Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Strong Inhibition of CYP3A and UGT1A9 and Strong Induction of CYP3A on the Pharmacokinetics, Safety, and Tolerability of Soticlestat: Two Drug-Drug Interaction Studies in Healthy Volunteers.

Two open-label, phase 1 studies (NCT05064449, NCT05098041) investigated the effects of CYP3A inhibition (via itraconazole), UGT1A9 inhibition (via mefenamic acid), and CYP3A induction (via rifampin) on the pharmacokinetics of soticlestat and its metabolites M-I and M3. In period 1 of both studies, participants received a single dose of soticlestat 300 mg. In period 2, participants received itraconazole on days 1-11 and soticlestat 300 mg on day 5 (itraconazole/mefenamic acid study; part 1); mefenamic acid on days 1-7 and soticlestat 300 mg on day 2 (itraconazole/mefenamic acid study; part 2); or rifampin on days 1-13 and soticlestat 300 mg on day 11 (rifampin study). Twenty-eight healthy adults participated in the itraconazole/mefenamic acid study (14 per part) and 15 participated in the rifampin study (mean age, 38.1-40.7 years; male, 79-93%). For maximum observed concentration, the geometric mean ratios (GMRs) of soticlestat + itraconazole, mefenamic acid, or rifampin to soticlestat alone were 116.6%, 107.3% and 13.2%, respectively, for soticlestat; 10.7%, 118.0% and 266.1%, respectively, for M-I, and 104.6%, 88.2% and 66.6%, respectively, for M3. For area under the curve from time 0 to infinity, the corresponding GMRs were 124.0%, 100.6%, and 16.4% for soticlestat; 13.3%, 117.0%, and 180.8% for M-I; and 120.3%, 92.6%, and 58.4% for M3. Soticlestat can be administered with strong CYP3A and UGT1A9 inhibitors, but not strong CYP3A inducers (except for antiseizure medications, which will be further evaluated in ongoing phase 3 studies). In both studies, all treatment-emergent adverse events were mild or moderate. ClinicalTrials.gov: NCT05064449, NCT05098041 Significance Statement These drug-drug interaction studies improve our understanding of the potential changes that may arise in soticlestat exposure in patients being treated with CYP3A inhibitors, UGT1A9 inhibitors, or CYP3A inducers. The results build on findings from previously published soticlestat studies and provide important information to help guide clinical practice. Soticlestat has shown positive phase 2 results and is currently in phase 3 development for the treatment of seizures in patients with Dravet syndrome and Lennox-Gastaut syndrome.
Nature of organic matter associated with particle-sized fractions of Thai soils.

The current knowledge about the content and composition of soil organic matter (SOM) associated with particle size fractions in Thai soils is generally scarce. This study was conducted by sampling 25 soils (each at 3 depths, n=75) with different texture and mineralogy. The samples were analyzed for organic carbon (OC) and total nitrogen (total N). The composition of OM was characterized using diffuse reflectance infrared Fourier transformed (DRIFT) spectroscopy. Mineralogy of the soils was classified as siliceous, mixed, kaolinitic and smectitic. The OC and total N contents of whole soils were linearly positively correlated with clay content of soils at all depths. The decrease of intercept and slope of these linear relationships with depths reflected the lesser influences of biomass input, and clay content on SOM. The clay fraction of the coarsetextured siliceous soils was more enriched with OC and total N than that of the fine-textured mixed mineralogy, kaolinitic and smectitic soils, attributed by the multi-layered-recalcitrant aliphatic-C coatings of small clay fraction, whereas the clay fraction of the fine-textured soils were more enriched with intermediate decomposed aromatic-C and amide-N. Less obvious relative difference of organic functional groups was observed in silt and sand fractions. The significant positive correlations of the aliphatic-C/polysaccharides ratio in clay fraction with proportion (%) of kaolinite, and its negative correlations with proportion (%) of smectite suggested the different role of clay type in governing decomposition rate of OM. The significant positive correlations of clay content and various forms of Fe/Al oxides with OC and total N contents in silt and sand fractions in all depths indicated the role of ternary OM-Fe/Al-clay interactions in protecting sandand silt-associated OM within aggregate fractions. The findings of this study provided basic insight into relevant OM management practices for different types of Thai soils.
METHOD FOR PREPARING A γ-UNSATURATED β-LACTONE AND USE THEREOF AS AN AROMATIC AND FLAVOURING INGREDIENT

The present invention for spices or fragrance (6R) - 4, 5, 6, 7 - tetrahydro-3,6-dimethyl-3H-benzo [b] furan - relates to a compound-on-2. The compounds can be used to provide a dental floss having a mild sweetness and vanilla flavor and gives rich flavor to be added to the composition.
Active Disparity Sampling for Stereo Matching With Adjoint Network

The sparse signals provided by external sources have been leveraged as guidance for improving dense disparity estimation. However, previous methods assume depth measurements to be randomly sampled, which restricts performance improvements due to under-sampling in challenging regions and over-sampling in well-estimated areas. In this work, we introduce an Active Disparity Sampling problem that selects suitable sampling patterns to enhance the utility of depth measurements given arbitrary sampling budgets. We achieve this goal by learning an Adjoint Network for a deep stereo model to measure its pixel-wise disparity quality. Specifically, we design a hard-soft prior supervision mechanism to provide hierarchical supervision for learning the quality map. A Bayesian optimized disparity sampling policy is further proposed to sample depth measurements with the guidance of the disparity quality. Extensive experiments on standard datasets with various stereo models demonstrate that our method is suited and effective in different stereo architectures and outperforms existing fixed and adaptive sampling methods under different sampling rates. Remarkably, the proposed method makes substantial improvements when generalized to heterogeneous unseen domains.
Beatrice Hill Tinsley: breaking through the glass ceiling

ABSTRACT Beatrice Hill Tinsley was one of New Zealand’s leading scientists. A theoretical astronomer who lost her life early to melanoma, she is remembered not only for her brilliant intellect but her generous spirit and her teaching ability. This short communication presents a case study comparison of Hill Tinsley’s life experiences, as documented in the two biographies Bright Star and My Daughter Beatrice, with points raised in the recent publication Why Science is Sexist. Through this assessment, it is demonstrated that women in the scientific community today continue to struggle with many of the obstacles that Hill Tinsley faced 40 years ago. A recognition of the pervasiveness of these issues provides a more complete picture of the scale of Hill Tinsley’s achievements, at the same time as enriching the wider narrative of the experiences of women in science.
Highly specific σ2R/TMEM97 ligand FEM-1689 alleviates neuropathic pain and inhibits the integrated stress response

Significance Neuropathic pain is a major medical problem that is poorly treated with existing therapeutics. Our findings demonstrate that targeting σ2R/TMEM97 with a modulator reduces pain hypersensitivity in a mouse model with exquisite selectivity. We also identify integrated stress response (ISR) inhibition as a potential mechanism of action that links the receptor to cellular signaling events that have preclinical and clinical validation for pain relief. Our work suggests that σ2R/TMEM97 can be selectively engaged by specific small molecules to produce ISR inhibition in a subset of cells that are critical for neuropathic pain. σ2R/TMEM97-targeted therapeutics thus have the potential to offer effective pain relief without engagement of opioid receptors.
Active faulting in a populated low-strain setting (Lower Rhine Graben, Central Europe) identified by geomorphic, geophysical and geological analysis

Abstract The Lower Rhine Graben (Central Europe) is a prime example of a seismically active low-strain rift zone characterized by pronounced anthropogenic and climatic overprint of structures, and long recurrence intervals of large earthquakes. These factors render the identification of active faults and surface ruptures difficult. We investigated two fault scarps in the Lower Rhine Graben, to decipher their structural character, offset and potential seismogenic origin. Both scarps were modified by anthropogenic activity. The Hemmerich site lies c. 20 km SW of Cologne, along the Erft Fault. The Untermaubach site lies SW of Düren, where the Schafberg Fault projects into the Rur River valley. At the Hemmerich site, geomorphic and geophysical data, as well as exploratory coring reveal evidence of repeated normal faulting. Geophysical analysis and palaeoseismological excavation at the Untermaubach site reveal a complex fault zone in Holocene gravels characterized by subtle gravel deformation. Differentiation of tectonic and fluvial features was only possible with trenching, because fault structures and grain sizes of the sediments were below the resolution of the geophysical data. Despite these issues, our investigation demonstrates that valuable insight into past earthquakes and seismogenic deformation in a low-strain environment can be revealed using a multidisciplinary approach.
Target-enhanced whole-genome sequencing (TE-WGS) shows clinical validity equivalent to commercially available targeted oncology panel

Cancer poses a significant global health challenge, with increasing incidence rates demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the potential medical application of WGS. Methods: This study evaluates the power of target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. A cohort of forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches currently used in the clinic. Results: TE-WGS methods detected all the variants reported from TSO500 (100%, 498/498). A high correlation in the detection of variant allele fractions (VAF) was observed between the TE-WGS and TSO500 methodologies (r=0.977). Notably, within the pool of 498 variants commonly detected by both approaches, 223 variants (44.8%) were discerned within peripheral blood samples exclusively through the TE-WGS technique, suggesting their presence as constitutional variants inherent to the germline. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS method, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion-genes, MSI- and homologous-recombination deficiency (HRD) scores, which were essential for clinical decision making. Conclusion: TE-WGS proves to be a comprehensive approach in personalized oncology, matching the key biomarker detection capabilities of the established TSO500 panel. Additionally, TE-WGS uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness further underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.
Diabetes related emergency department visits among adults during the COVID-19 pandemic - an analysis of data from the New York City syndromic surveillance system

Objective: New York City was an early epicenter of the COVID-19 pandemic. We aim to describe population level epidemiological trends in diabetes related emergency department (ED) visits among adults in New York City, for the period prior to and encompassing the first four waves of the pandemic. Research Design and Methods: We used data from the New York City ED syndromic surveillance system during December 30, 2018 through May 21, 2022. This system captures all visits from EDs in the city in near-real time. We matched these visits to laboratory confirmed COVID-19 positivity data beginning with February 15, 2020. Results: Compared to pre-pandemic baseline levels, diabetes related ED visits noticeably increased during the first wave in spring 2020, though this did not necessarily translate to net increases overall during that period. Visits for diabetic ketoacidosis, particularly among adults with type 2 diabetes, sharply increased before returning to pre-pandemic levels, most notably during wave 1 and wave 4 in winter 2021-2022. Trajectories of diabetes-related ED visits differed by diabetes type, age, and sex. Some ED visit trends did not return to pre-pandemic baseline levels. Conclusions: The COVID-19 pandemic, especially the first wave in the spring of 2020, coincided with a dramatic shift in diabetes related ED utilization in New York City. Our findings highlight the importance of on-going surveillance of health care utilization for chronic diseases during population-level emergencies like pandemics. A robust syndromic surveillance system that includes infectious and non-infectious syndromes is useful to better prepare, mitigate, and respond to population-level events.
Improving satellite data products for open oceans with a scheme to correct the residual errors in remote sensing reflectance

An approach to semianalytically derive waters' inherent optical properties (IOPs) from remote sensing reflectance (Rrs) and at the same time to take into account the residual errors in satellite Rrs is developed for open-ocean clear waters where aerosols are likely of marine origin. This approach has two components: (1) a scheme of combining a neural network and an algebraic solution for the derivation of IOPs, and (2) relationships between Rrs residual errors at 670 nm and other spectral bands. This approach is evaluated with both synthetic and Sea-viewing Wide Field-of-view Sensor (SeaWiFS) data, and the results show that it can significantly reduce the effects of residual errors in Rrs on the retrieval of IOPs, and at the same time remove partially the Rrs residual errors for “low-quality” and “high-quality” data defined in this study. Furthermore, more consistent estimation of chlorophyll concentrations between the empirical blue-green ratio and band-difference algorithms can be derived from the corrected “low-quality” and “high-quality” Rrs. These results suggest that it is possible to improve both data quality and quantity of satellite-retrieved Rrs over clear open-ocean waters with a step considering the spectral relationships of the residual errors in Rrs after the default atmospheric correction procedure and without fixing Rrs at 670 nm to one value for clear waters in a small region such as 3 × 3 box.
Frobenius structure on hypergeometric equations, p-adic polygamma values and p-adic L-values

Recently, Kedlaya proves certain formula describing explicitly the Frobenius structure on a hypergeometric equation. In this paper, we give a generalization of it. In our case, the Frobenius matrix is no longer described by p-adic gamma function, and then we describe it by the p-adic polygamma functions. Since the p-adic polygamma values are linear combinations of p-adic L-values of Dirichlet characters, it turns out that the Frobenius matrix is described by p-adic L-values. Our result has an application to the study on Frobenius on p-adic cohomology. We show that, for a projective smooth family such that the Picard-Fuchs equation is a hypergeometric equation, the Frobenius matrix on the log-crystalline cohomology is described by some values of the logarithmic function and p-adic L-functions of Dirichlet characters.
A combinatorial remark on equivariant Ehrhart theory with applications to poset polytopes

We consider an equivariant analogue of the Betke-McMullen theorem relating the equivariant Ehrhart series of a lattice polytope to the equivariant Hilbert series of a unimodular triangulation of the given polytope. Under additional hypotheses on the group action, we find an alternative rational expression for the equivariant Ehrhart series and write its numerator as a positive integer combination of irreducible characters. As an application, we study the equivariant Ehrhart series of order polytopes and of Lipschitz poset polytopes with respect to any action by poset automorphisms.
MixEHR-SurG: a joint proportional hazard and guided topic model for inferring mortality-associated topics from electronic health records

Existing survival models either do not scale to high dimensional and multi-modal data or are difficult to interpret. In this study, we present a supervised topic model called MixEHR-SurG to simultaneously integrate heterogeneous EHR data and model survival hazard. Our contributions are three-folds: (1) integrating EHR topic inference with Cox proportional hazards likelihood; (2) integrating patient-specific topic hyperparameters using the PheCode concepts such that each topic can be identified with exactly one PheCode-associated phenotype; (3) multi-modal survival topic inference. This leads to a highly interpretable survival topic model that can infer PheCode-specific phenotype topics associated with patient mortality. We evaluated MixEHR-SurG using a simulated dataset and two real-world EHR datasets: the Quebec Congenital Heart Disease (CHD) data consisting of 8,211 subjects with 75,187 outpatient claim records of 1,767 unique ICD codes; the MIMIC-III consisting of 1,458 subjects with multi-modal EHR records. Compared to the baselines, MixEHR-SurG achieved a superior dynamic AUROC for mortality prediction, with a mean AUROC score of 0.89 in the simulation dataset and a mean AUROC of 0.645 on the CHD dataset. Qualitatively, MixEHR-SurG associates severe cardiac conditions with high mortality risk among the CHD patients after the first heart failure hospitalization and critical brain injuries with increased mortality among the MIMIC- III patients after their ICU discharge. Together, the integration of the Cox proportional hazards model and EHR topic inference in MixEHR-SurG not only leads to competitive mortality prediction but also meaningful phenotype topics for in-depth survival analysis. The software is available at GitHub: https://github.com/li-lab-mcgill/MixEHR-SurG.
EmphAssess : a Prosodic Benchmark on Assessing Emphasis Transfer in Speech-to-Speech Models

We introduce EmphAssess, a prosodic benchmark designed to evaluate the capability of speech-to-speech models to encode and reproduce prosodic emphasis. We apply this to two tasks: speech resynthesis and speech-to-speech translation. In both cases, the benchmark evaluates the ability of the model to encode emphasis in the speech input and accurately reproduce it in the output, potentially across a change of speaker and language. As part of the evaluation pipeline, we introduce EmphaClass, a new model that classifies emphasis at the frame or word level.
Accretion, emission, mass and spin evolution

Throughout the cosmic history, PBHs may experience an efficient phase of baryonic mass accretion from the surrounding medium. Its main consequences on their cosmological evolution are characteristic growths of the PBH masses and spins, as well as the emission of radiation, which is ultimately responsible for feedback effects that could weaken the efficiency of the process. In this chapter we review the basic formalism to describe the accretion rate, luminosity function and feedback effects, in order to provide distinctive predictions for the evolution of the PBH mass and spin parameters.
On a sufficient condition for explosion in CMJ branching processes and applications to recursive trees

We provide sufficient criteria for explosion in Crump-Mode-Jagers branching process, via the process producing an infinite path in finite time. As an application, we deduce a curious phase-transition in the infinite tree associated with a class of recursive tree models with fitness, showing that in one regime every node in the tree has infinite degree, whilst in another, the tree is locally finite, with a unique infinite path. The latter class encompasses many models studied in the literature, including the weighted random recursive tree, the preferential attachment tree with additive fitness, and the Bianconi-Barab\'asi model, or preferential attachment tree with multiplicative fitness.
Insertion algorithms for Type $\mathrm{B}$ and $\mathrm{D}$ Gelfand $W$-graphs

Like the RSK correspondence for symmetric groups, Garfinkle defined a domino correspondence for type $\mathrm{B}$ and $\mathrm{D}$ Coxeter groups. Similar to the Knuth relations, Taskin and Pietraho give the plactic relations for the domino correspondence and Bonnaf\'e use them to classify the cells for type $\mathrm{B}$ Coxeter groups. We give some further properties of the plactic relations and use these relations to describe the bidirected edges and the molecules of Gelfand $W$-graphs for type $\mathrm{B}$ and $\mathrm{D}$ Coxeter groups.
Dimension-Accuracy Tradeoffs in Contrastive Embeddings for Triplets, Terminals & Top-k Nearest Neighbors

Metric embeddings traditionally study how to map $n$ items to a target metric space such that distance lengths are not heavily distorted; but what if we only care to preserve the relative order of the distances (and not their length)? In this paper, we are motivated by the following basic question: given triplet comparisons of the form ``item $i$ is closer to item $j$ than to item $k$,'' can we find low-dimensional Euclidean representations for the $n$ items that respect those distance comparisons? Such order-preserving embeddings naturally arise in important applications and have been studied since the 1950s, under the name of ordinal or non-metric embeddings. Our main results are: 1. Nearly-Tight Bounds on Triplet Dimension: We introduce the natural concept of triplet dimension of a dataset, and surprisingly, we show that in order for an ordinal embedding to be triplet-preserving, its dimension needs to grow as $\frac n2$ in the worst case. This is optimal (up to constant) as $n-1$ dimensions always suffice. 2. Tradeoffs for Dimension vs (Ordinal) Relaxation: We then relax the requirement that every triplet should be exactly preserved and present almost tight lower bounds for the maximum ratio between distances whose relative order was inverted by the embedding; this ratio is known as (ordinal) relaxation in the literature and serves as a counterpart to (metric) distortion. 3. New Bounds on Terminal and Top-$k$-NNs Embeddings: Going beyond triplets, we then study two well-motivated scenarios where we care about preserving specific sets of distances (not necessarily triplets). The first scenario is Terminal Ordinal Embeddings and the second scenario is top-$k$-NNs Ordinal Embeddings. To the best of our knowledge, these are some of the first tradeoffs on triplet-preserving ordinal embeddings and the first study of Terminal and Top-$k$-NNs Ordinal Embeddings.