Transl Res. 2025 Feb 12:S1931-5244(25)00023-4. doi: 10.1016/j.trsl.2025.02.002. Online ahead of print.

ABSTRACT

Mitochondrial dysfunction is closely associated with idiopathic pulmonary fibrosis (IPF). However, the causal association between mitochondria-related genes and IPF remains to be determined. We obtained gene expression, protein abundance, and methylation quantitative trait locus data for mitochondria-related genes from previous studies. Genome-wide association study data for patients with IPF were obtained from the FinnGen study. A two-sample Mendelian randomisation analysis was conducted to assess the association between mitochondria-related genes and IPF. Furthermore, we conducted validation of expression differences utilizing transcriptome data derived from the BLM-induced pulmonary fibrosis mouse model (n=15). Concurrently, multiphoton imaging was utilized to quantify collagen contents and structural assessment. The direction of causality was verified using the Steiger test, and colocalisation analysis was used to better validate causality. Single-cell data were used to explore the localisation and expression of positive genes across different cell types. The study identified significant associations between mitochondria-related genes and IPF, with POLG and NDUFB10 classified as Grade 1; LYRM4, NBR1, and ACSF3 as Grade 2; MCL1, GFER, MFN2, IVD, and SLC25A35 as Grade 3; and METAP1D and MTX1 as Grade 4. Single-cell analysis showed elevated expression of NBR1, MCL1, and MTX1 in pulmonary myofibroblasts of IPF. This study elucidated the causal effects of mitochondria-related genes on IPF, underscoring their significance in pathogenesis. These findings contribute to an improved understanding of the mechanisms underlying IPF, offering new potential therapeutic targets for interventions.

PMID:39952317 | DOI:10.1016/j.trsl.2025.02.002

J Vasc Access. 2025 Feb 14:11297298251320269. doi: 10.1177/11297298251320269. Online ahead of print.

ABSTRACT

BACKGROUND: This study investigates the relationship between national catheter use among hemodialysis (HD) patients and kidney transplantation (KTX) activity, exploring the hypothesis that higher KTX activity may be associated with increased catheter usage. The rationale is based on the idea that shorter waiting times for transplants in high-activity countries could make central venous catheters (CVCs) more favorable as a temporary bridge to transplantation compared to arteriovenous fistulas or grafts which require longer maturation times.

METHODS: Nine national dialysis and transplant registries (Argentina, Australia, Austria, New Zealand, Portugal, Scotland, Sweden, USA, Turkey) were included in this analysis. The included descriptive analysis of baseline information from included countries, followed by crude association analyses using correlation and regression analyses to explore the relationship between CVC usage and kidney transplants per million inhabitants, considering relevant confounders. Adjusted analyses were performed to account for these confounders, providing a more nuanced understanding of the relationship.

RESULTS: Data from nine different national registries was analyzed. CVC use and KTX activity had a weak to moderate positive correlation (r = 0.23, 95% CI: 0.07, 0.39). In all included countries CVC use increased over time. Adjusting for temporal patterns, country-specific factors, and the proportion of female HD patients, there was still strong evidence for a moderate increase of CVCs among prevalent HD patients with increasing KTX activity.

CONCLUSION: Higher national KTX activity is associated with a moderate increase in CVCs among prevalent HD patients.

PMID:39953649 | DOI:10.1177/11297298251320269

Sci Rep. 2025 Feb 14;15(1):5512. doi: 10.1038/s41598-025-89783-7.

ABSTRACT

The early sequence of respiratory failure events after the onset of sepsis is still unknown. We hypothesize that the lung should signal through circulating extracellular vesicles (EVs) when it is affected by a systemic inflammatory response. Blood samples were obtained from septic patients with (n = 5) and without acute respiratory distress syndrome (ARDS) (n = 13) at 24 h of intensive care unit admission and 3 days later at Sírio-Libanês Hospital. Pulmonary-originated sepsis was not considered. The characteristics of the plasma-isolated EVs were compatible with exosomes. 48 miRNAs were evaluated by real-time PCR. Comparing all samples from patients with sepsis + ARDS to sepsis only, 9 miRNAs are transported in smaller amounts: miR-766 (-35.7, p = 0.002), miR-127 (-23.8, p = 0.001), miR-340 (-13.5, p = 0.006), miR-29b (-12.8, p = 0.001), miR-744 (-7.1, p = 0.05), miR-618 (-4.0, p = 0.02), miR-598 (-3.8, p = 0.035), miR-1260 (-2.5, p = 0.035); and miR-885-5p is expressed at higher levels (9.5; p = 0.028). In paired samples, the set of altered miRNAs is generally different (p < 0.05) between sepsis + ARDS (miR-1183,-1267,-1290,-17,-192,-199a-3p,-25,-485-3p,-518d,-720) or sepsis only (miR-148a,-193a-5p,-199a-3p,-222,-25,-340,744). Bioinformatic analysis showed that when sepsis is associated with ARDS, those differentially expressed miRNAs potentially target messenger RNAs from the Glycoprotein VI/GP6 signaling pathway. Circulating EV-miRNA cargo could be potential biomarkers of lung inflammation during sepsis in patients requiring mechanical ventilation.

PMID:39953195 | DOI:10.1038/s41598-025-89783-7

Nat Rev Rheumatol. 2025 Feb 14. doi: 10.1038/s41584-024-01217-2. Online ahead of print.

ABSTRACT

Systemic sclerosis (SSc) remains a challenging and enigmatic systemic autoimmune disease, owing to its complex pathogenesis, clinical and molecular heterogeneity, and the lack of effective disease-modifying treatments. Despite a century of research in SSc, the interconnections among microvascular dysfunction, autoimmune phenomena and tissue fibrosis in SSc remain unclear. The absence of validated biomarkers and reliable animal models complicates diagnosis and treatment, contributing to high morbidity and mortality. Advances in the past 5 years, such as single-cell RNA sequencing, next-generation sequencing, spatial biology, transcriptomics, genomics, proteomics, metabolomics, microbiome profiling and artificial intelligence, offer new avenues for identifying the early pathogenetic events that, once treated, could change the clinical history of SSc. Collaborative global efforts to integrate these approaches are crucial to developing a comprehensive, mechanistic understanding and enabling personalized therapies. Challenges include disease classification, clinical heterogeneity and the establishment of robust biomarkers for disease activity and progression. Innovative clinical trial designs and patient-centred approaches are essential for developing effective treatments. Emerging therapies, including cell-based and fibroblast-targeting treatments, show promise. Global cooperation, standardized protocols and interdisciplinary research are vital for advancing SSc research and improving patient outcomes. The integration of advanced research techniques holds the potential for important breakthroughs in the diagnosis, treatment and care of individuals with SSc.

PMID:39953141 | DOI:10.1038/s41584-024-01217-2

Nat Commun. 2025 Feb 14;16(1):1643. doi: 10.1038/s41467-025-56901-y.

ABSTRACT

C4 photosynthesis exemplifies convergent evolution of complex traits. Herein, we construct chromosome-scale genome assemblies and perform multi-omics analysis for five Flaveria species, which represent evolutionary stages from C3 to C4 photosynthesis. Chromosome-scale genome sequence analyses reveal a gradual increase in genome size during the evolution of C4 photosynthesis attributed to the expansion of transposable elements. Systematic annotation of genes encoding C4 enzymes and transporters identify additional copies of three C4 enzyme genes through retrotranspositions in C4 species. C4 genes exhibit elevated mRNA and protein abundances, reduced protein-to-RNA ratios, and comparable translation efficiencies in C4 species, highlighting a critical role of transcriptional regulation in C4 evolution. Furthermore, we observe an increased abundance of ethylene response factor (ERF) transcription factors and cognate cis-regulatory elements associated with C4 genes regulation. Altogether, our study provides valuable genomic resources for the Flaveria genus and sheds lights on evolutionary and regulatory mechanisms underlying C4 photosynthesis.

PMID:39952962 | DOI:10.1038/s41467-025-56901-y

Pharmacol Rev. 2025 Jan;77(1):100001. doi: 10.1124/pharmrev.123.001140. Epub 2024 Nov 22.

ABSTRACT

For most vertebrates, bitter perception plays a critical role in the detection of potentially harmful substances in food items. The detection of bitter compounds is facilitated by specialized receptors located in the taste buds of the oral cavity. This work focuses on these receptors, including their sensitivities, structure-function relationships, agonists, and antagonists. The existence of numerous bitter taste receptor variants in the human population and the fact that several of them profoundly affect individual perceptions of bitter tastes are discussed as well. Moreover, the identification of bitter taste receptors in numerous tissues outside the oral cavity and their multiple proposed roles in these tissues are described briefly. Although this work is mainly focused on human bitter taste receptors, it is imperative to compare human bitter taste with bitter taste of other animals to understand which forces might have shaped the evolution of bitter taste receptors and their functions and to distinguish apparently typical human features from rather general ones. For readers who are not very familiar with the gustatory system, short descriptions of taste anatomy, signal transduction, and oral bitter taste receptor expression are included in the beginning of this article. SIGNIFICANCE STATEMENT: Apart from their role as sensors for potentially harmful substances in the oral cavity, the numerous additional roles of bitter taste receptors in tissues outside the gustatory system have recently received much attention. For careful assessment of their functions inside and outside the taste system, a solid knowledge of the specific and general pharmacological features of these receptors and the growing toolbox available for studying them is imperative and provided in this work.

PMID:39952694 | DOI:10.1124/pharmrev.123.001140

Annu Rev Plant Biol. 2025 Feb 14. doi: 10.1146/annurev-arplant-083123-050311. Online ahead of print.

ABSTRACT

The target of rapamycin (TOR) is a central regulator of growth, development, and stress adaptation in plants. This review delves into the molecular intricacies of TOR signaling, highlighting its conservation and specificity across eukaryotic lineages. We explore the molecular architecture of TOR complexes, their regulation by a myriad of upstream signals, and their consequential impacts on plant physiology. The roles of TOR in orchestrating nutrient sensing, hormonal cues, and environmental signals are highlighted, illustrating its pivotal function in modulating plant growth and development. Furthermore, we examine the impact of TOR on plant responses to various biotic and abiotic stresses, underscoring its potential as a target for agricultural improvements. This synthesis of current knowledge on plant TOR signaling sheds light on the complex interplay between growth promotion and stress adaptation, offering a foundation for future research and applications in plant biology.

PMID:39952681 | DOI:10.1146/annurev-arplant-083123-050311

Adv Med Sci. 2025 Feb 12:S1896-1126(25)00009-4. doi: 10.1016/j.advms.2025.01.009. Online ahead of print.

NO ABSTRACT

PMID:39952431 | DOI:10.1016/j.advms.2025.01.009

J Adv Res. 2025 Feb 12:S2090-1232(25)00111-0. doi: 10.1016/j.jare.2025.02.013. Online ahead of print.

ABSTRACT

BACKGROUND: Despite notable advancements in AML therapy in recent years, a substantial proportion of patients remain refractory or at high risk of recurrence with limited efficacy. Therefore, it's urgent to develop novel drugs for treating AML.

METHODS: The small molecule drug library was utilized to screen for drugs that elicit the inflammatory death of AML cells. Cell viability, cell morphological analysis, western blotting, and RNA-seq were used to determine the pathway of Mebendazole (MBD)-induced AML cell death. Cell cycle analysis, protein expression profiling, molecular docking, western blotting and lentivirus overexpression were used to analyze the target protein of MBD in AML cells. The anti-AML activity of MBD in vivo was evaluated using tumor xenograft models constructed by AML cell lines and patient-derived primary AML cells.

RESULTS: In this study, we have identified Mebendazole (MBD), a conventional anthelmintic drug known for its low toxicity and cost, as a potent agent that exerts significant anti-AML effects in vitro. Furthermore, we have observed its inhibitory effects on the invasion of AML cell lines and primary AML cells in xenograft mouse models, while noting its negligible toxic side effects in normal mice in vivo. Mechanically, MBD inhibits the cell cycle in G2/M phase by inhibiting tubulin α1A (TUBA1A) and promotes ZBP-1 mediated PANoptosis in AML cells. Our results confirm that MBD exerts anti-AML activity in preclinical models.

CONCLUSION: These results highlight the remarkable clinical translational potential of MBD, providing new potential medicine for AML patients. In addition, TUBA1A can be used potential novel therapeutic target in tumors with abnormal TUBA1A expression.

PMID:39952321 | DOI:10.1016/j.jare.2025.02.013

Stem Cell Reports. 2025 Feb 8:102419. doi: 10.1016/j.stemcr.2025.102419. Online ahead of print.

ABSTRACT

Naive human pluripotent stem cells (hPSCs) model the pre-implantation epiblast. However, parent-specific epigenetic marks (imprints) are eroded in naive hPSCs, which represents an important deviation from the epiblast in vivo. To track the dynamics of imprint erasure during naive resetting in real time, we established a dual-colored fluorescent reporter at both alleles of the imprinted SNRPN locus. During primed-to-naive resetting, SNRPN expression becomes biallelic in most naive cells, and biallelic SNRPN expression is irreversible upon re-priming. We utilized this live-cell reporter to evaluate chemical and genetic strategies to minimize imprint erasure. Decreasing the level of MEK/ERK inhibition or overexpressing the KRAB zinc-finger protein ZFP57 protected a subset of imprints during naive resetting. Combining these two strategies protected imprint levels to a further extent than either strategy alone. This study offers an experimental tool to track and enhance imprint stability during transitions between human pluripotent states in vitro.

PMID:39952244 | DOI:10.1016/j.stemcr.2025.102419

Food Chem. 2025 Feb 10;475:143323. doi: 10.1016/j.foodchem.2025.143323. Online ahead of print.

ABSTRACT

Triterpenoid saponins, bioactive compounds with pharmaceutical relevance and functional food potential, are abundant in tea plants (Camellia sinensis), yet their structural diversity and tissue-specific distribution remain insufficiently explored. Using high-resolution mass spectrometry, Feature-based Molecular Networking, and imaging mass spectrometry (IMS), we profiled 52 tea saponins, including two novel trisaccharide saponins with unique glycosylation patterns. Aerial tissues, particularly buds and leaves, were enriched with cinnamoyl-decorated tetrasaccharide saponins, whereas roots predominantly accumulated di- and trisaccharide saponins, with significant cultivar-specific variation. IMS further revealed a compartmentalized root distribution, with di- and trisaccharide saponins localized in the epidermis and cortex, while tetrasaccharide saponins were concentrated in the stele. These findings advance understanding of the structural complexity and spatial accumulation of tea saponins, offering insights for bioactive compound extraction and informing breeding strategies to enhance saponin yield and diversity.

PMID:39952190 | DOI:10.1016/j.foodchem.2025.143323

Pediatr Radiol. 2025 Feb 14. doi: 10.1007/s00247-025-06182-w. Online ahead of print.

ABSTRACT

Tuberculosis (TB) remains a significant public health concern despite preventive measures, such as the use of the Bacille Calmette-Guérin (BCG) vaccine, which reduces the risk and severity of early-life TB infection. The adverse effects of the BCG vaccine include infection by the live-attenuated organism, more commonly seen in the immunocompromised host. This pictorial review aims to outline the imaging spectrum of BCG-vaccine-related infections in immunocompromised pediatric patients, which can be localized (BCGitis) or disseminated (BCGosis). We illustrate the more common imaging findings, including lymphadenopathy and involvement of solid organs, as well as less frequently encountered sites, such as the lungs and gastrointestinal tract, emphasizing their distinct imaging patterns. Interpretation of these findings in the context of prior administration of the BCG vaccine not only helps in the diagnosis of BCG-vaccine-related infections and guiding timely management, but can also be an early indicator of an underlying immunodeficiency disorder, prompting comprehensive immunological investigation.

PMID:39953302 | DOI:10.1007/s00247-025-06182-w

PLoS One. 2025 Feb 14;20(2):e0316721. doi: 10.1371/journal.pone.0316721. eCollection 2025.

ABSTRACT

BACKGROUND: Non-cystic fibrosis bronchiectasis (NCFBE) is a disease that exhibits dilatation of airways, airflow obstruction, persistent cough, excessive sputum production, and refractory respiratory infections. NCFBE exhibits clinical and pathological manifestations similar to key features of cystic fibrosis (CF) lung disease. In CF, pathogenesis results from dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR), and diagnosis is made by demonstrating elevated sweat chloride concentrations (typically ≥60 mEq/L), two CFTR mutations known to be causal, multi-organ tissue injury, or combination(s) of these findings.

OBJECTIVE: Based on a considerable body of evidence, we believe many patients with NCFBE have disease likely to benefit from drugs such as elexacaftor/tezacaftor/ivacaftor (ETI) that activate CFTR-dependent ion transport. ETI is currently prescribed solely for treatment of CF and has not been adequately tested or proposed for patients with NCFBE, many of whom exhibit decreased CFTR function. Accordingly, we are conducting a clinical trial of ETI in subjects carrying a diagnosis of NCFBE.

METHODS: Participants will exhibit one disease-causing CFTR mutation and/or sweat chloride measurements of 30-59 mEq/L. Cutaneous punch biopsy or blood samples will be obtained for iPS cell differentiation into airway epithelial monolayers-which will then be tested for response to ETI. Each patient will be given CFTR modulator treatment for approximately four weeks, with monitoring of clinical endpoints that include FEV1 (forced expiratory volume in one second), sweat chloride, quality of life questionnaire, and weight. The study will evaluate response of patients with NCFBE to ETI, and test usefulness of iPSC-derived airway epithelial monolayers as a novel in vitro technology for predicting clinical benefit.

TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov (Identifier: NCT05743946. Date: 02/23/2023).

PMID:39951444 | DOI:10.1371/journal.pone.0316721

Opt Lett. 2025 Feb 15;50(4):1269-1272. doi: 10.1364/OL.547399.

ABSTRACT

Fourier-inspired single-pixel holography (FISH) is an effective digital holography (DH) approach that utilizes a single-pixel detector instead of a conventional camera to capture light field information. FISH combines the Fourier single-pixel imaging and off-axis holography technique, allowing one to acquire useful information directly, rather than recording the hologram in the spatial domain and filtering unwanted terms in the Fourier domain. Furthermore, we employ a deep learning technique to jointly optimize the sampling mask and the imaging enhancement model, to achieve high-quality results at a low sampling ratio. Both simulations and experimental results demonstrate the effectiveness of FISH in single-pixel phase imaging. FISH combines the strengths of single-pixel imaging (SPI) and DH, potentially expanding DH's applications to specialized spectral bands and low-light environments while equipping SPI with capabilities for phase detection and coherent gating.

PMID:39951780 | DOI:10.1364/OL.547399

Opt Lett. 2025 Feb 15;50(4):1261-1264. doi: 10.1364/OL.544342.

ABSTRACT

Self-interference digital holography extends the application of digital holography to non-coherent imaging fields such as fluorescence and scattered light, providing a new solution, to the best of our knowledge, for wide field 3D imaging of low coherence or partially coherent signals. However, cross talk information has always been an important factor limiting the resolution of this imaging method. The suppression of cross talk information is a complex nonlinear problem, and deep learning can easily obtain its corresponding nonlinear model through data-driven methods. However, in real experiments, it is difficult to obtain such paired datasets to complete training. Here, we propose an unsupervised cross talk suppression method based on a cycle-consistent generative adversarial network (CycleGAN) for self-interference digital holography. Through the introduction of a saliency constraint, the unsupervised model, named crosstalk suppressing with unsupervised neural network (CS-UNN), can learn the mapping between two image domains without requiring paired training data while avoiding distortions of the image content. Experimental analysis has shown that this method can suppress cross talk information in reconstructed images without the need for training strategies on a large number of paired datasets, providing an effective solution for the application of the self-interference digital holography technology.

PMID:39951778 | DOI:10.1364/OL.544342

Anal Chem. 2025 Feb 14. doi: 10.1021/acs.analchem.4c02796. Online ahead of print.

ABSTRACT

Surface-enhanced Raman spectroscopy (SERS) has emerged as a crucial analytical tool in the field of oncology, particularly presenting significant challenges for the diagnosis and treatment of head and neck cancer. This Review provides an overview of the current status and prospects of SERS applications, highlighting their profound impact on molecular biology-level diagnosis, tissue-level identification, HNC therapeutic monitoring, and integration with emerging technologies. The application of SERS for single-molecule assays such as epidermal growth factor receptors and PD-1/PD-L1, gene expression analysis, and tumor microenvironment characterization is also explored. This Review showcases the innovative applications of SERS in liquid biopsies such as high-throughput lateral flow analysis for ctDNA quantification and salivary diagnostics, which can offer rapid and highly sensitive assays suitable for immediate detection. At the tissue level, SERS enables cancer cell visualization and intraoperative tumor margin identification, enhancing surgical precision and decision-making. The role of SERS in radiotherapy, chemotherapy, and targeted therapy is examined along with its use in real-time pharmacokinetic studies to monitor treatment response. Furthermore, this Review delves into the synergistic relationship between SERS and artificial intelligence, encompassing machine learning and deep learning algorithms, marking the dawn of a new era in precision oncology. The integration of SERS with genomics, metabolomics, transcriptomics, proteomics, and single-cell omics at the multiomics level will revolutionize our comprehension and management of HNC. This Review offers an overview of the transformative impacts of SERS and examines future directions as well as challenges in this dynamic research field.

PMID:39951652 | DOI:10.1021/acs.analchem.4c02796

PLoS One. 2025 Feb 14;20(2):e0315143. doi: 10.1371/journal.pone.0315143. eCollection 2025.

ABSTRACT

The smart grid is on the basis of physical grid, introducing all kinds of advanced communications technology and form a new type of power grid. It can not only meet the demand of users and realize the optimal allocation of resources, but also improve the safety, economy and reliability of power supply, it has become a major trend in the future development of electric power industry. But on the other hand, the complex network architecture of smart grid and the application of various high-tech technologies have also greatly increased the probability of equipment failure and the difficulty of fault diagnosis, and timely discovery and diagnosis of problems in the operation of smart grid equipment has become a key measure to ensure the safety of power grid operation. From the current point of view, the existing smart grid equipment fault diagnosis technology has problems that the application program is more complex, and the fault diagnosis rate is generally not high, which greatly affects the efficiency of smart grid maintenance. Therefore, Based on this, this paper adopts the multimodal semantic model of deep learning and knowledge graph, and on the basis of the original target detection network YOLOv4 architecture, introduces knowledge graph to unify the characterization and storage of the input multimodal information, and innovatively combines the YOLOv4 target detection algorithm with the knowledge graph to establish a smart grid equipment fault diagnosis model. Experiments show that compared with the existing fault detection algorithms, the YOLOv4 algorithm constructed in this paper is more accurate, faster and easier to operate.

PMID:39951439 | DOI:10.1371/journal.pone.0315143

PLoS One. 2025 Feb 14;20(2):e0318998. doi: 10.1371/journal.pone.0318998. eCollection 2025.

ABSTRACT

Alzheimer's disease (AD) is a leading cause of disability worldwide. Early detection is critical for preventing progression and formulating effective treatment plans. This study aims to develop a novel deep learning (DL) model, Hybrid-RViT, to enhance the detection of AD. The proposed Hybrid-RViT model integrates the pre-trained convolutional neural network (ResNet-50) with the Vision Transformer (ViT) to classify brain MRI images across different stages of AD. The ResNet-50 adopted for transfer learning, facilitates inductive bias and feature extraction. Concurrently, ViT processes sequences of image patches to capture long-distance relationships via a self-attention mechanism, thereby functioning as a joint local-global feature extractor. The Hybrid-RViT model achieved a training accuracy of 97% and a testing accuracy of 95%, outperforming previous models. This demonstrates its potential efficacy in accurately identifying and classifying AD stages from brain MRI data. The Hybrid-RViT model, combining ResNet-50 and ViT, shows superior performance in AD detection, highlighting its potential as a valuable tool for medical professionals in interpreting and analyzing brain MRI images. This model could significantly improve early diagnosis and intervention strategies for AD.

PMID:39951414 | DOI:10.1371/journal.pone.0318998

Sci Adv. 2025 Feb 14;11(7):eadp4008. doi: 10.1126/sciadv.adp4008. Epub 2025 Feb 14.

ABSTRACT

Chimeric antigen receptor (CAR) T cells offer a promising cancer treatment, yet challenges such as limited T cell persistence hinder efficacy. Given its critical role in modulating T cell responses, it is crucial to understand how the CAR signaling architecture influences T cell function. Here, we designed a combinatorial CAR signaling domain library and performed repeated antigen stimulation assays, pooled screens, and single-cell sequencing to systematically investigate the impact of modifying CAR signaling domains on T cell activation and persistence. Our data reveal the predominant influence of membrane-proximal domains in driving T cell phenotype. Notably, CD40 costimulation was crucial for fostering robust and lasting T cell responses. Furthermore, we correlated in vitro generated CAR T cell phenotypes with clinical outcomes in patients treated with CAR T therapy, establishing the foundation for a clinically informed screening approach. This work deepens our understanding of CAR T cell biology and may guide future CAR engineering efforts.

PMID:39951542 | DOI:10.1126/sciadv.adp4008

JAMA Netw Open. 2025 Feb 3;8(2):e2459557. doi: 10.1001/jamanetworkopen.2024.59557.

ABSTRACT

IMPORTANCE: Textbooks attribute 80% of meconium-related small bowel obstructions to cystic fibrosis and 15% of colonic obstructions to Hirschsprung disease. It is unknown whether these estimates are accurate, particularly among preterm infants, whose immature bowel predisposes them to meconium-related obstruction (MRO).

OBJECTIVE: To estimate the incidence of MRO by type and to assess its association with clinical outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of live-born infants included in the National Inpatient Sample from January 1, 2016, to December 31, 2020, used survey weighting methods to estimate the national incidence of MRO by etiology. Data were analyzed from November 27, 2023, to November 12, 2024.

EXPOSURE: MRO.

MAIN OUTCOMES AND MEASURES: The primary outcome was diagnosis with MRO. Secondary outcomes included mortality, need for abdominal surgery, hospitalization duration, and cost. Multivariable regression models were developed to evaluate characteristics associated with MRO and to assess the association of MRO of prematurity with clinical outcomes after adjusting for demographic and clinical covariates.

RESULTS: Of 3 550 796 infants, 51.2% were male and 46.7% were privately insured. Overall, 9.1% (n = 322 499) were born preterm. Of 1844 (0.1%) infants treated for MRO, 41 (2.2%) had cystic fibrosis, 60 (3.3%) had Hirschsprung disease, and 1743 (94.5%) had neither predisposing condition. Preterm infants were at highest risk for MRO, with 4.7 MRO cases per 100 000 births associated with cystic fibrosis, 4.7 MRO cases per 100 000 births associated with Hirschsprung disease, and 187.3 MRO cases per 100 000 births associated with neither predisposing condition. Among infants with neither cystic fibrosis nor Hirschsprung disease, those with gestational ages from 28 weeks to 31 weeks 6 days were most likely to develop MRO compared with term infants (adjusted odds ratio, 6.08 [95% CI, 4.27-8.67]). Among preterm infants, having an MRO was associated with a 4.2 percentage point increase in the probability of abdominal surgery (95% CI, 3.1-5.4 percentage points), a 7.3-day increase in length of stay (95% CI, 5.8-8.8 days), and a $23 215 increase in hospitalization costs (95% CI, $17 739-$28 690) compared with infants who did not have an obstruction, with no change in mortality rate (0.1 percentage point change [95% CI, -0.6 to 0.8 percentage points]).

CONCLUSIONS AND RELEVANCE: In this cohort study of over 3.5 million infants, MRO was most likely to occur among preterm infants without cystic fibrosis or Hirschsprung disease. These infants more frequently required surgery and had longer and more costly hospitalizations, indicating a need for dedicated prevention and treatment pathways for this understudied disease.

PMID:39951267 | DOI:10.1001/jamanetworkopen.2024.59557