Miracle-dz/UniFAR-FTUs huggingface dataset:
The natural history of complicated falciparum malaria--a prospective study.

OBJECTIVE Despite a substantial disease burden, little is known about the natural history of complicated falciparum malaria. Therefore, the present prospective study was undertaken to assess the clinical course, outcome, and resolution time of various complications of falciparum malaria. METHODS This prospective study has been conducted in a tertiary health care institution with high prevalence of malaria. A cohort of 608 patients of complicated falciparum malaria with single and multiple complications were enrolled. After discharge, all patients were followed up for 1 month except patients with anaemia who were followed up for 3 months. The onset time, interval of progression of one complication to other, resolution time of complications and mortality were determined. RESULTS At the time of admission there were 288 (46.8%) patients with single complication (SC) and 320 (53.2%) patients with multiple complications (MC). Majority (n=214, 74.3%) of patients with SC had cerebral malaria, followed by jaundice (14.6%), anaemia (6.9%), hypoglycaemia (2.1%), and respiratory distress (2.1%). The multiple complications were found in various combinations and majority (n=136, 42.5%) had constellation of 3 different complications. Cerebral malaria, jaundice, and renal failure (102 of 136, 75.3%) were the most common combination. Regardless of number of complications, cerebral malaria was present in 91.6% (293 of 320) patients with MC. As the population of patients progressed from single to multiple complications, increasing proportions had jaundice, renal failure, and anaemia. 12.8% to 36.2% of patients in any category progressed from one complication to other complication within 72 hrs. There mortality rate was 14.6%, 21.3%, 30.9%, 38.5%, 100%, and 100% among patients with 1, 2 , 3, 4, 5, and 6 complications respectively. CONCLUSION This is the first prospective study that provides the clinical evidence that complicated malaria represents a hierarchical continuum of abnormalities resulting from malaria infection. All complications developed within 5 days (median 72 hrs, range-2 to l20 hrs.) of onset of fever. Pre-pernicious stage had been recognised in cases of cerebral malaria. Each complication is unique in its onset and recovery time. Not only the number but also the type of complication influences the outcome of complicated malaria.
Different results on tetrachorical correlations in Mplus and Stata – Stata announces modified procedure

To identify the structure of mental disorders in large‐scale epidemiological data sets, investigators frequently use tetrachoric correlations as a first step for subsequent application of latent class and factor analytic methods. It has been possible to do this with Stata since 2005, whereas the corresponding Mplus routine has been on the market for some years. Using an identical data set we observed considerable differences between the results of the packages. This paper illustrates the differences with several examples from the Early Developmental Stages of Psychopathology Study data set, which consists of 3021 subjects, with diagnostic information assessed by the CIDI. Results reveal that tetrachoric correlations resulting from Mplus were often considerably smaller than those computed with Stata. The results were dramatically different, especially where there were few observation per cell or even empty cells. These findings were put to Mplus and Stata, whose responses clarified the discrepancies by describing the different mathematical assumptions and procedures used. Stata announced that it intended to launch a modified procedure. Copyright © 2006 John Wiley & Sons, Ltd.
Revenue sharing from tourism in terrestrial African protected areas

ABSTRACT A prerequisite for the sustainability of protected areas in Africa is the meaningful inclusion of local populations in conservation and tourism. This has been demonstrated in numerous destinations where communities receive benefits from tourism in terrestrial protected areas, they are more inclined to view it positively and conserve natural resources. This paper presents a review of revenue-sharing literature, and also an analysis of the evidence of quantified benefits accrued by local communities in Africa through institutional arrangements to share revenue or finance development projects by (1) protected areas, and (2) tourism enterprises. The review highlights the challenges of revenue sharing as well as four key components of successful revenue-sharing systems: (1) economic benefits must be clearly identified and communicated, (2) benefits are appropriate to the scale of threats to biodiversity, (3) involvement of communities in decision-making on the structure and process of the distribution system, and also how the revenues are used and (4) sufficient regulatory and institutional support is necessary to develop clear objectives, aims, goals and responsibilities. This paper constitutes the first multi-country, multi-scheme analysis of revenue sharing in terrestrial African protected areas.
The Hunger Games: Catching Fire: Using Digital and Social Media for Brand Storytelling

After the successful release of the first Hunger Games film in 2012, the film's distributor, Lionsgate, was preparing to release the next movie in the series, Hunger Games: Catching Fire. Fan expectations had grown after the success of the first film, and Lionsgate faced the challenge of keeping moviegoers interested and engaged in another Hunger Games movie. In an era marked by the rising popularity of digital and social media, Lionsgate knew that attracting fans to a sequel meant pushing the boundaries of traditional marketing tactics. Digital brand storytelling is about using digital media in a holistic way to tell a brand story and build excitement for an audience. Brand storytelling seeks to make a connection with the audience by giving them an emotional experience that resonates with them. While Lionsgate was aware that traditional marketing would need to be blended with a digital campaign to bring in moviegoers, it also needed to strike a careful balance between the two and choose the appropriate platforms to tell a cohesive story. Should Lionsgate launch a brand storytelling campaign to appeal to fans? Lionsgate's comparatively small marketing team gathered to brainstorm about how to execute such a campaign and position the film for another big success.
Determinants of Under-Five Mortality in Ethiopia: an Application of Cox Proportional Hazard and Frailty Models

Objective: Under-five mortality is an essential indicator of the development of a country. In Ethiopia under-five mortality rate is among the highest in the world. Nearly one out of 10 babies born in Ethiopia does not survive to celebrate its first birthday. Material and Methods: The data for the study was obtained from Ethiopian Demography and Health Survey data conducted in 2016. The Kaplan-Meier, Cox’sproportional hazards and gamma shared frailty models were employed for the analysis of under-five children data. Results: Results obtained by fitting both Cox-proportional hazard model and gamma shared frailty model: place of residence, Type of Birth, Birth order, sex of a child and preceding birth intervalwere found to be significant factors. Further more a high risk death of under-five children was found to be associated with place of residence at rural, multiple births, birth order at fifth and above, male children and preceding birth interval less than 24 months. From gamma shared frailty model (θ=0.145) we had enough evidence that the existence of unobserved heterogeneity at the regional level. Conclusion: The findings of this paper highlighted the potential associated with under-five child mortality in Ethiopia. The shared frailty model provided better estimates and also justified the presence of unobserved heterogeneity at regional level. Therefore, special attention should be given to these significant predictors, which ultimately reduce the under-five mortality.
A Novel Virus-Like Particle Based Vaccine Platform Displaying the Placental Malaria Antigen VAR2CSA

Placental malaria caused by Plasmodium falciparum is a major cause of mortality and severe morbidity. Clinical testing of a soluble protein-based vaccine containing the parasite ligand, VAR2CSA, has been initiated. VAR2CSA binds to the human receptor chondroitin sulphate A (CSA) and is responsible for sequestration of Plasmodium falciparum infected erythrocytes in the placenta. It is imperative that a vaccine against malaria in pregnancy, if administered to women before they become pregnant, can induce a strong and long lasting immune response. While most soluble protein-based vaccines have failed during clinical testing, virus-like particle (VLP) based vaccines (e.g., the licensed human papillomavirus vaccines) have demonstrated high efficacy, suggesting that the spatial assembly of the vaccine antigen is a critical parameter for inducing an optimal long-lasting protective immune response. We have developed a VLP vaccine display platform by identifying regions of the HPV16 L1 coat protein where a biotin acceptor site (AviTagTM) can be inserted without compromising VLP-assembly. Subsequent biotinylation of Avi-L1 VLPs allow us to anchor monovalent streptavidin (mSA)-fused proteins to the biotin, thereby obtaining a dense and repetitive VLP-display of the vaccine antigen. The mSA-VAR2CSA antigen was delivered on the Avi-L1 VLP platform and tested in C57BL/6 mice in comparison to two soluble protein-based vaccines consisting of naked VAR2CSA and mSA-VAR2CSA. The mSA-VAR2CSA Avi-L1 VLP and soluble mSA-VAR2CSA vaccines induced higher antibody titers than the soluble naked VAR2CSA vaccine after three immunizations. The VAR2CSA Avi-L1 VLP vaccine induced statistically significantly higher endpoint titres compared to the soluble mSA-VAR2CSA vaccine, after 1st and 2nd immunization; however, this difference was not statistically significant after 3rd immunization. Importantly, the VLP-VAR2CSA induced antibodies were functional in inhibiting the binding of parasites to CSA. This study demonstrates that the described Avi-L1 VLP-platform may serve as a versatile system for facilitating optimal VLP-display of large and complex vaccine antigens.
Monodisperse spherical mesoporous silica particles: fast synthesis procedure and fabrication of photonic-crystal films

A procedure for the synthesis of monodisperse spherical mesoporous silica particles (MSMSPs) via the controlled coagulation of silica/surfactant clusters into spherical aggregates with mean diameters of 250–1500 nm has been developed. The synthesis is fast (taking less than 1 h) because identical clusters are simultaneously formed in the reaction mixture. The results of microscopic, x-ray diffraction, adsorption and optical measurements allowed us to conclude that the clusters are ∼15 nm in size and have hexagonally packed cylindrical pore channels. The channel diameters in MSMSPs obtained with cethyltrimethylammonium bromide and decyltrimethylammonium bromide as structure-directing agents were 3.1 ± 0.15 and 2.3 ± 0.12 nm, respectively. The specific surface area and the pore volume of MSMSP were, depending on synthesis conditions, 480–1095 m2 g−1 and 0.50–0.65 cm3 g−1. The MSMSP were used to grow opal-like photonic-crystal films possessing a hierarchical macro-mesoporous structure, with pores within and between the particles. A selective filling of mesopore channels with glycerol, based on the difference between the capillary pressures in macro- and mesopores, was demonstrated. It is shown that this approach makes it possible to control the photonic bandgap position in mesoporous opal films by varying the degree of mesopore filling with glycerol.
Inflammation Induces Myeloid-Derived Suppressor Cells that Facilitate Tumor Progression1

Epidemiological and experimental observations support the hypothesis that chronic inflammation contributes to cancer development and progression; however, the mechanisms underlying the relationship between inflammation and cancer are poorly understood. To study these mechanisms, we have transfected the mouse 4T1 mammary carcinoma with the proinflammatory cytokine IL-1β to produce a chronic inflammatory microenvironment at the tumor site. Mice with 4T1/IL-1β tumors have a decreased survival time and elevated levels of immature splenic Gr1+CD11b+ myeloid-derived cells. These myeloid suppressor cells (MSC) are present in many patients with cancer and inhibit the activation of CD4+ and CD8+ T lymphocytes. 4T1/IL-1β-induced MSC do not express the IL-1R, suggesting that the cytokine does not directly activate MSC. Neither T or B cells nor NKT cells are involved in the IL-1β-induced increase of MSC because RAG2−/− mice and nude mice with 4T1/IL-1β tumors also have elevated MSC levels. MSC levels remain elevated in mice inoculated with 4T1/IL-1β even after the primary tumor is surgically removed, indicating that the IL-1β effect is long lived. Collectively, these findings suggest that inflammation promotes malignancy via proinflammatory cytokines, such as IL-1β, which enhance immune suppression through the induction of MSC, thereby counteracting immune surveillance and allowing the outgrowth and proliferation of malignant cells.
Structure, dynamics and electrostatics of the active site of glutaredoxin 3 from Escherichia coli: comparison with functionally related proteins.

The chemistry of active-site cysteine residues is central to the activity of thiol-disulfide oxidoreductases of the thioredoxin superfamily. In these reactions, a nucleophilic thiolate is required, but the associated pK(a) values differ vastly in the superfamily, from less than 4 in DsbA to greater than 7 in Trx. The factors that stabilize this thiolate are, however, not clearly established. The glutaredoxins (Grxs), which are members of this superfamily, contain a Cys-Pro-Tyr-Cys motif in their active site. In reduced Grxs, the pK(a) of the N-terminal active-site nucleophilic cysteine residue is lowered significantly, and the stabilization of the corresponding thiolate is expected to influence the redox potential of these enzymes. Here, we use a combination of long molecular dynamics (MD) simulations, pK(a) calculations, and experimental investigations to derive the structure and dynamics of the reduced active site from Escherichia coli Grx3, and investigate the factors that stabilize the thiolate. Several different MD simulations converged toward a consensus conformation for the active-site cysteine residues (Cys11 and Cys14), after a number of local conformational changes. Key features of the model were tested experimentally by measurement of NMR scalar coupling constants, and determination of pK(a) values of selected residues. The pK(a) values of the Grx3 active-site residues were calculated during the MD simulations, and support the underlying structural model. The structure of Grx3, in combination with the pK(a) calculations, indicate that the pK(a) of the N-terminal active-site cysteine residue in Grx3 is intermediate between that of its counterpart in DsbA and Trx. The pK(a) values in best agreement with experiment are obtained with a low (<4) protein dielectric constant. The calculated pK(a) values fluctuate significantly in response to protein dynamics, which underscores the importance of the details of the underlying structures when calculating pK(a) values. The thiolate of Cys11 is stabilized primarily by direct hydrogen bonding with the amide protons of Tyr13 and Cys14 and the thiol proton of Cys14, rather than by long-range interactions from charged groups or from a helix macrodipole. From the comparison of reduced Grx3 with other members of the thioredoxin superfamily, a unifying theme for the structural basis of thiol pK(a) differences in this superfamily begins to emerge.
Towards a circular economy - how business model innovation will help to make the shift

The overall aim of this paper is to develop a new conceptual framework for the role of business models in a circular economy. The shift towards a circular economy will be mandatory in order to sustain growth despite the limited amount of resources on our earth. Yet, a fundamental understanding of the business models needed to achieve this goal is still missing. Reviewing existing research as well as professional and for-business publications, the author develops a conceptual model by clustering and abstraction. The first part of this paper demonstrates that, despite wording differences, a predominant agreement on a basic structure for new business models in a circular economy has emerged in the field. The second part develops a conceptual model for the transition towards a circular economy by introducing a hierarchical structure of new business models. By outlining the roadmap towards result-oriented business models, this structure will contribute to a faster transition into a circular economy.
Isolation and Characterization of Mini-Tn5Km2 Insertion Mutants of Enterohemorrhagic Escherichia coliO157:H7 Deficient in Adherence to Caco-2 Cells

ABSTRACT Adherence of enterohemorrhagic Escherichia coli (EHEC) to intestinal epithelium is essential for initiation of the infection. To identify genes involved in adherence, an EHEC O157:H7 strain (O157Sakai) was mutagenized by mini-Tn5Km2, where Km refers to kanamycin resistance, and 4,677 insertion mutants were screened for their ability to form microcolonies (MC) on Caco-2 cells. The less adherent mutants were divided into three groups: those with no adherent ability (designated as class 1 mutants, n = 10), those less adherent than the wild type (class 2 mutants, n = 16), and those unable to form MC but which adhered in a diffuse manner (class 3 mutants, n = 1). The sites of insertion in class 1 mutants were all found within genes of the locus for enterocyte effacement (LEE) thought to be required for type III protein secretion. Indeed, the class 1 mutants failed to secrete type III secreted proteins such as EspA and Tir into the culture medium. The insertions in class 2 mutants were outside the LEE, and all the mutants except one were able to secrete type III proteins into the culture medium. The class 3 mutant had the insertion in the tir gene in the LEE and was deficient in Tir and intimin expression, suggesting that in the absence of intimin-Tir, O157Sakai can still adhere to Caco-2 cells but in a diffused manner. This was confirmed by construction of a nonpolareae (encoding intimin) mutant. Examination of theeae mutant together with O157Sakai and one of the class 1 mutants for the ability to form MC revealed that EHEC initially adhered diffusely at 1.5 h after infection. Following washing out of the nonadherent bacteria, while wild-type EHEC bacteria developed MC for another 2 to 3 h on Caco-2 cells, the eae mutant diffusely adhered throughout the infection without forming MC. MC with O157Sakai but not the diffusely adherent eae mutant could evoke F-actin condensation beneath the bacterium. Our results suggest that EHEC encodes additional adherence-associated loci and that the type III secreted proteins are involved in the initial diffuse adherence, while the intimin-Tir interaction is required for the subsequent development of MC.
Incidence and clinical features of trigeminal neuralgia, Rochester, Minnesota, 1945–1984

The overall crude incidence rate of trigeminal neuralgia per 100,000 population in Rochester, Minnesota, for 1945 through 1984 was 4.3 for both sexes combined. The age‐adjusted (to total 1980 US population) rate for women (5.9) was significantly higher than that for men (3.4). Annual incidence rates increased significantly with age in both women and men. Data based on evidence in the medical records suggest that trigeminal neuralgia is a rather rare and unpredictable disease: The number of episodes varies from 1 to 11, and length of episode from 1 day to 4 years. This study indicates an elevated relative risk associated with hypertension (both overall and among women in the cohort). Also, prevalence of multiple sclerosis was significantly greater among the group of 75 patients who had trigeminal neuralgia. Since the data on treatment in this study do not correspond to a randomized clinical trial, they are presented as empirical results only and show no single treatment of choice for trigeminal neuralgia.
Biochemical Kinetics Model of DSB Repair and Induction of γ-H2AX Foci by Non-homologous End Joining

Abstract Cucinotta, F. A. , Pluth, J. M. , Anderson, J. A. , Harper, J. V. and O'Neill, P. Biochemical Kinetics Model of DSB Repair and Induction of γ-H2AX Foci by Non-homologous End Joining. Radiat. Res. 169, 214–222 (2008). We developed a biochemical kinetics approach to describe the repair of double-strand breaks (DSBs) produced by low-LET radiation by modeling molecular events associated with non-homologous end joining (NHEJ). A system of coupled nonlinear ordinary differential equations describes the induction of DSBs and activation pathways for major NHEJ components including Ku70/80, DNA-PKcs, and the ligase IV-XRCC4 heterodimer. The autophosphorylation of DNA-PKcs and subsequent induction of γ-H2AX foci observed after ionizing radiation exposure were modeled. A two-step model of regulation of repair by DNA-PKcs was developed with an initial step allowing access of other NHEJ components to breaks and a second step limiting access to ligase IV-XRCC4. Our model assumes that the transition from the first to the second step depends on DSB complexity, with a much slower rate for complex DSBs. The model faithfully reproduced several experimental data sets, including DSB rejoining as measured by pulsed-field gel electrophoresis (PFGE) at 10 min postirradiation or longer and quantification of the induction of γ-H2AX foci. A process that is independent of DNA-PKcs is required for the model to reproduce experimental data for rejoining before 10 min postirradiation. Predictions are made for the behaviors of NHEJ components at low doses and dose rates, and a steady state is found at dose rates of 0.1 Gy/h or lower.
Central nervous system toxicity of cyclosporine in a rat model.

The central nervous system toxicity of cyclosporine, which is known to be neurotoxic clinically, was investigated in a rat model. Munich-Wistar rats were divided into 3 groups for a 2-week protocol. After baseline EEG and behavioral testing, group 1 (control) received a weight-adjusted volume of parenteral cyclosporine vehicle i.p., group 2 (low-dose) received 5 or 10 mg/kg/day i.p., and group 3 (high-dose) received 20 mg/kg/day i.p. Spontaneous behavior was observed, simple sensorimotor testing performed daily, and awake EEG's recorded 3 times per week. Four of 12 high-dose animals died during study, one after a witnessed tonic-clonic seizure, and two after recording of frankly epileptiform EEG's; there were no deaths in control or low-dose animals. Significant EEG abnormalities developed only at high-dose, with frankly epileptiform EEG's and/or seizures seen in 58 +/- 15% of these rats (P = 0.005, different from controls by life-table analysis). Although some high-dose animals demonstrated hyperirritability and dystonic posturing, behavioral changes were subtle, and animals were often still or rocking slightly during recording of frankly epileptiform EEG's. Walking latency and alley escape behaviors were delayed in high-dose rats, the latter correlating with abnormal EEG's. Serum urea nitrogens were mildly elevated in high-dose animals, but serum creatinine, electrolytes, bilirubin, body magnesium stores, and blood pressure remained normal in all groups. Kidneys showed only mild vacuolation histologically. The brain showed only very focal cortical injury sites related to electrode placement, which did not correlate with EEG changes or mortality. These results suggest that there may be a direct effect of cyclosporine on the central nervous system. This model system should prove useful in defining mechanisms of cyclosporine-related neurotoxicity.