Miracle-dz/UniFAR-FTUs huggingface dataset:
Length of myelin internodes of individual oligodendrocytes is controlled by microenvironment influenced by normal and input‐deprived axonal activities in sensory deprived mouse models

Oligodendrocytes myelinate neuronal axons to increase conduction velocity in the vertebrate central nervous system (CNS). Recent studies revealed that myelin formed on highly active axons is more stable compared to activity‐silenced axons, and length of the myelin sheath is longer in active axons as well in the zebrafish larva. However, it is unclear whether oligodendrocytes preferentially myelinate active axons compared to sensory input‐deprived axons in the adult mammalian CNS. It is also unknown if a single oligodendrocyte forms both longer myelin sheaths on active axons and shorter sheaths on input‐deprived axons after long‐term sensory deprivation. To address these questions, we applied simultaneous labeling of both neuronal axons and oligodendrocytes to mouse models of long‐term monocular eyelid suturing and unilateral whisker removal. We found that individual oligodendrocytes evenly myelinated normal and input‐deprived axons in the adult mouse CNS, and myelin sheath length on normal axons and input‐deprived axons formed by a single oligodendrocyte were comparable. Importantly, the average length of the myelin sheath formed by individual oligodendrocytes did change depending on relative abundance of normal against sensory‐input deprived axons, indicating an abundance of deprived axons near an oligodendrocyte impacts on myelination program by a single oligodendrocyte.
Cell-free DNA derived from cancer cells facilitates tumor malignancy through Toll-like receptor 9 signaling-triggered interleukin-8 secretion in colorectal cancer

Circulating cell-free DNA (cfDNA) has become a potential diagnostic and prognostic biomarker for colorectal cancer (CRC). In non-cancerous diseases, it has been confirmed that cfDNA can be recognized by Toll-like receptor 9 (TLR9), leading to a significant biological change. Nevertheless, the biological significance of cfDNA and its relationship with TLR9 in tumor malignancy is still unclear. Therefore, the purpose of this study is to explore the biological role of cfDNA in colorectal cancer (CRC). The expression of TLR9 was measured in different CRC cell lines and cancerous samples by RT-PCR or immunohistochemistry, which showed that high expression of TLR9 was significantly correlated with the tumor metastasis, advanced TNM stage and poor prognosis of patients. Then, cfDNA was obtained from fluorouracil (5FU)-induced apoptotic cancer cells in vitro and transfection techniques were used to transfect siRNA and cDNA plasmid for TLR9. Cancer cells were stimulated using isolated cfDNA fragments, and results showed that cfDNA could promote colorectal cancer cell proliferation via TLR9. Meanwhile, we demonstrated that the cfDNA binding to TLR9 could facilitate cell migration and invasion. Finally, we demonstrated that cfDNA initiated downstream TLR9-MyD88 signaling and induced robust release of chemokine interleukin 8 (IL-8), which helped to elucidate the mechanisms underlying these phenomena. Our data suggest that cancer cell-derived cfDNA contributes to cancer progression through activation of TLR9-MyD88 signaling and IL-8 secretion in CRC. These findings provide a novel perspective for understanding of tumor progression and provoke a potential therapeutic target for CRC treatment.
Randomized Trial of Motivational Interviewing to Prevent Early Childhood Caries in American Indian Children

Introduction: In a randomized controlled trial, the effectiveness of motivational interviewing (MI) combined with enhanced community services (MI + ECS) was compared with ECS alone for reducing dental caries in American Indian children on the Pine Ridge Reservation. The intervention was developed and delivered with extensive tribal collaboration. Methods: A total 579 mother-newborn dyads were enrolled and randomized to the MI + ECS and ECS groups. They were followed for 36 mo. Four MI sessions were provided, the first shortly after childbirth and then 6, 12, and 18 mo later. Both groups were exposed to ECS, which included public service announcements through billboards and tribal radio, as well as broad distribution of brochures on behavioral risk factors for early childhood caries (ECC), toothbrushes, and toothpaste. MI impact was measured as decayed, missing, and filled tooth surfaces (dmfs). Secondary outcomes included decayed surfaces, caries prevalence, and maternal oral health knowledge and behaviors. Modified intention-to-treat analyses were conducted. Eighty-eight percent of mothers completed at least 3 of 4 MI sessions offered. Results: After 3 y, dmfs was not significantly different for the 2 groups (MI + ECS = 10, ECS = 10.38, P = 0.68). In both groups, prevalence of caries experience was 7% to 9% after 1 y, 35% to 36% at 2 y, and 55% to 56% at 3 y. Mean knowledge scores increased by 5.0, 5.3, and 5.9 percentage points at years 1, 2, and 3 in the MI + ECS group and by 1.9, 3.3, and 5.0 percentage points in the ECS group (P = 0.03), respectively. Mean maternal oral health behavior scores were not statistically significantly different between the treatment arms. Conclusion: In summary, the MI intervention appeared to improve maternal knowledge but had no effect on oral health behaviors or on the progression of ECC (ClinicalTrials.gov NCT01116726). Knowledge Transfer Statement: The findings of this study suggest that motivational interviewing focusing on parental behaviors may not be as effective as previously hoped for slowing the development of childhood caries in some high-risk groups. Furthermore, social factors may be even more salient determinants of oral health than what we previously supposed, perhaps interfering with the capacity to benefit from behavioral strategies that have been useful elsewhere. The improvement of children’s oral health in high-risk populations characterized by poverty and multiple related life stresses may require more holistic approaches that address these formidable barriers.
Analysis of the Impact of Human Resources Management, Intellectual Capital, Organizational Entrepreneurship on Organizational Performance

Purpose: Purpose of this study is Analysis of the Impact of Human Resources Management, Intellectual Capital, Organizational Entrepreneurship on Organizational Performance. The statistical population of this study is employees of a government university of Kermanshah Province. This study is descriptive-survey type of correlation research. Methodology : For data collection, the Standard questionnaires was used. in this field. To review the validity of the questionnaires was used content validity and on the other side of convergent validity, this illustrates the fact that the validity of the questionnaires is suitable. Reliability of the questionnaires was calculated with The Cronbach's alpha coefficient for the questionnaires was examined (0.86, 0.80, 0.87 and 0.70) respectively. Findings : The results of testing hypotheses by SMART-PLS software and using the t-test statistics and path coefficients (=), showed that a Human resource management has strong, strong, moderate, and significant impact on intellectual capital, organizational entrepreneurship and organizational performance, respectively. The results indicate that intellectual capital has moderate, weak, and significant impact on organizational entrepreneurship and organizational performance, respectively. Finally, organizational entrepreneurship has a strong and significant impact on organizational performance. Discussion: University studied must pay attention to human resource management and intellectual capital and organizational entrepreneurship to achieve good organizational performance.
Arterial stiffness during controlled ovarian hyperstimulation and early pregnancy in women exposed to assisted reproduction

ABSTRACT Introduction: Female sex hormones have vasorelaxing effects in non-pregnant and pregnant women. We aimed to investigate the effect of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF), and early pregnancy, on arterial stiffness as assessed by digital pulse wave analysis (DPA), hypothesizing reduced arterial stiffness as an effect of increased estrogen levels. Material and methods: A total of 68 women undergoing IVF were examined with DPA before conception and during IVF treatment with COH and embryo transfer (ET), and in gestational week seven in 19 women who became pregnant. Heart rate (HR), mean arterial pressure (MAP) and the DPA variables cardiac ejection elasticity index (EEI), b/a, dicrotic index (DI), d/a and aging index (AI) were measured. Results: HR was significantly increased at all measuring points (p ≤ 0.003) but MAP only at ET (p 0.007). DPA variables representing large arteries (EEI, b/a) and peripheral arteries (DI, but not d/a), and the global variable AI, indicated increased arterial stiffness at ET compared with baseline (p ≤ 0.035). No DPA variable was significantly changed at pregnancy measurements compared to baseline. Conclusion: During COH for IVF treatment, DPA showed no changes in arterial stiffness during the follicular phase or in early pregnancy, but increased arterial stiffness in central and peripheral arteries in the early luteal phase. The result suggests a hormonal hemodynamic activation counteracting the effects of estrogen.
Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age

Background: Among the many cannabinoids in the cannabis plant, cannabidiol (CBD) is a compound that does not produce the typical subjective effects of marijuana. Objectives: The aim of the present review is to describe the main advances in the development of the experimental and clinical use of cannabidiol CBD in neuropsychiatry. Methods: A non-systematic search was performed for studies dealing with therapeutic applications of CBD, especially performed by Brazilian researchers. Results: CBD was shown to have anxiolytic, antipsychotic and neuroprotective properties. In addition, basic and clinical investigations on the effects of CBD have been carried out in the context of many other health conditions, including its potential use in epilepsy, substance abuse and dependence, schizophrenia, social phobia, post-traumatic stress, depression, bipolar disorder, sleep disorders, and Parkinson. Discussion: CBD is an useful and promising molecule that may help patients with a number of clinical conditions. Controlled clinical trials with different neuropsychiatric populations that are currently under investigation should bring important answers in the near future and support the translation of research findings to clinical settings.
Frostbite in the Norwegian Armed Forces.

BAKGRUNN Det finnes lite forskning på forekomst av frostskader, både sivilt og militært. Prognosen og tidsforløpet ved slike skader har ikke tidligere vært undersøkt i større kohorter. MATERIALE OG METODE Deltagerne var personer registrert i Forsvarets helseregister med kulde- og frostskade i tidsrommet 1.1. 2010-31.12. 2014. Data om diagnostikk, forløp og behandling ble innhentet fra i alt 460 personer ved hjelp av et spørreskjema. Svarprosenten på undersøkelsen var 66. RESULTATER 397 av 460 personer (86,3 %) som var registrert med frostskade i Forsvarets helseregister bekreftet at de hadde hatt en kulde- og frostskade. 123 av 397 personene som svarte (30,1 %) anga at de hadde hatt blemmer, noe som gir mistanke om at de hadde pådratt seg annengrads frostskade. 225 av 397 (56,7 %) anga at de hadde hatt frostskade, men ikke blemmer. De aller fleste fikk frostskaden under feltøvelse/vinterøvelse (81,1 %), og ⅔ av de som pådro seg skader var vernepliktige. Langt de fleste hadde skader på fingre/hender eller tær/føtter (96,0 %). To av tre (69,8 %) hadde fortsatt plager fra sin frostskade mer enn to år etter skadetidspunktet. FORTOLKNING Mange i militæret pådrar seg frostskader under tjenestegjøring. En femdel anga kroniske helseplager som påvirker arbeidsevnen. Kunnskap om forekomsten av frostskader hos militært mannskap er viktig for Forsvarets videre skadeforebyggende arbeid.
Human cerebral circuitry related to cardiac control: A neuroimaging meta‐analysis

Serious arrhythmias often follow stroke, highlighting the important role that the cerebral cortex has in neural regulation of the heart. Neuroimaging studies reveal patterns of activation associated with autonomic cardiovascular responses. Using the activation likelihood estimation, a meta‐analysis was performed to identify cortical activation patterns related to heart rate and heart rate variability across studies that used differing stimuli of cardiovascular arousal. Consistent associations with heart rate and heart rate variability were observed in the anterior cingulate, amygdala, insula, and prefrontal cortex, among others. Also, evidence is provided of insular lateralization associated with autonomic cardiac responses. Ann Neurol 2016;79:709–716
A nuclear membrane-derived structure associated with Atg8 is involved in the sequestration of selective cargo, the Cvt complex, during autophagosome formation in yeast

ABSTRACT Macroautophagy (hereafter autophagy) is a conserved intracellular degradation mechanism required for cell survival. A double-membrane structure, the phagophore, is generated to sequester cytosolic cargos destined for degradation in the vacuole. The mechanism involved in the biogenesis of the phagophore is still an open question. We focused on 4 autophagy-related (Atg) proteins (Atg2, Atg9, Atg14, and Atg18), which are involved in the formation of the phagophore in order to gain a more complete understanding of the membrane dynamics that occur during formation of the autophagosome. The corresponding mutants, while defective in autophagy, nonetheless generate the membrane-bound form of Atg8, allowing us to use this protein as a marker for the nascent autophagosome precursor membrane. Using electron microscopy (EM), we discovered in these atg mutants a novel single-membrane structure (~120 to 150 nm in size). Electron tomography revealed that this structure originates from a part of the nuclear membrane, and we have named it the alphasome. Our data suggest that the alphasome is associated with Atg8, and sequesters selective cargo, the Cvt complex, during autophagy. Abbreviations: 3D: three-dimensional; AB: autophagic body; AP: autophagosome; Atg: autophagy-related; Cvt: cytoplasm-to-vacuole targeting; EM: electron microscopy; IEM: immunoelectron microscopy; L: lipid droplet; N: nucleus; NM: nuclear membrane; PAS: phagophore assembly site; PE: phosphatidylethanolamine; prApe1: precursor aminopeptidase I; rER: rough endoplasmic reticulum; TEM: transmission electron microscopy; V: vacuole; VLP: virus-like particle;
Engaging in Creativity Broadens Attentional Scope

Previous studies have shown that creativity is enhanced by a broad attentional scope, defined as an ability to utilize peripheral stimuli and process information globally. We propose that the reverse relationship also holds, and that breadth of attention also is a consequence of engaging in a creative activity. In Study 1, participants showed increased breadth of attention in a visual scanning task after performing a divergent thinking task as opposed to an analytic thinking task. In Study 2, participants recognized peripheral stimuli displayed during the task better after performing a divergent thinking task as compared to an analytic task, whereas recognition performance of participants performing a task that involves a mix of divergent and analytic thinking (the Remote Associates Test) fell in between. Additionally, in Study 2 (but not in Study 1), breadth of attention was positively correlated with performance in a divergent thinking task, but not with performance in an analytic thinking task. Our findings suggest that the adjustment of the cognitive system to task demands manifests at a very basic, perceptual level, through changes in the breadth of visual attention. This paper contributes a new, motivational perspective on attentional breadth and discusses it as a result of adjusting cognitive processing to the task requirements, which contributes to effective self-regulation.
High expression of PD-1 and PD-L1 in ocular adnexal sebaceous carcinoma

ABSTRACT Ocular adnexal sebaceous carcinoma (OASC) is an aggressive malignancy that frequently recurs locally and metastasizes. Surgical extirpation may produce significant aesthetic morbidity, and effective systemic therapies for locally advanced or metastatic disease are largely ineffective. Immune checkpoint inhibitors have shown efficacy in the management of several solid tumors where tumor cell PD-L1 expression correlates with improved response. To determine whether OASC might be amenable to immune checkpoint blockade, we performed comprehensive immune profiling for CD3, CD8, PD-1, FOXP3, and PD-L1 in 24 patients with primary OASC. The composition, distribution and density of the tumor associated immune infiltrate were quantified by automated image analysis and correlated with measures of clinical outcome. Tumor cells in 12 OASCs (50%) expressed PD-L1. Higher densities of CD3+ (p = 0.01), CD8+ (p = 0.006), and PD-1+ (p = 0.024) tumor-associated T cells were associated with higher T category (≥T3a per the 7th edition of the American Joint Committee on Cancer staging manual). Higher tumor cell expression of PD-L1 correlated with higher density of PD-1+ tumor-associated T cells (p = 0.021). Since a CD3+ CD8+ PD-1 + T-cell infiltrate represents a “suppressed T-cell phenotype” apparently permissive toward OASC progression, our findings provide a mechanistic rationale for the effective application of immune checkpoint blockade in OASC to abrogate PD-1/PD-L1 interaction and effectively unleash the immune infiltrate to treat higher-stage tumors.
A [Glyco]biomarker that Predicts Failure to Standard Therapy in Ulcerative Colitis Patients

Background and Aims There is a clinical need to identify biomarkers able to select patients who are most likely to develop aggressive/complicated disease, for early selection for appropriate therapy. Changes in the glycosylation profile of intestinal lymphocytic infiltrate were previously demonstrated to regulate T cell activity, being associated with disease severity in ulcerative colitis [UC] patients. We interrogated whether this heterogeneous expression of branched N-glycans in intestinal inflammatory infiltrate predicts therapy response early in disease course. Methods The expression levels of the branched N-glycans in colonic biopsies collected around time of diagnosis from a well-characterised cohort of 131 UC patients were correlated with response to standard therapy. Receiver operating characteristic analysis and specificity/sensitivity were determined. Results Branched N-glycans levels around time of diagnosis predict non-response to conventional therapy with 75% specificity. Moreover, high levels of branched N-glycans predict 78% of UC patients who will display a favourable disease course [exclusively under 5-aminosalicylate therapy for more than 5 years of disease]. The best predictive performance was observed in severe UC patients with Mayo endoscopic subscore 3 and in those that were naïve to therapy. Multivariable analysis revealed that low levels of branched N-glycans and high levels of C-reactive protein [CRP] around time of diagnosis act as independent predictors of non-response to standard therapy. A powerful effect of the combined use of the branched N-glycans and CRP was observed. Conclusions Our results reveal a potential [glyco]biomarker that predicts, early in the disease course, patients who will fail to respond to standard therapy, benefiting thereby from other therapeutic strategies such as biologics.
Factors of depression among patients with rheumatoid arthritis

Objectives The aim of this study was to assess the correlation between symptoms of depression and the course and clinical picture of rheumatoid arthritis (RA). Material and methods 120 patients with RA were included in the study: 104 (87%) female patients and 16 (13%) male patients. All studied patients completed the following questionnaires: Beck Depression Inventory (BDI), Ford Insomnia Response to Stress Test (FIRST), Athens Insomnia Scale (AIS) and Health Assessment Questionnaire (HAQ). The serum levels of IL-1β, TNF-α, and IL-6 were measured using standard ELISA assays at the time of the first questionnaire assessment. Results Symptoms of depression were found in 91 patients (76%), including 79 (87%) women and 12 (13%) men. There were no significant differences between the prevalence of depression in women and men (p = 0.93). Symptoms of depression occurred more often in patients who were professionally inactive, compared with the professionally active patients (p = 0.04). Significant correlations was demonstrated between the value of BDI and the patient’s pain assessed by the visual analogue scale (VAS) value (r = 0.36), the disease activity assessed by the patient and the physician evaluated in millimetres on the VAS scale (r = 0.38 and r = 0.30, respectively), the number of painful and swollen joints (r = 0.22 and r = 0.26, respectively), DAS28 (r = 0.31) as well as the Health Assessment Questionnaire (HAQ) value (r = 0.46). Longer duration of the disease was observed in patients with symptoms of depression (p = 0.02). Also a significant difference in the assessment of BDI between patients treated with biological drugs and those receiving no such treatment was observed (p = 0.042). Conclusions Professional inactivity and longer disease duration are important factors influencing symptoms of depression in patients with RA. Higher values of HAQ increase the probability of the occurrence of depression symptoms. The use of biological drugs that reduce the level of proinflammatory cytokines may have a positive effect on reducing the severity of depressive symptoms.
The GIS2 Gene Is Repressed by a Zinc-Regulated Bicistronic RNA in Saccharomyces cerevisiae

Zinc homeostasis is essential for all organisms. The Zap1 transcriptional activator regulates these processes in the yeast Saccharomyces cerevisiae. During zinc deficiency, Zap1 increases expression of zinc transporters and proteins involved in adapting to the stress of zinc deficiency. Transcriptional activation by Zap1 can also repress expression of some genes, e.g., RTC4. In zinc-replete cells, RTC4 mRNA is produced with a short transcript leader that is efficiently translated. During deficiency, Zap1-dependent expression of an RNA with a longer transcript leader represses the RTC4 promoter. This long leader transcript (LLT) is not translated due to the presence of small open reading frames upstream of the RTC4 coding region. In this study, we show that the RTC4 LLT RNA also plays a second function, i.e., repression of the adjacent GIS2 gene. In generating the LLT transcript, RNA polymerase II transcribes RTC4 through the GIS2 promoter. Production of the LLT RNA correlates with the decreased expression of GIS2 mRNA and mutations that prevent synthesis of the LLT RNA or terminate it before the GIS2 promoter renders GIS2 mRNA expression and Gis2 protein accumulation constitutive. Thus, we have discovered an unusual regulatory mechanism that uses a bicistronic RNA to control two genes simultaneously.