Miracle-dz/UniFAR-FTUs huggingface dataset:
Combined HAT/EZH2 modulation leads to cancer-selective cell death

Epigenetic alterations have been associated with both pathogenesis and progression of cancer. By screening of library compounds, we identified a novel hybrid epi-drug MC2884, a HAT/EZH2 inhibitor, able to induce bona fide cancer-selective cell death in both solid and hematological cancers in vitro, ex vivo and in vivo xenograft models. Anticancer action was due to an epigenome modulation by H3K27me3, H3K27ac, H3K9/14ac decrease, and to caspase-dependent apoptosis induction. MC2884 triggered mitochondrial pathway apoptosis by up-regulation of cleaved-BID, and strong down-regulation of BCL2. Even aggressive models of cancer, such as p53–/– or TET2–/– cells, responded to MC2884, suggesting MC2884 therapeutic potential also for the therapy of TP53 or TET2-deficient human cancers. MC2884 induced massive apoptosis in ex vivo human primary leukemia blasts with poor prognosis in vivo, by targeting BCL2 expression. MC2884-treatment reduced acetylation of the BCL2 promoter at higher level than combined p300 and EZH2 inhibition. This suggests a key role for BCL-2 reduction in potentiating responsiveness, also in combination therapy with BCL2 inhibitors. Finally, we identified both the mechanism of MC2884 action as well as a potential therapeutic scheme of its use. Altogether, this provides proof of concept for the use of epi-drugs coupled with epigenome analyses to ‘personalize’ precision medicine.
Anxiety, Depression, and Quality of Life in Women with Polycystic Ovarian Syndrome

Background: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. Symptoms include amenorrhea, hirsutism, infertility, obesity, acne vulgaris, and androgenic alopecia. PCOS is a stigmatizing condition that affects a woman's identity, mental health and quality of life (QOL). This aspect has not received adequate attention in India. Aims and Objectives: (1) To study the prevalence of anxiety and depression among women suffering from PCOS (2) To determine if symptoms of PCOS were associated with psychiatric morbidity, and (3) To determine the impact of psychiatric morbidity on the QOL. Materials and Methods: Seventy females in the reproductive age group (18–45 years) diagnosed with PCOS as per Rotterdam criteria and without any preexisting psychiatric illness were clinically interviewed for anxiety and depressive disorders which were then rated according to the Hamilton scales. QOL was assessed using the World Health Organization-QOL-BREF. Binary logistic regression was performed to study the association of the symptoms with the psychiatric morbidity. QOL scores of patients with and without psychiatric morbidity were compared using Mann–Whitney U-test. Results and Conclusions: The prevalence of anxiety and depression in our sample was 38.6% and 25.7%, respectively. Infertility and alopecia were associated with anxiety, while acne was associated with depression. Hirsutism was associated with a lower psychological QOL. Patients with psychiatric morbidity had a significantly lower QOL than those without.
Manipulation of working memory contents selectively impairs metacognitive sensitivity in a concurrent visual discrimination task

Abstract What are the cognitive mechanisms underlying perceptual metacognition? Prior research indicates that prefrontal cortex (PFC) contributes to metacognitive performance, suggesting that metacognitive judgments are supported by high-level cognitive operations. We explored this hypothesis by investigating metacognitive performance for a visual discrimination task in the context of a concurrent working memory (WM) task. We found that, overall, high WM load caused a nonspecific decrease in visual discrimination performance as well as metacognitive performance. However, active manipulation of WM contents caused a selective decrease in metacognitive performance without impairing visual discrimination performance. These behavioral findings are consistent with previous neuroscience findings that high-level PFC is engaged by and necessary for (i) visual metacognition, and (ii) active manipulation of WM contents, but not mere maintenance. The selective interference of WM manipulation on metacognition suggests that these seemingly disparate cognitive functions in fact recruit common cognitive mechanisms. The common cognitive underpinning of these tasks may consist in (i) higher-order re-representation of lower-level sensory information, and/or (ii) application of decision rules in order to transform representations in PFC into definite cognitive/motor responses.
Enhancing Teacher Education in Primary Mathematics with Mobile Technologies.

A challenge of teacher education is to produce graduate primary school teachers who are confident and competent teachers of mathematics. Various approaches to primary school teacher education in mathematics have been investigated, but primary teacher education graduates still tend to be diffident in their teaching of mathematics. In an age where personal use of mobile technologies is becoming ubiquitous, such technologies could provide a conduit into making mathematics teaching and learning more accessible to primary teacher education students. This paper introduces the use of a pedagogical framework which can scaffold mobile learning in mathematics teacher education programs. The paper discusses ways in which this framework, the Mobile Pedagogical Framework, can contribute to enhanced primary teacher education in mathematics, using mobile technologies. The Framework has three major dimensions: authenticity, collaboration and personalisation. Each of these will be discussed in terms of their alignment with current ideas about quality teaching in mathematics.
A Tale of Two Internet News Platforms-Real vs. Fake: An Elaboration Likelihood Model Perspective

This paper presents findings from a field analysis of real vs. fake news propagated on the Internet. Elaboration Likelihood Model (ELM) was used as a theoretical framework to investigate information presentation mechanisms used by real and fake content generators to persuade readers. ELM theorizes two routes through which information can inform attitudinal changes: a central route of high cognitive effort, and a peripheral route of low cognitive effort. We hypothesize that fake news sites favor the peripheral route by providing less information overall, and by providing more negative affective cues. Data was gathered from Internet platforms that publish real news and fake news. Results indicate that the amount of information disseminated by fake news platforms is lower than that of reputable platforms. Content analysis reveals that fake news with business impact are typically more negative in their valence compared to real news. Implications of our findings for theory and practice are discussed.
Factors influencing the willingness to participate in medical research: a nationwide survey in Taiwan

Background Participation rate is one of the main challenges medical researchers face. We examined how demographic background and trust in medical research affect the willingness of people to participate in medical research in Taiwan. Methods Data from the 2011 Taiwan Genomic Survey (a nationwide representative face-to-face survey) were analyzed. The survey included a vignette of a researcher conducting a clinical trial of an investigative medicinal product, and questions for interviewees regarding their willingness to participate in research after they were informed of the scenario description. A total of 3,159 people, aged 18 to 70 years, were sampled, and 1,538 of them completed the survey. With missing data excluded, a total of 1,389 respondents were included in the final analysis. Results About 12 percent of the respondents answered that they would be willing to participate in medical research. Respondents who had college degrees or above and were married or lived with significant others were less likely to participate in medical research. By contrast, male respondents, and respondents whose household family members had biomedicine-related degrees or had one themselves were more likely to participate in medical research. After adjustment for demographic factors, respondents were more likely to participate in medical research if: (1) they expressed trust in doctors conducting medical research; (2) they agreed that doctors would never ask them to join medical research studies that might harm them; (3) they thought that participating in a medical research study would be safe; and (4) they agreed that researchers had no selfish reasons for doing the medical research. Discussion Some of our findings, such as the effects of education level and marital status on participation in medical research, are different from most findings of previous studies conducted in other countries. This study is useful for developing strategies to improve participant recruitment. Relevant discussions on research ethics and policies, such as the importance of public trust in medical researchers, could also be based on this study.
Unique Challenges of Decision-Making Process on Crowdfunding Platforms - An Exploratory Study

Crowdfunding gives opportunities to novice entrepreneurs to raise funding for their novel ideas. However, lack of monitoring of projects and funds coupled with the lack of experience of project initiators create high levels of uncertainty for potential funders. In this study, we aim to examine how funders’ decision making process is affected by different types of uncertainty related to the project initiators. Unlike traditional e-commerce where consumers buy a finished product, in patronage based crowdfunding platforms, funders invest in and buy a product that is yet to be finished. This creates a unique uncertainty based on project initiators’ competence. Our results show that uncertainty based on project initiators’ competence and opportunism increase product performance uncertainty. Moreover, the dynamics of project initiator and product uncertainty are affected by the complexity of the product.
Calcium signalling and related ion channels in neutrophil recruitment and function

The recruitment of neutrophils to sites of inflammation, their battle against invading microorganisms through phagocytosis and the release of antimicrobial agents is a highly coordinated and tightly regulated process that involves the interplay of many different receptors, ion channels and signalling pathways. Changes in intracellular calcium levels, caused by cytosolic Ca2+ store depletion and the influx of extracellular Ca2+ via ion channels, play a critical role in synchronizing neutrophil activation and function. In this review, we provide an overview of how Ca2+ signalling is initiated in neutrophils and how changes in intracellular Ca2+ levels modulate neutrophil function.
Contribution of the Axon Initial Segment to Action Potentials Recorded Extracellularly

Abstract Action potentials (APs) are electric phenomena that are recorded both intracellularly and extracellularly. APs are usually initiated in the short segment of the axon called the axon initial segment (AIS). It was recently proposed that at the onset of an AP the soma and the AIS form a dipole. We study the extracellular signature [the extracellular AP (EAP)] generated by such a dipole. First, we demonstrate the formation of the dipole and its extracellular signature in detailed morphological models of a reconstructed pyramidal neuron. Then, we study the EAP waveform and its spatial dependence in models with axonal AP initiation and contrast it with the EAP obtained in models with somatic AP initiation. We show that in the models with axonal AP initiation the dipole forms between somatodendritic compartments and the AIS, and not between soma and dendrites as in the classical models. The soma–dendrites dipole is present only in models with somatic AP initiation. Our study has consequences for interpreting extracellular recordings of single-neuron activity and determining electrophysiological neuron types, but also for better understanding the origins of the high-frequency macroscopic extracellular potentials recorded in the brain.
Hydrogen Sulfide Reverses Aging-Associated Amygdalar Synaptic Plasticity and Fear Memory Deficits in Rats

As an endogenous neuromodulator, hydrogen sulfide (H2S) exerts multiple biological effects in the brain. Previous studies have shown that H2S is involved in the regulation of neural synaptic plasticity and cognition in healthy rodents. It is well known that there is a progressive decline of cognitive function that occurs with increased age. The purpose of this study was to investigate the role of H2S in aging-associated amygdalar synaptic plasticity and cued fear memory deficits as well as to explore the underlying mechanisms. We found that H2S levels in the amygdala were significantly lower in aged rats when compared with healthy adult rates, which displayed significant deficits in long-term potentiation (LTP) in the thalamo-lateral amygdala (LA) pathway and amygdala-dependent cued fear memory. Bath application of an H2S donor, sodium hydrogen sulfide (NaHS), significantly reversed the impaired LTP in brain slices from aged rats, and intra-LA infusion of NaHS restored the cued fear memory in aged rats. Mechanismly, we found that H2S treatment significantly enhanced NMDAR-mediated synaptic responses in the thalamo-LA pathway of aged rats. Notably, GluN2B-containing NMDARs, but not GluN2A-containing NMDARs, contributed to the effects of H2S on aging-associated impairments of amygdalar LTP and fear memory, because applying GluN2B antagonist could abolish the beneficial effects of NaHS treatment on amygdalar LTP and cognitive performance in aged rats. Collectively, these results show that H2S can reverse aging-associated amygdalar synaptic plasticity and fear memory deficits by restoring the function of GluN2B-containing NMDARs, suggesting that supplement of H2S might be a therapeutic approach for aging-related cognitive disorders.
Prevalence of Obsessive-Compulsive Spectrum Disorders in Obsessive-Compulsive Disorder

Introduction: There is growing awareness of the heterogeneity of obsessive-compulsive disorder (OCD) and of the multiple systems involved in its pathogenesis. Identification of obsessive-compulsive spectrum disorders (OCSDs) may have important implications in the management and prognosis of OCD, but there is a paucity of research in the domain of identification of OCSD in probands with OCD. There are few studies that have examined OCSD in the first-degree relatives (FDR) of OCD patients, some of these were not controlled, and these studies have no final agreements over outcomes, and therefore, this area needs to be further explored. Objectives: The objective of this study was to assess the prevalence of OCSDs in OCD probands; and its relationship to sociodemographic and clinical variables, comparing each aspect by a control group of schizophrenia probands. Materials and Methods: Sixty patients each of OCD and schizophrenia, diagnosed by the Diagnostic and Statistical Manual of Mental Disorders IV Text Revision,[1] above 18 years of age and giving informed consent, were interviewed using the Structured Clinical Interview for OCSD, Yale–Brown Obsessive-Compulsive Rating Scale, Hamilton Rating Scale for Depression, and Hamilton Rating Scale for Anxiety. Results: In OCD group, 22 OCSDs were found in 11 subjects whereas in schizophrenia group, 2 OCSDs (self-injury) were found in two probands. When the two groups were compared in terms of individual OCSDs, there was no significant difference between them. However, when the comparison was made taking into account all OCSDs taken together, it was significantly higher (P = 0.016) in the OCD group compared to the schizophrenia group. Conclusion: OCSDs were significantly more in OCD probands as compared to schizophrenia probands. This suggests a familial aggregation of these disorders.
Self-reported adherence supports patient preference for the single tablet regimen (STR) in the current cART era

Objective To analyze self-reported adherence to antiretroviral regimens containing ritonavir-boosted protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTI), raltegravir, and maraviroc. Methods Overall, 372 consecutive subjects attending a reference center for HIV treatment in Florence, Italy, were enrolled in the study, from December 2010 to January 2012 (mean age 48 years). A self-report questionnaire was filled in. Patients were defined as “nonadherent” if reporting one of the following criteria: <90% of pills taken in the last month, ≥1 missed dose in the last week, spontaneous treatment interruptions reported, or refill problems in the last 3 months. Gender, age, CD4, HIV-RNA, years of therapy, and type of antiretroviral regimen were analyzed with respect to adherence. Results At the time of the questionnaire, 89.8% of patients had <50 copies/mL HIV-RNA and 14.2% were on their first combined antiretroviral therapy. 57% of patients were prescribed a regimen containing ritonavir boosted protease inhibitors (boosted PI), 41.7% NNRTI, 17.2% raltegravir, and 4.8% maraviroc; 49.5% of the subjects were on bis-in-die regimens, while 50.5% were on OD regimens, with 23.1% of these on the single tablet regimen (STR): tenofovir/emtricitabine/efavirenz. The nonadherence proportion was lower in NNRTI than in boosted-PI treatments (19.4% vs 30.2%), and even lower in STR patients (17.4%). In multivariable logistic regression, patients with the NNRTI regimen (OR: 0.56, 95% CI: 0.34–0.94) and the STR (OR: 0.45, 95% CI: 0.22–0.92) reported lower nonadherence. Efavirenz regimens were also associated with lower nonadherence (OR: 0.42, 95% CI: 0.21–0.83), while atazanavir/ritonavir regimens were associated with higher nonadherence. No other relation to specific antiretroviral drugs was found. A higher CD4 count, lower HIV-RNA, and older age were also found to be associated with lower nonadherence, while a longer time on combined antiretroviral therapy was related to higher nonadherence. Conclusion STR maintains an advantage in improving adherence with respect to other combined antiretroviral therapies, even though new antiretroviral drugs and drug classes have become available in recent years.
Adequate statistical power in clinical trials is associated with the combination of a male first author and a female last author

Clinical trials have a vital role in ensuring the safety and efficacy of new treatments and interventions in medicine. A key characteristic of a clinical trial is its statistical power. Here we investigate whether the statistical power of a trial is related to the gender of first and last authors on the paper reporting the results of the trial. Based on an analysis of 31,873 clinical trials published between 1974 and 2017, we find that adequate statistical power was most often present in clinical trials with a male first author and a female last author (20.6%, 95% confidence interval 19.4-21.8%), and that this figure was significantly higher than the percentage for other gender combinations (12.5-13.5%; P<0.0001). The absolute number of female authors in clinical trials gradually increased over time, with the percentage of female last authors rising from 20.7% (1975-85) to 28.5% (after 2005). Our results demonstrate the importance of gender diversity in research collaborations and emphasize the need to increase the number of women in senior positions in medicine.
Heterozygosity–fitness correlation at the major histocompatibility complex despite low variation in Alpine ibex (Capra ibex)

Crucial for the long‐term survival of wild populations is their ability to fight diseases. Disease outbreaks can lead to severe population size reductions, which makes endangered and reintroduced species especially vulnerable. In vertebrates, the major histocompatibility complex (MHC) plays an important role in determining the immune response. Species that went through severe bottlenecks often show very low levels of genetic diversity at the MHC. Due to the known link between the MHC and immune response, such species are expected to be at particular risk in case of disease outbreaks. However, so far, only few studies have shown that low MHC diversity is correlated with increased disease susceptibility in species after severe bottlenecks. We investigated genetic variation at the MHC and its correlations with disease resistance and other fitness‐related traits in Alpine ibex (Capra ibex), a wild goat species that underwent a strong bottleneck in the last century and that is known to have extremely low genetic variability, both genome‐wide and at the MHC. We studied MHC variation in male ibex of Gran Paradiso National Park, the population used as a source for all postbottleneck reintroductions. We found that individual MHC heterozygosity (based on six microsatellites) was not correlated with genome‐wide neutral heterozygosity. MHC heterozygosity, but not genome‐wide heterozygosity, was positively correlated with resistance to infectious keratoconjunctivitis and with body mass. Our results show that genetic variation at the MHC plays an important role in disease resistance and, hence, should be taken into account for successfully managing species conservation.
Real-time Surgical Tools Recognition in Total Knee Arthroplasty Using Deep Neural Networks

Total knee arthroplasty (TKA) is a surgical procedure to mitigate knee pain and improve functions for people with knee arthritis. The procedure is complicated due to the different surgical tools used in the stages of surgery. Real-time surgical tool recognition can be used to simplify surgical procedures for the surgeon. Also, the presence and movement of tools in surgery are crucial information for the recognition of the operational phase and to identify the surgical workflow. Therefore, this research proposes a real-time system for recognizing surgical tools using a convolutional neural network (CNN). Surgeons wearing smart glasses can see essential information about tools during surgery that may reduce the complication of the procedures. The performance of the proposed method was evaluated by using mean average precision (MAP) with conventional methods which are fast R-CNN and deformable part models. We achieved 87.6% mAP which is better in comparison to the existing methods. With the additional improvements of our proposed method, it can be a future point of reference, also the baseline for operational phase recognition.
Topic and Keyword Identification for Low-resourced Speech Using Cross-Language Transfer Learning

This paper studies topic and keyword identiﬁcation for languages in which we have no transcribed speech data. We adopt a transfer learning framework to transfer what is learned from rich-resourced languages (RRL) to low-resourced languages (LRL). Speciﬁcally, we propose that a convolutional neural network (CNN) trained as a topic classiﬁer in an RRL learns features (hidden layer activations) that can be used for the same purpose in an LRL. The CNN observes acoustic features, RRL phones, or segment clusters generated by an unsupervised phone clustering system; its hidden layers are retained, and its output layer re-trained from scratch on the LRL. Our results are compared with the state-of-the-art topic classiﬁcation methods on cross-language ASR transcripts. We also discuss the successful detection of topic dependent keywords and the use of unsupervised learning based clusters in our approach for low-resourced language topic detection.