Miracle-dz/UniFAR-FTUs huggingface dataset:
LncRNA FENDRR promotes high-glucose-induced proliferation and angiogenesis of human retinal endothelial cells

ABSTRACT The study aimed to investigate the role of lncRNA FENDRR in proliferation and angiogenesis of human retinal endothelial cells (HRECs). HRECs were cultured in high-glucose medium to mimic diabetic retinopathy (DR) model. We overexpressed or knocked down FENDRR in HRECs to evaluate the effect of FENDRR expression on cell proliferation, migration, and capillary morphogenesis of HRECs under either normal glucose or high glucose condition. Results showed that VEGF and FENDRR expression were increased in blood from DR patients compared with the control subjects. Furthermore, high glucose treatment upregulated expression of VEGF and FENDRR secreted from HRECs, in a dose- and time-dependent manner. Importantly, FENDRR overexpression significantly promoted the high-glucose-induced proliferation, migration, capillary morphogenesis, and VEGF expression in HRECs. In contrast, FENDRR knockdown exerted the opposite effects. In conclusion, lncRNA FENDRR promotes the high-glucose-induced proliferation and angiogenesis of HRECs and may serve as a potential target for anti-angiogenic therapy for DR. Graphical abstract Effect of FENDRR expression on the high-glucose-induced HRECs proliferation, migration, and capillary morphogenesis.
Routine CT scan one year after surgery can be used to estimate the level of central ligation in colon cancer surgery

In recent years, there has been an increasing focus on improving the quality of colon cancer surgery according to the principle of complete mesocolic excision (CME) [1]. CME surgery provides a standardized approach with the intention of reducing the rate of recurrence and improving survival. One of the key principles of CME is central ligation of the tumor feeding artery at its origin with removal of the central lymph nodes. Along with the increased uptake of CME, a pathological evaluation method was developed in order to evaluate the quality of surgical specimens and to give feedback [2]. The level of division of the tumor feeding artery is often assessed by pathologists through measuring the distance between the tumor and the artery ligation on the specimen. In a recent study, we measured the residual arterial stump left behind on a CT-scan performed 2 days after colon cancer surgery [3]. We found no statistically significant correlation between the pathological measurement on the specimen and the radiological measurement of the arterial stump. Even though a CT scan 2 days after surgery may be technically feasible to the measure the level of arterial division, this will not be acceptable in routine clinical practice due to the increased costs and patient radiation exposure. Therefore, the aim of this study was to clarify whether a routine CT-scan performed 1 year after colon cancer surgery could be used to identify and measure the residual arterial stump and thereby give an objective measure of the level of central division.
HER3 Targeting Sensitizes HNSCC to Cetuximab by Reducing HER3 Activity and HER2/HER3 Dimerization: Evidence from Cell Line and Patient-Derived Xenograft Models

Purpose: Our previous work suggested that HER3 inhibition sensitizes head and neck squamous cell carcinoma (HNSCC) to EGFR inhibition with cetuximab. This study aimed to define the role of HER3 in cetuximab resistance and the antitumor mechanisms of EGFR/HER3 dual targeting in HNSCC. Experimental Design: We treated cetuximab-resistant HNSCC UMSCC1-C and parental UMSCC1-P cell lines with anti-EGFR antibody cetuximab, anti-HER3 antibody MM-121, and their combination. We assessed activities of HER2, HER3, and downstream signaling pathways by Western blotting and cell growth by sulforhodamine B (SRB) and colony formation assays. HER3-specific shRNA was used to confirm the role of HER3 in cetuximab response. The combined efficacy and alterations in biomarkers were evaluated in UMSCC1-C xenograft and patient-derived xenograft (PDX) models. Results: Cetuximab treatment induced HER3 activation and HER2/HER3 dimerization in HNSCC cell lines. Combined treatment with cetuximab and MM-121 blocked EGFR and HER3 activities and inhibited the PI3K/AKT and ERK signaling pathways and HNSCC cell growth more effectively than each antibody alone. HER3 knockdown reduced HER2 activation and resensitized cells to cetuximab. Cetuximab-resistant xenografts and PDX models revealed greater efficacy of dual EGFR and HER3 inhibition compared with single antibodies. In PDX tissue samples, cetuximab induced HER3 expression and MM-121 reduced AKT activity. Conclusions: Clinically relevant PDX models demonstrate that dual targeting of EGFR and HER3 is superior to EGFR targeting alone in HNSCC. Our study illustrates the upregulation of HER3 by cetuximab as one mechanism underlying resistance to EGFR inhibition in HNSCC, supporting further clinical investigations using multiple targeting strategies in patients who have failed cetuximab-based therapy. Clin Cancer Res; 23(3); 677–86. ©2016 AACR.
Replication of G Quadruplex DNA

A cursory look at any textbook image of DNA replication might suggest that the complex machine that is the replisome runs smoothly along the chromosomal DNA. However, many DNA sequences can adopt non-B form secondary structures and these have the potential to impede progression of the replisome. A picture is emerging in which the maintenance of processive DNA replication requires the action of a significant number of additional proteins beyond the core replisome to resolve secondary structures in the DNA template. By ensuring that DNA synthesis remains closely coupled to DNA unwinding by the replicative helicase, these factors prevent impediments to the replisome from causing genetic and epigenetic instability. This review considers the circumstances in which DNA forms secondary structures, the potential responses of the eukaryotic replisome to these impediments in the light of recent advances in our understanding of its structure and operation and the mechanisms cells deploy to remove secondary structure from the DNA. To illustrate the principles involved, we focus on one of the best understood DNA secondary structures, G quadruplexes (G4s), and on the helicases that promote their resolution.
Design and Experimental Research of a Rotary Micro-Actuator Based on a Shearing Piezoelectric Stack

The working principle of a rotating micro-actuator based on a piezoelectric stack was theoretically analyzed and experimentally verified. The actuator is compact in structure, and the key component is the shearing piezoelectric stack. The piezoelectric stack is used to drive the micro-rotor via an electromechanical transition, which produces high-speed rotation of the micro-rotor. We first established the dynamic model of the micro-actuator and numerically analyzed the motion of this model. The step displacement output was observed by simulation, and the step increment is quite large. For experimental verification, we fabricated the piezoelectric micro-actuator with a size of 12 mm × 10 mm × 8 mm and mass of 4.12 g and conducted a series of experiments. The results show qualitative agreement with the theoretical results; the maximum output speed of the micro-actuator is 5.86 × 105 μrad/s, and the motion resolution is 0.64 μrad, which is greater than that of most traditional piezoelectric actuators. The proposed micro-actuator offers superior performance in driving of selected small objects, such as in micro-/nano-processing and cell operation.
Obesity-dependent CDK1 signaling stimulates mitochondrial respiration at complex I in pancreatic β-cells

β-Cell mitochondria play a central role in coupling glucose metabolism with insulin secretion. Here, we identified a metabolic function of cyclin-dependent kinase 1 (CDK1)/cyclin B1—the activation of mitochondrial respiratory complex I—that is active in quiescent adult β-cells and hyperactive in β-cells from obese (ob/ob) mice. In WT islets, respirometry revealed that 65% of complex I flux and 49% of state 3 respiration is sensitive to CDK1 inhibition. Islets from ob/ob mice expressed more cyclin B1 and exhibited a higher sensitivity to CDK1 blockade, which reduced complex I flux by 76% and state 3 respiration by 79%. The ensuing reduction in mitochondrial NADH utilization, measured with two-photon NAD(P)H fluorescence lifetime imaging (FLIM), was matched in the cytosol by a lag in citrate cycling, as shown with a FRET reporter targeted to β-cells. Moreover, time-resolved measurements revealed that in ob/ob islets, where complex I flux dominates respiration, CDK1 inhibition is sufficient to restrict the duty cycle of ATP/ADP and calcium oscillations, the parameter that dynamically encodes β-cell glucose sensing. Direct complex I inhibition with rotenone mimicked the restrictive effects of CDK1 inhibition on mitochondrial respiration, NADH turnover, ATP/ADP, and calcium influx. These findings identify complex I as a critical mediator of obesity-associated metabolic remodeling in β-cells and implicate CDK1 as a regulator of complex I that enhances β-cell glucose sensing.
PCR-Based Method for Shigella flexneri Serotyping: International Multicenter Validation

Shigella spp. are a leading cause of human diarrheal disease worldwide, with Shigella flexneri being the most frequently isolated species in developing countries. ABSTRACT Shigella spp. are a leading cause of human diarrheal disease worldwide, with Shigella flexneri being the most frequently isolated species in developing countries. This serogroup is presently classified into 19 serotypes worldwide. We report here a multicenter validation of a multiplex-PCR-based strategy previously developed by Q. Sun, R. Lan, Y. Wang, A. Zhao, et al. (J Clin Microbiol 49:3766–3770, 2011) for molecular serotyping of S. flexneri. This study was performed by seven international laboratories, with a panel of 71 strains (researchers were blind to their identity) as well as 279 strains collected from each laboratory’s own local culture collections. This collaborative work found a high extent of agreement among laboratories, calculated through interrater reliability (IRR) measures for the PCR test that proved its robustness. Agreement with the traditional method (serology) was also observed in all laboratories for 14 serotypes studied, while specific genetic events could be responsible for the discrepancies among methodologies in the other 5 serotypes, as determined by PCR product sequencing in most of the cases. This work provided an empirical framework that allowed the use of this molecular method to serotype S. flexneri and showed several advantages over the traditional method of serological typing. These advantages included overcoming the problem of availability of suitable antisera in testing laboratories as well as facilitating the analysis of multiple samples at the same time. The method is also less time-consuming for completion and easier to implement in routine laboratories. We recommend that this PCR be adopted, as it is a reliable diagnostic and characterization methodology that can be used globally for laboratory-based shigella surveillance.
High School Student Driving Perceptions Following Participation in a Distracted Driving Curriculum

Objectives. Distracted driving is a major public health issue in the United States. In response to requests from high school students participating in a university-based initiative, the authors describe the collaborative development and implementation of a curriculum designed to address distracted driving behaviors among students in four high-needs school districts in the northeastern United States. Method. The curriculum integrates current statistics on distracted and drowsy driving and three interactive learning stations: driving while distracted, walking while distracted, and driving while drowsy. Pre- and postsurveys were conducted to collect student driving data, assess student satisfaction with the program, and assess their likelihood of speaking up as a passenger in a high-risk situation. Results. The majority of students reported that they learned new information and would recommend the program to others. A Wilcoxon signed-rank test showed that students were more likely to speak up as a passenger with a distracted or drowsy driver (p < .001) after the program. Conclusion. This experience demonstrates a voluntary, multidisciplinary, university-based collaboration in the development of a novel public health education initiative. Based on the success of this phase, school districts elected to participate in Train the Trainer sessions to continue the program within their local high-needs school district.
Electron Highways into Nanochannels of Covalent Organic Frameworks for High Electrical Conductivity and Energy Storage.

To enhance the electron transfer within the covalent organic frameworks (COFs), we obtained a nanocomposite of conductive poly(3,4-ethylenedioxythiophene) (PEDOT) and redox-active AQ-COF by performing a facile in situ solid-state polymerization inside the nanochannels of COFs. The PEDOT chains functioned like electron highways within the nanochannels, resulting in a PEDOT@AQ-COF nanocomposite with an excellent electrical conductivity of 1.1 S cm-1 and a remarkably improved performance in faradaic energy storage. The all-organic PEDOT@AQ-COF electrode showed specific capacitance as high as 1663 F g-1 (at 1 A g-1), ultrafast charge/discharge rate performance (998 F g-1 at 500 A g-1), and excellent stability for 10 000 cycles. This research demonstrates a promising strategy for increasing the conductivity of COF-based materials and broadening their applications.
Traumatic Event Exposure, Posttraumatic Stress Disorder, and Sleep Disturbances in a National Sample of U.S. Adults.

Posttraumatic stress disorder (PTSD) is a highly prevalent, debilitating disorder found to develop after exposure to a potentially traumatic event (PTE). Individuals with PTSD often report sleep disturbances, specifically nightmares and insomnia, which are listed within the criteria for PTSD. This research examined prevalence of insomnia and nightmares within a national sample of 2,647 adults (data weighted by age and sex to correct for differences in sample distribution) who had been exposed to one or more PTEs. Prevalence of self-reported sleep disturbance, sleep disturbances by PTE type, and gender differences were examined. All participants completed a self-administered, structured online interview that assessed exposure to stressful events and PTSD symptoms. Among individuals who met DSM-5 criteria for PTSD, a large majority (more than 92%) reported at least one sleep disturbance. Insomnia was relatively more prevalent than PTE-related nightmares among individuals with PTSD and among all PTE-exposed individuals. A higher number of PTEs experienced significantly increased the likelihood of both trauma-related nightmares and insomnia, McFadden's pseudo R2 = . 07, p < . 001. Women exposed to PTEs were more likely to endorse experience of insomnia, χ2 (1, N = 2,647) = 99.13, p < . 001, φ = . 194, and nightmares compared to men, χ2 (1, N = 2,648) = 82.98, p < . 001, φ = . 177, but this gender difference was not significant among individuals with PTSD, ps = . 130 and . 050, respectively. Differences in sleep disturbance prevalence by PTE type were also examined. Implications for treatment and intervention and future directions are discussed.
Body Mass Index and Risk of Intestinal Metaplasia: A Cohort Study

Background: We examined the association between body mass index (BMI) and development of endoscopic intestinal metaplasia. Methods: This retrospective cohort study included 142,832 Korean adults free of endoscopic intestinal metaplasia and atrophic gastritis who underwent upper endoscopy at baseline and subsequent visits and were followed for up to 5 years. A parametric proportional hazards model was used to estimate the adjusted HR with 95% confidence interval (CI) for incident intestinal metaplasia. Results: In more than 444,719.1 person-years of follow-up, 2,281 participants developed endoscopic intestinal metaplasia (incidence rate, 5.1 per 1,000 person-years). Increased BMI categories were associated with increased risk of new-onset intestinal metaplasia in a dose-response manner. After adjustment for age, sex, center, year of screening exam, smoking status, alcohol intake, exercise, total calorie intake, history of diabetes and hypertension, and history of Helicobacter pylori infection, the multivariable adjusted HRs (95% CIs) for incident intestinal metaplasia comparing BMIs of <18.5, 23–24.9, 25.0–29.9, and >30 kg/m2 with a BMI of 18.5–22.9 kg/m2 were 0.84 (0.64–1.09), 1.03 (0.93–1.16), 1.07 (0.96–1.20), and 1.48 (1.20–1.83), respectively. These associations did not differ by clinically relevant subgroups. Risk of endoscopic atrophic gastritis also increased as the baseline BMI category increased. Conclusions: In a large cohort of Korean men and women, obesity was independently associated with increased incidence of endoscopic atrophic gastritis and intestinal metaplasia. Impact: Excessive adiposity appears to play a role in development of stomach precursor lesions of stomach cancer, requiring further studies to determine whether strategies to reduce obesity will also help reduce precancerous lesions and, in turn, gastric cancer.
Surface‐Mounted Metal–Organic Frameworks: Crystalline and Porous Molecular Assemblies for Fundamental Insights and Advanced Applications

Metal–organic frameworks (MOFs) are crystalline coordination polymers, assembled from inorganic nodes connected by organic linker molecules. An enormous surface area, huge compositional variety, regular structure, and favorable mechanical properties are among their outstanding properties. Monolithic MOF thin films, i.e., surface‐mounted metal–organic frameworks (SURMOFs), with high degree of structural order and adjustable defect density, can be prepared on solid substrates using layer‐by‐layer techniques. Recent studies where SURMOFs served as model systems for quantitative studies of molecular interactions in porous media, including diffusion, are reviewed. Moreover, SURMOFs are ideally suited for the incorporation of photoactive molecules as well as to study electrical transport through crystalline molecular assemblies. Recent work has demonstrated that the realization of crystalline chromophore assemblies via the SURMOF approach allows the study of fundamental aspects of exciton transport, exciton channeling, and photon upconversion at internal interfaces in organic semiconductor materials. Due to their crystalline nature, MOF materials are well suited for quantitative comparisons with theoretical results; especially, since defect densities and types can be characterized and varied in a straightforward fashion. The active role of these nanoporous films in advanced applications, like for remote‐controlled release of molecules, membranes with photoswitchable selectivity, and ion‐conductors with adjustable conductivity, are also emphasized.
Patient Experience in a Spanish Pediatric Emergency Department.

OBJECTIVES To study the experience reported by pediatric patients when visiting a pediatric emergency department (PED). METHODS This was a prospective descriptive study, carried out in November 2014. A 12-question survey was developed, based on the Picker Patient Experience Questionnaire. The aim was to assess patient experience of children between 8 and 18 years old, attended in the PED of a high-complexity pediatric hospital. Questions were about the waiting time and setting, medical staff explanations and actions, treatment, and discharge. The questionnaires were administered and filled in by the children themselves at discharge. RESULTS One-hundred seventy questionnaires were completed; 17.1% of respondents had to wait longer than expected, and 44.7% said that there was not enough to do when waiting to be seen. Pain was not correctly treated (3%), there was a lack of privacy (14.7%), and the information provided to the patients during the visit was wanting (10%). However, 80% said that they had been well treated. CONCLUSIONS The patient experience of children in our PED was positive, although some aspects should be improved such as offering entertainment in the waiting area, increasing privacy during the medical visit, and giving better explanations to the children.
DF-Fit: A Robust Algorithm for Detection of Crystallographic Information in Atom Probe Tomography Data

Abstract We report on a new algorithm for the detection of crystallographic information in three-dimensional, as retained in atom probe tomography (APT), with improved robustness and signal detection performance. The algorithm is underpinned by one-dimensional distribution functions (DFs), as per existing algorithms, but eliminates an unnecessary parameter as compared to current methods. By examining traditional DFs in an automated fashion in real space, rather than using Fourier transform approaches, we utilize an error metric based upon the expected value for a spatially random distribution for detecting crystallography. We show cases where the metric is able to successfully obtain orientation information, and show that it can function with high levels of additive and displacive background noise. We additionally compare this metric to Fourier transform methods, showing fewer artifacts when examining simulated datasets. An extension of the approach is used to aid the automatic detection of high-quality data regions within an entire dataset, albeit with a large increase in computational cost. This extension is demonstrated on acquired aluminum and tungsten APT datasets, and shown to be able to discern regions of the data which have relatively improved spatial data quality. Finally, this program has been made available for use in other laboratories undertaking their own analyses.