Positive Plasma Research Articles

Analysis of clinicopathological characteristics of IgG4-related sialadenitis

Objective: To analyze the clinicopathological characteristics of IgG4-related sialadenitis (IgG4-RS). Methods: A total of 40 cases diagnosed with IgG4-RS were collected from the Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2019 to December 2022. Among them, there were 26 males and 14 females. The age range was 29-77 years old [(59.4±11.8) years old], with 23 patients being older than 60 years. The lesion site, imaging manifestations, histopathological features, serological test and treatment information of patients were collected. The expression of IgG4 and IgG proteins was detected by immunohistochemistry. Results: Submandibular region swelling was the most common initial symptom of IgG4-RS (38/40, 95.0%). All the patients having serum IgG4 levels> 1.35 g/L. Serum IgG4 levels were significantly increased in patients aged>60 years (Z=-2.45, P=0.014) and those involving multiple glands (Z=-2.04, P=0.042). Thirty six cases received major salivary gland biopsy, and all the cases showed dense lymphocyte and plasma cell infiltration. Lymphoid follicle, storiform fibrosis and obliterative phlebitis were seen in 88.9% (32/36), 63.9% (23/36), 30.6% (11/36) of the cases, respectively. Twenty one cases received labial salivary gland biopsy, 66.7% (14/21) showed lymphocyte and plasma cell infiltration, 19.0% (4/21) had lymphoid follicle structures, and 33.3% (7/21) showed no obvious histological abnormalities. No signs of fibrosis or obliterative phlebitis were observed in all labial salivary gland biopsies. And 95.0% (38/40) of cases had IgG4 positive plasma cell>10/HPF, 82.5% (33/40) of cases had IgG4/IgG positive plasma cell ratio>40%. All the patients had a decrease in serum IgG4 levels after glucocorticoid treatment, but only 21.4% (6/28) of cases had reduced to normal levels (≤1.35 g/L), and there were still significant fluctuations in serum IgG4 levels thereafter. Conclusions: IgG4-RS has a predilection for middle-aged and elderly male patients, and serum IgG4 levels are significantly related to the patient's age and whether multiple glands are involved. Labial salivary gland biopsy cannot replace submandibular gland for histopathological evaluation. It is a common phenomenon that serum IgG4 levels cannot restored to normal levels after glucocorticoid treatment. This study provides certain assistance for clinical and pathological diagnosis of IgG4-RS. This study is beneficial for further understanding IgG4-RS and improving the clinical and pathological diagnosis of the disease.

Codetection of Plasmodium falciparum in Children Hospitalized With Dengue Fever in the Dominican Republic.

Cases of malaria and dengue in the Dominican Republic both spiked in 2019, but their rates of codetection are poorly characterized, especially in children. We performed a prospective, observational study in January to December 2019 at the Hospital Infantil Robert Reid Cabral, in the Dominican Republic, enrolling hospitalized children with a clinical suspicion of dengue fever. Participants with a positive plasma dengue IgM antibodies were included in this study. Clinical and hospital data were abstracted, and dried blood spot samples were collected from participants and tested with quantitative polymerase chain reaction to detect the presence of Plasmodium falciparum DNA. A total of 429 children with serological evidence of acute dengue were included in this study, of whom 1.4% (n = 6/429) had codetection of dengue and malaria. There were no significant differences in fever duration or presence of vomiting, abdominal pain and rash between both groups. Children with dengue and malaria codetection were numerically more often admitted to the pediatric intensive care unit, despite no differences found in overall clinical severity. The codetection of malaria and dengue in children was overall uncommon in our Dominican Republic cohort despite the rise in cases in 2019 but may be associated with a more severe hospital course. Further epidemiological and cohort studies to characterize the risk of both pathogens as case numbers fluctuate will be important to better understand the dynamics of coinfections.

A clinical analysis of Candida tropicalis bloodstream infections associated with hematological diseases, and antifungal susceptibility: a retrospective survey.

To assess the clinical features and outcomes of hematological disease patients with Candida tropicalis bloodstream infections and determine the antifungal susceptibility of C. tropicalis. This is a retrospective, single-center, observational study conducted in the Department of Hematology at The First Affiliated Hospital of Guangxi Medical University from January 2013 to December 2021. A total of 26 hematological disease patients with C. tropicalis bloodstream infections were enrolled, and their clinical features, treatment plans, and prognoses were assessed. Univariate analysis was performed by Kaplan-Meier analysis and multivariate analysis was conducted using a Cox regression model. The antifungal susceptibility of C. tropicalis was determined from patient blood cultures. The patients had a mean age of 35 years (range: 10-65 years), 50% were male (13/26) and 88.5% had hematologic malignancies (23/26) while the remaining three patients included two cases of severe aplastic anemia and one case of β-thalassemia. All patients had neutropenia. Seven patients were initially given azole alone (26.9%), five of whom failed treatment and died (71.4%). Fifteen patients were treated with echinocandin (57.7%), three of whom failed treatment and died (20.0%), and eight patients were treated with amphotericin B (30.8%), two of whom failed treatment and died (25.0%). The total and attributable mortality rates were 42.3 and 34.6%, respectively. Univariate analysis showed that there are six risk factors for attributable deaths among hematological disease patients with C. tropicalis blood infections. These risk factors included septic shock, Pitt bacteremia scores ≥4, procalcitonin levels ≥10 ng/mL, positive plasma (1,3)- β-D glucan assay, serum albumin levels <30.0 g/L, time from fever to antifungal treatment initiation ≥5 days and time between neutropenia and antifungal treatment ≥10 days. Moreover, skin and mucosal infections and a treatment schedule that included amphotericin B and drug combinations are protective factors for attributable deaths. Multivariate analysis showed that septic shock (p = 0.006) was an independent risk factor for attributable death. All isolates were sensitive to flucytosine and amphotericin B. The intermediate or resistance of C. tropicalis to fluconazole, itraconazole and voriconazole were 41.7, 50, and 41.7%, respectively. Hematological disease patients with C. tropicalis bloodstream infections had a high mortality rate, and early antifungal therapy significantly reduced mortality. Candida tropicalis was highly resistant to azole drugs and sensitive to flucytosine and amphotericin B. According to our study, the preferred agent is amphotericin B and drug combinations should be considered for severe infections.

Xanthogranulomatous cholecystitis with histologic features suggestive of IgG4 related cholecystitis - A morphologic overlap with IgG4 related disease

AimsBoth xanthogranulomatous cholecystitis (XGC) and IgG4-related cholecystitis (IgG4-CC) are rare chronic fibroinflammatory tumefactive diseases of the gallbladder, which cause a strong confusion with resectable malignancy in view of their mass forming tendency with extension into the liver. We aim to study the histopathologic features of xanthogranulomatous cholecystitis with regard to IgG4-related cholecystitis in extended cholecystectomy specimens. Methods and resultsSixty cases of extended cholecystectomy with liver wedge resection, diagnosed as XGC on histopathology from January 2018 to December 2021 were retrieved from the archives. Representative sections were reviewed by two pathologists independently. Immunohistochemistry was performed for IgG4 and IgG4/IgG was derived. The cases were dichotomized in two groups on the basis of IgG4 positive plasma cells. Six cases with >50 IgG4 positive plasma cells had storiform fibrosis, IgG4/IgG ratio >0.40 and extra-cholecystic extension. Of these, 50 % had obliterative phlebitis and 66.7 % had perineural plasma cell wrapping. ConclusionsA small subset of XGC cases (~10 %) had morphologic overlap with IgG4-CC, but should not be overcalled as the diagnosis of IgG4-RD requires an integrative approach based on clinical, serologic and imaging criteria and not solely on histopathology.

Role of electron temperature at extremely low density in negative positive ion plasma

It is pointed out that the role of electrons in the dynamics of pair ion and negative positive ion plasmas cannot be neglected even at extremely low density of electrons, i.e., ne0n+0≪mem+ (where nj0 is the background density of jth species and mj is the mass of the particles of the j-species while j = e, +, −) because electron thermal velocity is almost always larger than thermal velocities of ions, i.e., vT± ≪ vTe. An analysis of electrostatic waves in unmagnetized negative positive ion electron (NPIE) and pair ion electron (PIE) plasmas is presented for the case ωpe ≪ ωp+ (where ωpj=(4πnj0e2mj)1/2 is the plasma oscillation frequency corresponding to j-species). The electron dynamics contribute to electrostatic perturbations at ion plasma oscillation time scale at longer wavelengths for λDe2k2&amp;lt;1 where λDe=(Te4πne0)1/2 is the electron Debye length. On the other hand, the electron plasma wave turns into thermal wave when the conditions ωpe ≪ ωp± and 1≪λDe2k2 hold simultaneously and ion acoustic wave approaches the sum of ion plasma oscillation frequencies of positive and negative ions. The only electrostatic normal mode of such a plasma is the ion plasma wave corresponding to longer wavelengths, which also includes the contribution of electrons. The electron thermal wave is separated from plasma oscillations and electron time scale disappears with respect to electrostatic perturbations. Similar situation also occurs in plasmas having negatively charged dust particles. To elaborate these points, the analytical results are applied to the two experiments with NPIE and PIE plasmas.

P-625 Artificial intelligence-enabled analysis of endometrial CD138 positive plasma cells in infertility-associated conditions; Polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF)

Abstract Study question Can artificial intelligence (AI) algorithm identify CD138+ cells in the endometrial stroma, and is the expression altered in PCOS and RIF? Summary answer CD138+ cell detection by AI shows high accuracy. The cell count in controls was comparable to that in PCOS cases but differed in RIF patients. What is known already Immunohistochemical (IHC) staining for CD138+ plasma cells has been applied to detect endometrial inflammation; however, due to a lack of cost-effective and reliable tools, there is no golden standard for CD138+ analysis. PCOS is a common endocrine disorder characterized by irregular menstrual cycles and hyperandrogenism. The women are also affected by systemic low-grade inflammation, and the PCOS endometrium shows dysregulated immune profile. RIF is one of the main causes of a low IVF success rate, and chronic endometrial inflammation has been detected in women with RIF. To date, AI technology has been applied in the diagnostics of various clinical conditions. Study design, size, duration In this study, AI analysis was done for CD138+ cells in a total of 193 endometrial biopsy samples: 73 were obtained from healthy and fertile controls, 91 from women with PCOS (ovulatory samples; n = 78, anovulatory samples; n = 13, Rotterdam criteria), and 29 samples from RIF patients on day five after the initiation of P4 administration. Participants/materials, setting, methods The biopsy samples were collected by suction curette (Pipelle), and endometrial receptivity was assessed by gene expression profiling (beREADY test). The tissues were stained with CD138 antibody, and the AI algorithm, AITAH, was trained with 150 whole slide images (WSIs) to segment epithelium and stroma and segregate CD138- and CD138+ cells in the stroma. AITAH was validated by three external pathologists. The cell counts were compared according to cycle phases, ovulatory status, and endometrial receptivity. Main results and the role of chance The performance of AITHA was excellent, as the final training error for CD138+ cells was 3.23%, and the decisions for the cells between pathologists and AITAH were in complete agreement. The CD138+ cell percentages were higher in the proliferative phase (PE) endometrial tissue than in the ones obtained in the secretory phase (PCOS, p &amp;lt;0.001 or control, p &amp;lt;0.001), regardless of PCOS diagnosis. Similar CD138+ cell percentages were observed between PE endometrium and anovulatory endometrium in PCOS cases (p &amp;lt;0.001). The count of CD138+ plasma cells was negatively correlated with the endometrial thickness (PCOS, p =0.001 or control, p =0.009) and P4 (PCOS, p =0.001 or control, p =0.003), and positive correlations between the cell counts and gonadotropin levels were observed in ovulatory PCOS samples (FSH, p =0.001 and LH, p =0.031). More CD138+ cells were seen in RIF patients compared to the controls at the receptive stage (p = 0.046); however, there was no difference between RIF samples of three different receptivity statuses (p =0.426). Limitations, reasons for caution Further validation for AITAH using confirmed chronic endometritis cases as positive controls is required. And further analysis using control samples obtained during the hormone replacement treatment is required. The small number of anovulatory PCOS subjects may explain the absence of correlations between the CD138+ plasma cell counts and clinical characteristics. Wider implications of the findings AI-enabled analysis tools could improve histological examination of endometrial immune cells by analyzing high amounts of whole tissue slides within a short time with a high pixel resolution, thus overcoming many current impediments in manual microscopic evaluation. Trial registration number NA

Validation of a whole exome/whole transcriptome liquid biopsy assay with correction for clonal hematopoiesis.

e15049 Background: Liquid biopsies have become integral to the management of patients with advanced malignancies, however significant deficiencies exist in currently used platforms. Liquid biopsy data often show unacceptably high discordance compared to gold standard tissue-based data; this is often due to false positives (FP) resulting from clonal hematopoiesis (CH) or increased false negatives due to inherently poor sensitivity as well as the confounding intra-patient or tumor stage dependent ‘non-shedder’ problem. Caris Assure is a novel whole exome (WES) and whole transcriptome (WTS) NGS assay performed on plasma and buffy coat (BC) fractions of whole blood that maximizes the number of unique nucleic acids, thereby increasing sensitivity as well as identifying incidental germline variants and correcting for CH. Methods: Matched tissue and whole blood specimens were obtained from 184 patients with solid tumors. Whole blood was collected in PAXgene ccfDNA tubes. DNA &amp; RNA were co-extracted from matched plasma, BC, and FFPE tumor tissue specimens and prepared for NGS using hybrid bait capture methodology. Plasma and BC samples were tested using the Caris Assure WES/WTS assay as well as orthogonal assays. Tissue specimens were tested using Caris’ validated WES/WTS tissue assay. Results were compared between the plasma assays and matched tissues as well as using a majority-rules calling model. A positive plasma assay variant was counted a true positive if it was also identified in the matched tissue or the orthogonal plasma result. Similarly, a negative result was considered a true negative if either of the other two test results were also negative. Results: When data were analyzed from patients with metastatic disease and were focused on only those genes included in the limited orthogonal liquid panel, and tissue was treated as the gold standard, Caris Assure achieved a PPA for SNVs and INDELS of 81.4% and PPV of 85.1%, while the orthogonal assay achieved a PPA and PPV of 79.1% and 53.1%. When the majority rules approach was used, Assure PPA and PPV were 93.3% and 93.3%, respectively, compared to 91.1% and 64.1%. Germline variants detected by Caris Assure had 100% PPA &amp; PPV when compared to the external germline assay. There were 444 pathogenic/likely pathogenic mutations detected across all assays. Of those, 77 (17.3%) were derived from CH and identified as such in the Caris Assure results, though they are inaccurately reported as tumor-derived variants using the comparator assay. Using Caris Assure corrected for CH-derived false positives, the correlation between plasma and tissue TMB was very strong (r = 0.9) when tissue and blood specimens were collected within 4 weeks of each other. Conclusions: The novel Caris Assure liquid biopsy platform demonstrates high sensitivity and specificity for somatic variants, while mitigating against FPs from CH, and identifying incidental germline pathogenic alterations.

Plasma cell-free RNA PD-L1 expression and survival with immune checkpoint inhibitor-based treatment in advanced non-small-cell lung cancer.

e21090 Background: Tissue PD-L1 protein expression is predictive of immune checkpoint inhibitor (ICI)-based treatment outcomes in advanced non-small-cell lung cancer (aNSCLC). However, tissue PD-L1 can be fraught with tissue acquisition difficulties and tumor heterogeneity. Plasma cell-free RNA (cfRNA) PD-L1 expression assessed with a liquid biopsy potentially overcomes these tissue limitations and could identify additional patients likely to benefit from ICI therapy. Outcome studies validating this novel approach have not been previously reported. Methods: An observational cohort of patients with aNSCLC treated in an academic medical center with 1st-line ICI-based therapies were retrospectively evaluated for a pre-planned endpoint of overall survival (OS) based upon plasma cfRNA PD-L1 expression by a proprietary exosome-free real-time qPCR assay and/or tissue PD-L1 protein expression (Dako 22C3) performed in commercial CLIA/CAP accredited laboratories. Results: Of 75 consecutive aNSCLC patients, 16 (21.3%) were plasma cfRNA PD-L1 positive expression with 6 of these 16 (37%) tissue PD-L1 negative or quantity not sufficient. 35 patients were both tissue and plasma PD-L1 negative and 24 patients tissue PD-L1 positive but plasma PD-L1 negative. Median follow-up 34 months. The plasma PD-L1 or tissue PD-L1 positive patients demonstrated no difference in OS outcomes (median OS 16 months; 3-year landmark OS 30%; hazard ratio (HR) 0.97; 95% CI, 0.44-2.10). The plasma PD-L1 positive patients demonstrated superior OS outcomes compared to tissue and plasma PD-L1 negative patients (median OS 16 months versus 8 months; landmark 3-year OS 30% versus 20%; HR 0.59; 95% CI, 0.31-1.11). The plasma PD-L1 positive patients demonstrated no differing OS outcomes whether tissue PD-L1 positive or negative (median OS 13-16 months; 3-year landmark OS 30%; HR 1.15; 95% CI, 0.32-4.05). Conclusions: In this single-institution aNSCLC patients receiving 1st-line ICI therapy OS outcomes were the same for plasma PD-L1 positive patients vs. tissue PD-L1 positive patients. OS outcomes were superior for patients with positive plasma PD-L1 expression vs. similarly treated patients negative for tissue PD-L1 or plasma PD-L1 expression. In patients with plasma cfRNA PD-L1 expression, there was no OS differences whether tissue PD-L1 protein was positive or negative, suggesting that liquid biopsy might identify additional patients who could benefit from ICI therapy.

Insights into the response mechanism of Fusarium sp. NF01 during lignite biodegradation using proteomic analysis

Coal biodegradation is promising for sustainable energy development. Studying proteomics in coal biodegradation is effective for identifying different proteins and analyzing corresponding biological strategies. However, previous research on this topic is limited. Here, Fusarium sp. NF01 was proven to degrade lignite based on surface morphology, functional groups, and chemical composition for the first time. The proteomics of Fusarium sp. NF01 were then quantitatively and qualitatively analyzed using isobaric tandem mass tags and bioinformatics profiling during lignite biodegradation. The results showed that 1.8 g of lignite was biodegraded into 4.7 mL of black droplets, with microstructural changes. The abundance of 18 proteins, including eight upregulated and ten downregulated proteins (fold change, FC ≥ 1.2 or FC ≤ 0.83 and P-value ≤0.05), significantly changed during the lignite biodegradation process. These proteins were mainly involved in spermidine synthase, PM H+-ATPase, GGT, 6-HDNO, IPS, and AST. Fusarium sp. NF01 adopted multilevel protein-based strategies, such as nutrient transport and synthesis, positive plasma membrane regulation, immunity optimization, and prevention of cell damage and death to respond to the influence of the lignite environment on its growth and metabolism. These findings provide valuable bioinformation for identifying degradation-specific protein molecules and elucidating the biodegradation mechanism of coal.

Spatial Development of Strong Storm-Induced Ionospheric Perturbations during 25–27 August 2018

The 25–27 August 2018 geomagnetic storm was the third largest storm in the 24th solar cycle. It was a surprising space event that originated from low-level solar activity. This study provides an overview of the temporal–spatial behaviors of plasma irregularities as functions of geographic longitude, latitude, and altitude using ground-based (GNSS receivers and ionosonde) instruments and space-borne Swarm satellites. The results not only reveal enhanced equatorial ionization anomaly (EIA) and hemispheric asymmetry over the Asian–Australian and American sectors at a particular time but also hemispheric asymmetric features of global ROT in the main and recovery phases. Additionally, this storm triggered positive plasma irregularities in altitudes of 100 to 150 km near the Auroral zone, and the changed ratio of bottom-side plasma irregularities exceeded 250%. This finding has been cross-validated by other instruments and models. Furthermore, the storm significantly affected the thermospheric O/N2 density ratio, equatorial electrojet, and vertical E×B drifts. The equatorial and mid-latitude plasma irregularities may be a combined action of thermospheric composition change, equatorial electrojet, and vertical E×B drifts. Finally, the storm induced positive Joule heating irregularities in the Auroral ionosphere in altitudes of 100 to 400 km with a maximum changed ratio of over 200%, as well as enhanced cross-Polar voltage to ~90 kv. The Polar ionospheric irregularities may be associated with additional energy input through particle precipitation, Joule heating, and ionospheric current intensification.

Maternal HIV infection drives altered placental Mtb-specific antibody transfer.

Placental transfer of maternal antibodies is essential for neonatal immunity over the first months of life. In the setting of maternal HIV infection, HIV-exposed uninfected (HEU) infants are at higher risk of developing severe infections, including active tuberculosis (TB). Given our emerging appreciation for the potential role of antibodies in the control of Mycobacterium tuberculosis (Mtb), the bacteria that causes TB, here we aimed to determine whether maternal HIV status altered the quality of Mtb-specific placental antibody transfer. Antigen-specific antibody systems serology was performed to comprehensively characterize the Mtb-specific humoral immune response in maternal and umbilical cord blood from HIV infected and uninfected pregnant people in Uganda. Significant differences were noted in overall antibody profiles in HIV positive and negative maternal plasma, resulting in heterogeneous transfer of Mtb-specific antibodies. Altered antibody transfer in HIV infected dyads was associated with impaired binding to IgG Fc-receptors, which was directly linked to HIV viral loads and CD4 counts. These results highlight the importance of maternal HIV status on antibody transfer, providing clues related to alterations in transferred maternal immunity that may render HEU infants more vulnerable to TB than their HIV-unexposed peers.

Identification of potential resistance mechanisms and therapeutic targets for the relapse of BCMA CAR-T therapy in relapsed/refractory multiple myeloma through single-cell sequencing

BackgroundBCMA CAR-T is highly effective for relapsed/refractory multiple myeloma(R/R-MM) and significantly improves the survival of patients. However, the short remission time and high relapse rate of MM patients treated with BCMA CAR-T remain bottlenecks that limit long-term survival. The immune microenvironment of the bone marrow (BM) in R/R-MM may be responsible for this. The present study aims to present an in-depth analysis of resistant mechanisms and to explore potential novel therapeutic targets for relapse of BCMA CAR-T treatment via single-cell RNA sequencing (scRNA-seq) of BM plasma cells and immune cells.MethodsThis study used 10X Genomic scRNA-seq to identify cell populations in R/R-MM CD45+ BM cells before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. Cell Ranger pipeline and CellChat were used to perform detailed analysis.ResultsWe compared the heterogeneity of CD45+ BM cells before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. We found that the proportion of monocytes/macrophages increased, while the percentage of T cells decreased at relapse after BCMA CAR-T treatment. We then reclustered and analyzed the alterations in plasma cells, T cells, NK cells, DCs, neutrophils, and monocytes/macrophages in the BM microenvironment before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. We show here that the percentage of BCMA positive plasma cells increased at relapse after BCMA CAR-T cell therapy. Other targets such as CD38, CD24, SLAMF7, CD138, and GPRC5D were also found to be expressed in plasma cells of the R/R-MM patient at relapse after BCMA CAR-T cell therapy. Furthermore, exhausted T cells, TIGIT+NK cells, interferon-responsive DCs, and interferon-responsive neutrophils, increased in the R/R-MM patient at relapse after BCMA CAR-T cell treatment. Significantly, the proportion of IL1βhi Mφ, S100A9hi Mφ, interferon-responsive Mφ, CD16hi Mφ, MARCO hi Mφ, and S100A11hi Mφ significantly increased in the R/R-MM patient at relapse after BCMA CAR-T cell therapy. Cell–cell communication analysis indicated that monocytes/macrophages, especially the MIF and APRIL signaling pathway are key players in R/R-MM patient at relapse after BCMA CAR-T cell therapy.ConclusionTaken together, our data extend the understanding of intrinsic and extrinsic relapse of BCMA CAR-T treatment in R/R-MM patient and the potential mechanisms involved in the alterations of antigens and the induced immunosuppressive microenvironment, which may provide a basis for the optimization of BCMA CAR-T strategies. Further studies should be performed to confirm these findings.

Surveillance of anti-SARS-CoV-2 antibodies in plasma pools and in immunoglobulin medicinal products manufactured since 2020 has shown high neutralizing activity against SARS-CoV-2 and current variants

BackgroundPatients with primary and secondary immunodeficiencies have shown an impaired humoral immune response to COVID-19 vaccination. It is therefore of paramount importance to investigate anti-SARS-CoV-2 antibody levels in plasma pools and in immunoglobulin (IgG) products used to treat these patients. AIM: To assess the evolution of anti-SARS-CoV-2 antibodies (S protein) in plasma pools and IgG products and its neutralizing activity to original-type virus (Wuhan) and the variants of concern (VOC), including Omicron. MethodsHealthy donors plasma pools collected in the US and Europe, and the subsequent intravenous (Flebogamma DIFand Gamunex-C, Grifols) and subcutaneous (Xembify, Grifols) IgG manufactured batches were followed from March 2020. Anti-SARS-CoV-2 S protein IgG titers were determined in plasma pools and in IgG batches by ELISA. Neutralization assays analyzed the capacity of IgG products to neutralize original-type virus and VOC (Alpha, Beta, Delta, Omicron BA.1 and BA.5), using pseudo viruses expressing S protein. Results were expressed as the dilution producing 50% neutralization (ID50). ResultsIn plasma pools, anti-SARS-CoV-2 S antibodies continuously increased throughout the study period regardless of the geographic origin. In the US, the first positive plasma pools were collected at the end of 2020. Since July 2021, an exponential increase over 30-fold of anti-SARS-CoV-2 S antibodies was reported. This trend continued increasing until the end of study period. Similarly, IgG products showed a similar evolution of anti-SARS-CoV-2 S antibodies. As expected, IgG batches released at the end of 2020 presented low SARS-CoV-2 neutralization activity. However, IgG products manufactured since August 2021 showed high neutralization activity against original-type virus and the rest of VOC. Regarding Omicron BA.5, a 5 to 10-fold increase was observed over time. ConclusionThis study reported the onset of elevated anti-SARS-CoV-2 antibody titers in plasma pools and IgG products since mid-2021, reflecting the evolution of the pandemic and vaccine campaigns. Intravenous and subcutaneous IgG products efficiently neutralized the current circulating VOC, Omicron BA.5. Further research is warranted to assess whether a clinical protective titer against SARS-CoV-2 and passive immunization is achieved in patients with immunodeficiencies treated with IgG products.

Prevalence of Antiphospholipid Antibodies and Association With Incident Cardiovascular Events

The prevalence of antiphospholipid antibodies (aPL) and their association with future atherosclerotic cardiovascular disease (ASCVD) risk has yet to be thoroughly investigated. To determine the association between measurements of aPL at a single time point and ASCVD risk in a diverse population. This cohort study measured 8 aPL (anticardiolipin [aCL] IgG/IgM/IgA, anti-beta-2 glycoprotein I [aβ2GPI] IgG/IgM/IgA, and antiphosphatidylserine/prothrombin [aPS/PT] IgG/IgM) by solid-phase assays in plasma from participants of the Dallas Heart Study (DHS) phase 2, a multiethnic, population-based cohort study. Blood samples were collected between 2007 and 2009. The median follow-up was 8 years. Statistical analysis was performed from April 2022 to January 2023. Associations of aPL with future ASCVD events (defined as first nonfatal myocardial infarction, first nonfatal stroke, coronary revascularization, or death from cardiovascular cause) were assessed by Cox proportional hazards models, adjusting for known risk factors, medications, and multiple comparisons. Among the 2427 participants (mean [SD] age, 50.6 [10.3] years; 1399 [57.6%] female; 1244 [51.3%] Black, 339 [14.0%] Hispanic, and 796 [32.8%] White), the prevalence of any positive aPL tested at a single time point was 14.5% (353 of 2427), with approximately one-third of those detected at a moderate or high titer; aCL IgM had the highest prevalence (156 individuals [6.4%]), followed by aPS/PT IgM (88 [3.4%]), aβ2GPI IgM (63 [2.6%]), and aβ2GPI IgA (62 [2.5%]). The IgA of aCL (adjusted hazard ratio [HR], 4.92; 95% CI, 1.52-15.98) and aβ2GPI (HR, 2.91; 95% CI, 1.32-6.41) were independently associated with future ASCVD events. The risk further increased when applying a positivity threshold of at least 40 units (aCL IgA: HR, 9.01 [95% CI, 2.73-29.72]; aβ2GPI IgA: HR, 4.09 [95% CI, 1.45-11.54]). Levels of aβ2GPI IgA negatively correlated with cholesterol efflux capacity (r = -0.055; P = .009) and positively correlated with circulating oxidized LDL (r = 0.055; P = .007). aβ2GPI IgA-positive plasma was associated with an activated endothelial cell phenotype as evidenced by increased surface expression of surface E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. In this population-based cohort study, aPL detectable by solid-phase assays were present in a substantial proportion of adults; positive aCL IgA and aβ2GPI IgA at a single time point were independently associated with future ASCVD events. Longitudinal studies with serial aPL measurements are needed to further explore these findings.

An improved resistance model of positive subsonic plasma channels in water

The subsonic plasma channel and water can be regarded as series resistors in the pre-breakdown stage of sub-millisecond pulsed discharge in conductive water. An improved resistance model of the positive subsonic plasma channel is proposed. The gap resistance and the morphology of the bubble cluster and the plasma channel inside it are obtained from the electrical measurement and optical observation, respectively. The resistance of the plasma channel in the strong-ionization stage is calculated using the small-current arc resistance model. The improved model of the water resistance is established by analyzing the relationship between its equivalent cross-sectional area and its length in an uneven electric field. The resistance of the plasma channel in the weak-ionization stage is calculated. The resistance, voltage, and energy in the gap are analyzed based on the improved resistance model. The plasma channel's resistance is far less than the water resistance. The low voltage drop in the plasma channel leads to a high electric potential in the plasma channel's head, which is conducive to the plasma channel's development. 97% of the total energy in the pre-breakdown stage is consumed by the water resistor. The improved resistance model is helpful to supplement the development mechanism of the sub-millisecond pulsed discharge in water.

Expression and clinical significance of plasma methylated SEPT 9 gene in patients with primary liver cancer

Objective: To investigate the expression and clinical significance of plasma methylated SEPT9 (mSEPT9) gene in patients with primary liver cancer. Methods: 393 cases who visited our hospital from May 2016 to October 2018 were selected. Among them, 75 cases were in the primary liver cancer (PLC) group, 50 cases were in the liver cirrhosis (LC) group, and 268 cases were in the healthy control group (HC). The three groups' positive rates of mSEPT9 expression in the peripheral plasma were detected by the polymerase chain reaction (PCR) fluorescent probe method. The correlational clinical features of liver cancer were analyzed. At the same time, the electrochemiluminescence detection method was used to compare the AFP positive rate. Statistical analysis was conducted using chi-square tests or continuity-corrected chi-square tests. Results: 367 cases actually had valid samples. There were 64, 42, and 64 cases in the liver cancer group, cirrhosis group, and healthy control group, respectively. Among them, 34 cases of liver cancer were verified from pathological tissues. The positive rate of plasma mSEPT9 was significantly higher in the liver cancer group than that in the liver cirrhosis and healthy control groups [76.6% (49/64), 35.7% (15/42), and 3.8% (10/261), respectively], and the differences were statistically significant (χ (2) = 176.017, P < 0.001). The sensitivity of plasma mSEPT9 detection (76.6%) was significantly better in liver cancer (76.6%) than that of AFP patients (54.7%), and the difference was statistically significant (χ (2) = 6.788, P < 0.01). Compared with the single detection, the sensitivity and specificity of plasma mSEPT9 combined with AFP were significantly improved (89.7% vs. 96.3%, respectively). Patients with liver cancer aged≥50 years, with clinical stage II or above, and those with pathological signs of moderate to low differentiation had higher levels of plasma mSEPT9 positive expression, and the differences were statistically significant (χ (2) = 6.41, 9.279, 6.332, P < 0.05). During the follow-up period, the survival time of liver cancer patients with positive plasma mSEPT9 expression was significantly shorter than that of those with negative expression (310 ± 26 days vs. 487 ± 59 days, respectively), with statistically significant differences (Log Rank P = 0.039). Conclusion: In China, the positive rate of plasma mSEPT9 detection in liver cancer patients is higher than that of AFP in relation to age, clinical stage, and degree of tissue differentiation; additionally, it has certain survival predictive values. As a result, detecting this gene has important clinical significance and potential clinical application value in the non-invasive diagnosis and prognosis assessment of patients with primary liver cancer.

First measurements of a scintillator-based fast-ion loss detector in reversed Ip/Bt at the ASDEX Upgrade tokamak

Fast-α losses in future fusion power plants are expected to follow the co- and counter-current directions due to the isotropy of the fusion reaction. At the ASDEX Upgrade tokamak, the co-current direction (achieved with positive plasma current and negative toroidal magnetic field) has been extensively studied thanks to an array of five fast-ion loss detectors (FILD). A new fast-ion loss detector compatible with reversed Ip/Bt (negative plasma current and positive magnetic toroidal field, defining positive as counter-clockwise when the machine is viewed from the top), namely RFILD, has been designed and commissioned to study the behaviour of counter-current fast-ion losses and to expand our knowledge on QH-mode, I-mode, and the L-H transition. The detector is a modified version of the midplane manipulator fast-ion loss detector that features a new probe head orientation and collimator geometry, optimised using the FILDSIM code. A fast CMOS camera is used as a high spatial resolution acquisition system, while an array of photomultipliers (up to 1 MHz) serves as a fast channel.First measurements have been taken in I-mode, QH-mode, L-mode and H-mode with core densities ranging between 4·1019 and 9·1019 m−3, IP between -0.8 and -0.6 MA and Bt of 2.5 T approximately. NBI fast-ion losses were observed for the first time in reversed Ip/Bt, producing high pitch (60 – 80°) losses. ICRH losses in H-minority heating configuration have also been observed in I-mode experiments. These losses correspond to the outer leg of banana particle trajectories. An upgraded double collimator detector design is also presented, that will increase the measurable particle range in future experimental campaigns (co- and counter-current particles simultaneously). Thus, we expand our understanding on the mechanisms behind fast-ion losses at the ASDEX Upgrade tokamak in the reversed Ip/Bt configuration.

INVESTIGATION OF THERMAL PLASMA OF ARC DISCHARGE BETWEEN NOVEL COMPOSITE Cu-W MATERIALS

In this work, the plasma emission of electric arc discharges between pairs of composite Cu-W electrodes was investigated by optical emission spectroscopy. Electrodes manufactured of Cu-W 50 vol.% composite materials by shock sintering technology at temperatures of 750, 850, 950, and 1050°C were used. The radial distributions of plasma temperature were determined by Boltzmann plot technique on the basis of the absolute values of intensity of both copper and tungsten spectral lines. The concentration of metal atoms of electrode origin (copper and tungsten) in the positive plasma column of electric arc discharges between studied electrodes manufactured of composite Cu-W materials was determined by the method of absolute intensities. The intensity of erosion of individual components of composite materials is estimated in an indirect way by comparing the radial distributions of atoms of materials of electrode origin for each type of the investigated arc discharge.

Characteristics of plasma Epstein-Barr virus DNA in children with primary infection

Objective: To explore the characteristics of plasma Epstein-Barr virus (EBV) DNA in primary infection in pediatric cases. Methods: The laboratory and clinical data of 571 children diagnosed with EBV primary infection in Children's Hospital of Fudan University during September 1st, 2017 to September 30th, 2018 were retrospectively analyzed. According to the results of plasma EBV DNA, they were divided into positive group and negative group. According to the EBV DNA, they were devided into high plasma virol load group and low plasma virol load group. The Chi-square test, Wilcoxon rank sum test were used to compare the differences between groups. Results: Among the 571 children with EBV primary infection, 334 were males and 237 were females. The age of first diagnosis was 3.8 (2.2, 5.7) years. There were 255 cases in positive group and 316 cases in negative group. The percentage of cases with fever,hepatomegaly and (or) splenomegaly, elevated transaminase in the positive group were higher than those in the negative group (235 cases (92.2%) vs. 255 cases (80.7%), χ2=15.22, P<0.001; 169 cases (66.3%) vs. 85 cases (26.9%), χ2=96.80, P<0.001; and 144 cases (56.5%) vs. 120 cases (38.0%), χ2=18.27, P<0.001; respectively).In the positive group, 70 cases were followed up for 46 (27, 106) days, 68 cases (97.1%) turned negative within 28 days, with the exception of 2 cases (2.9%) developed chronic active EBV infection by follow-up revision.There were 218 cases in high plasma viral DNA copies group and 37 cases in low copies group. More cases presented with elevated transaminases in the high plasma viral DNA copies group than those in the low group (75.7% (28/37) vs. 56.0%(116/207), χ2=5.00, P=0.025).Both the positive rate of EBV DNA in peripheral blood leukocytes (84.2% (266/316) vs. 44.7% (255/571), χ2=76.26, P<0.001) and the copies of EBV DNA (7.0×107 (1.3×107, 3.0×108) vs. 3.1×106 (1.6×106, 6.1×106) copies /L, Z=15.23, P<0.001) were higher than that of plasma. Conclusions: In immunocompetent pediatric cases diagnosed as EBV primary infection, cases with positive plasma EBV DNA were prone to have fever, hepatomegaly and (or) splenomegaly, and elevated transaminase than those with negative plasma viral DNA. The plasma EBV DNA usually turns negative within 28 days after initial diagnosis.Most cases with high viral load in plasma showed elevated aminotransferase.

Performance of Cytomegalovirus Real-Time Polymerase Chain Reaction Assays of Fecal and Plasma Specimens for Diagnosing Cytomegalovirus Colitis.

Cytomegalovirus (CMV) viral load detected by real-time polymerase chain reaction (PCR) in plasma or stool may facilitate detection of CMV colitis. This prospective study enrolled 117 patients with clinically suspected CMV colitis. Patients presenting with gastrointestinal symptoms and having increased risk of CMV infection were eligible. All participants underwent colonoscopy with tissue biopsy. Five patients underwent colonoscopy twice because of clinical recurrence, resulting in a total of 122 colonoscopies. Stool CMV-PCR and plasma CMV-PCR were performed within 7 days before/after colonoscopy. Twenty asymptomatic volunteers also underwent the same protocol. Twenty-seven (23.1%) of 122 colonoscopies yielded positive for CMV colitis. The sensitivity and specificity was 70.4% and 91.6% for stool CMV-PCR and 66.7% and 94.7% for plasma CMV-PCR, respectively. The sensitivity of either positive plasma or positive stool CMV-PCR was 81.5%, which is significantly higher than that of plasma CMV-PCR alone ( P = 0.045). However, positive results from both tests yielded a specificity of 95.8%, which is significantly higher than that of stool CMV-PCR alone ( P = 0.045). There was a good and significant correlation between stool CMV-PCR and plasma CMV-PCR ( r = 0.71, P < 0.01), and both tests significantly correlated with the cytomegalic cell count ( r = 0.62, P < 0.01 for stool and r = 0.64, P < 0.01 for plasma). There were no positive stool or plasma CMV-PCR assays among volunteers. The results of this study strongly suggest that the combination of stool CMV-PCR and plasma CMV-PCR can be used to confidently rule in (both positive) or rule out (both negative) a diagnosis of CMV colitis.