Development and validation of a model for the early prediction of progression from essential thrombocythemia to post-essential thrombocythemia myelofibrosis: a multicentre retrospective study.

Background: Essential thrombocythemia (ET), a myeloproliferative neoplasm (MPN), has a substantial risk of evolving into post-essential thrombocythemia myelofibrosis (post-ET MF). This study aims to establish a prediction nomogram for early prediction of post-ET MF in ET patients. Methods: The training cohort comprised 558 patients from 8 haematology centres between January 1, 2010, and May 1, 2023, while the external validation cohort consisted of 165 patients from 6 additional haematology centres between January 1, 2010, and May 1, 2023. Univariable and multivariable Cox regression analysis was performed to identified independent risk factors and establish a nomogram to predict the post-ET MF free survival. Both bias-corrected area under the curve (AUC), calibration curves and concordance index (C-index) were employed to assess the predictive accuracy of the nomogram. Findings: Multivariate Cox regression demonstrated that elevated red blood cell distribution width (RDW), elevated levels of lactate dehydrogenase (LDH) and the level of haemoglobin (Hb), a history of smoking and the presence of splenomegaly were independent risk factors for post-ET MF. The C-index displayed of the training and validation cohorts were 0.877 and 0.853. The 5 years, 10 years AUC values in training and external validation cohorts were 0.948, 0.769 and 0.978, 0.804 respectively. Bias-corrected curve is close to the ideal curve and revealed a strong consistency between actual observation and prediction. Interpretation: We developed a nomogram capable of predicting the post-ET MF free survival probability at 5 years and 10 years in ET patients. This tool helps doctors identify patients who need close monitoring and appropriate counselling. Funding: This research was funded by the Key R&D Program of Zhejiang (No. 2022C03137); the Public Technology Application Research Program of Zhejiang, China (No. LGF21H080003); and the Zhejiang Medical Association Clinical Medical Research special fund project (No. 2022ZYC-D09).

A Novel Inflammatory-Nutritional Prognostic Scoring System for Patients with Diffuse Large B Cell Lymphoma.

Purpose: This study aimed to examine the predictive ability of inflammatory and nutritional markers and further establish a novel inflammatory nutritional prognostic scoring (INPS) system. Patients and Methods: We collected clinicopathological and baseline laboratory data of 352 patients with DLBCL between April 2010 and January 2023 at the First affiliated hospital of Ningbo University. Eligible patients were randomly divided into training and validation cohorts (n = 281 and 71, respectively) in an 8:2 ratio. We used the least absolute shrinkage and selection operator (LASSO) Cox regression model to determine the most important factors among the eight inflammatory-nutritional variables. The impact of INPS on OS was evaluated using the Kaplan-Meier curve and the Log rank test. A prognostic nomogram was developed based on the multivariate Cox regression method. Then, we used the concordance index (C-index), calibration plot, and time-dependent receiver operating characteristic (ROC) analysis to evaluate the prognostic performance and predictive accuracy of the nomogram. Results: Seven inflammatory-nutritional biomarkers, including neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), body mass index (BMI), monocyte-lymphocyte ratio (MLR), prealbumin, C reactive protein, and D-dimer were selected using the LASSO Cox analysis to construct INPS, In the multivariate analysis, IPI-High-intermediate group, IPI-High group, high INPS were independently associated with OS, respectively. The prognostic nomogram for overall survival consisting of the above two indicators showed excellent discrimination. The C-index for the nomogram was 0.94 and 0.95 in the training and validation cohorts. The time-dependent ROC curves showed that the predictive accuracy of the nomogram for OS was better than that of the NCCN-IPI system. Conclusion: The INPS based on seven inflammatory-nutritional indexes was a reliable and convenient predictor of outcomes in DLBCL patients.

Silencing of PD-1 combined with EBV-specific killer T cells for the treatment of EBV-associated B lymphoma.

Epstein-Barr Virus (EBV) infection is closely associated with the development of lymphoma, as it plays a significant role in the malignant transformation of lymphocytes. The expression of programmed death-1 (PD-1), which binds to PD-L1 in tumor cells, can lead to immune evasion by lymphoma cells and promote tumor progression. In this study, immortalized B lymphoblastoid cell lines (B-LCLs) positive for EBV-specific proteins were established from human peripheral mononuclear cells (PBMCs) using EBV induction along with CpG-ODN 2006 and cyclosporin A. EBV-specific T cells (EBVST) were generated by multiple immunizations of CD3+ T lymphocytes using irradiated B-LCLs. Flow cytometry analysis confirmed the activation of EBVST through the detection of CD3+, CD4+, and CD8+ markers. Co-incubation of EBVST with EBV-positive B lymphocyte cell lines resulted in the secretion of perforin by EBVST, leading to granzyme B-mediated cell death and an increase in LDH levels. Silencing PD-1 in EBVST cells enhanced perforin production, increased granzyme B release, and upregulated cell death in co-incubated B lymphocytes. In a nude mice tumor transplantation model, silencing PD-1 in combination with EBV-specific killer T cells exhibited the maximum inhibition of B-lymphoblastoma. This treatment upregulated the expression of proteins associated with apoptosis and immune response, while inhibiting anti-apoptotic protein expression in tumor tissues. Silencing PD-1 also increased the infiltration of EBV-specific killer T cells in the tumor tissues. Overall, PD-1 silencing enhanced the tumor targeting effect of EBV-specific killer T cells on EBV-infected B lymphocytes and attenuated the immune escape effect mediated by the PD-1 pathway.

Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders.

This study aimed to assess the feasibility of diagnosing secondary pulmonary fungal infections (PFIs) in patients with hematological malignancies (HM) using computerized tomography (CT) imaging and a support vector machine (SVM) algorithm. A total of 100 patients with HM complicated by secondary PFI underwent CT scans, and they were included in the training group. Concurrently, 80 patients with the same underlying disease who were treated at our institution were included in the test group. The types of pathogens among different PFI patients and the CT imaging features were compared. Radiomic features were extracted from the CT imaging data of patients, and a diagnostic SVM model was constructed by integrating these features with clinical characteristics. Aspergillus was the most common pathogen responsible for PFIs, followed by Candida, Pneumocystis jirovecii, Mucor, and Cryptococcus, in descending order of occurrence. Patients typically exhibited bilateral diffuse lung lesions. Within the SVM algorithm model, six radiomic features, namely the square root of the inverse covariance of the gray-level co-occurrence matrix (square root IV), the square root of the inverse covariance of the gray-level co-occurrence matrix, and small dependency low gray-level emphasis, significantly influenced the diagnosis of secondary PFIs in patients with HM. The area under the curve values for the training and test sets were 0.902 and 0.891, respectively. Therefore, CT images based on the SVM algorithm demonstrated robust predictive capability in diagnosing secondary PFIs in conjunction with HM.

Evaluation of Three Automated Nontreponemal Rapid Plasma Reagin (RPR) Tests for the Laboratory Diagnosis of Syphilis.

Automated nontreponemal rapid plasma reagin (RPR) tests were recently introduced in the United States for syphilis testing and limited performance data are available. In collaboration with the Association of Public Health Laboratories, three public health laboratories (PHL) were chosen through a competitive selection process to evaluate the performance of three FDA-cleared automated RPR test systems: BioPlex 2200 Syphilis Total & RPR assay (Bio-Rad Laboratories), AIX 1000 (Gold Standard Diagnostics), and ASI Evolution (Arlington Scientific). Panels prepared at the CDC included: a qualitative panel comprised of 734 syphilis reactive/nonreactive sera; a quantitative panel of 50 syphilis reactive sera (RPR titer 1:64 to 1:1,024); and a reproducibility panel of 15 nonreactive and reactive sera (RPR titer 1:1 to 1:64). Panels were shipped frozen to the PHL and tested on the automated RPR systems following manufacturers' instructions. Prior test results were blinded to all laboratories. When compared to manual RPR (Arlington Scientific) performed at the CDC as a reference test, the qualitative panel results demonstrated an overall concordance of 95.9% for AIX 1000, 94.6% for ASI Evolution, and 92.6% for Bioplex RPR; quantitative panel showed within range titer of 2-fold for 94% of specimens for AIX 1000, 68% for ASI Evolution, and 64% for BioPlex RPR, and the reproducibility testing panel demonstrated point estimates ranging from 69 to 95%. Automated RPR instruments could reduce turnaround time and minimize interpretation errors. However, additional evaluations with more specimens could assist laboratories with implementing automated RPR tests and understanding their limitations.

The gut microbiota correlate with the disease characteristics and immune status of patients with untreated diffuse large B-cell lymphoma.

Background: Gut microbiota characteristics in patients with diffuse large B-cell lymphoma (DLBCL) are reportedly different when compared with the healthy population and it remains unclear if the gut microbiota affects host immunity and clinical disease features. This research investigated the gut microbiota in patients with untreated DLBCL and analyzed its correlation with patient clinical characteristics, humoral, and cell immune status. Methods: Thirty-five patients with untreated DLBCL and 20 healthy controls (HCs) were recruited to this study and microbiota differences in stool samples were analyzed by 16S rDNA sequencing. Absolute ratios of immune cell subset counts in peripheral blood were detected by flow cytometry and peripheral blood cytokine levels were detected by enzyme-linked immunosorbent assay. Relationships between changes in patient microbiomes and clinical characteristics, such as clinical stage, international prognostic index (IPI) risk stratification, cell origin, organ involved and treatment responses were investigated and correlations between differential microbiota and host immune indices were analyzed. Results: The alpha-diversity index of intestinal microecology in DLBCL patients was not significantly different when compared with HCs (P>0.05), nonetheless beta-diversity was significantly decreased (P=0.001). p_Proteobacteria were dominant in DLBCL, while p_Bacteroidetes abundance was significantly decreased when compared with HCs (P<0.05). Gut microbiota characteristics were identified that were associated with clinical features, such as tumor load, risk stratification and cell origin, and correlation analyses were performed between differential flora abundance associated with these clinical features and host immune status. The p_Firmicutes was positively correlated with absolute lymphocyte values, g_Prevotella_2 and s_un_g_Prevotella_2 were negatively correlated with absolute lymphocyte values, T cell counts and CD4 cell counts, while g_Pyramidobacter, s_un_g_Pyramidobacter, and f_Peptostreptococcaceae were negatively correlated with IgA. Conclusions: Dominant gut microbiota, abundance, diversity, and structure in DLBCL were influenced by the disease, correlated with patient immune status and this suggested that the microecology-immune axis may be involved in regulating lymphoma development. In the future, it may be possible to improve immune function in patients with DLBCL by regulating the gut microbiota, improve treatment response rates and increase patient survival rates.

Selective Whole-Genome Amplification as a Tool to Enrich Specimens with Low Treponema pallidum Genomic DNA Copies for Whole-Genome Sequencing.

Downstream next-generation sequencing (NGS) of the syphilis spirochete Treponema pallidum subspecies pallidum (T. pallidum) is hindered by low bacterial loads and the overwhelming presence of background metagenomic DNA in clinical specimens. In this study, we investigated selective whole-genome amplification (SWGA) utilizing multiple displacement amplification (MDA) in conjunction with custom oligonucleotides with an increased specificity for the T. pallidum genome and the capture and removal of 5'-C-phosphate-G-3' (CpG) methylated host DNA using the NEBNext Microbiome DNA enrichment kit followed by MDA with the REPLI-g single cell kit as enrichment methods to improve the yields of T. pallidum DNA in isolates and lesion specimens from syphilis patients. Sequencing was performed using the Illumina MiSeq v2 500 cycle or NovaSeq 6000 SP platform. These two enrichment methods led to 93 to 98% genome coverage at 5 reads/site in 5 clinical specimens from the United States and rabbit-propagated isolates, containing >14 T. pallidum genomic copies/µL of sample for SWGA and >129 genomic copies/µL for CpG methylation capture with MDA. Variant analysis using sequencing data derived from SWGA-enriched specimens showed that all 5 clinical strains had the A2058G mutation associated with azithromycin resistance. SWGA is a robust method that allows direct whole-genome sequencing (WGS) of specimens containing very low numbers of T. pallidum, which has been challenging until now. IMPORTANCE Syphilis is a sexually transmitted, disseminated acute and chronic infection caused by the bacterial pathogen Treponema pallidum subspecies pallidum. Primary syphilis typically presents as single or multiple mucocutaneous lesions and, if left untreated, can progress through multiple stages with various clinical manifestations. Molecular studies often rely on direct amplification of DNA sequences from clinical specimens; however, this can be impacted by inadequate samples due to disease progression or timing of patients seeking clinical care. While genotyping has provided important data on circulating strains over the past 2 decades, WGS data are needed to better understand strain diversity, perform evolutionary tracing, and monitor antimicrobial resistance markers. The significance of our research is the development of an SWGA DNA enrichment method that expands the range of clinical specimens that can be directly sequenced to include samples with low numbers of T. pallidum.

Evaluation of the effect of extended refrigerated storage of serum and plasma specimens on syphilis serologic test results.

The effect of extended refrigerated storage of 14 serum and plasma specimens on 5 syphilis serologic tests was evaluated for 16 weeks. Higher stability of nontreponemal and treponemal antibodies in serum was recorded compared to plasma. Described work may provide insights on refrigerated specimens' stability and suitability for syphilis tests.

Next-generation sequencing technology for diagnosis and efficacy evaluation of a patient with visceral leishmaniasis: A case report.

BACKGROUND: Visceral leishmaniasis (VL) is a parasitic disease caused by Leishmania and transmitted by infected sand flies. VL has a low incidence in China, and its clinical presentation is complex and atypical. This disease is easily misdiagnosed and can become life-threatening within a short period of time. Therefore, early, rapid and accurate diagnosis and treatment of the disease are essential. CASE SUMMARY: A 25-year-old male patient presented with the clinical manifestations of irregular fever, hepatosplenomegaly, increased polyclonal globulin, and pancytopenia. The first bone marrow puncture biopsy did not provide a clear diagnosis. In order to relieve the pressure and discomfort of the organs caused by the enlarged spleen and to confirm the diagnosis, splenectomy was performed, and hemophagocytic syndrome was diagnosed by pathological examination of the spleen biopsy. Following bone marrow and spleen pathological re-diagnosis and metagenomic next-generation sequencing (mNGS) technology detection, the patient was finally diagnosed with VL. After treatment with liposomal amphotericin B, the body temperature quickly returned to normal and the hemocytes recovered gradually. Post-treatment re-examination of the bone marrow puncture and mNGS data showed that Leishmania was not detected. CONCLUSION: As a fast and accurate detection method, mNGS can diagnose and evaluate the efficacy of treatment in suspicious cases of leishmaniasis.

Chemically defined and xeno-free culture condition for human extended pluripotent stem cells.

Extended pluripotent stem (EPS) cells have shown great applicative potentials in generating synthetic embryos, directed differentiation and disease modeling. However, the lack of a xeno-free culture condition has significantly limited their applications. Here, we report a chemically defined and xeno-free culture system for culturing and deriving human EPS cells in vitro. Xeno-free human EPS cells can be long-term and genetically stably maintained in vitro, as well as preserve their embryonic and extraembryonic developmental potentials. Furthermore, the xeno-free culturing system also permits efficient derivation of human EPS cells from human fibroblast through reprogramming. Our study could have broad utility in future applications of human EPS cells in biomedicine.

Transformation from acute promyelocytic leukemia to acute myeloid leukemia with a CEBPA double mutation: A case report and review of the literature.

INTRODUCTION: The transformation of acute promyelocytic leukemia (APL) to acute mononuclear leukemia during treatment is a rare clinical phenomenon, and no CCAAT/enhancer-binding protein alpha (CEBPA) double mutations have been reported. PATIENT CONCERNS: A 42-year-old male was hospitalized for ecchymosis of the left lower limb for more than 1 month, gingival bleeding, and fatigue for 10 days, with aggravation of symptoms for 2 days. DIAGNOSIS: A diagnosis of APL was based on bone marrow (BM) morphology, immunophenotyping, fusion gene analysis, and fluorescence in situ hybridization. At a 1-year follow-up of maintenance treatment, he developed thrombocytopenia and was diagnosed with acute myeloid leukemia (AML) with a CEBPA double mutation by BM morphology, immunotyping, chromosomal analysis, polymerase chain reaction, and next generation sequencing. INTERVENTIONS: Complete remission of APL was achieved after all-trans retinoic acid and arsenic trioxide double induction therapy, followed by 2 cycles of mitoxantrone and cytarabine, and 1 cycle of idarubicin and cytarabine. Thereafter, sequential maintenance therapy of arsenic trioxide + all-trans retinoic acid + methotrexate was started. In the fourth cycle of maintenance therapy, APL was transformed into AML with a CEBPA double mutation. After 1 cycle of idarubicin and cytarabine, the patient achieved complete remission and received 3 cycles of idarubicin and cytarabine and three cycles of high-dose cytarabine as consolidation therapy. OUTCOMES: At present, the patient is in continuous remission with minimal residual disease negative for both of APL and AML. CONCLUSION: AML with a CEBPA double mutation after APL treatment is very rare, thus the prognosis of this event will require further observation.

Turning a hot spot into a cold spot: polarization-controlled Fano-shaped local-field responses probed by a quantum dot.

Optical nanoantennas can convert propagating light to local fields. The local-field responses can be engineered to exhibit nontrivial features in spatial, spectral and temporal domains, where local-field interferences play a key role. Here, we design nearly fully controllable local-field interferences in the nanogap of a nanoantenna, and experimentally demonstrate that in the nanogap, the spectral dispersion of the local-field response can exhibit tuneable Fano lineshapes with nearly vanishing Fano dips. A single quantum dot is precisely positioned in the nanogap to probe the spectral dispersions of the local-field responses. By controlling the excitation polarization, the asymmetry parameter q of the probed Fano lineshapes can be tuned from negative to positive values, and correspondingly, the Fano dips can be tuned across a broad spectral range. Notably, at the Fano dips, the local-field intensity is strongly suppressed by up to ~50-fold, implying that the hot spot in the nanogap can be turned into a cold spot. The results may inspire diverse designs of local-field responses with novel spatial distributions, spectral dispersions and temporal dynamics, and expand the available toolbox for nanoscopy, spectroscopy, nano-optical quantum control and nanolithography.

[Effects of Dasatinib on the Expansion, Subsets, Receptor Expression and Cytotoxic Function of NK Cells in Vitro].

OBJECTIVE: To investigate the effect of dasatinib on the expansion of NK cells in vitro, as well as the subsets, receptor expression and cytotoxic function of NK cells. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy adult volunteers and cultured with SCGM added IL-2 and IL-15 for expansion of NK cells. In this culture system, dasatinib of different concentrations were added. Cell counting and phenotyping by flow cytometry were used to evaluate the amplification efficiency of NK cells. FCM was used to detect the expression of receptors on the surface of NK cells and the distribution of subsets. Subsequently, degranulation assay and CFSE/7AAD based cytotoxicity assay were used to detect the effects of dasatinib on NK cytotoxicity against leukemia cell line K562 cells. RESULTS: The expansion efficiency of NK cells in vitro could be increased by dasatinib at the concentration range of 5-50 nmol/L, and the expansion efficiency of NK cells reached the peak at 20 nmol/L of dasatinib. The NK cytotoxicity against K562 cells in dasatinib cultured group at the concentration of 20 nmol/L was significantly higher than that in control group. For the cells cultured by disatinib in vitro, the MFI of CD226, NKP46 and NKG2D was up-regulated; the ratio of NKG2A+CD57- subset was down-regulated, while the ratio of NKG2A-CD57+ subset was up-regulated.The degranulation response of NKG2A-CD57+ NK cells to K562 cells was stronger than that of NKG2A+CD57- NK cells. CONCLUSION: The results shows that appropriate dose of dasatinib(20 nmol/L) can increases the amplification efficiency of NK cells, simultaneously up-regulates the expression of NK activating receptors and increases the NKG2A-CD57+ subset, which lead to the enhancement of NK cytotoxicty against leukemia cell lines.

Cytotoxicity of Donor Natural Killer Cells to Allo-Reactive T Cells Are Related With Acute Graft-vs.-Host-Disease Following Allogeneic Stem Cell Transplantation.

Objectives: The mechanism and immunoregulatory role of human natural killer (NK) cells in acute graft-vs.-host-disease (aGVHD) remains unclear. This study quantitatively analyzed the cytotoxicity of donor NK cells toward allo-reactive T cells, and investigated their relationship with acute GVHD (aGVHD). Methods: We evaluated NK dose, subgroup, and receptor expression in allografts from 98 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). A CD107a degranulating assay was used as a quantitative detection method for the cytotoxic function of donor NK cells to allo-reactive T cells. In antibody-blocking assay, NK cells were pre-treated with anti-DNAM-1(CD226), anti-NKG2D, anti-NKP46, or anti-NKG-2A monoclonal antibodies (mAbs) before the degranulating assay. Results: NK cells in allografts effectively inhibited auto-T cell proliferation following alloantigen stimulation, selectively killing alloantigen activated T cells. NKG2A- NK cell subgroups showed higher levels of CD107a degranulation toward activated T cells, when compared with NKG2A- subgroups. Blocking NKG2D or CD226 (DNAM-1) led to significant reductions in degranulation, whereas NKG2A block resulted in increased NK degranulation. Donor NK cells in the aGVHD group expressed lower levels of NKG2D and CD226, higher levels of NKG2A, and showed higher CD107a degranulation levels when compared with NK cells in the non-aGVHD group. Using univariate analysis, higher NK degranulation activities in allografts (CD107ahigh) were correlated with a decreased risk in grade I-IV aGVHD (hazard risk [HR] = 0.294; P < 0.0001), grade III-IV aGVHD (HR = 0.102; P < 0.0001), and relapse (HR = 0.157; P = 0.015), and improved overall survival (HR = 0.355; P = 0.028) after allo-HSCT. Multivariate analyses showed that higher NK degranulation activities (CD107ahigh) in allografts were independent risk factors for grades, I-IV aGVHD (HR = 0.357; P = 0.002), and grades III-IV aGVHD (HR = 0.13; P = 0.009). Conclusions: These findings reveal that the degranulation activity of NK in allografts toward allo-activated T cells was associated with the occurrence and the severity of aGVHD, after allogeneic stem cell transplantation. This suggested that cytotoxicity of donor NK cells to allo-reactive T cells have important roles in aGVHD regulation.

Successful isolation of Treponema pallidum strains from patients' cryopreserved ulcer exudate using the rabbit model.

Clinical isolates of Treponema pallidum subspecies pallidum (T. pallidum) would facilitate study of prevalent strains. We describe the first successful rabbit propagation of T. pallidum from cryopreserved ulcer specimens. Fresh ulcer exudates were collected and cryopreserved with consent from syphilis-diagnosed patients (N = 8). Each of eight age-matched adult male rabbits were later inoculated with a thawed specimen, with two rabbits receiving 1.3 ml intratesticularly (IT), and six receiving 0.6 ml intravenously (IV) and IT. Monitoring of serology, blood PCR and orchitis showed that T. pallidum grew in 2/8 rabbits that were inoculated IV and IT with either a penile primary lesion specimen (CDC-SF003) or a perianal secondary lesion specimen (CDC-SF007). Rabbit CDC-SF003 was seroreactive by T. pallidum Particle Agglutination (TP-PA) and Rapid Plasma Reagin (RPR) testing, PCR+, and showed orchitis by week 6. Euthanasia was performed in week 7, with treponemal growth in the testes confirmed and quantified by qPCR and darkfield microscopy (DF). Serial passage of the extract in a second age-matched rabbit also yielded treponemes. Similarly, rabbit CDC-SF007 showed negligible orchitis, but was seroreactive and PCR+ by week 4 and euthanized in week 6 to yield T. pallidum, which was further propagated by second passage. Using the 4-component molecular typing system for syphilis, 3 propagated strains (CDC-SF003, CDC-SF007, CDC-SF008) were typed as 14d9f, 14d9g, and 14d10c, respectively. All 3 isolates including strain CDC-SF011, which was not successfully propagated, had the A2058G mutation associated with azithromycin resistance. Our results show that immediate cryopreservation of syphilitic ulcer exudate can maintain T. pallidum viability for rabbit propagation.

Development of a syphilis serum bank to support research, development, and evaluation of syphilis diagnostic tests in the United States.

The Centers for Disease Control and Prevention's (CDC) Division of STD Prevention, in collaboration with the Association of Public Health Laboratories (APHL), is developing a nationally available syphilis serum repository for research of Food and Drug Administration (FDA)-cleared or investigational syphilis diagnostic assays in the United States. State and local public health laboratories (PHL) submitted de-identified residual sera with information on collection date, volume, storage conditions, freeze-thaw cycles, PHL serology results, reported syphilis stage and demographic details if available. Previous test results were blinded and sera (N = 152 reported syphilis stage, N = 131 unknown status) were tested at CDC using five FDA-cleared and one investigational syphilis tests. Treponemal and nontreponemal test sensitivity ranged from 76.3-100% and 63.2-100%, respectively, among staged specimens. The conventional treponemal assays showed high concordance of 95.4%. By providing syphilis stage and comprehensive serological test data, developed repository may serve as a valuable resource for diagnostic test validation studies.

Colossal Enhancement of Near-Field Thermal Radiation Across Hundreds of Nanometers between Millimeter-Scale Plates through Surface Plasmon and Phonon Polaritons Coupling.

Coupling modes between surface plasmon polaritons (SPPs) and surface phonon polaritons (SPhPs) play a vital role in enhancing near-field thermal radiation but are relatively unexplored, and no experimental result is available. Here, we consider the NFTR enhancement between two identical graphene-covered SiO2 heterostructures with millimeter-scale surface area and report an experimentally record-breaking ∼64-fold enhancement compared to blackbody (BB) limit at a gap distance of 170 nm. The energy transmission coefficient and radiation spectra show that the physical mechanism behind the colossal enhancement is the coupling between the surface plasmon and phonon polaritons.

Evaluation of a Rapid Syphilis Test in an Emergency Department Setting in Detroit, Michigan.

BACKGROUND: Syphilis transmission can be prevented by prompt diagnosis and treatment of primary and secondary infection. We evaluated the performance of a point-of-care rapid syphilis treponemal (RST) test in an emergency department (ED) setting. METHODS: Between June 2015 and April 2016, men aged 18 to 34 years seeking services in a Detroit ED, and with no history of syphilis, were screened for syphilis with the RST test, rapid plasma reagin (RPR) test, and Treponema pallidum particle agglutination assay (TP-PA). A positive reference standard was both a reactive RPR and a reactive TP-PA. We compared test results in self-reported men who have sex with men (MSM) to non-MSM. RESULTS: Among 965 participants, 10.9% of RST tests were reactive in MSM and only 1.5% in non-MSM (P < 0.001). Sensitivity of the RST test was 76.9% and specificity was 99.0% (positive predictive value, 50.0%) compared with the positive reference standard. Three discordant specimens found negative with the RST test but positive with the reference standard had an RPR titer of 1:1, compared with 10 specimens with concordant positive results that had a median RPR titer of 1:16. The RST sensitivity was 50.0% (positive predictive value, 68.4%) compared to the TP-PA test alone. Among men seeking care in an ED, the RST detected 76.9% of participants with a reactive RPR and TP-PA. CONCLUSIONS: The RST test detected all of the participants with an RPR titer ≥1:2 but less than 20% of participants with a positive TP-PA and negative RPR. The RST test was useful to detect a high proportion of participants with an active syphilis in an urban ED.

Clinically useful flow cytometry approach to identify immunophenotype in acute leukemia.

OBJECTIVES: Acute leukemia (AL) is a highly heterogeneous malignant disease caused by hematopoietic cell abnormalities. Our study investigated the potential for immunophenotyping of leukemic cells via flow cytometry and the clinical usefulness of this approach in treatment of AL. METHODS: Bone marrow (BM) specimens were collected to detect antigen expression on hematopoietic cells in pre-treatment samples from patients with AL. In addition, fraction survival curves were calculated using the Kaplan-Meier method to explore the effect of markers on prognosis in AL. RESULTS: Expression levels of immunophenotypic markers in patients with acute lymphoblastic leukemia (ALL) were significantly different from those in patients with acute myeloid leukemia (AML). In addition, there was a potential association between the surface marker, cluster of differentiation 2 (CD2), and fraction survival in AML. However, no similar result was found in ALL. Moreover, genetic tests showed greater positive variation of the break point cluster-Abelson tyrosine kinase ( BCR-ABL) fusion gene in samples from patients with ALL than in samples from patients with AML. CONCLUSIONS: We have shown a rapid and effective flow cytometry method that enables the identification of immunophenotype in AL. Moreover, CD2 may constitute a predictive marker for prognosis in patients with AML.