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Whole genome sequencing (WGS) is increasingly accessible in clinical practice, enabling pharmacogenomics (PGx) integration, including in pediatric oncology. However, the lack of validated software to accurately annotate clinically actionable PGx variants from WGS limits routine implementation. We therefore aimed to identify and validate a PGx annotation tool suitable for clinical use in pediatric oncology. We evaluated several tools for technical performance and clinical integration. The Pharmacogenomics Clinical Annotation Tool (PharmCAT) was selected for its alignment with expert-reviewed PGx guidelines, inclusion of relevant gene-drug pairs and prescribing recommendations. PharmCAT was validated using an in silico dataset by introducing known diplotypes into the Genome in a Bottle (GIAB) reference sample, complemented by four clinically confirmed diplotypes from three patients. Diplotype and phenotype outputs from WGS were compared against the GIAB and patient reference data. We tested 71 diplotypes across seven genes (TPMT, NUDT15, CYP3A5, CYP2C9, CYP2C19, DPYD, UGT1A1), using ≥ 95% sensitivity and specificity as validation criteria. CYP2D6 was excluded from this validation due to genotyping limitations from the input data used by PharmCAT. The tool was integrated into our WGS analysis pipeline using containerization for consistent, reproducible execution. Diplotype and phenotype results from PharmCAT fully matched the in silico GIAB set and patient samples, achieving 100% sensitivity and specificity. These findings confirm PharmCAT as a reliable tool for preemptive PGx annotation, supporting implementation in pediatric oncology. Its clinical integration supports individualized dosing, reducing adverse effects and improving efficacy. Further validation of additional gene-drug pairs will broaden its clinical utility.
The quest for the next-generation probiotics has highlighted non-conventional lactic acid bacteria in recent decades, and among these, Weissella has been a genus exhibiting multifaceted health-benefiting characteristics. Weissella spp., such as Weissella cibaria, Weissella confusa, and Weissella koreensis, are traditionally found in fermented foods and other ecological niches, having encouraging probiotic properties such as robust survivability under gastrointestinal conditions and capability to modulate host health. This review focuses on various health-beneficial properties of Weissella strains, including their antimicrobial activities, chiefly through the production of organic acids, hydrogen peroxide, and bacteriocins, such as weissellicin, which suppress growth of both Gram-positive and Gram-negative pathogens. Several studies have reported the anticancer properties of Weissella, where certain strains are known to induce apoptosis among cancer cell lines and exhibit anti-proliferative properties. Further, Weissella spp. secrete antioxidant compounds that can scavenge free radicals and inhibit oxidative stress, a crucial causal factor in chronic conditions. Weissella also exhibits hypocholesterolemic activity through the assimilation of cholesterol, resulting in the reduction of serum cholesterol, thus showing its application in cardiovascular health management as well. Looking forward, the development of Weissella-based biotherapeutic formulations offer exciting opportunities in preventive and therapeutic strategies for managing infections, metabolic disorders, inflammation, and cancer. Despite these promising attributes of Weissella genus, there are some safety concerns related to certain strains, which need to be carefully assessed before clinical usage. Furthermore, in vivo and clinical studies are warranted in future to elucidate the underlying mechanisms for establishing complete regulatory approval.
Cisplatin-induced hearing loss (CIHL) in pediatric cancer patients is an irreversible and highly prevalent adverse effect with a devastating impact on quality of life. Sodium thiosulfate (STS) has recently been approved for systemic administration as an otoprotective agent in children. However, implementation of systemic STS has its challenges, and there is currently limited evidence to support local STS for children. This review investigates the potential value of locally administered otoprotective agents other than STS with a focus on future pediatric implementation. We conducted a systematic review on the efficacy and safety of locally applied non-STS otoprotective agents in in vivo settings. This included a summary of investigated drug delivery methods and administration routes. We identified 70 preclinical and eight clinical studies. Agents were categorized based on their biological mechanisms: anti-inflammatory, chemical deactivators, calcium blockers, biologicals, and miscellaneous mechanisms. Preclinical studies investigated 45 different agents. Dexamethasone and N-acetylcysteine were identified as efficacious agents recurrently and progressed to clinical trials. Dexamethasone was investigated in three randomized clinical trials (RCTs) and three non-randomized clinical studies and showed statistically significant but not clinically relevant benefit in two trials. N-acetylcysteine was investigated in two clinical trials and one RCT and was minimally effective in the RCT and in one clinical study. Our review did not identify available studies of local alternative otoprotective agents that could reliably replace systemic STS in terms of safety and efficacy for pediatric patients. Further research on the optimal dosage, delivery method, and timing of otoprotective agents is needed.
Over the past decade, various large observational studies have suggested an association between silicone breast implants (SBIs) and autoimmune and rheumatic diseases (ARDs), rekindling long-standing breast implant-safety concerns among breast cancer survivors with breast reconstructions and newly diagnosed breast cancer patients. We investigated the association between SBIs and ARDs in a large multicenter cohort of women treated for breast cancer, part of whom received SBIs for reconstructive purposes. Clinical data and events of interest were identified through linkages with prospectively maintained nationwide- and institutional registries. Hazard Ratios (HRs) for ARDs were calculated using Cox proportional hazards regression models adjusted for potential confounders. Of 12,262 women in the cohort, 3,082 (25%) had received SBI-based breast reconstructions. Median follow-up time was 12.0 (IQR, 7.0) years. The event rate of ARD-diagnoses was 62.5 per 10,000 person-years. Compared with women without SBI-exposure, women with an implant-based breast reconstruction did not have an increased risk of ARDs (multivariably adjusted HR, 1.06, 95% CI [0.89 to 1.27]). In addition, no statistically significant association was found between SBI-exposure and inflammatory arthritis, systematic rheumatic disease, inflammatory dermatosis, inflammatory bowel disease or any specific condition. Sensitivity analyses in which SBI-exposure was analyzed as a time-dependent variable confirmed the results of the main analysis. The findings of this study indicate that SBI-exposure is not associated with an increased risk of ARDs in women with breast cancer and challenge the results of earlier studies in women with cosmetic implants. This study is registered at ClinicalTrials.gov on June 2nd 2022 (NCT05400954).
In this study, whole-genome analyses were employed to resolve the taxonomic status of two closely related Chromohalobacter species. Among the eight type strains with publicly available data, C. beijerinckii Peçonek et al. (Int J Syst Evol Microbiol 56:1953-1957, 2006) and C. japonicus Sánchez-Porro et al. (Int J Syst Evol Microbiol 57:2262-2266, 2007) repeatedly converged as a single evolutionary unit. The 16S rRNA gene sequences of C. beijerinckii ATCC 19372 T and C. japonicus 43 T possess 99.26% sequence similarity. Furthermore, whole-genome sequence comparisons showed that C. beijerinckii DSM 7218 T and C. japonicus CECT 7219 T shared 96.82% BLAST-based average nucleotide identity (ANIb), 97.69% average amino acid identity (AAI) and 73.1% digital DNA-DNA hybridization (dDDH) values. Although originally described as distinct taxa, these results exceed the criteria for species-level differentiation, confirming that both strains belong to the same species. Phylogenomic reconstruction of core genes further highlighted their placement in one robust clade. Overall, the combined analyses support the conclusion that C. japonicus Sánchez-Porro et al. (Int J Syst Evol Microbiol 57:2262-2266, 2007) is a later heterotypic synonym of C. beijerinckii Peçonek et al. (Int J Syst Evol Microbiol 56:1953-1957, 2006).
Pleural mesothelioma (PM) is an aggressive malignancy with limited therapeutic options and poor long-term prognosis. Platinum-based chemotherapy has been the standard-of-care for most patients for decades. While the decoding of the genomic alterations in PM has triggered renewed interest in mesothelioma biology and targeted therapies, these have yet to reach clinical practice. The recent introduction of dual immune checkpoint blockade (ICB) with nivolumab plus ipilimumab has marked the first major advance in PM treatment for decades, yet, many patients do not respond to these drugs and durable long-term responses remain rare. A range of alternative treatment modalities are currently under clinical investigation in PM, including antibody-drug conjugates, bi-specific antibodies, chimeric antigen receptor T-cells, cancer vaccines, and oncolytic viruses. Here we review recent progress in the understanding of PM biology and evaluate relevant phase I-III clinical trials aimed at improving treatment for this disease. We also highlight ongoing and future clinical trials with promising candidates for PM therapy.
The 2026 European Association of Urology and American Society of Clinical Oncology (EAU-ASCO) guideline update reflects significant developments in the diagnosis and management of penile cancer. This review summarises the key changes and contrasts them with previous recommendations, with particular focus on staging, treatment, quality of life and emerging personalised approaches. The summary is based on a critical appraisal of the full 2026 guideline and its underpinning systematic reviews, with comparison to earlier versions. Recommendations were informed by structured literature assessment and expert panel consensus, incorporating evaluation of benefits and harms, evidence uncertainty and patient values. Major updates include refined pathological risk stratification, routine ultrasound (US)-guided nodal assessment, and broader guidance on organ-preserving surgery. There is support for selective genomic testing and clearer, restructured algorithms are introduced, including newly developed flow diagrams for nodal management, alongside an expanded evidence base for systemic therapy. Greater emphasis is placed on survivorship, centralisation of care and rationalisation of follow-up. However, many recommendations remain informed by retrospective data and expert consensus, reflecting the rarity of the disease and limited prospective evidence. The updated guideline promotes more nuanced selection of organ-preserving strategies, earlier detection of regional lymphatic disease, and holistic palliative care, while reinforcing the central role of shared decision-making. The new guidance for penile cancer aims to improve care, personalise treatment and better address quality of life, while acknowledging that further research is still needed.
The gut microbiota (GM) is a complex microbial ecosystem, and its alteration contributes to the development of several diseases including multiple sclerosis (MS). Progressive research concerning neurodegenerative diseases and GM reveals that GM dysbiosis has been linked to fostering the development and progression of MS. Among existing bacteria, F.prausnitzii and A.muciniphila are key species implicated in this disease. Thus, the present study systematically reviewed and synthesized the research on the involvement of F. prausnitzii and A. muciniphila in MS patients versus healthy individuals. We systematically searched PubMed, MEDLINE, EMBASE, and Web of Science databases for relevant published articles from January 2010 till January 2023. Out of 400 articles, 16 met the required criteria. The included research investigations originated from the US, Germany, Norway, Egypt, Iran, Brazil, China, the UK, and Romania. Most publications reported decreased levels of F. prausnitzii and increased levels of A. muciniphila in MS patients compared to controls. This review underscored the importance of the F. prausnitzii and A. muciniphila in MS, which could explain the chronic inflammation that characterizes this disease and not only help in understanding its etiology and progression but also open new avenues for the treatment strategies focusing on gut health. Moreover, understanding the role of F. prausnitzii and A. muciniphila could lead to novel biomarkers for early detection and progression monitoring MS.
Vibriosis is a major bacterial disease that causes significant mortality in farmed shrimp worldwide. Numerous studies have explored strategies to prevent mass mortalities associated with vibriosis outbreaks. This study aimed to identify microalgal species with immunostimulant and anti-Vibrio properties for shrimp culture. Microalgal screening began with centrifugal supernatant extraction, followed by metabolite extraction using ethyl acetate. The metabolites were subjected to an anti-quorum sensing (QS) bioassay via the disc diffusion method, using Chromobacterium violaceum as an indicator strain on LB agar. Clear inhibition zones around the discs indicated anti-QS activity. Anti-Vibrio activity was assessed using the microalgae metabolites, with Vibrio harveyi as the target strain on TSA medium. Microalgal supernatant extracts were further tested for anti-Vibrio activity under both in vitro and in vivo conditions. The experiment followed a completely randomized design with five treatments and three replicates. Based on the bioassays, Melosira sp., Porphyridium sp., and Phaeodactylum tricornutum demonstrated the ability to inhibit Vibrio growth. Challenge test results indicated that extracts of P. tricornutum and Porphyridium sp. have strong potential to suppress pathogenic Vibrio in shrimp aquaculture.
The significance of intermediate-risk adverse pathological features in oral squamous cell carcinoma (OSCC) remains unclear. Consequently, the indications for postoperative radiotherapy (PORT) vary between hospitals. This study evaluates treatment patterns and outcomes of PORT for OSCC patients with intermediate-risk adverse pathological features in a real-world national cohort. All first primary OSCC patients (n = 683) with intermediate-risk adverse pathological features from the tumor treated between 2018 and 2021 in the Netherlands were included. Features were 1-5 mm resection margins, pT3-T4 classification, perineural invasion, worst pattern of invasion (WPOI) 4-5, or vaso-invasive growth. Odds ratios (ORs) for receiving PORT were calculated using multivariable regression analysis. Hospital variation was assessed using funnel plots. Two-year overall survival (OS) and local control (LC) were evaluated using multivariable Cox regression analysis. The percentage of patients receiving PORT increased when more features were present (4.0% for 1 feature, 67% for all features). Significant predictors for PORT were pT3-T4 (OR 23.3), 1-5 mm margin (OR 3.72), WPOI 4-5 (OR 1.83) and perineural invasion (OR4.75). Patients with vaso-invasive growth (OR 0.19) and increasing age (OR 0.96) received PORT less often. Hospital differences in PORT treatment remained after correction for confounders. PORT did not significantly improve the adjusted hazard ratio for LC (1.56, p = 0.36) and OS (0.55, p = 0.08). Of the tumor-related pathological features, pT3-pT4 contributed the most to PORT treatment in OSCC. Significant hospital differences remained after correction for confounding factors. Future research should focus on guideline consensus to prevent over- and undertreatment.
Prostate-specific antigen (PSA)-based prostate cancer (PCa) screening can be improved by individualised, risk-stratified strategies. Comorbidity influences life expectancy, so may affect benefits of screening. We evaluated whether the effect of PSA-screening on PCa-specific mortality (PCSM) differed between men with and without comorbidity at baseline. In the screening arm of the European Randomized Study of Screening for PCa Rotterdam, PSA-testing was offered every four years. Comorbidity was assessed at randomisation using a self-reported questionnaire, defined as no versus ≥ 1 according to the Charlson Comorbidity Index. Cumulative incidences for metastases and PCSM, accounting for competing risks, were estimated for both comorbidity strata. Rate ratios (RRs) of screening versus control were estimated, adjusted for age at randomisation, with an interaction-term. Absolute risk reductions were calculated. Main analyses were conducted in men 55-69 years; men ≥ 70 years were analysed separately. At 21 years, among men with comorbidity at baseline the risks of metastases (RR:0.87; 95%CI 0.64-1.17) and PCSM (RR:1.09; 95%CI 0.76-1.56) did not differ significantly between the screening and control arm. Without comorbidity, metastases (RR:0.62; 95%CI 0.52-0.72) and PCSM (RR:0.67; 95%CI 0.54-0.83) were lower in the screening arm than in the control arm. The absolute PCSM risk reduction was 5.4 per 1000 men (95%CI 2.4-8.2). No difference in PCSM was observed among men ≥ 70 years, regardless of comorbidity at baseline. PSA-screening did not reduce metastases and PCSM in men ≥ 55 years with comorbidity. In contrast, it did in men 55-69 years without comorbidity. This supports consideration of comorbidities in screening.
Tomato productivity and fruit quality are often constrained by low nutrient availability and reliance on chemical fertilizers. The present study aimed to provide sustainable alternatives to chemicals by evaluating the potential of indigenous endophytic bacterial isolates of plants grown in sandy loam soils of semi-arid region, Haryana, India to enhance tomato growth and yield. Out of twenty isolates, Bacillus cereus L6, Bacillus cereus S4, and Alcaligenes faecalis TMG-5, exhibited the maximum production of Indole-3- Acetic acid, siderophore, ammonia and phosphate solubilisation. B. cereus L6 treatment enhanced seed germination (16.5%), radicle length (83.9%), plumule length (67.8%) and vigor index versus chemical fertilizer control in-vitro conditions. A consortium of B. cereus L6, B. cereus S4, and A. faecalis TMG-5 increased root length (49.0%), plant height (25.0%), stem girth (9.0%), leaf area (25.0%), relative water content (26.0%) and fruit yield (33.0%) versus chemical fertilizer control under pot experiment. The bacterial treatment increased the quality traits of tomato, including β-carotene (24%), chlorophyll content (34%), ascorbic acid (15.7%), firmness (21%), and total soluble solids (14%) that leads to increase the shelf life of tomato. The bacterial consortium significantly improved root fresh weight (63.0%), root dry weight (57.0%), shoot fresh weight (56.0%), shoot dry weight (36.0%) and soil dehydrogenase activity at mid (27.0%) and harvest stage (39.0%). The employment of indigenous endophytic bacteria having plant growth promoting traits synergistically increased tomato yield, quality and nutritional content. The single time application of such biofertilizers is an economic and user-friendly approach and caters to Sustainable Development Goals.
The diagnosis and treatment of hematologic malignancies has undergone significant advancements over the past few decades, resulting in enhanced outcomes. For hematologic malignancies diagnosed during pregnancy, this poses new questions. As possibilities continue to expand and the rising global incidence results in an increasing number of diagnoses within the pregnant population, there is a pressing need to gain a deeper understanding of the potential options for pregnant women and the impact on the newborn. As knowledge of the effects of cancer treatment increases, more women are receiving adequate cancer diagnosis and treatment during pregnancy. This paper presents an expert opinion on the use of diagnostic modalities and treatment options, including chemotherapy, radiation therapy, and immunotherapy, for acute leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, myeloproliferative neoplasms, aplastic anemia, and multiple myeloma during pregnancy.
BRCA1/2 pathogenic variant (PV) carriers have an increased risk of tubo-ovarian cancer. They are recommended to have a risk-reducing salpingo-oophorectomy around age 40, resulting in premature menopause. The alternative risk-reducing salpingectomy (RRS) with delayed oophorectomy (DO) postpones this. We present the five year results of a nationwide preference trial (TUBA study) comparing menopause-related quality of life (QoL) after RRS/DO to salpingo-oophorectomy. Premenopausal BRCA1/2-PV carriers aged 25 to 40 (BRCA1) or 25 to 45 (BRCA2) chose RRS/DO or salpingo-oophorectomy with or without hormonal replacement therapy (HRT). We compared QoL (Greene Climacteric Scale) between RRS/DO and salpingo-oophorectomy without HRT five years after surgery using linear mixed models. Secondarily, RRS/DO was compared to salpingo-oophorectomy with HRT. Women who underwent oophorectomy in the RRS/DO group were excluded in a sensitivity analysis. In total 410 (71.9%) participants chose RRS/DO and 160 (28.1%) salpingo-oophorectomy. Seventy-three (17.8%) participants underwent oophorectomy within five years after salpingectomy. The adjusted mean difference (aMD) in QoL was 1.8 (95%-confidence interval (CI) -0.6; 4.3) after salpingo-oophorectomy without HRT and 1.4 (95%-CI -0.4; 3.1) after salpingo-oophorectomy with HRT compared to RRS (with and without oophorectomy) at five years follow-up. The sensitivity analysis showed that QoL decreased less after RRS before oophorectomy compared to salpingo-oophorectomy without (aMD 2.4, 95%-CI 0.1; 4.8) and with HRT (aMD 1.9, 95% CI 0.1; 3.7). Postponing oophorectomy is key in preventing deterioration of QoL. QoL was similar five years after salpingectomy (with and without oophorectomy) compared to salpingo-oophorectomy (regardless of HRT use). However, QoL was higher when comparing salpingectomy without oophorectomy to salpingo-oophorectomy (regardless of HRT use).
Intestinal barrier dysfunction contributes to the progression of inflammatory bowel disease (IBD), yet current therapies provide limited symptom relief, are associated with substantial long-term adverse effects, and exhibit high recurrence rates. Lactobacillus reuteri (L. reuteri), a probiotic with strong colonisation capacity in the gastrointestinal tract, produces metabolites that regulate intestinal microecology. This study explored the therapeutic efficacy and underlying mechanisms of a newly isolated strain, L. reuteri MRD01, in a dextran sodium sulfate (DSS)-induced colitis model. Our results showed that L. reuteri MRD01 effectively mitigated DSS-induced colitis in mice. Administration of MRD01 alleviated body weight loss and partially recovered body weight, attenuated colon shortening, and significantly reduced the disease activity index (DAI), spleen index, and histopathological damage scores. The strain increased MUC2 expression and goblet cell numbers, possibly enhancing mucin secretion and reinforcing the intestinal mucosal barrier. Additionally, MRD01 improved epithelial integrity by upregulating zonula occludens-1 (ZO-1) and occludin expression, and reducing the leakage of fluorescein isothiocyanate-dextran (FITC-dextran; FD4). The strain modulated the inflammatory response by downregulating interleukin (IL)-1β, IL-6, and tumour necrosis factor-α (TNF-α), whereas enhancing IL-10 expression. This cytokine modulation rebalanced macrophage polarisation and inhibited the Toll-like receptor 4 (TLR4)-nuclear factor-κB (NF-κB)-NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway, thereby attenuating systemic inflammation. Mechanistically, L. reuteri MRD01 altered the gut microbial composition, contributing to the restoration of intestinal homeostasis. These results substantially revealed that L. reuteri MRD01 alleviated colitis by synergistically enhancing mucosal protection, epithelial integrity, immune homeostasis, and microbial balance. These findings support its therapeutic potential as a probiotic-based strategy for IBD management.
The human microbiota represents one of the body's most influential biological systems, engaging in constant metabolic, immunological, and neuroendocrine communication with the host. Disruption of this intricate ecosystem, or dysbiosis, has emerged as a fundamental determinant in the onset and progression of numerous chronic diseases. This review consolidates contemporary evidence on how alterations in microbial composition, metabolite production, and barrier integrity contribute to pathophysiological changes across multiple organ systems. Gut-derived metabolites-including short-chain fatty acids, bile acid derivatives, trimethylamine-N-oxide, and lipopolysaccharide-serve as key mediators linking microbial imbalance to systemic inflammation, metabolic dysfunction, autoimmunity, and neurodegeneration. We outline the mechanistic pathways through which dysbiosis promotes hypertension, atherosclerosis, obesity, type 2 diabetes, Parkinson's disease, Alzheimer's disease, rheumatoid arthritis, inflammatory bowel disease, asthma, chronic obstructive pulmonary disease, urinary tract infections, and chronic kidney disease. Particular emphasis is placed on the gut-brain, gut-lung, and gut-kidney axes, which facilitate bidirectional immune and metabolic signalling between the intestine and distant tissues. Additionally, the review highlights emerging therapeutic interventions aimed at restoring microbial homeostasis, including targeted dietary strategies, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and microbiome-directed pharmacological approaches. Collectively, the evidence positions the microbiota as a central regulator of human health and disease, offering a compelling platform for next-generation diagnostic and therapeutic innovation. Advancing mechanistic understanding of host-microbe interactions will be essential to developing personalized microbiome-based strategies capable of preventing, mitigating, or reversing disease across diverse clinical contexts.
Bovine mastitis is one of the major challenges in dairy production, causing significant economic losses and emphasizing the need for alternatives to the indiscriminate use of antibiotics. Palo Santo (Bursera graveolens) essential oil (BEO) presents recognized biological properties that can be enhanced through nanoengineered delivery systems. This study aimed to chemically characterize the BEO of B. graveolens, develop a nanoemulsion containing the essential oil (BEO-NE), and evaluate its toxicological, antinociceptive, and antimicrobial activities against bovine mastitis-associated pathogens. The chemical composition of the BEO was determined by gas chromatography-mass spectrometry (GC-MS), identifying D-limonene (38.70%) as the major constituent. The BEO-NE was formulated using avocado oil as the oil phase and sodium alginate as a stabilizing agent. Toxicological and antinociceptive effects were assessed through in vivo assays, including acute toxicity, acetic acid-induced writhing, and the formalin test. Antimicrobial activity was evaluated by minimum inhibitory and bactericidal concentration assays against Staphylococcus spp., Corynebacterium bovis, Streptococcus uberis, and Prototheca bovis. The BEO-NE showed enhanced antimicrobial activity against Staphylococcus aureus, including MRSA isolates, while exhibiting lower efficacy against C. bovis and S. uberis compared with the free BEO, indicating pathogen-dependent selectivity. The formulation demonstrated a favorable safety profile, with no evidence of hepatotoxicity or behavioral alterations. The BEO also exhibited significant antinociceptive activity, mainly in the neurogenic phase of the formalin test (p < 0.05). In conclusion, the BEO-NE represents a promising strategy for controlling S. aureus, the main etiological agent of bovine mastitis, combining selective antimicrobial and antinociceptive effects.
Two novel anaerobic bacterial strains, designated JC010T and JC022T, were isolated from seawater samples collected in the Yongle Blue Hole, South China Sea. Phylogenetic analysis based on 16S rRNA gene sequences placed both strains within a distinct clade of the genus Maridesulfovibrio. Comparative 16S rRNA gene sequencing showed that the sequence similarity between the two isolates was 98.42%, while their similarities to all validly published Maridesulfovibrio species were below the 98.65% species threshold (JC010T: < 97.9%; JC022T: < 97.36%). Cells of both strains were Gram-stain-negative, motile vibrios with polar flagella, and exhibited obligately anaerobic metabolism. Strain-specific growth parameters were characterized: JC010T proliferated at 4-37 °C (optimum 28 °C), pH 4.0-9.0 (optimum 7.0) and in the presence of 1.0-5.5% NaCl (optimum 4.0%), whereas JC022T demonstrated a narrower temperature range (10-37 °C; optimum 28 ℃), similar pH tolerance (4.0-8.0; optimum 7.0), and a distinct salinity preference (2.5-6.0% NaCl; optimum 3.0%). Chemotaxonomic analyses revealed that while the two strains exhibited several common characteristics, including menaquinone-7 (MK-7) as the predominant respiratory quinone, and major fatty acids comprising summed features 3 (C16:1 ω6c/ω7c), 9 (iso-C17:1 ω9c/C16:0 10-methyl), C16:0, and iso-C15:0, certain differences between them were also identified. The conserved polar lipid profiles included one phosphatidylcholine (PC), one phosphatidylethanolamine (PE), one phosphatidylglycerol (PG), and two phospholipids (PL1-2). Notably, JC022T contained three additional unidentified lipids that were not present in JC010T. Genomic comparisons further reinforced their taxonomic distinctness. The DNA G+C content was 49.8 mol% for JC010T and 48.0 mol% for JC022T. Based on the polyphasic characterization, we propose two novel species: Maridesulfovibrio caeruleilacunae sp. nov. (type strain JC010T = JCM 39061T = MCCC 1K03847T) and Maridesulfovibrio oucae sp. nov. (type strain JC022T = JCM 39062T = MCCC 1K03848T).
Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer after invasive breast cancer of no special type (IBC-NST). This retrospective analysis of the MINDACT trial investigated transcriptomic differences between estrogen receptor-positive/HER2-negative (ER+/HER2-) ILC versus ER+/HER2- IBC-NST, classic and non-classic ER+/HER2- ILC, and, recurring and non-recurring ER+/HER2- ILC in patients with a low genomic risk and either a low (cL/gL) or high clinical risk (cH/gL). We analyzed 4261 ER+/HER2- tumors (63.7%, 464 ILC, 3798 IBC-NST) with central pathology review. Differential gene expression analysis was adjusted for age and grade, followed by gene set enrichment analysis. Adjusted regression models evaluated associations of transcriptomic profiles with disease-free (DFS) and distant recurrence-free survival (DRFS). An increased expression of CDH1 (E-cadherin) in IBC-NST compared to ILC was observed. ILC showed more uptake of extracellular lipid sources (LPL, CD36, LEP, LEPR), while IBC-NST favored lipid synthesis (FASN). Decreased ER-signaling, increased PI3K/Akt-signaling, and differences related to the extracellular matrix was also observed in ILC. Classic and non-classic ILC differed subtly, notably in cell cycle regulation. In ER+/HER2- ILC patients with a cL/gL risk, enrichment of apoptosis, inflammatory response, hypoxia and oncogenic signaling (PI3K/Akt, Ras, c-Myc) was associated with worse survival. In contrast, in the cH/gL group, associations between ILC transcriptomic features and survival were more subtle. This represents the largest transcriptomic dataset for ILC from a clinical trial with central histology review. Findings may provide insights to refine treatment and relapse risk assessment for ILC patients.