Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone Induction Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma: Final Part 1 Analysis of the GMMG-HD7 Trial.

Previously, addition of isatuximab (Isa) to standard-of-care lenalidomide-bortezomib-dexamethasone (RVd) in transplant-eligible patients with newly diagnosed multiple myeloma in the GMMG-HD7 trial (ClinicalTrials.gov identifier: NCT03617731) resulted in a significant increase of minimal residual disease negativity (MRD-) rates after induction therapy. A total of 662 patients were randomly assigned to receive induction therapy with Isa-RVd (n = 331) or RVd (n = 329), followed by single or tandem autologous stem-cell transplant and second random assignment to maintenance with lenalidomide alone or Isa-lenalidomide.

Glycemic control contributes to the neuroprotective effects of Mediterranean and green-Mediterranean diets on brain age: the DIRECT PLUS brain-magnetic resonance imaging randomized controlled trial.

Background: We recently reported that Mediterranean (MED) and green-MED diets significantly attenuated age-related brain atrophy by ∼50% within 18 mo.

Objective: The objective of this study was to explore the contribution of specific diet-induced parameters to brain-volume deviation from chronologic age.

Methods: A post hoc analysis of the 18-mo DIRECT PLUS trial, where participants were randomly assigned to the following groups: 1) healthy dietary guidelines, 2) MED diet, or 3) green-MED diet, high in polyphenols, and low in red meat.

Temporal Genomic Dynamics Shape Clinical Trajectory in Multiple Myeloma.

To comprehensively unravel the temporal relationship between initiating and driver events and its impact on clinical outcomes, we analyzed 421 whole-genome sequencing profiles from 382 patients. Using clock-like mutational signatures, we estimated a time lag of 2-4 decades between initiating events and diagnosis. In patients with hyperdiploidy, we demonstrate that trisomies of odd-numbered chromosomes can be acquired simultaneously with other chromosomal gains, such as 1q gain.

Assessment of Heat Exposure and Health Outcomes in Rural Populations of Western Kenya by Using Wearable Devices: Observational Case Study.

Background: Climate change increasingly impacts health, particularly of rural populations in sub-Saharan Africa due to their limited resources for adaptation. Understanding these impacts remains a challenge, as continuous monitoring of vital signs in such populations is limited. Wearable devices (wearables) present a viable approach to studying these impacts on human health in real time.

The biological and clinical impact of deletions before and after large chromosomal gains in multiple myeloma.

Acquisition of a hyperdiploid (HY) karyotype or immunoglobulin heavy chain (IgH) translocations are considered key initiating events in multiple myeloma (MM). To explore if other genomic events can precede these events, we analyzed whole-genome sequencing data from 1173 MM samples. By integrating molecular time and structural variants within early chromosomal duplications, we indeed identified pregain deletions in 9.

Elotuzumab, lenalidomide, bortezomib, dexamethasone, and autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GMMG-HD6): results from a randomised, phase 3 trial.

Background: The aim of this trial was to investigate the addition of the anti-SLAMF7 monoclonal antibody elotuzumab to lenalidomide, bortezomib, and dexamethasone (RVd) in induction and consolidation therapy as well as to lenalidomide maintenance treatment in transplant-eligible patients with newly diagnosed multiple myeloma.

Methods: GMMG-HD6 was a phase 3, randomised trial conducted at 43 main trial sites and 26 associated trial sites throughout Germany. Adult patients (aged 18-70 years) with previously untreated, symptomatic multiple myeloma, and a WHO performance status of 0-3, with 3 being allowed only if caused by myeloma disease and not by comorbid conditions, were randomly assigned 1:1:1:1 to four treatment groups.

Sequence diversity of kappa light chains from patients with AL amyloidosis and multiple myeloma.

Background: AL amyloidosis (AL) results from the misfolding of immunoglobulin light chains (IG LCs). Aim of this study was to comprehensively analyse kappa LC sequences from AL patients in comparison with multiple myeloma (MM).

Objective: We analysed usage and associated organ tropism and in terms of mutational analysis and theoretical biochemical properties.

Rel governs loser elimination during stem cell competition in the Drosophila testis.

In the Drosophila testis, a group of stromal cells termed hub provides multiple niche signals for the surrounding germline and somatic stem cells. Stem cells of both populations compete for physical retention in the niche, and clones unable to transduce any one niche signal are rapidly eliminated from the stem cell pool by differentiation. We have mapped the transcriptomes of isolated somatic cyst stem cells and differentiated cyst cells, and found that the stem cells but not their differentiated progeny exhibit the signature of an innate immune response including the NF-κB transcription factor Relish (Rel).

Assessing the Effect of Extreme Weather on Population Health Using Consumer-Grade Wearables in Rural Burkina Faso: Observational Panel Study.

Background: Extreme weather, including heat and extreme rainfall, is projected to increase owing to climate change, which can have adverse impacts on human health. In particular, rural populations in sub-Saharan Africa are at risk because of a high burden of climate-sensitive diseases and low adaptive capacities. However, there is a lack of data on the regions that are anticipated to be most exposed to climate change.

Transcriptomics and cell painting analysis reveals molecular and morphological features associated with fed-batch production performance in CHO recombinant clones.

Stable, highly productive mammalian cells are critical for manufacturing affordable and effective biological medicines. Establishing a rational design of optimal biotherapeutic expression systems requires understanding how cells support the high demand for efficient biologics production. To that end, we performed transcriptomics and high-throughput imaging studies to identify putative genes and morphological features that underpin differences in antibody productivity among clones from a Chinese hamster ovary cell line.

Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis.

Intratumor heterogeneity as a clinical challenge becomes most evident after several treatment lines, when multidrug-resistant subclones accumulate. To address this challenge, the characterization of resistance mechanisms at the subclonal level is key to identify common vulnerabilities. In this study, we integrate whole-genome sequencing, single-cell (sc) transcriptomics (scRNA sequencing), and chromatin accessibility (scATAC sequencing) together with mitochondrial DNA mutations to define subclonal architecture and evolution for longitudinal samples from 15 patients with relapsed or refractory multiple myeloma.

Genomic features of recombinant CHO clones arising from transposon-based and randomized integration.

The use of transposase in cell line development (CLD) programs has experienced increased popularity over the past decade. However, few studies have described the mechanism of action and the genomic and phenotypic characteristics of clones derived from transposase. Additionally, how these traits impact long-term bioproduction is unknown.

Comparison of IGLV2-14 light chain sequences of patients with AL amyloidosis or multiple myeloma.

Light chain amyloidosis (AL) is one of the most common forms of systemic amyloidosis and is caused by the deposition of insoluble fibrils derived from misfolded and aggregated immunoglobulin light chains (LC). To uncover the causes leading to this aggregation, we compared AL LC sequences with those of patients with the related disease multiple myeloma (MM), which do not aggregate in insoluble fibrils in vivo. IGLV2-14 is one of the most common AL-associated IGLV subfamilies.

Investigation of Rare Non-Coding Variants in Familial Multiple Myeloma.

Multiple myeloma (MM) is a plasma cell malignancy whereby a single clone of plasma cells over-propagates in the bone marrow, resulting in the increased production of monoclonal immunoglobulin. While the complex genetic architecture of MM is well characterized, much less is known about germline variants predisposing to MM. Genome-wide sequencing approaches in MM families have started to identify rare high-penetrance coding risk alleles.

Implications and prognostic impact of mass spectrometry in patients with newly-diagnosed multiple myeloma.

Mass spectrometry (MS) is a promising tool for monitoring monoclonal protein in plasma cell dyscrasias. We included 480 transplant-eligible newly-diagnosed multiple myeloma (MM) patients from the GMMG-MM5 trial (EudraCT No. 2010-019173-16) and performed a retrospective MS analysis at baseline (480 patients) and at the pre-defined, consecutive time points after induction (444 patients), prior to maintenance (305 patients) and after one year of maintenance (227 patients).

Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): part 1 of an open-label, multicentre, randomised, active-controlled, phase 3 trial.

Background: Anti-CD38 monoclonal antibodies have consistently shown increased efficacy when added to standard of care for patients with multiple myeloma. We aimed to assess the efficacy of isatuximab in addition to lenalidomide, bortezomib, and dexamethasone in patients with newly diagnosed transplantation-eligible multiple myeloma.

Methods: This open-label, multicentre, randomised, active-controlled, phase 3 trial was done at 67 academic and oncology practice centres in Germany.

Using wearable devices to generate real-world, individual-level data in rural, low-resource contexts in Burkina Faso, Africa: A case study.

Background: Wearable devices may generate valuable data for global health research for low- and middle-income countries (LMICs). However, wearable studies in LMICs are scarce. This study aims to investigate the use of consumer-grade wearables to generate individual-level data in vulnerable populations in LMICs, focusing on the acceptability (quality of the devices being accepted or even liked) and feasibility (the state of being workable, realizable, and practical, including aspects of data completeness and plausibility).

Fast algorithms for nonlinear and constrained phase retrieval in near-field X-ray holography based on Tikhonov regularization.

Based on phase retrieval, lensless coherent imaging and in particular holography offers quantitative phase and amplitude images. This is of particular importance for spectral ranges where suitable lenses are challenging, such as for hard x-rays. Here, we propose a phase retrieval approach for inline x-ray holography based on Tikhonov regularization applied to the full nonlinear forward model of image formation.

Diversity and trends of human milk banking: a scoping review from 1946 to 2021.

Background: The provision of donor human milk (DHM) through human milk banks is now widely practised globally. The study aimed to describe the current state, identify major topics and map out the emerging trends in human milk banking.

Methods: PubMed was systematically searched for publications related to DHM, with the last update on 14 May 2021, for papers published between 1946 and 2021.

Variants Are Associated with the Risk for COPD and NSCLC Development, Better Overall Survival of the NSCLC Patients and Increased Chemosensitivity in the H1299 Cell Line.

Chronic obstructive pulmonary disease (COPD) is considered as the strongest independent risk factor for lung cancer (LC) development, suggesting an overlapping genetic background in both diseases. A common feature of both diseases is aberrant immunity in respiratory epithelia that is mainly regulated by Toll-like receptors (TLRs), key regulators of innate immunity. The function of the flagellin-sensing TLR5 in airway epithelia and pathophysiology of COPD and LC has remained elusive.

Wearables for Measuring Health Effects of Climate Change-Induced Weather Extremes: Scoping Review.

Background: Although climate change is one of the biggest global health threats, individual-level and short-term data on direct exposure and health impacts are still scarce. Wearable electronic devices (wearables) present a potential solution to this research gap. Wearables have become widely accepted in various areas of health research for ecological momentary assessment, and some studies have used wearables in the field of climate change and health.