Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of Machine Learning-Based Assessment of Tumor-Infiltrating Lymphocytes on Standard Histologic Images With Outcomes of Immunotherapy in Patients With NSCLC.

Importance Currently, predictive biomarkers for response to immune checkpoint inhibitor (ICI) therapy in lung cancer are limited. Identifying such biomarkers would be useful to refine patient selection and guide precision therapy. Objective To develop a machine-learning (ML)-based tumor-infiltrating lymphocytes (TILs) scoring approach, and to evaluate TIL association with clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC). Design, Setting, and Participants This multicenter retrospective discovery-validation cohort study included 685 ICI-treated patients with NSCLC with median follow-up of 38.1 and 43.3 months for the discovery (n = 446) and validation (n = 239) cohorts, respectively. Patients were treated between February 2014 and September 2021. We developed an ML automated method to count tumor, stroma, and TIL cells in whole-slide hematoxylin-eosin-stained images of NSCLC tumors. Tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) expression were assessed separately, and clinical response to ICI therapy was determined by medical record review. Data analysis was performed from June 2021 to April 2022. Exposures All patients received anti-PD-(L)1 monotherapy. Main Outcomes and Measures Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were determined by blinded medical record review. The area under curve (AUC) of TIL levels, TMB, and PD-L1 in predicting ICI response were calculated using ORR. Results Overall, there were 248 (56%) women in the discovery cohort and 97 (41%) in the validation cohort. In a multivariable analysis, high TIL level (≥250 cells/mm2) was independently associated with ICI response in both the discovery (PFS: HR, 0.71; P = .006; OS: HR, 0.74; P = .03) and validation (PFS: HR = 0.80; P = .01; OS: HR = 0.75; P = .001) cohorts. Survival benefit was seen in both first- and subsequent-line ICI treatments in patients with NSCLC. In the discovery cohort, the combined models of TILs/PD-L1 or TMB/PD-L1 had additional specificity in differentiating ICI responders compared with PD-L1 alone. In the PD-L1 negative (<1%) subgroup, TIL levels had superior classification accuracy for ICI response (AUC = 0.77) compared with TMB (AUC = 0.65). Conclusions and Relevance In these cohorts, TIL levels were robustly and independently associated with response to ICI treatment. Patient TIL assessment is relatively easily incorporated into the workflow of pathology laboratories at minimal additional cost, and may enhance precision therapy.
Local Linear Estimation in Partly Linear Models

Let (X, B, Y) denote a random vector such thatBandYare real-valued, andX? R2. Local linear estimates are used in the partial regression method for estimating the regression functionE(Y? X, B)=? B+m(X), where? is an unknown parameter, andm(·) is a smooth function. Under appropriate conditions, asymptotic distributions of estimates of? andm(·) are established. Moreover, it is shown that these estimates achieve the best possible rates of convergence in the indicated semi-parametric problems.
Effects of atmospheric turbulence on the interference of sound waves near a hard boundary

The mean sound levels resulting from the interference between direct waves and those reflected from the ground are strongly influenced, especially at frequencies near interference minima, by fluctuations in phase and amplitude of the sound waves induced by propagation through atmospheric turbulence. Since it was found experimentally that the correlation length (∠1.1 m) of the meteorological fluctuations is comparable to the separation between the interfering sound paths, previous theoretical work by Ingard and Maling [J. Acoust. Soc. Am. 35, 1056–1058 (1963)] has been extended to allow for partial covariance between the two waves. The theory has been further extended to use the calculations of fluctuations in phase and amplitude of spherical waves, and to include the explicit calculation of the fluctuating acoustical index of refraction from the fluctuating values of temperature and wind velocity. Measurements (1–6 kHz) have been made of the interference spectrum at 15, 30, and 45 m from a point source 1.
Analyzing Herbicide Interactions: A Statistical Treatment of Colby's Method

A model and a proposed method for testing herbicide interactions were modified from an analysis of variance (ANOVA) model for a 2 by 2 factorial experiment. Statistical tests for either synergism, antagonism, or additivity of herbicide combinations were developed through transforming growth data to logarithms followed by significance tests of 2 by 2 contrasts of the form μii - μi0 - μ0i + μ00 with respect to the log-transformed data. Using actual experimental data, heterogeneity of variance was less severe on the log scale compared to the original measurement scale. An expedient SAS(R) program for obtaining the desired significance tests was developed.
learnMSA: learning and aligning large protein families

Abstract Background The alignment of large numbers of protein sequences is a challenging task and its importance grows rapidly along with the size of biological datasets. State-of-the-art algorithms have a tendency to produce less accurate alignments with an increasing number of sequences. This is a fundamental problem since many downstream tasks rely on accurate alignments. Results We present learnMSA, a novel statistical learning approach of profile hidden Markov models (pHMMs) based on batch gradient descent. Fundamentally different from popular aligners, we fit a custom recurrent neural network architecture for (p)HMMs to potentially millions of sequences with respect to a maximum a posteriori objective and decode an alignment. We rely on automatic differentiation of the log-likelihood, and thus, our approach is different from existing HMM training algorithms like Baum–Welch. Our method does not involve progressive, regressive, or divide-and-conquer heuristics. We use uniform batch sampling to adapt to large datasets in linear time without the requirement of a tree. When tested on ultra-large protein families with up to 3.5 million sequences, learnMSA is both more accurate and faster than state-of-the-art tools. On the established benchmarks HomFam and BaliFam with smaller sequence sets, it matches state-of-the-art performance. All experiments were done on a standard workstation with a GPU. Conclusions Our results show that learnMSA does not share the counterintuitive drawback of many popular heuristic aligners, which can substantially lose accuracy when many additional homologs are input. LearnMSA is a future-proof framework for large alignments with many opportunities for further improvements.
Health Disparities by Sexual Orientation: Implications of Genetic and Environmental Explanations

ABSTRACT Xu and colleagues add to the growing research literature on the role of potential familial (i.e., genetic and shared environment) causes in sexual orientation and in the relation between sexual orientation and poor mental health, in which lesbian, gay, bisexual, and other sexual minority individuals have poorer mental health than heterosexual individuals. I address several implications of the findings by Xu et al. and others. First, the nuance or complexity of genetics is considered, given the implications of genetics for health via a single gene, epistasis, or epigenetics. Second, I highlight the magnitude of the genetic relation between sexual orientation and psychopathology, suggesting some, but not all, sexual minority individuals may differ from heterosexual individuals on psychiatric vulnerability. In turn, this suggests that research should identify for whom or under what circumstances the relation holds. Third, I underscore the need for a within-subjects design, in which attention turns to differences among sexual minority individuals. Fourth, the need to reevaluate Minority Stress Theory, the predominant theory accounting for health disparities by sexual orientation, is addressed because of the implications of genetics for health. Fifth, I acknowledge the concern attached to genetic research for potentially compounding the stigmatization already experienced by sexual minority individuals. Nevertheless, this research is occurring and will likely increase in volume. It will inform understanding of sexual minority individuals.
Understanding the What and When of Analogical Reasoning Across Analogy Formats: An Eye‐Tracking and Machine Learning Approach

Abstract Starting with the hypothesis that analogical reasoning consists of a search of semantic space, we used eye‐tracking to study the time course of information integration in adults in various formats of analogies. The two main questions we asked were whether adults would follow the same search strategies for different types of analogical problems and levels of complexity and how they would adapt their search to the difficulty of the task. We compared these results to predictions from the literature. Machine learning techniques, in particular support vector machines (SVMs), processed the data to find out which sets of transitions best predicted the output of a trial (error or correct) or the type of analogy (simple or complex). Results revealed common search patterns, but with local adaptations to the specifics of each type of problem, both in terms of looking‐time durations and the number and types of saccades. In general, participants organized their search around source‐domain relations that they generalized to the target domain. However, somewhat surprisingly, over the course of the entire trial, their search included, not only semantically related distractors, but also unrelated distractors, depending on the difficulty of the trial. An SVM analysis revealed which types of transitions are able to discriminate between analogy tasks. We discuss these results in light of existing models of analogical reasoning.
Non-expanding Plebański–Demiański space-times

The aim of this work is to describe the complete family of non-expanding Plebański–Demiański type D space-times and to present their possible interpretation. We explicitly express the most general form of such (electro)vacuum solutions with any cosmological constant, and we investigate the geometrical and physical meaning of the seven parameters they contain. We present various metric forms, and by analyzing the corresponding coordinates in the weak-field limit we elucidate the global structure of these space-times, such as the character of possible singularities. We also demonstrate that members of this family can be understood as generalizations of classic B-metrics. In particular, the BI-metric represents an external gravitational field of a tachyonic (superluminal) source, complementary to the AI-metric which is the well-known Schwarzschild solution for exact gravitational field of a static (standing) source.
Defining the characteristics of interferon-alpha–stimulated human genes: insight from expression data and machine learning

Abstract Background A virus-infected cell triggers a signalling cascade, resulting in the secretion of interferons (IFNs), which in turn induces the upregulation of the IFN-stimulated genes (ISGs) that play a role in antipathogen host defence. Here, we conducted analyses on large-scale data relating to evolutionary gene expression, sequence composition, and network properties to elucidate factors associated with the stimulation of human genes in response to IFN-α. Results We find that ISGs are less evolutionary conserved than genes that are not significantly stimulated in IFN experiments (non-ISGs). ISGs show obvious depletion of GC content in the coding region. This influences the representation of some compositions following the translation process. IFN-repressed human genes (IRGs), downregulated genes in IFN experiments, can have similar properties to the ISGs. Additionally, we design a machine learning framework integrating the support vector machine and novel feature selection algorithm that achieves an area under the receiver operating characteristic curve (AUC) of 0.7455 for ISG prediction. Its application in other IFN systems suggests the similarity between the ISGs triggered by type I and III IFNs. Conclusions ISGs have some unique properties that make them different from the non-ISGs. The representation of some properties has a strong correlation with gene expression following IFN-α stimulation, which can be used as a predictive feature in machine learning. Our model predicts several genes as putative ISGs that so far have shown no significant differential expression when stimulated with IFN-α in the cell/tissue types in the available databases. A web server implementing our method is accessible at http://isgpre.cvr. gla.ac. uk/. The docker image at https://hub.docker. com/r/hchai01/isgpre can be downloaded to reproduce the prediction.
Re: Ling L and Li X. A dorsalis pedis venous flap containing a U-shaped venous arch for the reconstruction of fingertip defects. J Hand Surg Eur. 2022. DOI: 10.1177/17531934221098064

In our article, we reported the use of a dorsalis pedis venous flap containing a cutaneous nerve to repair soft tissue defects of the finger pulp. We reported the sensory function but did not specifically report our measurement instrument and method of measuring the two point discrimination (2PD) at the postoperative follow-up. Some readers have questioned our data soon after online publication The instrument that we used to measure the 2PD in the above article was a stainless-steel eyelid calliper (Yishu Technology Co., Tianjin, China) (Figure 1 (a)), which is different from the disk that is commonly used by many other investigators (Figure 1(b)). The calliper that we used has the ability to adjust the distance between two points by turning the knob, and the scale can be accurate to 0.5mm. When we first adopted this instrument, we thought it was a
Recent advances in surveillance colonoscopy for dysplasia in inflammatory bowel disease

Inflammatory bowel disease (IBD) has a global presence with rapidly increasing incidence and prevalence. Patients with IBD including those with ulcerative colitis and Crohn’s disease have a higher risk of developing colorectal cancer (CRC) compared to the general population. Risk factors for CRC in patients with IBD include long disease duration, extensive colitis, primary sclerosing cholangitis, family history of CRC, stricture, and prior dysplasia. Surveillance colonoscopy for CRC in patients with IBD should be tailored to individualized risk factors and requires careful monitoring every year to every five years. The current surveillance techniques are based on several guidelines. Chromoendoscopy with targeted biopsy is being recommended increasingly, and high-definition colonoscopy is gradually replacing standard-definition colonoscopy. However, it remains unclear whether chromoendoscopy, virtual chromoendoscopy, or white-light endoscopy has better efficiency when a high-definition scope is used. With the development of new endoscopic instruments and techniques, the paradigm of surveillance strategy has gradually changed. In this review, we discuss cutting-edge surveillance colonoscopy in patients with IBD including a review of literature.
Local tetragonal distortion in La 0.7 Sr 0.3 MnO 3 strained thin films probed by x-ray absorption spectroscopy

We report on an angular resolved x-ray absorption spectroscopy study of ${\mathrm{La}}_{0.7}{\mathrm{Sr}}_{0.3}{\mathrm{MnO}}_{3}$ thin films epitaxially grown by pulsed laser deposition on slightly mismatched substrates which induce tensile or compressive strains. XANES spectra give evidence of tetragonal distortion within the ${\mathrm{MnO}}_{6}$ octahedra, with opposite directions for tensile and compressive strains. Quantitative analysis has been done and a model of tetragonal distortion reflecting the strain has been established. EXAFS data collected in plane for tensile substrate confirm the change in the $\mathrm{Mn}\text{\ensuremath{-}}\mathrm{O}$ average bond distance and the increase of $\mathrm{Mn}\text{\ensuremath{-}}\mathrm{Mn}$ length matching with the enlargement of the cell parameter. From these results we conclude that there is no significant change in the $\mathrm{Mn}\text{\ensuremath{-}}\mathrm{O}\text{\ensuremath{-}}\mathrm{Mn}$ angle. Our observations conflict with the scenarios in which this angle is the main driving parameter in the sensitivity of manganite films properties to external strains and suggest that the distortion within the octahedra plays a key role in the modification of the transport and magnetic properties.
Tables of SU(3) isoscalar factors

The Clebsch-Gordan coefficients of SU(3) are useful in calculations involving baryons and mesons, as well as in calculations involving arbitrary numbers of quarks. For the latter case, one needs the coupling constants between states of nonintegral hypercharges. The existing published tables are insufficient for many such applications, and therefore we have compiled this collection. This report supplies the isoscalar factors required to reconstruct the Clebsch-Gordan coefficients for a large set of products of representations.
Inflammation as Treatment Target for Status Epilepticus

Background Status epilepticus (SE) is a serious neurological disease that manifests as prolonged seizures that last more than 5 minutes and between such episodes, patients do not regain consciousness. It can result in cognitive defects, brain damage, or even death. It is commonly known that one of the causes can be an inflammatory process, but here we will focus on inflammation as a result of new onset refractory status epilepticus and, related to this, new promising forms of SE treatment. Particular emphasis has been focused on new-onset refractory status epilepticus (NORSE). Methods Based on public research databases, drugs with anti-inflammatory activity – commonly used in different spheres of medicine – have been reviewed as potentially treating status epilepticus. Results There is seizable clinical research suggesting that drugs that decrease inflammatory processes might be effective in terminating status epilepticus. Conclusion There is growing evidence showing that adding anti-inflammatory drugs to basic antiepileptic treatment enhances the efficiency of the therapeutic process, with special potential in NORSE cases.
Telomere length is causally connected to brain MRI image derived phenotypes: A mendelian randomization study

Recent evidence suggests that shorter telomere length (TL) is associated with neuro degenerative diseases and aging related outcomes. The causal association between TL and brain characteristics represented by image derived phenotypes (IDPs) from different magnetic resonance imaging (MRI) modalities remains unclear. Here, we use two-sample Mendelian randomization (MR) to systematically assess the causal relationships between TL and 3,935 brain IDPs. Overall, the MR results suggested that TL was causally associated with 193 IDPs with majority representing diffusion metrics in white matter tracts. 68 IDPs were negatively associated with TL indicating that longer TL causes decreasing in these IDPs, while the other 125 were associated positively (longer TL leads to increased IDPs measures). Among them, ten IDPs have been previously reported as informative biomarkers to estimate brain age. However, the effect direction between TL and IDPs did not reflect the observed direction between aging and IDPs: longer TL was associated with decreases in fractional anisotropy and increases in axial, radial and mean diffusivity. For instance, TL was positively associated with radial diffusivity in the left perihippocampal cingulum tract and with mean diffusivity in right perihippocampal cingulum tract. Our results revealed a causal role of TL on white matter integrity which makes it a valuable factor to be considered when brain age is estimated and investigated.
Vicarious experiences of touch (mirror touch) in a Chinese sample: Cross-cultural and individual differences

Mirror-touch synaesthesia (MTS) refers to tactile sensations people have on their own body when they see another person being touched. This trait has been linked to individual differences in computing body awareness and ownership (e.g., on questionnaires, cognitive tests) as well as differences in the brain. Here it is assessed for the first time in a non-Western (Chinese) population. Study 1 shows that reports of mirror-touch are elevated in a Chinese sample (N = 298) relative to comparable Western samples shown identical stimuli. In other respects, they are qualitatively similar (e.g., showing a difference between whether humans or inanimate objects are touched) and, overall, these differences could not be attributed to an acquiescence bias. The Chinese sample also completed a battery of questionnaires relating to body awareness and social-emotional functioning including mental health (Study 2) and had participated in brain imaging (the structural scans were analysed using voxel-based morphometry in Study 3). Participants reporting higher levels of mirror touch reported higher levels of anxiety. There were no reliable differences in the VBM analysis. It is suggested instead that cross-cultural differences in embodied cognition can manifest themselves in different rates of vicarious experience such as mirror touch.
Tidal Interaction between a Fluid Star and a Kerr Black Hole in Circular Orbit

We present a semianalytic study of the equilibrium models of close binary systems containing a Newtonian fluid star (mass m and radius R0) and a Kerr black hole (mass M) in a circular orbit. We consider the limit M ≫ m where spacetime is described by the Kerr metric. The tidally deformed star is approximated by an ellipsoid and satisfies the polytropic equation of state. The models also include fluid motion in the stellar interior, allowing binary models with nonsynchronized stellar spin (as expected for coalescing neutron star-black hole binaries) to be constructed. Our relativistic, compressible Roche-Riemann model is a generalization of the incompressible, corotating Roche model studied earlier by Fishbone. Tidal disruption occurs at orbital radius rtide ~ R0(M/m)1/3, but the dimensionless ratio r̂tide = rtide/[R0(M/m)1/3] depends on the spin parameter of the black hole as well as on the equation of state and the internal rotation of the star. We find that the general relativistic tidal field disrupts the star at a larger r̂tide than the Newtonian tide; the difference is particularly prominent if the disruption occurs in the vicinity of the black hole's horizon. In general, r̂tide is smaller for a (prograde rotating) Kerr black hole than for a Schwarzschild black hole. We apply our results to coalescing black hole-neutron star and black hole-white dwarf binaries. The tidal disruption limit is important for characterizing the expected gravitational wave signals and is relevant for determining the energetics of gamma-ray bursts that may result from such disruptions.
A classification of four-state spin edge Potts models

We classify four-state spin models with interactions along the edges according to their behaviour under a specific group of symmetry transformations. This analysis uses the measure of complexity of the action of the symmetries, in the spirit of the study of discrete dynamical systems on the space of parameters of the models, and aims at uncovering solvable ones. We find that the action of these symmetries has low complexity (polynomial growth, zero entropy). We obtain natural parametrizations of various models, among which an unexpected elliptic parametrization of the four-state chiral Potts model, which we use to localize possible integrability conditions associated with high genus curves.