Miracle-dz/UniFAR-FTUs huggingface dataset:
Down-regulation of FZD3 receptor suppresses growth and metastasis of human melanoma independently of canonical WNT signaling

Significance In malignant melanoma, one of the most aggressive cancers, the components of the WNT pathway are frequently deregulated and have been shown to drive self-renewal and metastatic progression of melanoma cells. Identifying tumorigenic properties of key members of the WNT signaling network in the pathogenesis of melanoma represents a pivotal task in the field and underlies successful design of targeted therapeutic approaches. In the present study, we characterized Frizzled 3 receptor (FZD3) as a critical factor underlying tumorigenic properties of aggressive human melanoma. Using in vivo and in vitro tumorigenic assays, combined with functional transcriptomics analysis of FZD3 knockdown in human patient-derived cells, we determined key signaling nodes regulated by FZD3 activity during malignant transformation. Frizzled 3 receptor (FZD3) plays an important role in the homeostasis of the neural crest and its derivatives, which give rise to pigment-synthesizing cells, melanocytes. While the role for FZD3 in specification of the melanocytic lineage from neural crest is well established, its significance in the formation of melanoma, its associated malignancy, is less understood. In this study we identified FZD3 as a critical regulator of human melanoma tumorigenesis. Down-regulation of FZD3 abrogated growth, colony-forming potential, and invasive capacity of patient-derived melanoma cells. Xenotransplantation of tumor cells with down-regulated FZD3 levels originating from melanomas carrying the BRAF(V600) mutation uniformly suppressed their capacity for tumor and metastasis formation. FZD3 knockdown leads to the down-regulation of the core cell cycle protein components (cyclins D1, E2, B1, and CDKs 1, 2, and 4) in melanomas with a hyperactive BRAF oncogene, indicating a dominant role of this receptor during melanoma pathogenesis. Enriched pathway analysis revealed that FZD3 inhibits transcriptional networks controlled by CREB5, FOXD1, and ATF3, which suppress the activity of MAPK-mediated signaling. Thus, FZD3 establishes a positive-feedback mechanism that activates MAPK signal transduction network, critical to melanoma carcinogenesis. Importantly, high levels of FZD3 mRNA were found to be correlated with melanoma advancement to metastatic stages and limited patient survival. Changes in gene-expression patterns mediated by FZD3 activity occur in the absence of nuclear β-catenin function, thus representing an important therapeutic target for the melanoma patients whose disease progresses independent of canonical WNT signaling.
A Qualitative Investigation of Music Use among Amateur and Semi-Professional Golfers

Music use in golf receives minimal attention from both applied and empirical perspectives. Golfers, coaches, and sport psychology practitioners alike may benefit from understanding and utilizing music within their work. Since music use in golf has become an increasingly common practice, the purpose of the current study was to investigate current music use among golfers using a qualitative approach. Researchers aimed to identify potential psychological and physiological effects derived from music use during golf practice and pre-performance, given the limited empirical research in this area to date. Semi-structured interviews were conducted with ten amateur and semi-professional golfers (five male, five female, Mage = 22.9 years, SD = 5.04 years). Consensual qualitative research (CQR) methodology was used to analyze the interview data. Six domains emerged from the CQR analysis regarding participants’ self-reported music use in golf: tempo, attention, physiological regulation, psychological regulation, effects of music on performance perceptions, and context (to use or not to use). Given the capacity of carefully selected music to elicit profound affective, neurophysiological, and behavioral responses, there is clear potential for mental performance consultants to utilize music in working with golfers in training contexts. Implications, caveats, and future research recommendations are provided.
Diurnal Patterns of Energy Intake Derived via Principal Component Analysis and Their Relationship with Adiposity Measures in Adolescents: Results from the National Diet and Nutrition Survey RP (2008–2012)

Mounting evidence points towards the existence of an association between energy intake in the evening and an increased prevalence and risk of being overweight and of obesity. The present study aimed to describe diurnal eating patterns (DEP) in a nationally representative sample of UK adolescents and to relate the derived DEP to anthropometrical measures. Data from four-day food records of adolescents aged 11–18 years participating in the 2008–2012 UK National Diet and Nutrition Survey Rolling Programme (NDNS RP) was utilised. The DEP were derived using a principal component analysis on the correlation matrix. Three orthogonal diurnal patterns were interpretable as (i) a linear contrast (8% of total system variation) between breakfast and an earlier lunch vs. a later lunch, late dinner, and evening/night snack, renamed “phase shift” DEP; (ii) a linear contrast (6.0% of system variation) between midmorning snacks, late lunch, and early dinner vs. breakfast, early and late morning snacks, early lunch, midafternoon snacks, and late dinner, renamed “early eating and grazing” DEP; (iii) a linear contrast (6.0% of system variation) between late main meals vs. early main meals and night snacks which was renamed “early main meals and night snacks vs. late main meals” DEP. After the adjustment for confounders, every 1 unit increase in the “early main meals and night snacks vs. late main meals”’ DEP score was significantly associated with a 0.29 kg/m2 and 11.6 mm increase in Body Mass Index (BMI) and waist circumference, respectively. There were no significant associations with the other two main DEPs. In conclusion, adolescents who tended to eat large early main meals and night snacks rather than slightly later main meals without night snacks had higher BMI and waist circumference. Further research is required to explore the determinants of DEP and to explore the impact of the context of eating and socioecological factors in the development of specific DEP.
Impact of decompression surgery without fusion for lumbar spinal stenosis on sagittal spinopelvic alignment: minimum 2-year follow-up.

OBJECTIVEThe importance of global sagittal alignment is well known. Patients with lumbar spinal stenosis (LSS) generally tend to bend forward to relieve their neurological symptoms, i.e., they have a positive sagittal vertical axis (SVA). We hypothesized that the positive SVA associated with LSS is symptom related and should improve after surgery. However, little is known about the changes in sagittal alignment in LSS patients after decompression surgery. In this study the authors aimed to evaluate midterm radiographical changes in sagittal spinopelvic alignment after decompression surgery for LSS and to determine the factors influencing the improvement in sagittal spinopelvic alignment.METHODSThe authors retrospectively reviewed 89 patients who underwent lumbar decompression without fusion between January 2014 and September 2015 with a minimum follow-up of 2 years. Standing whole-spine radiographs at the preoperative stage and at the final follow-up were examined. We analyzed SVA, lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), thoracolumbar kyphosis (TLK), and thoracic kyphosis (TK). RESULTSLL and TK were significantly increased postoperatively. SVA and PI minus LL (PI-LL) were significantly decreased. There were no significant differences between the preoperative and postoperative PT, PI, SS, or TLK. Twenty-nine patients had preoperative sagittal malalignment with SVA > 50 mm. Thirteen of the 29 patients improved to SVA < 50 mm after decompression surgery. Lower ASA grade, preoperative higher LL, and lower PI-LL were related to patient improvement. A receiver operating characteristic curve for the preoperative PI-LL had an area under the curve value of 0.821, indicating moderate accuracy (p = 0.003). A cutoff value for preoperative PI-LL of 19.2° showed a sensitivity of 93.5% and a specificity of 71.4%. CONCLUSIONSLumbar decompression can lead to a reactive improvement in the lumbar and global sagittal alignment. However, some of the sagittal malalignment in LSS was irreversible. Preoperative PI-LL was a useful predictor to distinguish reversible from irreversible sagittal malalignment.
Gabapentin-Associated Urinary Incontinence: A Case Verified by Rechallenge

Introduction Gabapentin (GBP) is an analog of &ggr;-aminobutyric acid and was originally designed as an anticonvulsant. Because its mechanism of action is unclear, assumed to have no abuse potential, and apparent lack of toxicity, GBP is used widely off-label to treat an array of disorders, including essential tremor. Case Report We present a case of an elderly woman diagnosed with essential tremor, in which GBP was initiated. In the following day, she complained of urinary incontinence with the absence of dysuria and urgency. It was not worse with movement, coughing, sneezing, or laughing. The vaginal parity of the patient was one. Laboratory tests and urinalysis were within normal limits. Assuming that the urinary symptom was an adverse drug reaction, the GBP was withdrawn and the patient's incontinence completely resolved within 2 days. Several weeks later, a rechallenge with GBP was tried. In the day 1 of GBP use, the subject reported intermittent urinary incontinence. Medication was discontinued and her continence returned. One year later, in the follow-up, the subject remained continent. Conclusions Only a few cases with GBP-associated urinary incontinence have been reported in the literature. To the authors' knowledge, these cases described individuals with only 1 attempt of the use of GBP. In this way, the present case was the first to describe a subject with the recurrence of urinary incontinence with the GBP rechallenge. This adverse effect, although not potentially fatal, can be very embarrassing to patients and lead to poor compliance with therapy.
Primordial prevention of cardiovascular disease.

While primary prevention is about treating risk factors to prevent cardiovascular disease, primordial prevention refers to avoiding the development of risk factors in the first place. Because atherosclerosis starts in youth and is related to dyslipidemia, to smoking, and to higher blood pressure, glucose levels, and body mass index, the implication is that primordial prevention must start early in life.1 Additional support for early prevention arises from recent data on ideal cardiovascular health. Using similar definitions of ideal cardiovascular health, comprising 3 health factors and 4 health behaviors, both the Cardiovascular Risk in Young Finns Study and the Special Turku Coronary Risk Factor Intervention Project for Children (STRIP) showed that the number of ideal metrics is lower in late versus early adolescence.2,3 In cross-sectional National Health and Nutrition Examination Survey (NHANES) data, this apparent pattern of declining prevalence of ideal cardiovascular health with age continues from adolescence through adulthood.4,5 Article see p 605 When and how to intervene to maintain the ideal cardiovascular health factors with which almost all babies are born are vexing but critical questions. Over the past 2 decades, a literature has emerged suggesting that starting interventions very early—as early as infancy and perhaps before—may be an especially effective approach to prevent chronic disease over the life course.6,7 The first 1000 days from conception to preschool ages are a period of maximal developmental plasticity. Prevention interventions during this period may thus set individuals on the best possible trajectories of lifelong cardiovascular health, …
Systematic and standardized comparison of reported amyloid-β receptors for sufficiency, affinity, and Alzheimer's disease relevance

Oligomeric assemblies of amyloid-β (Aβ) peptide (Aβo) in the brains of individuals with Alzheimer's disease (AD) are toxic to neuronal synapses. More than a dozen Aβ receptor candidates have been suggested to be responsible for various aspects of the molecular pathology and memory impairment in mouse models of AD. A lack of consistent experimental design among previous studies of different receptor candidates limits evaluation of the relative roles of these candidates, producing some controversy within the field. Here, using cell-based assays with several Aβ species, including Aβo from AD brains obtained by autopsy, we directly compared the Aβ-binding capacity of multiple receptor candidates while accounting for variation in expression and confirming cell surface expression. In a survey of 15 reported Aβ receptors, only cellular prion protein (PrPC), Nogo receptor 1 (NgR1), and leukocyte immunoglobulin-like receptor subfamily B member 2 (LilrB2) exhibited direct binding to synaptotoxic assemblies of synthetic Aβ. Both PrPC and NgR1 preferentially bound synaptotoxic oligomers rather than nontoxic monomers, and the method of oligomer preparation did not significantly alter our binding results. Hippocampal neurons lacking both NgR1 and LilrB2 exhibited a partial reduction of Aβo binding, but this reduction was lower than in neurons lacking PrPC under the same conditions. Finally, binding studies with soluble Aβo from human AD brains revealed a strong affinity for PrPC, weak affinity for NgR1, and no detectable affinity for LilrB2. These findings clarify the relative contributions of previously reported Aβ receptors under controlled conditions and highlight the prominence of PrPC as an Aβ-binding site.
Laparoendoscopic Single-Site Retroperitoneoscopic Adrenalectomy versus Conventional Retroperitoneoscopic Adrenalectomy: Initial Experience by the Same Laparoscopic Surgeon

Purpose: The purpose of this study was to demonstrate our initial experience with and the feasibility of laparoendoscopic single-site retroperitoneoscopic adrenalectomy (LESS-RA). Patients and Methods: 54 patients undergoing conventional retroperitoneoscopic adrenalectomy were compared with 27 patients undergoing LESS-RA. The adrenal tumors were considered to be benign preoperatively and <6 cm. Age, sex, laterality, body mass index, surgical indications, time to resuming oral intake, tumor size, operation time, estimated blood loss, intravenous or intramuscular analgesics (pethidine) and postoperative hospital stay were compared between the two groups. Analysis of covariance was applied to analyze postoperative hospital stay and time to resuming oral intake. Results: The length of postoperative hospital stay was significantly higher in the conventional retroperitoneoscopic adrenalectomy group in the adjusted and unadjusted model. The time to resuming oral intake was significant shorter in the LESS-RA group, but was not significant after adjusting opioid analgesics dosage. No conversions to an open or conventional retroperitoneoscopic approach were necessary. There were neither complications nor blood transfusions in both groups. Conclusions: LESS-RA for benign adrenal tumors is a feasible surgical procedure when tumors are <6 cm. Further clinical research is warranted to define the role of LESS in adrenal surgery and to prove its efficacy over conventional laparoscopic surgery.
Strategies for Success: A Qualitative Study of Caregiver and Dentist Approaches to Improving Oral Care for Children with Autism Spectrum Disorder

Correspondence concerning this article should be addressed to The authors declare that there are no conflicts of interest regarding the publication of this paper. All authors have made substantive contribution to this study and/or manuscript, and all have reviewed the final paper prior to its submission. Purpose: Oral health is important to physical and psychological health. Individuals with autism spectrum disorder (ASD) experience significant oral care challenges, but little research exists examining efficacious interventions to improve care. This study qualitatively explored parent-and dentist-reports of successful strategies implemented during dental care with children with ASD. Methods: Focus groups were conducted with parents of children with ASD (n=2 groups) and dentists treating children with ASD (n=2 groups). Focus group transcripts were transcribed verbatim and analyzed using a thematic analysis approach. Results: Three key themes were identified from the parent focus groups: (1) What makes a good dentist, (2) Flexibility and techniques: strategies used by the dentist, and (3) Preparation: strategies for parents and caregivers of children with ASD. Four themes emerged from the dentist groups: (1) Parents know best, (2) Practice, (3) Flexibility, and (4) Network of colleagues. Areas of overlap between the parents and dental providers included the importance of preparation, the necessity of flexibility and creativity, and the value of collaboration. Conclusions: Findings provide insight into techniques perceived by parents and dental providers to facilitate successful dental encounters for children with ASD.
Comparison of the Long-Term Remission of Rituximab and Conventional Treatment for Acquired Thrombotic Thrombocytopenic Purpura: A Systematic Review and Meta-Analysis

The current systematic review and meta-analysis aimed to summarize the results of all available studies to compare the efficacies of rituximab and conventional treatment for acquired thrombotic thrombocytopenic purpura (TTP). Three investigators independently searched studies in the MEDLINE and EMBASE databases published before December 11, 2018. To be included in the meta-analysis, studies needed to be randomized-controlled or cohort studies comparing the efficacies of rituximab and conventional therapy for TTP treatment. The effect estimates and 95% confidence intervals (CIs) from each study were collected, and Mantel-Haenszel methods were used to pool the data. A total of 570 patients from 9 eligible studies were included in the meta-analysis (280 patients in the rituximab arm and 290 in the conventional treatment arm). Patients receiving rituximab in an acute phase to induce disease remission had a significantly lower relapse rate than those given conventional treatment (odds ratio [OR]: 0.40, 95% CI: 0.19-0.85, P = .02, I2 = 43%). Similarly, the relapse rate in the rituximab group for preemptive therapy to prevent clinical relapse was also significantly lower than in the control group (OR: 0.09, 95% CI: 0.04-0.24, P < .00001, I2 = 11%). Furthermore, the conventional treatment group had a significantly higher mortality rate than the rituximab group during the follow-up (OR: 0.41, 95% CI: 0.18-0.91, P = .03, I2 = 0%). Rituximab offered high efficacy for the prevention of relapses and lower mortality rate in cases of acquired TTP.
Neuroimaging characterization of recovery of impaired consciousness in patients with disorders of consciousness

Elucidation of critical brain areas or structures that are responsible for recovery of impaired consciousness in patients with disorders of consciousness is important because it can provide information that is useful when developing therapeutic strategies for neurorehabilitation or neurointervention in patients with disorders of consciousness. In this review, studies that have demonstrated brain changes during recovery of impaired consciousness were reviewed. These studies used positron emission tomography, electroencephalography/transcranial magnetic stimulation, diffusion tensor tractography, and diffusion tensor tractography/electroencephalography. The majority of these studies reported on the importance of supratentorial areas or structures in the recovery of impaired consciousness. The important brain areas or structures that were identified were the prefrontal cortex, basal forebrain, anterior cingulate cortex, and parietal cortex. These results have a clinically important implication that these brain areas or structures can be target areas for neurorehabilitation or neurointervention in patients with disorders of consciousness. However, most of studies were case reports; therefore, further original studies involving larger numbers of patients with disorders of consciousness are warranted. In addition, more detailed information on the brain areas or structures that are relevant to the recovery of impaired consciousness is needed.
The complete mitochondrial genome of Motacilla cinerea (Passeriformes: Motacillidae)

Abstract Motacilla cinerea is a species of small- and medium-sized songbird in the Family Motacillidae, which is widely distributed. In this study, we determined the complete mitochondrial genome of M. cinerea. The result showed that the total length of the mitogenome was 16 825 bp and contained two ribosomal RNA genes, 22 transfer RNA genes, 13 protein-coding genes, and one control region. All the genes in M. cinerea were distributed on the H-strand, except for the ND6 subunit gene and eight tRNA genes which are encoded on the L-strand. The phylogenetic tree was reconstructed using Bayesian analysis methods, and containing two clades: Motacilla and Anthus. The first lineage is Motacilla including M. cinerea and other nine species. The genus Anthus makes up the second group, which containing 17 species.
Pharmacogenetic Profile and the Occurrence of Visual Hallucinations in Patients With Sporadic Parkinson's Disease

Visual hallucinations are significant nonmotor symptoms in the course of treatment of Parkinson's disease. Previous studies have shown that the interindividual variability and pharmacogenetic profile of Parkinson's disease patients seem to influence the occurrence of visual hallucinations. In our study, we investigated a possible relationship of sequence variants in DRD1, DRD2, DRD3, DAT1, and COMT genes with the presence of visual hallucinations in Parkinson's disease patients. A total of 224 Brazilian patients from the Pro‐Parkinson service at the Clinical Hospital of the University of Pernambuco, diagnosed with sporadic Parkinson's disease, were enrolled. Parkinson's disease patients were divided into 2 groups based on the presence or absence of visual hallucinations. The sequence variants for DRD1, DRD2, DRD3, DAT1, and COMT were determined through the polymerase chain reaction‐restriction fragment length polymorphism technique. Multiple Poisson regression analyses showed that individuals carrying the DRD3 Ser/Ser and Ser/Gly genotypes presented increased prevalence ratios of visual hallucinations (9.7‐fold and 4.4‐fold, respectively; P < .001). Regarding DAT1 rs28363170, there was a 9.82‐fold increase in the prevalence ratio in patients with the 10/11 genotype, 8.78‐fold for the 10/8 genotype, and 2.44‐fold for the 9/8 genotypes (P < .001, for all). In addition, visual hallucinations were also associated with use of transdermal patches with rotigotine (PR, 3.7; 95%CI, 1.2‐10.9; P = .017) and rasagiline (PR, 2.8; 95%CI, 1.3‐6.0; P = .006). Our results suggest that the genetic variants DRD3 and DAT1, along with other therapeutic confounders, may influence the prevalence ratio of visual hallucinations.