tbuckley/cabot-search huggingface dataset:
Clonal Hematopoietic Mutations in Plasma Cell Disorders: Clinical Subgroups and Shared Pathogenesis
Authors: Xuezhu Wang, Liping Zuo, Yanying Yu, Xinyi Xiong, Jian Xu, Bing Qiao, Jia Chen, Hao Cai, Qi Yan, Hongxiao Han, Xin-xin Cao, Jun Deng, Chunyan Sun, Jian Li
Journal: Genomics Proteomics & Bioinformatics (2025)

Abstract Plasma cell disorders (PCDs) are marked by the clonal proliferation of abnormal plasma cells and bone marrow plasma cells (BMPCs), causing various clinical complications. These PCDs include subtypes with distinct clinical features. Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are more common and relatively well-studied. In contrast, primary light-chain amyloidosis (AL) and POEMS syndrome (POEMS) are rare and remain less understood. To investigate the role of clonal hematopoietic (CH) mutations and potential interconnections in these diseases, we sequenced CH mutations in lymphoid and myeloid lineages, and myeloma driver gene mutations, in BMPCs from affected patients. Recurrent lymphoid CH mutations (in FAT1, KMT2D, MGA, and SYNE1) and myeloma driver gene mutations (in ZFHX3 and DIS3) were found in the dominant clonal and subclonal plasma cell populations. These moderately aging-associated lymphoid CH mutations had a higher burden in MM than in AL or POEMS. Binary matrix factorization of these mutations revealed the subgroups associated with progression-free survival (PFS) (observed in MM, AL, and POEMS), age at diagnosis (in AL and POEMS), serum differences in free light chain (dFLC) levels, and plasma cell burden (in AL), and serum vascular endothelial growth factor (VEGF) levels (in POEMS). Also, the poor PFS associated with MGA or SYNE1 mutations was confirmed across MM, AL, and POEMS. CH mutations partially explained the shared pathogenesis of MM, AL, POEMS, and MGUS, and helped identify patient subgroups with specific clinical features.
Ultrasound‐Driven Innervated Bone Regeneration in Additively Manufactured Degradable Metallic Scaffolds
Authors: Wencheng Song, Danlei Zhao, Jiajia Wang, Zhengshuo Han, Yijun Liu, Yifan Wang, Cheng Yang
Journal: Advanced Healthcare Materials (2025)

Abstract Bone tissues are densely innervated by nerve fibers throughout the periosteum and mineralized bone. The impairment of innervated bone regeneration is a critical factor contributing to the challenges in osteoporotic bone remodeling and repair. Herein, an “ultrasound‐driven innervated bone regeneration” strategy is proposed in additively manufactured degradable Zn‐Cu scaffolds. The in vitro investigations with RSC96 cells elucidated the synergistic promotion of low‐intensity pulsed ultrasound (LIPUS) and metal cations on Schwann cell proliferation and exosome secretion. Notably, these Schwann cell‐derived exosomes, once internalized by neighboring bone marrow stromal cells (BMSCs), significantly enhanced their migration, osteogenic differentiation, and extracellular matrix deposition, indicating a potent mechanism for innervated bone regeneration. Furthermore, the in vivo evaluation validated that LIPUS stimulation significantly activated S100β‐positive Schwann cells and facilitated the regeneration of peripheral nerve fibers within cranial defects, leading to accelerated bone healing of osteoporotic rats with Zn‐Cu implantation over 2‐ and 6‐week recovery periods. This work provides an innervated bone regeneration strategy by focusing on the activation of Schwann cells and enhancement of paracrine effect, especially exosome secretion, which further recruited surrounding BMSCs and promoted their osteogenic differentiation. This study holds considerable promise for clinical applications and translation in the treatment of osteoporotic bone defects.
Blueberry muffin rash in neonatal leukemia
Authors: Zeqiao Zhang, Zhimiao Lin
Journal: British Journal of Dermatology (2025)

A male infant presented with a midfacial nodule at birth, progressing to multiple violaceous papulonodules. Laboratory and imaging studies, including skin and bone marrow biopsies, led to the diagnosis of neonatal acute leukemia. This case highlights the importance of early recognition of the ‘blueberry muffin’ rash, which can be associated with a variety of neonatal conditions, including leukemia.
Plant Polyphenol‐Based Injectable Hydrogels: Advances and Biomedical Applications
Authors: Renkai Zhang, Qiuyue Ma, Nannan Zheng, Ruiwen Wang, Sonja Visentin, Liangcan He, Shaoqin Liu
Journal: Advanced Healthcare Materials (2025)

Plant polyphenol-based hydrogels, known for their biocompatibility and adhesive properties, have emerged as promising materials in biomedical applications. These hydrogels leverage the catechol group's ability to form stable bonds in moist environments, similar to mussel adhesive proteins. This review provides a comprehensive overview of their synthesis, adhesion mechanisms, and applications, particularly in wound healing, tissue regeneration, and drug delivery. However, challenges related to in vivo stability and long-term biocompatibility remain critical barriers to clinical translation. Future research should focus on enhancing the bioactivity, biocompatibility, and scalability of these hydrogels, while addressing concerns related to toxicity, immune responses, and large-scale manufacturing. Advances in artificial intelligence-assisted screening and 3D/4D bioprinting are expected to accelerate their development and clinical translation. Furthermore, the integration of biomimetic designs and responsive functionalities, such as pH or temperature sensitivity, holds promise for further improving their therapeutic efficacy. In conclusion, the development of multifunctional plant polyphenol-based hydrogels represents a promising frontier in advancing personalized medicine and minimally invasive treatments.
Transcriptional Regulators YAP and TAZ Have Distinct Abilities to Compensate for One Another in Podocytes
Authors: Lioba Ester, Eva Wiesner, He Chen, Michel Ventzke, Paul Diefenhardt, Amrei M. Mandel, Francesca Fabretti, Paul T. Brinkkoetter, Thomas Benzing, Sandra Habbig, Martin Kann, Inês Cabrita, Bernhard Schermer
Journal: Journal of the American Society of Nephrology (2025)

Kidney function depends on the filtration of enormous volumes of plasma, exposing the filtration barrier to mechanical forces. Podocytes must adapt to these forces for the lifetime of an organism as they cannot self-renew. The molecular mechanisms of podocyte adaptation to mechanical stress remain unclear. YAP and TAZ are key mechanotransducers that relay mechanical stimuli to control transcription. We made use of podocyte-specific knockout mouse models for Yap (YAPpKO), Taz (TAZpKO), or both (YAPpKO/ TAZpKO) and analyzed single-nucleus RNA sequencing (snRNA-seq) data of isolated glomeruli to delineate the distinct and shared roles of YAP and TAZ in podocyte homeostasis. Here, we found that YAP and TAZ have only partially overlapping functions and compensatory potential in podocytes in vivo. YAPpKO mice displayed podocyte damage and progressive kidney failure. In contrast, TAZpKO animals did not develop any overt disease, while the combined deletion of Yap and Taz caused a neonatal lethal phenotype. snRNA-seq analysis revealed that in both YAPpKO or TAZpKO mice, a subpopulation of podocytes showed a similar stress response driven by AP1, revealing a protective compensatory mechanism. However, TAZ failed to compensate sufficiently for the loss of YAP, resulting in dysregulation of Rho-GTPases and subsequently the actin cytoskeleton in diseased YAPpKO. Furthermore, we observed loss of ERBB4 expression exclusively in YAPpKO, underscoring the role of ERBB4-signaling as additional layer of YAP-specific regulation in maintaining podocyte survival. In summary, we identified common and distinct roles for the two transcriptional regulators in podocyte homeostasis. YAP and TAZ can compensate for the loss of the other in podocytes to preserve viability. Still, while YAP can entirely compensate for the loss of TAZ securing podocyte health, TAZ fails to maintain all the YAP-specific functions leading to podocyte injury.
Co-occurrence of congenital anomalies and childhood brain tumors in 22 million live births
Authors: Thanh T Hoang, Jeremy M Schraw, Charles Shumate, Tania A Desrosiers, Wendy N Nembhard, Mahsa Yazdy, Eirini Nestoridi, Amanda E Janitz, Russell S Kirby, Jason L Salemi, Jean Paul Tanner, Tiffany M Chambers, Michael D Taylor, Chad D Huff, Sharon E Plon, Philip J Lupo, Michael E Scheurer
Journal: Neuro-Oncology (2025)

Abstract Background Children born with a congenital anomaly have a higher risk of developing a brain tumor during childhood or adolescence, but the co-occurrence between specific types of congenital anomalies and specific types of childhood brain tumors (CBTs) is not well described. This study characterized the associations between specific congenital anomalies and CBTs. Methods We leveraged a population-based registry linkage study of births (1990–2018), congenital anomalies, and cancer from 9 states (n = 22,599,099 births). Congenital anomalies were classified as major structural without a known chromosomal or genetic syndrome, chromosomal, neurofibromatosis, and/or tuberous sclerosis complex. CBT classification was based on the International Classification of Childhood Cancer for children diagnosed &amp;lt; 20 years. Cox regression analyses were conducted separately by congenital anomaly for anomaly-CBT combinations with at least 5 co-occurring cases. We conducted analyses for any CBT and separately for astrocytoma, atypical teratoid/rhabdoid tumor, ependymoma, medulloblastoma, mixed and unspecified gliomas, and primitive neuroectodermal tumors. Results There were 6,247 children diagnosed with a CBT. Having any major structural anomaly was associated with risk of any CBT and across all subgroups (aHR range: 1.48–3.69) except ependymoma, particularly among children diagnosed with a tumor by 1 year of age. Of the 66 anomaly-CBT combinations analyzed, 42 were significant (P &amp;lt; .05), including 25 in an earlier version of this study and 16 novel associations (aHR range: 1.46–525). Anomaly–CBT associations also differed by astrocytoma histology. Conclusions We observed consistent evidence that having a structural congenital anomaly increases risk of developing a CBT, particularly in infancy, which may provide insights into etiology.
Association of Ambient Air Pollution and Temperature Exposure with Placental Abruption: A Nested Case-Control Study Based on Live Birth Registrations
Authors: Tong Wang, Wenzheng Zhou, Han Liu, Yu Zhan, Die Tang, Ying Guo, Chenran Yin, Dongyan Wu, Yayun Cao, Xi Ling, Huan Yang, Niya Zhou, Jia Cao, Wei Zhou, Qing Chen
Journal: Environmental Health Perspectives (2025)

Placental abruption, a rare disorder of unclear etiology, lacks evidence to illustrate its relationship with exposure to air pollution and temperature. To investigate the association between exposure to ambient pollutants and temperatures and placental abruption, so as to identify susceptible time windows and subpopulations. A nested case-control study was based on a live birth registration database in Chongqing, the largest Chinese municipality in China, from 2018 to 2022. The placental abruption cases were each matched with four controls by maternal age at delivery, gestational week, gravidity, parity, and delivery date. Six ambient pollutants (PM2.5, PM10, NO2, CO, O3, and SO2) and temperature were estimated using machine learning algorithms. A conditional logistic regression model analyzed associations of exposure to air pollution and temperature with placental abruption in five time windows (pre-pregnancy, the entire pregnancy, and each of the three trimesters). Stratification analyses were applied to examine potential modifiers including gravidity, parity, mothers' residential area (urban/rural), pandemic experience, and delivery season. After data quality control, 798 cases were identified and matched with 3,192 controls. An exposure relationship was identified between NO2 during the pregnancy period and placental abruption (p<0.001). Compared with the 1st quartile level of NO2, the odds ratios (ORs) of abruption associated with exposure to the 2nd, 3rd and 4th quartile levels of NO2 were 1.42 (95% CI: 1.03, 1.96), 1.90 (95% CI: 1.30, 2.76), and 2.27 (95% CI: 1.39, 3.71), respectively. The association for NO2 exposure existed in the three trimesters but not pre-pregnancy. Exposure to locally extreme low temperatures (<5th percentile) in the third trimester was associated with increased risks of abruption (OR=3.68; 95% CI: 1.67, 8.08) compared to locally moderate temperatures (25th to 75th percentile). Stratified analysis showed no statistical significances within the effect modifiers. Based on a large-scale live birth record, the study suggested that exposure to air pollutants, mainly NO2, during pregnancy may be a substantial risk factor for placental abruption. https://doi.org/10.1289/EHP14714.
Combination of exhaled volatile organic compounds with serum biomarkers predicts respiratory infection severity
Authors: Patricia Esteban, Santiago Letona-Gimenez, Maria Pilar Domingo, Elena Morte, Galadriel Pellejero-Sagastizabal, Maria Del Mar Encabo, Ariel Ramírez-Labrada, Rebeca Sanz-Pamplona, Julián Pardo, José Ramón Paño, Eva M Galvez
Journal: Pulmonology (2025)

During respiratory infections, host-pathogen interaction alters metabolism, leading to changes in the composition of expired volatile organic compounds (VOCs) and soluble immunomodulators. This study aims to identify VOC and blood biomarker signatures to develop machine learning-based prognostic models capable of distinguishing infections with similar symptoms. Twenty-one VOCs and fifteen serum biomarkers were quantified in samples from 86 COVID-19 patients, 75 patients with non-COVID-19 respiratory infections, and 72 healthy donors. The populations were categorized into severity subgroups based on their oxygen support requirements. Descriptive and statistical analyses were conducted to assess group differentiation. Additionally, machine learning classifiers were developed to predict disease severity in both COVID-19 and non-COVID-19 patients. VOC and biomarker profiles differed significantly among groups. Random Forest models demonstrated the best performance for severity prediction. The COVID-19 model achieved 93% accuracy, 100% sensitivity, and 89% specificity, identifying IL-6, IL-8, thrombomodulin, and toluene as key severity predictors. In non-COVID-19 patients, the model reached 89% accuracy, 100% sensitivity, and 67% specificity, with CXCL10 and methyl-isobutyl-ketone as key markers. VOCs and serum biomarkers differentiated HD, COVID-19, and non-COVID-19 patients, and enabled the development of high-performance severity prediction models. While promising, these findings require validation in larger independent cohorts.
Reconstruction of Ancestral Protein Sequences Using Autoregressive Generative Models
Authors: Matteo De Leonardis, Andrea Pagnani, Pierre Barrat-Charlaix
Journal: Molecular Biology and Evolution (2025)

Abstract Ancestral sequence reconstruction (ASR) is an important tool to understand how protein structure and function changed over the course of evolution. It essentially relies on models of sequence evolution that can quantitatively describe changes in a sequence over time. Such models usually consider that sequence positions evolve independently from each other and neglect epistasis: the context-dependence of the effect of mutations. On the other hand, the last years have seen major developments in the field of generative protein models, which learn constraints associated with structure and function from large ensembles of evolutionarily related proteins. Here, we show that it is possible to extend a specific type of generative model to describe the evolution of sequences in time while taking epistasis into account. We apply the developed technique to the problem of ASR: given a protein family and its evolutionary tree, we try to infer the sequences of extinct ancestors. Using both simulations and data coming from experimental evolution we show that our method outperforms state-of-the-art ones. Moreover, it allows for sampling a greater diversity of potential ancestors, allowing for a less biased characterization of ancestral sequences.
Calpain 2 Isoform‐Specific Cleavage of Filamin A Enhances HIF1α Nuclear Translocation, Promoting Metastasis in Triple‐Negative Breast Cancer
Authors: Kyung‐Hwa Jeon, Seojeong Park, Eun Seon Pak, Jeong‐Ahn Kim, Yi Liu, Soo‐Yeon Hwang, Younghwa Na, Youngjoo Kwon
Journal: MedComm (2025)

Triple-negative breast cancer (TNBC) remains a challenge due to its aggressive nature and limited therapeutic options. Calpain 2, a member of the calcium-dependent cysteine protease family, is particularly associated with poor prognosis in TNBC. This study explores the isoform-specific role of calpain 2 in TNBC, examining its correlation with prognosis and its mechanistic impact on metastasis. Bioinformatic analyses, including Kaplan-Meier survival plots, univariate Cox proportional analysis, and gene set enrichment analysis (GSEA), assessed CAPN2 expression and its association with mesenchymal genes in TNBC. Results of cell-based experiments with CAPN2 knockdown or overexpression indicate that elevated CAPN2 expression correlates with poor clinical outcomes and enhanced metastatic potential in TNBC. CAPN2 knockdown inhibited the epithelial-mesenchymal transition (EMT), reducing cancer cell proliferation, migration, and invasion. Calpain 2 downregulation reversed the EMT by reducing isoform-specific cleavage of filamin A, HIF1α nuclear localization and TWIST1 transcription. CNa 29, a calpain 2-specific inhibitor, reduced cancer cell proliferation, decreased filamin A cleavage, downregulated TWIST1 expression, and significantly retarded metastasis,. In conclusion, calpain 2 plays a critical role in TNBC progression by modulating HIF1α and TWIST1, to promote the EMT and metastasis. Isoform-selective inhibition of calpain 2 with CNa 29 presents a promising therapeutic strategy for managing TNBC.
Estimating the proportions of allele frequencies for <i>SERPINA12</i> pathogenic variants in Japanese patients with Nagashima-type palmoplantar keratosis/keratoderma
Authors: Aoi Ebata, Takuya Takeichi, Kazuki Nishida, Basile Chretien, Akira Miyazaki, Takenori Yoshikawa, Yuika Suzuki, Kana Tanahashi, Ryo Fukaura, Mariko Seishima, Yasushi Suga, Yoshinao Muro, Yuka Nakazawa, Tomoo Ogi, Masashi Akiyama
Journal: British Journal of Dermatology (2025)

Nagashima-type palmoplantar keratoderma (NPPK) is the most common form of palmoplantar keratoderma in Asian populations and is primarily caused by biallelic variants in SERPINB7. As SERPINA12 variants were reported in Chinese patients with NPPK, we analysed SERPINA12 variants in 18 Japanese patients with NPPK lacking biallelic SERPINB7 variants and found significantly higher frequencies of SERPINA12 variants c.635-7A&amp;gt;G and c.656A&amp;gt;G compared with the general population. This suggests a potential digenic effect involving SERPINB7 and SERPINA12, highlighting the need for considering digenic inheritance in NPPK diagnosis and genetic counselling.
Maternal Janus kinase inhibitor use is associated with increased risk of aborted pregnancy: a systematic review and meta-analysis
Authors: Ajay S Dulai, Krisha Tripathy, Emi M Murase, Anurag Tarmaster, Zill-e-huma Khan, Mildred Min, Raja Sivamani, Jenny E Murase
Journal: British Journal of Dermatology (2025)

There are currently no clinical trials in humans to understand the teratogenic effects of JAKi use during pregnancy. After performing a systematic review, we discovered that JAKi use is associated with higher risks of stillbirth or spontaneous abortions. Thus, we recommend the use of two effective forms of birth control if this medication is used in a person of childbearing potential.
Transforming Growth Factor Beta2 Promotes Migration and Inhibits the Proliferation of Gastric Cancer Cells by Regulating the pSmad2/3‐NDRG1 Signaling Pathway
Authors: Feng‐Jun He, Xiao‐Long Chen, Yun‐Feng Zhu, Hua‐Yang Pang, Ze‐Dong Li, Pan‐Ping Liang, Tao Jin, Zheng‐Wen Chen, Ze‐Hua Chen, Jian‐Kun Hu, Kun Yang
Journal: MedComm (2025)

Transforming growth factor beta2 (TGFβ2) is upregulated in gastric cancer (GC), playing a crucial role in driving its progression. However, the biological effects of TGFβ2 in GC metastasis and proliferation remain not fully understood. Our study reveals that TGFβ2 enhances N-myc downstream-regulated gene 1 (NDRG1) protein expression by activating the TGFβR/Smad2/3-dependent pathway, accelerating GC progression. TGFβ2 knockdown downregulates NDRG1 by inhibiting the TGFβR/Smad2/3 signaling pathway, which in turn inhibits GC cell migration and epithelial-mesenchymal transition (EMT) but stimulates proliferation. Both TGFβ2 upregulation and NDRG1 upregulation enhance GC cell migration in vitro and promote lung metastasis in mouse models. Interfering with NDRG1 reverses TGFβ2-induced migration, and inhibiting Smad2/3 or TGFβR reverses TGFβ2-induced NDRG1 upregulation and GC cell migration. Clinical sample analysis shows high TGFβ2 and NDRG1 expression in GC, associated with poor prognosis. Our study reveals that TGFβ2 upregulates NDRG1 via the TGFβR/Smad2/3 pathway, driving GC progression and highlighting the potential role of the TGFβ2NDRG1 axis in GC-targeted therapies.
Global trends and epidemiological shifts in gastrointestinal cancers: insights from the past four decades
Authors: Mengmeng Li, Sumei Cao, Rui‐Hua Xu
Journal: Cancer Communications (2025)

Abstract Background The epidemiological profiles of gastrointestinal (GI) cancers vary across countries and over time, largely reflecting variations in risk factors and screening practices. We aimed to provide an overview of the current global burden of the five major types of GI cancers and conduct an updated evaluation of the long‐term trends of GI cancers. Methods The updated numbers of new cases and deaths, and age‐standardized rates (ASR), of the five GI cancers for 185 countries were sourced from the GLOBOCAN 2022, and presented by cancer site, continent, and human development index (HDI). For 43 countries, annual incidence and mortality data were obtained from the Cancer Incidence in Five Continents Plus and World Health Organization mortality databases, supplemented by the mortality data from the Disease Surveillance Points system for China. We compared the long‐term trends of ASRs across countries since 1980, and estimated average annual percent changes (AAPCs) for the recent period 2003‐2017. Results In 2022, there were 4,783,391 new cases and 3,235,719 deaths from the five GI cancers, accounting for 23.9% and 33.2% of all new cancer cases and deaths worldwide, respectively. Cancers of oesophagus, stomach, and liver were more common in Asian and high HDI countries, and colorectal and pancreatic cancer in western and very high HDI countries. Downward trends were observed in almost all countries for gastric cancer and most countries for oesophageal cancer. For colorectal cancer, the most favorable and unfavorable trends were found in 10 and 19 countries respectively. The largest decreases in liver cancer burden were mainly in eastern and southeastern Asia, while increases were seen in North America, Oceania, and Northern Europe, with AAPCs of 3%∼7% for incidence and 2%∼9% for mortality during 2003‐2017. Half of the included countries showed increases in pancreatic cancer burden, with the largest AAPCs in Cyprus, Thailand, India,Türkiye, France, and Belarus for incidence, and Türkiye, Thailand, and China for mortality. Conclusions Deviating patterns were found for GI cancers worldwide. Multi‐setting studies might provide insights into the underlying etiologies of these cancers, and identify areas where urgent cancer control strategies are needed.