Miracle-dz/UniFAR-FTUs huggingface dataset:
Semi-supervised peak calling with SPAN and JBR genome browser

Abstract The widespread application of ChIP-seq led to a growing need for consistent analysis of multiple epigenetics profiles, for instance, in human studies where multiple replicates are a common element of design. Such multi-samples experimental designs introduced analytical and computational challenges. For example, when peak calling is done independently for each sample, small differences in signal strength/quality lead to a very different number of peaks for individual samples, making group-level analysis difficult. On the other side, when samples are pooled together for joint analysis, individual-level statistical differences are averaged out. Recently, we have demonstrated that a semi-supervised peak calling approach (SPAN) allows for robust analysis of multiple epigenetic profiles while preserving individual sample statistics. Here, we present this approach’s implementation, centered around the JBR genome browser, a stand-alone tool that allows for accessible and streamlined annotation, analysis and visualization. Specifically, JBR supports graphical interactive manual region selection and annotation, thereby addressing supervised learning’s key procedural challenge. Furthermore, JBR includes the capability for peak optimization, i.e. calibration of sample-specific peak calling parameters by leveraging manual annotation. This procedure can be applied to a broad range of ChIP-seq datasets of different quality and chromatin accessibility ATAC-seq, including single-cell experiments. JBR was designed for efficient data processing, resulting in fast viewing and analysis of multiple replicates, up to thousands of tracks. Accelerated execution and integrated semi-supervised peak calling make JBR and SPAN next-generation visualization and analysis tools for multi-sample epigenetic data. Availability and implementation SPAN and JBR run on Linux, Mac OS and Windows, and is freely available at https://research.jetbrains. org/groups/biolabs/tools/span-peak-analyzer and https://research.jetbrains. org/groups/biolabs/tools/jbr-genome-browser. Supplementary information Supplementary data are available at Bioinformatics online.
Patterns in transitions of visual attention during baseline driving and during interaction with visual–manual and voice-based interfaces

Abstract Voice interfaces reduce visual demand compared with visual-manual interfaces, but the extent depends on design. This study compared visual demand during baseline driving with driving while using voice or manual inputs to place calls with Chevrolet MyLink, Volvo Sensus, or a smartphone. Mean glance duration and total eyes-off-road-time increased when using manual input compared with baseline driving; only eyes off road time increased with voice input. Confusion matrices developed with hidden Markov modelling characterise the similarity of glance sequences during baseline driving and while making phone calls. Glance sequences with the MyLink voice interface were misclassified as baseline driving more frequently than the other voice interfaces. Conversely, glance sequences with the Sensus and smartphone voice interfaces were more often misclassified as manual phone calling. Thus, the MyLink voice interface not only reduced the overall visual demand of placing calls, but produced glance patterns more similar to driving without another task. Practitioner Summary: The attention map and confusion matrix methodologies provide ways of characterising similarities and differences in glance behaviour across secondary task conditions, complementing traditional temporally based metrics (e.g. mean glance duration, long duration glances) while addressing some of the limitations of total-eyes-off-road-time (TEORT) for comparing secondary task behaviour to baseline driving.
A Single Cell Gene Expression Atlas of 28 Human Livers

The liver is the largest solid organ in the human body and is responsible for a multitude of essential functions for survival. Chronic liver injury affects over 1 billion people worldwide and therapeutic options other than liver transplantation are a critical unmet medical need. Thus, advances in molecular hepatology are essential to facilitate the discovery of new therapeutic targets. Here we describe the aggregation and integration of single cell RNA-sequencing in more than 36,000 cells from 28 human livers reported in five independent studies. Noteworthy, the merged data shows a high degree of overlap, demonstrating the robustness of liver gene expression at single cell level independent of age, gender, liver collection, processing and sequencing methods. Hence, this data allowed us to develop a user-friendly web browser for quick and easy interrogation and comparison of gene expression across a variety of parenchymal and non-parenchymal liver cell populations. Collectively, this study provides the largest human liver transcriptomic single cell atlas accessible for interactive visualization via an open-access web portal to the research community worldwide.
A bacterial tyrosine phosphatase modulates cell proliferation through targeting RGCC

Tyrosine phosphatases are often weaponized by bacteria colonizing mucosal barriers to manipulate host cell signal transduction pathways. Porphyromonas gingivalis is a periodontal pathogen and emerging oncopathogen which interferes with gingival epithelial cell proliferation and migration, and induces a partial epithelial mesenchymal transition. P. gingivalis produces two tyrosine phosphatases, and we show here that the low molecular weight tyrosine phosphatase, Ltp1, is secreted within gingival epithelial cells and translocates to the nucleus. An ltp1 mutant of P. gingivalis showed a diminished ability to induce epithelial cell migration and proliferation. Ltp1 was also required for the transcriptional upregulation of Regulator of Growth and Cell Cycle (RGCC), one of the most differentially expressed genes in epithelial cells resulting from P. gingivalis infection. A phosphoarray and siRNA showed that P. gingivalis controlled RGCC expression through Akt, which was activated by phosphorylation on S473. Akt activation is opposed by PTEN, and P. gingivalis decreased the amount of PTEN in epithelial cells. Ectopically expressed Ltp1 bound to PTEN, and reduced phosphorylation of PTEN at Y336 which controls proteasomal degradation. Ltp-1 induced loss of PTEN stability was prevented by chemical inhibition of the proteasome. Knockdown of RGCC suppressed upregulation of Zeb2 and mesenchymal markers by P. gingivalis. RGCC inhibition was also accompanied by a reduction in production of the proinflammatory cytokine IL-6 in response to P. gingivalis. Elevated IL-6 levels can contribute to periodontal destruction, and the ltp1 mutant of P. gingivalis incited less bone loss compared to the parental strain in a murine model of periodontal disease. These results show that P. gingivalis can deliver Ltp1 within gingival epithelial cells, and establish PTEN as the target for Ltp1 phosphatase activity. Disruption of the Akt1/RGCC signaling axis by Ltp1 facilitates P. gingivalis-induced increases in epithelial cell migration, proliferation, EMT and inflammatory cytokine production.
Utilizing the Microbiota and Machine Learning Algorithms to Assess Risk of Salmonella Contamination in Poultry Rinsate.

Traditional microbiological testing methods are slow, and many molecular-based techniques rely on culture-based enrichment to overcome low limits of detection. Recent advancements in sequencing technologies may make it possible to utilize machine learning (ML) to identify patterns in microbiome data to potentially predict the presence or absence of pathogens. In this study, 299 poultry rinsate samples from various points in the processing chain were analyzed to determine if microbiota could inform about a sample's risk for containing Salmonella . Samples were culture confirmed as Salmonella -positive or -negative following modified USDA MLG protocols. The culture confirmation result was used as a reference to compare with 16S sequencing data. Pre-chill samples tested positive (71/82) at a higher frequency than post-chill samples (30/217) and contained greater microbial diversity. Due to their larger sample size, post-chill samples were analyzed more deeply. Analysis of variance (ANOVA) identified a significant effect of chilling on the number of genera (p<0.001), but analysis of similarities (ANOSIM) failed to provide evidence for microbial dissimilarity between pre- and post-chill samples (p=0.001, R=0.443). Various ML models were trained using post-chill samples to predict if a sample contained Salmonella based on the samples' microbiota pre-enrichment. The optimal model was a Random Forest-based model with a performance as follows: accuracy (88%), sensitivity (85%), specificity (90%). While the algorithms described in this paper are prototypes, these risk-based algorithms demonstrate the potential and need for further studies to provide insight alongside diagnostic tests. Combining risk-based information with diagnostic tools can help poultry processors make informed decisions to help identify and prevent the spread of Salmonella . These data add to the growing body of literature exploring novel ways to utilize microbiome data for predictive food safety.
Evolution of cancer stem cell lineage involving feedback regulation

Tumor emergence and progression is a complex phenomenon that assumes special molecular and cellular interactions. The hierarchical structuring and communication via feedback signaling of different cell types, which are categorized as the stem, progenitor, and differentiated cells in dependence of their maturity level, plays an important role. Under healthy conditions, these cells build a dynamical system that is responsible for facilitating the homeostatic regulation of the tissue. Generally, in this hierarchical setting, stem and progenitor cells are yet likely to undergo a mutation, when a cell divides into two daughter cells. This may lead to the development of abnormal characteristics, i.e. mutation in the cell, yielding an unrestrained number of cells. Therefore, the regulation of a stem cell’s proliferation and differentiation rate is crucial for maintaining the balance in the overall cell population. In this paper, a maturity based mathematical model with feedback regulation is formulated for healthy and mutated cell lineages. It is given in the form of coupled ordinary and partial differential equations. The focus is laid on the dynamical effects resulting from acquiring a mutation in the hierarchical structure of stem, progenitor and fully differentiated cells. Additionally, the effects of nonlinear feedback regulation from mature cells into both stem and progenitor cell populations have been inspected. The steady-state solutions of the model are derived analytically. Numerical simulations and results based on a finite volume scheme underpin various expected behavioral patterns of the homeostatic regulation and cancer evolution. For instance, it has been found that the mutated cells can experience significant growth even with a single somatic mutation, but under homeostatic regulation acquire a steady-state and thus, ensuing healthy cell population to either a steady-state or a lower cell concentration. Furthermore, the model behavior has been validated with different experimentally measured tumor values from the literature.
Ethical Discourse of Medical Students on the Phenomenon of Death: A Qualitative Study

The aim of this study is to discover medical students’ ideas on the phenomenon of death; produce information on how these students interpret the value-related problems regarding death that they come across in different units of hospitals; and assess this data in ethical terms. This study included a qualitative research in which 12 focus group interviews were conducted with 92 fifth- and sixth-year medical students. Data obtained from interviews were assessed using a thematic content secondary analysis. The main themes were specified according to the medical students’ statements and were reviewed under the contexts of the “dying process”; “effects of death”; “attitude and behavior of health professionals”; “seeing a dead body/looking at a dead body”; “accepting death”; and “forms of expressions of death. ” Medical students’ encounters with death in different units of hospitals leads them to question their values and familiarize themselves with the borders of their areas of profession.
Too much to know? The cognitive demands of daily knowledge seeking and the buffering role of coworker contact quality.

To get their work done and achieve their daily work-related goals, employees seek knowledge from their coworkers. While the benefits of knowledge seeking have been established in the literature, we have yet to understand the potential downsides of daily knowledge seeking. We adopt a cognitive perspective to carve out the negative effect of daily knowledge seeking, while controlling for its established positive effect via perceived learning. Based on cognitive load theory, we argue that daily knowledge seeking produces intrinsic cognitive load that can hinder daily goal attainment through the experience of knowledge overload and subsequent resource depletion. However, the relational context in which knowledge seekers interact with knowledge sources represents an important contextual boundary condition. Coworker contact quality can mitigate the effect of knowledge seeking on knowledge overload because high coworker contact quality reduces extraneous (i.e., ineffective) and increases germane (i.e., productive) cognitive load that knowledge seekers experience when navigating the social interaction with knowledge sources. Under this condition, cognitive capacity is freed up and knowledge overload is less likely to occur. Based on an experience sampling study in which we collected data across 10 working days from 189 German employees, we found support for our hypotheses. An employee's knowledge seeking had a negative indirect effect on goal attainment via knowledge overload and subsequent resource depletion, however, the downsides of daily knowledge seeking became less pronounced when coworker contact quality increased. We discuss the implications of our findings for research on knowledge seeking and resource exchange behaviors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Pseudoprevotella muciniphila gen. nov., sp. nov., a mucin-degrading bacterium attached to the bovine rumen epithelium

A Gram-negative, strictly anaerobic mucin-degrading bacterium, which we designated strain E39T, was isolated from the rumen epithelium of Korean cattle. The cells were non-motile and had a coccus morphology. Growth of strain E39T was observed at 30–45°C (optimum, 39°C), pH 6.5–8.5 (optimum, pH 7.5), and in the presence of 0.0–1.0% (w/v) NaCl (optimum, 0.0–0.5%). Strain E39T contained C16:0, C18:0, C18:1 ω9c, iso-C15:0, and anteiso-C15:0 as the major fatty acids. The major polar lipids were phosphatidylethanolamine, unidentified aminophospholipid, and unidentified lipids. The major respiratory isoprenoid quinones were MK-8 and MK-9. The major fermented end-products of mucin were acetate and succinate. The G+C content of the genomic DNA was 46.4 mol%. Strain E39T was most closely related to Alloprevotella rava 81/4-12T with an 87.3% 16S rRNA gene sequence similarity. On the basis of phenotypic, chemotaxonomic, and molecular properties, strain E39T represents a novel genus of the family Prevotellaceae; as such, the name Pseudoprevotella muciniphila gen. nov., sp. nov. is proposed. A functional annotation of the whole genome sequences of P. muciniphila E39T revealed that this bacterium has a putative mucin-degrading pathway and biosynthetic pathways of extracellular polymeric substances and virulence factors which enable bacteria to adhere to the epithelial cells and avoid the host’s immune responses.
Development and validation of a sensitive MEDLINE search strategy to identify literature relevant to limb prostheses

Background: Researchers and clinicians may find it challenging to identify relevant articles about limb prostheses in online databases. Searches may be improved by using standardized strategies, also known as filters or hedges. Objectives: To develop and validate a highly sensitive MEDLINE (EBSCOHost) search strategy for limb prostheses. Study Design: Search strategy development/validation. Methods: A gold standard (GS) list of peer-reviewed articles on the topic of limb prostheses was created using a relative recall method. This involved identifying and including relevant systematic reviews/meta-analyses and then adding articles that were included in the analysis section of these reviews. Possible terms for the search strategy were identified through brainstorming and exploration of medical subject headings in MEDLINE (MeSH) and standards from the International Organization for Standardization (ISO). Concepts were grouped using relevant Boolean operators (e.g. AND and OR) and database record search fields (i.e. MeSH terms, title, and abstract). Part of the GS was used to refine the search strategy and reduce the number of records retrieved in total. The remaining GS set was used to validate and calculate sensitivity of the search strategy. Performance of the search strategy was compared against searches using only relevant MeSH terms. Results: After screening, the final GS totaled 853 records. The developed search strategy was highly sensitive (99.80%) and performed with higher relative recall than searches with relevant MeSH terms. Conclusions: This study provides a highly sensitive search strategy that can be used by clinicians and researchers when searching for relevant literature on limb prostheses in MEDLINE (EBSCOHost).
The FTZ-F1 gene encodes two functionally distinct nuclear receptor isoforms in the ectoparasitic copepod salmon louse (Lepeophtheirus salmonis)

The salmon louse, Lepeophtheirus salmonis, is an ectoparasitic crustacean that annually inflicts substantial losses to the aquaculture industry in the northern hemisphere and poses a threat to the wild populations of salmonids. The salmon louse life cycle consists of eight developmental stages each separated by a molt. Fushi Tarazu Factor-1 (FTZ-F1) is an ecdysteroid-regulated gene that encodes a member of the NR5A family of nuclear receptors that is shown to play a crucial regulatory role in molting in insects and nematodes. Characterization of an FTZ-F1 orthologue in the salmon louse gave two isoforms named αFTZ-F1 and βFTZ-F1, which are identical except for the presence of a unique N-terminal domain (A/B domain). A comparison suggest conservation of the FTZ-F1 gene structure among ecdysozoans, with the exception of nematodes, to produce isoforms with unique N-terminal domains through alternative transcription start and splicing. The two isoforms of the salmon louse FTZ-F1 were expressed in different amounts in the same tissues and showed a distinct cyclical expression pattern through the molting cycle with βFTZ-F1 being the highest expressed isoform. While RNA interference knockdown of βFTZ-F1 in nauplius larvae and in pre-adult males lead to molting arrest, knockdown of βFTZ-F1 in pre-adult II female lice caused disruption of oocyte maturation at the vitellogenic stage. No apparent phenotype could be observed in αFTZ-F1 knockdown larvae, or in their development to adults, and no genes were found to be differentially expressed in the nauplii larvae following αFTZ-F1 knockdown. βFTZ-F1 knockdown in nauplii larvae caused both down and upregulation of genes associated with proteolysis and chitin binding and affected a large number of genes which are in normal salmon louse development expressed in a cyclical pattern. This is the first description of FTZ-F1 gene function in copepod crustaceans and provides a foundation to expand the understanding of the molecular mechanisms of molting in the salmon louse and other copepods.
Examining the potential applicability of the minority stress model for explaining suicidality in individuals with disabilities.

PURPOSE/OBJECTIVE The purpose of this conceptual article is to discuss the minority stress model and its potential applicability as a model for examining the higher rates of suicidality in people with disabilities. METHOD This conceptual article is based in the empirical literature on the minority stress model and the literature exploring the experiences of both proximal (e.g., internalized stigma, self-concealment) and distal (e.g., harassment, violence, and discrimination) minority stress among people with disabilities. It also draws from the literature on suicidality and disability. RESULTS After establishing the higher rates of suicidality among people with disabilities as evidenced in the existing literature and discussing our gaps in the knowledge about the factors that drive this phenomenon, I discuss the minority stress model, which posits that elevated rates of suicidality among individuals with disabilities can be explained by a combination of proximal and distal stressors related to one's marginalized status. I then discuss the ways in which this model could be applied to suicidality and psychological distress in individuals with disabilities, drawing on research that establishes that they experience these proximal and distal stressors at high rates. CONCLUSIONS The minority stress model is potentially useful for conceptualizing the higher rates of suicidality among people with disabilities, both alone and in conjunction with other models of suicide, in a manner that addresses disability justice and the experiences and effects of chronic, pervasive marginalization. Recommendations for research, and policy, including strategies for addressing both internalized ableism and disability-related discrimination and harassment, are provided. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
The clinical application value of miR-1269 as an unfavorable prognostic indicator of lung cancer.

BACKGROUND Thanks to microRNAs (miR), a myriad of outstanding achievements have been made in multiple fields in recent years. miR-1269, a newly discovered miR, presents high expression profiles in lung cancer (LC), but its clinical implications in LC have not been clarified yet. METHODS The miR-1269 expressions in the peripheral blood of LC patients, benign pulmonary disease (BPD) patients, and healthy controls were measured using qRT-PCR. Receiver operating characteristic (ROC) curves were employed for the identification of the diagnostic value of miR-1269 in LC, as were Kaplan-Meier (K-M) analyses and a Cox regression model to determine miR-1269's prognostic value in LC. RESULTS qRT-PCR revealed higher miR-1269 expressions in the LC patients than in the BPD patients and the controls (P < 0.001). The LC patients with high miR-1269 expressions had advanced tumor stages (III-IV) and an increased probability of lymph node metastasis (LNM) (P < 0.01). Also, evidently elevated miR-1269 levels were observed in the peripheral blood of patients with the advanced tumor stages (III-IV) and LNM. Via ROC curves, we found that miR-1269 is of high clinical significance in the diagnosis of LC and advanced tumor stages. Our K-M survival analysis revealed a lowered 5-year survival rate in patients with high miR-1269 expressions, and our Cox regression analysis found that miR-1269 is an independent prognostic factor for LC. CONCLUSIONS miR-1269, with high expression profiles in LC, indicates unfavorable patient prognoses, so it may be a viable diagnostic and prognostic indicator of LC.