Miracle-dz/UniFAR-FTUs huggingface dataset:
The Prognostic Value and Clinical Utility of the 40-Gene Expression Profile (40-GEP) Test in Cutaneous Squamous Cell Carcinoma: Systematic Review and Meta-Analysis

Simple Summary A subset of cutaneous squamous cell carcinoma (cSCC) that is associated with high-risk features carries an increased risk for aggressive disease, local recurrence, and regional metastasis, which leads to significant morbidity and mortality. The current available systems for cSCC risk stratification are considered inadequate and fail to accurately distinguish high-risk cSCC patients who can benefit from aggressive management, emphasizing a great need for an accurate metastatic risk tool for early identification of high-risk cSCC patients. A 40-gene expression profile (40-GEP) was developed to biologically distinguish high-risk tumors that would benefit from more aggressive management. This systematic review and meta-analysis aimed to evaluate the reported prognostic value and clinical utility of the 40-GEP test. The results indicated that the 40-GEP test improved cSCC risk stratification both independently and in combination with other clinicopathologic risk factors. Abstract Background: The current tumor staging systems for cutaneous squamous cell carcinoma (cSCC) are considered inadequate and insufficient for evaluating the risk of metastasis and for identifying patients at high risk of cSCC. This meta-analysis aimed to assess the prognostic significance of a 40-gene expression profile (40-GEP) both independently and integrated with clinicopathologic risk factors and established staging systems (American Joint Committee on Cancer, eighth edition (AJCC8) and Brigham and Women’s Hospital (BWH)). Methods: Electronic databases, including PubMed (MEDLINE), Embase, the Cochrane Library, and Google Scholar, were systematically searched to identify cohort studies and randomized controlled trials on evaluations of the prediction value of 40-GEP in cSCC patients up to January 2023. The metastatic risk analysis of a given 40-GEP class combined with tumor stage and/or other clinicopathologic risk factors was based upon log hazard ratios (HRs) and their standard error (SE). Heterogeneity and subgroup analyses were performed, and data quality was assessed. Results: A total of 1019 patients from three cohort studies were included in this meta-analysis. The overall three-year metastatic-free survival rates were 92.4%, 78.9%, and 45.4% for class 1 (low risk), class 2A (Intermediate risk), and class 2B (high risk) 40-GEP, respectively, indicating a significant variation in survival rates between the risk classification groups. The pooled positive predictive value was significantly higher in class 2B when compared to AJCC8 or BWH. The subgroup analyses demonstrated significant superiority of integrating 40-GEP with clinicopathologic risk factors or AJCC8/BWH, especially for class 2B patients. Conclusions: The integration of 40-GEP with staging systems can improve the identification of cSCC patients at high risk of metastasis, potentially leading to improved care and outcomes, especially in the high-risk class 2B group.
Molecular Basis for the Selectivity of DHA and EPA in Sudlow’s Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations

Medium- and long-chain saturated and unsaturated free fatty acids (FFAs) are known to bind to human serum albumin (HSA), the main plasma carrier protein. Atomic-level structural data regarding the binding mode in Sudlow’s sites I (FA7) and II (FA4, FA3) of the polyunsaturated ω-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), however, are largely unknown. Herein, we report the combined use of saturation transfer difference (STD) and Interligand NOEs for Pharmacophore Mapping (INPHARMA) NMR techniques and molecular docking calculations to investigate the binding mode of DHA and EPA in Sudlow’s sites Ι and ΙΙ of HSA. The docking calculations and the significant number of interligand NOEs between DHA and EPA and the drugs warfarin and ibuprofen, which are stereotypical ligands for Sudlow’s sites I and II, respectively, were interpreted in terms of competitive binding modes and the presence of two orientations of DHA and EPA at the binding sites FA7 and FA4. The exceptional flexibility of the long-chain DHA and EPA and the formation of strongly folded structural motives are the key properties of HSA–PUFA complexes.
Large Displacement Analysis of Rectangular Orthotropic Membranes Under Stochastic Impact Loading

This paper studies the calculation method about the displacement response mean function of rectangular orthotropic membranes with four edges fixed under stochastic impact loading. We set up the nonlinear stochastic governing differential equation, solve it according to the perturbation method and the random vibration theory and obtain the displacement response mean value function of the membrane surface. Furthermore, this paper makes a random simulation test for ZZF membrane material which is commonly applied in the membrane structural engineering and obtains abundant deflection response sample curves about the feature points of the membrane surface. For sample curves statistical analysis at some fixed time, sample means can be obtained, which verify the correctness of the theoretical calculation method. The calculation method provides a theoretical basis for vibration control of building membrane structures to control the occurrence of natural disasters.
Model Uncertainty and Model Averaging in Regression Discontinuity Designs

Abstract Parametric (polynomial) models are popular in research employing regression discontinuity designs and are required when data are discrete. However, researchers often choose a parametric model based on data inspection or pretesting. These approaches lead to standard errors and confidence intervals that are too small because they do not incorporate model uncertainty. I propose using Frequentist model averaging to incorporate model uncertainty into parametric models. My Monte Carlo experiments show that Frequentist model averaging leads to mean square error and coverage probability improvements over pretesting. An application to [Lee, D. S. 2008. “Randomized Experiments From Non-Random Selection in US House Elections. ” Journal of Econometrics 142 (2): 675–697. ] shows how this approach works in practice, and how conventionally selected models may not be ideal.
Clamping Modulation Technique for Balancing Power Losses of Dual Inverter With Isolated DC Bus

This paper proposes a clamping modulation technique to reduce and balance power losses in a dual inverter with an isolated DC bus. To drive an open-end winding permanent magnet synchronous motor (OEW-PMSM), dual inverter consisting of six legs has twelve switching actions, twice as many as a two-level voltage source inverter (VSI) per switching period. However, many switching actions cause power losses in switching devices, reducing the efficiency of the system. In this paper, a four-leg clamping modulation technique is presented to reduce the switching actions by analyzing the relationship between two reference voltage vectors of primary and secondary inverters on a space vector plane. To clamp four of the six legs overall, the switching states are determined by combining active and zero vectors during the switching period. The selected vector combinations differ according to 18 sectors divided by the magnitude and angle of the reference voltage vector. The zero vectors required for 18 sectors are then distributed to balance the power losses in upper and lower switching devices of each leg. This technique is implemented with carrier-based pulse width modulation (PWM) by calculating each three-phase reference voltage from two reference voltage vectors composed of the vector combinations. Balancing of the power losses between the upper and lower switching devices is achieved by adding offset voltages corresponding to the zero vector of each sector. The validity of the proposed technique is verified experimentally.
Design and Construction of a Synthetic Nanobody Library: Testing Its Potential with a Single Selection Round Strategy

Nanobodies (Nbs) are single domain antibody fragments derived from heavy-chain antibodies found in members of the Camelidae family. They have become a relevant class of biomolecules for many different applications because of several important advantages such as their small size, high solubility and stability, and low production costs. On the other hand, synthetic Nb libraries are emerging as an attractive alternative to animal immunization for the selection of antigen-specific Nbs. Here, we present the design and construction of a new synthetic nanobody library using the phage display technology, following a structure-based approach in which the three hypervariable loops were subjected to position-specific randomization schemes. The constructed library has a clonal diversity of 108 and an amino acid variability that matches the codon distribution set by design at each randomized position. We have explored the capabilities of the new library by selecting nanobodies specific for three antigens: vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF) and the glycoprotein complex (GnGc) of Andes virus. To test the potential of the library to yield a variety of antigen-specific Nbs, we introduced a biopanning strategy consisting of a single selection round using stringent conditions. Using this approach, we obtained several binders for each of the target antigens. The constructed library represents a promising nanobody source for different applications.
Effectiveness of Polyclonal Antibody Immunoconjugate Treatment with Propamidine Isethionate for Amoebic Keratitis in Golden Hamsters

Acanthamoeba griffini is known to cause amoebic keratitis (AK); its main causes are inadequate hygiene when contact lenses are handled and/or its prolonged use at night, as well as the use of contact lenses during underwater activities. The most used treatment for AK is the combination of propamidine isethionate combined with polyhexamethylene biguanide, which disrupts the cytoplasmic membrane, and damages cellular components and respiratory enzymes. We proposed an immunoconjugate treatment obtained from Acanthamoeba immunized rabbit serum combined with propamidine isethionate; the corneas of hamsters inoculated with A. griffini (MYP2004) were treated with the combined, at 1, 2, and 3 weeks. Propamidine isethionate is frequently used for AK treatment, in vivo study we are found IL-1β and IL-10 expression and caspase 3 activity is significantly increased with respect to the group that was inoculated with the amoeba without receiving any treatment, suggesting that it may be an effect of the toxicity of this drug on the corneal tissue. Application of the immunoconjugate showed enhanced amoebicidal and anti-inflammatory activities, with comparison to propamidine isethionate only. The aim of this study is to evaluate the effect of the immunoconjugate of propamidine isethionate and polyclonal antibodies as a treatment of AK in golden hamsters (Mesocricetus auratus).
Unusual Martian Foreshock Waves Triggered by a Solar Wind Stream Interaction Region

Planetary bow shocks noncollisionally dissipate the incident bulk flow energy of solar wind into some other forms. To what extent and how solar wind disturbances affect the energy dissipation processes at the bow shocks on different planets remain unclear. With the Chinese Tianwen-1 and American Mars Atmosphere and Volatile EvolutioN missions, we present the first observation of significant modifications by a solar wind stream interaction region to the Martian foreshock waves, which are an important energy dissipation product of the bow shock. After the stream interface hitting Mars, an unusual band of foreshock waves emerged, with a central frequency of ∼0.4 Hz and frequency width of ∼0.2 Hz. These waves exhibited highly distorted waveforms, with peak-to-peak amplitudes of 10–25 nT in contrast to a background magnetic field of 6–9 nT. They were approximately elliptically polarized with respect to the wavevector and propagated highly obliquely to the background magnetic field. These waves reported here differed greatly from the commonly known Martian foreshock “30 s waves” and “1 Hz waves,” but resembled, to some extent, the less frequently occurring terrestrial foreshock “3 s waves. ” Our present findings may imply an unexpected energy dissipation pattern of the Martian bow shock to the disturbed solar wind, which needs further observational, theoretical, and numerical investigations.
Troponin level at presentation as a prognostic factor among patients presenting with non‐ST‐segment elevation myocardial infarction

Introduction: Timely reperfusion within 120 minutes is strongly recommended in patients presenting with non-ST segment myocardial infarction (NSTEMI) with very high-risk features. Evidence regarding the use of high sensitivity cardiac troponin (hs-cTn) concentration upon admission for the risk-stratification of patients presenting with NSTEMI in order to expedite percutaneous coronary intervention (PCI) and thus potentially improve outcomes is limited. Methods: All patients admitted to a tertiary care center intensive cardiac care unit (ICCU) between July 2019 -- July 2022 were included and were followed for up to 3 years. Hs-cTnI level on presentation was recorded and patients were divided into four quartiles according to their hs-cTnI level on admission. Association between the initial hs-cTnI level and all-cause mortality during the follow-up period was examined. Results: A total of 544 NSTEMI patients with a median age of 67 were included. There was no difference between the initial hs-cTnI level groups regarding age and comorbidities. A higher mortality rate was observed in the highest hs-cTnI quartile as compared with the lowest hs-cTnI quartile (16.2% vs. 7.35%, p=0.03) with Hazard ratio (HR) for mortality of 2.6 (CI: 1.23-5.4; p=0.012). Conclusions: Patients presenting with NSTEMI and higher Hs-cTnI levels on admission were at higher risk for mortality during follow-up. This finding supports further prospective studies to examine the impact of early reperfusion strategy on mortality in patients presenting with NSTEMI according to degree of troponin elevation on admission.
Provable Symmetric Nonnegative Matrix Factorization for Overlapping Clustering

The problem of finding overlapping communities in networks has gained much attention recently. Algorithmic approaches often employ non-negative matrix factorization (NMF) or variants, while model-based approaches (such as the widely used mixed-membership stochastic blockmodel, or MMSB) assume a distribution over communities for each node and run standard inference techniques to recover these parameters. However, few of these approaches have provable consistency guarantees. We investigate the use of the symmetric NMF (or SNMF) for the MMSB model, and provide conditions under which an optimal SNMF algorithm can recover the MMSB parameters consistently. Since we are unaware of general-purpose optimal SNMF algorithms, we develop an SNMF variant, called GeoNMF, designed specifically for the MMSB model. GeoNMF is provably consistent, and experiments on both simulated and real-world datasets show its accuracy.
Contribution of rare variants to heritability of a disease is much greater than conventionally estimated: modification of allele distribution model

Missing heritability is a current problem in human genetics. I previously reported a method to estimate heritability of a polymorphism (hp2) for a common disease without calculating the genetic variance under dominant and the recessive models. Here, I extended the method to the co-dominant model and carry out trial calculations of hp2. I also calculated hp2 applying the allele distribution model originally reported by Pawitan et al. for a comparison. Unexpectedly, hp2 calculated for rare variants with high odds ratios was much higher. I noticed that conventional methods use the allele frequency (AF) of a variant in the general population. However, this implicitly assumes that the unaffected are included among the phenotypes: an assumption that is inconsistent with case-control studies in which unaffected individuals belong to the control group. Therefore, I modified the allele distribution model by using the AF in the patient population. Consequently, the hp2 of rare variants was quite high. Recalculating hp2 of several rare variants reported in the literature with the modified allele distribution model, yielded results were 3.2 - 53.7 times higher than the original model. These results suggest that the contribution of rare variants to heritability of a disease has been considerably underestimated.
A pre-registered decoded neurofeedback intervention for specific phobias

Background: Treatment attrition rates can be high for specific phobia, partly due to the subjectively aversive nature of exposure therapy that involves direct exposure to fear- and panic-inducing stimuli. A new closed-loop fMRI method called multi-voxel neuro-reinforcement has the potential to alleviate the subjective aversiveness of interventions by directly inducing phobic representations in the brain, outside of conscious awareness. The current study seeks to test this method as an intervention for specific phobia. Methods: In a pre-registered clinical trial, individuals (N=18) with at least two animal subtype specific phobias underwent double-blind multi-voxel neuro-reinforcement for one of the two feared animals, with the untargeted one serving as control. Unaware of the target of neuro-reinforcement (i.e., the target animal), participants were guided with visual feedback and rewarded for implicit activation of the target representation. Amygdala response to phobic stimuli was assessed pre-treatment and post-treatment using photographic image presentations. Attentional capture to phobic stimuli was assessed using an affective Stroop task. Results: Confirming our pre-registered hypothesis, a significant interaction between phobia type (target/control) and time (pre-treatment/post-treatment) was found for amygdala response. There was also a nonsignificant trend (p=0.055) for the hypothesized attentional capture during the affective Stroop. In both measures, responding to the phobia targeted with neuro-reinforcement was selectively reduced compared to the placebo control. Conclusions: Results suggest multi-voxel neuro-reinforcement has the potential to be a successful intervention for specific phobia. Multi-voxel neuro-reinforcement decreased physiological and behavioral responses to specific phobia through reduced amygdala activation and attentional capture by phobic stimuli. Consequently, multi-voxel neuro-reinforcement may complement current conventional psychotherapy approaches while providing a non-distressing experience for patients seeking treatment.
Trust regions in Kriging-based optimization with expected improvement

The Kriging-based Efficient Global Optimization (EGO) method works well on many expensive black-box optimization problems. However, it does not seem to perform well on problems with steep and narrow global minimum basins and on high-dimensional problems. This article develops a new Kriging-based optimization method called TRIKE (Trust Region Implementation in Kriging-based optimization with Expected improvement) that implements a trust-region-like approach where each iterate is obtained by maximizing an Expected Improvement (EI) function within some trust region. This trust region is adjusted depending on the ratio of the actual improvement to the EI. This article also develops the Kriging-based CYCLONE (CYClic Local search in OptimizatioN using Expected improvement) method that uses a cyclic pattern to determine the search regions where the EI is maximized. TRIKE and CYCLONE are compared with EGO on 28 test problems with up to 32 dimensions and on a 36-dimensional groundwater bioremediation application in appendices supplied as an online supplement available at http://dx.doi. org/10.1080/0305215X.2015. 1082350. The results show that both algorithms yield substantial improvements over EGO and they are competitive with a radial basis function method.
Mathematical modeling of the performance of wild and transgenic mosquitoes in malaria transmission

A mathematical model that simulates malaria transmission under the influence of transgenic mosquitoes refractory to malaria is presented in this paper. The zygosity of transgenic mosquitoes is taken into account and, consequently, the total population of mosquitoes is comprised of wild type and heterozygous and homozygous transgenic mosquitoes. These three mosquito varieties interact by mating and competition, and the genetic characteristics of their resulting offspring are in accordance with Mendelian genetics or the mutagenic chain reaction (MCR) technique. Although the incorporation of transgenic mosquitoes into the ecosystem reduces the incidence of malaria, the model also takes into account the importance of completing treatment in individuals with confirmed infection and the imminent risk of increased environmental temperature.
Saliency Variation Based Quality Assessment for Packet-loss-impaired Videos

This paper presents a saliency variation based full-reference objective quality assessment metric for packet-loss-impaired videos. The method explores the application of visual saliency information. Motivated by the observation that packet-loss induced errors often change the spatial-temporal visual attention and correspondingly the saliency map, we explore the spatial changes in the saliency values between the original and distorted videos, and the temporal variation of the saliency map of the distorted video. The proposed metric was tested on 17 packet-loss-impaired videos and evaluated by a subjective test. Experiment results showed that the proposed method provides significant improvement in correlation with subjective results over traditional non-saliency quality metrics and the saliency/ROI (region of interest) weighted pixel-error quality measurements. This demonstrates that saliency variation is effective in evaluating the perceptual quality of videos affected by packet loss induces errors.
Modeling SARS-CoV-2 nucleotide mutations as a stochastic process

This study analyzes the SARS-CoV-2 genome sequence mutations by modeling its nucleotide mutations as a stochastic process in both the time-series and spatial domain of the gene sequence. In the time-series model, a Markov Chain embedded Poisson random process characterizes the mutation rate matrix, while the spatial gene sequence model delineates the distribution of mutation inter-occurrence distances. Our experiment focuses on five key variants of concern that had become a global concern due to their high transmissibility and virulence. The time-series results reveal distinct asymmetries in mutation rate and propensities among different nucleotides and across different strains, with a mean mutation rate of approximately 2 mutations per month. In particular, our spatial gene sequence results reveal some novel biological insights on the characteristic distribution of mutation inter-occurrence distances, which display a notable pattern similar to other natural diseases. Our findings contribute interesting insights to the underlying biological mechanism of SARS-CoV-2 mutations, bringing us one step closer to improving the accuracy of existing mutation prediction models. This research could also potentially pave the way for future work in adopting similar spatial random process models and advanced spatial pattern recognition algorithms in order to characterize mutations on other different kinds of virus families.