Miracle-dz/UniFAR-FTUs huggingface dataset:
Towards Risk Minimizing Trajectory Planning in On-Road Scenarios

Trajectory planning for autonomous vehicles should attempt to minimize expected risk given noisy sensor data and uncertain predictions of the near future. In this paper, we present a trajectory planning approach for on-road scenarios where we use a graph search approximation. Uncertain predictions of other vehicles are accounted for by a novel inference technique that allows efficient calculation of the probability of dangerous outcomes for set of modeled situation types.
Genome-Wide and Abdominal MRI Data Provide Evidence That a Genetically Determined Favorable Adiposity Phenotype Is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease, and Hypertension

Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such favorable adiposity alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined MRI data with genome-wide association studies of body fat percentage (%) and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity but a favorable metabolic profile. Consistent with previous studies, individuals carrying more favorable adiposity alleles had higher body fat % and higher BMI but lower risk of type 2 diabetes, heart disease, and hypertension. These individuals also had higher subcutaneous fat but lower liver fat and a lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14, and IRS1, whereas the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified favorable adiposity alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglycerides in metabolically low-risk depots.
Exposure to wild-type AAV drives distinct capsid immunity profiles in humans

Recombinant adeno-associated virus (AAV) vectors have been broadly adopted as a gene delivery tool in clinical trials, owing to their high efficiency of transduction of several host tissues and their low immunogenicity. However, a considerable proportion of the population is naturally exposed to the WT virus from which AAV vectors are derived, which leads to the acquisition of immunological memory that can directly determine the outcome of gene transfer. Here, we show that prior exposure to AAV drives distinct capsid immunity profiles in healthy subjects. In peripheral blood mononuclear cells (PBMCs) isolated from AAV-seropositive donors, recombinant AAV triggered TNF-&agr; secretion in memory CD8+ T cells, B cell differentiation into antibody-secreting cells, and anti-capsid antibody production. Conversely, PBMCs isolated from AAV-seronegative individuals appeared to carry a population of NK cells reactive to AAV. Further, we demonstrated that the AAV capsid activates IL-1&bgr; and IL-6 cytokine secretion in monocyte-related dendritic cells (moDCs). IL-1&bgr; and IL-6 blockade inhibited the anti-capsid humoral response in vitro and in vivo. These results provide insights into immune responses to AAV in humans, define a possible role for moDCs and NK cells in capsid immunity, and open new avenues for the modulation of vector immunogenicity.
Should heart rate variability be “corrected” for heart rate? Biological, quantitative, and interpretive considerations

Abstract Metrics of heart period variability are widely used in the behavioral and biomedical sciences, although somewhat confusingly labeled as heart rate variability (HRV). Despite their wide use, HRV metrics are usually analyzed and interpreted without reference to prevailing levels of cardiac chronotropic state (i.e., mean heart rate or mean heart period). This isolated treatment of HRV metrics is nontrivial. All HRV metrics routinely used in the literature exhibit a known and positive relationship with the mean duration of the interval between two beats (heart period): as the heart period increases, so does its variability. This raises the question of whether HRV metrics should be “corrected” for the mean heart period (or its inverse, the heart rate). Here, we outline biological, quantitative, and interpretive issues engendered by this question. We provide arguments that HRV is neither uniformly nor simply a surrogate for heart period. We also identify knowledge gaps that remain to be satisfactorily addressed with respect to assumptions underlying existing HRV correction approaches. In doing so, we aim to stimulate further progress toward the rigorous use and disciplined interpretation of HRV. We close with provisional guidance on HRV reporting that acknowledges the complex interplay between the mean and variability of the heart period.
MicroRNA‐132 directs human periodontal ligament‐derived neural crest stem cell neural differentiation

Neurogenesis is the basis of stem cell tissue engineering and regenerative medicine for central nervous system (CNS) disorders. We have established differentiation protocols to direct human periodontal ligament‐derived stem cells (PDLSCs) into neuronal lineage, and we recently isolated the neural crest subpopulation from PDLSCs, which are pluripotent in nature. Here, we report the neural differentiation potential of these periodontal ligament‐derived neural crest stem cells (NCSCs) as well as its microRNA (miRNA) regulatory mechanism and function in NCSC neural differentiation. NCSCs, treated with basic fibroblast growth factor and epidermal growth factor‐based differentiation medium for 24 days, expressed neuronal and glial markers (βIII‐tubulin, neurofilament, NeuN, neuron‐specific enolase, GFAP, and S100) and exhibited glutamate‐induced calcium responses. The global miRNA expression profiling identified 60 upregulated and 19 downregulated human miRNAs after neural differentiation, and the gene ontology analysis of the miRNA target genes confirmed the neuronal differentiation‐related biological functions. In addition, overexpression of miR‐132 in NCSCs promoted the expression of neuronal markers and downregulated ZEB2 protein expression. Our results suggested that the pluripotent NCSCs from human periodontal ligament can be directed into neural lineage, which demonstrate its potential in tissue engineering and regenerative medicine for CNS disorders.
Aging Alters the Relative Contributions of the Sympathetic and Parasympathetic Nervous System to Blood Pressure Control in Women

Autonomic support of blood pressure increases with age in humans. Large differences exist in the dose of trimethaphan (TMP) required for ganglionic blockade in young and older women. We asked whether differences in the dose of TMP required to achieve ganglionic blockade are because of differences in the relative contributions of the sympathetic and parasympathetic nervous system in control of blood pressure with age. Muscle sympathetic nerve activity (microneurography, peroneal nerve), heart rate (HR), and blood pressure were recorded before and during incremental doses of TMP camsylate until ganglionic blockade was achieved (absence of muscle sympathetic nerve activity and <5-bpm increase in HR during a valsalva maneuver; final TMP dose, 1–7 mg/min). HR variability was analyzed from the ECG waveform (WinCPRS). The dose of TMP required to achieve ganglionic blockade is positively related to basal HR variability, where women with high HR variability require a higher dose of TMP to achieve ganglionic blockade. In contrast, baseline muscle sympathetic nerve activity is inversely related with the dose of TMP required to achieve ganglionic blockade, such that women with high basal muscle sympathetic nerve activity required a lower dose of TMP. As such, the change in HR with ganglionic blockade was positively related, and the change in mean arterial pressure was inversely related, with the dose of TMP required to achieve ganglionic blockade. These data suggest loss of parasympathetic tone and increased sympathetic tone with aging contribute to the increase in blood pressure with age in women and dictate the dose of TMP that is necessary to achieve ganglionic blockade.
DNA hypermethylation within TERT promoter upregulates TERT expression in cancer

Replicative immortality is a hallmark of cancer cells governed by telomere maintenance. Approximately 90% of human cancers maintain their telomeres by activating telomerase, driven by the transcriptional upregulation of telomerase reverse transcriptase (TERT). Although TERT promoter mutations (TPMs) are a major cancer-associated genetic mechanism of TERT upregulation, many cancers exhibit TERT upregulation without TPMs. In this study, we describe the TERT hypermethylated oncological region (THOR), a 433-bp genomic region encompassing 52 CpG sites located immediately upstream of the TERT core promoter, as a cancer-associated epigenetic mechanism of TERT upregulation. Unmethylated THOR repressed TERT promoter activity regardless of TPM status, and hypermethylation of THOR counteracted this repressive function. THOR methylation analysis in 1,352 human tumors revealed frequent (>45%) cancer-associated DNA hypermethylation in 9 of 11 (82%) tumor types screened. Additionally, THOR hypermethylation, either independently or along with TPMs, accounted for how approximately 90% of human cancers can aberrantly activate telomerase. Thus, we propose that THOR hypermethylation is a prevalent telomerase-activating mechanism in cancer that can act independently of or in conjunction with TPMs, further supporting the utility of THOR hypermethylation as a prognostic biomarker.
Poisoning deaths among late-middle aged and older adults: comparison between suicides and deaths of undetermined intent

ABSTRACT Background: Given the rapid increase in prescription and illicit drug poisoning deaths in the 50+ age group, we examined precipitating/risk factors and toxicology results associated with poisoning deaths classified as suicides compared to intent-undetermined death (UnD) among decedents aged 50+. Methods: Data were from the 2005–2015 US National Violent Death Reporting System (N = 15,453). χ2 tests and multinomial logistic regression models were used to compare three groups of decedents: suicide decedent who left a suicide note, suicide decedent who did not leave a note, and UnD cases. Results: Compared to suicide decedents without a note (37.7% of the sample), those with a note (29.4%) were more likely to have been depressed and had physical health problems and other life stressors, while UnD cases (32.9%) were less likely to have had mental health problems and other life stressors but more likely to have had substance use and health problems. UnD cases were also more likely to be opioid (RRR = 2.65, 95% CI = 2.42–2.90) and cocaine (RRR = 2.59, 95% CI = 2.09–3.21) positive but less likely to be antidepressant positive. Blacks were more than twice as likely as non-Hispanic Whites to be UnDs. Results from separate regression models in the highest UnD states (Maryland and Utah) and in states other than Maryland/Utah were similar. Conclusions: Many UnDs may be more correctly classified as unintentional overdose deaths. Along with more accurate determination processes for intent/manner of death, substance use treatment and approaches to curbing opioid and other drug use problems are needed to prevent intentional and unintentional poisoning deaths.
A retrospective analysis of the performance of the RosettaGX® Reveal™ thyroid miRNA and the Afirma Gene Expression Classifiers in a cohort of cytologically indeterminate thyroid nodules

Molecular tests are increasingly used to triage cytologically indeterminate thyroid nodules for surgery and/or follow‐up. We retrospectively compared the performance of the Afirma Gene Expression Classifier (AGEC) with that of the more recently developed RosettaGX® Reveal™ miRNA Classifier (Reveal) in a cohort of Bethesda III–V thyroid FNAs with surgical follow‐up.
A Prospective Cohort Study Examining the Associations of Maternal Arsenic Exposure With Fetal Loss and Neonatal Mortality

Arsenic crosses the placenta, possibly increasing the risk of adverse reproductive outcomes. We aimed to examine the association between maternal arsenic exposure and fetal/neonatal survival using data from a prospective cohort study of 1,616 maternal-infant pairs recruited at a gestational age of ≤16 weeks in Bangladesh (2008-2011). Arsenic concentration in maternal drinking water was measured at enrollment. Extended Cox regression (both time-dependent coefficients and step functions) was used to estimate the time-varying association between maternal arsenic exposure and fetal/neonatal death (all mortality between enrollment and 1 month after birth). In a sensitivity analysis, we assessed gestational arsenic exposure using maternal urine samples taken at enrollment. We observed 203 fetal losses and 20 neonatal deaths. Higher arsenic exposure was associated with a slightly decreased mortality rate up to the middle of the second trimester, and then the mortality rate switched directions around 20 weeks' gestation. In the step function model, the hazard ratios for combined mortality (fetal loss and neonatal death) per unit increase in the natural log of drinking water arsenic concentration (μg/L) ranged from 1.35 (95% CI: 1.08, 1.69) in weeks 25-28 to 0.81 (95% CI: 0.65, 1.02) in weeks 9-12. This nonlinear association suggests that arsenic may exert survival pressure on developing fetuses, potentially contributing to survival bias, and may also indicate that arsenic toxicity differs by fetal developmental stage.
Parental Adjustment following Pediatric Burn Injury: The Role of Guilt, Shame, and Self-Compassion

Objective The purpose of this study was to examine the association between factors: guilt, shame, self-compassion, and parents' psychological adjustment to their child's burn injury. Methods Participants were 91 parents and primary caregivers (63 mothers, 25 fathers, 3 other) of 71 children recruited on the ward or at outpatient clinics during the first 8 weeks following their child's burn injury. In 20 cases, both parents participated, while for 51 children only one parent participated. Participants completed questionnaires which assessed adjustment (symptoms of depression, anxiety, and posttraumatic stress syndrome [PTSS]) as well as guilt, shame, and self-compassion. Results Multilevel analysis indicated that feelings of guilt and shame were associated with poorer adjustment in parents, while parents who rated high in self-compassion reported fewer symptoms of depression and PTSS. Guilt and shame showed a differing pattern of effects with shame explaining more variance for anxiety and depression. Length of hospitalization predicted PTSS; however, the remaining injury factors (size of burn, requiring a skin graft) were unrelated to parental adjustment. Conclusions Health-care professionals should pay close attention to families' subjective injury experiences. Screening for psychological distress should be offered to all families regardless of the size and severity of the burn injury.
Blood Pressure Pattern and Target Organ Damage in Patients With Chronic Kidney Disease

In patients with chronic kidney disease, data on blood pressure (BP) pattern and its association with target organ damage, which indicates elevated cardiovascular risk, are sparse. In 305 treated hypertensive chronic kidney disease patients, we assessed BP pattern, left ventricular mass (magnetic resonance imaging), intima-media thickness (ultrasound), 24-hour–pulse wave velocity and 24-hour–central augmentation index (Mobil-O-Graph). Controlled hypertension (normal office and ambulatory BP) was found in 41% and sustained uncontrolled hypertension (elevated office and ambulatory BP) in 30% of patients. Misclassification of BP status occurred in 29%: white coat uncontrolled hypertension (elevated office but normal ambulatory BP) was detected in 11% and masked uncontrolled hypertension (normal office but elevated ambulatory BP) in 18% of patients. Left ventricular mass was increased in white coat uncontrolled hypertension (+11.2 g), masked uncontrolled hypertension (+9.4 g), and sustained uncontrolled hypertension (+16.6 g) compared with controlled hypertension. Intima-media thickness was similar across all 4 BP groups. Twenty-four hour–pulse wave velocity and 24-hour–central augmentation index were increased in masked uncontrolled hypertension (+0.5 m/sec and +2.5%) and sustained uncontrolled hypertension (+0.5 m/sec and +2.9%) compared with controlled hypertension. In conclusion, based on office BP measurements, misclassification of true BP status occurred in almost one-third of chronic kidney disease patients. Both types of misclassification (white coat uncontrolled hypertension and masked uncontrolled hypertension) were associated with parameters of target organ damage. Ambulatory BP monitoring should be used routinely to identify chronic kidney disease patients at high cardiovascular risk.
Noggin rescues age-related stem cell loss in the brain of senescent mice with neurodegenerative pathology

Significance Alzheimer’s disease (AD) is the most common cause of age-related neurodegeneration. Damage initially occurs in the hippocampus, a neurogenic brain region essential in forming memories. Since there is no cure for AD, therapeutic strategies that may aid to slow hippocampal dysfunction are necessary. We describe the precocious hippocampal stem cell loss of a mouse model that mimics the onset of pathological AD-like neurodegeneration. The loss is due to an increase in BMP6 that limits neurogenesis. We demonstrate that blocking BMP signaling by means of Noggin administration is beneficial to the hippocampal microenvironment, restoring stem cell numbers, neurogenesis, and behavior. Our findings support further development of BMP antagonists into translatable molecules for the rescue of stem cells and neurogenesis in neurodegeneration/aging. Increasing age is the greatest known risk factor for the sporadic late-onset forms of neurodegenerative disorders such as Alzheimer’s disease (AD). One of the brain regions most severely affected in AD is the hippocampus, a privileged structure that contains adult neural stem cells (NSCs) with neurogenic capacity. Hippocampal neurogenesis decreases during aging and the decrease is exacerbated in AD, but the mechanistic causes underlying this progressive decline remain largely unexplored. We here investigated the effect of age on NSCs and neurogenesis by analyzing the senescence accelerated mouse prone 8 (SAMP8) strain, a nontransgenic short-lived strain that spontaneously develops a pathological profile similar to that of AD and that has been employed as a model system to study the transition from healthy aging to neurodegeneration. We show that SAMP8 mice display an accelerated loss of the NSC pool that coincides with an aberrant rise in BMP6 protein, enhanced canonical BMP signaling, and increased astroglial differentiation. In vitro assays demonstrate that BMP6 severely impairs NSC expansion and promotes NSC differentiation into postmitotic astrocytes. Blocking the dysregulation of the BMP pathway and its progliogenic effect in vivo by intracranial delivery of the antagonist Noggin restores hippocampal NSC numbers, neurogenesis, and behavior in SAMP8 mice. Thus, manipulating the local microenvironment of the NSC pool counteracts hippocampal dysfunction in pathological aging. Our results shed light on interventions that may allow taking advantage of the brain’s natural plastic capacity to enhance cognitive function in late adulthood and in chronic neurodegenerative diseases such as AD.
K-core Minimization: An Edge Manipulation Approach

In social networks, dense relationships among users contribute to stable networks. Breakdowns of some relationships may cause users to leave the network hence decrease the network stability. A popular metric to measure the stability of a network is k-core, i.e., the maximal subgraph of a social network in which each node has at least k neighbors. In this paper, we propose a novel problem, called k-core minimization. Given a graph G, an integer k and a budget b, we aim to identify a set B of edges with size b, so that we can get the minimum k-core by deleting B from G. We first formally define the problem and prove its NP-hardness. Then a baseline greedy algorithm is proposed. To handle large graphs, an optimized algorithm, named KC-Edge, is developed by adopting novel pruning rules. Finally, comprehensive experiments on 6 real social networks are conducted to demonstrate the efficiency and effectiveness of our proposed methods.
Visual Place Recognition in Long-term and Large-scale Environment based on CNN Feature

With the universal application of camera in intelligent vehicles, visual place recognition has become a major problem in intelligent vehicle localization. The traditional solution is to make visual description of place images using hand-crafted feature for matching places, but this description method is not very good for extreme variability, especially for seasonal transformation. In this paper, we propose a new method based on convolutional neural network (CNN), by putting images into the pre-trained network model to get automatically learned image descriptors, and through some operations of pooling, fusion and binarization to optimize them, then the similarity result of place recognition is presented with the Hamming distance of the place sequence. In the experimental part, we compare our method with some state-of-the-art algorithms, FABMAP, ABLE-M and SeqSLAM, to illustrate its advantages. The experimental results show that our method based on CNN achieves better performance than other methods on the representative public datasets.
Contraceptive patterns after use of emergency contraception among female undergraduate students in Brazil

Abstract Objective: The aim of our study was to describe contraceptive patterns 30 days after use of emergency contraception (EC) among female undergraduate students in São Paulo, Brazil. Methods: This study was part of a larger project conducted in 2015 among 1679 female students aged 18–24 enrolled at the University of São Paulo. Analysis was restricted to the 916 students who reported lifetime use of EC. Logistic regression models were used to examine factors related to the use of contraception within the 30 day period following the last use of EC, changes in contraceptive behaviour before and after EC use, and gaps in contraceptive use within 30 days after EC use. Results: Most women (75.4%) used contraception after accessing EC; 92.9% who used contraception prior to EC exposure resumed use of contraception afterwards, compared with 40.7% who did not use contraception prior to EC exposure. Only 6.3% of women switched to a less effective contraceptive method after EC use. Few women (7.5%) reported post-EC gaps in contraception. Conclusions: The results of this study suggest that EC may serve as a potential precursor to regular contraception among undergraduates in Brazil, with few women reporting contraceptive gaps after EC use. These patterns may contribute to reducing the risk of unintended pregnancy in this population.