Miracle-dz/UniFAR-FTUs huggingface dataset:
Recombinant Isfahan Virus and Vesicular Stomatitis Virus Vaccine Vectors Provide Durable, Multivalent, Single-Dose Protection against Lethal Alphavirus Challenge

ABSTRACT The demonstrated clinical efficacy of a recombinant vesicular stomatitis virus (rVSV) vaccine vector has stimulated the investigation of additional serologically distinct Vesiculovirus vectors as therapeutic and/or prophylactic vaccine vectors to combat emerging viral diseases. Among these viral threats are the encephalitic alphaviruses Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV), which have demonstrated potential for natural disease outbreaks, yet no licensed vaccines are available in the event of an epidemic. Here we report the rescue of recombinant Isfahan virus (rISFV) from genomic cDNA as a potential new vaccine vector platform. The rISFV genome was modified to attenuate virulence and express the VEEV and EEEV E2/E1 surface glycoproteins as vaccine antigens. A single dose of the rISFV vaccine vectors elicited neutralizing antibody responses and protected mice from lethal VEEV and EEEV challenges at 1 month postvaccination as well as lethal VEEV challenge at 8 months postvaccination. A mixture of rISFV vectors expressing the VEEV and EEEV E2/E1 glycoproteins also provided durable, single-dose protection from lethal VEEV and EEEV challenges, demonstrating the potential for a multivalent vaccine formulation. These findings were paralleled in studies with an attenuated form of rVSV expressing the VEEV E2/E1 glycoproteins. Both the rVSV and rISFV vectors were attenuated by using an approach that has demonstrated safety in human trials of an rVSV/HIV-1 vaccine. Vaccines based on either of these vaccine vector platforms may present a safe and effective approach to prevent alphavirus-induced disease in humans. IMPORTANCE This work introduces rISFV as a novel vaccine vector platform that is serologically distinct and phylogenetically distant from VSV. The rISFV vector has been attenuated by an approach used for an rVSV vector that has demonstrated safety in clinical studies. The vaccine potential of the rISFV vector was investigated in a well-established alphavirus disease model. The findings indicate the feasibility of producing a safe, efficacious, multivalent vaccine against the encephalitic alphaviruses VEEV and EEEV, both of which can cause fatal disease. This work also demonstrates the efficacy of an attenuated rVSV vector that has already demonstrated safety and immunogenicity in multiple HIV-1 phase I clinical studies. The absence of serological cross-reactivity between rVSV and rISFV and their phylogenetic divergence within the Vesiculovirus genus indicate potential for two stand-alone vaccine vector platforms that could be used to target multiple bacterial and/or viral agents in successive immunization campaigns or as heterologous prime-boost agents.
Dacryoadenitis with Ptosis and Diplopia as the Initial Presentation of Granulomatosis with Polyangiitis

A 77-year-old Japanese woman presented to an ophthalmologist with an erythematous swollen upper eyelid and diplopia which was initially diagnosed to be idiopathic dacryoadenitis on the basis of a histological evaluation of an orbital mass that was in remission following a 3.5-month period of systemic corticosteroid therapy. She subsequently developed respiratory symptoms, and was finally diagnosed with systemic granulomatosis with polyangiitis (GPA) based on the clinical and histological features. She was successfully treated with corticosteroids and azathioprine. Dacryoadenitis in the form of an orbital inflammatory pseudotumor may be an initial presenting feature of GPA, sometimes as the limited phenotype, and occasionally progressing to systemic disease.
Commissioning and comprehensive evaluation of the ArcCHECK cylindrical diode array for VMAT pretreatment delivery QA

We present commissioning and comprehensive evaluation for ArcCHECK as a QA equipment for volumetric‐modulated arc therapy (VMAT), using the 6 MV photon beam with and without the flattening filter, and the SNC patient software (version 6.2). In addition to commissioning involving absolute dose calibration, array calibration, and PMMA density verification, ArcCHECK was evaluated for its response dependency on linac dose rate, instantaneous dose rate, radiation field size, beam angle, and couch insertion. Scatter dose characterization, consistency and symmetry of response, and dosimetry accuracy evaluation for fixed aperture arcs and clinical VMAT patient plans were also investigated. All the evaluation tests were performed with the central plug inserted and the homogeneous PMMA density value. Results of gamma analysis demonstrated an overall agreement between ArcCHECK‐measured and TPS‐calculated reference doses. The diode based field size dependency was found to be within 0.5% of the reference. The dose rate‐based dependency was well within 1% of the TPS reference, and the angular dependency was found to be ± 3% of the reference, as tested for BEV angles, for both beams. Dosimetry of fixed arcs, using both narrow and wide field widths, resulted in clinically acceptable global gamma passing rates on the 3%/3 mm level and 10% threshold. Dosimetry of narrow arcs showed an improvement over published literature. The clinical VMAT cases demonstrated high level of dosimetry accuracy in gamma passing rates. PACS numbers: 87.56. Fc, 87.55. kh, 87.55. Qr
Do shame and perfectionistic self-presentation explain the link between early affiliative memories and eating psychopathology?

Abstract This study tested a model examining the impact that early affiliative memories (both with family and peers) on eating psychopathology, and whether these links are carried by the mechanisms of external shame and body image-related perfectionistic self-presentation, in a sample of 480 female college students. Path analyses’ results revealed that this model accounted for 48% of disordered eating’s variance and suggests that the lack of early positive emotional memories is associated with higher levels of shame (feelings of inferiority and unattractiveness), and with higher tendency to adopt body image-related perfectionistic strategies, that seem to explain excessive eating concern and rigid control of one’s eating behaviors. This study offers important insights for future research and for the development of intervention programs, by revealing the importance of assessing and targeting shame and perfectionistic strategies and suggesting the importance of promoting adaptive emotion regulation strategies.
How to regress and predict in a Bland–Altman plot? Review and contribution based on tolerance intervals and correlated‐errors‐in‐variables models

Two main methodologies for assessing equivalence in method‐comparison studies are presented separately in the literature. The first one is the well‐known and widely applied Bland–Altman approach with its agreement intervals, where two methods are considered interchangeable if their differences are not clinically significant. The second approach is based on errors‐in‐variables regression in a classical (X,Y) plot and focuses on confidence intervals, whereby two methods are considered equivalent when providing similar measures notwithstanding the random measurement errors. This paper reconciles these two methodologies and shows their similarities and differences using both real data and simulations. A new consistent correlated‐errors‐in‐variables regression is introduced as the errors are shown to be correlated in the Bland–Altman plot. Indeed, the coverage probabilities collapse and the biases soar when this correlation is ignored. Novel tolerance intervals are compared with agreement intervals with or without replicated data, and novel predictive intervals are introduced to predict a single measure in an (X,Y) plot or in a Bland–Atman plot with excellent coverage probabilities. We conclude that the (correlated)‐errors‐in‐variables regressions should not be avoided in method comparison studies, although the Bland–Altman approach is usually applied to avert their complexity. We argue that tolerance or predictive intervals are better alternatives than agreement intervals, and we provide guidelines for practitioners regarding method comparison studies. Copyright © 2016 John Wiley & Sons, Ltd.
Salient Parts based Multi-people Tracking

The saliency of an object or area is the quality to stand out from its neighborhood, it is an important component when we observe objects in the real world. The detection of saliency has been studied for years and has already been applied in many areas. In this paper, salient parts based framework is proposed for multi-people tracking. The framework follows tracking-by-detection approach and performs multi-people tracking from frame to frame. Salient parts are detected inside the human body area by finding high contrasts to their local neighborhood. Short-term tracking of salient parts are applied to help locating targets when the association with detections fails. And supporting models are on-line learnt to indicate the locations of targets based on the tracking results of salient parts. Experiments are carried out on PETS09 and Town Center datasets to validate the proposed method. The experimental result shows the promising performance of the proposed method and comparison with state-of-the-art works is provided.
Congenital Myasthenic Syndromes

By the mid-1970s the autoimmune origin of myasthenia gravis had been well established. Once this feat had been accomplished, it also became apparent that myasthenic disorders occurring in a genetic or congenital setting had a different etiology. As a result, a number of distinct myasthenic syndromes have been recognized and investigated by electrophysiological and ultrastructural methods. The newly recognized disorders are conditioned by divergent causes, such as a failure of acetylcholine resynthesis or packaging, absence of acetylcholinesterase from the neuromuscular junction, abnormal gating properties of the acetylcholine receptor-associated ion channel, or an abnormality in the regulation of the density of acetylcholine receptor molecules in the postsynaptic membrane. These genetic defects either impair neuromuscular transmission directly or result in secondary derangements that eventually compromise the safety margin of neuromuscular transmission. (J Child Neurol 1988;3:233-246).
A pilot randomised controlled trial of the feasibility, acceptability and impact of giving information on personalised genomic risk of melanoma to the public

Personalised ABSTRACT Background: Communication of personalised melanoma genomic risk information may improve melanoma prevention behaviours. Methods: We evaluated the feasibility and acceptability of communicating personalised genomic risk of melanoma to the public, and its preliminary impact on behaviours and psychosocial outcomes. 118 people aged 22-69 years provided a saliva sample and were randomised to the control (non-personalised educational materials), or intervention (personalised booklet presenting melanoma genomic risk as absolute and relative risks and a risk category based on variants in 21 genes, telephone-based genetic counselling, and non-personalised educational materials). Intention-to-treat analyses overall and by risk category were conducted using ANCOVA adjusted for baseline values. Results: Consent to participate was 41%, 99% were successfully genotyped, 92% completed 3-month follow-up. Intervention participants reported high satisfaction with the personalised booklet (mean=8.6, SD=1.6; on a 0-10 scale) and genetic counselling (mean=8.1, SD=2.2). No significant behavioural effects at 3-months follow-up were identified between intervention and control groups overall: objectively-measured standard erythemal doses per day (-16%, 95% confidence interval (CI): -43%, 24%), sun protection index (0.05, 95% CI: -0.07, 0.18). There was increased confidence identifying melanoma at 3-months (0.40, 95% CI: 0.10, 0.69). Stratified by risk category, effect sizes for intentional tanning and some individual sun protection items appeared stronger for the average-risk group. There were no appreciable group differences in skin cancer related worry or psychological distress. Conclusion: Our results demonstrate feasibility and acceptability of providing personalised genomic risk of melanoma to the public. Impact: Genomic risk information has potential as a melanoma prevention strategy.
Dynamics of the IFT machinery at the ciliary tip

Intraflagellar transport (IFT) is essential for the elongation and maintenance of eukaryotic cilia and flagella. Due to the traffic jam of multiple trains at the ciliary tip, how IFT trains are remodeled in these turnaround zones cannot be determined by conventional imaging. Using Photogate, we visualized the full range of movement of single IFT trains and motors in Chlamydomonas flagella. Anterograde trains split apart and IFT complexes mix with each other at the tip to assemble retrograde trains. Dynein-1b is carried to the tip by kinesin-II as inactive cargo on anterograde trains. Unlike dynein-1b, kinesin-II detaches from IFT trains at the tip and diffuses in flagella. As the flagellum grows longer, diffusion delays return of kinesin-II to the basal body, depleting kinesin-II available for anterograde transport. Our results suggest that dissociation of kinesin-II from IFT trains serves as a negative feedback mechanism that facilitates flagellar length control in Chlamydomonas.
Evolutionary radiation of lanthipeptides in marine cyanobacteria

Significance Lanthipeptides are a large family of microbial natural products of ribosomal origin. Prochlorosins are a group of unusually diverse lanthipeptides found in strains of the marine cyanobacteria Prochlorococcus and Synechococcus—the most abundant photosynthetic microorganisms on Earth. By analyzing the prochlorosin biosynthesis genes from cultured strains and wild cyanobacteria, we show that the global collective of these microorganisms has evolved thousands of structurally distinct lanthipeptides via a process of evolutionary radiation favoring the sustained emergence of new structures over refinement of an existing one. The evolutionary history of prochlorosins suggests a fundamentally different structure-to-function relationship compared with other lanthipeptides and opens the question of how structural diversification contributes to their function and mode of action in the marine environment. Lanthipeptides are ribosomally derived peptide secondary metabolites that undergo extensive posttranslational modification. Prochlorosins are a group of lanthipeptides produced by certain strains of the ubiquitous marine picocyanobacteria Prochlorococcus and Synechococcus. Unlike other lanthipeptide-producing bacteria, picocyanobacteria use an unprecedented mechanism of substrate promiscuity for the production of numerous and diverse lanthipeptides using a single lanthionine synthetase. Through a cross-scale analysis of prochlorosin biosynthesis genes—from genomes to oceanic populations—we show that marine picocyanobacteria have the collective capacity to encode thousands of different cyclic peptides, few of which would display similar ring topologies. To understand how this extensive structural diversity arises, we used deep sequencing of wild populations to reveal genetic variation patterns in prochlorosin genes. We present evidence that structural variability among prochlorosins is the result of a diversifying selection process that favors large, rather than small, sequence changes in the precursor peptide genes. This mode of molecular evolution disregards any conservation of the ancestral structure and enables the emergence of extensively different cyclic peptides through short mutational paths based on indels. Contrary to its fast-evolving peptide substrates, the prochlorosin lanthionine synthetase evolves under a strong purifying selection, indicating that the diversification of prochlorosins is not constrained by commensurate changes in the biosynthetic enzyme. This evolutionary interplay between the prochlorosin peptide substrates and the lanthionine synthetase suggests that structure diversification, rather than structure refinement, is the driving force behind the creation of new prochlorosin structures and represents an intriguing mechanism by which natural product diversity arises.
Reconstruction and Recognition of Tensor-Based Objects With Concurrent Subspaces Analysis

Principal components analysis (PCA) has traditionally been utilized with data expressed in the form of 1-D vectors, but there exists much data such as gray-level images, video sequences, Gabor-filtered images and so on, that are intrinsically in the form of second or higher order tensors. For representations of image objects in their intrinsic form and order rather than concatenating all the object data into a single vector, we propose in this paper a new optimal object reconstruction criterion with which the information of a high-dimensional tensor is represented as a much lower dimensional tensor computed from projections to multiple concurrent subspaces. In each of these subspaces, correlations with respect to one of the tensor dimensions are reduced, enabling better object reconstruction performance. Concurrent subspaces analysis (CSA) is presented to efficiently learn these subspaces in an iterative manner. In contrast to techniques such as PCA which vectorize tensor data, CSA's direct use of data in tensor form brings an enhanced ability to learn a representative subspace and an increased number of available projection directions. These properties enable CSA to outperform traditional algorithms in the common case of small sample sizes, where CSA can be effective even with only a single sample per class. Extensive experiments on images of faces and digital numbers encoded as second or third order tensors demonstrate that the proposed CSA outperforms PCA-based algorithms in object reconstruction and object recognition.
Anatomic variation of prescription points and treatment volume with fractionated high‐dose rate gynecological brachytherapy

The purpose of this report is to evaluate the geometric movement (relative to the bony pelvis) and dose variation of brachytherapy reference points in the same patient at repeated high‐dose rate (HDR) intracavitary implants. A study was also concluded to find the variation in treatment volume from repeated fractions. Twenty‐five consecutive cervical cancer patients (all stages) treated with external beam and fractionated HDR intracavitary implants at the University of Wisconsin were reviewed. Each brachytherapy insertion had a different plan generated prior to treatment delivery. ICRU #38 prescription points (A, B, P, bladder, and rectum) were used. Dose volume histogram was generated and treated volume to the prescription dose was recorded for each fraction. Motion analysis of the various points (from a common origin) in subsequent fractions relative to the first fraction revealed a shift of 2–9 mm in a single plane. Vector analysis revealed the magnitude of the average shift ranged from 10–13 mm. These shifts resulted in a dose difference of >20% for the bladder and rectum points, but < than 8% for the other points. Dose volume histograms revealed that with the change in the anatomy of the cervix and upper vagina during a patient's course of treatment, the treatment volume changes considerably. Thirty‐six percent of all patients (9/16) had a reduction in the size of the ovoid during the treatment course. Sixty percent of all patients (15/25) had volume changes <10%. Sixty‐two and one half percent of patients (10/16) who did not undergo a reduction of avoid size during the entire course of the treatment had volume change <10%. Since there is a change in the anatomy of the cervix and upper vagina during the course of a treatment along with the irre‐producibility of the packing, there is movement of the absolute position of the prescription points between fractions, thus emphasizing the importance of individual dosimetry. Moreover, due to the same reasons, there are significant changes in the treatment volume among implants for the same patient. Volume reduction caused by reduction in ovoid size alone could not be extracted from this study. PACS number(s): 87.53. –j
Development of real‐time motion verification system using in‐room optical images for respiratory‐gated radiotherapy

Phase‐based respiratory‐gated radiotherapy relies on the reproducibility of patient breathing during the treatment. To monitor the positional reproducibility of patient breathing against a 4D CT simulation, we developed a real‐time motion verification system (RMVS) using an optical tracking technology. The system in the treatment room was integrated with a real‐time position management system. To test the system, an anthropomorphic phantom that was mounted on a motion platform moved on a programmed breathing pattern and then underwent a 4D CT simulation with RPM. The phase‐resolved anterior surface lines were extracted from the 4D CT data to constitute 4D reference lines. In the treatment room, three infrared reflective markers were attached on the superior, middle, and inferior parts of the phantom along with the body midline and then RMVS could track those markers using an optical camera system. The real‐time phase information extracted from RPM was delivered to RMVS via in‐house network software. Thus, the real‐time anterior‐posterior positions of the markers were simultaneously compared with the 4D reference lines. The technical feasibility of RMVS was evaluated by repeating the above procedure under several scenarios such as ideal case (with identical motion parameters between simulation and treatment), cycle change, baseline shift, displacement change, and breathing type changes (abdominal or chest breathing). The system capability for operating under irregular breathing was also investigated using real patient data. The evaluation results showed that RMVS has a competence to detect phase‐matching errors between patient's motion during the treatment and 4D CT simulation. Thus, we concluded that RMVS could be used as an online quality assurance tool for phase‐based gating treatments. PACS number: 87.55. Qr
A prospective study of parentally bereaved youth, caregiver depression, and body mass index.

OBJECTIVE To examine the relationship between body mass index (BMI) in bereaved youth and nonbereaved controls 5 years after a parent's death. The study was conducted from August 9, 2002, through December 31, 2013. DESIGN A prospective, longitudinal, controlled study of the effects of sudden parental death on youth. SETTING Bereaved families were recruited through coroner records and by advertisement. Nonbereaved families were recruited using random-digit dialing and by advertisement. PARTICIPANTS 123 parentally bereaved offspring were compared with 122 nonbereaved control offspring, all of whom were aged 11-25 years at the 5-year assessment. MAIN EXPOSURE Bereavement status, type of parental death (accident, suicide, or sudden natural death), and history of depression in caregivers prior to parental death. OUTCOME MEASURES BMI categories (normal, overweight, and obese), according to International Obesity Task Force guidelines for adults and Centers for Disease Control and Prevention guidelines for children, and DSM-IV psychiatric disorder in offspring and caregivers before and after time of parental death. RESULTS Bereaved offspring were more likely to have a BMI in the obese range compared to nonbereaved controls (χ2(2) = 7.13, P < . 01). There were no differences in BMI category by death type among bereaved offspring. Caregiver history of depression was a significant correlate of offspring obesity in nonbereaved youth but had a protective effect on the BMI of bereaved youth. CONCLUSIONS Bereaved youth were more likely to be obese than nonbereaved youth 5 years after parental death, and caregiver history of depression was associated with increased risk for obesity in nonbereaved youth only. Future studies are necessary to identify mechanisms that increase risk for obesity in parentally bereaved youth.