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Importance: While nipple-sparing mastectomy (NSM) for breast cancer was only performed using the open method in the past, its frequency using endoscopic and robotic surgical instruments has been increasing rapidly. However, there are limited studies regarding postoperative complications and the benefits and drawbacks of minimal access NSM (M-NSM) compared with conventional NSM (C-NSM). Objective: To examine the differences in postoperative complications between C-NSM and M-NSM. Design, Setting, Participants: This was a retrospective multicenter cohort study enrolling 1583 female patients aged 19 years and older with breast cancer who underwent NSM at 21 university hospitals in Korea between January 2018 and December 2020. Those with mastectomy without preserving the nipple-areolar complex (NAC), clinical or pathological malignancy in the NAC, inflammatory breast cancer, breast cancer infiltrating the chest wall or skin, metastatic breast cancer, or insufficient medical records were excluded. Data were analyzed from November 2021 to March 2024. Exposures: M-NSM or C-NSM. Main Outcomes and Measures: Clinicopathological factors and postoperative complications within 3 months of surgery were assessed. Statistical analyses, including logistic regression, were used to identify the factors associated with complications. Results: There were 1356 individuals (mean [SD] age, 45.47 [8.56] years) undergoing C-NSM and 227 (mean [SD] age, 45.41 [7.99] years) undergoing M-NSM (35 endoscopy assisted and 192 robot assisted). There was no significant difference between the 2 groups regarding short- and long-term postoperative complications (<30 days: C-NSM, 465 of 1356 [34.29%] vs M-NSM, 73 of 227 [32.16%]; P = .53; <90 days: C-NSM, 525 of 1356 [38.72%] vs M-NSM, 73 of 227 [32.16%]; P = .06). Nipple-areolar complex necrosis was more common in the long term after C-NSM than M-NSM (C-NSM, 91 of 1356 [6.71%] vs M-NSM, 5 of 227 [2.20%]; P = .04). Wound infection occurred more frequently after M-NSM (C-NSM, 58 of 1356 [4.28%] vs M-NSM, 18 of 227 [7.93%]; P = .03). Postoperative seroma occurred more frequently after C-NSM (C-NSM, 193 of 1356 [14.23%] vs M-NSM, 21 of 227 [9.25%]; P = .04). Mild or severe breast ptosis was a significant risk factor for nipple or areolar necrosis (odds ratio [OR], 4.75; 95% CI, 1.66-13.60; P = .004 and OR, 8.78; 95% CI, 1.88-41.02; P = .006, respectively). Conversely, use of a midaxillary, anterior axillary, or axillary incision was associated with a lower risk of necrosis (OR for other incisions, 32.72; 95% CI, 2.11-508.36; P = .01). Necrosis occurred significantly less often in direct-to-implant breast reconstruction compared to other breast reconstructions (OR, 2.85; 95% CI, 1.11-7.34; P = .03). Conclusions and Relevance: The similar complication rates between C-NSM and M-NSM demonstrates that both methods were equally safe, allowing the choice to be guided by patient preferences and specific needs.
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To investigate whether environmental concentrations of fragmented polyethylene terephthalate (PET) microplastics (MPs) have additional or combined effects on endocrine-disrupting activity, Java medaka (Oryzias javanicus) were exposed to 17ß-estradiol (E2; 5, 10, 50, and 100 ng L-1), bisphenol A (BPA; 5, 10, 50, and 100 µg L-1), and E2 and BPA combined with PET MPs (1 and 100 particles L-1) for 200 days. The growth parameters, such as body length and weight, were significantly decreased by the highest concentrations of E2 and BPA. A significant reduction in egg production was observed in female fish exposed to BPA, with an additive toxic effect of PET MPs. A female-biased sex ratio was observed in fish exposed to both chemicals. Exposure to E2 significantly increased the hepatosomatic index (HSI) in both sexes, while no significant effect was observed in the gonadosomatic index (GSI). Exposure to BPA significantly increased the HSI in female fish and decreased the GSI in both sexes of fish. An additive effect of PET MPs was observed on the GSI value of female exposed to BPA. Significant elevations in vitellogenin (VTG) levels were observed in both sexes due to exposure to E2 and BPA. Additive effects of PET MPs were observed on VTG levels in males exposed to E2 and BPA. Taken together, even long-term treatment with PET MPs induced only a negligible additive effect on the endocrine-disrupting activity in Java medaka at environmentally relevant concentrations.
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Compuestos de Bencidrilo , Estradiol , Microplásticos , Oryzias , Fenoles , Tereftalatos Polietilenos , Reproducción , Contaminantes Químicos del Agua , Animales , Oryzias/fisiología , Oryzias/crecimiento & desarrollo , Compuestos de Bencidrilo/toxicidad , Fenoles/toxicidad , Microplásticos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Femenino , Masculino , Reproducción/efectos de los fármacos , Tereftalatos Polietilenos/toxicidad , Disruptores Endocrinos/toxicidad , Vitelogeninas/metabolismoRESUMEN
The pale chub, Zacco platypus (Cypriniformes; Xenocyprididae; homotypic synonym: Opsariichthys platypus; Jordan & Evermann, 1902), is widely distributed in the freshwater ecosystems throughout East Asia, including South Korea. In this study, we constructed a de novo genome assembly of Z. platypus to serve as a reference for fundamental and applied research. The assembly was generated using a combination of long-read Pacific Bioscience (PacBio) sequencing, short-read Illumina sequencing, and Hi-C sequencing technologies. The draft genome of Z. platypus consisted of 16,422,113 reads from the HiFi library, 702,143,130 reads from the Illumina TruSeq library, and 250,789,660 reads from the Hi-C library. Assembly with Hifiasm resulted in 336 contigs, with an N50 length of 31.9 Mb. The final assembled genome size was 838.6 Mb. Benchmarking Universal Single-Copy Orthologs (BUSCO) analysis indicated that 3,572 (98.1 %) of the expected genes were found in the assembly, with 3,521 (96.7 %) being single-copy and 51 (1.4 %) duplicated after searching against the Actinopterygii database. Of the 319 Hi-C scaffolds, 24 exceeded 10 Mb were thus classified as chromosome-level scaffolds. The assembled genome comprises 41.45 % repeat sequences. Gene annotation was performed using Illumina RNA-Seq and PacBio Iso-Seq data, based on repeat-masked genome sequences. The final annotation resulted in 34,036 protein-coding genes. This chromosomal-level genome assembly is expected to be a valuable resource for future health assessments in aquatic ecosystems, providing insights into the developmental, environmental, and ecological aspects of Z. platypus.
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Purpose: The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is involved in the progression of various cancers, but its biological roles in breast cancer (BRCA) remain unclear. Therefore, we performed a systematic multiomic analysis to expound on the prognostic value and underlying mechanism of CTLA4 in BRCA. Methods: We assessed the effect of CTLA4 expression on BRCA using a variety of bioinformatics platforms, including Oncomine, GEPIA, UALCAN, PrognoScan database, Kaplan-Meier plotter, and R2: Kaplan-Meier scanner. Results: CTLA4 was highly expressed in BRCA tumor tissue compared to normal tissue (P < 0.01). The CTLA4 messenger RNA levels in BRCA based on BRCA subtypes of Luminal, human epidermal growth factor receptor 2, and triple-negative BRCA were considerably higher than in normal tissues (P < 0.001). However, the overexpression of CTLA4 was associated with a better prognosis in BRCA (P < 0.001) and was correlated with clinicopathological characteristics including age, T stage, estrogen receptors, progesterone receptors, and prediction analysis of microarray 50 (P < 0.01). The infiltration of multiple immune cells was associated with increased CTLA4 expression in BRCA (P < 0.001). CTLA4 was highly enriched in antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. Conclusion: This study provides suggestive evidence of the prognostic role of CTLA4 in BRCA, which may be a therapeutic target for BRCA. Furthermore, CTLA4 may influence BRCA prognosis through antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. These findings help us understand how CTLA4 plays a role in BRCA and set the stage for more research.
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PURPOSE: Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. METHODS: The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuum-assisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years. DISCUSSION: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05505357. Registered on August 17, 2022. Clinical Research Information Service Identifier: KCT0007638. Registered on July 25, 2022.
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We conducted a comprehensive assessment involving acute effects on 96-hour survival and biochemical parameters, as well as chronic effects on growth and reproduction spanning three generations of the marine mysid Neomysis awatschensis exposed to filtered wastewater to evaluate the potential impact of ship hull-cleaning wastewater on crustaceans. The analyzed wastewater exhibited elevated concentrations of metals, specifically zinc (Zn) and copper (Cu) and metal-based antifoulants, i.e., Cu pyrithoine (CuPT) and Zn pyrithoine (ZnPT). The results revealed dose-dependent reductions in survival rates, accompanied by a notable increase in oxidative stress, in response to the sublethal values of two wastewater samples: 1) mechanically filtered using the cleaning system (MF) and 2) additionally filtered in the laboratory (LF) for 96 h. Mysids exposed to MF displayed higher mortality than those exposed to LF. Furthermore, mysids subjected to continuous exposure of 0.001% LF across three generations exhibited significant inhibition of the feeding rate, more pronounced growth retardation along with an extended intermolt duration, and a diminished rate of reproduction compared to the control. A noteworthy inhibition of the feeding rate and growth was observed in the first generation exposed only to the LF sample. However, although the reproduction rate was not significantly affected. Collectively, these findings underscore the potential harm posed by sublethal concentrations of wastewater to the health of mysid populations under consistent exposure.
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Aguas Residuales , Contaminantes Químicos del Agua , Animales , Aguas Residuales/toxicidad , Contaminantes Químicos del Agua/toxicidad , Metales/farmacología , Crustáceos , Cobre/toxicidad , ZincRESUMEN
Breast cancer, with its global prevalence and impact on women's health, necessitates effective early detection and accurate staging for optimal patient outcomes. Traditional imaging modalities such as mammography, ultrasound, and dynamic contrast-enhanced magnetic resonance imaging (MRI) play crucial roles in local-regional assessment, while bone scintigraphy and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) aid in evaluating distant metastasis. Despite the proven utility of 18F-FDG PET/CT in various cancers, its limitations in breast cancer, such as high false-negative rates for small and low-grade tumors, have driven exploration into novel targets for PET radiotracers, including estrogen receptor, human epidermal growth factor receptor-2, fibroblast activation protein, and hypoxia. The advent of PET/MRI, which combines metabolic PET information with high anatomical detail from MRI, has emerged as a promising tool for breast cancer diagnosis, staging, treatment response assessment, and restaging. Technical advancements including the integration of PET and MRI, considerations in patient preparation, and optimized imaging protocols contribute to the success of dedicated breast and whole-body PET/MRI. This comprehensive review offers the current technical aspects and clinical applications of PET/MRI for breast cancer. Additionally, novel targets in breast cancer for PET radiotracers beyond glucose metabolism are explored.
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Harmful algal blooms (HABs) caused by dinoflagellates can be detrimental to aquaculture and fisheries. However, little is known regarding their ichthyotoxic effects on fish, particularly after chronic exposure to sublethal levels. In this study, significant modulations in physiology, immunity, antioxidant components, and hepatic indicators owing to non-toxin-producing dinoflagellate strains (Alexandrium affine and Cochlodinium polykrikoides) were analyzed in juvenile red seabream, Pagrus major, exposed to sublethal concentrations (0, 1, and 100 cells mL-1) for 60 days. At 60 days, higher mortality was induced by A. affine than by C. polykrikoides. Significant increases in respiration rate and plasma cortisol were observed in red seabream exposed to 100 cells mL-1 of the two dinoflagellates. Intracellular reactive oxygen species and malondialdehyde levels were significantly elevated in the gill and liver tissues in response to 100 cells mL-1 of either dinoflagellate. Immunity parameters such as alternative complement activity, lysozyme activity, and total immunoglobulin content were significantly decreased during exposure to 100 cells mL-1 of the two dinoflagellates. Although no significant change was observed in the gonadosomatic index, the hepatosomatic index was significantly decreased by exposure to 100 cells mL-1 of the two dinoflagellates on day 60. The significant decrease in enzymatic activities of ethoxyresorufin-O-deethylase, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase upon exposure to 100 cells mL-1 of either dinoflagellate suggested impaired hepatic function through prolonged exposure. Our results suggest that consistent exposure to sublethal concentrations of HAB-forming dinoflagellates is detrimental to fish physiology and biochemical defenses.
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Dinoflagelados , Perciformes , Dorada , Animales , Floraciones de Algas Nocivas , Estrés OxidativoRESUMEN
BACKGROUND: We conducted this study to assess preliminary 2-year safety outcomes of an implant-based augmentation mammaplasty using the BellaGel® SmoothFine in the context of the first Korean case of a medical device fraud. METHODS: Our clinical series of the patients (n = 579; 1,158 breasts) received augmentation using the BellaGel® SmoothFine, Naturgel™, Motiva Ergonomix™, Eurosilicone Round Collection™, Natrelle® INSPIRA™, Natrelle® 410, Mentor® MemoryGel Xtra or Microthane®. The patients were evaluated for incidences of postoperative complications and Kaplan-Meier survival and hazards. RESULTS: Overall, there were a total of 101 cases (17.4%) of postoperative complications; these include 31 cases (5.4%) of shape deformity, 21 cases (3.6%) of CC, 18 cases (3.1%) of early seroma, 8 cases (1.4%) of infection, 5 cases (0.9%) of early hematoma, 1 case (0.2%) of delayed hematoma, 1 case (0.2%) of rupture and 1 case (0.2%) of ripping. Moreover, there were also 15 cases (2.6%) of other complications. There were significant differences in incidences of postoperative complications between the breast implants from different manufacturers (P = 0.034). The Natrelle® 410 showed the longest survival (333.3±268.2 [141.5-525.1] days). A subgroup analysis showed that there were no significant differences in incidences of postoperative complications between the breast implants (P = 0.831). Moreover, the Natrelle® INSPIRA™ showed the longest survival (223.7±107.1 [-42.3-489.6] days). CONCLUSIONS: Here, we describe preliminary 2-year safety outcomes of an implant-based augmentation mammaplasty using the BellaGel® SmoothFine in the context of the first Korean case of a medical device fraud.
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Implantación de Mama , Implantes de Mama , Mamoplastia , Femenino , Humanos , Estudios Retrospectivos , Implantes de Mama/efectos adversos , Implantación de Mama/efectos adversos , Mamoplastia/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , República de Corea , Estudios de SeguimientoRESUMEN
SUMMARY: With the emergence of state-of-the art implant technology and advanced surgical techniques, plastic surgeons face challenging problems, such as identification of a specific type of a device and diagnosis of postoperative complications, in managing patients undergoing implant-based augmentation mammaplasty. In this article, the authors introduce a novel method for characterizing a breast implant based on diverse factors (eg, filler properties, type of pocket, surface topography, shape type, and manufacturer of the device) and detecting the presence and scope of rupture using high-resolution ultrasound.
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Implantación de Mama , Implantes de Mama , Mamoplastia , Femenino , Humanos , Implantes de Mama/efectos adversos , Implantación de Mama/métodos , Mamoplastia/efectos adversos , Mamoplastia/métodos , Complicaciones Posoperatorias/etiología , Ultrasonografía , Reoperación/métodosRESUMEN
The presence and toxicity of waterborne diuron in aquatic environments pose a severe threat to non-target organisms. However, the chronic impact of diuron in marine fish has been poorly investigated. In this study, we report the chronic effects (30 and 60 days) of environmentally relevant concentrations of diuron (0.1, 1, and 10 µg L-1) on economically important marine fish, red seabream (Pagrus major), and black rockfish (Sebastes schlegelii) by evaluating several parameters, including hormone levels, immunity, hepatic function, and antioxidant defense. Significant decreases in 17ß-estradiol and 11-ketotestosterone levels and gonadosomatic index were observed on day 60 in fish exposed to 10 µg L-1 diuron. Parameters of immunity, such as alternative complement activity, lysozyme activity, and total immunoglobulin levels, were significantly lowered by 60-day exposure to 10 µg L-1 diuron in both fish. Significant decreases in the hepatic enzyme activities of alanine transaminase and aspartate transaminase were observed with an induction of cortisol on day 60 in fish exposed to 10 µg L-1 diuron. Intracellular malondialdehyde and glutathione levels were significantly increased by 10 µg L-1 diuron at day 60 with an increase in the enzymatic activities of catalase and superoxide dismutase. Overall, black rockfish were more sensitive to diuron than red seabream. These results suggest that consistent exposure to environmentally relevant concentrations of diuron is detrimental to the reproduction, immunity, and health of marine fish.
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Diurona , Dorada , Animales , Diurona/toxicidad , Antioxidantes , Malondialdehído , EstradiolRESUMEN
Here, we sequenced and annotated the complete mitochondrial genome for the terebellid polychaete, Neoamphitrite affinis (Malmgren 1866). The complete mitogenome of N. affinis is 15,823 bp, with 33.4% A, 18.2% C, 11.5% G, and 37.0% T. The circular N. affinis mitochondrial genome comprises 13 protein-coding genes (PCGs), 23 transfer RNA (tRNA) genes including 2 methionine tRNA genes, 2 ribosomal RNA (rRNA) genes, and a non-coding region. Phylogenomic analysis based on 26 in-group taxa belonging to the two main clades, Sedentaria and Errantia, is congruent with published phylogenetic relationship for annelids, which N. affinis was grouped with Pista cristata (Terebellida; Terebellidae). This mitogenome resource will be useful for future phylogenetic studies of families belonging to Sedentaria.
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Purpose: The prognostic value of vitamin D receptor gene (VDR) expression in breast cancer development is unclear. Here, we aimed to investigate whether VDR expression can be used as a prognostic indicator of breast cancer. Methods: We used various public bioinformatics platforms: Oncomine, GEPIA, UALCAN, Kaplan-Meier plotter, UCSC XENA, bc-GenExMiner, WebGestalt, and STRING database. Results: We found that VDR was upregulated in breast cancer in comparison to normal tissues. Overexpression of VDR was significantly associated with worse overall survival in breast cancer. The expression of VDR was related to age, TNM stages, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, basal-like (PAM 50) status, triple-negative breast cancer (TNBC) status, and basal-like (PAM 50) & TNBC status (P < 0.05). Increased VDR expression in breast cancer was significantly associated with older age. The 5 hub genes for VDR were NCOA1, EP300, CREBBP, and RXRA. Conclusion: Our investigation offers hints about the prognostic role of VDR in breast cancer. The findings suggest that VDR expression might be used as a marker to determine a breast cancer patient's prognosis. Nevertheless, further validation is warranted.
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Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis and a lack of targeted therapy. Overexpression of FRAT1 is thought to be associated with this aggressive subtype of cancer. Here, we performed a comprehensive analysis and assessed the association between overexpression of FRAT1 and TNBC. Methods: First, using different web-based bioinformatics platforms (TIMER 2.0, UALCAN, and GEPIA 2), the expression of FRAT1 was assessed. Then, the expression of the FRAT1 protein and hormone receptors and HER2 status were assessed by immunohistochemical analysis. For samples of tumors with equivocal immunoreactivity, we performed silver in situ hybridization of the HER2 gene to determine an accurate HER2 status. Next, we used the R package and bc-GenExMiner 4.8 to analyze the relationship between FRAT1 expression and clinicopathological parameters in breast cancer patients. Finally, we determined the relationship between FRAT1 overexpression and prognosis in patients. Results: The expression of FRAT1 in breast cancer tissues is significantly higher than in normal tissue. FRAT1 expression was significantly related to worse overall survival (P < 0.05) and was correlated with these clinicopathological features: T stage, N stage, age, high histologic grade, estrogen receptor status, progesterone receptor status, Her-2 status, TNBC status, basal-like status, CK5/6 status, and Ki67 status. Conclusion: FRAT1 was overexpressed in breast cancer compared to normal tissue, and it may be involved in the progression of breast cancer malignancy. This study provides suggestive evidence of the prognostic role of FRAT1 in breast cancer and the therapeutic target for TNBC.
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Here, we report information on the complete mitochondrial genome of the firemouth cichlid, Thorichthys meeki (Brind 1918). Illumina HiSeq genome sequencing produced the assembly of a circular mitogenome of 16,527 base pairs (bp) from T. meeki consisting of 46.8% GC nucleotides, 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a putative control region as shown in the typical teleost gene composition. The gene order of the T. meeki mitogenome was identical to that of other cichlid species. A maximum likelihood phylogenetic tree based on mitochondrial PCGs showed a close relationship of T. meeki with Thorichthys aureus (Gunther 1862) within Heroini tribe.
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We report the complete mitochondrial genome information of the rainbow krib, Pelvicachromis pulcher (Boulenger 1901). Illumina HiSeq genome sequencing allowed the assembly of a circular mitogenome of 17,196 base pairs (bp) from P. pulcher consisting of 47% GC nucleotides, 13 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a putative control region in the typical teleost gene composition. The gene order of the P. pulcher mitogenome was identical to that of other cichlid species. A maximum likelihood phylogenetic tree based on mitochondrial PCGs showed a relationship of P. pulcher with a cichlid Tylochromis polylepis (Boulenger 1900), suggesting that more complete mitogenomes are needed to explore mitogenome evolution in West African tribes and riverine cichlids, as this genomic information is the first complete mitogenome in the tribe Chromidotilapiini.
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We sequenced and annotated the complete mitochondrial genome for the freshwater water flea Moina macrocopa (Straus, 1820). This is the first mitogenome for the family Moinidae. The complete mitogenome of M. macrocopa is 16,072 bp, with 35.8% A, 17.6% C, 12.8% G, and 33.8% T. The mitogenome comprises 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a non-coding region. Phylogenomic analysis based on 28 in-group taxa belonging to the orders Anostraca, Diplostraca, and Notostraca is congruent with published phylogenetic relationship for cladocerans, with M. macrocopa being grouped with members of the Daphniidae. This mitogenome resource will be useful for future phylogenetic studies of water fleas.
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BRCA1/2 are breast cancer susceptibility genes that are involved in DNA repair and transcriptional control. They are dysregulated in breast cancer, making them attractive therapeutic targets. Here, we performed a systematic multiomics analysis to expound BRCA1/2 functions as prognostic biomarkers in breast cancer. First, using different web-based bioinformatics platforms (Oncomine, TIMER 2.0, UALCAN, and cBioportal), the expression of BRCA1/2 was assessed. Then, the R package was used to analyze the diagnostic value of BRCA1/2 in patients. Next, we determined the relationship between BRCA1/2 mRNA expression and prognosis in patients (PrognoScan Database, R2: Kaplan Meier Scanner and Kaplan−Meier Plotter). Subsequently, the association of BRCA1/2 with mutation frequency alteration and copy number alterations in breast cancer was investigated using the cBioportal platform. After that, we identified known and predicted structural genes and proteins essential for BRCA1/2 functions using GeneMania and STRING db. Finally, GO and KEGG pathway enrichment analyses were performed to elucidate the potential biological functions of the co-expression genes of BRCA1/2. The BRCA1/2 mRNA level in breast cancer tissues was considerably higher than in normal tissues, with AUCs of 0.766 and 0.829, respectively. Overexpression of BRCA1/2 was significantly related to the worse overall survival (p < 0.001) and was correlated to clinicopathological characteristics including lymph nodes, estrogen receptors, and progesterone receptors (p < 0.01). The alteration frequencies of both the gens have been checked, and the results show that BRCA1 and BRCA2 show different alteration frequencies. Their mutation sites differ from each other. GO and KEGG showed that BRCA1/2 was mainly enriched in catalytic activity, acting on DNA, chromosomal region, organelle fission, cell cycle, etc. The 20 most frequently changed genes were closely related to BRCA1/2, including PALB2 and RAD51 relatively. Our study provides suggestive evidence of the prognostic role of BRCA1/2 in breast cancer and the therapeutic target for breast cancer. Furthermore, BRCA1/2 may influence BRCA prognosis through catalytic activity, acting on DNA, chromosomal regions, organelle fission, and the cell cycle. Nevertheless, further validation is warranted.
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Proteína BRCA2/genética , Biomarcadores de Tumor , Neoplasias de la Mama , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Mama/patología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Femenino , Genes BRCA2 , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
This study investigated the prognostic value of FDG PET/CT radiomic features for predicting recurrence in patients with early breast invasive ductal carcinoma (IDC). The medical records of consecutive patients who were newly diagnosed with primary breast IDC after curative surgery were reviewed. Patients who received any neoadjuvant treatment before surgery were not included. FDG PET/CT radiomic features, such as a maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), skewness, kurtosis, entropy, and uniformity, were measured for the primary breast tumor using LIFEx software to evaluate recurrence-free survival (RFS). A total of 124 patients with early breast IDC were evaluated. Eleven patients had a recurrence (8.9%). Univariate survival analysis identified large tumor size (>2 cm, p = 0.045), high Ki-67 expression (≥30%, p = 0.017), high AJCC prognostic stage (≥II, p = 0.044), high SUVmax (≥5.0, p = 0.002), high MTV (≥3.25 mL, p = 0.044), high TLG (≥10.5, p = 0.004), and high entropy (≥3.15, p = 0.003) as significant predictors of poor RFS. After multivariate survival analysis, only high MTV (p = 0.045) was an independent prognostic predictor. Evaluation of the MTV of the primary tumor by FDG PET/CT in patients with early breast IDC provides useful prognostic information regarding recurrence.
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In this study, the toxicity of hexavalent chromium [Cr(VI)] reduced by citric acid in ice was measured using representative aquatic model invertebrates (i.e., rotifer, water flea, amphipod, and polychaete) and a vertebrate (zebrafish) by analyzing short- and/or long-term endpoints that are frequently applied to each animal. Cr(VI) reduction in the presence of citric acid was markedly enhanced in the ice phase compared to that in an aqueous solution through the freeze concentration effect. The highly concentrated Cr(VI) and citric acid in ice grain boundaries were also confirmed using in situ cryogenic confocal Raman spectroscopy. Overall, exposure to Cr(VI) resulted in higher acute and/or chronic effects on aquatic animals, such as drastic mortality, growth inhibition, and decrease in offspring number, whereas the animals were increasingly tolerant to Cr(VI) that was reduced in the ice phase. Sublethal concentrations of Cr(VI) significantly decreased the antioxidant capacity in the aquatic animals. However, when the same concentrations of Cr(VI) were reduced in ice, these treatments showed no modulation or increase in the antioxidant defense system. Taken together, our results suggest that Cr(VI) reduction into Cr(III) was successfully achieved in ice and that this methodology can decrease the actual toxicity of Cr(VI) in aquatic animals.