Miracle-dz/UniFAR-FTUs huggingface dataset:
PP2A Deficiency Enhances Carcinogenesis of Lgr5+ Intestinal Stem Cells Both in Organoids and In Vivo

In most cancers, cellular origin and the contribution of intrinsic and extrinsic factors toward transformation remain elusive. Cell specific carcinogenesis models are currently unavailable. To investigate cellular origin in carcinogenesis, we developed a tumorigenesis model based on a combination of carcinogenesis and genetically engineered mouse models. We show in organoids that treatment of any of three carcinogens, DMBA, MNU, or PhIP, with protein phosphatase 2A (PP2A) knockout induced tumorigenesis in Lgr5+ intestinal lineage, but not in differentiated cells. These transformed cells increased in stem cell signature, were upregulated in EMT markers, and acquired tumorigenecity. A mechanistic approach demonstrated that tumorigenesis was dependent on Wnt, PI3K, and RAS-MAPK activation. In vivo combination with carcinogen and PP2A depletion also led to tumor formation. Using whole-exome sequencing, we demonstrate that these intestinal tumors display mutation landscape and core driver pathways resembling human intestinal tumor in The Cancer Genome Atlas (TCGA). These data provide a basis for understanding the interplay between extrinsic carcinogen and intrinsic genetic modification and suggest that PP2A functions as a tumor suppressor in intestine carcinogenesis.
A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs

In late 2012 it was evidenced that most of the human genome is transcribed but only a small percentage of the transcripts are translated. This observation supported the importance of non-coding RNAs and it was confirmed in several organisms. The most abundant non-translated transcripts are long non-coding RNAs (lncRNAs). In contrast to protein-coding RNAs, they show a more cell-specific expression. To understand the function of lncRNAs, it is fundamental to investigate in which cells they are preferentially expressed and to detect their subcellular localization. Recent improvements of techniques that localize single RNA molecules in tissues like single-cell RNA sequencing and fluorescence amplification methods have given a considerable boost in the knowledge of the lncRNA functions. In recent years, single-cell transcription variability was associated with non-coding RNA expression, revealing this class of RNAs as important transcripts in the cell lineage specification. The purpose of this review is to collect updated information about lncRNA classification and new findings on their function derived from single-cell analysis. We also retained useful for all researchers to describe the methods available for single-cell analysis and the databases collecting single-cell and lncRNA data. Tables are included to schematize, describe, and compare exposed concepts.
Circulating epithelial tumor cell analysis in CSF in patients with leptomeningeal metastases

Objective The primary objective was to determine the sensitivity and specificity of epithelial cell adhesion molecule (EpCAM) immunoflow cytometry circulating tumor cells (CTC) analysis in CSF in patients with suspected leptomeningeal metastases (LM). The secondary objective was to explore the distribution of driver mutations in the primary tumor, plasma, cell free CSF (cfCSF), and isolated CTC from CSF in non-small cell lung cancer (NSCLC). Methods We tested the performance of the CTC assay vs CSF cytology in a prospective study in 81 patients with a clinical suspicion of LM but a nonconfirmatory MRI. In an NSCLC subcohort, we analyzed circulating tumor (ct)DNA of the selected driver mutations by digital droplet PCR (ddPCR). Results The sensitivity of the CTC assay was 94% (95% confidence interval [CI] 80–99) and the specificity was 100% (95% CI 91–100) at the optimal cutoff of 0.9 CTC/mL. The sensitivity of cytology was 76% (95% CI 58–89). Twelve of the 23 patients with NSCLC had mutated epidermal growth factor receptor (EGFR). All 5 tested patients with LM demonstrated the primary EGFR driver mutation in cfCSF. The driver mutation could also be detected in CTC isolated from CSF. Conclusion CTC in CSF are detected with a high sensitivity for the diagnosis of LM. ddPCR can determine EGFR mutations in both cfCSF and isolated CTC from CSF of patients with EGFR-mutated NSCLC and LM. Classification of evidence This study provides Class III evidence that EpCAM-based immunoflow cytometry analysis of CSF accurately identifies patients with LM.
High-Dose Chloroquine for Uncomplicated Plasmodium falciparum Malaria Is Well Tolerated and Causes Similar QT Interval Prolongation as Standard-Dose Chloroquine in Children

Higher chloroquine doses can effectively treat up to 93 to 96% of malaria infections caused by Plasmodium falciparum carrying the resistance-conferring chloroquine resistance transporter (pfcrt) 76T allele. The tolerability of 50 (double the standard dose) and 70 mg/kg total chloroquine doses were assessed in this study. Fifteen 4- to 8-year-old children with uncomplicated malaria were given 10 mg/kg of chloroquine twice daily for 2 days and 5 mg/kg twice daily on the third day. ABSTRACT Higher chloroquine doses can effectively treat up to 93 to 96% of malaria infections caused by Plasmodium falciparum carrying the resistance-conferring chloroquine resistance transporter (pfcrt) 76T allele. The tolerability of 50 (double the standard dose) and 70 mg/kg total chloroquine doses were assessed in this study. Fifteen 4- to 8-year-old children with uncomplicated malaria were given 10 mg/kg of chloroquine twice daily for 2 days and 5 mg/kg twice daily on the third day. Fifteen additional children were given 5 mg/kg twice daily for 2 more days. Chloroquine concentrations, blood pressure, electrocardiograms (ECGs), parasite density, and adverse events were assessed until day 28. Both dosages were well tolerated, and symptoms resolved by day 3 in parallel with increasing chloroquine concentrations. The median corrected QT (QTc) interval was 12 to 26 ms higher at expected peak concentrations than at day 0 (P < 0.001). Pfcrt 76T was associated with delayed parasite clearance. Day 28 clinical and parasitological responses against P. falciparum with pfcrt 76T were 57% (4/7) and 67% (4/6) after treatment with 50 and 70 mg/kg, respectively. Dosages were well tolerated, and no severe cardiac adverse events occurred. The QTc interval increase was similar to that found in adults taking 25 mg/kg of chloroquine. (This study has been registered at ClinicalTrials.gov under identifier NCT01814423.)
Socioeconomic Disparities in Vape Shop Density and Proximity to Public Schools in the Conterminous United States, 2018

We conducted an environmental justice assessment examining the distribution of specialty vape shops in relation to where minority and low-income youth live and attend school. We collated and examined the density of vape shops in public school districts in 2018 throughout the conterminous United States using geographic information systems. We calculated the proximity of vape shops to public middle and high schools through nearest neighbor analysis in QGIS software. We examined the statistical relationships between the density of vape shops in school districts, and proximity to schools, with the proportion of racial/ethnic minorities and those living in poverty. We found that vape shops are more densely distributed, and are in closer proximity to schools, in school districts with higher proportions of Asian and Black or African American populations. However, vape shops were further away from schools in school districts with higher proportions of the population in poverty. The proximity and higher density of vape shops in relationship to schools in Asian and Black or African American communities may result in disproportionate health impacts due to greater access and exposure to vape products and advertisements. Our results may help school district administrators prioritize and target efforts to curb youth vaping (e.g., health education curricula) in these school districts with high density and closer proximity of vape shops to schools. Policy efforts, such as local ordinances restricting the promotion and sale of vaping products close to schools, could help prevent disproportionate human and environmental health impacts to minorities.
A Novel Testing Approach for Oxidative Degradation Dependent Incompatibility of Amine Moiety Containing Drugs with PEGs in Solid-State

Reactive impurities originating from excipients can cause drug stability issues, even at trace amounts. When produced during final dosage form storage, they are especially hard to control, and often, factors inducing their formation remain unidentified. Oxidative degradation dependent formation of formaldehyde and formic acid is responsible for N-methylation and N-formylation of amine-moiety-containing drug substances. A very popular combination of polyethylene glycols and iron oxides, used in more than two-thirds of FDA-approved tablet formulation drugs in 2018, was found to be responsible for increased concentrations of N-methyl impurity in the case of paroxetine hydrochloride. We propose a novel testing approach for early identification of potentially problematic combinations of excipients and drug substances. The polyethylene glycol 6000 degradation mechanism and kinetics in the presence of iron oxides is studied. The generality of the proposed stress test setup in view of the susceptibility of amine-moiety-containing drug substances to N-methylation and N-formylation is evaluated.
Facile Synthesis of FAPbI3 Nanorods

Metal halide perovskites are promising materials for a range of applications. The synthesis of light-emitting perovskite nanorods has become popular recently. Thus far, the facile synthesis of perovskite nanorods remains elusive. In this work, we have developed a facile synthesis to fabricate FAPbI3 nanorods for the first time, demonstrating a high photoluminescence quantum yield of 35–42%. The fabrication of the nanorods has been made possible by carefully tuning the concentration of formamidine-oleate as well as the amount of oleic acid with pre-dissolved PbI2 in toluene with oleic acid/oleylamine.
Two Different Methods to Measure the Stability of Acetabular Implants: A Comparison Using Artificial Acetabular Models

The total number of total hip arthroplasties is increasing every year, and approximately 10% of these surgeries are revisions. New implant design and surgical techniques are evolving quickly and demand accurate preclinical evaluation. The initial stability of cementless implants is one of the main concerns of these preclinical evaluations. A broad range of initial stability test methods is currently used, which can be categorized into two main groups: Load-to-failure tests and relative micromotion measurements. Measuring relative micromotion between implant and bone is recognized as the golden standard for implant stability testing as this micromotion is directly linked to the long-term fixation of cementless implants. However, specific custom-made set-ups are required to measure this micromotion, with the result that numerous studies opt to perform more straightforward load-to-failure tests. A custom-made micromotion test set-up for artificial acetabular bone models was developed and used to compare load-to-failure (implant push-out test) with micromotion and to assess the influence of bone material properties and press-fit on the implant stability. The results showed a high degree of correlation between micromotion and load-to-failure stability metrics, which indicates that load-to-failure stability tests can be an appropriate estimator of the primary stability of acetabular implants. Nevertheless, micromotions still apply as the golden standard and are preferred when high accuracy is necessary. Higher bone density resulted in an increase in implant stability. An increase of press-fit from 0.7 mm to 1.2 mm did not significantly increase implant stability.
Does height matter for earnings? Evidence from Russia

Abstract This study explores the link between height and earnings, using data from the Russian Longitudinal Monitoring Survey for the year 2015 (24th wave). The dependent variable was average monthly income and the key independent variable was self-reported height, measured in centimetres. The empirical model also included a rich vector of personal and job-related factors that have been shown to be associated with earnings in the relevant literature. Sequential multiple regression and one-way analyses of variance (ANOVA) were used to analyse the data. The results suggest that height is a significant predictor of earnings in Russia. The results were found to be robust for a set of controls and tests.
High MYC mRNA Expression Is More Clinically Relevant than MYC DNA Amplification in Triple-Negative Breast Cancer

DNA abnormalities are used in inclusion criteria of clinical trials for treatments with specific targeted molecules. MYC is one of the most powerful oncogenes and is known to be associated with triple-negative breast cancer (TNBC). Its DNA amplification is often part of the targeted DNA-sequencing panels under the assumption of reflecting upregulated signaling. However, it remains unclear if MYC DNA amplification is a surrogate of its upregulated signaling. Thus, we investigated the difference between MYC DNA amplification and mRNA high expression in TNBCs utilizing publicly available cohorts. MYC DNA amplified tumors were found to have various mRNA expression levels, suggesting that MYC DNA amplification does not always result in elevated MYC mRNA expression. Compared to other subtypes, both MYC DNA amplification and mRNA high expression were more frequent in the TNBCs. MYC mRNA high expression, but not DNA amplification, was significantly associated with worse overall survival in the TNBCs. The TNBCs with MYC mRNA high expression enriched MYC target genes, cell cycle related genes, and WNT/β-catenin gene sets, whereas none of them were enriched in MYC DNA amplified TNBCs. In conclusion, MYC mRNA high expression, but not DNA amplification, reflects not only its upregulated signaling pathway, but also clinical significance in TNBCs.
Prescription Opioid Misuse and Risky Adolescent Behavior

Prescription opioid misuse is associated with higher rates of 22 different risky behaviors in a nationally representative US adolescent sample. BrightcoveDefaultPlayer10.1542/6138650569001PEDS-VA_2019-2470 Video Abstract OBJECTIVES: Misuse of opioid medications (ie, using opioids differently than how a doctor prescribed the medication) is common among US adolescents and associated with preventable health consequences (eg, severe respiratory depression, seizures, heart failure, and death). 1 New guidelines and recommendations have made providers more attuned to overprescribing and more vigilant about screening for opioid misuse.2 We hypothesized that youth who misused prescription opioids were more likely to report engaging in a broad range of other risky behaviors. METHODS: We used the Centers for Disease Control and Prevention’s 2017 Youth Risk Behavior Surveillance Survey (n = 14 765), a cross-sectional, nationally representative survey of high school students. Students were sampled by using a 3-stage random cluster design. We conducted weighted logistic regressions to determine the strength of the association between our independent variable, ever misusing prescription opioids, and 22 dependent variables in the following categories: risky driving behaviors (4 variables), violent behaviors (3 variables), risky sexual behaviors (4 variables), substance use (10 variables), and suicide attempt (1 variable). RESULTS: In 2017, 14% of US adolescents reported ever misusing opioids. Those who misused prescription opioids were significantly more likely to have engaged in all 22 risky behaviors (adjusted odds ratios ranged from 2.0 to 22.3; P < .0001 for all tests) compared with other adolescents. CONCLUSIONS: Adolescents reporting ever misusing prescription opioids were more likely to have engaged in a broad range of risky behaviors. Health care providers screening for prescription opioid misuse may be ideally positioned to identify these high-risk youth and initiate early interventions.
Sedentariness of College Students Is Negatively Associated with Perceived Neighborhood Greenness at Home, but Not at University

Previous studies reported contradictory evidence for associations between perceived greenness and obesity mediated by physical activity, focusing on people’s homes or general greenness. Data are lacking in other environments. We studied the association of perceived greenness at home and at university with BMI and physical activity. An online survey collected data from 601 participants, living and studying in and around the city of Graz, Austria; mean age of 24 years. Greenness was assessed using questions on quality of and access to green space; Body mass index (BMI) was derived from self-reported measures; physical activity and sedentariness were measured using the IPAQ questionnaire (short version). On average, BMI was 22.6 (SD = 3.7), physical activity was 63.3 (SD = 51.7) METh/week, and participants spent 5.8 (SD = 4.0) h/day sitting. Regression analyses revealed no associations between perceived greenness and BMI and physical activity for all environments, but a negative association for sedentariness and perceived greenness at home, but not at university. The results indicate a relation between perceived greenness and sedentariness, which differs for the home-and study environment.
The Influence of Lycopene, [6]-Gingerol, and Silymarin on the Apoptosis on U-118MG Glioblastoma Cells In Vitro Model

Background: Lycopene, gingerol, and silymarin have a potential anticancer activity in many types of neoplasms. Healthy lifestyle and proper diet are associated with a reduced risk of cancer and other diseases. Increasingly, clinical research focuses on the mechanisms of action of natural compounds and their impact on the development of cancer. The aim of the present study was to determine the effect of lycopene, gingerol, and silymarin on apoptosis, mitochondrial potential and caspase-3/7 activity in the U118-MG cell line. Methods: Human glioblastoma cells were incubated with lycopene, [6]-gingerol, and silymarin for 24 and 48 h. Apoptosis was monitored using the Annexin V labelling, caspase-3/7 activity, and early hallmark of apoptosis were determined with mitochondrial membrane potential changes. Results: Our data showed a significant decrease in the viability glioblastoma cells U118-MG after 48 h treatment with lycopene, [6]-gingerol, and silymarin. Conclusions: Our data could confirm the stimulative effects of used compounds on apoptosis and changes in mitochondrial potential in a dose-dependent manner.
Can Milk Affect Recovery from Simulated Team-Sport Match Play?

This study investigated the effects of cow’s milk on recovery from repeated simulated team games (STGs) in females. Twenty female team-sport athletes completed an STG circuit (2x ~ 30 min, with 10 min ‘half-time’). Measures of muscle function, soreness and tiredness, symptoms of stress and serum markers of muscle damage and oxidative stress were determined pre- and 24 h, 48 h, 72 h and 96 h following the circuit. At 48 h, a second STG was completed. Sprint performance (5 m, 15 m), lap time, countermovement jump (CMJ), heart rate and RPE were recorded during each STG. Immediately following each STG, participants consumed either 500 mL of cow’s milk (MILK) or 500 mL of an energy-matched carbohydrate (CHO) solution. Compared to CHO, MILK had a beneficial effect in attenuating losses in peak torque for knee extension (60°/s) (likely; effect size (ES) = 0.26 to 0.28) knee flexion (60°/s) (likely; ES = 0.45 to 0.61). A benefit for MILK was observed for 5 m sprint (possible-likely; ES = 0.40 to 0.58), 10 m sprint (likely; ES = 0.30 to 0.53) and symptoms of stress (likely–very likely, small). Mostly unclear outcomes for other variables were observed. For STG variables, trivial (HR, CMJ) and unclear (5 m sprint, 15 m sprint, lap-time, RPE) outcomes were recorded. In conclusion, the consumption of 500 mL of milk attenuated losses in muscle function and perceptions of stress following repeated simulated team-sports games. However, further investigation is warranted to determine whether MILK can influence subsequent team-sport performance.
Short- and long-term outcomes of pancreaticoduodenectomy in elderly patients with periampullary cancer

Purpose Pancreaticoduodenectomy (PD) is recently performed in older cancer patients. The complication rate of PD is high. The present study was to compare the postoperative short- and long-term outcomes of PD in between older patients and younger patients. Methods Between 2000 and 2014, patients who underwent PD due to periampullary cancers were enrolled. Patients aged 75 years or over were included in the older group. Results Total 1,249 patients were enrolled in this study and 168 patients (13.5%) were included in the older group. Postoperative complication rates, duration of postoperative hospital stay, and 30-day mortality were comparable between the 2 groups, although the admission rate of intensive care unit postoperatively was higher in the older adult group (20.8% vs. 10.5%, P < 0.001). In terms of long-term outcomes, 5-year overall survival rate was lower in the older group (23.4% vs. 41.8%, P < 0.001), and 5-year cumulative recurrence rate was higher in the older group without statistical significance (63.9% vs. 57.9%, P = 0.095). However, there were no statistical differences of cumulative recurrence in pancreatic cancer patients (81.5% vs. 82.5%, P = 0.805). Conclusion PD for periampullary cancer is a safe and feasible treatment in the older patients. The treatment modality for obtaining better survival outcomes will be investigated.
Negative valence specific deficits in judgements of musical affective quality in alexithymia

ABSTRACT Alexithymia is characterised by a lack of words for emotional experiences and it has been implicated in deficits in emotion processing. Research in this area has typically focused on judgements of discrete emotions rather than of affect, which is a precursor to emotion construction. In the current study, higher alexithymia was predicted to be related to more neutral judgements of valence and arousal of music representing a range of emotions. Participants (N = 162) listened to ten 15-second musical pieces that represented five target emotions (happy, sad, tender, angry, and fearful) and rated the valence and arousal of each. Participants also listed emotion words they knew to be expressed in music. Analyses revealed that alexithymia was not related to the number of emotion words generated but was related to valence-specific affect judgements of music. Participants higher in alexithymia rated sad, angry, and fearful pieces as more neutral in valence and arousal. Alexithymia was not related to ratings of valence or arousal for happy and tender pieces. These findings suggest that perceptual deficits in alexithymia may be specific to negative emotions. Our results are consistent with the idea that alexithymia is related to the direction of attention away from negative stimuli.