Clinical and genetic characteristics in lymphoma patients with a second solid malignancy

Diagnosis and treatment of multiple primary malignancies are becoming a new challenge in clinical practice worldwide. The present study aimed to characterize the clinical and genetic features of multiple primary malignancies in patients with synchronous or metachronous lymphoma and another solid tumor. We retrospectively analyzed 11 cases with lymphoma and another solid tumor. The germline mutations in plasma cell-free DNA samples and somatic mutations in lymphoma and solid tumor tissue samples were identified using targeted next-generation sequencing. In the 11 lymphoma patients, the most common type of concurrent solid tumor was colon adenocarcinoma (case 3, 5, 9 11) followed by papillary thyroid carcinoma (case 1, 7, 10). Metachronous lymphoma and solid tumor in 6 patients were treated with corresponding standard therapy asynchronously. Chemotherapy for colon adenocarcinoma during the interval of lymphoma chemotherapy led to excellent outcome in two patients. Immediate chemotherapy for lymphoma plus elective surgery for synchronous papillary thyroid carcinoma also yielded good prognosis in two patients with synchronous double primaries. Interestingly, we found that 10 of 11 patients with lymphoma and another solid tumor harbored germline mutations in Fanconi anemia complementation group (FANC) genes, including FANCI, FANCA, FANCG, FANCL, FANCD1, FANCF, FANCJ, and FANCS. In summary, comprehensive study of the clinical and genetic features of patients with multiple primary malignancies may improve diagnosis and treatment in the future. Mutations in FANC genes might be a predisposition to tumorigenesis of lymphoma patients with a second solid malignancy

Characterization of subcellular localization of duck enteritis virus UL51 protein

<p>Abstract</p> <p>Background</p> <p>Knowledge of the subcellular localization of a protein can provide useful insights about its function. While the subcellular localization of many alphaherpesvirus UL51 proteins has been well characterized, little is known about where duck enteritis virus (DEV) UL51 protein (pUL51) is targeted to. Thus, in this study, we investigated the subcellular localization and distribution of DEV pUL51 by computer aided analysis, as well as indirect immunofluorescence (IIF) and transmission immunoelectron microscopy (TIEM) approaches in DEV-infected cells.</p> <p>Results</p> <p>The DEV UL51 gene product was identified as an approximate 34 kDa protein in DEV-infected cells analyzed by western blotting. Computer aided analysis suggested that DEV pUL51 is not targeted to the mitochondrial, extra-cellular or nucleus, but be targeted to the cytoplasmic in host cells, more specifically, palmitoylation of the pUL51 through the N-terminal cysteine at position 9 makes membrane association and Golgi localization possible. Using IIF analysis, we found that DEV pUL51 was first detected in a juxtanuclear region of DEV-infected cells at 9 h postinfection (p.i.), and then was detected widely distributed in the cytoplasm and especially was stronger in the juxtanuclear region from 12 to 60 h p.i. TIEM analysis revealed that DEV pUL51 was mainly associated with cytoplasmic virions and also with some membranous structure near the pUL51-specific immuno-labeling intracellular virion in the cytoplasmic vesicles; moreover, the pUL51 efficiently accumulated in the Golgi apparatus at first, and then was sent to the plasma membrane from the Golgi by some unknown mechanism.</p> <p>Conclusion</p> <p>In this work, we described the basic characteristics of pUL51 subcellular localization and distribution for the first time. From these results, we concluded that palmitoylation at the N-terminal cysteine, which is conserved in all alphaherpesvirus UL51 homologs, is required for its membrane association and Golgi localization, and the pUL51 mainly localized to the juxtanuclear region of DEV-infected cells, as well seemed to be incorporated into mature virions as a component of the tegument. The research will provide useful clues for DEV pUL51 functional analysis, and will be usefull for further understanding the localization properties of alphaherpesvirus UL51 homologs.</p

Development and evaluation of an immunochromatographic strip test based on the recombinant UL51 protein for detecting antibody against duck enteritis virus

<p>Abstract</p> <p>Background</p> <p>Duck enteritis virus (DEV) infection causes substantial economic losses to the worldwide duck-producing areas. The monitoring of DEV-specific antibodies is a key to evaluate the effect of DEV vaccine and develop rational immunization programs. Thus, in this study, an immunochromatographic strip (ICS) test was developed for detecting DEV serum antibodies.</p> <p>Results</p> <p>The ICS test is based on membrane chromatography, and uses both the purified recombinant UL51 protein conjugated with colloidal gold and goat anti-rabbit IgG conjugated with colloidal gold as tracers, the purified recombinant UL51 protein as the capture reagent at the test line, and rabbit IgG as the capture reagent at the control line. The specificity of the ICS was evaluated by sera against DEV, Duck hepatitis virus (DHV), Riemerella anatipestifer (RA), Duck E. coli, Muscovy duck parvovirus (MPV), or Duck Influenza viruses (DIV). Only sera against DEV showed the strong positive results. In order to determine the sensitivity of the ICS, anti-DEV serum diluted serially was tested, and the minimum detection limit of 1:128 was obtained. The ICS components, which are provided in a sealed package, require no refrigeration and are stable for 12 months. To evaluate the effect of the ICS, 110 duck serum samples collected from several non-immune duck flocks were simultaneously tested by the ICS test, enzyme-linked immunosorbent assay (ELISA) and neutralization test (NT). The results showed that the sensitivity of the ICS test was almost consistent with ELISA and much higher than NT, has low cost, and is rapid (15 min) and easy to perform with no requirement of specialized equipment, reagent or technicians.</p> <p>Conclusions</p> <p>In this work, we successfully developed a simple and rapid ICS test for detecting DEV serum antibodies for the first time. The ICS test was high specific and sensitive for the rapid detection of anti-DEV antibodies, and has great potential to be used for the serological surveillance of DEV infection in the field.</p

Functional connectivity of the anterior cingulate cortex in depression and in health

The first voxel-level resting-state functional connectivity (FC) neuroimaging analysis of depression of the anterior cingulate cortex (ACC) showed in 282 patients with major depressive disorder compared with 254 controls, some higher, and some lower FCs. However, in 125 unmedicated patients, primarily increases of FC were found: of the subcallosal anterior cingulate with the lateral orbitofrontal cortex, of the pregenual/supracallosal anterior cingulate with the medial orbitofrontal cortex, and of parts of the anterior cingulate with the inferior frontal gyrus, superior parietal lobule, and with early cortical visual areas. In the 157 medicated patients, these and other FCs were lower than in the unmedicated group. Parcellation was performed based on the FC of individual ACC voxels in healthy controls. A pregenual subdivision had high FC with medial orbitofrontal cortex areas, and a supracallosal subdivision had high FC with lateral orbitofrontal cortex and inferior frontal gyrus. The high FC in depression between the lateral orbitofrontal cortex and the subcallosal parts of the ACC provides a mechanism for more non-reward information transmission to the ACC, contributing to depression. The high FC between the medial orbitofrontal cortex and supracallosal ACC in depression may also contribute to depressive symptoms

A Thymidine Kinase recombinant protein-based ELISA for detecting antibodies to Duck Plague Virus

<p>Abstract</p> <p>Background</p> <p>Duck plague virus (DPV) is the causative agent of Duck Plague (DP) that causes significant morbidity and mortality throughout duck-producing areas of the world. The diagnosis of DP currently relies on the use of live or inactivated whole DPV virion as antigens in ELISA, but it is too laborious and expensive for routine application, and it is still difficult to get purified DPV virion with current technology.</p> <p>Results</p> <p>In this study, we describe the expression and purification of a recombinant Thymidine Kinase (TK) protein which makes antigen in an in-house developed, optimized and standardized ELISA. The specificity of the optimized TK-ELISA was evaluated by antisera against Duck Plague Virus (DPV), Duck Hepatitis B Virus (DHBV), Duck Hepatitis Virus (DHV), <it>Riemerella Anatipestifer</it>(<it>R. A</it>), <it>Escherichia coli </it>(<it>E. coli</it>) and <it>Salmonella anatum </it>(<it>S. anatum</it>). Only antisera against DPV yielded a specific and strong signal. In order to determine the sensitivity of the TK-ELISA, a panel of diluted sera was tested, and the minimum detection limit of 1:2560 (OD450 nm = 0.401) was obtained according to the endpoint cut-off (0.2438). The repeatability and reproducibility under the experimental conditions demonstrates a low variability (P > 0.05). The suspected sera samples (n = 30) were determined by TK-ELISA and the positive rate is 90% (27/30), and the TK-ELISA showed 83.33% (22+3/30) coincidence rate with the Serum Neutralization Test (SNT) and 90% (24+3/30) coincidence rate with the whole DPV virion based-ELISA (DPV-ELISA). When defining the dynamics of antibody response to attenuated live DPV vaccine, the maximum antibodies is reached after 4 weeks.</p> <p>Conclusions</p> <p>The results suggest that the TK-ELISA provides high specificity, sensitivity, repeatability and reproducibility for detection of anti-DPV antibodies in duck sera, and has the potential to be much simpler than DPV-ELISA and SNT for the sera epidemiological investigation.</p

A retrospective analysis of factors associated with the length of hospital stay in COVID-19 patients treated with Nirmatrelvir / Ritonavir

Objectives: This study reviewed factors influencing the length of hospital stay in adult inpatients with confirmed Coronavirus disease (COVID-19) who were treated with Nirmatrelvir/Ritonavir.Methods: We did a retrospective analysis of data from a cohort of inpatients with confirmed diagnosis of Omicron variant of SARS-CoV-2 infection who were treated with Nirmatrelvir/Ritonavir. We included patients who were treated from 13th March 2022 to 6th May 2022 in various in-patient treatment units in Quanzhou, Fujian Province, China. The primary study outcome was the length of hospital stay. Secondary study outcome was viral elimination defined as negative for ORF1ab and N genes [cycle threshold (Ct) value ≥35 in real-time PCR], according to local guidelines. Hazard ratios (HR) of event outcomes were analyzed using Multivariate Cox regression models.Results: We studied 31 inpatients with high risk for severe COVID-19 who were treated with Nirmatrelvir/Ritonavir. We found that inpatients with shorter length of hospital stay (≤17 days) were mostly females with lower body mass index (BMI) and Charlson Comorbidity Index (CCI) index. Their treatment regimen with Nirmatrelvir/Ritonavir was started within 5 days of diagnosis (p &lt; 0.05). Multivariate Cox regression indicated that inpatients starting treatment of Nirmatrelvir/Ritonavir within 5 days had a shorter length of hospital stay (HR 3.573, p = 0.004) and had a faster clearance of viral load (HR 2.755, p = 0.043).Conclusion: This study assumes relevance during the Omicron BA.2 epidemic as our findings suggest that early treatment with Nirmatrelvir/Ritonavir within 5 days of diagnosis (≤5 days) was highly effective in shortening the length of hospital stay and faster viral load clearance

Value of deep learning models based on ultrasonic dynamic videos for distinguishing thyroid nodules

ObjectiveThis study was designed to distinguish benign and malignant thyroid nodules by using deep learning(DL) models based on ultrasound dynamic videos.MethodsUltrasound dynamic videos of 1018 thyroid nodules were retrospectively collected from 657 patients in Zhejiang Cancer Hospital from January 2020 to December 2020 for the tests with 5 DL models.ResultsIn the internal test set, the area under the receiver operating characteristic curve (AUROC) was 0.929(95% CI: 0.888,0.970) for the best-performing model LSTM Two radiologists interpreted the dynamic video with AUROC values of 0.760 (95% CI: 0.653, 0.867) and 0.815 (95% CI: 0.778, 0.853). In the external test set, the best-performing DL model had AUROC values of 0.896(95% CI: 0.847,0.945), and two ultrasound radiologist had AUROC values of 0.754 (95% CI: 0.649,0.850) and 0.833 (95% CI: 0.797,0.869).ConclusionThis study demonstrates that the DL model based on ultrasound dynamic videos performs better than the ultrasound radiologists in distinguishing thyroid nodules

Metabolite identification in fecal microbiota transplantation mouse livers and combined proteomics with chronic unpredictive mild stress mouse livers

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Major depressive disorder (MDD) is a common mood disorder. Gut microbiota may be involved in the pathogenesis of depression via the microbe–gut–brain axis. Liver is vulnerable to exposure of bacterial products translocated from the gut via the portal vein and may be involved in the axis. In this study, germ-free mice underwent fecal microbiota transplantation from MDD patients and healthy controls. Behavioral tests verified the depression model. Metabolomics using gas chromatography–mass spectrometry, nuclear magnetic resonance, and liquid chromatography–mass spectrometry determined the influence of microbes on liver metabolism. With multivariate statistical analysis, 191 metabolites were distinguishable in MDD mice from control (CON) mice. Compared with CON mice, MDD mice showed lower levels for 106 metabolites and higher levels for 85 metabolites. These metabolites are associated with lipid and energy metabolism and oxidative stress. Combined analyses of significantly changed proteins in livers from another depression model induced by chronic unpredictive mild stress returned a high score for the Lipid Metabolism, Free Radical Scavenging, and Molecule Transports network, and canonical pathways were involved in energy metabolism and tryptophan degradation. The two mouse models of depression suggest that changes in liver metabolism might be involved in the pathogenesis of MDD. Conjoint analyses of fecal, serum, liver, and hippocampal metabolites from fecal microbiota transplantation mice suggested that aminoacyl-tRNA biosynthesis significantly changed and fecal metabolites showed a close relationship with the liver. These findings may help determine the biological mechanisms of depression and provide evidence about “depression microbes” impacting on liver metabolism

Transcriptional profiles of drought-responsive genes in modulating transcription signal transduction, and biochemical pathways in tomato

To unravel the molecular mechanisms of drought responses in tomato, gene expression profiles of two drought-tolerant lines identified from a population of Solanum pennellii introgression lines, and the recurrent parent S. lycopersicum cv. M82, a drought-sensitive cultivar, were investigated under drought stress using tomato microarrays. Around 400 genes identified were responsive to drought stress only in the drought-tolerant lines. These changes in genes expression are most likely caused by the two inserted chromosome segments of S. pennellii, which possibly contain drought-tolerance quantitative trait loci (QTLs). Among these genes are a number of transcription factors and signalling proteins which could be global regulators involved in the tomato responses to drought stress. Genes involved in organism growth and development processes were also specifically regulated by drought stress, including those controlling cell wall structure, wax biosynthesis, and plant height. Moreover, key enzymes in the pathways of gluconeogenesis (fructose-bisphosphate aldolase), purine and pyrimidine nucleotide biosynthesis (adenylate kinase), tryptophan degradation (aldehyde oxidase), starch degradation (β-amylase), methionine biosynthesis (cystathionine β-lyase), and the removal of superoxide radicals (catalase) were also specifically affected by drought stress. These results indicated that tomato plants could adapt to water-deficit conditions through decreasing energy dissipation, increasing ATP energy provision, and reducing oxidative damage. The drought-responsive genes identified in this study could provide further information for understanding the mechanisms of drought tolerance in tomato