Miracle-dz/UniFAR-FTUs huggingface dataset:
Knockdown of heterochromatin protein 1 binding protein 3 recapitulates phenotypic, cellular, and molecular features of aging

Identifying genetic factors that modify an individual's susceptibility to cognitive decline in aging is critical to understanding biological processes involved and mitigating risk associated with a number of age‐related disorders. Recently, heterochromatin protein 1 binding protein 3 (Hp1bp3) was identified as a mediator of cognitive aging. Here, we provide a mechanistic explanation for these findings and show that targeted knockdown of Hp1bp3 in the hippocampus by 50%–75% is sufficient to induce cognitive deficits and transcriptional changes reminiscent of those observed in aging and Alzheimer's disease brains. Specifically, neuroinflammatory‐related pathways become activated following Hp1bp3 knockdown in combination with a robust decrease in genes involved in synaptic activity and neuronal function. To test the hypothesis that Hp1bp3 mediates susceptibility to cognitive deficits via a role in neuronal excitability, we performed slice electrophysiology demonstrate transcriptional changes after Hp1bp3 knockdown manifest functionally as a reduction in hippocampal neuronal intrinsic excitability and synaptic plasticity. In addition, as Hp1bp3 is a known mediator of miRNA biogenesis, here we profile the miRNA transcriptome and identify mir‐223 as a putative regulator of a portion of observed mRNA changes, particularly those that are inflammatory‐related. In summary, work here identifies Hp1bp3 as a critical mediator of aging‐related changes at the phenotypic, cellular, and molecular level and will help inform the development of therapeutics designed to target either Hp1bp3 or its downstream effectors in order to promote cognitive longevity.
Combining multimodal imaging and treatment features improves machine learning‐based prognostic assessment in patients with glioblastoma multiforme

For Glioblastoma (GBM), various prognostic nomograms have been proposed. This study aims to evaluate machine learning models to predict patients' overall survival (OS) and progression‐free survival (PFS) on the basis of clinical, pathological, semantic MRI‐based, and FET‐PET/CT‐derived information. Finally, the value of adding treatment features was evaluated.
Enhanced Transparency for Physical Human-Robot Interaction Using Human Hand Impedance Compensation

In a physical human-robot interaction (pHRi) system, improving transparency that allows humans to move as if there is no robot is a challenging topic. In general pHRi, usage of the multiaxial force sensor for robot control is the norm. However, the signal measured from the force sensor contains not only the force applied to the robot by the human motion intention but also the influence of the natural force feedback between the robot and the human hand produced by the robot motion. Therefore, in order to improve the transparency, it is necessary to characterize the dynamics of the human hand as well as the dynamics of the robot. In this paper, an algorithm to improve the transparency is proposed. The proposed algorithm uses only a multiaxial force sensor and compensates the natural force feedback by using the human hand impedance. And it further improves the transparency of the pHRi system, which has a limitation adjusting admittance parameters. In order to verify the algorithm, a device that can measure the impedance of the human hand is introduced, and a system model analysis and experiments using the hydraulic upper limb exoskeleton are carried out.
Effects of Malaria in the First Trimester of Pregnancy on Poor Maternal and Birth Outcomes in Benin.

Background In sub-Saharan Africa, malaria in the first half of pregnancy is harmful for both the mother and her fœtus. However, malaria in the 1st trimester of pregnancy, when women are usually not protected against malaria, has been little investigated. For the first time, we assessed the effects of malaria in the 1st trimester on maternal and birth outcomes using a preconceptional study design. Methods From June 2014 to March 2017, 1214 women of reproductive age were recruited and followed monthly until 411 became pregnant. Pregnant women were then followed from 5-6 weeks of gestation until delivery. Path analysis was used to assess the direct effect (i.e., not mediated by malaria in the 2nd or 3rd trimester) of malaria in the 1st trimester on maternal anaemia and poor birth outcomes. The cumulative effect of infections during pregnancy on the same outcomes was also evaluated. Results The prevalence of malaria infection in the 1st trimester was 21.8%. Malaria in the 1st trimester was significantly associated with maternal anaemia in the 3rd trimester (adjusted odds ratio [aOR]: 2.25, 95% CI 1.11, 4.55). While we did not evidence any direct effect of 1st trimester malaria infections on birth outcomes, their association with infections later in pregnancy tended to increase the risk of low birthweight. Conclusions alaria infections in the 1st trimester were highly prevalent and have deleterious effects on maternal anaemia. They highlight the need for additional preventive measures starting in early pregnancy, or even before conception.
Sleep Deprivation Selectively Upregulates an Amygdala–Hypothalamic Circuit Involved in Food Reward

Sleep loss is associated with increased obesity risk, as demonstrated by correlations between sleep duration and change in body mass index or body fat percentage. Whereas previous studies linked this weight gain to disturbed endocrine parameters after sleep deprivation or restriction, neuroimaging studies revealed upregulated neural processing of food rewards after sleep loss in reward-processing areas such as the anterior cingulate cortex, ventral striatum, and insula. To address this ongoing debate between hormonal versus hedonic factors underlying sleep-loss-associated weight gain, we rigorously tested the association between sleep deprivation and food cue processing using high-resolution fMRI and assessment of hormones. After taking blood samples from 32 lean, healthy, human male participants, they underwent fMRI while performing a neuroeconomic, value-based decision-making task with snack food and trinket rewards following a full night of habitual sleep and a night of sleep deprivation in a repeated-measures crossover design. We found that des-acyl ghrelin concentrations were increased after sleep deprivation compared with habitual sleep. Despite similar hunger ratings due to fasting in both conditions, participants were willing to spend more money on food items only after sleep deprivation. Furthermore, fMRI data paralleled this behavioral finding, revealing a food-reward-specific upregulation of hypothalamic valuation signals and amygdala–hypothalamic coupling after a single night of sleep deprivation. Behavioral and fMRI results were not significantly correlated with changes in acyl, des-acyl, or total ghrelin concentrations. Our results suggest that increased food valuation after sleep loss might be due to hedonic rather than hormonal mechanisms. SIGNIFICANCE STATEMENT Epidemiological studies suggest an association between overweight and reduced nocturnal sleep, but the relative contributions of hedonic and hormonal factors to overeating after sleep loss are a matter of ongoing controversy. Here, we tested the association between sleep deprivation and food cue processing in a repeated-measures crossover design using fMRI. We found that willingness to pay increased for food items only after sleep deprivation. fMRI data paralleled this behavioral finding, revealing a food-reward-specific upregulation of hypothalamic valuation signals and amygdala-hypothalamic coupling after a single night of sleep deprivation. However, there was no evidence for hormonal modulations of behavioral or fMRI findings. Our results suggest that increased food valuation after sleep loss is due to hedonic rather than hormonal mechanisms.
Deoxynivalenol Impairs Porcine Intestinal Host Defense Peptide Expression in Weaned Piglets and IPEC-J2 Cells

Host defense peptides (HDPs) are efficient defense components of the innate immune system, playing critical roles in intestinal homeostasis and protection against pathogens. This study aims to investigate the interference effects of DON on the intestinal porcine HDPs expression in piglets and intestinal porcine epithelial cell line (IPEC-J2) cells, and elucidate the underlying mechanisms through which it functions. In an animal experiment, intestinal HDPs were determined in weaned piglets fed control and 1.28 mg/kg or 2.89 mg/kg DON-contaminated diets. Dietary exposure to DON significantly decreased piglet average daily gain, increased intestinal permeability and depressed the expression of porcine β-defensin1 (pBD1), pBD2, pBD3, epididymis protein 2 splicing variant C (pEP2C), PMAP23, and proline/arginine-rich peptide of 39 amino acids (PR39) in the intestine (p < 0.05). In IPEC-J2 cells, DON decreased cell viability and inhibited the expression of pBD1, pBD3, pEP2C, PG1-5, and PR39 (p < 0.05). NOD2, key regulator that is responsible for HDPs production, was markedly downregulated, whereas caspase-12 was activated in the presence of DON. In conclusion, DON induced caspase-12 activation and inhibited the NOD2-mediated HDPs production, which led to an impaired intestinal barrier integrity of weaned piglets. Our study provides a promising target for future therapeutic strategies to prevent the adverse effects of DON.
Optimal Decentralized Output-Feedback LQG Control With Random Communication Delay

This paper is concerned with the optimal decentralized output-feedback control of the large-scale systems. A random information pattern is considered, where the information is transmitted among the subsystems with random communication delays. For the random information pattern, the optimal LQG problems for both global estimation case and local estimation case are studied. It is difficult to derive the optimal controller under random framework, because the gains of the controller must be designed to satisfy the random sparse structure constraints. In this paper, we design the optimal controller by Hadamard product method. For global estimation case, the gains of the controller are obtained by solving linear matrix equation. For local estimation case, an iterative algorithm is exploited to compute the gains. In addition, the value of the cost function achieved by the designed controller is found and shown to monotonically increase with the increase of the delay probability for both global and local estimation cases. Finally, the theoretical results are illustrated by two numerical examples.
Assessment of Burden Among Family Caregivers of Schizophrenia: Psychometric Testing for Short-Form Zarit Burden Interviews

Objective: Although various short forms of Zarit Burden Interview (ZBI) have been developed, there is a lack of standard psychometric testing and comparison among them. The study aims to examine the psychometric properties of ten short versions of the most frequently used ZBI among a sample of schizophrenia caregivers and to find the one with the best performance. Methods: Cross-sectional door-to-door survey of ZBI-22 and a series of validated instrument data from 327 family caregivers of schizophrenia patients in a Chinese rural community were conducted from October 2015 to January 2016. Reliability was assessed using McDonald's omega coefficient (ω). Validity including concurrent validity, known group's validity, and criterion validity were assessed by Spearman correlations and Mann-Whitney U tests. Overall discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Results: Reliability was generally good for all short forms (ω = 0.69–0.84), except for the Gort ZBI-4 (ω = 0.58), which is acceptable considering its small item numbers. Concurrent validity was good across all various ZBI forms with significant negative correlations with patient's function (r = −0.34 to −0.48, p < 0.01), as well as significant positive correlations with caregiver's depression (r = 0.49–0.65, p < 0.01), and anxiety symptoms (r = 0.45–0.58, p < 0.01). Known groups' validity (carers with disease vs. without disease; carers being parents vs. spouse vs. others) showed inconsistent results among various short forms. Criterion validity was generally good for all short forms with significant positive correlations with Family Burden Interview Schedule (r = 0.67–0.75, p < 0.01), except for the Higginson ZBI-1(r = 0.57, p < 0.01). Discriminative ability was also good for all short forms (AUC range: 0.85–0.99), with various cutpoints proposed. Among all ten short forms, the Ballesteros ZBI-12 and the Gort ZBI-7 outperformed others with almost equally good performance in comprehensive psychometric testing. Conclusions: This study provides support for the reliability, validity, and discriminative ability of the ten various short forms of ZBI for use among schizophrenia family caregivers, with the Ballesteros ZBI-12 and the Gort ZBI-7 endorsed as the best ones.
EventNet: Asynchronous Recursive Event Processing

Event cameras are bio-inspired vision sensors that mimic retinas to asynchronously report per-pixel intensity changes rather than outputting an actual intensity image at regular intervals. This new paradigm of image sensor offers significant potential advantages; namely, sparse and non-redundant data representation. Unfortunately, however, most of the existing artificial neural network architectures, such as a CNN, require dense synchronous input data, and therefore, cannot make use of the sparseness of the data. We propose EventNet, a neural network designed for real-time processing of asynchronous event streams in a recursive and event-wise manner. EventNet models dependence of the output on tens of thousands of causal events recursively using a novel temporal coding scheme. As a result, at inference time, our network operates in an event-wise manner that is realized with very few sum-of-the-product operations---look-up table and temporal feature aggregation---which enables processing of 1 mega or more events per second on standard CPU. In experiments using real data, we demonstrated the real-time performance and robustness of our framework.
Personal Mutanomes Meet Modern Oncology Drug Discovery and Precision Health

Recent remarkable advances in genome sequencing have enabled detailed maps of identified and interpreted genomic variation, dubbed “mutanomes. ” The availability of thousands of exome/genome sequencing data has prompted the emergence of new challenges in the identification of novel druggable targets and therapeutic strategies. Typically, mutanomes are viewed as one- or two-dimensional. The three-dimensional protein structural view of personal mutanomes sheds light on the functional consequences of clinically actionable mutations revealed in tumor diagnosis and followed up in personalized treatments, in a mutanome-informed manner. In this review, we describe the protein structural landscape of personal mutanomes and provide expert opinions on rational strategies for more streamlined oncological drug discovery and molecularly targeted therapies for each individual and each tumor. We provide the structural mechanism of orthosteric versus allosteric drugs at the atom-level via targeting specific somatic alterations for combating drug resistance and the “undruggable” challenges in solid and hematologic neoplasias. We discuss computational biophysics strategies for innovative mutanome-informed cancer immunotherapies and combination immunotherapies. Finally, we highlight a personal mutanome infrastructure for the emerging development of personalized cancer medicine using a breast cancer case study.
Primary care in the Calais Jungle

Backgrou d: Urinary tract infections (UTIs) are one of the most common reasons for women to tte d primary care. The e are four different antibiotics currently recommended in Engl nd for reatme t f uncomplicated UTI bu little evidenc on their comparative c st-effectiveness. Aim: To assess the relative cost-effectiveness of the four antibiotics currently recommended in England for treatment of uncomplicated UTI in adult women. Design & setting: A cost-effectiveness model in adult women with signs and symptoms of uncomplicated UTI in primary care in England treated with fosfomycin, nitrofurantoin, pivmecillinam, or trimethoprim. Method: A decision tree economic model of the treatment pathway encompassed up to two rounds of treatment, accounting for different resistance levels. End points included recovery, persistence, pyelonephritis, and/or hospitalisation. Prescription, primary and secondary care treatment, and diagnostic testing costs were aggregated. Cost-effectiveness was assessed as cost per UTI resolved. Results: Trimethoprim 200 mg twice daily (for 3 or 7 days) was estimated to be the most costeffective trea ment (£70 per UTI resolved) when resistance was <30%. However, if resistance to trimethoprim was 30%, fosfomycin 3 g once became more cost-eff ctive; at esistance levels of 35% for trimethop im, both fosf mycin 3 g once and nitrofurantoin 100 mg twice daily for 7 days were shown to be m re cost-effective. Conclusion: Knowing local resistance levels is key to effective and cost-effective empirical prescribing. Recent estimates of trimethoprim resistance rates are close to 50%, in which case a single 3 g dose of fosfomycin is likely to be the most cost-effective treatment option. How this fits in Four different antibiotics are currently recommended for treatment of uncomplicated urinary tract infection (UTI) in adult women in England. It is usual practice to treat empirically at first presentation, Sadler S et al. BJGP Open 2017; DOI: 10.3399/bjgpopen17X101097 1 of 15 RESEARCH
The unreliability of egocentric bias across self–other and memory–belief distinctions in the Sandbox Task

Humans are often considered egocentric creatures, particularly (and ironically) when we are supposed to take another person's perspective over our own (i.e. when we use our theory of mind). We investigated the underlying causes of this phenomenon. We gave young adult participants a false belief task (Sandbox Task) in which objects were first hidden at one location by a protagonist and then moved to a second location within the same space but in the protagonist's absence. Participants were asked to indicate either where the protagonist remembered the item to be (reasoning about another's memory), believed it to be (reasoning about another's false belief), or where the protagonist would look for it (action prediction of another based on false belief). The distance away from Location A (the original one) towards Location B (the new location) was our measure of egocentric bias. We found no evidence that egocentric bias varied according to reasoning type, and no evidence that participants actually were more biased when reasoning about another person than when simply recalling the first location from memory. We conclude that the Sandbox Task paradigm may not be sensitive enough to draw out consistent effects related to mental state reasoning in young adults.
NPY deficiency prevents postmenopausal adiposity by augmenting estradiol-mediated browning.

The orexigenic hormone neuropeptide Y (NPY) plays a pivotal role in the peripheral regulation of fat metabolism. However, the mechanisms underlying the effects of sex on NPY function have not been extensively analyzed. In this study, we examined the effects of NPY deficiency on fat metabolism in male and female mice. Body weight was slightly decreased, whereas white adipose tissue (WAT) mass was significantly decreased as the thermogenic program was upregulated in NPY-/- female mice compared with that in wild type mice; these factors were not altered in response to NPY deficiency in male mice. Moreover, lack of NPY resulted in an increase in luteinizing hormone (LH) expression in the pituitary gland, with concomitant activation of the estradiol-mediated thermogenic program in inguinal WAT, and alleviated age-related modification of adiposity in female mice.Taken together, these data revealed a novel intracellular mechanism of NPY in the regulation of fat metabolism and highlighted the sexual dimorphism of NPY as a promising target for drug development to reduce postmenopausal adiposity.
An Entropy-Guided Monte Carlo Tree Search Approach for Generating Optimal Container Loading Layouts

In this paper, a novel approach to the container loading problem using a spatial entropy measure to bias a Monte Carlo Tree Search is proposed. The proposed algorithm generates layouts that achieve the goals of both fitting a constrained space and also having “consistency” or neatness that enables forklift truck drivers to apply them easily to real shipping containers loaded from one end. Three algorithms are analysed. The first is a basic Monte Carlo Tree Search, driven only by the principle of minimising the length of container that is occupied. The second is an algorithm that uses the proposed entropy measure to drive an otherwise random process. The third algorithm combines these two principles and produces superior results to either. These algorithms are then compared to a classical deterministic algorithm. It is shown that where the classical algorithm fails, the entropy-driven algorithms are still capable of providing good results in a short computational time.
African‐American parents’ and daughters’ beliefs about HPV infection and the HPV vaccine

OBJECTIVE To increase our understanding about the health beliefs of African-American parents and their daughters toward HPV infection and HPV vaccine acceptance. METHODS The Health Belief Model was used as a guiding framework. Principles of grounded theory, theoretical sampling, and constant comparison analysis were used to qualitatively analyze data generated from personal interviews of African-American parents (n = 30) and their 12- to 17-year-old daughters (n = 34). RESULTS Mothers and daughters perceived low susceptibility to HPV infection and perceived the HPV vaccine as beneficial in protecting against genital warts and cervical cancer. Compared to daughters, parents placed particular emphasis on the vaccine's protection against genital warts. A major HPV vaccine acceptance barrier among parents and daughters was the politicization of the HPV vaccine by government figures. In addition, concerns about unknown side effects, safety, and effectiveness of HPV vaccination emerged. Cues to action varied among parents and daughters, and self-efficacy was higher among parents than daughters. CONCLUSION Understanding the health beliefs that promote HPV vaccine acceptance, while identifying and addressing beliefs that are barriers among parents and daughters, will assist in the development of appropriate HPV vaccine promotion initiatives for African-American parents and daughters.