Health system financing fragmentation and maternal mortality transition in Mexico, 2000-2022.

Objective: To analyze the temporal and territorial relationship between health system financing fragmentation and maternal mortality in the last two decades in Mexico.

Methods: We conducted an ecological-longitudinal study of the maternal mortality ratio (MMR) in the 32 states of Mexico during the period 2000-2022. Annual MMRs were estimated at the national and state levels according to health insurance.

Comparison of the sociodemographic and clinical profiles of cancer patients admitted to a tertiary palliative care unit before and during the COVID-19 pandemic.

Objective: To compare the sociodemographic and clinical profiles of patients with advanced cancer admitted to a tertiary palliative care unit before and during the COVID-19 pandemic.

Methods: This is an analysis of data from patients receiving care before (10/21/2019 to 03/16/2020) and during (09/23/2020 to 08/26/2021) the COVID-19 pandemic. Sociodemographic and clinical data were evaluated.

Tegaserod maleate exerts anti-tumor effects on prostate cancer via repressing sonic hedgehog signaling pathway.

Prostate cancer (PCa) is a highly common type of malignancy and affects millions of men in the world since it is easy to recur or emerge therapy resistance. Therefore, it is urgent to find novel treatments for PCa patients. In the current study, we found that tegaserod maleate (TM), an FDA-approved agent, inhibited proliferation, colony formation, migration as well as invasion, caused the arrest of the cell cycle, and promoted apoptosis of PCa cells in vitro.

Prediction of pulmonary function decline in fibrous interstitial lung abnormalities based on quantitative chest CT parameters.

Background: Interstitial lung abnormalities (ILA) are a proposed imaging concept. Fibrous ILA have a higher risk of progression and death. Clinically, computed tomography (CT) examination is a frequently used and convenient method compared with pulmonary function tests.

Fully automated segmentation and classification of renal tumors on CT scans via machine learning.

Background: To develop and test the performance of a fully automated system for classifying renal tumor subtypes via deep machine learning for automated segmentation and classification.

Materials And Methods: The model was developed using computed tomography (CT) images of pathologically proven renal tumors collected from a prospective cohort at a medical center between March 2016 and December 2020. A total of 561 renal tumors were included: 233 clear cell renal cell carcinomas (RCCs), 82 papillary RCCs, 74 chromophobe RCCs, and 172 angiomyolipomas.

ADSL promotes autophagy and tumor growth through fumarate-mediated Beclin1 dimethylation.

As an enzyme with a critical role in de novo purine synthesis, adenylosuccinate lyase (ADSL) expression is upregulated in various malignancies. However, whether ADSL possesses noncanonical functions that contribute to cancer progression remains poorly understood. Here, we demonstrate that protein kinase R-like endoplasmic reticulum kinase (PERK) activated by lipid deprivation or ER stress phosphorylates ADSL at S140, leading to an enhanced association between ADSL and Beclin1.

SLC25A1 and ACLY maintain cytosolic acetyl-CoA and regulate ferroptosis susceptibility via FSP1 acetylation.

Ferroptosis, an iron-dependent form of programmed cell death characterized by excessive lipid hydroperoxides accumulation, emerges as a promising target in cancer therapy. Among the solute carrier (SLC) superfamily, the cystine/glutamate transporter system antiporter components SLC3A2 and SLC7A11 are known to regulate ferroptosis by facilitating cystine import for ferroptosis inhibition. However, the contribution of additional SLC superfamily members to ferroptosis remains poorly understood.

Identification of novel 7-hydroxycoumarin derivatives as ELOC binders with potential to modulate CRL2 complex formation.

The VHL-containing cullin-RING E3 ubiquitin ligase (CRL2) complex is an E3 ligase commonly used in targeted protein degradation (TPD). Hydroxyproline-based ligands that mimic VHL substrates have been developed as anchor molecules for proteolysis-targeting chimeras (PROTACs) in TPD. To expand the chemical space for VHL ligands, we conducted fragment screening using VHL-ELOB-ELOC (VBC) proteins.

Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells.

Somatic stem cell pools comprise diverse, highly specialized subsets whose individual contribution is critical for the overall regenerative function. In the bone marrow, myeloid-biased hematopoietic stem cells (myHSCs) are indispensable for replenishment of myeloid cells and platelets during inflammatory response but, at the same time, become irreversibly damaged during inflammation and aging. Here we identify an extrinsic factor, semaphorin 4A (Sema4A), which non-cell-autonomously confers myHSC resilience to inflammatory stress.

Outside-in engineering of cadherin endocytosis using a conformation strengthening antibody.

P-cadherin, a crucial cell-cell adhesion protein which is overexpressed in numerous malignant cancers, is a popular target for drug delivery antibodies. However, molecular guidelines for engineering antibodies that can be internalized upon binding to P-cadherin are unknown. Here, we use a combination of biophysical, biochemical, and cell biological methods to demonstrate that trapping the P-cadherin extracellular region in an X-dimer adhesive conformation triggers cadherin endocytosis via an outside-in signaling mechanism.

A Multidisciplinary Multimodal Aligned Dataset for Academic Data Processing.

Academic data processing is crucial in scientometrics and bibliometrics, such as research trending analysis and citation recommendation. Existing datasets in this domain have predominantly concentrated on textual data, overlooking the importance of visual elements. To bridge this gap, we introduce a multidisciplinary multimodal aligned dataset (MMAD) specifically designed for academic data processing.

Intricacies of human-AI interaction in dynamic decision-making for precision oncology.

AI decision support systems can assist clinicians in planning adaptive treatment strategies that can dynamically react to individuals' cancer progression for effective personalized care. However, AI's imperfections can lead to suboptimal therapeutics if clinicians over or under rely on AI. To investigate such collaborative decision-making process, we conducted a Human-AI interaction study on response-adaptive radiotherapy for non-small cell lung cancer and hepatocellular carcinoma.

AAV Capsid Modification and Its Influence on Viral Protein Stoichiometry and Packaging Fitness: Current Understandings and Future Direction.

The field of gene therapy has witnessed significant advancements in the utilization of Adeno-associated virus (AAV) owing to its inherent biological advantages. Targeted AAV vectors are generated through genetic or chemical modification of the capsid for user-directed purposes. However, this process can result in imbalances in viral protein sequence homogeneity, stoichiometry, and functional transduction vector units, thereby introducing new challenges.

Hallmark discoveries in the biology of non-Wilms tumour childhood kidney cancers.

Approximately 20% of paediatric and adolescent/young adult patients with renal tumours are diagnosed with non-Wilms tumour, a broad heterogeneous group of tumours that includes clear-cell sarcoma of the kidney, congenital mesoblastic nephroma, malignant rhabdoid tumour of the kidney, renal-cell carcinoma, renal medullary carcinoma and other rare histologies. The differential diagnosis of these tumours dates back many decades, when these pathologies were identified initially through clinicopathological observation of entities with outcomes that diverged from Wilms tumour, corroborated with immunohistochemistry and molecular cytogenetics and, subsequently, through next-generation sequencing. These advances enabled near-definitive recognition of different tumours and risk stratification of patients.

Integrating single-cell RNA and T cell/B cell receptor sequencing with mass cytometry reveals dynamic trajectories of human peripheral immune cells from birth to old age.

A comprehensive understanding of the evolution of the immune landscape in humans across the entire lifespan at single-cell transcriptional and protein levels, during development, maturation and senescence is currently lacking. We recruited a total of 220 healthy volunteers from the Shanghai Pudong Cohort (NCT05206643), spanning 13 age groups from 0 to over 90 years, and profiled their peripheral immune cells through single-cell RNA-sequencing coupled with single T cell and B cell receptor sequencing, high-throughput mass cytometry, bulk RNA-sequencing and flow cytometry validation experiments. We revealed that T cells were the most strongly affected by age and experienced the most intensive rewiring in cell-cell interactions during specific age.

Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence.

Black men suffer disproportionately from prostate cancer (PCa) compared to men of other races and ethnicities. Comparing the molecular landscape of PCa among Black and White patients has the potential to identify targets for development of new precision medicine interventions. Herein, we conducted transcriptomic analysis of prostate tumors and paired tumor-adjacent normals from self-reported Black and White PCa patients and estimated patient genetic ancestry.

TERT-TP53 mutations: a novel biomarker pair for hepatocellular carcinoma recurrence and prognosis.

Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, and ranks among the most lethal malignancies globally, primarily due to its high rates of recurrence and metastasis. Despite the urgency, no reliable biomarkers currently exist for predicting tumor recurrence in HCC. Telomerase reverse transcriptase (TERT) promoter mutations (TERTpm) and cellular tumor antigen p53 mutations (TP53m) have been frequently documented in HCC, but their combined clinical significance remains undefined.

VSTM2L protects prostate cancer cells against ferroptosis via inhibiting VDAC1 oligomerization and maintaining mitochondria homeostasis.

Ferroptosis is a form of iron-dependent programmed cell death, which is distinct from apoptosis, necrosis, and autophagy. Mitochondria play a critical role in initiating and amplifying ferroptosis in cancer cells. Voltage-Dependent Anion Channel 1 (VDAC1) embedded in the mitochondrial outer membrane, exerts roles in regulation of ferroptosis.

Molecular and pharmacological heterogeneity of ETV6::RUNX1 acute lymphoblastic leukemia.

ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL) associated with favorable prognosis, but the optimal therapy for this subtype remains unclear. Profiling the genomic and pharmacological landscape of 194 pediatric ETV6::RUNX1 ALL cases, we uncover two transcriptomic clusters, C1 (61%) and C2 (39%). Compared to C1, the C2 subtype features higher white blood cell counts and younger age at diagnosis, as well as better early treatment responses.

Time-resolved Brownian tomography of single nanocrystals in liquid during oxidative etching.

Colloidal nanocrystals inherently undergo structural changes during chemical reactions. The robust structure-property relationships, originating from their nanoscale dimensions, underscore the significance of comprehending the dynamic structural behavior of nanocrystals in reactive chemical media. Moreover, the complexity and heterogeneity inherent in their atomic structures require tracking of structural transitions in individual nanocrystals at three-dimensional (3D) atomic resolution.

Molecular regulation of mitophagy signaling in tumor microenvironment and its targeting for cancer therapy.

Aberrations emerging in mitochondrial homeostasis are restrained by mitophagy to control mitochondrial integrity, bioenergetics signaling, metabolism, oxidative stress, and apoptosis. The mitophagy-accompanied mitochondrial processes that occur in a dysregulated condition act as drivers for cancer occurrence. In addition, the enigmatic nature of mitophagy in cancer cells modulates the cellular proteome, creating challenges for therapeutic interventions.

Identification of the molecular characterization and tumor microenvironment of thoracic inflammatory myofibroblastic tumors.

Background: Inflammatory myofibroblastic tumors (IMTs), rare soft tissue neoplasms, are characterized by a blend of myofibroblastic proliferation and inflammatory features. While generally characterized by slow growth, IMTs can exhibit locally aggressive behavior, and in rare instances, metastasize to distant sites. This study elucidated the clinical characteristics, molecular profile, and tumor microenvironment of thoracic IMTs.

Doing 'detective work' to find a cancer: how are non-specific symptom pathways for cancer investigation organised, and what are the implications for safety and quality of care? A multisite qualitative approach.

Background: Over the past two decades, the UK has actively developed policies to enhance early cancer diagnosis, particularly for individuals with non-specific cancer symptoms. Non-specific symptom (NSS) pathways were piloted and then implemented in 2015 to address delays in referral and diagnosis. The aim of this study was to outline the functions that enable NSS teams to investigate cancer and other diagnoses for patients with NSSs.

Analytical and Clinical Validation of the Plasma-Based Guardant360 CDx Test for Assessing HER2 (ERBB2) Mutation Status in Patients with Non-Small-Cell Lung Cancer for Treatment with Trastuzumab Deruxtecan in DESTINY-Lung01/02.

This study demonstrates the analytical and clinical validity of the approved (United States and Japan) plasma-based Guardant360 companion diagnostic (CDx) test for selecting patients with human epidermal growth factor receptor 2 (HER2 [ERBB2])-mutated (HER2m) non-small-cell lung cancer (NSCLC) for trastuzumab deruxtecan (T-DXd) treatment. Concordance between the Guardant360 CDx test and the plasma-based AVENIO ctDNA Expanded Kit Assay (AVENIO), as well as the tissue-based clinical trial assays (CTAs) was investigated. Clinical utility was assessed by comparing T-DXd clinical efficacy results of patients in DESTINY-Lung01/02 who tested positive for HER2 mutations using the Guardant360 CDx test to benchmark efficacy results from DESTINY-Lung01/02.

Self-reported determinants for subjective financial distress: a qualitative interview study with German cancer patients.

Objectives: Patient-reported financial effects of a tumour disease in a universal healthcare setting are a multidimensional phenomenon. Actual and anticipated objective financial burden caused by direct medical and non-medical costs as well as indirect costs such as loss of income can lead to subjective financial distress. To better understand subjective financial distress, the presented study explores self-reported determinants for subjective financial distress in German patients with cancer, aiming to inform a new German-language patient-reported outcome measure for determining the financial effects of a tumour disease.