Miracle-dz/UniFAR-FTUs huggingface dataset:
Epigenetic gene expression links heart failure to memory impairment

In current clinical practice care of diseased patients is often restricted to separated disciplines. However, such an organ-centered approach is not always suitable. For example, cognitive dysfunction is a severe burden in heart failure patients. Moreover, these patients have an increased risk for age-associated dementias. The underlying molecular mechanisms are presently unknown and thus corresponding therapeutic strategies to improve cognition in heart failure patients are missing. Using mice as model organisms we show that heart failure leads to specific changes in hippocampal gene-expression, a brain region intimately linked to cognition. These changes reflect increased cellular stress pathways which eventually lead to loss of neuronal euchromatin and reduced expression of a hippocampal gene cluster essential for cognition. Consequently, mice suffering from heart failure exhibit impaired memory function. These pathological changes are ameliorated via the administration of a drug that promotes neuronal euchromatin formation. Our study provides first insight to the molecular processes by which heart failure contributes to neuronal dysfunction and point to novel therapeutic avenues to treat cognitive defects in heart failure patients.
Individual Differences in Hemodynamic Responses Measured on the Head Due to a Long-Term Stimulation Involving Colored Light Exposure and a Cognitive Task: A SPA-fNIRS Study

When brain activity is measured by neuroimaging, the canonical hemodynamic response (increase in oxygenated hemoglobin ([O2Hb]) and decrease in deoxygenated hemoglobin ([HHb]) is not always seen in every subject. The reason for this intersubject-variability of the responses is still not completely understood. This study is performed with 32 healthy subjects, using the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) approach. We investigate the intersubject variability of hemodynamic and systemic physiological responses, due to a verbal fluency task (VFT) under colored light exposure (CLE; blue and red). Five and seven different hemodynamic response patterns were detected in the subgroup analysis of the blue and red light exposure, respectively. We also found that arterial oxygen saturation and mean arterial pressure were positively correlated with [O2Hb] at the prefrontal cortex during the CLE-VFT independent of the color of light and classification of the subjects. Our study finds that there is substantial intersubject-variability of cerebral hemodynamic responses, which is partially explained by subject-specific systemic physiological changes induced by the CLE-VFT. This means that both subgroup analyses and the additional assessment of systemic physiology are of crucial importance to achieve a comprehensive understanding of the effects of a CLE-VFT on human subjects.
Polyunsaturated fatty acids as modulators of fat mass and lean mass in human body composition regulation and cardiometabolic health

It is now recognized that the amount and type of dietary fat consumed play an important role in metabolic health. In humans, high intake of polyunsaturated fatty acids (PUFAs) has been associated with reductions in cardiovascular disease risk, improvements in glucose homeostasis, and changes in body composition that involve reductions in central adiposity and, more recently, increases in lean body mass. There is also emerging evidence, which suggests that high intakes of the plant‐based essential fatty acids (ePUFAs)—n‐6 linoleic acid (LA) and n‐3 α‐linolenic acid (ALA)—have a greater impact on body composition (fat mass and lean mass) and on glucose homeostasis than the marine‐derived long‐chain n‐3 PUFA—eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In addition, high intake of both ePUFAs (LA and ALA) may also have anti‐inflammatory effects in humans. The purpose of this review is to highlight the emerging evidence, from both epidemiological prospective studies and clinical intervention trials, of a role for PUFA, in particular ePUFA, in the long‐term regulation of body weight and body composition, and their impact on cardiometabolic health. It also discusses current notions about the mechanisms by which PUFAs modulate fat mass and lean mass through altered control of energy intake, thermogenesis, or lean–fat partitioning.
Stigmatization of 'gay-sounding' voices: The role of heterosexual, lesbian, and gay individuals' essentialist beliefs.

Voice-based sexual orientation (SO) judgements can prompt group-based discrimination. However, the relationships between stigmatization and essentialist beliefs about vocal cues to SO have not been researched. Two studies examined heterosexuals' and gay men's and lesbian women's essentialist beliefs about voice as a cue of SO to uncover essentialist beliefs' role in the perpetration and experience of stigma. In Study 1 (N = 363), heterosexual participants believed voice was a better cue to SO for men than for women, and participants' belief in the discreteness, immutability, and controllability of 'gay-sounding' voices was correlated with higher avoidant discrimination towards gay-sounding men. In Study 2 (N = 147), endorsement of essentialist beliefs about voice as a SO cue was associated with self-perceptions of sounding gay amongst gay men and lesbians. Sexual minority participants, especially gay men, who believed that they sounded gay reported more anticipation of rejection and engaged in vigilance in response. Essentialist beliefs about vocal cues to SO are relevant to explaining both the perpetration of stigma by heterosexuals and the experience of stigma for lesbians and gay men.
A Phenomenographic Study on Chemical Bonding

This study aims to reveal how students perceive and identify the concept of chemical bonding, and to identify and explain the misconceptions of students on this subject through phenomenographic research method, as well. The present study included 17 2 nd grade students who enrolled to Inorganic Chemistry course in the Faculty of Education. Concept maps and lotus blossom technique were used as data collection tools in order to determine the perceptions and definitions of students about chemical bonding. Data analysis results determined the misconceptions of students about chemical bonding classified misconceptions under seven categories, which are, according to the results of the study, physical changes and bonding, ionic bond, formation of chemical bonding, the existence of chemical bonding, covalent bonds, metallic bonds and intermolecular bonding.
Synthesis, Characterization, and Antibacterial Evaluation of a Cost-Effective Endodontic Sealer Based on Tricalcium Silicate-White Portland Cement

Mineral trioxide aggregate (MTA) is an ideal yet costly endodontic sealer material. Tricalcium silicate-white Portland cement (TS-WPC) seems to have similar characteristics to those of MTA. This work aims to characterize a modified TS-WPC and evaluate its antibacterial properties as a potential endodontic sealer material. The modified TS-WPC was synthesized from a 4:1 mixture of sterilized Indocement TS-WPC and bismuth trioxide using a simple solution method with 99.9% isopropanol. The mixture was stirred until it was homogenous, centrifuged, and dried. The material was then characterized using infrared spectroscopy, X-ray diffraction, and electron microscopy and subjected to antibacterial evaluation against Enterococcus faecalis using a Mueller–Hinton agar inhibition test. The results showed that the material was characterized by main functional groups of hydroxyls, silicate, bismuth trioxide, and tricalcium silicate, like those of a commercial MTA-based sealer, both tested after hydration. Modified TS-WPC before hydration showed similar powder morphology and size to the commercial one, indicating the ease of manipulation. Both materials exhibited antibacterial activity due to calcium dihydroxide’s ability to absorb carbon dioxide, which is essential for the anaerobic E. faecalis, with minimum inhibitory effect and bactericidal concentrations of 12,500 ppm and 25,000 ppm, respectively. The modified TS-WPC has the potential to become a cost-effective alternative endodontic sealer material.
Highly Reliable Radical SiO2 Films on Atomically Flat Silicon Surface Formed by Low Temperature Pure Ar Annealing

The gate oxide films are formed by the microwave exited high density plasma on Si(100) surfaces of various flatness to discuss the reliabilities. By annealing in ultra pure Ar ambient below 900 °C at atmosphere pressure, the whole surface of 200-mm-diameter (100) orientation silicon wafers can be atomically flattened without slip-line defects generation. For the capacitors, the intrinsic life time in charge-to-breakdown (Qbd) characteristics and the breakdown field (Ebd) of radical oxide films are much larger than those of thermal oxide films, and the extrinsic Qbd of radical oxide film is drastically improved by forming on atomically flat silicon surface composed with that on conventional Czochralski (Cz)-wafer surface. Moreover, fabricating radical oxide films on the atomically flat wafers, flattened at 800 or 1100 °C in Ar ambient, the equivalent gate oxide breakdown characteristics are obtained.
Dysmetabolisms Can Affect Total Antioxidant Capacity (TAC) of Human Plasma: Determination of Reference Intervals of TAC by Way of CUPRAC-BCS Method

The total antioxidant capacity (TAC) of human plasma is an index of the redox buffer capacity of this biological fluid and could be a biomarker for those disorders affecting redox status. Distinguishing physiological from pathological conditions needs a reference. Therefore, this work aims to define the reference intervals for TAC of human plasma of apparently healthy adult individuals. TAC was measured using the CUPRAC-BCS (CUPric reducing antioxidant capacity-bathocuproinedisulfonic acid) method previously optimized and tested in a clinical laboratory. A population of 500 blood donors was selected, plus an additional 222 pathological patients carrying specific defective metabolisms, namely, hyperuricemia, hyperbilirubinemia, and type 2 diabetic mellitus. The reference intervals of TAC were calculated according to international guidelines. Due to the response of a partitioning test, the reference intervals for healthy population were separately defined for male (258) and female (151) groups. The reference intervals (µmol L−1) resulted: 727–1248 for the male subgroup and 637–1048 for the female subgroup. The absence of an age effect on TAC values was verified. The reference intervals evaluated allow a discussion on some pathological conditions overloading the plasma with redox-active waste substances.
Cross-Hemispheric Complementary Prefrontal Mechanisms during Task Switching under Perceptual Uncertainty

Flexible adaptation to changing environments is a representative executive control function implicated in the frontoparietal network that requires appropriate extraction of goal-relevant information through perception of the external environment. It remains unclear, however, how the flexibility is achieved under situations where goal-relevant information is uncertain. To address this issue, the current study examined neural mechanisms for task switching in which task-relevant information involved perceptual uncertainty. Twenty-eight human participants of both sexes alternated behavioral tasks in which they judged motion direction or color of visually presented colored dot stimuli that moved randomly. Task switching was associated with frontoparietal regions in the left hemisphere, and perception of ambiguous stimuli involved contralateral homologous frontoparietal regions. On the other hand, in stimulus-modality-dependent occipitotemporal regions, task coding information was increased during task switching. Effective connectivity analysis revealed that the frontal regions signaled toward the modality-dependent occipitotemporal regions when a relevant stimulus was more ambiguous, whereas the occipitotemporal regions signaled toward the frontal regions when the stimulus was more distinctive. These results suggest that complementary prefrontal mechanisms in the left and right hemispheres help to achieve a behavioral goal when the external environment involves perceptual uncertainty. SIGNIFICANCE STATEMENT In our daily life, environmental information to achieve a goal is not always certain, but we make judgments in such situations, and change our behavior accordingly. This study examined how the flexibility of behavior is achieved in a situation where goal-relevant information involves perceptual uncertainty. fMRI revealed that the lateral prefrontal cortex (PFC) in the left hemisphere is associated with behavioral flexibility, and the perception of ambiguous stimuli involves the PFC in the right hemisphere. These bilateral PFC signaled to stimulus-modality-dependent occipitotemporal regions, depending on perceptual uncertainty and the task to be performed. These top-down signals supplement task coding in the occipitotemporal regions, and highlight interhemispheric prefrontal mechanisms involved in executive control and perceptual decision-making.
Alteration of Neural Stem Cell Functions in Ataxia and Male Sterility Mice: A Possible Role of β-Tubulin Glutamylation in Neurodegeneration

Ataxia and Male Sterility (AMS) is a mutant mouse strain that contains a missense mutation in the coding region of Nna1, a gene that encodes a deglutamylase. AMS mice exhibit early cerebellar Purkinje cell degeneration and an ataxic phenotype in an autosomal recessive manner. To understand the underlying mechanism, we generated neuronal stem cell (NSC) lines from wild-type (NMW7), Nna1 mutation heterozygous (NME), and Nna1 mutation homozygous (NMO1) mouse brains. The NNA1 levels were decreased, and the glutamylated tubulin levels were increased in NMO1 cultures as well as in the cerebellum of AMS mice at both 15 and 30 days of age. However, total β-tubulin protein levels were not altered in the AMS cerebellum. In NMO1 neurosphere cultures, β-tubulin protein levels were increased without changes at the transcriptional level. NMO1 grew faster than other NSC lines, and some of the neurospheres were attached to the plate after 3 days. Immunostaining revealed that SOX2 and nestin levels were decreased in NMO1 neurospheres and that the neuronal differentiation potentials were reduced in NMO1 cells compared to NME or NMW7 cells. These results demonstrate that the AMS mutation decreased the NNA1 levels and increased glutamylation in the cerebellum of AMS mice. The observed changes in glutamylation might alter NSC properties and the neuron maturation process, leading to Purkinje cell death in AMS mice.
Insomnia Status of Middle School Students in Indonesia and Its Association with Playing Games before Sleep: Gender Difference

The excessive use of online gaming before sleep in adolescents could be a risk factor of sleep disorders such as insomnia. This study aimed to assess the association between playing online games before sleep and insomnia based on gender perspective among middle school students in Indonesia. This was a retrospective study and the data came from a cross-sectional survey that included 315 of Grade 8 and 9 students from four middle schools in Jakarta, Indonesia. Self-reported data were collected via a structured questionnaire, which consisted of demographic variables, sleep duration per day, frequency of playing online games before sleep and the Insomnia Severity Index (ISI). Insomnia status was classified into “none or mild” and “moderate to severe” according to ISI score. The proportions of male and female students who often or always played online games before sleep were 50.3% and 21.7%, respectively. Grade 9 students were more likely to have moderate to severe insomnia than Grade 8 students for males (odds ratio—OR = 4.34, p = 0.005) but not for females (OR = 0.69, p = 0.363). However, female students who often or always played online games before sleep were more likely to have moderate to severe insomnia (OR = 4.60, p = 0.001); such an association was relatively smaller for male students (OR = 3.09, p = 0.061). Gender differences should be taken into account when developing health education or interventions.
Downregulation of hepatitis C virus replication by miR‐196a using lentiviral vectors

Hepatitis C virus (HCV) is a positive‐sense, single‐stranded RNA virus that causes chronic hepatitis and hepatocellular carcinoma. Cellular microRNAs (miRNAs) directly modulate the viral infectivity and indirectly through targeting virus‐related host factors. They play an essential role in the progression of different stages of HCV infection. The roles of miR‐196 family in HCV infection and hepatocellular carcinoma progression remain poorly understood. Using ViTa databases, miR‐196a as a high‐score miRNA targeting the NS5A region of HCV genome was selected. Using dual luciferase assay and an established cell‐cultured HCV (HCVcc) system, the effect of miR‐196a on HCV genome was assessed. In silico analysis demonstrated the significant role of miR‐196a in the downregulation of HCV replication. Using dual luciferase assay, the liver‐specific miR‐196a and NS5A gene binding was confirmed. To assess the experimental role of miR‐196a, an HCVcc system was established in the Huh 7.5 cell lines. The HCV‐RNA 1b derived from an infected patient was transfected into Huh 7.5 cells containing miR‐196a lentiviral vectors (Huh 7.5/miR‐196a), mocks (Huh 7.5/mock vector), and naïve Huh 7.5 cells. The rate of reduction of the HCV genome replication was assessed using relative real‐time PCR assay. These results represent miR‐196a overexpression and its roles in regulating HCV genome replication. However, miR‐196a may inhibit HCV replication and accelerate the early stages of apoptosis. Overexpression of miR‐196a in Huh 7.5 replicon cell is a potential new strategy to prevent hepatitis C infection. The results of this study suggest that miR‐196a directly downregulates HCV replication and may serve as a new antiviral therapy.
Influence of lived experience on risk perception among women who received a breast cancer polygenic risk score: ‘Another piece of the pie’

Polygenic risk scores (PRS) are personalized assessments of disease risk based on the cumulative effect of common low‐risk genetic variants. PRS have been shown to accurately predict women's breast cancer risk and are likely to be incorporated into personalized breast cancer risk management programs. However, there are few studies investigating the individual impact of receiving a breast cancer PRS. Existing studies have not demonstrated significant changes in perceived risk or risk management behaviors after receipt of polygenic risk information. The aim of this qualitative study was to explore how women with a family history of breast cancer construct breast cancer risk perceptions after receipt of a breast cancer PRS. Unaffected women with a family history of breast cancer who had not previously received genetic counseling regarding their breast cancer risk were invited to participate in this study. In‐depth, semi‐structured interviews were conducted with 20 women who attended a familial cancer clinic in the Australian states of Victoria and Tasmania. Data were analyzed using an inductive thematic approach. Women's lived experience played a significant role in the construction and maintenance of their breast cancer risk perception. Women's pre‐existing risk perceptions were informed by their family history and their knowledge that breast cancer is a multifactorial disease. Knowing that breast cancer is a multifactorial disease enabled most women to integrate genetic information with their pre‐existing notions of risk. Women reported that the information they received was consistent with their existing notions of personal risk and screening advice. Therefore, the PRS did not lead to a change in perceived risk or risk management behaviors for most women. The results of this study provide insight into how polygenic risk information is integrated with pre‐existing notions of risk, which will inform its implementation into clinical practice.
Association of First-Week Nutrient Intake and Extrauterine Growth Restriction in Moderately Preterm Infants: A Regional Population-Based Study

The purpose of this study was to determine the influence of first-week nutrition intake on neonatal growth in moderate preterm (MP) infants. Data on neonatal morbidity and nutrition intake on day of life 7 (DoL7) were prospectively collected from 735 MP infants (320/7–346/7 weeks gestational age (GA)). Multivariable regression was used to assess the factors associated with extrauterine growth restriction (EUGR) defined as a decrease of more than 1 standard deviation (SD) in the weight z-score during hospitalization. Mean (SD) gestational age and birth weight were 33.2 (0.8) weeks and 2005 (369) g. The mean change in the weight z-score during hospitalization was −0.64 SD. A total of 138 infants (18.8%) had EUGR. Compared to adequate growth infants, EUGR infants received 15% and 35% lower total energy and protein intake respectively (p < 0.001) at DoL7. At DoL7, each increase of 10 kcal/kg/d and 1 g/kg/d of protein was associated with reduced odds of EUGR with an odds ratio of 0.73 (95% CI, 0.66–0.82; p < 0.001) and 0.54 (0.44–0.67; p < 0.001), respectively. Insufficient energy and protein intakes on DoL7 negatively affected neonatal growth of MP infants. Nutritional support should be optimized from birth onwards to improve neonatal weight growth.
Breast cancer is marked by specific, Public T-cell receptor CDR3 regions shared by mice and humans

The partial success of tumor immunotherapy induced by checkpoint blockade, which is not antigen-specific, suggests that the immune system of some patients contain antigen receptors able to specifically identify tumor cells. Here we focused on T-cell receptor (TCR) repertoires associated with spontaneous breast cancer. We studied the alpha and beta chain CDR3 domains of TCR repertoires of CD4 T cells using deep sequencing of cell populations in mice and applied the results to published TCR sequence data obtained from human patients. We screened peripheral blood T cells obtained monthly from individual mice spontaneously developing breast tumors by 5 months. We then looked at identical TCR sequences in published human studies; we used TCGA data from tumors and healthy tissues of 1,256 breast cancer resections and from 4 focused studies including sequences from tumors, lymph nodes, blood and healthy tissues, and from single cell dataset of 3 breast cancer subjects. We now report that mice spontaneously developing breast cancer manifest shared, Public CDR3 regions in both their alpha and beta and that a significant number of women with early breast cancer manifest identical CDR3 sequences. These findings suggest that the development of breast cancer is associated, across species, with biomarker, exclusive TCR repertoires.