tbuckley/cabot-search huggingface dataset:
Multifunctional Prosthesis Surface: Modification of Titanium with Cinnamaldehyde‐Loaded Hierarchical Titanium Dioxide Nanotubes
Authors: Yi Mao, Xinru Xie, Guangxin Sun, Shiqi Yu, Mingqi Ma, Rui Chao, Tianhao Wan, Weifeng Xu, Xuzhuo Chen, Lei Sun, Shanyong Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract Orthopedic prostheses are the ultimate therapeutic solution for various end‐stage orthopedic conditions. However, aseptic loosening and pyogenic infections remain as primary complications associated with these devices. In this study, a hierarchical titanium dioxide (TiO 2 ) nanotube drug delivery system loaded with cinnamaldehyde for the surface modification of titanium implants, is constructed. These specially designed dual‐layer TiO 2 nanotubes enhance material reactivity and provide an extensive drug‐loading platform within a short time. The introduction of cinnamaldehyde enhances the bone integration performance of the scaffold (simultaneously promoting bone formation and inhibiting bone resorption), anti‐inflammatory capacity, and antibacterial properties. In vitro experiments have demonstrated that this system promoted osteogenesis by upregulating both Wnt/β‐catenin and MAPK signaling pathways. Furthermore, it inhibits osteoclast formation, suppresses macrophage‐mediated inflammatory responses, and impedes the proliferation of Staphylococcus aureus and Escherichia coli. In vivo experiments shows that this material enhances bone integration in a rat model of femoral defects. In addition, it effectively enhances the antibacterial and anti‐inflammatory properties in a subcutaneous implant in a rat model. This study provides a straightforward and highly effective surface modification strategy for orthopedic Ti implants.
A randomized, double‐blind placebo‐controlled study on the efficacy of Omalizumab on food allergy threshold in children with severe food allergy
Authors: Charlotte G. Mortz, Louise Parke, Helene M. Rasmussen, Henrik Fomsgaard Kjaer, Carsten Bindslev‐Jensen
Journal: Allergy (2024)

Abstract Background Food allergy is common in childhood with some children having a low threshold and being difficult to protect from accidental ingestion of the offending food. Therapies for this potentially life‐threatening condition are highly needed. The aim of this study was to evaluate the efficacy of Omalizumab in food‐allergic children. Methods This is a single‐center, double‐blind, placebo‐controlled study. Food allergic children with a cumulative threshold ≤443 mg food protein at DBPCFC were randomized to Omalizumab (asthma dose) or placebo (3:1). After 3 months, a second DBPCFC was performed (steps 3, 10, 30, 100, 300, 1000, and 3000 mg food protein), followed by a separate open challenge up to 10,000 and 30,000 mg food protein if negative. Responders were defined as ≥2‐step increases in threshold. Non‐responders received high‐dose Omalizumab. A third DBPCFC was performed after 6 months. Skin testing, blood samples, and the severity of atopic co‐morbidity were registered during the study and 3 months after treatment. Results In total, 20 children were evaluated at 3 months (14 Omalizumab, 6 placebo). All treated with Omalizumab increased their threshold at least two steps and with a significant difference between the Omalizumab and the placebo group ( p = .003), although the intended number of included children was not reached. The threshold before Omalizumab treatment was 13–443 mg food protein while the threshold after 3 months of treatment increased up to 44,000 mg (1143–44,000). In the placebo group, two children improved threshold during the study. Conclusion An increase in the threshold level during Omalizumab treatment significantly improve patient safety and protected all children against small amount of allergen.
Che-1/miR-590-3p/TAZ axis sustains multiple myeloma disease
Authors: Tiziana Bruno, Valeria Catena, Giacomo Corleone, Clelia Cortile, Maria Chiara Cappelletto, Barbara Bellei, Francesca De Nicola, Bruno Amadio, Svitlana Gumenyuk, Francesco Marchesi, Ombretta Annibali, Giovanni Blandino, Maurizio Fanciulli, Silvia Di Agostino
Journal: Leukemia (2024)
Navigating the blurred path of mixed neuroimmune signaling
Authors: Surbhi Gupta, Alice Viotti, Tuany Eichwald, Anais Roger, Eva Kaufmann, Rahmeh Othman, Nader Ghasemlou, Moutih Rafei, Simmie L Foster, Sebastien Talbot
Journal: Journal of Allergy and Clinical Immunology (2024)

Evolution has created complex mechanisms to sense environmental danger and protect tissues, with the nervous and immune systems playing pivotal roles. These systems work together, coordinating local and systemic reflexes to restore homeostasis in response to tissue injury and infection. By sharing receptors and ligands, they influence the pathogenesis of various diseases. Recently, a less-explored aspect of neuroimmune communication has emerged: the release of neuropeptides from immune cells and cytokines/chemokines from sensory neurons. This article reviews evidence of this unique neuroimmune interplay and its impact on the development of allergy, inflammation, itch, and pain. We highlight the effects of this neuroimmune signaling on vital processes such as host defense, tissue repair, and inflammation resolution, providing avenues for exploration of the underlying mechanisms and therapeutic potential of this signaling.
Cancer risks among first-degree relatives of women with a genetic predisposition to breast cancer
Authors: Qingyang Xiao, Xinhe Mao, Alexander Ploner, Felix Grassmann, Juan Rodriguez, Mikael Eriksson, Per Hall, Kamila Czene
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Associations between germline alterations in women and cancer risks among their relatives are largely unknown. Methods We identified women from 2 Swedish cohorts Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) and prevalent KARMA (pKARMA), including 28 362 women with genotyping data and 13 226 with sequencing data. Using Swedish Multi-Generation Register, we linked these women to 133 389 first-degree relatives. Associations between protein-truncating variants in 8 risk genes and breast cancer polygenic risk score in index women and cancer risks among their relatives were modeled via Cox regression. Results Female relatives of index women who were protein-truncating variant carriers in any of the 8 risk genes had an increased breast cancer risk compared with those of noncarriers (hazard ratio [HR] = 1.85, 95% confidence interval [CI] = 1.52 to 2.27), with the strongest association found for protein-truncating variants in BRCA1 and 2. These relatives had a statistically higher risk of early onset than late-onset breast cancer (P = .001). Elevated breast cancer risk was also observed in female relatives of index women with higher polygenic risk score (HR per SD = 1.28, 95% CI = 1.23 to 1.32). The estimated lifetime risk was 22.3% for female relatives of protein-truncating variant carriers and 14.4% for those related to women in the top polygenic risk score quartile. Moreover, relatives of index women with protein-truncating variant presence (HR = 1.30, 95% CI = 1.06 to 1.59) or higher polygenic risk score (HR per SD = 1.04, 95% CI = 1.01 to 1.07) were also at higher risk of nonbreast hereditary breast and ovary cancer syndrome-related cancers. Conclusions Protein-truncating variants of risk genes and higher polygenic risk score in index women are associated with an increased risk of breast and other hereditary breast and ovary syndrome–related cancers among relatives.
Engineered M2 macrophage-derived extracellular vesicles with platelet membrane fusion for targeted therapy of atherosclerosis
Authors: Lan Xie, Jinyong Chen, Haochang Hu, Yuan Zhu, Xiying Wang, Siyu Zhou, Feifan Wang, Meixiang Xiang
Journal: Bioactive Materials (2024)

Atherosclerosis is featured as chronic low-grade inflammation in the arteries, which leads to the formation of plaques rich in lipids. M2 macrophage-derived extracellular vesicles (M
Management of patients with rare adult solid cancers: objectives and evaluation of European reference networks (ERN) EURACAN
Authors: Jean-Yves Blay, Paolo Casali, Isabelle Ray-Coquard, Michael J. Seckl, Jourik Gietema, Wouter W. de Herder, Martyn Caplin, Heinz-Josef Klümpen, Olivier Glehen, Lucjan Wyrwicz, Robin Peeters, Lisa Licitra, Nicolas Girard, Sophie Piperno-Neumann, Ellen Kapiteijn, Ahmed Idbaih, Enrico Franceschi, Annalisa Trama, Anna-Maria Frezza, Peter Hohenberger, Nadia Hindi, Javier Martin-Broto, Johanna Schell, Muriel Rogasik, Stephane Lejeune, Kathy Oliver, Francesco de Lorenzo, Ariane Weinman
Journal: The Lancet Regional Health - Europe (2024)

About 500,000 patients with rare adult solid cancers (RASC) are diagnosed yearly in Europe. Delays and unequal quality of management impact negatively their survival. Since 2017, European reference networks (ERN) aim to improve the quality of care of patients with rare disease. The steering committee of EURACAN, including physicians, researchers and patients review here the previous actions, present objectives of the ERN EURACAN dedicated to RASC. EURACAN promoted management in reference centres, and equal implementation of excellence and innovation in Europe and developed 22 clinical practice guidelines (CPGs). Additionally, fourteen information brochures translated in 24 EU languages were developed in collaboration with patient advocacy groups (ePAGs) and seventeen training session were organized. Nevertheless, connections to national networks in the 26 participating countries (106 centres), simplification of cross-border healthcare, international multidisciplinary tumour boards, registries and monitoring of the quality of care are still required. In this Health Policy, evaluation criteria of the performances of the network and of health care providers are proposed.
Prevalence and Predictive Factors for Celiac Disease in Children With Type 1 Diabetes: Whom and When to Screen? A Nationwide Longitudinal Cohort Study of Swedish Children
Authors: Marie Lindgren, Fredrik Norström, Martina Persson, Helena Elding Larsson, Gun Forsander, Karin Åkesson, Ulf Samuelsson, Johnny Ludvigsson, Annelie Carlsson
Journal: Diabetes Care (2024)

To examine the prevalence and predictive factors for celiac disease (CD) after a diagnosis of type 1 diabetes (T1D) in children and adolescents, to improve the current screening guidelines.
Type II collagen scaffolds repair critical-sized osteochondral defects under induced conditions of osteoarthritis in rat knee joints via inhibiting TGF-β-Smad1/5/8 signaling pathway
Authors: Xu Hu, Min Jin, Kang Sun, Zhen Zhang, Zhonglian Wu, Junli Shi, Peilai Liu, Hang Yao, Dong-An Wang
Journal: Bioactive Materials (2024)

The bidirectional relationship between osteochondral defects (OCD) and osteoarthritis (OA), with each condition exacerbating the other, makes OCD regeneration in the presence of OA challenging. Type II collagen (Col2) is important in OCD regeneration and the management of OA, but its potential applications in cartilage tissue engineering are significantly limited. This study investigated the regeneration capacity of Col2 scaffolds in critical-sized OCDs under surgically induced OA conditions and explored the underlying mechanisms that promoted OCD regeneration. Furthermore, the repair potential of Col2 scaffolds was validated in over critical-sized OCD models. After 90 days or 150 days since scaffold implantation, complete healing was observed histologically in critical-sized OCD, evidenced by the excellent integration with surrounding native tissues. The newly formed tissue biochemically resembled adjacent natural tissue and exhibited comparable biomechanical properties. The regenerated OA tissue demonstrated lower expression of genes associated with cartilage degradation than native OA tissue but comparable expression of genes related to osteochondral anabolism compared with normal tissue. Additionally, transcriptome and proteome analysis revealed the hindrance of TGF-β-Smad1/5/8 in regenerated OA tissue. In conclusion, the engrafting of Col2 scaffolds led to the successful regeneration of critical-sized OCDs under surgically induced OA conditions by inhibiting the TGF-β-Smad1/5/8 signaling pathway.
Biomaterial-based mechanical regulation facilitates scarless wound healing with functional skin appendage regeneration
Authors: Ying-Ying Li, Shuai-Fei Ji, Xiao-Bing Fu, Yu-Feng Jiang, Xiao-Yan Sun
Journal: Military Medical Research (2024)

Abstract Scar formation resulting from burns or severe trauma can significantly compromise the structural integrity of skin and lead to permanent loss of skin appendages, ultimately impairing its normal physiological function. Accumulating evidence underscores the potential of targeted modulation of mechanical cues to enhance skin regeneration, promoting scarless repair by influencing the extracellular microenvironment and driving the phenotypic transitions. The field of skin repair and skin appendage regeneration has witnessed remarkable advancements in the utilization of biomaterials with distinct physical properties. However, a comprehensive understanding of the underlying mechanisms remains somewhat elusive, limiting the broader application of these innovations. In this review, we present two promising biomaterial-based mechanical approaches aimed at bolstering the regenerative capacity of compromised skin. The first approach involves leveraging biomaterials with specific biophysical properties to create an optimal scarless environment that supports cellular activities essential for regeneration. The second approach centers on harnessing mechanical forces exerted by biomaterials to enhance cellular plasticity, facilitating efficient cellular reprogramming and, consequently, promoting the regeneration of skin appendages. In summary, the manipulation of mechanical cues using biomaterial-based strategies holds significant promise as a supplementary approach for achieving scarless wound healing, coupled with the restoration of multiple skin appendage functions.
A multicenter, randomized, double-blinded, placebo-controlled, phase Ⅲ study evaluating the efficacy and safety of Xeligekimab (GR1501) in patients with moderate-to-severe plaque psoriasis
Authors: Lin Cai, Congjun Jiang, Guoqiang Zhang, Hong Fang, Jinyan Wang, Yumei Li, Hui Xu, Rong Xiao, Yangfeng Ding, Kun Huang, Chunlei Zhang, Litao Zhang, Bin Chen, Xinsuo Duan, Weili Pan, Guangming Han, Rongyi Chen, Lunfei Liu, Shoumin Zhang, Juan Tao, Xiaowen Pang, Jianbin Yu, Huiping Wang, Yi Zhao, Chengxin Li, Xiaojing Kang, Lanying Qin, Xiaofang Zhu, Juan Su, Shanshan Li, Chunjun Yang, Wenli Feng, Tiechi Lei, Shan Jiang, Ruihua Fang, Mao Lin, Qianjin Lu, Chunxing Xu, Wei Wang, Jianzhong Zhang
Journal: British Journal of Dermatology (2024)

Abstract Background Xeligekimab (GR1501) is a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A and has shown potential efficacy in treating moderate-to-severe psoriasis in preliminary trials. Objectives To evaluate the efficacy and safety of xeligekimab in Chinese patients with moderate-to-severe psoriasis. Methods A total of 420 Chinese patients were randomized to 200 mg xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by an extension of the treatment schedule to xeligekimab every 4 weeks for a further 40 weeks. Efficacy was assessed by evaluating achievement of Physician Global Assessment (PGA) 0/1 and 75%, 90% and 100% improvement in Psoriasis Area and Severity Index (PASI 75, PASI 90 and PASI 100, respectively). The safety profile was also evaluated. Results At week 12, PASI 75, PASI 90 and PASI 100 were achieved in 90.7%, 74.4% and 30.2% of patients in the xeligekimab group vs. 8.6%, 1.4% and 0% of patients in the placebo group, respectively. PGA 0/1 was achieved in 74.4% patients in the xeligekimab group and 3.6% of patients in the placebo group. PASI 75 and PGA 0/1 were maintained until week 52. No unexpected adverse events were recorded. Conclusions Xeligekimab showed high efficacy and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.
Plasma N-terminal containing tau fragments (NTA-tau): a biomarker of tau deposition in Alzheimer’s Disease
Authors: Juan Lantero-Rodriguez, Gemma Salvadó, Anniina Snellman, Laia Montoliu-Gaya, Wagner S Brum, Andrea L Benedet, Niklas Mattsson-Carlgren, Pontus Tideman, Shorena Janelidze, Sebastian Palmqvist, Erik Stomrud, Nicholas J Ashton, Henrik Zetterberg, Kaj Blennow, Oskar Hansson
Journal: Molecular Neurodegeneration (2024)

Abstract Background Novel phosphorylated-tau (p-tau) blood biomarkers (e.g., p-tau181, p-tau217 or p-tau231), are highly specific for Alzheimer’s disease (AD), and can track amyloid-β (Aβ) and tau pathology. However, because these biomarkers are strongly associated with the emergence of Aβ pathology, it is difficult to determine the contribution of insoluble tau aggregates to the plasma p-tau signal in blood. Therefore, there remains a need for a biomarker capable of specifically tracking insoluble tau accumulation in brain. Methods NTA is a novel ultrasensitive assay targeting N-terminal containing tau fragments (NTA-tau) in cerebrospinal fluid (CSF) and plasma, which is elevated in AD. Using two well-characterized research cohorts (BioFINDER-2, n = 1,294, and BioFINDER-1, n = 932), we investigated the association between plasma NTA-tau levels and disease progression in AD, including tau accumulation, brain atrophy and cognitive decline. Results We demonstrate that plasma NTA-tau increases across the AD continuum ¸ especially during late stages, and displays a moderate-to-strong association with tau-PET (β = 0.54, p &lt; 0.001) in Aβ-positive participants, while weak with Aβ-PET (β = 0.28, p &lt; 0.001). Unlike plasma p-tau181, GFAP, NfL and t-tau, tau pathology determined with tau-PET is the most prominent contributor to NTA-tau variance (52.5% of total R 2 ), while having very low contribution from Aβ pathology measured with CSF Aβ42/40 (4.3%). High baseline NTA-tau levels are predictive of tau-PET accumulation ( R 2 = 0.27), steeper atrophy ( R 2 ≥ 0.18) and steeper cognitive decline ( R 2 ≥ 0.27) in participants within the AD continuum . Plasma NTA-tau levels significantly increase over time in Aβ positive cognitively unimpaired (β std = 0.16) and impaired (β std = 0.18) at baseline compared to their Aβ negative counterparts. Finally, longitudinal increases in plasma NTA-tau levels were associated with steeper longitudinal decreases in cortical thickness ( R 2 = 0.21) and cognition ( R 2 = 0.20). Conclusion Our results indicate that plasma NTA-tau levels increase across the AD continuum , especially during mid-to-late AD stages, and it is closely associated with in vivo tau tangle deposition in AD and its downstream effects. Moreover, this novel biomarker has potential as a cost-effective and easily accessible tool for monitoring disease progression and cognitive decline in clinical settings, and as an outcome measure in clinical trials which also need to assess the downstream effects of successful Aβ removal.
CircPCNXL2 promotes tumor growth and metastasis by interacting with STRAP to regulate ERK signaling in intrahepatic cholangiocarcinoma
Authors: Shuochen Liu, Yirui Wang, Tianlin Wang, Kuangheng Shi, Shilong Fan, Chang Li, Ruixiang Chen, Jifei Wang, Wangjie Jiang, Yaodong Zhang, Yananlan Chen, Xiao Xu, Yue Yu, Changxian Li, Xiangcheng Li
Journal: Molecular Cancer (2024)

Abstract Background circular RNAs (circRNAs) have been reported to exert important effects in the progression of numerous cancers. However, the functions of circRNAs in intrahepatic cholangiocarcinoma (ICC) are still unclear. Methods circPCNXL2 (has_circ_0016956) were identified in paired ICC by circRNA microarray. Then, we assessed the biological functions of circPCNXL2 by CCK8, EdU, clone formation, transwell, wound healing assays, and xenograft models. RNA pull-down, mass spectrometry, and RNA immunoprecipitation (RIP) were applied to explore the interaction between cirrcPCNXL2 and serine-threonine kinase receptor-associated protein (STRAP). RNA pull-down, RIP and luciferase reporter assays were used to investigate the sponge functions of circPCNXL2. In the end, we explore the effects of circPCNXL2 and trametinib (a MEK1/2 inhibitor) in vivo. Results circPCNXL2 was upregulated in ICC tissues and cell lines, which promoted the proliferation and metastasis of ICC in vitro and in vivo. In terms of the mechanisms, circPCNXL2 could directly bind to STRAP and induce the interaction between STRAP and MEK1/2, resulting in the tumor promotion in ICC by activation of ERK/MAPK pathways. Besides, circPCNXL2 could regulate the expression of SRSF1 by sponging miR-766-3p and subsequently facilitated the growth of ICC. Finally, circPCNXL2 could partially inhibit the anti-tumor activity of trametinib in vivo. Conclusion circPCNXL2 played a crucial role in the progression of ICC by interacting with STRAP to activate the ERK signaling pathway, as well as by modulating the miR-766-3p/SRSF1 axis. These findings suggest that circPCNXL2 may be a promising biomarker and therapeutic target for ICC.
Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application
Authors: Zongyao Huang, Yao Fu, Hong Yang, Yehan Zhou, Min Shi, Qingyun Li, Weiping Liu, Junheng Liang, Liuqing Zhu, Sheng Qin, Huangming Hong, Yang Liu
Journal: Molecular Cancer (2024)

Abstract T-cell lymphoma is a highly invasive tumor with significant heterogeneity. Invasive tissue biopsy is the gold standard for acquiring molecular data and categorizing lymphoma patients into genetic subtypes. However, surgical intervention is unfeasible for patients who are critically ill, have unresectable tumors, or demonstrate low compliance, making tissue biopsies inaccessible to these patients. A critical need for a minimally invasive approach in T-cell lymphoma is evident, particularly in the areas of early diagnosis, prognostic monitoring, treatment response, and drug resistance. Therefore, the clinical application of liquid biopsy techniques has gained significant attention in T-cell lymphoma. Moreover, liquid biopsy requires fewer samples, exhibits good reproducibility, and enables real-time monitoring at molecular levels, thereby facilitating personalized health care. In this review, we provide a comprehensive overview of the current liquid biopsy biomarkers used for T-cell lymphoma, focusing on circulating cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), Epstein-Barr virus (EBV) DNA, antibodies, and cytokines. Additionally, we discuss their clinical application, detection methodologies, ongoing clinical trials, and the challenges faced in the field of liquid biopsy.