Miracle-dz/UniFAR-FTUs huggingface dataset:
A multicenter study of viral hepatitis in a United States hemophilic population.

Hemophilia A and B patients seen at nine US regional treatment centers were tested for serologic markers of hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) during 1987 and 1988. Because human immunodeficiency virus (HIV) infection, a potentially confounding variable, was present in 53% of the group, the population was divided by HIV status for analysis purposes. In the HIV-positive group (N = 382), less than 1% had not been infected with HBV, HCV, or HDV, whereas 75% had evidence of infection with HBV and 98% with HCV. HBsAg, a marker of active HBV infection, was present in 12% of subjects; 96% of these were HCV positive. Anti-HDV was detected in 35 subjects (9.1%); all were anti-HBc positive. Ten of the 35 (29%) also were positive for IgM anti-HDV, indicating current infection. All 10 were HBsAg positive and 7 of the 9 tested were HDV RNA positive. Severe/moderate hemophilia B patients were more likely to have experienced an HBV infection and to be anti-HDV positive than were similar hemophilia A patients (22% v 8%, P < .05). In the HIV-negative group (N = 345), the subjects were younger and had less severe hemophilia than the HIV-positive patients. No evidence of HBV, HCV, or HDV infection was found in 18%, whereas 33% had experienced HBV infection and 79% were anti-HCV positive. Within this group, 4% were HBsAg positive. All 13 subjects with anti-HDV (4% of the HIV-negative group) also possessed anti-HBc. One (7.7%) was IgM anti-HDV positive and the serum from another contained HDV RNA. Both of these individuals were HBsAg positive. As in the HIV-positive group, severe/moderate hemophilia B patients were more likely to be HBV and HDV positive than were hemophilia A patients (9% v 3%, P < .05). A prevalence study of viral hepatitis in a large US hemophilic population showed that active infection with HCV is common, occurring in 89% of all study patients regardless of HIV status. Evidence of active HBV infection was found in 8%; 19% of these were actively infected with HDV. HDV was more common in hemophilia B patients after controlling for disease severity.
Evolutionary algorithms in iterative channel estimation for MLSD application

This article presents iterative estimation method with usage of evolutionary algorithms of the narrowband propagation channel impulse response, which can be used in reception based on maximum likehood sequence detection (MLSD). This method relies on minimization of an additional objective function, based on the knowledge of frequency characteristics of the narrowband channel. In the article, data reception in maximum likehood sequence detection sense, conception of the iterative channel impulse response estimation and simulation results in MATLAB/Simulink enviroment have been presented.
INSTRUCTIONAL DESIGN AND ASSESSMENT Pharmacy Student Engagement, Performance, and Perception in a Flipped Satellite Classroom

Pharmacy Student Engagement, Performance, and Perception in a Flipped Satellite Classroom Jacqueline E. McLaughlin, PhD, MS, LaToya M. Griffin, PhD, Denise A. Esserman, PhD, Christopher A. Davidson, ME, Dylan M. Glatt, Mary T. Roth, PharmD, Nastaran Gharkholonarehe, PharmD and Russell J. Mumper, PhD UNC Eshelman School of Pharmacy, UNC Chapel Hill, Chapel Hill, North Carolina Departments of Medicine and Biostatistics, UNC Chapel Hill, Chapel Hill, North Carolina
Dynamical Analysis and Active Control for Flow Instabilities in Boiling Microchannel

Received: 1 December 2018 Accepted: 4 March 2019 The purpose of this study is to investigate dynamical behaviors and active control synthesis of mass flowrate in the flow boiling of microchannel, which provides the inspiration to effective pressure drop treatments under parameter variations, exogenous disturbances, and measurement noises. The nonlinear mathematical model has been established through the momentum balance of surge tank and boiling microchannel. The pressure drop oscillations are one of the most severe dynamical instabilities for the boiling two-phase flow microchannel system under various uncertainties and disturbances, certainly leading to thermal and mechanical fatigues and breakage with excessive wear on the microchannel constituents. The boiling microchannel system exhibits complex dynamical behaviors; periodic, quasi-periodic, and chaotic behaviors. Those behaviors are characterized by using phase portrait, bifurcation diagram, and time series analysis. Based on Jacobian linearization around the equilibrium points, the dynamical system can be expressed in the state-space representation with parametric uncertainty. Through this study, it was found that the robust control synthesis can cope with flow oscillations as well as flow instability in an uncertain microchannel system. The extensive simulation results indicate that the proposed control scheme has offered robust performances and stability of the microchannel system under various uncertainties.
The Sharing Economy and Sustainability: a Case Study of India

Abstract The ongoing debates and discussions about sharing economy revolve round its definition, regulations and impact on economy, business and consumers. The paper attempts to develop a theoretical framework that define the sharing economy and analyse the possible association between the sharing economy and sustainability. The paper also assesses the need for an institutional and regulatory framework to strengthen sharing economy as an economic driver, potentially contributing to the more sustainable growth of the world economy.
Endothelin‐1 induced lesions of the frontoparietal cortex of the rat. A possible model of focal cortical ischemia

ENDOTHELIN 1 (ET-1) was unilaterally applied onto the surface of the dorsal frontoparietal cortex of the rat. Cortical blood flow measurements using laser-Doppler flowmetry demonstrated dose-dependent reductions of frontoparietal cortical blood flow. Histological analysis demonstrated dose-related lesions and the time course was followed using MRI. The lesions appear to be associated with a large penumbra area indicated by morphological characteristics. Thus, cortical surface exposure to ET-1 may produce graded lesions of the frontoparietal cortex related to local ischemia.
Cone signals in monostratified and bistratified amacrine cells of adult zebrafish retina

Strata within the inner plexiform layer (IPL) of vertebrate retinas are suspected to be distinct signaling regions. Functions performed within adult zebrafish IPL strata were examined through microelectrode recording and staining of stratified amacrine types. The stimulus protocol and analysis discriminated the pattern of input from red, green, blue, and UV cones as well as the light‐response waveforms in this tetrachromatic species. A total of 36 cells were analyzed. Transient depolarizing waveforms at ON and OFF originated with bistratified amacrine types, whose dendritic planes branched either in IPL sublaminas a & b, or only within sublamina a. Monophasic‐sustained depolarizing waveforms originated with types monostratified in IPL s4 (sublamina b). OFF responses hyperpolarized at onset, depolarized at offset, and in some cases depolarized during mid‐stimulus. These signals originated with types monostratified in s1 or s2 (sublamina a). Bistratified amacrines received depolarizing signals only from red cones, at both ON and OFF, while s4 stratified ON cells combined red and green cone signals. The s1/s2 stratified OFF cells utilized hyperpolarizing signals from red, red and green, or red and blue cones at ON, but only depolarizing red cone signals at OFF. ON and OFF depolarizing transients from red cones appear widely distributed within IPL strata. “C‐type” physiologies, depolarized by some wavelengths, hyperpolarized by others, in biphasic or triphasic spectral patterns, originated with amacrine cells monostratified in s5. Collectively, cells in this stratum processed signals from all cone types. J. Comp. Neurol. 525:1532–1557, 2017. © 2016 Wiley Periodicals, Inc.
Cerebral oxygenation during exercise in patients with terminal lung disease.

STUDY OBJECTIVES In patients with terminal lung disease who were exercising, we assessed whether improved arterial O2 saturation with an increased fraction of inspired oxygen (FIO2) affects cerebral oxygenation. DESIGN Randomized, crossover. PATIENTS AND METHODS The cerebral changes in oxyhemoglobin (DeltaHbO2) and changes in deoxyhemoglobin (DeltaHb) levels were evaluated using near-infrared spectrophotometry and the middle cerebral artery (MCA) mean velocity (V(mean)) was determined by transcranial Doppler ultrasonography in 13 patients with terminal lung disease (New York Heart Association class III-IV). Patients were allocated to an FIO2 of either 0.21 or 0.35 during incremental exercise with 15 min between trials. RESULTS Peak exercise intensity (mean [+/- SE], 26 +/- 4 W) reduced the arterial O2 pressure (at rest, 64 +/- 3 mm Hg; during exercise, 56 +/- 3 mm Hg) and the arterial oxygen saturation (SaO2) [at rest, 92 +/- 2%; 87 +/- 2%; p < 0.05], while the arterial CO2 pressure was not significantly affected. The MCA V(mean) increased from 49 +/- 5 to 63 +/- 7 cm/s (p < 0.05) as did the DeltaHb, while the DeltaHbO2 remained unaffected by exercise. With an elevated FIO2, the SaO2 level (at rest, 95.8 +/- 0.7%; during exercise, 96.0 +/- 1.0%) and arterial O2 pressure (at rest, 102 +/- 11 mm Hg; during exercise, 100 +/- 8 mm Hg) were not significantly affected by exercise, and the levels of blood oxygenation remained higher than the values established at normoxia (p < 0.05). The MCA V(mean) increased to a level similar to that achieved during control exercise (ie, to 70 +/- 11 cm/s). In contrast to control exercise, DeltaHb decreased while DeltaHbO2 increased during exercise with 35% O2 (p < 0.05). CONCLUSION An O2-enriched atmosphere enabled patients with terminal lung disease to maintain arterial O2 saturation during exercise. An exercise-induced increase in cerebral perfusion was not affected by hyperoxia, whereby the enhanced availability of oxygenated hemoglobin increases cerebral oxygenation. The clinical implication of the study is that during physical activity patients with terminal lung disease are recommended to use an elevated FIO2 to protect cerebral oxygenation.
Implications for interrelationships between nuclear architecture and control of gene expression under microgravity conditions

Components of nuclear architecture are functionally interrelated with control of gene expression. There is growing appreciation that multiple levels of nuclear organization integrate the regulatory cues that support activation and suppression of genes as well as the processing of gene transcripts. The linear representation of genes and promoter elements provide the potential for responsiveness to physiological regulatory signals. Parameters of chromatin structure and nucleosome organization support synergism between activities at independent regulatory sequences and render promoter elements accessible or refractory to transcription factors. Association of genes, transcription factors, and the machinery for transcript processing with the nuclear matrix facilitates fidelity of gene expression within the three‐dimensional context of nuclear architecture. Mechanisms must be defined that couple nuclear morphology with enzymatic parameters of gene expression. The recent characterization of factors that mediate chromatin remodeling and identification of intranuclear targeting signals that direct transcription factors to subnuclear domains where gene expression occurs link genetic and structural components of transcriptional control. Nuclear reorganization and aberrant intranuclear trafficking of transcription factors for developmental and tissue‐specific control occurs in tumor cells and in neurological disorders. Compromises in nuclear structure‐function interrelationships can occur as a consequence of microgravity‐mediated perturbations in cellular architecture. —Stein, G. S. , van Wijnen, A. J., Stein, J. L. , Lian, J. B. , Pockwinse, S. H. , McNeil, S. Implications for interrelationships between nuclear architecture and control of gene expression under microgravity conditions. FASEB J. 13 (Suppl.), S157–S166 (1999)
Novel Ryanodine Receptor Mutation That May Cause Malignant Hyperthermia

Background:Malignant hyperthermia (MH) is a hypermetabolic condition caused by a genetic disposition leading to increased Ca2+ release from the sarcoplasmic reticulum after exposure to triggering agents. In the authors' ongoing evaluation of patients undergoing MH testing in Austria, they detected a family with a new variant of the ryanodine receptor 1. Guidelines suggest that genetic tests are possible only for individuals from families in which the mutations are known. The aim of this study was to provide functional data that establish a potential link between this new variant and susceptibility to MH, and thus enable application in genetic tests. Methods:Messenger RNA was isolated from skeletal muscle cells grown in culture and used for synthesis of complementary DNA, which served as a template for 23 polymerase chain reactions. The sequences of all reaction products were analyzed. Functional studies in differentiated muscle cells included the Ca2+ releasing activity of caffeine and 4-chloro-m-cresol. The authors measured the intracellular Ca2+ concentration and, in combined patch clamp–Ca2+ detection experiments, the voltage dependence of the Ca2+ release. Results:In a single family, the authors found a transition from a highly conserved thymine to cysteine at position 11953, leading to the exchange of tryptophan to arginine at position 3985. This variant was absent in 100 MH-nonsusceptible individuals. Functionally, cells carrying this variant were more sensitive to caffeine and 4-chloro-m-cresol than wild-type cells and showed a shift in the voltage-dependent Ca2+ release to more negative potentials. Conclusion:These data document a role of the new W3985R variant in MH susceptibility.
Spinal cord markers in ALS: Diagnostic and biomarker considerations

Abstract Despite considerable involvement of the spinal cord in amyotrophic lateral sclerosis (ALS), current biomarker research is primarily centred on brain imaging and CSF proteomics. In clinical practice, spinal cord imaging in ALS is performed primarily to rule out alternative conditions in the diagnostic phase of the disease. Quantitative spinal cord imaging has traditionally been regarded as challenging, as it requires high spatial resolution while minimizing partial volume effects, physiological motion and susceptibility distortions. In recent years however, as acquisition and post-processing methods have been perfected, a number of exciting and promising quantitative spinal imaging and electrophysiology techniques have been developed. We performed a systematic review of the trends, methodologies, limitations and conclusions of recent spinal cord studies in ALS to explore the diagnostic and prognostic potential of spinal markers. Novel corrective techniques for quantitative spinal cord imaging are systematically reviewed. Recent findings demonstrate that imaging techniques previously used in brain imaging, such as diffusion tensor, functional and metabolic imaging can now be successfully applied to the human spinal cord. Optimized electrophysiological approaches make the non-invasive assessment of corticospinal pathways possible, and multimodal spinal techniques are likely to increase the specificity and sensitivity of proposed spinal markers. In conclusion, spinal cord imaging is an emerging area of ALS biomarker research. Novel quantitative spinal modalities have already been successfully used in ALS animal models and have the potential for development into sensitive ALS biomarkers in humans.
Role of chemotaxis in the association of motile bacteria with intestinal mucosa: in vivo studies

In vivo loops were prepared in the small intestine of rabbits and injected with mixtures of Vibrio cholerae and polystyrene spheres (1.1-micrometers diameter). The loops were removed and frozen after 15 min and then sectioned in a cryostat. The locations of particles and vibrios were determined microscopically. The vibrio/particle ratio was unity in the lumen of the loops, but increased 10-fold in the deep intervillous spaces, indicating active invasion of the mucus gel by the chemotactic parent strain. Motile nonchemotactic mutants and nonmotile mutants of this strain invaded the mucus at the same rate as inert particles. Similar results were obtained with intestinal loops prepared in germfree mice. When germfree mice were disassociated with mixtures of chemotactic (parent or revertant) and nonchemotactic mutant vibrios in equal proportions, the chemotactic strain rapidly outgrew its nonchemotactic counterpart in the intestine. Nonchemotactic mutants introduced as monoassociates into germfree mice were rapidly overgrown by nonmotile mutants which apparently arose spontaneously in the gut. Motility was therefore beneficial to survival only when it was directed by chemotactic stimuli, whereas it was a liability in the absence of such stimuli. Growth of chemotactic vibrios in small intestinal loops of rabbits paralleled that of nonchemotactic mutants for the first 4 to 6 h. Thereafter, the growth rate of the chemotactic vibrios was significantly faster. This was correlated with a significantly higher degree of association with the mucosa on the part of the chemotactic vibrios.
Specific interchain cross-linking of antibodies using bismaleimides. Repression of ligand leakage in immunoaffinity chromatography.

The extensive use of antibody-containing affinity columns in the purification of biologically active compounds (e.g., genetically engineered proteins) is severely hampered by the leaching of antibody (or portions thereof) from the immunoaffinity resin during elution of the target antigen. One of the major problems in this context is the combined use of reducing (i.e., thiols) and chaotropic (e.g., detergents and denaturants) agents in the elution step, which causes the disassociation of heavy and/or light chains from the immobilized antibody, thereby contaminating the resultant product. In order to overcome this problem, we have cross-linked the four antibody chains at their sites of disulfide interlinkage, thus producing a single antibody chain. To accomplish this, interchain disulfide bonds were reduced, and the resultant thiol groups were cross-linked by using bifunctional SH-specific reagents (particularly bismaleimides). Cross-linking of up to 95% of the available SH groups produced was achieved with concomitant retention of antigen-binding activity. The cross-linked antibody was immobilized onto CNBr-activated Sepharose, and the resultant column was found to be substantially more stable to harsh elution conditions than similar columns which contain the un-cross-linked antibody.
Comparative Evaluation of Preemptive Analgesic Effect of Injected Intramuscular Diclofenac and Ketorolac after Third Molar Surgery- A Randomized Controlled Trial.

INTRODUCTION Analgesia pre-emptively administered effect-ively aid in management of pain. Pre-emptive analgesia is anti-nociceptive treatment which prevents altered central sensitization of afferent inputs. AIM To compare and evaluate the pre-emptive analgesic efficacy of preoperatively administered ketorolac and diclofenac for controlling postoperative pain after third molar surgery. MATERIALS AND METHODS A total of 50 patients with symmetrically impacted third molars were divided into two groups, 30mg intramuscular injection of ketorolac and 75 mg diclofenac sodium were used in the respective groups. The visual analogue scale was used to assess post operative pain for three days and the patients were also evaluated for the number of rescue analgesia. RESULTS The data was statistically evaluated with paired t- test. The maximum time taken for pain perception for Group A Ketoralac was 5.48 hrs and Group B Diclofenac sodium was 4.9 hrs and p=0.235 which was not significant. The mean number of tablets taken by the patients in the first three post operative days was 3.24 in Group A i.e., Ketorolac and 4.04 in Group B i.e., Diclofenac sodium. The values were compared using the paired t test. The p value = 0.004, which was significant. CONCLUSION Ketoralac showed better pre-emptive analgesic effect for post-operative pain management after third molar extraction. The immediate post-operative pain free period provided by both ketorolac and diclofenac by intramuscular route was same.
A New Method to Quantify Ifosfamide Blood Levels Using Dried Blood Spots and UPLC-MS/MS in Paediatric Patients with Embryonic Solid Tumours

Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS). Blood samples were collected on Whatman 903® filter paper cards. Five 3 mm disks were punched out from each dried blood spot. Acetonitrile and ethyl acetate were used for drug extraction. Chromatographic separation was carried out in an Acquity UPLC equipment with a BEH-C18 column, 2.1 x 100 mm, 1.7 μm (Waters®). The mobile phase consisted in 5 mM ammonium formate and methanol:acetonitrile (40:48:12 v/v/v) at 0.2 mL/min. LC-MS/MS detection was done by ESI+ and multiple reaction mode monitoring, ionic transitions were m/z1+ 260.99 > 91.63 for ifosfamide and 261.00 > 139.90 for cyclophosphamide (internal standard). This method was linear within a 100–10000 ng/mL range and it was accurate, precise and selective. Ifosfamide samples in DBS were stable for up to 52 days at -80°C. The procedure was tested in 14 patients, ages 1 month to 17 years (9 males and 5 females), with embryonic tumours treated with ifosfamide, alone or combined, at a public tertiary referral hospital. Ifosfamide blood levels ranged from 11.1 to 39.7 μmol/L at 12 hours after the last infusion, while 24-hour levels ranged from 0.7–19.7 μmol/L. The median at 12 hours was 19.5 μmol/L (Q25 14.4–Q75 29.0) and 3.8 μmol/L (Q25 1.5–Q75 9.9) at 24 hours, p<0.001. This method is feasible to determine ifosfamide plasma levels in paediatric patients.
Modulation of inflammatory changes in early stages of colon cancer through activation of PPARγ by diclofenac

The role of peroxisome proliferator-activated receptor γ (PPARγ) was investigated in 1,2-dimethylhydrazine dihydrochloride (DMH)-induced colon carcinogenesis for 6 weeks (early stage) and its chemoprevention by diclofenac in a rat model. Morphological analysis revealed a marked occurrence of preneoplastic features, that is, multiple plaque lesions in the colonic mucosa. Administration of diclofenac at the anti-inflammatory dose along with DMH resulted a significant weakening of these lesions, thus proving the chemopreventive efficacy of diclofenac, which is a preferentially selective inhibitor for the proinflammatory enzyme, cyclooxygenase-2 (COX-2). The colonic mucosa showed increased protein expression and the enhanced activity of COX-2 in the DMH group, whereas the constitutively expressed COX-1 remained unaltered. Diclofenac treatment resulted in a significant reduction in COX-2 expression and its activity. The inflammatory changes were also demonstrated by nuclear factor-κB DNA binding activity, which was found to be increased after DMH treatment, thereby leading to the procarcinogenic effects, which were also adequately corrected by diclofenac. PPARγ expression was found to be decreased after DMH treatment as seen both by western blot and immunohistochemistry. In addition, the protein expression of the apoptotic protease activating factor-1 was studied in the colonic mucosa to observe the role of apoptosis in this study, which showed a distinct decline in the DMH-treated animals. The expression of the protein was, however, recovered by diclofenac treatment to the level of the controls. It is possible that diclofenac may be exerting its chemopreventive action through PPARγ, a ligand dependent transcription factor, which in turn activates apoptosis through inhibition of COX-2 and simultaneous activation of apoptotic protease activating factor-1.