Miracle-dz/UniFAR-FTUs huggingface dataset:
The opioid renewal clinic: a primary care, managed approach to opioid therapy in chronic pain patients at risk for substance abuse.

OBJECTIVE To measure the impact of a structured opioid renewal program for chronic pain run by a nurse practitioner (NP) and clinical pharmacist in a primary care setting. PATIENTS AND SETTING Patients with chronic noncancer pain managed with opioid therapy in a primary care clinic staffed by 19 providers serving 50,000 patients at an urban academic Veterans hospital. DESIGN Naturalistic prospective outcome study. INTERVENTION Based on published opioid prescribing guidelines and focus groups with primary care providers (PCPs), a structured program, the Opioid Renewal Clinic (ORC), was designed to support PCPs managing patients with chronic noncancer pain requiring opioids. After training in the use of opioid treatment agreements (OTAs) and random urine drug testing (UDT), PCPs worked with a pharmacist-run prescription management clinic supported by an onsite pain NP who was backed by a multi-specialty Pain Team. After 2 years, the program was evaluated for its impact on PCP practice and satisfaction, patient adherence, and pharmacy cost. RESULTS A total of 335 patients were referred to the ORC. Of the 171 (51%) with documented aberrant behaviors, 77 (45%) adhered to the OTA and resolved their aberrant behaviors, 65 (38%) self-discharged, 22 (13%) were referred for addiction treatment, and seven (4%) with consistently negative UDT were weaned from opioids. The 164 (49%) who were referred for complexity including history of substance abuse or need for opioid rotation or titration, with no documented aberrant drug-related behaviors, continued to adhere to the OTA. Use of UDT and OTAs by PCPs increased. Significant pharmacy cost savings were demonstrated. CONCLUSION An NP/clinical pharmacist-run clinic, supported by a multi-specialty team, can successfully support a primary care practice in managing opioids in complex chronic pain patients.
Promotion of regeneration of corticospinal tract axons in rats with recombinant vascular endothelial growth factor alone and combined with adenovirus coding for this factor.

OBJECT After spinal cord transection in adult rats, the axons of the corticospinal tract (CST) degenerate retrogradely and do not regenerate. This phenomenon is thought to be related to either secondary ischemia or deficiency of growth factors. To overcome the deficiency of both blood flow and growth factors, the authors added exogenous vascular endothelial growth factor (VEGF165) to the transected spinal cord either as recombinant protein alone or combined with an adenovirus coding for VEGF165. Because most growth factors are rapidly inactivated in the extracellular environment, the authors used an adenovirus coding for VEGF165 to maintain its activity for several days. METHODS In adult rats, the dorsal two thirds of the spinal cord were transected at the T-8 level. In experimental rats, either human recombinant VEGF165 or a combination of this factor and a replication-defective adenovirus coding for VEGF165 (Ad.CMV.VEGF165) was applied at the lesion site. Both recombinant VEGF165 alone and combined with Ad.CMV. VEGF165 were mixed with Matrigel, which is a reconstituted membrane basement protein extract. Control rats received Matrigel alone or Matrigel plus an adenoviral vector containing the LACZ gene (Ad.CMV.LACZ). Thirty days after spinal cord injury, the number of newly formed blood vessels was assessed in the injured area. In addition, the sensorimotor cortex was injected with anterogradely transported horseradish peroxidase (HRP) to label the CST axons in the spinal cord and to evaluate the extent of retrograde axonal degeneration and regeneration. Gene transfer was assessed using semiquantitative reverse transcription-polymerase chain reaction analysis, enzyme-linked immunosorbent assay for human VEGF and beta-galactosidase expression in injured rats treated with Matrigel plus Ad.CMV. LACZ, Matrigel plus Ad.CMV. VEGF165, and untreated injured rats. A strong gene transfer in the spinal cord tissue of adenovirus-treated rats was found from Day 3 to Day 10 postinjury, confirming infection. In the injured spinal cord area, a significant increase of blood vessels (300% over control, p < 0.005) occurred both in rats treated with recombinant VEGF165 alone and in those treated with the combination of recombinant VEGF165 and Ad.CMV. VEGF165. Also, in both of these groups of animals the retrograde degeneration of CST axons was significantly reduced compared with rats treated with Matrigel alone or Matrigel plus Ad.CMV. LACZ. Furthermore, in rats treated with recombinant VEGF165 alone or combined with Ad.CMV. VEGF165, a few HRP-labeled CST axons, which were not detectable in control rats, were seen distal to the spinal cord injury, indicating some regeneration across the injured area. CONCLUSIONS These results indicate that locally applied VEGF exerts angiogenic as well as neurotrophic effects in the injured spinal cord of rats.
Excess iodine induces the expression of thyroid solid cell nests in lymphocytic thyroiditis-prone BB/W rats.

Previous epidemiological studies have suggested that lymphocytic thyroiditis and/or an increased iodine intake may be risk factors for the development of thyroid cancer. We previously reported that excess iodine accelerated the development of thyroid lymphocytic infiltration (LI) in the autoimmune BB/W rat model. We also found that excess iodine increased thyroid cell proliferation in a disordered manner. The present study was designed to further explore these observations and to address the question as to whether excess iodine under certain conditions predisposes the thyroid gland to neoplasia. To test this hypothesis, the lymphocytic thyroiditis-prone BB/W rat was exposed to excess iodine in drinking water. Ten BB/W rats at 4 weeks of age were given iodine water (NaI 0.05%) for 10 weeks, whilst another 10 BB/W rats were given tap water and served as controls. Eighteen normal Wistar rats were also divided into excess iodine and control groups, served as a comparison to the BB/W rats. We found that an excess iodine intake accelerated the development of LI in the BB/W rat. Severe LI was usually accompanied by prominent thyroid cell proliferation, evident as numerous microfollicles and cell masses, not forming normal thyroid follicles. Numerous lymphocytes and plasma cells often encroached on these areas of increased cellular proliferation. The surprising feature, and a possible indicator of activated thyroid cell proliferation, was the high incidence of thyroid solid cell nest-like lesions (SCN) in the iodine treated BB/W rats. (ABSTRACT TRUNCATED AT 250 WORDS)
Human CD8+ and CD4+ T Cell Memory to Lymphocytic Choriomeningitis Virus Infection

ABSTRACT Although cellular immunity to acute lymphocytic choriomeningitis virus (LCMV) infection has been well characterized in experimental studies in mice, the T cell response to this virus in humans is incompletely understood. Thus, we analyzed the breadths, magnitudes, and differentiation phenotypes of memory LCMV-specific CD8+ and CD4+ T cells in three human donors displaying a variety of disease outcomes after accidental needle stick injury or exposure to LCMV. Although only a small cohort of donors was analyzed at a single time point postinfection, several interesting observations were made. First, we were able to detect LCMV-specific CD8+ and CD4+ T cell responses directly ex vivo at 4 to 8 years after exposure, demonstrating the longevity of T cell memory in humans. Second, unlike in murine models of LCMV infection, we found that the breadths of memory CD8+ and CD4+ T cell responses were not significantly different from one another. Third, it seemed that the overall CD8+ T cell response was augmented with increasing severity of disease, while the LCMV-specific CD4+ T cell response magnitude was highly variable between the three different donors. Next, we found that LCMV-specific CD8+ T cells in the three donors analyzed seemed to undergo an effector memory differentiation program distinct from that of CD4+ T cells. Finally, the levels of expression of memory, costimulatory, and inhibitory receptors on CD8+ and CD4+ T cell subsets, in some instances, correlated with disease outcome. These data demonstrate for the first time LCMV-specific CD8+ and CD4+ T cells in infected humans and begin to provide new insights into memory T cell responses following an acute virus infection.
Association study between growth differentiation factor 5 polymorphism and non-contact anterior cruciate ligament rupture in Chinese Han population.

BACKGROUND Anterior cruciate ligament (ACL) rupture is the most common ligamentous injury for active adolescents and young adults each year. However, the precise etiologies of ACL injury are not fully understood. The present study was to investigate +104T/C polymorphism of growth differentiation factor 5 (GDF5) gene in patients with ACL rupture, and evaluate the effects of polymorphism on GDF5 mRNA levels in ligament of patients with ACL rupture in central China. METHODS A total of 286 Chinese patients with ACL rupture and 500healthy controls were enrolled in this study. The +104T/C polymorphism in GDF5 gene were genotyped by DNA sequencing. GDF5 mRNA expressions levels in ligament were determined by quantitative PCR. RESULTS The frequency of the TT genotype tended to be higher in ACL rupture group than in control group (62.6% vs. 48.0%, P< 0.001, OR = 1.81, 95% CI: 1.35-2.44). T allele of the GDF5 +104T/C polymorphism was more common in ACL rupture group than in control group (P< 0.001). Patients carrying TT genotype expressed lower levels of GDF5 mRNA than C carriers (P = 0.005) among ACL rupture. CONCLUSION Our study indicated that GDF5 +104T/C polymorphism was associated with ACL rupture patients in central China. This is likely from decreased expressions of GDF5 mRNA. Further studies are necessary to explore the functional implication of the GDF5 +104T/C polymorphism in Chinese ACL rupture patients.
Quantification of Sleepiness Through Principal Component Analysis of the Electroencephalographic Spectrum

Although circadian and sleep research has made extraordinary progress in the recent years, one remaining challenge is the objective quantification of sleepiness in individuals suffering from sleep deprivation, sleep restriction, and excessive somnolence. The major goal of the present study was to apply principal component analysis to the wake electroencephalographic (EEG) spectrum in order to establish an objective measure of sleepiness. The present analysis was led by the hypothesis that in sleep-deprived individuals, the time course of self-rated sleepiness correlates with the time course score on the 2nd principal component of the EEG spectrum. The resting EEG of 15 young subjects was recorded at 2-h intervals for 32–50 h. Principal component analysis was performed on the sets of 16 single-Hz log-transformed EEG powers (1–16 Hz frequency range). The time course of self-perceived sleepiness correlated strongly with the time course of the 2nd principal component score, irrespective of derivation (frontal or occipital) and of analyzed section of the 7-min EEG record (2-min section with eyes open or any of the five 1-min sections with eyes closed). This result indicates the possibility of deriving an objective index of physiological sleepiness by applying principal component analysis to the wake EEG spectrum. (Author correspondence: putilov@ngs.ru)
Multilevel, multiresolution integral equation analysis of printed antennas

A new approach is presented for the integral equation analysis of printed structures, based on the definition of multiresolution vector functions with properties similar to those of the scalar wavelets; in particular, they both possess spatial and spectral resolution. The resulting MoM impedance matrix shows strongly improved features, and especially a good conditioning, that makes the matrix stable against sparsification and the use of iterative methods convenient for the solution of the linear system. Numerical results for a recess-fed patch and an array of monolithically fed rectangular patches are presented.
Improved locality of the phase-field lattice-Boltzmann model for immiscible fluids at high density ratios.

Based on phase-field theory, we introduce a robust lattice-Boltzmann equation for modeling immiscible multiphase flows at large density and viscosity contrasts. Our approach is built by modifying the method proposed by Zu and He [Phys. Rev. E 87, 043301 (2013)PLEEE81539-375510.1103/PhysRevE.87. 043301] in such a way as to improve efficiency and numerical stability. In particular, we employ a different interface-tracking equation based on the so-called conservative phase-field model, a simplified equilibrium distribution that decouples pressure and velocity calculations, and a local scheme based on the hydrodynamic distribution functions for calculation of the stress tensor. In addition to two distribution functions for interface tracking and recovery of hydrodynamic properties, the only nonlocal variable in the proposed model is the phase field. Moreover, within our framework there is no need to use biased or mixed difference stencils for numerical stability and accuracy at high density ratios. This not only simplifies the implementation and efficiency of the model, but also leads to a model that is better suited to parallel implementation on distributed-memory machines. Several benchmark cases are considered to assess the efficacy of the proposed model, including the layered Poiseuille flow in a rectangular channel, Rayleigh-Taylor instability, and the rise of a Taylor bubble in a duct. The numerical results are in good agreement with available numerical and experimental data.
Comparative persistence and adherence with newer anti-hyperglycemic agents to treat patients with type 2 diabetes in the United States

Abstract Objectives: Non-adherence and non-persistence to anti-hyperglycemic agents are associated with worse clinical and economic outcomes in patients with type 2 diabetes. This study evaluated treatment persistence and adherence across newer anti-hyperglycemic agents (canagliflozin, dapagliflozin, sitagliptin, saxagliptin, linagliptin, liraglutide, or exenatide). Methods: This retrospective cohort study of Truven Health Analytics Marketscan databases included adult patients with type 2 diabetes whose first pharmacy claim for a newer anti-hyperglycemic agent was between February 1, 2014 and July 31, 2014. Treatment persistence and adherence were assessed for 12 months after the first claim (post-index). Persistence was defined as no gap ≥90 days between the end of one pharmacy claim and the start of the next pharmacy claim post-index. Adherence used two definitions: proportion of days covered (PDC) and medication possession ratio (MPR). Multivariable analyses of non-persistence (hazard ratios) and adherence (odds ratios) were adjusted for baseline demographics, drug cost, clinical characteristics, and other anti-hyperglycemic agents. Results: A total of 11,961 patients met all study selection criteria. Persistence rates at 12 months were significantly greater (p < 0.05 for each comparison) for canagliflozin 100 mg (61%) compared with dapagliflozin 5 mg (40%), dapagliflozin 10 mg (41%), sitagliptin (48%), saxagliptin (42%), linagliptin (52%), liraglutide (47%), exenatide (23%), and long-acting exenatide (39%). The persistence rate was greater (p < 0.05) for canagliflozin 300 mg (64%) vs canagliflozin 100 mg. Median adherence rates for canagliflozin 100 mg (MPR = 0.83; PDC = 0.79) and canagliflozin 300 mg (MPR = 0.92; PDC = 0.81) were greater than for the other index anti-hyperglycemic agents (MPR = 0.33–0.75; PDC = 0.33–0.72). Consistent results for treatment persistence and adherence were observed in multivariable analyses that were adjusted baseline characteristics. Conclusions: Canagliflozin was associated with better treatment persistence and treatment adherence compared with other anti-hyperglycemic agents in real-world settings.
Impaired ability of interferon‐alpha‐primed dendritic cells to stimulate Th1‐type CD4 T‐cell response in chronic hepatitis C virus infection

Summary. In interferon‐alpha (IFN‐α)/ribavirin combination therapy for chronic hepatitis C (CHC), an enhanced T helper 1 (Th1) response is essential for the eradication of hepatitis C virus (HCV). We aimed to elucidate the role of IFN‐α or IFN‐α/ribavirin in dendritic cell (DC) ability to induce Th1 response in HCV infection. We generated monocyte‐derived DC from 20 CHC patients and 15 normal subjects driven by granulocyte–macrophage colony‐stimulating factor and interleukin 4 (IL‐4) without IFN‐α (GM/4‐DC), with IFN‐α (IFN‐DC), with ribavirin (R‐DC) or with IFN‐α/ribavirin (IFN/R‐DC) and compared their phenotypes and functions between the groups. We also compared them in 14 CHC patients between who subsequently attained sustained virological response (SVR) and who did not (non‐SVR) by 24 weeks of IFN‐α/ribavirin therapy. Compared with GM/4‐DC, IFN‐DC displayed higher CD86 expression, but lesser ability to secrete IL‐10 and were more potent to prime CD4+ T cells to secrete IFN‐γ and IL‐2. Such differences were more significant in healthy subjects than in CHC patients. No additive effect of ribavirin was observed in DC phenotypes and functions in vitro either which was used alone or in combined with IFN‐α. However, in the SVR patients, an ability of IFN/R‐DC to prime T cells to secrete IFN‐γ and IL‐2 was higher than those of IFN‐DC and those of IFN/R‐DC in the non‐SVR group, respectively. In conclusion, DC from CHC patients are impaired in the ability to drive Th1 in response to IFN‐α. Such DC impairment is restored in vitro by the addition of ribavirin in not all but some patients who cleared HCV by the combination therapy.
Cryoelectron microscopy of λ phage DNA condensates in vitreous ice: The fine structure of DNA toroids

DNA toroids produced by the condensation of λ phage DNA with hexammine cobalt (III) have been investigated by cryoelectron microscopy. Image resolution obtained by this technique has allowed unprecedented views of DNA packing within toroidal condensates. Toroids oriented coplanar with the microscope image plane exhibit circular fringes with a repeat spacing of 2.4 nm. For some toroids these fringes are observed around almost the entire circumference of the toroid. However, for most toroids well-defined fringes are limited to less than one-third of the total toroid circumference. Some toroids oriented perpendicular to the image plane reveal DNA polymers organized in a hexagonal close-packed lattice; however, for other toroids alternative packing arrangements are observed. To aid interpretation of electron micrographs, three-dimensional model toroids were generated with perfect hexagonal DNA packing throughout, as well as more physically realistic models that contain crossover points between DNA loops. Simulated transmission electron microscopy images of these model toroids in different orientations faithfully reproduce most features observed in cryoelectron micrographs of actual toroids.
A Decade of Alternative Beta

We provide first empirical evidence of the long-term realized performance of alternative beta strategies. Despite diversified risk premia portfolios achieving satisfactory Sharpe ratios of 0.80 – 1.07 over the past decade, we show that up to two thirds of the performance can be explained by exposure to traditional benchmarks. We find no evidence of positive alpha in the aggregate industry returns, and document a pattern of time-varying, asymmetric, and statistically significant betas to global equities and bonds. We highlight the sensitivity of the results to strategy fees and identify an economically meaningful survivorship bias in publicly available strategy data.
Clustering, duplication and chromosomal distribution of mouse SINE retrotransposons

We analyzed potential mechanisms determining chromosomal distributions of the mouse B1 and B2 non-LTR retrotransposons, also known as SINE elements. We report that young B1 and B2 SINEs are underrepresented on chromosome X relative to autosomes, which is consistent with their integration in male germ lines. As the age of the SINE elements progresses, their densities on chromosome X increase relative to autosomal densities, possibly due to differences in ectopic recombination rates between chromosome X and autosomes. Furthermore, unlike young human Alus that tend to be integrated outside Alu-dense regions, young B1 and B2 elements are found mostly in SINE-rich clusters. The B1- or B2-rich clusters are more likely to contain duplicated elements than B1- or B2-poor chromosomal regions. We also present evidence indicating potential association of B1 and B2 elements with intra-chromosomal segmental duplications. No such association was found with inter-chromosomal duplications. We propose that the accumulation of mouse SINE elements observed in GC-rich regions may be due to the excess of DNA duplications over deletions in gene-rich regions that tend to be GC rich.
Induction of the antigen 85 complex of Mycobacterium tuberculosis in sputum: a determinant of outcome in pulmonary tuberculosis treatment.

Sputum quantitative culture, acid-fast smear, days-to-positive by BACTEC, and Mycobacterium tuberculosis antigen 85 complex were monitored during therapy in 42 patients with pulmonary tuberculosis (TB). By BACTEC, 4 patients were persistently positive on days 90-180, and treatment ultimately failed in 2 of these. Antigen 85 expression increased in subjects in whom disease persisted (persisters) from days 0 to 14 when the difference between persisters and nonpersisters was statistically significant (P = .002). Only antigen 85 complex values at day 14 suggested TB persistence at or after day 90. All subjects with day 14 antigen 85 complex values < 60 pg/mL responded rapidly to treatment and were cured. Of those with values > 60 pg/mL, in 33% TB persisted at or after day 90 and treatment failed in 17%. Biologic factors expressed early in therapy, not related to compliance or resistance, may exert a substantial influence on outcome. The antigen 85 complex is critical in cell wall biosynthesis and is induced by isoniazid in vitro. Its induction may represent an adaptive transition to a persistent state during therapy.
Inhibiting Integrin αvβ5 Reduces Ischemia–Reperfusion Injury in an Orthotopic Lung Transplant Model in Mice

Primary graft dysfunction after lung transplantation is the leading cause of morbidity and mortality in the immediate posttransplant period and is characterized by endothelial and epithelial barrier disruption and the leakage of protein‐rich edema fluid. Integrins are cell surface receptors that have an important role in maintenance of the cell barrier, and inhibition of integrins, such as αvβ5, can diminish alveolar flooding in lung injury models. We hypothesized that inhibition of αvβ5 during donor lung cold ischemia would reduce endothelial permeability during reperfusion. Using an orthotopic single lung transplantation model with and without cold ischemia, donor lungs were perfused with αvβ5‐blocking antibody (ALULA) or control antibody at the time of collection, followed by transplantation, 8 h of reperfusion, and the measurement of lung injury parameters. Prolonged cold ischemia (18 h) produced increases in extravascular lung water, protein permeability, and neutrophilic alveolitis and decreased oxygenation compared with lungs without cold ischemia. Perfusion of lungs with αvβ5 antibody versus control antibody protected donor lungs from injury and significantly improved oxygenation. In summary, αvβ5 integrin blockade protects from the development of ischemia–reperfusion lung injury and is a promising approach to preventing primary graft dysfunction in human lung transplant procedures.