Antioxidant Peptides and Protein Hydrolysates from Tilapia: Cellular and In Vivo Evidences for Human Health Benefits.

Antioxidant peptides derived from aquatic organisms have attracted tremendous research interest due to their potential applications in human health. Tilapia is one of the most widely farmed aquaculture species globally. The current understanding of tilapia-derived antioxidant peptides is gradually expanding. This review discusses the current knowledge of peptides and protein hydrolysates derived from tilapia muscle, skin, and scales, whose antioxidant capacity has been validated in various cellular and in vivo models. To date, at least 16 peptides and several hydrolysates have been identified from tilapia that protect human and non-human cell models against oxidative injury. Tilapia hydrolysates and peptide mixtures have also shown protective effects in animal models of oxidative stress-associated diseases and exercise-induced oxidative injury and fatigue. The key mechanisms of tilapia hydrolysates and peptide mixtures involve enhancing antioxidant enzyme activities and suppressing radical production. Notably, such hydrolysates also exerted additional in vivo functions, such as anti-inflammatory, anti-diabetic, wound healing, and antiaging properties. Taken together, tilapia-derived antioxidant peptides and hydrolysates represent a valuable source of functional ingredients for applications in functional food, dietary supplements, and therapeutic applications. Continued research into their health benefits is warranted in the future.

A survey exploring ophthalmologists' attitudes and beliefs in performing immediate sequential bilateral cataract surgery in Singapore.

BACKGROUND: To evaluate current practice patterns of Immediate Sequential Bilateral Cataract Surgery (ISBCS) by ophthalmologists in Singapore and assess their attitudes towards performing ISBCS in future cataract care. METHODS: An anonymised electronic survey, modified to local context from a similar study conducted in the United Kingdom, was distributed to members of the College of Ophthalmologists, Academy of Medicine, Singapore, from 20 June to 1 September 2023. An initial screening question on prior experience with ISBCS directed the rest of the survey. Questions explored ophthalmologists' current ISBCS practice patterns and the importance of factors affecting their willingness to perform ISBCS. Results were descriptively analysed. RESULTS: Results collated 2 months upon survey dissemination saw a total of 58 respondents from 235 eligible members (24.7% response rate). Of these, 16 (27.6%) were currently performing ISBCS, 37 (63.8%) had never performed, and 5 (8.6%) had stopped performing. In considering ISBCS, patient convenience (n = 11, 68.8%) and reduced hospital visits (n = 8, 50.0%) were the most important factors nominated. The most important barriers to performing ISBCS were medico-legal issues (n = 31, 83.8%) and risk of endophthalmitis (n = 27, 73.0%), followed by perceived lack of evidence for its effectiveness (n = 19, 51.4%). CONCLUSION: This is one of the first studies evaluating ophthalmologists' sentiments towards performing ISBCS in an Asian country. It highlights some of the most pertinent barriers and concerns that ophthalmologists face in performing and offering ISBCS. This study provides a better understanding of the potential role and prospects of ISBCS in future cataract care in Singapore.

Tiger Milk Mushroom: A Comprehensive Review of Nutritional Composition, Phytochemicals, Health Benefits, and Scientific Advancements with Emphasis on Chemometrics and Multi-Omics.

This article presents a comprehensive overview of tiger milk mushroom (TMM), covering its nutritional composition, phytochemicals, health benefits, and related scientific advancements. It describes various potential positive health benefits of TMM, including anticancer, anti-inflammatory, respiratory function enhancement, antioxidant, anti-aging, neuroprotective, photoprotective, antidiabetic, wound-healing, and anti-HIV, among others. This article also underlines the importance of further research into the phytochemicals present in TMM for additional discoveries. It underscores the importance of further research into phytochemicals content of TMM for additional discoveries and emphasizes the potential applications of TMM in nutrition, health, and well-being. Sophisticated techniques, such as chemometrics and multi-omics technologies revealed latest scientific advancements of TMM. This comprehensive overview provides a foundation for future research and development in harnessing TMM's potential for human health.

Chemical structures, extraction and analysis technologies, and bioactivities of edible fungal polysaccharides from Poria cocos: An updated review.

Poria cocos is a popular medicinal food. Polysaccharides are the key component of Poria cocos, forming 70-90 % of the dry sclerotia mass. Recent studies indicate that Poria cocos polysaccharides (PCP-Cs) have multiple beneficial functions and applications. A literature search was conducted using the Web of Science Core Collection and PubMed databases. For this review, we provided an updated research progress in chemical structures, various extraction and analysis technologies, bioactivities of PCP-Cs, and insights into the directions for future research. The main polysaccharides identified in Poria cocos are water-soluble polysaccharides and acidic polysaccharides. Hot water, alkali, supercritical fluid, ultrasonic, enzyme, and deep eutectic solvent-based methods are the most common methods for PCP-Cs extraction. Technologies such as near-infrared spectroscopy, high-performance liquid chromatography, and ultraviolet-visible spectrophotometry, are commonly used to evaluate the qualities of PCP-Cs. In addition, PCP-Cs have antioxidant, immunomodulatory, neuroregulatory, anticancer, hepatoprotective, and gut microbiota regulatory properties. Future research is needed to focus on scaling up extraction, enhancing quality control, elucidating mechanisms of bioactivities, and the utilisation of PCP-Cs in food industries. Overall, Poria cocos is a good source of edible fungi polysaccharides, which can be developed into functional foods with potential health benefits.

Computational pathology in cancer diagnosis, prognosis, and prediction - present day and prospects.

Computational pathology refers to applying deep learning techniques and algorithms to analyse and interpret histopathology images. Advances in artificial intelligence (AI) have led to an explosion in innovation in computational pathology, ranging from the prospect of automation of routine diagnostic tasks to the discovery of new prognostic and predictive biomarkers from tissue morphology. Despite the promising potential of computational pathology, its integration in clinical settings has been limited by a range of obstacles including operational, technical, regulatory, ethical, financial, and cultural challenges. Here, we focus on the pathologists' perspective of computational pathology: we map its current translational research landscape, evaluate its clinical utility, and address the more common challenges slowing clinical adoption and implementation. We conclude by describing contemporary approaches to drive forward these techniques. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Ginger-Enriched Honey Attenuates Antibiotic Resistant Pseudomonas aeruginosa Quorum Sensing Virulence Factors and Biofilm Formation.

Quorum sensing (QS) in Pseudomonas aeruginosa plays an essential role in virulence factors, biofilm formation as well as antibiotic resistance. Approaches that target virulence factors are known to be more sustainable than antibiotics in weakening the infectivity of bacteria. Although honey has been shown to exert antipseudomonal activities, the enhancement of such activity in ginger-enriched honey is still unknown. The main objective of this study was to determine the impacts of honey and ginger-enriched honey on the QS virulence factors and biofilm formation of antibiotic resistant P. aeruginosa clinical isolates. Outcomes showed honey and/or ginger-enriched honey significantly reduced the protease activity, pyocyanin production and exotoxin A concentration of the isolates. The swarming and swimming motility together with biofilm formation in all clinical isolates were also significantly inhibited by both honey samples. Notable morphological alteration of bacterial cells was also observed using scanning electron microscopy. A principal component analysis (PCA) managed to distinguish the untreated group and treatment groups into two distinct clusters, although honey and ginger-enriched honey groups were not well differentiated. This study revealed the effectiveness of honey including ginger-enriched honey to attenuate QS virulence factors and biofilm formation of P. aeruginosa.

A review on matcha: Chemical composition, health benefits, with insights on its quality control by applying chemometrics and multi-omics.

This review discussed the origin, manufacturing process, chemical composition, factors affecting quality and health benefits of matcha (Camellia sinensis), and the application of chemometrics and multi-omics in the science of matcha. The discussion primarily distinguishes between matcha and regular green tea with processing and compositional factors, and demonstrates beneficial health effects of consuming matcha. Preferred Reporting Items for Systematic Reviews and Meta-Analyses was adopted to search for relevant information in this review. Boolean operators were incorporated to explore related sources in various databases. Notably, climate, cultivar, maturity of tea leaves, grinding process and brewing temperature impact on the overall quality of matcha. Besides, sufficient shading prior to harvesting significantly increases the contents of theanine and chlorophyll in the tea leaves. Furthermore, the ground whole tea leaf powder delivers matcha with the greatest benefits to the consumers. The health promoting benefits of matcha are mainly contributed by its micro-nutrients and the antioxidative phytochemicals, specifically epigallocatechin-gallate, theanine and caffeine. Collectively, the chemical composition of matcha affected its quality and health benefits significantly. To this end, more studies are required to elucidate the biological mechanisms of these compounds for human health. Chemometrics and multi-omics technologies are useful to fill up the research gaps identified in this review.

Self-Assessment of INTERHEART Risk Stratification among the Middle-Aged Community in Malaysia.

Research background and Objectives: Age is an independent risk factor for cardiovascular disease (CVD), but CVD risk factors are preventable, and lack of awareness of its risk factors is a contributing factor to CVDs. Middle-aged people may be more likely to engage in unhealthy lifestyle behaviours which can increase the risk of CVD. Health self-assessment is crucial for early detection and management of health issues and early lifestyle intervention for better personalised health management. This study aims to determine the self-assessment of INTERHEART risk classification among the middle-aged community in Malaysia. Method: Local community members aged 40-60 years and who are currently residing in Malaysia were recruited via non-randomised sampling. Sociodemographic characteristics and dietary pattern related to salt, fibre, fat (deep fried/snacks), poultry/meat intakes, and other cardiovascular risk factors (waist-hip ratio, medical history related to diabetes/hypertension, history/exposure of tobacco use, psychosocial status, and level of physical activity) were assessed; INTERHEART risk scores were then computed and stratified into low, medium and high risks. Results: Approximately 45% (n = 273/602) of middle-aged respondents in Malaysia are at moderate-to-high risk of cardiovascular events, with men being more likely to develop CVD compared to women. The results of the survey indicated that poultry/meat intake (61%), physical inactivity (59%), and second-hand smoke (SHS) exposure (54%) are the most prevalent risk factors among the respondents. One-third of the respondents consumed excessive salty food and deep fried foods/snacks/fast food, and only one-third of them consumed vegetables/fruits at a recommended level. It is worrying that about a quarter of the respondents felt several periodical/permanent stresses and even felt sad/blue/depressed for two weeks or more in a row. Males, labour workers, and those with lower educational levels are more likely to develop CVD events. Conclusions: This study found that 45% of the middle-aged respondents were having moderate-to-high risk for cardiovascular events with multiple risk factors related to unhealthy lifestyle habits and environmental factors. In addition to non-modifiable factors such as gender and age, sociodemographic factors, i.e., educational level and occupation, are equally important factors to determine CVD risk. Overall, the findings of this study emphasize the clinical relevance of assessing multiple factors in the determination of CVD risks for early prevention and management of cardiovascular diseases.

Prevalence and risk factors for alcohol use disorders, substance use disorders, and depression anxiety and stress among users of sexual health services in Singapore: a cross-sectional survey study.

Syndemics of poor mental health also drive poorer sexual health outcomes. This study used three scales, the Alcohol Use Disorders Identification Test (AUDIT), the Drug Abuse Screening Test (DAST-10), and the Depression Anxiety Stress Scale (DASS-21) among beneficiaries of sexual health services in Singapore (n =975), respectively. We found that a prevalence of 20.4% and 18.6% of hazardous and moderate-severe alcohol use disorders and substance use risks, respectively. About 13.7%, 18.1% and 10.5% of participants reported severe to extremely severe symptoms of depression, anxiety, and stress, respectively. Further investigation and integrated interventions for mental health in sexual health settings are warranted.

High-precision mapping reveals rare N6-deoxyadenosine methylation in the mammalian genome.

N6-deoxyadenosine methylation (6mA) is the most widespread type of DNA modification in prokaryotes and is also abundantly distributed in some unicellular eukaryotes. However, 6mA levels are remarkably low in mammals. The lack of a precise and comprehensive mapping method has hindered more advanced investigations of 6mA. Here, we report a new method MM-seq (modification-induced mismatch sequencing) for genome-wide 6mA mapping based on a novel detection principle. We found that modified DNA bases are prone to form a local open region that allows capture by antibody, for example, via a DNA breathing or base-flipping mechanism. Specified endonuclease or exonuclease can recognize the antibody-stabilized mismatch-like structure and mark the exact modified sites for sequencing readout. Using this method, we examined the genomic positions of 6mA in bacteria (E. coli), green algae (C. reinhardtii), and mammalian cells (HEK239T, Huh7, and HeLa cells). In contrast to bacteria and green algae, human cells possess a very limited number of 6mA sites which are sporadically distributed across the genome of different cell types. After knocking out the RNA m6A methyltransferase METTL3 in mouse ES cells, 6mA becomes mostly diminished. Our results imply that rare 6mA in the mammalian genome is introduced by RNA m6A machinery via a non-targeted mechanism.

Clinicopathological predictors of survival in resected primary lung adenocarcinoma.

AIMS: Primary lung adenocarcinoma consists of a spectrum of clinical and pathological subtypes that may impact on overall survival (OS). Our study aims to evaluate the impact of adenocarcinoma subtype and intra-alveolar spread on survival after anatomical lung resection and identify different prognostic factors based on stage and histological subtype. METHODS: Newly diagnosed patients undergoing anatomical lung resections without induction therapy, for pT1-3, N0-2 lung adenocarcinoma from April 2011 to March 2013, were included. The effect of clinical-pathological factors on survival was retrospectively assessed. RESULTS: Two hundred and sixty-two patients were enrolled. The 1-year, 3-year and 5-year OS were 88.8%, 64.3% and 51.1%, respectively. Univariate analysis showed lymphovascular, parietal pleural and chest wall invasion to confer a worse 1-year and 5-year prognosis (all p<0.0001). Solid predominant adenocarcinomas exhibited a significantly worse OS (p=0.014). Multivariate analysis did not identify solid subtype as an independent prognostic factor; however, identified stage >IIa, lymphovascular invasion (p=0.002) and intra-alveolar spread (p=0.009) as significant independent predictors of worse OS. Co-presence of intra-alveolar spread and solid predominance significantly reduced OS. Disease-free survival (DFS) was reduced with parietal pleural (p=0.0007) and chest wall invasion (p<0.0001), however, adenocarcinoma subtype had no significant impact on DFS. CONCLUSIONS: Our study demonstrates that solid predominant adenocarcinoma, intra-alveolar spread and lymphovascular invasion confer a worse prognosis and should be used as a prognostic tool to determine appropriate adjuvant treatment.

Botanical Origin Differentiation of Malaysian Stingless Bee Honey Produced by Heterotrigona itama and Geniotrigona thoracica Using Chemometrics.

Stingless bee honey, specifically honeydew honey, is generally valued for its better health benefits than those of most blossom types. However, scientific studies about the differentiation of stingless bee honey based on honeydew and blossom origins are very limited. In this study, 13C NMR spectroscopy was employed to quantify the seven major sugar tautomers in stingless bee honey samples, and the major sugar compositions of both honeydew and blossom types were found not significantly different. However, several physicochemical properties of honeydew honey including moisture content, free acidity, electrical conductivity, ash content, acetic acid, diastase, hydrogen peroxide, and mineral elements levels were significantly higher; while total soluble solid, proline, and hydroxymethylfurfural were significantly lower than blossom honey. Greater antioxidant capacity in honeydew honey was proven with higher total phenolic compounds, ABTS, DPPH, superoxide radical scavenging activities, peroxyl radical inhibition, iron chelation, and ferric reducing power. Using principal component analysis (PCA), two clusters of stingless bee honey from the honeydew and blossom origin were observed. PCA also revealed that the differentiation between honeydew and blossom origin of stingless bee honey is possible with certain physicochemical and antioxidant parameters. The combination of NMR spectroscopy and chemometrics are suggested to be useful to determine the authenticity and botanical origin of stingless bee honey.

Systematic calibration of epitranscriptomic maps using a synthetic modification-free RNA library.

Recent years have witnessed rapid progress in the field of epitranscriptomics. Functional interpretation of the epitranscriptome relies on sequencing technologies that determine the location and stoichiometry of various RNA modifications. However, contradictory results have been reported among studies, bringing the biological impacts of certain RNA modifications into doubt. Here, we develop a synthetic RNA library resembling the endogenous transcriptome but without any RNA modification. By incorporating this modification-free RNA library into established mapping techniques as a negative control, we reveal abundant false positives resulting from sequence bias or RNA structure. After calibration, precise and quantitative mapping expands the understanding of two representative modification types, N6-methyladenosine (m6A) and 5-methylcytosine (m5C). We propose that this approach provides a systematic solution for the calibration of various RNA-modification mappings and holds great promise in epitranscriptomic studies.

Asperuloside Enhances Taste Perception and Prevents Weight Gain in High-Fat Fed Mice.

Asperuloside is an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results in animal models. In previous studies, three months of asperuloside administration reduced food intake, body weight, and adipose masses in rats consuming a high fat diet (HFD). However, the mechanisms by which asperuloside exerts its anti-obesity properties were not clarified. Here, we investigated homeostatic and nutrient-sensing mechanisms regulating food intake in mice consuming HFD. We confirmed the anti-obesity properties of asperuloside and, importantly, we identified some mechanisms that could be responsible for its therapeutic effect. Asperuloside reduced body weight and food intake in mice consuming HFD by 10.5 and 12.8% respectively, with no effect on mice eating a standard chow diet. Fasting glucose and plasma insulin were also significantly reduced. Mechanistically, asperuloside significantly reduced hypothalamic mRNA ghrelin, leptin, and pro-opiomelanocortin in mice consuming HFD. The expression of fat lingual receptors (CD36, FFAR1-4), CB1R and sweet lingual receptors (TAS1R2-3) was increased almost 2-fold by the administration of asperuloside. Our findings suggest that asperuloside might exert its therapeutic effects by altering nutrient-sensing receptors in the oral cavity as well as hypothalamic receptors involved in food intake when mice are exposed to obesogenic diets. This signaling pathway is known to influence the subtle hypothalamic equilibrium between energy homeostasis and reward-induced overeating responses. The present pre-clinical study demonstrated that targeting the gustatory system through asperuloside administration could represent a promising and effective new anti-obesity strategy.

Shrinking Tonlé Sap and the recent intensification of sand mining in the Cambodian Mekong River.

This paper investigates the impacts of extensive riverbed mining in the Lower Mekong on the water level, extent and volume of the Tonlé Sap Lake, the largest freshwater lake in Southeast Asia. Our results indicate that the lake's volume has decreased from 1980 to 2018 (p-value = 0.016), with water levels at Phnom Penh Port and Phnom Penh Bassac showing decreasing trends since 1980 (p-values <0.0001). However, discharge at Phnom Penh Bassac (1960-2002) presented an insignificant trend (p-value = 0.147), indicating that riverbed incision due to extensive sand mining in Phnom Penh has affected the Mekong's water levels more than basin-scale climatic factors. Similarly, the modulation of a limited portion of water by upstream dams is unlikely to have caused dramatic inundation variation along the Lower Mekong River around Tonlé Sap. A hysteretic relationship between water levels at Prek Kdam and Tonlé Sap indicates that Tonlé Sap's water level is largely controlled by Tonlé Sap River and the Mekong, and declining water levels at Prek Kdam due to extensive sand mining in Phnom Penh is directly related to the shrinking of the lake. Although there are three main inflows into Tonlé Sap (from the Mekong, local tributaries and direct precipitation), the Mekong's contribution is the largest; tributary discharge and rainfall did not display any significant trend over the investigated period as well. Additionally, the analysis of high-resolution images revealed a recent intensification of riverbed mining, with Phnom Penh being a mining hotspot in the Lower Mekong. Considering its economic and ecological importance, the shrinking of Tonlé Sap would have grave repercussions for the region. Since sand demand is unlikely to weaken in the foreseeable future, these new insights can potentially help inform regulatory frameworks in ensuring sustainable sand extraction rates.

Variability in grading of ductal carcinoma in situ among an international group of pathologists.

The prognostic value of cytonuclear grade in ductal carcinoma in situ (DCIS) is debated, partly due to high interobserver variability and the use of multiple guidelines. The aim of this study was to evaluate interobserver agreement in grading DCIS between Dutch, British, and American pathologists. Haematoxylin and eosin-stained slides of 425 women with primary DCIS were independently reviewed by nine breast pathologists based in the Netherlands, the UK, and the USA. Chance-corrected kappa (κma ) for association between pathologists was calculated based on a generalised linear mixed model using the ordinal package in R. Overall κma for grade of DCIS (low, intermediate, or high) was estimated to be 0.50 (95% confidence interval [CI] 0.44-0.56), indicating a moderate association between pathologists. When the model was adjusted for national guidelines, the association for grade did not change (κma = 0.53; 95% CI 0.48-0.57); subgroup analysis for pathologists using the UK pathology guidelines only had significantly higher association (κma = 0.58; 95% CI 0.56-0.61). To assess if concordance of grading relates to the expression of the oestrogen receptor (ER) and HER2, archived immunohistochemistry was analysed on a subgroup (n = 106). This showed that non-high grade according to the majority opinion was associated with ER positivity and HER2 negativity (100 and 89% of non-high grade cases, respectively). In conclusion, DCIS grade showed only moderate association using whole slide images scored by nine breast pathologists. As therapeutic decisions and inclusion in ongoing clinical trials are guided by DCIS grade, there is a pressing need to reduce interobserver variability in grading. ER and HER2 might be supportive to prevent the accidental and unwanted inclusion of high-grade DCIS in such trials.

Identification of antioxidant peptides derived from tropical jackfruit seed and investigation of the stability profiles.

Jackfruit is a sweet tropical fruit with very pleasant aroma, and the ripe seeds are edible. In this study, jackfruit seed proteins were isolated and subjected to trypsin digestion. The resultant protein hydrolysate was then subjected to antioxidant assay-guided purification, using centrifugal filtration, C18 reverse-phase and strong cation exchange (SCX) fractionations. The purified SCX fraction was further analyzed by de novo peptide sequencing, and two peptide sequences were identified and synthesized. Peptide JFS-2 (VGPWQK) was detected with antioxidant potential, with EC50 value comparable to that of commercial GSH antioxidant peptide. Additionally, the identified peptides were tested with protein protection potential, in an albumin protein denaturation inhibitory assay. Concurrently, we also investigated the pH, temperature, and gastrointestinal-digestion stability profiles for the identified peptide. With further research efforts, the identified peptides could potentially be developed into preservative agent for protein-rich food systems or as health-promoting diet supplements.

The Antibacterial Potential of Honeydew Honey Produced by Stingless Bee (Heterotrigona itama) against Antibiotic Resistant Bacteria.

Scientific studies about the antibacterial effects of honeydew honey produced by the stingless bee are very limited. In this study, the antibacterial activities of 46 blossom and honeydew honeys produced by both honey bees and stingless bees were evaluated and compared. All bacterial isolates showed varying degrees of susceptibility to blossom and honeydew honeys produced by the honey bee (Apis cerana) and stingless bee (Heterotrigona itama and Geniotrigona thoracica) in agar-well diffusion. All stingless bee honeys managed to inhibit all the isolates but only four out of 23 honey bee honeys achieved that. In comparison with Staphylococcus aureus, Escherichia coli was found to be more susceptible to the antibacterial effects of honey. Bactericidal effects of stingless bee honeys on E. coli were determined with the measurement of endotoxins released due to cell lysis. Based on the outcomes, the greatest antibacterial effects were observed in honeydew honey produced by H. itama. Scanning electron microscopic images revealed the morphological alteration and destruction of E. coli due to the action of this honey. The combination of this honey with antibiotics showed synergistic inhibitory effects on E. coli clinical isolates. This study revealed that honeydew honey produced by H. itama stingless bee has promising antibacterial activity against pathogenic bacteria, including antibiotic resistant strains.

Genomic analysis in short- and long-term patients with malignant pleura mesothelioma treated with palliative chemotherapy.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumour with poor prognosis. The aim of this study was to identify genetic mutations associated with poor or extended survival in patients who received palliative chemotherapy. METHODS: A total of 720 patients diagnosed with MPM between 2005 and 2015 were identified. Overall survival (OS) was longer than 30 months from diagnosis for 27 patients. Twelve of 27 (44%) of the pleural biopsies from long-term survivors were retrieved and matched with 12 biopsies from patients who survived less than 12 months; one biopsy was then excluded for poor DNA quality. RESULTS: A total of 11 patients had a mean OS of 5.5 months, whereas 12 patients lived more than 30 months (mean OS: 55.8 ± 25). Mutational analysis identified 428 alterations; of which, 148, classified as somatic and functional, were considered further. Among these, 85% were missense variants, 8% were variants causing a stop gain and 6% were splice variants. Loss-of-function mutations in UQCRC1 were significantly associated with reduced survival in patients with MPM (p = 0.027), while a higher frequency of mutations in MXRA5 and RAPGEF6 was registered in long-term survivors. CONCLUSION: This is the first study evaluating the relationship between the mutational profile and outcome in patients with MPM after palliative chemotherapy. UQCRC1 codes for cytochrome b-c1 complex subunit 1 which plays a fundamental role in normal mitochondrial functions and in cell metabolism. Recent studies described UQCRC1 deregulation in other cancers. Our results suggest a possible role for mitochondrial metabolism in the biology of mesothelioma.

Differential Survival Characteristics of Sarcomatoid Subtype in Biphasic Pleural Mesothelioma.

BACKGROUND: Biphasic pleural mesothelioma (BPM) accounts for approximately 10% of all pleural mesothelioma. Our aim was to assess the clinical, radiologic, and pathologic factors impacting survival in BPM and to better identify patients most likely to benefit from active treatment. METHODS: A 10-year retrospective review was made of 214 biopsy-proven BPM cases with minimum 2-year follow-up. Patients with insufficient tissue for analysis were excluded (n = 96). Clinical and pathologic factors were evaluated along with radiologic assessment of pleural thickness. Survival was measured from time of diagnosis. Univariable and multivariable predictors of survival were evaluated. RESULTS: In all, 118 patients were included; 28 underwent pleurectomy/decortication, with 27 receiving additional modalities. Ninety patients underwent chemotherapy (n = 18) or radiotherapy alone (n = 9), 63 received combination therapy, and 27 received best supportive care. Median overall survival was 11.2 months (range, 0.3 to 36.2). At univariable analysis, pleurectomy/decortication (p = 0.0061), radiotherapy (p < 0.0001), and chemotherapy (p < 0.0001) were associated with superior survival when compared with best supportive care alone. Pleurectomy/decortication demonstrated 40% survival improvement compared with no surgery (p = 0.122). In a multivariable model, necrosis was negatively prognostic (hazard ratio 2.1, SE 0.76). Furthermore, increased sarcomatoid component was associated with worse survival without radiotherapy. CONCLUSIONS: BPM prognosis remains poor despite multimodality treatment. Anticancer treatment is associated with superior outcome in this nonrandomized retrospective series. Our findings suggest superior survival for patients with a lower proportion of sarcomatoid disease, with selective benefit of radiotherapy in higher proportions of sarcomatoid disease. When planning active treatment, the potential survival benefits require balancing against associated morbidity and recovery period.