Validation of crAssphage microbial source tracking markers and comparison with Bacteroidales markers for detection and quantification of faecal contaminations in surface water.

Human-specific faecal contamination has been affecting surface water and is a threat to both the environment and public health due to its potential co-occurrence with pathogens. Extended studies were conducted to detect and quantify faecal contamination using microbial source tracking (MST) markers targeting bacteria and viruses. The prototypical crAssphage, a presumed Bacteroides-infecting phage discovered in 2014, showed superior specificity to human faeces and high abundance in untreated sewage water.

The prolyl dipeptidyl peptidase cleaves the N-terminal peptide of the immunoprotein CXCL-10.

Dipeptidyl peptidases constitute a class of non-classical serine proteases that regulate an array of biological functions, making them pharmacologically attractive enzymes. With this work, we identified and characterized a dipeptidyl peptidase from (MtDPP) displaying a strong preference for proline residues at the P substrate position and an unexpectedly high thermal stability. MtDPP was also characterized with alanine replacements of residues of its active site that yielded, for the most part, loss of catalysis.

Activation of a cGAS-STING-mediated immune response predicts response to neoadjuvant chemotherapy in early breast cancer.

Background: The DNA-damage immune-response (DDIR) signature is an immune-driven gene expression signature retrospectively validated as predicting response to anthracycline-based therapy. This feasibility study prospectively evaluates the use of this assay to predict neoadjuvant chemotherapy response in early breast cancer.

Methods: This feasibility study assessed the integration of a novel biomarker into clinical workflows.

Molecular classification of non-invasive breast lesions for personalised therapy and chemoprevention.

Breast cancer screening has led to a dramatic increase in the detection of pre-invasive breast lesions. While mastectomy is almost guaranteed to treat the disease, more conservative approaches could be as effective if patients can be stratified based on risk of co-existing or recurrent invasive disease.Here we use a range of biomarkers to interrogate and classify purely non-invasive lesions (PNL) and those with co-existing invasive breast cancer (CEIN).

The prognostic significance of the aberrant extremes of p53 immunophenotypes in breast cancer.

Aims: The utility of p53 as a prognostic assay has been elusive. The aims of this study were to describe a novel, reproducible scoring system and assess the relationship between differential p53 immunohistochemistry (IHC) expression patterns, TP53 mutation status and patient outcomes in breast cancer.

Methods And Results: Tissue microarrays were used to study p53 IHC expression patterns: expression was defined as extreme positive (EP), extreme negative (EN), and non-extreme (NE; intermediate patterns).

BRCA1 is both a prognostic and predictive biomarker of response to chemotherapy in sporadic epithelial ovarian cancer.

Objectives: We investigated the relationship between BRCA1 protein expression by immunohistochemistry (IHC) and clinical outcome following platinum and platinum/taxane chemotherapy in sporadic epithelial ovarian cancer (EOC).

Methods: BRCA1 IHC was performed on a cohort of 292 ovarian tumours from two UK oncology centres. BRCA1 protein expression levels were correlated with overall survival (OS), progression free survival (PFS) and clinical response to chemotherapy by multivariate analysis.

Breast cancer in women under 40 years of age: a series of 57 cases from Northern Ireland.

Background: There are few studies examining breast cancer in women under the age of 40 years, particularly in western European populations. Such tumours are reported to be more aggressive, possibly due to a different pathophysiology compared to older patients.

Methods: We performed a retrospective review of all women less than 40 years of age, diagnosed or treated with breast cancer, from June 2001 to June 2007 to assess pathophysiological factors that may influence clinical outcome and prognosis including patient demographics, clinical presentation, pre-operative investigations, surgical and pathological findings, treatment and outcome.

Completion mastectomy after breast conserving surgery.

Background: Breast conserving surgery (BCS) is increasingly offered to suitable patients diagnosed with early stage breast cancer. Occasionally the pathological margins on specimens following BCS are positive. The objective of this study is to assess the proportion of patients within our unit who required completion mastectomy after BCS and to determine if predictive factors could be identified to assist the breast surgeon identifying those patients at risk of positive margins following BCS.

In vivo evidence for the role of CD44s in promoting breast cancer metastasis to the liver.

The hyaluronan receptor CD44 plays an important role in facilitating invasion and metastasis of a variety of tumors, including breast carcinomas. CD44 functions as a bioactive signaling transmitter. Although a number of studies have implicated CD44 in breast tumor invasion, the evidence is still circumstantial.

Role of polymerase chain reaction and immunocytochemistry in the cytological assessment of lymphoid proliferations.

Background: Fine-needle aspiration cytology (FNAC) is used as a screening test to evaluate lymphadenopathy. The combined use of genetic analysis and flow cytometry for immunophenotyping has increased the accuracy of diagnosis and correct categorisation of lymphomas on cytological preparations.

Aim: To show the utility of immunocytochemistry and polymerase chain reaction (PCR) in the evaluation of cytological preparations of lymph nodes.

Fine needle aspiration cytology (FNAC) in the diagnosis of granulomatous lymphadenitis.

Objective: To determine the final histological and clinical diagnosis of patients with granulomatous lymphadenitis on fine needle aspiration cytology (FNAC).

Method: A retrospective cohort study was carried out over a five year period in a tertiary referral hospital. FNAC of 22 patients with granulomatous lymphadenitis was reviewed and correlated with the final histological diagnosis and clinical outcome.

The effect of ultra violet B (TL-01) phototherapy on epidermal expression of p53 protein in psoriatic plaques.

Background: Psoriasis is a genetically determined inflammatory skin disease. It is now recognized that narrow band TL-01 phototherapy is an effective treatment for psoriasis. However, ultraviolet (UV) exposure induces p53 mutations in keratinocytes and repeated exposure of skin to UV radiation results in clonal expansion of these initiated p53-mutant cells within the epidermis.

Prognostic significance of glycoprotein pMQ1 in breast cancer.

Background: A novel glycoprotein, pMQ1, is positively correlated with increasing histological grade in malignant astrocytomas. Cerebral metastases from breast cancer have also been found to contain pMQ1-positive cells. This study aimed to determine the role of pMQ1 in primary breast cancer.

BRCA1 and c-Myc associate to transcriptionally repress psoriasin, a DNA damage-inducible gene.

Evidence is accumulating to suggest that some of the diverse functions associated with BRCA1 may relate to its ability to transcriptionally regulate key downstream target genes. Here, we identify S100A7 (psoriasin), S100A8, and S100A9, members of the S100A family of calcium-binding proteins, as novel BRCA1-repressed targets. We show that functional BRCA1 is required for repression of these family members and that a BRCA1 disease-associated mutation abrogates BRCA1-mediated repression of psoriasin.

Surgical treatment for invasive lobular carcinoma of the breast.

The management and outcome of 131 women with infiltrating lobular carcinoma treated in the Belfast City Hospital between October 1987 and February 1999 were reviewed. Two patients had primary hormonal treatment and were excluded from the statistical analysis, and 129 patients were followed up. Fifty-four patients (41%) had initial breast conservation surgery, which was followed by re-excision of margins in eight patients (14.

Rhabdomyosarcoma of the uterus: report of two cases, including one of the spindle cell variant.

Most uterine sarcomas fall into the category of leiomyosarcoma, endometrial stromal sarcoma, or undifferentiated sarcoma. Pure rhabdomyosarcomas are extremely rare, although a rhabdomyosarcomatous element may be present as a component of an adenosarcoma or carcinosarcoma (malignant mixed müllerian tumor). This report describes two uterine rhabdomyosarcomas in 28- and 67-year-old women.

Thyroid papillary carcinoma in lateral neck cyst: missed primary tumour or ectopic thyroid carcinoma within a branchial cyst?

We report a case of thyroid papillary carcinoma lying within a lateral cervical cyst for which no occult primary tumour of the thyroid was identified. We explore the possible diagnoses and include a discussion of how ectopic thyroid tissue may come to lie within a branchial cyst.

The role of fine needle aspiration cytology (FNAC) in the investigation of superficial lymphadenopathy; uses and limitations of the technique.

Aspirates (n = 163) from 157 patients with enlarged superficial lymph nodes were obtained over a 5-year period in a combined surgical/FNAC clinic. A definitive diagnosis was achieved in over 77% of the cases: benign 52.7%, malignant 25.

A 3-year audit of thyroid fine needle aspirates.

Fine needle aspiration (FNA) cytology is an important adjunct to the preoperative management of thyroid swellings. It is a simple and highly cost effective procedure with a higher sensitivity for the detection of malignancy than ultrasound and radio-isotope scans. We audited a total of 208 aspirates performed over a 3-year period.