Breast cancer (BC) is the most frequently diagnosed cancer among women and the leading cause of cancer deaths in females globally. In the United States, more than 300,000 new cases of invasive BC are diagnosed annually, and more than 40,000 patients die of metastatic BC. Herein, we discuss the current and evolving management of invasive BC. Despite major progress, ongoing challenges include how best to optimize treatment based on BC subtype and how to address treatment resistance for patients with metastatic BC. Efforts to further refine surgical approaches, radiation therapy, and preoperative and postoperative systemic therapies are under way, as are attempts to further elucidate the utility of immunotherapy and targeted therapies in various BC care settings.

Accurate cancer subtype classification from single-transcriptome data remains challenging because of biological heterogeneity, measurement noise, and limited sample sizes. This study examined whether disease-gene priors add predictive information under strict separation of association-edge, patient-sample, and external-transfer boundaries. It also audited a historically selected 12-gene subset without claiming de novo discovery. Important mRNA Identification through Hybrid Fusion (ImRIHF) uses a layer attention graph convolutional network to learn cancer-specific association scores. A graph convolutional network for disease classification (GCNDC) then classifies subtypes after score-guided expression weighting. Association folds were masked before both Gaussian kernels and the heterogeneous graph were rebuilt. Patient preprocessing, feature selection, graph construction, tuning, and fitting remained training-contained. Twenty repeated five-fold refits described stability, while separate locked audits supplied paired effects. Patient-disjoint external transfer used frozen development predictors and no target-cohort fitting. Matched GCNDC and full-transcriptome controls bounded interpretation within one fixed 29-coordinate multiplicity family. UCEC remained feasibility-only because its locked audit contained 10 MSEAC cases. Leakage-controlled association AUPR and AUROC were 0.932 and 0.941, respectively. Non-UCEC locked effects versus matched GCNDC ranged from $+0.027$ to $+0.035$; the UCEC effect was $+0.032$ and remained descriptive. Strict-common external effects were $+0.034$ in METABRIC, $+0.026$ in CGGA, and $+0.036$ in GSE14333. Of 12 historical challenge genes, 11 mapped, 4 were BH-significant, and 2 were both direction-concordant and BH-significant. The frozen disease-guided rule showed modest positive differences from matched controls in the named retrospective cohorts. Full-transcriptome controls, UCEC feasibility limits, and source-specific transfer boundaries restrict this result. The analyses do not establish generic superiority, prospective validity, clinical utility, population generalization, causality, or a validated biomarker panel.

IntroductionMedullary thyroid carcinoma (MTC) is an aggressive neuroendocrine malignancy with limited diagnostic strategies and inherent resistance to conventional therapies. Novel multifunctional Nanotheranostics are urgently needed to improve MTC treatment outcomes. This study aimed to construct a low-intensity focused ultrasound (LIFU)-responsive biomimetic nanoparticle system integrating multiple therapeutic modalities and dual-modal imaging for in vitro combined treatment of MTC.MethodsA tumor cell membrane-camouflaged lipid nanoparticle (MHGA@P-LNs) was fabricated to co-load hematoporphyrin monomethyl ether (HMME), glucose oxidase (GOx), AQ4N, and perfluorohexane (PFH). In vitro assays characterized physicochemical properties, LIFU responsiveness, cellular uptake, reactive oxygen species production, cytotoxicity, apoptosis, migration, and hemocompatibility. All experiments were repeated in triplicate (n = 3).ResultsMHGA@P-LNs exhibited a uniform core-shell morphology, favorable colloidal stability, and high drug encapsulation efficiency. Under LIFU irradiation, the system generated ultrasound/photoacoustic signals, increased intracellular ROS-associated fluorescence, and enhanced uptake by MZ-CRC-1 cells. Cell viability decreased to 0.9%, the total apoptosis rate reached 86.8%, and wound closure was 3.7%. The hemolysis rate remained below 3% in a mouse red blood cell assay. These results are limited to the in vitro experimental conditions.ConclusionThe in vitro data support further investigation of MHGA@P-LNs as a LIFU-responsive, image-guided combination-therapy platform for medullary thyroid carcinoma. The present findings do not establish in vivo tumor accumulation, prolonged circulation, immune evasion, metastatic targeting, systemic safety, or clinical translatability; these outcomes require dedicated animal studies.

Stereotactic radiosurgery and radiotherapy (SRS/SRT) for brain metastases is a rapidly evolving field, driven by continuous refinement of dosimetric strategies and technological advances in treatment platforms. This narrative review synthesizes current evidence on the dosimetric characteristics of major SRS/SRT platforms-Gamma Knife, CyberKnife, ZAP-X, linear accelerators, helical tomotherapy, and proton therapy-and evaluates their comparative strengths, limitations, and optimal clinical applications. We identify distinct dosimetric trade-offs among platforms with respect to dose conformity, gradient fall-off, normal tissue sparing, and treatment efficiency. Gamma Knife remains a dosimetric benchmark for dose gradient steepness, particularly for small targets (e.g., <1 cm in diameter). CyberKnife offers high conformity and may benefit lesions adjacent to critical organs, although treatment efficiency diminishes with increasing numbers of metastases. The novel, self-shielded ZAP-X system delivers a dose gradient comparable to that of Gamma Knife and achieves favorable sparing of normal brain tissue at intermediate-to-high dose levels. Linear accelerator-based techniques-especially single-isocenter non-coplanar volumetric modulated arc therapy and dynamic conformal arc therapy-are widely adopted for multiple brain metastases owing to their high delivery efficiency and continually improving plan quality. Helical tomotherapy provides reliable plan deliverability, whereas proton therapy offers a theoretical advantage in reducing low-dose exposure to the whole brain and sparing adjacent organs at risk, owing to the Bragg peak. The available evidence indicates that no single platform is universally optimal, and dosimetric differences should be interpreted with caution given the absence of prospective comparative clinical outcome data. Treatment platform selection should therefore be individualized, integrating disease characteristics (e.g., number, volume, location, and geometry of targets), institutional resources, and established clinical priorities. Future integration of advanced technologies-including FLASH radiotherapy and artificial intelligence-may further personalize the management of brain metastases.

TP53 myeloid neoplasms are being increasingly encountered in clinical practice and have been recognised in 2022, as a unique entity in the setting of functional loss of the two copies of the gene. The classification of myeloid neoplasm based on presence of biallelic (multi-hit) TP53 should precede morphological classification. The identification of biallelic (multi-hit) inactivation continues to evolve and is a matter of great debate balancing definitive biallelic identification via assays, pathology classifications, and clinical applicability. There is clear interplay between myeloblast percentage, TP53 allelic state, and cytogenetics as most TP53 cases encountered (~90%) are associated with poor outcomes driven by those variables and can be approached similarly. Only a small subset of individuals with monoallelic (single-hit) TP53 mutation status and no concomitant increased myeloblasts or complex cytogenetics have better outcomes and perhaps can be managed as non-TP53 cases. In this paper, we review definition and classification of TP53 myeloid neoplasms, highlight outcomes, and discuss the current standard of care and clinical research efforts crucially needed for this subtype of disease.

Complement-dependent cytotoxicity (CDC) of CD38 monoclonal antibodies has been associated with infusion-related reactions and might contribute to reduced clinical efficacy of CDC-reliant CD38 antibodies, particularly in patients with relapsed or refractory multiple myeloma with 1q21+. We aimed to evaluate felzartamab, a novel anti-CD38 monoclonal antibody that retains potent antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis while exhibiting markedly attenuated CDC activity in Chinese patients with relapsed or refractory multiple myeloma.

In this open-label, parallel-controlled, randomised, phase 3 trial conducted at 41 hospitals in China, adults aged 18 years or older with relapsed or refractory multiple myeloma who had received at least one previous line of systemic therapy, and were not refractory to lenalidomide were enrolled. Patients were randomly assigned (2:1) through a central interactive web response system, stratified by International Staging System stage, number of previous lines of therapy, and previous lenalidomide exposure, to receive intravenous felzartamab (16 mg/kg on days 1 and 4 during week 1, weekly week 2-12, every 2 weeks week 13-24, and every 4 weeks thereafter) plus once daily lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) and once weekly oral dexamethasone (40 mg for patients aged ≤75 years and 20 mg for those >75 years) or lenalidomide and dexamethasone alone. The primary endpoint was progression-free survival, defined as the time from randomisation to disease progression or death from any cause, whichever occurred first, assessed by an independent review committee in the full analysis set (all randomly assigned patients who received at least one dose of study treatment). Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT03952091) and is closed to enrolment.

Between March 27, 2019, and Oct 20, 2021, 390 patients were assessed for eligibility, 295 of whom were enrolled and randomly assigned to felzartamab plus lenalidomide-dexamethasone (n=195) or lenalidomide-dexamethasone (n=100). The full analysis set included 289 patients (191 in the felzartamab plus lenalidomide-dexamethasone group and 98 in the lenalidomide-dexamethasone group). 185 (64%) of 289 patients were male, 104 (36%) were female, and all were of Asian ethnicity. At a median follow-up of 34·5 months (IQR 16·8-40·2) in the felzartamab plus lenalidomide-dexamethasone group and 28·7 months (10·8-38·8) in the lenalidomide-dexamethasone group, median progression-free survival was 18·9 months (95% CI 13·6-24·0) with felzartamab plus lenalidomide-dexamethasone versus 10·4 months (5·8-13·9) with lenalidomide-dexamethasone (hazard ratio 0·62 [95% CI 0·45-0·86]; p=0·0035). The most common grade 3-4 adverse events were neutropenia (105 [55%] of 192 vs 22 [23%] of 97), lymphopenia (79 [41%] vs 15 [15%]), leukopenia (74 [39%] vs 11 [11%]), thrombocytopenia (49 [26%] vs 11 [11%]), pneumonia (44 [23%] vs 13 [13%]), anaemia (33 [17%] vs 19 [20%]), hypokalaemia (30 [16%] vs ten [10%]), and upper respiratory tract infection (15 [8%] vs two [2%]). The most common serious adverse event was pneumonia (42 [22%] vs ten [10%]). Treatment-related deaths occurred in 11 (6%) of 192 patients in the felzartamab plus lenalidomide-dexamethasone group (five of unknown cause [possibly related to treatment], two due to pneumonia, one due to febrile infection, one due to cardiac arrest, one due to cerebral infarction, and one due to pneumonitis) and two (2%) of 97 patients in the lenalidomide-dexamethasone group (one due to pneumonia and one due to a fall]).

Felzartamab plus lenalidomide-dexamethasone significantly prolonged progression-free survival compared with lenalidomide-dexamethasone alone, supporting felzartamab plus lenalidomide-dexamethasone as a potential new treatment option for Chinese patients with relapsed or refractory multiple myeloma.

TJ Biopharma.

Peri-implant neoplasia (PIN) is a descriptive term introduced in this review to categorize neoplasms present adjacent to dental implants. Understanding its clinicopathological spectrum and pathogenesis is essential for timely diagnosis and management.

This systematic review evaluated evidence on the clinicopathological features, risk factors, pathogenetic mechanisms, and survival outcomes of peri-implant neoplasia.

Following PRISMA guidelines (PROSPERO ID: CRD42024586140), a systematic search of PubMed, Embase, Scopus, and Web of Science identified studies published until December 2025. Eligible studies included case reports, case series, and cross-sectional studies with histopathologically confirmed peri-implant neoplasia. Extracted data included demographics, clinical presentation, risk factors, histopathology, treatment, and outcomes. Risk of bias was assessed using Joanna Briggs Institute checklists, and pooled survival analysis was performed using Kaplan-Meier curves.

Fifty-six studies involving 187 patients were included. Malignant epithelial neoplasms accounted for 92.3% of lesions, with oral squamous cell carcinoma predominating. The mean patient age was 66.3 years, with a slight female predominance. The mandible was the most common implant and lesion site, and most cases occurred within 1-5 years post-implantation. Clinical misdiagnosis as peri-implantitis occurred in 54% of cases. Factors associated with recurrence or death included prior OPMD/malignancy, radiographic bone loss, and treatment modality. Kaplan-Meier analysis showed mean survival time of 64.1 months (95% CI: 46.8-81.4), with poorer outcomes for sarcoma and metastasis.

Peri-implant neoplasia is predominantly malignant and often mimics peri-implantitis. Clinicians should promptly biopsy non-healing peri-implant lesions and ensure close surveillance in high-risk patients.

In a recent paper published in Nature, Yuan et al. described an acid-responsive membranolytic peptide that temporally separates lysosomes from later plasma membrane rupture, thereby converting oncolysis into immunogenic cell death. This elegant design permits systemic administration, elicits antigen-specific immunity, and sensitizes tumors to programmed death ligand 1 blockade with remarkably limited toxicity.

Castellaniella defragrans is an environmental Gram-negative, non-fermenting β-proteobacterium that is not known as a human pathogen. Here, we report the first documented case of C. defragrans bacteraemia in an 82-year-old man with monoclonal B-cell lymphocytosis, subsequently diagnosed with chronic lymphocytic leukaemia, who presented with fever, confusion and clinical signs of sepsis. Blood cultures showed sustained growth of C. defragrans for 7 days. Imaging revealed pulmonary consolidations and mediastinal infiltration suggestive of mediastinitis. Further investigations did not identify a clear additional infectious focus. In addition, an immunological evaluation revealed severe cellular and humoral immunosuppression. Antimicrobial therapy with high-dose meropenem led to bacteraemia clearance and progressive clinical improvement. Treatment was completed with oral sulfamethoxazole-trimethoprim for a total of five weeks. This case highlights the potential of environmental microorganisms to cause severe infections in immunocompromised hosts.

TP53 mutations represent one of the strongest adverse prognostic factors in myelodysplastic neoplasms (MDS). While multi-hit TP53 (TP53multiHit) alterations uniformly lead to very poor outcomes, the prognostic relevance of monoallelic TP53 (TP53mono) mutations remains controversial. TP53 variants can cause dominant-negative, loss-of-function, or gain-of-function effects. We hypothesized that functional heterogeneity among TP53 variants contributes to the variable clinical behavior observed in TP53mono-mutated MDS. Therefore, we analyzed pretreatment samples from 4,505 patients with MDS from two independent cohorts (IWG: n=3,173; J-MDS: n=1,332), including 271 patients with TP53mono and 499 with TP53multiHit. Functional annotation of TP53 variants was performed using a previously published phenotype score (PS) derived from saturation mutagenesis screens, capturing dominant-negative and loss-of-function effects. Median leukemia-free survival (LFS) differed significantly by TP53 allelic state (TP53 wild-type (TP53wt) 37.2 months; TP53mono 19.2 months; TP53multiHit 7.8 months; p<0.001). Within the TP53mono subgroup, functional annotation identified marked heterogeneity. Patients with high PS (≥7) showed a significantly inferior median LFS compared with those with low PS (12.6 vs. 43.3 months; p<0.001), particularly for IPSS-R and IPSS-M low-risk cases. Combining PS and variant allele frequency (VAF) further improved risk stratification. TP53mono patients with PS ≥7 and VAF ≥22% had a median LFS comparable to TP53multiHit cases (9.2 vs. 7.8 months, p=0.3), whereas those with PS <7 and VAF <22% exhibited a median LFS similar to TP53wt cases (44.7 vs. 37.2 months, p=0.8). Overall, functional annotation of TP53 variants refines prognostication in TP53mono-mutated MDS and may enhance individualized risk assessment.