Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Lexical Cohort Size Is Independent of Semantic Context Effects in a Picture–Word Interference Task: A Combined ERP and sLORETA Study

Lexical cohort size is known to play an important role in the magnitude of semantic interference during picture naming in continuous and blocking naming tasks. Nevertheless, whether and how lexical cohort size influences semantic context effects in a picture–word interference (PWI) task remains unclear. To address this issue, participants were required to name pictures, which were paired with both semantically related and unrelated distractors, from both large and small lexical cohorts while electroencephalogram (EEG) signals were recorded. Behavior results showed a semantic interference effect but no interaction between semantic relatedness and lexical cohort size in naming latencies. ERPs and correlation analyses revealed that semantic interference effects occurred at the lexical level in the time windows of 200–400 and 400–600 ms, and lexical cohort size effects occurred at the conceptual level in the time window of 100–200 ms and at the lexical level in the time windows of 200–400 ms. Critically, no interaction between two variables was found, reflecting that lexical cohort size is independent of semantic interference for categorical relations in the PWI. sLORETA results found stronger brain activations for large lexical cohorts at the left superior temporal gyrus and inferior frontal gyrus in the time interval of 250–300 ms, which may relate to lexical selection and self-monitoring. Our findings provide evidence for the swinging lexical network rather than the response exclusion hypothesis in spoken production.
Electrospun Nanofibrous Poly (Lactic Acid)/Titanium Dioxide Nanocomposite Membranes for Cutaneous Scar Minimization

Poly (lactic acid) (PLA) has been increasingly used in cutaneous tissue engineering due to its low cost, ease of handling, biodegradability, and biocompatibility, as well as its ability to form composites. However, these polymers possess a structure with nanoporous that mimic the cellular environment. In this study, nanocomposites are prepared using PLA and titanium dioxide (TiO2) (10 and 35%—w/w) nanoparticles that also function as an active anti-scarring agent. The nanocomposites were prepared using an electrospinning technique. Three different solutions were prepared as follows: PLA, 10% PLA/TiO2, and 35% PLA/TiO2 (w/w%). Electrospun PLA and PLA/TiO2 nanocomposites were characterized morphologically, structurally, and chemically using electron scanning microscopy, transmission electron microscopy, goniometry, and X-ray diffraction. L929 fibroblast cells were used for in vitro tests. The cytotoxic effect was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Versicam (VCAN), biglicam (BIG), interleukin-6 (IL6), interleukin-10 (IL-10), and type-1 collagen (COL1A1) genes were evaluated by RT-qPCR. In vivo tests using Wistar rats were conducted for up to 15 days. Nanofibrous fibers were obtained for all groups that did not contain residual solvents. No cytotoxic effects were observed for up to 168 h. The genes expressed showed the highest values of versican and collagen-1 (p < 0.05) for PLA/TiO2 nanocomposite scaffolds when compared to the control group (cells). Histological images showed that PLA at 10 and 35% w/w led to a discrete inflammatory infiltration and expression of many newly formed vessels, indicating increased metabolic activity of this tissue. To summarize, this study supported the potential of PLA/TiO2 nanocomposites ability to reduce cutaneous scarring in scaffolds.
Microbial Communities in Human Milk Relate to Measures of Maternal Weight

The process of breastfeeding exposes infants to bioactive substances including a diversity of bacteria from breast milk as well as maternal skin. Knowledge of the character of and variation in these microbial communities, as well as the factors that influence them, is limited. We aimed to identify profiles of breastfeeding-associated microbial communities and their association with maternal and infant factors. Bilateral milk samples were collected from women in the New Hampshire Birth Cohort Study at approximately 6 weeks postpartum without sterilization of the skin in order to capture the infant-relevant exposure. We sequenced the V4–V5 hypervariable region of the bacterial 16S rRNA gene in 155 human milk samples. We used unsupervised clustering (partitioning around medoids) to identify microbial profiles in milk samples, and multinomial logistic regression to test their relation with maternal and infant variables. Associations between alpha diversity and maternal and infant factors were tested with linear models. Four breastfeeding microbiome types (BMTs) were identified, which differed in alpha diversity and in Streptococcus, Staphylococcus, Acinetobacter, and Pseudomonas abundances. Higher maternal pre-pregnancy BMI was associated with increased odds of belonging to BMT1 [OR (95% CI) = 1.13 (1.02, 1.24)] or BMT3 [OR (95% CI) = 1.12 (1.01, 1.25)] compared to BMT2. Independently, increased gestational weight gain was related to reduced odds of membership in BMT1 [OR (95% CI) = 0.66 (0.44, 1.00) per 10 pounds]. Alpha diversity was positively associated with gestational weight gain and negatively associated with postpartum sample collection week. There were no statistically significant associations of breastfeeding microbiota with delivery mode. Our results indicate that the breastfeeding microbiome partitions into four profiles and that its composition and diversity is associated with measures of maternal weight.
Self-Esteem and Problematic Smartphone Use Among Adolescents: A Moderated Mediation Model of Depression and Interpersonal Trust

Research has found that self-esteem is negatively associated with problematic smartphone use (PSU). However, the internal mechanisms underlying that relationship need further investigation. The purpose of this study was to investigate the roles of depression and interpersonal trust in the relationship between self-esteem and PSU among adolescents. A questionnaire comprised of the Rosenberg Self-esteem Scale, Inclusive General Trust Scale (IGTS), Self-rating Depression Scale (SDS), and personal questions was administered to 637 students (female = 355) at two middle schools in Shanghai, China. Correlation analyses, mediation analysis, and moderated mediation analysis were performed. A moderated mediation model was established, which revealed: (1) a significant negative association between self-esteem and PSU, (2) depression mediated the relationship between self-esteem and PSU, and (3) the influence of depression on the relationship between self-esteem and PSU was moderated by interpersonal trust. The results indicated that low self-esteem was a risk factor, and interpersonal trust was a moderating factor for PSU among adolescents in the sample. Building adolescents’ self-esteem and increasing their interpersonal trust might decrease their PSU.
The Effect of Organizational Changes on the Psychosocial Work Environment: Changes in Psychological and Social Working Conditions Following Organizational Changes

Purpose: The present study aimed to clarify the prospective effects of various types and frequencies of organizational changes on aspects in the psychosocial work environment. Methods: The study had a prospective, full-panel, repeated measures design. Data were collected by self-administered, online questionnaires, with a 2-year interval between measurement occasions. Five types of organizational change were assessed – company restructuring, downsizing, layoffs, partial closure, and partial outsourcing. The effects of change on eleven, specific work factors were measured utilizing QPS Nordic. At baseline, 12652 employees participated, while 8965 responded at follow-up. Generalized estimating equations were utilized to estimate the effects of change taking place within the last 12 months or more than 24 months prior. Results: Cross-sectional analyses, i.e., changes occurring within the last 12 months, showed all 11 work factors to be statistically significantly associated with the organizational changes restructuring, downsizing, and partial closure (coefficients ranging −0.28 to 0.04). In the prospective analyses, i.e., the effects of change taking place more than 24 months prior, associations were no longer significant for a number of work factors, although all types of organizational change remained significantly associated with at least three work factors (coefficients ranging −0.14 to 0.05). Following repeated organizational changes, statistically significant associations were shown for all 11 work factors (coefficients ranging from 0.39 to −0.04). Conclusion: Following both separate and repeated organizational change, various psychological and social work factors were altered, with the most pronounced effects following repeated change. These results suggest the implementing organizational change, especially repeated change, may have an adverse effect on various parts of the psychosocial work environment. The negative effects of a company’s psychosocial working conditions may contribute to the adverse health effects often observed following such changes and help explain why many change initiatives fail to reach its intended results.
Commentary: Measuring Counterintuitiveness in Supernatural Agent Dream Imagery

Nordin and Bjälkebring’s research on counterintuitiveness (CI) in the dreams of Nepali Hindus is seemingly the first case of applying Barrett’s (2008) coding scheme to dream reports. This commentary briefly addresses Nordin and Bjälkebring’s main findings with the coding scheme before considering their proposal for the manifestation of supernatural agents (SAs) in dreams. As discussed below, their proposal is vague and ignores other factors that are relevant to oneiric SA manifestation.
Goethite Reduction by a Neutrophilic Member of the Alphaproteobacterial Genus Telmatospirillum

In tropical iron ore regions, biologically mediated reduction of crystalline iron oxides drives ongoing iron cycling that contributes to the stability of surface duricrusts. This represents a biotechnological opportunity with respect to post-mining rehabilitation attempts, requiring re-formation of these duricrusts. However, cultivated dissimilatory iron reducing bacteria typically reduce crystalline iron oxides quite poorly. A glucose-fermenting microbial consortium capable of reducing at least 27 mmol/L goethite was enriched from an iron duricrust region. Metagenome analysis led to the recovery of a metagenome assembled genome (MAG) of an iron reducer belonging to the alphaproteobacterial genus Telmatospirillum. This is the first report of iron reduction within the Telmatospirillum and the first reported genome of an iron-reducing, neutrophilic member of the Alphaproteobacteria. The Telmatospirillum MAG encodes putative metal transfer reductases (MtrA, MtrB) and a novel, multi-heme outer membrane cytochrome for extracellular electron transfer. In the presence of goethite, short chain fatty acid production shifted significantly in favor of acetate rather than propionate, indicating goethite is a hydrogen sink in the culture. Therefore, the presence of fermentative bacteria likely promotes iron reduction via hydrogen production. Stimulating microbial fermentation has potential to drive reduction of crystalline iron oxides, the rate limiting step for iron duricrust re-formation.
Dead in the Water: The Vicious Cycle of Blanks During Natural Level 14 C Manipulation of Marine Algal Cultures

Authentic biomarker standards were obtained from algal cultures in an attempt to accurately determine blank C added during sample processing for compound-specific radiocarbon analysis. Emiliania huxleyi and Thalassiosira pseudonana were grown under manipulated Δ14C dissolved inorganic carbon (DIC) levels and chlorophyll a and either alkenones (E. huxleyi) or low molecular weight (LMW) alkanoic acids (T. pseudonana) were isolated from the respective biomass using preparative liquid chromatography (LC), wet chemical techniques or preparative gas chromatography, respectively. DI14C in the seawater medium was determined pre- and post-growth. Biomarker Δ14C values mostly agree within 1-2 analytical uncertainties. In those cases where biomarker Δ14C values differ significantly, chlorophyll a is up to 104‰ more 14C-depleted than alkenones or LMW alkanoic acids, consistent with a larger LC blank compared to the other purification methods. However, in the majority of experimental setups pre- and post-growth DIC Δ14C values seem to be compromised by an unknown and variable blank C contribution. DIC Δ14C values deviate strongly from the anticipated Δ14C values (by up to ca. 560‰), pre- and post-growth Δ14C values differ significantly (by up to ca. 460‰), and changes are not unidirectional. Accordingly, since the substrate Δ14C value cannot unequivocally be constrained, blank C contributions for the different biomarker purification methods cannot be accurately calculated. This study illustrates the challenges and problems of producing authentic standards that are not readily commercially available and exemplifies how a laborious and time-consuming culturing approach may enter a vicious cycle of blank C contamination hampering accurate blank C determination.
The Effect of 20-Minute Mindful Breathing on the Perception of Suffering and Changes in Bispectral Index Score (BIS) in Palliative Care Informal Caregivers: A Randomized Controlled Study

Informal caregivers are at risk of being overwhelmed by various sources of suffering while caring for their significant others. It is, therefore, important for caregivers to take care of themselves. In the self-care context, mindfulness has the potential to reduce caregiver suffering. We studied the effect of a single session of 20-minute mindful breathing on the perceived level of suffering, together with the changes in bispectral index score (BIS) among palliative care informal caregivers. This was a randomized controlled study conducted at the University of Malaya Medical Centre, Malaysia. Forty adult palliative care informal caregivers were recruited and randomly assigned to either 20-minute mindful breathing or 20-minute supportive listening. The changes in perceived suffering and BIS were measured preintervention and postintervention. The reduction in suffering score in the intervention group was significantly more than the control group at minute 20 (U = 124.0, n1 = n2 = 20, mean rank1 = 24.30, mean rank2 = 16.70, z = −2.095, P = .036). The reduction in BIS in the intervention group was also significantly greater than the control group at minute 20 (U = 19.5, n1 = n2 = 20, mean rank1 = 29.52, mean rank2 = 11.48, z = −4.900, P < .0001). Twenty minutes of mindful breathing was more efficacious than 20 minutes of supportive listening in the reduction in suffering among palliative care informal caregivers.
Interaction Energetics and Druggability of the Protein-Protein Interaction between Kelch-like ECH-associated Protein 1 (KEAP1) and Nuclear Factor, Erythroid 2 Like 2 (Nrf2).

Development of small-molecule inhibitors of protein-protein interactions (PPI) is hampered by our poor understanding of the druggability of PPI target sites. Here, we describe the combined application of alanine-scanning mutagenesis, fragment screening, and FTMap computational hot spot mapping to evaluate the energetics and druggability of the highly charged PPI interface between Kelch like ECH Associated Protein-1 (KEAP1) and Nuclear Factor, Erythroid 2 Like 2 (Nrf2), an important drug target. FTMap identifies four binding energy hot spots at the active site. Only two of these are exploited by Nrf2, which alanine scanning of both proteins shows to bind primarily though E79 and E82 interacting with KEAP1 residues S363, R380, R415, R483 and S508. We identify fragment hits, and obtain X-ray complex structures for three fragments via crystal soaking using a new crystal form of KEAP1. Combining these results provides a comprehensive and quantitative picture of the origins of binding energy at the interface. Our findings additionally reveal non-native interactions that might be exploited in the design of uncharged synthetic ligands to occupy the same site on KEAP1 that has evolved to bind the highly charged DEETGE binding loop of Nrf2. These include pi-stacking with KEAP1 Y525, plus interactions at an FTMap-identified hot spot deep in the binding site. Finally, we discuss how the complementary information provided by alanine-scanning mutagenesis, fragment screening and computational hot spot mapping can be integrated to more comprehensively evaluate PPI druggability.
Reassessing the contribution of the Na+/H+ exchanger Nhe3b to Na+ uptake in zebrafish (Danio rerio) using CRISPR/Cas9 gene editing

ABSTRACT Freshwater fishes absorb Na+ from their dilute environment using ion-transporting cells. In larval zebrafish (Danio rerio), Na+ uptake is coordinated by (1) Na+/H+ exchanger 3b (Nhe3b) and (2) H+-ATPase-powered electrogenic uptake in H+-ATPase-rich (HR) cells and by (3) Na+-Cl−-cotransporter (Ncc) expressed in NCC cells. The present study aimed to better understand the roles of these three proteins in Na+ uptake by larval zebrafish under ‘normal’ (800 µmol l−1) and ‘low’ (10 µmol l−1) Na+ conditions. We hypothesized that Na+ uptake would be reduced by CRISPR/Cas9 knockout (KO) of slc9a3.2 (encoding Nhe3b), particularly in low Na+ where Nhe3b is believed to play a dominant role. Contrary to this hypothesis, Na+ uptake was sustained in nhe3b KO larvae under both Na+ conditions, which led to the exploration of whether compensatory regulation of H+-ATPase or Ncc was responsible for maintaining Na+ uptake in nhe3b KO larvae. mRNA expression of the genes encoding H+-ATPase and Ncc was not altered in nhe3b KO larvae. Moreover, morpholino knockdown of H+-ATPase, which significantly reduced H+ flux by HR cells, did not reduce Na+ uptake in nhe3b KO larvae, nor did rearing larvae in chloride-free conditions, thereby eliminating any driving force for Na+-Cl−-cotransport via Ncc. Finally, simultaneously treating nhe3b KO larvae with H+-ATPase morpholino and chloride-free conditions did not reduce Na+ uptake under normal or low Na+. These findings highlight the flexibility of the Na+ uptake system and demonstrate that Nhe3b is expendable to Na+ uptake in zebrafish and that our understanding of Na+ uptake mechanisms in this species is incomplete. Summary: CRISPR/Cas9 knockout of the Na+/H+ exchanger Nhe3b has no effect on Na+ uptake in larval zebrafish. H+-ATPase and Na+-Cl−-cotransporter are not responsible for maintaining Na+ uptake in nhe3b knockout mutants.
Longitudinal DNA methylation changes at MET may alter HGF/c-MET signalling in adolescents at risk for depression

ABSTRACT Unrecognized depression during adolescence can result in adult suicidal behaviour. The aim of this study was to identify, replicate and characterize DNA methylation (DNAm) shifts in depression aetiology, using a longitudinal, multi-tissue (blood and brain) and multi-layered (genetics, epigenetics, transcriptomics) approach. We measured genome-wide blood DNAm data at baseline and one-year follow-up, and imputed genetic variants, in 59 healthy adolescents comprising the discovery cohort. Depression and suicidal symptoms were determined using the Development and Well-Being Assessment (DAWBA) depression band, Montgomery-Åsberg Depression Rating Scale-Self (MADRS-S) and SUicide Assessment Scale (SUAS). DNAm levels at follow-up were regressed against depression scores, adjusting for sex, age and the DNAm residuals at baseline. Higher methylation levels of 5% and 13% at cg24627299 within the MET gene were associated with higher depression scores (praw<1e-4) and susceptibility for suicidal symptoms (padj.<0.005). The nearby rs39748 was discovered to be a methylation and expression quantitative trait locus in blood cells. mRNA levels of hepatocyte growth factor (HGF) expression, known to strongly interact with MET, were inversely associated with methylation levels at cg24627299, in an independent cohort of 1180 CD14+ samples. In an open-access dataset of brain tissue, lower methylation at cg24627299 was found in 45 adults diagnosed with major depressive disorder compared with matched controls (padj.<0.05). Furthermore, lower MET expression was identified in the hippocampus of depressed individuals compared with controls in a fourth, independent cohort. Our findings reveal methylation changes at MET in the pathology of depression, possibly involved in downregulation of HGF/c-MET signalling the hippocampal region.
Human genetics and neuropathology suggest a link between miR-218 and amyotrophic lateral sclerosis pathophysiology

Genetics, pathology, and molecular studies demonstrate that microRNA-218 is modulated and might play a role in amyotrophic lateral sclerosis. A micro(RNA) contribution to ALS Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by selective motor neuron degeneration and consequent progressive paralysis. Recent data have shown that microRNA-218 (miR-218) is enriched in motor neurons. However, whether neuronal miR-218 is modulated in ALS and plays a role in the disease is unknown. Now, Reichenstein et al. show that miR-218 controls neuronal activity by modulating the potassium channel Kv10.1 and its expression is reduced in motor neuron from patients with ALS. Screening of ALS genomes, the authors also identified miR-218 variants associated with reduced function, suggesting that this microRNA might play a role in ALS pathophysiology. Motor neuron–specific microRNA-218 (miR-218) has recently received attention because of its roles in mouse development. However, miR-218 relevance to human motor neuron disease was not yet explored. Here, we demonstrate by neuropathology that miR-218 is abundant in healthy human motor neurons. However, in amyotrophic lateral sclerosis (ALS) motor neurons, miR-218 is down-regulated and its mRNA targets are reciprocally up-regulated (derepressed). We further identify the potassium channel Kv10.1 as a new miR-218 direct target that controls neuronal activity. In addition, we screened thousands of ALS genomes and identified six rare variants in the human miR-218-2 sequence. miR-218 gene variants fail to regulate neuron activity, suggesting the importance of this small endogenous RNA for neuronal robustness. The underlying mechanisms involve inhibition of miR-218 biogenesis and reduced processing by DICER. Therefore, miR-218 activity in motor neurons may be susceptible to failure in human ALS, suggesting that miR-218 may be a potential therapeutic target in motor neuron disease.
Prognostic effect of different etiologies in patients with gastric cardia cancer

Abstract There are still many controversies about the characteristics and prognosis of gastric cardia cancer. We aimed to evaluate the clinical characteristics and outcome between cardia and noncardia cancer. Also, we evaluated the clinical outcome according to etiologic factors. We performed a retrospective cohort study of 92 patients with gastric cardia cancer from January 2003 to December 2013. The patients with noncardia cancer were selected as age- and sex-matched control. The frequencies of gastroesophageal reflux disease (GERD) and negative Helicobacter pylori infection without atrophy were significantly higher in gastric cardia cancers, but there was no difference in the frequency of obesity. The frequency of early gastric cancers was 40.0%, which was significantly lower than that of noncardia cancer. The rate of recurrence, disease-free survival, and overall survival duration were significantly lower in gastric cardia cancers (P < .01), even though there was no significant difference in the rate of curative resection (R0). In terms of the etiologic factors, there were no differences of disease prognosis, regardless of the presence of GERD, obesity, and H pylori infection with associated gastritis. Gastric cardia cancer showed distinct clinical characteristics and a negative prognostic impact compared with gastric noncardia cancer.