Miracle-dz/UniFAR-FTUs huggingface dataset:
Nystatin prophylaxis and treatment in severely immunodepressed patients.

BACKGROUND Nystatin is sometimes used prophylactically in patients with severe immunodeficiency or in the treatment of fungal infection in such patients, although the effect seems to be equivocal. OBJECTIVES To study whether nystatin decreases morbidity and mortality when given prophylactically or therapeutically to patients with severe immunodeficiency. SEARCH STRATEGY MEDLINE and The Cochrane Library using a comprehensive search strategy, date of last search November 2001. Contacted industry and scanned reference lists. SELECTION CRITERIA Randomised trials comparing nystatin with placebo, an untreated control group, fluconazole or amphotericin B. DATA COLLECTION AND ANALYSIS Data on mortality, invasive fungal infection and colonisation were extracted by both authors independently. The outcomes were weighted by the inverse variance. A random effects model was used unless p>0.10 for the test of heterogeneity. MAIN RESULTS We included 12 trials (1,464 patients). The drugs were given prophylactically in ten trials and as treatment in two. Seven trials were in acute leukaemia, two in cancer, one in liver transplant patients, one in critically ill surgical and trauma patients, and one in AIDS patients. Nystatin had been compared with placebo in three trials and with fluconazole in nine; the dose varied from 1.5 MIE to 72 MIE daily. The effect of nystatin was similar to that of placebo on fungal colonisation (relative risk 0.85, 95% confidence interval 0.65 to 1.13). There was no statistically significant difference between fluconazole and nystatin on mortality (relative risk 0.76, 0.49 to 1.18) whereas fluconazole was more effective in preventing invasive fungal infection (relative risk 0.37, 0.15 to 0.91) and colonisation (relative risk 0.49, 0.34 to 0.70). The results were very similar if the three studies which were not performed in cancer patients were excluded. REVIEWER'S CONCLUSIONS Nystatin cannot be recommended for prophylaxis or treatment of Candida infections in immunodepressed patients.
An antiretroviral regimen containing 6 months of stavudine followed by long‐term zidovudine for first‐line HIV therapy is optimal in resource‐limited settings: a prospective, multicenter study in China

Background An zidovudine (AZT)‐substitution regimen containing 24‐week stavudine (d4T) followed by long‐term AZT for HIV therapy is potential to trade off short‐term AZT‐related anemia and long‐term risks associated with d4T in resourcelimited settings. However, evidence is scarce. This study aims to assess the efficacy and safety of AZT‐substitution regimen, aiming to find a regimen with better efficacy, less adverse events, and more affordability in resource‐limited settings. Methods This prospective, multicenter study enrolled 499 (190 on d4T regimen, 172 on AZT regimen, and 137 on AZTsubstitution regimen) HIV‐1‐infected subjects who initiated combined antiretroviral therapy and attended follow‐up visits over 96 weeks from 2009 to 2011. Lamivudine (3TC) and either nevirapine (NVP) or efavirenz (EFV) were the other two drugs in the antiretroviral regimens. Virologic and immunologic responses and adverse events were monitored at baseline and at weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96. Results In terms of hematological adverse effects, AZT‐substitution group had similar safety profiles to d4T group and was superior to AZT group. In comparison with AZT‐substitution group, AZT group was associated with higher risk of developing anemia (adjusted hazard ratio (aHR) for anemia ≥ grade II, 8.44, 95% CI 1.81–39.46) and neutropenia (aHR for neutropenia ≥ grade II, 1.86, 95% CI 1.19–2.93). The prevalence of lipodystrophy in d4T group was 19.5%, while that in AZT‐substitution group was zero. As to antiretroviral efficacy, these three groups showed no differences. Conclusion AZT‐substitution regimen provides a relatively safe and effective first‐line antiretroviral strategy in resource‐limited settings.
Gene Expression and Cytokine Profile Correlate With Mycobacterial Growth in a Human BCG Challenge Model

Background. Bacillus Calmette-Guerin (BCG) vaccine is the most widely administered vaccine in the world, yet its mechanism of action remains unclear. We hypothesize that certain immune pathways are associated with reduced mycobacterial growth following BCG challenge in human volunteers. Methods. We used samples from a mycobacterial challenge in which previously BCG-vaccinated or BCG-naive adults in the United Kingdom were challenged intradermally with a standard dose of BCG. Any remaining BCG was quantified in a skin biopsy specimen obtained 2 weeks after challenge and used as a measure of BCG growth and functional antimycobacterial immunity. We measured the immune response over the 2-week challenge, using DNA microarrays and flow cytometry, and correlated this with mycobacterial growth. Results. The magnitude of the immune response to BCG is greater in previously vaccinated volunteers, and this correlates with reduced mycobacterial growth but increased scarring at the vaccination site. In particular, the interferon γ and interleukin 17 pathways are strongly induced in previously vaccinated volunteers and correlate with reduced mycobacterial growth in this population. Conclusion. This study identifies pathways associated with control of mycobacterial growth in vivo in human volunteers and supports the use of BCG challenge as a tool for evaluating vaccine efficacy and identifying mechanisms of antimycobacterial immunity.
Claudin-based tight junctions are crucial for the mammalian epidermal barrier

The tight junction (TJ) and its adhesion molecules, claudins, are responsible for the barrier function of simple epithelia, but TJs have not been thought to play an important role in the barrier function of mammalian stratified epithelia, including the epidermis. Here we generated claudin-1–deficient mice and found that the animals died within 1 d of birth with wrinkled skin. Dehydration assay and transepidermal water loss measurements revealed that in these mice the epidermal barrier was severely affected, although the layered organization of keratinocytes appeared to be normal. These unexpected findings prompted us to reexamine TJs in the epidermis of wild-type mice. Close inspection by immunofluorescence microscopy with an antioccludin monoclonal antibody, a TJ-specific marker, identified continuous TJs in the stratum granulosum, where claudin-1 and -4 were concentrated. The occurrence of TJs was also confirmed by ultrathin section EM. In claudin-1–deficient mice, claudin-1 appeared to have simply been removed from these TJs, leaving occludin-positive (and also claudin-4–positive) TJs. Interestingly, in the wild-type epidermis these occludin-positive TJs efficiently prevented the diffusion of subcutaneously injected tracer (∼600 D) toward the skin surface, whereas in the claudin-1–deficient epidermis the tracer appeared to pass through these TJs. These findings provide the first evidence that continuous claudin-based TJs occur in the epidermis and that these TJs are crucial for the barrier function of the mammalian skin.
Innovative versus incremental new business services : Different keys for achieving success

In companies where new product development plays an important strategic role, managers necessarily contend with a portfolio of projects that range from high technology, new-to-the-world, innovations to relatively simple improvements, adaptations, line extensions, or imitations of competitive offerings. Recent studies indicate that achieving successful outcomes for projects that differ radically in terms of innovativeness requires that firms adjust their NPD practices in line with the type of new product project they are developing. Based on a large-scale survey of managers knowledgeable about new product development in their firm, this study focuses on new business-to-business service projects in an attempt to gain insights about the influence of product innovativeness on the factors that are linked to new service success and failure. The research results indicate that there are a small number of “global” success factors which appear to govern the outcome of new service ventures, regardless of their degree of newness. These include: ensuring an excellent customer/need fit, involving expert front line personnel in creating the new service and in helping customers appreciate its distinctiveness and benefits, and implementing a formal and planned launch program for the new service offering. Several other factors, however, were found to play a more distinctive role in the outcome of new service ventures, depending on how really new or innovative the new service was. For low innovativeness new business services, the results suggest that managers can enhance performance by: leveraging the firm’s unique competencies, experiences and reputation through the introduction of new services that have a strong corporate fit; installing a formal “stage-gate” new service development system, particularly at the front-end and during the design stage of the development process; and ensuring that efforts to differentiate services from competitive or past offerings do not lead to high cost or unnecessarily complex service offerings. For new-to-the-world business services, the primary distinguishing feature impacting performance is the corporate culture of the firm: one that encourages entrepreneurship and creativity, and that actively involves senior managers in the role of visionary and mentor for new service development. In addition, good market potential and marketing tactics that offset the intangibility of “really new” service concepts appear to have a positive performance effect. © 2001 Elsevier Science Inc. All rights reserved.
Human Immunodeficiency Virus Type 1 Clade B Superinfection: Evidence for Differential Immune Containment of Distinct Clade B Strains

ABSTRACT Sequential infection with different strains of human immunodeficiency virus type 1 (HIV-1) is a rarely identified phenomenon with important implications for immunopathogenesis and vaccine development. Here, we identify an individual whose good initial control of viremia was lost in association with reduced containment of a superinfecting strain. Subject 2030 presented with acute symptoms of HIV-1 infection with high viremia and an incomplete seroconversion as shown by Western blotting. A low set point of viremia (∼1,000 HIV-1 copies/ml) was initially established without drug therapy, but a new higher set point (∼40,000 HIV-1 copies/ml) manifested about 5 months after infection. Drug susceptibility testing demonstrated a multidrug-resistant virus initially but a fully sensitive virus after 5 months, and an analysis of pol genotypes showed that these were two phylogenetically distinct strains of virus (strains A and B). Replication capacity assays suggested that the outgrowth of strain B was not due to higher fitness conferred by pol, and env sequences indicated that the two strains had the same R5 coreceptor phenotype. Delineation of CD8+-T-lymphocyte responses against HIV-1 showed a striking pattern of decay of the initial cellular immune responses after superinfection, followed by some adaptation of targeting to new epitopes. An examination of targeted sequences suggested that differences in the recognized epitopes contributed to the poor immune containment of strain B. In conclusion, the rapid overgrowth of a superinfecting strain of HIV-1 of the same subtype raises major concerns for effective vaccine development.
Comparing Online and Offline SON Solutions for Concurrent Capacity and Coverage Optimization

Self-organizing networks (SONs) can carry out their optimization procedures in an on- or off-line manner. On one hand, an online SON solution optimizes network parameters during operation. On the other hand, an offline SON solution employs a simulation environment of the network to be optimized in order to perform an offline parameter optimization before applying changes to the network. Thus far, researchers have not yet compared the characteristics of on- and offline SON solutions and they typically do not comment their SON solution's operational mode. However, specifying the SONs operational mode is crucial because it determines the type and number of measurements to be performed, and it decides whether it is required to accurately model the network to be optimized or not. In this work, we compare the general properties of on and off-line SON solutions qualitatively and compare an on and an off-line algorithm for coverage and capacity optimization quantitatively, using a realistic LTE simulation scenario. Based on the results obtained, we can conclude that offline SON solutions should be preferred as long as the required inputs are available. However, online SON solutions provide an adequate alternative to offline SON solutions if some of the inputs required are missing.
Usefulness of the Simplified Cough Test in Evaluating Cough Reflex Sensitivity as a Screening Test for Silent Aspiration

Objective To assess cough reflex sensitivity using the simplified cough test (SCT) and to evaluate the usefulness of SCT to screen for silent aspiration. Methods The healthy control group was divided into two subgroups: the young (n=29, 33.44±9.99 years) and the elderly (n=30, 63.66±4.37 years). The dysphagic elderly group (n=101, 72.95±9.19 years) consisted of patients with dysphagia, who suffered from a disease involving central nervous system (ischemic stroke 47, intracerebral hemorrhage 27, traumatic brain injury 11, encephalitis 5, hypoxic brain damage 3, and Parkinson disease 8). The SCT was performed using the mist of a 1% citric acid from a portable nebulizer. The time from the start of the inhalation to the first cough was measured as the cough latency. All the dysphagic patients underwent the videofluoroscopic swallowing study. Results The cough latency was more significantly prolonged in the healthy elderly group than in the healthy young group (p<0.001), and in the dysphagic elderly group than in the healthy elderly group (p<0.001). The sensitivity and specificity of SCT were 73.8% and 72.5% for detecting aspiration in the dysphagic patients, and 87.1% and 66.7% for detecting silent aspiration in the aspirated patients. Conclusion Cough latency measured with the SCT reflects the impairment of cough reflex in healthy elderly and dysphasic subjects. The results of this study show that the SCT test can be a valuable method of screening aspiration with or without cough in dysphasic patients.
Rapid anti-helminthic response of B lymphocytes in the intestinal mucosal tissues of rats.

B cell response to Trichinella spiralis (Ts) adult antigen (Ag) was studied in rats 1-20 days postinfection. B cell recoveries from the mesenteric lymph node (MLN), Peyer's patches (PP), thoracic duct lymph (TDL), and the spleen were determined by FACS analysis and Ag-specific antibody-producing cells (Ab-pc) in these tissues were enumerated using the immunoplaque assay. Total B cell numbers increased 2-70 times from day 3 postinfection in the MLN and TDL obtained from MLN-resected rats (MX) and such proliferation was not found in the PP or the spleen. Ab-pc of all isotypes increased from day 3 in the MLN and from day 2 in the MX-TDL. Among all isotypes, IgE- and IgG1-pc showed the strongest response. Immunofluorescence study revealed that these B cells were activated in the non-PP region of the small intestine. These results indicate an early isotype switch to IgG1 and IgE production in Ts-infected small intestine.
Hypoglossal-Facial Nerve Reconstruction Using a Y-Tube-Conduit Reduces Aberrant Synkinetic Movements of the Orbicularis Oculi and Vibrissal Muscles in Rats

The facial nerve is the most frequently damaged nerve in head and neck trauma. Patients undergoing facial nerve reconstruction often complain about disturbing abnormal synkinetic movements of the facial muscles (mass movements, synkinesis) which are thought to result from misguided collateral branching of regenerating motor axons and reinnervation of inappropriate muscles. Here, we examined whether use of an aorta Y-tube conduit during reconstructive surgery after facial nerve injury reduces synkinesis of orbicularis oris (blink reflex) and vibrissal (whisking) musculature. The abdominal aorta plus its bifurcation was harvested (N = 12) for Y-tube conduits. Animal groups comprised intact animals (Group 1), those receiving hypoglossal-facial nerve end-to-end coaptation alone (HFA; Group 2), and those receiving hypoglossal-facial nerve reconstruction using a Y-tube (HFA-Y-tube, Group 3). Videotape motion analysis at 4 months showed that HFA-Y-tube group showed a reduced synkinesis of eyelid and whisker movements compared to HFA alone.
Cdh5 Is Specifically Activated in Glioblastoma Stemlike Cells and Contributes to Vasculogenic Mimicry Induced by Hypoxia Neuro-onco Lo Gy Materials and Methods

Background. A proportion of glioblastoma stemlike cells (GSCs) expressing endothelial cell marker CDH5 (vascu-lar-endothelial–cadherin or CD144) can transdifferentiate into endothelial cells and form blood vessels. However, the implications of CDH5 expression in gliomas and how it is regulated in GSCs remain to be clarified. Methods. The mRNA and protein levels of CDH5 were detected in glioma samples and cultured cell lines, and the prognostic value of the CDH5 expression level for GBM patients was evaluated. Bioinformatics analysis was performed to reveal the potential functional roles of CDH5 in glioblastoma multiforme. Gene knockdown induced by short hairpin RNA, chromatin immunoprecip-itation analysis, and a vasculogenic tube formation assay were performed to investigate the relationships among hypoxia, CDH5 expression level, and angiogenesis. Results. CDH5 was overexpressed in gliomas, correlated with tumor grades, and was an independent adverse prog-nostic predictor for glioblastoma multiforme patients. CDH5 was specifically activated in GSCs but not in non-GSCs or neural stem cells, and CDH5 + cells could produce xenografts in immunocompromised mice. Bioinformatics analysis demonstrated that CDH5 might interact directly with hypoxia-inducible factor (HIF)2a. CDH5 expression was significantly upregulated in GSCs, but not in non-GSCs or normal neural stem cells, under a 1% O 2 condition. Both HIF1a and HIF2a positively regulated CDH5 level in GSCs and could bind to the promoter of CDH5. Furthermore, CDH5 contributed to the vasculogenic mimicry of GSCs, especially under hypoxic conditions. Conclusions. The specific expression of CDH5 in GSCs may contribute to GSC-derived neovasculogenesis in glio-blastoma multiforme, especially under hypoxic conditions, revealing novel tumorigenic mechanisms contributed by GSCs. G lioblastoma multiforme (GBM), a World Health Organization (WHO) grade IV glioma that is the most common primary malignant brain tumor in adulthood, is among the most aggressive and lethal cancers in humans. 1 Despite advances in neurosurgery and adjuvant treatment, the median survival of patients with GBM is only about 1 year. 2 In recent years, one of the most promising advances in understanding the mechanism underlying the tumorigenesis of GBM has been promoted by the concept of cancer stem cells. 3 – 6 A sub-population of glioblastoma stemlike cells (GSCs) 7 – 11 in GBM not only retain multipotency and an extraordinary potential to initiate tumors, but also contribute to the chemo-and radioresistance of GBM. 4,5,12 – 14 In addition, GSCs are located in a perivascular niche and are regulated by hypoxia. These observations suggest that GSCs may be important therapeutic targets …
Display of individuality in avoidance behavior and risk assessment of inbred mice

Factors determining individuality are still poorly understood. Rodents are excellent model organisms to study individuality, due to a rich behavioral repertoire and the availability of well-characterized isogenic populations. However, most current behavioral assays for rodents have short test duration in novel test environments and require human interference, which introduce coercion, thereby limiting the assessment of naturally occurring individuality. Thus, we developed an automated behavior system to longitudinally monitor conditioned fear for assessing PTSD-like behavior in individual mice. The system consists of a safe home compartment connected to a risk-prone test compartment (TC). Entry and exploration of the TC is solely based on deliberate choice determined by individual fear responsiveness and fear extinction. In this novel ethological assay, C57BL/6J mice show homogeneous responses after shock exposure (innate fear), but striking variation in long-lasting fear responses based on avoidance and risk assessment (learned fear), including automated stretch-attend posture quantification. TC entry (retention) latencies after foot shock differed >24 h and the re-explored TC area differed >50% among inbred mice. Next, we compared two closely related C57BL/6 substrains. Despite substantial individual differences, previously observed higher fear of C57BL/6N vs. C57BL/6J mice was reconfirmed, whereas fear extinction was fast and did not differ. The observed variation in fear expression in isogenic mice suggests individual differences in coping style with PTSD-like avoidance. Investigating the assumed epigenetic mechanisms, with reduced interpretational ambiguity and enhanced translational value in this assay, may help improve understanding of personality type-dependent susceptibility and resilience to neuropsychiatric disorders such as PTSD.
Intercommunication Between Prefrontal and Posterior Brain Regions for Protecting Visual Working Memory From Distractor Interference

Because visual working memory has a very restricted capacity, good filtering mechanisms are essential for its successful functioning. A neuronal signal emitted by the prefrontal cortex is considered to be an important contributor to filtering. Proof of the functional significance of this signal during normal cognitive functioning is, however, still missing. Furthermore, research has so far neglected that the prefrontal cortex must receive input from posterior brain areas that report the necessity to filter. From human electroencephalograms, we extracted several event-related components that reflect the different subprocesses of filtering. On the basis of their timing and a clear pattern of correlations, we reason that filtering might consist of a causal chain of events that involve prefrontal and posterior cortex regions: After distractors are detected in posterior regions, a prefrontal mechanism is activated, which in turn prevents subsequent unnecessary parietal storage of distractor information.
Influence of thickness of individual elastomer layers (first shape factor) on the response of unbonded fiber-reinforced elastomeric bearings

The objective of this paper is to study the influence of thickness of individual elastomer layers (first shape factor) on the vertical and horizontal responses of fiber reinforced elastomeric bearings that are not bonded or mechanically fastened to their top and bottom supports. By definition, the first shape factor, S1, is the ratio of the plan area to the perimeter stress-free area of a single elastomer layer within the bearing. Results of a comprehensive 2D-finite element study on a large group of bearings with different shape factors of 10, 15, 20, 30, and 40 suggest that the shape factor S1 is a critical parameter in controlling both the vertical compression modulus of the bearing and the level of stress in the fiber-reinforcing layers. Furthermore, the secant horizontal stiffness and the stress demand in the bearing elastomer material are to a limited extent influenced by the parameter S1.