Miracle-dz/UniFAR-FTUs huggingface dataset:
Economic Burden of Patients with Inadequate Response to Targeted Immunomodulators for Rheumatoid Arthritis

BACKGROUND: Targeted immunomodulators (TIMs), including biologic disease-modifying antirheumatic drugs (DMARDs) and JAK/STAT inhibitors, are effective therapies for rheumatoid arthritis (RA), but some patients fail to respond or lose response over time. This study estimated the real-world prevalence of RA patients with inadequate responses to an initial TIM (nonresponders) in the United States and assessed their direct and indirect economic burden compared with treatment responders. METHODS: Administrative claims data (January 1999-March 2014) from a large private-insurer database were used, which included work-loss data from a subset of reporting companies. Eligible patients (classified as responders and nonresponders) had ≥ 1 claim for a TIM approved for the treatment of RA and ≥ 2 RA diagnoses in the claims history, with continuous pharmaceutical and medical benefit eligibility for 6 months before (baseline) and 12 months after (study period) the date of the first TIM claim (index date). All-cause and RA-related health care resource use (HCRU) and costs, work loss, and indirect costs during the study period were compared for responders versus nonresponders. Multivariable regression was used to adjust for baseline covariates. Sensitivity analyses of HCRU and direct costs were conducted for patients with index dates before and after 2008 to account for different approval dates of TIMs. RESULTS: Of 7,540 eligible patients with RA, 2,527 (34%) were classified as responders, and 5,013 (66%) were classified as nonresponders; 407 and 723 had work-loss data, respectively. After adjusting for baseline covariates, nonresponders had significantly higher HCRU, including inpatient admissions (incidence rate ratio [IRR] = 1.94), outpatient visits (IRR = 1.19), emergency department visits (IRR = 1.53), and number of prescription fills (IRR = 1.09; all, P < 0.001). Nonresponders also had significantly higher adjusted all-cause ($12,868 vs. $9,621, respectively) and RA-related ($5,740 vs. $4,495; both, P < 0.001) medical costs compared with responders. In addition, nonresponders reported significantly more days of work lost compared with responders (22.1 vs. 16.7 days, respectively; IRR = 1.21; P = 0.007) and higher indirect costs ($3,548 vs. $2,890; P = 0.002). Sensitivity analyses of HCRU and direct costs by index date (before and after 2008) were consistent with the full sample. CONCLUSIONS: A large portion of patients with RA had inadequate responses to their initial TIM therapy with significantly higher economic burden, including higher HCRU, medical costs, and indirect costs due to work loss, compared with TIM therapy responders.
Hedgehog Signaling in Endochondral Ossification

Hedgehog (Hh) signaling plays crucial roles in the patterning and morphogenesis of various organs within the bodies of vertebrates and insects. Endochondral ossification is one of the notable developmental events in which Hh signaling acts as a master regulator. Among three Hh proteins in mammals, Indian hedgehog (Ihh) is known to work as a major Hh input that induces biological impact of Hh signaling on the endochondral ossification. Ihh is expressed in prehypertrophic and hypertrophic chondrocytes of developing endochondral bones. Genetic studies so far have demonstrated that the Ihh-mediated activation of Hh signaling synchronizes chondrogenesis and osteogenesis during endochondral ossification by regulating the following processes: (1) chondrocyte differentiation; (2) chondrocyte proliferation; and (3) specification of bone-forming osteoblasts. Ihh not only forms a negative feedback loop with parathyroid hormone-related protein (PTHrP) to maintain the growth plate length, but also directly promotes chondrocyte propagation. Ihh input is required for the specification of progenitors into osteoblast precursors. The combinatorial approaches of genome-wide analyses and mouse genetics will facilitate understanding of the regulatory mechanisms underlying the roles of Hh signaling in endochondral ossification, providing genome-level evidence of the potential of Hh signaling for the treatment of skeletal disorders.
Adenosine prevents permeability increase in oxidant-injured endothelial monolayers.

Adenosine is thought to prevent or reduce the increase in permeability, which is a hallmark of oxidant injury to endothelium. However, the effect of adenosine on endothelial cells directly exposed to oxidant species has not been demonstrated in vitro. By measuring the passage of Evan's blue dye-labeled albumin across confluent monolayers, we demonstrated the ability of adenosine (0.1-100 μM) to lower basal permeability of human umbilical vein endothelial cells in a concentration-dependent fashion and prevent the permeability increase induced by exposure of the cells to xanthine plus xanthine oxidase (X/XO). Whereas pretreatment of monolayers for 10 min with adenosine (10 and 100 μM) prevented the X/XO-induced permeability increase, these same concentrations of adenosine failed to increase intracellular adenosine 3',5'-cyclic monophosphate in X/XO-exposed cells. The protective effect of adenosine on endothelial monolayers was mimicked by adenosine amine congener and 5'-( N-ethylcarboxamido)adenosine but not by other agonists examined. Hence, the protective effect of adenosine against oxidant injury may include an adenosine 3',5'-cyclic monophosphate-independent mechanism by direct action of adenosine at A1 receptors on endothelial cells.
Tissue spaces in rat heart, liver, and skeletal muscle in vivo.

Tissue spaces were determined in rat heart, liver, and skeletal muscle in vivo using isotopically labeled [14C]inulin. Tracer was injected into the jugular vein of pentobarbital-anesthetized male Sprague-Dawley rats. After a 30-min equilibration period, a blood sample was taken, and heart, liver, and gastrocnemius muscle were excised and immediately freeze clamped at liquid nitrogen temperatures. The extracellular inulin space was 0.209 ± 0.006 ( n = 13), 0.203 ± 0.080 ( n = 7), and 0.124 ± 0.006 (SE) ml/g wet wt tissue ( n = 8) for heart, liver, and skeletal muscle, respectively. Total tissue water was 0.791 ± 0.005 ( n = 9), 0.732 ± 0.002 ( n = 9), and 0.755 ± 0.005 ml/g wet wt tissue ( n = 10) for heart, liver, and skeletal muscle, respectively. Expressed as a percentage of total tissue water, the intracellular space was 73.6, 72.2, and 83.7% for heart, liver, and skeletal muscle, respectively. With use of 2,3-diphospho-d-glyceric acid as a vascular marker, the interstitial space was calculated by subtracting the counts in tissue due to whole blood from total tissue counts and dividing by plasma counts. The interstitial space was 18.8, 22.4, and 14.5% of total tissue water, with accompanying plasma spaces of 7.7, 5.3, and 1.8% for heart, liver, and gastrocnemius muscle, respectively. The tracer method used in this study provides a quantitative assessment of water distribution in tissues of nonnephrectomized rats that has applications for calculation of tissue ion and metabolite concentrations, gradients, and fluxes under normal and pathophysiological conditions.
Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans.

Glucagon-like peptide 1 (GLP-1) has been shown to inhibit gastric emptying of liquid meals in type 2 diabetic patients. It was the aim of the present study to compare the action of physiological and pharmacological doses of intravenous GLP-1-(7-36) amide and GLP-1-(7-37) on gastric emptying in normal volunteers. Nine healthy subjects participated (26 ± 3 yr; body mass index 22.9 ± 1.6 kg/m2; hemoglobin A1C 5.0 ± 0.2%) in five experiments on separate occasions after an overnight fast. A nasogastric tube was positioned for the determination of gastric volume by use of a dye-dilution technique (phenol red). GLP-1-(7-36) amide (0.4, 0.8, or 1.2 pmol ⋅ kg-1 ⋅ min-1), GLP-1-(7-37) (1.2 pmol ⋅ kg-1 ⋅ min-1), or placebo was infused intravenously from -30 to 240 min. A liquid meal (50 g sucrose, 8% amino acids, 440 ml, 327 kcal) was administered at 0 min. Glucose, insulin, and C-peptide were measured over 240 min. Gastric emptying was dose dependently slowed by GLP-1-(7-36) amide ( P < 0.0001). Effects of GLP-1-(7-37) at 1.2 pmol ⋅ kg-1 ⋅ min-1were virtually identical. GLP-1 dose dependently stimulated fasting insulin secretion (-30 to 0 min) and slightly reduced glucose concentrations. After the meal (0-240 min), integrated incremental glucose ( P < 0.0001) and insulin responses ( P = 0.01) were reduced (dose dependently) rather than enhanced. In conclusion, 1) GLP-1-(7-36) amide or -(7-37) inhibits gastric emptying also in normal subjects, 2) physiological doses (0.4 pmol ⋅ kg-1 ⋅ min-1) still have a significant effect, 3) despite the known insulinotropic actions of GLP-1-(7-36) amide and -(7-37), the net effect of administering GLP-1 with a meal is no change or a reduction in meal-related insulin responses. These findings suggest a primarily inhibitory function for GLP-1 (ileal brake mechanisms).
Standards for Quantitative Metalloproteomic Analysis Using Size Exclusion ICP-MS

Metals are essential for protein function as cofactors to catalyze chemical reactions. Disruption of metal homeostasis is implicated in a number of diseases including Alzheimer's and Parkinson's disease, but the exact role these metals play is yet to be fully elucidated. Identification of metalloproteins encounters many challenges and difficulties. Here we report an approach that allows metalloproteins in complex samples to be quantified. This is achieved using size exclusion chromatography coupled with inductively coupled plasma - mass spectrometry (SEC-ICP-MS). Using six known metalloproteins, the size exclusion column can be calibrated and the respective trace elements (iron, copper, zinc, cobalt, iodine) can be used for quantification. SEC-ICP-MS traces of human brain and plasma are presented. The use of these metalloprotein standards provides the means to quantitatively compare metalloprotein abundances between biological samples. This technique is poised to help shed light on the role of metalloproteins in neurodegenerative disease as well as other diseases where imbalances in trace elements are implicated.
Skeletal muscle phosphatidylcholine fatty acids and insulin sensitivity in normal humans.

The fatty acid composition of skeletal muscle membrane phospholipids (PL) is known to influence insulin responsiveness in humans. However, the contribution of the major PL of the outer (phosphatidylcholine, PC) and inner (phosphatidylethanolamine, PE) layers of the sarcolemma to insulin sensitivity is not known. Fatty acid composition of PC and PE from biopsies of vastus lateralis from 27 normal men and women were correlated with insulin sensitivity determined by the hyperinsulinemic euglycemic clamp technique at insulin infusion rates of 0.4, 1.0, and 10.0 mU ⋅ kg-1 ⋅ min-1. Significant variation in the half-maximal insulin concentration (ED50) was observed in the normal volunteers (range 24.0-146.0 μU/ml), which correlated directly with fasting plasma insulin ( r = 0.75, P < 0.0001). ED50 was inversely correlated with the degree of membrane unsaturation (C20-C22polyunsaturated fatty acids; r = 0.58, P < 0.01) and directly correlated with fatty acid elongation (ratio of 16:0 to 18:0, r = 0.45, P < 0.05) in PC. However, no relationship between fatty acid composition and insulin sensitivity was observed in PE (NS). These studies suggest that the fatty acid composition of PC may be of particular importance in the relationship between fatty acids and insulin sensitivity in normal humans.
Structure of promoter-bound TFIID and insight into human PIC assembly

The general transcription factor IID (TFIID) plays a central role in the initiation of RNA polymerase II-dependent transcription by nucleating pre-initiation complex (PIC) assembly at the core promoter. TFIID comprises the TATA-binding protein (TBP) and 13 TBP-associated factors (TAF1-13), which specifically interact with a variety of core promoter DNA sequences. Here we present the structure of human TFIID in complex with TFIIA and core promoter DNA, determined by single-particle cryo-electron microscopy (cryo-EM) at sub-nanometer resolution. All core promoter elements are contacted by subunits of TFIID, with TAF1 and TAF2 mediating major interactions with the downstream promoter. TFIIA bridges the TBP-TATA complex with lobe B of TFIID. We also present the cryo-EM reconstruction of a fully-assembled human TAF-less PIC. Superposition of common elements between the two structures provides novel insights into the general role of TFIID in promoter recognition, PIC assembly, and transcription initiation. and -8, and implicates specific elements within TAF1 and TAF2 in mediating interactions with downstream core promoter DNA. We also present the cryo-EM reconstruction of a human TAF-less PIC containing Pol II, promoter DNA, TBP, TFIIA, -B, -F, -S, -E, and -H. By superimposing the common elements between the two structures, we propose a model for the complete TFIID-based PIC that provides novel insights into the intertwined roles of TFIID in promoter recognition, PIC assembly, and transcription initiation.
Analysis of suitability of elastomeric woven tape for strain sensor application and measurement of elbow angle

Textile-based body worn sensors are preferred due to its comfortability for continuous monitoring of the body vital signs and kinematics. This research discusses the development and characterization of elastomeric tape for strain sensor application and is used for the measurement of elbow angle. The stress strain properties of commercially available elastomeric tapes have been analyzed for the selection of suitable specifications of elastomeric tape. The actual sensor has been developed with the help of narrow width tape loom by introducing the silver-coated nylon yarn in the middle of the tape structure. The effect of linear density of conductive yarn and number and strands of conductive threads used on sensitivity of the sensor was studied. The repeatability of the developed sensor was characterized by cyclic testing using Zwick tensile tester. Based on the results, polyester yarns were used as base threads along with rubber threads for the sensor development. It was found that sensor developed using finer yarn with six conductive threads has higher sensitivity. The developed sensor was integrated on to elbow sleeve and elbow angle measurement was done. The results of the developed tape sensor have been compared with the hospital goniometer for 10 male subjects. The results showed that the developed tape sensor is suitable for measuring the elbow angles up to 150°.
Umbilical cord blood mononuclear cell therapy induces clinical remission of steroid-dependent or -resistant ulcerative colitis patients

To compare the efficacy and safety of umbilical cord blood mononuclear cells (CBMNC) and azathioprine (AZA) in the treatment of patients with steroid-dependent or -resistant ulcerative colitis. One hundred and six patients diagnosed with steroid-dependent or -resistant ulcerative colitis were studied retrospectively, including 36 patients treated with CBMNC and 70 treated with AZA. To reduce confounding bias due to retrospective nature of this study, the propensity score matching system was applied to equipoise the pretreatment data of two groups. After matching, 35 matched pairs (1:1) were created. The ratios of clinical remission, clinical response and endoscopic mucosal healing, Mayo score, and major complications were compared between two groups at weeks 8, 16, and 36 after treatment. The results demonstrated that the ratios of clinical remission (80% vs. 57%, P < 0.05) and mucosal healing (74% vs. 51%, P < 0.05) were significantly higher in CBMNC-treated patients compared with those in AZA-treated patients at week 8. The erythrocyte sedimentation rate was significantly decreased in CBMNC group compared with that in AZA-treated group (14.5 ± 3.9 mm/h vs. 18.0 ± 5.7 mm/h, P < 0.01) at week 8. In AZA group, 2 patients had neutropenia and 3 patients had elevated alanine aminotransferase levels, whereas no obvious side-effects were observed in CBMNC-treated group. Our results reveal that CBMNC therapy appears to be an effective and safe strategy for patients with steroid-dependent or -resistant ulcerative colitis. Further prospective studies are needed to define the potential roles and mechanisms of CBMNC in the treatment of refractory ulcerative colitis.
Ship Detection in Harbour Surveillance based on Large-Scale Data and CNNs

This paper aims at developing a real-time vessel detection and tracking system using surveillance cameras in harbours with the purpose to improve the current Vessel Tracking Systems (VTS) performance. To this end, we introduce a novel maritime dataset, containing 70,513 ships in 48,966 images, covering 10 camera viewpoints indicating real-life ship traffic situations. For detection, a Convolutional Neural Network (CNN) detector is trained, based on the Single Shot Detector (SSD) from literature. This detector is modified and enhanced to support the detection of extreme variations of ship sizes and aspect ratios. The modified SSD detector offers a high detection performance, which is based on explicitly exploiting the aspect-ratio characteristics of the dataset. The performance of the original SSD detector trained on generic object detection datasets (including ships) is significantly lower, showing the added value of a novel surveillance dataset for ships. Due to the robust performance of over 90% detection, the system is able to accurately detect all types of vessels. Hence, the system is considered a suitable complement to conventional radar detection, leading to a better operational picture for the harbour authorities.
Plant Stems: Functional Design and Mechanics

Plant stems are one of nature's most impressive mechanical constructs. Their sophisticated hierarchical structure and multifunctionality allow trees to grow more than 100 m tall. This review highlights the advanced mechanical design of plant stems from the integral level of stem structures down to the fiber-reinforced-composite character of the cell walls. Thereby we intend not only to provide insight into structure-function relationships at the individual levels of hierarchy but to further discuss how growth forms and habits of plant stems are closely interrelated with the peculiarities of their tissue and cell structure and mechanics. This concept is extended to a further key feature of plants, namely, adaptive growth as a reaction to mechanical perturbation and/or changing environmental conditions. These mechanical design principles of plant stems can serve as concept generators for advanced biomimetic materials and may inspire materials and engineering sciences research.
Hydrogen peroxide inhibits cAMP-induced Cl- secretion across colonic epithelial cells.

We examined the effects of H2O2on Cl- secretion across human colonic T84 cells grown on permeable supports and mounted in modified Ussing chambers. Forskolin-induced short-circuit current, a measure of Cl- secretion, was inhibited in a concentration-dependent fashion when monolayers were pretreated with H2O2for 30 min (30-100% inhibition between 500 μM and 5 mM). Moreover, H2O2inhibited 76% of the Cl-current across monolayers when the basolateral membranes were permeabilized with nystatin (200 μg/ml). When the apical membrane was permeabilized with amphotericin B, H2O2inhibited the Na+ current (a measure of Na+-K+-ATPase activity) by 68% but increased the K+ current more than threefold. In addition to its effects on ion transport pathways, H2O2also decreased intracellular ATP levels by 43%. We conclude that the principal effect of H2O2on colonic Cl- secretion is inhibitory. This may be due to a decrease in ATP levels following H2O2treatment, which subsequently results in an inhibition of the apical membrane Cl- conductance and basolateral membrane Na+-K+-ATPase activity. Alternatively, H2O2may alter Cl- secretion by direct action on the transporters or alterations in signal transduction pathways.
Fabrication and Characterization of Antibacterial Tantalum Oxide Thin Films Deposited by Reactive Magnetron Sputtering

Tantalum oxide (TaO) thin films were deposited by dc reactive magnetron sputtering at room temperature. A target of tantalum (99.995%) and a mixture of argon and oxygen gases were used to deposit TaO films on to silicon wafers (100) and BK7 glass substrate. The effects of annealing temperature (300–700 °C) on structural, morphology and anti-bacterial properties were investigated. Grazing incident X-ray diffraction (GIXRD), atomic force microscope (AFM) measurements are carried out to identify the crystalline structure, film morphology and surface roughness, respectively. The antibacterial behavior of the tantalum oxide thin films will be discussed in this paper.
Blockade of RAGE ± amphoterin signalling suppresses tumour growth and metastases

351 selected by the following criteria: (1) stable intertrial baseline, without statistically signi®cant differences in average ®ring rate between pre-low-tone and pre-high-tone baselines (the overall average baseline ®ring for the 94 cells was 10.03 spike s-1 ; and (2) statistically signi®cant differences in ®ring between the two tones, at tone presentation or in the subsequent delay. These cells were submitted to the correlational analysis of average tone-and colour-related differences (deltas) between trial periods. Four such periods were the object of analysis: (1) ®rst 1 s of tone; (2) 10-s delay; (3) ®rst 1 s of colour presentation; and (4) 400-ms period immediately preceding manual choice of colour. Tone and colour periods (1, 3 and 4) were divided in 200-ms bins, and the entire delay period was treated as a 10-s bin. Four tone-or colour-related differences or deltas (Fig. 2e) were determined between high-tone (red choice) trials and low-tone (green choice) trials: D 1 (tone), largest 1-bin difference between responses to the two tones; D 2 (delay), tone-related difference in delay ®ring; D 3 (colours), largest 1-bin difference in response to the two simultaneous colours; and D 4 (chosen colour), largest 1-bin difference in pre-choice ®ring. Table 1 tabulates cells by correlation of delta sign across trial periods. Figure 4a, b shows delta correlations by magnitude. Expected correlations by chance were calculated by shuf¯ing 1,000 times the delta values from both animals (94 differential units) in correct-response trials: the mean coef®cient (r) thus obtained for all four interperiod correlations (D 1 versus D 2 , D 3 versus D 2 , D 3 versus D 1 , and D 4 versus D 1) ranged between minus 0.002 and plus 0.003 (s.d. 0.103±0.105). Unit activity in prefrontal cortex during delayed-response performance: Neuronal correlates of transient memory. Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex.selective properties of inferior temporal neurons in the macaque. gradients in the neuronal receptive ®eld complexity in the ®nger region of the alert monkey's postcentral gyrus. modality speci®city of neural activity related to memory in visual cortex. properties of neurons in the anterior bank of the caudal superior temporal sulcus of the macaque monkey. activity of somatosensory cortex in a cross-modal (visuo-haptic) memory task. Functional interactions between inferotemporal and prefrontal cortex in a cognitive task. prefrontal cortex in executive control of memory retrieval. The effect of periarcuate lesions in the monkey on the performance of symmetrically …