Abstract
We report NMR experiments on heavily electron-doped Fe-based superconductor in comparison with the results on the parent Fe-based compounds. The typical parent Fe-based compound LaFe(As
1-
x
...′
P
x
′
)O exhibits the re-emergent antiferromagnetic (AFM) order at
x
′ ~ 0.6 (AFM2) separated from the parent AFM order at
x
′ =0 (AFM1). Systematic
31
P-NMR study on Sr
4
Sc
2
O
6
Fe
2
(As
1−
x
P
x
)
2
(SrSc42622), which has local lattice parameters of iron-pnictogen (Fe
Pn
) layer similar to the series of LaFe(As
1−
x
′
/P
x
′
)O, also revealed that the presence of AFM1 order is universal for most of parent Fe-based compounds. In contrast, the static AFM2 order was absent in this series, however, the dynamical low-energy AFM spin fluctuations are enhanced at around
x
~ 0.8, indicating that the onset of the static AFM2 is quite sensitive to the local lattice parameters of Fe
Pn
layer. In order to elucidate the further universality and diversity, we have carried out
77
Se-NMR measurement on Li
x
(NH
3
)
y
Fe
2−
δ
Se
2
(
T
c
= 44 K) in heavily electron-doped regime. Although the spin fluctuations at low energies does not significantly develops upon cooling, the moderate spin fluctuations were extracted at high temperatures from comparison of the temperature (
T
) dependences of Knight shift and nuclear relaxation rate (1/
T
1
T
). We discuss the universality and diversity of the relationship between the
T
c
and the characteristics of the spin fluctuations in the Fe-based compounds from a microscopic point of the NMR measurements.
The burden of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections is unknown in Georgia. This analysis describes the prevalence of hepatitis B and coinfection with HDV and the demographic ...characteristics and risk factors for persons with HBV infection in Georgia.
This is a cross-sectional seroprevalence study.
A cross-sectional, nationwide survey to assess hepatitis B prevalence among the general adult Georgian population (age ≥18 years) was conducted in 2015. Demographic and risk behavior data were collected. Blood specimens were screened for anti–hepatitis B core total antibody (anti-HBc). Anti-HBc–positive specimens were tested for hepatitis B surface antigen (HBsAg). HBsAg-positive specimens were tested for HBV and HDV nucleic acid. Nationally weighted prevalence estimates and adjusted odds ratios (aORs) for potential risk factors were determined for anti-HBc and HBsAg positivity.
The national prevalence of anti-HBc and HBsAg positivity among adults were 25.9% and 2.9%, respectively. Persons aged ≥70 years had the highest anti-HBc positivity (32.7%), but the lowest HBsAg positivity prevalence (1.3%). Anti-HBc positivity was associated with injection drug use (aOR = 2.34; 95% confidence interval CI = 1.46–3.74), receipt of a blood transfusion (aOR = 1.68; 95% CI = 1.32–2.15), and sex with a commercial sex worker (aOR = 1.46; 95% CI = 1.06–2.01). HBsAg positivity was associated with receipt of a blood transfusion (aOR = 2.72; 95% CI = 1.54–4.80) and past incarceration (aOR = 2.72; 95% CI = 1.25–5.93). Among HBsAg-positive persons, 0.9% (95% CI = 0.0–2.0) were HDV coinfected.
Georgia has an intermediate to high burden of hepatitis B, and the prevalence of HDV coinfection among HBV-infected persons is low. Existing infrastructure for hepatitis C elimination could be leveraged to promote hepatitis B elimination.
•Georgia's anti-hepatitis B core total antibody prevalence is 25.9% and hepatitis B surface antigen prevalence is 2.9%.•Risk factors for hepatitis B include injecting drugs, blood transfusion, sex with a commercial sex worker, and incarceration.•Among HBsAg-positive persons, the rate of hepatitis D virus coinfection is low (0.9%).•Georgia's existing hepatitis C elimination infrastructure could be leveraged to facilitate hepatitis B elimination.
Brigatinib is a next-generation tyrosine kinase inhibitor (TKI) targeting ALK and ROS1. The Barossa study is a multicenter, phase II basket study of brigatinib in patients with ROS1-rearranged solid ...tumors. ROS1 TKI-naive patients with ROS1-rearranged non-small-cell lung cancer (NSCLC) were enrolled in cohort 1, and ROS1-rearranged NSCLC patients treated previously with crizotinib were enrolled in cohort 2. Patients with ROS1-rearranged solid tumors other than NSCLC were enrolled in cohort 3.
Eligible patients received brigatinib at the dose of 180 mg once daily with a 7-day lead-in period at 90 mg. The primary endpoint was the objective response rate (RECIST 1.1) assessed by independent central review in cohorts 1 and 2.
Between July 2019 and June 2021, 51 patients were enrolled into the study. Of the 51, 47 patients had ROS1-rearranged NSCLC; 28 and 19 of these patients were enrolled in cohort 1 and cohort 2, respectively. The remaining four patients had other ROS1-rearranged solid tumors, including rectal, brain, and pancreas tumor in one patient each, and primary unknown tumor in one patient. The confirmed objective response rate was 71.4% 95% confidence interval (CI) 51.3% to 86.8% in cohort 1 (TKI-naive NSCLC patients) and 31.6% (95% CI 12.6% to 56.6%) in cohort 2 (NSCLC patients treated previously with crizotinib). The median progression-free survival was 12.0 months (95% CI 5.5-22.9 months) in cohort 1 and 7.3 months (95% CI 1.3-17.5 months) in cohort 2. None of the patients in cohort 3 showed any treatment response. Pneumonitis was observed in 9.8% of all the patients.
Brigatinib was effective in TKI-naive patients with ROS1-rearranged NSCLC. The safety profile of brigatinib was consistent with that reported from previous studies.
•Our study was the first study conducted to evaluate the efficacy of brigatinib in patients with ROS1-rearranged solid tumors.•The objective response rate was 71.4% in ROS1 tyrosine kinase inhibitor-naive non-small-cell lung cancer patients.•The objective response rate was 31.6% in non-small-cell lung cancer patients treated previously with crizotinib.•None of the four patients with ROS1-positive solid tumors other than non-small-cell lung cancer showed any treatment response.
Recent studies have indicated that prostate cancer patients with the TMPRSS2-ERG gene fusion have a higher risk of recurrence. To identify markers associated with TMPRSS2-ERG fusion and prognostic of ...biochemical recurrence, we analysed a cohort of 139 men with prostate cancer for 502 molecular markers.
RNA from radical prostatectomy tumour specimens was analysed using cDNA-mediated, annealing, selection, extension and ligation (DASL) to determine mRNAs associated with TMPRSS2-ERG T1/E4 fusion and prognostic of biochemical recurrence. Differentially expressed mRNAs in T1/E4-positive tumours were determined using significance analysis of microarrays (false discovery rate (FDR) <5%). Univariate and multivariate Cox regression determined genes, gene signatures and clinical factors prognostic of recurrence (P-value <0.05, log-rank test). Analysis of two prostate microarray studies (GSE1065 and GSE8402) validated the findings.
In the 139 patients from this study and from a 455-patient Swedish cohort, 15 genes in common were differentially regulated in T1/E4 fusion-positive tumours (FDR <0.05). The most significant mRNAs in both cohorts coded ERG. Nine genes were found prognostic of recurrence in this study and in a 596-patient Minnesota cohort. A molecular recurrence score was significant in prognosticating recurrence (P-value 0.000167) and remained significant in multivariate analysis of a mixed clinical model considering Gleason score and TMPRSS2-ERG fusion status.
TMPRSS2-ERG T1/E4 fusion-positive tumours had differentially regulated mRNAs observed in multiple studies, the most significant one coded for ERG. Several mRNAs were consistently associated with biochemical recurrence and have potential clinical utility but will require further validation for successful translation.
Formalin-fixed, paraffin-embedded (FFPE) tumour tissue represents an immense but mainly untapped resource with respect to molecular profiling. The DASL (cDNA-mediated Annealing, Selection, extension, ...and Ligation) assay is a recently described, RT-PCR-based, highly multiplexed high-throughput gene expression platform developed by Illumina specifically for fragmented RNA typically obtained from FFPE specimens, which enables expression profiling. In order to extend the utility of the DASL assay for breast cancer, we have custom designed and validated a 512-gene human breast cancer panel.
The RNA from FFPE breast tumour specimens were analysed using the DASL assay. Breast cancer subtype was defined from pathology immunohistochemical (IHC) staining. Differentially expressed genes between the IHC-defined subtypes were assessed by prediction analysis of microarrays (PAM) and then used in the analysis of two published data sets with clinical outcome data.
Gene expression signatures on our custom breast cancer panel were very reproducible between replicates (average Pearson's R²=0.962) and the 152 genes common to both the standard cancer DASL panel (Illumina) and our breast cancer DASL panel were similarly expressed for samples run on both panels (average R²=0.877). Moreover, expression of ESR1, PGR and ERBB2 corresponded well with their respective pathology-defined IHC status. A 30-gene set indicative of IHC-defined breast cancer subtypes was found to segregate samples based on their subtype in our data sets and published data sets. Furthermore, several of these genes were significantly associated with overall survival (OS) and relapse-free survival (RFS) in these previously published data sets, indicating that they are biomarkers of the different breast cancer subtypes and the prognostic outcomes associated with these subtypes.
We have demonstrated the ability to expression profile degraded RNA transcripts derived from FFPE tissues on the DASL platform. Importantly, we have identified a 30-biomarker gene set that can classify breast cancer into subtypes and have shown that a subset of these markers is prognostic of OS and RFS.
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