Miracle-dz/UniFAR-FTUs huggingface dataset:
A 10‐year prediagnostic follow‐up study shows that serum RNA signals are highly dynamic in lung carcinogenesis

The majority of lung cancer (LC) patients are diagnosed at a late stage, and survival is poor. Circulating RNA molecules are known to have a role in cancer; however, their involvement before diagnosis remains an open question. In this study, we investigated circulating RNA dynamics in prediagnostic LC samples, focusing on smokers, to identify if and when disease‐related signals can be detected in serum. We sequenced small RNAs in 542 serum LC samples donated up to 10 years before diagnosis and 519 matched cancer‐free controls coming from 905 individuals in the Janus Serum Bank. This sample size provided sufficient statistical power to independently analyze time to diagnosis, stage, and histology. The results showed dynamic changes in differentially expressed circulating RNAs specific to LC histology and stage. The greatest number of differentially expressed RNAs was identified around 7 years before diagnosis for early‐stage LC and 1–4 years prior to diagnosis for locally advanced and advanced‐stage LC, regardless of LC histology. Furthermore, NSCLC and SCLC histologies have distinct prediagnostic signals. The majority of differentially expressed RNAs were associated with cancer‐related pathways. The dynamic RNA signals pinpointed different phases of tumor development over time. Stage‐specific RNA profiles may be associated with tumor aggressiveness. Our results improve the molecular understanding of carcinogenesis. They indicate substantial opportunity for screening and improved treatment and will guide further research on early detection of LC. However, the dynamic nature of the RNA signals also suggests challenges for prediagnostic biomarker discovery.
Menagerie: A text-mining tool to support animal-human translation in neurodegeneration research

Discovery studies in animals constitute a cornerstone of biomedical research, but suffer from lack of generalizability to human populations. We propose that large-scale interrogation of these data could reveal patterns of animal use that could narrow the translational divide. We describe a text-mining approach that extracts translationally useful data from PubMed abstracts. These comprise six modules: species, model, genes, interventions/disease modifiers, overall outcome and functional outcome measures. Existing National Library of Medicine natural language processing tools (SemRep, GNormPlus and the Chemical annotator) underpin the program and are further augmented by various rules, term lists, and machine learning models. Evaluation of the program using a 98-abstract test set achieved F1 scores ranging from 0.75–0.95 across all modules, and exceeded F1 scores obtained from comparable baseline programs. Next, the program was applied to a larger 14,481 abstract data set (2008–2017). Expected and previously identified patterns of species and model use for the field were obtained. As previously noted, the majority of studies reported promising outcomes. Longitudinal patterns of intervention type or gene mentions were demonstrated, and patterns of animal model use characteristic of the Parkinson’s disease field were confirmed. The primary function of the program is to overcome low external validity of animal model systems by aggregating evidence across a diversity of models that capture different aspects of a multifaceted cellular process. Some aspects of the tool are generalizable, whereas others are field-specific. In the initial version presented here, we demonstrate proof of concept within a single disease area, Parkinson’s disease. However, the program can be expanded in modular fashion to support a wider range of neurodegenerative diseases.
Development and characterization of CD73-siRNA-loaded nanoemulsion: effect on C6 glioma cells and primary astrocytes

Abstract Introduction: Glioblastoma (GB) is the most common malignant brain tumor and is characterized by high invasiveness, poor prognosis, and limited therapeutic options. Silencing gene expression, through the use of small interfering RNA (siRNA), has been proposed as an alternative to conventional cancer therapy. Here, we evaluated the potential of CD73 as a new therapeutic target, since it is overexpressed in solid tumors and has emerged as a promising target to control GB progression. Methods: A cationic nanoemulsion (NE) as an intravenous siRNA-CD73 delivery system was developed and its effect on C6 glioma cell viability was determined. Results: The nanostructured system was effective in complexing oligonucleotides for delivery to target cells. In addition, we observed that the NE-siRNA-CD73 complex was effective in reducing CD73 protein levels and AMPase activity, which were related to decreased C6 glioma cell viability. Conclusions: These findings indicate the potential of siRNA-CD73-loaded cationic NE as a therapeutic alternative for glioma treatment.
Associations Among Taste Perception, Food Neophobia and Preferences in Type 1 Diabetes Children and Adolescents: A Cross-Sectional Study

Type 1 diabetes (T1D) is one of the most common systemic diseases in childhood which predisposes the patient to serious short-term and long-term complications, affecting all body systems. Taste and olfactory impairments were first described a long time ago in adult patients affected by diabetes (both type 1 and type 2 diabetes). However, studies evaluating taste perception, behavioral attitudes (e.g., food neophobia), and preferences toward foods in children and adolescents affected by T1D are globally lacking. Therefore, the purpose of this study was to assess taste sensitivity, food neophobia, and preferences among children and adolescents affected by T1D and healthy controls in a cross-sectional study. T1D patients presented a significantly lower ability in general to correctly identify taste qualities, especially bitter and sour tastes. Moreover, they were characterized by fewer fungiform papillae compared to controls, as well as a lower responsiveness to the bitter compound 6-n-propylthiouracil (PROP). There were no significant differences in food neophobia scores between the two groups, but differences were observed in the mean hedonic ratings for some product categories investigated. Diabetic patients showed a greater liking for certain type of foods generally characterized by sourness and bitterness, an observation probably linked to their impaired ability to perceive taste stimuli, e.g., sourness and bitterness. These results may help to enhance the understanding of these relationships in populations with elevated diet-related health risks.
RETINAL OXIMETRY IS ALTERED IN EYES WITH CHOROIDAL MELANOMA BUT NOT IN EYES WITH CHOROIDAL NEVI

Supplemental Digital Content is Available in the Text. Noninvasive retinal oximetry demonstrates alterations in eyes with untreated choroidal melanoma, including an increased difference between arterial and venous saturation. These changes were not observed in eyes with choroidal nevi and may be related to the tumour's metabolism or inflammatory changes.
High-Energy Diet and Shorter Light Exposure Drives Markers of Adipocyte Dysfunction in Visceral and Subcutaneous Adipose Depots of Psammomys obesus

Dysfunctional adipose tissue phenotype underpins type 2 diabetes mellitus (T2DM) development. The disruption of circadian rhythms contributes to T2DM development. We investigated the effects of high-energy diet and photoperiod length on visceral and subcutaneous adipose tissue phenotype. Psammomys obesus sand rats exposed to neutral (12 light:12 dark) or short (5 light:19 dark) photoperiod were fed a low- (LE) or high- (HE) energy diet. The HE diet and/or short photoperiod reduced subcutaneous expression of adipocyte differentiation/function markers C/ebpα, Pparδ, Pparγ and Adipoq. Visceral Pparα levels were elevated in the 5:19HE group; however, the HE diet and/or short photoperiod decreased visceral Pparγ and Adipoq expression. 5:19HE animals had elevated Ucp1 yet lower Pgc-1α levels. The HE diet increased visceral Tgf-β1, Ccl2 and Cd68 levels, suggestive of a pro-inflammatory state. Daily visceral rhythms of these genes were affected by a short photoperiod and/or HE diet. The 12:12HE, 5:19LE or 5:19HE animals had a higher proportion of larger adipocytes, indicating increased adipocyte hypertrophy. Collectively, the HE diet and/or shorter light exposure drives a dysfunctional adipose tissue phenotype. Daily rhythms are affected by a short photoperiod and HE diet in a site-specific manner. These findings provide mechanistic insight on the influence of disrupted circadian rhythms and HE diet on adipose tissue phenotype.
Preoperative Statin Use and 90-Day Mortality After Noncardiac Surgery

Supplemental Digital Content is available in the text Objective: The aim of this study was to investigate the association between preadmission statin use and 90-day mortality after planned elective noncardiac surgery in adult patients. Summary Background Data: Statin therapy is known to have pleiotropic effects, which improve the outcomes of various diseases. However, the effect of perioperative statin therapy on postoperative mortality remains controversial. Methods: This retrospective cohort study analyzed the medical records of adult patients who were admitted to a single tertiary academic hospital for elective noncardiac surgery between January 2012 and December 2018. The primary endpoint was 90-day mortality, which was defined as any mortality within 90 days after surgery. The secondary endpoint was overall survival. Results: After propensity score matching, a total of 33,514 patients (16,757 patients in each group) were included in the analysis. The logistic regression analysis of the propensity score-matched cohort indicated that the odds ratio (OR) of 90-day mortality in the statin group was 26% lower than that of the nonstatin group [OR: 0.74; 95% confidence interval (CI): 0.59 to 0.92; P = 0.009]. The sensitivity analysis indicated that the high-dose intensity statin group had a 61% lower 90-day mortality rate than the nonstatin group (OR: 0.39; 95% CI: 0.18–0.84; P = 0.016). The overall survival time was significantly longer in the statin group than in the nonstatin group after propensity score matching (P < 0.001 by log-rank test). Conclusions: Preoperative statin use was associated with lower 90-day mortality and longer overall survival for adult patients who underwent elective noncardiac surgery. This association was more evident for high-intensity statin users.
Circulation Fluidized Bed Combustion Fly Ash as Partial Replacement of Fine Aggregates in Roller Compacted Concrete

Recently, many people around the world have been concerned with environmental protection and sustainability. The goal of various countries’ research has been focused on how to regenerate existing resources. Circulation fluidized bed combustion (CFBC) technology is one of the emerging combustion technologies for electricity generation and produces more than 800,000 tons of CFBC fly ash (CFA) per year for combustion. CFA has been widely applied in cement additive, new building materials and cement-based materials. The goal of this study was to discuss the engineering properties of roller-compacted concrete containing CFA. Test subjects included compressive strength, flexural strength, absorption, setting time, unit weight, sulfate resistance, SEM microscopic observations and XRD ingredient analysis. Test results indicate the following: (1) using CFA as a substitute of fine aggregates up to 10 wt. % would improve the development of later flexural strength; (2) the increases in pre-pressure would increase the compressive strength and unit weight and decrease absorption; (3) using CFA would reduce the initial setting time by 30%–60% and reduce the final setting time by 16%–20%; (4) using CFA would reduce the absorption; (5) using CFA would reduce the unit weight by 0.5%–2.8%, and the increases in pre-pressure would increase the unit weight by about 0.9%–2.1%; (6) CaO in CFA helps to improve sulfate resistance; (7) scanning electron microscopy (SEM) observation shows that the increases in pre-pressure would reduce the pores; and (8) X-ray diffraction (XRD) analysis shows that the inclusion of CFA would increase the content of Ca(OH)2 in concrete.
Toscana, West Nile, Usutu and tick-borne encephalitis viruses: external quality assessment for molecular detection of emerging neurotropic viruses in Europe, 2017

Background Neurotropic arboviruses are increasingly recognised as causative agents of neurological disease in Europe but underdiagnosis is still suspected. Capability for accurate diagnosis is a prerequisite for adequate clinical and public health response. Aim To improve diagnostic capability in EVD-LabNet laboratories, we organised an external quality assessment (EQA) focusing on molecular detection of Toscana (TOSV), Usutu (USUV), West Nile (WNV) and tick-borne encephalitis viruses (TBEV). Methods Sixty-nine laboratories were invited. The EQA panel included two WNV RNA-positive samples (lineages 1 and 2), two TOSV RNA-positive samples (lineages A and B), one TBEV RNA-positive sample (Western subtype), one USUV RNA-positive sample and four negative samples. The EQA focused on overall capability rather than sensitivity of the used techniques. Only detection of one, clinically relevant, concentration per virus species and lineage was assessed. Results The final EQA analysis included 51 laboratories from 35 countries; 44 of these laboratories were from 28 of 31 countries in the European Union/European Economic Area (EU/EEA). USUV diagnostic capability was lowest (28 laboratories in 18 countries), WNV detection capacity was highest (48 laboratories in 32 countries). Twenty-five laboratories were able to test the whole EQA panel, of which only 11 provided completely correct results. The highest scores were observed for WNV and TOSV (92%), followed by TBEV (86%) and USUV (75%). Conclusion We observed wide variety in extraction methods and RT-PCR tests, showing a profound absence of standardisation across European laboratories. Overall, the results were not satisfactory; capacity and capability need to be improved in 40 laboratories.
Biallelic loss-of-function mutations in JAM2 cause primary familial brain calcification.

Primary familial brain calcification is a monogenic disease characterized by bilateral calcifications in the basal ganglia and other brain regions, and commonly presents motor, psychiatric, and cognitive symptoms. Currently, four autosomal dominant (SLC20A2, PDGFRB, PDGFB, XPR1) and one autosomal recessive (MYORG) causative genes have been identified. Compared with patients with autosomal dominant primary familial brain calcification, patients with the recessive form of the disease present with more severe clinical and imaging phenotypes, and deserve more clinical and research attention. Biallelic mutations in MYORG cannot explain all autosomal recessive primary familial brain calcification cases, indicating the existence of novel autosomal recessive genes. Using homozygosity mapping and whole genome sequencing, we detected a homozygous frameshift mutation (c.140delT, p.L48*) in the JAM2 gene in a consanguineous family with two affected siblings diagnosed with primary familial brain calcification. Further genetic screening in a cohort of 398 probands detected a homozygous start codon mutation (c.1A>G, p.M1? ) and compound heterozygous mutations [c.504G>C, p.W168C and c. (67+1_68-1)_(394+1_395-1), p.Y23_V131delinsL], respectively, in two unrelated families. The clinical phenotypes of the four patients included parkinsonism (3/4), dysarthria (3/4), seizures (1/4), and probable asymptomatic (1/4), with diverse onset ages. All patients presented with severe calcifications in the cortex in addition to extensive calcifications in multiple brain areas (lenticular nuclei, caudate nuclei, thalamus, cerebellar hemispheres, ± brainstem; total calcification scores: 43-77). JAM2 encodes junctional adhesion molecule 2, which is highly expressed in neurovascular unit-related cell types (endothelial cells and astrocytes) and is predominantly localized on the plasma membrane. It may be important in cell-cell adhesion and maintaining homeostasis in the CNS. In Chinese hamster ovary cells, truncated His-tagged JAM2 proteins were detected by western blot following transfection of p.Y23_V131delinsL mutant plasmid, while no protein was detected following transfection of p.L48* or p.1M? mutant plasmids. In immunofluorescence experiments, the p.W168C mutant JAM2 protein failed to translocate to the plasma membrane. We speculated that mutant JAM2 protein resulted in impaired cell-cell adhesion functions and reduced integrity of the neurovascular unit. This is similar to the mechanisms of other causative genes for primary familial brain calcification or brain calcification syndromes (e.g. PDGFRB, PDGFB, MYORG, JAM3, and OCLN), all of which are highly expressed and functionally important in the neurovascular unit. Our study identifies a novel causative gene for primary familial brain calcification, whose vital function and high expression in the neurovascular unit further supports impairment of the neurovascular unit as the root of primary familial brain calcification pathogenesis.
Social distance mediates the association between fear of infection and better-off-dead beliefs about people living with HIV

Objectives The better-off-dead belief, the idea that death is preferable for people living with human immunodeficiency virus, is a highly devaluing attitude, but little is known about its determinants among the general population. Guided by the instrumental model of stigma, this study examined the contributive roles of fear of infection and social distance to this stigmatizing belief. Methods A total of 304 Chinese university students recruited in Guangzhou and Hong Kong responded to questionnaires assessing the better-off-dead belief, fear of infection and social distance. Structural equation modelling was used to test associations among the variables. Results Fear of infection and social distance were associated with higher levels of the better-off-dead belief. Social distance mediated the association between fear of infection and the better-off-dead belief. Conclusions Fear of infection and social distance are determinants of the better-off-dead belief, with social distance serving as a mediator. This study highlights the importance of addressing fear and avoidance in future public health efforts to reduce the prevalence of the better-off-dead belief.
Shaping of Innate Immune Response by Fatty Acid Metabolite Palmitate

Innate immune cells monitor invading pathogens and pose the first-line inflammatory response to coordinate with adaptive immunity for infection removal. Innate immunity also plays pivotal roles in injury-induced tissue remodeling and the maintenance of tissue homeostasis in physiological and pathological conditions. Lipid metabolites are emerging as the key players in the regulation of innate immune responses, and recent work has highlighted the importance of the lipid metabolite palmitate as an essential component in this regulation. Palmitate modulates innate immunity not only by regulating the activation of pattern recognition receptors in local innate immune cells, but also via coordinating immunological activity in inflammatory tissues. Moreover, protein palmitoylation controls various cellular physiological processes. Herein, we review the updated evidence that palmitate catabolism contributes to innate immune cell-mediated inflammatory processes that result in immunometabolic disorders.
Involvement of the basal nucleus of Meynert on regional cerebral cortical vasodilation associated with masticatory muscle activity in rats

We examined the neural mechanisms for increases in regional cerebral blood flow (rCBF) in the neocortex associated with mastication, focusing on the cortical vasodilative system derived from the nucleus basalis of Meynert (NBM). In pentobarbital-anesthetized rats, parietal cortical rCBF was recorded simultaneously with electromyogram (EMG) of jaw muscles, local field potentials of frontal cortex, multi-unit activity of NBM neurons, and systemic mean arterial pressure (MAP). When spontaneous rhythmic EMG activity was observed with cortical desynchronization, an increase in NBM activity and a marked rCBF increase independent of MAP changes were observed. A similar rCBF increase was elicited by repetitive electrical stimulation of unilateral cortical masticatory areas. The magnitude of rCBF increase was partially attenuated by administration of the GABAergic agonist muscimol into the NBM. The rCBF increase persisted after immobilization with systemic muscle relaxant (vecuronium). rCBF did not change when jaw muscle activity was induced by electrical stimulation of the pyramidal tract. The results suggest that activation of NBM vasodilator neurons contributes at least in part to the rCBF increase associated with masticatory muscle activity, and that the NBM activation is induced by central commands from the motor cortex, independently of feedback from brainstem central pattern generator or contracting muscles.
Mobile device applications and treatment of autism spectrum disorder: a systematic review and meta-analysis of effectiveness

Objective The current study was performed to assess the evidence for effects of therapeutic intervention with mobile device applications (apps) for individuals with autism spectrum disorder (ASD). Design The main methodology of the current study was systematic review with meta-analysis. Setting Only randomised controlled trials (RCTs) for mobile device apps for individuals with ASD were considered for review in the current study. Patients The target population was individuals clinically diagnosed with ASD. Interventions Applications that are operable on a smart (mobile) device and interactive with users. Main outcome measures The main outcomes were based on standardised mean differences in pretrial and post-trial scales in each control and intervention group. Results Out of a total of 1100 studies (after duplicate removal), 7 RCTs were selected for final analysis. Of the seven studies, two RCTs were further analysed for effects based on the visual and fine motor subscales of the Mullen Scales of Early Learning, which favoured the intervention groups (standardised mean difference (SMD)=0.41, 95% CI 0.03 to 0.80; SMD=0.41, 95% CI 0.03 to 0.80), without either having any heterogeneity (p>0.1) or publication bias. Conclusions Although it is still early to draw a conclusion, available studies are showing promise for use of mobile device apps for treatment of individuals with ASD. More well-designed and large-scale studies focused on improving behavioural symptoms of ASD are warranted. PROSPERO registration number CRD42019128362.
Social support of families with tracheostomized children.

OBJECTIVE To understand the social support of families with tracheostomized children. METHOD Qualitative study using the Model of Dimensions of Social Support together with the Family System-Illness model as theoretical frameworks, based on the hybrid model of thematic analysis. Nine families with tracheostomized children were interviewed in an outpatient pediatric otorhinolaryngology department of a public hospital in the inner state of São Paulo. RESULTS The experience of social support to each phase of the family experience was presented in three themes: "Knowing the need for a tracheostomy", "Performing a tracheostomy" and "Living with a tracheostomy". FINAL CONSIDERATIONS Understanding how the experience of social support occurs can support assessment and intervention strategies, aiming to meet the demands of the family at each phase of its trajectory, collaborating for a continuous and integral nursing care.