Miracle-dz/UniFAR-FTUs huggingface dataset:
Strategies for Designing and Monitoring Malaria Vaccines Targeting Diverse Antigens

After more than 50 years of intensive research and development, only one malaria vaccine candidate, “RTS,S,” has progressed to Phase 3 clinical trials. Despite only partial efficacy, this candidate is now forecast to become the first licensed malaria vaccine. Hence, more efficacious second-generation malaria vaccines that can significantly reduce transmission are urgently needed. This review will focus on a major obstacle hindering development of effective malaria vaccines: parasite antigenic diversity. Despite extensive genetic diversity in leading candidate antigens, vaccines have been and continue to be formulated using recombinant antigens representing only one or two strains. These vaccine strains represent only a small fraction of the diversity circulating in natural parasite populations, leading to escape of non-vaccine strains and challenging investigators’ abilities to measure strain-specific efficacy in vaccine trials. Novel strategies are needed to overcome antigenic diversity in order for vaccine development to succeed. Many studies have now cataloged the global diversity of leading Plasmodium falciparum and Plasmodium vivax vaccine antigens. In this review, we describe how population genetic approaches can be applied to this rich data source to predict the alleles that best represent antigenic diversity, polymorphisms that contribute to it, and to identify key polymorphisms associated with antigenic escape. We also suggest an approach to summarize the known global diversity of a given antigen to predict antigenic diversity, how to select variants that best represent the strains circulating in natural parasite populations and how to investigate the strain-specific efficacy of vaccine trials. Use of these strategies in the design and monitoring of vaccine trials will not only shed light on the contribution of genetic diversity to the antigenic diversity of malaria, but will also maximize the potential of future malaria vaccine candidates.
Quantitative proteomics and dynamic imaging reveal that G3BP-mediated stress granule assembly is poly(ADP-ribose)-dependent following exposure to MNNG-induced DNA alkylation

Summary Poly(ADP-ribose) (pADPr) is a heterogenic molecule synthesised from NAD by poly(ADP-ribose) polymerases (PARPs). Many cellular functions from genome integrity surveillance, cell cycle progression and DNA repair to apoptosis are affected by pADPr through its network of associated proteins. Using quantitative proteomics, we established a temporal map of pADPr-associated complexes upon genotoxic stress. Results suggested a strong pADPr association to many proteins involved in stress granule formation, notably the ras-GAP SH3-binding protein G3BP, as well as in the later phases of alkylation-stress-induced responses. Further investigation with dynamic imaging clearly demonstrated a pADPr-dependent initiation of stress granule assembly originating from the nucleus. The co-transfection of G3BP with poly(ADP-ribose) glycohydrolase (PARG) indicates that pADPr is involved in modulating the nuclear translocation of G3BP. Moreover, a peptide pADPr blot assay of G3BP revealed that pADPr binds to the glycine–arginine-rich domain of G3BP. Thereafter, we established a comprehensive G3BP interactome in the presence of pADPr. Our findings establish a novel function for pADPr in the formation of G3BP-induced stress granules upon genotoxic stress.
Efficient sensor node authentication via 3GPP mobile communication networks

Energy efficiency is one of important issues in the resource constrained wireless sensor network. In this paper, we propose the authentication and key agreement protocol that efficiently reduces the overall computational and communication costs in the next generation converged network. The enhanced security procedures are operated through the mobile network in order to maximize the lifetime of the sensor networks and to apply the combined capabilities of both networks.
Oral sodium clodronate for nonmetastatic prostate cancer--results of a randomized double-blind placebo-controlled trial: Medical Research Council PR04 (ISRCTN61384873).

BACKGROUND The most frequent site of metastases from prostate cancer is bone. Adjuvant bisphosphonate treatment improves outcomes of patients with bone metastasis-negative breast cancer, but the effects of bisphosphonates on bone metastases in prostate cancer are not known. METHODS We performed a randomized double-blind placebo-controlled trial to determine whether a first-generation bisphosphonate could improve symptomatic bone metastasis-free survival (time to symptomatic bone metastases or death from prostate cancer) in men with nonmetastatic prostate cancer who were at high risk of developing bone metastases. Between June 1, 1994, and December 31, 1997, 508 men from 26 UK sites and one New Zealand site who were within 3 years of initial prostate cancer diagnosis with no evidence of metastases from current bone scanning were randomly assigned to daily oral sodium clodronate (2080 mg/day, n = 254) or placebo (n = 254) for a maximum of 5 years. Estimates of outcome risks were compared using Kaplan-Meier analyses. RESULTS The groups allocated to each treatment were well balanced. After a median follow-up of nearly 10 years, no evidence of benefit to the clodronate group was observed in terms of bone metastases-free survival (clodronate versus placebo, 80 events versus 68 events; hazard ratio [HR] = 1.22; 95% confidence interval [CI] = 0.88 to 1.68) or overall survival (clodronate versus placebo, 130 deaths versus 127 deaths; HR = 1.02; 95% CI = 0.80 to 1.30). Adverse events, notably gastrointestinal problems and increased lactate dehydrogenase levels, were more frequent in the clodronate group than in the placebo group; otherwise, clodronate was well tolerated. Modification of trial drug dose was more frequent in the clodronate group than the placebo group (HR = 1.63, 95% CI = 1.21 to 2.19). CONCLUSION Adjuvant sodium clodronate does not modify the natural history of nonmetastatic prostate cancer.
Compartmentation of hexokinase in rat heart. A critical factor for tracer kinetic analysis of myocardial glucose metabolism.

Radiolabeled analogues of 2-deoxyglucose are widely used to trace glucose metabolism in cell cultures, whole organs, and intact animals, although kinetic differences in transport and phosphorylation between these compounds and glucose exist. The present studies were undertaken to determine the effects of insulin stimulation on the phosphorylation of 2-deoxyglucose compared to glucose in the intact, saline-perfused working rat heart. Rates of glucose utilization determined from tritiated glucose differed from rates estimated from the accumulation of [14C]2-deoxyglucose in a nonconstant manner when comparing rates in the absence or presence of physiologic levels of insulin (13 microU/ml). The fraction of monophosphorylated hexoses that was accounted for by [14C]2-deoxyglucose 6-phosphate was dramatically decreased in hearts perfused in the presence of insulin. Additionally, hexokinase activity associated with the mitochondrial fraction of tissue extracts was increased in hearts stimulated by insulin. While this redistribution of hexokinase to the mitochondria did not affect the apparent affinity constant for glucose, hexokinase bound to mitochondria exhibited an 8.5-fold decrease in the affinity for 2-deoxyglucose when compared with hexokinase present in the cytosolic fraction. The findings are consistent with an insulin-mediated preferential uptake and phosphorylation of glucose compared to deoxyglucose. The results also imply that the redistribution of hexokinase and the differential effect of insulin on its affinity for tracer and tracee are responsible for changes in the "lumped constant" (i.e., the correction factor used to equate 2-deoxyglucose to glucose uptake). These changes must be taken into account when regional myocardial glucose metabolism is assessed by the 2-deoxyglucose method.
Guidelines for the physiotherapy management of the adult, medical, spontaneously breathing patient

### Steering group Julia Bott (Chair), support to Section 6, Consultant Physiotherapist, Surrey PCT NW Locality Sheric Ellum, support to Section 5, Consultant Physiotherapist, Guy's & St Thomas' NHS Trust, London Dr Rachel Garrod, support to Section 1, Reader, School of Physiotherapy, Faculty of Health and Social Care Sciences, Kingston University and St George's, University of London. Dr Jennifer Pryor, support to Sections 3 and 4, Senior Research Fellow in Physiotherapy, Royal Brompton & Harefield NHS Trust Dr Lesley Rimington, support to Section 2, Lecturer School of Health and Rehabilitation, Keele University ### Section 1—COPD Sharon Baines, Clinical Specialist Physiotherapist, Chronic Lung Disease Service, NHS Central Lancashire Amanda Dryer, Physiotherapy Clinical Lead in Respiratory Care, Central Manchester and Manchester Children's University Hospital Robert Goddard, Superintendent Physiotherapist, County Durham and Darlington NHS Foundation Trust Catherine Thompson, Senior Lecturer, York St John University Dr John White (Chair), Respiratory Physician, York Hospitals NHS Trust ### Section 2—Asthma and disordered breathing Caroline Falconer (Co-Chair), Senior Physiotherapist, Papworth Hospital NHS Foundation Trust Lianne Jongepier, Respiratory Specialist Physiotherapist, Service Lead COPD Team, Primary Care Centre, Colchester Melanie Lincoln (Co-Chair), Team Leader Physiotherapist, Papworth Hospital NHS Foundation Trust Christine Mikelsons, Consultant Respiratory Physiotherapist, Royal Free Hospital Dr Mike Thomas, General Practitioner, Asthma UK Senior Research Fellow, University of Aberdeen Jo Williams, Senior Pulmonary Rehabilitation Specialist Glenfield Hospital, University Hospitals of Leicester NHS Trust ### Section 3—Cystic fibrosis On behalf of the Association of Chartered Physiotherapists in Cystic Fibrosis Penny Agent, Service Lead Physiotherapist, Royal Brompton & Harefield NHS Trust Gillian Davie, Senior I Physiotherapist, Cystic Fibrosis Team, Aberdeen Royal Infirmary Mary Dodd, Consultant Physiotherapist in Cystic Fibrosis, University Hospital of South Manchester NHS Foundation Trust Dr Sarah Elkin, Respiratory Physician, St Mary's Hospital, London Tracey Hughes (Chair), Senior I Physiotherapist, Leeds Regional Adult Cystic Fibrosis Unit, Leeds Teaching Hospitals NHS Trust Margaret MacLeod, Senior I Physiotherapist, Cystic Fibrosis Team, Aberdeen Royal Infirmary Nicola …
Difference of Sagittal Spinopelvic Alignments between Degenerative Spondylolisthesis and Isthmic Spondylolisthesis

Objective The purpose of this study was to analyze the differences of spinopelvic parameters between degenerative spondylolisthesis (DSPL) and isthmic spondylolisthesis (ISPL) patients. Methods Thirty-four patients with DSPL and 19 patients with ISPL were included in this study. Spinopelvic parameters were evaluated on whole spine X-rays in a standing position. The following spinopelvic parameters were measured : pelvic incidence (PI), sacral slope, pelvic tilt (PT), lumbar lordosis (LL), and sagittal vertical axis from C7 plumb line (SVA). The population of patients was compared with a control population of 30 normal and asymptomatic adults. Results There were statistically significant differences in LL (p=0.004) and SVA (p=0.005) between the DSPL and ISPL group. The LL of DSPL (42±13°) was significantly lower than that of the control group (48±11°; p=0.029), but that of ISPL (55±6°) was significantly greater than a control group (p=0.004). The SVA of DSPL (55±49 mm) was greater than that of a control group (<40 mm), but that of ISPL (21±22 mm) was within 40 mm as that of a control group. The PT of DSPL (24±7°) and ISPL (21±7°) was significantly greater than that of a control group (11±6°; p=0.000). Conclusion Both symptomatic DSPL and ISPL patients had a greater PI than that of the asymptomatic control group. In conclusion, DSPL populations are likely to have global sagittal imbalance (high SVA) compared with ISPL populations because of the difference of lumbar lordosis between two groups.
A Validation Metrics Framework for safety-critical software-intensive Systems

As software complexity continues to increase in today's systems of systems, conveyance of stakeholder requirements, development to these requirements, and validation of these requirements has become exceedingly more difficult. Safety-critical software-intensive systems of systems require significant verification to ensure that they function as per requirements. Verification is only one portion of ensuring systems function correctly and is typically a well defined activity for software development. Validation is the other portion of ensuring that software is developed to the customer's satisfaction, however is not so well defined. The traditional validation model of matching system specification to stakeholder requirements and expectations does not cater for software safety, where stakeholder requirements and expectations are simply that of a “safe” system. We introduce a new model for validation of software safety requirements by proxy. Measurement of software safety is a relatively unexplored aspect of software engineering. Proactive validation of software safety requirements necessitates metrics acting as indicators of requirements validity. This paper presents the Validation Metrics Framework, which is based on a new model for validation of software safety requirements. We demonstrate the application of the framework with a representative safety-critical software-intensive system.
Genetic counselor review of genetic test orders in a reference laboratory reduces unnecessary testing

Genetic tests are routinely ordered by health care providers (HCPs) within a wide range of medical specialties. Many providers have limited knowledge or experience with ordering and interpreting genetic tests; thus, test order errors are common. Rigorous review of genetic test orders by genetic counselors (GCs) can provide a direct financial benefit to medical institutions, patients and insurers. GCs at ARUP (Associated Regional University Pathologists) Laboratories routinely perform a preanalytic assessment of complex molecular genetic test orders that includes reviewing clinical and family history information and considering the clinical utility and cost‐effectiveness of ordered tests. GCs contact the ordering institution and/or HCP as needed to collect additional clinical information and confirm the test order or suggest alternative testing based on the provided information. A retrospective review of the GC‐facilitated test changes over a 21‐month period at ARUP laboratories was performed. Approximately 26% of all requests for complex genetic tests assessing germ line mutations were changed following GC review. Testing fees associated with canceled tests were summed to estimate the cost‐savings resulting from GC‐facilitated test reviews. The test review process resulted in an average reduction in charges to the referring institutions of $48,000.00 per month. GC review of genetic test orders for appropriateness and clinical utility reduces healthcare costs to hospitals, insurers, and patients. © 2014 Wiley Periodicals, Inc.
Apolipoprotein E (APOE) genotype has dissociable effects on memory and attentional–executive network function in Alzheimer’s disease

The ε4 allele of the apolipoprotein E (APOE) gene is the major genetic risk factor for Alzheimer’s disease (AD), but limited work has suggested that APOE genotype may modulate disease phenotype. Carriers of the ε4 allele have been reported to have greater medial temporal lobe (MTL) pathology and poorer memory than noncarriers. Less attention has focused on whether there are domains of cognition and neuroanatomical regions more affected in noncarriers. Further, a major potential confound of prior in vivo studies is the possibility of different rates of clinical misdiagnosis for carriers vs. noncarriers. We compared phenotypic differences in cognition and topography of regional cortical atrophy of ε4 carriers (n = 67) vs. noncarriers (n = 24) with mild AD from the Alzheimer’s Disease Neuroimaging Initiative, restricted to those with a cerebrospinal fluid (CSF) molecular profile consistent with AD. Between-group comparisons were made for psychometric tests and morphometric measures of cortical thickness and hippocampal volume. Carriers displayed significantly greater impairment on measures of memory retention, whereas noncarriers were more impaired on tests of working memory, executive control, and lexical access. Consistent with this cognitive dissociation, carriers exhibited greater MTL atrophy, whereas noncarriers had greater frontoparietal atrophy. Performance deficits in particular cognitive domains were associated with disproportionate regional brain atrophy within nodes of cortical networks thought to subserve these cognitive processes. These convergent cognitive and neuroanatomic findings in individuals with a CSF molecular profile consistent with AD support the hypothesis that APOE genotype modulates the clinical phenotype of AD through influence on specific large-scale brain networks.
3D Motion Compensated Tomographic Reconstruction of Coronary Stents from X-ray Rotational Sequence : An Experimental Study

Percutaneous transluminal coronary angioplasty consists in conducting a balloon and a stent through a coronary lesion and deploying the stent by balloon inflation. A coronary stent is a 3D complex mesh hardly visible in X-Ray images. The control of stent deployment is difficult from the 2D projection images inspection although insufficient deployment of the stent may lead to post intervention complications. In previous works, we have proposed a way to improve the clinical control of the intervention in the continuity of the angiographic procedure. We suggest to reconstruct 3D stent images from a set of 2D cone-beam projections acquired in rotational acquisition mode, using a motion compensation technique. In this paper, we investigate the feasibility of this method on coronary stents in-vivo. We first introduce one synthetic realistic case to illustrate the incorrect deployment problematic and control requirements. In-vivo experiments have been carried out on ten pigs, the porcine model is known to get anatomical and physiological similarities with humans. The cross-sectional area and the diameter along the motion compensated reconstructed deployed stent are measured in 3D slices (parallel or orthogonal to the axis of the stent). This feasibility study shows that a three-dimensional stent tomographic reconstruction can be obtained in a conventional interventional suite from a rotational X-ray sequence. So 3D quantitative measurements not available from the actual angiographic procedure are provided to the physician and help him to assess the quality of his intervention.
Effects of voids on quasi-static and tension fatigue behaviour of carbon-fibre composite laminates

The effect of voids on quasi-isotropic carbon-fibre reinforced plastic laminates under quasi-static loading is compared with that under cyclic tension loading. Emphasis is placed on following damage development at the non-crimp fabric ply-level by investigating the influence of voids on damage accumulation, most notably transverse cracking and delamination. Details from experiments include micrographs of voids taken in both scanning-electron and light microscopy, measurements of void content and crack density using light microscopy, and stiffness plots from both quasi-static and cyclic tests. The stiffness results are compared with theoretical predictions accounting for transverse cracks. Voids have a significantly more detrimental effect on the mechanical properties in cyclic loading compared with quasi-static loading. Specifically, the stiffness reduction development, the underlying transverse cracking in layers and the number of cycles to failure are affected. Quality control by only quasi-static testing for void-containing composite materials to be used in components subjected to fatigue cannot therefore be recommended.
Open‐configuration MRI study of femoro‐acetabular impingement

Femoro‐acetabular impingement has been proposed as a causative factor of primary hip osteoarthritis. However, primary osteoarthritis of the hip is infrequent in Japan and other Asian countries, even though the hips of Asians frequently sustain impingement, since the Asian lifestyle commonly requires a larger range of hip motion than the Western lifestyle. Therefore, using open‐configuration MRI, we investigated whether impingement actually occurs during some traditional Japanese hip positions. The hips of 5 healthy Japanese females were examined in 5 sitting postures: 1) sitting straight; 2) bowing while sitting straight; 3) sitting cross‐legged; 4) W‐sitting; and 5) squatting. The impingement point was detected by multiple plane reconstructed (MPR) views along with the acetabular rim depicted circumferentially. Impingement was considered to have occurred when, on MRI, the anterior femoral head‐neck junction approached the acetabular rim and the femoral head was seen to float from the bottom of the acetabulum with the acetabular rim acting as a fulcrum. Impingement was observed in all volunteers in the W‐sitting position, and in 2 of 5 volunteers during squatting. These findings show that impingement occurs frequently during daily Japanese activities. Thus, depending on race, femoro‐acetabular impingement might not always cause primary osteoarthritis of the hip. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1582–1588, 2007
Long-term angiographic follow-up of 169 intracranial berry aneurysms occluded with detachable coils.

PURPOSE To evaluate the stability of aneurysm occlusion at follow-up angiography after endovascular treatment (EVT) with detachable coils in intracranial berry aneurysms. MATERIALS AND METHODS A total of 203 berry aneurysms (< 1.5 cm) were treated with EVT. Follow-up angiography at least 3 months later was performed in 169 cases. RESULTS Complete occlusion of the aneurysm sac and neck was achieved in 148 aneurysms, subtotal occlusion in 18, and incomplete occlusion in three. Recurrence occurred between 3 and 40 months in 20 (14%) of the 148 totally occluded aneurysms. A second treatment was performed in five cases, was scheduled in one, and failed in one. The small neck remnant increased in size but did not require any retreatment in three cases, and the size of the neck remnant remained stable in 10 cases. Remnant regrowth occurred in six of the 18 subtotally occluded aneurysms. A second treatment was performed in three. Of the 169 cases, last follow-up angiography showed total occlusion in 133 cases, subtotal in 30, and incomplete in six. No rebleeding occurred. CONCLUSION A very small recurrence may be observed at the level of the neck of the aneurysm at long-term follow-up angiography despite achieving total occlusion initially with detachable coils.