Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical phenotype, atrophy, and small vessel disease in APOEε2 carriers with Alzheimer disease

Objective To examine the clinical phenotype, gray matter atrophy patterns, and small vessel disease in patients who developed prodromal or probable Alzheimer disease dementia, despite carrying the protective APOEε2 allele. Methods We included 36 β-amyloid-positive (by CSF or PET) APOEε2 carriers (all ε2/ε3) with mild cognitive impairment or dementia due to Alzheimer disease who were matched for age and diagnosis (ratio 1:2) to APOEε3 homozygotes and APOEε4 carriers (70% ε3/ε4 and 30% ε4/ε4). We assessed neuropsychological performance across 4 cognitive domains (memory, attention, executive, and language functions), performed voxelwise and region of interest analyses of gray matter atrophy on T1-weighted MRI, used fluid-attenuated inversion recovery images to automatically quantify white matter hyperintensity volumes, and assessed T2*-weighted images to identify microbleeds. Differences in cognitive domain scores, atrophy, and white matter hyperintensities between ε2 carriers, ε3 homozygotes, and ε4 carriers were assessed using analysis of variance analyses, and Pearson χ2 tests were used to examine differences in prevalence of microbleeds. Results We found that ε2 carriers performed worse on nonmemory domains compared to both ε3 homozygotes and ε4 carriers but better on memory compared to ε4 carriers. Voxelwise T1-weighted MRI analyses showed asymmetric (left > right) temporoparietal-predominant atrophy with subtly less involvement of medial–temporal structures in ε2 carriers compared to ε4 carriers. Finally, ε2 carriers had larger total white matter hyperintensity volumes compared to ε4 carriers (mean 10.4 vs 7.3 mL) and a higher prevalence of microbleeds compared to ε3 homozygotes (37.5% vs 18.3%). Conclusion APOEε2 carriers who develop Alzheimer disease despite carrying the protective allele display a nonamnestic clinical phenotype with more severe small vessel disease.
Air quality and health benefits from potential coal power plant closures in Texas

ABSTRACT As power production from renewable energy and natural gas grows, closures of some coal-fired power plants in Texas become increasingly likely. In this study, the potential effects of such closures on air quality and human health were analyzed by linking a regional photochemical model with a health impacts assessment tool. The impacts varied significantly across 13 of the state’s largest coal-fired power plants, sometimes by more than an order of magnitude, even after normalizing by generation. While some power plants had negligible impacts on concentrations at important monitors, average impacts up to 0.5 parts per billion (ppb) and 0.2 µg/m3 and maximum impacts up to 3.3 ppb and 0.9 µg/m3 were seen for ozone and fine particulate matter (PM2.5), respectively. Individual power plants impacted average visibility by up to 0.25 deciviews in Class I Areas. Health impacts arose mostly from PM2.5 and were an order of magnitude higher for plants that lack scrubbers for SO2. Rankings of health impacts were largely consistent across the base model results and two reduced form models. Carbon dioxide emissions were relatively uniform, ranging from 1.00 to 1.26 short tons/MWh, and can be monetized based on a social cost of carbon. Despite all of these unpaid externalities, estimated direct costs of each power plant exceeded wholesale power prices in 2016. Implications: While their CO2 emission rates are fairly similar, sharply different NOx and SO2 emission rates and spatial factors cause coal-fired power plants to vary by an order of magnitude in their impacts on ozone, particulate matter, and associated health and visibility outcomes. On a monetized basis, the air pollution health impacts often exceed the value of the electricity generated and are of similar magnitude to climate impacts. This suggests that both air pollution and climate should be considered if externalities are used to inform decision making about power-plant dispatch and retirement.
Efficacy of a mandibular advancement intraoral appliance (MOA) for the treatment of obstructive sleep apnea syndrome (OSAS) in pediatric patients: A pilot-study

Background To evaluate the treatment efficacy of a mandibular advancement intraoral appliance (MOA) for treatment of obstructive sleep apnea syndrome (OSAS) in pediatric patients. Material and Methods Eighteen patients (mean=8.39 years old, women=44.4%) were selected. Sleep disorders, sleep bruxism, and temporomandibular disorders were assessed by the Sleep Disturbance Scale for Children (SDSC), the BiteStrip® (portable SB device), and the Research Diagnostic Criteria for Temporomandibular Disorders, respectively. The clinical diagnosis of OSAS was confirmed with a type 3 portable monitor device (ApneaLinkTM Plus). A silicon-based material MOA was used by patients for 60 days, and the results were compared to baseline. Results The median RDI was significantly reduced from 10 to 4.5 events/hour. Nadir SpO2 significantly increased from 82.6% to 88.9%. Total snoring events/hour have also significantly decreased from 205.5 to 91.5. Signs and symptoms of TMD remained unaltered. There was also a reduction from moderate to absence of SB in 12 patients. Similarly, all variables measured by the SDSC have had very significant reductions: disorders of initiating and maintaining sleep, sleep disordered breathing, disorders of arousal, nightmares, sleep wake transition disorders, disorders of excessive somnolence, and sleep hyperhidrosis. Conclusions In selected cases, OA maybe considered as an alternative for the OSAS treatment. Key words:Snoring appliances, sleep apnea, bruxism, sleep disorders, children
Boron Nitride as a Novel Support for Highly Stable Palladium Nanocatalysts by Atomic Layer Deposition

The ability to prepare controllable nanocatalysts is of great interest for many chemical industries. Atomic layer deposition (ALD) is a vapor phase technique enabling the synthesis of conformal thin films and nanoparticles (NPs) on high surface area supports and has become an attractive new route to tailor supported metallic NPs. Virtually all the studies reported, focused on Pd NPs deposited on carbon and oxide surfaces. It is, however, important to focus on emerging catalyst supports such as boron nitride materials, which apart from possessing high thermal and chemical stability, also hold great promises for nanocatalysis applications. Herein, the synthesis of Pd NPs on boron nitride (BN) film substrates is demonstrated entirely by ALD for the first time. X-ray photoelectron spectroscopy indicated that stoichiometric BN formed as the main phase, with a small amount of BNxOy, and that the Pd particles synthesized were metallic. Using extensive transmission electron microscopy analysis, we study the evolution of the highly dispersed NPs as a function of the number of ALD cycles, and the thermal stability of the ALD-prepared Pd/BN catalysts up to 750 °C. The growth and coalescence mechanisms observed are discussed and compared with Pd NPs grown on other surfaces. The results show that the nanostructures of the BN/Pd NPs were relatively stable up to 500 °C. Consequent merging has been observed when annealing the samples at 750 °C, as the NPs’ average diameter increased from 8.3 ± 1.2 nm to 31 ± 4 nm. The results presented open up exciting new opportunities in the field of catalysis.
Dental and oral manifestations of celiac disease

Background The objective of this study was to evaluate the dental and oral manifestations in patients with celiac disease. Material and Methods The sample consisted of 40 patients with the disease and 40 without the disease matched by age in southern Brazil. The CD group included patients previously diagnosed by positive anti-endomysial (IgA) examination and confirmed by small intestine biopsy. The presence of dental enamel defects and dental caries was evaluated by a calibrated researcher according to AINE’s and WHO’s criteria, respectively. The history of recurrent aphthous ulcers and dry mouth was obtained through reporting. For the evaluation of the salivary flow, the saliva samples were obtained through the non-stimulated and stimulated saliva collection method. Results There was a significant association between CD and dental enamel defects (OR=2.38, P=0.045) and dry mouth (OR=9.15, P=0.002). No difference was found for the report of recurrent aphthous ulcers and caries experience between the two groups. Patients with CD had normal pattern of unstimulated and stimulated saliva flow rates (0.67 ± 0.38 ml / min and 1.14 ± 0.47 ml / min, respectively). A higher occurrence of dental enamel defects was observed in patients with classic CD (P=0.054). Of the 1,962 permanent teeth, 59 presented dental enamel defects, 71.8% of which were in patients with CD (P=0.001), predominantly in molars (P=0.009). Conclusions CD increased the likelihood of dental enamel defects and dry mouth sensation. The oral examination can be an important auxiliary tool for the identification of cases of the disease. Key words:Celiac disease, oral manifestations, dental enamel hypoplasia.
Visual Object Tracking Using Structured Sparse PCA-Based Appearance Representation and Online Learning

Visual object tracking is a fundamental research area in the field of computer vision and pattern recognition because it can be utilized by various intelligent systems. However, visual object tracking faces various challenging issues because tracking is influenced by illumination change, pose change, partial occlusion and background clutter. Sparse representation-based appearance modeling and dictionary learning that optimize tracking history have been proposed as one possible solution to overcome the problems of visual object tracking. However, there are limitations in representing high dimensional descriptors using the standard sparse representation approach. Therefore, this study proposes a structured sparse principal component analysis to represent the complex appearance descriptors of the target object effectively with a linear combination of a small number of elementary atoms chosen from an over-complete dictionary. Using an online dictionary for learning and updating by selecting similar dictionaries that have high probability makes it possible to track the target object in a variety of environments. Qualitative and quantitative experimental results, including comparison to the current state of the art visual object tracking algorithms, validate that the proposed tracking algorithm performs favorably with changes in the target object and environment for benchmark video sequences.
Molecular Disorder of Bicalutamide—Amorphous Solid Dispersions Obtained by Solvent Methods

The effect of solvent removal techniques on phase transition, physical stability and dissolution of bicalutamide from solid dispersions containing polyvinylpyrrolidone (PVP) as a carrier was investigated. A spray dryer and a rotavapor were applied to obtain binary systems containing either 50% or 66% of the drug. Applied techniques led to the formation of amorphous solid dispersions as confirmed by X-ray powder diffractometry and differential scanning calorimetry. Moreover, solid–solid transition from polymorphic form I to form II was observed for bicalutamide spray dried without a carrier. The presence of intermolecular interactions between the drug and polymer molecules, which provides the stabilization of molecularly disordered bicalutamide, was analyzed using infrared spectroscopy. Spectral changes within the region characteristic for amide vibrations suggested that the amide form of crystalline bicalutamide was replaced by a less stable imidic one, characteristic of an amorphous drug. Applied processes also resulted in changes of particle geometry and size as confirmed by scanning electron microscopy and laser diffraction measurements, however they did not affect the dissolution significantly as confirmed by intrinsic dissolution study. The enhancement of apparent solubility and dissolution were assigned mostly to the loss of molecular arrangement by drug molecules. Performed statistical analysis indicated that the presence of PVP reduces the mean dissolution time and improve the dissolution efficiency. Although the dissolution was equally affected by both applied methods of solid dispersion manufacturing, spray drying provides better control of particle size and morphology as well as a lower tendency for recrystallization of amorphous solid dispersions.
Connectivity as a Predictor of Responsiveness to Transcranial Direct Current Stimulation in People with Stroke: Protocol for a Double-Blind Randomized Controlled Trial

Background Stroke can have devastating consequences for an individual’s quality of life. Interventions capable of enhancing response to therapy would be highly valuable to the field of neurological rehabilitation. One approach is to use noninvasive brain stimulation techniques, such as transcranial direct current stimulation, to induce a neuroplastic response. When delivered in combination with rehabilitation exercises, there is some evidence that transcranial direct current stimulation is beneficial. However, responses to stimulation are highly variable. Therefore biomarkers predictive of response to stimulation would be valuable to help select appropriate people for this potentially beneficial treatment. Objective The objective of this study is to investigate connectivity of the stimulation target, the ipsilesional motor cortex, as a biomarker predictive of response to anodal transcranial direct current stimulation in people with stroke. Methods This study is a double blind, randomized controlled trial (RCT), with two parallel groups. A total of 68 participants with first ever ischemic stroke with motor impairment will undertake a two week (14 session) treatment for upper limb function (Graded Repetitive Arm Supplementary Program; GRASP). Participants will be randomized 2:1 to active:sham treatment groups. Those in the active treatment group will receive anodal transcranial direct current stimulation to the ipsilesional motor cortex at the start of each GRASP session. Those allocated to the sham treatment group will receive sham transcranial direct current stimulation. Behavioural assessments of upper limb function will be performed at baseline, post treatment, 1 month follow-up and 3 months follow-up. Neurophysiological assessments will include magnetic resonance imaging (MRI), electroencephalography (EEG) and transcranial magnetic stimulation (TMS) and will be performed at baseline, post treatment, 1 month follow-up (EEG and TMS only) and 3 months follow-up (EEG and TMS only). Results Participants will be recruited between March 2018 and December 2018, with experimental testing concluding in March 2019. Conclusions Identifying a biomarker predictive of response to transcranial direct current stimulation would greatly assist clinical utility of this novel treatment approach. Trial Registration Australia New Zealand Clinical Trials Registry ACTRN12618000443291; https://www.anzctr. org.au/Trial/Registration/TrialReview.aspx? ACTRN=12618000443291 (Archived by WebCite at http://www.webcitation.org/737QOXXxt) Registered Report Identifier RR1-10.2196/10848
Lung function in adults born preterm

Very preterm birth, before the gestational age (GA) of 32 weeks, increases the risk of obstructed airflow in adulthood. We examined whether all preterm births (GA<37 weeks) are associated with poorer adult lung function and whether any associations are explained by maternal, early life/neonatal, or current life factors. Participants of the ESTER Preterm Birth Study, born between 1985 and 1989 (during the pre-surfactant era), at the age of 23 years participated in a clinical study in which they performed spirometry and provided detailed medical history. Of the participants, 139 were born early preterm (GA<34 weeks), 239 late preterm (GA: 34-<37 weeks), and 341 full-term (GA≥37 weeks). Preterm birth was associated with poorer lung function. Mean differences between individuals born early preterm versus full-term were -0.23 standard deviation (SD) (95% confidence interval (CI): -0.40, -0.05)) for forced vital capacity z-score (zFVC), -0.44 SD (95% CI -0.64, -0.25) for forced expiratory volume z-score (zFEV1), and -0.29 SD (95% CI -0.47, -0.10) for zFEV1/FVC. For late preterm, mean differences with full-term controls were -0.02 SD (95% CI -0.17, 0.13), -0.12 SD (95% CI -0.29, 0.04) and -0.13 SD (95% CI -0.29, 0.02) for zFVC, zFEV1, and zFEV1/FVC, respectively. Examination of finer GA subgroups suggested an inverse non-linear association between lung function and GA, with the greatest impact on zFEV1 for those born extremely preterm. The subgroup means were GA<28 weeks: -0.98 SD; 28-<32 weeks: -0.29 SD; 32-<34 weeks: -0.44 SD; 34-<36 weeks: -0.10 SD; 36-<37weeks: -0.11 SD; term-born controls (≥37weeks): 0.02 SD. Corresponding means for zFEV1/FVC were -1.79, -0.44, -0.47, -0.48, -0.29, and -0.02. Adjustment for maternal pregnancy conditions and socioeconomic and lifestyle factors had no major impact on the relationship. Preterm birth is associated with airflow limitation in adult life. The association appears to be attributable predominantly to those born most immature, with only a modest decrease among those born preterm at later gestational ages.
Chromosome assembly of large and complex genomes using multiple references

Despite the rapid development of sequencing technologies, assembly of mammalian-scale genomes into complete chromosomes remains one of the most challenging problems in bioinformatics. To help address this difficulty, we developed Ragout, a reference-assisted assembly tool that now works for large and complex genomes. Taking one or more target assemblies (generated from an NGS assembler) and one or multiple related reference genomes, Ragout infers the evolutionary relationships between the genomes and builds the final assemblies using a genome rearrangement approach. Using Ragout, we transformed NGS assemblies of 15 different Mus musculus and one Mus spretus genomes into sets of complete chromosomes, leaving less than 5% of sequence unlocalized per set. Various benchmarks, including PCR testing and realigning of long PacBio reads, suggest only a small number of structural errors in the final assemblies, comparable with direct assembly approaches. Additionally, we applied Ragout to Mus caroli and Mus pahari genomes, which exhibit karyotype-scale variations compared to other genomes from the Muridae family. Chromosome color maps confirmed most large-scale rearrangements that Ragout detected.
Heme oxygenase‐1 induction attenuates senescence in chronic obstructive pulmonary disease lung fibroblasts by protecting against mitochondria dysfunction

Chronic obstructive pulmonary disease (COPD) is associated with lung fibroblast senescence, a process characterized by an irreversible proliferation arrest associated with secretion of inflammatory mediators. ROS production, known to induce senescence, is increased in COPD fibroblasts and mitochondria dysfunction participates in this process. Among the battery of cellular responses against oxidative stress damage, heme oxygenase (HO)‐1 plays a critical role in defending the lung against oxidative stress and inflammation. Therefore, we investigated whether pharmacological induction of HO‐1 by chronic hemin treatment attenuates senescence and improves dysfunctional mitochondria in COPD fibroblasts. Fibroblasts from smoker controls (S‐C) and COPD patients were isolated from lung biopsies. Fibroblasts were long‐term cultured in the presence or absence of hemin, and/or ZnPP or QC‐15 (HO‐1 inhibitors). Lung fibroblasts from smokers and COPD patients displayed in long‐term culture a senescent phenotype, characterized by a reduced replicative capacity, an increased senescence and inflammatory profile. These parameters were significantly higher in senescent COPD fibroblasts which also exhibited decreased mitochondrial activity (respiration, glycolysis, and ATP levels) which led to an increased production of ROS, and mitochondria biogenesis and impaired mitophagy process. Exposure to hemin increased the gene and protein expression level of HO‐1 in fibroblasts and diminished ROS levels, senescence, the inflammatory profile and simultaneously rescued mitochondria dysfunction by restoring mitophagy in COPD cells. The effects of hemin were abolished by a cotreatment with ZnPP or QC‐15. We conclude that HO‐1 attenuates senescence in COPD fibroblasts by protecting, at least in part, against mitochondria dysfunction and restoring mitophagy.
Ethical governance is essential to building trust in robotics and artificial intelligence systems

This paper explores the question of ethical governance for robotics and artificial intelligence (AI) systems. We outline a roadmap—which links a number of elements, including ethics, standards, regulation, responsible research and innovation, and public engagement—as a framework to guide ethical governance in robotics and AI. We argue that ethical governance is essential to building public trust in robotics and AI, and conclude by proposing five pillars of good ethical governance. This article is part of the theme issue ‘Governing artificial intelligence: ethical, legal, and technical opportunities and challenges’.
Histamine pharmacology: from Sir Henry Dale to the 21st century

Histamine has been one of the most studied substances in medicine, playing a major role in diverse (patho)physiological processes. It elicits its multifaceted modulatory functions by activating four types of GPCRs, designated as H1–4. Despite the heterogeneity and the complexity of histamine receptor pharmacology, many discoveries over the past 100 years resulted in the development of H1 antihistamines and H2‐targeting ‘blockbuster’ therapeutics for the management of allergies and gastrointestinal disorders respectively. Recently, a first‐in‐class H3 inverse agonist was approved for the treatment of narcolepsy, whereas H4 antagonists are under clinical evaluation for their potential therapeutic exploitation in immune‐related diseases. This review critically presents the past successes and drawbacks in histamine research, complemented by the modern conceptual innovations in molecular and receptor pharmacology. It targets both young and experienced researchers in an ongoing effort to stimulate novel insights for the dissection of the translational potential of histamine pharmacology.
IDH-CAN: A Hardware-Based ID Hopping CAN Mechanism With Enhanced Security for Automotive Real-Time Applications

Cybersecurity is increasingly important for the safety and reliability of autonomous vehicles. The controller area network (CAN) is the most widely used in-vehicle network for automotive safety-critical applications. Enhancing the cybersecurity ability of CAN while considering the real-time, schedulability, and cost constraints becomes an urgent issue. To address this problem, a real-time, and schedulability analysis-guaranteed security mechanism [identification hopping CAN (IDH-CAN)] is proposed in this paper, which aims to improve the security performance of CAN under the constraints of automotive real-time applications. In order to support the operation of the IDH-CAN mechanism, an IDH-CAN controller is also designed and implemented on a field-programmable gate array, which can work as a hardware firewall in the data link layer of CAN to isolate cyberattacks from the physical layer. Meanwhile, to maximize the information entropy of the CAN message ID on the physical layer, the ID hopping table generation and optimization algorithms for IDH-CAN are also proposed. Then, information security evaluation experiments based on information entropy comparison are deployed. The simulation and practical evaluations demonstrate the effectiveness of the proposed mechanism in defending reverse engineering, targeted denial of service, and replay attacks without violating real-time and schedulability constraints.