Daratumumab with lenalidomide as maintenance after transplant in newly diagnosed multiple myeloma: the AURIGA study.

No randomized trial has directly compared daratumumab and lenalidomide (D-R) maintenance with standard-of-care lenalidomide (R) alone after transplant. Herein, we report the primary results of the phase 3 AURIGA study evaluating D-R vs R maintenance in patients with newly diagnosed multiple myeloma (NDMM) who had very good or better partial response, were minimal residual disease (MRD)-positive (10-5) and anti-CD38-naïve after transplant. Two hundred patients were randomly assigned (1:1) to D-R (n = 99) or R (n = 101) maintenance for up to 36 cycles.

Measurable residual disease (MRD) dynamics in multiple myeloma and the influence of clonal diversity analyzed by artificial intelligence.

Minimal residual disease (MRD) assessment is a known surrogate marker for survival in multiple myeloma (MM). Here, we present a single institution's experience assessing MRD by NGS of Ig genes and the long-term impact of depth of response as well as clonal diversity on the clinical outcome of a large population of MM patients; 482 MM patients at the University of California, San Francisco (UCSF) diagnosed from 2008 to 2020 were analyzed retrospectively. MRD assessment was performed by NGS.

The Parkinson's Disease Composite of Executive Functioning: A Measure for Detecting Cognitive Decline in Clinical Trials.

Background And Objectives: Executive functioning is one of the first domains to be impaired in Parkinson disease (PD), and the majority of patients with PD eventually develop dementia. Thus, developing a cognitive endpoint measure specifically assessing executive functioning is critical for PD clinical trials. The objective of this study was to develop a cognitive composite measure that is sensitive to decline in executive functioning for use in PD clinical trials.

Scanning the aged to minimize missed injury: An Eastern Association for the Surgery of Trauma multicenter study.

Background: Despite the high incidence of blunt trauma in older adults, there is a lack of evidence-based guidance for computed tomography (CT) imaging in this population. We aimed to identify an algorithm to guide use of a pan-scan (head/cervical spine [C-spine]/torso) or a selective scan (head/C-spine ± torso). We hypothesized that a patient's initial history and examination could be used to guide imaging.

Ambulatory Blood Pressure in Patients With Rheumatoid Arthritis: Association With Immune Activation.

Objective: The prevalence of hypertension, a major cardiovascular risk factor, is increased in patients with rheumatoid arthritis (RA) and may be driven by immune activation. The purpose of this study was to determine if ambulatory 24-hour blood pressure (BP) is elevated in RA vs control participants and whether it is associated with immune activation.

Methods: We conducted a cross-sectional study of 46 patients with RA and 23 control participants.

Synthetic BZLF1-targeted transcriptional activator for efficient lytic induction therapy against EBV-associated epithelial cancers.

The unique virus-cell interaction in Epstein-Barr virus (EBV)-associated malignancies implies targeting the viral latent-lytic switch is a promising therapeutic strategy. However, the lack of specific and efficient therapeutic agents to induce lytic cycle in these cancers is a major challenge facing clinical implementation. We develop a synthetic transcriptional activator that specifically activates endogenous BZLF1 and efficiently induces lytic reactivation in EBV-positive cancer cells.

Recessive Mutations in Korean Nonaka Distal Myopathy Patients with or without Peripheral Neuropathy.

Autosomal recessive Nonaka distal myopathy is a rare autosomal recessive genetic disease characterized by progressive degeneration of the distal muscles, causing muscle weakness and decreased grip strength. It is primarily associated with mutations in the gene, which encodes a key enzyme of sialic acid biosynthesis (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase). This study was performed to find mutations in six independent distal myopathy patients with or without peripheral neuropathy using whole-exome sequencing (WES).

Transitioning from Methanol to Olefins (MTO) toward a Tandem CO Hydrogenation Process: On the Role and Fate of Heteroatoms (Mg, Si) in MAPO-18 Zeotypes.

The tandem CO hydrogenation to hydrocarbons over mixed metal oxide/zeolite catalysts (OXZEO) is an efficient way of producing value-added hydrocarbons (platform chemicals and fuels) directly from CO methanol intermediate in a single reactor. In this contribution, two MAPO-18 zeotypes (M = Mg, Si) were tested and their performance was compared under methanol-to-olefins (MTO) conditions (350 °C, = 0.04 bar, 6.

Safety of Administering Intravenous CT Contrast Agents Repeatedly or Using Both CT and MRI Contrast Agents on the Same Day: An Animal Study.

Objective: To investigate molecular and functional consequences of additional exposures to iodine- or gadolinium-based contrast agents within 24 hours from the initial intravenous administration of iodine-based contrast agents through an animal study.

Materials And Methods: Fifty-six Sprague-Dawley male rats were equally divided into eight groups: negative control, positive control (PC) with single-dose administration of CT contrast agent, and additional administration of either CT or MR contrast agents 2, 4, or 24 hours from initial CT contrast agent injection. A 12 µL/g of iodinated contrast agent or a 0.

Expert-centered Evaluation of Deep Learning Algorithms for Brain Tumor Segmentation.

Purpose To present results from a literature survey on practices in deep learning segmentation algorithm evaluation and perform a study on expert quality perception of brain tumor segmentation. Materials and Methods A total of 180 articles reporting on brain tumor segmentation algorithms were surveyed for the reported quality evaluation. Additionally, ratings of segmentation quality on a four-point scale were collected from medical professionals for 60 brain tumor segmentation cases.

A novel RNF125 variant associated with Tenorio syndrome alters ubiquitin chain binding.

A key signalling pathway required for clearance of viruses from host cells relies on the receptor protein, retinoic acid-inducible gene I (RIG-I). The activity of RIG-I is tightly controlled, and once bound to viral dsRNA, addition of lysine 63-linked ubiquitin chains activates signalling. Meanwhile, the addition of lysine 48-linked ubiquitin chains to RIG-I is required to terminate signalling when the infection has been resolved.

PLS3 missense variants affecting the actin-binding domains cause X-linked congenital diaphragmatic hernia and body-wall defects.

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families.

A dynamic model of the intestinal epithelium integrates multiple sources of preclinical data and enables clinical translation of drug-induced toxicity.

We have built a quantitative systems toxicology modeling framework focused on the early prediction of oncotherapeutic-induced clinical intestinal adverse effects. The model describes stem and progenitor cell dynamics in the small intestinal epithelium and integrates heterogeneous epithelial-related processes, such as transcriptional profiles, citrulline kinetics, and probability of diarrhea. We fitted a mouse-specific version of the model to quantify doxorubicin and 5-fluorouracil (5-FU)-induced toxicity, which included pharmacokinetics and 5-FU metabolism and assumed that both drugs led to cell cycle arrest and apoptosis in stem cells and proliferative progenitors.

Influence of knee flexion angle on graft bending angle during anterior cruciate ligament reconstruction using the transportal technique.

This study aimed to examine change in the graft bending angle (GBA) according to various knee flexion angles in creating femoral tunnel by the transportal technique in ACL reconstruction, and to reveal knee flexion angle minimizing GBA while maintaining stable femoral tunnel characteristics. Patients who underwent ACL reconstruction using the transportal technique between January 2017 and December 2018 were retrospectively reviewed. Patients were classified into three groups according to knee flexion angle when creating femoral tunnel (group 1: < 120° (n = 19); group 2: 120-129° (n = 32); group 3: ≥ 130° (n = 33).

KMnO(OH)(VO)(VO) with Sawtooth Chains of Multivalent Manganese Triangular Trimer Units: Magnetic Susceptibility Shrouding a Long-Range Antiferromagnetic Order of Ferromagnetic Triangles.

-Pyrovanadate (or -diorthovanadate) KMnMnO(OH)(VO)(VO) synthesized hydrothermally crystallizes in the orthorhombic space group with = 17.9155(5), = 5.8940(2), = 10.

Pro-inflammatory cytokines and reproductive hormone responses in bucks post-challenge with Mannheimia haemolytica A2 and its outer membrane protein.

The lipopolysaccharide (LPS) endotoxin and outer membrane protein (OMP) are among the virulence factors of Gram-negative bacteria responsible for inducing pathogenicity in the infected host. OMP and LPS occur on the outer membrane of M. haemolytica A2, the primary aetiological agent of pneumonic mannheimiosis in small ruminants.

Prenatal diagnosis of Myhre syndrome with a heterozygous pathogenic variant in SMAD4 gene presented with thick nuchal translucency and cardiac abnormalities.

Prenatal testing was performed in a 39-year-old Chinese pregnant woman referred for increased nuchal translucency measuring 5.7 mm. Non-invasive prenatal testing and SNP array study on amniotic fluid samples were normal.

Large language models encode clinical knowledge.

Large language models (LLMs) have demonstrated impressive capabilities, but the bar for clinical applications is high. Attempts to assess the clinical knowledge of models typically rely on automated evaluations based on limited benchmarks. Here, to address these limitations, we present MultiMedQA, a benchmark combining six existing medical question answering datasets spanning professional medicine, research and consumer queries and a new dataset of medical questions searched online, HealthSearchQA.

Genome-Wide Association Study of CKD Progression.

Significance Statement: Rapid progression of CKD is associated with poor clinical outcomes. Most previous studies looking for genetic factors associated with low eGFR have used cross-sectional data. The authors conducted a meta-analysis of genome-wide association studies of eGFR decline among 116,870 participants with CKD, focusing on longitudinal data.

Risk for Bleeding-Related Hospitalizations During Use of Amiodarone With Apixaban or Rivaroxaban in Patients With Atrial Fibrillation : A Retrospective Cohort Study.

Background: Amiodarone, the most effective antiarrhythmic drug in atrial fibrillation, inhibits apixaban and rivaroxaban elimination, thus possibly increasing anticoagulant-related risk for bleeding.

Objective: For patients receiving apixaban or rivaroxaban, to compare risk for bleeding-related hospitalizations during treatment with amiodarone versus flecainide or sotalol, antiarrhythmic drugs that do not inhibit these anticoagulants' elimination.

Design: Retrospective cohort study.

The Synthetic Collagen-Binding Peptide NIPEP-OSS Delays Mouse Myeloma Progression.

Multiple myeloma (MM) is the second most common hematological malignancy. It is a clonal B-cell disorder characterized by the proliferation of malignant plasma cells in the bone marrow, the presence of monoclonal serum immunoglobulin, and osteolytic lesions. An increasing amount of evidence shows that the interactions of MM cells and the bone microenvironment play a significant role, suggesting that these interactions may be good targets for therapy.

Contribution of Previously Unrecognized RNA Splice-Altering Variants to Congenital Heart Disease.

Background: Known genetic causes of congenital heart disease (CHD) explain <40% of CHD cases, and interpreting the clinical significance of variants with uncertain functional impact remains challenging. We aim to improve diagnostic classification of variants in patients with CHD by assessing the impact of noncanonical splice region variants on RNA splicing.

Methods: We tested de novo variants from trio studies of 2649 CHD probands and their parents, as well as rare (allele frequency, <2×10) variants from 4472 CHD probands in the Pediatric Cardiac Genetics Consortium through a combined computational and in vitro approach.