Miracle-dz/UniFAR-FTUs huggingface dataset:
Extraction of Geriatric Syndromes From Electronic Health Record Clinical Notes: Assessment of Statistical Natural Language Processing Methods

Background Geriatric syndromes in older adults are associated with adverse outcomes. However, despite being reported in clinical notes, these syndromes are often poorly captured by diagnostic codes in the structured fields of electronic health records (EHRs) or administrative records. Objective We aim to automatically determine if a patient has any geriatric syndromes by mining the free text of associated EHR clinical notes. We assessed which statistical natural language processing (NLP) techniques are most effective. Methods We applied conditional random fields (CRFs), a widely used machine learning algorithm, to identify each of 10 geriatric syndrome constructs in a clinical note. We assessed three sets of features and attributes for CRF operations: a base set, enhanced token, and contextual features. We trained the CRF on 3901 manually annotated notes from 85 patients, tuned the CRF on a validation set of 50 patients, and evaluated it on 50 held-out test patients. These notes were from a group of US Medicare patients over 65 years of age enrolled in a Medicare Advantage Health Maintenance Organization and cared for by a large group practice in Massachusetts. Results A final feature set was formed through comprehensive feature ablation experiments. The final CRF model performed well at patient-level determination (macroaverage F1=0.834, microaverage F1=0.851); however, performance varied by construct. For example, at phrase-partial evaluation, the CRF model worked well on constructs such as absence of fecal control (F1=0.857) and vision impairment (F1=0.798) but poorly on malnutrition (F1=0.155), weight loss (F1=0.394), and severe urinary control issues (F1=0.532). Errors were primarily due to previously unobserved words (ie, out-of-vocabulary) and a lack of context. Conclusions This study shows that statistical NLP can be used to identify geriatric syndromes from EHR-extracted clinical notes. This creates new opportunities to identify patients with geriatric syndromes and study their health outcomes.
Emissions, Transmission, and the Environmental Value of Wind Energy

Growth in renewable electricity generation has spurred substantial private and public interest in increasing transmission capacity to export electricity from renewable-rich, demand-poor regions to urban demand centers. While the primary motives for these transmission investments are market-based (e.g., arbitraging regional electricity prices), they can also have large non-market impacts (e.g., altering the level and location of pollution). In this paper, we examine how transmission congestion alters the environmental benefits provided by wind generation. Using hourly wind and emissions data from the Texas and Mid-Continent electricity markets, we find that relaxing transmission constraints between the wind-rich areas of the respective markets and the demand centers results in 33% and 13% increases in the non-market value of a MWh of wind for Texas and the Mid-Continent markets, respectively. Much of this increase in the non-market value arises from a redistribution in where emissions are avoided – in transmission unconstrained periods, wind offsets much more pollution from fossil fuel units located near highly populated demand centers. ∗Department of Agricultural and Resource Economics, North Carolina State University; hfell@ncsu.edu †Department of Economics, University of Colorado Boulder; daniel.kaffine@colorado.edu ‡Department of Agricultural and Resource Economics, University of CaliforniaDavis; knovan@ucdavis.edu
Epigenetic Suppression of the T-box Subfamily 2 (TBX2) in Human Non-Small Cell Lung Cancer

(1) The TBX2 subfamily of transcription factors (TBXs 2, 3, 4 and 5) are markedly down-regulated in human non-small cell lung cancer (NSCLC) and exert tumor suppressor effects in lung malignancy. Yet, mechanisms underlying suppressed expression of the TBX2 subfamily in NSCLC are elusive. Here, we interrogated probable epigenetic mechanisms in suppressed expression of the TBX2 subfamily in human NSCLC. (2) TBX2 subfamily gene expression and methylation levels in NSCLC and normal lung tissues were surveyed using publicly available RNA-sequence and genome-wide methylation datasets. Methylation β-values of the four genes were statistically compared between NSCLCs and normal lung tissues, correlated with gene expression levels, and interrogated with clinicopathological variables. Expression and methylation levels of TBXs were quantified in NSCLC cells using real-time PCR and methylation-specific PCR assays, respectively. Effects of the DNA methyltransferase inhibitor 5-azacytidine (Aza) on TBX2 subfamily expression were assessed in NSCLC cells. Impact of TBX2 subfamily expression on Aza-treated cells was evaluated by RNA interference. (3) All four TBXs were significantly hypermethylated in NSCLCs relative to normal lung tissues (p < 0.05). Methylation β-values of the genes, with exception of TBX2, were significantly inversely correlated with corresponding mRNA expression levels (p < 0.05). We found no statistically significant differences in hypermethylation levels of the TBX2 subfamily by clinicopathological features including stage and tobacco history. Expression levels of the TBX genes were overall suppressed in NSCLC cells relative to normal alveolar cells. Members of the subfamily were significantly hypermethylated in all tested NSCLC cell lines relative to normal alveolar cells. Treatment with Aza induced the expression of the TBX2 subfamily concomitant with NSCLC cell growth inhibition. Further, simultaneous knockdown of the four TBX genes markedly reduced anti-growth effects of Aza in NSCLC cells. (4) Our study sheds light on new epigenetic profiles in the molecular pathogenesis of human NSCLC.
Exercise training promotes a GDF15-associated reduction in fat mass in older adults with obesity.

Obesity is a major risk factor for metabolic disease. Growth differentiation factor 15 (GDF15) has shown promise as a weight loss agent for obesity in animal studies. In healthy lean humans, fasting plasma GDF15 increases after acute exercise. However, the role of GDF15 in human obesity and the response of plasma GDF15 to exercise training in patients with obesity is unknown. Here, 24 sedentary volunteers with obesity [age: 65 ± 1 yr; body mass index (BMI): 35.3 ± 0.9 kg/m2] participated in a supervised 12-wk aerobic exercise intervention: 1 h/day, 5 days/wk at ~85% maximum heart rate with controlled isocaloric diet. As a result, plasma GDF15 was significantly increased (PRE: 644.1 ± 42.6 pg/ml, POST: 704.4 ± 47.2 pg/ml, P < 0.01) after the exercise intervention. Inconsistent with animal models, ΔGDF15 was not correlated with change in weight, BMI, or resting energy expenditure. However, ΔGDF15 was correlated with a reduction in total fat mass (P < 0.05), abdominal fat mass (P < 0.05), and android fat mass (P ≤ 0.05). Participants with a positive GDF15 response to exercise had increased total fat oxidation (PRE: 0.25 ± 0.05 mg·kg-1·min-1, POST: 0.43 ± 0.07 mg·kg-1·min-1, P ≤ 0.05), metabolic flexibility [PRE: -0.01 ± 0.01 delta respiratory quotient (RQ), POST: 0.06 ± 0.01 delta RQ, P < 0.001], and insulin sensitivity (PRE: 0.33 ± 0.01 QUICKI index, POST: 0.34 ± 0.01 QUICKI index, P < 0.01), suggesting a link between GDF15 and fat mass loss as well as exercise-induced metabolic improvement in humans with obesity. We conclude that the exercise-induced increase in plasma GDF15 and the association with reduced fat mass may indicate a role for GDF15 as a therapeutic target for human obesity.
Chemosensitivity of Phox2b‐expressing retrotrapezoid neurons is mediated in part by input from 5‐HT neurons

Neurons of the retrotrapezoid nucleus (RTN) and medullary serotonin (5‐HT) neurons are both candidates for central CO2/pH chemoreceptors, but it is not known how interactions between them influence their responses to pH. We found that RTN neurons in brain slices were stimulated by exogenous 5‐HT and by heteroexchange release of endogenous 5‐HT, and these responses were blocked by antagonists of 5‐HT7 receptors. The pH response of RTN neurons in brain slices was markedly reduced by the same antagonists of 5‐HT7 receptors. Similar results were obtained in dissociated, primary cell cultures prepared from the ventral medulla, where it was also found that the pH response of RTN neurons was blocked by preventing 5‐HT synthesis and enhanced by blocking 5‐HT reuptake. Exogenous 5‐HT did not enable latent intrinsic RTN chemosensitivity. RTN neurons may play more of a role as relays from other central and peripheral chemoreceptors than as CO2 sensors.
Comparison of Direct Syringe Filtration and Membrane Filtration for the Selective Isolation of Campylobacter jejuni from Ready-to-Eat Sprouts.

Culture method using enrichment broth and selective agar is one of the most common isolation methods for detecting Campylobacter jejuni from food. However, the overgrowth of competing bacteria in enrichment culture complicates the selective isolation of C. jejuni. In this study, we compared an enrichment/plating method for the isolation of C. jejuni from sprout samples with an enrichment/plating method with syringe or membrane filtration when transferring enriched broths to plates. Four types of sprout samples were artificially contaminated with various levels of C. jejuni and incubated in 100 mL of Bolton broth for 48 h. Enrichment broths were either directly transferred onto modified charcoal-cefoperazone-deoxycholate agar or filtered through membrane or with a syringe. A significantly higher (p < 0.05) isolation rate of Campylobacter positives was obtained with both filtration methods (58-61%) than with the method without filtration (10%). Membrane filtrations yielded 61%, whereas syringe yielded 58% positives. In most cases of unfiltered samples (98%), high competing flora covered most of the plate, making differentiation and picking of suspicious colonies difficult. However, less plates were contaminated with competing flora in both filtration methods. Only 5% of plates were contaminated in the syringe filtration method, whereas no competing flora was observed in membrane filtration (0%).
Co-Crystal Structures of Furosemide:Urea and Carbamazepine:Indomethacin Determined from Powder X-Ray Diffraction Data

Co-crystallization is a promising approach to improving both the solubility and the dissolution rate of active pharmaceutical ingredients. Crystal structure determination from powder diffraction data plays an important role in determining co-crystal structures, especially those generated by mechanochemical means. Here, two new structures of pharmaceutical interest are reported: a 1:1 co‑crystal of furosemide with urea formed by liquid-assisted grinding and a second polymorphic form of a 1:1 co‑crystal of carbamazepine with indomethacin, formed by solvent evaporation. Energy minimization using dispersion-corrected density functional theory was used in finalizing both structures. In the case of carbamazepine:indomethacin, this energy minimization step was essential in obtaining a satisfactory final Rietveld refinement.
Does Community-Level Social Capital Predict Decline in Instrumental Activities of Daily Living? A JAGES Prospective Cohort Study

Instrumental activities of daily living (IADL) represent the most relevant action capacity in older people with regard to independent living. Previous studies have reported that there are geographical disparities in IADL decline. This study examined the associations between each element of community-level social capital (SC) and IADL disability. This prospective cohort study conducted between 2010 and 2013 by the Japan Gerontological Evaluation Study (JAGES) surveyed 30,587 people aged 65 years or older without long-term care requirements in 380 communities throughout Japan. Multilevel logistic-regression analyses were used to determine whether association exists between community-level SC (i.e., civic participation, social cohesion, and reciprocity) and IADL disability, with adjustment for individual-level SC and covariates such as demographic variables, socioeconomic status, health status, and behavior. At three-year follow-up, 2886 respondents (9.4%) had suffered IADL disability. Residents in a community with higher civic participation showed significantly lower IADL disability (odds ratio: 0.90 per 1 standard deviation increase in civic participation score, 95% confidence interval: 0.84–0.96) after adjustment for covariates. Two other community-level SC elements showed no significant associations with IADL disability. Our findings suggest that community-based interventions to promote community-level civic participation could help prevent or reduce IADL disability in older people.
Induction of entosis in prostate cancer cells by nintedanib and its therapeutic implications

Entosis is a homogeneous cell-in-cell phenomenon and a non-apoptotic cell death process. Tyrosine kinase inhibitors have been used in the treatment of prostate cancer and have already demonstrated efficacy in a clinical setting. The present study investigated the role of entosis in prostate cancer treated with the tyrosine kinase inhibitor nintedanib. Prostate cancer cells were treated with nintedanib in vitro and entosis was observed. Mice xenografts were created to evaluate whether nintedanib is able to induce entosis in vivo. The reverse transcription-quantitative polymerase chain reaction, western blotting and immunofluorescence were performed to investigate whether the entosis pathway is induced by nintedanib. It was also investigated whether entosis can contribute to cell survival and progression under nintedanib stress, and nintedanib was revealed to enhance prostate cancer cell entosis. Nintedanib-induced entosis in prostate cancer cells occurred through phosphoinositide 3-kinase/cell division cycle 42 (CDC42) inhibition, followed by the upregulation of epithelial (E-)cadherin and components of the Rho kinase (ROCK) signaling pathway. In addition, nintedanib-resistant cells exhibiting entosis had a higher invasive ability. In addition, in vivo treatment of mice xenografts with nintedanib also increased the expression of E-cadherin and components of the ROCK signaling pathway. Nintedanib can promote entosis during prostate cancer treatment by modulating the CDC42 pathway. Furthermore, prostate cancer cells acquired nintedanib resistance and survived by activating entosis.
Expression of ventral telencephalon transcription factors ASCL1 and DLX2 in the early fetal human cerebral cortex

In rodent ventral telencephalon, diffusible morphogens induce expression of the proneural transcription factor ASCL1, which in turn induces expression of the transcription factor DLX2 that controls differentiation of cortical interneuron precursors and their tangential migration to the cerebral cortex. RNAseq analysis of human fetal samples of dorsal telencephalon revealed consistently high cortical expression of ASCL1 and increasing expression of DLX2 between 7.5 and 17 post‐conceptional weeks (PCW). We explored whether cortical expression of these genes represented a population of intracortically derived interneuron precursors. Immunohistochemistry revealed an ASCL1+/DLX2+ population of progenitor cells in the human ganglionic eminences between 6.5 and 12 PCW, but in the cortex there also existed a population of ASCL1+/DLX2– progenitors in the subventricular zone (SVZ) that largely co‐expressed cortical markers PAX6 or TBR2, although a few ASCL1+/PAX6– progenitors were observed in the ventricular zone (VZ) and ASCL1+ cells expressing the interneuron marker GAD67 were present in the SVZ. Although rare in the VZ, DLX2+ cells progressively increased in number between 8 and 12 PCW across the cortical wall and the majority co‐expressed LHX6 and originated either in the MGE, migrating to the lateral cortex, or from the septum, populating the medial wall. A minority co‐expressed COUP‐TFII, which identifies cells from the caudal ganglionic eminence (CGE). By 19 PCW, a significant increase in expression of DLX2 and ASCL1 was observed in the cortical VZ with a small proportion expressing both proteins. The DLX2+ cells did not co‐express a cell division marker, so were not progenitors. The majority of DLX2+ cells throughout the cortical plate expressed COUP‐TFII rather than LHX6+. As the VZ declined as a proliferative zone it appeared to be re‐defined as a migration pathway for COUP‐TFII+/DLX2+ interneurons from CGE to cortex. Therefore, in developing human cortex, ASCL1 expression predominantly marks a population of intermediate progenitors giving rise to glutamatergic neurons. DLX2 expression predominantly defines post‐mitotic interneuron precursors.
Near infrared imaging of epidermal growth factor receptor positive xenografts in mice with domain I/II specific antibody fragments

Epidermal growth factor receptor (EGFR) is a transmembrane cell surface receptor that is frequently overexpressed and/or mutated in many cancers. Therapies targeting EGFR have poor outcomes due to the lack of reliable diagnostic tests to monitor EGFR. Current in vitro EGFR diagnostic methods are invasive, requiring biopsies, which limits tumor sampling and availability. EGFR molecular imaging provides non-invasive whole-body images capable of detecting primary tumors and metastases, which can be used to diagnose and monitor response to therapy. Methods: We evaluated properties of two anti-EGFR fragments, 8708 and 8709, as molecular-targeted imaging probes. 8708 and 8709 are anti-EGFR antigen binding fragments (Fabs) that recognize domain I/II of EGFR, which is distinct from epitopes recognized by current anti-EGFR therapeutic antibodies. We used complementarity determining region sequences from 8708 and 8709 Fabs to generate an anti-EGFR IgG and (scFv)2 and scFv-Fc antibody fragments. We expressed, purified, and labeled the IgG and fragments with IRDye800CW and used them to image EGFR-positive and -negative xenografts in CD-1 nude mice. 8709 scFv-Fc was also tested for competitive binding with the therapeutic anti-EGFR antibody nimotuzumab and for quantifying ratios of EGFR and EGFRvIII deletion mutant. Results: IRDye800CW-labeled 8708 (scFv)2 and 8709 scFv-Fc imaging probes showed high levels of accumulation and good retention in EGFR-positive xenografts, with peak accumulation occurring at 24 and 48 hours post injection, respectively. IRDye680RD-labeled 8709 scFv-Fc did not compete with IRDye800CW-labeled nimotuzumab for EGFR binding as assayed by flow cytometry using an EGFR-positive cell line. IRDye680RD-labeled 8709 scFv-Fc and IRDye800CW-labeled nimotuzumab used in combination were able to determine the ratio of cells expressing EGFR and a deletion mutant EGFRvIII. Conclusion: IRDye800CW-labeled 8708 (scFv)2 and 8709 scFv-Fc had desirable binding affinities, clearance times, and tumor accumulation to be used for imaging in combination with current EGFR targeted therapies. This study highlights the potential for using 8708 (scFv)2 and 8709 scFv-Fc as EGFR diagnostic and therapy monitoring tools.
A Non-Linear Minimum Mean Square Error Estimator for the Mixture-Maximization Approximation

In many speech separation, enhancement, and recognition techniques, we need to express the log spectrum of a mixture speech signal in terms of the log spectra of the underlying speech signals. For this purpose, the mixture-maximization (MIXMAX) approximation is commonly used. In this paper, we present a proof for this approximation in a statistical framework. We conclude that this approximation is a non-linear minimum mean square error (MMSE) estimator with the assumption of uniform distributions for phase information of the underlying speech signals
Adenosine A2A receptor (A2AR) activation triggers Akt signaling and enhances nuclear localization of β‐catenin in osteoblasts

Osteoblast differentiation and proliferation are regulated by several modulators, among which are adenosine A2a receptors (A2ARs) and Wingless/Integrated‐β‐catenin pathways. Cytosolic β‐catenin stabilization promotes its nuclear translocation and transcriptional activity. In the present study, we seek to determine whether there is a connection between A2AR stimulation and cellular β‐catenin levels in osteoblasts. Osteoblast precursor cell line (MC3T3‐E1) and primary murine osteoblasts were treated with CGS21680, a highly selective A2AR agonist. We analyzed cellular content and nuclear translocation of phosphorylated (p)‐serine 552 (S552) β‐catenin in response to A2AR stimulation in MC3T3‐E1 cells, in both wild‐type and A2AR knockout (A2AKO) mice. Moreover, we measured cellular β‐catenin levels in MC3T3‐E1 cells transfected with scrambled or protein kinase B (Akt) small interfering RNA following A2AR activation. CGS21680 (1 µM) stimulated an increase in both the cellular content and nuclear translocation of p‐S552 β‐catenin after 15 min of incubation. A2AR activation had no tangible effect on the cellular β‐catenin level either in A2AKO mice or in osteoblasts with diminished Akt content. Our findings demonstrate an interaction between A2AR, β‐catenin, and Akt signaling in osteoblasts. The existence of such a crosstalk has significant repercussions in the development of novel therapeutic approaches targeting medical conditions associated with reduced bone density. —Borhani, S. , Corciulo, C. , Larranaga‐Vera, A. , Cronstein, B. N. Adenosine A2a receptor (A2AR) activation triggers Akt signaling and enhances nuclear localization of β‐catenin in osteoblasts. FASEB J. 33, 7555–7562 (2019). www.fasebj. org
NUMERICAL MODELLING OF ISOTHERMAL BURNER JETS

Isothermal slot burners, based on those found in conventional coal fed tangentially fired furnaces, have been numerically modelled using the Computational Fluid Dynamics (CFD) code CFX 4.2. Three different burner geometries have been studied in detail, and the predictions are compared to the existing data obtained experimentally for the same geometries. An orthogonal grid arrangement was constructed for the first geometry, minimising complications due to numerical diffusion that can impact heavily on predictions. Good agreement between CFD prediction and experimental data was achieved with this geometry, even using a simple kε turbulence model and first order differencing scheme. The grid for the second geometry was more complex because the jet discharged at an angle to the computational domain, and grid orthagonality was not inherent in the problem set up as it was in the first geometry. Good agreement was still obtained between the predictions and the experimental data. However, higher order differencing schemes such as bounded quadratic schemes, and more complex turbulence models are required to achieve more accurate predictions. Typical differences between the predictions and experiment were of the order of 10 to 15% A third burner geometry was modelled, which contained a recess into which the jets discharged. This introduced complex flow behaviour, which was correctly predicted in a two dimensional model .
Flat-plate single-crystal silicon sample holders for neutron powder diffraction studies of highly absorbing gadolinium compounds

The extreme absorption cross section of natural gadolinium has so far precluded routine neutron diffraction work on its alloys and compounds. However, it is shown here that an easily constructed flat-plate sample holder with silicon single-crystal windows can be used to place a thin layer of material in a neutron beam and obtain Rietveld refinement quality diffraction data in a modest time. The flat-plate geometry uses a large area to compensate for the necessarily thin sample. Demonstration data are presented on two intermetallic compounds, Sm3Ag4Sn4 and Gd3Ag4Sn4, and it is shown that both structural and magnetic information can be derived from the diffraction patterns. By working at a wavelength of 2.37 Å, it is possible to observe the low-Q diffraction peaks associated with magnetic ordering. This simple methodology should now enable routine measurements on even the most highly absorbing materials.