Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic Profiling of Blood-Derived Circulating Tumor DNA from Patients with Colorectal Cancer: Implications for Response and Resistance to Targeted Therapeutics

Molecular profiling of circulating tumor DNA (ctDNA) is a promising noninvasive tool. Here, next-generation sequencing (NGS) of blood-derived ctDNA was performed in patients with advanced colorectal cancer. We investigated ctDNA-derived genomic alterations, including potential actionability, concordance with tissue NGS, and serial dynamics in 78 patients with colorectal cancer using a clinical-grade NGS assay that detects single nucleotide variants (54–73 genes) and selected copy-number variants, fusions, and indels. Overall, 63 patients [80.8% (63/78)] harbored ctDNA alterations; 59 [75.6% (59/78)], ≥1 characterized alteration (variants of unknown significance excluded). All 59 patients had actionable alterations potentially targetable with FDA-approved drugs [on-label and/or off-label (N = 54) or with experimental drugs in clinical trials (additional five patients); University of California San Diego Molecular Tumor Board assessment]: 45, by OncoKB (http://oncokb.org/#/). The tissue and blood concordance rates for common specific alterations ranged from 62.3% to 86.9% (median = 5 months between tests). In serial samples from patients on anti-EGFR therapy, multiple emerging alterations in genes known to be involved in therapeutic resistance, including KRAS, NRAS, BRAF, EGFR, ERBB2, and MET were detected. In conclusion, over 80% of patients with stage IV colorectal cancer had detectable ctDNA, and the majority had potentially actionable alterations. Concordance between tissue and blood was between 62% and 87%, despite a median of 5 months between tests. Resistance alterations emerged on anti-EGFR therapy. Therefore, biopsy-free, noninvasive ctDNA analysis provides data relevant to the clinical setting. Importantly, sequential ctDNA analysis detects patterns of emerging resistance allowing for precision planning of future therapy.
Human Cord Blood‐Derived Unrestricted Somatic Stem Cell Infusion Improves Neurobehavioral Outcome in a Rabbit Model of Intraventricular Hemorrhage

Intraventricular hemorrhage (IVH) is a severe complication of preterm birth, which leads to hydrocephalus, cerebral palsy, and mental retardation. There are no available therapies to cure IVH, and standard treatment is supportive care. Unrestricted somatic stem cells (USSCs) from human cord blood have reparative effects in animal models of brain and spinal cord injuries. USSCs were administered to premature rabbit pups with IVH and their effects on white matter integrity and neurobehavioral performance were evaluated. USSCs were injected either via intracerebroventricular (ICV) or via intravenous (IV) routes in 3 days premature (term 32d) rabbit pups, 24 hours after glycerol‐induced IVH. The pups were sacrificed at postnatal days 3, 7, and 14 and effects were compared to glycerol‐treated but unaffected or nontreated control. Using in vivo live bioluminescence imaging and immunohistochemical analysis, injected cells were found in the injured parenchyma on day 3 when using the IV route compared to ICV where cells were found adjacent to the ventricle wall forming aggregates; we did not observe any adverse events from either route of administration. The injected USSCs were functionally associated with attenuated microglial infiltration, less apoptotic cell death, fewer reactive astrocytes, and diminished levels of key inflammatory cytokines (TNFα and IL1β). In addition, we observed better preservation of myelin fibers, increased myelin gene expression, and altered reactive astrocyte distribution in treated animals, and this was associated with improved locomotor function. Overall, our findings support the possibility that USSCs exert anti‐inflammatory effects in the injured brain mitigating many detrimental consequences associated with IVH. Stem Cells Translational Medicine 2019;8:1157–1169
Medial prefrontal cortex exacerbates gastric dysfunction of rats upon restraint water-immersion stress

Restraint water-immersion stress (RWIS) can induce a gastric mucosal lesions within a few hours. The medial prefrontal cortex (mPFC) is involved in the RWIS process. The present study investigated the modulatory effects and molecular mechanisms of the mPFC on gastric function under an RWIS state. Male Wistar rats were divided into four groups; namely, the control, RWIS 4 h (RWIS for 4 h only), sham-operated and bilateral-lesioned (bilateral-lesioned mPFC) groups. The gastric erosion index (EI) and gastric motility (GM) were determined, and the proteomic profiles of the mPFC were assessed by isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two-dimensional liquid chromatography and tandem mass spectrometry. Additionally, iTRAQ results were verified by western blot analysis. Compared with the RWIS 4 h group and the sham-control group, the bilateral-lesioned group exhibited a significantly lower EI (P<0.01). In the bilateral-lesioned group, RWIS led to a significant decrease in EI and GM. When comparing the control and RWIS 4 h groups, 129 dysregulated proteins were identified, of which 88 were upregulated and 41 were downregulated. Gene Ontology functional analysis demonstrated that 29 dysregulated proteins, including postsynaptic density protein 95, were directly associated with axon morphology, axon growth and synaptic plasticity. Ingenuity pathway analysis revealed that the dysregulated proteins were mainly involved in neurological disease signaling pathways, including the NF-κB and ERK signaling pathways. These data indicated that the presence of the mPFC exacerbates gastric mucosal injury in awake rats during RWIS. Although the quantitative proteomic analysis elucidated the nervous system molecular targets associated with the production of gastric mucosal lesions, such as the role of PSD95. The underlying molecular mechanisms of synaptic plasticity need to be further elucidated.
sEH Inhibitor Tppu Ameliorates Cecal Ligation and Puncture-Induced Sepsis by Regulating Macrophage Functions

ABSTRACT Background: Sepsis is a life-threatening organ dysfunction initiated by a dysregulated response to infection, with imbalanced inflammation and immune homeostasis. Macrophages play a pivotal role in sepsis. N-[1-(1-oxopropyl)-4-piperidinyl]-N’-[4-(trifluoromethoxy)phenyl)-urea (TPPU) is an inhibitor of soluble epoxide hydrolase (sEH), which can rapidly hydrolyze epoxyeicosatrienoic acids (EETs) to the bio-inactive dihydroxyeicosatrienoic acids. TPPU was linked with the regulation of macrophages and inflammation. Here, we hypothesized that sEH inhibitor TPPU ameliorates cecal ligation and puncture (CLP)-induced sepsis by regulating macrophage functions. Methods: A polymicrobial sepsis model induced by CLP was used in our study. C57BL/6 mice were divided into four groups: sham+ phosphate buffer saline (PBS), sham+TPPU, CLP+PBS, CLP+TPPU. Mice were observed 48 h after surgery to assess the survival rate. For other histological examinations, mice were sacrificed 6 h after surgery. Macrophage cell line RAW264.7 was used for in vitro studies. Results: TPPU treatment, accompanied with increased EETs levels, markedly improved the survival of septic mice induced by CLP surgery, which was associated with alleviated organ damage and dysfunction triggered by systemic inflammatory response. Moreover, TPPU treatment significantly inhibited systemic inflammatory response via EETs-induced inactivation of mitogen-activated protein kinase signaling due to enhanced macrophage phagocytic ability and subsequently reduced bacterial proliferation and dissemination, and decreased inflammatory factors release. Conclusion: sEH inhibitor TPPU ameliorates cecal ligation and puncture-induced sepsis by regulating macrophage functions, including improved phagocytosis and reduced inflammatory response. Our data indicate that sEH inhibition has potential therapeutic effects on polymicrobial-induced sepsis.
Variation of Interfacial Interactions in PC61BM-like Electron Transporting Compounds for Perovskite Solar Cells.

The synthesis, characterization and incorporation of pheyl-C61-butyric acid methyl ester (PC61BM)-like derivatives as electron transporting materials (ETMs) in inverted perovskite solar cells (PSCs) is reported. These compounds have the same structure except for the ester substituent, which was varied from methyl to phenyl to thiophene and to pyridyl. The latter three derivatives performed better than PC61BM in PSCs, mainly attributed to the specific interactions of the fullerenes with the perovskite layer, as evidenced by X-ray photoelectron spectroscopy (XPS), and steady-state and time-resolved photoluminescence (SSPL and TRPL) measurements. The experimental results were fully supported by density functional theory (DFT) calculations, which showed that the strongest interactions were exhibited by the compound possessing the pyridyl substituent.
Hydroxypropylsulfonation/Caproylation of Cornstarch to Enhance Its Adhesion to PLA Fibers for PLA Sizing

The impact of hydroxypropylsulfonation/caproylation on the adhesion of cornstarch to polylactic acid (PLA) fibers was investigated for ameliorating the applications such as PLA sizing. The hydroxypropylsulfonated and caproylated cornstarch (HCS) samples with different degrees of substitution (DS) were synthesized by a hydroxypropylsulfonation of acid-converted cornstarch (ACS) with 3-chloro-2-hydroxy-1-propanesulfonic acid sodium salt (CHPS-Na) and subsequently a caproylation with caproic anhydride (CA). The HCS granules were characterized by Fourier transform infrared spectroscopic and scanning electron microscopy. The adhesion was evaluated by measuring the bonding forces of the PLA roving impregnated. The mechanical behaviors of the adhesive layers were estimated by determining the properties of the films. The results of adhesion measurement were also analyzed especially through the wetting and spreading of the paste on the fiber surfaces, as well as the failure type, internal stress and mechanical behaviors of the adhesive layers among fibers. Additionally, apparent viscosity and its stability of the pastes were also determined. It was found that hydroxypropylsulfonation/caproylation was not only able to obviously improve the adhesion of ACS to PLA fibers, but also capable of further improving the adhesion of hydroxypropylsulfonated starch (HS) to the fibers. With the rise in the total DS, the adhesion gradually increased. The two substituents improved the wetting and spreading, reduced the internal stress, lowered the probabilities of interfacial failure and cohesive failure, decreased the film brittleness, and increased the van der Waals force at the interfaces. Moreover, the HCS samples with a stability of above 85% could meet the demand on the stability for sizing. Considering the experimental results of the adhesion and the analysis of the results, HCS showed potential in the application of PLA sizing.
Survey on challenges in clustering analysis research

Clustering analysis is an important tool for data mining and its purpose is to find the cluster structures in dataset. However, several fundamental challenges associated with clustering still exist. Therefore, the representative methods are briefly surveyed in this paper. Moreover, the major challenges in current work are summarized and the solutions are also discussed in detail. A valuable reference can be provided to the related research work.
Inflammation and (secondary) genotoxicity of Ni and NiO nanoparticles

Abstract Nanoparticle-induced genotoxicity can arise through different mechanisms, and generally, primary and secondary genotoxicity can be distinguished where the secondary is driven by an inflammatory response. It is, however, yet unclear how a secondary genotoxicity can be detected using in vitro methods. The aim of this study was to investigate inflammation and genotoxicity caused by agglomerated nickel (Ni) and nickel oxide (NiO) nanoparticles and, furthermore, to explore the possibility to test secondary (inflammation-driven) genotoxicity in vitro. As a benchmark particle to compare with, we used crystalline silica (quartz). A proteome profiler antibody array was used to screen for changes in release of 105 different cytokines and the results showed an increased secretion of various cytokines including vascular endothelial growth factor (VEGF) following exposure of macrophages (differentiated THP-1 cells). Both Ni and NiO caused DNA damage (comet assay) following exposure of human bronchial epithelial cells (HBEC) and interestingly conditioned media (CM) from exposed macrophages also resulted in DNA damage (2- and 3-fold increase for Ni and NiO, respectively). Similar results were also found when using a co-culture system of macrophages and epithelial cells. In conclusion, this study shows that it is possible to detect a secondary genotoxicity in lung epithelial cells by using in vitro methods based on conditioned media or co-cultures. Further investigation is needed in order to find out what factors that are causing this secondary genotoxicity and whether such effects are caused by numerous nanoparticles.
Capillary flow in open microgrooves: bifurcations and networks.

Open capillary flows are increasingly used in biotechnology, biology, thermics, and space science. So far, the dynamics of capillary flows has been studied mostly for confined channels. However, the theory of open microfluidics has considerably progressed during the last years, and an expression for the travel distance has been derived, generalizing the well-known theory of Lucas, Washburn, and Rideal. This generalization is based on the use of the average friction length and generalized Cassie angle. In this work, we successively study the spontaneous capillary flow in uniform cross-section open rounded U-grooves-for which methods to determine the friction lengths are proposed-the flow behavior at a bifurcation, and finally in a simple-loop network. We show that after a bifurcation, the Lucas-Washburn-Rideal law needs to be adapted and the relation between the travel distance and time is more complicated than the square root of time dependency.
Sexual violence at each stage of human trafficking cycle and associated factors: a retrospective cohort study on Ethiopian female returnees via three major trafficking corridors

Objectives Evidence showed that the prevalence of sexual violence during the whole human trafficking period was high. However, the distribution of sexual violence along the stages of the trafficking cycle is unclear. This study aimed to determine the prevalence of sexual violence at each stage of trafficking and factors associated with it among Ethiopian trafficked females. Design A retrospective cohort study was conducted to study trafficking returnees regarding their previous experiences at each stage of trafficking. Settings Data were collected at immigration offices in three border towns of Ethiopia located bordering Sudan, Kenya and Djibouti. Participants Six hundred and seventy-one women who were trafficked from Ethiopia were recruited into the study consecutively. They were recruited when they came back home via the three border towns either by deportation or voluntary return. Outcome measure The outcome variable was sexual violence. Results The prevalence of sexual violence was estimated at 10% (95% CI 7.9 to 12.5) during predeparture, 35.0% (95% CI 31.5 to 38.7) travelling period, 58.1% (95% CI 54.2 to 61.8) at destination and 19.5% (95% CI 15.2 to 24.6) detention stages. The odds of sexual violence among returnees aged 14–17 years was about twofold when compared with that of women aged 26–49 years (adjusted OR (AOR)=1.97; 95% CI 1.11 to 3.52). Similarly, being smuggled initially (AOR=1.54; 95% CI 1.09 to 1.93), restricted freedom (AOR=1.45; 95% CI 1.13 to 1.86) and time spent at each stage of trafficking (AOR=1.028; 95% CI 1.024 to 1.033) were positively associated with sexual violence. Conclusions The prevalence of sexual violence at each stage of trafficking after departure was high. This could imply that victims might be affected by subsequent negative sexual health outcomes. Young age, initially being smuggled and time spent at each stage of the trafficking process were positively associated with the events of sexual violence. Efforts must be made on modifiable factors such as ‘smuggling’ to minimise subsequent sexual violence during trafficking.
Deep-Learning Approach to Automatic Identification of Facial Anomalies in Endocrine Disorders

Background: Deep learning has the potential to assist the medical diagnostic process. We aimed to identify facial anomalies associated with endocrinal disorders using a deep-learning approach to facilitate the process of diagnosis and follow-up. Methods: We collected facial images of patients with hypercortisolism and acromegaly, and we augmented these images with additional negative samples from public databases. A model with a pretrained deep-learning network was constructed to automatically identify these hypersecretion statuses based on characteristic facial changes. We compared its performance to that of endocrine experts and further investigated key factors upon which the best performing model focused. Findings: The model achieved areas under the receiver operating characteristic curve of 0.9647 (Cushing’s syndrome) and 0.9556 (acromegaly), accuracies of 0.9593 (Cushing’s syndrome) and 0.9479 (acromegaly), and recalls of 0.7593 (Cushing’s syndrome) and 0.8089 (acromegaly). It performed better than any level of our endocrine experts. Furthermore, the regions of interest on the part of the machine were primarily the same as those upon which the humans focused. Interpretation: Our findings suggest that the deep-learning model learned the facial characters based merely on labeled data without learning prerequisite medical knowledge, and its performance was comparable with professional medical practitioners. The model has the potential to assist in the diagnosis and follow-up of these hypersecretion statuses.
Mobile botnet detection model based on retrospective pattern recognition

The dynamic nature of Botnets along with their sophisticated characteristics makes them one of the biggest threats to cyber security. Recently, the HTTP protocol is widely used by Botmaster as they can easily hide their command and control traffic amongst the benign web traffic. This paper proposes a Neural Network based model to detect mobile HTTP Botnets with random intervals independent of the packet payload, commands content, and encryption complexity of Bot communications. The experimental test results that were conducted on existing datasets and real world Bot samples show that the proposed method is able to detect mobile HTTP Botnets with high accuracy.
BRAF Mutation Status in Circulating Tumor DNA from Patients with Metastatic Colorectal Cancer: Extended Mutation Analysis from the AGEO RASANC Study

In patients with metastatic colorectal cancer (mCRC), RAS and BRAF mutations are currently determined by tumor sample analysis. Here, we report BRAF mutation status analysis in paired tumor tissue and plasma samples of mCRC patients included in the AGEO RASANC prospective cohort study. Four hundred and twenty-five patients were enrolled. Plasma samples were analyzed by next-generation sequencing (NGS). When no mutation was identified, we used two methylated specific biomarkers (digital droplet PCR) to determine the presence or absence of circulating tumor DNA (ctDNA). Patients with conclusive ctDNA results were defined as those with at least one mutation or one methylated biomarker. The kappa coefficient and accuracy were 0.79 (95% CI: 0.67–0.91) and 97.3% (95% CI: 95.2–98.6%) between the BRAF status in plasma and tissue for patients with available paired samples (n = 405), and 0.89 (95% CI: 0.80–0.99) and 98.5% (95% CI: 96.4–99.5%) for those with conclusive ctDNA (n = 323). The absence of liver metastasis was the main factor associated to inconclusive ctDNA results. In patients with liver metastasis, the kappa coefficient was 0.91 (95% CI, 0.81–1.00) and accuracy was 98.6% (95% CI, 96.5–99.6%). We demonstrate satisfying concordance between tissue and plasma BRAF mutation detection, especially in patients with liver metastasis, arguing for plasma ctDNA testing for routine BRAF mutation analysis in these patients.
Relationship between employee engagement scores and service quality ratings: analysis of the National Health Service staff survey across 97 acute NHS Trusts in England and concurrent Care Quality Commission outcomes (2012–2016)

Objective This research explores measures of employee engagement in the National Health Service (NHS) acute Trusts in England and examines the association between organisation-level engagement scores and quality ratings by the Care Quality Commission (CQC). Design Cross-sectional. Setting 97 acute NHS Trusts in England. Participants 97 NHS acute Trusts in England (2012–2016). Data include provider details, staff survey results and CQC reports. Hybrid Trusts or organisations affected by recent mergers are excluded. Outcome measures Analysis uses organisation-level employee engagement and CQC quality ratings. Results Employee engagement is affected by organisational factors, including patient bed numbers (β=−0.46, p<0.05) and financial revenue (β=0.38, p<0.05). CQC ratings are predicted by overall employee engagement score (β=0.57, p<0.001) and financial deficit (β=−0.19, p<0.05). The most influential employee engagement dimension on provider ratings is ‘advocacy’ (λ=0.54, p<0.001). Analysis supports the notion that employee engagement can be predicted from advocacy scores alone (eigenvalue=4.03). Better still, combining advocacy scores from the previous year’s survey or adding in motivation scores is a highly reliable indication of overall employee engagement (95.4% of total variance). Conclusions NHS acute Trusts with high employee engagement scores tend to have better CQC ratings. Trusts with a high financial deficit tend to have lower ratings. Employee engagement subdimensions have different associations with CQC ratings, the most influential dimension being advocacy score. A two subdimension model of engagement efficiently predicts overall employee engagement in NHS acute Trusts in England. Healthcare leaders should pay close attention to the proportion of employees who would recommend their organisation as a place to work or receive treatment, because this is a proxy for the level of engagement, and it predicts CQC ratings.