Miracle-dz/UniFAR-FTUs huggingface dataset:
Engrailed-2 promotes a malignant phenotype of esophageal squamous cell carcinoma through upregulating the expression of pro-oncogenic genes

Background A number of homeobox genes have been implicated in the development of various cancers. However, the role of engrailed 2 (EN2), a member of the homeobox gene superfamily, in esophageal squamous cell carcinoma (ESCC) remains unknown. Methods The expression of EN2 was examined using quantitative real-time PCR and immunohistochemistry. A stable cell line was established to express exogenous EN2 using a lentivirus system. The malignant phenotype was analyzed with proliferation, clonogenicity, wound-healing and invasion assays. The CRISPR/Cas9 system was adopted to deplete endogenous EN2. RNA profiling was performed using gene expression microarray. The ShRNA-mediated method was used to knock down the expression of SPARC. The structure-function relationship was determined using site-directed mutagenesis. Results EN2 is highly expressed in ESCC. The malignant phenotype of the ESCC cell line was amplified by an overexpression of EN2 but was attenuated by a disruption of EN2. RNA profiling analysis revealed that distinct sets of genes were modulated by the expression of EN2 in various ESCC cell lines and oncogenes were among these. EN2 greatly increased the expression of SPARC in Eca109. Site-directed mutagenesis revealed that the induction of SPARC was closely correlated with the protumor function of EN2. ShRNA-mediated knockdown of SPARC attenuated the malignant phenotype of EN2-infected cells. These data suggest that SPARC is crucial for mediating the protumor function of EN2. Discussion EN2 has an oncogenic function in ESCC that is mediated by upregulating the expression of pro-oncogenic genes downstream. EN2 may potentially act as a diagnostic marker or therapeutic target for ESCC treatment in the future.
CAD-CAP: a 25,000-image database serving the development of artificial intelligence for capsule endoscopy

Abstract Background and study aims Capsule endoscopy (CE) is the preferred method for small bowel (SB) exploration. With a mean number of 50,000 SB frames per video, SBCE reading is time-consuming and tedious (30 to 60 minutes per video). We describe a large, multicenter database named CAD-CAP (Computer-Assisted Diagnosis for CAPsule Endoscopy, CAD-CAP). This database aims to serve the development of CAD tools for CE reading. Materials and methods Twelve French endoscopy centers were involved. All available third-generation SB-CE videos (Pillcam, Medtronic) were retrospectively selected from these centers and deidentified. Any pathological frame was extracted and included in the database. Manual segmentation of findings within these frames was performed by two pre-med students trained and supervised by an expert reader. All frames were then classified by type and clinical relevance by a panel of three expert readers. An automated extraction process was also developed to create a dataset of normal, proofread, control images from normal, complete, SB-CE videos. Results Four-thousand-one-hundred-and-seventy-four SB-CE were included. Of them, 1,480 videos (35 %) containing at least one pathological finding were selected. Findings from 5,184 frames (with their short video sequences) were extracted and delimited: 718 frames with fresh blood, 3,097 frames with vascular lesions, and 1,369 frames with inflammatory and ulcerative lesions. Twenty-thousand normal frames were extracted from 206 SB-CE normal videos. CAD-CAP has already been used for development of automated tools for angiectasia detection and also for two international challenges on medical computerized analysis.
Unilateral versus bilateral endoscopic stenting in patients with unresectable malignant hilar obstruction: a systematic review and meta-analysis

Abstract Background and study aims Endoscopic stent placement is used for palliative management of unresectable malignant hilar obstruction, which could be achieved by either unilateral or bilateral stent insertion. Materials and methods A literature search was performed to identify studies that reported outcomes of metallic biliary stent placement in patients with malignant hilar obstruction. Weighted pooled rates (WPR) along with 95 % confidence intervals (95 %CI) were calculated to determine and compare outcomes including technical and functional success, early and late adverse events, post procedure cholangitis, and stent occlusion between two groups. Results A total of 21 studies with 1292 patients were included. WPR of technical success was significantly higher in the unilateral group (97 %, 95 %CI: 93 –98 %) vs. bilateral group (89 %, 95 %CI: 84 –92 %) (P = 0.0.003). WPR for functional success in the unilateral and bilateral groups were 96 % (95 %CI: 91 –98 %) and 94 % (95 %CI: 91 –97 %), respectively (P = 0.48). The rate of early and late complications was comparable between the two groups. Conclusion In patients with unresectable malignant hilar obstruction, unilateral and bilateral metallic stenting techniques are comparable in terms of efficacy and safety.
Eosinophil accumulation predicts response to melanoma treatment with immune checkpoint inhibitors

ABSTRACT Eosinophils have been identified as a prognostic marker in immunotherapy of melanoma and suggested to contribute to anti-tumor host defense. However, the influence of immune checkpoint inhibitors (ICI) on the eosinophil population is poorly studied. Here, we applied routine laboratory tests, multicolor flow cytometry, RNA microarray analysis, and bio-plex assay to analyze circulating eosinophils and related serum inflammatory factors in 32 patients treated with pembrolizumab or the combination of nivolumab and ipilimumab. We demonstrated that clinical responses to ICI treatment were associated with an eosinophil accumulation in the peripheral blood. Moreover, immunotherapy led to the alteration of the eosinophil genetic and activation profile. Elevated serum concentrations of IL-16 during ICI treatment were found to be associated with increased frequencies of eosinophils in the peripheral blood. Using immunohistochemistry, we observed an enhanced eosinophil degranulation and a positive correlation between eosinophil and CD8+ T cell infiltration of tumor tissues from melanoma patients treated with ICI. Our findings highlight additional mechanisms of ICI effects and suggest the level of eosinophils as a novel predictive marker for melanoma patients who may benefit from this immunotherapy.
The niche is not the range: Dispersal and persistence shape mismatches between ecological niches and geographic distributions of plants

The ecological niche of a species describes the variation in population growth rates along environmental gradients that drives geographic range dynamics. Niches are thus central for understanding and forecasting species’ geographic distributions. However, theory predicts that migration limitation, source-sink dynamics and time-lagged local extinction can cause mismatches between niches and geographic distributions. It is still unclear how relevant these niche-distribution mismatches are for biodiversity dynamics and how they depend on species life history traits. This is mainly due to a lack of the comprehensive, range-wide demographic data needed to directly infer ecological niches for multiple species. Here we quantify niches from extensive demographic measurements along environmental gradients across the geographic ranges of 26 plant species (Proteaceae; South Africa). We then test whether life history explains variation in species’ niches and niche-distribution mismatches. Niches are generally wider for species with high seed dispersal or persistence abilities. Life history traits also explain the considerable interspecific variation in niche-distribution mismatches: poorer dispersers are absent from larger parts of their potential geographic ranges, whereas species with higher persistence ability more frequently occupy environments outside their ecological niche. Our study thus identifies major demographic and functional determinants of species’ niches and geographic distributions. It highlights that the inference of ecological niches from geographical distributions is most problematic for poorly dispersed and highly persistent species. We conclude that the direct quantification of ecological niches from demographic responses to environmental variation is a crucial step towards a better predictive understanding of biodiversity dynamics under environmental change.
Endogenous 3-Iodothyronamine (T1AM) and Synthetic Thyronamine-Like Analog SG-2 Act as Novel Pleiotropic Neuroprotective Agents through the Modulation of SIRT6

3-iodothyronamine (T1AM) and the recently developed analog SG-2 are rapidly emerging as promising multi-target neuroprotective ligands able to reprogram lipid metabolism and to produce memory enhancement in mice. To elucidate the molecular mechanisms underlying the multi-target effects of these novel drug candidates, here we investigated whether the modulation of SIRT6, known to play a key role in reprogramming energy metabolism, might also drive the activation of clearing pathways, such as autophagy and ubiquitine-proteasome (UP), as further mechanisms against neurodegeneration. We show that both T1AM and SG-2 increase autophagy in U87MG cells by inducing the expression of SIRT6, which suppresses Akt activity thus leading to mTOR inhibition. This effect was concomitant with down-regulation of autophagy-related genes, including Hif1α, p53 and mTOR. Remarkably, when mTOR was inhibited a concomitant activation of autophagy and UP took place in U87MG cells. Since both compounds activate autophagy, which is known to sustain long term potentiation (LTP) in the entorhinal cortex (EC) and counteracting AD pathology, further electrophysiological studies were carried out in a transgenic mouse model of AD. We found that SG-2 was able to rescue LTP with an efficacy comparable to T1AM, further underlying its potential as a novel pleiotropic agent for neurodegenerative disorders treatment.
The Arabidopsis Hypoxia Inducible AtR8 Long Non-Coding RNA also Contributes to Plant Defense and Root Elongation Coordinating with WRKY Genes under Low Levels of Salicylic Acid

AtR8 lncRNA was previously identified in the flowering plant Arabidopsis thaliana as an abundant Pol III-transcribed long non-coding RNA (lncRNA) of approximately 260 nt. AtR8 lncRNA accumulation is responsive to hypoxic stress and salicylic acid (SA) treatment in roots, but its function has not yet been identified. In this study, microarray analysis of an atr8 mutant and wild-type Arabidopsis indicated a strong association of AtR8 lncRNA with the defense response. AtR8 accumulation exhibited an inverse correlation with an accumulation of two WRKY genes (WRKY53/WRKY70) when plants were exposed to exogenous low SA concentrations (20 µM), infected with Pseudomonas syringae, or in the early stage of development. The highest AtR8 accumulation was observed 5 days after germination, at which time no WRKY53 or WRKY70 mRNA was detectable. The presence of low levels of SA resulted in a significant reduction of root length in atr8 seedlings, whereas wrky53 and wrky70 mutants exhibited the opposite phenotype. Taken together, AtR8 lncRNA participates in Pathogenesis-Related Proteins 1 (PR-1)-independent defense and root elongation, which are related to the SA response. The mutual regulation of AtR8 lncRNA and WRKY53/WRKY70 is mediated by Nonexpressor of Pathogenesis-Related Gene 1 (NPR1).
DISOLV: A Python Package for the Interpretation of Borehole Dilution Tests

Single borehole dilution tests (SBDTs) are an inexpensive but effective technique for hydrogeological characterization of hard‐rock aquifers. We present a freely available, easy‐to‐use, open‐source Python package, DISOLV, for plotting, analyzing, and modeling SBDT data. DISOLV can significantly reduce the time spent interpreting field data by helping to identify flowing fractures intersecting the borehole and estimate the corresponding flow rates. DISOLV is successfully benchmarked against two analytical solutions. We also present an example application to real data collected in a borehole in a crystalline basement aquifer in southern India.
Targeting the receptor for advanced glycation end products (RAGE) in type 1 diabetes

Type 1 diabetes (T1D) is one of the most common chronic diseases manifesting in early life, with the prevalence increasing worldwide at a rate of approximately 3% per annum. The prolonged hyperglycaemia characteristic of T1D upregulates the receptor for advanced glycation end products (RAGE) and accelerates the formation of RAGE ligands, including advanced glycation end products, high‐mobility group protein B1, S100 calcium‐binding proteins, and amyloid‐beta. Interestingly, changes in the expression of RAGE and these ligands are evident in patients before the onset of T1D. RAGE signals via various proinflammatory cascades, resulting in the production of reactive oxygen species and cytokines. A large number of proinflammatory ligands that can signal via RAGE have been implicated in several chronic diseases, including T1D. Therefore, it is unsurprising that RAGE has become a potential therapeutic target for the treatment and prevention of disease. In this review, we will explore how RAGE might be targeted to prevent the development of T1D.
Surprising simplicities and syntheses in limbless self-propulsion in sand

ABSTRACT Animals moving on and in fluids and solids move their bodies in diverse ways to generate propulsion and lift forces. In fluids, animals can wiggle, stroke, paddle or slap, whereas on hard frictional terrain, animals largely engage their appendages with the substrate to avoid slip. Granular substrates, such as desert sand, can display complex responses to animal interactions. This complexity has led to locomotor strategies that make use of fluid-like or solid-like features of this substrate, or combinations of the two. Here, we use examples from our work to demonstrate the diverse array of methods used and insights gained in the study of both surface and subsurface limbless locomotion in these habitats. Counterintuitively, these seemingly complex granular environments offer certain experimental, theoretical, robotic and computational advantages for studying terrestrial movement, with the potential for providing broad insights into morphology and locomotor control in fluids and solids, including neuromechanical control templates and morphological and behavioral evolution. In particular, granular media provide an excellent testbed for a locomotion framework called geometric mechanics, which was introduced by particle physicists and control engineers in the last century, and which allows quantitative analysis of alternative locomotor patterns and morphology to test for control templates, optimality and evolutionary alternatives. Thus, we posit that insights gained from movement in granular environments can be translated into principles that have broader applications across taxa, habitats and movement patterns, including those at microscopic scales. Summary: Dry sandy environments present challenges to animal locomotion, but are also amenable to several useful experimental and theoretical methods, which can generate uncommonly rich insights into animal locomotion.
Similar composition of functional roles in Andean seed-dispersal networks, despite high species and interaction turnover.

The species composition of local communities varies in space, and its similarity generally decreases with increasing geographic distance between communities, a phenomenon known as distance decay in similarity. It is, however, not known how changes in local species composition affect ecological processes, that is, whether they lead to differences in the local composition of species' functional roles. We studied eight seed-dispersal networks along the South American Andes and compared them with regard to their species composition and their composition of functional roles. We tested (1) if changes in bird species composition lead to changes in the composition of bird functional roles, and (2) if the similarity in species composition and functional-role composition decreased with increasing geographic distance between the networks. We also used cluster analysis to (3) identify bird species with similar roles across all networks based on the similarity in the plants they consume, (i) considering only the species identity of the plants and (ii) considering the functional traits of the plants. Despite strong changes in species composition, the networks along the Andes showed similar composition of functional roles. (1) Changes in species composition generally did not lead to changes in the composition of functional roles. (2) Similarity in species composition, but not functional-role composition, decreased with increasing geographic distance between the networks. (3) The cluster analysis considering the functional traits of plants identified bird species with similar functional roles across all networks. The similarity in functional roles despite the high species turnover suggests that the ecological process of seed-dispersal is organized similarly along the Andes, with similar functional roles fulfilled locally by different sets of species. The high species turnover, relative to functional turnover, also indicates that a large number of bird species are needed to maintain the seed-dispersal process along the Andes.
RDI −a regression detectability index for quality assurance in: x-ray imaging

Novel iterative image reconstruction methods can help reduce the required radiation dose in x-ray diagnostics such as computed tomography (CT), while maintaining sufficient image quality. Since some of the established image quality measures are not appropriate for reliably judging the quality of images derived by iterative methods, alternative approaches such as task-specific quality assessment would be highly desirable for acceptance or constancy testing. Task-based image quality methods are also closer to tasks performed by the radiologists, such as lesion detection. However, this approach is usually hampered by a huge workload, since hundreds of images are usually required for its application. It is demonstrated that the proposed approach works reliably on the basis of significantly fewer images, and that it correlates well with results obtained from human observers.
Presence of The NLRP3 Inflammasome Components in Semen of Varicocele Patients

Background Varicocele is a common cause of male infertility with multifactorial etiology. Inflammation is a characteristic pathological event that occurs in the testis tissue following the varicocele. The aim of this study was to investigate expression of nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome components and cytokines in semen of varicocele and control subjects. Materials and Methods In this case-control study, seminal plasma was collected from 32 varicocele patients (with grades 2 and 3) and 20 fertile men as control group. Semen analysis was performed in all subjects. Concentrations of interleukin-1b (IL-1b), IL-18 and caspase-1 in seminal plasma were measured by enzyme-linked immunosorbent assay (ELISA). Apoptosis-associated speck-like protein containing a caspase activation and recruitment domain, in addition to NALP3 were identified in seminal plasma by Western blot. Statistical significance between the mean values was determined by student’s t test. Results According to our data, the level of IL-1b was significantly (P=0.03) increased in the seminal plasma of varicocele patients, compared to the control subjects. We analyzed amount of IL-18 in the both groups. The level of this interleukin was markedly (P=0.002) decreased in varicocele patients. No change was observed in the level of caspase-1 in both groups. Western blot analysis revealed that apoptosis associated speck-like protein (ASC, P=0.0002) and NLRP3 (P=0.005) were significantly elevated in the semen of varicocele patients. Conclusion This study provides the first evidence of activation of NLRP3 components in semen of men with varicocele.
Harvesting microalgae using ozone-air flotation for recovery of biomass, lipids, carbohydrates, and proteins

ABSTRACT The objective of this research was to study a novel ozone-air flotation microalgae harvesting method and evaluate its effect on the recovery of biomass and biocomponents (lipids, carbohydrates, proteins). Best processing conditions were established using a response surface methodology (RSM). Microalgae separation and biocomponent recovery were evaluated according to changes in gas concentration (13, 18 and 25 mgO3/L), ozone dose (0.04, 0.09 and 0.16 mg O3/mg biomass) and airflow rate (0.5, 1.0 and 1.5 L/min). More than 95% of the biomass was recovered from wastewater at an ozone-air combination of 0.09 mgO3/mg biomass and 1.5 L air/min. Using ozone-air represented a reduction of 59% in the ozone dose compared to the flotation process solely using ozone (0.22 mgO3/mg biomass). In addition, there was an improved yield in the recovery of all microalgae biocomponents. A maximum yield of 0.18 mg lipids/mg biomass was achieved at: 0.16 mg O3/mg biomass, 25 mg gas O3/L and 1.5 L air/min. In conclusion, combining the use of ozone-air for separation of microalgae reduces ozone requirement and enhances lipids and proteins post-extraction. GRAPHICAL ABSTRACT
A Highly Sensitive Impedimetric DNA Biosensor Based on Hollow Silica Microspheres for Label-Free Determination of E. coli

A novel label-free electrochemical DNA biosensor was constructed for the determination of Escherichia coli bacteria in environmental water samples. The aminated DNA probe was immobilized onto hollow silica microspheres (HSMs) functionalized with 3-aminopropyltriethoxysilane and deposited onto a screen-printed electrode (SPE) carbon paste with supported gold nanoparticles (AuNPs). The biosensor was optimized for higher specificity and sensitivity. The label-free E. coli DNA biosensor exhibited a dynamic linear response range of 1 × 10−10 µM to 1 × 10−5 µM (R2 = 0.982), with a limit of detection at 1.95 × 10−15 µM, without a redox mediator. The sensitivity of the developed DNA biosensor was comparable to the non-complementary and single-base mismatched DNA. The DNA biosensor demonstrated a stable response up to 21 days of storage at 4 ℃ and pH 7. The DNA biosensor response was regenerable over three successive regeneration and rehybridization cycles.
The Epworth sleepiness scale: Reliably unreliable in a sleep clinic population

The Epworth Sleepiness Scale is used frequently to measure excessive daytime sleepiness in research and clinical settings, although there is limited evidence on test–retest reliability, particularly among sleep clinic populations. The objective of this study was to evaluate the reliability of this instrument among adult patients recruited from a public hospital sleep clinic in Sydney, Australia. English‐speaking participants self‐completed the Epworth Sleepiness Scale on two occasions, at the specialist clinic visit and on the night of diagnostic polysomnography. Of the 108 participants included in the study, the majority were male (64%) and the mean age was 51 years. The median retest interval was 64 days. The primary outcome of test–retest reliability as measured using the intraclass correlation coefficient was 0.73 (95% confidence interval, 0.61–0.82). Despite moderate statistical reliability and a low mean difference of 1.1, Bland‐Altman analysis showed an unacceptably wide distribution of between‐score differences. The 95% limits of agreement were −8.5 to +10.6, and an absolute difference in scores of at least 3 was observed in 60 (56%) of the participants. Our results suggest that the Epworth Sleepiness Scale should not be used in clinical settings to make individual‐level comparisons, such as the effect of therapeutic interventions, or to prioritise access to services.