Miracle-dz/UniFAR-FTUs huggingface dataset:
Unified Hypersphere Embedding for Speaker Recognition

Incremental improvements in accuracy of Convolutional Neural Networks are usually achieved through use of deeper and more complex models trained on larger datasets. However, enlarging dataset and models increases the computation and storage costs and cannot be done indefinitely. In this work, we seek to improve the identification and verification accuracy of a text-independent speaker recognition system without use of extra data or deeper and more complex models by augmenting the training and testing data, finding the optimal dimensionality of embedding space and use of more discriminative loss functions. Results of experiments on VoxCeleb dataset suggest that: (i) Simple repetition and random time-reversion of utterances can reduce prediction errors by up to 18%. (ii) Lower dimensional embeddings are more suitable for verification. (iii) Use of proposed logistic margin loss function leads to unified embeddings with state-of-the-art identification and competitive verification accuracies.
Adaptation and Therapeutic Exploitation of the Plasma Membrane of African Trypanosomes

African trypanosomes are highly divergent from their metazoan hosts, and as part of adaptation to a parasitic life style have developed a unique endomembrane system. The key virulence mechanism of many pathogens is successful immune evasion, to enable survival within a host, a feature that requires both genetic events and membrane transport mechanisms in African trypanosomes. Intracellular trafficking not only plays a role in immune evasion, but also in homeostasis of intracellular and extracellular compartments and interactions with the environment. Significantly, historical and recent work has unraveled some of the connections between these processes and highlighted how immune evasion mechanisms that are associated with adaptations to membrane trafficking may have, paradoxically, provided specific sensitivity to drugs. Here, we explore these advances in understanding the membrane composition of the trypanosome plasma membrane and organelles and provide a perspective for how transport could be exploited for therapeutic purposes.
Feeling for and as a group member: Understanding LGBT victimization via group‐based empathy and intergroup emotions

In two experimental studies (N = 120; N = 102), we apply intergroup emotions theory (IET) to examine the effects of hate crime on other community members. With participants from an oft-targeted group - Lesbian, Gay, Bisexual, and Trans people, we are the first to show empirically that hate crimes elicit more pronounced emotional and behavioural responses in other members of the victims' community than comparable non-hate crimes. The findings also reveal the psychological processes behind these effects. Consistent with IET, hate crimes were seen to pose more of a group-based threat and so led to heightened emotional reactions (anger and anxiety) and, subsequently, to behavioural intentions (avoidance and pro-action). Importantly, we also show that hate crime victims, due to increased perceptions of similarity, received more empathy than non-hate crime victims. Such empathy, although neglected in previous research, was shown to be a potential mediator in understanding the indirect effects of hate crime. Results are discussed in terms of their contribution to psychological theory and their potential to support the argument for the utility and appropriateness of hate crime legislation.
Early Exposure to Child Maltreatment and Academic Outcomes

Early childhood trauma increases the risk of academic difficulties. The purpose of this study was to investigate the prevalence of early contact with child protection services (CPS) and to determine whether early exposure to maltreatment investigations was associated with important academic outcomes. The authors focused specifically on standardized test scores (math and reading), grade retention, and special education status in third grade. The sample was diverse and included all children born between 2000 and 2006 and enrolled in Michigan’s public schools (N = 732,838). By the time these students reached third grade, approximately 18% were associated with a formal CPS investigation. In some school districts, more than 50% of third graders were associated with an investigation. African American and poor students were more likely to be investigated for maltreatment. Children associated with maltreatment investigations scored significantly lower on standardized math and reading tests, were more likely to be identified as needing special education, and were more likely to be held back at least one grade. These findings indicate that involvement with CPS is not an infrequent event in the lives of young children and that within some school districts, maltreatment investigations are the norm. Child welfare and educational systems must collaborate so that the early academic struggles experienced by victims of maltreatment do not mature into more complicated difficulties later in life.
The POST trial: initial post-market experience of the Penumbra system: revascularization of large vessel occlusion in acute ischemic stroke in the United States and Europe

Background and purpose The purpose of this study was to assess the initial post-market experience of the device and how it is compared with the Penumbra Pivotal trial used to support the 510k application. Methods A retrospective case review of 157 consecutive patients treated with the Penumbra system at seven international centers was performed. Primary endpoints were revascularization of the target vessel (TIMI score of 2 or 3), good functional outcome as defined by a modified Rankin scale (mRS) score of ≤2 and incidence of procedural serious adverse events. Results were compared with those of the Penumbra pivotal trial. Results A total of 157 vessels were treated. Mean baseline values at enrollment were: age 65 years, NIHSS score 16. After use of the Penumbra system, 87% of the treated vessels were revascularized to TIMI 2 (54%) or 3 (33%) as compared with 82% reported in the Pivotal trial. Nine procedural serious adverse events were reported in 157 patients (5.7%). All-cause mortality was 20% (32/157), and 41% had a mRS of ≤2 at 90-day follow-up as compared with only 25% in the Pivotal trial. Patients who were successfully revascularized by the Penumbra system had significantly better outcomes than those who were not. Conclusion Initial post-market experience of the Penumbra system revealed that the revascularization rate and safety profile of the device are comparable to those reported in the Pivotal trial. However, the proportion of patients who had good functional outcome was higher than expected.
Parental Presence and Activities in a Dutch Neonatal Intensive Care Unit: An Observational Study

The presence of parents during a neonatal intensive care unit (NICU) admission is important for the well-being of both infants and their parents. Therefore, the aim of this study was to identify parental presence in terms of frequency, duration, and activities in the NICU in relation to characteristics of both infants and parents. An observational study was performed in a Dutch level III NICU. All infants admitted for more than 24 hours were included. One hundred sixty-two infants were included. For a median duration of 3 to 4 hours a day, at least one of the parents was present. After the first week after birth, 80% of both parents participated in the care of their infant. A vaginal delivery, longer duration of kangaroo care, higher birth weight, bronchopulmonary dysplasia, being a first child, the second and following admission week(s) after birth, and a short driving distance led to a significantly longer duration of presence for both parents. Mothers were present for a significantly longer duration of time than fathers (P = .00). It is recommended that public and employer policies, as well as physical conditions and necessary facilities, in the NICU be examined for their support of parental presence.
Conditionally Poissonian random digraphs

In this short note we define a Poissonian model of directed random graphs which generalises the undirected Poissonian random graph process introduced in [Norros, I. ; Reittu, H. "On a conditionally Poissonian graph process. " Adv. in Appl. Probab. 38 (2006), no. 1, 59--75]. We discuss the relation of our model to the Norros-Reittu model, characterise the limiting distribution of the degree of a typical vertex and discuss the component structure of the model in some special cases which are relevant to the theory of infection processes.
Network Pharmacology Uncovers Anticancer Activity of Mammea-Type Coumarins from Calophyllum brasiliense

Abstract Mammea-type coumarins are a particular type of secondary metabolites biosynthesized by the tropical rainforest tree Calophyllum Brasiliense, which is distributed from South America to Mexico. Particularly, mammea A/BA and A/BB (alone or as a mixture) possess biological properties such as cytotoxic and antitumoral activities, however, most of its molecular targets remain unknown. In this context, novel bioinformatic approaches, such as network pharmacology analysis, have been successfully used in herbal medicine to accelerate research in this field, and the support of experimental validations has been shown to be quite robust. In the present study, we performed a network pharmacology analysis to assess the possible molecular biological networks that interact with mammea A/BA and A/BB. Moreover, we validated the most relevant networks experimentally in vitro on K562 cancer cells. The results of the network pharmacology analysis indicate that mammea A/BA and A/BB interacts with cell death, PI3K/AKT, MAPK, Ras, and cancer pathways. The in vitro model shows that mammea A/BA and A/BB induce apoptosis through the overexpression of the proapoptotic proteins Bax and Bak, disrupt the autophagic flux as seen by the cytosolic accumulation of LC3-II and p62, disrupting the mitochondria ultrastructure and concomitantly increase the intracellular calcium concentration. Additionally, docking analysis predicted a possible interaction with a rapamycin-binding domain of mTOR. In conclusion, we validated network pharmacology analysis and report, for the first time, that mammea A/BA and A/BB coumarins induce apoptosis through the inhibition of the autophagic flux, possibly interacting with mTOR.
The role of targeted therapy for melanoma in the immunotherapy era

Over the past 10 years of remarkable development of both molecularly targeted and immune-targeted therapy for the treatment of melanoma, a clear preference of immunotherapy over molecularly targeted therapy has emerged among melanoma treatment providers. Still, the clinical data remain remarkable for patients with BRAF-mutant stage III and IV melanoma, and there seems to be a clear benefit of BRAF-targeted therapy for these patients. The key, then, is to identify the best way to use BRAF-targeted therapy. In this review, the clinical data of molecular-targeted therapy are summarized, mechanisms of resistance to single-agent BRAF and combined BRAF with mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor are discussed, and strategies to overcome this resistance are presented; then, we review a number of clinical dilemmas that influence the decision-making of using targeted therapy over immunotherapy, and vice-versa, and help define the specific role of targeted therapy in the immunotherapy era.
Neural detection of socially valued community members

Significance To form successful communities, people must be able to detect socially valued individuals: people who are generous, supportive, and well-connected. Here, we provide evidence that people accomplish this detection by monitoring how the broader community views individuals. We used social network analysis to identify highly socially valued individuals in two college dormitories. We then scanned dorm residents using fMRI as they passively viewed pictures of dormmates. Activity in brain systems related to mentalizing and reward increased when people viewed highly valued, versus less valued, dormmates—even when controlling for individuals’ own impressions of their dormmates. These data suggest that people robustly monitor peers’ social value, potentially allowing them to efficiently locate high-quality social ties. As people form social groups, they benefit from being able to detect socially valuable community members—individuals who act prosocially, support others, and form strong relationships. Multidisciplinary evidence demonstrates that people indeed track others’ social value, but the mechanisms through which such detection occurs remain unclear. Here, we combine social network and neuroimaging analyses to examine this process. We mapped social networks in two freshman dormitories (n = 97), identifying how often individuals were nominated as socially valuable (i.e., sources of friendship, empathy, and support) by their peers. Next, we scanned a subset of dorm members (“perceivers”; n = 50) as they passively viewed photos of their dormmates (“targets”). Perceiver brain activity in regions associated with mentalizing and value computation differentiated between highly valued targets and other community members but did not differentiate between targets with middle versus low levels of social value. Cross-validation analysis revealed that brain activity from novel perceivers could be used to accurately predict whether targets viewed by those perceivers were high in social value or not. These results held even after controlling for perceivers’ own ratings of closeness to targets, and even though perceivers were not directed to focus on targets’ social value. Overall, these findings demonstrate that individuals spontaneously monitor people identified as sources of strong connection in the broader community.
Elesclomol restores mitochondrial function in genetic models of copper deficiency

Significance Inherited pathogenic mutations in genes required for copper delivery to cytochrome c oxidase (CcO) perturb mitochondrial energy metabolism and result in fatal mitochondrial disease. A prior attempt to treat human patients with these mutations by direct copper supplementation was not successful, possibly because of inefficient copper delivery to the mitochondria. We performed a targeted search to identify compounds that can efficiently transport copper across biological membranes and identified elesclomol (ES), an investigational anticancer drug, as the most efficient copper delivery agent. ES rescues CcO function in yeast, zebrafish, and mammalian models of copper deficiency by increasing cellular and mitochondrial copper content. Thus, our study offers a possibility of repurposing this anticancer drug for the treatment of disorders of copper metabolism. Copper is an essential cofactor of cytochrome c oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain. Inherited loss-of-function mutations in several genes encoding proteins required for copper delivery to CcO result in diminished CcO activity and severe pathologic conditions in affected infants. Copper supplementation restores CcO function in patient cells with mutations in two of these genes, COA6 and SCO2, suggesting a potential therapeutic approach. However, direct copper supplementation has not been therapeutically effective in human patients, underscoring the need to identify highly efficient copper transporting pharmacological agents. By using a candidate-based approach, we identified an investigational anticancer drug, elesclomol (ES), that rescues respiratory defects of COA6-deficient yeast cells by increasing mitochondrial copper content and restoring CcO activity. ES also rescues respiratory defects in other yeast mutants of copper metabolism, suggesting a broader applicability. Low nanomolar concentrations of ES reinstate copper-containing subunits of CcO in a zebrafish model of copper deficiency and in a series of copper-deficient mammalian cells, including those derived from a patient with SCO2 mutations. These findings reveal that ES can restore intracellular copper homeostasis by mimicking the function of missing transporters and chaperones of copper, and may have potential in treating human disorders of copper metabolism.
Rationale and Protocol for a Randomized Controlled Trial Comparing Fast versus Slow Weight Loss in Postmenopausal Women with Obesity—The TEMPO Diet Trial

Very low energy diets (VLEDs), commonly achieved by replacing all food with meal replacement products and which result in fast weight loss, are the most effective dietary obesity treatment available. VLEDs are also cheaper to administer than conventional, food-based diets, which result in slow weight loss. Despite being effective and affordable, these diets are underutilized by healthcare professionals, possibly due to concerns about potential adverse effects on body composition and eating disorder behaviors. This paper describes the rationale and detailed protocol for the TEMPO Diet Trial (Type of Energy Manipulation for Promoting optimal metabolic health and body composition in Obesity), in a randomized controlled trial comparing the long-term (3-year) effects of fast versus slow weight loss. One hundred and one post-menopausal women aged 45–65 years with a body mass index of 30–40 kg/m2 were randomized to either: (1) 16 weeks of fast weight loss, achieved by a total meal replacement diet, followed by slow weight loss (as for the SLOW intervention) for the remaining time up until 52 weeks (“FAST” intervention), or (2) 52 weeks of slow weight loss, achieved by a conventional, food-based diet (“SLOW” intervention). Parameters of body composition, cardiometabolic health, eating disorder behaviors and psychology, and adaptive responses to energy restriction were measured throughout the 3-year trial.
Willingness to participate in HIV research at the end of life (EOL)

Introduction Animal models have been vital for scientific discovery but have limitations, especially in infectious disease research. It is essential to develop a means to study these diseases in human models. We hypothesized that altruistic people would willingly participate in research near the end-of-life (EOL), for the benefit of science and to provide one last gift to society. Methodology Two surveys were administered to 377 self-reported HIV-negative and 96 HIV-positive individuals. Hypothetical questions assessed their willingness to participate in altruistic research in the last 6 months of life, which might result in a shortened lifespan or physical discomforts. The self-reported HIV-negative group was also asked about willingness to be exposed to infectious pathogens for the sake of research. Results Almost all responders expressed willingness to participate in research at the EOL, regardless of HIV-status. The majority of participants were willing to endure physical discomfort for the sake of research. ‘Blood draws’ was identified as the most tolerable physical discomfort (>70% in both groups). In both groups, >60% were willing to shorten their lifespans for the sake of research. A third of the self-reported HIV-negative group expressed willingness to be exposed to at least one infectious agent to participate in EOL research. Conclusions Our exploratory study demonstrates that people would welcome the opportunity to participate in altruistic research near the EOL. Such research could greatly impact the way infectious disease research is conducted. This study is limited however by its hypothetical nature. Further research is necessary to confirm this interest in those with terminal illness before any further clinical research effort at the EOL can be performed.
Heterogeneity in local density allows a positive evolutionary relationship between self-fertilisation and dispersal

Theoretical work predicts that dispersal and self-fertilisation (selfing) should always be negatively correlated and the Good Coloniser Syndrome (GCS) of high dispersal and selfing should not occur when both traits are free to evolve. This contradicts positive relationships between selfing and dispersal in empirical data. Critically, previous work assumes density of adults is spatially and temporally homogeneous, so selfing results in homogeneity in propagule production and competition, which eliminates the benefit of dispersal for escaping from local resource competition. We investigate the joint evolution of dispersal and selfing in a demographically structured metapopulation model where local density varies due to stochastic extinction-recolonisation dynamics. Increasing local extinction rate reduces local density across the metapopulation, which favours high selfing to mitigate mate limitation, but increases heterogeneity in density, which favours high dispersal for escape from competition. Together, these effects produce a positive relationship between selfing and dispersal, and evolution of the GCS. Nevertheless, the relationship between selfing and dispersal is context-dependent, as varying dispersal cost yields a negative relationship. Our results imply that if spatiotemporal heterogeneity in environmental suitability increases towards the range edge, the GCS may evolve there, favouring further range expansion (Cf. Baker’s Law).
Suboptimal Iodine Status and Low Iodine Knowledge in Young Norwegian Women

Previous studies have documented mild to moderate iodine deficiency in pregnant and lactating women in Norway. This study focused on non-pregnant young women because their future children may be susceptible to the adverse effects of iodine deficiency. We assessed urinary iodine concentration (UIC), iodine intake from food and supplements, and iodine knowledge in 403 non-pregnant women, mainly students, aged 18–30 years. Iodine concentration was measured in spot urine samples analyzed by inductively coupled plasma mass spectrometry and iodine intake was calculated from a self-reported food frequency questionnaire. Knowledge about iodine was collected through the self-administered, paper-based questionnaire. Median (p25–p75) UIC was 75 (42–130) µg/L and 31% had UIC < 50 µg/L. Habitual iodine intake was 100 (69–136) µg/day. In multiple regression models, supplemental iodine, use of thyroid medication, and iodine intake from food were positively associated with UIC, while vegetarian practice was negatively associated, explaining 16% of the variance. Approximately 40% of the young women had low iodine knowledge score and no differences were found between women in different study programs. Young women in Norway are mild to moderately iodine-deficient, and public health strategies are needed to improve and secure adequate iodine status.
Children Residing in Low-Income Households Like a Variety of Vegetables

Child vegetable intake falls far below the minimum recommended levels. Knowing which vegetables children may like help those responsible for providing vegetables to children to improve intake. The objective of this study was to measure vegetable liking for a wide variety of vegetables by a racially and ethnically diverse population of 9–12-year old children from low-income families. Children rated their liking of 35 vegetables using a 10-point hedonic scale. We tabulated the number of children that found each vegetable acceptable (ratings of ‘okay’ or above) and the number that found each vegetable unacceptable (ratings below ‘okay’). More than 50% of children who had tried a vegetable considered it acceptable. A large majority of the vegetables had mean ratings in the acceptable range. Corn was the most liked vegetable, closely followed by potatoes, lettuce, and carrots. Artichoke had the lowest mean liking, followed by onion and beets. We found children liked a wide variety of vegetables which offers counter evidence to the commonly held perception that children do not like vegetables.