Miracle-dz/UniFAR-FTUs huggingface dataset:
European Society of Gastrointestinal Endoscopy (ESGE): Recommendations (2009) on clinical use of video capsule endoscopy to investigate small-bowel, esophageal and colonic diseases

These recommendations on video capsule endoscopy, an emerging technology with an impact on the practice of endoscopy, were developed by the European Society of Gastrointestinal Endoscopy (ESGE) Guidelines Committee. The first draft of each section was prepared by one or two members of the writing team, who were selected as experts on the content of that section on the basis of their published work. They used evidence-based methodology, performing MEDLINE and PubMed literature searches to identify relevant clinical studies. Abstracts from scientific meetings were included only if there was no published full paper on a particular topic. If there was disagreement, the first author of the Guideline made the final decision. Recommendations were graded according to the strength of the supporting evidence. The draft guideline was critically reviewed by all authors and submitted to the ESGE councillors for their critical review before approval of the final document. The ESGE Guidelines Committee acknowledges that this document is based on a critical review of the data available at the time of preparation and that further studies may be needed to clarify some aspects. Moreover, this Guideline may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. This document should be regarded as supplying recommendations only to gastroenterologists in providing care to their patients. It is not a set of rules and should not be construed as establishing a legal standard of care, or as encouraging, advocating, requiring, or discouraging any particular treatment. These recommendations must be interpreted according to the clinician's knowledge, expertise, and clinical judgment in the management of individual patients and, if necessary, a course of action that varies from recommendations must be undertaken.
Distribution of RET Mutations in Multiple Endocrine Neoplasia 2 in Denmark 1994–2014: A Nationwide Study

Background: Germline mutations of the REarranged during Transfection (RET) proto-oncogene cause multiple endocrine neoplasia 2 (MEN2). It is unclear whether the distribution of RET mutations varies among populations. The first nationwide study of the distribution of RET mutations was conducted, and the results were compared to those of other populations. Methods: This retrospective cohort study included 1583 patients who underwent RET gene testing in one of three centers covering all of Denmark between September 1994 and December 2014. Primary testing method was Sanger sequencing, which included exons 8–11 and 13–16. Mutations were defined according to the ARUP database July 1, 2016. Results: RET mutations were identified in 163 patients from 36 apparently unrelated families. Among the 36 families 13 (36.1%) carried mutations in codon 611, four (11.1%) in codon 618, three (8.3%) in codon 620, one (2.8%) in codon 631, six (16.7%) in codon 634, one (2.8%) in codon 790, one (2.8%) in codon 804, one (2.8%) in codon 852, one (2.8%) in codon 883, and five (13.9%) in codon 918. Among the 13 families with codon 611 mutations, 12 had the p.C611Y mutation. Conclusions: The distribution of RET mutations in Denmark appears to differ from that of other populations. Mutations in codon 611 were the most prevalent, followed by more frequently reported mutations. This might be due to a possible founder effect for the p.C611Y mutation. However, further studies are needed to find possible explanations for the skewed mutational spectrum in Denmark.
Offspring Sex Is Not Related to Maternal Allocation of Yolk Steroids in the Lizard Bassiana duperreyi (Scincidae)

The eggs of birds and reptiles contain detectable levels of several steroid hormones, and experimental application of such steroids can reverse genetically determined sex of the offspring. However, any causal influence of maternally derived yolk steroids on sex determination in birds and reptiles remains controversial. We measured yolk hormones (dihydrotestosterone, testosterone, and 17 β‐estradiol) in newly laid eggs of the montane scincid lizard Bassiana duperreyi. This species is well suited to such an analysis because (1) offspring sex is influenced by incubation temperatures and egg size as well as by sex chromosomes, suggesting that yolk hormones might somehow be involved in the complex pathways of sex determination, and (2) experimental application of either estradiol or fadrozole to such eggs strongly influences offspring sex. We obtained yolk by biopsy, before incubating the eggs at a temperature that produces a 50:50 sex ratio. Yolk steroid levels varied over a threefold range between eggs from different clutches, but there were no significant differences in yolk steroids, or in relative composition of steroids, between eggs destined to become male versus female. Further, yolk steroid concentrations were not significantly related to egg size. Thus, yolk steroid hormones do not appear to play a critical role in sex determination for B. duperreyi.
Joint partially linear model for longitudinal data with informative drop‐outs

In biomedical research, a steep rise or decline in longitudinal biomarkers may indicate latent disease progression, which may subsequently cause patients to drop out of the study. Ignoring the informative drop‐out can cause bias in estimation of the longitudinal model. In such cases, a full parametric specification may be insufficient to capture the complicated pattern of the longitudinal biomarkers. For these types of longitudinal data with the issue of informative drop‐outs, we develop a joint partially linear model, with an aim to find the trajectory of the longitudinal biomarker. Specifically, an arbitrary function of time along with linear fixed and random covariate effects is proposed in the model for the biomarker, while a flexible semiparametric transformation model is used to describe the drop‐out mechanism. Advantages of this semiparametric joint modeling approach are the following: 1) it provides an easier interpretation, compared to standard nonparametric regression models, and 2) it is a natural way to control for common (observable and unobservable) prognostic factors that may affect both the longitudinal trajectory and the drop‐out process. We describe a sieve maximum likelihood estimation procedure using the EM algorithm, where the Akaike information criterion (AIC) and Bayesian information criterion (BIC) are considered to select the number of knots. We show that the proposed estimators achieve desirable asymptotic properties through empirical process theory. The proposed methods are evaluated by simulation studies and applied to prostate cancer data.
Dynamic release of gentamicin sulfate (GS) from alginate dialdehyde (AD)-crosslinked casein (CAS) films for antimicrobial applications

Abstract In the present work, antibiotic drug gentamicin sulfate (GS) has been loaded into alginate dialdehyde-crosslinked casein (CAS) films for wound dressing applications. The films have been characterized by Fourier transform infrared spectroscopy, X-ray diffraction analysis and scanning electron microscopy. The dynamic release of model drug GS has been investigated in the physiological fluid at 37 °C. The drug release data has been interpreted in the terms of various kinetic models such as Power function model, first order model and Schott model. The release data was found to be well fitted by Schott model. The various diffusion coefficients are also evaluated. The adsorption of model therapeutic protein BSA on the film has been investigated. The maximum adsorption is found to be 5.7 mg/cm2.The films were tested for their antibacterial and anti-fungal action. Finally, the in vivo wound healing study was carried out on Albino wistar rats.
Genetic Analysis of Virulence Potential of Escherichia coli O104 Serotypes Isolated From Cattle Feces Using Whole Genome Sequencing

Escherichia coli O104:H4, a Shiga toxin-producing hybrid pathotype that was implicated in a major foodborne outbreak in Germany in 2011, has not been detected in cattle. However, serotypes of O104, other than O104:H4, have been isolated from cattle feces, with O104:H7 being the most predominant. In this study, we investigated, based on whole genome sequence analyses, the virulence potential of E. coli O104 strains isolated from cattle feces, since cattle are asymptomatic carriers of E. coli O104. The genomes of ten bovine E. coli O104 strains (six O104:H7, one O104:H8, one O104:H12, and two O104:H23) and five O104:H7 isolated from human clinical cases were sequenced. Of all the bovine O104 serotypes (H7, H8, H12, and H23) that were included in the study, only E. coli O104:H7 serotype possessed Shiga toxins. Four of the six bovine O104:H7 strains and one of the five human strains carried stx1c. Three human O104 strains carried stx2, two were of subtype 2a, and one was 2d. Genomes of stx carrying bovine O104:H7 strains were larger than the stx-negative strains of O104:H7 or other serotypes. The genome sizes were proportional to the number of genes carried on the mobile genetic elements (phages, prophages, transposable elements and plasmids). Both bovine and human strains were negative for intimin and other genes associated with the type III secretory system and non-LEE encoded effectors. Plasmid-encoded virulence genes (ehxA, epeA, espP, katP) were also present in bovine and human strains. All O104 strains were negative for antimicrobial resistance genes, except one human strain. Phylogenetic analysis indicated that bovine E. coli O104 strains carrying the same flagellar antigen clustered together and STEC strains clustered separately from non-STEC strains. One of the human O104:H7 strains was phylogenetically closely related to and belonged to the same sequence type (ST-1817) as the bovine O104:H7 STEC strains. This suggests that the bovine feces could be a source of human illness caused by E. coli O104:H7 serotype. Because bovine O104:H7 strains carried virulence genes similar to human clinical strains and one of the human clinical strains was phylogenetically related to bovine strains, the serotype has the potential to be a diarrheagenic pathogen in humans.
Triploidy in a sexually dimorphic passerine provides new evidence for the effect of the W chromosome on secondary sexual traits in birds

In birds, there are two main models for the determination of sex: the Z Dosage model in which the number, or dose, of Z chromosomes determines sex, and the Dominant W model which argues that a specific gene in the W chromosome may influence Z gene expression and determine sex. The best evidence for W determination of sex comes from birds with 2 copies of the Z chromosome paired with a single W (e.g. ZZW) which are nonetheless females. Here, we expand the species where such a mechanism may operate by reporting a case of a triploid Neotropical passerine bird with sexually dimorphic plumage, the Sao Paulo marsh antwren Formicivora paludicola. Evidence from 17 autosomal unlinked microsatellite loci, and CHD1 sex-linked locus, indicate that this individual is a 3n ZZW triploid with intermediate plumage pattern. This example expands our knowledge of sex determination mechanisms in birds by demonstrating that both the W and the two Z chromosomes affect the expression of morphological secondary sexual traits in a non-galliform bird.
Integrative gene ontology and network analysis of coronary artery disease associated genes suggests potential role of ErbB pathway gene EGFR

Coronary artery disease (CAD) is a major cause of mortality in India, more importantly the young Indians. Combinatorial and integrative approaches to evaluate pathways and genes to gain an improved understanding and potential biomarkers for risk assessment are required. Therefore, 608 genes from the CADgene database version 2.0, classified into 12 functional classes representing the atherosclerotic disease process, were analyzed. Homology analysis of the unique list of gene ontologies (GO) from each functional class gave 8 GO terms represented in 11 and 10 functional classes. Using disease ontology analysis 80 genes belonging to 8 GO terms, using FunDO suggested that 29 of them were identified to be associated with CAD. Extended network analysis of these genes using STRING version 9.1 gave 328 nodes and 4,525 interactions of which the top 5% had a node degree of ≥75 associated with pathways including the ErbB signaling pathway with epidermal growth factor receptor (EGFR) gene as the central hub. Evaluation of EFGR protein levels in age and gender-matched 342 CAD patients vs. 342 control subjects demonstrated significant differences [controls=149.76±2.47 pg/ml and CAD patients stratified into stable angina (SA)=161.65±3.40 pg/ml and myocardial infarction (MI)=171.51±4.26 pg/ml]. Logistic regression analysis suggested that increased EGFR levels exhibit 3-fold higher risk of CAD [odds ratio (OR) 3.51, 95% confidence interval [CI] 1.96–6.28, P≤0.001], upon adjustment for hypertension, diabetes and smoking. A unit increase in EGFR levels increased the risk by 2-fold for SA (OR 2.58, 95% CI 1.25–5.33, P=0.01) and 3.8-fold for MI (OR 3.82, 95% CI 1.94–7.52, P≤0.001) following adjustment. Thus, the use of ontology mapping and network analysis in an integrative manner aids in the prioritization of biomarkers of complex disease.
The Neighborhood Built Environment and Cognitive Function of Older Persons: Results from the Singapore Longitudinal Ageing Study

Background: We investigated the association of subjective (perceived) and objective (geographical information system [GIS]-based) measures of the neighborhood built environment (BE) attributes with cognitive function among older persons, and the mediating effect of transportation physical activity (TPA) and leisure time (physical, social and productive) activities (LTA). Method: A cross-sectional study of 402 residents aged 55 years and above in the Singapore Longitudinal Ageing Study. Perceived neighborhood BE attributes (residential density, street connectivity, land use mix - diversity, land use mix - access, infrastructure for walking or cycling, aesthetics, traffic safety, and crime safety) and objective GIS measures of walkability and accessibility were related to participants' cognitive global and domain-specific performance measured by Repeatable Battery for the Assessment of Neurocognitive Status (RBANS). Results: Controlling for age, sex, education, race, chronic medical illnesses, self-rated health, Geriatric Depression Scale depression score, POMA measures of balance and gait, and other BE attributes, the subjective measure of land use mix-diversity (standardized coefficient β = 0.161, p = 0.008) and GIS measure of walkability (β = 0.163, p = 0.002) were positively and significantly associated with RBANS global z-score, and immediate and delayed memory recall, visuospatial/ constructional ability and language, except attention. In hierarchical modeling, TPA and LTA attenuated the effect estimates, but the associations remained significant. Conclusion: BE features which increase opportunities and easy access to a diversity of destinations for services and facilities that promote physical, social and cognitively stimulating activities is associated with better cognitive functioning in older people.
Insectivorous birds eavesdrop on the pheromones of their prey

Chemical cues play a fundamental role in mate attraction and mate choice. Lepidopteran females, such as the winter moth (Operophtera brumata), emit pheromones to attract males in the reproductive period. However, these chemical cues could also be eavesdropped by predators. To our knowledge, no studies have examined whether birds can detect pheromones of their prey. O. brumata adults are part of the winter diet of some insectivorous tit species, such as the great tit (Parus major) and blue tit (Cyanistes caeruleus). We performed a field experiment aimed to disentangle whether insectivorous birds can exploit the pheromones emitted by their prey for prey location. We placed artificial larvae and a dispenser on branches of Pyrenean oak trees (Quercus pyrenaica). In half of the trees we placed an O. brumata pheromone dispenser and in the other half we placed a control dispenser. We measured the predation rate of birds on artificial larvae. Our results show that more trees had larvae with signs of avian predation when they contained an O. brumata pheromone than when they contained a control dispenser. Furthermore, the proportion of artificial larvae with signs of avian predation was greater in trees that contained the pheromone than in control trees. Our results indicate that insectivorous birds can exploit the pheromones emitted by moth females to attract males, as a method of prey detection. These results highlight the potential use of insectivorous birds in the biological control of insect pests.
Low-molecular-weight polysaccharides from Agaricus blazei Murrill modulate the Th1 response in cancer immunity

To assess the effect of low-molecular-weight polysaccharides from Agaricus blazei Murrill (ABP-AW1) as an immunoadjuvant therapy for type 1 T-helper (Th1) responses in tumorigenesis, C57BL/6 mice were inoculated subcutaneously with ovalbumin (E.G7-OVA). After 3, 10 and 17 days, the mice were immunized with PBS, OVA alone, or OVA and ABP-AW1, at low (50 µg), intermediate (100 µg) or high (200 µg) doses. Tumor growth was examined and compared among the groups, as were the following parameters: Splenocyte viability/proliferation, peripheral blood CD4+/CD8+ T cell ratio, serum OVA-specific IgG1 and IgG2b, secretion of interleukin (IL)-2 and interferon (IFN)-γ, and IFN-γ production on a single cell level from cultured splenocytes. Tumor growth in mice treated with OVA and ABP-AW1 (100 or 200 µg) was significantly slower, compared with in the other groups at the same time-points. OVA with 100 or 200 µg ABP-AW1 was associated with a higher number of total splenocytes, a higher ratio of peripheral blood CD4+/CD8+ T-lymphocytes, higher serum levels of OVA-specific Th1-type antibody IgG2b and greater secretion of the Th1 cytokines IL-1 and IFN-γ from splenocytes. ABP-AW1 is a promising immunoadjuvant therapy candidate, due to its ability to boost the Th1 immune response when co-administered with a cancer vaccine intended to inhibit cancer progression.
Resistance of oral cancer cells to 5‐ALA‐mediated photodynamic therapy

Photodynamic therapy (PDT) has been indicated for oral squamous cell carcinoma (OSCC) at early stages. Chemo and radio‐resistance are frequently observed in OSCC, but it is unknown whether this tumor can develop resistance to PDT. It was investigated the process of acquiring resistance to multiple cycles of PDT by using OSCC cells. We also analyzed the expression of anti‐apoptotic proteins and those related to Akt/mTOR pathway. Sub‐lethal doses of PDT were applied, consisting of a constant concentration of 5‐aminolevulinic acid (5‐ALA) (1 mM, 4‐h incubation) and increasing irradiation dose with LED (from 5.86 to 10.54 J/cm2). Cell viability, migration capacity, intracellular expression of protoporphyrin IX (PpIX), mitochondrial density, and pro‐survival proteins were investigated in PDT‐resistant cells. Six OSCC cell generations resistant to PDT were isolated. The resistant cells exhibited a survival phenotype characterized by a reduction in the expression of endogenous PpIX, increase in mitochondrial density, increase in migration capacity, and up‐regulation of p‐NFκB, p‐survivin, iNOS, p‐Akt Ser473, cyclin D1, p‐mTOR Ser2481, and p‐mTOR Ser2448. OSCC cells are able to survive doses of 5‐ALA‐PDT by reducing PpIX synthesis and activating signaling pathways related to the inhibition of apoptosis and improvement of cell proliferation. Further studies are necessary to confirm whether this PDT‐resistance phenotype can be clinically present, mainly in OSCC showing clinical recurrences after exposure to different PDT protocols.
Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial

Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with <4 BMs/day on SSAs (or ≥1 symptom or ≥4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients (N = 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. Through week 12, TEAEs were generally mild to moderate in severity; 5 (placebo), 1 (telotristat ethyl 250 mg) and 3 (telotristat ethyl 500 mg) patients experienced serious events, and the rate of TEAEs in the OLE was comparable. At week 12, significant reductions in u5-HIAA from baseline were observed, with Hodges–Lehmann estimators of median treatment differences from placebo of −54.0% (95% confidence limits, −85.0%, −25.1%, P < 0.001) and −89.7% (95% confidence limits, −113.1%, −63.9%, P < 0.001) for telotristat ethyl 250 mg and 500 mg. These results support the safety and efficacy of telotristat ethyl when added to SSAs in patients with CS diarrhea (ClinicalTrials.gov identifier: Nbib2063659).
Latent Space Physics: Towards Learning the Temporal Evolution of Fluid Flow

We propose a method for the data‐driven inference of temporal evolutions of physical functions with deep learning. More specifically, we target fluid flow problems, and we propose a novel LSTM‐based approach to predict the changes of the pressure field over time. The central challenge in this context is the high dimensionality of Eulerian space‐time data sets. We demonstrate for the first time that dense 3D+time functions of physics system can be predicted within the latent spaces of neural networks, and we arrive at a neural‐network based simulation algorithm with significant practical speed‐ups. We highlight the capabilities of our method with a series of complex liquid simulations, and with a set of single‐phase buoyancy simulations. With a set of trained networks, our method is more than two orders of magnitudes faster than a traditional pressure solver. Additionally, we present and discuss a series of detailed evaluations for the different components of our algorithm.