Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimental Guidance for Discovering Genetic Networks through Iterative Hypothesis Reduction on Time Series

Large programs of dynamic gene expression, like cell cyles and circadian rhythms, are controlled by a relatively small “core” network of transcription factors and post-translational modifiers, working in concerted mutual regulation. Recent work suggests that system-independent, quantitative features of the dynamics of gene expression can be used to identify core regulators. We introduce an approach of iterative network hypothesis reduction from time-series data in which increasingly complex features of the dynamic expression of individual, pairs, and entire collections of genes are used to infer functional network models that can produce the observed transcriptional program. The culmination of our work is a computational pipeline, Iterative Network Hypothesis Reduction from Temporal Dynamics (Inherent Dynamics Pipeline), that provides a priority listing of targets for genetic perturbation to experimentally infer network structure. We demonstrate the capability of this integrated computational pipeline on synthetic and yeast cell-cycle data. Author Summary In this work we discuss a method for identifying promising experimental targets for genetic network inference by leveraging different features of time series gene expression data along a chained set of previously published software tools. We aim to locate small networks that control oscillations in the genome-wide expression profile in biological functions such as the circadian rhythm and the cell cycle. We infer the most promising targets for further experimentation, emphasizing that modeling and experimentation are an∗Corresponding author: breschine.cummins@montana.edu essential feedback loop for confident predictions of core network structure. Our major offering is the reduction of experimental time and expense by providing targeted guidance from computational methods for the inference of oscillating core networks, particularly in novel organisms.
Early steps of embryo implantation are regulated by exchange of extracellular vesicles between the embryo and the endometrium

In early pregnancy, as the embryo arrives in the uterus, intensive communication between the embryo and uterus begins. Hundreds of molecules are known to be involved, but despite numerous findings, full understanding of the complexity of the embryo–maternal dialog remains elusive. Recently, extracellular vesicles, nanoparticles able to transfer functionally active cargo between cells, have emerged as important players in cell–cell communication, and as such, they have gained great attention over the past decade also in reproductive biology. Here, we use a domestic animal model (Sus scrofa) with an epitheliochorial, superficial type of placentation because of its advantage in studding uterine luminal fluid extracellular vesicles. We show that during early pregnancy, the uterine lumen is abundant with extracellular vesicles that carry a plethora of miRNAs able to target genes involved in embryonic and organismal development. These extracellular vesicles, upon the delivery to primary trophoblast cells, affect genes governing development as well as cell‐to‐cell signaling and interactions, consequently having an impact on trophoblast cell proliferation, migration, and invasion. We conclude that the exchange of a unique population of extracellular vesicles and their molecular cargo at the maternal–embryo interface is the key to the success of embryo implantation and pregnancy.
Capacity and Bias of Learned Geometric Embeddings for Directed Graphs

A wide variety of machine learning tasks such as knowledge base completion, ontology alignment, and multi-label classiﬁcation can beneﬁt from incorporating into learning differentiable representations of graphs or taxonomies. While vectors in Euclidean space can theoretically represent any graph, much recent work shows that alternatives such as complex, hyperbolic, order, or box embeddings have geometric properties better suited to modeling real-world graphs. Experimentally these gains are seen only in lower dimensions, however, with performance beneﬁts diminishing in higher dimensions. In this work, we introduce a novel variant of box embeddings that uses a learned smoothing parameter to achieve better representational capacity than vector models in low dimensions, while also avoiding performance saturation common to other geometric models in high dimensions. Further, we present theoretical results that prove box embeddings can represent any DAG. We perform rigorous empirical evaluations of vector, hyperbolic, and region-based geometric representations on several families of synthetic and real-world directed graphs. Analysis of these results exposes correlations between different families of graphs, graph characteristics, model size, and embedding geometries, providing useful insights into inductive biases of various differentiable graph representations.
Pyrroloquinoline Quinone Regulates Enteric Neurochemical Plasticity of Weaned Rats Challenged With Lipopolysaccharide

The enteric nervous system (ENS) is important for the intestinal barrier to defend and regulate inflammation in the intestine. The aim of this study was to investigate the effect of pyrroloquinoline quinone (PQQ) on regulating neuropeptide secretion by ENS neurons of rats challenged with lipopolysaccharide (LPS) to create enteritis. Thirty Sprague Dawley rats were divided into five groups, namely, basal (CTRL), basal plus LPS challenge (LPS), basal with 2.5 mg/kg b.w. /day of PQQ plus challenge with LPS (PQQ 2.5), basal with 5.0 mg/kg b.w. /day PQQ plus challenge with LPS (PQQ 5), and basal with 10.0 mg/kg b.w. /day PQQ plus challenge with LPS (PQQ 10). After treatment with basal diet or PQQ for 14 days, rats were challenged with LPS except for the CTRL group. Rats were euthanized 6 h after the LPS challenge. Rats showed an increased average daily gain in PQQ treatment groups (P < 0.05). Compared with the LPS group, PQQ 5 and PQQ 10 rats showed increased villus height and villus height/crypt depth of jejunum (P < 0.05). In PQQ treatment groups, concentrations of IL-1β and TNF-α in serum and intestine of rats were decreased, and IL-10 concentration was increased in serum compared with the LPS group (P < 0.05). Compared with the LPS group, the concentration of neuropeptide Y (NPY), nerve growth factor (NGF), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), and brain-derived neurotropic factor (BDNF) in serum were decreased in PQQ treatment groups (P < 0.05). Compared with the LPS group, ileal mRNA levels of BDNF, NPY, and NGF were decreased in PQQ treatment groups (P < 0.05). Jejunal concentrations of SP, CGRP, VIP, BDNF, NPY, and NGF were decreased in PQQ treatment groups compared with the LPS group (P < 0.05). Compared with the LPS group, phosphor-protein kinase B (p-Akt)/Akt levels in jejunum and colon were decreased in PQQ treatment groups (P < 0.05). In conclusion, daily treatment with PQQ improved daily gain, jejunal morphology, immune responses. PQQ-regulated enteric neurochemical plasticity of ENS via the Akt signaling pathway of weaned rats suffering from enteritis.
Oral mRNA Vaccines Against Infectious Diseases- A Bacterial Perspective [Invited]

The mRNA vaccines from Pfizer/BioNTech and Moderna were granted emergency approval in record time in the history of vaccinology and played an instrumental role in limiting the pandemic caused by SARS-CoV-2. The success of these vaccines resulted from over 3 decades of research from many scientists. However, the development of orally administrable mRNA vaccine development is surprisingly underexplored. Our group specializing in Salmonella-based vaccines explored the possibility of oral mRNA vaccine development. Oral delivery was made possible by the exploitation of the Semliki Forest viral replicon and Salmonella vehicle for transgene amplification and gene delivery, respectively. Herein we highlight the prospect of developing oral replicon-based mRNA vaccines against infectious diseases based on our recent primary studies on SARS-CoV-2. Further, we discuss the potential advantages and limitations of bacterial gene delivery.
Survival of Children With Pulmonary Embolism Supported by Extracorporeal Membrane Oxygenation

The purpose of this study was to describe the demographics and in-hospital mortality of children (<18 years) from 2007 to 2018 supported by Extracorporeal Membrane Oxygenation (ECMO) for a primary diagnosis of pulmonary embolism and reported to the Extracorporeal Life Support Organization database. Fifty-six patients were identified and 54 were included in this analysis. A total of 33 patients (61%) survived. No differences in demographics or ECMO details (duration, mode, and support type) were found between survivors and non-survivors. When ECMO complications were compared, pulmonary bleeding occurred more frequently in non-survivors (23.8%, n = 5) compared to survivors (n = 0) (p = 0.006).
TAIM: Tool for Analyzing Root Images to Calculate the Infection Rate of Arbuscular Mycorrhizal Fungi

Arbuscular mycorrhizal fungi (AMF) infect plant roots and are hypothesized to improve plant growth. Recently, AMF is now available for axenic culture. Therefore, AMF is expected to be used as a microbial fertilizer. To evaluate the usefulness of AMF as a microbial fertilizer, we need to investigate the relationship between the degree of root colonization of AMF and plant growth. The method popularly used for calculation of the degree of root colonization, termed the magnified intersections method, is performed manually and is too labor-intensive to enable an extensive survey to be undertaken. Therefore, we automated the magnified intersections method by developing an application named “Tool for Analyzing root images to calculate the Infection rate of arbuscular Mycorrhizal fungi: TAIM. ” TAIM is a web-based application that calculates the degree of AMF colonization from images using automated computer vision and pattern recognition techniques. Experimental results showed that TAIM correctly detected sampling areas for calculation of the degree of infection and classified the sampling areas with 87.4% accuracy. TAIM is publicly accessible at http://taim.imlab. jp/.
A Study on the Effects of Cognitive Overloading and Distractions on Human Movement During Robot-Assisted Dressing

For robots that can provide physical assistance, maintaining synchronicity of the robot and human movement is a precursor for interaction safety. Existing research on collaborative HRI does not consider how synchronicity can be affected if humans are subjected to cognitive overloading and distractions during close physical interaction. Cognitive neuroscience has shown that unexpected events during interactions not only affect action cognition but also human motor control Gentsch et al. (Cognition, 2016, 146, 81–89). If the robot is to safely adapt its trajectory to distracted human motion, quantitative changes in the human movement should be evaluated. The main contribution of this study is the analysis and quantification of disrupted human movement during a physical collaborative task that involves robot-assisted dressing. Quantifying disrupted movement is the first step in maintaining the synchronicity of the human-robot interaction. The human movement data collected from a series of experiments where participants are subjected to cognitive loading and distractions during the human-robot interaction, are projected in a 2-D latent space that efficiently represents the high-dimensionality and non-linearity of the data. The quantitative data analysis is supported by a qualitative study of user experience, using the NASA Task Load Index to measure perceived workload, and the PeRDITA questionnaire to represent the human psychological state during these interactions. In addition, we present an experimental methodology to collect interaction data in this type of human-robot collaboration that provides realism, experimental rigour and high fidelity of the human-robot interaction in the scenarios.
Compulsive Sexual Behavior Online and Non-online in Adult Male Patients and Healthy Controls: Comparison in Sociodemographic, Clinical, and Personality Variables

Background and Aims Compulsive sexual behavior (CSB) is characterized by a persistent pattern of failure to control sexual impulses, resulting in repetitive sexual behavior over a prolonged period that causes marked discomfort in personal, family, social, school, work or in other functional areas. The evolution of the worldwide incidence of this disorder warrants further studies focused on examining the characteristics of the affected people. The purpose of this study was to compare online compulsive sexual behavior (when the problematic sexual practices were online) and non-online compulsive sexual behavior (when the problematic sexual practices were in-person) patients (OCSB and non-OCSB, respectively), and healthy controls in terms of sexual behavior, sociodemographic variables and psychopathology and personality characteristics. Method A sample of 80 CSB male patients consecutively admitted to our Behavioral Addictions Unit and 25 healthy male controls, participated in the study. The CSB group was comprised by 36 online CSB patients (mean age 42.25, SD: 10.0) and 44 non-online CSB patients (mean age 43.5, SD: 11.9). Scores on the Sexual Compulsivity Scale, Temperament and Character Inventory-Revised, Symptom CheckList-90 Items-Revised, State-Trait Anxiety Index, and additional demographic, clinical, and social/family variables related to sexual behaviors between the three groups were compared. Results When compared with healthy controls, both clinical groups showed higher psychopathology in all measures as well as higher harm avoidance and self-transcendence and lower self-directness and cooperativeness. When comparing OCSB and non-OCSB patients, results showed that non-OCSB patients exhibited higher prevalence of sexually transmitted diseases, higher percentage of homosexual and bisexual orientation and higher scores in anxiety and in sexual impulse control failure. Conclusion Both online and non-online CSB patients may experience a variety of comorbid psychological and medical problems. Patients with non-OCSB may suffer more consequences that are negative. Therefore, these results should be considered when designing the most convenient therapeutic approach. Whether sexual orientation plays a role in treatment needs and treatment response in CSB, should be further explored in future studies.
Conventional and Nonconventional Sources of Exosomes–Isolation Methods and Influence on Their Downstream Biomedical Application

Despite extensive study of extracellular vesicles (EVs), specifically exosomes (EXs) as biomarkers, important modulators of physiological or pathological processes, or therapeutic agents, relatively little is known about nonconventional sources of EXs, such as invertebrate or plant EXs, and their uses. Likewise, there is no clear information on the overview of storage conditions and currently used isolation methods, including new ones, such as microfluidics, which fundamentally affect the characterization of EXs and their other biomedical applications. The purpose of this review is to briefly summarize conventional and nonconventional sources of EXs, storage conditions and typical isolation methods, widely used kits and new “smart” technologies with emphasis on the influence of isolation techniques on EX content, protein detection, RNA, mRNA and others. At the same time, attention is paid to a brief overview of the direction of biomedical application of EXs, especially in diagnostics, therapy, senescence and aging and, with regard to the current situation, in issues related to Covid-19.
The Impact of Different Factors on Repeat Visits to Selected International Tourism Enterprises: Case Study From Czechia

The aim of this article is to identify the influence of the different factors on the repeat visits to selected international tourism enterprises based on the responses of customers in Czechia. The selected factors were divided into three main groups: service, environment, and offer, and each of these groups consists of other different factors. Primary data were analyzed using SPSS software. Statistical hypotheses were formed, reflecting the relationship between the difference in customer responses and selected quality factors, which can affect repeated visits to selected tourism enterprises. Most customers of repeat visits to selected tourism enterprises are affected by professional behavior, staff empathetic approach, offer knowledge and ability to provide as much information as possible, cleanliness and tidiness, overall atmosphere of the establishment, lighting and thermal comfort, air cleanliness, and plenty of space, taste and quality of food and ingredients, and last but not least also corresponding ratio of price/quality, good experience and attractive price level. Studying consumer behavior is important because it helps marketers understand what influences consumers’ buying decisions not only in the tourism area in the Czechia but can fill in the market gap and identify the new products and services that are needed.
Overhauling the Effect of Surface Sterilization on Analysis of Endophytes in Tea Plants

Increasing evidence shows that plant Endophytes play a crucial role in the fitness and productivity of hosts. Surface sterilization is an indispensable process before high-throughput sequencing (HTS) and tissue separation of plant endophytes, but its potential impact on the composition and diversity of endophytes has rarely been investigated. In the present work, the influence of sodium hypochlorite (NaClO) on the diversity of endophytic bacteria and fungi in leaves and stems of tea plants was investigated. We found that the diversity of bacterial endophytes was significantly affected by the concentration of NaClO as well as the pretreatment time. Pretreatment with 0.5% NaClO for 8 min and 2.0% NaClO for 3 min were suitable for the tea plant leaves and stems, respectively, but the effects of NaClO on the diversity of fungal endophytes were limited according to the results from HTS. Regardless of NaClO sterilization, most of the endophytes in tissues, such as the dominant taxa, could not be Isolated by using the regular culture-dependent approaches. Collectively, our results demonstrated that the pretreatment with NaClO should be modified to precisely understand the diversity of endophytes from different tissues of tea plants and also indicate that more attention should be paid to establish specific culture-dependent protocols for the isolation of plant endophytes.
Individual Watershed Areas in Sickle Cell Anemia: An Arterial Spin Labeling Study

Previous studies have pointed to a role for regional cerebral hemodynamic stress in neurological complications in patients with sickle cell anemia (SCA), with watershed regions identified as particularly at risk of ischemic tissue injury. Using single- and multi-inflow time (TI) arterial spin labeling sequences (ASL) in 94 patients with SCA and 42 controls, the present study sought to investigate cerebral blood flow (CBF) and bolus arrival times (BAT) across gray matter, white matter with early arrival times, and in individual watershed areas (iWSAs). In iWSAs, associations between hemodynamic parameters, lesion burden, white matter integrity, and general cognitive performance were also explored. In patients, increases in CBF and reductions in BAT were observed in association with reduced arterial oxygen content across gray matter and white matter with early arrival times using both sequences (all p < 0.001, d = −1.55–−2.21). Across iWSAs, there was a discrepancy between sequences, with estimates based on the single-TI sequence indicating higher CBF in association with reduced arterial oxygen content in SCA patients, and estimates based on the multi-TI sequence indicating no significant between-group differences or associations with arterial oxygen content. Lesion burden was similar between white matter with early arrival times and iWSAs in both patients and controls, and using both sequences, only trend-level associations between iWSA CBF and iWSA lesion burden were observed in patients. Further, using the multi-TI sequence in patients, increased iWSA CBF was associated with reduced iWSA microstructural tissue integrity and slower processing speed. Taken together, the results highlight the need for researchers to consider BAT when estimating CBF using single-TI sequences. Moreover, the findings demonstrate the feasibility of multi-TI ASL for objective delineation of iWSAs and for detection of regional hemodynamic stress that is associated with reduced microstructural tissue integrity and slower processing speed. This technique may hold promise for future studies and treatment trials.
Genetic and Biological Effects of SLC12A3, a Sodium-Chloride Cotransporter, in Gitelman Syndrome and Diabetic Kidney Disease

The SLC12A3 (Solute carrier family 12 member 3) gene encodes a sodium-chloride cotransporter and mediates Na+ and Cl− reabsorption in the distal convoluted tubule of kidneys. An experimental study has previously showed that with knockdown of zebrafish ortholog, slc12a3 led to structural abnormality of kidney pronephric distal duct at 1-cell stage, suggesting that SLC12A3 may have genetic effects in renal disorders. Many clinical reports have demonstrated that the function-loss mutations in the SLC12A3 gene, mainly including Thr60Met, Asp486Asn, Gly741Arg, Leu859Pro, Arg861Cys, Arg913Gln, Arg928Cys and Cys994Tyr, play the pathogenic effects in Gitelman syndrome. This kidney disease is inherited as an autosomal recessive trait. In addition, several population genetic association studies have indicated that the single nucleotide variant Arg913Gln in the SLC12A3 gene is associated with diabetic kidney disease in type 2 diabetes subjects. In this review, we first summarized bioinformatics of the SLC12A3 gene and its genetic variation. We then described the different genetic and biological effects of SLC12A3 in Gitelman syndrome and diabetic kidney disease. We also discussed about further genetic and biological analyses of SLC12A3 as pharmacokinetic targets of diuretics.
Surgical Planning in Penetrating Abdominal Crohn's Disease

Crohn's disease (CD) is increasing globally, and the disease location and behavior are changing toward more colonic as well as inflammatory behavior. Surgery was previously mainly performed due to ileal/ileocaecal location and stricturing behavior, why many anticipate the surgical load to decrease. There are, however, the same time data showing an increasing complexity among patients at the time of surgery with an increasing number of patients with the abdominal perforating disease, induced by the disease itself, at the time of surgery and thus a more complex surgery as well as the post-operative outcome. The other major cause of abdominal penetrating CD is secondary to surgical complications, e.g., anastomotic dehiscence or inadvertent enterotomies. To improve the care for patients with penetrating abdominal CD in general, and in the peri-operative phase in particular, the use of multidisciplinary team discussions is essential. In this study, we will try to give an overview of penetrating abdominal CD today and how this situation may be handled. Proper surgical planning will decrease the risk of surgically induced penetrating disease and improve the outcome when penetrating disease is already established. It is important to evaluate patients prior to surgery and optimize them with enteral nutrition (or parenteral if enteral nutrition is ineffective) and treat abdominal sepsis with drainage and antibiotics.