Miracle-dz/UniFAR-FTUs huggingface dataset:
Bias Analysis to Guide New Data Collection

Bias analysis serves multiple objectives in epidemiologic data analysis. The objectives most often emphasized are quantification of uncertainty due to systematic errors and reduction in overconfidence by specifying hypotheses that compete with the causal hypothesis. A third objective is the utility of bias analysis to identify strategies for new data collection that will be productive in evaluating the validity of an association. The authors illustrate the value of this objective using two examples. The first example examines the value of comprehensive CYP2D6 genotyping in a study of tamoxifen resistance. Tamoxifen is metabolized primarily by CYP2D6 to more active forms. More than thirty polymorphisms in the CYP2D6 gene reduce its function. We genotyped the most prevalent CYP2D6 polymorphism and found a null association between genotype and breast cancer recurrence in a Danish population. One possibility is that incomplete genotyping of the multiple functional polymorphisms introduced non-differential misclassification and biased the association toward the null. We used bias analysis to evaluate the plausibility of this explanation and to guide a decision about devoting study resources toward more comprehensive genotyping of other polymorphisms in the CYP2D6 gene. The second example examines the association between vitamin K antagonist (VKA) therapy and the incidence of 24 site-specific cancers, using heart valve replacement as an instrumental variable. Earlier studies suggested a protective association between VKA anticoagulants and the incidence of cancer. We observed a null-centered distribution of associations, which may be due to non-differential misclassification of VKA therapy by the instrument. We used bias analysis to evaluate whether this misclassification was likely to explain the null-centered distribution of associations and to guide decisions about conducting a more expensive validation study. In the first example, the bias analysis showed that new data collection would be required to resolve the uncertainty, whereas the second example showed that new data collection was unlikely to be a productive use of scarce study resources.
Embryo–fetal toxicity assessment of vonoprazan in rats and rabbits

Vonoprazan is a new potassium‐competitive acid blocker to treat acid‐related diseases. However, its safety during pregnancy is unclear. The aim of the study was to investigate the potential reproductive toxicity on the embryo–fetal development of vonoprazan. Vonoprazan acetate was administered by intravenous injection to pregnant rats (0, 2, 6 and 20 mg kg–1 day–1) and rabbits (0, 1.2, 3.6 and 12 mg kg–1 day–1) during the organogenetic period (gestation day 6–15 [rats] and 6–18 [rabbits]). Maternal reproductive endpoints were evaluated, together with effects on fetal growth and morphological development. In rats, no treatment‐related effects were found in the highest dose group (20 mg kg–1) and the maternal plasma exposure was ≥50‐fold the expected clinical human exposure. However, in rabbits, dose‐related clinical signs (soft or liquid feces) occurred in the 12 mg kg–1 group, which was regarded as a maternal toxicity. Besides, decreased maternal weight gain also was considered as a minimal maternal toxicity. At 12 mg kg–1, delayed fetal ossification was found as evidence of embryo–fetal growth retardation, which was related to decreased fetal and placental weights. There was no maternal and developmental toxicity in the 1.2 and 3.6 mg kg–1 groups. Thus, the no‐observed‐adverse‐effect levels of vonoprazan acetate in rabbits are considered 3.6 mg kg–1 day–1, which produced plasma exposure that was about 18‐fold human clinical exposure.
Penalized ensemble Kalman filters for high dimensional non-linear systems

The ensemble Kalman filter (EnKF) is a data assimilation technique that uses an ensemble of models, updated with data, to track the time evolution of a usually non-linear system. It does so by using an empirical approximation to the well-known Kalman filter. However, its performance can suffer when the ensemble size is smaller than the state space, as is often necessary for computationally burdensome models. This scenario means that the empirical estimate of the state covariance is not full rank and possibly quite noisy. To solve this problem in this high dimensional regime, we propose a computationally fast and easy to implement algorithm called the penalized ensemble Kalman filter (PEnKF). Under certain conditions, it can be theoretically proven that the PEnKF will be accurate (the estimation error will converge to zero) despite having fewer ensemble members than state dimensions. Further, as contrasted to localization methods, the proposed approach learns the covariance structure associated with the dynamical system. These theoretical results are supported with simulations of several non-linear and high dimensional systems.
CoCrMo alloy vs. UHMWPE Particulate Implant Debris Induces Sex Dependent Aseptic Osteolysis Responses In Vivo using a Murine Model

Background: The rate of revision for some designs of total hip replacements due to idiopathic aseptic loosening has been reported as higher for women. However, whether this is environmental or inherently sex-related is not clear. Objective: Can particle induced osteolysis be sex dependent? And if so, is this dependent on the type of implant debris (e.g. metal vs polymer)? The objective of this study was to test for material dependent inflammatory osteolysis that may be linked to sex using CoCrMo and implant grade conventional polyethylene (UHMWPE), using an in vivo murine calvaria model. Methods: Healthy 12 week old female and male C57BL/6J mice were treated with UHMWPE (1.0um ECD) or CoCrMo particles (0.9um ECD) or received sham surgery. Bone resorption was assessed by micro-computed tomography, histology and histomorphometry on day 12 post challenge. Results: Female mice that received CoCrMo particles showed significantly more inflammatory osteolysis and bone destruction compared to the females who received UHMWPE implant debris. Moreover, females challenged with CoCrMo particles exhibited 120% more inflammatory bone loss compared to males (p<0.01) challenged with CoCrMo implant debris (but this was not the case for UHMWPE particles). Conclusion: We demonstrated sex-specific differences in the amount of osteolysis resulting from CoCrMo particle challenge. This suggests osteo-immune responses to metal debris are preferentially higher in female compared to male mice, and supports the contention that there may be inherent sex related susceptibility to some types of implant debris.
Gradient Layer: Enhancing the Convergence of Adversarial Training for Generative Models

We propose a new technique that boosts the convergence of training generative adversarial networks. Generally, the rate of training deep models reduces severely after multiple iterations. A key reason for this phenomenon is that a deep network is expressed using a highly non-convex finite-dimensional model, and thus the parameter gets stuck in a local optimum. Because of this, methods often suffer not only from degeneration of the convergence speed but also from limitations in the representational power of the trained network. To overcome this issue, we propose an additional layer called the gradient layer to seek a descent direction in an infinite-dimensional space. Because the layer is constructed in the infinite-dimensional space, we are not restricted by the specific model structure of finite-dimensional models. As a result, we can get out of the local optima in finite-dimensional models and move towards the global optimal function more directly. In this paper, this phenomenon is explained from the functional gradient method perspective of the gradient layer. Interestingly, the optimization procedure using the gradient layer naturally constructs the deep structure of the network. Moreover, we demonstrate that this procedure can be regarded as a discretization method of the gradient flow that naturally reduces the objective function. Finally, the method is tested using several numerical experiments, which show its fast convergence.
Loss of GCN5L1 in cardiac cells limits mitochondrial respiratory capacity under hyperglycemic conditions

The mitochondrial acetyltransferase‐related protein GCN5L1 controls the activity of fuel substrate metabolism enzymes in several tissues. While previous studies have demonstrated that GCN5L1 regulates fatty acid oxidation in the prediabetic heart, our understanding of its role in overt diabetes is not fully developed. In this study, we examined how hyperglycemic conditions regulate GCN5L1 expression in cardiac tissues, and modeled the subsequent effect in cardiac cells in vitro. We show that GCN5L1 abundance is significantly reduced under diabetic conditions in vivo, which correlated with reduced acetylation of known GCN5L1 fuel metabolism substrate enzymes. Treatment of cardiac cells with high glucose reduced Gcn5l1 expression in vitro, while expression of the counteracting deacetylase enzyme, Sirt3, was unchanged. Finally, we show that genetic depletion of GCN5L1 in H9c2 cells leads to reduced mitochondrial oxidative capacity under high glucose conditions. These data suggest that GCN5L1 expression is highly responsive to changes in cellular glucose levels, and that loss of GCN5L1 activity under hyperglycemic conditions impairs cardiac energy metabolism.
The Birth Experiences Questionnaire: A Brief Measure Assessing Psychosocial Dimensions of Childbirth

Childbirth is an important life event that has been understudied by psychologists. Parents may find birth to be stressful, painful, and frightening, or feel supported and calm. Birth experiences can be shaped both by preexisting psychological vulnerabilities and by medical events that occur during childbirth. The birth experience may influence both parent and child well-being, helping to shape the health of the new family. This paper introduces the Birth Experiences Questionnaire (BEQ), a brief 10-item measure designed to assess stress, fear, and partner support during birth. We administered the BEQ to 51 couples (102 parents) within 1–2 days of their child’s birth. Categorical principal component analysis was used to test reliability and factor structure. The BEQ showed good reliability (Cronbach’s alpha = .81 for mothers, 0.80 for fathers) and internal consistency, suggesting it is acceptable for use as a unifactorial measure. The most variability was explained by a 3-factor solution, with the 3 factors reflecting Stress, Support, and Fear for mothers and Stress, Support, and Violation of Expectations for fathers. Prenatally assessed stress, depression, pregnancy-specific anxiety, and social support were all predictive of parents’ BEQ scores. BEQ scores were also associated with infant Apgar scores and with couples’ negative emotion word usage during an open-ended birth narrative. The BEQ differentiated between parents who had more medically complex births (e.g., labor induction, complications, and C-section delivery) versus less complex births. In conclusion, the BEQ can be administered shortly after birth to both parents, and may capture important dimensions of the perinatal experience.
Inverse Lidov-Kozai resonance for an outer test particle due to an eccentric perturber

Aims. We analyze the behavior of the argument of pericenter ω2 of an outer particle in the elliptical restricted three-body problem, focusing on the ω2 resonance or inverse Lidov-Kozai resonance. Methods. First, we calculated the contribution of the terms of quadrupole, octupole, and hexadecapolar order of the secular approximation of the potential to the outer particle’s ω2 precession rate (dω2∕dτ). Then, we derived analytical criteria that determine the vanishing of the ω2 quadrupole precession rate (dω2/dτ)quad for different values of the inner perturber’s eccentricity e1. Finally, we used such analytical considerations and described the behavior of ω2 of outer particles extracted from N-body simulations developed in a previous work. Results. Our analytical study indicates that the values of the inclination i2 and the ascending node longitude Ω2 associated with the outer particle that vanish (dω2/dτ)quad strongly depend on the eccentricity e1 of the inner perturber. In fact, if e1 < 0.25 (>0.40825), (dω2/dτ)quad is only vanished for particles whose Ω2 circulates (librates). For e1 between 0.25 and 0.40825, (dω2/dτ)quad can be vanished for any particle for a suitable selection of pairs (Ω2, i2). Our analysis of the N-body simulations shows that the inverse Lidov-Kozai resonance is possible for small, moderate, and high values of e1. Moreover, such a resonance produces distinctive features in the evolution of a particle in the (Ω2, i2) plane. In fact, if ω2 librates and Ω2 circulates, the extremes of i2 at Ω2 = 90° and 270° do not reach the same value, while if ω2 and Ω2 librate, the evolutionary trajectory of the particle in the (Ω2, i2) plane shows evidence of an asymmetry with respect to i2 = 90°. The evolution of ω2 associated with the outer particles of the N-body simulations can be very well explained by the analytical criteria derived in our investigation.
The TUM VI Benchmark for Evaluating Visual-Inertial Odometry

Visual odometry and SLAM methods have a large variety of applications in domains such as augmented reality or robotics. Complementing vision sensors with inertial measurements tremendously improves tracking accuracy and robustness, and thus has spawned large interest in the development of visual-inertial (VI) odometry approaches. In this paper, we propose the TUM VI benchmark, a novel dataset with a diverse set of sequences in different scenes for evaluating VI odometry. It provides camera images with 1024×1024 resolution at 20 Hz, high dynamic range and photometric calibration. An IMU measures accelerations and angular velocities on 3 axes at 200 Hz, while the cameras and IMU sensors are time-synchronized in hardware. For trajectory evaluation, we also provide accurate pose ground truth from a motion capture system at high frequency (120 Hz) at the start and end of the sequences which we accurately aligned with the camera and IMU measurements. The full dataset with raw and calibrated data is publicly available. We also evaluate state-of-the-art VI odometry approaches on our dataset.
IPSegNet : Deep Convolutional Neural Network Based Segmentation Framework for Iris and Pupil

In biometric based authentication system, Iris is one of the most extensively used biometric trait as it has seen ground breaking research in both region of interest extraction and recognition. Several researchers in the field of biometric based authentication systems have claimed that the main reason for several matching errors is the poor segmentation of the trait. The task of segmentation for a biometric based authentication system is one of the most crucial, as most of the matching and recognition algorithms are performed on the particular region of interest in an acquired image. In this paper we propose two novel end to end convolutional neural network based architectures for region of interest extraction in an iris. The proposed architectures take the image of an eye as input and produce two circular regions of interests for the Iris and Pupil respectively. The two networks proposed were inspired from two state of the art object detection networks Faster RCNN (Region based Convolutional Neural Network) and SSD (Single Shot Multi-Box Detector), both these modified networks were trained for 8000 images. Experimental analysis performed proves that both of our techniques have very high performance in terms of accuracy's and overlaps.
The development of Neoechinorhynchus buttnerae (Eoacanthocephala: Neoechinorhynchidae) in its intermediate host Cypridopsis vidua in Brazil

The family Neoechinorhynchidae includes seven species of Neoechinorhynchus from freshwater fishes of Brazil. Although several Neoechinorhynchus species are cited infecting different fish species in Brazil, there is a lack of information concerning to their life cycle and the identification of the intermediate hosts. Thus, the aim of the present study was to describe the development of Neoechinorhynchus buttnerae in its intermediate host collected in a fish farm located in Rio Preto da Eva, Amazonas, Brazil. To verify the presence of N. buttnerae in the fish pond, twenty Colossoma macropomum were captured and analyzed, being corroborated the presence of this parasite species. Samples of plankton were also collected, finding the ostracod Cypridopsis vidua as the intermediate host. For the description of the larvae development, a laboratory experimental procedure was conducted by feeding the collected ostracods with the eggs of the adult specimens taken from the sampled fish. To observe the stages of development an artificial hatch was performed. Every stage of development was photographed, measured, drawn and described. The time of development of the immature stages of N. buttnerae was 29 days, reporting the stages: acanthor, acanthella (with eight developmental changes) and cystacanth. As high infections by N. buttnerae causes morphological damages to the intestine and may compromise the quality of C. macropomum and in consequence the production of fish farmers in the Brazilian Amazon region, the knowledge of its intermediate host and the understanding of its life cycle represents a useful information to prevent and combat infections by this parasite.
Effect of Two Different Isolates of Leishmania mexicana in the Production of Cytokines and Phagocytosis by Murine Dendritic Cells

ABSTRACT Species of the genus Leishmania are the causal agents of leishmaniasis, a disease with diametrically different clinical manifestations that have been attributed to the species and host immune response. Some Leishmania species, including Leishmania mexicana, are capable of causing both localized cutaneous leishmaniasis (LCL) and diffuse cutaneous leishmaniasis (DCL). Therefore, it is possible that intraspecific differences may exist that contribute to the development of distinct clinical forms. Dendritic cells (DC) are important host cells of Leishmania spp. parasites, and cytokine production and phagocytosis upon infection with the parasite are significant for the outcome of the disease. In the present study we analyzed the production of IL-12, TNF-α, and IL-10 by DC infected with L. mexicana amastigotes isolated from a patient with LCL (amastigote = Lac) and from a patient with DCL (amastigote = Diact) by murine DC. Furthermore, we compared the frequency of phagocytosis of L. mexicana amastigotes of each isolate by fluorescence and optical microscopy and by flow cytometry. We show that the infection of DC with Diact amastigotes elicited the secretion of IL-10, TNF-α, and IL-12 by DC to a major extent as compared to the infection with Lac amastigotes. On the other hand, Lac and Diact amastigotes were similarly phagocytosed by DC, but interestingly there were more vacuoles in DC infected with Diact amastigotes. Our results suggest that isolates from a same species of Leishmania, such as L. mexicana, with different degrees of virulence according to the clinical manifestation they cause, differ in their capacity to elicit cytokine production and form vacuoles in DC.
Frequency of Care and Mortality Following an Incident Diagnosis of Peripheral Artery Disease in the Inpatient or Outpatient Setting: The ARIC (Atherosclerosis Risk in Communities) Study

BACKGROUND Available health services data for individuals with peripheral artery disease (PAD) are often from studies of those eligible for or undergoing intervention. Knowledge of the frequency of care and mortality following an initial PAD diagnosis by setting (outpatient versus inpatient) is limited and represents an opportunity to provide new benchmark information. METHODS AND RESULTS The purpose of this study was to characterize the frequency of care and mortality following an incident PAD diagnosis in the outpatient or inpatient setting using data from the ARIC (Atherosclerosis Risk in Communities) study cohort linked with Centers for Medicare and Medicaid Services fee-for-service claims data (2002-2012). Direct standardization was used to estimate age-standardized rates of encounters and mortality. PAD was defined by billing code in any claim position. We observed 1086 incident PAD cases (873 outpatient, 213 inpatient). At 1 year after diagnosis, participants diagnosed in the outpatient setting had 2.15 (95% confidence interval [CI], 2.10-2.21) PAD-related outpatient encounters per person-year, and 6.4% (95% CI, 4.8-8.1) had a PAD-related hospitalization. Conversely, participants diagnosed in the inpatient setting had 1.02 (95% CI, 0.94-1.10) PAD-related outpatient encounters per person-year, and 14.2% (95% CI, 9.3-18.7) had a PAD-related rehospitalization. One-year mortality was 7.1% (95% CI, 5.4-8.7) and 16.0% (95% CI, 11.0-21.1) among those diagnosed in outpatient and inpatient settings, respectively. CONCLUSIONS This study provides important data estimating frequency of care and mortality by the setting of initial PAD diagnosis. Individuals with PAD are frequent users of health care, and those diagnosed in the inpatient setting have high rates of rehospitalization and mortality.
Parvovirus Infection Is Associated With Myocarditis and Myocardial Fibrosis in Young Dogs

Perinatal parvoviral infection causes necrotizing myocarditis in puppies, which results in acute high mortality or progressive cardiac injury. While widespread vaccination has dramatically curtailed the epidemic of canine parvoviral myocarditis, we hypothesized that canine parvovirus 2 (CPV-2) myocardial infection is an underrecognized cause of myocarditis, cardiac damage, and/or repair by fibrosis in young dogs. In this retrospective study, DNA was extracted from formalin-fixed, paraffin-embedded tissues from 40 cases and 41 control dogs under 2 years of age from 2007 to 2015. Cases had a diagnosis of myocardial necrosis, inflammation, or fibrosis, while age-matched controls lacked myocardial lesions. Conventional polymerase chain reaction (PCR) and sequencing targeting the VP1 to VP2 region detected CPV-2 in 12 of 40 cases (30%; 95% confidence interval [CI], 18%–45%) and 2 of 41 controls (5%; 95% CI, 0.1%–16%). Detection of CPV-2 DNA in the myocardium was significantly associated with myocardial lesions (P = .003). Reverse transcription quantitative PCR amplifying VP2 identified viral messenger RNA in 12 of 12 PCR-positive cases and 2 of 2 controls. PCR results were confirmed by in situ hybridization, which identified parvoviral DNA in cardiomyocytes and occasionally macrophages of juvenile and young adult dogs (median age 61 days). Myocardial CPV-2 was identified in juveniles with minimal myocarditis and CPV-2 enteritis, which may indicate a longer window of cardiac susceptibility to myocarditis than previously reported. CPV-2 was also detected in dogs with severe myocardial fibrosis with in situ hybridization signal localized to cardiomyocytes, suggesting prior myocardial damage by CPV-2. Despite the frequency of vaccination, these findings suggest that CPV-2 remains an important cause of myocardial damage in dogs.