Miracle-dz/UniFAR-FTUs huggingface dataset:
Trends in medical use and abuse of opioid analgesics.

CONTEXT Pain often is inadequately treated due in part to reluctance about using opioid analgesics and fear that they will be abused. Although international and national expert groups have determined that opioid analgesics are essential for the relief of pain, little information has been available about the health consequences of the abuse of these drugs. OBJECTIVE To evaluate the proportion of drug abuse related to opioid analgesics and the trends in medical use and abuse of 5 opioid analgesics used to treat severe pain: fentanyl, hydromorphone, meperidine, morphine, and oxycodone. DESIGN AND SETTING Retrospective survey of medical records from 1990 to 1996 stored in the databases of the Drug Abuse Warning Network (source of abuse data) and the Automation of Reports and Consolidated Orders System (source of medical use data). PATIENTS Nationally representative sample of hospital emergency department admissions resulting from drug abuse. MAIN OUTCOME MEASURES Medical use in grams and grams per 100,000 population and mentions of drug abuse by number and percentage of the population. RESULTS From 1990 to 1996, there were increases in medical use of morphine (59%; 2.2 to 3.5 million g), fentanyl (1168%; 3263 to 41,371 g), oxycodone (23%; 1.6 to 2.0 million g), and hydromorphone (19%; 118,455 to 141,325 g), and a decrease in the medical use of meperidine (35%; 5.2 to 3.4 million g). During the same period, the total number of drug abuse mentions per year due to opioid analgesics increased from 32,430 to 34,563 (6.6%), although the proportion of mentions for opioid abuse relative to total drug abuse mentions decreased from 5.1% to 3.8%. Reports of abuse decreased for meperidine (39%; 1335 to 806), oxycodone (29%; 4526 to 3190), fentanyl (59%; 59 to 24), and hydromorphone (15%; 718 to 609), and increased for morphine (3%; 838 to 865). CONCLUSIONS The trend of increasing medical use of opioid analgesics to treat pain does not appear to contribute to increases in the health consequences of opioid analgesic abuse.
Adrenocorticotropic Hormone Enhances the Masculinity of an Electric Communication Signal by Modulating the Waveform and Timing of Action Potentials within Individual Cells

We report here that melanocortin peptides appear to serve as the mechanism by which weakly electric fish couple socially regulated and stress-regulated brain pathways to unique changes in the intrinsic excitability and action potential waveform of excitable membranes in peripheral cells involved in communication. Gymnotiform electric fish modulate their electric organ discharges (EODs) by reshaping the electric discharges of excitable cells in the periphery. These fish show circadian enhancement of the EOD waveform. They also enhance their EOD waveforms within minutes in response to stressors and changes in the social environment, thus altering the communication value of the signal. Changes in the EOD waveform that occur within minutes result from changes in the discharges of individual electrocytes (μEODs) mediated by the cAMP/protein kinase A (PKA) pathway acting on ion channel kinetics. What activates the cAMP/PKA pathway in electrocytes has not been identified. In vivo injections of the melanocortin peptide adrenocorticotropic hormone (ACTH) increase the amplitude and duration of the electric signal waveform of the gymnotiform Brachyhypopomus pinnicaudatus over the course of 1 h. Applied to single electrocytes in vitro, ACTH increases μEOD amplitude and duration within minutes by differentially modulating the action potentials of the two excitable membranes of the electrocyte and changing the timing of these two spikes. Serotonin modulates the EOD in vivo but has no effect on the μEOD in vitro. The cAMP analog 8-bromo-cAMP mimicked the effects of ACTH, whereas inhibition of PKA by protein kinase A inhibitor 14–22 amide blocked the modulatory effects of ACTH, confirming the role of the cAMP/PKA pathway in μEOD modulation by ACTH.
Privacy-preserving Edit Distance on Genomic Data

Suppose Alice holds a DNA sequence and Bob owns a database of DNA sequences. They want to determine whether there is a match for the Alice's input in the Bob's database for any purpose such as diagnosis of Alice's disease. However, Alice does not want to reveal her DNA pattern to Bob, since it would enable him to learn private information about her. For the similar reasons, Bob does not want to reveal any information about his database to Alice. This problem has attracted attention from bioinformatics community in order to protect privacy of users and several solutions have been proposed. Efficiency is always a bottleneck in cryptography domain. In this paper, we propose ESCOT protocol to address privacy preserving Edit distance using Oblivious Transfer (OT) for the first time. We evaluate our approach on a genome dataset over both LAN and WAN network. Experimental results confirm feasibility of our approach in real-world scenarios.
Incomplete Normalization of Regulatory T-Cell Frequency in the Gut Mucosa of Colombian HIV-Infected Patients Receiving Long-Term Antiretroviral Treatment

Introduction To evaluate the effect of late initiation of HAART and poor immune reconstitution on the frequency of regulatory T-cells (Treg) in the peripheral blood and gut of HIV-infected patients, we studied Colombian HIV-infected patients who had been on suppressive HAART for at least one year. They had undetectable viremia but were either immunological responders (HIR); (CD4 counts >500 cells/µl) or non-immunological responders (NIR); (CD4 T-cell count <300 cells/µl). Untreated HIV-infected patients and uninfected controls from the same region were also evaluated. Methods Frequency and phenotype of regulatory T-cells (Treg) were analyzed in gut biopsies and blood samples. The functional effect of Treg depletion on CMV and HIV responses was determined. Markers of immune activation and circulating LPS levels were quantified. Results Untreated patients exhibited high Treg frequency in PBMC and gut, and their Treg express high levels of CTLA-4 and PD-1. Although HAART significantly decreased mucosal Treg frequency, it did not normalize it in any of the treated groups (HIR and NIR patients). Treg normalization was observed in the blood of HIR patients following HAART, but did not occur in NIR patients. Treg from HIV-infected patients (treated or not) suppressed HIV and hCMV-specific T-cells from gut and blood. Plasma LPS levels and percentage of HLA-DR+CD38+ T-cells were significantly elevated in all infected groups compared to controls. Conclusions These findings suggest that control of viral replication is not sufficient to normalize gut Treg frequency in patients, independent of their response to HAART. Furthermore, persistence of functional Treg in the gut appears to be associated with the failure of HAART to repair mucosal damage.
State-space models for infinite-dimensional systems

Distributed effects are present in almost all physical systems. In some cases these can be safely ignored but there are many interesting problems where these effects must be taken into account. Most infinite dimensional systems which are important in control theory are specifiable in terms of a finite number of parameters and hence are, in principle, amenable to identification. The state-space theory of infinite dimensional systems has advanced greatly in the last few years and is now at a point where real applications can be contemplated. The realizability criteria provided by this work can be employed effectively in the first step of the identification procedure, i.e., in the selection of an appropriate infinite dimensional model. We show that there exists a natural classification of nonrational transfer functions, which is based on the character of their singularities. This classification has important implications for the problem of finite dimensional approximations of infinite dimensional systems. In addition, it reveals the class of transfer functions for which there exist models with spectral properties closely reflecting the properties of the singularities of the transfer functions. The study of models with infinitesimal generators having a connected resolvent sheds light on some open problems in classical frequency response methods. Finally, the methods used here allow one to see the finite dimensional theory itself more clearly as the result of placing it in the context of a larger theory.
Relationship between Blood Flow to Ischemic Regions and Extent of Myocardial Infarction: Serial Measurement of Blood Flow to Ischemic Regions in Dogs

This study was designed to measure early sequential changes in blood flow to ischemic regions after acute coronary occlusion and to determine the relationship between blood flow and the extent of subsequent myocardial infarction. Initial studies were carried out on five dogs which verified using radioisotope-labeled microspheres, 7–10 &mgr;m in diameter, to measure changes in blood flow in small myocardial regions after acute coronary artery occlusions. Studies then were carried out on 11 awake dogs chronically prepared with indwelling catheters in the aorta and left atrium and occluders on the left circumflex coronary artery. Microspheres were injected via the left atrial catheter 45 seconds and 2, 6, and 24 hours after complete circumflex coronary occlusion. Six days later myocardial blood flow and the extent of histological infarction were determined for multiple samples from four transmural layers of the entire ischemic zone. Average blood flow to the circumflex region was 0.25 ± 0.03 (se), 0.39 ± 0.05, 0.39 ± 0.04, and 0.53 ± 0.07 ml/min per g at 45 seconds, and 2, 6, and 24 hours, respectively. When samples from each transmural layer were grouped according to increasing ranges of blood flow, the extent of infarction in each layer was inversely related to blood flow. When samples in the same range of blood flow were compared, the extent of infarction in endocardial samples exceeded that in epicardial samples. These data indicate that the relationship between a given measurement of regional blood flow after acute coronary occlusion and the extent of subsequent myocardial infarction varies in different transmural layers and is a function of the time after occlusion that blood flow is measured.
Decomposition of Multiple Packings with Subquadratic Union Complexity

Suppose k is a positive integer and ${\cal X}$ is a k-fold packing of the plane by infinitely many arc-connected compact sets, which means that every point of the plane belongs to at most k sets. Suppose there is a function f(n) = o(n2) with the property that any n members of ${\cal X}$ determine at most f(n) holes, which means that the complement of their union has at most f(n) bounded connected components. We use tools from extremal graph theory and the topological Helly theorem to prove that ${\cal X}$ can be decomposed into at most p (1-fold) packings, where p is a constant depending only on k and f.
Small Ultra-Wideband (UWB) Bandpass Filter With Notched Band

A compact ultra-wideband (UWB) bandpass filter (BPF) with notched band has been proposed and implemented in this letter. H-shaped slot is studied and adopted to tighten the coupling of inter-digital capacitor in order to improve the BPF's performance. Three pairs of tapered defected ground structures (DGS) are formed to assign their transmission zeros towards the out of band signal, thereby suppressing the spurious passband. Combining these two structures we obtain a small sized UWB BPF. Meander line slot is developed to reject the undesired wireless local-area network (WLAN) radio signals. An experimental UWB filter with notched band was fabricated with 35% less length as compared to an embedded open-circuited stub. The measured BPF insertion loss is less than 1.0 dB throughout the pass band of 2.8 to 10.8 GHz, the variation of group delay less than 0.20 ns in this band except for the notched band, and a wide stopband bandwidth with 20 dB attenuation up to at least 20.0 GHz.
TICER: Realizable reduction of extracted RC circuits

Time Constant Equilibration Reduction (TICER) is a novel RC reduction method tailored for extract/reduce CAD tools. Geometry-minded extraction tools fracture nets into parasitics based on local changes in geometry. The resulting RC circuits can have a huge dynamic range of time-constants; by eliminating the extreme time-constants, TICER produces smaller, less-stiff RC networks. It produces realizable RC circuits; can retain original network topology; scales well to large networks (/spl sim/10/sup 7/ nodes); preserves dc and ac behavior; handles resistor loops and floating capacitors; has controllable accuracy; operates in linear time on most nets.
MATERIAL GAUGE FACTOR OF DIRECTIONAL ELECTRIC POTENTIAL DROP SENSORS FOR CREEP MONITORING

Directional electric potential drop measurements can be exploited for in‐situ monitoring of creep in metals. The sensor monitors the variation in the ratio of the resistances measured simultaneously in the axial and lateral directions using a square‐electrode configuration. This method can efficiently separate the mostly isotropic common part of the resistivity variation caused by reversible temperature variations from the mostly anisotropic differential part caused by direct geometrical (size and shape) and indirect material (resistivity) effects of creep. Similarly to ordinary strain gauges, the relative sensitivity of the sensor is defined as a gauge factor that can be approximated as the sum of geometrical and material parts. Initially, subtle material changes produce weak electric anisotropy via reversible and irreversible piezoresistivity due to elastic and plastic strains, respectively. At high temperature, much stronger irreversible resistivity changes also occur due to preferentially aligned clus.
Migraine, vascular risk, and cardiovascular events in women: prospective cohort study

Objectives To evaluate whether the association between migraine with aura and increased risk of cardiovascular disease is modified by vascular risk groups as measured by the Framingham risk score for coronary heart disease. Design Prospective cohort study. Setting Women’s health study, United States. Participants 27 519 women who were free from cardiovascular disease at baseline with available information on the Framingham risk score and migraine status. Main outcome measures Time to major cardiovascular disease event (non-fatal myocardial infarction, non-fatal ischaemic stroke, death from ischaemic cardiovascular disease), myocardial infarction, and ischaemic stroke. Results At baseline, 3577 (13.0%) women reported active migraine, of whom 1418 (39.6%) reported migraine with aura. During 11.9 years of follow-up, there were 697 cardiovascular disease events. We stratified participants based on 10 year risk of coronary heart disease estimated from the Framingham risk score (≤1%, 2-4%, 5-9%, and ≥10%). Compared with women without migraine, the age adjusted hazard ratios in women with active migraine with aura were 1.93 (95% confidence interval 1.45 to 2.56) for major cardiovascular disease, 1.80 (1.16 to 2.79) for ischaemic stroke, and 1.94 (1.27 to 2.95) for myocardial infarction. When stratified by Framingham risk score, the association between migraine with aura and major cardiovascular disease was strongest in the lowest risk score group. There was a diametric association pattern for ischaemic stroke and myocardial infarction. Compared with women without migraine, the age adjusted hazard ratios in women who reported migraine with aura in the lowest Framingham risk score group were 3.88 (1.87 to 8.08) for ischaemic stroke and 1.29 (0.40 to 4.21) for myocardial infarction. Hazard ratios in women with migraine with aura in the highest Framingham risk score group were 1.00 (0.24 to 4.14) for ischaemic stroke and 3.34 (1.50 to 7.46) for myocardial infarction. Women with migraine without aura were not at increased risk of ischaemic stroke or myocardial infarction in any of the Framingham risk score groups. Conclusion The association between migraine with aura and cardiovascular disease varies by vascular risk status. Information on history of migraine and vascular risk status might help to identify women at increased risk for specific future cardiovascular disease events. Trial registration Clinical trials NCT00000479.
Principle of smooth fit and diffusions with angles

We show that there exists a regular diffusion process X and a differentiable gain function G such that the value function V of the optimal stopping problem fails to satisfy the smooth fit condition at the optimal stopping point b. On the other hand, if the scale function S of X is differentiable at b, then the smooth fit condition holds (whenever X is regular and G is differentiable at b). We give an example showing that the latter can happen even when at b.
Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Integrity Is Required for Insulin Signaling and Is Implicated in Hepatic Insulin Resistance

Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are functional domains between both organelles involved in Ca2+ exchange, through the voltage-dependent anion channel (VDAC)-1/glucose-regulated protein 75 (Grp75)/inositol 1,4,5-triphosphate receptor (IP3R)-1 complex, and regulating energy metabolism. Whereas mitochondrial dysfunction, ER stress, and altered Ca2+ homeostasis are associated with altered insulin signaling, the implication of MAM dysfunctions in insulin resistance is unknown. Here we validated an approach based on in situ proximity ligation assay to detect and quantify VDAC1/IP3R1 and Grp75/IP3R1 interactions at the MAM interface. We demonstrated that MAM integrity is required for insulin signaling and that induction of MAM prevented palmitate-induced alterations of insulin signaling in HuH7 cells. Disruption of MAM integrity by genetic or pharmacological inhibition of the mitochondrial MAM protein, cyclophilin D (CypD), altered insulin signaling in mouse and human primary hepatocytes and treatment of CypD knockout mice with metformin improved both insulin sensitivity and MAM integrity. Furthermore, ER-mitochondria interactions are altered in liver of both ob/ob and diet-induced insulin-resistant mice and improved by rosiglitazone treatment in the latter. Finally, increasing organelle contacts by overexpressing CypD enhanced insulin action in primary hepatocytes of diabetic mice. Collectively, our data reveal a new role of MAM integrity in hepatic insulin action and resistance, providing a novel target for the modulation of insulin action.
The Duration of the Effects of Repeated Widespread Badger Culling on Cattle Tuberculosis Following the Cessation of Culling

Background In the British Isles, control of cattle tuberculosis (TB) is hindered by persistent infection of wild badger (Meles meles) populations. A large-scale field trial—the Randomised Badger Culling Trial (RBCT)—previously showed that widespread badger culling produced modest reductions in cattle TB incidence during culling, which were offset by elevated TB risks for cattle on adjoining lands. Once culling was halted, beneficial effects inside culling areas increased, while detrimental effects on adjoining lands disappeared. However, a full assessment of the utility of badger culling requires information on the duration of culling effects. Methodology/Principal Findings We monitored cattle TB incidence in and around RBCT areas after culling ended. We found that benefits inside culled areas declined over time, and were no longer detectable by three years post-culling. On adjoining lands, a trend suggesting beneficial effects immediately after the end of culling was insignificant, and disappeared after 18 months post-culling. From completion of the first cull to the loss of detectable effects (an average five-year culling period plus 2.5 years post-culling), cattle TB incidence was 28.7% lower (95% confidence interval [CI] 20.7 to 35.8% lower) inside ten 100 km2 culled areas than inside ten matched no-culling areas, and comparable (11.7% higher, 95% CI: 13.0% lower to 43.4% higher, p = 0.39) on lands ≤2 km outside culled and no-culling areas. The financial costs of culling an idealized 150 km2 area would exceed the savings achieved through reduced cattle TB, by factors of 2 to 3.5. Conclusions/Significance Our findings show that the reductions in cattle TB incidence achieved by repeated badger culling were not sustained in the long term after culling ended and did not offset the financial costs of culling. These results, combined with evaluation of alternative culling methods, suggest that badger culling is unlikely to contribute effectively to the control of cattle TB in Britain.
Differential effects of expression of the CD45 tyrosine protein phosphatase on the tyrosine phosphorylation of the lck, fyn, and c-src tyrosine protein kinases

Expression of the CD45 tyrosine protein phosphatase is required for the response of functional lymphocytes to stimulation through the antigen receptor. One or more of its substrates may therefore be essential for signal transduction during lymphocyte activation. We have studied the phosphorylation of the closely related lck, fyn, and c-src tyrosine protein kinases in leukemic murine T-cell lines that have lost the expression of CD45. The phosphorylation of the lck kinase at an inhibitory site of tyrosine phosphorylation, Tyr-505, was increased by two-, six-, and eightfold in three different cell lines. Phosphorylation of the fyn kinase at the homologous site, Tyr-531, was unaltered in one of these cell lines, but increased by 2.5-fold in the two others. The phosphorylation of p60c-src at the homologous tyrosine was essentially unchanged in the one CD45-negative cell line in which it was examined. The expression of CD45 therefore regulates the phosphorylation and potentially the activity of the lck and fyn tyrosine protein kinases, but the effect on the lck kinase is much greater than on the fyn kinase. This finding and the observation that CD45 had no effect on the phosphorylation of p60c-src suggest that CD45 exhibits polypeptide substrate specificity in vivo. Additionally, these findings are consistent with the hypothesis that the unresponsiveness of CD45-negative lymphoid cells to antigenic stimulation is due largely to hyperphosphorylation of the lck kinase.