tbuckley/cabot-search huggingface dataset:
Deciphering the Connection Between Atopic Dermatitis and Cardiovascular Diseases: Analysis of Clinical Associations and Cardiometabolic Proteins
Authors: Danielle Fehr, Van Hung Huynh‐Tran, Laura Maintz, David Niederseer, Milad Ameri, Anita Dreher, Cezmi A. Akdis, Roger Lauener, Claudio Rhyner, Claudia Traidl‐Hoffmann, Peter Schmid‐Grendelmeier, Thomas Bieber, Marie‐Charlotte Brüggen
Journal: Allergy (2025)

ABSTRACT Background There are conflicting data on a potential association between atopic dermatitis (AD) and cardiovascular diseases (CVD). The aim of this study was to further explore this connection and whether there are biomarkers indicating the risk for CVD in AD patients. Methods We included 677 AD patients and 79 nonatopic controls from an observational multicenter case–control study (ProRaD: Prospective longitudinal study investigating the remission phase in patients with atopic dermatitis and other allergy‐associated diseases). AD severity and atopic, metabolic, and cardiovascular conditions as well as risk factors were assessed. Serum samples were analyzed with targeted proteomics (cardiometabolics panel, Olink). Results We did not find an overall association between AD and CVD. However, AD patients without atopic comorbidities (pure AD) showed a significantly higher CVD prevalence than AD patients with atopic comorbidities (ADAC) (28.2% [37/131] vs. 14.7% [80/546], p &lt; 0.001). Yet, this association could not be confirmed when controlling for cardiovascular risk factors. In pure AD, patients with CVD showed a more severe AD than those without CVD (median EASI [Eczema Area and Severity Index] 12.9 vs. 4.0, p &lt; 0.001). In this subgroup of patients, EASI remained a significant predictor of CVD even in the adjusted model (adjusted odds ratio [aOR] = 1.05, p = 0.040). Forty serum cardiometabolic proteins were upregulated in AD patients compared with nonatopic controls. CC‐chemokine ligand 18 (CCL18) was upregulated in both AD ( p &lt; 0.001) and CVD ( p &lt; 0.001) and its increase correlated with AD severity. Conclusions Our study does not suggest an overall association between AD and CVD, but a more complex relation between the two conditions. Disease severity may be a risk factor for CVD in pure AD patients, but not in those with atopic comorbidities. CCL18 may be a biomarker for CVD.
Hand swelling and other non‐Raynaud's symptoms as the initial presentation of systemic sclerosis: prevalence and clinical associations in two U.S. cohorts
Authors: Iqtidar Hanif, Shervin Assassi, Maureen D. Mayes, Zsuzsanna H. McMahan, Meng Zhang, Julio Charles, John M. VanBuren, Jessica S. Alvey, Kimia Ghaffari, Elana J. Bernstein, Flavia V. Castelino, Lorinda Chung, Luke Evnin, Tracy M. Frech, Jessica K. Gordon, Faye N. Hant, Laura K. Hummers, Dinesh Khanna, Kimberly S. Lakin, Dorota Lebiedz‐Odrobina, Yiming Luo, Ashima Makol, Jerry A. Molitor, Duncan F. Moore, Carrie Richardson, Nora Sandorfi, Ami A. Shah, Ankoor Shah, Victoria K. Shanmugam, Virginia D. Steen, Elizabeth R. Volkmann, Carleigh Zahn, Brian Skaug
Journal: Arthritis & Rheumatology (2025)

Objective Raynaud's phenomenon (RP) is often the initial clinical manifestation of systemic sclerosis (SSc), but some patients develop other manifestations first. To help elucidate the diversity of SSc presentation in its early stages, we describe the initial clinical manifestations and antinuclear antibody (ANA) profiles of patients in two early SSc cohorts. Methods All patient data in the GENISOS and CONQUER cohorts were reviewed. Both studies enrolled patients within five years of the first non‐RP symptom. Results 194/439 (44.2%), and 292/938 (31.1%) patients in GENISOS and CONQUER, respectively, had a non‐RP initial symptom, most commonly puffy fingers/hands. Black patients had a non‐RP symptom prior to RP more commonly than other race and ethnicity categories. Non‐RP first patients were more likely than RP first patients to have diffuse cutaneous involvement and joint contractures at enrollment and had a higher prevalence of RNA Polymerase III antibody positivity. Conclusion In two large U.S. cohorts, &gt;30% of patients began to manifest SSc with puffy fingers/hands or other symptoms, without the “warning sign” of RP as their initial symptom. These patients presented with more severe skin and musculoskeletal disease on average, highlighting the importance of early recognition. The most common autoantibody associated with this presentation was RNA Polymerase III. These results should be considered in efforts to recognize SSc in its earliest stages. Puffy fingers/hands, even in the absence of RP, should prompt consideration of early SSc and testing for ANA and SSc‐associated autoantibodies including RNA Polymerase III.
Targeting Histone H3K9 Methyltransferase G9a as a Potential Therapeutic Strategy for Neuropsychiatric Disorders
Authors: Malak Hajar, Tobias Werner, Mihajlo Gajic, Holger Stark, Bassem Sadek
Journal: Medicinal Research Reviews (2025)

ABSTRACT Neuropsychiatric disorders present a multifaceted challenge, characterized by cognitive, social, and motor impairments with manifold underlying mechanisms. Recent attention has turned to epigenetic mechanisms, particularly histone lysine methyltransferases (HKMTs), such as G9a, in understanding fundamental pathogenesis. This review provides a concise overview of the structural and functional features of G9a and its involvement in neuropsychiatric disorders, including neurodevelopmental disorders (NDDs) like autism spectrum disorders (ASD) and Prader‐Willi syndrome (PWS), schizophrenia (SZ), epilepsy, anxiety, depression, and Alzheimer's disease (AD). Furthermore, it highlights the biochemical mechanisms of G9a‐mediated histone methylations and explores pharmacological interventions targeting G9a for potential therapeutic avenues. This current knowledge underlines G9a's significance as a therapeutic target and sets the stage for future investigations into its role in neuropsychiatric disorders.
A Combined‐Mode Machine Learning Model for Predicting Stroke Recurrence During Hospitalization in Patients with Acute Minor Ischemic Stroke
Authors: Wanxing Ye, Jin Gan, Meng Wang, Ziyang Liu, Hongqiu Gu, Xin Yang, Chunjuan Wang, Xia Meng, Yong Jiang, Hao Li, Liping Liu, Yongjun Wang, Zixiao Li
Journal: MedComm (2025)

ABSTRACT Acute minor ischemic stroke patients often experience recurrence shortly after symptom onset, highlighting the importance of predicting stroke recurrence for guiding treatment decisions. This study evaluated the effectiveness of machine learning models in predicting in‐hospital recurrence. The study cohort comprised 322,135 patients with acute minor ischemic stroke from 1439 centers, as established by Chinese Stroke Center Alliance. Patients were randomly allocated into training and test sets by different centers. Models including extreme gradient boosting (XGB), light gradient boosting (LGB), and adaptive boosting (ADA) were developed using fivefold cross‐validation on the training set. Optimization was performed for all models based on the most important variable, history of ischemic stroke. Compared with the traditional generalized linear model (GLM), the XGB, LGB, ADA models yielded area under the curve (AUC) values ranging from 0.788 to 0.803 after optimization. All models showed significant improvements in AUC compared with GLM, with LGB exhibiting the most substantial enhancement after optimization. For the first time, this study developed models specifically designed to predict in‐hospital stroke recurrence in acute minor ischemic stroke patients. This finding aids in identifying high‐risk patients and prompts physicians to provide targeted treatment. However, further external validation is warranted to confirm the model's generalizability.
Immune Reconstitution after Haploidentical Hematopoietic Stem Cell Transplantation with Different Non‐T‐Cell Depletion Protocols
Authors: Xiao‐Di Ma, Zheng‐Li Xu, Xiao‐Jun Huang
Journal: MedComm (2025)

ABSTRACT Haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) has emerged as a critical treatment for hematological diseases. However, challenges, such as graft rejection and graft‐versus‐host disease (GVHD), have historically been faced with this procedure. Immune reconstitution (IR) has been shown to have profound effects on posttransplantation complications, such as relapse, infections, and GVHD. Recent advances in non‐T‐cell depletion protocols including the Beijing protocol and Baltimore protocol have significantly influenced the outcomes of haplo‐HSCT by improving IR. Clinical studies and multiomic analyses have revealed that different protocols offer distinct mechanisms for IR patterns and further influence clinical outcomes. However, there is a lack of comprehensive reviews that systematically link the differences in IR between two protocols to their clinical outcomes, which leaves a critical gap in understanding the optimal strategies for IR in haplo‐HSCT. This review provides an analysis of IR following haplo‐HSCT with different protocols; it compares the clinical outcomes of various protocols, addresses the role of each immune cell subset in influencing outcomes and discusses emerging strategies aimed at improving IR. This review highlights the importance of ongoing research for improving immune reconstitution strategies, ultimately reducing posttransplant complications and offering targeted treatments to improve patient outcomes.
Bioinspired Carbon Dots with Multi‐Enzyme Activity, Single‐Atom Catalytic, High Efficiency ROS Scavenging and Antioxidant Therapy for Rheumatoid Arthritis
Authors: Qian He, Ruijiao Li, Jiawen Liu, Zewen Wu, Lin Liu, Bin Xu, Liyun Zhang
Journal: Advanced Healthcare Materials (2025)

Abstract Carbon dots (CDs) with enzyme‐like activity have garnered significant attention due to their ability to mimic the catalytic functions of natural enzymes, making them suitable for specific biochemical reactions in biological environments. However, the development of CDs with multi‐enzyme activities remains a challenge due to the inherent complexity of incorporating multiple catalytic functions into a single nanostructure. Here, the synthesis of multi‐enzyme active CDs are successfully demonstrated via a hydrothermal process utilizing hemin chloride and urea as precursors. Detailed structural and theoretical investigations reveal that the CDs possess a highly graphitized π‐electron system and single‐atom iron centers arranged in a monodisperse, four‐coordinate configuration with nitrogen atoms. This distinctive structural configuration imparts CDs with multiple enzyme‐like activities, including superoxide dismutase and catalase, which contribute to the efficient scavenging of reactive oxygen species. Furthermore, encapsulating these CDs within macrophage membranes enables selective targeting of inflammatory sites and circumvention of immune clearance in a collagen‐induced arthritis rat model, offering a targeted and effective antioxidant therapy for rheumatoid arthritis.
Flexible and Environmentally Friendly Calcium Polyphosphate Hydrogels: Toward Inorganic Functional Materials for Wearable Devices and Soft Actuators
Authors: Tongtong Zhou, Jiulong Zhou, Song Zhang, Shuxun Cui
Journal: Advanced Healthcare Materials (2025)

Abstract Inorganic hydrogels have attracted significant interest in materials science. However, it is a big challenge to fabricate flexible and multifunctional inorganic hydrogels due to the inherent rigidity of traditional inorganic materials. Herein, a flexible inorganic hydrogel is proposed, which is prepared by crosslinking long‐chain polyphosphate (LPP) with Ca 2+ ions. This pure‐inorganic CaLPP hydrogel exhibits excellent self‐healing ability, arbitrarily shapable ability, conductivity, degradability and biocompatibility. Furthermore, the CaLPP hydrogel can be used as strain sensors to monitor dynamic deformations (e.g., stretching and bending) with high sensitivity and reliability. The CaLPP hydrogel can also be used as ionic skins to detect human motions, such as bending of the joints and facial expressions. After functionalization, the CaLPP hydrogel can be used as a magnetic actuator. This fundamental work provides an environmentally friendly soft material with a purely inorganic composition, which can be used as a complement to organic‐based soft materials for wearable devices and actuators.
Harnessing Aggregation‐Induced Emission and Multi‐FRET Strategies in a Single Conjugated Polymer Nanosystem for Enhanced Antibacterial Phototheranostics at Minimal Dosage
Authors: Chunhong Zhu, Sameer Hussain, Ziyu Yue, Kaili Wang, Long Zhang, Mohammad Adil Afroz, Chunqiang Liu, Cibin Zhao, Xinyu Zhang, Ansar Abbas, Jingang An, Yi Hao, Ruixia Gao
Journal: Advanced Healthcare Materials (2025)

Abstract Developing effective antibacterial photosensitizers with excellent fluorescence properties, enhanced reactive oxygen species (ROS) generation, and low dosage requirements is highly desirable but remains a major challenge. Herein, a new aggregation‐induced emission (AIE)‐active conjugated polymer (FTDM) with remarkable light‐harvesting properties is designed and synthesized by smartly engineering AIE and multi‐FRET processes in its molecular structure. Thanks to donor‐π‐acceptor configuration, involvement of multi‐FRET mechanisms, and the notable AIE effect, the as‐fabricated water dispersible nanoparticles of FTDM (FTDM NPs) demonstrate outstanding fluorescence properties and high ROS generation ability compared to a non‐AIE model conjugated polymer (FDM) and the common photosensitizer Chlorin E6. Efficient fluorescence bioimaging and photodynamic antibacterial activity are achieved using FTDM NPs under white light irradiation (20 mW cm −2 ) for 15 min, demonstrating over 99.99% efficacy against E. coli at a remarkably low dosage of 0.6 µg mL −1 . Furthermore, a mechanically stable hydrogel matrix (FTDM NPs@gel) for use as a wound dressing is attained which demonstrated accelerated wound healing by inhibiting and eliminating bacteria through the photodynamic effect in an infected mouse model without causing any toxicity. Thus, intelligently designed photodynamic antimicrobial nanosystems can be revolutionary in minimizing the toxicity and combating the menace of drug resistance.
Injectable Alginate/β‐TCP Composite Hydrogel Incorporating P34HB/MgO+PEG Coaxial Electrospun Microfibers for Minimally Invasive Treatment of Osteonecrosis
Authors: Yu Hu Zhou, Zi Hao Zou, Jian Xiang Teng, Zhan Yu Wu, Si Wei Luo, Xu Ning, Chuan Ye, Long Yang, Wei Seong Toh
Journal: Advanced Healthcare Materials (2025)

Abstract Avascular necrosis of the femoral head (ANFH) is a debilitating musculoskeletal disorder that is typically caused by impaired blood supply to the hip joint. In treating irregular bone defects that resulted from ANFH, injectable hydrogels are particularly attractive as they can be administered in a minimally invasive manner and conform to the variable shape of a bone defect. However, they often lack the biochemical and mechanical properties for effective bone repair. To address these issues, an injectable composite hydrogel, SA/β‐TCP@PMP, composed of sodium alginate (SA) and β‐tricalcium phosphate (β‐TCP) crosslinked with glucono‐delta‐lactone (GDL), and enforced with varying concentrations of poly(3‐hydroxybutyrate‐ co ‐4‐hydroxybutyrate)/magnesium oxide and polyethylene glycol (P34HB/MgO+PEG; PMP) coaxial electrospun microfibers are formulated. By varying the concentrations (0%, 1%, 2%, 4%) of PMP microfibers, the physical properties of the composite hydrogel, including its injectability, surface morphology, swelling, degradation, and mechanical properties, as well as magnesium ions (Mg 2+ ) release can be finely tuned. Among all, SA/β‐TCP@2%PMP composite hydrogel demonstrates superior angiogenic and osteogenic properties, and promotes robust new bone formation in a rabbit model of steroid‐induced ANFH. Overall, this novel composite hydrogel offers significant application potential for minimally invasive treatment of irregular bone lesions in ANFH.
Detecting at-risk steatotic liver disease and liver fibrosis in the community
Authors: Leon A. Adams, Maja Thiele, Emmanuel A. Tsochatzis
Journal: Hepatology (2025)

Advanced liver fibrosis and ‘At-Risk’ metabolic dysfunction-associated steatohepatitis (At-Risk MASH) is present in 5% and 10% respectively of community based patients with steatotic liver disease (SLD) and metabolic risk factors and/or excess alcohol consumption. Identification of these patients is critical to guide prognosis and management due to their increased risk of liver decompensation and hepatocellular carcinoma. In addition, identification of At-Risk MASH will assist in targeting those eligible for pharmacotherapy. Screening pathways for detecting advanced liver fibrosis consisting of sequential FIB-4 and elastography or direct liver fibrosis biomarkers in patients with clinical risk factors are recommended, however have sub-optimal sensitivity and specificity. Biomarkers based on serum and/or elastography for At-Risk MASH have been developed in specialist centres however lack broad validation, particularly in the community. Currently a range of barriers have retarded adoption of liver fibrosis screening in primary care, including knowledge gaps regarding non-invasive testing, cost and limited access of non-invasive tests and lack of integrated ordering and reporting systems. Once target patients are identified, robust pathways for linkage to specialist care are needed. Despite these challenges, studies performed in primary care have confirmed that liver fibrosis screening programs increase the detection of unrecognized advanced liver disease and may reduce unnecessary specialist referrals. Furthermore, some data suggest community based screening of liver fibrosis in patients with metabolic dysfunction and alcohol-associated SLD is cost-effective. Wide-spread implementation of systematic evidence based diagnostic pathways in the community are needed to reduce the liver related morbidity related to SLD.
Resorbable 3D‐Printed Osteosynthetic Plates for Rib Fracture Repair
Authors: Emily K. Augustine, Adrian Camarena, Taylor R. Klein, Lillian Kang, Georgia Wimmer, Natasha C. Stinson, Joseph S. Fernandez‐Moure, Matthew L. Becker
Journal: Advanced Healthcare Materials (2025)

Abstract Rib fractures are common among blunt chest trauma patients and are a hallmark of severe thoracic injury with high morbidity and mortality rates. The standard treatment of most rib fracture cases is limited to pain control and respiratory support, with the surgical stabilization of rib fractures (SSRF) using titanium plates reserved for severely injured patients. Although SSRF has been shown to improve long‐term patient outcomes, its expanded use has been limited by the invasiveness of the procedure and a lack of safe and effective resorbable fixation materials. While resorbable metal and polymeric plates have each been used in the clinic, many failures have been reported and challenges remain to control the mechanical properties of the plate during the degradation process. The 3D printing of resorbable, fumarate‐based copolyester‐hydroxyapatite (HAp) composite osteosynthetic plates for use in SSRF is presented, and assess their efficacy in vivo in a rabbit rib fracture model. Compared to rigid titanium fixation plates, ribs fixed with 3D printed composite plates elicit fracture calluses with decreased inflammatory response, enhanced osseointegration, and bone morphometry at 2‐ and 4‐weeks post‐fracture comparable to clinically used titanium plates.
Immune-mediated adverse events and overall survival with tremelimumab plus durvalumab and durvalumab monotherapy in unresectable hepatocellular carcinoma: HIMALAYA phase 3 randomized clinical trial
Authors: George Lau, Bruno Sangro, Ann-Lii Cheng, Masatoshi Kudo, Robin Kate Kelley, Won Young Tak, Antonio Gasbarrini, Maria Reig, Ho Yeong Lim, David Tougeron, Enrico N. De Toni, Vincent C. Tam, Kabir Mody, Jun Gong, Oxana V. Crysler, Wattana Sukeepaisarnjaroen, Oleg Lipatov, Manabu Morimoto, Isabelle Archambeaud, Valentina Burgio, Le Thi Tuyet Phuong, Yee Chao, Jean-Marie Peron, Marie-Luise Berres, Yoo-Joung Ko, Di Ran, Mallory Makowsky, Alejandra Negro, Ghassan K. Abou-Alfa
Journal: Hepatology (2025)

Background and Aims: In the global, Phase 3 HIMALAYA study in unresectable hepatocellular carcinoma (HCC), STRIDE significantly improved overall survival (OS) versus sorafenib; durvalumab was noninferior to sorafenib. Immune checkpoint inhibitor studies have shown an association between the occurrence of immune-mediated adverse events (imAEs) and improved OS. We assessed potential associations between the occurrence of imAEs and OS, and temporal patterns of imAEs, in HIMALAYA. Approach and Results: OS in participants who did and did not experience imAEs and the frequency and timing of imAEs were assessed for STRIDE and durvalumab in the safety analysis set of HIMALAYA. imAEs occurred in 139/388 (35.8%) and 64/388 (16.5%) participants with STRIDE and durvalumab, respectively; most were low grade. OS hazard ratios (95% CI) in participants who experienced imAEs versus those who did not were 0.73 (0.56-0.95) for STRIDE and 1.14 (0.82-1.57) for durvalumab. The 36-month OS rate (95% CI) for STRIDE was 36.2% (28.1-46.7) and 27.7% (22.4-34.2) in participants who did and did not experience imAEs, respectively. The most common imAE category with STRIDE was endocrine events (16.5%). Most imAEs occurred ≤3 months after treatment initiation. Conclusions: Participants who experienced imAEs with STRIDE had a numerical improvement in OS versus those who did not, which was not observed for durvalumab. Long-term OS with STRIDE was observed regardless of imAEs. Most imAEs were low grade, manageable, and occurred in the first 3 months after treatment initiation. Results continue to support the benefits of STRIDE in a diverse population that reflects unresectable HCC globally.
CLDN18.2 CAR‐derived Extracellular Vesicle Immunotherapy Improves Outcome in Murine Pancreatic Cancer
Authors: Yue Qing, Ke Jiang, Hua Jiang, Yaru Zhao, Chu‐Hu Lai, Alexandra Aicher, Zonghai Li, Christopher Heeschen
Journal: Advanced Healthcare Materials (2025)

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with no current effective treatment options. Chimeric antigen receptor (CAR) T cell therapy represents a powerful immunotherapeutic approach but faces major limitations in PDAC due to complex manufacturing and reduces efficacy within the highly immunosuppressive tumor microenvironment (TME). Small extracellular vesicles (sEVs) derived from CAR‐T cells present a novel strategy to address these challenges. Here, CLDN18.2 CAR‐T cells are used to generate CAR‐sEVs via ultracentrifugation. The purified CAR‐sEVs exhibit typical sEV size and morphology, containing established sEV markers, and carry functional CAR proteins along with cytotoxic molecules such as granzyme B. In vitro, CAR‐sEVs displays potent cytotoxic activity against murine CLDN18.2 + PDAC cells, whereas no significant effects are observed in CLDN18.2 − non‐transformed cells. In an aggressive orthotopic murine PDAC model, CAR‐sEV administration reduces tumor growth as measured by bioluminescence imaging and significantly extends survival. Notably, CAR‐sEVs also significantly prolong survival compared to treatment with conventional CLDN18.2‐targeting CAR‐T cells, further supporting their therapeutic potential. Moreover, unlike CAR‐T cells, CAR‐sEVs do not induce systemic IL‐6 release in vivo. These findings position CLDN18.2 CAR‐sEVs as a promising therapeutic modality for PDAC, offering an innovative and potentially safer platform for solid tumor immunotherapy.