Effects of Smokeless Tobacco on Oral Health: A Cross-Sectional Study.

BACKGROUND: Smokeless tobacco (SLT) consumption poses a significant global public health challenge because of its adverse effects on oral health. Although the detrimental impact of SLT on oral tissues is well-documented, understanding its multifaceted effects is essential for effective prevention and intervention strategies. OBJECTIVE: This study aimed to comprehensively assess the impact of SLT on oral health, focusing on various clinical parameters and their differences between placement and non-placement sites of SLT. METHODS: A cross-sectional study involving 528 habitual users of SLT was conducted. Clinical parameters included the plaque index (PI), gingival index (GI), gingival bleeding index (GBI), gingival recession (GR), and probing depth (PD). Oral mucosal changes at SLT placement sites have also been reported. Statistical analysis was performed to compare parameters between the placement and non-placement sites. RESULTS:  The study involved 528 subjects, mostly male (82%) and aged 21-40 years (mean±SD=31.14±9.10), habitual users of SLT. Prevalent SLT types included tobacco with betel nuts/masala/gutkha (59.9%) and tobacco with lime (54.5%). Significant differences were observed between SLT placement and non-placement sites: higher gingival inflammation (GI) at placement sites (1.54±0.61 vs. 1.45±0.54, p=0.01), lower GBI at placement sites (40.0% vs. 84.3%, p=0.001), and more prevalent GR (65.7% vs. 34.3%, p=0.03) at placement sites. Probing depths ≥ 3 mm were also less frequent at placement sites (2.67±0.72) than non-placement sites (3.37±1.03, p=0.001). These results highlight the detrimental impact of SLT on periodontal health, emphasizing the need for targeted interventions among SLT users. CONCLUSION: SLT use is associated with adverse effects on oral health, including GI, plaque accumulation, gingival bleeding, GR, and changes in the oral mucosa. Targeted interventions and public health policies are needed to address these issues effectively.

Comparison of the analgesic efficacy of two different fascial blocks in patients undergoing laparoscopic inguinal hernia surgery: A randomized control trial.

Background and Aims: Moderate-to-severe intensity pain is reported on the first day following lower abdominal surgery. No study has compared transversus abdominis plane (TAP) block with retrolaminar block (RLB) in laparoscopic inguinal hernia surgery for postoperative pain relief. Material and Methods: In this prospective, randomized trial, 42 male patients of American Society of Anesthesiologists (ASA) physical status I and II, aged 18-65 years, and having a BMI <40 kg/m2 received TAP or RLB following laparoscopic inguinal hernia surgery. A standard general anesthetic technique was performed. Patients were randomized into two groups: single-shot TAP block (group I) (n = 21) or the RLB (group II) (n = 21) with bilateral 20 ml of 0.375% ropivacaine. Postoperatively, IV paracetamol 1 g was administered as rescue analgesia. Postoperative cumulative Visual Analogue Scale (VAS) score 24 hours after surgery was considered as the primary outcome. Results: Postoperative cumulative VAS score at rest at 24 h, represented as mean ± S.D (95% CI), in the TAP block group was 3.54 ± 3.04 (2.16-4.93) and in the RLB group was 6.09 ± 4.83 (3.89-8.29). P value was 0.112 and VAS on movement was 7.95 ± 3.41 (6.39-9.50 [2.5-15.0]) in TAP block group, whereas P value was 0.110 and VAS on movement was 10.83 ± 5.51 (8.32-13.34) in the RLB group. Conclusion: Similar postoperative cumulative pain score on movement at 24 h was present in patients receiving TAP block or RLB. However, VAS score at rest and on movement was reduced in patients receiving TAP block at 18 and 24 h postoperatively.

Influence of microbiome in intraprostatic inflammation and prostate cancer.

BACKGROUND: Chronic infection and inflammation have been linked to the development of prostate cancer. Dysbiosis of the oral and gut microbiomes and subsequent microbial translocation can lead to pathogenic prostate infections. Microbial-produced metabolites have also been associated with signaling pathways that promote prostate cancer development. A comprehensive discussion on the mechanisms of microbiome infection and the prostate microenvironment is essential to understand prostate carcinogenesis. METHODS: Published studies were used from the National Center for Biotechnology Information (NCBI) database to conduct a narrative review. No restrictions were applied in the selection of articles. RESULTS: Microbiome-derived short-chain fatty acids (SCFAs) have been found to upregulate multiple signaling pathways, including MAPK and PI3K, through IGF-1 signaling and M2 macrophage polarization. SCFAs can also upregulate Toll-like receptors, leading to chronic inflammation and the creation of a pro-prostate cancer environment. Dysbiosis of oral microbiota has been correlated with prostate infection and inflammation. Additionally, pathogenic microbiomes associated with urinary tract infections have shown a link to prostate cancer, with vesicoureteral reflux potentially contributing to prostate infection. CONCLUSIONS: This review offers a comprehensive understanding of the impact of microbial infections linked to intraprostatic inflammation as a causative factor for prostate cancer. Further studies involving the manipulation of the microbiome and its produced metabolites may provide a more complete understanding of the microenvironmental mechanisms that promote prostate carcinogenesis.

Prevalence of opportunistic pathogens and anti-microbial resistance in urban aquaculture ponds.

Bacterial antimicrobial resistance (AMR) has emerged as a significant concern worldwide. The microbial community profile and potential AMR level in aquaculture ponds are often undervalued and attract less attention than other aquatic environments. We used amplicon and metagenomic shotgun sequencing to study microbial communities and AMR in six freshwater polyculture ponds in rural and urban areas of Bangladesh. Amplicon sequencing revealed different community structures between rural and urban ponds, with urban ponds having a higher bacterial diversity and opportunistic pathogens including Streptococcus, Staphylococcus, and Corynebacterium. Despite proteobacterial dominance, Firmicutes was the most interactive in the community network, especially in the urban ponds. Metagenomes showed that drug resistance was the most common type of AMR found, while metal resistance was only observed in urban ponds. AMR and metal resistance genes were found mainly in beta and gamma-proteobacteria in urban ponds, while AMR was found primarily in alpha-proteobacteria in rural ponds. We identified potential pathogens with a high profile of AMR and metal resistance in urban aquaculture ponds. As these ponds provide a significant source of protein for humans, our results raise significant concerns for the environmental sustainability of this food source and the dissemination of AMR into the food chain.

Envirotype-based delineation of environmental effects and genotype × environment interactions in Indian soybean (Glycine max, L.).

Soybean is a rainfed crop grown across a wide range of environments in India. Its grain yield is a complex trait governed by many minor genes and influenced by environmental effects and genotype × environment interactions. In the current investigation, grain yield data of different sets of 41, 30 and 48 soybean genotypes evaluated during 2019, 2020 and 2021, respectively across 19 locations and twenty years' data on 19 different climatic parameters at these locations was used to study the environmental effects on grain yield, to understand the genotype × environment interactions and to identify the mega-environments. Through analysis of variance (ANOVA), it was found that predominant portion of the variation was explained by environmental effects (E) (53.89, 54.86 and 60.56% during 2019, 2020 and 2021, respectively), followed by genotype × environment interactions (GEI) (31.29, 33.72 and 28.82% during 2019, 2020 and 2021, respectively). Principal Component Analysis (PCA) revealed that grain yield was positively associated with RH (Relative humidity at 2 m height), FRUE (Effect of temperature on radiation use efficiency), WSM (Wind speed at 2 m height) and RTA (Global solar radiation based on latitude and Julian day) and negatively associated with VPD (Deficit of vapour pressure), Trange (Daily temperature range), ETP (Evapotranspiration), SW (Insolation incident on a horizontal surface), n (Actual duration of sunshine) and N (Daylight hours). Identification of mega-environments is critical in enhancing the selection gain, productivity and varietal recommendation. Through envirotyping and genotype main effect plus genotype by environment interaction (GGE) biplot methods, nineteen locations across India were grouped into four mega-environments (MEs). ME1 included five locations viz., Bengaluru, Pune, Dharwad, Kasbe Digraj and Umiam. Eight locations-Anand, Amreli, Lokbharti, Bidar, Parbhani, Ranchi, Bhawanipatna and Raipur were included in ME2. Kota and Morena constitutes ME3, while Palampur, Imphal, Mojhera and Almora were included in ME4. Locations Imphal, Bidar and Raipur were found to be both discriminative and representative; these test locations can be utilized in developing wider adaptable soybean cultivars. Pune and Amreli were found to be high-yielding locations and can be used in large scale breeder seed production.

Role of ONECUT family transcription factors in cancer and other diseases.

Members of ONECUT transcription factor play an essential role in several developmental processes, however, the atypical expression of ONECUT proteins lead to numerous diseases, including cancer. ONECUT family proteins promote cell proliferation, progression, invasion, metastasis, angiogenesis, and stemness. This family of proteins interacts with other proteins such as KLF4, TGF-ß, VEGFA, PRC2, SMAD3 and alters their expression involved in the regulation of various signaling pathways including Jak/Stat3, Akt/Erk, TGF-ß, Smad2/3, and HIF-1α. Furthermore, ONECUT proteins are proposed as predictive biomarkers for pancreatic and gastric cancers. The present review summarizes the involvement of ONECUT family proteins in the development and progression of various human cancers and other diseases.

Clinical Evaluation of Coronally Advanced Flap with or without a Platelet-Rich Fibrin Membrane for the Root Coverage.

Aim: To evaluate "coronally advanced flap" with or without "a platelet-rich fibrin membrane for the root coverage." Materials and Methods: All the clinical parameters were assessed at different time intervals (at baseline, 1, 3, and 6 months) in both experimental and control group. Following "clinical parameters" were recorded using "UNC-15" "Probe-Plaque Index (PI)" (Silness and Loe, 1964), "Gingival Index" (GI) (Loe and Silness, 1963), "Recession depth (RD)," "Recession width (RW)," "Clinical attachment level (CAL)," and "Width of keratinized gingiva (WKG)". Results: At final evaluation (i.e., mean change from baseline to 6 months), "the decrease in Plaque Index was 2.5% higher in Group B (66.0%) as compared to Group A (63.5%). The decrease in Gingival Index was 6.1% higher in Group B (91.4%) as compared to Group A (85.3%), and the decrease in recession width was 4.0% higher in Group B (75.2%) as compared to Group A (71.2%). The decrease in clinical attachment level was 4.4% higher in Group B (53.2%) as compared to Group A (48.4%). The increase in width of keratinized gingiva was 1.9% higher in Group A (28.8%) as compared to Group B (26.9%)." Conclusion: The controlled, randomized, split mouth design showed that CAF surgery, either by alone or in combination with PRF, is an efficient treatment method for covering denuded roots. "This design was used to treat bilateral isolated Miller's class I and II recessions in gingival part. When compared to the CAF approach, the results from a combination of CAF and PRF after a 6-month period showed additional advantages in addition to mean root coverage in the treatment of Miller's classes I and II recessions in gingival part."

Towards an optimal design of a functionally graded porous uncemented acetabular component using genetic algorithm.

Generation of polyethylene wear debris and peri­prosthetic bone resorption have been identified as potential causes of acetabular component loosening in Total Hip Arthroplasty. This study was aimed at optimization of a functionally graded porous acetabular component to minimize peri­prosthetic bone resorption and polyethylene liner wear. Porosity levels (porosity values at acetabular rim, and dome) and functional gradation exponents (radial and polar) were considered as the design parameters. The relationship between porosity and elastic properties were obtained from numerical homogenization. The multi-objective optimization was carried out using a non-dominated sorting genetic algorithm integrated with finite element analysis of the hemipelvises subject to various loading conditions of common daily activities. The optimal functionally graded porous designs (OFGPs -1, -2, -3, -4, -5) exhibited less strain-shielding in cancellous bone compared to solid metal-backing. Maximum bone-implant interfacial micromotions (63-68 µm) for OFGPs were found to be close to that of solid metal-backing (66 µm), which might facilitate bone ingrowth. However, OFGPs exhibited an increase in volumetric wear (3-10 %) compared to solid metal-backing. The objective functions were found to be more sensitive to changes in polar gradation exponent than radial gradation exponent, based on the Sobol' method. Considering the common failure mechanisms, OFGP-1, having highly porous acetabular rim and less porous dome, appears to be a better alternative to the solid metal-backing.

Safety and efficacy of percutaneous image-guided ablation for soft tissue sarcoma metastases to the liver.

PURPOSE: To evaluate outcomes following percutaneous image-guided ablation of soft tissue sarcoma metastases to the liver. MATERIALS AND METHODS: A single-institution retrospective analysis of patients with a diagnosis of metastatic soft tissue sarcoma who underwent percutaneous image-guided ablation of hepatic metastases between January 2011 and December 2021 was performed. Patients with less than 60 days of follow-up after ablation were excluded. The primary outcome was local tumor progression-free survival (LPFS). Secondary outcomes included overall survival, liver-specific progression-free survival. and chemotherapy-free survival. RESULTS: Fifty-five patients who underwent percutaneous ablation for 84 metastatic liver lesions were included. The most common histopathological subtypes were leiomyosarcoma (23/55), followed by gastrointestinal stromal tumor (22/55). The median treated liver lesions was 2 (range, 1-8), whereas the median size of metastases were 1.8 cm (0.3-8.7 cm). Complete response at 2 months was achieved in 90.5% of the treated lesions. LPFS was 83% at 1 year and 80% at 2 years. Liver-specific progression-free survival was 66% at 1 year and 40% at 2 years. The overall survival at 1 and 2 years was 98% and 94%. The chemotherapy-free holiday from the start of ablation was 71.2% at 12 months. The complication rate was 3.6% (2/55); one of the complications was Common Terminology Criteria for Adverse Events grade 3 or higher. LPFS subgroup analysis for leiomyosarcoma versus gastrointestinal stromal tumor suggests histology-agnostic outcomes (2 years, 89% vs 82%, p = .35). CONCLUSION: Percutaneous image-guided liver ablation of soft tissue sarcoma metastases is safe and efficacious.

Histologic grading of salivary gland mucoepidermoid carcinoma: A comparison of four grading systems and correlation with survival.

BACKGROUND: Mucoepidermoid carcinoma (MEC) is the most common malignant lesion of salivary glands. A number of histologic grading systems are in use for MEC with variable agreement between them. METHODS: This study was aimed at comparison of four grading systems for MEC: two qualitative (modified Healy and MSKCC grading) and two quantitative (AFIP and Brandwein grading). A retrospective search for diagnosed cases of MEC over eight years yielded 11 cases with adequate clinical details and histologic slides available for review. All cases were reviewed and graded as per the four grading systems. An inter-system agreement was assessed, and Kaplan-Meier analysis was performed to correlate the grading with clinical outcomes. RESULTS: A general agreement between all four grading systems was seen in 72.7% of cases. Brandwein grading assigned the highest percentage of high grades (18.2%), whereas Memorial Sloan-Kettering Cancer Center (MSKCC) assigned the highest percentage of low-grade MEC (72.7%). The agreement between MSKCC and modified Healy was highest at 90% of cases. There was generally a poor agreement between MSKCC and Brandwein grading systems. The MSKCC grading system showed a significant correlation with disease-free survival in MEC patients. CONCLUSION: Hence, the MSKCC grading system might serve as a better histologic grading system with a predictive value for the biologic behavior of the tumor. Further larger studies are required to validate these findings and implement the uniform use of MSKCC grading for MEC of salivary glands.

Assessment of Pre-operative Factors Associated With Blood Loss in Patients Undergoing Percutaneous Nephrolithotomy: A Prospective Study.

Background One of the main risks associated with percutaneous nephrolithotomy (PCNL) is bleeding. In the present study, efforts are made to evaluate the pre-operative predictive factors contributing to bleeding due to the procedure of PCNL. Materials and methods From December 2019 to November 2021, data were collected prospectively from 193 patients undergoing PCNL procedures at Indira Gandhi Institute of Medical Sciences, Patna, India. Following PCNL, to check for hematuria and the extent of blood loss, the urethral catheter's and nephrostomy tube's outputs were evaluated. Multivariate regression analysis was used to evaluate the relationship between blood loss and a variety of patient-related demographic and clinical characteristics. Results Included in the study were 193 patients who underwent PCNL. Male patients made up the majority. The average age of study participants was 33.5 years. No statistically significant difference was reported in the mean hemoglobin level drop in the age groups of up to 25 years (2.211 ± 1.540 g/dL), 26-50 years (2.023 ± 1.882 g/dL), and > 50 years (1.855 ± 0.986 g/dL) with P = 0.64. The mean hemoglobin level drop in patients with stone burden > 30 mm2 was reported to be higher, 2.359 ± 1.822 g/dL, compared to 1.859 ± 1.540 g/dL in patients with lower stone burden, reaching a statistically significant difference (P =0.0408). By univariate regression analysis, the presence of a horseshoe-shaped kidney (odds ratio = -0.158, 95% confidence interval (CI): -0.911, -0.059; P = 0.026) was associated with a higher risk for a drop in mean hemoglobin level. By multivariate regression analysis, the presence of a horseshoe-shaped kidney (odds ratio = 0.071, 95% CI: 0.006, 0.839; P = 0.036) remained significantly and independently associated with a higher risk of a drop in mean hemoglobin level. Conclusion In conclusion, the patients' burden of stones and the presence of a horseshoe-shaped kidney may be associated with a higher risk of bleeding following PCNL.

Contribution of Anatomy in Forensic Age Evaluation: A Systematic Review.

The field of forensic anthropology is characterised by its ongoing development and growth. Forensic anatomy is a burgeoning discipline that focuses on the analysis and identification of both preserved and unpreserved human body parts, both in deceased individuals and the living. This subject plays a crucial role in establishing the four key factors of forensic anthropology, namely sex, age, race, and height. The objective of this research endeavour was to evaluate the significance of anatomical information in the process of forensic age estimation. The researchers established the inclusion criteria in accordance with the globally recognised Population, Intervention, Comparison, Outcome (PICOS) framework, as advised by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The research included many methodologies in order to ascertain the age. Upon conducting a comprehensive review of the existing literature pertaining to anatomical knowledge in the field of forensic age estimate, we have identified many notable applications. These include the utilisation of various anatomical features such as the dental pulp chamber, fingerprints, acetabulum, sternal end of the fourth rib, as well as hand and wrist bones for the purpose of age estimation. It is important for anatomists and other forensic scientists to engage in collaborative efforts to facilitate the exchange of ideas and ensure thorough investigations. This cooperation is particularly crucial in areas where anatomical sciences play a significant role in forensic science and investigation. Nevertheless, in order to mitigate the potential for estimating error, it is still advisable to use a multi-factorial evaluation approach that involves examining many body areas.

Integrative epigenome-transcriptome analysis unravels cancer-specific over-expressed genes potentially regulating immune microenvironment in clear cell renal cell carcinoma.

BACKGROUND: Clear cell Renal Cell Carcinoma (ccRCC) is the frequently diagnosed histological life-threatening tumor subtype in the urinary system. Integrating multi-omics data is emerging as a tool to provide a comprehensive view of biology and disease for better therapeutic interventions. METHOD: We have integrated freely available ccRCC data sets of genome-wide DNA methylome, transcriptome, and active histone modification marks, H3K27ac, H3K4me1, and H3K4me3 specific ChIP-seq data to screen genes with higher expression. Further, these genes were filtered based on their effect on survival upon alteration in expression. RESULTS: The six multi-omics-based identified genes, RUNX1, MSC, ADA, TREML1, TGFA, and VWF, showed higher expression with enrichment of active histone marks and hypomethylated CpG in ccRCC. In continuation, the identified genes were validated by an independent dataset and showed a correlation with nodal and metastatic status. Furthermore, gene ontology and pathway analysis revealed that immune-related pathways are activated in ccRCC patients. CONCLUSIONS: The network analysis of six overexpressed genes suggests their potential role in an immunosuppressive environment, leading to tumor progression and poor prognosis. Our study shows that the multi-omics approach helps unravel complex biology for patient subtyping and proposes combination strategies with epi-drugs for more precise immunotherapy in ccRCC.

Chimeric Antigen Receptor-Modified T Cell Therapy in Metastatic Castrate-Resistant Prostate Cancer: Promise and Potential.

Prostate cancer, the most common cancer among males, has a mortality rate of approximately 29,000 deaths each year in the United States alone [...].

Mechanical Venous Thrombectomy for Deep Venous Thrombosis in Cancer Patients: A Single-Center Retrospective Study.

PURPOSE: Venous thromboembolism (VTE) is a major contributor to the mortality of cancer patients. Mechanical thrombectomy (MT) is an endovascular technique that physically removes a thrombus without thrombolytics. The purpose of this study was to evaluate safety, efficacy, and clinical outcomes following MT for lower extremity DVT in cancer patients. METHODS: This single-center, retrospective study evaluated outcomes following MT of lower extremity DVT in cancer patients from November 2019 to May 2023. The primary outcome measure was clinical success, defined as a decrease in Villalta score by at least 2 points following the intervention. Secondary outcomes included repeat intervention-free survival and overall survival. Technical success was defined as restoring venous flow with mild (< 10%) or no residual filling defect. RESULTS: In total, 90 patients and 113 procedures were included. Technical and clinical success was achieved in 81% and 87% of procedures performed. Repeat intervention-free survival at 1 month, 3 months, and 6 months post-procedure was 92%, 82%, and 77%, respectively. The complication rate was 2.7%. Pathologic analysis of the extracted thrombus revealed tumor thrombus in 18.4% (18/98) samples. Overall survival for the study cohort was 87% at 1 month, 74% at 3 months, and 62% at 6 months. Patients who were found to have tumor thrombi were noted to have a decreased overall survival compared to patients with non-tumor thrombi (P = 0.012). CONCLUSION: MT is safe and efficacious in reducing cancer patients' VTE-related symptoms. The high rate of tumor thrombus in thrombectomy specimens suggests this phenomenon is more common than suspected.

Ligand-gated ion channels as potential biomarkers for ADT-mediated cognitive decline in prostate cancer patients.

Men with prostate cancer are at increased risk of developing cognitive decline by the use of second-generation androgen signaling inhibitors. To date, reliable and sensitive biomarkers that could distinguish men at high risk of cognitive dysfunction under androgen deprivation therapy (ADT) have not been characterized. We used high-throughput transcriptional profiling utilizing human prostate cancer cell culture models mimicking ADT, biomarker selection using minimal common oncology data elements-cytoscape, and bioinformatic analyses employing Advaita® iPathwayGuide and DisGeNET for identification of disease-related gene associations. Validation analysis of genes was performed on brain neuronal and glial cells by quantitative real-time polymerase chain reaction assay. Our systematic analysis of androgen deprivation-associated genes involved multiple biological processes, including neuroactive ligand-receptor interaction, axon guidance, cytokine-cytokine receptor interaction, and metabolic and cancer signaling pathways. Genes associated with neuroreceptor ligand interaction, including gamma-aminobutyric acid (GABA) A and B receptors and nuclear core proteins, were identified as top upstream regulators. Functional enrichment and protein-protein interaction network analysis highlighted the role of ligand-gated ion channels (LGICs) and their receptors in cognitive dysfunction. Gene-disease association assigned forgetfulness, intellectual disability, visuospatial deficit, bipolar disorder, and other neurocognitive impairment with upregulation of type-1 angiotensin II receptor, brain-derived neurotrophic factor, GABA type B receptor subunit 2 (GABBR2), GABRA3, GABRA5, GABRB1, glycine receptor beta, glutamate ionotropic receptor N-methyl-D-aspartate receptor (NMDA) type subunit 1, glutamate ionotropic receptor NMDA type subunit 2D, 5-hydroxytryptamine receptor 1D, interferon beta 1, and nuclear receptor subfamily 3 group C member 1 as top differentially expressed genes. Validation studies of brain glial cells, neurons, and patients on ADT demonstrated the association of these genes with cognitive decline. Our findings highlight LGICs as potential biomarkers for ADT-mediated cognitive decline. Further validation of these biomarkers may lead to future practical clinical use.

Assessment of the comparative agreement between chest radiographs and CT scans in intensive care units.

PURPOSE: Chest radiographs in critically ill patients can be difficult to interpret due to technical and clinical factors. We sought to determine the agreement of chest radiographs and CT scans, and the inter-observer variation of chest radiograph interpretation, in intensive care units (ICUs). METHODS: Chest radiographs and corresponding thoracic computerised tomography (CT) scans (as reference standard) were collected from 45 ICU patients. All radiographs were analysed by 20 doctors (radiology consultants, radiology trainees, ICU consultants, ICU trainees) from 4 different centres, blinded to CT results. Specificity/sensitivity were determined for pleural effusion, lobar collapse and consolidation/atelectasis. Separately, Fleiss' kappa for multiple raters was used to determine inter-observer variation for chest radiographs. RESULTS: The median sensitivity and specificity of chest radiographs for detecting abnormalities seen on CTs scans were 43.2% and 85.9% respectively. Diagnostic sensitivity for pleural effusion was significantly higher among radiology consultants but no specialty/experience distinctions were observed for specificity. Median inter-observer kappa coefficient among assessors was 0.295 ("fair"). CONCLUSIONS: Chest radiographs commonly miss important radiological features in critically ill patients. Inter-observer agreement in chest radiograph interpretation is only "fair". Consultant radiologists are least likely to miss thoracic radiological abnormalities. The consequences of misdiagnosis by chest radiographs remain to be determined.

Roles of Androgen Receptor Signaling in Urothelial Carcinoma.

Preclinical and clinical data suggest that androgen receptor signaling strongly contributes to bladder cancer development. The roles of the androgen receptor in bladder carcinogenesis have obvious implications for understanding the strong male sex bias in this disease and for potential therapeutic strategies as well. In this review, we summarize what is known about androgen receptor signaling in urothelial carcinoma as well as in tumor-infiltrating immune cells, reviewing preclinical and clinical data. We also highlight clinical trial efforts in this area.

EZH2-mediated development of therapeutic resistance in cancer.

Enhancer of zeste homolog 2 (EZH2) regulates gene expression and plays a definite role in cell proliferation, apoptosis, and senescence. Overexpression of EZH2 has been found in various human malignancies, including prostate, breast, and ovarian cancers, and is associated with increased metastasis and poor prognosis. EZH2 catalyzes trimethylation of lysine 27 of histone H3 (H3K27me3) as a canonical role in a PRC2-dependent manner. This mechanism silences various tumor suppressor genes through EZH2-mediated histone lysine methyltransferase activity. As a non-canonical role, EZH2 partners with other signaling molecules to undergo post-translational modification to orchestrate its function as a co-activator playing a critical role in cancer progression. Dysregulation of EZH2 has also been associated with therapeutic resistance in cancer cells. Given the role of EZH2 in promoting carcinogenesis and therapy resistance, both canonical and non-canonical EZH2 inhibitors have been used to combat multiple cancer types. Moreover, combining EZH2 inhibitors with other therapeutic modalities have shown to enhance the therapeutic efficacy and overcome potential resistance mechanisms in these cancerous cells. Therefore, targeting EZH2 through canonical and non-canonical modes appears to be a promising therapeutic strategy to enhance efficacy and overcome resistance in multiple cancers.