Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of WNT signaling reduces differentiation and induces sensitivity to doxorubicin in human malignant neuroblastoma SH-SY5Y cells

Neuroblastoma is one of the most common cancers in infancy, arising from the neuroblasts during embryonic development. This cancer is difficult to treat and resistance to chemotherapy is often found; therefore, clinical trials of novel therapeutic approaches, such as targeted-cancer signaling, could be an alternative for a better treatment. WNT signaling plays significant roles in the survival, proliferation, and differentiation of human neuroblastoma. In this report, WNT signaling of a malignant human neuroblastoma cell line, SH-SY5Y cells, was inhibited by XAV939, a specific inhibitor of the Tankyrase enzyme. XAV939 treatment led to the reduction of &bgr;-catenin within the cells, confirming its inhibitory effect of WNT. The inhibition of WNT signaling by XAV939 did not affect cell morphology, survival, and proliferation; however, the differentiation and sensitivity to anticancer drugs of human neuroblastoma cells were altered. The treatment of XAV939 resulted in the downregulation of mature neuronal markers, including &bgr;-tubulin III, PHOX2A, and PHOX2B, whereas neural progenitor markers (PAX6, TFAP2&agr;, and SLUG) were upregulated. In addition, the combination of XAV939 significantly enhanced the sensitivity of SH-SY5Y and IMR-32 cells to doxorubicin in both 2D and 3D culture systems. Microarray gene expression profiling suggested numbers of candidate target genes of WNT inhibition by XAV939, in particular, p21, p53, ubiquitin C, ZBED8, MDM2, CASP3, and FZD1, and this explained the enhanced sensitivity of SH-SY5Y cells to doxorubicin. Altogether, these results proposed that the altered differentiation of human malignant neuroblastoma cells by inhibiting WNT signaling sensitized the cells to anticancer drugs. This approach could thus serve as an effective treatment option for aggressive brain malignancy.
The provider perspective: investigating the effect of the Electronic Patient-Reported Outcome (ePRO) mobile application and portal on primary care provider workflow

Aim This qualitative study investigates how the Electronic Patient-Reported Outcome (ePRO) mobile application and portal system, designed to capture patient-reported measures to support self-management, affected primary care provider workflows. Background The Canadian health system is facing an ageing population that is living with chronic disease. Disruptive innovations like mobile health technologies can help to support health system transformation needed to better meet the multifaceted needs of the complex care patient. However, there are challenges with implementing these technologies in primary care settings, in particular the effect on primary care provider workflows. Methods Over a six-week period interdisciplinary primary care providers (n=6) and their complex care patients (n=12), used the ePRO mobile application and portal to collaboratively goal-set, manage care plans, and support self-management using patient-reported measures. Secondary thematic analysis of focus groups, training sessions, and issue tracker reports captured user experiences at a Toronto area Family Health Team from October 2014 to January 2015. Findings Key issues raised by providers included: liability concerns associated with remote monitoring, increased documentation activities due to a lack of interoperability between the app and the electronic patient record, increased provider anxiety with regard to the potential for the app to disrupt and infringe upon appointment time, and increased demands for patient engagement. Primary care providers reported the app helped to focus care plans and to begin a collaborative conversation on goal-setting. However, throughout our investigation we found a high level of provider resistance evidenced by consistent attempts to shift the app towards fitting with existing workflows rather than adapting much of their behaviour. As health systems seek innovative and disruptive models to better serve this complex patient population, provider change resistance will need to be addressed. New models and technologies cannot be disruptive in an environment that is resisting change.
Stink Bug (Hemiptera: Heteroptera: Pentatomidae) Feeding and Phenology on Early-Maturing Soybean in Minnesota

ABSTRACT The invasion by Halyomorpha halys (Stål) and an increasing abundance of native Pentatomidae pose a threat to soybean, Glycine max (L.) Merrill, production in northern states. A risk assessment framework was used to provide an initial assessment of the risk of Pentatomidae affecting soybean production in northern states. A caged field study was performed over two years to assess the response of soybean to H. halys feeding. Cages placed over R4 soybean were infested with 0, 1, 2, 4, or 8 fourth-instar H. halys nymphs per 0.3 row-m, and the insects were allowed to feed for 15 to 16 days. Feeding by H. halys on soybean affected yield components, maturity, and quality (i.e., seed injury). Season-long monitoring of soybean fields was performed via sweep net sampling to assess the likelihood of herbivorous Pentatomidae occurring on soybean during plant growth stages susceptible to feeding injury. Adults of herbivorous species were collected at low densities in fields in mid- to late July before collection of herbivorous nymphs. Herbivorous nymphs were first collected in the R3 and R4 soybean growth stages and their abundance peaked during the R6 soybean growth stage. This preliminary assessment indicates that if populations of exotic and native herbivorous Pentatomidae continue to increase in abundance, they will pose a threat to northern soybean production.
Ileal digestibility and urinary excretion of D-xylose and L-arabinose in ileostomized adult roosters.

An experiment with ileostomized adult roosters was conducted to determine the ileal digestibility and urinary excretion of D-xylose and L-arabinose. As a reference, D-glucose was included in the experiment. The sugars were tested at graded dietary levels of 2.5, 5.0, 7.5, and 10.0%. Mean ileal digestibility of D-glucose and D-xylose was nearly 100%. Ileal digestibility of L-arabinose decreased linearly (P less than .05) with increasing dose level. The corresponding ileal digestibilities for L-arabinose at dietary levels of 2.5, 5.0, 7.5, and 10.0% were 95.5, 93.6, 80.3, and 74.6%. Both pentose sugars were partly excreted in the urine. The extent of this urinary excretion in percentage of intake increased linearly (P less than .05) as the dietary level increased. In roosters fed the 2.5% D-xylose diet, 7.2% of the D-xylose consumed appeared in the urine. This level increased to 20.2% when roosters were fed a diet containing 10.0% D-xylose. Corresponding values for L-arabinose at these dietary inclusion levels were 8.7 and 16.6%.
A comparison of operative and margin outcomes from surgeon learning curves in robot assisted radical prostatectomy in a changing referral practice

INTRODUCTION The aim of this study was to explore the impact of increasing proportions of high risk referrals on surgical margin outcomes of a surgeon's learning curve in robotic prostatectomy. METHODS All patients in this study underwent robot assisted radical prostatectomy (RARP) performed by three different consultant urological surgeons. Data collected included preoperative clinical stage, Gleason score and prostate specific antigen levels, which were used to risk stratify patients according to National Institute for Health and Care Excellence criteria. Oncological clearance was assessed by overall and stage specific positive margin status. Comparisons were made between each surgeon for the first and second 50 consecutive cases. RESULTS For the three surgeons, there was a progressive increase in the proportion of high risk cases referred accompanied by a corresponding decline in low risk disease (p<0.001). Postoperative pathology also showed an upward trend in pT3 cases across the three eras. There was no statistical difference in overall positive margin rates between the surgeons. The overall rates were 12%, 20% and 23% for the first 50 cases, and 32%, 36% and 21% for the second 50 cases for the three surgeons respectively. CONCLUSIONS Our series demonstrates an upward trend in the risk profile of men referred for robotic prostatectomy over a nine‐year period. Despite this, there was minimal impact on pathological and surgical outcomes among our surgeons, who were at the initial stages of their RARP learning curve. Our results suggest that there is no requirement for an active case selection bias against patients with high risk disease for surgeons newly embarking on their RARP learning experience.
Uncertainty-Dependent Extinction of Fear Memory in an Amygdala-mPFC Neural Circuit Model

Uncertainty of fear conditioning is crucial for the acquisition and extinction of fear memory. Fear memory acquired through partial pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) is more resistant to extinction than that acquired through full pairings; this effect is known as the partial reinforcement extinction effect (PREE). Although the PREE has been explained by psychological theories, the neural mechanisms underlying the PREE remain largely unclear. Here, we developed a neural circuit model based on three distinct types of neurons (fear, persistent and extinction neurons) in the amygdala and medial prefrontal cortex (mPFC). In the model, the fear, persistent and extinction neurons encode predictions of net severity, of unconditioned stimulus (US) intensity, and of net safety, respectively. Our simulation successfully reproduces the PREE. We revealed that unpredictability of the US during extinction was represented by the combined responses of the three types of neurons, which are critical for the PREE. In addition, we extended the model to include amygdala subregions and the mPFC to address a recent finding that the ventral mPFC (vmPFC) is required for consolidating extinction memory but not for memory retrieval. Furthermore, model simulations led us to propose a novel procedure to enhance extinction learning through re-conditioning with a stronger US; strengthened fear memory up-regulates the extinction neuron, which, in turn, further inhibits the fear neuron during re-extinction. Thus, our models increased the understanding of the functional roles of the amygdala and vmPFC in the processing of uncertainty in fear conditioning and extinction.
Bilateral Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson Disease Dementia: A Randomized Clinical Trial

Importance Deep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a treatment option for Parkinson disease dementia. Objective To evaluate the safety and potential symptomatic effects of NBM DBS in patients with Parkinson disease dementia. Design, Setting, and Participants A randomized, double-blind, crossover clinical trial evaluated the results of 6 patients with Parkinson disease dementia who were treated with NBM DBS at a neurosurgical referral center in the United Kingdom from October 26, 2012, to July 31, 2015. Eligible patients met the diagnostic criteria for Parkinson disease dementia, had motor fluctuations, were appropriate surgical candidates aside from the coexistence of dementia, were age 35 to 80 years, were able to give informed consent, had a Mini-Mental State Examination score of 21 to 26, had minimal atrophy seen on results of brain magnetic resonance imaging, and lived at home with a caregiver-informant. Interventions After surgery, patients were assigned to receive either active stimulation (bilateral, low-frequency [20 Hz] NBM DBS) or sham stimulation for 6 weeks, followed by the opposite condition for 6 weeks. Main Outcomes and Measures The primary outcome was the difference in scores on each item of an abbreviated cognitive battery (California Verbal Learning Test-II, Wechsler Adult Intelligence Scale-III digit span, verbal fluency, Posner covert attention test, and simple and choice reaction times) between the 2 conditions. Secondary outcomes were exploratory and included differences in scores on standardized measurements of cognitive, psychiatric, and motor symptoms and resting state functional magnetic resonance imaging. Results Surgery and stimulation were well tolerated by all 6 patients (all men; mean [SD] age, 65.2 [10.7] years), with no serious adverse events during the trial. No consistent improvements were observed in the primary cognitive outcomes or in results of resting state functional magnetic resonance imaging. An improvement in scores on the Neuropsychiatric Inventory was observed with NBM DBS (8.5 points [range, 4-26 points]) compared with sham stimulation (12 points [range, 8-38 points]; median difference, 5 points; 95% CI, 2.5-8.5 points; P = .03) and the preoperative baseline (13 points [range, 5-25 points]; median difference, 2 points; 95% CI, −8 to 5.5 points; P = .69). Conclusions and Relevance Low-frequency NBM DBS was safely conducted in patients with Parkinson disease dementia; however, no improvements were observed in the primary cognitive outcomes. Further studies may be warranted to explore its potential to improve troublesome neuropsychiatric symptoms. Trial Registration clinicaltrials.gov Identifier: NCT01701544
Campaigns and counter campaigns: reactions on Twitter to e-cigarette education

Background Social media present opportunities for public health departments to galvanise interest in health issues. A challenge is creating content that will resonate with target audiences, and determining reactions to educational material. Twitter can be used as a real-time surveillance system to capture individuals’ immediate reactions to education campaigns and such information could lead to better campaigns in the future. A case study testing Twitter's potential presented itself when the California Department of Public Health launched its ‘Still Blowing Smoke’ media campaign about the potential harmful effects of e-cigarettes. Pro-e-cigarette advocacy groups, in response, launched a counter campaign titled ‘Not Blowing Smoke’. This study tracked the popularity of the two campaigns on Twitter, analysed the content of the messages and determined who was involved in these discussions. Methods The study period was from 22 March 2015 to 27 June 2015. A stratified sampling procedure supplied 2192 tweets for analysis. Content analysis identified pro, anti and neutral e-cigarette tweets, and five additional themes: Marketing Elements, Money, Regulation/propaganda, Health, and Other. Metadata were analysed to obtain additional information about Twitter accounts. Results ‘Not Blowing Smoke’ was referenced more frequently than ‘Still Blowing Smoke’ on Twitter. Messages commonly objected to government regulation of e-cigarettes, refuted claims that e-cigarette manufactures were aligned with big tobacco, and touted the health benefits of e-cigarette use. E-cigarette companies and vape shops used campaign slogans to communicate with customers on Twitter. Conclusions Findings showed the time dynamics of Twitter and the possibility for real-time monitoring of education campaigns.
Evaluation of two novel biochemicals on plasma and egg yolk lipid composition and laying hen performance.

PD132301-2, an inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT; EC 2.3.1.26), and 1-stearylboronic acid (SBA), a fatty acid analogue, were orally administered to White Leghorn hens in separate experiments to evaluate their effects on layer performance and plasma and egg yolk lipids. Five 60-wk-old hens each were fed either a corn-soybean meal basal layer ration, or the basal diet supplemented with . 0121, . 0363, or . 1089% PD132301-2. In a second experiment, 12 37-wk-old hens each were fed either a basal layer ration, or the basal diet supplemented with . 20 or . 40% SBA. The duration of the experiments were 21 and 16 days, respectively. Neither compound significantly affected hen-day production, egg weight, yolk weight, BW gain, feed consumption, feed efficiency, plasma total cholesterol and triglyceride concentrations, or egg yolk cholesterol content. PD132301-2 had no effect on yolk fatty acid profiles, and C22:6n3 was the only fatty acid altered by SBA. Although 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors have been successful in reducing egg cholesterol, ACAT inhibitors and fatty acid analogues apparently hold little promise in this regard. The results of the present work also support the concept that, in order to pharmacologically alter the cholesterol content of eggs, direct inhibition of key enzymes in the cholesterol biosynthetic pathway is necessary.
Preliminary Outcomes of a Cross‐Site Cognitive–Behavioral and Neuromuscular Integrative Training Intervention for Juvenile Fibromyalgia

Cognitive–behavioral therapy (CBT) is effective in reducing disability among youth with juvenile fibromyalgia (FM); however, engagement in moderate to vigorous physical activity remains poor, even after CBT. The purpose of this study was to evaluate the feasibility and preliminary outcomes of an innovative program combining CBT with specialized neuromuscular exercise: the Fibromyalgia Integrative Training for Teens (FIT Teens) program.
Birth Weight, School Sports Ability, and Adulthood Leisure-Time Physical Activity

Purpose This study aimed to examine the associations of birth weight with ability in school sports in adolescence and participation in leisure-time physical activity (LTPA) across adulthood and to investigate whether associations between birth weight and LTPA change with age. Methods Study participants were British singletons born in 1946 and followed up to age 68 yr (the Medical Research Council National Survey of Health and Development). Birth weights were extracted from birth records. Teacher reports of ability in school sports were collected at age 13 yr. LTPA was self-reported at ages 36, 43, 53, 60–64, and 68 yr and categorized at each age as participating in sports, exercise, and other vigorous LTPA at least once per month versus no participation. Associations were examined using standard and mixed-effects logistic regression models. Results Relevant data were available for 2739 study participants (50.1% female). When compared with the low birth weight group (⩽2.50 kg), those with heavier birth weights were more likely to be rated as above average or average at school sports (vs below average); fully adjusted odds ratio = 1.78 (95% confidence interval = 1.14–2.77). Across adulthood, those with heavier birth weights were more likely to participate in LTPA than those with low birth weight; fully adjusted odds ratio of LTPA across adulthood = 1.52 (95% confidence interval = 1.09–2.14). This association did not vary by age (P = 0.5 for birth weight by age interaction). Conclusions Low birth weight was associated with lower ability in school sports and with nonparticipation in LTPA across adulthood. Identifying the underlying developmental and social processes operating across life for low birth weight infants may inform the design of appropriate interventions to support participation in LTPA across life.
Immune modulation by altered nutrient metabolism: nutritional control of immune-induced growth depression.

The ability of conjugated isomers of linoleic acid (CLA) to prevent reduced growth rate following endotoxin (lipopolysaccharide, LPS) injection was studied in two chick trials and one rat trial. Chicks (10 per treatment) were fed a corn and soybean meal-based diet with or without . 5% CLA. At 21 days of age, chicks were weighed and injected i.p. with 1 mg/kg BW Escherichia coli LPS and sterile PBS. Body weights were again determined 24 h later. Antibody responses to SRBC were also determined. Rats fed . 5% stearic acid or CLA for 4 wk (seven per treatment) were also injected with LPS, and BW change over a 24-h postinjection period was determined. Antibody responses to BSA, phytohemagglutinin foot pad swelling, and phagocytosis of elicited peritoneal macrophages were also determined. The CLA had no adverse effects on any immune variables measured in the chicks and rats. The CLA enhanced the phytohemagglutinin response and macrophage phagocytosis in rats. Chicks fed CLA and injected with LPS continued to grow, whereas those not fed CLA either failed to grow or lost weight following LPS injection. Both control and CLA-fed rats lost weight over the 24-h period after LPS injection; however, the loss of weight in rats fed CLA was only half of the weight loss of the control rats. Thus, CLA is effective in preventing the catabolic effects of immune stimulation.
miR-106b-responsive gene landscape identifies regulation of Kruppel-like factor family

MicroRNA dysregulation is a common feature of cancer and due to the promiscuity of microRNA binding this can result in a wide array of genes whose expression is altered. miR-106b is an oncomiR overexpressed in cholangiocarcinoma and its upregulation in this and other cancers often leads to repression of anti-tumorigenic targets. The goal of this study was to identify the miR-106b-regulated gene landscape in cholangiocarcinoma cells using a genome-wide, unbiased mRNA analysis. Through RNA-Seq we found 112 mRNAs significantly repressed by miR-106b. The majority of these genes contain the specific miR-106b seed-binding site. We have validated 11 genes from this set at the mRNA level and demonstrated regulation by miR-106b of five proteins. Combined analysis of our miR-106b-regulated mRNA data set plus published reports indicate that miR-106b binding is anchored by G:C pairing in and near the seed. Novel targets Kruppel-like factor 2 (KLF2) and KLF6 were verified both at the mRNA and at the protein level. Further investigation showed regulation of four other KLF family members by miR-106b. We have discovered coordinated repression of several members of the KLF family by miR-106b that may play a role in cholangiocarcinoma tumor biology. List of abbreviations MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide DAPI 4’,6-diamidine-2’-phenylindole dihydrochloride CLASH Crosslinking, ligation, and sequencing of hybrids DR5 Death receptor-5 DMEM Dulbecco’s Modified Eagle’s Medium FDR False discovery rate FBS Fetal bovine serum KLF Kruppel-like factor LNA Locked-nucleic acid qRT-PCR Quantitative reverse-transcription PCR SDS-PAGE Sodium dodecylsulfate-polyacrylamide gel electrophoresis UTR Untranslated region
Pharmacokinetics of furosemide administered 4 and 24 hours prior to high‐speed exercise in horses

Furosemide is a diuretic agent used commonly in racehorses to attenuate the bleeding associated with exercise-induced pulmonary hemorrhage (EIPH). The current study describes serum and urine concentrations and the pharmacokinetics of furosemide following administration at 4 and 24 hrs prior to maximal exercise. Eight exercised adult Thoroughbred horses received a single IV administration of 250 mg of furosemide at 4 and 24 hrs prior to maximal exercise on a high-speed treadmill. Blood and urine samples were collected at time 0 and at various times for up to 72 hrs and furosemide concentrations determined using liquid chromatography-tandem mass spectrometry. Serum furosemide concentrations remained above the LOQ (0.05 ng/ml) for 36 hrs in 3/8 and 1/8 horses in the 4- and 24-hrs groups, respectively. Serum concentration data were best fit by a two-compartment model. There was not a significant difference in the volume of distribution at steady-state (0.594 ± 0.178 [4 hrs] and 0.648 ± 0.147 [24 hrs] L/kg) or systemic clearance (0.541 ± 0.094 [4 hrs] and 0.617 ± 0.114 [24 hrs] L/hrs/kg) between horses that were exercised at 4- and 24 hrs postdrug administration. The mean ± SD elimination half-life was 3.12 ± 0.387 and 3.23 ± 0.407 hrs following administration at 4 and 24 hrs prior to exercise, respectively.