Pharmacological stabilization of the native state of full-length immunoglobulin light chains to treat light chain amyloidosis.

Immunoglobulin light chain amyloidosis (AL) is a cancer of plasma cells that secrete unstable full-length immunoglobulin light chains. These light chains misfold and aggregate, often with aberrant endoproteolysis, leading to organ toxicity. AL is currently treated by pharmacological elimination of the clonal plasma cells.

Quantifying physiological stability in the general ward using continuous vital signs monitoring: the circadian kernel density estimator.

Technological advances seen in recent years have introduced the possibility of changing the way hospitalized patients are monitored by abolishing the traditional track-and-trigger systems and implementing continuous monitoring using wearable biosensors. However, this new monitoring paradigm raise demand for novel ways of analyzing the data streams in real time. The aim of this study was to design a stability index using kernel density estimation (KDE) fitted to observations of physiological stability incorporating the patients' circadian rhythm.

Context-dependent activation of STING-interferon signaling by CD11b agonists enhances anti-tumor immunity.

Chronic activation of inflammatory pathways and suppressed interferon are hallmarks of immunosuppressive tumors. Previous studies have shown that CD11b integrin agonists could enhance anti-tumor immunity through myeloid reprograming, but the underlying mechanisms remain unclear. Herein we find that CD11b agonists alter tumor-associated macrophage (TAM) phenotypes by repressing NF-κB signaling and activating interferon gene expression simultaneously.

Teaching open and reproducible scholarship: a critical review of the evidence base for current pedagogical methods and their outcomes.

In recent years, the scientific community has called for improvements in the credibility, robustness and reproducibility of research, characterized by increased interest and promotion of open and transparent research practices. While progress has been positive, there is a lack of consideration about how this approach can be embedded into undergraduate and postgraduate research training. Specifically, a critical overview of the literature which investigates how integrating open and reproducible science may influence is needed.

Changes in Dietary Inflammatory Index Score over Time and Cancer Development in Rural Post-Menopausal Women.

Inflammation plays a key role in cancer development. As an important modulator of inflammation, the role of diet should be explored. The purpose of this study was to determine the association between diets with a higher inflammatory potential, as measured by the Dietary Inflammatory Index (DII), and cancer development in a cohort of rural post-menopausal women.

Human cortical spheroids with a high diversity of innately developing brain cell types.

Background: Three-dimensional (3D) human brain spheroids are instrumental to study central nervous system (CNS) development and (dys)function. Yet, in current brain spheroid models the limited variety of cell types hampers an integrated exploration of CNS (disease) mechanisms.

Methods: Here we report a 5-month culture protocol that reproducibly generates H9 embryonic stem cell-derived human cortical spheroids (hCSs) with a large cell-type variety.

Systematic screening versus clinical gestalt in the diagnosis of pulmonary embolism in COVID-19 patients in the emergency department.

Background: Diagnosing concomitant pulmonary embolism (PE) in COVID-19 patients remains challenging. As such, PE may be overlooked. We compared the diagnostic yield of systematic PE-screening based on the YEARS-algorithm to PE-screening based on clinical gestalt in emergency department (ED) patients with COVID-19.

Determinants of Depressive Symptoms in People Living with HIV: Findings from a Population-Based Study with a Gender Perspective.

Depressive symptoms are common among people living with HIV (PLWH). The aim of this study was to identify the determinants of depressive symptoms in PLWH in Spain. A total of 1060 PLWH participated in this cross-sectional study and completed the Patient Health Questionnaire-9.

A fast linkage method for population GWAS cohorts with related individuals.

Linkage analysis, a class of methods for detecting co-segregation of genomic segments and traits in families, was used to map disease-causing genes for decades before genotyping arrays and dense SNP genotyping enabled genome-wide association studies in population samples. Population samples often contain related individuals, but the segregation of alleles within families is rarely used because traditional linkage methods are computationally inefficient for larger datasets. Here, we describe Population Linkage, a novel application of Haseman-Elston regression as a method of moments estimator of variance components and their standard errors.

Alternative splicing in multiple myeloma is associated with the non-homologous end joining pathway.

Alternative splicing plays a pivotal role in tumorigenesis and proliferation. However, its pattern and pathogenic role has not been systematically analyzed in multiple myeloma or its subtypes. Alternative splicing profiles for 598 newly diagnosed myeloma patients with comprehensive genomic annotation identified primary translocations, 1q amplification, and DIS3 events to have more differentially spliced events than those without.

Comparing the Validity of the Rorschach Performance Assessment System and Exner's Comprehensive System to Differentiate Patients and Nonpatients.

Building on the comparative nonpatient study of Pianowski et al., we examine data from the Rorschach Performance Assessment System (R-PAS) and Comprehensive System (CS) in 100 nonpatients and 100 patients, 50 of each per system. Replicating their results but now in a patient sample, R-PAS produced more patient protocols having an optimal number of responses (R) for interpretation and eliminated the need for readministration due to low R.

A pooled analysis of outcomes according to cytogenetic abnormalities in patients receiving ixazomib- vs placebo-based therapy for multiple myeloma.

Some cytogenetic abnormalities (CAs) are associated with poorer prognosis in multiple myeloma (MM); proteasome inhibitors appear to benefit patients with high-risk CAs. We evaluated 2247 MM patients from the TOURMALINE-MM1/-MM2/-MM3/-MM4 trials to assess the PFS benefit of ixazomib plus lenalidomide-dexamethasone (Rd) vs placebo-Rd (TOURMALINE-MM1/-MM2) or ixazomib vs placebo (TOURMALINE-MM3/-MM4) in specific high-risk CAs. After a pooled median follow-up of 25.

Optimizing the value of lenalidomide maintenance by extended genetic profiling: an analysis of 556 patients in the Myeloma XI trial.

Prediction of individual patient benefit from lenalidomide (Len) maintenance after autologous stem cell transplant (ASCT) remains challenging. Here, we investigated extended molecular profiling for outcome prediction in patients in the National Cancer Research Institute Myeloma XI (MyXI) trial. Patients in the MyXI trial randomized to Len maintenance or observation after ASCT were genetically profiled for t(4;14), t(14;16), t(14;20), del(1p), gain(1q), and del(17p) and co-occurrence of risk markers was computed.

Sample preparation for lipid analysis of intra-articular adipose tissue by using matrix-assisted laser desorption/ionization imaging.

Mass spectrometry imaging (MSI) is a powerful technique enabling the visualization of the spatial distribution of different molecules in tissue biopsies with different pathologies. Sample handling and preparing adipose tissue for MSI is challenging and prone to molecular delocalization due to tissue melting. In this work, we developed a method for matrix-assisted laser desorption/ionization (MALDI)-MSI to study lipids in human infrapatellar fat pad (IPFP), a biomarker source in musculoskeletal pathologies, while preserving molecular spatial distribution.

Electronic Structure and Chemical Bonding in Methylammonium Lead Triiodide and Its Precursor Methylammonium Iodide.

A detailed examination of the electronic structures of methylammonium lead triiodide (MAPI) and methylammonium iodide (MAI) is performed with molecular dynamics (AIMD) simulations based on density functional theory, and the theoretical results are compared to experimental probes. The occupied valence bands of a MAPI single crystal and MAI powder are probed with X-ray photoelectron spectroscopy, and the conduction bands are probed from the perspective of nitrogen K-edge X-ray absorption spectroscopy. Combined, the theoretical simulations and the two experimental techniques allow for a dissection of the electronic structure unveiling the nature of chemical bonding in MAPI and MAI.

Overcoming the low reactivity of biobased, secondary diols in polyester synthesis.

Shifting away from fossil- to biobased feedstocks is an important step towards a more sustainable materials sector. Isosorbide is a rigid, glucose-derived secondary diol, which has been shown to impart favourable material properties, but its low reactivity has hampered its use in polyester synthesis. Here we report a simple, yet innovative, synthesis strategy to overcome the inherently low reactivity of secondary diols in polyester synthesis.