CTC together with Shh and Nrf2 are prospective diagnostic markers for HNSCC.

BACKGROUND: The lack of appropriate prognostic biomarkers remains a significant obstacle in the early detection of Head and Neck Squamous Cell Carcinoma (HNSCC), a cancer type with a high mortality rate. Despite considerable advancements in treatment, the success in diagnosing HNSCC at an early stage still needs to be improved. Nuclear factor erythroid 2-related factor 2 (Nrf2) and Sonic Hedgehog (Shh) are overexpressed in various cancers, including HNSCC, and have recently been proposed as possible therapeutic targets for HNSCC. Circulating Tumor Cell (CTC) is a novel concept used for the early detection of cancers, and studies have suggested that a higher CTC count is associated with the aggressiveness of HNSCC and poor survival rates. Therefore, we aimed to establish molecular markers for the early diagnosis of HNSCC considering Shh/Nrf2 overexpression in the background. In addition, the relation between Shh/Nrf2 and CTCs is still unexplored in HNSCC patients. METHODS: In the present study, we selected a cohort of 151 HNSCC patients and categorized them as CTC positive or negative based on the presence or absence of CTCs in their peripheral blood. Data on demographic and clinicopathological features with the survival of the patients were analyzed to select the patient cohort to study Shh/Nrf2 expression. Shh and Nrf2 expression was measured by qRT-PCR. RESULTS: Considering significant demographic [smoking, betel leaf (p-value < 0.0001)] and clinicopathological risk factors [RBC count (p < 0.05), Platelet count (p < 0.05), Neutrophil count (p < 0.005), MCV (p < 0.0001), NLR (p < 0.05), MLR (p < 0.05)], patients who tested positive for CTC also exhibited significant overexpression of Shh/Nrf2 in both blood and tissue compared to CTC-negative patients. A strong association exists between CTCs and tumor grade. Following chemotherapy (a combination of Cisplatin, 5FU, and Paclitaxel), the frequency of CTCs was significantly decreased in patients with HNSCC who had tested positive for CTCs. The Kaplan-Meier plot illustrated that a higher number of CTCs is associated with poorer overall survival (OS) in patients with HNSCC. CONCLUSIONS: Detecting CTCs, and higher expression of Shh and Nrf2 in HNSCC patients' blood, can be a promising tool for diagnosing and prognosticating HNSCC.

Early-Life Fecal Transplantation from High Muscle Yield Rainbow Trout to Low Muscle Yield Recipients Accelerates Somatic Growth through Respiratory and Mitochondrial Efficiency Modulation.

Previous studies conducted in our lab revealed microbial assemblages to vary significantly between high (ARS-FY-H) and low fillet yield (ARS-FY-L) genetic lines in adult rainbow trout. We hypothesized that a high ARS-FY-H donor microbiome can accelerate somatic growth in microbiome-depleted rainbow trout larvae of the ARS-FY-L line. Germ-depleted larvae of low ARS-FY-L line trout reared in sterile environments were exposed to high- or low-fillet yield-derived microbiomes starting at first feeding for 27 weeks. Despite weight-normalized diets, somatic mass was significantly increased in larvae receiving high fillet yield microbiome cocktails at 27 weeks post-hatch. RNA-seq from fish tails reveals enrichment in NADH dehydrogenase activity, oxygen carrier, hemoglobin complex, gas transport, and respiratory pathways in high fillet yield recolonized larvae. Transcriptome interrogation suggests a relationship between electron transport chain inputs and body weight assimilation, mediated by the gut microbiome. These findings suggest that microbiome payload originating from high fillet yield adult donors primarily accelerates juvenile somatic mass assimilation through respiratory and mitochondrial input modulation. Further microbiome studies are warranted to assess how increasing beneficial microbial taxa could be a basis for formulating appropriate pre-, pro-, or post-biotics in the form of feed additives and lead to fecal transplantation protocols for accelerated feed conversion and fillet yield in aquaculture.

Fecal Microbiome Analysis Distinguishes Bacterial Taxa Biomarkers Associated with Red Fillet Color in Rainbow Trout.

The characteristic reddish-pink fillet color of rainbow trout is an important marketing trait. The gastrointestinal microbiome is vital for host health, immunity, and nutrient balance. Host genetics play a crucial role in determining the gut microbiome, and the host-microbiome interaction impacts the host's phenotypic expression. We hypothesized that fecal microbiota could be used to predict fillet color in rainbow trout. Fish were fed Astaxanthin-supplemented feed for six months, after which 16s rDNA sequencing was used to investigate the fecal microbiome composition in rainbow trout families with reddish-pink fillet coloration (red fillet group, average saturation index = 26.50 ± 2.86) compared to families with pale white fillet color (white fillet group, average saturation index = 21.21 ± 3.53). The linear discriminant analysis effect size (LEFse) tool was used to identify bacterial biomarkers associated with fillet color. The alpha diversity measure shows no difference in the red and white fillet groups. Beta diversity principal component analysis showed clustering of the samples along the white versus red fillet group. The red fillet group has enrichment (LDA score > 1.5) of taxa Leuconostoc lactis, Corynebacterium variabile, Jeotgalicoccus halotolerans, and Leucobacter chromiireducens. In contrast, the white fillet group has an enriched presence of mycoplasma, Lachnoclostridium, and Oceanobacillus indicireducens. The enriched bacterial taxa in the red fillet group have probiotic functions and can generate carotenoid pigments. Bacteria taxa enriched in the white fillet group are either commensal, parasitic, or capable of reducing indigo dye. The study identified specific bacterial biomarkers differentially abundant in fish families of divergent fillet color that could be used in genetic selection to improve feed carotenoid retention and reddish-pink fillet color. This work extends our understanding of carotenoid metabolism in rainbow trout through the interaction between gut microbiota and fillet color.

RNA-Seq analysis of the pyloric caecum, liver, and muscle reveals molecular mechanisms regulating fillet color in rainbow trout.

BACKGROUND: The characteristic pink-reddish color in the salmonids fillet is an important, appealing quality trait for consumers and producers. The color results from diet supplementation with carotenoids, which accounts for up to 20-30% of the feed cost. Pigment retention in the muscle is a highly variable phenotype. In this study, we aimed to understand the molecular basis for the variation in fillet color when rainbow trout (Oncorhynchus mykiss) fish families were fed an Astaxanthin-supplemented diet. We used RNA-Seq to study the transcriptome profile in the pyloric caecum, liver, and muscle from fish families with pink-reddish fillet coloration (red) versus those with lighter pale coloration (white). RESULTS: More DEGs were identified in the muscle (5,148) and liver (3,180) than in the pyloric caecum (272). Genes involved in lipid/carotenoid metabolism and transport, ribosomal activities, mitochondrial functions, and stress homeostasis were uniquely enriched in the muscle and liver. For instance, the two beta carotene genes (BCO1 and BCO2) were significantly under-represented in the muscle of the red fillet group favoring more carotenoid retention. Enriched genes in the pyloric caecum were involved in intestinal absorption and transport of carotenoids and lipids. In addition, the analysis revealed the modulation of several genes with immune functions in the pyloric caecum, liver, and muscle. CONCLUSION: The results from this study deepen our understanding of carotenoid dynamics in rainbow trout and can guide us on strategies to improve Astaxanthin retention in the rainbow trout fillet.

Reduced IFN-γ levels along with changes in hematologic and immunologic parameters are key to COVID-19 severity in Bangladeshi patients.

The manifestation of coronavirus disease 2019 (COVID-19) severity and mortality has been associated with dysregulation of the immune response, often influenced by racial disparities and conferred by changes in hematologic and immunologic parameters. These biological and hematologic parameters as well as cytokine profiles were investigated in a cohort of 61 COVID-19-positive patients (categorized into mild, moderate, and severe groups) from Bangladesh using standard analytical methods. The data reported that the interleukin (IL)-4 and IL-6 levels were significantly increased, whereas the levels of interferon (IFN)-γ were significantly reduced in patients with severe COVID-19 (p < 0.05) compared with those in patients with mild and/or moderate COVID-19. The extent of erythrocyte sedimentation rate (ESR); neutrophil count; and levels of ferritin, C-reactive protein (CRP), and D-dimer (p < 0.05) were found to be significantly increased, whereas the white blood cell (WBC), lymphocyte, eosinophil, and platelet counts (p < 0.05) were observed to be significantly reduced in patients with severe COVID-19 compared with those in the patients in other 2 groups. Our study exhibited a significantly higher IL-6-to-lymphocyte ratio in patients with severe COVID-19 than in those with mild and moderate COVID-19. The calculated neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and ferritin-to-ESR ratio were significantly increased in patients with severe COVID-19. The increase in the IL-4 and IL-6 levels along with CRP and D-dimer levels may envisage a hyperinflammatory environment and immune dysregulation, which contribute to prolonged viral persistence, leading to severe disease. However, the reduced level of IFN-γ can be attributed to a less fatality toll in Bangladesh compared with that in the rest of the world.

Research Note: Association of single nucleotide polymorphism of AKT3 with egg production traits in White Muscovy ducks (Cairina moschata).

Prior studies on transcriptomes of hypothalamus and ovary revealed that AKT3 is one of the candidate genes that might affect egg production in White Muscovy ducks. The role of AKT3 in the uterus during reproductive processes cannot be overemphasized. However, functional role of this gene in the tissues and on egg production traits of Muscovy ducks remains unknown. To identify the relationship between AKT3 and egg production traits in ducks, relative expression profile was first examined prior to identifying the variants within AKT3 that may underscore egg production traits [age at first egg (AFE), number of eggs at 300 d (N300D), and number of eggs at 59 wk (N59W)] in 549 ducks. The mRNA expression of AKT3 gene in high producing (HP) ducks was significantly higher than low producing (LP) ducks in the ovary, oviduct, and hypothalamus (P < 0.05 or 0.001). Three variants in AKT3 (C-3631A, C-3766T, and C-3953T) and high linkage block between C-3766T and C-3953T which are significantly (P < 0.05) associated with N300D and N59W were discovered. This study elucidates novel knowledge on the molecular mechanism of AKT3 that might be regulating egg production traits in Muscovy ducks.

Stability Enhancement and Microstructural Modification of Ni-Rich Cathodes via Halide Doping.

Elemental doping is an effective strategy to modify surface and bulk chemistry in NMC cathode materials. By adding small amounts of lithium halide salts during the calcination process, the Ni-rich NMC811 cathode is doped with Br, Cl, or F halogens. The dopant type has a significant impact on the lithiation process and heavily influences the final cathode porosity and surface morphology. Utilizing a variety of electrochemical, surface, and bulk characterization techniques, it is demonstrated that an initial content of 5 mol % LiBr or LiCl in the lithium source is effective in improving capacity retention while also providing excellent rate performance. The improvements are attributed to a substantial increase in specific surface area, the formation of a stable cathode electrolyte interface (CEI) layer, and suppressed surface reconstruction. In addition, the particle microstructure is better equipped to handle cyclic volume changes with increased values of critical crack lengths. Overall, it is demonstrated that anion doping via the addition of lithium halide salts is a facile approach toward Ni-rich NMC modification for enhanced cathode performance.

Weighted Single-Step GWAS Identifies Genes Influencing Fillet Color in Rainbow Trout.

The visual appearance of the fish fillet is a significant determinant of consumers' purchase decisions. Depending on the rainbow trout diet, a uniform bright white or reddish/pink fillet color is desirable. Factors affecting fillet color are complex, ranging from the ability of live fish to accumulate carotenoids in the muscle to preharvest environmental conditions, early postmortem muscle metabolism, and storage conditions. Identifying genetic markers of fillet color is a desirable goal but a challenging task for the aquaculture industry. This study used weighted, single-step GWAS to explore the genetic basis of fillet color variation in rainbow trout. We identified several SNP windows explaining up to 3.5%, 2.5%, and 1.6% of the additive genetic variance for fillet redness, yellowness, and whiteness, respectively. SNPs are located within genes implicated in carotenoid metabolism (ß,ß-carotene 15,15'-dioxygenase, retinol dehydrogenase) and myoglobin homeostasis (ATP synthase subunit ß, mitochondrial (ATP5F1B)). These genes are involved in processes that influence muscle pigmentation and postmortem flesh coloration. Other identified genes are involved in the maintenance of muscle structural integrity (kelch protein 41b (klh41b), collagen α-1(XXVIII) chain (COL28A1), and cathepsin K (CTSK)) and protection against lipid oxidation (peroxiredoxin, superoxide dismutase 2 (SOD2), sestrin-1, Ubiquitin carboxyl-terminal hydrolase-10 (USP10)). A-to-G single-nucleotide polymorphism in ß,ß-carotene 15,15'-dioxygenase, and USP10 result in isoleucine-to-valine and proline-to-leucine non-synonymous amino acid substitutions, respectively. Our observation confirms that fillet color is a complex trait regulated by many genes involved in carotenoid metabolism, myoglobin homeostasis, protection against lipid oxidation, and maintenance of muscle structural integrity. The significant SNPs identified in this study could be prioritized via genomic selection in breeding programs to improve fillet color in rainbow trout.

A comparison of clinicopathologic features of prostate cancer between Nigerian and South African black men.

Background: Globally, prostate cancer (PCa) is the commonest non-cutaneous male malignancy. It is more aggressive among black men with little known reasons as to the cause and continued trend among black men. This disproportionate pattern of PCa especially among black men of African ancestry resident in Africa calls for a closer look. Nigeria and South Africa, combined, have the highest cumulative risk incidence of PCa in Africa. The present study investigated the clinicopathologic behaviour of PCa among Nigerian and South African black men and the relationship between the disease and socio-demographic characteristics alongside medical co-morbidities. Methods: A retrospective cross-sectional study was undertaken in which de-identified records of 234 black men with pathologically confirmed PCa between 2007 and 2017 from two tertiary hospitals, in Nigeria (National Hospital, Abuja) and South Africa (Tygerberg Hospital, Cape Town), were reviewed. Results: Median age at presentation from both countries was 66 years (interquartile range, IQR 61-73 years) while the median PSA at presentation was 46 ng/ml (IQR 16-336.5 ng/ml). Half of the men (117/234) presented with locally advanced disease while metastatic disease was observed in 65.9% (27/41) of Nigerian men and 34.1% (14/41) of South African men. Thirty-three per cent of the men presented with organ-confined disease. Overall, Nigerian men presented with less organ-confined disease and significantly higher stage of disease (p < 0.001). Risk stratification using PSA, Gleason scores and T-staging showed that 84.2% (n = 197) of all the men presented with high-risk PCa disease. There was a statistically significant difference between Nigerian and South African black men (p = 0.003) in terms of disease risk at presentation. Logistic regression analysis showed that age (Adjusted OR 1.053 (95% CI 1.003-1.106), p = 0.003) and country of residence (Adjusted OR 4.281 (95% CI 1.690-10.844), p = 0.002) had a statistically significant relationship with high risk of PCa while disease co-morbidities (like diabetes and hypertension) and rural/urban location in both countries did not. Conclusions: Disparities exist between PCa presentation and clinicopathologic behaviour among Nigerian and South African black men. Nigerian men showed higher disease risk at presentation. Environmental-genetic interactions need further exploration in the aetio-pathogenesis of PCa in black men of African ancestry.

NEWS2 to assess suspected COVID-19 in the community: a service evaluation of a primary care assessment centre.

BACKGROUND: Primary care has played a central role in the community response to the coronavirus disease-19 (COVID-19) pandemic. The use of the National Early Warning Score 2 (NEWS2) has been advocated as a tool to guide escalation decisions in the community. The performance of this tool applied in this context is unclear. AIM: To evaluate the process of escalation of care to the hospital within a primary care assessment centre (PCAC) designed to assess patients with suspected COVID-19 in the community. DESIGN AND SETTING: A retrospective service evaluation of all adult patients assessed between 30 March and 22 April 2020 within a COVID-19 primary care assessment centre within Sandwell West Birmingham CCG. METHOD: A database of patient demographics, healthcare interactions and physiological observations was constructed. NEWS2 and CRB65 scores were calculated retrospectively. The proportion of patients escalated was within risk groups defined by NHSE guidelines in place during the evaluation period was determined. RESULTS: A total of 150 patients were identified. Following assessment 13.3% (n = 20) patients were deemed to require escalation. The proportion of patients escalated with a NEWS2 greater than or equal to 3 was 46.9% (95% CI 30.8-63.6%). The proportion of patients escalated to secondary care using NHSE defined risk thresholds was 0% in the green group, 22% (n = 4) in the amber group, and 81.3% (n = 13) in the red group. CONCLUSION: Clinical decisions to escalate care to the hospital did not follow initial guidance written for the COVID-19 outbreak but were demonstrated to be safe.

In most cases, coronavirus disease-19 (COVID-19) is a mild illness that resolves on its own. Some patients develop severe disease requiring hospital treatment. Identifying which patients are likely to need hospital treatment is a challenge. Many GP practices have developed specific services designed to assess patients with suspected COVID-19 and establish whether hospital treatment is necessary. We evaluated a service providing this function in Birmingham. We examined the care pathway of 150 patients assessed within the service to established factors associated with the need for hospital assessment. We found a national decision tool designed to aid the process was a poor descriptor of what happened in practice.