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Abstract Background Although persistent negative symptoms (PNS) are known to contribute significantly to poor functional outcome, they remain poorly understood. We examined the heuristic value of various PNS definitions and their respective prevalence in patients with first episode psychosis (FEP). We also contrasted those definitions to the Proxy for the Deficit Syndrome (PDS) to identify deficit syndrome (DS) in the same FEP cohort. Methods One hundred and fifty-eight FEP patients were separated into PNS and non-PNS groups based on ratings from the Scale for Assessment of Negative Symptoms (SANS). PNS was defined in the following ways: 1) having a score of 3 or greater on at least 1 global subscale of the SANS (PNS_1); 2) having a score of 3 or more on at least 2 global subscales of the SANS (PNS_2); and 3) having a score of 3 or more on a combination of specific SANS subscales and items (PNS_H). For all three definitions, symptoms had to be present for a minimum of six consecutive months. Negative symptoms were measured upon entry to the program and subsequently at 1,2,3,6,9 and 12 months. Functional outcome was quantified at first assessment and month 12. Results PNS prevalence: PNS_1 (27%); PNS_2 (13.2%); PNS_H (13.2%). The prevalence of DS was found to be 3% when applying the PDS. Regardless of the definition being applied, when compared to non-PNS, patients in the PNS group were shown to have significantly worse functioning at month 12. All three PNS definitions showed similar associations with functional outcome at month 12. Conclusion Persistent negative symptoms are present in about 27% of FEP patients with both affective and non-affective psychosis. Although there has previously been doubt as to whether PNS represents a separate subdomain of negative symptoms, the current study suggests that PNS may be more applicable to FEP when compared to DS. Although all three PNS definitions were comparable in predicting functional outcome, we suggest that the PNS definition employed is dependent on the clinical or research objective at hand.

Introduction: Due to its lack of conventional surface receptors, triple-negative breast cancer (TNBC) is inherently resistant to most targeted therapies. MAL2 overexpression prompts endocytosis, conferring resistance to novel therapeutics. This study explores the role of MAL2 and PD-L1 in TNBC patients' prognosis., Methods: We performed immunohistochemical analysis on 111 TNBC samples collected from 76 patients and evaluated the expression of MAL2 and PD-1. We expanded the study by including The Cancer Genome Atlas (TCGA) cohort., Results: MAL2 expression did not correlate with stage, grade, tumor size, lymph node invasion, metastasis, and PD-1 expression. Patients with high MAL2 had significantly lower 5-year survival rates (71.33% vs. 89.59%, p = 0.0224). In the tissue microarray cohort (TMA), node invasions, size, recurrence, and low MAL2 (HR 0.29 [CI 95% 0.087-0.95]; p < 0.05) predicted longer patients' survival. In the TCGA cohort, patients with low MAL2 had significantly longer overall survival and disease-specific survival than patients with high MAL2. Older age and high MAL2 expression were the only independent predictors of shorter patient survival in the BRCA TCGA cohort., Conclusion: High MAL2 predicts unfavorable prognosis in triple-negative breast cancer, and its expression is independent of PD-1 levels and clinicopathological features of TNBC., (© 2024. The Author(s).)

Purpose: Claudins are tight junction proteins partaking in epithelial-mesenchymal transition and cancer progression. In this study, we investigated the expression patterns of claudin-1 and claudin-4 in thyroid pathologies, discussed their links with the pathogenesis of thyroid cancers, and reviewed the therapeutic potential of targeting claudins in cancers. Methods: The research group 162 cores of thyroid samples from patients (70 female and 11 male) diagnosed with thyroid adenoma, goiter, papillary, medullary, and anaplastic thyroid cancers. All samples were stained for the expression of claudin-1 and claudin-4, and the analysis of IHC was performed. Results: Goiter samples showed negative claudin-1 and mostly positive expression of claudin-4. Papillary thyroid cancer and thyroid adenoma showed positive expression of claudin-1, while claudin-4 was positive in papillary thyroid cancers, goiters, and adenomas. In The Cancer Genome Atlas cohort, claudin-1 and claudin-4 were overexpressed in papillary thyroid cancer compared to normal thyroid tissues. Patients with high claudin-1 expression had significantly lower 5-year overall survival than patients with low claudin-1 levels (86.75% vs. 98.65, respectively). In multivariate analysis, high claudin-1 expression (HR 7.91, CI 95% 1.79-35, p = 0.006) and advanced clinical stage remained statistically significant prognostic factors of poor prognosis in papillary thyroid cancer. Conclusions: The pattern of claudin-1 staining was pathology-specific and changed between cancers of different histology. This phenomenon may be associated with the different pathogenesis of thyroid cancers and early metastasis. The loss of claudin-1 and claudin-4 characterized more aggressive cancers. Several studies have shown the benefits of targeting claudins in cancers, but their implementation into clinical practice requires further trials.

Our review aims to clarify the incidence of carotid artery stenosis, risks of development, screening, management, and primary prevention strategies documented in the literature after radiation therapy for head and neck cancers. The high prevalence of carotid stenosis after radiation therapy for head and neck cancers has made surveillance and risk stratification critical. In addition to general cardiovascular risk factors such as smoking, diabetes, and dyslipidemia, risk factors for carotid artery stenosis after head and neck radiation included total plaque score, radiotherapy use and dosage, length of time after radiotherapy, and age greater than 50. Cancer subtype, namely nasopharyngeal cancer, may be correlated with increased risk as well, though contrasting results have been found. Interestingly, however, no significant relationship has been found between radiotherapy dose and stroke risk. Surgical management of post-radiation carotid stenosis is similar to that of stenosis unrelated to radiation, with carotid endarterectomy considered to be the gold standard treatment and carotid artery stenting being an acceptable, less-invasive alternative. Medical management of these patients has not been well-studied, but antiplatelet therapy, statins, and blood pressure control may be beneficial. The mainstay of screening for radiation-induced stenosis has been Doppler ultrasound, with measurement of changes in the intima-media thickness being a primary marker of disease development. A literature review was carried out using the MeSH terms "Carotid Artery Stenosis," "Head and Neck Neoplasms," and "Radiotherapy.", Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Studies have described poor transfusion medicine (TM) knowledge in postgraduate trainees. The impact of undergraduate medical TM education on postgraduate knowledge is unclear., Methods: Canadian medical schools were surveyed on the number of hours dedicated to TM teaching and topics covered by curricula during 2016-2020. Postgraduate trainees attending Transfusion Camp in 2021 completed a pretest of 20 multiple-choice questions. The survey results and pretest scores were compared to evaluate the association between undergraduate medical TM education and pretest scores., Results: The survey was completed by 16 of 17 Canadian medical schools. The number of hours (h) of TM teaching were <2 h (25%), 3-4 h (25%), and >4 h (50%). Twelve of 19 Transfusion Camp topics were covered in ≥50% of schools. Eleven medical schools provided ethics approvals/waivers to include trainee pretest scores in the analysis (N = 200). The median pretest scores by medical school ranged from 48% to 70%. No association was found between number of TM teaching hours and average pretest scores (p = .60). There was an association between higher postgraduate year level and individual pretest score (p < .0001). The analysis by topic demonstrated questions where trainees from different schools performed uniformly well or poorly; other topics showed considerable variation., Conclusion: Variation in quantity and content of undergraduate TM teaching exists across Canadian medical schools. In this limited assessment, the number of TM teaching hours was not associated with performance on the pretest. This study raises the opportunity to re-evaluate the delivery (content, timing, consistency) of TM education in undergraduate medical schools., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: SARS-CoV-2 can damage human placentas, leading to pregnancy complications, such as preeclampsia and premature birth. This study investigates the histopathological changes found in COVID-19-affected placentas., Materials and Methods: This study included 23 placentas from patients with active COVID-19 during delivery and 22 samples from patients without COVID-19 infection in their medical history. The samples underwent histopathological examination for pathology, such as trophoblast necrosis, signs of vessel damage, or fetal vascular malperfusion., Results: Newborns from the research group have lower weights and Apgar scores than healthy newborns. In the COVID-19 group, calcifications and collapsed intervillous space were more frequent, and inflammation was more severe than in the healthy group. At the same time, the placenta of SARS-CoV-2-positive patients showed signs of accelerated vascular maturation. Trophoblast necrosis was found only in the placentas of the research group. The expression of CD68+ was elevated in the COVID-19 cohort, suggesting that macrophages constituted a significant part of the inflammatory infiltrate. The increase in lymphocyte B markers was associated with placental infarctions, while high levels of CD3+, specific for cytotoxic T lymphocytes, correlated with vascular injury., Conclusions: SARS-CoV-2 is associated with pathological changes in the placenta, including trophoblast necrosis, calcification, and accelerated villous maturation. Those changes appear to be driven by T cells and macrophages, whose increased expression reflects ongoing histiocytic intervillositis in the placenta.

Hypergranulation is the abnormal accumulation of granulation tissue in a wound and is commonly seen in burns. It impairs wound healing and can predispose patients to infection. There is no gold standard treatment for hypergranulation tissue, but some options include surgical debridement, chemical cautery with silver nitrate, and topical steroids. Silver nitrate treatment is painful and can lead to scarring, so topical steroid use is on the rise. A retrospective review, between January 1, 2017 and August 30, 2021, at a tertiary burn center was performed to analyze outcomes of hypergranulation tissue after treatment with a topical 50/50 mixture of triamcinolone (Perrigo, Dublin, Ireland) and Polysporin (Johnson & Johnson, New Brunswick, NJ). One hundred and sixteen patients were treated with triamcinolone and Polysporin for hypergranulation tissue, although 24 did not meet inclusion criteria. Eighty-eight out of 92 patients were successfully treated until hypergranulation resolution, while 4/92(4.3%) required silver nitrate or surgery despite the topical cream to achieve resolution. In the 88 patients successfully treated until hypergranulation resolution, 99 areas of hypergranulation were treated. Forty-one of 99 (41.4%) hypergranulation areas resolved within 2 weeks. The average time to hypergranulation resolution was 27.5 ± 2.5 days. We found that a novel 50/50 mixture of triamcinolone and Polysporin topical ointment is an effective and safe treatment for hypergranulation tissue in burn wounds. Further prospective studies are needed to determine its efficacy and safety profile., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Objectives: The practice regarding the selection and preparation of red blood cells (RBCs) for intrauterine transfusion (IUT) is variable reflecting historical practice and expert opinion rather than evidence-based recommendations. The aim of this survey was to assess Canadian hospital blood bank practice with respect to red cell IUT., Materials and Methods: A survey was sent to nine hospital laboratories known to perform red cell IUT. Questions regarding component selection, processing, foetal pre-transfusion testing, transfusion administration, documentation and traceability were assessed., Results: The median annual number of IUTs performed in Canada was 109 (interquartile range, 103-118). RBC selection criteria included allogeneic, Cytomegalovirus seronegative, irradiated, fresh units with most sites preferentially providing HbS negative, group O, RhD negative, Kell negative and units lacking the corresponding maternal antibody without extended matching to the maternal phenotype. Red cell processing varied with respect to target haematocrit, use of saline reconstitution (n = 4), use of an automated procedure for red cell concentration (n = 1) and incorporation of a wash step (n = 2). Foetal pre-transfusion testing uniformly included haemoglobin measurement, but additional serologic testing varied. A variety of strategies were used to link the IUT event to the neonate post-delivery, including the creation of a unique foetal blood bank identifier at three sites., Conclusion: This survey reviews current practice and highlights the need for standardized national guidelines regarding the selection and preparation of RBCs for IUT. This study has prompted a re-examination of priorities for RBC selection for IUT and highlighted strategies for transfusion traceability in this unique setting., (© 2023 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Purpose: Despite its limitations, the cytology of body fluids is widely used in diagnosing neoplastic cells. Flow cytometry detects and identifies individual cells, enabling the detection of circulating tumor cells and facilitating diagnosis. This study compared the diagnostic utility of flow cytometry and cytology for detecting cancer cells in peritoneal and pleural fluids., Methodology: We used flow cytometry and cytology to examine 119 pleural and peritoneal effusions received for routine screening. Antibodies against clusters of differentiation 45 (CD45), 14 (CD14), and Epithelial cell adhesion molecule (EpCAM) were used to detect malignant cells. Based on combined clinical and diagnostic information, 37 fluid specimens were malignant, and 77 were benign., Results: Flow cytometry correctly identified 34 cancers, while cytology identified 26 cancers (sensitivity 91.89 % vs. 70.27, respectively). Both methods had equal specificity (98.7 %). At a cut-off of > 0.29 % EpCAM(+) cells to all cells in the samples, flow cytometry accurately detected cancer cells, achieving 89.2 % sensitivity, 90.9 % specificity, and an AUC of 0.959 (p < 0.001)., Conclusion: Flow cytometry improves the detection of epithelial cancer cells in peritoneal and pleural fluids compared to conventional cytology. Due to similar specificity and higher sensitivity, flow cytometry offers a promising alternative to cytology for patient screening., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The widespread occurrence of SARS-CoV-2 infections and the diverse range of symptoms have placed significant strain on healthcare systems worldwide. Pregnancy has also been affected by COVID-19, with an increased risk of complications and unfavorable outcomes for expectant mothers. Multiple studies indicate that SARS-CoV-2 can infiltrate the placenta, breach its protective barrier, and infect the fetus. Although the precise mechanisms of intrauterine transmission remain unclear, factors such as perinatal infection, macrophages, sexual intercourse, and the virus' interaction with host angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP-1) proteins appear to play a role in this process. The integrity of the placental barrier fluctuates throughout pregnancy and appears to influence the likelihood of fetal transmission. The expression of placental cell receptors, like ACE2, changes during pregnancy and in response to placental damage. However, due to the consistent presence of others, such as NRP-1, SARS-CoV-2 may potentially enter the fetus at different stages of pregnancy. NRP-1 is also found in macrophages, implicating maternal macrophages and Hofbauer cells as potential routes for viral transmission. Our current understanding of SARS-CoV-2's vertical transmission pathways remains limited. Some researchers question the ACE2-associated transmission model due to the relatively low expression of ACE2 in the placenta. Existing studies investigating perinatal transmission and the impact of sexual intercourse have either involved small sample sizes or lacked statistical significance. This review aims to explore the current state of knowledge regarding the potential mechanisms of COVID-19 vertical transmission, identifying areas where further research is needed to fill the gaps in our understanding., (© 2023 Karol Gostomczyk et al., published by Sciendo.)

Background: Accurate antibody titration is crucial in prenatal evaluations to identify patients who need clinical monitoring for hemolytic disease of the fetus and newborn (HDFN) causing fetal anemia. This study compares the established gold standard method of manual tube saline indirect antiglobulin testing (SIAT) with the newer automated solid phase (ASP) method of antibody titration and aims to establish the critical titer threshold for ASP that corresponds to the previously established SIAT critical threshold of ≥16 used in our laboratory., Study Design and Methods: One hundred fifty-seven prenatal and donor plasma samples with known antibodies were tested using both SIAT and ASP methodologies and results were compared., Results: The study found that ASP titers were, on average, 1.33 dilutions higher than SIAT titers. The critical titer cutoff for ASP was determined to be ≥32, which is one tube higher than the SIAT cutoff of ≥16., Discussion: The ASP method for antibody titration offers greater reproducibility and efficiency compared with manual SIAT titration. This study suggests that a titer cutoff of ≥32 is appropriate for most clinically significant antibodies using ASP. However, further research is needed to determine the comparability of ASP with SIAT in samples with multiple antibodies, anti-M antibodies, and other less common antibodies. Validation of the ASP titer cutoff against HDFN clinical outcomes is required before implementing this test for routine use in perinatal antibody titration., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: As a result of constrained supply, it is sometimes necessary to provide patients with ABO-mismatched platelets. Such practices increase the risk of acute hemolytic transfusion reaction (AHTR). Providing patients with platelets suspended in O plasma having low-titer Anti-A and Anti-B antibodies (LtABO) could reduce the incidence of AHTR. However, natural scarcity limits the number of such units that can be produced. In this paper we present a study to evaluate strategies for deploying LtABO at regional hospitals in Canada., Study Design and Methods: Regional hospitals often experience demand for platelets on an irregular basis. They are, however, required to stock some number of platelets (typically one A-unit and one O-unit) for emergencies; outdates are common, with discard rates sometimes >>50%. A simulation study was completed to determine the impact of replacing a (1A, 1O) inventory with 2 or 3 units of LtABO at regional hospitals., Results: A significant decreases in wastage and shortage can be expected by replacing a (1A, 1O) inventory policy with 2 units of LtABO. In tested cases, a 2-unit LtABO dominated a (1A, 1O) policy, resulting in statistically fewer outdates and instances of shortage. Holding 3 units of LtABO, increases product availability, but results in an increase in outdates when compared to a (1A, 1O) policy., Conclusion: Providing LtABO platelets to smaller, regional hospitals will lower wastage rates and improve patient access to care, when compared to existing (1A, 1O) inventory policies., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Purpose: The mutation of p53 is considered a pivotal step in bladder cancer pathogenesis. Recently, distinct interactions between p53 and CDK9, a transcription regulator, have been described. In this work, we explored the prognostic role of p53 expression and evaluated its associations with CDK9 in urothelial carcinoma., Materials and Methods: The research group consisted of 67 bladder cancer samples and 32 normal urothelial mucosa samples. All specimens were analyzed using ImageJ and the IHC profiler plugin. To validate the results, 406 cases from The Cancer Genome Atlas database were analyzed., Results: P53 and CDK9 are overexpressed in urothelial cancer tissues when compared to normal urothelial tissues (p < 0.05). High p53 expression was observed in metastatic tumors and tumors with high CDK9 expression (p < 0,05). High p53 expression was predictive for shorter survival in patients with non-muscle-invasive bladder cancer (HR = 0.107 [0.012-0.96]; p = 0.046) but did not correlate with prognosis in the muscle-invasive group. In high CDK9 cancers, high p53 expression correlated with the occurrence of high-grade and muscle-invasive tumors (p < 0.05)., Conclusion: High expression of p53 correlates with unfavorable clinical features of bladder cancer. CDK9 is associated with the expression of p53, possibly through interactions with p53 inhibitors. Since the blockade of CDK9 in other malignancies reactivates wild-p53 activity, confirming the crosstalk between p53 and CDK9 in bladder cancer may be another step to explain the mechanism of tumor progression in its early stages., (© 2022. The Author(s).)

Recurrent respiratory papillomatosis is strictly connected with human papillomavirus (HPV) infection of the epithelium of the upper respiratory tract. The main treatment of lesions located in the larynx or lower pharynx includes microsurgical excision by using a CO 2 laser. To decrease the amount of surgical procedures gain in importance combined therapy with antiviral agents. The aim of this study was to investigate the effect of the intralesional application of Cidofovir on the tissue of laryngeal papillomas. We have shown that simultaneous microsurgery with adjuvant therapy of Cidofovir reduces chronic inflammation (by measuring the expression of CD4 and CD8 in tissue samples), cell proliferation, and regulates the cell cycle of HPV-infected cells by reducing the expression of p53 and p63 proteins. In addition, this strategy reduces the multiple surgical procedures and regrowth of the pathology., (© 2022 Wiley Periodicals LLC.)

Aims: The aim of the study is to correlate p16 Ink4a expression with the clinical courses of pleomorphic adenoma (PA), its malignant transformation (CaexPA) and treatment outcomes., Methods: Retrospective analysis (1998-2019) of 47 CaexPA, 148 PA and 22 normal salivary gland samples was performed. PAs were divided into two subsets: clinically 'slow' tumours characterised by stable size or slow growth; and 'fast' tumours with rapid growth rate., Results: Positive p16 Ink4a expression was found in 68 PA and 23 CaexPA, and borderline expression in 80 and 20, respectively. All 22 (100%) normal salivary gland samples presented with no p16 Ink4a expression. Significant difference in p16 Ink4a expression was observed between normal tissue, PA and CaexPA (χ 2 (4)=172,19; p=0.0001). The PA clinical subgroups were also evaluated separately, revealing additional statistical relations: 'fast' PA and CaexPA differed significantly in p16Ink4a expression (χ 2 (2)=8.06; p=0.01781) while 'slow' PA and CaexPA did not (χ 2 (2)=3.09; p=0.2129). 3-year, 5-year and 10-year survival among p16 Ink4a positive CaexPA patients was 100%, 90.56% and 60.37%, respectively, and in CaexPA patients with borderline p16 Ink4a expression was 90.0%, 73.64% and 22.20%, respectively. Statistically significant difference between expression pattern and survival rate was observed (F Cox test - F (16, 24)=2.31; p=0.03075)., Conclusions: Our study confirms no p16 Ink4a expression in normal tissue, but reveals differences in expression between 'fast' and 'slow' PA. We suggest that p16 Ink4a overexpression is connected to PA proliferation and subsequent malignant transformation to CaexPA. Borderline p16 Ink4a staining correlates with worse prognosis of CaexPA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We report a draft genome sequence of a previously undescribed calicivirus from a single brown bullhead inhabiting Lake Memphremagog, Vermont/Quebec. The genome is 7,413 nucleotides long and is most similar to the Atlantic salmon calicivirus (nucleotide identity; 64.7%).

Introduction: Most patients with urothelial carcinoma are diagnosed with non-invasive tumors, but the prognosis worsens with the progression of the disease. Overexpression of cyclin-dependent kinase 9 has been recently linked to increased cancer proliferation, faster progression, and worse prognosis. However, some cancers seem to contradict this rule. In this work, we explored the prognostic role of CDK9 expression in urothelial carcinoma. Materials and Methods: We performed immunohistochemical analysis on 72 bladder cancer samples. To assess a larger group of patients, the Cancer Genome Atlas (TCGA) database containing 406 cases and transcriptomics information through the Human Pathology Atlas were analyzed. Results: CDK9 is overexpressed in urothelial cancer tissues when compared to normal urothelial tissues (p < 0.05). High CDK9 expression was observed in low-stage, low-grade, and non-muscle-invasive tumors (p < 0.05). The patients with high CDK9 expression had a significantly higher 5-year overall survival rate than those with low CDK9 expression (77.54% vs. 53.6% in the TMA group and 57.75% vs. 35.44% in the TCGA group, respectively) (p < 0.05). The results were consistent in both cohorts. Multivariate Cox regression analysis indicated that low CDK9 status was an independent predictor for poor prognosis in the TCGA cohort (HR 1.60, CL95% 1.1−2.33, p = 0.014). Conclusions: High CDK9 expression predicts a favorable prognosis in urothelial carcinoma and is associated with clinicopathological features characteristic for early-stage disease. The decrease in CDK9 expression can be associated with the build-up of genetic instability and may indicate a key role for CDK9 in the early stages of urothelial carcinoma.

Current strategies in urinary bladder augmentation include use of gastrointestinal segments, however, the technique is associated with inevitable complications. An acellular biologic scaffold seems to be a promising option for urinary bladder augmentation. The aim of this study was to evaluate the utility of bladder acellular matrix (BAM) for reconstruction of clinically significant large urinary bladder wall defects in a long-term porcine model. Urinary bladders were harvested from 10 pig donors. Biological scaffolds were prepared by chemically removing all cellular components from urinary bladder tissue. A total of 10 female pigs underwent hemicystectomy and subsequent bladder reconstruction with BAM. The follow-up study was 6 months. Reconstructed bladders were subjected to radiological, macroscopic, histological, immunohistochemical, and molecular evaluations. Six out of ten animals survived the 6-month follow-up period. Four pigs died during observation due to mechanical failure of the scaffold, anastomotic dehiscence between the scaffold and native bladder tissue, or occluded catheter. Tissue engineered bladder function was normal without any signs of postvoid residual urine in the bladder or upper urinary tracts. Macroscopically, graft shrinkage was observed. Urothelium completely covered the luminal surface of the graft. Smooth muscle regeneration was observed mainly in the peripheral graft region and gradually decreased toward the center of the graft. Expression of urothelial, smooth muscle, blood vessel, and nerve markers were lower in the reconstructed bladder wall compared to the native bladder. BAM seems to be a promising biomaterial for reconstruction of large urinary bladder wall defects. Further research on cell-seeded BAM to enhance urinary bladder regeneration is required., (© 2021 Wiley Periodicals LLC.)

Persistent negative symptoms (PNS) are an important factor of first episode of psychosis (FEP) that present early on in the course of illness and have a major impact on long-term functional outcome. Lack of clinical insight is consistently associated with negative symptoms during the course of schizophrenia, yet only a few studies have explored its evolution in FEP. We sought to explore clinical insight change over a 24-month time period in relation to PNS in a large sample of FEP patients. Clinical insight was assessed in 515 FEP patients using the Scale to assess Unawareness of Mental Disorder. Data on awareness of illness, belief in response to medication, and belief in need for medication were analyzed. Patients were divided into 3 groups based on the presence of negative symptoms: idiopathic (PNS; n = 135), secondary (sPNS; n = 98), or absence (non-PNS; n = 282). Secondary PNS were those with PNS but also had clinically relevant levels of positive, depressive, or extrapyramidal symptoms. Our results revealed that insight improved during the first 2 months for all groups. Patients with PNS and sPNS displayed poorer insight across the 24-month period compared to the non-PNS group, but these 2 groups did not significantly differ. This large longitudinal study supported the strong relationship known to exist between poor insight and negative symptoms early in the course of the disorder and probes into potential factors that transcend the distinction between idiopathic and secondary negative symptoms., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: journals.permissions@oup.com.)

MAF is a transcription factor that may act either as a tumor suppressor or as an oncogene, depending on cell type. We have shown previously that the overexpressed miR-1290 influences MAF protein levels in LSCC (laryngeal squamous cell carcinoma) cell lines. In this study, we shed further light on the interaction between miR-1290 and MAF , as well as on cellular MAF protein localization in LSCC. We confirmed the direct interaction between miR-1290 and MAF 3'UTR by a dual-luciferase reporter assay. In addition, we used immunohistochemistry staining to analyze MAF protein distribution and observed loss of MAF nuclear expression in 58% LSCC samples, of which 10% showed complete absence of MAF, compared to nuclear and cytoplasmatic expression in 100% normal mucosa. Using TCGA data, bisulfite pyrosequencing and CNV analysis, we excluded the possibility that loss-of-function mutations, promoter region DNA methylation or CNV are responsible for MAF loss in LSCC. Finally, we identified genes involved in the regulation of apoptosis harboring the MAF binding motif in their promoter region by applied FIMO and DAVID GO analysis. Our results highlight the role of miR-1290 in suppressing MAF expression in LSCC. Furthermore, MAF loss or mislocalization in FFPE LSCC tumor samples might suggest that MAF acts as a LSCC tumor suppressor by regulating apoptosis.

The chronic inflammation influences a microenvironment, where as a result of losing control over tissue homeostatic mechanisms, the carcinogenesis process may be induced. Inflammatory response cells can secrete a number of factors that support both initiation and progression of cancer and also they may consequently induct an epithelial-mesenchymal transition (EMT), the process responsible for development of distant metastasis. Macrophage migration inhibitory factor (MIF) acts as a pro-inflammatory cytokine that is considered as a link between chronic inflammation and tumor development. MIF can function as a modulator of important cancer-related genes expression, as well as an activator of signaling pathways that promotes the development of prostate cancer. The study was performed on FFPE tissues resected from patients who underwent radical prostatectomy. To investigate the relationship of studied proteins with involvement in tumor progression and initiation of epithelial-to-mesenchymal transition (EMT) process, we selected clinicopathological parameters related to tumor progression. Immunohistochemical analyses of MIF, SOX-4, β-catenin and E-cadherin were performed on TMA slides. We found a statistically significant correlation of overall β-catenin expression with the both lymph node metastasis (p<0.001) and presence of angioinvasion (p = 0.012). Membrane β-catenin expression was associated with distant metastasis (p = 0.021). In turn, nuclear MIF was correlated with lymph node metastasis (p = 0.003). The positive protein-protein correlations have been shown between the total β-catenin protein expression level with level of nuclear SOX-4 protein expression (r = 0.27; p<0.05) as well as negative correlation of β-catenin expression with level of nuclear MIF protein expression (r = -0.23; p<0.05). Our results seem promising and strongly highlight the potential role of MIF in development of nodal metastases as well as may confirm an involvement of β-catenin in disease spread in case of prostate cancer., Competing Interests: The authors have declared that no competing interests exist.

Negative symptoms are present at the onset of psychosis and their persistence is significantly associated with poor psychosocial functioning and lower quality of life. Persistent negative symptoms (PNS) may be idiopathic or secondary to other factors such as depression, positive symptoms, and medication side-effects. Several studies have examined neurocognitive functions in early psychosis patients with PNS relative to non-PNS, but have not systematically controlled for secondary PNS (sPNS). The latter may have a distinct neurocognitive profile that could obscure differences between PNS and non-PNS. Using a large (n = 425) sample, we examined neurocognitive functions in PNS, sPNS, and non-PNS and hypothesized that PNS would be associated with greater impairments relative to non-PNS. Following admission to an early intervention program, a neurocognitive battery was administered after at least 3 months of treatment, and symptom data collected during a subsequent 6-month period were used to classify patients as PNS, sPNS and non-PNS. At month 12, both PNS and sPNS groups had significantly lower level of functioning relative to the non-PNS group but the sPNS group experienced higher levels of depressive and positive symptoms and were on a higher dose of antipsychotics. Relative to non-PNS, PNS patients exhibited significant impairments in verbal memory and working memory, whereas sPNS patients exhibited a trend towards greater impairments in verbal memory. This study confirms that the presence of PNS or sPNS negatively influences functioning with more selective cognitive impairments found in PNS, providing evidence that these groups of patients could benefit from different personalised interventions., Competing Interests: Declaration of Competing Interest Salary awards include: FRSQ to J.L.S., R.J., M.B., and M.L.; a Canada Research Chair to A.M.; and a James McGill Professorship to M.L. M.L. reports grants from Otsuka Lundbeck Alliance, diaMentis personal fees from Otsuka Canada, personal fees from Lundbeck Canada, grants and personal fees from Janssen, and personal fees from MedAvante-Prophase, outside the submitted work. R.J. reports receipt of grants, speaker's and consultant's honoraria from Janssen, Lundbeck, Otsuka, Pfizer, Shire, Perdue, HLS and Myelin and royalties from Henry Stewart Talks. A.M. reports research funding for an investigator-initiated project from BMS Canada and honoraria for lectures and consulting activities (e.g. advisory board participation) with Otsuka and Lundbeck, all unrelated to the present article. All other authors report no competing interests., (Copyright © 2021. Published by Elsevier B.V.)

This study developed a new procedure of urinary bladder transplantation on a rat model (n = 40). Heterotopic urinary bladder transplantation (n = 10) in the right groin vessels was performed. Direct urinary bladder examination, microangiography, histological analysis, and India ink injection were performed to evaluate the proposed method's functionality. Observation time was four weeks. One week after the procedure, the graft survival rate was 80%, two urinary bladders were lost due to anastomosis failure. The rest of the grafts survived two weeks without any complications. Lack of transitional epithelium or smooth muscle layer loss and lack of inflammatory process development were observed. This study was performed in order to obtain the necessary knowledge about urinary bladder transplantation. The proposed technique offers a new approach to the existing orthotropic models.

The ability of tumor cells to spread from their origin place and form secondary tumor foci is determined by the epithelial-mesenchymal transition process. In epithelial tumors such as prostate cancer (PCa), the loss of intercellular interactions can be observed as a change in expression of polarity proteins. Epithelial cells acquire ability to migrate, what leads to the formation of distal metastases. In recent years, the interest in miRNA molecules as potential future treatment options has increased. In tumor microenvironment, miRNAs have the ability to regulate signal transduction pathways, where they can act as suppressors or oncogenes. MiRNAs are secreted by cancer cells, and the changes in their expression levels are closely related to a cancer progression, including epithelial-mesenchymal transition. These molecules offer new diagnostic and therapeutic possibilities. Therapeutics which make use of synthesized RNA fragments and mimic or block miRNAs affected in PCa, may lead to inhibition of tumor progression and even disease re-emission. Based on appropriate qualification criteria, we conducted a selection process to identify scientific articles describing miRNAs and their relation to epithelial-mesenchymal transition in PCa patients. The studies were published in English on Pubmed, Scopus and the Web of Science before August 08, 2019. Hazard ratios (HRs) and 95% confidence intervals (CI) as well as total Gleason score were used to assess the concordance between miRNAs and presence of metastases. A total of 13 studies were included in our meta-analysis, representing 1608 PCa patients and 15 miRNA molecules. Our study clarifies a relationship between the clinicopathological features of PCa and the aberrant expression of several miRNA as well as the complex mechanism of miRNA molecules involvement in the induction and promotion of the metastatic mechanism in PCa.

We study the effects of strategy-dependent time delays on the equilibria of evolving populations. It is well known that time delays may cause oscillations in dynamical systems. Here we report a novel behavior. We show that microscopic models of evolutionary games with strategy-dependent time delays lead to a new type of replicator dynamics. It describes the time evolution of fractions of the population playing given strategies and the size of the population. Unlike in all previous models, the stationary states of such dynamics depend continuously on time delays. We show that in games with an interior stationary state (a globally asymptotically stable equilibrium in the standard replicator dynamics), at certain time delays it may disappear or there may appear another interior stationary state. In the Prisoner's Dilemma game, for time delays of cooperation smaller than time delays of defection, there appears an unstable interior equilibrium, and therefore for some initial conditions the population converges to the homogeneous state with just cooperators.

Melanoma is the most dangerous type of skin cancer. Cancer stem cells (CSCs) are suspected to be responsible for the cancer recurrence and in the consequence for cancer therapy failure. CD133 is a potential marker for detection of melanoma CSCs. Experiments were performed on the B16-F10 mouse melanoma cell line. CD133+ cells were isolated using an immunomagnetic cell sorting technique. After isolation proliferative and clonogenic potential of CD133+, CD133- and CD133+/- were evaluated. The potential of CD133+ and CD133- cells for tumor induction was conducted on C57BL/6J mouse model. Three different cell quantities (100, 1000, 10000) were tested. Tumor morphology, number of mitoses, and tumor necrosis area were analyzed. Average 0.12% CD133+ cells were isolated. Compared to CD133- and unsorted CD133+/- cells, CD133+ cells were characterized by the higher proliferative and clonogenic potential. These properties were not confirmed in vivo , as both CD133+ and CD133- cells induced tumor growth in mouse model. No statistical differences in mitosis number and tumor necrosis area were observed. Simultaneous detection of CD133 antigen with other markers is necessary for accurate identification of these melanoma cancer stem cells., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Tomasz Kloskowski et al.)

Hippocampal circuitry has been posited to be fundamental to positive symptoms in psychosis, but its contributions to other factors important for outcome remains unclear. We hypothesized that longitudinal changes in the hippocampal circuit and concomitant changes of intracortical microstructure are altered in first episode psychosis (FEP) patients and that such changes are associated with negative symptoms and verbal memory. Longitudinal brain scans (2-4 visits over 3-15 months) were acquired for 27 FEP and 29 age- and sex-matched healthy controls. Quantitative T1 maps, sensitive to myelin content, were used to sample the microstructure of the hippocampal subfields and output circuitry (fimbria, alveus, fornix, mammillary bodies), and intracortical regions. Dynamic anatomical covariance in pair-wise regional trajectories were assessed for each subject, and graph theory was used to calculate a participation coefficient metric that quantifies the similarity/divergence between hippocampal and intracortical microstructure. The mean participation coefficient of the hippocampus was significantly reduced in FEP patients compared with controls, reflecting differences in output hippocampal regions. Importantly, lower participation coefficient of the hippocampal circuit was associated with worse negative symptoms, a relationship that was mediated by changes in verbal memory. This study provides evidence for reduced hippocampal centrality in FEP and concomitant changes in intracortical anatomy. Myelin-rich output regions of the hippocampus may be an important biological trigger in early psychosis, with cascading effects on broader cortical networks and resultant clinical profiles., (© 2020 Wiley Periodicals, Inc.)

Background: Cognitive difficulties are a core deficit for people with schizophrenia and are generally assessed with neuropsychological tests. Self-report assessments are also useful in understanding difficulties from the service user's perspective. This study aims to introduce and test the shorter version of the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) to improve its acceptability and comprehensibility. Methods: In consultation with service users and clinicians, we identified items from the original 21-item SSTICS that were found difficult and these were excluded. The reduced scale was explored with Confirmatory Factor Analysis (CFA) in two independent samples in the UK and Canada. Convergent validity with symptoms and IQ was assessed and compared between the original and the reduced scale. Results: Six-hundred and seven people with schizophrenia and first-episode psychosis took part in this study. Seven items were removed to produce the SSTICS-Brief. This had good reliability and the CFA confirmed a unidimensional structure. Convergent validity with symptoms and IQ were optimal between the long and short versions. Conclusions: The SSTICS-B has better acceptability than its longer form and could be administered in less time. The resulting measure is likely to be a valuable short self-assessment of cognitive complaints for people with schizophrenia.

Background/aim: Hirschsprung disease (HD) is caused by the congenital absence of ganglion cells in the distal bowel (aganglionosis). Rectal biopsy is considered important for its diagnosis. The aim of this study was to apply immunohistochemical staining using a minimal set of antibodies and develop an algorithm that will assist in the diagnosis of HD., Patients and Methods: Rectal or colonic biopsies were performed in patients with HD (n=26) or patients treated for other bowel diseases (n=34). Immunohistochemical staining was performed for MAP1b, peripherin, S-100, calretinin, NSE, bcl-2 and CD56 proteins., Results: Staining for CD56, S-100, peripherin and calretinin facilitated the identification of ganglion cells. The use of CD56 and S-100 antibodies together resulted in the highest rate of ganglion cell staining intensity (94%)., Conclusion: We propose a practical diagnostic algorithm with the application of CD56 and S-100 antibodies that can be used in clinical practice in children suspected of Hirschsprung's disease., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Laryngeal squamous cell carcinoma is a major medical problem worldwide. Although our understanding of genetic changes and their consequences in laryngeal cancer has opened new therapeutic pathways over the years, the diagnostic as well as treatment options still need to be improved. In our previous study, we identified CRKL (22q11) as a novel putative oncogene overexpressed and amplified in a subset of LSCC tumors and cell lines. Here we analyze to what extent CRKL DNA copy number gains correlate with the higher expression of CRKL protein by performing IHC staining of the respective protein in LSCC cell lines (n = 3) and primary tumors (n = 40). Moreover, the importance of CRKL gene in regard to proliferation and motility of LSCC cells was analyzed with the application of RNA interference (siRNA). Beside the physiological cytoplasmic expression, the analysis of LSCC tumor samples revealed also nuclear expression of CRKL protein in 10/40 (25%) cases, of which three (7.5%), presented moderate or strong nuclear expression. Similarly, we observed a shift towards aberrantly strong nuclear abundance of the CRKL protein in LSCC cell lines with gene copy number amplifications. Moreover, siRNA mediated silencing of CRKL gene in the cell lines showing its overexpression, significantly reduced proliferation (p < 0.01) as well as cell migration (p < 0.05) rates. Altogether, these results show that the aberrantly strong nuclear localization of CRKL is a seldom but recurrent phenomenon in LSCC resulting from the increased DNA copy number and overexpression of the gene. Moreover, functional analyses suggest that proliferation and migration of the tumor cells depend on CRKL expression.

Background: To examine whether the duration of unremitted psychotic symptoms after the onset of a first episode of psychosis (FEP) is associated with cortical thickness and hippocampal volume, as well as structural covariance of these measures., Method: Longitudinal MRI scans were obtained for 80 FEP patients shortly after entry to FEP clinic (baseline), and then 12 months and 24 months later. The proportion of time patients experienced unremitted positive symptoms for 2 interscan intervals (baseline to 12 mo, 12 mo to 24 mo) was calculated. Changes in cortical thickness and hippocampal volumes were calculated for each interscan interval and associated with duration of unremitted psychotic symptoms. Significant regions were then used in seed-based structural covariance analyses to examine the effect of unremitted psychotic symptoms on brain structural organization. Importantly, analyses controlled for antipsychotic medication., Results: Cortical thinning within the left medial/orbitofrontal prefrontal cortex and superior temporal gyrus were significantly associated with the duration of unremitted psychotic symptoms during the first interscan interval (ie, baseline to 12 mo). Further, changes in cortical thickness within the left medial/orbitofrontal cortex positively covaried with changes in thickness in the left dorsal and ventrolateral prefrontal cortex during this period. No associations were observed during the second interscan interval, nor with hippocampal volumes., Conclusions: These results demonstrate that cortical thickness change can be observed shortly after an FEP, and these changes are proportionally related to the percentage of time spent with unremitted psychotic symptoms. Altered structural covariance in the prefrontal cortex suggests that unremitted psychotic symptoms may underlie reorganization in higher-order cortical regions., (© The Author(s) 2020. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

Purpose: To investigate the frequency and activation status of peripheral plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) as well as gastric mucosa DC subset distribution in Helicobacter pylori - ( H. pylori -) infected and noninfected children., Materials and Methods: Thirty-six children were studied; twenty-one had H. pylori . The frequencies of circulating pDCs (lineage - HLA-DR + CD123 + ) and mDCs (lineage - HLA-DR + CD11c + ) and their activation status (CD83, CD86, and HLA-DR expression) were assessed by flow cytometry. Additionally, the densities of CD11c + , CD123 + , CD83 + , CD86 + , and LAMP3 + cells in the gastric mucosa were determined by immunohistochemistry., Results: The frequency of circulating CD83 + mDCs was higher in H. pylori -infected children than in the noninfected controls. The pDCs demonstrated upregulated HLA-DR surface expression, but no change in CD86 expression. Additionally, the densities of gastric lamina propria CD11c + cells and epithelial pDCs were increased. There was a significant association between frequency of circulating CD83 + mDCs and gastric lamina propria mDC infiltration., Conclusion: This study shows that although H. pylori -infected children had an increased population of mature mDCs bearing CD83 in the peripheral blood, they lack mature CD83 + mDCs in the gastric mucosa, which may promote tolerance to local antigens rather than immunity. In addition, this may reduce excessive inflammatory activity as reported for children compared to adults., Competing Interests: There are no conflicts of interest for any author., (Copyright © 2019 Anna Helmin-Basa et al.)

Introduction: Metalloproteinases and their tissue inhibitors play an important role in the metastases formation. A multistage process of carcinogenesis requires the involvement of numerous enzymes and compounds that facilitate the expansion of tumor cells. The formation of metastases depends on both metalloproteinases and tissue inhibitors activation leading to the activation of neoangiogenesis. The changes of the expression in stromal and tumor proteins could be prognostic factors in patients with oropharyngeal squamous cell carcinoma., Materials and Methods: This study was conducted on a total of 34 patients with squamous cell carcinoma of the oropharynx divided into 2 groups, including 20 patients with neck metastasis and 14 patients without lymph node metastasis. Immunohistochemistry was performed with a standard protocol., Results: The results of the present analysis indicated a higher expression of metalloproteinases 2 in the stroma than in tumor with increasing tumor grade. The dynamics of changes in the expression of metalloproteinases showed the increase in metalloproteinases 2 and the decrease in metalloproteinases 9 depending on the tumor size. Dynamics of changes in the expression of tissue inhibitor 1 in the tumor stroma significantly increased with the tumor stage. In the assessment of nodal staging from N0 to N3, the expression of tissue inhibitor 1 and 2 were higher in the tumor tissues. The increase of metalloproteinases 2, tissue inhibitor 1 in the tumor, and metalloproteinases 9 in the stroma were characterized by a reduction in the odds ratio of patient's survival., Conclusion: The complex evaluation of the expression of metalloproteinases and tissue inhibitors may be used for the prognosis of the patient's survival.

The objective of this study was to evaluate the quality of instructional sterile compounding videos posted on a popular video-sharing website (YouTube). YouTube was systematically searched using relevant terms (aseptic compounding, sterile compounding) to identify all videos demonstrating aseptic manipulations of compounded sterile preparations in a cleanroom. Promotional videos, news stories, interviews, and videos with manipulations performed outside a cleanroom, without audio or spoken in a language other than English, were excluded. Three experts independently reviewed each video and assessed the quality of key sterile compounding processes, information delivery, and overall suitability for workforce training using a standardized assessment tool. Kendall's coefficient of concordance (W) was calculated to assess agreement. Included were 66 videos with a median of 839 (IQR 62-3935) views. There was moderate to substantial agreement among assessors when determining the quality of each step of the compounding process (W 0.48 to 0.72; all P<0.002). Only one in five videos demonstrated an acceptable standard of gloving and garbing, while product inspection and waste disposal processes were more likely to be appropriately demonstrated. Most videos had acceptable sound/image quality and English pronunciation, but not all videos had a comprehensive narration. Six videos (9%) were recommended for training compounding personnel by two assessors and a further 17 (26%) videos were recommended by one assessor. No videos were recommended by all three assessors. The conclusions of this study are: 1) there is considerable variation in the quality of instructional sterile compounding videos available on the YouTube website; 2) few videos are suitable for training compounding personnel., Competing Interests: Authors Jodie G. Hobbs and Karen J. Reynolds report grant funding from the South Australian Premier’s Research and Industry Fund Collaboration Pathways Program during the conduct of this study., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Loss of B cell-specific transcription factors (TFs) and the resulting loss of B-cell phenotype of Hodgkin and Reed-Sternberg (HRS) cells is a hallmark of classical Hodgkin lymphoma (cHL). Here we have analysed two members of ETS domain containing TFs, ELF1 and ELF2, regarding (epi)genomic changes as well as gene and protein expression. We observed absence or lower levels of ELF1 protein in HRS cells of 31/35 (89%) cases compared to the bystander cells and significant (P < 0·01) downregulation of the gene on mRNA as well as protein level in cHL compared to non-cHL cell lines. However, no recurrent loss of ELF2 protein was observed. Moreover, ELF1 was targeted by heterozygous deletions combined with hypermethylation of the remaining allele(s) in 4/7 (57%) cell lines. Indeed, DNA hypermethylation (range 95-99%, mean 98%) detected in the vicinity of the ELF1 transcription start site was found in all 7/7 (100%) cHL cell lines. Similarly, 5/18 (28%) analysed primary biopsies carried heterozygous deletions of the gene. We demonstrate that expression of ELF1 is impaired in cHL through genetic and epigenetic alterations, and thus, it may represent an additional member of a TF network whose downregulation contributes to the loss of B-cell phenotype of HRS cells., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Objectives: Angiogenesis underlies tumour growth and metastasis through hepatocyte growth factor (HGF), epithelial growth factor (EGF), and vascular endothelial growth factor (VEGF). The aim of this study was to determine the levels of VEGF, EGF, HGF, HGFR (hepatocyte growth factor receptor), and SRSF1 (serine-rich protein splicing factor-1) in patients with parotid gland tumours and in healthy controls via ELISA in parotid saliva. Immunohistochemical expression of anti-angiogenic isoform of VEGF 165 b subunit, VEGFR1, VEGFR2, and microvessel density (CD34) were assessed in the tumour tissue and in the non-tumorous surrounding margins., Materials and Methods: The study included 48 patients with benign and malignant parotid gland tumours and 15 healthy controls., Results: Comparison of VEGF, EGF, and HGF in tumour and non-tumorous tissues showed no significant differences and no correlations with tumour stage. The salivary VEGF concentration was significantly higher in patients with pleomorphic adenoma and Warthin's tumour. No significant correlation was found between expression of VEGF 165 b and VEGFR2 in tumours and non-tumor surgical margins., Conclusions: The increased salivary VEGF reflects changes in affected parotid glands, but it cannot be used as a prognostic and differentiative factor for parotid tumours., Clinical Relevance: Reciprocal relations between growth factors suggest an overlapping pathway of secretion and activity.