Electron localization and possible phase separation in the absence of a charge density wave in single-phase 1T-VS2_2

We report on a systematic study of the structural, magnetic and transport properties of high-purity 1T-VS$_2$ powder samples prepared under high pressure. The results differ notably from those previously obtained by de-intercalating Li from LiVS$_2$. First, no Charge Density Wave (CDW) is found by transmission electron microscopy down to 94 K. Though, \textit{ab initio} phonon calculations unveil a latent CDW instability driven by an acoustic phonon softening at the wave vector ${\bf q}_{CDW} \approx$ (0.21,0.21,0) previously reported in de-intercalated samples. A further indication of latent lattice instability is given by an anomalous expansion of the V-S bond distance at low temperature. Second, infrared optical absorption and electrical resistivity measurements give evidence of non metallic properties, consistent with the observation of no CDW phase. On the other hand, magnetic susceptibility and NMR data suggest the coexistence of localized moments with metallic carriers, in agreement with \textit{ab initio} band structure calculations. This discrepancy is reconciled by a picture of electron localization induced by disorder or electronic correlations leading to a phase separation of metallic and non-metallic domains in the nm scale. We conclude that 1T-VS$_2$ is at the verge of a CDW transition and suggest that residual electronic doping in Li de-intercalated samples stabilizes a uniform CDW phase with metallic properties.Comment: 22 pages, 10 Figures. Full resolution pictures available at http://journals.aps.org/prb/abstract/10.1103/PhysRevB.89.23512

Baseline total metabolic tumor volume is prognostic for refractoriness to Iimunochemotherapy in DLBCL: results from GOYA

Introduction A good response to initial therapy is key to maximizing survival in patients with diffuse large B-cell lymphoma (DLBCL), but patients with chemorefractory disease and early progression have poor outcomes. Patients and Methods Data from the GOYA study in patients with DLBCL who received first-line rituximab or obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were analyzed. Positron emission tomography/computed tomography (PET/CT)-derived characteristics associated with total metabolic tumor volume (TMTV) and clinical risk factors for primary chemorefractory disease and disease progression within 12 months (POD12) were explored. Results Of those patients fulfilling the criteria for analysis, 108/1126 (10%) were primary chemorefractory and 147/1106 (13%) had POD12. Primary chemorefractory and POD12 status were strongly associated with reduced overall survival. After multivariable analysis of clinical and imaging-based risk factors by backward elimination, only very high TMTV (quartile [Q] 1 vs. Q4 odds ratio [OR]: 0.45; P = .006) and serum albumin levels (low vs. normal OR of 1.86; P = .004) were associated with primary chemorefractoriness. After additionally accounting for BCL2/MYC translocation in a subset of patients, TMTV and BCL2/MYC double-hit status remained as significant predictors of primary chemorefractoriness (Q1 vs. Q4 OR: 0.32, P = .01 and double-hit vs. no-hit OR of 4.47, P = .02, respectively). Risk factors including very high TMTV, high sum of the product of the longest diameters (SPD), geographic region (Asia), short time since diagnosis, extranodal involvement and low serum albumin were retained for POD12. Conclusion PET-derived TMTV has prognostic value in identifying patients at risk of early treatment failure

Integration of cell of origin into the clinical CNS International Prognostic Index improves CNS relapse prediction in DLBCL

Central nervous system (CNS) relapse carries a poor prognosis in diffuse large B-cell lymphoma (DLBCL). Integrating biomarkers into the CNS-International Prognostic Index (CNS-IPI) risk model may improve identification of patients at high risk for developing secondary CNS disease. CNS relapse was analyzed in 1418 DLBCL patients treated with obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy in the phase 3 GOYA study. Cell of origin (COO) was assessed using gene-expression profiling. BCL2 and MYC protein expression was analyzed by immunohistochemistry. The impact of CNS-IPI, COO, and BCL2/MYC dual-expression status on CNS relapse was assessed using a multivariate Cox regression model (data available in n = 1418, n = 933, and n = 688, respectively). High CNS-IPI score (hazard ratio [HR], 4.0; 95% confidence interval [CI], 1.3-12.3; P = .02) and activated B-cell\u2012like (ABC) (HR, 5.2; 95% CI, 2.1-12.9; P = .0004) or unclassified COO subtypes (HR, 4.2; 95% CI, 1.5-11.7; P = .006) were independently associated with CNS relapse. BCL2/MYC dual-expression status did not impact CNS relapse risk. Three risk subgroups were identified based on the presence of high CNS-IPI score and/or ABC/unclassified COO (CNS-IPI-C model): low risk (no risk factors, n = 450 [48.2%]), intermediate risk (1 factor, n = 408 [43.7%]), and high risk (both factors, n = 75 [8.0%]). Two-year CNS relapse rates were 0.5%, 4.4%, and 15.2% in the respective risk subgroups. Combining high CNS-IPI and ABC/unclassified COO improved CNS relapse prediction and identified a patient subgroup at high risk for developing CNS relapse. The study was registered at www.clinicaltrials.gov as #NCT01287741

The Candida genome database incorporates multiple Candida species: multispecies search and analysis tools with curated gene and protein information for Candida albicans and Candida glabrata

The Candida Genome Database (CGD, http://www.candidagenome.org/) is an internet-based resource that provides centralized access to genomic sequence data and manually curated functional information about genes and proteins of the fungal pathogen Candida albicans and other Candida species. As the scope of Candida research, and the number of sequenced strains and related species, has grown in recent years, the need for expanded genomic resources has also grown. To answer this need, CGD has expanded beyond storing data solely for C. albicans, now integrating data from multiple species. Herein we describe the incorporation of this multispecies information, which includes curated gene information and the reference sequence for C. glabrata, as well as orthology relationships that interconnect Locus Summary pages, allowing easy navigation between genes of C. albicans and C. glabrata. These orthology relationships are also used to predict GO annotations of their products. We have also added protein information pages that display domains, structural information and physicochemical properties; bibliographic pages highlighting important topic areas in Candida biology; and a laboratory strain lineage page that describes the lineage of commonly used laboratory strains. All of these data are freely available at http://www.candidagenome.org/. We welcome feedback from the research community at [email protected]

Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

Individualising biologic disease-modifying anti-rheumatic drugs (bDMARDs) to maximise outcomes and deliver safe and cost-effective care is a key goal in the management of rheumatoid arthritis (RA). Investigation to identify predictive tools of bDMARD response is a highly active and prolific area of research. In addition to clinical phenotyping, cellular and molecular characterisation of synovial tissue and blood in patients with RA, using different technologies, can facilitate predictive testing. This narrative review will summarise the literature for the available bDMARD classes and focus on where progress has been made. We will also look ahead and consider the increasing use of ‘omics’ technologies, the potential they hold as well as the challenges, and what is needed in the future to fully realise our ambition of personalised bDMARD treatment

Using RNA-seq to determine the transcriptional landscape and the hypoxic response of the pathogenic yeast Candida parapsilosis

<p>Abstract</p> <p>Background</p> <p><it>Candida parapsilosis </it>is one of the most common causes of <it>Candida </it>infection worldwide. However, the genome sequence annotation was made without experimental validation and little is known about the transcriptional landscape. The transcriptional response of <it>C. parapsilosis </it>to hypoxic (low oxygen) conditions, such as those encountered in the host, is also relatively unexplored.</p> <p>Results</p> <p>We used next generation sequencing (RNA-seq) to determine the transcriptional profile of <it>C. parapsilosis </it>growing in several conditions including different media, temperatures and oxygen concentrations. We identified 395 novel protein-coding sequences that had not previously been annotated. We removed > 300 unsupported gene models, and corrected approximately 900. We mapped the 5' and 3' UTR for thousands of genes. We also identified 422 introns, including two introns in the 3' UTR of one gene. This is the first report of 3' UTR introns in the Saccharomycotina. Comparing the introns in coding sequences with other species shows that small numbers have been gained and lost throughout evolution. Our analysis also identified a number of novel transcriptional active regions (nTARs). We used both RNA-seq and microarray analysis to determine the transcriptional profile of cells grown in normoxic and hypoxic conditions in rich media, and we showed that there was a high correlation between the approaches. We also generated a knockout of the <it>UPC2 </it>transcriptional regulator, and we found that similar to <it>C. albicans</it>, Upc2 is required for conferring resistance to azole drugs, and for regulation of expression of the ergosterol pathway in hypoxia.</p> <p>Conclusion</p> <p>We provide the first detailed annotation of the <it>C. parapsilosis </it>genome, based on gene predictions and transcriptional analysis. We identified a number of novel ORFs and other transcribed regions, and detected transcripts from approximately 90% of the annotated protein coding genes. We found that the transcription factor Upc2 role has a conserved role as a major regulator of the hypoxic response in <it>C. parapsilosis </it>and <it>C. albicans</it>.</p

Arthritis in primary Sjögren&#039;s syndrome: Characteristics, outcome and treatment from French multicenter retrospective study

Objective To describe the characteristics and the outcome of primary Sjögren Syndrome (pSS) associated arthritis and to compare the efficacy of different therapeutic regimen. Methods We conducted a retrospective study using Club Rhumatisme and Inflammation (CRI) and French Internal Medicine Society (SNFMI) networks. All patients with a diagnosis of pSS and at least one episode of clinical and/or echographic synovitis were included. Patients with synovitis (cases) were compared to pSS patients without synovitis (controls). Results 57 patients (93% women) were included with a median age of 54 years [45–63]. Patients with synovitis had more frequently lymph node enlargement (12.3% vs. 1.8%, p = .007) and a higher ESSDAI score (8 [6–12] vs. 2 [1–4], p &lt; .0001). There was no difference concerning CRP levels, rheumatoid factor and cyclic citrullinated peptide (CCP)-antibodies positivity. Among 57 patients with synovitis, 101 various treatment courses have been used during the follow-up of 40 [22.5–77] months. First treatment course consisted in steroids alone (3.5%), steroids in association (79%) with hydroxychloroquine (HCQ) (49%), methotrexate (MTX) (35%), rituximab (RTX) (5.3%) or other immunosuppressive drugs (7%). HCQ, MTX, and RTX were associated with a significant reduction of tender and swollen joint count, and a significant steroids-sparing effect. No difference could be shown for the joint response between these treatment regimens. Conclusion pSS articular manifestations may include synovitis which could mimic rheumatoid arthritis but differ by the absence of structural damage. Even if the use of HCQ, MTX, and RTX seem to be effective for joint involvement, the best regimen remains to be determined

Pathway of Toll-Like Receptor 7/B Cell Activating Factor/B Cell Activating Factor Receptor Plays a Role in Immune Thrombocytopenia In Vivo

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by anti-platelet autoantibody-mediated platelet destruction. Antigen-presenting cell (APC) dysfunction is considered to play crucial roles in ITP. However, how APC affects autoreactive B cells in ITP is still unknown. Using a mouse model of immune thrombocytopenia, we demonstrated an increase in levels of TLR7 in splenic mononuclear cells (SMCs). Using both TLR7 agonist and TLR7 silencing lentivirus, we found stimulation of TLR7 decreased platelet counts and increased levels of platelet-associated IgG (PAIgG) in ITP mice, which correlates TLR7 with platelet destruction by autoantibodies. Levels of serum BAFF increased significantly in ITP mice and stimulation of TLR7 promoted secretion of BAFF. Among the three BAFF receptors, only BAFF receptor (BAFF-R) increased in ITP mice. However, activation of TLR7 showed no effect on the expression of BAFF receptors. These findings indicate that upregulation of TLR7 may augment BAFF secretion by APC and through ligation of BAFF-R promote autoreactive B cell survival and thus anti-platelet autoantibody production. The pathway of TLR7/BAFF/BAFF-R provides us with an explanation of how activation of APC affects autoantibody production by B cells in ITP and thus might provide a reasonable therapeutic strategy for ITP