Highly sensitive detection of Carbohydrate Antigen 19-9 (CA19-9) is of critical importance for early cancer screening, treatment monitoring, and prognosis assessment. In this study, a colorimetric immunoassay was developed for the detection of CA19-9, utilizing Cu-Trp nanoparticles as a nanozyme. The Cu-Trp nanoparticles exhibit specific ascorbic acid oxidase-like activity, enabling the catalytic oxidation of ascorbic acid (AA) to dehydroascorbic acid (DHAA). In the presence of AA, the chromophore Fe(BPT)33+ is reduced to form a red-colored Fe(BPT)32+ complex, which exhibits a characteristic absorption peak at 534 nm. The introduction of Cu-Trp nanoparticles inhibits this colorimetric reaction by depleting AA. Based on the specific recognition between antigen and antibody, a sandwich-type colorimetric immunoassay was constructed. Under optimized conditions, a linear relationship was observed between the UV absorbance and the logarithm of CA19-9 concentration in the range of 4 to 1000 U mL-1, with a detection limit of 0.38 U mL-1. This analytical strategy enables highly sensitive and accurate detection of CA19-9 and holds promising potential for application in the detection of other tumor biomarkers.

Accurate compensation of brain deformation is critical for reliable image-guided neurosurgery. Surgical manipulation and tumor resection induce tissue motion, causing preoperative planning images to become misaligned with the intraoperative anatomy. In this review, we examine data-driven methods developed between 2020 and 2025 for brain deformation registration and modeling, with a particular focus on learning-based approaches. A comprehensive literature search was conducted in PubMed, IEEE Xplore, Scopus, and Web of Science using predefined inclusion and exclusion criteria for computational methods addressing brain deformation in neurosurgical imaging, resulting in 46 eligible studies. We provide a unified analysis of methodological strategies, including deep learning-based image registration, direct deformation field regression, synthesis-driven multimodal alignment, resection-aware architectures for handling missing correspondences, and hybrid models integrating biomechanical priors. We also examine dataset utilization, evaluation metrics, validation protocols, and the assessment of uncertainty and generalization across studies. While learning-based methods demonstrate promising accuracy and computational efficiency, current approaches remain limited by out-of-distribution robustness, standardized benchmarking, interpretability, and readiness for clinical deployment. Our review highlights these gaps and outlines future directions toward more robust, generalizable, and clinically translatable solutions for neurosurgical guidance. By organizing recent advances and critically assessing evaluation practices, this work provides a comprehensive reference for researchers and clinicians working on data-driven registration and modeling of brain deformation.

Localised anal squamous cell carcinoma (ASCC) is treated with radical chemoradiotherapy, which achieves durable disease control in most patients. However, treatment failure is stage-dependent, with approximately 25-30% of patients with locally advanced disease relapsing after treatment, supporting investigation of novel approaches such as radiotherapy-immunotherapy (RT-IO) combinations. Combining radiotherapy (RT) with immunotherapy (IO) shows promise, with multiple trials investigating different combinations. This review evaluates trial design for RT-IO trials in ASCC. A systematic review was conducted on PubMed, ClinicalTrials.gov, and EudraCT databases to identify interventional clinical trials evaluating RT combined with immune-modulating treatments for ASCC. The review was prospectively registered on PROSPERO (CRD42023384068). Information on trial design, patient selection, and treatment regimens was collected. Twelve trials were identified, with three reporting results for a combined total of 69 patients. Across all trials, 14 different IO regimens were used before, during, and after RT. Substantial heterogeneity was observed in patient selection, statistical design, chemotherapy, and RT regimens. Data on exploratory and translational analyses was available for six trials. No trials used biomarkers for enrolment, although INTERACT-ION used cHPV-DNA to guide post-induction treatment allocation. Full trial comparisons were hindered by protocol publication and commercial sensitivities. The diversity in IO regimens and timing relative to RT offers valuable data on RT-IO combinations for ASCC. However, heterogeneity in trial design and translational analysis will limit comparisons between trials. Two possible solutions to improve comparisons are a core minimal translational component and federated learning.

Breastfeeding is associated with enhanced renal growth and improved kidney function in infants. Formula-fed infants do not experience these benefits. A closer look at the nutritional composition of infant formula (IF) products in comparison to human breast milk (HBM) is thus warranted, particularly with regard to the potential renal acid load (PRALR) - an acknowledged risk factor for acid stress-induced kidney disease. We reviewed the PRALR of 783 IF products for infants aged 0-6 months and 786 IF products for children aged 6 to 12 months from China (2017-2024). In an additional exploratory analysis, data for IF products for infants aged 0-6 months were contrasted to HBM. The median PRALR of 783 IF products for infants aged 0-6 months was -0.97 (IQR: 1.76) mEq/100 g of IF powder; PRALR varied widely and ranged from -5.62 mEq/100 g (alkaline) to +1.80 mEq/100 g (acidic). A typical daily consumption of 800 ml of IF milk resulted in a slightly alkalizing potential (median PRALR: -0.97 (IQR: 1.76)), whereas the same amount of HBM exerted stronger alkalizing effects (PRALR: -3.06 mEq). Protein and phosphate content differences may explain these findings. Infant formulas for children aged 6 to 12 months exerted stronger acidifying effects. This is the first study to quantify the PRALR of IF products available in China. Results suggests that HBM and IF products exert a different acid load to the human kidneys. This could be relevant for the postprandial metabolic response of breast-fed and formula-fed infants and warrants consideration in future studies.

Squamous cell carcinoma of the anus is an uncommon malignancy, with an increasing incidence globally. For most patients, primary treatment is nonsurgical. Despite this, surgeons are essential in the clinical teams that manage patients with squamous cell carcinoma of the anus. This review examines both supportive and therapeutic roles carried out by the anal cancer surgeon, within the anal cancer multi-disciplinary team platform. The indications for pretherapeutic stoma, fistula management, and primary surgical treatment are described. The role of the anal cancer surgeon in early follow-up and results following salvage surgery, including perineal reconstruction, are discussed. In addition, potential routes for future research are outlined.

Oligometastatic squamous-cell carcinoma of the anus (omSCCA) is a very rare condition. The literature is sparse, and treatment guidelines are lacking. The aim of the present work was to carry out a literature review and to propose an algorithm for intensified treatment of patients with omSCCA. A PubMed search was carried out, which resulted in 15 relevant publications that included any type of definitive metastasis-directed therapy of mSCCA. All of the studies were retrospective. The local treatments were mostly surgical resections of liver metastases, but also radiofrequency ablation and radiotherapy were used, for metastases located in the liver, lungs, or other organs. The reported median overall survival across the studies ranged from 22 to 53 months. Three of the studies described extended-field chemoradiation of para-aortic lymph node metastases (M1 disease), suggesting long-term survival in up to half of the patients. Taken together, these results indicate that a subset of patients with omSCCA may benefit from a multimodal approach, including definitive metastasis-directed therapy given with curative intent. Based on the literature review and clinical experience, we propose a treatment algorithm, including metastasis-directed treatment as well as chemoradiation and induction chemotherapy. The choice of treatment and sequencing depends on the location and extent of the metastases and whether the metastases are synchronous or metachronous. In the absence of strong evidence, the proposed algorithm should be regarded as a starting point for discussions rather than detailed guidelines. Further studies and international collaborations are needed to optimize the treatment of omSCCA.

Long-acting (LA) injectable cabotegravir (CAB) and rilpivirine (RPV) are recommended for maintenance treatment in virologically suppressed people with HIV-1. A key concern with this strategy is the prolonged pharmacokinetic "tail" after treatment discontinuation, during which declining drug concentrations may increase the risk of viral rebound and resistance selection. Current clinical guidance therefore recommends prompt initiation of alternative antiretroviral therapy if injections are interrupted. We report two people with HIV who remained virologically suppressed (HIV-1 RNA <50 copies/mL) for several months after discontinuation of LA CAB/RPV without any documented alternative antiretroviral therapy. The first case involved a 54-year-old man with well-controlled HIV-1 disease who had received 13 CAB/RPV injections over approximately two years before treatment interruption. After missing scheduled visits, he returned to care seven months after his last injection with persistent viral suppression and plasma drug concentrations who had received 13 CAB/RPV injections over approximately two years before treatment interruption, both above commonly used pharmacokinetic target thresholds. The second case involved a 60-year-old woman with advanced HIV-1 infection and metastatic anal cancer who discontinued treatment after three injections. Five months later, HIV-1 RNA remained undetectable despite very low plasma CAB/RPV concentrations, both below commonly used pharmacokinetic target thresholds. The literature reports another similar case of sustained virologic control 18 months after LA CAB/RPV discontinuation despite inadequate adherence on oral antiretroviral treatment. Altogether, these cases underscore the need for further research to better understand the pharmacological and viro-immunological mechanisms underlying this phenomenon.

Osteosarcoma is a highly aggressive bone malignancy requiring precise tools for early diagnosis and effective evaluation of chemotherapy efficacy. Here, we report an "off-on" fluorescent nanosensor based on nitrogen-doped carbon nanodots (N-CNDs) for the sensitive and selective detection of caspase-3 activity, a key apoptosis executor. The sensor is constructed by conjugating carboxyl-functionalized N-CNDs with a BHQ1-labeled peptide substrate containing the caspase-3-specific DEVD cleavage motif. In the absence of caspase-3, fluorescence is quenched via FRET. Upon caspase-3 activation, the peptide is cleaved, releasing BHQ1 and restoring fluorescence. The nanosensor exhibits high sensitivity (detection limit of 0.0106 U/mL), excellent selectivity, and robust performance in complex biological media. As a proof-of-concept application, it detects elevated caspase-3 activity in osteosarcoma cell lysates (MG-63) compared to normal osteoblast lysates (hFOB1.19) and enables quantitative, dose-dependent assessment of apoptosis induced by cisplatin and doxorubicin directly in cancer cell lysates. With its current format, this cell-lysate-based platform provides a practical and sensitive tool for preclinical drug screening and rapid comparison of chemotherapeutic potency, while laying a foundation for future adaptation toward live-cell and in vivo imaging applications.