Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibodies to West Nile Virus in Raccoons and Other Wild Peridomestic Mammals in Iowa

Surveillance for evidence of West Nile virus (WNV) infection in small- and medium-sized wild mammals was conducted in Iowa, USA, from May 2005 to June 2007. Sera were collected from 325 mammals belonging to nine species and tested for antibodies to WNV and other flaviviruses by epitope-blocking enzyme-linked immunosorbent assay (ELISA). All sera that had antibodies to flaviviruses by blocking ELISA were further examined by plaque reduction neutralization test (PRNT). Thirteen mammals were seropositive for WNV by PRNT, including 10 raccoons (Procyon lotor). The seroprevalence for WNV in raccoons was 34%. Although a moderately high seroprevalence for WNV has been detected in raccoons in other surveillance studies in the United States, this has not been reported previously in Iowa or most bordering states. Together, these data indicate that raccoons are exposed to WNV at high rates throughout the United States. Two Virginia opossums (Didelphis virginiana) and one fox squirrel (Sciurus niger) were also seropositive for WNV. Nineteen mammals had antibodies to an undetermined flavivirus(es). In summary, we provide serologic evidence that raccoons in Iowa are commonly exposed to WNV.
Late-phase investigational approaches for the treatment of relapsed/refractory acute myeloid leukemia

Introduction: Acute myeloid leukemia (AML) is a malignant hematologic disorder that affects more than 13,000 adults each year in the USA. Despite continued advances in the understanding of the molecular pathogenesis of the disease and patient management, the cure rate for AML remains relatively low, largely due to a high rate of relapsed or refractory disease. Areas covered: The purpose of this review is to provide an understanding of the unmet needs in relapsed/refractory AML, and to assess promising investigational agents with ongoing or planned Phase III clinical trials. Expert opinion: Although the treatment of relapsed/refractory AML remains a challenge, numerous new chemotherapeutics are currently in development. Enrollment in clinical trials should be strongly considered for patients with relapsed/refractory disease, and emerging data may help identify new agents with significant activity in this setting.
Replacement Therapy with Protein C Concentrate in Infants and Adolescents with Meningococcal Sepsis and Purpura Fulminans

We report the effects of substitution with a virus-inactivated protein C (PC) concentrate in disseminated intravascular coagulation (DIC) in infants and children with meningococcal sepsis associated with purpura fulminans. It was a prospective open-label study. Eight pediatric and adolescent patients age 0.2 to 18.25 years with DIC associated with severe acquired PC deficiency (range 0.02 to 0.48 IU/mL; median, 0.22 IU/mL) in meningococcal septic shock and purpura fulminans were studied. Replacement therapy was initiated with a virus-inactivated PC concentrate with an initial intravenous bolus of 80 to 120 IU/kg followed by 50 IU/kg up to six times per day as an adjunctive therapeutic regimen to otherwise optimal intensive care treatment. After initial PC administration, plasma PC levels rose to normal ranges and were maintained under PC replacement therapy. Improving or even normalizing global hemostatic parameters were assessed in all patients. Markedly elevated plasminogen activator inhibitor type 1 (PAI-1) levels prior to treatment, reflecting a reduced fibrinolytic potential, decreased rapidly under PC substitution. Concomitantly improving signs of purpura fulminans reflected by decreasing size of skin lesions, demonstrated a restoring microcirculation. Six of the eight patients survived. One patient required limb amputation; two patients died because of multiorgan failure. Both presented with a severely low plasma PC activity of 0.02 IU/mL on admission to the hospital. No adverse effects were observed with the PC concentrate administration. It can be concluded that the administration of PC concentrate had a marked benefit on the deranged coagulation status of patients with purpura fulminans and meningococcal septicemia. Normalization or even partial correction of hemostasis as well as improvement of microcirculation accompanied by improving signs of purpura fulminans were demonstrated in all patients.
Bronchodilatation by tachykinins and capsaicin in the mouse main bronchus

1 The effect of sensory neuropeptides and capsaicin on basal and stimulated tone of mouse bronchial smooth muscle has been evaluated. 2 In basal conditions neither sensory neuropeptides (subtance P, neurokinin A or calcitonin gene‐related peptide (CGRP)) nor capsaicin exerted any contractile effects. However, when a tonic contraction was induced with carbachol (1 μm) a prompt relaxation was induced by substance P (1– 100 nm) and by neurokinin A (1– 100 nm), with substance P being more potent. A second application of substance P was without effect. CGRP (10 nm) produced only a very small and erratic relaxation. Relaxation was also induced by capsaicin (1 μm), and this response could be evoked only once in each preparation. In 4 out of 6 preparations a cross‐desensitization between substance P and capsaicin was observed. 3 The selective NK1 tachykinin agonist, [Pro9]‐SP sulphone (1 μm), exerted potent bronchodilator actions on carbachol‐contracted mouse bronchial preparations. In contrast, neither [β Ala8]‐NKA (4–10) nor [MePhe7]‐NKB (both at a concentration of 1 μm), selective synthetic agonists for NK2 and NK3 receptors, exerted significant relaxant effects. Furthermore, the selective NK1 tachykinin antagonist, (±)‐CP 96,345 (1 μm), abolished substance P (1 nm)‐ but not isoprenaline (0.1 μm)‐induced relaxations. 4 Application of electrical field stimulation (EFS) (20 Hz, supramaximal voltage, 0.5 ms for 10 s) to carbachol‐contracted preparations evoked a transient contraction followed by a relaxation. The tetrodotoxin‐sensitive slow component of this relaxation was reduced following capsaicin desensitization. 5 In the presence of indomethacin (5 μm) the relaxation induced by substance P, capsaicin or EFS was suppressed. 6 In conclusion, the mouse main bronchus appears to be a monoreceptorial tissue containing only NK1 receptors which subserve bronchodilator functions. Such receptors could be activated by exogenous or endogenously (capsaicin or EFS) released tachykinins and the consequent relaxation is probably mediated by the generation of prostanoids.
Targeting Pyk2 for therapeutic intervention

Importance of the field: The focal adhesion tyrosine kinases FAK and Pyk2 are uniquely situated to act as critical mediators for the activation of signaling pathways that regulate cell migration, proliferation and survival. By coordinating adhesion and cytoskeletal dynamics with survival and growth signaling, FAK and Pyk2 represent molecular therapeutic targets in cancer as malignant cells often exhibit defects in these processes. Areas covered in this review: This review examines the structure and function of the focal adhesion kinase Pyk2 and intends to provide a rationale for the employment of modulating strategies that include both catalytic and extra-catalytic approaches that have been developed in the last 3 – 5 years. What the reader will gain: Targeting tyrosine kinases in oncology has focused on the ATP binding pocket as means to inhibit catalytic activity and downregulate pathways involved in tumor invasion. This review discusses the available catalytic inhibitors and compares them to the alternative approach of targeting protein–protein interactions that regulate kinase activity. Take home message: Development of specific catalytic inhibitors of the focal adhesion kinases has improved but significant challenges remain. Thus, approaches that inhibit the effector function of Pyk2 by targeting regulatory modules can increase specificity and will be a welcome asset to the therapeutic arena.
Requirement of TRAP/Mediator for Both Activator-Independent and Activator-Dependent Transcription in Conjunction with TFIID-Associated TAFIIs

ABSTRACT The multiprotein human TRAP/Mediator complex, which is phylogenetically related to the yeast SRB/Mediator coactivator, facilitates activation through a wide variety of transcriptional activators. However, it remains unclear how TRAP/Mediator functions in the context of other coactivators. Here we have identified a previously uncharacterized integral subunit (TRAP25) of the complex that is apparently metazoan specific. An antibody that is specific for TRAP25 allowed quantitative immunodepletion of essentially all TRAP/Mediator components from HeLa nuclear extract, without detectably affecting levels of RNA polymerase II and corresponding general transcription factors. Surprisingly, the TRAP/Mediator-depleted nuclear extract displayed severely reduced levels of both basal and activator-dependent transcription from DNA templates. Both activities were efficiently restored upon readdition of purified TRAP/Mediator. Moreover, restoration of basal and activator-dependent transcription to extracts that were simultaneously depleted of TRAP/Mediator and TFIID (TBP plus the major TAFIIs) required addition of both TBP and associated TAFIIs, as well as TRAP/Mediator. These observations indicate that TAFIIs and Mediator are jointly required for both basal and activated transcription in the context of a more physiological complement of nuclear proteins. We propose a close mechanistic linkage between these components that most likely operates at the level of combined effects on the general transcription machinery and, in addition, a direct role for Mediator in relaying activation signals to this machinery.
New Leads on the 'How' of Alzheimer's

Although the idea is still controversial, evidence is mounting that triggers for Alzheimer9s disease kill neurons by activating their internal cell-death programs. Working with a variety of experimental systems, including brain samples taken from patients at autopsy, researchers have found several signs that the cellular machinery involved in apoptosis has been activated in Alzheimer9s. Not everyone agrees that nerve cells die this way in Alzheimer9s, but if the findings are confirmed, they could provide new targets for drugs aimed at slowing the progression of Alzheimer9s, or even preventing it.
Deficient conditioned pain modulation after spinal cord injury correlates with clinical spontaneous pain measures

Abstract The contribution of endogenous pain modulation dysfunction to clinical and sensory measures of neuropathic pain (NP) has not been fully explored. Habituation, temporal summation, and heterotopic noxious conditioning stimulus–induced modulation of tonic heat pain intensity were examined in healthy noninjured subjects (n = 10), and above the level of spinal cord injury (SCI) in individuals without (SCI-noNP, n = 10) and with NP (SCI-NP, n = 10). Thermoalgesic thresholds, Cz/AFz contact heat evoked potentials (CHEPs), and phasic or tonic (30 seconds) heat pain intensity were assessed within the C6 dermatome. Although habituation to tonic heat pain intensity (0-10) was reported by the noninjured (10 s: 3.5 ± 0.3 vs 30 s: 2.2 ± 0.5 numerical rating scale; P = 0.003), loss of habituation was identified in both the SCI-noNP (3.8 ± 0.3 vs 3.6 ± 0.5) and SCI-NP group (4.2 ± 0.4 vs 4.9 ± 0.8). Significant temporal summation of tonic heat pain intensity was not observed in the 3 groups. Inhibition of tonic heat pain intensity induced by heterotopic noxious conditioning stimulus was identified in the noninjured (−29.7% ± 9.7%) and SCI-noNP groups (−19.6% ± 7.0%), but not in subjects with SCI-NP (+1.1% ± 8.0%; P < 0.05). Additionally, the mean conditioned pain modulation response correlated positively with Cz/AFz CHEP amplitude (&rgr; = 0.8; P = 0.015) and evoked heat pain intensity (&rgr; = 0.8; P = 0.007) in the SCI-NP group. Stepwise regression analysis revealed that the mean conditioned pain modulation (R2 = 0.72) correlated with pain severity and pressing spontaneous pain in the SCI-NP group. Comprehensive assessment of sensory dysfunction above the level of injury with tonic thermal test and conditioning stimuli revealed less-efficient endogenous pain modulation in subjects with SCI-NP.
CD4+/CD56+ Hematodermic Neoplasm: Presentation of 2 Cases and Review of the Concept of an Uncommon Tumor Originated in Plasmacytoid Dendritic Cells Expressing CD123 (IL-3 Receptor α)

CD4+/CD56+ hematodermic neoplasm is a rare neoplasm presenting with cutaneous nodules, lymphadenopathy, bone marrow infiltration, and an aggressive clinical course. Recently, the plasmacytoid dendritic cell origin of this neoplasm has been demonstrated. Plasmacytoid dendritic cell is a hematopoietic-derived cell implicated in the regulation of innate and adaptive cell immunity and in the production of certain regulatory cytokines. Recently it has been demonstrated that these cells express cell surface markers such as IL-3 receptor α (CD123). In the present report, we describe the clinical, histologic, and immunohistochemical characteristics of 2 cases of CD4+/CD56+ hematodermic neoplasm. Both patients were male and the age at the time of diagnosis was 36 and 75 years, respectively. Clinical findings were limited to the skin and consisted of multiple cutaneous nodules located in the thorax and extremities, some of them ulcerated. Histologically, the tumors were characterized by a nonepidermotropic, dermal and subdermal infiltration of homogeneous medium-sized cells resembling lymphoblasts or myeloblasts. Immunohistochemical characterization of the tumors showed expression of CD4, CD56, CD43, and CD123, whereas CD8, CD20, and MPO were negative. Immunoreactivity for CD3, which has been described in rare occasions, was found only in one of the cases. This characteristic profile in addition to the expression of CD123, which was detected in both cases, can be used as valuable tools in the diagnosis of this rare neoplasm.
Self-care behaviors among patients with heart failure.

BACKGROUND One way to prevent frequent hospitalizations and promote positive health outcomes among patients with heart failure (HF) is to ensure that the amount and quality of self-care used is appropriate to the patient's situation. OBJECTIVES The following are the purposes of this study: (a) examine the frequency of performance of self-care behaviors, (b) describe personal and environmental factors (basic conditioning factors [BCFs]) that affect self-care behaviors, and (c) describe the relationship between the level of knowledge patients have to empower their performance of self-care and the actual performance of self-care behaviors. METHODS This descriptive correlational study was guided by Orem's theory of self-care. One hundred ten participants, predominantly African Americans, who were outpatients or inpatients ready for hospital discharge, 18 years or older, and diagnosed with HF that was confirmed by an ejection fraction of 40% or less were conveniently selected from 1 of 2 sites. Data were collected with 2 investigator-developed instruments: the Revised Heart Failure Self-Care Behavior Scale and the Heart Failure Knowledge Test. Descriptive statistics, correlational analyses, and t tests for independent samples were used to analyze the data. RESULTS Three of the top 5 most frequently performed self-care behaviors were related to taking prescribed medications, and the 5 least frequently performed self-care behaviors were concerned with symptom monitoring or management. There were no significant relationships between the total self-care behavior score and any of the BCFs; however, a number of significant relationships between BCFs and individual self-care behaviors were observed. There was a significant relationship between the mean total knowledge score and the total mean self-care score (r = 0.21, P =.026). CONCLUSION Detailed information about the influence of BCFs on the performance of specific HF self-care behaviors can help nurses tailor interventions to the patient's situation.
Aero-allergen sensitisation patterns amongst atopic Zimbabwean children.

OBJECTIVE To characterize children presenting with atopic conditions using the RAST test. DESIGN Retrospective descriptive study. SETTING General paediatric clinic in the private sector. SUBJECTS 84 children aged below 12 years, who had the RAST test, who presented to a general paediatric clinic between 1993 and 1998 with atopic conditions for care. RESULTS The median age for all children in the study was 52 months. Forty eight were male and 36 female. Eczema (33.9%) was the most frequent clinical diagnosis especially in those less than 24 months of age, followed by asthma (25.5%), allergic conjunctivitis (24.0%) and allergic rhinitis (15.6%). Total IgE was not statistically significantly associated with clinical diagnosis(p = 0.889), age of the child (p = 0.102), gender (p = 0.687) or absolute eosinophil count (p = 0.318). The commonest allergens identified were dust mite (Dermatophygoides pteronissinus and D. farinae) and Bermuda grass. While antibody reaction to weeds, particularly plantain, were also common, these reactions were mostly mild to moderate. Allergy to cats and moulds was rare. CONCLUSION In the absence of routine testing for specific allergens avoidance of dust mite and Bermuda grass seem important strategies in the management of difficult children with atopy. There is need for a prospective study to shed more light on the allergens that cause these common atopic conditions in our environment.
Empowering front office employees with counseling affordances

Purpose – The purpose of this paper is to investigate the face-to-face citizen service encounter in public administrations’ front offices, and present a novel qualification approach to empower service personnel on-the-job, and thereby deepen the knowledge on the role of information and communication technology for advancing governmental reforms. Design/methodology/approach – The presented study follows a design science research methodology, conducted in collaboration with the public administration of a major German city. Data were collected using multiple quantitative and qualitative methods, including questionnaires, semi-structured interviews and video analysis. Findings – A novel on-the-job qualification approach for empowering public employees in their job-related skills, building on the concept of affordances, is developed. Thereto, six design principles for equipping artifacts with counseling affordances are presented. Evaluations in real-world environments provide first evidence that “learning with.
Mucinous syringometaplasia with prominent epithelial hyperplasia and deep dermal involvement

This report describes two patients with mucinous syringometaplasia whose findings expand the microscopic and clinical spectrum of the entity. The first patient had an eroded nodule that exhibited multiple epidermal invaginations that penetrated deeply into the dermis. In addition to mucinous metaplasia, there was also exuberant papillary epithelial hyperplasia. Expanded eccrine ducts with similar changes appeared as lobules isolated in the dermis but were shown to connect with the invaginations. In the second patient, a clinical “cyst” drained serous fluid. Multiple papillary‐cystic epithelial lobules similar to those seen in the first case were located in the dermis. A few approached the epidermis, but epidermal connections were not identified. The epithelium in these lesions was identical to that previously described in mucinous syringometaplasia. The tumors differed from prior cases by virtue of the number of eccrine apparatus involved, the extent and depth of involvement, and the presence of prominent papillary epithelial hyperplasia.
From the desk to the field: Recent trends in deploying Wireless Sensor Networks for monitoring civil structures

Wireless Sensor Networks (WSNs) leverage battery-powered embedded devices to sense from and act on the environment. Their characteristics are at odds with the lifetime requirements in monitoring of civil structures. In this paper, we briefly describe the challenges at stake and how to address them, drawing from recent literature and our own real-world experience. Hardware solutions include MEMS sensors and power-efficient memories. Duty-cycled and batch operation, as well as forms of distributed processing are software techniques to reduce the energy invested in radio communication—the major energy drain in WSNs. We then conclude with an outlook on an ongoing Indo-Swedish project on monitoring the integrity of railway bridges using WSNs.
Analytical and Experimental Results on System Maximum Reach Increase Through Symbol Rate Optimization

We investigated the reach increase obtained through nonlinearity mitigation by means of transmission symbol rate optimization (SRO). First, we did this theoretically and simulatively. We showed that the nonlinearity model that properly accounts for the phenomenon is the EGN model, in its version that specifically includes four-wave mixing. We then found that for PM-QPSK systems at full C-band, the reach increase may be substantial, on the order of 10-25%, with optimum symbol rates on the order of 2-6 GBd. We show that for C-band PM-QPSK systems over SMF, the potential mitigation due to SRO is greater than that ideally granted by digital backpropagation (the latter applied over a bandwidth of a 32-GBd channel). We then set up an experiment to obtain confirmation of the theoretical and simulative predictions. It consisted of 19 PM-QPSK channels, operating at 128 Gb/s per channel, over PSCF, with span length 108 km and EDFA-only amplification. We demonstrated a reach increase of about 13.5%, when going from single-carrier per channel transmission, at 32 GBd, to eight subcarrier per channel, at 4 GBd, in line with the EGN model predictions. We also extended the theoretical investigation of SRO to PM-16QAM, where we found a qualitatively similar effect to PM-QPSK, although the potential reach increase appears to be typically only about 50% to 60% that of PM-QPSK. Further investigation is, however, in order, specifically to explore the effect on PM-16QAM SRO of the removal of long-correlated phase and polarization noise.
An Immunogenic and Protective Alphavirus Replicon Particle-Based Dengue Vaccine Overcomes Maternal Antibody Interference in Weanling Mice

ABSTRACT A candidate pediatric dengue virus (DENV) vaccine based on nonpropagating Venezuelan equine encephalitis virus replicon particles (VRP) was tested for immunogenicity and protective efficacy in weanling mice in the presence and absence of potentially interfering maternal antibodies. A gene cassette encoding envelope proteins prM and E from mouse-adapted DENV type 2 (DENV2) strain NGC was cloned into a VEE replicon vector and packaged into VRP, which programmed proper in vitro expression and processing of DENV2 envelope proteins upon infection of Vero cells. Primary immunization of 3-week-old weanling BALB/c mice in the footpad with DENV2 VRP resulted in high levels of DENV-specific serum immunoglobulin G antibodies and significant titers of neutralizing antibodies in all vaccinates. A booster immunization 12 weeks after the prime immunization resulted in increased neutralizing antibodies that were sustained for at least 30 weeks. Immunization at a range of doses of DENV2 VRP protected mice from an otherwise-lethal intracranial DENV2 challenge. To model vaccination in the presence of maternal antibodies, weanling pups born to DENV2-immune or DENV2-naïve dams were immunized with either DENV2 VRP or live DENV2 given peripherally. The DENV2 VRP vaccine induced neutralizing-antibody responses in young mice regardless of the maternal immune status. In contrast, live-DENV2 vaccination performed poorly in the presence of preexisting anti-DENV2 antibodies. This study demonstrates the feasibility of a VRP vaccine approach as an early-life DENV vaccine in populations with high levels of circulating DENV antibodies and suggests the utility of VRP-based vaccines in other instances where maternal antibodies make early vaccination problematic.