Browse Articles

CD3×CD20 bispecifics + chemotherapy: good news for R/R DLBCL

Research on the optimization of optimal blasting parameters and fragmentation control based on coal seam geological conditions

How Europe aims to woo US scientists and protect academic freedom

SMAC mimetics in action in chronic myeloid leukemia

Knowledge, attitudes, and practices regarding intrinsic capacity in the elderly population: A cross-sectional study in Shanghai, China

The United Kingdom Infected Blood Inquiry: its findings and lessons for the future of transfusion

Abstract The UK Infected Blood Inquiry report was published in May 2024 after 6 years of taking oral and written evidence from patients, clinicians, blood services, government officials, and politicians about the transmission of infection by blood transfusion to thousands of patients in the 1970s through to the 1990s. The same problems with transfusion-transmitted infection occurred in many other countries in the same period, but their reviews, inquiries, and decisions about compensation occurred many years earlier than in the United Kingdom. The publication of the report has been welcomed but begs 2 important questions. Why was the inquiry so delayed in the United Kingdom? And why did it take so long to report? Furthermore, the report itself deserves scrutiny. What were its findings and lessons learned? How will the findings be implemented, and what are the implications, if any, for other countries?

The usefulness of different imaging modalities in mandibular osteonecrosis and osteomyelitis diagnosis

IL-1R1 and IL-18 signals regulate mesenchymal stromal cells in an aged murine model of myelodysplastic syndromes

Abstract Myelodysplastic syndromes (MDS) are age-related diseases characterized by bone marrow (BM) dysfunction and an increased risk for developing acute leukemia. Although there is growing evidence that highlight the crucial role of the BM microenvironment (BMME) in MDS, the specific influence of inflammation on BMME changes and the potential benefits of targeting cytokines therapeutically remain to be elucidated. We previously found that interleukin-1 (IL-1) is a driver of aging phenotypes of the BMME and hematopoietic stem and progenitor cells (HSPCs). In this study, BM samples from patients with MDS demonstrated upregulated levels of IL-1 family cytokines, including IL-18. Using highly purified primary BM-derived mesenchymal stromal cells (MSCs), both IL-1b and IL-18 were found to exert direct effects on MSCs, thus influencing their ability to support HSPCs and erythroid progenitors. This confirms the significant involvement of both these IL-1 family cytokines in regulating the BM niche. Furthermore, targeting IL-1 receptor type 1 mitigated these aging phenotypes in older mice. We subsequently employed an age-appropriate murine model of MDS by transplanting NUP98-HOXD13 transgenic mice (NHD13Tg) cells into aged wild-type mice. Treatment with inhibitors that targeted IL-1 receptor-associated kinase 4 (IRAK4) and NOD-like receptor family pyrin domain containing 3 (NLRP3) reversed the proliferation of dysfunctional MSCs and enhanced their functionality. In addition, IRAK4 inhibition selectively suppressed MDS clonal cells while sparing non-MDS cells in the BM. These findings suggest that targeting IL-1 signaling holds promise for MDS treatment by addressing the underlying myeloid malignancy and restoring the altered BMME via BM-MSCs.

Author Correction: Predictive model development combining CT-FFR and SYNTAX score for major adverse cardiovascular events in complex coronary artery disease

El Niños that linger are becoming less of a rarity

sBCMA and MTV prediction of outcome for CART

Author Correction: Passenger physiology in self-driving vehicles during unexpected events

Targeting IL-1/IL-18 mitigates MDS in aged mice

Publisher Correction: Predictors of presence of and search for meaning in life among Omani students during the COVID-19 pandemic: a cross-sectional study

High-throughput drug screening identifies SMAC mimetics as enhancers of NK-cell cytotoxicity in chronic myeloid leukemia

Abstract Natural killer (NK) cells have proven to be safe and effective immunotherapies, associated with favorable treatment responses in chronic myeloid leukemia (CML). Augmenting NK-cell function with oncological drugs could improve NK-cell–based immunotherapies. Here, we used a high-throughput drug screen consisting of >500 small-molecule compounds, to systematically evaluate the effects of oncological drugs on primary NK cells against CML cells. We identified second mitochondrially derived activator of caspases (SMAC) mimetics as potent enhancers of NK-cell cytotoxicity in both cell lines and primary patient samples. In contrast, several drug classes, including glucocorticoids and tyrosine kinase inhibitors such as dasatinib, inhibited NK-cell cytotoxicity. Single-cell RNA sequencing revealed drug-induced transcriptomic changes in both NK and target CML cells. SMAC mimetics upregulated NF-κB target genes in NK cells, potentially contributing to their enhanced cytotoxicity. Inhibitory drugs dexamethasone, dasatinib, and sotrastaurin prevented NK-cell transition to an activated state and suppressed the expression of interferon gamma (IFN-γ) by NK cells, thus preventing IFN-γ–mediated target cell transcriptomic response. In conclusion, we discovered that SMAC mimetics sensitize cancer cells to NK-cell–mediated killing, with potential clinical applications especially in patients with advanced phase CML.

Trajectories of sleep disturbance and self-management of chronic conditions during COVID-19 among middle-aged and older adults

Hitting the bullseye in GVHD

Unique N-glycosylation signatures in human iPSC derived microglia activated by Aβ oligomer and lipopolysaccharide

Abstract Microglia are the immune cells in the central nervous system (CNS) and become pro-inflammatory/activated in Alzheimer’s disease (AD). Cell surface glycosylation plays an important role in immune cells; however, the N-glycosylation and glycosphingolipid (GSL) signatures of activated microglia are poorly understood. Here, we study comprehensively combined transcriptomic and glycomic profiles using human induced pluripotent stem cells-derived microglia (hiMG). Distinct changes in N-glycosylation patterns in amyloid-β oligomer (AβO) and LPS-treated hiMG were observed. In AβO-treated cells, the relative abundance of bisecting N-acetylglucosamine (GlcNAc) N-glycans decreased, corresponding with a downregulation of MGAT3. The sialylation of N-glycans increased in response to AβO, accompanied by an upregulation of genes involved in N-glycan sialylation (ST3GAL4 and 6). Unlike AβO-induced hiMG, LPS-induced hiMG exhibited a decreased abundance of complex-type N-glycans, aligned with downregulation of mannosidase genes (MAN1A1, MAN2A2, and MAN1C1) and upregulation of ER degradation related-mannosidases (EDEM1-3). Fucosylation increased in LPS-induced hiMG, aligned with upregulated fucosyltransferase 4 (FUT4) and downregulated alpha-L-fucosidase 1 (FUCA1) gene expression, while sialofucosylation decreased, aligned with upregulated neuraminidase 4 (NEU4). Inhibition of sialylation and fucosylation in AβO- and LPS-induced hiMG alleviated pro-inflammatory responses. However, the GSL profile did not exhibit significant changes in response to AβO or LPS activation, at least in the 24-hour stimulation timeframe. AβO- and LPS- specific glycosylation changes could contribute to impaired microglia function, highlighting glycosylation pathways as potential therapeutic targets for AD.

How I manage patients with unexplained cytopenia

Abstract The term “unexplained cytopenia” is used to describe a condition characterized by peripheral blood cytopenia that cannot be attributed to identifiable causes using conventional tests or to any concomitant diseases. Unexplained cytopenia requires clinical attention and further investigation to identify individuals at risk of developing a hematologic neoplasm. The available evidence suggests that somatic mutation analysis may effectively complement the diagnostic workup and clinical management of unexplained cytopenia. Indeed, the presence or absence of somatic mutation(s) in myeloid genes shows high positive and negative predictive values for myeloid neoplasms (MNs). Mutation analysis is also crucial for identifying patients with clonal cytopenia of undetermined significance (CCUS), a condition at increased risk of developing a MN. Recently, clinical/molecular prognostic models have been developed, providing valuable tools for the personalization of clinical and molecular surveillance. Most patients with CCUS show mild cytopenia and do not require therapeutic intervention. Currently, there is no treatment approved for CCUS, and transfusion therapy is the sole therapeutic option for patients with severe symptomatic cytopenia. However, this field has been emerging as a domain of active clinical investigation. This article presents 4 case studies of patients with unexplained cytopenia, which hematologists may encounter in their clinical practice.

ATCodeR: a dictionary-based R-tool to standardize medication free-text

Abstract Over the past decades, oncology treatment paradigms have developed significantly. Yet, the often unstructured nature of substance-related documentation in medical records presents a time-consuming challenge for analyzing treatment patterns and outcomes. To advance oncological research further, clinical data science must offer solutions that facilitate research and analysis with real-world data (RWD). The present contribution introduces a user-friendly R-tool designed to transform free-text medication entries into the structured Anatomical Therapeutic Chemical (ATC) Classification System by applying a dictionary-based approach. The resulting output is a structured data frame containing columns for antineoplastic medication, other medications, and supplementary information. For accuracy validation, 561 data entries from an evaluation data set were reviewed, consisting of 935 tokens. 88.5% of these tokens were successfully transformed into their respective ATC codes. Additional information was extracted from 129 data entries (23%), while 23 entries (4.1%) presented no usable information. All tokens underwent a manual review; 8.9% (84 tokens) failed transformations. This approach improves the standardization and analysis of systemic anti-cancer treatment data in German-speaking regions by optimizing efficiency while maintaining relevant accuracy.