Miracle-dz/UniFAR-FTUs huggingface dataset:
Linguistic Distributional Knowledge and Sensorimotor Grounding both Contribute to Semantic Category Production

The human conceptual system comprises simulated information of sensorimotor experience and linguistic distributional information of how words are used in language. Moreover, the linguistic shortcut hypothesis predicts that people will use computationally cheaper linguistic distributional information where it is sufficient to inform a task response. In a pre-registered category production study, we asked participants to verbally name members of concrete and abstract categories and tested whether performance could be predicted by a novel measure of sensorimotor similarity (based on an 11-dimensional representation of sensorimotor strength) and linguistic proximity (based on word co-occurrence derived from a large corpus). As predicted, both measures predicted the order and frequency of category production but, critically, linguistic proximity had an effect above and beyond sensorimotor similarity. A follow-up study using typicality ratings as an additional predictor found that typicality was often the strongest predictor of category production variables, but it did not subsume sensorimotor and linguistic effects. Finally, we created a novel, fully grounded computational model of conceptual activation during category production, which best approximated typical human performance when conceptual activation was allowed to spread indirectly between concepts, and when candidate category members came from both sensorimotor and linguistic distributional representations. Critically, model performance was indistinguishable from typical human performance. Results support the linguistic shortcut hypothesis in semantic processing and provide strong evidence that both linguistic and grounded representations are inherent to the functioning of the conceptual system. All materials, data, and code are available at https://osf.io/vaq56/.
Imbalance in Carbon and Nitrogen Metabolism in Comamonas testosteroni R2 Is Caused by Negative Feedback and Rescued by L-arginine

The collapse of Comamonas testosteroni R2 under chemostat conditions and the aerobic growth of strain R2 under batch conditions with phenol as the sole carbon source were investigated using physiological and transcriptomic techniques. Phenol-/catechol-degrading activities under chemostat conditions gradually decreased, suggesting that metabolites produced from strain R2 accumulated in the culture, which caused negative feedback. The competitive inhibition of phenol hydroxylase and catechol dioxygenase was observed in a crude extract of the supernatant collected from the collapsed culture. Transcriptomic analyses showed that genes related to nitrogen transport were up-regulated; the ammonium transporter amtB was up-regulated approximately 190-fold in the collapsed status, suggesting an increase in the concentration of ammonium in cells. The transcriptional levels of most of the genes related to gluconeogenesis, glycolysis, the pentose phosphate pathway, and the TCA and urea cycles decreased by ~0.7-fold in the stable status, whereas the activities of glutamate synthase and glutamine synthetase increased by ~2-fold. These results suggest that ammonium was assimilated into glutamate and glutamine via 2-oxoglutarate under the limited supply of carbon skeletons, whereas the synthesis of other amino acids and nucleotides was repressed by 0.6-fold. Furthermore, negative feedback appeared to cause an imbalance between carbon and nitrogen metabolism, resulting in collapse. The effects of amino acids on negative feedback were investigated. L-arginine allowed strain R2 to grow normally, even under growth-inhibiting conditions, suggesting that the imbalance was corrected by the stimulation of the urea cycle, resulting in the rescue of strain R2.
Age‐Related Changes in Bone Density, Microarchitecture, and Strength in Postmenopausal Black and White Women: The SWAN Longitudinal HR‐pQCT Study

Higher fracture risk in White versus Black women is partly explained by lower BMD and worse bone microarchitecture in White women. However, whether rates of decline in bone density, microarchitecture and strength differ between postmenopausal Black and White women is unknown. Further, factors that influence rates of age‐related bone microarchitecture deterioration remain ill‐defined. Thus, over 6.7 years, longitudinal changes were measured in peripheral volumetric bone mineral density (vBMD), microarchitecture, and strength at the distal radius and tibia using HR‐pQCT in postmenopausal Black (n = 80) and White (n = 137) women participating in the Study of Women's Health Across the Nation. It was assessed whether age‐related changes in vBMD and microarchitecture were influenced by body weight, body composition, and/or weight change. It was found that at the radius, where White women appeared to have slightly greater rates of loss in total vBMD, cortical bone volume, and porosity than Black women, those differences were attenuated after adjusting for clinical covariates. At the tibia, Black and White women had similar rates of bone loss. Independent of race and other clinical covariates, women with the lowest baseline body weight experienced the greatest decline in total and trabecular vBMD at the radius. Furthermore, women who lost weight over the follow‐up period had higher rates of bone loss, particularly at the tibia, compared with those who maintained or gained weight. Higher baseline total body fat mass was also protective of bone loss at both the radius and tibia. In conclusion, these findings indicate that lower fracture risk among postmenopausal Black women is not caused by slower rates of bone deterioration, and highlight the importance for postmenopausal women to avoid lower body weight and excessive weight loss to avert rapid bone loss and subsequent fractures. © 2021 American Society for Bone and Mineral Research (ASBMR).
A prospective cohort study on association of first-trimester serum biomarkers and risk of isolated foetal congenital heart defects

Abstract Background This study aims to assess the association between first-trimester biomarkers in foetuses with a non-chromosomal congenital heart defect (CHD) and compares it to the matched healthy foetuses. Method Nuchal Translucency (NT), Pregnancy-Associated Plasma Protein-A (PAPP-A) and free beta-human Chorionic Gonadotropin (β-hCG) were evaluated in 56 isolated foetal heart defects and 224 controls. The CHDs were further divided into Critical CHD (C-CHD) and Non-critical CHD (N-CHD) groups. Results The multiple of the median (MoM) values for PAPP-A were significantly lower (0.87 MoM vs. 0.92 MoM; p = 0.008) in the total CHD group than in controls. The median of foetal NT values was significantly higher in the total CHDs than in controls (1.16 MoM vs. 1.03 MoM; p < 0.001), especially for C-CHDs (1.28 MoM; P < 0.001). There were no significant differences in terms of PAPP-A (p = 0.779) and foetal NT values (p = 0.760) between the N-CHDs and control groups. There were no significant differences within the groups based on free β-hCG, except for a lower β-hCG in C-CHD group than in the control group (0.95 MoM vs. 1.11 MoM; p = 0.022). Conclusion Lower PAPP-A levels and increased NT thickness were associated with an increased risk of CHDs, especially the critical type of CHDs. Clinical significance Maternal serum PAPP-A, measured in the first trimester, is significantly lower in CHD. Foetal NT is significantly thicker in foetuses with CHD, especially those with critical CHD. Maternal serum β-hCG was only decreased among critical CHD group.
Prediction of in‐hospital mortality with machine learning for COVID‐19 patients treated with steroid and remdesivir

We aimed to create the prediction model of in‐hospital mortality using machine learning methods for patients with coronavirus disease 2019 (COVID‐19) treated with steroid and remdesivir. We reviewed 1571 hospitalized patients with laboratory confirmed COVID‐19 from the Mount Sinai Health System treated with both steroids and remdesivir. The important variables associated with in‐hospital mortality were identified using LASSO (least absolute shrinkage and selection operator) and SHAP (SHapley Additive exPlanations) through the light gradient boosting model (GBM). The data before February 17th, 2021 (N = 769) was randomly split into training and testing datasets; 80% versus 20%, respectively. Light GBM models were created with train data and area under the curves (AUCs) were calculated. Additionally, we calculated AUC with the data between February 17th, 2021 and March 30th, 2021 (N = 802). Of the 1571 patients admitted due to COVID‐19, 331 (21.1%) died during hospitalization. Through LASSO and SHAP, we selected six important variables; age, hypertension, oxygen saturation, blood urea nitrogen, intensive care unit admission, and endotracheal intubation. AUCs using training and testing datasets derived from the data before February 17th, 2021 were 0.871/0.911. Additionally, the light GBM model has high predictability for the latest data (AUC: 0.881) (https://risk-model.herokuapp.com/covid). A high‐value prediction model was created to estimate in‐hospital mortality for COVID‐19 patients treated with steroid and remdesivir.
ELM-Based Adaptive Faster Fixed-Time Control of Robotic Manipulator Systems

This article addresses the problem of fast fixed-time tracking control for robotic manipulator systems subject to model uncertainties and disturbances. First, on the basis of a newly constructed fixed-time stable system, a novel faster nonsingular fixed-time sliding mode (FNFTSM) surface is developed to ensure a faster convergence rate, and the settling time of the proposed surface is independent of initial values of system states. Subsequently, an extreme learning machine (ELM) algorithm is utilized to suppress the negative influence of system uncertainties and disturbances. By incorporating fixed-time stable theory and the ELM learning technique, an adaptive fixed-time sliding mode control scheme without knowing any information of system parameters is synthesized, which can circumvent chattering phenomenon and ensure that the tracking errors converge to a small region in fixed time. Finally, the superior of the proposed control strategy is substantiated with comparison simulation results.
Kinomics platform using GBM tissue identifies BTK as being associated with higher patient survival

BTK is a dominant bioactive kinase expressed within both cancer and immune cells of GBM tissue. Complex cell co-cultures might better model the impact of kinase inhibitors as therapeutics in GBM. Better understanding of GBM signalling networks in-vivo would help develop more physiologically relevant ex vivo models to support therapeutic discovery. A “functional proteomics” screen was undertaken to measure the specific activity of a set of protein kinases in a two-step cell-free biochemical assay to define dominant kinase activities to identify potentially novel drug targets that may have been overlooked in studies interrogating GBM-derived cell lines. A dominant kinase activity derived from the tumour tissue, but not patient-derived GBM stem-like cell lines, was Bruton tyrosine kinase (BTK). We demonstrate that BTK is expressed in more than one cell type within GBM tissue; SOX2-positive cells, CD163-positive cells, CD68-positive cells, and an unidentified cell population which is SOX2-negative CD163-negative and/or CD68-negative. The data provide a strategy to better mimic GBM tissue ex vivo by reconstituting more physiologically heterogeneous cell co-culture models including BTK-positive/negative cancer and immune cells. These data also have implications for the design and/or interpretation of emerging clinical trials using BTK inhibitors because BTK expression within GBM tissue was linked to longer patient survival.
Screening for SARS-CoV-2 infection in asymptomatic individuals using the Panbio COVID-19 antigen rapid test (Abbott) compared with RT-PCR: a prospective cohort study

Background Antigen-based point-of-care tests for identification of SARS-CoV-2 may markedly enhance effectiveness of population-based controlling strategies. Previous studies have demonstrated >70% sensitivity and high specificity compared with reverse transcriptase real-time PCR (RT-PCR) in symptomatic individuals, but test performance for asymptomatic individuals is unknown. Methods Test performance of the Panbio COVID-19 Ag Rapid Test (Abbott) was compared with RT-PCR in a longitudinal cohort study of asymptomatic football players and staff members of professional football clubs. Based on timing of symptoms and prior and subsequent test results, positive RT-PCR tests were categorised as presymptomatic, early or late infection, or persistent RNA shedding. Findings 2425 tests were performed in 824 individuals, of which 52 (6.3%) were SARS-CoV-2 positive based on RT-PCR. There were 2406 paired sets from asymptomatic subjects for analysis. Sixteen Panbio tests were inconclusive, for which sensitivity analyses were performed (considering results as either positive or negative or being excluded). Sensitivity of Panbio for screening of asymptomatic individuals ranged from 80.0% (61.4–92.3) to 86.67% (69.2–96.2) and specificity from 99.53% (95% CI 99.2 to 99.8) to 100% (95% CI 99.8 to 100). Sensitivity of Panbio to detect subjects with presymptomatic/early infection (n=42) ranged from 81.82% (95% CI 67.3 to 91.8) to 90.91% (95% CI 78.3 to 97.5) with specificity always above 99%. Interpretation The Panbio COVID-19 Ag rapid test identifies 81%–90% of presymptomatic and early asymptomatic SARS-CoV-2 infections with high specificity. This test may therefore be adopted in testing strategies such as targeted screening of specific populations where prevalence is low.
Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder.

BACKGROUND Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder. METHODS We conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ. RESULTS Of the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was -3.7 in the oxytocin group and -3.5 in the placebo group (least-squares mean difference, -0.2; 95% confidence interval, -1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONS This placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.).
Long Noncoding RNA MIAT Controls Advanced Atherosclerotic Lesion Formation and Plaque Destabilization

Supplemental Digital Content is available in the text. Background: Long noncoding RNAs (lncRNAs) are important regulators of biological processes involved in vascular tissue homeostasis and disease development. The present study assessed the functional contribution of the lncRNA myocardial infarction-associated transcript (MIAT) to atherosclerosis and carotid artery disease. Methods: We profiled differences in RNA transcript expression in patients with advanced carotid artery atherosclerotic lesions from the Biobank of Karolinska Endarterectomies. The lncRNA MIAT was identified as the most upregulated noncoding RNA transcript in carotid plaques compared with nonatherosclerotic control arteries, which was confirmed by quantitative real-time polymerase chain reaction and in situ hybridization. Results: Experimental knockdown of MIAT, using site-specific antisense oligonucleotides (LNA-GapmeRs) not only markedly decreased proliferation and migration rates of cultured human carotid artery smooth muscle cells (SMCs) but also increased their apoptosis. MIAT mechanistically regulated SMC proliferation through the EGR1 (Early Growth Response 1)-ELK1 (ETS Transcription Factor ELK1)-ERK (Extracellular Signal-Regulated Kinase) pathway. MIAT is further involved in SMC phenotypic transition to proinflammatory macrophage-like cells through binding to the promoter region of KLF4 and enhancing its transcription. Studies using Miat–/– and Miat–/–ApoE–/– mice, and Yucatan LDLR–/– mini-pigs, as well, confirmed the regulatory role of this lncRNA in SMC de- and transdifferentiation and advanced atherosclerotic lesion formation. Conclusions: The lncRNA MIAT is a novel regulator of cellular processes in advanced atherosclerosis that controls proliferation, apoptosis, and phenotypic transition of SMCs, and the proinflammatory properties of macrophages, as well.
Relationship between rainfall-adjusted nitrogen nutrition index and yield of wheat in Western Australia

Abstract Insufficient nitrogen applications may contribute to yield gaps in low rainfall environments of Western Australia (WA). This study tested a nitrogen nutrition index (NNI) for wheat tailored for low rainfall regions, which is based on rainfall-scaled dilution curves. We analyzed yield, shoot biomass, and nitrogen concentration from 32 field trials in WA. An empirical rainfall threshold of 400 mm (summer + growing season rainfall) returned two parallel dilution curves accounting for the reduction of critical N in drier and lower yielding conditions. Scatterplots of relative yield and rainfall-adjusted NNI returned a robust boundary function that may lead to greater adoption by growers. The NNI defined in this research study can be applied and further tested by growers in WA, but may also apply to other low rainfall environments, to close nitrogen related yield gaps.
Urinary caffeine and caffeine metabolites, asthma, and lung function in a nationwide study of U.S. adults

Abstract Objective Coffee intake has been inversely associated with asthma in adults. We examined the relation between urinary levels of caffeine or caffeine metabolites and asthma, lung function, and fractional exhaled nitric oxide (FeNO) in adults. Methods Cross-sectional study of 2,832 adults aged 18-79 years in the US National Health and Nutrition Examination Survey (NHANES). Multivariable logistic or linear regression was used for the analysis of urinary levels of caffeine or each of its three major metabolites (paraxanthine, theobromine, and theophylline) and current asthma, lung function, and FeNO. Results Subjects with urinary paraxanthine levels in the fourth quartile (Q4) had 53% lower odds of current asthma than those whose urinary paraxanthine levels were in the first quartile (Q1; 95% confidence = 0.22 to 1.00). Among never and former smokers, subjects with urinary theophylline levels above Q1 had 49% lower odds of current asthma than those whose urinary theophylline level was in Q1 (95% CI = 0.31 to 0.85). Among subjects without current asthma, each log10-unit increment in paraxanthine level was associated with a 0.83% increment in percent predicted (%pred) FEV1 and a 1.27% increment in %pred FVC, while each log10-unit in theophylline was associated with a 1.24% increment in %pred FVC. Neither urinary caffeine nor any urinary caffeine metabolite was associated with bronchodilator response or FeNO. Conclusions Our findings suggest that two caffeine metabolites (theophylline and paraxanthine) may contribute to the previously reported inverse association between coffee intake and asthma in adults.
COVID-19 Vaccine Type and Humoral Immune Response in Patients Receiving Dialysis

Background Patients on dialysis vaccinated with the attenuated adenovirus SARS-CoV-2 vaccine might mount an impaired response to vaccination. Methods We evaluated the humoral vaccination response among 2,099 fully vaccinated patients receiving dialysis. We used commercially available assays (Siemens) to assess prevalence of no response or diminished response to COVID-19 vaccination by vaccine type. We defined “no seroconversion” as lack of change from negative to positive in total RBD Ig antibody, no detectable response on semiquantitative RBD IgG antibody (index value <1) as “no RBD IgG response”, and a semiquantitative RBD IgG index value <10 as “diminished RBD IgG response” vaccination.
Maternal Iron Status in Early Pregnancy and Blood Pressure Throughout Pregnancy, Placental Hemodynamics, and the Risk of Gestational Hypertensive Disorders

ABSTRACT Background In nonpregnant populations, higher serum ferritin, which reflects high iron stores, is associated with an increased risk of hypertension. We hypothesized that a dysregulated maternal iron status in early pregnancy may lead to impaired gestational hemodynamic adaptations, leading to an increased risk of gestational hypertensive disorders. Objectives We examined the associations of maternal iron status with maternal blood pressure, placental hemodynamic parameters, and the risks of gestational hypertensive disorders. Methods In a population-based prospective cohort study among 5983 pregnant women, we measured maternal serum ferritin, transferrin saturation, serum iron, and transferrin concentrations at a median of 13.2 weeks gestation (95% range, 9.6–17.6). Maternal blood pressure was measured in early pregnancy, mid pregnancy, and late pregnancy, and placental hemodynamic parameters in mid pregnancy and late pregnancy were measured by ultrasound. Information on gestational hypertensive disorders was collected from medical records. We examined the associations of maternal early pregnancy iron status with maternal systolic and diastolic blood pressure, placental hemodynamic parameters, and the risks of gestational hypertensive disorders using linear and logistic regression models. Results Higher maternal early pregnancy serum ferritin concentrations were associated with higher systolic and diastolic blood pressure throughout pregnancy in the basic models (P values < 0.05). After adjustment for maternal inflammation, sociodemographic and lifestyle factors, higher maternal early pregnancy serum ferritin concentrations were only associated with a higher early pregnancy diastolic blood pressure [0.27 (95% CI, 0.03–0.51) mmHg per SD score increase in serum ferritin] and with a higher mid pregnancy umbilical artery pulsatility index (P < 0.05). No associations with the risk of gestational hypertensive disorders were present. Conclusions No consistent associations were present of maternal iron status in early pregnancy with gestational hemodynamic adaptations or the risks of gestational hypertensive disorders. Further studies are needed to examine the potential role of iron metabolism in the development of gestational hypertensive disorders within higher-risk populations.