Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatment.

Background: Immunosenescence is accelerated by chronic infectious and autoimmune diseases and could contribute to the pathobiology of multiple sclerosis (MS). How MS and disease-modifying therapies (DMTs) impact age-sensitive immune biomarkers is only partially understood.

Methods: We analyzed 771 serum samples from 147 healthy controls and 289 people with MS (PwMS) by multiplex immunoassays.

Clinicopathologic and Molecular Characterization of NUP98-Rearranged Acute Leukemias.

Introduction: NUP98 rearrangements are rare in acute leukemias and portend a poor prognosis.

Methods: This study explored clinicopathologic and molecular features of five patients with NUP98 rearranged (NUP98-r) acute leukemias, including three females and two males with a median age of 34 years.

Results: NUP98 fusion partners were associated with distinctive leukemia characteristics and biology.

Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies.

Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer.

Impact of Genomic Classifiers on Risk Stratification and Treatment Intensity in Patients With Localized Prostate Cancer : A Systematic Review.

Background: Tissue-based genomic classifiers (GCs) have been developed to improve prostate cancer (PCa) risk assessment and treatment recommendations.

Purpose: To summarize the impact of the Decipher, Oncotype DX Genomic Prostate Score (GPS), and Prolaris GCs on risk stratification and patient-clinician decisions on treatment choice among patients with localized PCa considering first-line treatment.

Data Sources: MEDLINE, EMBASE, and Web of Science published from January 2010 to August 2024.

Design and validation of cell-based potency assays for frataxin supplementation treatments.

Friedreich's ataxia (FRDA) is a multisystem, autosomal recessive disorder caused by mutations in the frataxin () gene. As FRDA is considered an FXN deficiency disorder, numerous therapeutic approaches in development or clinical trials aim to supplement FXN or restore endogenous expression. These include gene therapy, protein supplementation, genome editing or upregulation of transcription.

Antithrombotic therapy and the risk of pocket hematoma after subcutaneous implantable cardioverter-defibrillator implantation.

Background: Little data exists regarding the optimal antithrombotic strategy during S-ICD implantation to prevent pocket hematomas. This study explores the association between perioperative antithrombotic management and the occurrence of pocket hematoma following S-ICD implantation.

Methods: All patients who underwent de novo S-ICD implantation between February 2009 and January 2023 at Amsterdam UMC were included.

Comparison of RT-qPCR With Branched DNA to Quantify a Lipid Nanoparticle-Encapsulated mRNA Therapeutic in Serum and Liver Tissue Samples From Nonclinical PK Studies.

While the branched DNA (bDNA) assay is an established bioanalytical method for measurement of lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA) pharmacokinetic parameters, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) has been considered as an alternative platform. RT-qPCR and bDNA platforms were compared for sensitivity, specificity, correlation, and overall assay performance using serum and tissue samples from 2 nonclinical mouse studies of a therapeutic mRNA candidate, LNP-PAH-mRNA, which encodes for human phenylalanine hydroxylase enzyme. Pharmacokinetic parameter noncompartmental analysis was completed using Phoenix WinNonlin.

Recommendations for mitochondria transfer and transplantation nomenclature and characterization.

Intercellular mitochondria transfer is an evolutionarily conserved process in which one cell delivers some of their mitochondria to another cell in the absence of cell division. This process has diverse functions depending on the cell types involved and physiological or disease context. Although mitochondria transfer was first shown to provide metabolic support to acceptor cells, recent studies have revealed diverse functions of mitochondria transfer, including, but not limited to, the maintenance of mitochondria quality of the donor cell and the regulation of tissue homeostasis and remodelling.

Phase I study of CD19 CAR T-cell therapy harboring a fully human scFv in CAR-naïve adult B-ALL patients.

CD19-directed chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy elicits high response rates but fails to induce durable responses in most adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). In a previous clinical trial (NCT01865617), we observed anti-CAR immune responses associated with impaired in vivo CAR T-cell expansion after second infusions. Because these CD8+ T-cell responses were predominantly directed at peptides derived from the murine single chain variable fragment (scFv) in the CAR, we conducted a clinical trial investigating the safety and efficacy of CD19 CAR T-cells engineered with a CAR incorporating a fully human scFv (JCAR021) in adults with R/R B-ALL (NCT03103971).

Neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin in women with early HER2-positive breast cancer: the randomized phase 2 ABCSG-52/ATHENE trial.

The role of anthracyclines in the treatment of early breast cancer (EBC) is increasingly being challenged, especially in de-escalation strategies. However, owing to their immunogenic effects, anthracyclines are promising combination partners with immunotherapies. In the randomized phase 2 trial ABCSG-52 (EudraCT no.

Echocardiography of the right heart in pulmonary arterial hypertension: insights from the ULTRA RIGHT VALUE study.

Aims: Outcome in pulmonary arterial hypertension (PAH) is determined by right ventricular (RV) function adaptation to increased afterload. Echocardiography is easily available to assist bedside evaluation of the RV. However, no agreement exists about the feasibility and most relevant measurements.

Multi-modal integration of MRI and global chamber charge density mapping for the evaluation of atrial fibrillation.

Atrial fibrillation (AF) is the most prevalent clinical arrhythmia, posing significant mortality and morbidity challenges. Outcomes of current catheter ablation treatment strategies are suboptimal, highlighting the need for innovative approaches. A major obstacle lies in the inability to comprehensively assess both structural and functional remodelling in AF.

A phase 1 trial of prizloncabtagene autoleucel, a CD19/CD20 CAR T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma.

Prizloncabtagene autoleucel (prizlon-cel), a novel bispecific chimeric antigen receptor (CAR) T-cell, targets and eliminates CD19/CD20 positive tumor cells. This phase 1, open-label study investigated the safety and efficacy of prizlon-cel in patients with relapsed/refractory B-cell non-Hodgkin Lymphoma (r/r B-NHL). Patients with CD19 and/or CD20-positive r/r B-NHL received a 3-day lymphodepletion (cyclophosphamide: 300 mg/m2/d; fludarabine: 30 mg/m2/d) followed by an intravenous dose of prizlon-cel.

Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer.

Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease after neoadjuvant systemic therapy have a high risk of recurrence and death. The primary analysis of KATHERINE, a phase 3, open-label trial, showed that the risk of invasive breast cancer or death was 50% lower with adjuvant trastuzumab emtansine (T-DM1) than with trastuzumab alone.

Methods: We randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles.

Randomized clinical trial of a digital integrative medicine intervention among patients undergoing active cancer treatment.

Exercise and mindfulness-based interventions have growing evidence for managing fatigue and comorbid symptoms; however, packaging them in a cohesive digital way for patients undergoing cancer treatment has not been evaluated. We conducted a randomized controlled trial to assess the impact of a 12 week digital integrative medicine program, Integrative Medicine at Home (IM@Home), versus enhanced usual care on fatigue severity (primary outcome), comorbid symptoms and acute healthcare utilization (secondary outcomes), in 200 patients with solid tumors experiencing fatigue during treatment. Fatigue severity decreased more in IM@Home than in the control (1.

Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling.

Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. We report analyses of rare variants that impact birth weight when carried by either fetus or mother, using whole exome sequencing data in up to 234,675 participants. Rare protein-truncating and deleterious missense variants are collapsed to perform gene burden tests.

Rhodium-mediated Assembly of New Heterocycles: From Borylenes to Oxaboroles.

Base-stabilized rhodium borylene complex κ-L(CO)Rh(BMes), 2; κ-L=κ-NN'-Rh,κ-N-B-(2,5-[PrP=N(4-PrCH)]-N'(CH)); Mes=mesityl, reacts with a series of alkynes (PhC≡C-R; R=Ph, Me, COEt, H) to yield unique structures whereby the alkyne has regioselectively added across boron and the carbon atom of a CO ligand. The resulting complexes, LRh[C(O)C(Ph)C(R)B(Mes)], 3, react with additional CO to afford cycle-containing products, L(CO)Rh ), 5, that ultimately release highly functionalized organic heterocycles of the form =NPipp (Pipp=4-PrCH), 6. These oxaboroles, which were assembled from a primary hydroborane, CO, an alkyne, and an azide-generated NPipp, are structurally analogous to two of the five boron-containing therapeutics approved by the FDA.

Photon-Counting CT Effects on Sensitivity for Liver Lesion Detection: A Reader Study Using Virtual Imaging.

Background Detection of hepatic metastases at CT is a daily task in radiology departments that influences medical and surgical treatment strategies for oncology patients. Purpose To compare simulated photon-counting CT (PCCT) with energy-integrating detector (EID) CT for the detection of small liver lesions. Materials and Methods In this reader study (July to December 2023), a virtual imaging framework was used with 50 anthropomorphic phantoms and 183 generated liver lesions (one to six lesions per phantom, 0.

Identifying core symptom clusters based on symptom distress levels in patients with maintenance hemodialysis: a cross-sectional network analysis.

Background: To explore the symptom clusters of patients undergoing maintenance hemodialysis and construct a symptom network to identify the core symptoms and core symptom clusters, to provide reference for precise symptom management.

Methods: Conveniently selected 354 patients with maintenance hemodialysis were surveyed cross-sectionally using the general information questionnaire, the Dialysis Symptom Index and the Kidney Disease Questionnaire. Symptom clusters were extracted using exploratory factor analysis, and core symptom clusters were identified using hierarchical regression and network analysis.

Increased BMI is associated with an altered decision-making process during healthy food choices in males and females.

Unhealthy diets (rich in calories, sugar, fat, and sodium) are a major cause of obesity. Why individuals struggle to make healthy food choices remains unclear. This study examined how body mass index, biological sex, and eating context influence food attribute perception, the food choice process, and the percentage of healthy food choices.

Oral obeldesivir provides postexposure protection against Marburg virus in nonhuman primates.

The recent outbreak of Marburg virus (MARV) in Rwanda underscores the need for effective countermeasures against this highly fatal pathogen, with case fatality rates reaching 90%. Currently, no vaccines or approved treatments exist for MARV infection, distinguishing it from related viruses such as Ebola. Our study demonstrates that the oral drug obeldesivir (ODV), a nucleoside analog prodrug, shows promising antiviral activity against filoviruses in vitro and offers significant protection in animal models.

Novel combination therapy targeting oncogenic signaling kinase P21 activated Kinase-1 and chemotherapeutic drugs against triple negative breast cancer.

Most of the triple negative phenotype or basal-like molecular subtypes of breast cancers are associated with aggressive clinical behaviour and show poor disease prognosis. Current treatment options are constrained, emphasizing the need for novel combinatorial therapies for this particular tumor subtype. Our group has demonstrated that functionally active p21 activated kinase 1 (PAK1) exhibits significantly higher expression levels in clinical triple negative breast cancer (TNBC) samples compared to other subtypes, as well as adjacent normal tissues.

The Efficacy and Safety of Angiotensin II for Treatment of Vasoplegia in Critically Ill Patients: A Systematic Review.

Objectives: To summarize evidence regarding intravenous angiotensin II administration in critical illness and provide an updated understanding of its effects on various organ dysfunction and renin-angiotensin system (RAS) biomarkers.

Design: A systematic review.

Setting: A search of PubMed, Embase, and the Cochrane Library from inception to May 3, 2024.

Depletion of alloreactive B cells by drug-resistant chimeric alloantigen receptor T cells to prevent transplant rejection.

Antibody-mediated rejection (AMR) remains a major complication after solid organ transplantation (SOT). Current treatment options are inefficient and result in drastic impairment of the general immunity. To selectively eliminate responsible alloreactive B cells characterized by anti-donor-HLA B cell receptors (BCRs), we generated T cells overcoming rejection by antibodies (CORA-Ts) engineered with a novel chimeric receptor comprising a truncated donor-HLA molecule as antigen recognition domain.