Miracle-dz/UniFAR-FTUs huggingface dataset:
Adaptive response‐dependent two‐phase designs: Some results on robustness and efficiency

Large cohort studies now routinely involve biobanks in which biospecimens are stored for use in future biomarker studies. In such settings, two‐phase response‐dependent sampling designs involve subsampling individuals in the cohort, assaying their biospecimen to measure an expensive biomarker, and using this data to estimate key parameters of interest under budgetary constraints. When analyses are based on inverse probability weighted estimating functions, recent work has described adaptive two‐phase designs in which a preliminary phase of subsampling based on a standard design facilitates approximation of an optimal selection model for a second subsampling phase. In this article, we refine the definition of an optimal subsampling scheme within the framework of adaptive two‐phase designs, describe how adaptive two‐phase designs can be used when analyses are based on likelihood or conditional likelihood, and consider the setting of a continuous biomarker where the nuisance covariate distribution is estimated nonparametrically at the design stage and analysis stage as required; efficiency and robustness issues are investigated. We also explore these methods for the surrogate variable problem and describe a generalization to accommodate multiple stages of phase II subsampling. A study involving individuals with psoriatic arthritis is considered for illustration, where the aim is to assess the association between the biomarker MMP‐3 and the development of joint damage.
Hepatocellular carcinoma chemoprevention by targeting the angiotensin-converting enzyme and EGFR transactivation

Hepatocellular carcinoma (HCC) is a leading cause of death among cirrhotic patients, for which chemopreventive strategies are lacking. Recently, we developed a simple human cell-based system modeling a clinical prognostic liver signature (PLS) predicting liver disease progression and HCC risk. In a previous study, we applied our cell-based system for drug discovery and identified captopril, an approved angiotensin converting enzyme (ACE) inhibitor, as a candidate compound for HCC chemoprevention. Here, we explored ACE as a therapeutic target for HCC chemoprevention. Captopril reduced liver fibrosis and effectively prevented liver disease progression toward HCC development in a diethylnitrosamine (DEN) rat cirrhosis model and a diet-based rat model for nonalcoholic steatohepatitis–induced (NASH-induced) hepatocarcinogenesis. RNA-Seq analysis of cirrhotic rat liver tissues uncovered that captopril suppressed the expression of pathways mediating fibrogenesis, inflammation, and carcinogenesis, including epidermal growth factor receptor (EGFR) signaling. Mechanistic data in liver disease models uncovered a cross-activation of the EGFR pathway by angiotensin. Corroborating the clinical translatability of the approach, captopril significantly reversed the HCC high-risk status of the PLS in liver tissues of patients with advanced fibrosis. Captopril effectively prevents fibrotic liver disease progression toward HCC development in preclinical models and is a generic and safe candidate drug for HCC chemoprevention.
The prevalence, risk factors analysis and evaluation of two diagnostic techniques for the detection of Cryptosporidium infection in diarrheic sheep from Pakistan

Background Cryptosporidium spp. is recognized as an opportunistic zoonotic parasite that infects humans as well as wild and domestic animals. This enteric protozoan is a major cause of diarrhea in humans and animals and often result in death due to severe dehydration. The present study was designed to investigate the prevalence, identification of various risk factors and evaluation of sensitivity of the two diagnostic techniques for rapid and correct detection of Cryptosporidium infection in diarrheic sheep in Pakistan. Methods A total of 360 fecal samples were collected and processed for detection of Cryptosporidium infection after proper preservation. These samples were properly stained with modified Ziehl-Neelsen acid staining and then examined under simple microscope at 100x magnification for confirmation of Cryptosporidium oocysts. The same samples were again processed through simple PCR for confirmation of the Cryptosporidium spp. Results The age wise prevalence was detected through simple microscopy and PCR. We found highest prevalence at the age of ≤1 year followed by 1–2 years of age while the lowest prevalence was recorded at the age of ≥ 2–3 years of sheep and found significant difference between different ages (P<0.05). The sex wise prevalence showed the highest prevalence in male (♂) animals detected compared to female (♀). The overall prevalence was detected 27.08% and 18.80% through PCR and simple microscopy, respectively, and significant difference between two diagnostic techniques were observed (P<0.05). Considering the seasonality, the highest prevalence was recorded through simple microscopy in autumn, summer, and spring, while the lowest in winter. These results were confirmed through PCR. Conclusion It was concluded that molecular detection is the most efficient, specific and sensitive technique for detection of Cryptosporidium infection than simple microscopy. Moreover sheep is the major potential source of infection to other wild and domestic animals including humans.
Altered States of Consciousness during Exercise, Active-Alert Hypnosis, and Everyday Waking State

ABSTRACT This retrospective study was a nonrandomized comparison of exercisers’ (runners and participants of a spinning class) states of consciousness with subjects of active-alert hypnosis (AAH) and students in a class (control). Three hundred and seventy-five participants completed the Phenomenology of Consciousness Inventory (PCI). Runners, spinners, and participants of AAH scored higher on the altered experience and altered state of awareness dimensions of the PCI than the control group. Runners scored higher than participants of AAH and the control condition on the rationality dimension, and spinners scored higher than participants in the AAH condition. The AAH group scored lowest on the self-awareness dimension. On the volitional control dimension, the spinning and control groups scored significantly higher than the runner and AAH groups. The results suggest that exercise may lead to states of consciousness similar to AAH and thus increase responsiveness to a coach’s training suggestions.
Theoretical Analysis and Empirical Comparison of Different Population Initialization Techniques for Evolutionary Algorithms

Evolutionary Algorithms (EAs) are the potential tools for solving optimization problems. The EAs are the population based algorithms and they search for the optimal solution(s) from an initial set of candidates solutions known as population. This population is to be initialized at first before the evolution of the algorithm starts. There exists different ways to initialize this population. Understanding and choosing the right population initialization technique for the given problem is a difficult task for the researchers and problem solvers. To alleviate this issue, this paper is framed with two objectives. The first objective is to present the details of various Population Initialization (PI) techniques of EAs, for the readers to give brief description of all the PI techniques. The second objective is to present the steps and empirical comparison of the results of two different PI techniques implemented for Differential Evolution (DE) algorithm. Theoretical insights and empirical results of the PI techniques are presented in this paper.
Three-Dimensional Volume Calculation of Intrachoroidal Cavitation Using Deep-Learning–Based Noise Reduction of Optical Coherence Tomography

Purpose Intrachoroidal cavitations (ICCs) are peripapillary pathological lesions generally associated with high myopia that can cause visual field (VF) defects. The current study aimed to evaluate a three-dimensional (3D) volume parameter of ICCs segmented from volumetric swept-source optical coherence tomography (SS-OCT) images processed using deep learning (DL)-based noise reduction and to investigate its correlation with VF sensitivity. Methods Thirteen eyes of 12 consecutive patients with peripapillary ICCs were enrolled. DL-based denoising and further analyses were applied to parapapillary 6 × 6-mm volumetric SS-OCT scans. Then, 3D ICC volume and two-dimensional depth and length measurements of the ICCs were calculated. The correlations between ICC parameters and VF sensitivity were investigated. Results The ICCs were located in the inferior hemiretina in all eyes. ICC volume (P = 0.02; regression coefficient [RC], −0.007) and ICC length (P = 0.04; RC, −4.51) were negatively correlated with the VF mean deviation, whereas ICC depth (P = 0.15) was not. All of the parameters, including ICC volume (P = 0.01; RC, −0.004), ICC depth (P = 0.02; RC, −0.008), and ICC length (P = 0.045; RC, −2.11), were negatively correlated with the superior mean total deviation. Conclusions We established the volume of ICCs as a new 3D parameter, and it reflected their influence on visual function. The automatic delineation and 3D rendering may lead to improved detection and pathological understanding of ICCs. Translational Relevance This study demonstrated the correlation between the 3D volume of ICCs and VF sensitivity.
Comparison of Seegene Anyplex II HPV28 assay with BD Onclarity HPV assay for human papillomavirus genotyping

Presently, human papillomavirus (HPV)-based cervical cancer screening is commonly used and is replacing conventional cytology screening tests. The HPV genotyping assay is useful for triage in cervical cancer screening and the evaluation of HPV vaccination effects. In this study, we evaluated the clinical performance of two HPV genotyping assays, BD Onclarity HPV (Onclarity) and Seegene Anyplex II HPV28 (Anyplex) in the detection of relevant cervical lesions and for HPV genotyping concordance. Anyplex and Onclarity assays were performed on 920 consecutive liquid-based specimens. Anyplex, sensitivity, specificity, and genotyping concordance with Onclarity were optimal when restricted to ≥2+ (medium) viral loads. HPV genotyping agreement between the two assays ranged between 0.75 and 0.9 (excellent), except for HPV 33/58, which was 0.73 (good). With Onclarity as a reference, the relative sensitivity of Anyplex for the detection of ≥CIN 2 was 1.05 (95% CI: 0.99–1.1) and the relative specificity for detection of negative for intraepithelial lesion and malignancy (NILM) was 0.89 (95% CI: 0.85–0.93). For most ≥CIN 2 lesions, high-risk HPV was detected by Onclarity (66/72) and Anyplex (69/72) assays. For high-risk HPV negative ≥CIN 2 lesions, possible high-risk HPV genotypes were detected by Anyplex. In conclusion, the genotyping agreement between the tests was good to excellent. Full genotyping with Anyplex might confer additional benefits to patients with ≥CIN 2, although the difference is small. We also suggest an optimal cutoff value when reporting HPV infections using the Anyplex assay (≥2+; medium viral loads).
Relaxation spectra of surface waves

A new method is described for computing free surface flows. The method allows for arbitrary wind profiles to be imposed above the surface as well as arbitrary subsurface current and density profiles. The method combines recent advances in projection methods for stratified flows with level set strategies for computing the motion of a distinguished interface. High resolution discretization. schemes provide robust and accurate treatment of advection, even for singular initial data and in the limit of vanishing viscosity. The method is applied to the modulation of a nonlinear Stokes wave by wind applied at the surface. Speeds of 4,6, and 8 m/s relative to the rest frame are considered. The initial relaxation rate, {beta}, is calculated. The phase and phase speeds of the complex Fourier coefficient of the fundamental are found to increase with wind speed.
Fixed-Time Stable Neurodynamic Flow to Sparse Signal Recovery via Nonconvex L1-β2-Norm

Abstract This letter develops a novel fixed-time stable neurodynamic flow (FTSNF) implemented in a dynamical system for solving the nonconvex, nonsmooth model L1-β2, β∈[0,1] to recover a sparse signal. FTSNF is composed of many neuron-like elements running in parallel. It is very efficient and has provable fixed-time convergence. First, a closed-form solution of the proximal operator to model L1-β2, β∈[0,1] is presented based on the classic soft thresholding of the L1-norm. Next, the proposed FTSNF is proven to have a fixed-time convergence property without additional assumptions on the convexity and strong monotonicity of the objective functions. In addition, we show that FTSNF can be transformed into other proximal neurodynamic flows that have exponential and finite-time convergence properties. The simulation results of sparse signal recovery verify the effectiveness and superiority of the proposed FTSNF.
Potential proteomic alteration in the brain of Tg(SOD1*G93A)1Gur mice: A new pathogenesis insight of amyotrophic lateral sclerosis

The pathogenesis of amyotrophic lateral sclerosis (ALS) remains unclear. The recent studies have suggested that the protein abnormalities could play some important roles in ALS because several protein mutations were found in individuals with this disease. However, proteins that are currently known to be associated with ALS only explain the pathogenesis of this disease in a minority of cases, thus, further screening is needed to identify other ALS‐related proteins. In this study, we systematically analyzed and compared the brain proteomic alterations between a mouse model of ALS, the Tg(SOD1*G93A)1Gur model, and wild‐type mice using isobaric tags for relative and absolute quantitation (iTRAQ) as well as bioinformatics methods. The results revealed some significant up‐ and downregulated proteins at the different developmental stages in the ALS‐like mice as well as the possibly related cellular components, molecular functions, biological processes, and pathways in the development of ALS. Our results identified some possible proteins that participate in the pathogenesis of ALS as well as the cellular components that are damaged by these proteins, we additionally identified the molecular functions, the biological processes, and the pathways of these proteins as well as the molecules that are associated with these pathways. This study represents an important preliminary investigation of the role of proteomic abnormalities in the pathogenesis of ALS, both in human patients and other animal models. We present some novel findings that may serve as a basis for further investigation of abnormal proteins that are involved in the pathogenesis of ALS.
Dual cytoplasmic‐peroxisomal engineering for high‐yield production of sesquiterpene α‐humulene in Yarrowia lipolytica

The sesquiterpene α‐humulene is an important plant natural product, which has been used in the pharmaceutical industry due to its anti‐inflammatory and anticancer activities. Although phytoextraction and chemical synthesis have previously been applied in α‐humulene production, the low efficiency and high costs limit the development. In this study, Yarrowia lipolytica was engineered as the robust cell factory for sustainable α‐humulene production. First, a chassis with high α‐humulene output in the cytoplasm was constructed by integrating α‐humulene synthases with high catalytic activity, optimizing the flux of mevalonate and acetyl‐CoA pathways. Subsequently, the strategy of dual cytoplasmic‐peroxisomal engineering was adopted in Y. lipolytica; the best strain GQ3006 generated by introducing 31 copies of 12 different genes could produce 2280.3± 38.2 mg/l (98.7 ± 4.2 mg/g dry cell weight) α‐humulene, a 100‐fold improvement relative to the baseline strain. To further improve the titer, a novel strategy for downregulation of squalene biosynthesis based on Cu2+‐repressible promoters was firstly established, which significantly improved the α‐humulene titer by 54.2% to 3516.6 ± 34.3 mg/l. Finally, the engineered strain could produce 21.7 g/l α‐humulene in a 5‐L bioreactor, 6.8‐fold higher than the highest α‐humulene titer reported before this study. Overall, system metabolic engineering strategies used in this study provide a valuable reference for the highly sustainable production of terpenoids in Y. lipolytica.
Characterization of Biomarkers of Hemostasis and Bleeding-Related Outcomes in Children With Cirrhosis

Objectives: We aimed to evaluate differences in laboratory tests, bleeding, transfusions, and thrombosis between (1) children without and with cirrhosis and (2) children and adults with cirrhosis, and to correlate thromboelastography (TEG) parameters with biomarkers of hemostasis, bleeding, and transfusions in children and adults with cirrhosis. Methods: This single-center, retrospective study included 20 children without cirrhosis, 40 children with cirrhosis, and 40 adults with cirrhosis who underwent a liver transplant (LT). We collected demographic data, preoperative laboratory values, and intraoperative TEG parameters. Biomarkers of hemostasis just prior to the start of LT surgery were analyzed including international normalized ratio (INR), platelet, fibrinogen level, R time, K time, alpha angle (α), and maximum amplitude (MA). We also collected outcome data including blood loss, transfusion requirements, and thrombosis. Results: A significantly higher proportion of children with cirrhosis had abnormal PT (P = 0.001), platelet (P = 0.001), K time (P = 0.02), and MA (P = 0.05) compared to children without cirrhosis. The incidences of thrombosis, bleeding events, blood loss or PRBC transfusion were not significantly different between these 2 groups. A significantly higher proportion of adults with cirrhosis had abnormal R time (P = 0.01) and alpha angle (P = 0.01) than children with cirrhosis. Conclusions: Children with cirrhosis had defects in fibrinogen and platelets compared to children without cirrhosis at time of LT; however, these abnormalities did not translate into higher rates of bleeding in the former. Adults with cirrhosis had more defects in clotting factors compared to children with cirrhosis.
Towards high-accuracy classifying attention-deficit/hyperactivity disorders using CNN-LSTM model

Objective. The neurocognitive attention functions involve the cooperation of multiple brain regions, and the defects in the cooperation will lead to attention-deficit/hyperactivity disorder (ADHD), which is one of the most common neuropsychiatric disorders for children. The current ADHD diagnosis is mainly based on a subjective evaluation that is easily biased by the experience of the clinicians and lacks the support of objective indicators. The purpose of this study is to propose a method that can effectively identify children with ADHD. Approach. In this study, we proposed a CNN-LSTM model to solve the three-class problems of classifying ADHD, attention deficit disorder (ADD) and healthy children, based on a public electroencephalogram (EEG) dataset that includes event-related potential (ERP) EEG signals of 144 children. The convolution visualization and saliency map methods were used to observe the features automatically extracted by the proposed model, which could intuitively explain how the model distinguished different groups. Main results. The results showed that our CNN-LSTM model could achieve an accuracy as high as 98.23% in a five-fold cross-validation method, which was significantly better than the current state-of-the-art CNN models. The features extracted by the proposed model were mainly located in the frontal and central areas, with significant differences in the time period mappings among the three different groups. The P300 and contingent negative variation (CNV) in the frontal lobe had the largest decrease in the healthy control (HC) group, and the ADD group had the smallest decrease. In the central area, only the HC group had a significant negative oscillation of CNV waves. Significance. The results of this study suggest that the CNN-LSTM model can effectively identify children with ADHD and its subtypes. The visualized features automatically extracted by this model could better explain the differences in the ERP response among different groups, which is more convincing than previous studies, and it could be used as more reliable neural biomarkers to help with more accurate diagnosis in the clinics.
Strong and reliable synaptic communication between pyramidal neurons in adult human cerebral cortex

Abstract Synaptic transmission constitutes the primary mode of communication between neurons. It is extensively studied in rodent but not human neocortex. We characterized synaptic transmission between pyramidal neurons in layers 2 and 3 using neurosurgically resected human middle temporal gyrus (MTG, Brodmann area 21), which is part of the distributed language circuitry. We find that local connectivity is comparable with mouse layer 2/3 connections in the anatomical homologue (temporal association area), but synaptic connections in human are 3-fold stronger and more reliable (0% vs 25% failure rates, respectively). We developed a theoretical approach to quantify properties of spinous synapses showing that synaptic conductance and voltage change in human dendritic spines are 3–4-folds larger compared with mouse, leading to significant NMDA receptor activation in human unitary connections. This model prediction was validated experimentally by showing that NMDA receptor activation increases the amplitude and prolongs decay of unitary excitatory postsynaptic potentials in human but not in mouse connections. Since NMDA-dependent recurrent excitation facilitates persistent activity (supporting working memory), our data uncovers cortical microcircuit properties in human that may contribute to language processing in MTG.
A New effective interaction for 0 - h-bar - omega shell model calculations in the sdpf valence space

The neutron rich isotopes with Z<20, in particular those with neutron numbers around N=28,have been at the focus of a lot experimental and theoretical scrutiny during the last few years.Shell model calculations using the effective interaction SDPF-NR, were able to predictor to explain most of the properties featured by these nuclei. Prominent among them is the disappearance of the N=28 shell closure for Z<=16. We have incorporated to SDPF-NR some modifications, either on purely theoretical grounds or guided by new experimental information. The proposed interaction, SDPF-U, contains USD as its sd-shell part and KB3G as its pf-shell-part. Its range of applicability is enlarged and its reliability enhanced with respect to the earlier version.