PCA-based spatial domain identification with state-of-the-art performance.

Motivation: The identification of biologically meaningful domains is a central step in the analysis of spatial transcriptomic data.

Results: Following Occam's razor, we show that a simple PCA-based algorithm for unsupervised spatial domain identification rivals the performance of ten competing state-of-the-art methods across six single-cell spatial transcriptomic datasets. Our reductionist approach, NichePCA, provides researchers with intuitive domain interpretation and excels in execution speed, robustness, and scalability.

Evolution of frontline treatment for multiple myeloma: clinical investigation of quadruplets containing carfilzomib and anti-CD38 monoclonal antibodies.

Although survival rates for patients with newly diagnosed multiple myeloma (NDMM) have improved over recent decades, multiple myeloma (MM) remains without a cure for most. There is increasing consensus that achievement of deep remissions, especially minimal residual disease negativity (MRD -), in frontline treatment is crucial and translates into improved survival. The standard of care (SOC) for NDMM consists at minimum of a triplet regimen of therapies, with or without an autologous stem cell transplant, or a doublet regimen for certain ineligible, particularly frail patients who may have specific limitations.

Endogenous CD4 T cells that recognize ALK and the NPM1::ALK fusion protein can be expanded from human peripheral blood.

Anaplastic lymphoma kinase (ALK)-fusion proteins resulting from chromosomal rearrangements are promising targets for cancer immunotherapy. While ALK-specific CD8+ T cells and epitopes presented on MHC class I have been identified in patients with ALK-positive malignancies, little is known about ALK-specific CD4+ T cells. We screened peripheral blood of ten ALK-positive anaplastic large cell lymphoma (ALK+ALCL) patients in remission and six healthy donors for CD4+ T-cell responses to the whole ALK-fusion protein, nucleophosmin (NPM1)::ALK.

Identification of optimal portal pressure decrease to control ascites while minimizing hepatic encephalopathy after TIPS: A multicenter study.

Background Aims: Clinically-significant portal hypertension (CSPH) in liver cirrhosis patients can lead to refractory ascites. A transjugular-intrahepatic-portosystemic shunt (TIPS) treats CSPH but may cause overt hepatic encephalopathy (oHE). Our aim was to determine the optimal reduction of the portal pressure gradient (PPG) via TIPS to control ascites without raising oHE risk.

Safety and efficacy of the therapeutic DNA-based vaccine VB10.16 in combination with atezolizumab in persistent, recurrent or metastatic HPV16-positive cervical cancer: a multicenter, single-arm phase 2a study.

Background: Second-line treatment options for persistent, recurrent or metastatic (r/m) cervical cancer are limited. We investigated the safety, efficacy, and immunogenicity of the therapeutic DNA-based vaccine VB10.16 combined with the immune checkpoint inhibitor atezolizumab in patients with human papillomavirus (HPV)16-positive r/m cervical cancer.

Immune Response to SARS-CoV-2 XBB.1.5 and JN.1 Variants Following XBB.1.5 Booster Vaccination in Liver Transplant Recipients.

Background/objectives: The efficacy of monovalent BNT162b2 Omicron XBB.1.5 booster vaccination in liver transplant recipients (LTRs) has yet to be described, particularly regarding the immune response to emerging variants like JN.

Association of Molecular Detections of Microsporidia in Stool Samples with Clinical and Immunological Parameters in Ghanaian HIV Patients.

Although the etiological relevance of the detection of microsporidia in human stool samples remains uncertain, the immunological status of patients has been posited as an important determinant of potential clinical impact of these parasites. To further assess the interplay between the epidemiology of microsporidia and immunological markers, we conducted a study utilizing real-time PCR targeting , , , and , combined in a single fluorescence channel. The study involved a cohort of 595 clinically and immunologically well-characterized Ghanaian HIV patients, alongside 82 HIV-negative control individuals from Ghana.

Whole-Exome Sequencing, Mutational Signature Analysis, and Outcome in Multiple Myeloma-A Pilot Study.

The complex and heterogeneous genomic landscape of multiple myeloma (MM) and many of its clinical and prognostic implications remains to be understood. In other cancers, such as breast cancer, using whole-exome sequencing (WES) and molecular signatures in clinical practice has revolutionized classification, prognostic prediction, and patient management. However, such integration is still in its early stages in MM.

A Hybrid Transformer-Convolutional Neural Network for Segmentation of Intracerebral Hemorrhage and Perihematomal Edema on Non-Contrast Head Computed Tomography (CT) with Uncertainty Quantification to Improve Confidence.

Intracerebral hemorrhage (ICH) and perihematomal edema (PHE) are key imaging markers of primary and secondary brain injury in hemorrhagic stroke. Accurate segmentation and quantification of ICH and PHE can help with prognostication and guide treatment planning. In this study, we combined Swin-Unet Transformers with nnU-NETv2 convolutional network for segmentation of ICH and PHE on non-contrast head CTs.

Minimizing Long-Term Toxicities for Patients with Primary Mediastinal B-Cell Lymphoma Undergoing Modern Radiotherapy: Results from a Monocentric Biophysical Risk Evaluation.

Primary mediastinal B-cell lymphoma (PMBCL) is a rare form of aggressive B-cell lymphoma with a predominant onset in young patients. The minimization of potential (late) side effects is of cardinal interest for these patients. An anticipation of the individual risk profile is desirable to counsel the patient on the putative impact of radiotherapy (RT).

Biglycan-driven risk stratification in ZFTA-RELA fusion supratentorial ependymomas through transcriptome profiling.

Recent genomic studies have allowed the subdivision of intracranial ependymomas into molecularly distinct groups with highly specific clinical features and outcomes. The majority of supratentorial ependymomas (ST-EPN) harbor ZFTA-RELA fusions which were designated, in general, as an intermediate risk tumor variant. However, molecular prognosticators within ST-EPN ZFTA-RELA have not been determined yet.

Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standard for PET imaging of brain metastases: version 1.0.

This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neuro-Oncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO). Brain metastases are the most common malignant central nervous system (CNS) tumors. PET imaging with radiolabeled amino acids and to lesser extent [F]FDG has gained considerable importance in the assessment of brain metastases, especially for the differential diagnosis between recurrent metastases and treatment-related changes which remains a limitation using conventional MRI.

Transforming literature screening: The emerging role of large language models in systematic reviews.

Systematic reviews (SR) synthesize evidence-based medical literature, but they involve labor-intensive manual article screening. Large language models (LLMs) can select relevant literature, but their quality and efficacy are still being determined compared to humans. We evaluated the overlap between title- and abstract-based selected articles of 18 different LLMs and human-selected articles for three SR.

Association of radiation-induced normal tissue toxicity with a high genetic risk for rheumatoid arthritis.

Purpose: Overlapping genes are involved with rheumatoid arthritis (RA) and DNA repair pathways. Therefore, we hypothesised that patients with a high polygenic risk score (PRS) for RA will have an increased risk of radiotherapy (RT) toxicity given the involvement of DNA repair.

Methods: Primary analysis was performed on 1494 prostate cancer, 483 lung cancer and 1820 breast cancer patients assessed for development of RT toxicity in the REQUITE study.

Cost-effectiveness of a multicomponent intervention against cognitive decline.

Introduction: The societal costs of dementia and cognitive decline are substantial and likely to increase during the next decades due to the increasing number of people in older age groups. The aim of this multicenter cluster-randomized controlled trial was to assess the cost-effectiveness of a multi-domain intervention to prevent cognitive decline in older people who are at risk for dementia.

Methods: We used data from a multi-centric, two-armed, cluster-randomized controlled trial ( trial, ID: DRKS00013555).

Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial.

Background: In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes.

Methods: In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 10 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone).

The sarcoma ring trial: a case-based analysis of inter-center agreement across 21 German-speaking sarcoma centers.

Purpose: The management of soft tissue sarcoma (STS) at reference centers with specialized multidisciplinary tumor boards (MTB) improves patient survival. The German Cancer Society (DKG) certifies sarcoma centers in German-speaking countries, promoting high standards of care. This study investigated the variability in treatment recommendations for localized STS across different German-speaking tertiary sarcoma centers.

Transthoracic Echocardiography for Central Venous Catheter Tip Positioning in Children: An Observational Study Using Transesophageal Echocardiography as Reference Method.

Background: Children who need to have major surgery or are critically ill often require the insertion of a central venous catheter (CVC). To avoid serious complications, it is important to correctly position the CVC tip at the junction of the distal superior vena cava and the right atrium (cavoatrial junction). Transthoracic echocardiography (TTE) can be used to confirm the correct position of the CVC tip.

Impact of number of passes and futile reperfusion in basilar artery occlusion acute ischaemic stroke.

Introduction: Mechanical thrombectomy (MT) is the standard of care in anterior circulation large vessel occlusion. A vital modifiable factor is successful reperfusion. While multiple passes improve the rates of successful reperfusion, previous studies have reported progressively diminishing returns.

Circulating tumor cell plasticity determines breast cancer therapy resistance via neuregulin 1-HER3 signaling.

Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance in the circulation, robust CTC expansion protocols are urgently needed to effectively study disease progression and therapy responses. Here we present the establishment of long-term CTC-derived organoids from female individuals with metastatic breast cancer.

Synaptoneurolipidomics: lipidomics in the study of synaptic function.

The brain is an exceptionally lipid-rich organ with a very complex lipid composition. Lipids are central in several neuronal processes, including membrane formation and fusion, myelin packing, and lipid-mediated signal transmission. Lipid diversity is associated with the evolution of higher cognitive abilities in primates, is affected by neuronal activity, and is instrumental for synaptic plasticity, illustrating that lipids are not static components of synaptic membranes.

Immunoadsorption is equally effective as plasma exchange in paediatric neuroimmunological disorders - A retrospective multicentre study.

Background: Therapeutic apheresis (TA) are promising treatment option for neuroimmunological disorders. In paediatrics, the available data is limited, particularly for the use of IA. The aim of this study was to analyse the use of PE and IA in children and adolescents, with emphasis on outcome and neurological course after treatment as well as the safety of the two modalities.