tbuckley/cabot-search huggingface dataset:
Pregnancy-Associated Mortality Due to Homicide, Suicide, and Drug Overdose
Authors: Maeve E. Wallace, Jaquelyn L. Jahn
Journal: JAMA Network Open (2025)

Importance Despite growing national concern about high and increasing rates of pregnancy-associated mortality due to homicide, suicide, and drug overdose, state-level incidence has previously not been available. Objective To identify cases of pregnancy-associated homicide, suicide, drug overdose, and deaths involving firearms in the US from calendar year 2018 to 2022 and estimate 5-year proportionate mortality and mortality ratios per 100 000 live births by state and cause of death. Design, Setting, and Participants This cross-sectional study is a population-based analysis of the 2018-2022 restricted-use mortality files provided by the National Center for Health Statistics. These data include all deaths occurring in the US, with geographic identifiers for state of residence. All records in which the decedent was female aged 10 to 44 years and pregnant at the time of death or up to 1 year earlier were included in the analysis. Data were analyzed from July 1 to December 1, 2024. Main Outcomes and Measures International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for underlying cause of death were used to identify cases of homicide, suicide, drug overdose, and deaths involving firearms occurring in each state from 2018 to 2022. Proportionate mortality was estimated as the count of cases divided by the total count of deaths of pregnant and postpartum women in each state. Cause-specific mortality ratios were estimated as the count of cases divided by the total count of live births in each state from 2018 to 2022. Results Nationally, there were 10 715 deaths of people who were pregnant or within 1 year post partum from 2018 to 2022, including 837 homicides, 579 suicides, 2083 drug overdoses, and 851 that involved firearms. Proportionate mortality and mortality ratios for homicide, suicide, and drug overdose varied across the US. Of states with more than 9 cases, pregnancy-associated homicide mortality was highest in Mississippi (12.86 per 100 000 live births), pregnancy-associated suicide mortality was highest in Montana (21.55 deaths per 100 000 live births), and pregnancy-associated drug overdose was highest in Delaware (36.03 deaths per 100 000 live births). Firearms accounted for as many as 15.56% of pregnancy-associated deaths in Colorado, and pregnancy-associated firearm mortality was highest in Mississippi (13.42 deaths per 100 000 live births). Conclusions and Relevance The information in this study may provide relevant guidance for state and local intervention strategies to advance the health, safety, and well-being of women during pregnancy and beyond.
Advanced image-identified extranodal extension of retropharyngeal lymph nodes in the refinement of N classification for nasopharyngeal carcinoma
Authors: Wei Jiang, Gao-Yuan Wang, Guan-Jie Qin, Wu-Qi Zhang, Xiao-Dong Zhu, Ya-Qian Han, Feng Lei, Liang-Fang Shen, Kun-Yu Yang, Chun-Yan Cui, Ling-Long Tang, Yan-Ping Mao, Lei Chen, Rui Guo, Ling Li, Zheng Wu, Gui-Qiong Xu, Qin Zhou, Jing Huang, Shao-Hui Huang, Ji-Bin Li, Li-Zhi Liu, Jun Ma, Xiao-Jing Du
Journal: Cell Reports Medicine (2025)

Highlights•Anatomical factors of RLNs are positively correlated•Advanced RLN ENE is not an independent prognostic factor for NPC•N1/N2 NPC with advanced RLN ENE has a better prognosis than N3 diseaseSummaryAdvanced extranodal extension (ENE) in cervical lymph nodes (CLNs) increases the risk of distant metastasis in nasopharyngeal carcinoma (NPC). The 9th NPC staging system classifies N1/N2 patients with advanced CLN ENE as N3 due to similar outcomes. However, the prognostic impact of advanced ENE in retropharyngeal lymph nodes (RLNs) remains unclear. In this study of 4,485 patients with non-metastatic NPC, N1/N2 patients with advanced RLN ENE demonstrate better 5-year overall survival (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.38–0.93; HR: 0.57, 95% CI: 0.32–1.00) and failure-free survival (HR: 0.63, 95% CI: 0.44–0.92; HR: 0.52, 95% CI: 0.31–0.86) than N3 patients. Advanced RLN ENE shows a positive correlation with other RLN-related anatomical factors and is not identified as an independent prognostic factor. External validation in 3,849 patients from five centers supports these findings. Based on this evidence, upgrading advanced RLN ENE to N3 is not advised.Graphical abstract
HPV E6 and E7 mRNA Test for the Detection of High-Grade Cervical Lesions
Authors: Awoke Derbie, Melanie Maier, Bereket Amare, Eyaya Misgan, Endalkachew Nibret, Fantahun Biadglegne, Uwe G. Liebert, Tsion Zewdu Minas, Muluken Agage Yenesew, Dabere Nigatu, Tesfaye B. Mersha, Daniel A. Enquobahrie, Yimtubezinash Woldeamanuel, Tamrat Abebe
Journal: JAMA Network Open (2025)

This cross-sectional study examines whether human papillomavirus (HPV) messenger RNA (mRNA)–based testing can identify women with high-risk abnormal cervical lesions..
New horizons in Klinefelter syndrome: current evidence, gaps and research priorities
Authors: Angela K Lucas-Herald, Lise Aksglaede, Ida Dyhr Caspersen, Syed Faisal Ahmed, Francesco Carlomagno, Andrea M Isidori
Journal: Endocrine Reviews (2025)

Abstract Klinefelter Syndrome (KS) is caused by the presence of a supernumerary X-chromosome (conferring the classical 47,XXY karyotype) and is the commonest sex chromosome abnormality in men. The clinical features described in the early characterisation of the syndrome include tall stature, small testes, hypogonadism, gynecomastia and neurodevelopmental deficits. However, the syndrome presents a broad phenotypic spectrum that seems to be evolving, along with environmental and general health changes. Although a proportion of men with KS are asymptomatic, others experience numerous severe comorbidities, ranging from cardiovascular to autoimmune disorders. Once considered a hallmark of the syndrome, the inability to conceive can now be overcome with assisted reproductive technology. The neuropsychological stigmata, once overstated, thereafter inadvertently dismissed, now demand a more balanced and objective approach. Significant advances have been made in our understanding of KS over recent years, including the molecular machinery involved in the chromosomal disjunction that gives rise to the syndrome. Our understanding of the risk-benefit of testosterone replacement therapy has greatly improved; however, many gaps persist. Future work should be prioritised according to the needs of people with KS. There are opportunities for new research addressing the fields of fertility, cardiovascular prevention, neurodevelopment, quality of life and bone health. Above all, solid registries and extensive prospective longitudinal studies are needed to enrol people with KS to determine their evolving needs as they progress through their lifespan. These studies would be best initiated with international collaboration to ensure the results apply to all those with this condition worldwide.
Enhanced conversion of T cells into CAR T cells by modulation of the MAPK/ERK pathway
Authors: Elham Adabi, Filippos T. Charitidis, Frederic B. Thalheimer, Mar Guaza-Lasheras, Colin Clarke, Christian J. Buchholz
Journal: Cell Reports Medicine (2025)

Highlights•Bar-coded antibodies distinguish transduced and untransduced T cells by sc-multi-omics•Transduction-resistant cells upregulate interferon-stimulated genes•Differentially expressed genes are consistent between healthy donors and patients•Inhibitors of the ERK signaling pathway increase transduction and CAR T cell generationSummaryDelivery of chimeric antigen receptors (CARs) to T cells is usually mediated by lentiviral vectors (LVs), which can have broad tropism or be T cell targeted. To better understand the molecular events during CAR T cell generation, T cell transduction with four different LVs is followed by single-cell multi-omics analysis, distinguishing between transduced T cells and T cells with vector signal but no CAR. We find that only a fraction of the T cells that encounter vectors convert into CAR T cells. Single-cell transcriptome data reveal that interferon-stimulated genes are upregulated in non-transduced cells, whereas extracellular signal-regulated kinase (ERK)2 phosphatases are upregulated in CAR T cells. This expression pattern is evident in CAR T cells from healthy donors and patients. The role of the mitogen-activated protein kinase (MAPK)/ERK pathway in CAR T cell generation is confirmed by chemical inhibitors. These data provide molecular insights into T cell transduction with implications for improving CAR T cell generation.Graphical abstract
Author Correction: The architecture of the human default mode network explored through cytoarchitecture, wiring and signal flow
Authors: Casey Paquola, Margaret Garber, Stefan Frässle, Jessica Royer, Yigu Zhou, Shahin Tavakol, Raul Rodriguez-Cruces, Donna Gift Cabalo, Sofie Valk, Simon B. Eickhoff, Daniel S. Margulies, Alan Evans, Katrin Amunts, Elizabeth Jefferies, Jonathan Smallwood, Boris C. Bernhardt
Journal: Nature Neuroscience (2025)
Tumor dormancy and relapse: understanding the molecular mechanisms of cancer recurrence
Authors: Muhammad Tufail, Can-Hua Jiang, Ning Li
Journal: Military Medical Research (2025)

Abstract Cancer recurrence, driven by the phenomenon of tumor dormancy, presents a formidable challenge in oncology. Dormant cancer cells have the ability to evade detection and treatment, leading to relapse. This review emphasizes the urgent need to comprehend tumor dormancy and its implications for cancer recurrence. Despite notable advancements, significant gaps remain in our understanding of the mechanisms underlying dormancy and the lack of reliable biomarkers for predicting relapse. This review provides a comprehensive analysis of the cellular, angiogenic, and immunological aspects of dormancy. It highlights the current therapeutic strategies targeting dormant cells, particularly combination therapies and immunotherapies, which hold promise in preventing relapse. By elucidating these mechanisms and proposing innovative research methodologies, this review aims to deepen our understanding of tumor dormancy, ultimately facilitating the development of more effective strategies for preventing cancer recurrence and improving patient outcomes.
Accelerated Intermittent Theta-Burst Stimulation for Treatment-Resistant Bipolar Depression
Authors: Lawrence G. Appelbaum, Hadley Daniels, Liam Lochhead, Bianca Bacio, Robin Cash, Cory R. Weissman, Jordan N. Kohn, Itay Hadas, Zafiris J. Daskalakis
Journal: JAMA Network Open (2025)

This randomized clinical trial evaluates the effect of accelerated intermittent theta-burst stimulation, compared with sham stimulation, on depression severity in individuals with treatment-resistant bipolar depression.
Maternal-infant probiotic transmission mitigates early-life stress-induced autism in mice
Authors: Li Qing, Xin Qian, Huiyue Zhu, Jingyu Wang, Jingge Sun, Zhiying Jin, Xinyu Tang, Yingqi Zhao, Gang Wang, Jianxin Zhao, Wei Chen, Peijun Tian
Journal: Gut Microbes (2025)

Autism, a disorder influenced by both genetic and environmental factors, presents significant challenges for prevention and treatment. While maternal-infant gut microbiota has been a focus in autism research, preventive strategies targeting maternal gut microbiota remain underexplored. This study demonstrates that prenatal probiotic intake can effectively prevent maternal separation-induced autistic-like behaviors in offspring without altering the embryonic neurodevelopment in mice. Using specific PCR primers and cross-fostering experiments, we traced the vertical transmission of probiotics, primarily via fecal/vaginal contamination. Early probiotic colonization conferred resilience against stress-induced gut pathogenic microbes and Th17-mediated peripheral inflammation while significantly inhibiting hypermyelination and neuroinflammation linked to systemic inflammation. Microbial metabolites like tyrosol and xanthurenic acid alleviated neuroinflammation and hypermyelination in vitro, though the causal relationship among neuroinflammation, hypermyelination, and autism in vivo requires further validation. These findings underscore the importance of the maternal-infant microbiota transmission window in autism prevention and highlight the clinical potential of prenatal probiotic interventions.
AMPA receptor diffusional trapping machinery as an early therapeutic target in neurodegenerative and neuropsychiatric disorders
Authors: Daniel Choquet, Patricio Opazo, Hongyu Zhang
Journal: Translational Neurodegeneration (2025)

Abstract Over the past two decades, there has been a growing recognition of the physiological importance and pathological implications surrounding the surface diffusion of AMPA receptors (AMPARs) and their diffusional trapping at synapses. AMPAR surface diffusion entails the thermally powered random Brownian lateral movement of these receptors within the plasma membrane, facilitating dynamic exchanges between synaptic and extrasynaptic compartments. This process also enables the activity-dependent diffusional trapping and accumulation of AMPARs at synapses through transient binding to synaptic anchoring slots. Recent research highlights the critical role of synaptic recruitment of AMPARs via diffusional trapping in fundamental neural processes such as the development of the early phases of long-term potentiation (LTP), contextual fear memory, memory consolidation, and sensory input-induced cortical remapping. Furthermore, studies underscore that regulation of AMPAR diffusional trapping is altered across various neurological disease models, including Huntington’s disease (HD), Alzheimer’s disease (AD), and stress-related disorders like depression. Notably, pharmacological interventions aimed at correcting deficits in AMPAR diffusional trapping have demonstrated efficacy in restoring synapse numbers, LTP, and memory functions in these diverse disease models, despite their distinct pathogenic mechanisms. This review provides current insights into the molecular mechanisms underlying the dysregulation of AMPAR diffusional trapping, emphasizing its role as a converging point for multiple pathological signaling pathways. We propose that targeting AMPAR diffusional trapping represents a promising early therapeutic strategy to mitigate synaptic plasticity and memory deficits in a spectrum of brain disorders, encompassing but not limited to HD, AD, and stress-related conditions. This approach underscores an integrated therapeutic target amidst the complexity of these neurodegenerative and neuropsychiatric diseases.
Correction to “Confidential and non-confidential drug rebates in Switzerland, 2013–2023: empirical analysis of drug rebates, trends over time and re-evaluations” [The Lancet Regional Health—Europe, volume 46, November 2024, 101094]
Authors: Noah Rohner, Cascal Herrle, Luca Locher, Kerstin N Vokinger
Journal: The Lancet Regional Health - Europe (2025)
<i>BCR::ABL1</i>‐Positive Acute Myeloid Leukemia
Authors: Alban Canali, Jean‐Baptiste Rieu, Leopoldine Lapierre, Barbara J. Bain
Journal: American Journal of Hematology (2025)

Morphology Update has recently discussed a patient with chronic myeloid leukemia (CML) presenting in blast crisis [1]. For comparison, we present here a patient with BCR::ABL1-positive acute myeloid leukemia (AML). The patient was a 48-year-old man with no known history of CML, presenting with hepatomegaly and neurological abnormalities (headaches, agitation, and behavioral disturbance). His blood count showed hemoglobin concentration 64 g/L, white cell count 457.6 × 109/L, and platelet count 31 × 109/L. His blood film (images × 100 objective) showed 95% blast cells; these were large, with an intermediate nuclear-cytoplasmic ratio, irregular nuclei, sometimes nucleoli, and cytoplasm containing atypical pink to lilac granules and occasional inclusions. Promyelocytes were present but myelocytes, eosinophils, and basophils were infrequent. Neutrophils were dysplastic with hypogranular cytoplasm and abnormal nuclear forms (right image). A bone marrow aspirate was hypercellular with 84% blast cells, without prominence of eosinophils or basophils. Cytogenetic analysis showed 46,XY,t(9;22)(q34;q11)[21]. A BCR::ABL1 transcript, identified as BCR_E13::ABL1_E2, b2a2, p210, was detected on molecular analysis, together with mutations of SMC3 and WT1. In view of the molecular findings and the lack of prominent basophilia, a diagnosis of BCR::ABL1-positive AML appeared most likely but post-treatment follow-up was needed for confirmation. The patient was treated with cytarabine, idarubicin, and imatinib as induction treatment (preceded by cytoreduction with hydroxycarbamide), followed by cytarabine and imatinib for consolidation. Additionally, cytarabine, methotrexate, and methylprednisolone were administered intrathecally to treat demonstrated central nervous system infiltration. Complete remission was achieved with the marrow being morphologically normal without neutrophilic, eosinophilic or basophilic hyperplasia. Cytogenetic analysis was normal at 2 months from diagnosis and a deep molecular remission was demonstrated at 4 months. Diagnosis of BCR::ABL1-positive AML requires the features of AML and demonstration of BCR::ABL1. However an essential diagnostic criterion is that there should be "a lack of features of CML before or at diagnosis and after therapy" [2]. The diagnosis is thus provisional until post-treatment follow-up excludes an alternative diagnosis of blastic presentation of CML. De novo AML cases have less frequent splenomegaly, a higher blast percentage and lower basophil numbers [2]. The precise BCR::ABL1 transcript that is detected is not helpful because p210 is most often observed in both CML and BCR::ABL1-positive AML [2]. The authors declare no conflicts of interest.
Efficacy of MEK inhibitors in Erdheim-Chester disease: impact of MAPK pathway pathogenic variants
Authors: Aldo A. Acosta-Medina, Jithma P. Abeykoon, Saurabh Zanwar, Gordon J. Ruan, Karen L. Rech, Aishwarya Ravindran, N. Nora Bennani, Caroline J. Davidge-Pitts, Matthew J. Koster, Jay H. Ryu, Mithun V. Shah, W. Oliver Tobin, Robert Vassallo, Jason R. Young, Ronald S. Go, Gaurav Goyal
Journal: Leukemia (2025)
Undifferentiated Human Amniotic Fluid Progenitor Cells Promote Bone Regeneration in Vivo
Authors: Queralt Vallmajo‐Martin, Anna‐Sofia Kiveliö, Stéphanie Metzger, Vincent Milleret, Philipp S. Lienemann, Bianca M. Carrara, Christopher Millan, Chafik Ghayor, Nicole Ochsenbein‐Koelble, Martin Ehrbar
Journal: Advanced Healthcare Materials (2025)

Abstract The treatment of large bone defects requires bone tissue substitutes. However, the lack of accessible autologous bone, especially in newborns with spina bifida or cleft palate conditions, severely limits therapeutic options involving bone grafts. Here, an engineering approach to reconstruct bone is presented by combining human amniocentesis‐derived amniotic fluid progenitor cells (hAFCs) and a biomimetic, injectable, and fully synthetic poly(ethylene glycol) hydrogel that is crosslinked enzymatically by transglutaminase FXIII (TG‐PEG). hAFCs are isolated by their colony‐forming capacity, expanded in vitro, and undergo osteogenic, chondrogenic, or adipogenic differentiation under appropriate stimulation. When encapsulated in TG‐PEG hydrogels, hAFCs rapidly deposit endogenous extracellular matrix (ECM) in vitro. hAFC‐laden TG‐PEG hydrogels containing low concentrations of bone morphogenetic protein (BMP‐2) promote formation of ectopic bone organoids in vivo in a murine model without requiring prior in vitro differentiation. Strikingly, hAFC‐induced constructs form as much bone in this model as adult bone marrow‐derived stromal cells (hBMSCs), and significantly more than adipose‐derived stromal cells (hASCs). Utilization of autologous hAFCs embedded in TG‐PEG hydrogels presents a promising therapeutic strategy for bone replacement, particularly in fetuses and newborns where limited stem cell availability can be overcome through minimally invasive harvest of amniotic fluid.
Establishment of a machine learning model for predicting splenic hilar lymph node metastasis
Authors: Kenichi Ishizu, Satoshi Takahashi, Nobuji Kouno, Ken Takasawa, Katsuji Takeda, Kota Matsui, Masashi Nishino, Tsutomu Hayashi, Yukinori Yamagata, Shigeyuki Matsui, Takaki Yoshikawa, Ryuji Hamamoto
Journal: npj Digital Medicine (2025)

Upper gastrointestinal cancer (UGC) sometimes metastasizes to the splenic hilum lymph node (SHLN). However, surgical removal of SHLN is technically difficult, and the risk of postoperative complications is high. Although there are models that predict SHLN metastasis, they usually only provide point estimates of risk, and there is a lack of sufficient information. To address this issue, we aimed to develop a Bayesian logistic regression model called Bayes-SHLNM. The performance of the models was compared with that of the frequentist logistic regression (FLR) model as a benchmark, and the posterior probability distribution (PPD) was shown individually. The performance of Bayes-SHLNM was equivalent to that of the FLR model, and the PPD for each case was visualized as the uncertainty. These results indicate that the Bayes-SHLNM model has the potential to be used as a decision support system in clinical settings where uncertainty is high.
Comparing the efficacy and safety of venetoclax combined with hypomethylating agents versus intensive chemotherapy as induction therapy in newly diagnosed core binding factor acute myeloid leukemia patients
Authors: Jingyi Shen, Meng Shan, Mengqian Chu, Yiming Cai, Jingwen Rui, Suning Chen, Depei Wu, Yang Xu
Journal: Blood Cancer Journal (2025)
Interleukin-18 and interleukin-1β blockade to control inflammation in PAMI syndrome before and after HSCT
Authors: Benjamin Fournier, Laurye-Anne Eveillard, Agathe Escudier, Guilaine Boursier, Anne Welfringer, Bénédicte Neven, Brigitte Bader-Meunier
Journal: Annals of the Rheumatic Diseases (2025)
Human Single-Cell RNA-Sequencing Data Supports the Hypothesis of X Chromosome Insensitivity but Is Ineffective in Testing the Dosage Compensation Model
Authors: Jiabi Chen, Xiaoshu Chen
Journal: Molecular Biology and Evolution (2025)

Abstract A controversy in evolutionary genetics is whether active dosage compensation is necessary to resolve the gene dosage imbalance between the X chromosome and autosomes. ScRNA-seq data could provide insight into this issue. However, it's crucial to carefully evaluate whether inherent characteristics of scRNA-seq, such as the sparsity of detected genes, might bias the X:AA expression ratio in mammals. This study evaluated two common strategies for selecting genes in the calculation of X:AA, namely, filter-by-expression and filter-by-fraction, with simulated scRNA-seq and bulk RNA-seq datasets. We found that both strategies produce an inflated X:AA, thus artifactually supporting dosage compensation. Analyzing empirical human Smart-seq2 data, results from the filter-by-expression strategy suggested that X-linked genes were more highly expressed than autosomal genes, a pattern that is neither predicted by dosage compensation nor explained by genes escaping X chromosome inactivation. However, the results of the filter-by-fraction strategy are consistent with the simulation. Furthermore, despite biasing for mean expression levels, we found that scRNA-seq data could be used to detect X-to-autosome expression noise differences as small as 10%, which enabled investigation into the distribution of genes that are more likely insensitive to gene dosage changes. Analysis of the empirical Smart-seq2 data revealed a 10% to 15% increase in expression noise for X chromosomes compared with autosomes and a significant depletion of dosage-sensitive genes on X chromosomes. Overall, these results highlight the need to be cautious when interpreting scRNA-seq data, particularly when comparing the expression of different genes, and provide additional evidence for the hypothesis of X chromosome insensitivity.