Miracle-dz/UniFAR-FTUs huggingface dataset:
Extraction of Crohn's Disease Clinical Phenotypes from Clinical Text Using Natural Language Processing

Background: Crohn's Disease (CD) patient heterogeneity in clinical practice is captured by the Montreal Classification. While the underlying concepts, disease behavior and age at diagnosis, are relevant outcomes and covariates in studies from real-world data, extracting this clinical information through manual chart review is labor-intensive and with limited scalability. Methods: We developed and evaluated automated phenotyping algorithms to extract disease behavior and age at diagnosis from clinical narrative texts, using a rule-based approach based on the spaCy framework, and an approach based on zero-shot inference. The underlying data included 49,572 clinical notes and 2,204 radiology reports from 584 CD patients of the Mount Sinai Crohn's and Colitis Registry. A test set of 200 clinical texts per classification category was labeled at sentence-level, in addition to patient-level ground truth data. The algorithms were evaluated based on their recall, precision, specificity values, and F1-scores. Results: For the labeled dataset, an overall Cohen's kappa inter-annotator agreement of 0.84 was achieved. The rule-based approach yielded high recall and precision values (0.75 - 1.00) on a note level for the behavioral disease phenotype using clinical notes, with slightly reduced performance using radiology reports. For age at diagnosis, recall and precision values of 0.81 and 0.88 were achieved on note-level, respectively. For both categories, the performance on patient- compared to note-level was reduced, potentially due to the accumulation of false positives and limitations in the data availability. Conclusion: Based on our newly annotated dataset, we demonstrated the feasibility of automatically extracting disease behavior and age at diagnosis from clinical text. The resulting labels may facilitate extensive cohort analyses based on electronic health records, and support chart review processes in the future.
Improved reproducibility of γ‐aminobutyric acid measurement from short‐echo‐time proton MR spectroscopy by linewidth‐matched basis sets in LCModel

γ‐Aminobutyric acid (GABA), as the primary inhibitory neurotransmitter, is extremely important for maintaining healthy brain function, and deviations from GABA homeostasis are related to various brain diseases. Short‐echo‐time (short‐TE) proton MR spectroscopy (1H‐MRS) has been employed to measure GABA concentration from various human brain regions at high magnetic fields. The aim of this study was to investigate the effect of spectral linewidth on GABA quantification and explore the application of an optimized basis‐set preparation approach using a spectral‐linewidth‐matched (LM) basis set in LCModel to improve the reproducibility of GABA quantification from short‐TE 1H‐MRS. In contrast to the fixed‐linewidth basis‐set approach, the LM basis‐set preparation approach, where all metabolite basis spectra were simulated with a linewidth 4 Hz narrower than that of water, showed a smaller standard deviation of estimated GABA concentration from synthetic spectra with varying linewidths and lineshapes. The test–retest reproducibility was assessed by the mean within‐subject coefficient of variation, which improved from 19.2% to 12.0% in the thalamus, from 27.9% to 14.9% in the motor cortex, and from 9.7% to 2.8% in the medial prefrontal cortex using LM basis sets at 7 T. We conclude that spectral linewidth has a large effect on GABA quantification from short‐TE 1H‐MRS data and that using LM basis sets in LCModel can improve the reproducibility of GABA quantification.
DiGAS: Differential gene allele spectrum as descriptor in genetic studies

Diagnosing subjects in complex genetic diseases is a very challenging task. Computational methodologies exploit information at genotype level by taking into account single nucleotide polymorphisms (SNP). They leverage the result of genome-wide association studies analysis to assign a statistical significance to each SNP. Recent methodologies extend such an approach by aggregating SNP significance at genetic level in order to identify genes that are related to the condition under study. However, such methodologies still suffer from the initial single-SNP analysis. Here, we present DiGAS, a tool for diagnosing genetic conditions by computing significance, by means of SNP information, but directly at the gene level. Such an approach is based on a generalized notion of allele spectrum, which evaluates the complete genetic alterations of the SNP set composing a gene at population level. Statistical significance of a gene is then evaluated by means of a differential analysis between the healthy and ill portions of the population. Tests, performed on well-established data sets regarding Alzheimer's disease, show that DiGAS outperforms the stateof-the-art in distinguishing between ill and healthy subjects.
Increased physical activity is not related to markers of cardiometabolic health in two lemur species

Insufficient physical activity is a major risk factor for cardiometabolic disease (i.e., unhealthy weight gain, heart disease, and diabetes) in humans and may also negatively affect health of primates in human care. Effects of physical activity on energy expenditure and cardiometabolic health are virtually unstudied in nonhuman primates. We investigated physical activity and metabolic markers in 15 adult ring‐tailed lemurs (Lemur catta) and 11 Coquerel's sifakas (Propithecus coquereli) at the Duke Lemur Center during a period of low activity in winter when the animals were housed in buildings (with outdoor access) and a period of high activity when individuals were free‐ranging in large, outdoor, forested enclosures. We compared body mass, blood glucose, triglycerides, HDL‐ and LDL‐cholesterol, physical activity via accelerometry, and total energy expenditure (TEE) via the doubly labeled water method (in ring‐tailed lemurs only) between both conditions. Both species were more active and had a lower body mass in summer. Ring‐tailed lemurs had a higher TEE and lower triglyceride levels in summer, whereas sifaka had higher triglyceride levels in summer. Individuals that increased their activity more, also lost more body mass. Individuals that lost more body mass, also had a positive change in HDL‐cholesterol (i.e., higher values in summer). Changes in activity were not associated with changes in markers of metabolic health, body fat percentage and TEE (both unadjusted and adjusted for body composition). Older age was associated with lower activity in both species, and decreased glucose in ring‐tailed lemurs, but was otherwise unrelated to metabolic markers and, for ring‐tailed lemurs, adjusted TEE. Overall, body mass was lower during summer but the increase in physical activity did not strongly influence metabolic health or TEE in these populations.
Limitations in the enhancement of visible light absorption due to mixing state

[1] Absorption by light-absorbing carbon (LAC) particles increases when the carbon is mixed with other material, and this change affects climate forcing. We investigate this increase theoretically over a realistic range of particle sizes. Perfect mixing at the molecular level often overestimates absorption. Assuming that LAC is coated by a concentric shell of weakly absorbing material, we calculate absorption by a range of realistic particle sizes and identify regimes in which absorption behaves similarly. We provide fits to amplification in five regions: (1) small cores and (2) intermediate cores, both with large shells; (3) small to intermediate cores with intermediate shells; (4) cores with growing shells; and (5) intermediate to large cores with large shells. Amplification in region 1 is highest but is physically implausible. Amplification in region 5 is constant at about 1.9 and represents an asymptote for particles with broad size distributions. Because absorption by aggregates is amplified by about 1.3 above spherical particles, and that factor is lost when particles are coated, we suggest that absorption by aged aerosol is about 1.5 times greater than that of fresh aerosol. The rate at which particles acquire sufficient coating to increase their original diameter by 60% is important in determining total absorption during their atmospheric lifetimes. Fitted amplification factors are not very sensitive to assumed refractive index of LAC and can be used even in simple models.
Sex differences in cocaine self-administration by Wistar rats after predator odor exposure

Traumatic stress disorders are defined in part by persistent avoidance of trauma-related contexts. Our lab uses a preclinical model of traumatic stress using predator odor (i.e., bobcat urine) in which some but not all rats exhibit persistent avoidance of odor-paired stimuli, similar to what is seen in humans. Bobcat urine exposure increases alcohol consumption in male Avoider rats, but it has not been tested for its effects on intake of other drugs. Here, we tested the effect of bobcat urine exposure on cocaine self-administration in adult male and female Wistar rats. We did not observe any effect of bobcat urine exposure on cocaine self-administration in male or female rats. We observed that (1) female rats with long access (6 hours) to cocaine self-administer more cocaine than long-access males, (2) long-access males and females exhibit escalation of cocaine intake over time, (3) stressed rats gain less weight than unstressed rats following acute predator odor exposure, (4) baseline cocaine self-administration is predictive of subsequent cocaine self-administration. The results of this study may inform future work on predator odor effects on cocaine self-administration.
Cryopreservation of assay-ready hepatocyte monolayers by chemically-induced ice nucleation: preservation of hepatic function and hepatotoxicity screening capabilities

Cell culture plays a critical role in biomedical discovery and drug development. Primary hepatocytes and hepatocyte-derived cell lines are especially important cellular models for drug discovery and development. To enable high-throughput screening and ensure consistent cell phenotypes, there is a need for practical and efficient cryopreservation methods for hepatocyte-derived cell lines and primary hepatocytes in an assay-ready format. Cryopreservation of cells as adherent monolayers in 96-well plates presents unique challenges due to low volumes being susceptible to supercooling, leading to low recovery and well-to-well variation. Primary cell cryopreservation is also particularly challenging due to the loss of cell viability and function. In this study, we demonstrate the use of soluble ice nucleator materials (IN) to cryopreserve a hepatic-derived cell line (HepG2) and primary mouse hepatocytes, as adherent monolayers. HepG2 cell recovery was near 100% and ∼75% of primary hepatocytes were recovered 24 hours post-thaw compared to just 10% and 50% with standard 10% DMSO, respectively. Post-thaw assessment showed that cryopreserved HepG2 cells retain membrane integrity, metabolic activity, proliferative capacity and differentiated hepatic functions including urea secretion, cytochrome P450 levels and lipid droplet accumulation. Cryopreserved primary hepatocytes exhibited reduced hepatic functions compared to fresh hepatocytes, but functional levels were similar to commercial suspension-cryopreserved hepatocytes, with the added benefit of being stored in an assay-ready format. In addition, normal cuboidal morphology and minimal membrane damage were observed 24 hours post-thaw. Cryopreserved HepG2 and mouse hepatocytes treated with a panel of pharmaceutically active compounds produced near-identical dose–response curves and EC50 values compared to fresh hepatocytes, confirming the utility of cryopreserved bankable cells in drug metabolism and hepatotoxicity studies. Cryopreserved adherent HepG2 cells and primary hepatocytes in 96 well plates can significantly reduce the time and resource burden associated with routine cell culture and increases the efficiency and productivity of high-throughput drug screening assays.
Construction of molecular subgroups of ulcerative colitis.

OBJECTIVE Ulcerative colitis (UC), a chronic inflammatory disease of the colon with unknown etiology, is characterized by remission and recurrence. At present, a considerable number of UC cases are misdiagnosed or delayed in diagnosis and treatment. We aimed to identify UC-related genes to aid the development of drugs for this condition. PATIENTS AND METHODS Transcriptome data of 362 patients with UC and 126 control subjects were obtained from the Gene Expression Omnibus. The 362 patients with UC were subgrouped using unsupervised machine learning. R software was used to analyze the clinical characteristics of the subgroups, screen subgroup-specific genes, assess the relationships between gene modules and clinical characteristics using weighted gene co-expression network analysis, and perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the subgroups. RESULTS Patients with UC were classified into two subgroups. Genes specific to subgroup I included IL21R, ATP8B2, and PLEKHO1. Severe disease tended to be associated with immune cell infiltration; anti-tumor necrosis factor (TNF)-α antibodies and ustekinumab may have been effective in this subgroup. Subgroup II-specific genes included SLC4A4, EPB41L4B, and PLCE1. Patients in this subgroup had mild clinical conditions; however, their disease was more likely to progress to colorectal cancer. Thus, 5-aminosalicylic acid-based drugs may be effective for the treatment of UC in these patients. CONCLUSIONS We divided UC into two molecular subgroups based on transcriptome data, providing molecular evidence for the development of diagnostic methods and individualized treatment strategies for UC.
A Comprehensive Comparison of Tissue Processing Methods for High-Quality MALDI Imaging of Lipids in Reconstructed Human Epidermis

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has become an important tool for skin analysis, as it allows the simultaneous detection and localization of diverse molecular species within a sample. The use of in vivo and ex vivo human skin models is costly and presents ethical issues; therefore, reconstructed human epidermis (RHE) models, which mimic the upper part of native human skin, represent a suitable alternative to investigate adverse effects of chemicals applied to the skin. However, there are few publications investigating the feasibility of using MALDI MSI on RHE models. Therefore, the aim of this study was to investigate the effect of sample preparation techniques, i.e., substrate, sample thickness, washing, and matrix recrystallization, on the quality of MALDI MSI for lipids analysis of the SkinEthic RHE model. Images were generated using an atmospheric pressure MALDI source coupled to a high-resolution mass spectrometer with a pixel size of 5 μm. Masses detected in a defined region of interest were analyzed and annotated using the LipostarMSI platform. The results indicated that the combination of (1) coated metallic substrates, such as APTES-coated stainless-steel plates, (2) tissue sections of 6 μm thickness, and (3) aqueous washing before HCCA matrix spraying (without recrystallization), resulted in images with a significant signal intensity as well as numerous m/z values. This refined methodology using AP-MALDI coupled to a high-resolution mass spectrometer should improve the current sample preparation workflow to evaluate changes in skin composition after application of dermatocosmetics.
Ninety years of change, from commercial extinction to recovery, range expansion and decline for Antarctic fur seals at South Georgia

With environmental change, understanding how species recover from overharvesting and maintain viable populations is central to ecosystem restoration. Here, we reconstruct 90 years of recovery trajectory of the Antarctic fur seal at South Georgia (S.W. Atlantic), a key indicator species in the krill‐based food webs of the Southern Ocean. After being harvested to commercial extinction by 1907, this population rebounded and now constitutes the most abundant otariid in the World. However, its status remains uncertain due to insufficient and conflicting data, and anthropogenic pressures affecting Antarctic krill, an essential staple for millions of fur seals and other predators. Using integrated population models, we estimated simultaneously the long‐term abundance for Bird Island, northwest South Georgia, epicentre of recovery of the species after sealing, and population adjustments for survey counts with spatiotemporal applicability. Applied to the latest comprehensive survey data, we estimated the population at South Georgia in 2007–2009 as 3,510,283 fur seals [95% CI: 3,140,548–3,919,604] (ca. 98% of global population), after 40 years of maximum growth and range expansion owing to an abundant krill supply. At Bird Island, after 50 years of exponential growth followed by 25 years of slow stable growth, the population collapsed in 2009 and has thereafter declined by −7.2% [−5.2, −9.1] per annum, to levels of the 1970s. For the instrumental record, this trajectory correlates with a time‐varying relationship between coupled climate and sea surface temperature cycles associated with low regional krill availability, although the effects of increasing krill extraction by commercial fishing and natural competitors remain uncertain. Since 2015, fur seal longevity and recruitment have dropped, sexual maturation has retarded, and population growth is expected to remain mostly negative and highly variable. Our analysis documents the rise and fall of a key Southern Ocean predator over a century of profound environmental and ecosystem change.
The variation of the deuterium content of natural waters in the hydrologic cycle

Exploratory dnta from more than 1000 analyses of the distribution of deuterium in waters of the North American continent and the surface oceans contiguous to the continent are presented. The elementary theory of the processes that appear to explain the changes in the deuterium content of natural waters is developed. Quantitntive expressions of the deuterium fractionation thnt can be expected to occur are presented for all phases of the hydrologic cycle from the evaporation of wnter from the oceans, its precipitation as rain and snow, and its travel back to the sea. Processes such as the freezing of water under equilibrium and nonequilibrium conditions, the evaporation of water from closed lakes and from lakes with an outlet, the formntion of fog, frost, and dew are also discussed. The regional characteristics of the surface waters of Nonth America are described and interpreted as reflecting the history of the water in the course of the hydrologic cycle. (auth)
Micro Raman spectroscopy of amphiboles and pyroxenes in the martian meteorites Zagami and Lewis Cliff 88516

Abstract— We studied micro Raman spectroscopy of amphiboles and pyroxenes in the martian meteorites Zagami and Lewis Cliff (LEW) 88516. The obtained Raman spectra of the amphiboles are similar to those of kaersutite, reconfirming the previous studies that they are kaersutitic amphiboles enriched in Ca, Al, and Ti. Even though actinolite belongs to the same amphibole group (calcic amphibole) as kaersutite, the Raman spectra of terrestrial actinolite are distinct from those of kaersutite, probably reflecting complex amphibole crystal structures. The Al‐Ti‐rich pyroxene observed in the magmatic inclusions within LEW 88516 olivine is compositionally similar to kaersutite but shows Raman spectra nearly identical to the regular pyroxene rather than amphibole. In contrast to amphibole, this will be due to relatively simple crystal structures of pyroxene. Thus, the Raman spectra of Al‐Ti‐rich phases in the martian meteorites are distinct between kaersutite and Al‐Ti‐rich pyroxene, and this study demonstrates that micro Raman spectroscopy is one of the best tools to perform mineralogical characterization of mineral phases in martian meteorites.
The Multidrug Resistance Transporter P-glycoprotein Confers Resistance to Ferroptosis Inducers

Ferroptosis is a form of cell death caused by direct or indirect inhibition of glutathione peroxidase 4 that leads to lethal lipid peroxidation. Several small molecule ferroptosis inducers (FINs) have been reported, yet little information is available regarding resistance mechanisms, particularly their interaction with the ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp, ABCB1) and ABCG2. Given the role that ABC transporters play in absorption, distribution, and excretion of many drugs, characterizing these interactions could provide information regarding oral bioavailability and brain penetration and may predict drug-drug interactions. Using ferroptosis-sensitive A673 cells transfected to express P-gp or ABCG2, we found that P-gp overexpression was able to confer resistance to FIN56 and the erastin derivatives imidazole ketone erastin and piperazine erastin. Results were confirmed with OVCAR8-derived NCI/ADR-RES cells that overexpress P-gp, where the P-gp inhibitor valspodar completely inhibited resistance to the FINs. P-gp-mediated resistance to imidazole ketone erastin and piperazine erastin was also reversed in UO-31 renal cancer cells by CRISPR-mediated knockout of ABCB1. At a concentration of 10 μM, the FINs ML-162, GPX inhibitor 26a, and PACMA31 were able to increase intracellular rhodamine 123 fluorescence over 10-fold in P-gp-expressing MDR-19 cells and GPX inhibitor 26a was able to increase intracellular purpurin-18 fluorescence over 4-fold in ABCG2-expressing R-5 cells. Expression of P-gp may reduce the efficacy of these FINs in cancers that express the transporter and may prevent access to sanctuary sites such as the brain. The ability of some FINs to inhibit P-gp and ABCG2 suggests potential drug-drug interactions. SIGNIFICANCE STATEMENT While several small-molecule ferroptosis inducers have been described, little work has addressed potential interactions with ABC transporters such as P-glycoprotein or ABCG2 that might limit bioavailability or brain penetration. We find that the ferroptosis inducers FIN56, imidazole ketone erastin, and piperazine erastin are substrates of P-glycoprotein. ML-162, GPX inhibitor 26a, and PACMA31 were found to inhibit P-glycoprotein, while GPX inhibitor 26a was additionally able to inhibit ABCG2, suggesting the potential for drug-drug interactions.
The Role of the “Atmospheric Bridge” in Linking Tropical Pacific ENSO Events to Extratropical SST Anomalies

Abstract The role of the atmospheric circulation as a “bridge” between sea surface temperature (SST) anomalies in the tropical Pacific and those in the midlatitude northern oceans is assessed. The key processes associated with this atmospheric bridge are described using output from four independent simulations with a general circulation model subjected to month to month SST variations observed in the tropical Pacific during the 1946–1988 period and to climatological SST conditions elsewhere (the “TOGA” runs). In episodes with prominent SST anomalies in the tropical Pacific, extratropical perturbations in the simulated atmospheric temperature, humidity, and wind fields induce changes in the latent and sensible heat fluxes across the air-sea interface of the midlatitude oceans. These anomalous fluxes in turn lead to extratropical SST changes. The relevance of the atmospheric bridge mechanism is evaluated by driving a motionless, 50-m deep oceanic negative mixed layer model at individual grid points with the.