Miracle-dz/UniFAR-FTUs huggingface dataset:
Upregulation of microRNA‐133a and downregulation of connective tissue growth factor suppress cell proliferation, migration, and invasion in human glioma through the JAK/STAT signaling pathway

Recently, microRNA‐133a (miR‐133a) has been found to function in many diseases in previous studies, yet few studies have been focused on its role in glioma. This study aims to investigate the mechanism of miR‐133a/CTGF on regulating the malignant phenotypes of glioma cells via the JAK/STAT signaling pathway. Sixty‐five human glioma specimens were collected and 30 normal brain tissues were selected as controls. The expression of connective tissue growth factor (CTGF) and miR‐133a in tissues was detected, and the relationship between their expression and the clinicopathological features as well as prognosis of glioma was analyzed. MiR‐133a and CTGF expression in U87, A172, and HEB cell lines was determined. The expression of CTGF, signaling pathway‐, proliferation‐, migration‐, invasion‐, apoptosis‐ and epithelial‐mesenchymal transition (EMT)–related factors was detected. A number of assays were used to detect cell proliferation, migration, invasion, cell cycle, apoptosis, glioma growth, and the targeting site between CTGF and miR‐133a. MiR‐133a was downregulated and CTGF was upregulated in human glioma tissues and cells. MiR‐133a and CTGF expression was related to glioma's WHO staging and size. Downregulated miR‐133a and upregulated CTGF caused unfavorable prognosis in glioma. Upregulated miR‐133a suppressed CTGF expression and the activation of JAK/STAT signaling pathway, thereby constraining cell colony formation, proliferation, migration and invasion, and promoting apoptosis in glioma. Our study reveals that upregulated miR‐133a and downregulated CTGF suppress cell proliferation, migration, and invasion in human glioma through the inhibition of the JAK/STAT signaling pathway.
Continuing commentary: challenges or misunderstandings? A defence of the two-factor theory against the challenges to its logic

ABSTRACT Corlett, P. R. (2019. Factor one, familiarity and frontal cortex: A challenge to the two-factor theory of delusions. Cognitive Neuropsychiatry, 24(3), 165–177. doi:10.1080/13546805.2019. 1606706) raises two groups of challenges against the two-factor theory of delusions: One focuses on weighing “the evidence for … the two-factor theory”; the other aims to question “the logic of the two-factor theory” (ibid., p. 166). McKay, R. (2019. Measles, magic and misidentifications: A defence of the two-factor theory of delusions. Cognitive Neuropsychiatry, 24(3), 183–190. doi:10.1080/13546805.2019. 1607273) has robustly defended the two-factor theory against the first group. But the second group, which Corlett believes is in many aspects independent of the first group and Darby, R. R. (2019. A network-based response to the two-factor theory of delusion formation. Cognitive Neuropsychiatry, 24(3), 178–182. doi:10.1080/13546805.2019. 1606709, p. 180) takes as “[t]he most important challenge to the two-factor theory raised by Dr. Corlett”, has by large remained. Here I offer my two cents in response to the second group. More specifically, I argue that Corlett’s challenges to the logic of the two-factor theory, concerning modularity, double dissociation and cognitive penetration, seem to be based on some misunderstandings of the two-factor theory.
Identification of Inflammatory Mediators in Tendinopathy Using a Murine Subacromial Impingement Model

Subacromial impingement is associated with a spectrum of disorders—including rotator cuff disease—but their relationship is complex. We have established a novel murine model of subacromial impingement to study supraspinatus tendinopathy. The purpose of this study was to evaluate changes in gene expression in this murine shoulder impingement model to further elucidate the mechanisms underlying the development of tendinopathy. Twenty‐eight C57BL/6 mice were used in this study. All mice underwent bilateral surgery with insertion of a small metal clip in the subacromial space or a sham procedure. The supraspinatus tendons underwent histological analyses, biomechanical testing, and RNA extraction for multiplex gene expression analysis (NanoString, Seattle, WA). Histology demonstrated increased cellularity and disorganized collagen fibers of the supraspinatus tendon in the clip impingement group. Mean load to failure (5.20 vs. 1.50 N, p < 0.001) and mean stiffness (4.95 vs. 1.47 N/mm, p < 0.001) were lower in the impingement group than the sham group. NanoString analyses revealed 111 differentially expressed genes (DEGs) between the impingement and sham groups. DEGs of interest included Mmp3 (expression ratio [ER]: 2.68, p = 0.002), Tgfb1 (ER: 1.76, p = 0.01), Col3a1 (ER: 1.66, p = 0.03), and Tgfbr2 (ER: 1.53, p = 0.01). Statement of clinical significance: We identified 111 DEGs that may contribute to the development of tendinopathy in this model. Further studies of these specific genes will allow identification of their roles in the initiation and regulation of tendon damage, and their potential to serve as novel therapeutic targets in the treatment of rotator cuff disease. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2575–2582, 2019
Regional variations in amputation rates: are regional diabetic foot services the reason?

Diabetic foot disease is a significantly under‐recognized leading cause of global amputation, hospitalization, disability and mortality burdens.1-4 Fortunately, these large burdens appear to be substantially reducible with evidence‐based diabetic foot services.1, 3-5 In this issue of ANZ Journal of Surgery, Gurney et al.6 report large variations in diabetes‐related amputation rates in New Zealand. They conclude, ‘these observations could help to inform the funding and provision of diabetic foot care services across New Zealand’. 6.
Results of the Brief Jail Mental Health Screen Across Repeated Jail Bookings.

OBJECTIVE The Brief Jail Mental Health Screen (BJMHS) is widely used at intake in county jails to identify detainees who may have serious mental illness and who should be referred for further mental health evaluation. The BJMHS may be administered multiple times across repeated jail bookings; however, the extent to which results may change over time is unclear. To that end, the authors examined the odds of screening positive on the BJMHS across repeated jail bookings. METHODS Data were drawn from the administrative and medical records of a large, urban county jail that used the BJMHS at jail booking. The study sample comprised BJMHS results for the 12,531 jail detainees who were booked at least twice during the 3.5-year period (N=41,965 bookings). Multilevel logistic modeling was used to examine changes over time overall and within the four decision rules (current psychiatric medication, prior hospitalization, two or more current symptoms, and referral for any other reason). RESULTS Results show that the odds of a positive screen overall increased with each jail booking, as did the odds of referral for any other reason. In contrast, the odds of screening positive for two or more current symptoms and prior hospitalization decreased. There was no change in the odds of screening positive for current psychiatric medication across bookings. CONCLUSIONS Findings show that BJMHS results changed across bookings. Further research is needed to determine whether changes reflect true changes in mental health status, issues with fidelity, the repeated nature of the screening process, or other factors.
LBD29-Involved Auxin Signaling Represses NAC Master Regulators and Fiber Wall Biosynthesis1[OPEN]

The NAC domain master regulators of secondary cell wall biosynthesis are negatively regulated by auxin signaling through a pathway that involves ARF7/ARF19 and LBD29 in Arabidopsis stem fibers. NAM, ATAF1/2 and CUC2 (NAC) domain transcription factors function as master switches in regulating secondary cell wall (SCW) biosynthesis in Arabidopsis (Arabidopsis thaliana) stems. Despite the importance of these NACs in fiber development, the upstream signal is still elusive. Using a large-scale mutant screening, we identified a dominant activation-tagging mutant, fiberless-d (fls-d), showing defective SCW development in stem fibers, similar to that of the nac secondary wall thickening promoting factor1-1 (nst1-1)nst3-3 double mutant. Overexpression of LATERAL ORGAN BOUNDARIES DOMAIN29 (LBD29) is responsible for the fls-d mutant phenotypes. By contrast, loss-of-function of LBD29, either in the dominant repression transgenic lines or in the transfer-DNA (T-DNA) insertion mutant lbd29-1, enhanced SCW development in fibers. Genetic analysis and transgenic studies demonstrated LBD29 depends on master regulators in mediating SCW biosynthesis, specifically NAC SECONDARY WALL THICKENING PROMOTING FACTOR1 (NST1), NST2, and NST3. Increasing indole-3-acetic acid (IAA) levels, either in stem tissues above a N-1-naphthylphthalamic acid–treated region or in plants directly sprayed with IAA, inhibits fiber wall thickening. The inhibition effect of naphthylphthalamic acid treatment and exogenous IAA application depends on a known auxin signaling pathway involving AUXIN RESPONSE FACTOR7 (ARF7)/ARF19 and LBD29. These results demonstrate auxin is upstream of LBD29 in repressing NAC master regulators, and therefore shed new light on the regulation of SCW biosynthesis in Arabidopsis.
Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brain

ABSTRACT DNA methylation is dynamically modulated during postnatal brain development, and plays a key role in neuronal lineage commitment. This epigenetic mark has also recently been implicated in the development of neural sex differences, many of which are found in the hypothalamus. The level of DNA methylation depends on a balance between the placement of methyl marks by DNA methyltransferases (Dnmts) and their removal, which is catalyzed by ten-eleven translocation (Tet) methylcytosine dioxygenases. Here, we examined developmental changes and sex differences in the expression of Tet and Dnmt enzymes from birth to adulthood in two hypothalamic regions (the preoptic area and ventromedial nucleus) and the hippocampus of mice. We found highest expression of all Tet enzymes (Tet1, Tet2, Tet3) and Dnmts (Dnmt1, Dnmt3a, Dnmt3b) in newborns, despite the fact that global methylation and hydroxymethylation were at their lowest levels at birth. Expression of the Dnmt co-activator, Dnmt3l, followed a pattern opposite to that of the canonical Dnmts (i.e., was very low in newborns and increased with age). Tet enzyme activity was much higher at birth than at weaning in both the hypothalamus and hippocampus, mirroring developmental changes in gene expression. Sex differences in Tet enzyme expression were seen in all brain regions examined during the first week of life, whereas Dnmt expression was more balanced between the sexes. Neonatal testosterone treatment of females only partially masculinized enzyme expression. Thus, Tet expression and activity are elevated during neonatal brain development, and may play important roles in sexual differentiation of the brain.
Examining Gender Differences in Neurocognitive Functioning Across Adulthood

Abstract Objective: Previous research has shown that women have an advantage on verbal episodic memory and processing speed tasks, while men show an advantage on spatial ability measures. Previous work has also found differences in cognition across age. The current study examines gender differences in neurocognitive functioning across adulthood, whether age moderates this effect, and whether these differences remain consistent with practice across multiple testing sessions. Method: Data from the Virginia Cognitive Aging Project were used, which included participants between the ages of 18 and 99 years (N = 5125). Participants completed measures assessing five cognitive domains: episodic memory, processing speed, reasoning, spatial visualization, and vocabulary. Results: Results showed that gender was significantly related to memory, speed, and spatial visualization, but not to vocabulary or reasoning. Results of invariance analyses across men and women provided evidence of configural and metric invariance, along with partial scalar invariance. Additionally, there was little evidence that age or practice influenced the gender effect on neurocognition. Conclusions: Consistent with the previous research, these results suggest that there is a female advantage in episodic memory and processing speed, and a male advantage in spatial visualization. Gender was shown to influence cognition similarly across adulthood. Furthermore, the influence of gender remained the same across three sessions, which is consistent with the previous work that has shown that training does not differentially impact performance on spatial ability measures for females compared to males.
Inability to improve performance with control shows limited access to inner states

Any repeatedly performed action is characterised by endogenous variability, affecting both speed and accuracy – for a large part presumably caused by fluctuations in underlying brain and body states. The current research questions were: 1) whether such states are accessible to us, and 2) whether we can act upon this information to reduce variability. For example, when playing a game of darts, there is an implicit assumption that people can wait to throw until they are in the ‘right’ perceptual-attentional state. If this is true, taking away the ability to self-pace the game should worsen performance. We first tested precisely this assumption asking participants to play darts in a self-paced and a fixed-paced condition. There was no benefit of self-pacing, showing that participants were unable to use such control to improve their performance and reduce their variability. Next, we replicated these findings in two computer-based tasks, in which participants performed a rapid action-selection and a visual detection task in one self-paced and three forced-paced conditions. Over four different empirical tests, we show that the self-paced condition did not lead to improved performance or reduced variability, nor to reduced temporal dependencies in the reaction time series. Overall, it seems that, if people have any access to their fluctuating performance-relevant inner states, this access is limited and not relevant for upcoming performance.
Genome-wide Target Mapping Shows Histone Deacetylase Complex1 Regulates Cell Proliferation in Cucumber Fruit1[OPEN]

Histone Deacetylase Complex1 is specifically expressed in meristematic tissues and recruits histone deacetylase complexes to regulate multiple phytohormone pathway genes, regulating cell proliferation. Histone deacetylase (HDAC) proteins participate in diverse and tissue-specific developmental processes by forming various corepressor complexes with different regulatory subunits. An important HDAC machinery hub, the Histone Deacetylase Complex1 (HDC1) protein, participates in multiple protein–protein interactions and regulates organ size in plants. However, the mechanistic basis for this regulation remains unclear. Here, we identified a cucumber (Cucumis sativus) short-fruit mutant (sf2) with a phenotype that includes repressed cell proliferation. SF2 encodes an HDC1 homolog, and its expression is enriched in meristematic tissues, consistent with a role in regulating cell proliferation through the HDAC complex. A weak sf2 allele impairs HDAC targeting to chromatin, resulting in elevated levels of histone acetylation. Genome-wide mapping revealed that SF2 directly targets and promotes histone deacetylation associated with key genes involved in multiple phytohormone pathways and cell cycle regulation, by either directly repressing or activating their expression. We further show that SF2 controls fruit cell proliferation through targeting the biosynthesis and metabolism of cytokinin and polyamines. Our findings reveal a complex regulatory network of fruit cell proliferation mediated by HDC1 and elucidate patterns of HDC1-mediated regulation of gene expression.
Observing Alcohol Myopia in the Context of a Trauma Film Paradigm: Differential Recall of Central and Peripheral Details.

BACKGROUND A major tenet of the Alcohol Myopia Model is that intoxication results in a narrowing of attention to the most central environmental cues, at the cost of more peripheral information. Though long hypothesized, no known study of alcohol myopia has demonstrated differential immediate recall of central and peripheral cues using a standardized task. To address this gap, we conducted an alcohol administration study with a clear, standardized focus-a trauma film. METHODS Ninety-eight female social drinkers completed self-report measures, and then were randomized to consume a placebo beverage, a low dose of alcohol (mean Breath Alcohol Concentration [BrAC] = .04%), or a high dose of alcohol (mean BrAC = .11%). Participants then moved to a staged room where they viewed a film clip depicting a sexual assault. After leaving the room, participants completed a written free recall task of the film and the room. RESULTS The distinction between recall of central and peripheral details was supported by confirmatory factor analysis. Consistent with the Alcohol Myopia Model, relative to placebo, a high dose of alcohol led to impaired recall of peripheral (but not central) details. Although the interaction between BrAC and information type (central vs. peripheral) was not statistically significant, simple effects revealed a strong association between BrAC and peripheral information, and no association between BrAC and central information. Bolstering myopia as an explanation for our findings, neither central nor peripheral information correlated with self-reported tendencies to dissociate or distract oneself, or typical alcohol consumption or expectancies. CONCLUSIONS Alcohol myopia can be observed through an immediate free recall task following a stressful film. Additional research is needed to continue evaluating dose-dependent differential recall in larger samples. This task may be useful for clarifying the role of alcohol myopia in clinical phenomena, such as aggressive behavior and processing traumatic events. This article is protected by copyright. All rights reserved.
Isolation and characterization of a novel strain (YH01) of Micropterus salmoides rhabdovirus and expression of its glycoprotein by the baculovirus expression system

As one of the most important aquatic fish, Micropterus salmoides suffers lethal and epidemic disease caused by rhabdovirus at the juvenile stage. In this study, a new strain of M. salmoides rhabdovirus (MSRV) was isolated from Yuhang, Zhejiang Province, China, and named MSRV-YH01. The virus infected the grass carp ovary (GCO) cell line and displayed virion particles with atypical bullet shape, 300–500 nm in length and 100–200 nm in diameter under transmission electron microscopy. The complete genome sequence of this isolate was determined to include 11 526 nucleotides and to encode five classical structural proteins. The construction of the phylogenetic tree indicated that this new isolate is clustered into the Vesiculovirus genus and most closely related to the Siniperca chuatsi rhabdovirus. To explore the potential for a vaccine against MSRV, a glycoprotein (1–458 amino acid residues) of MSRV-YH01 was successfully amplified and cloned into the plasmid pFastBac1. The high-purity recombinant bacmid-glycoprotein was obtained from DH10Bac through screening and identification. Based on polymerase chain reaction (PCR), western blot, and immunofluorescence assay, recombinant virus, including the MSRV-YH01 glycoprotein gene, was produced by transfection of SF9 cells using the pFastBac1-gE2, and then repeatedly amplified to express the glycoprotein protein. We anticipate that this recombinant bacmid system could be used to challenge the silkworm and develop a corresponding oral vaccine for fish.
Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing

Corticosteroids are intra‐articularly injected to relieve pain in joints with osteoarthritis (OA) or acute tissue damage such as ligament or tendon tears, despite its unverified contraindication in unstable joints. Biomaterial‐based sustained delivery may prolong reduction of inflammatory pain, while avoiding harmful peak drug concentrations.
Secular Trends in Procedural Stroke or Death Risks of Stenting Versus Endarterectomy for Symptomatic Carotid Stenosis.

BACKGROUND Over the past decades, stroke risk associated with carotid disease has decreased, reflecting improvements in medical therapy and a more rigorous control of vascular risk factors. It is less clear whether the procedural risk of carotid revascularization has declined over time. METHODS We analyzed temporal changes in procedural risks among 4597 patients with symptomatic carotid stenosis treated with carotid artery stenting (n=2326) or carotid endarterectomy (n=2271) in 4 randomized trials between 2000 and 2008, using generalized linear mixed-effects models with a random intercept for each source trial. Models were additionally adjusted for age and other baseline characteristics predicting treatment risk. The primary outcome event was any procedural stroke or death, occurring during or within 30 days after revascularization. RESULTS The procedural stroke or death risk decreased significantly over time in all patients (unadjusted odds ratio per year, 0.91; 95% CI, 0.85-0.97; P=0.006). This effect was driven by a decrease in the carotid endarterectomy group (unadjusted odds ratio per year, 0.82; 95% CI, 0.73-0.92; P=0.003), whereas no significant decrease was found after carotid artery stenting (unadjusted odds ratio, 0.96; 95% CI, 0.88-1.04; P=0.33). Carotid endarterectomy patients had a lower procedural stroke or death risk compared with carotid artery stenting patients, and the difference significantly increased over time (interaction P=0.031). After adjustment for baseline characteristics, the results remained essentially the same. CONCLUSIONS The risk of stroke or death associated with carotid endarterectomy for symptomatic carotid stenosis decreased over an 8-year period, independent of clinical predictors of procedural risk. No corresponding reduction in procedural risk was seen in patients treated with stenting. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials. gov; http://www.isrctn. com. Unique identifier: NCT00190398 (EVA-3S), NCT00004732 (CREST), ISRCTN57874028 (SPACE), and ISRCTN25337470 (ICSS).
Neuropathological correlates of amyloid PET imaging in Down syndrome

Down syndrome (DS) results in an overproduction of amyloid‐β (Aβ) peptide associated with early onset of Alzheimer's disease (AD). DS cases have Aβ deposits detectable histologically as young as 12–30 years of age, primarily in the form of diffuse plaques, the type of early amyloid pathology also seen at pre‐clinical (i.e., pathological aging) and prodromal stages of sporadic late onset AD. In DS subjects aged >40 years, levels of cortical Aβ deposition are similar to those observed in late onset AD and in addition to diffuse plaques involve cored plaques associated with dystrophic neurites (neuritic plaques), which are of neuropathological diagnostic significance in AD. The purpose of this review is to summarize and discuss findings from amyloid PET imaging studies of DS in reference to postmortem amyloid‐based neuropathology. PET neuroimaging applied to subjects with DS has the potential to (a) track the natural progression of brain pathology, including the earliest stages of amyloid accumulation, and (b) determine whether amyloid PET biomarkers predict the onset of dementia. In addition, the question that is still incompletely understood and relevant to both applications is the ability of amyloid PET to detect Aβ deposits in their earliest form.