to understand the underlying mechanisms of the numerical deficits faced by PD patients in daily life.