Knudsenlivingston3210

Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

Histone post-translational modifications (PTMs) are involved in a variety of essential regulatory processes in the cell, including transcription control. Recent studies have shown that histone PTMs can be accurately predicted from the knowledge of transcription factor binding or DNase hypersensitivity data. Similarly, it has been shown that one can predict PTMs from the underlying DNA primary sequence.

In this study, we introduce a deep learning architecture called DeepPTM for predicting histone PTMs from transcription factor binding data and the primary DNA sequence. Extensive experimental results show that our deep learning model outperforms the prediction accuracy of the model proposed in Benveniste et al. (PNAS 2014) and DeepHistone (BMC Genomics 2019). The competitive advantage of our framework lies in the synergistic use of deep learning combined with an effective pre-processing step. Our classification framework has also enabled the discovery that the knowledge of a small subset of transcription factors (which are histone-PTM and cell-type specific) can provide almost the same prediction accuracy that can be obtained using all the transcription factors data.

https//github.com/dDipankar/DeepPTM.

https//github.com/dDipankar/DeepPTM.Mapping protein-protein interactions at a proteome scale is critical to understanding how cellular signaling networks respond to stimuli. Since eukaryotic genomes encode thousands of proteins, testing their interactions one-by-one is a challenging prospect. High-throughput yeast-two hybrid (Y2H) assays that employ next-generation sequencing to interrogate complementary DNA (cDNA) libraries represent an alternative approach that optimizes scale, cost and effort. We present NGPINT, a robust and scalable software to identify all putative interactors of a protein using Y2H in batch culture. NGPINT combines diverse tools to align sequence reads to target genomes, reconstruct prey fragments and compute gene enrichment under reporter selection. Central to this pipeline is the identification of fusion reads containing sequences derived from both the Y2H expression plasmid and the cDNA of interest. To reduce false positives, these fusion reads are evaluated as to whether the cDNA fragment forms an in-frame translational fusion with the Y2H transcription factor. NGPINT successfully recognized 95% of interactions in simulated test runs. As proof of concept, NGPINT was tested using published data sets and it recognized all validated interactions. Capivasertib in vitro NGPINT can process interaction data from any biosystem with an available genome or transcriptome reference, thus facilitating the discovery of protein-protein interactions in model and non-model organisms.

The forskolin-induced swelling (FIS) assay has become the preferential assay to predict the efficacy of approved and investigational CFTR-modulating drugs for individuals with cystic fibrosis (CF). Currently, no standardized quantification method of FIS data exists thereby hampering inter-laboratory reproducibility.

We developed a complete open-source workflow for standardized high-content analysis of CFTR function measurements in intestinal organoids using raw microscopy images as input. The workflow includes tools for (i) file and metadata handling; (ii) image quantification and (iii) statistical analysis. Our workflow reproduced results generated by published proprietary analysis protocols and enables standardized CFTR function measurements in CF organoids.

All workflow components are open-source and freely available the htmrenamer R package for file handling https//github.com/hmbotelho/htmrenamer; CellProfiler and ImageJ analysis scripts/pipelines https//github.com/hmbotelho/FIS_image_analysis; the Organoid Analyst application for statistical analysis https//github.com/hmbotelho/organoid_analyst; detailed usage instructions and a demonstration dataset https//github.com/hmbotelho/FIS_analysis. Distributed under GPL v3.0.

Supplementary information and a stepwise guide for software installation and data analysis for training purposes are available at Bioinformatics online.

Supplementary information and a stepwise guide for software installation and data analysis for training purposes are available at Bioinformatics online.

To summarize cases submitted to the 2019 Society for Hematopathology/European Association for Haematopathology Workshop under the category of myeloid/lymphoid neoplasms with eosinophilia and PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2 rearrangements, focusing on recent updates and relevant practice findings.

The cases were summarized according to their respective gene rearrangement to illustrate the spectrum of clinical, laboratory, and histopathology manifestations and to explore the appropriate molecular genetic tests.

Disease presentations were heterogeneous, including myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDSs), MDS/MPN, acute myeloid leukemia, acute B- or T-lymphoblastic lymphoma/acute lymphoblastic lymphoma (ALL/LBL), or mixed-lineage neoplasms. Frequent extramedullary involvement occurred. Eosinophilia was common but not invariably present. With the advancement of RNA sequencing, cryptic rearrangements were recognized in genes other than PDGFRA. Additional somatic mutations were more frequent in the FGFR1-rearranged cases. Cases with B-ALL presentations differed from Philadelphia-like B-ALL by the presence of an underlying MPN. Cases with FLT3 and ABL1 rearrangements could be potential candidates for future inclusion in this category.

Accurate diagnosis and classification of this category of myeloid/lymphoid neoplasms has important therapeutic implications. With the large number of submitted cases, we expand our understanding of these rare neoplasms and improve our ability to diagnose these genetically defined disorders.

Accurate diagnosis and classification of this category of myeloid/lymphoid neoplasms has important therapeutic implications. With the large number of submitted cases, we expand our understanding of these rare neoplasms and improve our ability to diagnose these genetically defined disorders.

The aim of this multisite quality improvement study was to evaluate patients' experiences with the patient-centered pathology (PCP) consultation program and to determine whether PCP enhanced their care experience.

Patients were invited to attend PCP consultations to review their pathology report and slides and have their questions answered by the pathologist privately, with the option to attend the appointment with family members or friends for support. A patient experience questionnaire (PEQ) was administered to patients, who participated voluntarily in the PCP, and survey data were collected and stored in REDCap. Statistical analysis was performed using SAS 9.4 (SAS Institute).

Sixty-seven patients (95.5% female) aged 18 to 84 years across 4 institutions completed the PEQ. Overall, 58% and 15.8% of patients had breast and brain tumors, respectively, and 59.7% of tumors were newly diagnosed. Most patients thought it was important for them to learn as much as they could about their health condition. However, the majority of patients reported some degree of difficulty learning about their health condition based on written information, despite 97% having completed high school and/or further education. The majority of patients rated their pathologist as "excellent" across communication metrics. Ultimately, 100% of respondents were satisfied, found their visits to be useful, and would recommend the PCP to other patients.

Patients found that personalized clinical encounters with pathologists improved their understanding of their health condition and their satisfaction with their care experience. Patients thought pathologists communicated respectfully, effectively, and empathetically.

Patients found that personalized clinical encounters with pathologists improved their understanding of their health condition and their satisfaction with their care experience. Patients thought pathologists communicated respectfully, effectively, and empathetically.Porous organic polymers have gained great research interest in the field of adsorption. A benzoxazine porous organic polymer (BoxPOP) constructed from p-phenylenediamine, 1,3,5-trihydroxybenzene and paraformaldehyde was fabricated and explored as an adsorbent for solid-phase extraction (SPE) of four chlorophenols from water and honey samples. Under the optimized SPE conditions, the response linearity for the analysis of the SPE extract of the chlorophenols by high performance liquid chromatography-diode array detector was observed in the range of 0.2-40.0 ng mL-1 for water samples and 5.0-400.0 ng g-1 for honey samples. The method detection limits of the analytes were 0.06-0.08 ng mL-1 for water samples and 1.5-2.0 ng g-1 for honey samples. The recoveries of the analytes from fortified water and honey samples ranged from 84.8 to 119.0% with the relative standard deviations below 8.4%. The results indicate that the prepared BoxPOP is an effective adsorbent for the chlorophenols. The established method provides an alternative approach for the determination of chlorophenols in real samples.The human cerebral cortex undergoes profound structural and functional dynamic variations across the lifespan, whereas the underlying molecular mechanisms remain unclear. Here, with a novel method transcriptome-connectome correlation analysis (TCA), which integrates the brain functional magnetic resonance images and region-specific transcriptomes, we identify age-specific cortex (ASC) gene signatures for adolescence, early adulthood and late adulthood. The ASC gene signatures are significantly correlated with the cortical thickness (P-value less then 2.00e-3) and myelination (P-value less then 1.00e-3), two key brain structural features that vary in accordance with brain development. In addition to the molecular underpinning of age-related brain functions, the ASC gene signatures allow delineation of the molecular mechanisms of neuropsychiatric disorders, such as the regulation between ARNT2 and its target gene ETF1 involved in Schizophrenia. We further validate the ASC gene signatures with published gene sets associated with the adult cortex, and confirm the robustness of TCA on other brain image datasets. Availability All scripts are written in R. Scripts for the TCA method and related statistics result can be freely accessed at https//github.com/Soulnature/TCA. Additional data related to this paper may be requested from the authors.

To assess the reliability and reproducibility of linear and angular measurements of the cephalometric smartphone Android application OneCeph in comparison with the conventional method.

A total number of 22 landmarks were registered, and 26 skeletal and dental cephalometric parameters were measured on 30 pretreatment cephalograms. The measurements for both digital (OneCeph) and conventional tracings were performed twice with a 4-week interval. The reliability (intraexaminer error) was evaluated by using the Pearson correlation coefficient. The variation in measurements between the tracing techniques (reproducibility) was determined by paired t-test.

The Pearson correlation coefficients of all cephalometric measurements for each tracing technique were ≥ 0.95. Significant differences between the two tracing techniques were detected in five measurements (SNB angle, N I to Pog linear measurement, U1-Apoint linear measurement, U lip to S line, and nasiolabial angle; P < .05).

Using 26 measurements to compare both tracing methods, all mean differences between the digital (OneCeph) and conventional methods were below 1 degree/1 mm, indicating that differences between the tracing methods were clinically insignificant.