Miracle-dz/UniFAR-FTUs huggingface dataset:
Lack of Restoration in Vivo by K+-Channel Modulators of Jejunal Fluid Absorption after Heat Stable Escherichia coli Enterotoxin (STa) Challenge

Enhanced potassium ion permeability at the enterocyte basolateral membrane is assumed to facilitate sustained chloride ion and fluid secretion into the intestinal lumen during episodes of secretory diarrhoeal disease. To examine this concept in vivo, two potassium ion channel blockers and a channel opener were coperfused with E. coli heat stable STa enterotoxin to determine whether such compounds improved or worsened the inhibited fluid absorption. In the STa (80 ng/mL) challenged jejunal loop, the fluid absorption rate of 28.6 ± 5.8 (14) μL/cm/hr was significantly below (P < .001) the normal rate of 98.8 ± 6.2 (17) μL/cm/hr. Intraluminal (300 uM) glibenclamide added to STa perfused loops failed to improve the inhibited fluid absorption rate, which was 7.4 ± 3.2 (6) μL/cm/hr on coperfusion with STa. Similarly, on coperfusion with 30 uM clotrimazole, the fluid absorption rate with STa present remained inhibited at 11.4 ± 7.0 (4) μL/cm/hr. On coperfusion with intraluminal 1 uM cromakalim, STa reduced fluid absorption significantly (P < .02) to 24.7 ± 8.0 (10) μL/cm/hr, no different from STa challenge in the absence of cromakalim. Infusion i.v. with these agents also failed to restore fluid absorption after STa challenge. These observations do not support the proposed potassium ion permeability event as a necessary corollary of enterotoxin-mediated secretion. This makes it unlikely that modulators of such permeability prevent enterocyte secretion in diarrhoeal disease.
A method for the improvement of threading‐based protein models

A new method for the homology‐based modeling of protein three‐dimensional structures is proposed and evaluated. The alignment of a query sequence to a structural template produced by threading algorithms usually produces low‐resolution molecular models. The proposed method attempts to improve these models. In the first stage, a high‐coordination lattice approximation of the query protein fold is built by suitable tracking of the incomplete alignment of the structural template and connection of the alignment gaps. These initial lattice folds are very similar to the structures resulting from standard molecular modeling protocols. Then, a Monte Carlo simulated annealing procedure is used to refine the initial structure. The process is controlled by the model's internal force field and a set of loosely defined restraints that keep the lattice chain in the vicinity of the template conformation. The internal force field consists of several knowledge‐based statistical potentials that are enhanced by a proper analysis of multiple sequence alignments. The template restraints are implemented such that the model chain can slide along the template structure or even ignore a substantial fraction of the initial alignment. The resulting lattice models are, in most cases, closer (sometimes much closer) to the target structure than the initial threading‐based models. All atom models could easily be built from the lattice chains. The method is illustrated on 12 examples of target/template pairs whose initial threading alignments are of varying quality. Possible applications of the proposed method for use in protein function annotation are briefly discussed. Proteins 1999;37:592–610. ©1999 Wiley‐Liss, Inc.
Mammalian cell growth dynamics in mitosis

The extent and dynamics of animal cell biomass accumulation during mitosis are unknown, primarily because growth has not been quantified with sufficient precision and temporal resolution. Using the suspended microchannel resonator and protein synthesis assays, we quantify mass accumulation and translation rates between mitotic stages on a single-cell level. For various animal cell types, growth rates in prophase are commensurate with or higher than interphase growth rates. Growth is only stopped as cells approach metaphase-to-anaphase transition and growth resumes in late cytokinesis. Mitotic arrests stop growth independently of arresting mechanism. For mouse lymphoblast cells, growth in prophase is promoted by CDK1 through increased phosphorylation of 4E-BP1 and cap-dependent protein synthesis. Inhibition of CDK1-driven mitotic translation reduces daughter cell growth. Overall, our measurements counter the traditional dogma that growth during mitosis is negligible and provide insight into antimitotic cancer chemotherapies.
Bioconversion of Flavonoid Glycosides from Hippophae rhamnoides Leaves into Flavonoid Aglycones by Eurotium amstelodami

The flowering process has been reported to play crucial roles in improving the flavor and efficacy of fermented tea. Hippophae rhamnoides leaves containing many beneficial ingredients are a suitable plant source for tea processing. In this study, we isolated a β-glucosidase-producing fungus Eurotium amstelodami BSX001 from the fermented tea and used Hippophae rhamnoides leaves (HRL) as a substrate to explore the detailed process of bioconversion of some important functional factors. The results show that the contents of total phenolic compounds and flavonoids increased significantly after seven days, especially flavonoid aglycones (e.g., quercetin, kaempferol, and isorhamnetin). Such compounds greatly enhance the antioxidative activity of fermented products. Metabolic analysis of the standard compounds (rutin, quercetin-3-glucoside, kaempferol-3-glucoside, quercetin, isorhamnetin-3-glucoside, isorhamnetin, and kaempferol) further confirmed the effective biotransformation by E. amstelodami. Mechanisms of the bioconversion could be involved in deglycosylation, dihydroxylation, and O-methylation. Our findings expand the understanding of tea fermentation process and provide further guidance for the fermented tea industry.
Symbolic model checking for Dynamic Epistemic Logic - S5 and beyond

Dynamic Epistemic Logic (DEL) can model complex information scenarios in a way that appeals to logicians. However, existing DEL implementations are ad-hoc, so we do not know how the framework really performs. For this purpose, we want to hook up with the best available model checking and SAT techniques in computational logic. We do this by first providing a bridge: a new faithful representation of DEL models as so-called knowledge structures that allow for symbolic model checking. For more complex epistemic change we introduce knowledge transformers analogous to action models. Next, we show that we can now solve well-known benchmark problems in epistemic scenarios much faster than with existing methods for DEL. We also compare our approach to model checking for temporal logics. Finally, we show that our method is not just a matter of implementation, but that it raises significant issues about logical representation and update.
Pharmacological management of obesity: an endocrine Society clinical practice guideline.

OBJECTIVE To formulate clinical practice guidelines for the pharmacological management of obesity. PARTICIPANTS An Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer. This guideline was co-sponsored by the European Society of Endocrinology and The Obesity Society. EVIDENCE This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence. CONSENSUS PROCESS One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the European Society of Endocrinology, and The Obesity Society reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize some of the supporting evidence. CONCLUSIONS Weight loss is a pathway to health improvement for patients with obesity-associated risk factors and comorbidities. Medications approved for chronic weight management can be useful adjuncts to lifestyle change for patients who have been unsuccessful with diet and exercise alone. Many medications commonly prescribed for diabetes, depression, and other chronic diseases have weight effects, either to promote weight gain or produce weight loss. Knowledgeable prescribing of medications, choosing whenever possible those with favorable weight profiles, can aid in the prevention and management of obesity and thus improve health.
Health professional beliefs, knowledge, and concerns surrounding medicinal cannabis – A systematic review

Background The number of jurisdictions allowing access to medicinal cannabis has been steadily increasing since the state of California introduced legislation in 1996. Although there is a high degree of legislative heterogeneity across jurisdictions, the involvement of a health professional is common among all. This places health professionals at the forefront of therapy, yet no systematic review of literature has offered insight into the beliefs, knowledge, and concerns of health professionals regarding medicinal cannabis. Methods Using a predetermined study protocol, PubMed, EMBASE, PsycINFO, CINAHL, and Scopus databases were searched for studies indexed up to the 1st August 2018. Pre-defined inclusion and exclusion criteria were applied uniformly. Screening for relevancy, full-text review, data extraction, and risk of bias were completed by two independent investigators. Risk of bias was assessed using CASP criteria (qualitative) and a modified domain-based risk assessment tool (quantitative). Results Of the 15,775 studies retrieved, 106 underwent full-text review and of these, 26 were included. The overall risk of bias was considered low across all included studies. The general impression was that health professionals supported the use of medicinal cannabis in practice; however, there was a unanimous lack of self-perceived knowledge surrounding all aspects of medicinal cannabis. Health professionals also voiced concern regarding direct patient harms and indirect societal harms. Conclusion This systematic review has offered a lens through which to view the existing literature surrounding the beliefs, knowledge, and concerns of health professionals regarding medicinal cannabis. These results are limited, however, by the implicit common-sense models of behaviour utilised by the included studies. Before strategies can be developed and implemented to change health professional behaviour, a more thorough understanding of the factors that underpin the delivery of medicinal cannabis is necessary.
Treatment of stable chronic obstructive pulmonary disease: protocol for a systematic review and evidence map

Introduction Chronic obstructive pulmonary disease (COPD) is a progressive lung disease, usually caused by tobacco smoking, but other important risk factors include exposures to combustion products of biomass fuels and environmental pollution. The introduction of several new (combination) inhaler therapies, increasing uncertainty about the role of inhaled corticosteroids and a rapid proliferation of the literature on management of stable COPD in general, call for novel ways of evidence synthesis in this area. A systematic review and evidence map can provide the basis for shared decision-making tools and help to establish a future research agenda. Methods and analysis This systematic review will follow an umbrella systematic review design (also called overview of reviews). We plan to conduct a comprehensive literature search of Ovid MEDLINE (including epub ahead of print, in process and other non-indexed citations), Ovid Embase, Ovid Cochrane Database of Systematic Reviews and Scopus from database inception to the present. We will include systematic reviews that assessed the effectiveness of any pharmacological or non-pharmacological intervention on one or more patient-important outcomes and/or lung function in patients with stable COPD. For every intervention/outcome pair, one systematic review will be included. An a priori protocol will guide, which systematic reviews will be chosen, how their credibility will be evaluated, and how the quality of the body of evidence will be rated. Data will be synthesised into an evidence map that will present a matrix that depicts each available treatment for stable COPD with a quantitative estimate on symptoms/outcomes from the patient perspective, along with an indication of the size and certainty in the evidence. Ethics and dissemination Approval by a research ethics committee is not required since the review will only include published data. The systematic review will be published in a peer-reviewed journal. PROSPERO registration number CRD42018095079
Bullying in Nursing: Is it in the Eye of the Beholder?

The nursing profession is presented with numerous definitions of workplace bullying. This study provides an in-depth analysis of the concept of bullying in the nursing profession in Australia through a scoping review of definitions presented in literature published up until 2018. The research questions used to guide the search were as follows: How has the definition of bullying in nursing in Australia been conceptualized in the literature? How do these definitions of bullying differ? How has the definition of bullying, as used in the literature, evolved over time? The review was informed by the approach of Arksey and O’Malley, containing explicit definitions of bullying in nursing literature. The findings reveal that the literature does not reflect a shared and integrated vision of the exact nature of bullying in the nursing profession. The conceptualization of bullying in the nursing profession has become more dynamic over time. The myriad ways in which bullying in nursing is defined in Australia has important implications for research, practice, education, and policy.
Visual loss in pregnancy

Visual loss in pregnancy may be caused by a variety of reasons including pituitary adenomas. Prolactinomas (PRLs) are the most common hormone-secreting tumours in pregnant women. As most PRLs present with menstrual abnormalities, infertility or galactorrhoea, they are most commonly diagnosed before pregnancy. We present the case of a 30-year-old primigravida who presented at 36+5 weeks gestation with headaches and left-sided visual loss. MRI of the pituitary gland confirmed a 10×11 mm left suprasellar mass. Results of her anterior pituitary function were unremarkable for her gestational age. Postpartum, she underwent an endoscopic endonasal resection of the pituitary tumour. The histology was consistent with a PRL. Literature review reveals only one possible case of a new diagnosis of a PRL during pregnancy. It highlights the importance to consider a wide range of differential diagnoses when assessing visual loss in pregnancy.
Edge-Aided Reliable Data Transmission for Heterogeneous Edge-IoT Sensor Networks

Wireless sensor networks have been attracting research attention for the past decade and will continue to be a hot topic due to the emerging trend of Internet-of-Things (IoT). Edge computing for IoT (Edge-IoT) is a promising framework that can help low-powered sensor networks to conduct complex computational tasks. Different from the existing works that focus on cooperative task execution for edge and sensor networks, in this paper, we investigate the problem of reliable data transmission in edge-aided sensor networks. Firstly, we discuss how edge servers can help to improve the data transmission of sensor networks. Secondly, we propose a forwarding scheme for edge nodes to forward packets according to coverage and corresponding interference. Thirdly, we propose an edge-based error recovery approach. By employing edge servers for data transmission and error recovery, the efficiency and reliability of data transmissions can be largely improved.
Affective Working Memory: An Integrative Psychological Construct

When people ruminate about an unfortunate encounter with a loved one, savor a long-sought accomplishment, or hold in mind feelings from a marvelous or regretfully tragic moment, what mental processes orchestrate these psychological phenomena? Such experiences typify how affect interacts with working memory, which we posit can occur in three primary ways: emotional experiences can modulate working memory, working memory can modulate emotional experiences, and feelings can be the mental representations maintained by working memory. We propose that this last mode constitutes distinct neuropsychological processes that support the integration of particular cognitive and affective processes: affective working memory. Accumulating behavioral and neural evidence suggests that affective working memory processes maintain feelings and are partially separable from their cognitive working memory counterparts. Affective working memory may be important for elucidating the contribution of affect to decision making, preserved emotional processes in later life, and mechanisms of psychological dysfunction in clinical disorders. We review basic behavioral, neuroscience, and clinical research that provides evidence for affective working memory; consider its theoretical implications; and evaluate its functional role within the psychological architecture. In sum, the perspective we advocate is that affective working memory is a fundamental mechanism of mind.
Development of an algorithm to identify urgent referrals for suspected cancer from the Danish Primary Care Referral Database

Background Accurate identification of specific patient populations is a crucial tool in health care. A prerequisite for exploring the actions taken by general practitioners (GPs) on symptoms of cancer is being able to identify patients urgently referred for suspected cancer. Such system is not available in Denmark; however, all referrals are electronically stored. This study aimed to develop and test an algorithm based on referral text to identify urgent cancer referrals from general practice. Methods Two urgently referred reference populations were extracted from a research database and linked with the Primary Care Referral (PCR) database through the unique Danish civil registration number to identify the corresponding electronic referrals. The PCR database included GP referrals directed to private specialists and hospital departments, and these referrals were scrutinized. The most frequently used words were integrated in the first version of the algorithm, which was further refined by an iterative process involving two population samples from the PCR database. The performance was finally evaluated for two other PCR population samples against manual assessment as the gold standard for urgent cancer referral. Results The final algorithm had a sensitivity of 0.939 (95% confidence intervals [CI]: 0.905–0.963) and a specificity of 0.937 (95% CI: 0.925–0.963) compared to the gold standard. The positive and negative predictive values were 69.8% (95% CI: 65.0–74.3) and 99.0% (95% CI: 98.4–99.4), respectively. When applying the algorithm on referrals for a population without earlier cancer diagnoses, the positive predictive value increased to 83.6% (95% CI: 78.7–87.7) and the specificity to 97.3% (95% CI: 96.4–98.0). Conclusion The final algorithm identified 94% of the patients urgently referred for suspected cancer; less than 3% of the patients were incorrectly identified. It is now possible to identify patients urgently referred on cancer suspicion from general practice by applying an algorithm for populations in the PCR database.
Calculations of the atomic structure for the low-lying states of actinium

We employ a technique that combines the configuration interaction method with the singles-doubles coupled-cluster method to perform calculation of the energy levels, transition amplitudes, lifetimes, g-factors, and magnetic dipole and electric quadrupole hyperfine structure constants for many low-lying states of neutral actinium. We find very good agreement with existing experimental energy levels and make accurate predictions for missing levels. It has been noted that some of the levels have been previously misidentified; our analysis supports this claim. If spectroscopy is performed with actinium-225, our calculations will lead to values for nuclear structure constants. The accuracy of this can be constrained by comparing with actinium-227.
Bacterial TLR4 and NOD2 signaling linked to reduced mitochondrial energy function in active inflammatory bowel disease

ABSTRACT Inflammatory bowel disease (IBD) has been linked to active signaling with bacterial components and reduced mitochondrial ATP production; however, synergism between both of these disease characteristics remains unclear. We aimed to determine in human IBD transcriptomes the link between a transcriptional signature unique to intestinal cells (ICs) with reduced mitochondrial ATP production (Mito-0) and bacteria triggered signaling using a bioinformatics approach. We generated an IC Mito-0 panel comprised of 199 differentially expressed (DE) transcripts mediated by reduced mitochondrial ATP function (DEGseq, log2 fold-change > |2|, p < .001). Transcripts from this panel were involved in diverse biological functions including regulation of mitochondrial energy (lower ATP), extracellular matrix, cell–cell contact, cytoskeleton, growth, metabolism, and inflammation. Next, unsupervised hierarchical clustering showed that the Mito-0 panel distinctly separated inflamed IBD from non-inflamed transcriptomes, which was also supported by principal component analysis (PCA) revealing distinct variation between sample types based on presence of the Mito-0 signature (PCA, p = 8.77e–09). Utilizing three independent IBD cohorts, we validated that 60 novel transcripts from the Mito-0 panel were significantly increased in inflamed tissue. Subsequently, KEGG generated bacterial TLR4 and NOD2 transcriptional signatures strongly associated with inflamed IBD transcriptomes and with the Mito-0 signature as determined by Spearman’s analysis (coefficient of correlation, r = 0.92, p < .05). Herein, using a comprehensive analysis we demonstrated existence of an axis between bacteria triggered signaling and reduced mitochondrial energy function. Furthermore, we identified and validated novel transcripts within this axis as potential drivers and therapeutic targets for human IBD.
Identification of differentially expressed gene sets using the Generalized Berk-Jones statistic

MOTIVATION Cancer genomics studies frequently aim to identify genes that are differentially expressed between clinically distinct patient subgroups, generally by testing single genes one at a time. However, the results of any individual transcriptomic study are often not fully reproducible. A particular challenge impeding statistical analysis is the difficulty of distinguishing between differential expression comprising part of the genomic disease etiology and that induced by downstream effects. More robust analytical approaches that are well-powered to detect potentially causative genes, are less prone to discovering spurious associations, and can deliver reproducible findings across different studies are needed. RESULTS We propose a set-based procedure for testing of differential expression and show that this set-based approach can produce more robust results by aggregating information across multiple, correlated genomic markers. Specifically, we adapt the Generalized Berk-Jones (GBJ) statistic to test for the transcription factors that may contribute to the progression of estrogen receptor (ER) positive breast cancer. We demonstrate the ability of our method to produce reproducible findings by applying the same analysis to 21 publicly available datasets, producing a similar list of significant transcription factors across most studies. Our GBJ approach produces results that show improved consistency over three set-based testing algorithms: Generalized Higher Criticism (GHC), Gene Set Analysis (GSA), and Gene Set Enrichment Analysis (GSEA). AVAILABILITY AND IMPLEMENTATION Data are in the MetaGxBreast R package. Code is available at github.com/ryanrsun/gaynor_sun_GBJ_breast_cancer. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.