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Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event of treatment with immune checkpoint inhibitors (ICI). We hypothesize that genetic susceptibility to Crohns disease (CD) and ulcerative colitis (UC) predisposes to IMC. In this study, we first develop a polygenic risk scores for CD (PRSCD) and UC (PRSUC) in cancer-free individuals and then test these PRSs on IMC in a cohort of 1316 patients with ICI-treated non-small cell lung cancer and perform a replication in 873 ICI-treated pan-cancer patients. In a meta-analysis, the PRSUC predicts all-grade IMC (ORmeta=1.35 per standard deviation [SD], 95% CI = 1.12-1.64, P = 2×10-03) and severe IMC (ORmeta=1.49 per SD, 95% CI = 1.18-1.88, P = 9×10-04). PRSCD is not associated with IMC. Furthermore, PRSUC predicts severe IMC among patients treated with combination ICIs (ORmeta=2.20 per SD, 95% CI = 1.07-4.53, P = 0.03). Overall, PRSUC can identify patients receiving ICI at risk of developing IMC and may be useful to monitor patients and improve patient outcomes.

Abstract Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event of treatment with immune checkpoint inhibitors (ICI). We hypothesize that genetic susceptibility to Crohn’s disease (CD) and ulcerative colitis (UC) predisposes to IMC. In this study, we first develop a polygenic risk scores for CD (PRSCD) and UC (PRSUC) in cancer-free individuals and then test these PRSs on IMC in a cohort of 1316 patients with ICI-treated non-small cell lung cancer and perform a replication in 873 ICI-treated pan-cancer patients. In a meta-analysis, the PRSUC predicts all-grade IMC (ORmeta=1.35 per standard deviation [SD], 95% CI = 1.12–1.64, P = 2×10−03) and severe IMC (ORmeta=1.49 per SD, 95% CI = 1.18–1.88, P = 9×10−04). PRSCD is not associated with IMC. Furthermore, PRSUC predicts severe IMC among patients treated with combination ICIs (ORmeta=2.20 per SD, 95% CI = 1.07–4.53, P = 0.03). Overall, PRSUC can identify patients receiving ICI at risk of developing IMC and may be useful to monitor patients and improve patient outcomes.

Abstract In this paper we illustrate how normalised practices and strategies of waste management pay insufficient attention to social life and distributional impacts by excluding apartments and placing them at the margins of domestic waste management. In considering shifts towards more circular post-consumption systems, this paper describes the problematic policy and regulatory imaginary of apartment waste management within the Circular Economy narratives of sustainable domestic waste management. We present an argument for a relational approach to domestic waste as a counterpoint to technocentric and market-based approaches, with implications for governance and infrastructures of apartment waste management. We illustrate how spatio-temporal and socio-material bundles of practices could chart new directions for reduction and collection. We seek to demonstrate how relational place-based measures and shifts in practices in Victoria and elsewhere could counter exclusionary infrastructure by more purposefully including the marginal spaces that apartments inhabit.

BackgroundGenome-wide studies of gene-environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer.MethodsAnalyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs.ResultsAssuming a 1 × 10-5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability

Aggressive breast cancers portend a poor prognosis, but current polygenic risk scores (PRSs) for breast cancer do not reliably predict aggressive cancers. Aggressiveness can be effectively recapitulated using tumor gene expression profiling. Thus, we sought to develop a PRS for the risk of recurrence score weighted on proliferation (ROR-P), an established prognostic signature. Using 2363 breast cancers with tumor gene expression data and single nucleotide polymorphism (SNP) genotypes, we examined the associations between ROR-P and known breast cancer susceptibility SNPs using linear regression models. We constructed PRSs based on varying p-value thresholds and selected the optimal PRS based on model r2 in 5-fold cross-validation. We then used Cox proportional hazards regression to test the ROR-P PRS's association with breast cancer-specific survival in two independent cohorts totaling 10,196 breast cancers and 785 events. In meta-analysis of these cohorts, higher ROR-P PRS was associated with worse survival, HR per SD = 1.13 (95% CI 1.06-1.21, p = 4.0 × 10-4). The ROR-P PRS had a similar magnitude of effect on survival as a comparator PRS for estrogen receptor (ER)-negative versus positive cancer risk (PRSER-/ER+). Furthermore, its effect was minimally attenuated when adjusted for PRSER-/ER+, suggesting that the ROR-P PRS provides additional prognostic information beyond ER status. In summary, we used integrated analysis of germline SNP and tumor gene expression data to construct a PRS associated with aggressive tumor biology and worse survival. These findings could potentially enhance risk stratification for breast cancer screening and prevention.

BackgroundReproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.MethodsAnalyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided.ResultsCompared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like, and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.ConclusionsThis large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared with other subtypes, with implications for the understanding of disease etiology and risk prediction.

Anomalous coronary venous drainage is rare and likely to be under-reported, with many cases found incidentally in cardiac imaging and autopsy studies. It may also occasionally have an important clinical implication. We report a rare case of anomalous great cardiac vein bypassing the coronary sinus to drain directly into the left brachiocephalic vein in a patient with anomalous left coronary artery arising from the main pulmonary artery. This anomalous course resulted in a misdiagnosis of coronary aneurysm on echocardiography.

Vaccination is an essential method of immunological preventive care required for the health management of all animals, including fish. More particularly, immunization is necessary for in-land aquaculture to manage diseases in fish broodstocks and healthy seed production. According to the latest statistics in 2020, 90.3 million tons of capture fishery production was achieved from the aquaculture sector. Out of the above, 78.8 million tons were from marine water aquaculture sectors, and 11.5 million tons were from inland water aquaculture sectors. About a 4% decline in fish production was achieved in 2020 in comparison to 2018 from inland aquaculture sectors. On the other hand, the digestive protein content, healthy fats, and nutritional values of fish products are comparatively more affordable than in other meat sources. In 2014, about 10% of aquatic cultured animals were lost (costing global annual losses > USD 10 billion) due to infectious diseases. Therefore, vaccination in fish, especially in broodstocks, is one of the essential approaches to stop such losses in the aquaculture sector. Fish vaccines consist of whole-killed pathogens, protein subunits, recombinant proteins, DNA, or live-attenuated vaccines. Challenges persist in the adaption of vaccination in the aquaculture sector, the route of administration, the use of effective adjuvants, and, most importantly, the lack of effective results. The use of autogenous vaccines; vaccination via intramuscular, intraperitoneal, or oral routes; and, most importantly, adding vaccines in feed using top dressing methods or as a constituent in fish feed are now emerging. These methods will lower the risk of using antibiotics in cultured water by reducing environmental contamination.

This review article explores the multifaceted significance of fermented bamboo shoots, a culinary tradition deeply rooted in the practices of local tribes in Northeastern India. The therapeutic properties of fermented bamboo shoots span anti-aging, anticancer, antioxidant, cardioprotective, and weight loss benefits, positioning them as valuable functional foods enriched with probiotics. Northeast India, encompassing the states of Assam, Arunachal Pradesh, Nagaland, Meghalaya, Mizoram, Sikkim, Manipur, and Tripura, serves as a hub for the cultivation and consumption of fermented bamboo shoot-based products. The unique microbial ecosystem associated with bamboo shoots contributes to the synthesis of diverse health-promoting compounds, with rich concentrations of glycosides and flavones. Microorganisms, including Lactobacillus species, Bacillus species, Candida species, and Saccharomyces cerevisiae play a pivotal role in the fermentation process, contributing to the distinct characteristics of these products. The active involvement of tribal communities, constituting 75% of the regional population, underscores the cultural and traditional significance of this culinary practice. The review also delineates an array of fermented bamboo shoot-based products offerings, such as ekung, heccha, eup, mesu, lung-siej, soibum, soidon, soijim, and hirring, reflecting the rich culinary diversity arising from this traditional practice. Beyond their cultural importance, these products hold substantial industrial and economic value, and are integral to the livelihoods of local communities in Northeastern India. In summary, fermented bamboo shoots have emerged as a complex resource intertwining cultural heritage, health benefits, and economic dimensions within the unique context of Northeastern Indian communities.

The World Health Organization has reported that over one million individuals drink contaminated water, resulting in over 30,000 deaths daily. Every year, over 7×107 tons of synthetic dyes are produced globally, with the textile industry utilizing over 104 tons of such materials. To protect freshwater from pollutants, wastewater treatment methods such as permeable reactive barrier disinfection use activated carbon. Bamboo charcoal is an emerging substance with great potential in this area. Bamboos represent a renewable biological resource for long-term development. This paper reviews the dye removal processes that can be utilized to avoid water pollution, using bamboo charcoal as a natural adsorbent. A literature search using used various keywords from several bibliographic databases yielded seven studies that supported the adsorptive properties of bamboo charcoal. These investigations used FTIR, EDS, SEM and XRD to demonstrate the porous nature of bamboo charcoal, activated bamboo charcoal and/or modified bamboo charcoal, as well as showing the effects of pH and temperature on dye removal. The best-fitting kinetic model and isotherm data were identified. Bamboo charcoal was an effective adsorbent, while modified or activated bamboo charcoal rapidly increased absorptive capacity, indicating the future potential of bamboo charcoal in the cleaning up of water pollutants and contributing to a clean environment.

Background: Supreme laryngeal mask airway (SLMA) and i-gel airway devices are second generation supraglottic airway devices (SAD) and are good alternatives to intubation during elective surgeries. Aims and Objectives: This study was conducted with the objective of comparing the two SAD with respect to ease of insertion, number of attempts of insertion, insertion time, ease of gastric tube insertion, accompanying hemodynamic changes, incidence of adverse effects like regurgitation, lip and dental trauma, post-operative sore throat, dysphagia, and hoarseness. Materials and Methods: This study was conducted at M.G.M. Medical College and M.Y. hospital, Indore. Eighty patients belonging to ASA class 1 or 2, with Mallampati grading 1 or 2, between age group of 18–60 years and with BMI 0.05). Postoperatively, no significant complications were observed in terms of dental injury, laryngospasm. Ease of gastric tube insertion was found to be more in SLMA group than i-gel and the difference was statistically significant (P=0.0057). Incidence of sore throat after 1 h was found to be more in SLMA group than i-gel group (P=0.048). Conclusion: There was no significant difference between SLMA and i-gel in terms of insertion characteristics and hemodynamic changes. Ease of gastric tube insertion was found to be significantly more in SLMA group than i-gel. Incidence of post-operative sore throat at 1 h was more with SLMA as compared to i-gel.

Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values

Dual-functional aggregation-induced photosensitizers (AIE-PSs) with singlet oxygen generation (SOG) ability and bright fluorescence in aggregated state have received much attention in image-guided photodynamic therapy (PDT). However, designing an AIE-PS with both high SOG and intense fluorescence via molecular design is still challenging. In this work, we report a new nanohybrid consisting of gold nanostar (AuNS) and AIE-PS dots with enhanced fluorescence and photosensitization for theranostic applications. The spectral overlap between the extinction of AuNS and fluorescence emission of AIE-PS dots (665 nm) is carefully selected using five different AuNSs with distinct localized surface plasmon (LSPR) peaks. Results show that all the AuNSs can enhance the 1O2 production of AIE-PS dots, among which the AuNS with LSPR peak at 585 nm exhibited the highest 1O2 enhancement factor of 15-fold with increased fluorescence brightness. To the best of our knowledge, this is the highest enhancement factor reported for the metal-enhanced singlet oxygen generation systems. The Au585@AIE-PS nanodots were applied for simultaneous fluorescence imaging and photodynamic ablation of HeLa cancer cells with strongly enhanced PDT efficiency in vitro. This study provides a better understanding of the metal-enhanced AIE-PS nanohybrid systems, opening up new avenue towards advanced image-guided PDT with greatly improved efficacy.

BackgroundDespite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk.MethodsWe applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy.ResultsGenetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect.ConclusionOur MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.

Abstract Background Genome-wide studies of gene–environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene–environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 × 10–5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability

Abstract Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values

BackgroundIt is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype.MethodsWe analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype.ResultsThere was no evidence of heterogeneous associations between risk factors and mortality by subtype (P adj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5-25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age ≥30 years versus 0-

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.

Abstract Pomegranate crops are prone to wilt complex disease, which is known to severely hamper the crop yield. There have been limited studies that have explored bacteria–plant–host associations in wilt complex disease affecting pomegranate crops. In the present study, wilt infected rhizosphere soil samples (ISI, ASI) in pomegranate were studied in comparison to a healthy control (HSC). The 16S metagenomics sequencing approach using the MinION platform was employed for screening of bacterial communities and predictive functional pathways. Altered physicochemical properties in the soil samples were recorded showing a comparatively acidic pH in the ISI (6.35) and ASI (6.63) soil samples to the HSC soil (7.66), along with higher electrical conductivity in the ISI (139.5 µS/cm), ASI soil (180 µS/cm), HSC soil sample (123.33 µS/cm). While concentration of micronutrients such as Cl and B were significantly higher in the ISI and ASI soil as compared to the HSC, Cu and Zn were significantly higher in the ASI soil. The effectiveness and accuracy of 16S metagenomics studies in identifying beneficial and pathogenic bacterial communities in multi-pathogen–host systems depend on the completeness and consistency of the available 16S rRNA sequence repositories. Enhancing these repositories could significantly improve the exploratory potential of such studies. Thus, multiple 16S rRNA data repositories (RDP, GTDB, EzBioCloud, SILVA, and GreenGenes) were benchmarked, and the findings indicated that SILVA yields the most reliable matches. Consequently, SILVA was chosen for further analysis at the species level. Relative abundance estimates of bacterial species showed variations of growth promoting bacteria, namely, Staphylococcus epidermidis, Bacillus subtilis, Bacillus megatarium, Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas stutzeri and Micrococcus luteus. Functional profiling predictions employing PICRUSt2 revealed a number of enriched pathways such as transporter protein families involved in signalling and cellular processes, iron complex transport system substrate binding protein, peptidoglycan biosynthesis II (staphylococci) and TCA cycle VII (acetate-producers). In line with past reports, results suggest that an acidic pH along with the bioavailability of micronutrients such as Fe and Mn could be facilitating the prevalence and virulence of Fusarium oxysporum, a known causative pathogen, against the host and beneficial bacterial communities. This study identifies bacterial communities taking into account the physicochemical and other abiotic soil parameters in wilt-affected pomegranate crops. The insights obtained could be instrumental in developing effective management strategies to enhance crop yield and mitigate the impact of wilt complex disease on pomegranate crops.

Abstract Aggressive breast cancers portend a poor prognosis, but current polygenic risk scores (PRSs) for breast cancer do not reliably predict aggressive cancers. Aggressiveness can be effectively recapitulated using tumor gene expression profiling. Thus, we sought to develop a PRS for the risk of recurrence score weighted on proliferation (ROR-P), an established prognostic signature. Using 2363 breast cancers with tumor gene expression data and single nucleotide polymorphism (SNP) genotypes, we examined the associations between ROR-P and known breast cancer susceptibility SNPs using linear regression models. We constructed PRSs based on varying p-value thresholds and selected the optimal PRS based on model r2 in 5-fold cross-validation. We then used Cox proportional hazards regression to test the ROR-P PRS’s association with breast cancer-specific survival in two independent cohorts totaling 10,196 breast cancers and 785 events. In meta-analysis of these cohorts, higher ROR-P PRS was associated with worse survival, HR per SD = 1.13 (95% CI 1.06–1.21, p = 4.0 × 10–4). The ROR-P PRS had a similar magnitude of effect on survival as a comparator PRS for estrogen receptor (ER)-negative versus positive cancer risk (PRSER-/ER+). Furthermore, its effect was minimally attenuated when adjusted for PRSER-/ER+, suggesting that the ROR-P PRS provides additional prognostic information beyond ER status. In summary, we used integrated analysis of germline SNP and tumor gene expression data to construct a PRS associated with aggressive tumor biology and worse survival. These findings could potentially enhance risk stratification for breast cancer screening and prevention.

BackgroundEpidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk.MethodsWe carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry.ResultsFor pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 × 10-18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 × 10-8).ConclusionsThe CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.

Fish are among the best-studied aquatic animals due to their economic and ecological values. Fish meat is the most affordable protein source for the economically weaker section of people. The environment of almost all aquatic ecosystems has a specific influential role on or by fishes. Therefore, studying their stress biology, especially oxidative stress, is vital because it can influence their growth, production, reproduction, etc. To review the above topic, peer-reviewed electronic databases, including Web of Science, science direct, PubMed, Google Scholar, Scopus, and AGRICOLA, were searched with specific keywords associated with fish, oxidative stress, diseases, etc. The influence of abiotic stress, such as the effects of water dissolved oxygen, temperature, salinity, water hardness, alkalinity, pH, pollutants, heavy metals, and anthropogenic activities, was reviewed in the current article to draw a conclusion on the updated relation that exists between fish physiology, disease, and abiotic stressors. Oxidative stress and redox regulatory levels under the above parameters were reviewed as the stress or anti-stress responses differ in various fish models. Undoubtedly, the reviewed abiotic factors modulate fish oxidative health status to a greater extent, and therefore, these factors must be considered on a priority basis to improve the general health and immunity status of fish. The statement above remains valid in both saline and freshwater habitats.

BackgroundPrevious gene-environment interaction studies of breast cancer risk have provided sparse evidence of interactions. Using the largest available dataset to date, we performed a comprehensive assessment of potential effect modification of 205 common susceptibility variants by 13 established breast cancer risk factors, including replication of previously reported interactions.MethodsAnalyses were performed using 28 176 cases and 32 209 controls genotyped with iCOGS array and 44 109 cases and 48 145 controls genotyped using OncoArray from the Breast Cancer Association Consortium (BCAC). Gene-environment interactions were assessed using unconditional logistic regression and likelihood ratio tests for breast cancer risk overall and by estrogen-receptor (ER) status. Bayesian false discovery probability was used to assess the noteworthiness of the meta-analysed array-specific interactions.ResultsNoteworthy evidence of interaction at ≤1% prior probability was observed for three single nucleotide polymorphism (SNP)-risk factor pairs. SNP rs4442975 was associated with a greater reduction of risk of ER-positive breast cancer [odds ratio (OR)int = 0.85 (0.78-0.93), Pint = 2.8 x 10-4] and overall breast cancer [ORint = 0.85 (0.78-0.92), Pint = 7.4 x 10-5) in current users of estrogen-progesterone therapy compared with non-users. This finding was supported by replication using OncoArray data of the previously reported interaction between rs13387042 (r2 = 0.93 with rs4442975) and current estrogen-progesterone therapy for overall disease (Pint = 0.004). The two other interactions suggested stronger associations between SNP rs6596100 and ER-negative breast cancer with increasing parity and younger age at first birth.ConclusionsOverall, our study does not suggest strong effect modification of common breast cancer susceptibility variants by established risk factors.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.

Abstract Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values

Abstract The roots of Morus species are well described in the Pharmacopoeia of the People's Republic of China (ChP) for its traditional use in treating liver fibrosis due to its hepatoprotective property. However, little is known about the hepatoprotective effect of the roots of Morus indica L. (RoMi), and the pharmacological mechanism(s) are uncertain due to its intricacy. Therefore, this study evaluates the hepatoprotective activity of the ethanolic extract of RoMi (eRoMi) against the CCl4-induced in-vivo animal model at different dosages (100 and 200 mg/kg BW) in comparison with silymarin as a positive control. The hepatoprotective activity of eRoMi was evaluated by measuring the levels of serum biomarkers, hepatic antioxidant enzymes and was verified by histological studies. Interestingly, 1,2-bis(trimethylsilyl) benzene, 1,4-phenylenebis (trimethylsilane), 2,4,6-cycloheptatriene-1-one, 3,5-bis-trimethylsilyl and α-amyrin were the active components found in eRoMi as detected by GC–MS. Oral administration of eRoMi (200 mg/kg BW) to rats significantly protected serum biochemical parameters (increased ALT, AST, LDH, bilirubin and GGT as well as depletion of antioxidant enzymes and hepatic GSH) and elevation in hepatic lipid peroxidation as compared to CCl4-treated rats. The hematological indices such as erythrocytes, hemoglobin, monocytes and lymphocytes were also normal in eRoMi-treated rats. The histopathological evaluation indicated a significant restoration of liver structure as compared to silymarin. This study is the first scientific validation for the traditional use of eRoMi to understand its hepatoprotective activity.

Introduction: Breast cancer is the most common type of cancer globallyand its treatment with many FDA-approved synthetic drugs manifests various sideeffects. Alternatively, phytochemicals are natural reserves of novel drugsfor cancer therapy. Punica granatum commonly known as pomegranate is arich source of phytopharmaceuticals. Methods: The phytoconstituentsof Punica granatum leaves were profiled using GC-MS/MS in the presentwork. Cytoscape-assisted network pharmacology of principal and prognosticbiomarkers, which are immunohistochemically tested in breast cancer tissue, wascarried out for the identification of protein target. Followed by, rigorousvirtual screening of 145 phytoconstituents against the three ER isoforms(α, β and γ) was performed using Discovery Studio. Thedocked complexes were further evaluated for their flexibility and stability usingGROMACS2016 through 50 ns long molecular dynamic simulations. Results: In the current study, we report the precise and systematic GC-MS/MS profiling ofphytoconstituents (19 novel metabolites out of 145) of hydromethanolic extractof Punica granatum L. (pomegranate) leaves. These phytocompounds arevarious types of fatty acids, terpenes, heterocyclic compounds and flavonoids.4-coumaric acid methyl ester was identified as the best inhibitor of ER isoformswith drug-likeness and no toxicity from ADMET screening. γ-ligandbinding domain complex showed the best interactions with minimum RMSD, constantRg, and the maximum number of hydrogen bonds. Conclusion: We conclude that 4-coumaric acidmethyl ester exhibits favourable drug-like properties comparable to tamoxifen, anFDA-approved breast cancer drug and can be tested further in preclinical studies.

Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa-such as genetics-can impact PSA. Here we present findings from a genome-wide association study (GWAS) of PSA in 28,503 Kaiser Permanente whites and 17,428 men from replication cohorts. We detect 40 genome-wide significant (P

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Abstract Dual-functional aggregation-induced photosensitizers (AIE-PSs) with singlet oxygen generation (SOG) ability and bright fluorescence in aggregated state have received much attention in image-guided photodynamic therapy (PDT). However, designing an AIE-PS with both high SOG and intense fluorescence via molecular design is still challenging. In this work, we report a new nanohybrid consisting of gold nanostar (AuNS) and AIE-PS dots with enhanced fluorescence and photosensitization for theranostic applications. The spectral overlap between the extinction of AuNS and fluorescence emission of AIE-PS dots (665 nm) is carefully selected using five different AuNSs with distinct localized surface plasmon (LSPR) peaks. Results show that all the AuNSs can enhance the 1O2 production of AIE-PS dots, among which the AuNS with LSPR peak at 585 nm exhibited the highest 1O2 enhancement factor of 15-fold with increased fluorescence brightness. To the best of our knowledge, this is the highest enhancement factor reported for the metal-enhanced singlet oxygen generation systems. The Au585@AIE-PS nanodots were applied for simultaneous fluorescence imaging and photodynamic ablation of HeLa cancer cells with strongly enhanced PDT efficiency in vitro. This study provides a better understanding of the metal-enhanced AIE-PS nanohybrid systems, opening up new avenue towards advanced image-guided PDT with greatly improved efficacy.

The wonder fruit pomegranate (Punica granatum, family Lythraceae) is one of India’s economically important fruit crops that can grow in different agro-climatic conditions ranging from tropical to temperate regions. This study reports high-quality de novo draft hybrid genome assembly of diploid Punica cultivar “Bhagwa” and identifies its genomic features. This cultivar is most common among the farmers due to its high sustainability, glossy red color, soft seed, and nutraceutical properties with high market value. The draft genome assembly is about 361.76 Mb (N50 = 40 Mb), ∼9.0 Mb more than the genome size estimated by flow cytometry. The genome is 90.9% complete, and only 26.68% of the genome is occupied by transposable elements and has a relative abundance of 369.93 SSRs/Mb of the genome. A total of 30,803 proteins and their putative functions were predicted. Comparative whole-genome analysis revealed Eucalyptus grandis as the nearest neighbor. KEGG-KASS annotations indicated an abundance of genes involved in the biosynthesis of flavonoids, phenylpropanoids, and secondary metabolites, which are responsible for various medicinal properties of pomegranate, including anticancer, antihyperglycemic, antioxidant, and anti-inflammatory activities. The genome and gene annotations provide new insights into the pharmacological properties of the secondary metabolites synthesized in pomegranate. They will also serve as a valuable resource in mining biosynthetic pathways for key metabolites, novel genes, and variations associated with disease resistance, which can facilitate the breeding of new varieties with high yield and superior quality.

The vast majority of coding variants are rare, and assessment of the contribution of rare variants to complex traits is hampered by low statistical power and limited functional data. Improved methods for predicting the pathogenicity of rare coding variants are needed to facilitate the discovery of disease variants from exome sequencing studies. We developed REVEL (rare exome variant ensemble learner), an ensemble method for predicting the pathogenicity of missense variants on the basis of individual tools: MutPred, FATHMM, VEST, PolyPhen, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP, SiPhy, phyloP, and phastCons. REVEL was trained with recently discovered pathogenic and rare neutral missense variants, excluding those previously used to train its constituent tools. When applied to two independent test sets, REVEL had the best overall performance (p < 10-12) as compared to any individual tool and seven ensemble methods: MetaSVM, MetaLR, KGGSeq, Condel, CADD, DANN, and Eigen. Importantly, REVEL also had the best performance for distinguishing pathogenic from rare neutral variants with allele frequencies