Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with ...sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.5 and 6.0 months, respectively. Safety outcomes between cohorts were comparable. The prior BCMA-TT cohort had a lower overall response rate (74% versus 88%; p = 0.021), median duration of response (7.4 versus 9.6 months; p = 0.03), and median progression-free survival (3.2 months versus 9.0 months; p = 0.0002) compared to the cohort without prior BCMA-TT. All five patients who received a prior anti-BCMA CAR T responded to ide-cel, and survival outcomes were best for this subgroup. In conclusion, treatment with ide-cel yielded meaningful clinical responses in real-world patients exposed to a prior BCMA-TT, though response rates and durability were suboptimal compared to those not treated with a prior BCMA-TT.
Crimean-Congo haemorrhagic fever (CCHF) is the most prevalent human tick-borne viral disease, endemic to the Balkans, Africa, Middle East and Asia. There are currently no licensed vaccines or ...effective antivirals against CCHF. CCHF virus (CCHFV) has a negative sense segmented tripartite RNA genome consisting of the small (S), medium (M) and large (L) segments. Depending on the segment utilised for genetic affiliation, there are up to 7 circulating lineages of CCHFV. The current lack of geographical representation of CCHFV sequences in various repositories highlights a requirement for increased CCHFV sequencing capabilities in endemic regions.
We have optimised and established a multiplex PCR tiling methodology for the targeted enrichment of complete genomes of Europe 1 CCHFV lineage directly from clinical samples and compared its performance to a non-targeted enrichment approach on both short-read and long-read sequencing platforms.
We have found a statistically significant increase in mapped viral sequencing reads produced with our targeted enrichment approach. This has allowed us to recover near complete S segment sequences and above 90% of the M and L segment sequences for samples with Ct values as high as 31.3. This study demonstrates the superiority of a targeted enrichment approach for recovery of CCHFV genomic sequences from samples with low virus titre.
CCHFV is an important vector-borne human pathogen with wide geographical distribution. The validated methodology reported here adds value to front-line public health laboratories employing genomic sequencing for CCHFV Europe 1 lineage surveillance, particularly in the Balkan and Middle Eastern territories currently monitoring the spread of the pathogen. Tracking the genomic evolution of the virus across regions improves risk assessment and directly informs the development of diagnostics, therapeutics, and vaccines.
•A tiling, multiplex PCR enrichment strategy has been adapted to Crimean-Congo haemorrhagic fever virus and validated against a panel of clinical samples.•With a targeted, multiplex PCR tiling enrichment strategy, recovery of near-complete CCHFV genome sequences was possible from samples with low viraemia.•A statistically significant increase in number of mapped viral sequencing reads was produced with our targeted enrichment methodology compared to a non-targeted, random enrichment approach.•The presented methodology produced comparable results between short-read (Illumina) and long-read (Oxford Nanopore Technologies) sequencing data, and is amenable to both platforms.
Optimal vaccine dosing is important to ensure the greatest protection and safety. Analysis of dose-response data, from previous studies, may inform future studies to determine the optimal dose. ...Implementing more quantitative modelling approaches in vaccine dose finding have been recently suggested to accelerate vaccine development. Adenoviral vectored vaccines are in advanced stage of development for a variety of prophylactic and therapeutic indications, however dose-response has not yet been systematically determined. To further inform adenoviral vectored vaccines dose identification, historical dose-response data should be systematically reviewed. A systematic literature review was conducted to collate and describe the available dose-response studies for adenovirus vectored vaccines. Of 2787 papers identified by Medline search strategy, 35 were found to conform to pre-defined criteria. The majority of studies were in mice or humans and studied adenovirus serotype 5. Dose-response data were available for 12 different immunological responses. The majority of papers evaluated three dose levels, only two evaluated more than five dose levels. The most common dosing range was 10
-10
viral particles in mouse studies and 10
-10
viral particles in human studies. Data were available on adenovirus vaccine dose-response, primarily on adenovirus serotype 5 backbones and in mice and humans. These data could be used for quantitative adenoviral vectored vaccine dose optimisation analysis.
Crimean-Congo Haemorrhagic fever Virus (CCHFV) is a rapidly emerging vector-borne pathogen and the cause of a virulent haemorrhagic fever affecting large parts of Europe, Africa, the Middle East and ...Asia.
An isothermal recombinase polymerase amplification (RPA) assay was successfully developed for molecular detection of CCHFV. The assay showed rapid (under 10 minutes) detection of viral extracts/synthetic virus RNA of all 7 S-segment clades of CCHFV, with high target specificity. The assay was shown to tolerate the presence of inhibitors in crude preparations of mock field samples, indicating that this assay may be suitable for use in the field with minimal sample preparation. The CCHFV RPA was successfully used to screen and detect CCHFV positives from a panel of clinical samples from Tajikistan.
The assay is a rapid, isothermal, simple-to-perform molecular diagnostic, which can be performed on a light, portable real-time detection device. It is ideally placed therefore for use as a field-diagnostic or in-low resource laboratories, for monitoring of CCHF outbreaks at the point-of-need, such as in remote rural regions in affected countries.
This research was aimed at assessing the relationship between the follicular fluid (FF) antioxidants activity, aging and
fertilization (IVF) outcome.
The present cross-sectional study was carried out ...on 65 women undergoing IVF/intracytoplasmic sperm injection (IVF/ICSI) cycles due to unexplained infertility. Ovarian stimulation was performed using the long gonadotropin-releasing hormone (GnRH) agonist protocol. After ovum pickup, FF was collected and processed to measure the level of superoxide dismutase (SOD), catalase (CAT) activity, total antioxidant capacity (TAC) and glutathione (GSH). Day 3 after ICSI, fresh embryos were transferred and later, possible pregnancy was assessed. Patients participating in this study were divided into four groups on the basis of age and pregnancy outcome.
SOD activity was not significantly different between the groups (P=0.218). GSH in the group whose participants were aged ≤35 years and were pregnant was higher than that in other groups. CAT activity in groups with younger participants was higher compared to the other groups. The mean TAC was higher in groups with pregnant participants compared to the non-pregnant women. Correlation analysis showed that: GSH level had a significant negative correlation with age (P<0.001, R -0.55) and a significant positive correlation with pregnancy (P=0.015, R=0.30). CAT level also had a significant negative correlation with age (P<0.001, R=-0.42) and the level of TAC had a significant positive correlation with pregnancy (P<0.001, R=0.59).
According to our results, the levels of TAC, GSH and CAT in younger and pregnant women were higher compared with those undergoing ICSI cycles. Given the correlation of FF antioxidant activity with age and pregnancy, it is necessary to carry out more research on these compounds and the maintenance of pregnancy.
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•T1-T2* measurement permits speciation of different spin populations when a T1-T2 measurement is impossible.•Tracking the T1-T2* coordinate, and associated intensity may reveal ...structural changes.•The T1-T2* measurement permits a simple assignment of T1 to different T2* populations.•The T1-T2* measurement will permit discrimination solid-like species in mixtures.
The majority of low field Magnetic Resonance (MR) analyses rely on T2 lifetime measurements. Modification of the T2 measurement to include a T1 dimension has made the T1-T2 measurement a very powerful analytical technique. The T1-T2 measurement is uniquely well suited to characterization of different spin populations in porous materials, such as fluid bearing reservoir rocks, and in soft biopolymer materials, for example foods. However, the T1-T2 measurement is challenging or impossible if the T2 relaxation lifetime, or a component lifetime, is short-lived and the signal unobservable in an echo measurement. This occurs in many important classes of materials. A short lifetime T2 will not however, in general, preclude observation of a free induction decay with signal decay governed by T2*.
As outlined in this paper a T1-T2* measurement is a useful analog to the T1-T2 experiment. T1-T2* measurement enables one to differentiate species as a function of T2* in one dimension and T1 in the other dimension. Monitoring changes of the T1-T2* coordinate, and associated signal intensity changes, has the potential to reveal structural changes in materials evolving in time. These methods may also be employed to discriminate and identify solid-like species present in static samples.
The T1-T2* measurement is very general in application, but in this paper we focus on cement-based mortars to develop and illustrate the essential ideas. T1-T2* results show a multi-modal behaviour of the MR signal lifetimes, T1 and T2*, in mortar samples under study, indicating at least two different water populations. The short T2* lifetime was assigned to interlayer water (water between C–S–H layers) where the associated T1 is also short lived. The longer T2* lifetime was assigned to water in the pore space, where T1 is also longer lived. In addition to mortar samples we also show application of the method to a crystalline organic species, o-phenylenediamine, which features Sinc Gaussian and exponential decays of transverse magnetization.
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