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Summary: A consensus statement for the management for patients of all ages with all stages of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) — All StAGEs — is proposed by representatives of the UK National Cancer Research Institute (NCRI) Hodgkin lymphoma study group and the Children's Cancer & Leukaemia Group. Based on current practices and published evidence, a consensus has been reached regarding diagnosis, staging and risk‐ik7 stratified management which includes active surveillance, low‐ and standard‐dose immunochemotherapy and radiotherapy. [ABSTRACT FROM AUTHOR]

Ca 2 + is a ubiquitous signaling mechanism across different cell types. In T-cells, it is associated with cytokine production and immune function. Benson et al. have shown the coexistence of competing Ca 2 + oscillations during antigen stimulation of T-cell receptors, depending on the presence of extracellular Ca 2 + influx through the Ca 2 + release-activated Ca 2 + channel (Benson in J Biol Chem 29:105310, 2023). In this paper, we construct a mathematical model consisting of five ordinary differential equations and analyze the relationship between the competing oscillatory mechanisms.. We perform bifurcation analysis on two versions of our model, corresponding to the two oscillatory types, to find the defining characteristics of these two families. [ABSTRACT FROM AUTHOR]

Postmenopausal osteoporosis (PMOP) is a systemic skeletal disorder associated with disturbances in bone metabolism caused by estrogen deficiency during menopause. Major histocompatibility complex class II molecules (MHC-II), central to the protein presentation pathway, are regulated by estrogen and can participate in the adaptive immune response mediated by T and B lymphocytes and promote T cell-derived inflammatory factors, which ultimately promote osteoclast-mediated bone formation and bone resorption in the skeleton. In this paper, to better understand the possible role of MHC-II in postmenopausal osteoporosis, we review estrogen, MHC-II, and lymphocytes, and their potential mechanisms in the differentiation process and functional activity of osteoclasts. [ABSTRACT FROM AUTHOR]

Paroxysmal nocturnal haemoglobinuria (PNH) results from acquired mutations in the PIG-A gene of an haematopoietic stem cell, leading to defective biosynthesis of glycosylphosphatidylinositol (GPI) anchors and deficient expression of GPI-anchored proteins on the surface of the cell's progeny. Some laboratory and clinical findings have suggested genomic instability to be intrinsic in PNH; this possibility has been supported by mutation analysis of hypoxanthine-guanine phosphoribosyltransferase ( HPRT) gene abnormalities. However, the HPRT assay examines lymphocytes in peripheral blood (PB), and T cells may be related to the pathophysiology of PNH. We analysed the molecular and functional features of HPRT mutants in PB mononuclear cells from eleven PNH patients. CD8 T cells predominated in these samples; approximately half of the CD8 cells lacked GPI-anchored protein expression, while only a small proportion of CD4 cells appeared to derive from the PNH clone. The HPRT mutant frequency (Mf) in T lymphocytes from PNH patients was significantly higher than in healthy controls. The majority of the mutant T lymphocyte clones were of CD4 phenotype, and they had phenotypically normal GPI-anchored protein expression. In PNH patients, the majority of HPRT mutant clones were contained within the V β2 T cell receptor (TCR) subfamily, which was oligoclonal by complementarity-determining region three (CDR3) size analysis. Our results are more consistent with detection of uniform populations of expanded T cell clones, which presumably acquired HPRT mutations during antigen-driven cell proliferation, and not due to an increased Mf in PNH. HPRT mutant analysis does not support underlying genomic instability in PNH. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) cells express certain tumour-associated antigens (TAAs) that could serve as targets for active-specific immunotherapy. The aim of the present study was to test the MM/dendritic cell (DC) fusion as a vaccination strategy. We fused MM cells with DC to generate fusion cells (FCs) and tested their antigen presenting cell (APC) function in mixed lymphocyte reactions and cytotoxicity assays. First, the HS Sultan and SK0-007 HAT sensitive human MM cell lines and DCs generated from peripheral blood of normal donors were fused in the presence of 50% polyethylene glycol to form FCs. Next, tumour cells freshly isolated from patients were similarly fused with autologous DCs to generate FCs. The FCs demonstrated a biphenotypic profile, confirmed both by flow-cytometry and dual immunofluorescence microscopy. These FCs induced MM-specific cytotoxicity. FCs, but not MM cells or DCs alone, were potent stimulators of autologous patient T cells. More importantly, FC-primed autologous peripheral blood mononuclear cells demonstrated major histocompatibility complex-restricted MM-specific cytolysis. These studies therefore demonstrated that MM/DC FC can trigger an autologous immune response to MM cells and formed the framework for a clinical trial currently underway. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are important for the pathogenesis and progression of different tumours. MMPs-2 and -9 are the principal MMPs produced by lymphocytes; these enzymes can degrade a number of matrix proteins but are the two main MMPs that digest type IV collagen, the major component of basement membranes. Therefore, these enzymes are potentially important for tissue invasion and remodelling by malignant lymphocytes. This study showed that chronic lymphocytic leukaemia (CLL) cells produce and secrete variable amounts of pro-MMP-9, but no MMP-2 or tissue inhibitor of metalloproteinase  1 (TIMP-1). The pro-enzyme was found in monomeric and dimeric forms and also complexed with lipocalin. Moreover, a small fraction of secreted monomer became associated with the cell surface and activated upon cell adhesion to insolubilized type IV collagen. High levels of intracellular MMP-9 were associated with advanced (stage C) disease and with poor patient survival. Immunohistochemical studies demonstrated that MMP-9 was associated with areas of tissue invasion and remodelling. The relatively specific MMP-9 inhibitors, Ro31-9790 (3 μmol/l) and TIMP-1, reduced CLL-cell migration through type IV collagen and through endothelial monolayers suggesting that the enzyme may also be important in malignant cell entry and egress to and from involved tissue. Our data raise the possibility that MMP-9 modulation may have therapeutic potential in advanced CLL. [ABSTRACT FROM AUTHOR]

The role of repopulating lymphocytes after allogeneic stem cell transplantation (SCT) includes the prevention of serious infections and attacking residual tumour cells in the early post-transplant phase. Therefore, the current study analysed the role of the absolute lymphocyte count (ALC) on day 21 after SCT in predicting transplant outcomes of 82 patients in terms of the risk of opportunistic infections and recurrence of original disease. The median dose of CD34+, CD3+ and mononuclear cells (MNC) infused was 6·41 × 106/kg, 1·96 × 108/kg and 6·81 × 108/kg respectively. The high ALC group (high ALC on day 21; ≥0·35 × 109/l) was associated with the use of peripheral blood stem cells, matched sibling donors and higher cell doses of MNC, CD3+ and CD4+ cells. The high ALC group also exhibited a better overall survival (56·3% vs. 17·7%) and disease-free survival (50·1% vs. 15·9%) after 3 years and lower incidences of relapse (33·6% vs. 67·1%) and fungal infections (3·0% vs. 19·5%) after 1 year. The incidence of cytomegalovirus antigenaemia was lower in the high ALC group (47·7% vs. 73·7%). Accordingly, identifying the ALC on day 21 would appear to be a useful and simple measurement to predict those patients with a high risk of opportunistic infections and relapse after allogeneic SCT. [ABSTRACT FROM AUTHOR]

Multiple mechanisms exist by which tumour cells can escape CD95-mediated apoptosis. Previous studies by our laboratory have shown that primary B cells from non-Hodgkin's Lymphoma (B-NHL) were resistant to CD95-induced cell death. In the current study, we have analysed the mechanisms underlying CD95 resistance in primary human lymphoma B cells. We report that FADD (FAS-associated death domain protein) and caspase-8 were constitutively expressed in lymphoma B cells and that the CD95 pathway was blocked upstream to caspase-8 activation. However, caspase-8 was processed and functional after treatment with staurosporine (STS). We found that the expression levels of FLICE (FADD-like interleukin-1 beta-converting enzyme)-Inhibitory Protein (c-FLIP) and Bcl-2-related proteins were heterogeneous in B-NHL cells and were not related to CD95 resistance. Finally, we report the absence of a CD95-induced signalling complex [death-inducing signalling complex (DISC)] in lymphoma B cells, with no FADD and caspase-8 recruitment to CD95 receptor. In contrast, DISC formation was observed in CD95-resistant non-tumoural (NT) B cells. Therefore, we propose that the absence of DISC formation in primary lymphoma B cells may contribute to protect these cells from CD95-induced apoptosis. [ABSTRACT FROM AUTHOR]

We have investigated whether intracellular signal transduction molecules can be used as immunohistological markers of normal and neoplastic human leucocytes in routine tissue sections. We obtained selective labelling of white cells for eight such molecules (the ‘linker’ molecules SLP-76 and BLNK, the Src family kinases Lyn, Fyn, Syk and Hck, and the phospholipases PLC- γ1 and PLC- γ2). Antibodies to SLP-76 and PLC- γ1 selectively labelled T cells, and antibodies to BLNK, Lyn, Fyn, Syk and PLC- γ2 labelled B cells (although Fyn immunostaining was restricted to mantle zone B cells). Antibodies to the Syk and Hck kinases labelled probable thymocyte precursors at the periphery of the thymic cortex. In addition to lymphoid cells, several other leucocyte types were immunostained (e.g. SLP-76, Lyn, Syk and Hck were found in megakaryocytes, myeloid cells and/or macrophages, and PLC- γ2 was detected in arterial endothelium). SLP-76 and PLC- γ1 were found in most T-cell lymphomas studied, and some B-cell lymphomas were also positive for PLC- γ1 (e.g. diffuse large cell and Burkitt's lymphoma). The five B cell-associated markers were found in most B-cell non-Hodgkin's lymphomas, although some diffuse large B-cell lymphomas were negative (e.g. for Lyn) and anti-Fyn tended not to stain small B-cell neoplasms. The observation that a range of leucocyte signalling molecules can be detected in routine biopsies offers new possibilities for studying normal and neoplastic human white cells in diagnostic tissue samples. [ABSTRACT FROM AUTHOR]

Sources for allogeneic stem cells for patients with haematological disorders lacking a histocompatible sibling donor include matched unrelated donor (MUD) and umbilical cord blood (UCB). A total of 51 patients with haematological disorders, treated with myeloablation and transplantation with either unrelated human leucocyte antigen (HLA) partially matched UCB (28 patients) or HLA-matched MUD grafts (23 patients) during 1997–2003, were evaluated for life-threatening infections, haematological reconstitution, graft versus host disease, relapse and event-free survival (EFS). The median duration of neutropenia after transplantation was longer (29 d vs. 14 d) in the UCB group. The probability of donor-derived neutrophil engraftment by day 42 was 0·86 [95% confidence interval (CI) 0·71–1·0] in UCB recipients versus 0·96 (95% CI 0·87–1·0) in MUD recipients surviving >28 d. Overall infection rates were higher in UCB recipients, particularly at the early time points (before day +50) after transplantation. Graft failure occurred in five UCB recipients and two MUD recipients and was associated with the occurrence of bacteraemia during neutropenia. The EFS at 3-year follow-up was 0·25 in UCB and 0·35 in MUD recipients. UCB transplantation in adults is associated with delayed neutrophil and lymphocyte recovery compared with MUD grafting, and higher rates of bacteraemia at early time points after transplantation. [ABSTRACT FROM AUTHOR]

Ikaros is a Kruppel-type zinc finger protein that is essential for normal lymphocyte development and differentiation. Recently, it has been demonstrated that Ikaros is frequently inactivated in both human and mouse leukaemias/lymphomas. Although this inactivation is thought to be involved in leukaemogenesis, little is known about the molecular mechanisms that lead to neoplastic transformation. To identify the genes that may be controlled by Ikaros, we performed differential display analysis of RNAs from mouse 3T3-L1 cells that had been transfected with the Ikaros gene. Two cDNAs, the Trk-fused gene ( Tfg) and death-associated protein 3 gene ( Dap3) were upregulated in Ikaros-transfected cells. Expression of Tfg and Dap3 was consistently downregulated in radiation-induced T-cell lymphomas that exhibited defective Ikaros expression. These results suggest that Tfg and Dap3 function downstream of Ikaros and may be involved in radiation-induced lymphomagenesis. [ABSTRACT FROM AUTHOR]

Despite a successful outcome of the anti-D prophylaxis programme, alloimmunization still occurs. The aim of this study was to estimate the frequency of Rh-specific B lymphocytes in the peripheral blood of nine Rh-alloimmunized individuals at different time intervals after parturition. The donors’ B lymphocytes were transformed with Epstein–Barr virus (EBV) and cultured at different cell densities over a feeder of human fetal fibroblasts. Culture supernatants were screened for human immunoglobulin by enzyme-linked immunosorbent assay (ELISA) and for anti-Rh antibody by using a direct haemagglutination technique. The percentage of CD19+ B lymphocytes in peripheral blood was determined by flow cytometry, and the frequency of Rh-specific B lymphocytes was estimated by limiting-dilution assay (LDA). The frequency of Rh-specific B lymphocytes varied from 1 : 150 to 1 : 27 850 in different donors. There was a decrease in this frequency and level of anti-Rh antibody with increase in time interval between bleeding and last exposure to the antigen. Furthermore, a positive correlation was observed between the titre of Rh-specific antibody and frequency of Rh-specific B cells in each of three subjects bled at multiple time-points postdelivery. The magnitude of the specific antibody response to Rh antigens varies greatly in Rh-alloimmunized women, which partly reflects the difference in frequency of specific B cells in these individuals. [ABSTRACT FROM AUTHOR]

The article focuses on abstracts of papers presented at the 28th annual meeting of American Society of Dermatopathology. The paper "Lymphocyte Markers in Formalin Fixed Tissue in Jessner's Lymphocytic Infiltrate and Discord Lupus Erythematosus," by R. Akasu and H. Kahn presents a clinical and histological differentiation between Jessner's lymphocytic infiltrate and discoid lupus erythematosus. "Lysozyme in Abnormal Dernal Elastic Fibers of Cutaneous Aging, Solar Elastosis and Pseudozanthoma Elasticum," by S. Albrecht, L. From and H.J. Kahn presents a staining pattern of dermal elastic fibers in aging.

Erythema multiforme (EM)-like contact reactions are induced by exposure to various chemicals. We report two industrial workers from a paper mill who presented with generalized EM-like lesions 17 and 10 days, respectively, after accidental exposure to liquid-formulated 2,2-dibromo-3-nitrilopropionamide (DBNPA) 20%. The EM-like lesions appeared as subepidermal blisters associated with many necrotic or apoptotic keratinocytes and dense lymphocytic infiltration in the epidermis. Most of the infiltrating cells in the epidermis were CD8-positive T lymphocytes expressing cytotoxic molecules, including T cell-restricted intracellular antigen (TIA)-1, granzyme B and granulysin. Steroid pulse therapy failed to suppress the development of the lesions sufficiently, but ciclosporin 2.5–3 mg/kg successfully controlled the disease. DBNPA-induced, generalized EM-like eruptions may be mediated by cytotoxic T-lymphocytes. [ABSTRACT FROM AUTHOR]

Genetic testing represents a major asset for discriminating between normal antigenic stimulation of B or T cells and malignant, pathological findings. The main difference between those two situations is the heterogenicity of lymphocyte populations as a result of diverse antigenic stimulation for the first situation, compared to single and identical population (clones) for the second situation. The present paper describes one of the many genetic assays capable of discriminating between normal and malignant, characterized by low time-to-result interval, accuracy, simplicity, and low cost comparing to other tests. [ABSTRACT FROM AUTHOR]

Simple Summary: The extracellular matrix surrounding or infiltrating tumor tissues, tumor cells, endothelial cells, immune cells, fibroblasts, macrophages, as well as soluble molecules like cytokines and growth factors secreted by these cells, constitute the complex biological structure known as the tumor microenvironment (TME). The cellular and non-cellular components of TME have a role in the development of tumors and the immune response, which offers novel insights for targeted therapies. Depleting existing cells, stopping them from being attracted to tumor locations, and reprogramming them into antitumor subtypes are the three primary categories of therapeutic approaches. TME exhibits complicated connections between Hodgkin/Reed–Sternberg cells and microenvironment and plays a crucial role in classical Hodgkin lymphoma (CHL) as well. Numerous studies have demonstrated that an extensive understanding of the CHL microenvironment, including the identification of all cellular components and variables implicated in the pathogenesis, is essential for improving prognostic stratification and developing innovative targeted treatments. Although classical Hodgkin lymphoma (CHL) is typically curable, 15–25% of individuals eventually experience a relapse and pass away from their disease. In CHL, the cellular microenvironment is constituted by few percent of H/RS (Hodgkin/Reed–Sternberg) tumor cells surrounded from a heterogeneous infiltration of inflammatory cells. The interplay of H/RS cells with other immune cells in the microenvironment may provide novel strategies for targeted immunotherapies. In this paper we analyzed the microenvironment content in CHL patients with responsive disease (RESP) and patients with relapsed/refractory disease to treatment (REL). Our results indicate the increase of CD68+ and CD163+ macrophages, the increase of PDL-1+ cells and of CD34+ microvessels in REL patients respective to RESP patients. In contrast we also found the decrease of CD3+ and of CD8+ lymphocytes in REL patients respective to RESP patients. Finally, in REL patients our results show the positive correlation between CD68+ macrophages and PDL-1+ cells as well as a negative correlation between CD163+ and CD3+. [ABSTRACT FROM AUTHOR]

Introduction: Among the risk factors for squamous cell carcinoma of the head and neck, smoking is still the most important today. Several studies agree on the effect of smoking on tumor microenvironment, while the definition of former smokers and the time of smoking cessation on biologic effect differs among papers. Methods: We conducted a narrative review on smoking effects in HNSCC. Results: There is evidence that smoker patients have a poorer prognosis than never smokers and former smokers. Translational studies show a relationship between smoking status and gene expression and support the importance of smoking cessation, for instance, demonstrating an inverse relationship between tumor-infiltrating lymphocytes and smoking. Conclusion: Convincing data suggest that quitting smoking at any time may improve patient outcomes. We advocate smoking cessation also after cancer diagnosis. [ABSTRACT FROM AUTHOR]

Primary immunodeficiencies (PIDs) are characterized by an increased susceptibility to infections due to defects in one ore more components of the immune system. Although most PIDs are relatively rare, they are more frequent than generally acknowledged. Early diagnosis and treatment of PIDs save lives, prevent morbidity, and improve quality of life. This early diagnosis is the task of the pediatrician who encounters the child for the first time: he/she should suspect potential PID in time and perform the appropriate diagnostic tests. In this educational paper, the first in a series of five, we will describe the most common clinical presentations of PIDs and offer guidelines for the diagnostic process, as well as a brief overview of therapeutic possibilities and prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Systemic inflammation and changes in the inflammatory status are frequent features of lung cancer. There is a close interconnection between cancer development and the clinical, general, and inflammatory status of patients. In this paper, we evaluate a large panel of inflammatory indexes in patients who underwent lung resection for NSCLC lung cancer; we show that pre-operative inflammatory status strongly influences long-term prognosis in patients affected by NSCLC and undergoing surgery. Background (1): Our goal was to investigate if and how pre-operative inflammatory status can influence the long-term prognosis of patients undergoing lung surgery for cancer. Materials and Methods (2): This prospective observational study includes the agreement of all operable patients to the study, who were referred to our department between 1 January 2017 and 30 December 2018. The inflammatory pre-operative status of the patients was investigated by calculating albumin, CPR (c-protein reactive), complete blood count (neutrophils, lymphocytes, platelets, hemoglobin), and some other indexes referring to inflammatory status, namely the HALP amalgamated index, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocytes ratio (NLR), systemic immune-inflammation index (SII), and advanced lung cancer inflammation Index (ALI). The follow-up ended in November 2021. Patient overall survival was assessed using the Kaplan–Meier method. The log-rank test was used to compare survival rates. Variables significantly associated with survival at univariate analysis were entered int Cox multivariate analysis (stepwise mode) to assess their independent character. Hazard ratios and their 95% confidence intervals were calculated. Variables associated with p < 0.05 were considered significative. Results (3): We enrolled 257 patients in our study. The overall survival of the cohort was as follows: 1 year, 96.1%; 3 year, 81.3%; and 4 year, 74.2%. Univariate analysis showed risk factors for overall survival as follows: Thoracoscore ≥ 2 (p = 0.002); histology (p = 0.002); HALP < 32.2 (p = 0.0002); SII ≥ 808.9 (p = 0.0004); ALI < 34.86 (p = 0.0005); NLr ≥ 2.29 (p = 0.01); hemoglobin < 13 g/dl (p = 0.01); PLR ≥ 196.1 (p = 0.005); pN+ (p < 0.0001); pleural invasion (p = 0.0002); and presence of vascular or lymphatic tumor emboli (p = 0.0002). Multivariate Cox analysis (stepwise model) identified Thoracoscore ≥ 2 (p = 0.02); histology, HALP < 32.2 (p = 0.004), and pN (p < 0.0001) as independent predictors of death. Conclusion (4): Pre-operative inflammatory status strongly influences long-term prognosis in patients affected by NSCLC and undergoing surgery. [ABSTRACT FROM AUTHOR]

Recurrent Miscarriages are seen in 2%–5% of women and 50% of these are labelled as unexplained as no underlying cause is found in them. Various studies have explained possible alloimmune basis in these couples. Lymphocyte Immunization Therapy (LIT) was the earliest immunomodulatory method suggested in these cases. The efficacy of LIT was questioned by REMIS study in 1999 and subsequent Cochrane reviews. However, recent meta‐analyses have shown that LIT is not only effective in the treatment of repeated miscarriages but it is also safe. Review of the odds ratio for live birth of various meta‐analyses of studies in recurrent miscarriages has also shown that newer meta‐analyses have shown higher odds ratios. The purpose of this paper is to put forward the current perspective of LIT in reproductive failure and bring forth the recent evidence. In addition, we share our experience with the use of LIT in women with recurrent pregnancy losses. However, large multicentric RCTs are required to further prove efficacy of LIT. [ABSTRACT FROM AUTHOR]

Dengue fever, also known as break-bone fever, can be life-threatening. Caused by DENV, an RNA virus from the Flaviviridae family, dengue is currently a globally important public health problem. The clinical methods available for dengue diagnosis require skilled supervision. They are manual, time-consuming, labor-intensive, and not affordable to common people. This paper describes a method that can support clinicians during dengue diagnosis. It is proposed to automate the peripheral blood smear (PBS) examination using Artificial Intelligence (AI) to aid dengue diagnosis. Nowadays, AI, especially Machine Learning (ML), is increasingly being explored for successful analyses in the biomedical field. Digital pathology coupled with AI holds great potential in developing healthcare services. The automation system developed incorporates a blob detection method to detect platelets and thrombocytopenia from the PBS images. The results achieved are clinically acceptable. Moreover, an ML-based technique is proposed to detect dengue from the images of PBS based on the lymphocyte nucleus. Ten features are extracted, including six morphological and four Gray Level Spatial Dependance Matrix (GLSDM) features, out of the lymphocyte nucleus of normal and dengue cases. Features are then subjected to various popular supervised classifiers built using a ten-fold cross-validation policy for automated dengue detection. Among all the classifiers, the best performance was achieved by Support Vector Machine (SVM) and Decision Tree (DT), each with an accuracy of 93.62%. Furthermore, 1000 deep features extracted using pre-trained MobileNetV2 and 177 textural features extracted using Local binary pattern (LBP) from the lymphocyte nucleus are subjected to feature selection. The ReliefF selected 100 most significant features are then fed to the classifiers. The best performance was attained using an SVM classifier with 95.74% accuracy. With the obtained results, it is evident that this proposed approach can efficiently contribute as an adjuvant tool for diagnosing dengue from the digital microscopic images of PBS. [ABSTRACT FROM AUTHOR]

This article presents abstracts of several research papers presented at the 26th annual meeting of the American Society of Dermatopathology, held in Washington D.C. A research paper from the department of dermatology of General Hospital in Valencia, Spain reports two new cases of generalized eruptive histiocytoma. The disease was characterized by an asymptomatic, widespread, frequently symmetrical eruption of numerous small dark red or bluish red papules. The histology showed a monomorphic histiocytic infiltrate in papillary and mid portion of the dermis with a few lymphocytes.

The article presents abstracts of papers presented in the February 1986 issue of the Journal of Cutaneous Pathology. Some abstracts presented are as follows: The paper "An Immunophenotypic Comparison of the Lymphoid Infiltrates in Jessner's Lymphocytic Infiltration of the Skin and Chronic Discoid LE," by J. Ashworth, M.L. Turbutt and R.M. Mackie focuses on a comparative study of Jessner's lymphocytic infiltration of the skin; "Cutaneous Follicular Lymphomas," by C.F. Garcia, R.A. Warnke, A.J. Cox and G.S. Wood discusses 13 cases of cutaneous follicular lymphomas, which were evaluated clinically, histologically and immunologically.

Transmembrane protease serine 4 (TMPRSS4) is a cancer-associated protease associated with prognosis in various types of cancer. Mechanistically, TMPRSS4 mainly regulates malignant phenotypes, such as tumor invasion and metastasis, by either the epithelial to mesenchymal transition (EMT) program or promoting the proliferation of cancer cells. To date, TMPRSS4 and immune infiltration in thyroid carcinoma (TC) are largely unknown. Thus, this paper evaluated the expression of TMPRSS4 in tumor tissue through the Tumor Immune Estimation Resource (TIMER) database, and Oncomine, and its correlation with clinical parameters by UALCAN databases. Furthermore, we analyzed its prognostic value from Kaplan-Meier Plotter database, and the relationship between TMPRSS4 and the abundance of tumor-infiltrating lymphocytes (TILs) in TC in TISIDB, screening potential immune targets to explore novel mechanisms for the clinical management of TC. Finally, we assessed the correlation between TMPRSS4 and some immune markers to uncover a potential immune-related biomarker in TC patients by TIMER2.0. The results revealed that TMPRSS4 was highly expressed in TC and was also associated with lymphatic metastasis, advanced stage, histological subtype, and favorable clinical outcome. The stratified analysis based on immune cell content showed that decreased TMPRSS4 had worse prognosis in CD8+ T cell-enriched TC patients. TMPRSS4 was positively correlated with tumor immune infiltration and the expression of gene markers of immune cells. Notably, its expression was lower in the lymphocyte-depleted subtype than in other immunosubtypes in TC. Moreover, TMPRSS4 was closely related to chemokines as well as their receptors and the immunosuppressive checkpoints CTLA-4, PD-1, and HLA-G. In conclusion, TMPRSS4 may act as a novel biomarker predicting prognosis and immune infiltration in TC. [ABSTRACT FROM AUTHOR]

The relevance of this paper is that transfusion of allogeneic blood to recipient animals is always associated with immunological risks. In this regard, the purpose of this study was to assess the state of phagocytic activity of blood neutrophils by indicators of phagocytic index, phagocytic number, and oxygen-dependent bactericidal activity, as well as to establish changes in antibody-dependent cytotoxic activity of lymphocytes in recipient rabbits during allogeneic whole blood transfusion. Modelling of blood transfusions was performed on five clinically healthy rabbits by intravenous administration of whole blood at the rate of 5.5 ml/kg of body weight. Blood samples were taken from animals on Days 3, 7, and 23 after blood transfusion. Neutrophil populations were obtained from blood samples by centrifugation on a double density gradient of 1.077 and 1.093 Ficoll-Verografin. The absorption activity of phagocytes was determined in a microscopic test. To investigate the oxygen-dependent bactericidal activity of neutrophils, a spontaneous test with nitroblue tetrazolium was performed. Antibody-dependent cytotoxic activity of lymphocytes was investigated by colorimetric method. It was found that after the transfusion of whole blood, the phagocytic activity of neutrophils increases with a simultaneous decrease in their absorption capacity. On Days 3 and 7, the results of the spontaneous test with nitroblue tetrazolium decreased. This indicates inactivation of the oxygen-dependent bactericidal activity of neutrophil granulocytes during the first phase of post-transfusion immunological reactions. On Day 23, there was an increase in the values of the indicators of the spontaneous test with nitroblue tetrazolium, which indicates the activation of the bactericidal properties of phagocytes. It was found that on Day 3, the antibody-dependent cytotoxic activity of lymphocytes significantly decreased relative to the initial state, and on Days 7 and 23, it increased. An increase in the antibody-dependent cytotoxic activity of lymphocytes should be associated with the active synthesis of antibodies of the late phase of the immune response. Consequently, transfusion of allogeneic blood causes an immune response in recipient rabbits, without causing immediate and long-term transfusion reactions (changes in heart rate, respiratory rate, body temperature). The obtained results are of practical value both for scientists and practising doctors who use transfusion of whole blood and its components to animals with acute anaemia, impaired functional activity of blood coagulation factors, parasitic, and oncological diseases [ABSTRACT FROM AUTHOR]

Severe combined immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency characterized by absence of functional T lymphocytes. It is a paediatric emergency, which is life-threatening when recognized too late. The clinical presentation varies from the classical form of SCID through atypical SCID to Omenn syndrome. In addition, there is a considerable immunological variation, which can hamper the diagnosis. In this educational review, we describe the immunopathological background, clinical presentations and diagnostic process of SCID, as well as the therapeutic possibilities. [ABSTRACT FROM AUTHOR]

Cancer is a main life-threatening disease worldwide. Due to the adverse effects of conventional chemotherapies and radiotherapies, immunotherapy has emerged as a potent strategy to treat cancer. In cancer immunotherapy, cancer immune surveillance plays a crucial role in the cancer process, which contains various effector cells from innate and adaptive immunity. This review summarized the functions of innate and adaptive immune cells in cancer immunosurveillance and their main reported targets. Moreover, the potential targets about the modulatory effects of cancer immunosurveillance were predicted using network-based target analysis, with total predicted pathways not only reporting previously reported pathways, but also putative signaling pathways pending for investigation. In addition, the potential use of herbal medicines and their phytochemicals in the modulation of cancer immunosurveillance were also discussed. Taken together, this review paper aims to provide scientific insight into further drug development, particularly herbs, phytochemicals, and TCM formulae, in the modulatory effects of cancer immunosurveillance. [ABSTRACT FROM AUTHOR]

Presents a list of forthcoming papers on immunology, as of January 2003. Signaling transduction pathway for eotaxin- and interleukin-5 induced eosinophil shape change; Recognition of bovine respiratory syncytial virus proteins by bovine lymphocytes; Prevention of oral tolerance induction by administration of exogenous interleukins.

Simple Summary: The High Throughput Truthing project aims to develop a dataset of stromal tumor-infiltrating lymphocytes (sTILs) density evaluations in hematoxylin and eosin-stained invasive breast cancer specimens fit for a regulatory purpose. After completion of the pilot study, the analysis demonstrated inconsistencies and gaps in the provided training to pathologists. Select regions of interest (ROIs) were reviewed by an expert panel, who provided annotations and commentary on the challenges of the sTILs assessment. We used these annotations to develop a training document and reference standard for new training materials. These materials will train crowd-sourced pathologists to help create an algorithm validation dataset and contribute to sTILs evaluations in clinical practice. The High Throughput Truthing project aims to develop a dataset for validating artificial intelligence and machine learning models (AI/ML) fit for regulatory purposes. The context of this AI/ML validation dataset is the reporting of stromal tumor-infiltrating lymphocytes (sTILs) density evaluations in hematoxylin and eosin-stained invasive breast cancer biopsy specimens. After completing the pilot study, we found notable variability in the sTILs estimates as well as inconsistencies and gaps in the provided training to pathologists. Using the pilot study data and an expert panel, we created custom training materials to improve pathologist annotation quality for the pivotal study. We categorized regions of interest (ROIs) based on their mean sTILs density and selected ROIs with the highest and lowest sTILs variability. In a series of eight one-hour sessions, the expert panel reviewed each ROI and provided verbal density estimates and comments on features that confounded the sTILs evaluation. We aggregated and shaped the comments to identify pitfalls and instructions to improve our training materials. From these selected ROIs, we created a training set and proficiency test set to improve pathologist training with the goal to improve data collection for the pivotal study. We are not exploring AI/ML performance in this paper. Instead, we are creating materials that will train crowd-sourced pathologists to be the reference standard in a pivotal study to create an AI/ML model validation dataset. The issues discussed here are also important for clinicians to understand about the evaluation of sTILs in clinical practice and can provide insight to developers of AI/ML models. [ABSTRACT FROM AUTHOR]

Simple Summary: In patients with relapsed or metastasized squamous cell cancer of the head and neck (R/M SCCHN), the PD-L1 Combined Positive Score (CPS) is currently the only predictive biomarker for treatment with anti-PD-1 agents. However, ambiguous results have been determined regarding the overall response rates of immunotherapeutic agents based on PD-L1 status, which may be partially attributed to spatiotemporal heterogeneity. Furthermore, tumor-infiltrating lymphocytes (TILs) have proven to be of significant prognostic value, yet lack of a standardized method for quantification impedes their integration into the current armamentarium of biomarkers in SCCHN. In this paper, concordance of PD-L1 CPS and stromal TILs was investigated in different paired samples of SCCHN subtypes. The results were then linked to well-known clinicopathological variables and prognosis. Background: The clinical significance of tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression has been thoroughly researched in squamous cell carcinoma of the head and neck (SCCHN). To address the impact of intra- and intertumoral heterogeneity in these biomarkers, we explored the concordance of PD-L1 combined positive score (CPS) and stromal TILs in different paired tissue sample types, while evaluating their internal relationship and prognostic impact. Methods: A total of 165 tissue blocks from 80 SCCHN patients were reviewed for TILs and PD-L1 CPS. Concordance between paired tissue samples was evaluated, and their association with several clinicopathological variables, overall survival (OS), and disease-free survival (DFS) was determined. Results: Biopsies and paired resection material were severely discordant in 39% and 34% of samples for CPS and TIL count, respectively, of which CPS was underscored in 27% of biopsies. In paired primary tumor–metastatic lesions, the disagreement was lower for CPS (19%) but not for TIL count (44%). PD-L1 CPS was correlated with prolonged OS when calculated from tissue acquirement, while extended OS and DFS were observed for high TIL density. Conclusion: Intertumoral and, especially, intratumoral heterogeneity were confounding factors when determining PD-L1 CPS and TIL count on paired tissue samples, indicating the increasing necessity of assessing both biomarkers on representative tissue material. Although TILs hold valuable prognostic information in SCCHN, the robustness of PD-L1 as a biomarker in SCCHN remains ambiguous. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies have shown that severe depletion of the absolute lymphocyte count (ALC) induced by radiation therapy (RT) has been associated with poor overall survival of patients with many solid tumors. In this paper, we aimed to predict radiation‐induced lymphocyte depletion in esophageal cancer patients during the course of RT based on patient characteristics and dosimetric features. Methods: We proposed a hybrid deep learning model in a stacked structure to predict a trend toward ALC depletion based on the clinical information before or at the early stages of RT treatment. The proposed model consisted of four channels, one channel based on long short‐term memory (LSTM) network and three channels based on neural networks, to process four categories of features followed by a dense layer to integrate the outputs of four channels and predict the weekly ALC values. Moreover, a discriminative kernel was developed to extract temporal features and assign different weights to each part of the input sequence that enabled the model to focus on the most relevant parts. The proposed model was trained and tested on a dataset of 860 esophageal cancer patients who received concurrent chemoradiotherapy. Results: The performance of the proposed model was evaluated based on several important prediction metrics and compared to other commonly used prediction models. The results showed that the proposed model outperformed off‐the‐shelf prediction methods with at least a 30% reduction in the mean squared error (MSE) of weekly ALC predictions based on pretreatment data. Moreover, using an extended model based on augmented first‐week treatment, data reduced the MSE of predictions by 70% compared to the model based on the pretreatment data. Conclusions: In conclusion, our model performed well in predicting radiation‐induced lymphocyte depletion for RT treatment planning. The ability to predict ALC will enable physicians to evaluate individual RT treatment plans for lymphopenia risk and to identify patients at high risk who would benefit from modified treatment approaches. [ABSTRACT FROM AUTHOR]

The phagocytic actives of B cells in fish have been proven in recent years. In this study, five positive hybridomas secreting monoclonal antibodies (MAbs) against largemouth bass IgM were produced. Indirect immunofluorescence assay (IFA) demonstrated that five MAbs could specifically recognize membrane-bound IgM (mIgM) molecule of largemouth bass. Indirect ELISA and Western blotting analysis showed that all the five MAbs had no cross-reactions with the other two teleost IgMs. Flow cytometry analysis (FCM) revealed that the percentages of largemouth bass mIgM+ lymphocytes in head kidney, peripheral blood and spleen were 51.66 ± 0.608%, 16.5 ± 1.235% and 42.92 ± 1.091%, respectively. In addition, the phagocytosis rates of mIgM + lymphocytes ingesting Nocardia seriolae from head kidney, peripheral blood and spleen were calculated to be 5.413 ± 0.274%, 16.6 ± 0.289% and 26.3 ± 0.296%, respectively. The qPCR results of sorted cells indicated that most inflammatory cytokines (IFNγ, IL-1β, IL-2, IL-12β, IL-34, IL-10) , chemokine (CXCL12), chemokines receptors (CXCR2, CXCR4) and genes (FcγRⅠa, NCF1, CFL, ARP2/3, CD45, Syk, MARCKS) related to FcγR-mediated phagocytic signaling pathway in phagocytic mIgM+ lymphocytes were up-regulated significantly (P < 0.05). Taken together, the results suggested that the MAb (MM06H) produced in this paper could be used as a tool to study mIgM+ lymphocytes of largemouth bass, and FcγR may participate in the phagocytosis of mIgM+ lymphocytes, which is helpful to further study the role of mIgM+ lymphocytes in innate immunity. • Monoclonal antibodies against Micropterus salmoides were produced. • The phagocytosis of mIgM+ lymphocytes from largemouth bass was validated. • 33 immune-related genes of sorted phagocytic mIgM+ lymphocytes were up-regulated. • FcγR-mediated phagocytosis pathway may participate in the phagocytosis of mIgM+ lymphocytes. [ABSTRACT FROM AUTHOR]

No abstract available [ABSTRACT FROM AUTHOR]

Asthma is a chronic, recurrent and incurable allergy‐related respiratory disease characterized by inflammation, bronchial hyperresponsiveness and narrowing of the airways. Extracellular vesicles (EVs) are a universal feature of cellular function and can be detected in different bodily fluids. Recent evidence has shown the possibility of using EVs in understanding the pathogenesis of asthma, including their potential as diagnostic and therapeutic tools. Studies have reported that EVs released from key cells involved in asthma can induce priming and activation of other asthma‐associated cells. A literature review was conducted on all current research regarding the role and function of EVs in the pathogenesis of asthma via the PRISMA statement method. An electronic search was performed using EMBASE and PubMed through to November 2018. The EMBASE search returned 76 papers, while the PubMed search returned 211 papers. Following duplicate removal, titles and abstracts were screened for eligibility with a total of 34 studies included in the final qualitative analysis. The review found evidence of association between the presence of EVs and physiological changes characteristic of asthma, suggesting that EVs are involved in the pathogenesis, with the weight of evidence presently favouring deleterious effects of EVs in asthma. Numerous studies highlighted differences in exosomal contents between EVs of healthy and asthmatic individuals, which could be employed as potential diagnostic markers. In some circumstances, EVs were also found to be suppressive to disease, but more often promote inflammation and airway remodelling. In conclusion, EVs hold immense potential in understanding the pathophysiology of asthma, and as diagnostic and therapeutic markers. While more research is needed for definitive conclusions and their application in medical practice, the literature presented in this review should encourage further research and discovery within the field of EVs and asthma. [ABSTRACT FROM AUTHOR]

A list of forthcoming papers related to immunology is presented. These include "Variable influences of iodine on the T-cell recognition of a single thyroglobulin epitope," by Hong Jiang, "Triacylated lipoproteins derived from Mycoplasma pneumoniae activate NF-jB through TLR1 and TLR2," by Takashi Shimizu, and "Disruption of Rxra gene in thymocytes and T lymphocytes modestly alters lymphocyte frequencies, proliferation, survival and Th1/Th2 balance," by Alexander Borowsky and Kevin Kent Lloyd.

Immune checkpoint blockade (ICB) therapies are revolutionary cancer treatments; however, they only benefit about a third of patients. Therefore, extensive research is underway to find methods to improve their therapeutic efficacy. One avenue of study that has recently emerged is to consider the role the gut microbiome plays in therapeutic success. Several high‐impact studies have repeatedly shown that the presence, composition and level of diversity of the gut flora directly impact cancer treatment outcome in both mice and patients. These studies have also highlighted the danger of using antibiotics shortly before or during cancer treatments. However, there are still several questions that need to be answered, including which bacteria promote the greatest benefit, the mechanisms by which they act and how we can use this information to influence treatment outcome. In this review, we explain how the gut microbiome was realized to be of such importance and propose hypotheses for why gut flora have such a critical impact on ICB therapeutic success. We also describe a hypothetical mechanism involving bacterial translocation out of the gut and into the tumor, whereby the bacteria act in an adjuvant capacity to facilitate an antitumor response. By highlighting key papers in the field, we hope to hasten research on the subject so as to find a means to improve the therapeutic efficacy of these ground‐breaking cancer treatments. [ABSTRACT FROM AUTHOR]

Patients with primary immunodeficiency are at increased risk for malignancy, especially hematologic neoplasms. This paper reports a unique case of a 47‐year‐old man with X‐linked agammaglobulinemia who presented with progressive asymptomatic violaceous papules and plaques on his face, hands, and trunk for 1 year. Skin biopsies revealed deep, nodular infiltrates of histiocytes and CD8‐positive lymphocytes, with a CD4:CD8 ratio of 1:10. Laboratory studies showed cytopenias. Flow cytometry in the skin, blood, and bone marrow (BM) showed a CD3+/CD8+/CD57+ large granular lymphocyte population. BM biopsy showed 30% involvement with these atypical T‐cells. T‐cell gene rearrangement studies of skin, blood, and BM revealed identical T‐cell clones. He was diagnosed with T‐large granular lymphocyte leukemia (T‐LGLL) with an associated CD8+ cutaneous lymphoproliferation. Skin involvement was suspected to represent infiltration by T‐LGLL. However, co‐existence of two lymphoproliferative disorders (LPDs), T‐LGLL and CD8+ granulomatous LPD, remains a possibility. In general, cutaneous infiltrates associated with LGLL are rare and poorly understood. It has been suggested that they are markers of poor prognosis. Our case report describes skin, blood, and BM findings in an immunosuppressed patient with T‐LGLL in detail. These findings have not yet been reported and their significance requires further investigation. [ABSTRACT FROM AUTHOR]

The association between thyroid cancer and thyroid autoimmunity has long been suggested, but remains to be elucidated for several decades. Here the data on this issue are updated by summarizing relevant papers published between 2012 and early 2018. Although numerous papers demonstrated the significant increase in the prevalence of thyroid autoimmunity (positive intrathyroidal lymphocyte infiltration and/or anti-thyroglobulin/thyroid peroxidase antibodies) in patients with thyroid cancers as compared to those with benign nodules, and also the significant increase in the prevalence of papillary thyroid cancer (PTC) in patients with thyroid autoimmunity as compared to those without, there are some crucial biases that should be taken into account for their interpretation. However, a difference in the incidence of thyroid autoimmunity in patients with PTCs and those with other types of thyroid cancers appears to support the significant association of two conditions. Thyroid autoimmunity is, at least partly, likely to be elicited against antigens shared by normal and cancerous thyroid tissues, thereby inducing autoimmunity. At the same time, elevated TSH levels (even within the normal reference ranges), which often accompany Hashimoto's patients are a risk factor for thyroid cancer. However, it is still unclear whether or not the co-existence of thyroid autoimmunity impacts on cancer characteristics and prognosis. This issue needs to be further investigated with large-scale prospective studies. [ABSTRACT FROM AUTHOR]

Abstract B cells in some fish were recently found to have potent phagocytic activities. Sea bass ( Lateolabrax japonicus ) as an important economical marine fish species, it could be used as an appropriate model to study the functions of B cells in phagocytosis. In the paper, three positive hybridomas designated as 1E11, 2H4 and 3F3 secreting monoclonal antibodies (MAbs) against sea bass immunoglobulin M (IgM) were produced and used as research tools. Indirect enzyme-linked immunosorbent assay showed that all the three MAbs had a high binding capacity with sea bass serum IgM. Western blotting analysis showed that all the three MAbs were specific for the heavy chain of sea bass IgM. Indirect immunofluorescence assay (IFA) analysis suggested that both MAbs 1E11 and 2H4 could recognize membrane-bound IgM (mIgM) molecule of sea bass. Specificity analysis showed that three MAbs had no cross-reactions with other six teleosts IgMs. Flow cytometric analysis exhibited that the percentages of sea bass mIgM + lymphocytes in peripheral blood, spleen and pronephros were 25.6%, 21.1%, and 17.5%, respectively. Moreover, we found that the mIgM + lymphocytes of sea bass could phagocytose fluorescence microspheres and Lactococcus lactis , but lower phagocytosis rates of L. lactis was observed. These results demonstrated that the MAbs produced in this paper could be used as tools to study secretory IgM and mIgM + lymphocytes of sea bass, and mIgM + lymphocytes might also play an important role in innate immunity of sea bass. Highlights • MAbs against IgM of sea bass are produced and characterized. • The produced MAbs are special for the sIgM and mIgM of sea bass. • The produced MAbs don't cross-react with other six teleosts' IgMs. • The mIgM + lymphocytes of sea bass possess phagocytic capacity. • The phagocytosis rates of L. lactis are lower than those of fluorescence microsphere. [ABSTRACT FROM AUTHOR]

The article discusses research conducted by Dorian McGavern of the Scripps Research Institute and Jiyun Kim of New York University School of Medicine, along with colleagues, on the causes of viral meningitis. While scientists once believed that cytotoxic lymphocytes (CTLs) caused the condition, this study has found that CTLs actually recruit other immune cells that degrade the cells lining the brain.

The article analyzes the missing link between T lymphocytes and psoriasis. The observations of Immunologist Yan Zheng and his colleagues at the company Genentech in San Francisco, California are discussed in detail. An overview of the cause for the white cell infiltration into the skin and the role of IL-22 in causing the disease of psoriasis, through experimentation on mice, is presented. The article also presents the observations of Wenjun Ouyang on TH 17 and T22 to find the missing link.

The parameters and dynamics of the development of Meckel's diverticulum in large gray geese aged one day to 5 years were determined. The changes in the length, cross-sectional area and wall area of the Meckel's diverticulum indicate that its growth stops by 3 months of age. The age-related morphofunctional indicators of lymphoid tissue formation in the wall of Meckel's diverticulum were determined. Diffuse lymphoid tissue is predominant in the composition of lymphoid tissue. Full morphofunctional maturity of the lymphoid tissue with the development of four levels of its structural organization is observed at the age of 21 days in geese. The lymphoid tissue in the wall of Meckel's diverticulum reaches its maximum development by the age of 3 months, which must be taken into account when raising large gray geese and conducting experimental studies. [ABSTRACT FROM AUTHOR]

Currently, immunomodulation is an alternative in the fight against many diseases, being considered a possibility to fight against many infectious diseases that can affect pig herds. Selenium can be used for this purpose, the effect of its administration on the immune response being the main purpose of the present study. Following the administration of organic selenium, we found that in the case of WBC parameters, granulocytes and agranulocytes percentages and lymphoblastic transformation percentages of B lymphocytes, there are no major differences between the values recorded at the beginning of the experiment and the values recorded in the two experimental moments. Instead, following the administration of organic selenium, we observed significant increases in T lymphocytes percentages (by 9.94%, after 21 days, and respectively by 8.18%, after 30 days), percentages of lymphoblastic transformation of T lymphocytes (by 59.59% after 21 days, and respectively by 64.14% after 30 days), as well as the helper T lymphocytes/supressor T lymphocytes ratio (by 46.15% after 21 days, and respectively by 65.38% after 30 days). Regarding the percentage of B lymphocytes, a decrease of this parameter is observed by 38.34% after 21 days and by 21.84% after 30 days following the administration of the product based on organic selenium. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Zand Irani et al paper. To view this article, visit https://doi.org/10.1111/apt.16630 [ABSTRACT FROM AUTHOR]

Objective The aim of the research paper was to assess selected laboratory results in children with fever without seizures and febrile seizure. Materials and Methods The paper presents an analysis of a group of 306 children aged 6 months - 5 years who were admitted with diagnosed fever without seizures and febrile seizures in Specialized Health Care Centre for Mother and Child in Poznan between 1st January 2008 and 31st December 2009. Out of the diagnostics procedures performed in children the following ones were taken into consideration: BCC and CRP. Results Of the analyzed group of 306 children, 59.48% were boys and 40.52% were girls. In the studied group 61.93% were boys and control group 56.15% were boys. Mean age of admitted children was 22 months. In the study group mean body temperature was 39.0°C and in the control group 38.6°C. A statistically significant difference was found between body temperature of study and control group ( p = .005). The mean C-reactive protein level in the study group was 15.73 mg/L and in the control group 58.20 mg/L. There was a statistically significant difference ( p < .001). There was a statistically significant difference between the number of lymphocytes and neutrophils ( p < .001). There was also a statistically significant difference between the number of hemoglobin, hematocrit and platelets. Conclusions The study showed that children with FS, had statistically significant higher neutrophils level compared to those with fever without seizures. The number of lymphocytes was lower in children with FS than in children with fever without seizures. [ABSTRACT FROM AUTHOR]

After the outbreak of the Covid-19 pandemic, cases of SARSCoV- 2 infections may gradually decrease in the next months. Given the reduced prevalence of the disease, Emergency Departments (ED) are starting to receive more and more non- Covid19 patients. Thus, a way to quickly discriminate ED patients with potential Covid-19 infection from non-Covid19 patients is needed in order to keep potentially contagious patients isolated while awaiting second-level testing. In this paper, we present the derivation and validation of a simple, practical, and cheap score that could be helpful to rule out Covid-19 among ED patients with suspicious symptoms (fever and/or dyspnoea). The LCL score was derived from a cohort of 335 patients coming to the ED of our hospital from March 16th to April 1st, 2020. It was then retrospectively validated in a similar cohort of 173 patients admitted to our ED during April. The score is based on blood values of lactate dehydrogenase, C-reactive protein, and lymphocyte count. The LCL score performed well both in the derivation and in the validation cohort, with an AUC respectively of 0.81 (95% CI: 0.77 -- 0.86) and of 0.71 (95% CI: 0.63 -- 0.78), given the difference in Covid- 19 prevalence between the two cohorts (57% vs 41% respectively). An LCL score equal to 0 had a negative predictive value of 0.92 in the derivation cohort and of 0.81 in the validation cohort, with a negative likelihood ratio respectively of 0.08 and 0.36 for Covid- 19 exclusion. This score could, therefore, constitute a useful tool to help physicians manage patients in the ED. Non-commercial [ABSTRACT FROM AUTHOR]

Background: Iron metabolism and immune response to SARS-CoV-2 have not been described yet in intensive care patients, although they are likely involved in Covid-19 pathogenesis. Methods: We performed an observational study during the peak of pandemic in our intensive care unit, dosing D-dimer, C-reactive protein, troponin T, lactate dehydrogenase, ferritin, serum iron, transferrin, transferrin saturation, transferrin soluble receptor, lymphocyte count and NK, CD3, CD4, CD8 and B subgroups of 31 patients during the first 2 weeks of their ICU stay. Correlation with mortality and severity at the time of admission was tested with the Spearman coefficient and Mann–Whitney test. Trends over time were tested with the Kruskal–Wallis analysis. Results: Lymphopenia is severe and constant, with a nadir on day 2 of ICU stay (median 0.555 109/L; interquartile range (IQR) 0.450 109/L); all lymphocytic subgroups are dramatically reduced in critically ill patients, while CD4/CD8 ratio remains normal. Neither ferritin nor lymphocyte count follows significant trends in ICU patients. Transferrin saturation is extremely reduced at ICU admission (median 9%; IQR 7%), then significantly increases at days 3 to 6 (median 33%, IQR 26.5%, p value 0.026). The same trend is observed with serum iron levels (median 25.5 μg/L, IQR 69 μg/L at admission; median 73 μg/L, IQR 56 μg/L on days 3 to 6) without reaching statistical significance. Hyperferritinemia is constant during intensive care stay: however, its dosage might be helpful in individuating patients developing haemophagocytic lymphohistiocytosis. D-dimer is elevated and progressively increases from admission (median 1319 μg/L; IQR 1285 μg/L) to days 3 to 6 (median 6820 μg/L; IQR 6619 μg/L), despite not reaching significant results. We describe trends of all the abovementioned parameters during ICU stay. Conclusions: The description of iron metabolism and lymphocyte count in Covid-19 patients admitted to the intensive care unit provided with this paper might allow a wider understanding of SARS-CoV-2 pathophysiology. [ABSTRACT FROM AUTHOR]

Urban air pollution represents a global problem, since everyday many mutagenic and carcinogens compounds are emitted into the atmosphere, with consequent adverse health effects on humans and biota. Specifically, particulate matter air pollution was associated with increased risks in human mortality and morbidity. In this paper, we analyse the genomic effects on human lymphocytes of different concentrations of annual Turin PM2.5 extract by an in vitro micronuclei assay. Samplings were collected from an urban meteorological-chemical station positioned in Turin (Italy), one of the most polluted cities in Europe. PM2.5 sampled on filters was used for organic extraction in monthly pools and successively aggregated to produce a mixture representative for a full year PM2.5 collection. Lymphocytes were exposed to four concentrations of PM2.5: 5, 10, 15 and 20 μg/mL and micronuclei, nucleoplasmic bridges and nuclear buds were scored. With respect to controls, PM2.5 significantly increased the frequencies of all analysed biomarkers at all tested concentrations, whereas the CBPI index was significantly reduced only at the concentration of 20 μg/mL. Such in vitro effects can both to stimulate local authorities to adopt efficient measures for air pollution mitigation and to improve human monitoring to detect early precancer lesions. [ABSTRACT FROM AUTHOR]

Meta-analysis can be applied to study the effectiveness of the summary estimates for experimental papers, producing objective and unbiased results. We investigated the effects of phosphoinositide-3-kinase (PI3K) on the inflammatory profile in allergic mouse models, which are currently under development in signal transduction materials. PubMed, EMBASE and Web of Science databases were searched for relevant literature using the search terms " PI3K inhibitor" and "allergy" or "asthma". Cochrane Review Manager and R were used for handling continuous variables. The primary outcomes of the inflammatory profile were divided into cell counts and inflammatory cytokines. We used a random effects model to draw a forest plot. Through the database search and subsequent selection, 17 articles were identified. Regarding the cell counts, both the PI3K pan-inhibitors and PI3K-δ inhibitors effectively reduced the total cell counts, eosinophils, neutrophils and lymphocytes. In contrast to PI3K-δ inhibitors, PI3K pan-inhibitors effectively reduced macrophages. Regarding the inflammatory cytokines, PI3K pan-inhibitors and PI3K-δ inhibitors effectively reduced total IgE, IL-4, IL-5, IL-13, TNF-α, IL-1β, VEGF and had no effect on IL-6. Compared to the PI3K pan-inhibitors, which block all pathways, selective PI3K-δ inhibitors are expected to be relatively less toxic. Regarding the efficacy, PI3K-δ inhibitors have at least the same or better efficacy than PI3K pan-inhibitors in effector cells and inflammatory mediators. [ABSTRACT FROM AUTHOR]

In the routine commercial karyotype analysis on 5,481 boars, we identified 32 carriers of mosaic reciprocal translocations, half of which were carrying a specific recurrent translocation, mos t(7;9). An additional 7 mosaic translocations were identified through lymphocyte karyotype analysis from parents and relatives of mosaic carriers (n = 45), a control group of non-carrier boars (n = 73), and a mitogen assessment study (n = 20), bringing the total number of mosaic carriers to 39 cases. Mosaic translocations in all carriers were recognized to be confined to hematopoietic cells as no translocations were identified in fibroblasts cells of the carriers. In addition, negative impact on reproduction was not observed as the fertility of the carriers and their relatives were comparable to breed averages, and cryptic mosaicism was not detected in the family tree. This paper presents the first study of mosaic reciprocal translocations identified in swine through routine screening practices on reproductively unproven breeding boars while presenting evidence that these type of chromosome abnormalities are not associated with any affected phenotype on the carrier animals. In addition, the detection of recurrent mosaic translocations in this study may emphasize the non-random nature of mosaic rearrangements in swine and the potential role of genomic elements in their formation. [ABSTRACT FROM AUTHOR]