Dynamic imaging using Motion-Compensated SmooThness Regularization on Manifolds (MoCo-SToRM)

We introduce an unsupervised motion-compensated reconstruction scheme for high-resolution free-breathing pulmonary MRI. We model the image frames in the time series as the deformed version of the 3D template image volume. We assume the deformation maps to be points on a smooth manifold in high-dimensional space. Specifically, we model the deformation map at each time instant as the output of a CNN-based generator that has the same weight for all time-frames, driven by a low-dimensional latent vector. The time series of latent vectors account for the dynamics in the dataset, including respiratory motion and bulk motion. The template image volume, the parameters of the generator, and the latent vectors are learned directly from the k-t space data in an unsupervised fashion. Our experimental results show improved reconstructions compared to state-of-the-art methods, especially in the context of bulk motion during the scans

Long-term efficacy of dupilumab in severe asthma by baseline oral corticosteroid dose

FUNDING Regeneron Pharmaceuticals NCT0213402; NCT02528214 Sanofi NCT0213402; NCT02528214Peer reviewedPublisher PD

Long-term efficacy of dupilumab in severe asthma by baseline oral corticosteroid dose

Dupilumab has been shown to improve clinical outcomes long term while reducing oral corticosteroid (OCS) dose in patients with severe OCS-dependent asthma. This post hoc analysis assesses the impact of OCS dose at baseline (≤10 o

Dupilumab reduces OCS use and improves lung function in patients with severe OCS-dependent asthma

Peer reviewedPostprin

Sustained Improvement in Clinical Efficacy, Asthma Control, and Quality of Life in Patients With Severe, Oral Corticosteroid (OCS)-Dependent Asthma Treated With Dupilumab : LIBERTY ASTHMA TRAVERSE Study

Acknowledgments and funding sources Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifiers: NCT02528214 (VENTURE)/NCT02134028 (TRAVERSE). Medical writing/editorial assistance was provided by Nevena Krstić, PhD, of Excerpta Medica, and was funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice guideline.Peer reviewedPostprin

Dupilumab Treatment Leads to Sustained Reductions in Oral Corticosteroid Use in Patients With Oral Corticosteroid-Dependent Severe Asthma

Acknowledgments and funding sources Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifiers: NCT02528214 (VENTURE)/NCT02134028 (TRAVERSE). Medical writing/editorial assistance was provided by Éilis Sutton, PhD, of Excerpta Medica, and was funded by Sanofi and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice guideline.Peer reviewe

Health-related quality of life impairment among patients with severe chronic rhinosinusitis with nasal polyps in the SINUS-24 trial

Purpose: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease with a high symptom burden. Data are lacking on the comparative health status of patients with CRSwNP. This analysis compared baseline physical and mental health-related quality of life (HRQoL) and overall health status of patients with severe CRSwNP enrolled in a Phase 3 clinical trial with general population norms and with other chronic diseases. Methods: In this post hoc cross-sectional analysis of baseline data from the SINUS-24 study (NCT02912468), HRQoL was measured using the 36-item Short Form (SF-36) questionnaire and general health status was measured using the EuroQol-5 Dimension visual analog scale (EQ-VAS). Analyses included the intention-to-treat (ITT) population and subgroups defined by prior sinonasal surgery, systemic corticosteroid use, and coexisting asthma or non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD). Scores were compared with published values for population norms (50 for SF-36 physical component summary (PCS) and mental component summary (MCS), 70.4−83.3 for EQ-VAS) and for rheumatoid arthritis, type 2 diabetes, and asthma. Results: In the ITT population (n=276), mean SF-36 physical component summary (PCS), SF-36 mental component summary (MCS), and EQ-VAS scores were below general population norms (46.4, 48.6, and 66.0, respectively). Mean SF-36 PCS and EQ-VAS scores were below population norms across all subgroups; mean SF-36 MCS scores were below the population norm in all subgroups except no prior surgery. SF-36 PCS and MCS scores from SINUS-24 were generally similar to other chronic diseases, except SF-36 PCS which was lower in rheumatoid arthritis. EQ-VAS scores in SINUS-24 were lower than in other chronic diseases. HRQoL scores weakly correlated with objective measures of disease severity. Conclusion: In patients with severe CRSwNP, including those with coexisting asthma/NSAID-ERD, HRQoL was worse than population norms and as burdensome as diseases such as type 2 diabetes, asthma, and rheumatoid arthritis

Whole Genomes of Chandipura Virus Isolates and Comparative Analysis with Other Rhabdoviruses

The Chandipura virus (CHPV) belonging to the Vesiculovirus genus and Rhabdoviridae family, has recently been associated with a number of encephalitis epidemics, with high mortality in children, in different parts of India. No full length genome sequences of CHPV isolates were available in GenBank and little is known about the molecular markers for pathogenesis. In the present study, we provide the complete genomic sequences of four isolates from epidemics during 2003–2007. These sequences along with the deduced sequence of the prototype isolate of 1965 were analysed using phylogeny, motif search, homology modeling and epitope prediction methods. Comparison with other rhaboviruses was also done for functional extrapolations. All CHPV isolates clustered with the Isfahan virus and maintained several functional motifs of other rhabdoviruses. A notable difference with the prototype vesiculovirus, Vesicular Stomatitis Virus was in the L-domain flanking sequences of the M protein that are known to be crucial for interaction with host proteins. With respect to the prototype isolate, significant additional mutations were acquired in the 2003–2007 isolates. Several mutations in G mapped onto probable antigenic sites. A mutation in N mapped onto regions crucial for N-N interaction and a putative T-cell epitope. A mutation in the Casein kinase II phosphorylation site in P may attribute to increased rates of phosphorylation. Gene junction comparison revealed changes in the M-G junction of all the epidemic isolates that may have implications on read-through and gene transcription levels. The study can form the basis for further experimental verification and provide additional insights into the virulence determinants of the CHPV