Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of Polygenic Liability for Alcohol Dependence and EEG Connectivity in Adolescence and Young Adulthood

Differences in the connectivity of large-scale functional brain networks among individuals with alcohol use disorders (AUD), as well as those at risk for AUD, point to dysfunctional neural communication and related cognitive impairments. In this study, we examined how polygenic risk scores (PRS), derived from a recent GWAS of DSM-IV Alcohol Dependence (AD) conducted by the Psychiatric Genomics Consortium, relate to longitudinal measures of interhemispheric and intrahemispheric EEG connectivity (alpha, theta, and beta frequencies) in adolescent and young adult offspring from the Collaborative Study on the Genetics of Alcoholism (COGA) assessed between ages 12 and 31. Our findings indicate that AD PRS (p-threshold < 0.001) was associated with increased fronto-central, tempo-parietal, centro-parietal, and parietal-occipital interhemispheric theta and alpha connectivity in males only from ages 18–31 (beta coefficients ranged from 0.02–0.06, p-values ranged from 10−6–10−12), but not in females. Individuals with higher AD PRS also demonstrated more performance deficits on neuropsychological tasks (Tower of London task, visual span test) as well as increased risk for lifetime DSM-5 alcohol and opioid use disorders. We conclude that measures of neural connectivity, together with neurocognitive performance and substance use behavior, can be used to further understanding of how genetic risk variants from large GWAS of AUD may influence brain function. In addition, these data indicate the importance of examining sex and developmental effects, which otherwise may be masked. Understanding of neural mechanisms linking genetic variants emerging from GWAS to risk for AUD throughout development may help to identify specific points when neurocognitive prevention and intervention efforts may be most effective.
Human Radiation Dosimetry for Orally and Intravenously Administered 18F-FDG

Intravenous access is difficult in some patients referred for 18F-FDG PET imaging. Extravasation at the injection site and accumulation in central catheters can lead to limited tumor 18F-FDG uptake, erroneous quantitation, and significant image artifacts. In this study, we compared the human biodistribution and dosimetry for 18F-FDG after oral and intravenous administrations sequentially in the same subjects to ascertain the dosimetry and potential suitability of orally administered 18F-FDG as an alternative to intravenous administration. We also compared our detailed intravenous 18F-FDG dosimetry with older dosimetry data. Methods: Nine healthy volunteers (6 male and 3 female; aged 19–32 y) underwent PET/CT imaging after oral and intravenous administration of 18F-FDG. Identical preparation and imaging protocols (except administration route) were used for oral and intravenous studies. During each imaging session, 9 whole-body PET scans were obtained at 5, 10, 20, 30, 40, 50, 60, 120, and 240 min after 18F-FDG administration (370 ± 16 MBq). Source organ contours drawn using CT were overlaid onto registered PET images to extract time–activity curves. Time-integrated activity coefficients derived from time–activity curves were given as input to OLINDA/EXM for dose calculations. Results: Blood uptake after orally administered 18F-FDG peaked at 45–50 min after ingestion. The oral-to-intravenous ratios of 18F-FDG uptake for major organs at 45 min were 1.07 ± 0.24 for blood, 0.94 ± 0.39 for heart wall, 0.47 ± 0.12 for brain, 1.25 ± 0.18 for liver, and 0.84 ± 0.24 for kidneys. The highest organ-absorbed doses (μGy/MBq) after oral 18F-FDG administration were observed for urinary bladder (75.9 ± 17.2), stomach (48.4 ± 14.3), and brain (29.4 ± 5.1), and the effective dose was significantly higher (20%) than after intravenous administration (P = 0.002). Conclusion: 18F-FDG has excellent bioavailability after oral administration, but peak organ activities occur later than after intravenous injection. These data suggest PET at 2 h after oral 18F-FDG administration should yield images that are comparable in biodistribution to conventional clinical images acquired 1 h after injection. Oral 18F-FDG is a palatable alternative to intravenous 18F-FDG when venous access is problematic.
Asymmetric base-pair opening drives helicase unwinding dynamics

Significance Six decades after DNA structure was first revealed, fundamental questions remain open. How is the entwined embrace of double-stranded nucleic acids formed or disrupted? How does the energetics underlying this process influence nucleic-acid processing machineries? By combining simulations and experiments, our work addresses these questions and reveals that asymmetric base-pair dynamics drives the stepwise separation of nucleic acid duplexes, predicts the unwinding efficiency of helicases, and intimately relates the intrinsic dynamics of base pairs to the enzymatic mechanism evolved for their opening. Taken together, our data suggest a layer of regulation of the genetic material encoded in the “unwindability” of the double helix. The opening of a Watson–Crick double helix is required for crucial cellular processes, including replication, repair, and transcription. It has long been assumed that RNA or DNA base pairs are broken by the concerted symmetric movement of complementary nucleobases. By analyzing thousands of base-pair opening and closing events from molecular simulations, here, we uncover a systematic stepwise process driven by the asymmetric flipping-out probability of paired nucleobases. We demonstrate experimentally that such asymmetry strongly biases the unwinding efficiency of DNA helicases toward substrates that bear highly dynamic nucleobases, such as pyrimidines, on the displaced strand. Duplex substrates with identical thermodynamic stability are thus shown to be more easily unwound from one side than the other, in a quantifiable and predictable manner. Our results indicate a possible layer of gene regulation coded in the direction-dependent unwindability of the double helix.
Evidence for an Association Between Hearing Impairment and Disrupted Sleep: Scoping Review

Purpose Hearing impairment (HI) is the most common sensory impairment and may negatively impact sleep through reduced auditory input. Factors associated with HI such as anxiety regarding communication in daily life may also adversely impact an individual's sleep. Here, research on the relationship between HI and sleep disruption was catalogued using scoping review methodology. Method A systematic strategy was employed to search various electronic databases. This review is reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Scoping Review Extension. Results Sixteen records met inclusion criteria. Studies have investigated sleep in HI as a primary aim in noise-exposed workers or large surveys in older participants. Experimental and quasi-experimental studies report alterations to sleep architecture of potential neuroplastic origins. Studies reporting sleep as a secondary aim generally report poorer sleep in HI participants. Conclusions This scoping review has catalogued evidence that altered or negatively impacted sleep may be associated with HI. Potential confounding factors, mechanisms, and considerations for future research are discussed. Supplemental Material https://doi.org/10.23641/asha.9968369
Evaluation of the abuse potential of pitolisant, a selective H3-receptor antagonist/inverse agonist, for the treatment of adult patients with narcolepsy with or without cataplexy

Abstract Objectives To evaluate the human abuse potential of pitolisant, a selective histamine 3 (H3)-receptor antagonist/inverse agonist recently approved by the US Food and Drug Administration for the treatment of excessive daytime sleepiness in adult patients with narcolepsy. Methods Nondependent, recreational stimulant users able to distinguish phentermine HCl 60 mg from placebo in a drug discrimination test were randomized in a four-period, double-blind, crossover design to receive single doses of pitolisant 35.6 mg (therapeutic dose), pitolisant 213.6 mg (supratherapeutic dose), phentermine HCl 60 mg, and placebo. The primary endpoint was maximum effect (Emax) on the 100-point Drug Liking (“at this moment”) visual analog scale. Results In 38 study completers (73.7% male; 65.8% white; mean age, 33.3 years), mean Drug Liking Emax was significantly greater for phentermine versus pitolisant 35.6 mg (mean difference, 21.4; p < 0.0001) and pitolisant 213.6 mg (mean difference, 19.7; p < 0.0001). Drug Liking Emax was similar for pitolisant (both doses) and placebo. Similarly, for key secondary measures of Overall Drug Liking and willingness to Take Drug Again, mean Emax scores were significantly greater for phentermine versus pitolisant (both doses) and similar for pitolisant (both doses) versus placebo. The incidence of adverse events was 82.1% after phentermine HCl 60 mg, 72.5% after pitolisant 213.6 mg, 47.5% after pitolisant 35.6 mg, and 48.8% after placebo administration. Conclusions In this study, pitolisant demonstrated significantly lower potential for abuse compared with phentermine and an overall profile similar to placebo; this suggests a low risk of abuse for pitolisant. Clinical Trial Registration ClinicalTrials.gov NCT03152123. Determination of the abuse potential of pitolisant in healthy, nondependent recreational stimulant users. https://clinicaltrials.gov/ct2/show/NCT03152123.
Traffic Monitoring via Mobile Device Location

Measuring traffic in real time is one of the main functionalities of Smart Cities. To reduce the costs of deployment and operation, traffic measurement with mobile devices has been widely studied. In this paper, a traffic monitoring system using mobile devices is proposed. The proposed algorithm has the advantage of having a very low computational cost, allowing most of the pre-processing to be done in the mobile device and therefore making possible the centralized collection of a massive number of measurements. The proposed system is composed of three algorithms; a map-matching algorithm to correct minor location errors, a Virtual Inductive Loop that estimates the traffic and a traffic data collector that aggregates the information from many devices and combines it with other information sources. The system has been tested in a real scenario, comparing its accuracy with a traditional traffic sensor, showing its accuracy.
Abnormal lacuno-canalicular network and negative correlation between serum osteocalcin and Cobb angle indicate abnormal osteocyte function in adolescent idiopathic scoliosis

Adolescent idiopathic scoliosis (AIS) is a prevalent spinal deformity occurring during peripubertal growth period that affects 1‐4% of adolescents globally without clear etiopathogenetic mechanism. Low bone mineral density is an independent and significant prognostic factor for curve progression. Currently, the cause underlying low bone mass in AIS remains elusive. Osteocytes play an important role in bone metabolism and mineral homeostasis, but its role in AIS has not been studied. In the present study, iliac bone tissues were harvested from 21 patients with AIS (mean age of 14.3 ± 2.20 yr old) with a mean Cobb angle of 55.6 ± 10.61° and 13 non‐AIS controls (mean age of 16.5 ± 4.79 yr old) intraoperatively. Acid‐etched scanning electron microscopy (SEM) images of AIS demonstrated abnormal osteocytes that were more rounded and cobblestone‐like in shape and were aligned in irregular clusters with shorter and disorganized canaliculi. Further quantitative analysis with FITC‐Imaris technique showed a significant reduction in the canalicular number and length as well as an increase in lacunar volume and area in AIS. SEM with energy‐dispersive X‐ray spectroscopy analysis demonstrated a lower calcium‐to‐phosphorus ratio at the perilacunar/canalicular region. Moreover, microindentaion results revealed lower values of Vickers hardness and elastic modulus in AIS when compared with controls. In addition, in the parallel study of 99 AIS (27 with severe Cobb angle of 65.8 ± 14.1° and 72 with mild Cobb angle of 26.6 ± 9.1°) with different curve severity, the serum osteocalcin level was found to be significantly and negatively associated with the Cobb angle. In summary, the findings in this series of studies demonstrated the potential link of abnormal osteocyte lacuno‐canalicular network structure and function to the observed abnormal bone mineralization in AIS, which may shed light on etiopathogenesis of AIS. —Chen, H. , Zhang, J., Wang, Y. , Cheuk, K. ‐Y. , Hung, A. L. H. , Lam, T. ‐P., Qiu, Y. , Feng, J. Q. , Lee, W. Y. W. , Cheng, J. C. Y. Abnormal lacuno‐canalicular network and negative correlation between serum osteocalcin and Cobb angle indicate abnormal osteocyte function in adolescent idiopathic scoliosis. FASEB J. 33, 13882‐13892 (2019). www.fasebj. org
Changes in Manufacturing Processes of Biologic Therapies Can Alter the Immunogenicity Profile of the Product

Manufacturing process changes may alter the characteristics of a protein therapeutic. In 2009, somatropin (version 1.0), a recombinant human growth hormone therapeutic, underwent a manufacturing update (version 1.1). The immunogenicity of somatropin version 1.1 as a daily subcutaneous injection was evaluated in 2014 in a prospective, open‐label, single‐arm clinical study of treatment‐naive pediatric patients with idiopathic human growth hormone deficiency for 1 year. The primary end point was the proportion of patients who developed antidrug antibodies (ADAs) after treatment. Eighty‐two patients were enrolled. The mean (SD) treatment duration was 347 (53) days. The incidence of ADAs was 3.7%. No neutralizing antibodies were observed in the three patients with ADA‐positive samples. Two patients (2.6%) had growth attenuation, but they were not ADA positive. The manufacturing changes for somatropin version 1.1 resulted in a similar safety and efficacy profile compared with somatropin version 1.0 and a different immunogenicity profile with a lower incidence of ADAs.
Clinical diagnostic exome sequencing in dystonia: Genetic testing challenges for complex conditions

Patients with dystonia are particularly appropriate for diagnostic exome sequencing (DES), due to the complex, diverse features and genetic heterogeneity. Personal and family history data were collected from test requisition forms and medical records from 189 patients with reported dystonia and available family members received for clinical DES. Of them, 20.2% patients had a positive genetic finding associated with dystonia. Detection rates for cases with isolated and combined dystonia were 22.4% and 25.0%, respectively. 71.4% of the cohort had co‐occurring non‐movement‐related findings and a detection rate of 24.4%. Patients with childhood‐onset dystonia trended toward higher detection rates (31.8%) compared to infancy (23.6%), adolescence (12.5%), and early‐adulthood onset (16%). Uncharacterized gene findings were found in 6.7% (8/119) of cases that underwent analysis for genes without an established disease relationship. Patients with intellectual disability/developmental delay, seizures/epilepsy and/or multifocal dystonia were more likely to have positive findings (P = .0093, .0397, .0006). Four (2.1%) patients had findings in two genes, and seven (3.7%) had reclassification after the original report due to new literature, new clinical information or reanalysis request. Pediatric patients were more likely to have positive findings (P = .0180). Our observations show utility of family‐based DES in patients with dystonia and illustrate the complexity of testing.
Phosphorus-Containing Flame Retardants from Biobased Chemicals and Their Application in Polyesters and Epoxy Resins

Phosphorus-containing flame retardants synthesized from renewable resources have had a lot of impact in recent years. This article outlines the synthesis, characterization and evaluation of these compounds in polyesters and epoxy resins. The different approaches used in producing biobased flame retardant polyesters and epoxy resins are reported. While for the polyesters biomass derived compounds usually are phosphorylated and melt blended with the polymer, biobased flame retardants for epoxy resins are directly incorporated into the polymer structure by a using a phosphorylated biobased monomer or curing agent. Evaluating the efficiency of the flame retardant composites is done by discussing results obtained from UL94 vertical burning, limiting oxygen index (LOI) and cone calorimetry tests. The review ends with an outlook on future development trends of biobased flame retardant systems for polyesters and epoxy resins.
Factors Associated with Shortening of Prehospital Delay among Patients with Acute Ischemic Stroke

Background: Despite recent advances in acute stroke care, only 1–8% of patients can receive reperfusion therapies, mainly because of prehospital delay (PHD). Objective: This study aimed to identify factors associated with PHD from the onset of acute stroke symptoms until arrival at the hospital. Methods: A cross-sectional study was conducted including all patients consecutively admitted with stroke symptoms to Burgos University Hospital (Burgos, Spain). Socio-demographic, clinical, behavioral, cognitive, and contextualized characteristics were recorded, and their possible associations with PHD were studied using univariate and multivariable regression analyses. Results: The median PHD of 322 patients was 138.50 min. The following factors decreased the PHD and time until reperfusion treatment where applicable: asking for help immediately after the onset of symptoms (OR 10.36; 95% confidence interval (CI) 4.47–23.99), onset of stroke during the daytime (OR 7.73; 95% CI 3.09–19.34) and the weekend (OR 2.64; 95% CI 1.19–5.85), occurrence of stroke outside the home (OR 7.09; 95% CI 1.97–25.55), using a prenotification system (OR 6.46; 95% CI 1.71–8.39), patient’s perception of being unable to control symptoms without assistance (OR 5.14; 95% CI 2.60–10.16), previous knowledge of stroke as a medical emergency (OR 3.20; 95% CI 1.38–7.40), call to emergency medical services as the first medical contact (OR 2.77; 95% CI 1.32–5.88), speech/language difficulties experienced by the patient (OR 2.21; 95% CI 1.16–4.36), and the identification of stroke symptoms by the patient (OR 1.98; 95% CI 1.03–3.82). Conclusions: The interval between the onset of symptoms and arrival at the hospital depends on certain contextual, cognitive, and behavioral factors, all of which should be considered when planning future public awareness campaigns.
Aggregation State of Residual α-Helices and Their Influence on Physical Properties of S. c. ricini Native Fiber

Formation of the α-helical conformation in the poly-l-alanine (PA) sequence regions, subsequent structural transition to β-sheet during natural spinning, and presence of residual α-helices in Samia cynthia ricini (S. c. ricini) native silk fiber have been experimentally proven. However, the aggregation state of the residual α-helices, and their influence on the mechanical deformation behavior in native fiber remain unclear. Here we show that the α-helices form an ordered aggregation state with a hexagonal packing in the aqueous solution, some of which remain during natural spinning. X-ray scattering and differential scanning calorimetry (DSC) analyses revealed occurrence of a structural transition of the residual α-helices to the β-sheet structure, accompanied by disappearance of the plateau region in the force-strain curve, due to heat-treatment at ~220 °C. On the basis of X-ray scattering before and after tensile stretching of S. c. ricini native silk, a direct connection between the plateau region and the α-helix to β-sheet structural transition was confirmed. Our findings demonstrate the importance of the PA sequence regions in fiber structure formation and their influence on the tensile deformation behavior of S. c. ricini silk, features believed to be essentially similar in other saturniid silks. We strongly believe the residual ordered α-helices to be strategically and systematically designed by S. c. ricini silkworms to impart flexibility in native silk fiber. We anticipate that these knowledge forms a basis for fruitful strategies in the design and development of amino acid sequences for artificial silks with desired mechanical properties.
Passive Source Localization Using Compressive Sensing

This paper presents an underwater passive source localization method by forming an underdetermined linear inversion problem. The signal strength on a specified grid is evaluated using sparse reconstruction algorithms by exploiting the spatial sparsity of the source signals. Our strategy leads to a high ratio of measurements to sparsity (RMS), an increase in the peak sharpness with a low side lobe level, and minimization of the dimensionality of the problem due to the formulation of the system equation of the multiple snapshots based on the data correlation matrix. Furthermore, to reduce the computational burden, pre-locating with Bartlett is presented. Our proposed technique can perform close to Bartlet and white noise gain constraint processes in the single-source scenario, but it can give slightly better results while localizing multiple sources. It exhibits the respective characteristics of traditionally used Bartlett and white noise gain constraint methods, such as robustness to environmental/system mismatch and high resolution. Both the simulated and experimental data are processed to demonstrate the effectiveness of the method for underwater source localization.
Effects of Peptide YY on the Hypothalamic-Pituitary-Gonadal Axis in Healthy Men

Abstract Context Central and peripheral administration of peptide YY (PYY) has potent anorectic effects, and PYY analogs are under development as antiobesity treatments. Recent animal data suggest PYY may also influence the reproductive axis; however the effects of PYY on the human reproductive system are unknown. Objective To investigate the effects of PYY administration on the reproductive axis in healthy young men. Design Single-blind, randomized, placebo-controlled crossover study. Setting Clinical Research Facility, Imperial College Healthcare NHS Trust. Participants Eighteen healthy eugonadal men (mean age 24.1 ± 0.9 years, mean body mass index 22.2 ± 0.4 kg/m2). Intervention Eight-hour intravenous infusion of 0.4 pmol/kg/min PYY3-36 or rate-matched vehicle infusion. Main Outcome Measures Number of luteinizing hormone (LH) pulses, LH, follicle stimulating hormone (FSH), and testosterone levels. Results The number of LH pulses (mean number of LH pulses/8 hours: PYY 4.4 ± 0.3 vs vehicle 4.4 ± 0.4, P > .99), LH area under the curve (AUC) (PYY 1503 ± 79 IU.min/L vs vehicle 1574 ± 86 IU.min/L, P = .36), FSH AUC (PYY 1158 ± 513 IU.min/L vs vehicle 1199 ± 476 IU.min/L, P = .49) and testosterone AUC (PYY 10 485 ± 684 IU.min/L vs vehicle 11 133 ± 803 IU.min/L, P = .24) were similar during PYY and vehicle infusions. Conclusions Acute intravenous infusion of 0.4 pmol/kg/min PYY does not affect the reproductive axis in healthy men.