Breast density is a breast cancer risk factor. The accurate quantification of breast density requires reliable segmentation of dense tissue in mammograms, but it is a challenging task due to large variations in tissue appearance across hospitals and imaging devices. We propose MammoDenseSegNet, a new deep encoder-decoder convolutional neural network designed to enhance segmentation performance through two complementary modules: a) Adaptive dual attention module, which captures long-range spatial and channel interdependencies to provide focused attention on relevant dense tissue areas regardless of their location; and b) Multi kernel receptive field module, which enlarges the network's receptive field at the bottleneck layer to aggregate multi-scale contextual features. Additionally, a multi-scale dice loss with deep supervision guides learning across decoder levels to improve robustness. We evaluated MammoDenseSegNet on two public digital mammogram datasets (VinDR-Mammo and EMBED) and one private dataset, spanning a variety of breast densities and imaging artifacts in a total of 1499 images from 606 women. Statistical analysis was done using generalized linear models accounting for correlation among images from the same women and adjusting for potential confounders (proc genmod, proc mixed, SAS v.9.4, SAS Institute, Cary, NC). MammoDenseSegNet demonstrated consistently high performance across various conditions (with Recall ranging from 0.64 to 0.90 and Dice from 0.63 to 0.91) and significantly (p < 0.001) outperformed the publicly available state-of-the-art algorithm based on the VGG16 (with Recall from 0.04 to 0.91 and Dice from 0.06 to 0.82 across the same conditions). The improvement was largest for low-density tissue, where the baseline algorithm practically fails (with the mean Recall of 0.14 and Dice of 0.16) while MammoDenseSegNet remained clinically useful (with the mean Recall of 0.66 and Dice of 0.63).
Frozen shoulder, also known as adhesive capsulitis, is a common and disabling condition that causes shoulder pain and progressive stiffness. Patient information leaflets (PILs) are produced by UK National Health Service (NHS) Trusts to help patients understand frozen shoulder and treatment options. However, the content and consistency of these PILs and their alignment with national clinical guidance are currently unclear. This study aimed to identify, analyse and describe the non-surgical management recommendations presented in publicly available NHS Trust PILs for frozen shoulder and to assess their alignment with the National Institute for Health and Care Excellence (NICE) Clinical Knowledge Summary and British Elbow and Shoulder Society (BESS) best practice resources. An online search was undertaken by one reviewer to identify publicly available PILs produced by NHS Trusts detailing non-surgical management of frozen shoulder. Relevant data were extracted and analysed by one reviewer and verified by five reviewers. Descriptive statistics were used to summarise findings. Thirty-eight PILs were identified from 38 NHS Trusts with publication dates ranging from April 2013 to March 2025. Considerable variation was observed in the content, including reference to analgesia, activity modification, exercise prescription and corticosteroid injections. No single PIL reflected all key elements recommended in the NICE Clinical Knowledge Summary and BESS best practice. The findings demonstrate substantial variation in content, frequent misalignment with current national guidance and best practice exercise recommendations. Such variation may limit and may reduce the clarity, consistency and usefulness of information provided to patients.
People with HIV (PWH) exhibit persistent immune activation despite suppressive antiretroviral therapy, contributing to neurocognitive vulnerability. Marijuana use is common among PWH and may influence inflammatory pathways, but its in vivo immunologic effects in treated HIV remain unclear. In this cross-sectional study (Durham, NC; 2021-2023), 238 adults with and without HIV were grouped by chronic marijuana use. Soluble immune biomarkers were measured in plasma/serum, and log-transformed outcomes were analyzed using hierarchical multivariable regression. Seven biomarkers showed significant model fit: sCD163, IFN-γ, TNF-α, TNF-RII, CXCL10, CCL4, and VCAM-1. Among HIV-negative participants, marijuana use was linked to reduced CXCL10, suggesting disruption of IFN-γ-dependent chemotactic signaling. In contrast, HIV infection in the absence of marijuana use was associated with a broad, multi-pathway inflammatory profile, including TNF signaling, interferon activation, monocyte/macrophage activation, and endothelial recruitment. Among PWH, marijuana use did not modulate these effects, although CCL4 and VCAM-1 were not significantly elevated in this group compared to controls. However, these markers did not differ between marijuana-using and non-using PWH, suggesting a potential divergence from the broader inflammatory profile rather than a clear marijuana-associated attenuation. Cognitive analyses demonstrated a modest inverse association between memory performance and TNF-related markers, indicating that HIV-associated inflammatory signaling may relate to memory function, whereas marijuana-related cognitive effects require further study.
Fair distribution of limited health funding is a universal challenge for health systems. Decisions about funding new technologies provide a helpful lens on this complex issue. This study examined how two of the world's most mature centralised review processes for health technology funding, namely the Australian Pharmaceutical Benefits and Medical Services Advisory Committees (PBAC and MSAC) have approached fairness over time. Using the Accountability for Reasonableness (A4R) framework, which defines fair priority-setting through four conditions (Relevance, Publicity, Revision, and Enforcement), we conducted (i) a detailed document review of policy changes (2014-2022) and (ii) semi-structured interviews with decision-makers at PBAC and MSAC in 2014 (n = 12) and 2021/22 (n = 11). In both the document review and the interviews, we found increased alignment with A4R principles over time, including enhanced Relevance through increased consumer representation, increased Publicity of decision rationales, and greater Enforcement through broader committee deliberation. However, Revision was not a pressing concern of committee members at either time point despite notable policy changes that improved Revision. Persistent barriers to Publicity were identified, particularly the redaction of decision rationales in public summary documents due to sponsor confidentiality requirements and challenges of explaining nuanced deliberations rather than formulaic criteria. Our findings illustrate how A4R principles are applied in practice and highlight the challenge of balancing procedural fairness with substantive ethical considerations, such as equity and cost effectiveness, that underlie the criterion of Relevance.
The electrochemical co-reduction of CO2 and N2 to urea presents a sustainable alternative to conventional synthesis but faces substantial challenges. Here we design a catalyst by anchoring the ionic liquid (IL) 1-ethyl-2,3-dimethylimidazolium bromide onto a CuBi surface. The IL@CuBi catalyst delivers an exceptional Faradaic efficiency toward urea (FEurea) of 73.0% and a current density of 27.4 mA cm-2 in an H-type cell, with a production rate of 124.7 μmol cm-2 h-1. Detailed study indicates that during the co-reduction process, Emmim+ cations on IL@CuBi are first reduced to Emmim· radicals, which transfer electrons to H+ to generate H· radicals. This relayed electron-transfer pathway for H· radical generation bypasses the conventional formation from surface-adsorbed *H intermediates, thereby effectively suppressing the hydrogen evolution reaction. The generated H· radicals, acting as high-energy bullets, directly participate in subsequent hydrogenation steps, thereby substantially reducing the free energy barrier and enhancing reaction kinetics.
Regional diversity may influence the composition of human milk fat globule membrane (HMFGM) protein composition and protein glycosylation. Here, we first systematically evaluated the efficiency and stability of six methods for the extraction of HMFGM proteins from breast milk. The optimal method (methanol-chloroform precipitation of MFGM proteins, followed by solubilization in 0.4% SDS lysis buffer) was further applied to the proteome and N-glycoproteome analysis of 49 breast milk samples from five regions across China. Proteomic analysis revealed the geographically divergent expression of BST2, COCH, FUCA1 and FGFBP1 in MFGM. The parallel N-glycoproteomic profiling identified 4914 site-specific N-glycans mapping to 689 glycoproteins, 699 glycosylation sites, and 420 glycan structures. This multiomics study reveals region-specific variations in the molecular composition of HMFGM proteins and their N-glycoprotein derivatives, elucidating the structural and functional dynamics of the human HMFGM in representative regions of China.
Tetraspanin CD82/KAI1 inhibits cell movement and metastasis of malignant tumors, and reduced and lost expressions of CD82 predict worse outcomes of patients with malignant tumors. Here we found that CD82 inhibits both solitary and collective movement of tumor cells. The CD82 YVAA mutation, which affects CD82 trafficking, selectively abrogates CD82-mediated inhibition of collective migration. Cilengitide, at the concentration that specifically inhibits integrin αVβ3, also selectively blocks collective movement, underscoring a promotive role of integrin αVβ3 in this mode of cell motility. In contrast, integrin αVβ5 appears non-essential for collective migration, and both αVβ3 and αVβ5 are dispensable for solitary movement on fibronectin, highlighting distinct functions of different integrins in different modes of tumor cell movement. CD82 interacts with αVβ3 and αVβ5 integrins and downregulates their protein levels, while CD82 YVAA mutation relinquishes this downregulation without disrupting CD82 interactions with these integrins. Mechanistically, CD82, but not the YVAA mutant, considerably reduces digitation junction-the structure where integrin αVβ3 localizes-and likely directs integrin αVβ3 for lysosomal degradation, thereby lowering its level and suppressing collective migration. Thus, our study reveals that i) integrin αVβ3 promotes collective movement of tumor cells, ii) CD82 counteracts this by diminishing integrin αVβ3 and its presence in microextrusions, and iii) digitation junction likely participates in collective cell movement. Our study further demonstrates that endolysosomal trafficking of CD82 and integrin αVβ3 is needed for their collective movement-regulatory activities and that coupling of metastasis suppressor CD82/KAI1 with different partners regulates different modes of cell movement.
There is a complex relationship between gastroesophageal reflux disease (GORD), hiatus hernia, obesity, and metabolic bariatric surgery. We report the outcomes of laparoscopic hiatus hernia repair (HHR) with BIO-A® mesh in the management of GORD post LSG in patients who developed a hiatus hernia with migration of the proximal gastric sleeve. A retrospective review of 50 patients who previously underwent LSG and revisional surgery (HHR, n = 25; RYGB, n = 25) between 2011 and 2022. The modified DeMeester scoring system was used to assess the severity of the patient's GORD symptoms pre-HHR/pre-RYGB and 6 months post-op. Twenty-five patients underwent HHR with BIO-A® mesh following a previous LSG. The severity of GORD six months post-HHR was significantly lower (0.96 ± 0.84 vs. 2.60 ± 0.50, p = < 0.0001). After HHR, 3/25 (12%) patients had ongoing GORD symptoms that were not medically controlled and underwent conversion to RYGB. In contrast, 25 patients underwent direct conversion to RYGB following a previous LSG. The severity of GORD at 6 months post-RYBG was significantly lower (0.40 ± 0.50 vs. 2.36 ± 0.64, p = < 0.0001). At six months, there was no significant difference in GORD symptoms when HHR was compared with RYGB (3.32 ± 1.6 vs. 3.76 ± 1.54, p = 0.4296). In appropriately selected patients, HHR with BIO-A® mesh appears safe and effective in managing persistent GORD following LSG, within the limits of this study. However further research is needed to explore its role and the long-term outcomes.
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Ovarian cancer is a gynecological malignancy associated with high mortality and poses significant clinical challenges in early diagnosis and precision treatment. Although the rapid advancement of artificial intelligence (AI) has introduced novel approaches to this field, a comprehensive bibliometric overview remains lacking. This study aims to fill this gap by providing a systematic bibliometric analysis of this rapidly evolving domain. In this study, the Web of Science Core Collection (WoSCC) was used to retrieve literature on AI applications in ovarian cancer research published from 2006 to the search date (November 19, 2025). Using CiteSpace and VOSviewer, we conducted visual and quantitative analyses of publication trends, countries/regions, institutions, authors, journals, highly cited papers, and keywords. A total of 786 publications were included in the analysis. The annual publication output showed pronounced exponential growth, with a marked acceleration after 2019. China, the United States, and the United Kingdom were the leading contributing countries. Research hotspots centered on AI-assisted diagnosis, prognostic prediction models, radiomics, and biomarker discovery. The evolution of keywords indicated that frontier research has shifted from basic classification toward more advanced areas, including high-grade serous ovarian carcinoma, multimodal learning, and explainable AI. Research on AI in ovarian cancer has progressed rapidly, with international collaboration concentrated among leading contributors such as China, the USA, and the UK. Future efforts should prioritize the development of explainable and robust clinical AI systems, deeper integration of multimodal data, closer collaboration between clinicians and AI researchers, and high-quality data sharing to facilitate the translation of research findings into precise clinical practice.
The workshop on 'Reactive and therapy induced BM changes linked to systemic infectious and non-infectious disorders including MAS/HLH' of the 22nd meeting of the European Association for Haematopathology held in Dubrovnik, 2024, included 58 cases. These encompassed a broad range of infections, autoimmune disorders, malignancies and therapy-effects, or a combination of these factors, of which 28 had an associated Hemophagocytic Lymphohistiocytosis (HLH) / Macrophage Activation Syndrome (MAS). Histoplasmosis, the infection mostly associated with HLH, showed a wide variability of BM changes, with or without focal lesions. Leishmaniasis, less often associated with HLH, induced BM changes that mimic myelodysplastic syndrome. BM changes after COVID-19 infection included myeloid and megakaryocytic hypoplasia, erythroid hyperplasia, dyserythropoiesis, hemophagocytosis, and possibly ring granulomas. Other infectious causes included viruses (HHV-8, EBV, Parvovirus B19), mycobacterial infections, and human granulocytic anaplasmosis. HLH may arise in association with the full spectrum of EBV-related disorders, including acute infection, systemic chronic active EBV disease, viral reactivation, and EBV-associated malignancies. BM changes associated with autoimmune diseases included plasmacytosis, myeloid hyperplasia and hemophagocytosis, with or without meeting the criteria of MAS/HLH, the latter often triggered by a secondary infection or exacerbation of the disease. Haematologic malignancies (EBV-positive and negative) with HLH encompassed B-cell, T-/NK-cell, and myeloid neoplasms. In addition, the workshop included therapy-induced BM changes, such as differentiation syndrome, lenalidomide-associated B-ALL, therapy-related dysplasia, gelatinous transformation, CAR-T-induced BM hypoplasia, and CAR-T-associated HLH. Finally, the workshop demonstrated the presence of T-cell expansions in a variety of conditions, which should not be misinterpreted as T-cell malignancy.
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Migration is one of the most feared complications following lip filler. The use of a specific filler with a high degree of elasticity and cohesiveness could be the key to solve the problem if injections are performed in the correct anatomical plane. The purpose of this study was to describe the authors' 5-year experience with a new concept of lip filling, iLips. This reproducible approach combines elasticity and cohesiveness of a 25,5 mg/ml filler injected through superficial micro-tunnels in a virtual space between orbicularis muscle and mucosa creating a tridimensional net that respects lip dynamic also leading to a low risk of filler migration. A total of 4583 consecutive patients who underwent lip filler with iLips technique were enrolled in this prospective study. An objective evaluation on the aesthetic results was obtained by a jury composed of 3 external plastic surgeons using Lip Fullness Merz scale. PROMs were investigated through FACE-Q administration to the patients ("Psychological function", "Satisfaction with outcome" and "Satisfaction with lips" scales). Statistical analysis was performed through Prism10. Complications were reported. t-test with Welch's correction showed an improvement in Lip Fullness Merz score both in upper and lower lip (p<0.05). A similar trend was shown also for "Psychological function", "Satisfaction with outcome" and "Satisfaction with lips" mean values after the procedure. Just 2 cases of major vascular complications were reported. iLips ® seem to be a safe, highly reproducible, effective and satisfying approach for lip augmentation positively impacting also the patient's psychological sphere. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
N7-methylguanosine (m7G) modification plays a critical role in RNA metabolism and is increasingly recognized for its implications in cancer biology. It can influence RNA stability, translation efficiency, and gene expression regulation. However, the specific role of m7G modification and its downstream genes in thyroid carcinoma (THCA) is not well understood. To comprehensively explore the impact of m7G methylation modification and the m7G-related gene ZNF831 on THCA, this study aims to identify key genes influencing m7G modification in THCA, with a particular focus on clarifying the role of ZNF831. This study is expected to further elucidate the pathological mechanisms of THCA and fill the current research gap in this field. Weighted gene co-expression network (WGCNA) analysis was used to evaluate the expression of m7G-related genes in the THCA expression data from the GEO (Gene Expression Omnibus) datasets. Machine learning algorithms, including the least absolute shrinkage and selection operator (LASSO), gradient boosting decision tree (XGBoost), and random forest (RF), were used to identify the feature genes, including GPSM3 and ZNF831, in the TCGA-THCA dataset. Immunohistochemistry was used to identify the expression difference of ZNF831 in 3 THCA tissues and 3 normal tissues. Finally, the changes of proliferation and migration of THCA cells after overexpression of ZNF831 were investigated. This study investigated m7G-related genes in THCA, focusing on ZNF831 as a key tumor suppressor. Differential expression analysis revealed significant dysregulation of m7G-related genes in THCA. Functional and bioinformatics analyses, including gene set enrichment analysis and protein-protein interaction network construction, identified ZNF831 as a candidate gene. Experimental validation demonstrated that ZNF831 overexpression significantly reduced the proliferation and migration of THCA cells. Additionally, tumor microenvironment analysis showed a positive correlation between ZNF831 expression and immune cell infiltration, indicating its potential role in enhancing anti-tumor immunity. These findings underscore the importance of m7G modifications and m7G-related gene ZNF831 in THCA pathogenesis, highlighting their potential as therapeutic targets. Further research is needed to elucidate the molecular mechanisms and explore clinical applications of these findings.
Sexually transmitted infections (STIs) are continuing to rise in high-income countries, particularly among young adults. Increasing access to timely STI/HIV testing and treatment is key to reducing transmission. Web-accessed STI testing services have emerged as a pragmatic solution to improving access and uptake. However, these web-accessed alternatives do not always provide equivalent quality to in-person services. The scientific body of evidence around their development is limited and often not reported in detail, offering little guidance about design best practice. Translating a traditionally in-person service to a web-accessed one is a complex process that requires input from multiple stakeholders, including end users, clinical experts, and software developers, to support user acceptability, clinical safety, and technical feasibility. This manuscript outlines the evidence-based approach for establishing the clinical pathway for Test it, a statewide, publicly funded, web-accessed STI testing service targeting 16- to 29-year-olds in Victoria, Australia. We present the ten steps of the web-accessed clinical pathway and describe the iterative consultation and problem-solving process used to define them.
The role of periacetabular osteotomy (PAO) in symptomatic borderline hip dysplasia (borderline HD) remains controversial because the lateral centre-edge angle may not reflect global dysplastic morphology. We examined whether selected borderline dysplastic hips showed additional dysplastic features and compared mid- to long-term outcomes with frank hip dysplasia (frank HD). This retrospective comparative cohort study included 33 patients (35 hips) with borderline HD (18° ≤ lateral centre-edge angle < 25°) and 319 patients (357 hips) with frank HD (lateral centre-edge angle < 18°) treated with PAO from 1996 to 2009. Radiographic morphology, Kaplan-Meier total hip arthroplasty-free survival, and patient-reported outcome measures (PROMs) after 1:3 propensity score matching were analysed. In the borderline HD cohort, 33 hips (94.3%) met at least one frank HD criterion other than lateral centre-edge angle and 12 hips (34.3%) met three or more. Mean follow-up was 14.0 years in the borderline HD cohort and 13.9 years in the frank HD cohort. One borderline dysplastic hip and 50 frank dysplastic hips underwent total hip arthroplasty. The 20-year survival rate was 90.0% in borderline HD and 78.8% in frank HD (log-rank p = 0.101). Matched PROMs did not differ significantly between groups. Borderline dysplastic hips selected for PAO usually showed multidirectional dysplastic morphology resembling frank HD. In carefully selected symptomatic borderline HD, PAO was associated with favourable long-term survival and PROMs comparable with frank HD.