Consensus clustering methodology to improve molecular stratification of non-small cell lung cancer.

Recent advances in machine learning research, combined with the reduced sequencing costs enabled by modern next-generation sequencing, paved the way to the implementation of precision medicine through routine multi-omics molecular profiling of tumours. Thus, there is an emerging need of reliable models exploiting such data to retrieve clinically useful information. Here, we introduce an original consensus clustering approach, overcoming the intrinsic instability of common clustering methods based on molecular data. This approach is applied to the case of non-small cell lung cancer (NSCLC), integrating data of an ongoing clinical study (PROMOLE) with those made available by The Cancer Genome Atlas, to define a molecular-based stratification of the patients beyond, but still preserving, histological subtyping. The resulting subgroups are biologically characterized by well-defined mutational and gene-expression profiles and are significantly related to disease-free survival (DFS). Interestingly, it was observed that (1) cluster B, characterized by a short DFS, is enriched in KEAP1 and SKP2 mutations, that makes it an ideal candidate for further studies with inhibitors, and (2) over- and under-representation of inflammation and immune systems pathways in squamous-cell carcinomas subgroups could be potentially exploited to stratify patients treated with immunotherapy.

An immunofiltration device for the simultaneous detection of non-treponemal and treponemal antibodies in patients with syphilis.

OBJECTIVE: The development of a rapid immunofiltration (flow-through) test for the simultaneous detection of non-treponemal and treponemal antibodies in the serum of patients with syphilis. METHODS: The assay is rapid, inexpensive, and requires limited expertise in interpreting the results. The test is based on the principle of immunofiltration, with two antigens and control material spotted on the membrane of a through-flow device. A positive test is characterised by the appearance of three red/magenta spots within 2-10 min. RESULTS: A total of 376 banked serum samples obtained from the Georgia Public Health Laboratory was examined by the flow-through test, the rapid plasma reagin (RPR) test and the Treponema pallidum passive particle agglutination assay (TPPA). The sensitivity and specificity of the non-treponemal spot were 96.5% and 97.7%, respectively, when compared with the RPR test, and the sensitivity and specificity of the treponemal test spot were 97.3% and 99.1% when compared with the TPPA test. In addition, the test yielded equivalent results to those obtained in comparator tests when 104 sera from cases of syphilis of known stage, 49 sera from diseases other than syphilis and 23 sera known to exhibit biological false-positive reactions were tested in parallel. CONCLUSIONS: These results indicate that the dual treponemal and non-treponemal assay could be used as a screen and confirmatory test for the serological diagnosis of syphilis in remote or resource-poor settings where there is a need to provide counselling and treatment at the initial consultation.

Comparative study of sliced tragal cartilage and temporalis fascia in type I tympanoplasty.

OBJECTIVE: To compare anatomical and audiological results using sliced tragal cartilage and temporalis fascia in type I tympanoplasty. METHOD: A retrospective review was undertaken of primary tympanoplasties using sliced tragal cartilage and temporalis fascia from May 2005 to January 2008. In total, 223 ears were operated on using sliced tragal cartilage graft and 167 using temporalis fascia. Statistical analysis of the outcome data was performed. RESULTS: At the two-year and four-year follow ups, successful closure of the tympanic membrane was achieved in 98.20 per cent and 97.75 per cent, respectively, of the cartilage group compared with 87.42 per cent and 82.63 per cent, respectively, of the temporalis fascia group. At the four-year follow up, the average air-bone gap was 7.10 ± 3.01 dB in the cartilage group and 8.05 ± 3.22 dB in the temporalis fascia group. CONCLUSION: The overall success rate for primary cartilage tympanoplasty is higher when using sliced cartilage than with temporalis fascia grafting.

Average thickness of tragal cartilage for slicing techniques in tympanoplasty.

BACKGROUND: Cartilage-perichondrial grafts are often used for tympanic membrane and middle-ear reconstructions. Tragal and conchal cartilages are most frequently used for this purpose. Studies have shown that slicing the cartilage to less than 0.5 mm thickness improves acoustic benefit. However, the thickness of the cartilage in a given population may not be uniform. OBJECTIVE: This descriptive cross-sectional study aimed to determine the average thickness of tragal cartilage (in terms of age and sex) in an Indian population. METHOD: A prospective study of 61 tragal cartilages harvested during serial tympanoplasty and modified radical mastoidectomy were analysed according to thickness. RESULTS: The total average thickness of tragal cartilage was 1.228 ± 0.204 mm in males and 1.090 ± 0.162 mm in females. The overall thickness was 1.018 ± 0.139 mm in those aged less than 15 years, 1.139 ± 0.238 mm in those aged 15-30, and 1.189 ± 0.155 mm in those aged over 30 years. CONCLUSION: The findings help us to determine age-related cartilage thickness for slicing techniques in tympanoplasty.

Biliary sepsis: an ascending infection.

AIM: To study the bacteriology of normal and obstructed biliary tree and determine the mode of biliary infection. METHODS: Fifty seven patients undergoing elective biliary surgery for calculous biliary disease cholecystitis 45, obstructive jaundice 12) were studied. Bile samples collected separately from gall bladder, common bile duct and duodenum at the time of surgery were processed for aerobic and anaerobic cultures and antibiotic assays. To locate endogenous foci of infection, urine, nasal swab and throat swab cultures were done. Isolates from/biliary tract were compared with those from other sites. RESULTS: Thirty eight patients (66.7%) had bactobilia. The prevalence was higher in patients with obstructive jaundice (10/12, 83.3%) than (p = 0.5) in those with non-obstructed biliary tree. Single bacterial infection (31 cases, 81 %) was more common than mixed infection (7 cases, 19%). Colonization of more than one segment of the biliary tree was seen in 30 patients (79%). E coli was the most frequently isolated organism. In 24 cases (63.2%), strains of organisms from the common bile duct and gall bladder were similar to those from the duodenum, and in only 10 cases (23.2%) were similar to those found in the nose, throat and urine. The antibiotic concentrations in the common bile duct after single doses of preoperative antibiotic (gentamicin and cephazolin) were lower in the obstructed biliary tree (1.5 +/- 0.4 milligrams/mL and 2.8 milligrams/mL respectively) than in the non-obstructed system (3.9 +/- 1.7 milligrams and 12.6 milligrams/mL/mL respectively) (p = 0.5 for both antibiotics). CONCLUSION: Ascending infection forms the mode of biliary sepsis in a majority of cases. Prophylactic antibiotics give low levels in the bile in an obstructed biliary tree.

Microwave-assisted Heterocyclic Dicarboxylic Acids as Potential Antifungal and Antibacterial Drugs.

A series of new dicarboxylic acid derivatives of 1,3,4-thiadiazines, 1,4-benzopiperizines, 1,4-thiazines, 1,3-thiazoles, 1,3-oxazoles and 1,3-imidazoles have been synthesized in 80-87% yield by the environmentally benign microwave induced technique involving the cyclocondensation of 2,3-dibromosuccinic acid with 2-aminothiophenol, o-phenylene diamine, 1,2,4-triazole, amidinothiocarbamide, amidinocarbamide and guanidine hydrochloride. The structures of all newly synthesized compounds have been established on the basis of analytical and spectral data. Evaluation of antibacterial and antifungal activity showed that almost all compounds exhibited better results than reference drugs thus they could be promising candidates for novel drugs.