Ensembl 2021.

The Ensembl project (https://www.ensembl.org) annotates genomes and disseminates genomic data for vertebrate species. We create detailed and comprehensive annotation of gene structures, regulatory elements and variants, and enable comparative genomics by inferring the evolutionary history of genes and genomes. Our integrated genomic data are made available in a variety of ways, including genome browsers, search interfaces, specialist tools such as the Ensembl Variant Effect Predictor, download files and programmatic interfaces. Here, we present recent Ensembl developments including two new website portals. Ensembl Rapid Release (http://rapid.ensembl.org) is designed to provide core tools and services for genomes as soon as possible and has been deployed to support large biodiversity sequencing projects. Our SARS-CoV-2 genome browser (https://covid-19.ensembl.org) integrates our own annotation with publicly available genomic data from numerous sources to facilitate the use of genomics in the international scientific response to the COVID-19 pandemic. We also report on other updates to our annotation resources, tools and services. All Ensembl data and software are freely available without restriction.

PAH exposure-associated lung cancer: an updated meta-analysis.

Background: Occupational exposure to polycyclic aromatic hydrocarbons (PAHs) has been shown to be associated with lung cancer in various epidemiological studies in industries such as aluminium reduction/smelting, coal gasification, coke production, iron/steel foundries, coal/coke and related products and carbon/graphite electrodes production. Aims: To update data on the association between PAH exposure and morbidity and mortality due to lung cancer among workers in different occupations, including smoking data. Methods: A comprehensive literature search was conducted to retrieve relevant papers for meta-analysis. Cohort studies with standardized mortality ratios or standardized incidence ratios and calculated overall risk ratio with their corresponding 95% confidence intervals (CIs) were included in the analysis. Chi-square test for heterogeneity was used to evaluate the consistency of findings between the studies. Results: A significant risk of lung cancer was observed among the coal/coke and related product industry 1.55 (95% CI 1.01-2.37) and the iron/steel foundry industry 1.52 (95% CI 1.05-2.20). There was a wide variation in smoking habits and PAHs exposure among studies. Conclusions: Coal/coke industry and iron/steel industry workers showed a higher risk of lung cancer compared with other occupations exposed to PAHs. The confounding effects of smoking and individual exposure levels of PAH should be taken into account.

Anorectal melanoma: experience from a tertiary cancer care centre in South India.

Introduction Mucosal malignant melanoma of the anorectum is a rare and aggressive disease, in which early diagnosis is difficult. The prognosis remains extremely poor, irrespective of the treatment. We share our experience in treating this malignancy at our centre in South India. Methods This study describes a retrospective analysis of 31 cases of anorectal melanoma presented to our centre between January 2001 and December 2013. Results Twenty-two patients (71%) presented with metastasis and had a median overall survival of nine months. None of the 22 patients survived for two years. Nine patients (29%) had curative surgery, in the form of abdominoperineal resection (six patients), abdominoperineal resection with bilateral inguinal node dissection (one patient), abdominoperineal resection with liver resection (one patient) and posterior exenteration (one patient). In patients who underwent curative surgery, the median overall survival was 15 months and disease-free survival was nine months, with a two-year overall survival of 22%. Conclusions Anorectal melanoma is an aggressive disease with a poor prognosis. The majority of patients present with distant metastases. Prognosis depends on stage at presentation. Early diagnosis and surgical resection may improve the overall outcome. Newer modalities such as immunotherapy and targeted therapies such as anti-CTLA4 monoclonal antibody and anti-programmed cell death protein 1 monoclonal antibodies have radically changed the management of mucosal melanoma and may, in the future, improve the overall prognosis of anorectal melanoma.

Case Report of Salmonella gallinarum Urinary Tract Infection in a Renal Allograft Recipient.

Urinary tract infections (UTIs) caused by nontyphoidal Salmonella in a renal allograft recipient are a rare occurrence. Although there is some existing literature on Salmonella typhi bacteriuria and non-typhoidal bacteriuria, none of the cases has been reported in a renal transplant patient. This case report describes a rare instance in which group D Salmonella was isolated from a renal allograft recipient's urine culture and the patient was successfully treated with antibiotics.

Incidence of Buxtonella sulcata in bovines in R.S. Pura, Jammu.

Incidence of Buxtonella sulcata was recorded as 20.9 % in bovines (n = 374) of R.S. Pura, Jammu with cattle showing higher infection rate (23.6 %) than the buffaloes (18.5 %). The infection was significantly (p < 0.0001) higher in young animals (33.1 %) than the adults (13.9 %). Animals with diarrhoeic faeces had a significantly higher (p < 0.0001) infection rate (38.5 %) than the animals with normal faeces (9.9 %), suggesting the influence of protozoan on the incidence of diarrhoeal symptoms in bovines.

Hepatoid adenocarcinoma of the stomach - a rare pathological entity.

Hepatoid adenocarcinoma is a rare cancer with an extremely poor prognosis. Here, we describe two cases referred to our hospital with suspected gastric cancer. Gastrointestinal endoscopy revealed lesions in the stomach. Biopsy from the lesions was reported as adenocarcinoma. Both the patients underwent exploratory laparotomy. One was an operable lesion and the other was an inoperable lesion. Total gastrectomy was done in the operable lesion and feeding jejunostomy was done in the inoperable case. Histologically, both turned out to be hepatoid adenocarcinomas. Retrospective analysis showed the serum levels of alphafetoprotein (AFP) are markedly elevated in both cases. We describe this rare entity of hepatoid adenocarcinoma of the stomach, and review the literature concerning the clinicopathological aspects of the cases.

Pre-tertiary hospital care of patients with chronic kidney disease in India.

BACKGROUND & OBJECTIVES: There is paucity of data available on how chronic kidney disease (CKD) is treated before referral to a tertiary hospital. This study was conducted to assess pre-tertiary hospital care of patients with CKD 5 at their presentation to nephrology services at a tertiary care hospital. METHODS: Over a period of 8 months, consecutive patients with CKD 5 presenting at the Nephrology services at Christian Medical College, Vellore, Tamil Nadu, and their relatives were interviewed to assess the pre-tertiary hospital care and knowledge about CKD 5 and its treatment. RESULTS: A total of 561 patients with CKD 5 were enrolled. The mean duration (months) of known CKD was 12.4 +/- 23.1 and known CKD 5 was 3.2 +/- 3.5. Of these, 369 patients (65.8%) had been under the care of a nephrologist; 305 patients had CKD 5 as the initial presentation of renal illness. Vaccination against hepatitis B had been initiated in only 133 patients (23.7%). Only 172 patients(38%) had an adequately controlled blood pressure. Care under a nephrologist was more likely to result in appropriate investigation, treatment and patient education though blood pressure control did not differ. INTERPRETATION & CONCLUSION: Paucity of symptoms in the initial stages of certain forms of CKD probably led to 50 per cent of patients presenting with CKD 5 as the initial presentation of renal disease. Inadequate vaccination against hepatitis B infection highlights the need for appropriate vaccination. Prevention of CKD and its progression are important targets which requires physician awareness at all levels. Early referral to a nephrologist's care is more likely to result in appropriate investigations and treatment.

Nm23H1 and p53 proteins are differentially correlated to metastasis in breast carcinoma.

The prognostic significance of nm23H1 and p53 proteins as predictors of nodal involvement and distant recurrence was evaluated in 63 cancer and 47 benign lesions of the breast. Assessment was carried out by immunohistochemical staining using nm23H1 and p53 antibodies. Results show no relation of nm23H1 either to the malignant nature when compared to benign lesions or to the nodal status. P53 protein, on the other hand, showed significantly increased expression in malignant lesions (p=0.001) and correlated well with nodal positivity (p=0.03). A follow-up study of 5 years showed that among the cases showing recurrence, those with positive mn23H1 showed a shorter distant recurrence free survival (DRFS, p=0.01), while p53 expression had no effect. This result did not agree with the previous reports showing nm23H1 as an antimetastatic gene. This is the first report of positive correlation between nm231-11 and distant recurrence in breast cancers, though such a correlation was reported earlier in certain other cancers. Since nm23H1 is an NDP kinase, having more involvement in signal transduction of cell proliferation, it is not difficult to comprehend such a role for nm23H1 during recurrence. Combining the expression of both proteins, lesions positive for both p53 and nm23H1 had significantly reduced distant recurrence free survival (DRFS), when compared to those negative for both proteins (p=0.0006). It can be concluded that nni23H1 alteration has a potential in predicting DRFS, while p53 alteration has the potential to predict lymph node involvement.

Apoptotic index: use in predicting recurrence in breast cancer patients.

Apoptosis maintains tissue homeostasis through its ability to control cell population and has been extensively studied in human cancers. Relation of apoptosis to prognosis is still controversial. In this study, we analyzed the prognostic significance of apoptotic and mitotic indices (AI & MI) using hematoxylin and eosin stained slides by light microscopy in breast cancer patients. In our study, apoptotic index was significantly associated with predicting relapse free survival (RFS), distant recurrence free survival (DRFS) and overall survival (OS) with lesions having higher apoptotic index showing poor prognosis. Our results also point out that quantitation of apoptotic index by simple light microscopy as a routine practice along with histological diagnosis, could provide additional prognostic information in patients who are at high risk of developing recurrence with breast cancers.

Acute abdomen in patients receiving chemotherapy.

OBJECTIVE: To assess the incidence of acute abdomen in patients receiving chemotherapy and to evaluate the factors affecting the clinical decision-making. MATERIAL AND METHODS: Retrospective analysis of surgical oncology references for the patients developing acute abdomen while receiving chemotherapy was carried out. A surgical oncologist reviewed each referral and a full work-up was carried out. Surgical interventions were carried out as and when deemed necessary. Response to treatment, whether surgical or conservative, was used as main outcome variable. RESULTS: Mean age of the patients was 37 years (7-58 years). Half of the patients were receiving chemotherapy for lymphoproliferative disorders, 13 for haematological malignancies and 3 for ovarian cancer. Clinical diagnosis was of acute appendicitis in 13, paralytic ileus in 9, typhilitis in 3 and intestinal perforation in 2, acute intestinal obstruction in 3, and obstructed hernia and intussception in one each. Six patients underwent surgery. Two patients expired postoperatively of progressive septicaemia and multi-system organ failure. CONCLUSION: Evaluation of cancer patients on chemotherapy is difficult. Tenderness, presence of peritoneal signs and absence of exaggerated bowel sounds are most important clinical signs, however they may be blunted by progressive neutropenia or corticosteroid administration. Decision to operate, should be made with extreme caution as mortality and morbidity after surgery is high.

Sarcoma of the oral and maxillofacial soft tissue in adults.

AIMS: Sarcoma occurring in oral and maxillofacial soft tissue is rare. This study was carried out to evaluate the prevalence of oral soft tissue sarcoma and to record its natural history and survival. METHODS: Retrospective analysis of the patients with histologically proven oral and maxillofacial soft tissue sarcoma treated at the Regional Cancer Centre (RCC), Trivandrum, betweeen 1990-1998 was carried out. RESULTS: During this period, ten cases of oral and maxillofacial sarcomas were registered. Three lesions were located on the cheek mucosa, two on the tongue and two on the mandibular alveolus, while there was one lesion each in the parotid region, maxilla and face (NOS). Mean age at presentation was 31.3+/-14.1 years (range 15-54 years). Seven of the patients (70%) were males. There were three cases of rhabdomyosarcoma (RMS), three cases of spindle cell sarcoma and one case each of angiosarcoma, haemangioendothelioma, malignant schwannoma and malignant fibrous histiocytoma (MFH). All the patients were treated with surgery as a primary modality. Median follow-up time was 30 months (range 5-94 months). An overall srvival of 87.5% at 5 years was observed; however, 5-year disease free survival was 60.0% (95% CI 19.5-85.2). CONCLUSIONS: Soft tissue sarcomas are of comparatively less frequent occurrence in oral and maxillofacial soft tissue than in other tissues. A good survival rate can be achieved by multimodality treatment.

Primary malignant melanoma of the upper aero-digestive tract.

Malignant mucosal melanoma represents 0.3 to 10% of all melanomas. The majority of these lesions arise in the oral cavity or paranasal sinuses. Very few authors report reliable treatment results, however all suggest a uniformly poor outcome. A retrospective analysis of all cases of upper aero-digestive tract melanoma (UADT) treated since 1982 at our centre are presented. During the 15-year period, nine cases of UADT melanoma were identified. Three patients had a lesion in the palate, two in the maxillary alveolus, two in the oropharynx, while one each had a lesion in paranasal sinus and lower alveolus. Mean age was 43.25 years (28-62 years), with a male to female ratio of 1.6:1. Cervical lymphadenopathy was the commonest presenting symptom in seven patients. Radical surgery was carried out in three patients, wide excision in three and radical neck dissection in six, while no surgical intervention was undertaken in two patients. Median follow-up time was eleven months. In four patients, local recurrence occurred, while three developed pulmonary metastasis. One patient was lost to follow-up. We suggest that data from various centres be pooled together in order to carry out a meta-analysis to address the question of optimal treatment for malignant melanoma of the upper aero-digestive tract.

Primary malignant melanoma of the mucous membranes.

AIMS: To investigate malignant mucosal melanoma (MMM), a rare disease and one which has, till lately, remained unrecognized. Incidence of MMM ranges from 2 to 10% in various series. METHODS: We retrospectively reviewed the cases of malignant melanoma treated at the Regional Cancer Centre, Trivandrum, India, over a period of 15 years. RESULTS: A total of 163 cases of melanoma were identified, of which 21 had a lesion in mucosal sites. There were eight cases of upper aero-digestive tract (UADT) melanoma, seven cases of rectal melanoma, five cases with lesions in the vagina and one case with a lesion in the urethra. The mean age of the patients was 52.8 years; mean age of presentation in urogenital and anorectal lesions was similar to overall mean age, while this was lower (47.5 years) for UADT lesions. Almost half of the patients presented with ulcer or nodule with or without pigmentation. Pain was present in three-quarters and vaginal bleeding was present in all cases of vaginal lesions. Almost one-third of the patients failed locally while another third developed distant metastasis during the follow-up period. A 2-year disease-free survival rate of 13.2% (95% CI: 2.2-34.1) was observed, which dropped to 6.6% (95% CI: 0.4-25.7) after 3 years. Survival appeared a little better in UADT melanoma compared to urogenital and anorectal melanoma; however, the difference was not statistically significant. CONCLUSIONS: Malignant mucosal melanoma seems to have an aggressive biological behaviour with a high incidence of local failure and metastasis.