Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional Enhancers in the FOXP2 Locus Underwent Accelerated Evolution in the Human Lineage.

Unique human features such as complex language are the result of molecular evolutionary changes that modified developmental programs of our brain. The human-specific evolution of the forkhead box P2 (FOXP2) gene coding region has been linked to the emergence of speech and language in the human kind. However, little is known about how the expression of FOXP2 is regulated and if its regulatory machinery evolved in a lineage-specific manner in humans. In order to identify FOXP2 regulatory regions containing human-specific changes we used databases of human accelerated non-coding sequences or HARs. We found that the topologically associating domain (TAD) determined using developing human cerebral cortex containing the FOXP2 locus includes two clusters of 12 HARs, placing the locus occupied by FOXP2 among the top regions showing fast acceleration rates in non-coding regions in the human genome. Using in vivo enhancer assays in zebrafish, we found that at least five FOXP2-HARs behave as transcriptional enhancers throughout different developmental stages. In addition, we found that at least two FOXP2-HARs direct the expression of the reporter gene EGFP to foxP2 expressing regions and cells. Moreover, we uncovered two FOXP2-HARs showing reporter expression gain of function in the nervous system when compared with the chimpanzee ortholog sequences. Our results indicate that regulatory sequences in the FOXP2 locus underwent a human-specific evolutionary process suggesting that the transcriptional machinery controlling this gene could have also evolved differentially in the human lineage.
Partial Failure of Proteostasis Systems Counteracting TDP-43 Aggregates in Neurodegenerative Diseases

Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are progressive and fatal neurodegenerative disorders showing mislocalization and cytosolic accumulation of TDP-43 inclusions in the central nervous system. The decrease in the efficiency of the clearance systems in aging, as well as the presence of genetic mutations of proteins associated with cellular proteostasis in the familial forms of TDP-43 proteinopathies, suggest that a failure of these protein degradation systems is a key factor in the aetiology of TDP-43 associated disorders. Here we show that the internalization of human pre-formed TDP-43 aggregates in the murine neuroblastoma N2a cells promptly resulted in their ubiquitination and hyperphosphorylation by endogenous machineries, mimicking the post-translational modifications observed in patients. Moreover, our data identify mitochondria as the main responsible sites for the alteration of calcium homeostasis induced by TDP-43 aggregates, which, in turn, stimulates an increase in reactive oxygen species and, finally, caspase activation. The inhibition of TDP-43 proteostasis in the presence of selective inhibitors against the proteasome and macroautophagy systems revealed that these two systems are both severely involved in TDP-43 accumulation and have a strong influence on each other in neurodegenerative disorders associated with TDP-43.
Environmental Toxicology and Chemistry

Anticipating, identifying, and prioritizing strategic needs represent essential activities by research organizations. Decided benefits emerge when these pursuits engage globally important environment and health goals, including the United Nations Sustainable Development Goals. To this end, horizon scanning efforts can facilitate identification of specific research needs to address grand challenges. We report and discuss 40 priority research questions following engagement of scientists and engineers in North America. These timely questions identify the importance of stimulating innovation and developing new methods, tools, and concepts in environmental chemistry and toxicology to improve assessment and management of chemical contaminants and other diverse environmental stressors. Grand challenges to achieving sustainable management of the environment are becoming increasingly complex and structured by global megatrends, which collectively challenge existing sustainable environmental quality efforts. Transdisciplinary, systems‐based approaches will be required to define and avoid adverse biological effects across temporal and spatial gradients. Similarly, coordinated research activities among organizations within and among countries are necessary to address the priority research needs reported here. Acquiring answers to these 40 research questions will not be trivial, but doing so promises to advance sustainable environmental quality in the 21st century. Environ Toxicol Chem 2019;38:1607–1624. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Design, Implementation, and Evaluation of a Head and Neck MRI RF Array Integrated with a 511 keV Transmission Source for Attenuation Correction in PET/MR

The goal of this work is to further improve positron emission tomography (PET) attenuation correction and magnetic resonance (MR) sensitivity for head and neck applications of PET/MR. A dedicated 24-channel receive-only array, fully-integrated with a hydraulic system to move a transmission source helically around the patient and radiofrequency (RF) coil array, is designed, implemented, and evaluated. The device enables the calculation of attenuation coefficients from PET measurements at 511 keV including the RF coil and the particular patient. The RF coil design is PET-optimized by minimizing photon attenuation from coil components and housing. The functionality of the presented device is successfully demonstrated by calculating the attenuation map of a water bottle based on PET transmission measurements; results are in excellent agreement with reference values. It is shown that the device itself has marginal influence on the static magnetic field B0 and the radiofrequency transmit field B1 of the 3T PET/MR system. Furthermore, the developed RF array is shown to outperform a standard commercial 16-channel head and neck coil in terms of signal-to-noise ratio (SNR) and parallel imaging performance. In conclusion, the presented hardware enables accurate calculation of attenuation maps for PET/MR systems while improving the SNR of corresponding MR images in a single device without degrading the B0 and B1 homogeneity of the scanner.
Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multiantigen-Associated Specific Cytotoxic T Lymphocytes: A Phase I Study.

PURPOSE Tumor-associated antigen cytotoxic T cells (TAA-Ts) represent a new, potentially effective and nontoxic therapeutic approach for patients with relapsed or refractory solid tumors. In this first-in-human trial, we investigated the safety of administering TAA-Ts that target Wilms tumor gene 1, preferentially expressed antigen of melanoma, and survivin to patients with relapsed/refractory solid tumors. MATERIALS AND METHODS TAA-T products were generated from autologous peripheral blood and infused over three dose levels: 1, 2, and 4 × 107 cells/m2. Patients were eligible for up to eight infusions administered 4 to 7 weeks apart. We assessed dose limiting toxicity during the first 45 days after infusion. Disease response was determined within the context of a phase I trial. RESULTS There were no dose-limiting toxicities. Of 15 evaluable patients, 11 (73%) with stable disease or better at day 45 postinfusion were defined as responders. Six responders remain without progression at a median of 13.9 months (range, 4.1 to 19.9 months) after initial TAA-Ts. Patients who were treated at the highest dose level showed the best clinical outcomes, with a 6-month progression-free survival of 73% after TAA-T infusion compared with a 38% 6-month progression-free survival with prior therapy. Antigen spreading and a reduction in circulating tumor-associated antigens using digital droplet polymerase chain reaction was observed in patients after TAA-T infusion. CONCLUSION TAA-Ts safely induced disease stabilization, prolonged time to progression, and were associated with antigen spreading and a reduction in circulating tumor-associated antigen DNA levels in patients with relapsed/refractory solid tumors without lymphodepleting chemotherapy before infusion. TAA-Ts are a promising new treatment approach for patients with solid tumors.
Indocyanine green angiography for identifying telangiectatic capillaries in diabetic macular oedema

Aims During diabetic macular oedema (DME), a spectrum of capillary abnormalities is commonly observed, ranging from microaneurysms to large microvascular abnormalities. Clinical evidence suggests that targeted photocoagulation of large microvascular abnormalities may be beneficial, but their detection is not done in a routine fashion. It was reported that they are better identified by indocyanine green angiography (ICGA) than by fluorescein angiography. Here, we investigated the prevalence and ICGA and optical coherence tomography (OCT) features of retinal microvascular abnormalities in a group of patients with DME. Methods Observational study. The fundus photographs, ICGA and structural and angiographic OCT charts of 35 eyes from 25 consecutive patients with DME were reviewed. Results 22 eyes (63%) had at least one focal area of microvascular abnormalities showing prolonged indocyanine green (ICG) staining (ie, beyond 10 mins after injection). In particular, all eyes (n=9) with circinate hard exudates showed foci of late ICG staining. These areas were either isolated globular capillary ecstasies or a cluster of ill-defined capillary abnormalities. They were located at a median distance of 2708 µm from the fovea (range: 1064–4583 µm). Their diameter ranged from 153 to 307 µm. During ICGA, 91% showed increased their contrast and apparent size in late frames, whereas 79% of microaneurysms showed reduced contrast on late frames. OCT angiography was not contributive for the detection of these lesions. Conclusion Late ICG staining revealing large microvascular abnormalities is commonly observed during DME. Because of their specific angiographic and OCT features relative to microaneurysms, we propose to name them telangiectatic capillaries (TelCaps).
Substrate Integrated Slot Array Antenna with Required Radiation Pattern Envelope

A substrate integrated slot array antenna with a prescribed radiation pattern is investigated in this paper. To meet the requirement of a certain standard radiation pattern envelope, the array configuration and the element excitation coefficient should be considered together. An efficient and systematic method is proposed to determine the element number and element weights in a planar array. After that, the geometrical dimension of the substrate integrated slot array can be synthesized. As an example, a -band 16 × 22 slot array antenna based on the substrate integrated waveguide (SIW) technology is designed, fabricated, and measured. Its radiation pattern can meet the class 3 antenna radiation pattern envelope of the European Telecommunications Standards Institute (ETSI) standard pattern. Experimental results are in good agreement with simulated ones.
HS-GC/MS method development and exposure assessment of volatile organic compounds from food packaging into food simulants

ABSTRACT A simultaneous headspace-gas chromatography/mass spectrometry (HS-GC/MS) method was developed and validated to determine the migration of 12 volatile organic compounds (methanol, acetone, methylethylketone, ethylacetate, isopropylalcohol, benzene, toluene, ethylbenzene, xylene, cumene, propylbenzene, and styrene) from food contact materials into food simulants (water, 4% acetic acid, 50% ethanol, and n-heptane). The limits of detection and quantification were 0.007–0.201 mg L−1 and 0.023–0.668 mg L−1, respectively. The method was applied to 205 samples of paper/paperboard, polyethylene, polypropylene, polystyrene, and polyethylene terephthalate. The estimated daily intake (EDI) was calculated using the migration results. Exposure assessments were carried out to compare the EDI to the tolerable daily intake (TDI); the results indicated that the EDI of styrene represented only a small percentage (8.0%) of the TDI. This analytical method will be a useful tool to examine levels of various volatile compounds migrating from food packaging to food simulants using HS-GC/MS method.
Hearing Impairment and Prevalence of Mild Cognitive Impairment in Japan: Baseline Data From the Aidai Cohort Study in Yawatahama and Uchiko

Objectives: Hearing impairment (HI) in midlife may increase the risk of dementia. However, epidemiological research on the association between HI and mild cognitive impairment (MCI) is very limited. Design: The present cross-sectional study investigated the relationship between HI and MCI using baseline data from the Aidai Cohort Study. Study subjects were 995 Japanese adults aged 36 to 84 years. We used the audiometric definition of HI adopted by the World Health Organization, which identifies the speech-frequency pure-tone average hearing thresholds at 0.5, 1, 2, and 4 kHz tones. HI was defined as present when pure-tone average was >25 dB HL in the better hearing ear. MCI was defined as being present when a subject had a Japanese version of the Montreal Cognitive Assessment score of <26. Adjustment was made for age, sex, smoking status, alcohol consumption, leisure time physical activity, hypertension, dyslipidemia, diabetes mellitus, history of depression, body mass index, waist circumference, employment, education, and household income. Results: Among the 995 study subjects, the prevalence values of HI and MCI were 24.3% and 44.5%, respectively. HI was independently positively associated with MCI: the multivariate-adjusted odds ratio (95% confidence interval) was 1.86 (1.32 to 2.62). HI was independently related to a higher prevalence of MCI in those aged 60 to 69 years and those aged 70 years or older: the multivariate-adjusted odds ratios (95% confidence intervals) were 1.64 (1.03 to 2.62) and 2.30 (1.04 to 5.27), respectively. Conclusions: HI may be associated with a higher prevalence of MCI.
Research advances in reproduction for dairy goats

Considerable progress in reproduction of dairy goats has been made, with advances in reproductive technology accelerating dairy goat production since the 1980s. Reproduction in goats is described as seasonal. The onset and length of the breeding season is dependent on various factors such as breed, climate, physiological stage, male effect, breeding system, and photoperiod. The reproductive physiology of goats was investigated extensively, including hypothalamic and pituitary control of the ovary related to estrus behavior and cyclicity etc. Photoperiodic treatments coupled with the male effect allow hormone-free synchronization of ovulation, but the kidding rate is still less than for hormonal treatments. Different protocols have been developed to meet the needs and expectations of producers; dairy industries are subject to growing demands for year round production. Hormonal treatments for synchronization of estrus and ovulation in combination with artificial insemination (AI) or natural mating facilitate out-of-season breeding and the grouping of the kidding period. The AI with fresh or frozen semen has been increasingly adopted in the intensive production system, this is perhaps the most powerful tool that reproductive physiologists and geneticists have provided the dairy goat industry with for improving reproductive efficiency, genetic progress and genetic materials transportation. One of the most exciting developments in the reproduction of dairy animals is embryo transfer (ET), the so-called second generation reproductive biotechnology following AI. Multiple ovulation and ET (MOET) program in dairy goats combining with estrus synchronization (ES) and AI significantly increase annual genetic improvement by decreasing the generation interval. Based on the advances in reproduction technologies that have been utilized through experiments and investigation, this review will focus on the application of these technologies and how they can be used to promote the dairy goat research and industry development in the future.
A continual trials approach to recognition memory in mice

This thesis sought to address and improve resolve some issues surrounding tests of recognition memory in animals. Since these spontaneous object recognition memory tasks are widely used, especially in mice, there is a need to develop a recognition task that would reduce the variability, extend and translate the task to potential areas of neuroscience research. Study 1 sought to validate the continual trials approach that was originally designed for rats to mice and replicate the findings of Ameen-Ali et al., (2012) in the spontaneous object recognition and object-location task. Study 1 found that performance of mice was comparable to previous studies of object recognition and object location memory, and statistically meaningful results were obtained with approximately 30 – 50 % fewer mice than typically used in the standard one trial a day version of the spontaneous object recognition tasks. Study 2 sought to extend the continual trials apparatus to establish the age-related changes of object recognition and object-location memory in normal ageing mice; and found that ageing mice showed no age-related decline of recognition memory. Study 3 found no evidence of age-related changes of object recognition and object-location memory in a transgenic mouse model of Alzheimer’s Disease, TASTPM mice. In study 4, the continual trials apparatus was adapted to incorporate variable retention delays (by blocking the sample and test phases) and found no evidence of delay-dependent effect on object recognition memory. Study 5 provided novel evidence that NMDA blockade using the MK-801 drug had no effect on object recognition memory in mice when controlled for state-dependency of memory. The key findings of this thesis include the successful validation of the continual trials apparatus in mice and the evidence that studies using reduced number of mice can nonetheless provide valid results in object recognition memory tasks.
Implementation of a Potential Field-Based Decision-Making Algorithm on Autonomous Vehicles for Driving in Complex Environments

Autonomous driving is undergoing huge developments nowadays. It is expected that its implementation will bring many benefits. Autonomous cars must deal with tasks at different levels. Although some of them are currently solved, and perception systems provide quite an accurate and complete description of the environment, high-level decisions are hard to obtain in challenging scenarios. Moreover, they must comply with safety, reliability and predictability requirements, road user acceptance, and comfort specifications. This paper presents a path planning algorithm based on potential fields. Potential models are adjusted so that their behavior is appropriate to the environment and the dynamics of the vehicle and they can face almost any unexpected scenarios. The response of the system considers the road characteristics (e.g., maximum speed, lane line curvature, etc.) and the presence of obstacles and other users. The algorithm has been tested on an automated vehicle equipped with a GPS receiver, an inertial measurement unit and a computer vision system in real environments with satisfactory results.
Guilt in the Treatment of Posttraumatic Stress Disorder Among Active Duty Military Personnel.

The current study examined the role of trauma-related guilt on posttraumatic stress disorder (PTSD) symptom change during prolonged exposure therapy (PE) as well as the efficacy of PE in reducing three dimensions of guilt (responsibility, wrongdoing, and lack of justification) during treatment. Participants were 331 active duty U.S. military personnel seeking treatment for PTSD who were randomized to one of four groups: massed PE (10 sessions delivered over 2 weeks), spaced PE (10 sessions delivered over 8 weeks), present-centered therapy (PCT; 10 sessions delivered over 8 weeks), or minimal contact control (MCC; weekly therapist phone check-in for 4 weeks). The results showed that baseline guilt did not predict reductions in PTSD symptoms for spaced PE or for PCT, ps = . 178-. 387, ds = -0.02-0.07. Treatment condition (massed PE vs. MCC; spaced PE vs. PCT) did not moderate reductions in guilt for spaced PE versus PCT. Guilt decreased significantly over treatment in all groups, p < . 001 to p = . 038, ds = -0.19 to -0.42, except concerning justification in the spaced PE and PCT groups, p = . 140, d = -0.10. The findings suggest that guilt may be reduced significantly following active PTSD treatment and attention control and that PTSD recovery is not impacted by baseline levels of trauma-related guilt in military personnel with PTSD, although reported levels of guilt were low to moderate in this sample.
Design Guidelines for a Technology-Enabled Nutrition Education Program to Support Overweight and Obese Adolescents: Qualitative User-Centered Design Study

Background Childhood overweight and obesity are major health challenges in the United States. One of the recommendations to combat obesity is to maintain a healthy diet, which is often best supported by eating home-cooked meals to control cooking methods, ingredients, and portions. Diet control through home cooking is challenged because of the decline in culinary skills in the population and a paucity of effective culinary nutrition education (CNE) programs. Providing technology-enabled CNE (CNE-tech) to overweight and obese adolescents can equip them with life skills that can assist them in the future. Such skills can facilitate saving money, eating healthier, and creating social environments. In addition, CNE builds cooking confidence and food literacy that in turn can build adolescent self-efficacy, particularly toward managing their health behaviors. Objective This study aimed to inform functionalities, design requirements, and the context of use for CNE-tech that could enhance overweight and obese adolescents’ healthy food literacy, cooking confidence, and general self-efficacy with regard to self-management to ultimately promote healthy lifestyle management. Methods The design science study was completed in 2 distinct phases engaging overweight and obese adolescents, parents of overweight and obese adolescents, and the health care providers that treat adolescents with these conditions. Phase 2, our primary source of data, involved user-centered design methods including the following: (1) early stage prototype usability analysis, (2) semistructured interviews with 70 overweight or obese adolescents engaged in a healthy behavior program, and (3) semistructured interviews with 10 health care providers. Data were analyzed using constant comparison analysis to identify functionalities, design requirements, and inform the context of use of CNE-tech. Results Data revealed specific desired functionalities for the CNE-tech related to building cooking skills, populating a healthy recipe database, suggesting healthy alternatives, supporting the construction of a healthy plate, and the ability to share healthy recipes and cooking accomplishments. Moreover, the adolescents provided design requirements pertaining to the presentation (eg, vivid colors, semirealistic images, and cooking sounds), use of multimedia, and gaming. Data further revealed contextual factors, such as shared experiences with family members and enhanced continued use. Conclusions We demonstrate the potentiality of creating CNE-tech that could effectively lead to better self-care and induce sustainable behavioral change as it facilitates skill building, self-efficacy, and a pathway that enables overweight and obese adolescents to influence cooking habits in their family home and future dwellings. Our CNE-tech–proposed solution aligns with the goals of overweight and obese adolescents and also reflects existing theories about behavioral change.