Search Results (94)

Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to cancer cell plasticity and facilitates epithelial-to-mesenchymal transition (EMT). Key histone modifiers, including KLF5, EZH2, and the demethylases KDM4/6, regulate osteoclastogenic signaling pathways and the transition between metastatic dormancy and reactivation. Simultaneously, SWI/SNF chromatin remodelers such as BRG1 and BRM reconfigure enhancer–promoter interactions that promote bone tropism. Non-coding RNAs, including miRNAs, lncRNAs, and circRNAs (e.g., miR-34a, NORAD, circIKBKB), circulate via exosomes to modulate the RANKL/OPG axis, thereby conditioning the bone microenvironment and fostering the formation of a pre-metastatic niche. These mechanistic insights have accelerated the development of epigenetic therapies. DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling. Inhibitors targeting EZH2, BET proteins, and KDM1A are now advancing through early-phase clinical trials, often in combination with bisphosphonates or immune checkpoint inhibitors. Moreover, novel approaches such as CRISPR/dCas9-based epigenome editing and RNA-targeted therapies offer locus-specific reprogramming potential. Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases. Full article

Background and Objectives: This study investigated changes in quality of life (QOL), depression, and menopausal symptoms after surgical menopause, and the efficacy of hormone replacement therapy (HRT) in gynecological cancer survivors (GCS). Materials and Methods: Participants undergoing gynecologic cancer surgery (N = 155) were divided into those who received HRT after surgical menopause (SH, N = 47), those after surgical menopause (SM, N = 54), and those after natural menopause (NM, N = 54). QOL, depression, and menopausal symptoms were assessed using the Functional Assessment of Cancer Therapy-General (FACT-G), Center for Epidemiologic Studies Depression Scale (CES-D), and Endocrine Symptoms Subscale-19 (ESS-19), respectively. Assessments were conducted before and at 6 and 12 months after surgery. Results: In SH and SM, FACT-G and CES-D were worst before surgery, gradually improved by 6 months, and remained stable for the following 6 months. FACT-G and CES-D showed an inverse relationship. ESS-19 did not change in SH and SM for 12 months. Among the items on the ESS-19, worsened vasomotor symptoms (VMSs), assessed with ES1, showed more improvement in SH than in SM, while worsened arthralgia assessed with BRM1 was maintained in SM. Multivariate analysis showed that HRT was not independently correlated with changes in QOL and depression status. Conclusions: In GCS, the prevalence of depression was highest at cancer disclosure along with declining QOL. QOL gradually improved by 6 months after surgery in SH and SM, but not in NM. Although menopausal HRT is known to alleviate VMS, anxiety, and depression, its efficacy for cancer-related emotional distress and the associated decline in QOL seems limited. Full article

Utilizing supplementary cementitious materials is an effective way to fabricate low-carbon cement-based materials. In this paper, the composite mortars with good properties were prepared by mixing them with basic oxygen furnace slag (BOFS), Bayer red mud (BRM), and phosphogypsum (PG). The influences of the replacement amounts of BRM and PG on the mechanical properties, hydration characteristic, chloride corrosion resistance, and microstructure of the materials were investigated. The results showed that simply adding 10 wt% BRM slightly modified the properties of the composite mortars. With the increase in PG, the mechanical strength and corrosion resistance coefficient K_C of the mortars first increased and then decreased, in contrast to the chloride migration coefficient D_RCM and electric flux Q. Among the samples, sample S3, with 6 wt% BRM and 4 wt% PG, had the best properties, a flexural strength of 6.6 MPa, and a compressive strength of 43.5 MPa at a curing age of 28 d. And the values of D_RCM and Q of the sample, respectively, decreased by 44.06% and 22.83% compared with the control sample, along with the value of K_C corroded after 120 d increasing by 16.33%. The microstructure analysis indicated that the alkali activation of BRM promoted the generation of lamellar portlandite and reticular and granular C-S-H gel. The free aluminum in BRM could dissolve into C-S-H gel to induce the generation of C-A-S-H gel. Furthermore, the generated amount of ettringite increased by adding PG. The aforementioned improvement in mechanical properties is primarily attributed to BRM promoting the hydration of the composite mortars and inducing the transformation of the C-S-H gel into C-A-S-H gel, and PG promoting the generation of ettringite. Moreover, the filling effects of BRM and PG decreased the porosity and number of harmful pores. It increased the compactness of the microstructure to endow the composite mortars with excellent chloride corrosion resistance. Full article

Objective: We explored the impact of uncertain resection in lung cancer on overall survival and disease-free survival. Methods: We performed an exhaustive literature review of all studies comparing prognosis after resection according to the IASLC classification, from the PubMed, Cochrane, MEDLINE, and Google Scholar databases. Results: Overall, 68 original studies were included, of which 67 were retrospective and 1 was prospective, with 81 785 patients included over 46 years. R(un) reclassification was mostly caused by a lack of hilar or mediastinal node dissection, or because of metastasis in the highest node. R(un) is a strong factor for higher recurrence and mortality, while its effects seem limited in early stages. Carcinoma in situ at bronchial margin resection (CIS BRM) does not show an effect on survival, while positive pleural cytology (Cy+) and positive highest mediastinal lymph node (HMLN+) appear to be highly predictive of recurrence and death. Discussion: The R(un) classification of the IASLC appears highly relevant, especially in locally advanced stages IIb-IIIA, and helps to discriminate patients with poor prognosis despite being classified as R0 in the UICC classification. Conclusions: The use of this more precise classification would allow for better stratification of recurrence risk and more effective use of adjuvant therapies. Cy+ patients should receive adjuvant chemotherapy, while CIS BRM patients could likely benefit from endoscopic surveillance to detect local recurrences. HMLN+ patients should be considered at high risk of recurrence, and adjuvant radio-chemotherapy should be considered. Full article

Face anti-spoofing detection is crucial for identity verification and security monitoring. However, existing single-modal models struggle with feature extraction under complex lighting conditions and background variations. Moreover, the feature distributions of live and spoofed samples often overlap, resulting in suboptimal classification performance. To address these issues, we propose a jointly optimized framework integrating the Enhanced Channel Attention (ECA) mechanism and the Intra-Class Differentiator (ICD). The ECA module extracts features through deep convolution, while the Bottleneck Reconstruction Module (BRM) employs a channel compression–expansion mechanism to refine spatial feature selection. Furthermore, the channel attention mechanism enhances key channel representation. Meanwhile, the ICD mechanism enforces intra-class compactness and inter-class separability, optimizing feature distribution both within and across classes, thereby improving feature learning and generalization performance. Experimental results show that our framework achieves average classification error rates (ACERs) of 2.45%, 1.16%, 1.74%, and 2.17% on the CASIA-SURF, CASIA-SURF CeFA, CASIA-FASD, and OULU-NPU datasets, outperforming existing methods. Full article

Divergent thinking tests are popular instruments to measure a person’s creativity. They often involve scoring fluency, which refers to the count of ideas generated in response to a prompt. The two-parameter Poisson counts model (2PPCM), a generalization of the Rasch Poisson counts model (RPCM) that includes discrimination parameters, has been proposed as a useful approach to analyze fluency scores in creativity tasks, but its estimation was presented in the context of generalized structural equation modeling (GSEM) commercial software (e.g., Mplus). Here, we show how the 2PPCM (and RPCM) can be estimated in a Bayesian multilevel regression framework and interpreted using the R package brms, which provides an interface for the Stan programming language. We illustrate this using an example dataset, which contains fluency scores for three tasks and 202 participants. We discuss model specification, estimation, convergence, fit and comparisons. Furthermore, we provide instructions on plotting item response functions, comparing models, calculating overdispersion and reliability, as well as extracting factor scores. Full article

Background: Macromastia is a well-known issue in breast reconstruction. Skin-reducing mastectomy (SRM) was introduced as a skin-sparing mastectomy that utilizes a skin reduction pattern similar to breast reduction or breast lift surgery, specifically to manage hypertrophic and pendulous breasts. Over time, numerous authors have contributed to refining the SRM technique, leading to the development of various technical variants. However, the diversity of approaches inspired by SRM has created confusion, and clear surgical indications are lacking. Methods: We propose a unifying concept called breast reshaping mastectomy (BRM), which encompasses all techniques based on SRM principles. The BRM aims not only to preserve and reduce the breast skin envelope but also to immediately reshape it for a more aesthetic outcome. This approach is applicable to all mastectomies where skin envelope preservation (with or without the nipple-areola complex) is oncologically safe, a modification of breast skin coverage is needed for better aesthetic results, and an implant-based reconstruction is planned. Results: To define the BRM concept, we reviewed the existing literature on SRM and its related techniques. Our analysis focused on four key elements: skin incision pattern, implant coverage strategy, nipple-areola complex (NAC) management, and the choice between two-stage and direct-to-implant reconstruction. Conclusions: By integrating these four components into a single surgical framework, BRM provides a structured approach to breast reconstruction that enhances both oncologic safety and aesthetic outcomes. Standardizing these techniques could help clarify surgical indications and improve reconstructive planning for patients undergoing skin-sparing mastectomy. Full article

The massive stockpiles of Bayer-process red mud (BRM) severely compromise soil integrity, necessitating the urgent development of efficient large-scale utilization strategies. BRM contains large amounts of calcium, silicon, and aluminum. Theoretically, water glass and flue gas desulfurization gypsum (FGD) can increase the active substances in BRM, making it a cementitious raw material capable of replacing cement. This study pioneers a novel activation strategy utilizing water glass–FGD synergism to amplify the BRM reactivity, enabling an increased dosage in construction materials through enhanced pozzolanic activity. They were blended into the cement at different ratios to prepare a grouting material (BF-C) for fissure sealing in mine rock strata. The hydration mechanism of BF-C was analyzed from a micro perspective by XRD, FTIR, ICP-OES, and SEM-EDS, and combined with the Ca/(Si + Al) ratio to reveal its hydration synergy. The results showed that the 3 d and 28 d strength of 70% BRM-FGD reached 8.94 MPa and 13.71 MPa, respectively. At this ratio, the hydration synergy of BF-C was the strongest. The addition of water glass and FGD can directly modulate the Ca/(Si + Al) ratio of the system to an optimal value of 0.94, which promotes the formation of early hydration products. C-S-H gel, calcite, and C(N)-A-S-H are the main hydration products of BF-C. C-S-H gels are encapsulated on cancrinite, and their three-dimensional network structures are dense. Meanwhile, C(N)-A-S-H crystals are interspersed between C-S-H gels, making the structure more stable. This achievement introduces an innovative method for the large-scale utilization of Bayer red mud, providing an effective solution in grouting technology using solid waste as raw material. Full article

Lalguard C99 WP, based on the Cordyceps javanica BRM 27666 strain, is registered in Brazil for whitefly control. Spatial prediction is crucial for optimizing its field use and efficacy. In this study, the optimal temperature for mycelial growth and conidial production of C. javanica is 25–30 °C, with no growth at 33–35 °C. The highest nymphal mortality occurred at 25 and 30 °C, showing lower LT₅₀ values at 30 °C. Mycelial growth was similar at 15, 20, 25, 30, and 35 °C when the fungus was exposed for 6 h and then transferred to a 27.4 °C environment; however, growth was slower at 35 °C with daily 6 h exposure alternating over 18 h at room temperature (mean of 28.5 °C). When the second instar whitefly nymphs were exposed for 6 h or 6 h daily at 15, 20, 25, 30, and 35 °C, followed by 7 days at fluctuating temperatures (mean of 28.4–30.2 °C), nymphal mortality was similar across temperatures. Although other abiotic factors (solar radiation, humidity, rainfall, etc.) must be considered for fungal efficacy, spatial predictions based on fluctuating temperatures indicated that C. javanica is suitable for use throughout Brazil, though its performance varied at constant temperatures in different locations. Full article

Interocclusal records (IORs) created with bite registration materials (BRMs) accurately reflect the opposing teeth’s physiological and anatomical associations in digital and traditional dentistry. This study assessed the linear dimensional accuracy of vinyl polysiloxane-based scannable and transparent BRMs over obligatory clinical time intervals (1, 24, 72, and 168 h/s). A total of 3 scannable [Flexitime Bite, Occlufast CAD, Virtual CADBite] and 3 transparent [Maxill Bite, Charmflex Bite, Defend ClearBite] VPS-based BRMs were divided into 28 subgroups by time interval: 1, 24, 72, and 168 h/s. Stereomicroscope measurements of 420 standardised disk-shaped specimens with three distinct linear distances between crossing vertical and horizontal lines were taken. Comparisons with the conventional BRM determined the scannable and transparent BRMs’ accuracy, while comparisons with die dimensions yielded linear dimensional changes. Statistical analysis used median rank scores, interquartile range, and median. Using a one-way ANOVA rank and Dunn test, differences were assessed between and within groups at a probability ‘p’ value of 0.05 (p ≤ 0.05). Mean linear dimensions for CAD and transparent IOR materials were [−0.06 (−0.24%) to −0.15 (−0.6%)] and [−0.06 (0.24%) to −0.10 (0.40%)] millimetres, respectively. Virtual CADBite and Maxill Bite had the lowest linear disagreement after 1 h, but both showed significant variations at 7 days. Other commercial brands maintained their clinically acceptable linear accuracy (0.11). Flexitime Bite (CAD) was the sole material with a linear accuracy above the clinical threshold. IOR shrinkage reduced the linear dimensions in all materials. Until 7 days, all IOR materials except Flexitime bite (CAD) were clinically correct. Virtual CADBite and Maxill bite changed significantly during 1 h and 7 days. Full article

Background/Objectives: Respiratory syncytial virus (RSV) causes symptoms similar to a mild cold for adults, but in case of infants, it causes bronchitis and/or pneumonia, and in some cases, mortality. Mucosal immunity within the respiratory tract includes tissue-resident memory T (T_RM) cells and tissue-resident memory B (B_RM) cells, which provides rapid and efficient protection against RSV re-infection. Therefore, vaccine strategies should aim to generate mucosal immune responses. However, the interactions between RSV vaccines and mucosal immune responses within the respiratory tract are poorly understood. We evaluated a mucosal immune system following immunization by RSV vaccine with poly-sorbitol transporter (RSV-PST), a nanoparticle adjuvant. Methods: We intranasally immunized the RSV-PST and identified the systemic and mucosal immune responses. Furthermore, we challenged with RSV A2 strain after immunization and investigated the protective effects. Results: Consequently, antigen-specific CD8⁺ T_RM cells were markedly elevated in the lung parenchyma, yet exhibited impaired cytokine expression. In contrast, humoral immunity, with systemic antibody production from serum, but not in the respiratory tract, was significantly increased by RSV-PST immunization. Interestingly, the production of respiratory mucosal antigen-specific IgG after RSV A2 challenge dramatically increased in the bronchoalveolar lavage fluid (BALF) of the RSV-PST immunized group in the presence of FTY720, and the lung-infected RSV titer was significantly lower in this group. Furthermore, after RSV A2 challenge, CD69⁺ IgG⁺ B_RM cells were significantly increased in lung tissues in the RSV-PST group. Conclusions: The RSV-PST vaccine has protective effects against RSV infection by promoting both systemic and local humoral immunity rather than cellular immunity. Full article

Respiratory viruses present significant global health challenges due to their rapid evolution, efficient transmission, and zoonotic potential. These viruses primarily spread through aerosols and droplets, infecting respiratory epithelial cells and causing diseases of varying severity. While traditional intramuscular vaccines are effective in reducing severe illness and mortality, they often fail to induce sufficient mucosal immunity, thereby limiting their capacity to prevent viral transmission. Mucosal vaccines, which specifically target the respiratory tract’s mucosal surfaces, enhance the production of secretory IgA (sIgA) antibodies, neutralize pathogens, and promote the activation of tissue-resident memory B cells (BrMs) and local T cell responses, leading to more effective pathogen clearance and reduced disease severity. Bacillus subtilis spore surface display (BSSD) technology is emerging as a promising platform for the development of mucosal vaccines. By harnessing the stability and robustness of Bacillus subtilis spores to present antigens on their surface, BSSD technology offers several advantages, including enhanced stability, cost-effectiveness, and the ability to induce strong local immune responses. Furthermore, the application of BSSD technology in drug delivery systems opens new avenues for improving patient compliance and therapeutic efficacy in treating respiratory infections by directly targeting mucosal sites. This review examines the potential of BSSD technology in advancing mucosal vaccine development and explores its applications as a versatile drug delivery platform for combating respiratory viral infections. Full article

The need for antibiotics in commercial laying hens is increasing owing to intensive farming systems. Amoxicillin trihydrate (AMX), an aminopenicillin β-lactam antibiotic, exerts broad bactericidal activity. However, its short half-life necessitates frequent administration to ensure efficacy, thus limiting its use. Herein, we investigated the effect of concurrent administration of bromhexine hydrochloride (BRM), a mucolytic agent, on AMX pharmacokinetics, performing a comparative pharmacokinetic analysis of AMX administration alone and in combination with BRM. AMX (50 mg/kg) was administered by oral gavage once daily for three days alone or in combination with 10 mg/kg BRM. Plasma and egg samples were collected to evaluate pharmacokinetic profiles and egg residues. The area under the curve and maximum plasma concentration values were significantly higher in the AMX + BRM group than the AMX only group. However, there were no significant differences in AMX half-life in the elimination phase (T_1/2), elimination rate constant (k_el), or apparent clearance (CL/F) values. In the egg residue study, the withdrawal period for AMX was 5 days in both groups, with no significant difference when using the maximum residue limit (MRL) of 10 μg/kg. The concentration of BRM in the eggs remained at 100 μg/kg up to the fourth day following drug administration. Conclusion: These results confirmed that BRM co-administration increased systemic exposure to AMX, with a negligible residual impact of amoxicillin in eggs. Full article

Background/Objectives: Around 20% of cancer patients will develop brain metastases (BrMs), with 15–25% occurring in the posterior fossa (PF). Although the effectiveness of systemic therapies is increasing, surgery followed by stereotactic radiosurgery (S+SRS) versus definitive SRS remains the mainstay of treatment. Given the space restrictions within the PF, patients with BrMs in this location are at higher risk of brainstem compression, hydrocephalus, herniation, coma, and death. However, the criteria for treating large PF BrMs with S+SRS versus definitive SRS remains unclear. Methods: We reviewed a prospective registry database (2009 to 2020) and identified 64 patients with large PF BrMs (≥4 cc) treated with SRS or S+SRS. Clinical and radiological parameters were analyzed. The two endpoints were overall survival (OS) and local failure (LF). Results: Patients in the S+SRS group were more highly symptomatic than patients in the SRS group. Gait imbalance and intracranial pressure symptoms were 97% and 80%, and 47% and 35% for S+SRS and SRS, respectively. Radiologically, there were significant differences in the mean volume of the lesions [6.7 cm³ in SRS vs. 29.8 cm³ in the S+SRS cohort, (p < 0.001)]; compression of the fourth ventricle [47% in SRS vs. 96% in S+SRS cohort, (p < 0.001)]; and hydrocephalus [0% in SRS vs. 29% in S+SRS cohort, (p < 0.001)]. Patients treated with S+SRS had a higher Graded Prognostic Assessment (GPA). LF was 12 and 17 months for SRS and S+SRS, respectively. Moreover, the S+SRS group had improved OS (12 vs. 26 months, p = 0.001). Conclusions: A higher proportion of patients treated with S+SRS presented with hydrocephalus, fourth-ventricle compression, and larger lesion volumes. SRS-alone patients had a lower KPS, a lower GPA, and more brain metastases. S+SRS correlated with improved OS, suggesting that it should be seriously considered for patients with large PF-BrM. Full article

Background/Objectives: Brain metastases (BrMs) are a common complication of non-small cell lung cancer (NSCLC), present in up to 50% of patients. While the treatment of BrMs requires a multidisciplinary approach with surgery, radiotherapy (RT), and systemic therapy, the advances in molecular sequencing have improved outcomes in patients with targetable mutations. With a push towards the molecular characterization of cancers, we evaluated the outcomes by treatment modality at our institution with respect to prioritizing RT and targeted therapies. Methods: We identified the patients with NSCLC BrMs treated with surgical resection. The primary endpoints were in-brain freedom from progression (FFP) and overall survival (OS). The secondary endpoint included index lesion recurrence. The tumor molecular profiles were reviewed. The outcomes were evaluated by treatment modality: surgery followed by adjuvant RT and/or adjuvant systemic therapy. Results: In total, 155/272 (57%) patients who received adjuvant therapy with adequate follow-up were included in this analysis. The patients treated with combination therapy vs. monotherapy had a median FFP time of 10.72 months vs. 5.38 months, respectively (p = 0.072). The patients of Hispanic/Latino vs. non-Hispanic/Latino descent had a statistically significant worse OS of 12.75 months vs. 53.15 months, respectively (p = 0.015). The patients who received multimodality therapy had a trend towards a reduction in index lesion recurrences (χ² test, p = 0.063) with a statistically significant improvement in the patients receiving immunotherapy (χ² test, p = 0.0018). Conclusions: We found that systemic therapy combined with RT may have an increasing role in delaying the time to progression; however, there was no statistically significant relationship between OS and treatment modality. Full article