Miracle-dz/UniFAR-FTUs huggingface dataset:
Symmetry Breaking of Human Pluripotent Stem Cells (hPSCs) in Micropattern Generates a Polarized Spinal Cord‐Like Organoid (pSCO) with Dorsoventral Organization

Axis formation and related spatial patterning are initiated by symmetry breaking during development. A geometrically confined culture of human pluripotent stem cells (hPSCs) mimics symmetry breaking and cell patterning. Using this, polarized spinal cord organoids (pSCOs) with a self‐organized dorsoventral (DV) organization are generated. The application of caudalization signals promoted regionalized cell differentiation along the radial axis and protrusion morphogenesis in confined hPSC colonies. These detached colonies grew into extended spinal cord‐like organoids, which established self‐ordered DV patterning along the long axis through the spontaneous expression of polarized DV patterning morphogens. The proportions of dorsal/ventral domains in the pSCOs can be controlled by the changes in the initial size of micropatterns, which altered the ratio of center‐edge cells in 2D. In mature pSCOs, highly synchronized neural activity is separately detected in the dorsal and ventral side, indicating functional as well as structural patterning established in the organoids. This study provides a simple and precisely controllable method to generate spatially ordered organoids for the understanding of the biological principles of cell patterning and axis formation during neural development.
Saliva biopsy: Detecting the difference of EBV DNA methylation in the diagnosis of nasopharyngeal carcinoma

Saliva sampling is a non‐invasive method, and could be performed by donors themselves. However, there are few studies reporting biomarkers in saliva in the diagnosis of NPC. A total of 987 salivary samples were used in this study. First, EBV DNA methylation was profiled by capture sequencing in the discovery cohort (n = 36). Second, a q‐PCR based method was developed and five representative EBV DNA CpG sites (11 029 bp, 45 849 bp, 57 945 bp, 66 226 bp and 128 102 bp) were selected and quantified to obtain the methylated density in the validation cohort1 (n = 801). Third, a validation cohort2 (n = 108) was used to further verify the differences of EBV methylation in saliva. A significant increase of EBV methylation was found in NPC patients compared with controls. The methylated score of EBV genome obtained by capture sequencing could distinguish NPC from controls (sensitivity 90%, specificity 100%). Further, the methylated density of EBV DNA CpG sites revealed by q‐PCR showed a good diagnostic performance. The sensitivity and specificity of detecting a single CpG site (11 029 bp) could reach 75.4% and 99.7% in the validation cohort1, and 78.2% and 100% in the validation cohort2. Besides, the methylated density of the CpG site was found to decrease below the COV in NPC patients after therapy, and increase above the COV after recurrence. Our study provides an appealing alternative for the non‐invasive detection of NPC without clinical setting. It paves the way for conducting a home‐based large‐scale screening in the future.
Enantioselectivity in the Ecotoxicity of Amphetamine Using Daphnia magna as the Aquatic Model Organism: Morphophysiological, Behavioral, Reproductive and Biochemical Parameters

Amphetamine (AMP) is a chiral psychoactive substance that exhibits enantioselectivity in its pharmacological properties. It has been detected in wastewaters and surface waters and can occur as enantiomeric mixtures, but little is known about its environmental risk and potential enantioselective toxicity to aquatic organisms. Our study aimed to target enantioselectivity in AMP toxicity to the freshwater invertebrate Daphnia magna. Daphnids were subchronically exposed to the racemate (rac‐AMP: 0.1, 1.0, and 10 µg/L) and pure enantiomers, (R)‐AMP and (S)‐AMP (0.1, and 1.0 µg/L, respectively), for 8 days. Morphophysiological, swimming behavior, reproductive and biochemical variables were evaluated during critical life stages (juveniles vs. adults). Some responses were context‐dependent and often enantioselective, varying between racemate and enantiomers and across the life stage of the organisms. Overall, rac‐AMP stimulated D. magna growth, decreased heart rate and area, affected behavior, and stimulated reproduction. The effect of enantiomers was totally or partially concordant with rac‐AMP, except for swimming behavior and reproduction. Enantioselectivity was observed for body size, number of eggs/daphnia, and heart rate (steeper decrease caused by (R)‐AMP on day 3). Changes in biochemical parameters were also observed: AMP caused a significant decrease in catalase activity as racemate or pure enantiomers, whereas a decrease in acetylcholinesterase activity was found only for rac‐AMP. Evidence for oxidative stress was contradictory, although both enantiomers caused a significant decrease in reactive oxygen species (unlike rac‐AMP). Overall, these results show that AMP can interfere in an enantioselective way with aquatic organisms at low concentrations (e.g., 0.1 µg/L), demonstrating the relevance of this kind of study to an accurate environmental risk assessment regarding medium‐ to long‐term exposure to this psychoactive drug. Environ Toxicol Chem 2023;42:1743–1754. © 2023 SETAC.
Multilevel joint model of longitudinal continuous and binary outcomes for hierarchically structured data

Joint modeling has been a useful strategy for incorporating latent associations between different types of outcomes simultaneously, often focusing on a longitudinal continuous outcome characterized by an LME submodel and a terminal event subject to a Cox proportional hazard or parametric survival submodel. Applications to hierarchical longitudinal studies have been less frequent, particularly with respect to a binary process, which is commonly specified by a GLMM. Furthermore, many of the joint model developments have not allowed for investigations of nested effects, such as those arising from multicenter studies. To fill this gap, we propose a multilevel joint model that encompasses the LME submodel and GLMM through a Bayesian approach. Motivated by the need for timely detection of pulmonary exacerbation and characterization of irregularly observed lung function measurements in people living with cystic fibrosis (CF) receiving care across multiple centers, we apply the model to the data arising from US CF Foundation Patient Registry. In parallel, we examine the extent of bias induced by a non‐hierarchical model. Our simulation study and application results show that incorporating the center effect along with individual stochastic variation over time within the LME submodel improves model estimation and prediction. Given that the center effect is evident in lung function observed in the CF population, accounting for center‐specific power parameters by incorporating the symmetric power exponential power (spep) link function in the GLMM can facilitate more accurate conclusions in clinical studies.
Effect of Simultaneous Endothelial Keratoplasty and Cataract Surgery: A Secondary Analysis of the Descemet Endothelial Thickness Comparison Trial

Purpose: Combining cataract surgery with endothelial keratoplasty (triple EK) is a common practice and may be safer because it commits the patient to only one surgery. This study aimed to determine whether outcomes of pseudophakic endothelial keratoplasty and triple EK have similar outcomes. Methods: This was a non-prespecified secondary analysis of a multicenter, double-masked, randomized, controlled clinical trial. Enrollment centers included the Casey Eye Institute at Oregon Health and Sciences University and the Byers Eye Institute at Stanford University. Patients with damaged or diseased endothelium and were considered good candidates for either Descemet membrane endothelial keratoplasty or ultrathin Descemet stripping automated endothelial keratoplasty were randomized to one of the two surgeries 1-2 days prior to surgery. If the patient had a cataract, they underwent simultaneous cataract surgery. The primary outcome was visual acuity at 6 months. Visual acuity at 3, 12, and 24 months, 3, 6, 12, and 24 month endothelial cell density and intraoperative and postoperative complications were also recorded. Results: Those who had pseudophakic EK generally were older, more likely to be male, and more likely to have worse baseline vision with higher corneal densitometry values. After controlling for baseline visual acuity and type of keratoplasty, those that underwent Triple-EK had 0.09 better LogMAR lines better visual acuity at 6 (95% CI −0.17 to −0.10; P = 0.02) and 12 months (95% CI −0.21 to −0.07; P = 0.03). Although those receiving Triple- EK had nearly one-half LogMAR line better visual acuity at 24 months, it was no longer statistically significant (95% CI −0.20 to −0.05; P = 0.36). There was no statistically significant difference in ECD between groups at any timepoint. Those undergoing triple EK were more likely to have at least one adverse event (P = 0.02). Conclusions: Earlier intervention with Triple-EK may improve visual acuity outcomes after endothelial keratoplasty compared with staged procedures, but may also increase the risks of adverse events including the need for re-bubble.
Verification and Validation of Knowledge Bases Using Test Cases Generated by Restriction Rules

Knowledge based systems have been developed to solve many problems. Their main characteristic consists on the use of a knowledge representation of a specific domain to solve problems in such a way that it emulates the reasoning of a human specialist. As conventional systems, knowledge based systems are not free of failures. This justifies the need for validation and verification for this class of systems. Due to the lack of techniques which can guarantee their quality and reliability, this paper proposes a process to support validation of specific knowledge bases. In order to validate the knowledge base, restriction rules are used. These rules are elicit and represented as If Then Not rules and executed using a backward chaining reasoning process. As the result of this process test cases are created and submitted to the knowledge base in order to prove whether there are inconsistencies in the domain representation. Two main advantages can be highlighted here: the use of restriction rules which are considered as meta-knowledge (these rules improve the knowledge representation power of the system) and a process that can generate useful test cases (test cases are usually difficult and expensive to be created).
The oblique effect revealed by optical imaging in primary visual cortex of cats

The oblique effect is a ubiquitous visual psychological effect. To explore its underlying neural basis, we quantitatively analyzed the proportion and response amplitude of the cardinal preferred areas and the oblique preferred areas in a fairly large region of the primary visual cortex of cats, using optical imaging based on intrinsic signals. The results show that cardinal preferred areas were larger than oblique preferred areas, with a mean difference of 4.7%. Overall, the responses evoked by cardinal stimuli were generally greater than those by oblique stimuli. The present work provides an explanation for the differences in electrophysiological results reported for this issue, and gives a new insight into the neural basis of the oblique effect.
The Electric Field Induced by a Microcoil During Magnetic Stimulation

<italic>Objective:</italic> The purpose of this study is to calculate the electric field produced by an implanted microcoil during magnetic stimulation of the brain. <italic>Methods:</italic> The electric field of a microcoil was calculated numerically. <italic>Results:</italic> The maximum value of the induced electric field is approximately 0.000026 V/m for a 1 mA, 3 kHz current passed through the coil. <italic>Conclusion:</italic> This electric field value is too small to cause neural stimulation. <italic>Significance:</italic> Previous studies reporting magnetic stimulation using a microcoil must have been exciting neurons by some other mechanism.
The Two-Bag Method for Management of Adult Diabetic Ketoacidosis—Experience With 634 Patients

Purpose To compare key resource utilization and safety outcomes of adult emergency department (ED) patients in diabetic ketoacidosis (DKA) managed via the Two-Bag or traditional One-Bag method. Materials and Methods This is a retrospective review at an academic medical center ED. Patients were included if >18 years, met diagnostic criteria for DKA (pH ≤ 7.30, bicarbonate ≤ 18 mmol/L, anion gap ≥ 10), and were managed via a standardized order set (either Two-Bag or One-Bag Method). Comparisons used independent-groups t-tests for continuous variables and χ2 tests for binary variables. Results We identified 634 patients with DKA managed via the Two-Bag method, and 107 managed via the One-Bag method. Cohorts were similar in demographics and presenting laboratories. The Two-Bag Method was associated with 8.1 h shorter to first bicarbonate >18 mmol/L (11.9 vs 20.0, P < .001), and 24 fewer IV fluid bags (5.3 vs 29.7, P < .001). Incidence of hypokalemia (potassium <3.0 mmol/L) was 53% lower in the Two-Bag cohort (6.6 vs 14.0%, P = .03); incidence of hypoglycemia (glucose <70 mg/dL) was 5.8 versus 10.3%, P = . 16. Conclusions For adult ED patients in DKA, the Two-Bag Method was associated with faster resolution of acidosis, fewer IV fluid bags charged, lower incidence of hypokalemia, and trend toward lower incidence of hypoglycemia compared to the One-Bag Method.
Bifurcations of Periodic Solutions of Functional Differential Equations with Spatio-Temporal Symmetries

In this thesis, we study bifurcations of periodic solutions with spatio-temporal symmetries of functional differential equations (FDEs). The two main results are: (1) a centre manifold reduction around a periodic solution of FDEs with spatio-temporal symmetries, and (2) symmetry-breaking bifurcations for symmetric rings of delaycoupled lasers. For the case of ODEs, symmetry-breaking bifurcations from periodic solutions has already been studied. Our goal is to extend this result to the case of symmetric FDEs. We use a Centre Manifold Theorem for FDEs which reduces FDEs into ODEs on an integral manifold around a periodic solution. We prove a similar result that applies to symmetric FDEs, and show that the integral manifold is invariant under the spatio-temporal symmetries. This guarantees that the symmetry structure of the system of FDEs is preserved by this reduction. We also consider a problem in rings of delay-coupled lasers modelled using the Lang-Kobayashi rate equations. We classify the symmetry of bifurcating branches of solutions from steady-state and Hopf bifurcations that occur in 3-laser systems. This involves finding isotropy subgroups of the symmetry group of the system, and then using the Equivariant Branching Lemma and the Equivariant Hopf Theorem. We then utilize this result to find the bifurcating branches of solutions in DDE-Biftool. i Symmetry often causes eigenvalues to have multiplicity, and in some cases, this could lead DDE-Biftool to incorrectly predict the bifurcation points. We address this issue by developing a method of finding bifurcation points which can be used for the general case of n-laser systems with unidirectional and bidirectional coupling.
The Interactive Role of Sleep and Circadian Rhythms in Episodic Memory in Older Adults

Abstract Adequate sleep is essential for healthy physical, emotional, and cognitive functioning, including memory. However, sleep ability worsens with increasing age. Older adults on average have shorter sleep durations and more disrupted sleep compared with younger adults. Age-related sleep changes are thought to contribute to age-related deficits in episodic memory. Nonetheless, the nature of the relationship between sleep and episodic memory deficits in older adults is still unclear. Further complicating this relationship are age-related changes in circadian rhythms such as the shift in chronotype toward morningness and decreased circadian stability, which may influence memory abilities as well. Most sleep and cognitive aging studies do not account for circadian factors, making it unclear whether age-related and sleep-related episodic memory deficits are partly driven by interactions with circadian rhythms. This review will focus on age-related changes in sleep and circadian rhythms and evidence that these factors interact to affect episodic memory, specifically encoding and retrieval. Open questions, methodological considerations, and clinical implications for diagnosis and monitoring of age-related memory impairments are discussed.
The Projective Special Linear Group PSL(4,2).

The present study deals with conjugacy classes for the projective linear group. The study of conjugacy classes has a great and important role; in hand it is an introductory step to study the general linear group and also the maximal subgroup in it.We introduce the investigation of the canonical form which represent each class for the linear group of dimension 4 over a field GF(pr) and deals with canonical form which represents the conjugacy class of the groups with dimension 4 over a field GF(2).
Novel urinary tract obstruction marker discovery by multi-marker profiling of urinary extracellular vesicles derived from a rat UTO model.

INTRODUCTION Congenital urinary obstruction is a common cause of end-stage renal disease in the pediatric population. However, non-invasive diagnostics to predict which patients will benefit from early intervention are lacking. METHODS Using a rat model of upper and lower urinary tract partial obstruction and the Nanostring nCounter Fibrosis V2 Panel, we evaluated the mRNA cargo of urinary small extracellular vesicles (sEVs) and mRNA expression patterns of kidney and bladder tissues from rats with lower tract urinary obstruction and upper tract urinary obstruction. RESULTS While mRNA hierarchical clustering of urinary sEVs was unable to differentiate upper compared to lower tract urinary obstruction, clustering was able to detect overall disease state (UUTO or LUTO) versus healthy controls. Further, urinary sEVs carried genes unique to each treatment group (UUTO: 59 genes, LUTO: 17 genes), while only one gene was uniquely carried in the control group. Notable genes of interest found in urinary sEVs were VCAM-1 and NOS1 for UUTO, Egfr for LUTO, and Pck1 for healthy controls. CONCLUSION This study provides support that differential gene expression of urinary sEV mRNA has potential to act as biomarkers in the diagnosis and prognosis of UTO. Urinary sEVs demonstrated higher numbers of unique genes representative of injury to the kidney than that of injury to the bladder. Importantly, there were genes unique to UUTO sEVs, indicating the extent and reversibility of renal damage can be independent of the function, damage, and architecture of the bladder.
Hierachical basis preconditioners for second order elliptic problems in three dimensions

The discretization uses nodal basis functions and the preconditioner arises. We present preconditioners for a symmetric, positive definite linear system arising from the finite element discretization of a second order elliptic problem in three dimensions. The discretization uses nodal basis functions and the preconditioner arises from the use of hierarchical basis functions. We show that the condition number of the linear hierarchical basis coefficient matrix {cflx A} scaled by a coarse grid operator is O(N{sup 1/3} log N{sup 1/3}) when uniform tetrahedral refinement is used, where N is the number of unknowns. If additional diagonal scaling by levels is applied in the fine grid, a condition number of O(N{sup 1/3}) is obtained. The same result is obtained if {cflx A} is scaled by its block diagonal. Moreover, we show that any other block diagonal scaling of {cflx A} will yield a condition number that grows at least as O(N{sup 1/3}). These results compare favorably with the condition number of O(N{sup 2/3}) of the nodal coefficient matrix. We provide numerical results that confirm this theory. These results are extensions of those obtained by Yserentant for two dimensional problems. We also extend the analysis of the linear preconditioner to the case ofmore » non-uniform refinement. 74 refs., 78 figs., 14 tabs. « less
Behavioral effects induced by the cannabidiol analogs HU-502 and HU-556

Cannabidiol is a phytocannabinoid that lacks the psychotomimetic properties of Δ9-tetrahydrocannabinol (THC), the main psychoactive Cannabis sativa component. Cannabidiol has several potential therapeutic properties, including anxiolytic, antidepressant, and antipsychotic; however, cannabidiol has low oral bioavailability, which can limit its clinical use. Here, we investigated if two cannabidiol analogs, HU-502 and HU-556, would be more potent than cannabidiol in behavioral tests predictive of anxiolytic, antidepressant, and antipsychotic effects. Different doses (0.01–3 mg/kg; intraperitoneally) of HU-556 and HU-502 were tested in male Swiss mice submitted to the elevated plus maze (EPM), forced swimming test (FST), and amphetamine-induced-prepulse inhibition (PPI) disruption and hyperlocomotion. Cannabidiol is effective in these tests at a dose range of 15–60 mg/kg in mice. We also investigated if higher doses of HU-556 (3 and 10 mg/kg) and HU-502 (10 mg/kg) produced the cannabinoid tetrad (hypolocomotion, catalepsy, hypothermia, and analgesia), which is induced by THC-like compounds. HU-556 (0.1 and 1 mg/kg) increased the percentage of open arm entries (but not time) in the EPM, decreased immobility time in the FST, and attenuated amphetamine-induced PPI disruption. HU-502 (1 and 3 mg/kg) decreased amphetamine-induced hyperlocomotion and PPI impairment. HU-556, at high doses, caused catalepsy and hypolocomotion, while HU-502 did not. These findings suggest that similar to cannabidiol, HU-556 could induce anxiolytic, antidepressant, and antipsychotic-like effects and that HU-502 has antipsychotic properties. These effects were found at a dose range devoid of cannabinoid tetrad effects.
Step semantics and action refinement in event structures

An event structure acts as a denotational semantic model of concurrent systems. Action refinement is an essential operation in the design of concurrent systems. However, there exists an important problem about preserving equivalence under action refinement. If two processes are equivalent with each other, we hope that they still can preserve equivalence after action refinement. In linear time equivalence and branching time equivalence spectrum, step equivalences, which include step trace equivalence and step bisimulation equivalence are not preserved under action refinement [17]. In this paper, we define a class of concurrent processes with specific properties and put forward the concept of clustered action transition, which ensures that step equivalences are able to preserve under action refinement.
Source location in thin plates using cross-correlation

In this paper an alternative method to first threshold crossing for acoustic emission (AE) source location is presented. For wave propagation in dispersive media, the accuracy of source location can be improved by locating corresponding phase points on the transducer outputs to determine the difference in arrival times. The phase point location was done by cross‐correlating the transducer outputs with a single frequency cosine wave modulated by a Gaussian pulse. Experiments were performed using a lead break as the AE source on the surface of an aluminum plate. Due to the plate geometry and source orientation, the wave produced was highly dispersive. Although this wave was unsuitable for first threshold crossing techniques, the time differences needed for triangulation could be determined using the cross‐correlation technique.