tbuckley/cabot-search huggingface dataset:
Bottom‐up Assembling Hierarchical Enamel‐like Bulk Materials with Excellent Optical and Mechanical Properties for Tooth Restoration
Authors: Shan Zhang, Wu Xu, Leping Wu, Xiaxin Li, Xingzi Liu, Xiaoting Wu, Guomin Wu, Shunli Zheng, Chris Ying Cao, Zheng Zhou, Hai Ming Wong, Xu Zhang, Quan‐Li Li
Journal: Advanced Healthcare Materials (2024)

Enamel has good optical and mechanical properties because of its multiscale hierarchical structure. Biomimetic construction of enamel-like 3D bulk materials at nano-, micro-, mesh- and macro-levels is a challenge. A novel facile, cost-effective, and easy large-scale bottom-up assembly strategy to align 1D hydroxyapatite (HA) nanowires bundles to 3D hierarchical enamel structure with the nanowires bundles layer-by-layer interweaving orientation, is reported. In the strategy, the surface of oleate templated ultralong HA nanowires with a large aspect ratio is functionalized with amphiphilic 10-methacryloyloxydecyl dihydrogen phosphate (MDP). Furtherly, the MDP functionalized HA nanowire bundles are assembled layer-by-layer with oriented fibers in a single layer and cross-locked between layers at a certain angle at mesoscale and macroscale in the viscous bisphenol A-glycidyl methacrylate (Bis-GMA) ethanol solution by shear force induced by simple agitation and high-speed centrifugation. Finally, the excessive Bis-GMA and ethanol are removed, and (Bis-GMA)-(MDP-HA nanowire bundle) matrix is densely packed under hot pressing and polymerized to form bulk enamel-like materials. The composite has superior optical properties and comparable comprehensive mechanic performances through a combination of strength, hardness, toughness, and friction. This method may open new avenues for controlling the nanowires assembly to develop hierarchical nanomaterials with superior properties for many different applications.
Mixed Adenoma and Well-Differentiated Neuroendocrine Tumor (MANET) of the Middle Ear
Authors: Ivan J. Stojanov, Sylvia L. Asa
Journal: Endocrine Pathology (2024)

A 45-year-old male presented with acute mastoiditis and facial nerve paralysis.Computerized tomography of the temporal bone demonstrated complete opacification of left mastoid air cells, near complete middle ear cavity opacification, and bony erosion of the petrous apex extending to the left geniculate ganglion and proximal facial nerve canal.There was associated tympanic membrane thickening and external auditory canal debris.The patient was referred for mastoidectomy at which point a biopsy was performed.
Targeted Clearance of Senescent Cells Via Engineered Extracellular Vesicles Reprograms Tumor Immunosuppressive Microenvironment
Authors: Panpan Ji, Chen Wang, Yang Liu, Xin Guo, Yuan Liang, Jiangpeng Wei, Zhaoyou Liu, Li Gong, Guodong Yang, Gang Ji
Journal: Advanced Healthcare Materials (2024)

Abstract Unravelling the mechanisms for the immunosuppressive tumor microenvironment and developing corresponding therapeutic strategies are of great importance to improve the cancer immunotherapy. This study has revealed that there are abundant senescent cells accumulated in the colon cancer tissue, which contributes greatly to the immunosuppressive microenvironment. Oral delivery of Dasatinib and Quercetin (D+Q) eliminates the senescent cells with compromised efficiency due to the poor tumor penetration and short half‐life. To improve the efficacy of senescent cell clearance, this work has developed an extracellular vesicle (EV) based senolytic strategy. The engineered senolytic EVs have anti‐GPNMB (a senescent cell surface marker) displayed on the surface and D+Q loaded on the membrane. In a syngeneic mouse model, senolytic EVs efficiently and selectively eradicate the senescent cells and in turn unleashes the antitumor immunity. With the antitumor immunity boosted, cancer growth is inhibited and the survival is prolonged. In summary, this work has illuminated that senescent cells contribute to the immunosuppressive microenvironment in colon cancer and proposes a novel strategy to conquer the problem by EV‐based senolytics.
Genetically proxied IL-6 receptor inhibition is associated with increased risk of atopic dermatitis
Authors: Sizheng Steven Zhao, Zenas Z.N. Yiu
Journal: Journal of Allergy and Clinical Immunology (2024)

BackgroundDermatitis has been reported after initiation of IL-6 receptor (IL-6R) inhibitors (IL-6Ri), while genetic association studies of atopic dermatitis (AD) have implicated IL-6R pathway signaling. However, causality remains unclear. As the indications for IL-6Ri expand, so do the clinical importance of determining whether there is mechanistic evidence linking it to AD.ObjectiveOur aim was to examine the association between IL-6Ri and risk of AD.MethodsTo genetically mimic IL-6Ri, we selected single-nucleotide polymorphisms within or near the IL6R gene associated with C-reactive protein at genome-wide significance among 343,524 individuals. Genetic data were obtained from 10,788 individuals with AD and 30,047 controls of European ancestry. We used inverse variance–weighted and pleiotropy-robust methods and examined genetic confounding using colocalization. Analyses were replicated by using 13,473 Finnish and 2,385 East Asian individuals with AD. The results from 3 independent analyses were pooled by meta-analysis.ResultsGenetically proxied IL-6Ri was associated with increased risk of AD (odds ratio [OR] = 1.78 per 4.4-mg/L reduction in C-reactive protein level [95% CI = 1.28-2.48] [P = 6.5 × 10–4]). The results were replicated using Finnish outcome data (OR = 2.07 [95% CI = 1.58-2.72] [P = 1.57 × 10–7]) and Eastern Asian data (OR = 1.68 [95% CI = 1.12-2.54] [P = .013]). Meta-analysis of 3 independent populations (OR = 1.89 [95% CI = 1.57-2.28] [P = 2.68 × 10–11]) showed no evidence of heterogeneity (P = .65). We found no statistical evidence for pleiotropy or genetic confounding.ConclusionThis genetic investigation provides consistent evidence (across independent multiancestry populations) that IL-6R signaling is causally implicated in AD susceptibility. Clinicians should remain vigilant for adverse effects resembling AD when using IL-6R inhibitors for immune-mediated inflammatory diseases.
The three-year evolution of Germany’s Digital Therapeutics reimbursement program and its path forward
Authors: Linea Schmidt, Marc Pawlitzki, Bernhard Y. Renard, Sven G. Meuth, Lars Masanneck
Journal: npj Digital Medicine (2024)

Abstract The 2019 German Digital Healthcare Act introduced the Digital Health Application program, known in German as ‘Digitale Gesundheitsanwendungen’ (DiGA). The program has established a pioneering model for integrating Digital Therapeutics (DTx) into a healthcare system with scalable and effective reimbursement strategies. To date, the continuous upward trend enabled by this framework has resulted in more than 374,000 DiGA prescriptions, increasingly cementing its role in the German healthcare system. This perspective provides a synthesis of the DiGA program’s evolution since its inception three years ago, highlighting trends regarding prescriptions and pricing as well as criticisms and identified shortcomings. It further discusses forthcoming legislative amendments, including the anticipated integration of higher-risk medical devices, which have the potential to significantly transform the program. Despite encountering challenges related to effectiveness, evidence requirements, and integration within the healthcare system, the DiGA program continues to evolve and serves as a seminal example for the integration of DTx, offering valuable insights for healthcare systems globally.
Immune modulation of the liver metastatic colorectal cancer microenvironment via the oral CAPOX-mediated cGAS-STING pathway
Authors: Seong Jin Park, Seho Kweon, Mudhibadhi Knowledge Moyo, Ha Rin Kim, Jeong Uk Choi, Na Kyeong Lee, Ruby Maharjan, Young Seok Cho, Jin Woo Park, Youngro Byun
Journal: Biomaterials (2024)
A wearable sensor and machine learning estimate step length in older adults and patients with neurological disorders
Authors: Assaf Zadka, Neta Rabin, Eran Gazit, Anat Mirelman, Alice Nieuwboer, Lynn Rochester, Silvia Del Din, Elisa Pelosin, Laura Avanzino, Bastiaan R. Bloem, Ugo Della Croce, Andrea Cereatti, Jeffrey M. Hausdorff
Journal: npj Digital Medicine (2024)

Step length is an important diagnostic and prognostic measure of health and disease. Wearable devices can estimate step length continuously (e.g., in clinic or real-world settings), however, the accuracy of current estimation methods is not yet optimal. We developed machine-learning models to estimate step length based on data derived from a single lower-back inertial measurement unit worn by 472 young and older adults with different neurological conditions, including Parkinson's disease and healthy controls. Studying more than 80,000 steps, the best model showed high accuracy for a single step (root mean square error, RMSE = 6.08 cm, ICC(2,1) = 0.89) and higher accuracy when averaged over ten consecutive steps (RMSE = 4.79 cm, ICC(2,1) = 0.93), successfully reaching the predefined goal of an RMSE below 5 cm (often considered the minimal-clinically-important-difference). Combining machine-learning with a single, wearable sensor generates accurate step length measures, even in patients with neurologic disease. Additional research may be needed to further reduce the errors in certain conditions.
Senolytic Therapy Enabled by Senescent Cell‐Sensitive Biomimetic Melanin Nano‐senolytics
Authors: Hairui Zhang, Xiaoling Xu, Xin Shou, Wucan Liao, Chengkang Jin, Changjiang Chen, Chen Zhang, Wenhua Gao, Junfeng Zhang, Weihong Ge, Liyun Shi
Journal: Advanced Healthcare Materials (2024)

Cellular senescence is a significant risk factor for aging and age-related diseases (ARD). The canonical senolytics Dasatinib and Quercetin (DQ) have shown promise in clearing senescent cells (SnCs); however, the lack of selectivity poses a challenge in achieving optimal outcomes. Despite the recent occurrence of nanomaterial-based approaches targeting SnCs, limited therapeutic effects, and potential toxicity still remain a major concern. Herein, a "double locks-like" nanoplatform is developed that integrated Galactan coating and mesoporous polydopamine to encase the senolytic drug DQ. By this way, DQ is only released in SnCs that are featured with higher levels of β-galactosidase (β-gal) and low PH. Additionally, the nanoparticles are equipped with 2,2,6,6-Tetramethylpiperidine-1-oxyl (Tempo) to gain enhanced photothermal converting potential. Consequently, the synthesized nanosenolytics demonstrate remarkable specificity and efficacy in eradicating SnCs, and accordingly reverse pulmonary fibrosis in mice without affecting normal tissues. Upon exposure of near-infrared (NIR) light, the nanoparticles demonstrate to efficiently remove senescent tumor cells inducted by chemotherapy, thereby hindering the outgrowth and metastasis or breast cancer. Collectively, the present study develops an "On/Off" switchable nanoplatform in response to SnCs, and produces a more safe, efficient, and feasible way to delay aging or alleviate age-associated diseases.
EGFR-targeted ionizable lipid nanoparticles enhance in vivo mRNA delivery to the placenta
Authors: Hannah C Geisler, Aditi A Ghalsasi, Hannah C Safford, Kelsey L Swingle, Ajay S Thatte, Alvin J Mukalel, Ningqiang Gong, Alex G Hamilton, Emily L Han, Benjamin E Nachod, Marshall S Padilla, Michael J Mitchell
Journal: Journal of Controlled Release (2024)
Targeted Photodynamic Therapy using a Vectorized Photosensitizer coupled to Folic Acid Analog induces Ovarian Tumor Cell Death and inhibits IL-6-mediated Inflammation
Authors: Léa Boidin, Morgane Moinard, Albert Moussaron, Margaux Merlier, Olivier Moralès, Guillaume Paul Grolez, Martha Baydoun, Amirah Mohd-Gazzali, Mohammad Hafizie Dianel Mohd Tazizi, Hassan Hadi Abd Allah, Yohan Kerbage, Philippe Arnoux, Samir Acherar, Céline Frochot, Nadira Delhem
Journal: Journal of Controlled Release (2024)

Ovarian cancer (OC) is one of the most lethal cancers among women. Frequent recurrence in the peritoneum due to the presence of microscopic tumor residues justifies the development of new therapies. Indeed, our main objective is to develop a targeted photodynamic therapy (PDT) treatment of peritoneal carcinomatosis from OC to improve the life expectancy of cancer patients. Herein, we propose a targeted-PDT using a vectorized photosensitizer (PS) coupled with a newly folic acid analog (FAA), named PSFAA, in order to target folate receptor alpha (FRα) overexpressed on peritoneal metastasis. This PSFAA was the result of the coupling of pyropheophorbide-a (Pyro-a), as the PS, to a newly synthesized FAA via a polyethylene glycol (PEG) spacer. The selectivity and the PDT efficacy of PSFAA was evaluated on two human OC cell lines overexpressing FRα compared to fibrosarcoma cells underexpressing FRα. Final PSFAA, including the synthesis of a newly FAA and its conjugation to Pyro-a, was obtained after 10 synthesis steps, with an overall yield of 19%. Photophysical properties of PSFAA in EtOH were performed and showed similarity with those of free Pyro-a, such as the fluorescence and singlet oxygen quantum yields (Φf = 0.39 and ΦΔ = 0.53 for free Pyro-a, and Φf = 0.26 and ΦΔ = 0.41 for PSFAA). Any toxicity of PSFAA was noticed. After light illumination, a dose-dependent effect on PS concentration and light dose was shown. Furthermore, a PDT efficacy of PSFAA on OC cell secretome was detected inducing a decrease of a pro-inflammatory cytokine secretion (IL-6). This new PSFAA has shown promising biological properties highlighting the selectivity of the therapy opening new perspectives in the treatment of a cancer in a therapeutic impasse.
Multi‐omic integration reveals alterations in nasal mucosal biology that mediate air pollutant effects on allergic rhinitis
Authors: Haritz Irizar, Yoojin Chun, Hsiao‐Hsien Leon Hsu, Yan‐Chak Li, Lingdi Zhang, Zoe Arditi, Galina Grishina, Alexander Grishin, Alfin Vicencio, Gaurav Pandey, Supinda Bunyavanich
Journal: Allergy (2024)

Allergic rhinitis is a common inflammatory condition of the nasal mucosa that imposes a considerable health burden. Air pollution has been observed to increase the risk of developing allergic rhinitis. We addressed the hypotheses that early life exposure to air toxics is associated with developing allergic rhinitis, and that these effects are mediated by DNA methylation and gene expression in the nasal mucosa.
Comparing regularized Kelvinlet functions and the finite element method for registration of medical images to sparse organ data
Authors: Morgan J. Ringel, Jon S. Heiselman, Winona L. Richey, Ingrid M. Meszoely, William R. Jarnagin, Michael I. Miga
Journal: Medical Image Analysis (2024)

Image-guided surgery collocates patient-specific data with the physical environment to facilitate surgical decision making. Unfortunately, these guidance systems commonly become compromised by intraoperative soft-tissue deformations. Nonrigid image-to-physical registration methods have been proposed to compensate for deformations, but clinical utility requires compatibility of these techniques with data sparsity and temporal constraints in the operating room. While finite element models can be effective in sparse data scenarios, computation time remains a limitation to widespread deployment. This paper proposes a registration algorithm that uses regularized Kelvinlets, which are analytical solutions to linear elasticity in an infinite domain, to overcome these barriers. This algorithm is demonstrated and compared to finite element-based registration on two datasets: a phantom liver deformation dataset and an in vivo breast deformation dataset. The regularized Kelvinlets algorithm resulted in a significant reduction in computation time compared to the finite element method. Accuracy as evaluated by target registration error was comparable between methods. Average target registration errors were 4.6 ± 1.0 and 3.2 ± 0.8 mm on the liver dataset and 5.4 ± 1.4 and 6.4 ± 1.5 mm on the breast dataset for the regularized Kelvinlets and finite element method, respectively. Limitations of regularized Kelvinlets include the lack of organ-specific geometry and the assumptions of linear elasticity and infinitesimal strain. Despite limitations, this work demonstrates the generalizability of regularized Kelvinlets registration on two soft-tissue elastic organs. This method may improve and accelerate registration for image-guided surgery, and it shows the potential of using regularized Kelvinlets on medical imaging data.
The impact of gestational diabetes on functional capacity of the infant gut microbiome is modest and transient
Authors: Ryan V. Chieu, Katharine Hamilton, Paul M. Ryan, Julia Copeland, Pauline W. Wang, Ravi Retnakaran, David S. Guttman, John Parkinson, Jill K. Hamilton
Journal: Gut Microbes (2024)

Gestational diabetes mellitus (GDM) is a metabolic complication that manifests as hyperglycemia during the later stages of pregnancy. In high resource settings, careful management of GDM limits risk to the pregnancy, and hyperglycemia typically resolves after birth. At the same time, previous studies have revealed that the gut microbiome of infants born to mothers who experienced GDM exhibit reduced diversity and reduction in the abundance of several key taxa, including
The role of <i>Bifidobacterium</i> genus in modulating the neonate microbiota: implications for antibiotic resistance acquisition in early life
Authors: Anna Samarra, Raúl Cabrera-Rubio, Cecilia Martínez-Costa, Maria Carmen Collado
Journal: Gut Microbes (2024)

Resistance to antibiotics in newborns is a huge concern as their immune system is still developing, and infections and resistance acquisition in early life have short- and long-term consequences for their health.
Antireflux mucosectomy for gastroesophageal reflux disease: efficacy and the mechanism of action
Authors: Thijs Kuipers, Renske A.B. Oude Nijhuis, Roos E. Pouw, Albert J. Bredenoord
Journal: Endoscopy (2024)

Previous studies suggested that antireflux mucosectomy (ARMS) is effective in reducing reflux symptoms and total acid exposure, although the mechanism is unknown. Our objective was to investigate the effect of ARMS on reflux parameters and its mechanism of action.
Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group
Authors: M.F. Mosele, C.B. Westphalen, A. Stenzinger, F. Barlesi, A. Bayle, I. Bièche, J. Bonastre, E. Castro, R. Dienstmann, A. Krämer, A.M. Czarnecka, F. Meric-Bernstam, S. Michiels, R. Miller, N. Normanno, J. Reis-Filho, J. Remon, M. Robson, E. Rouleau, A. Scarpa, C. Serrano, J. Mateo, F. André
Journal: Annals of Oncology (2024)

Advancements in the field of precision medicine have prompted the European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update the recommendations for the use of tumour next-generation sequencing (NGS) for patients with advanced cancers in routine practice.
Coronary Atherosclerotic Plaque Activity and Risk of Myocardial Infarction
Authors: Kang-Ling Wang, Craig Balmforth, Mohammed N. Meah, Marwa Daghem, Alastair J. Moss, Evangelos Tzolos, Jacek Kwiecinski, Patrycja Molek-Dziadosz, Neil Craig, Anda Bularga, Philip D. Adamson, Dana K. Dawson, Parthiban Arumugam, Nikant K. Sabharwal, John P. Greenwood, Jonathan N. Townend, Patrick A. Calvert, James H.F. Rudd, Johan W. Verjans, Daniel S. Berman, Piotr J. Slomka, Damini Dey, Nicholas L. Mills, Edwin J.R. van Beek, Michelle C. Williams, Marc R. Dweck, David E. Newby
Journal: Journal of the American College of Cardiology (2024)
Reperfusion Injury in Patients With Acute Myocardial Infarction
Authors: Frederick G.P. Welt, Wayne Batchelor, J. Richard Spears, Claudia Penna, Pasquale Pagliaro, Borja Ibanez, Stavros G. Drakos, George Dangas, Navin K. Kapur
Journal: Journal of the American College of Cardiology (2024)
Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men
Authors: Yanxiao Gao, Yuewei Zhan, Yinghui Sun, Weiran Zheng, Weijie Zhang, Leiwen Fu, Zhihui Guo, Yi-Fan Lin, Yuwei Li, Lingling Zheng, Yiqiang Zhan, Zhiqiang Zhu, Junyi Duan, Guanghui Zhang, Tao Huang, Bin Su, Maohe Yu, Guohui Wu, Lin Ouyang, Jin Zhao, Guanghui Wang, Yepeng Zhou, Han-Zhu Qian, Thomas Fitzpatrick, Sten H. Vermund, Huachun Zou
Journal: Annals of Internal Medicine (2024)

Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this.
Extracorporeal Shock-Wave Lithotripsy and Endoscopy for the Treatment of Pain in Chronic Pancreatitis
Authors: Rupjyoti Talukdar, Søren S. Olesen, Misbah Unnisa, Akshay Bedarkar, Subhaleena Sarkar, Manu Tandan, Nitin Jagtap, Santosh Darisetty, Sekhramantri Kiran, Vinod Koppoju, Sundeep Lakhtakia, Mohan Ramchandani, Rakesh Kalapala, Rajesh Gupta, Vikesh K. Singh, Guduru Venkat Rao, Duvvur Nageshwar Reddy, Asbjørn M. Drewes
Journal: Annals of Internal Medicine (2024)

No randomized controlled trials have substantiated endoscopic decompression of the pancreatic duct in patients with painful chronic pancreatitis.
FAT1 as a tumor mutation burden specific gene affects the immunotherapy effect in head and neck squamous cancer
Authors: Haotian Cao, Tianjun Lan, Shijia Kuang, Liansheng Wang, Jintao Li, Qunxin Li, Yanyan Li, Qiuping Xu, Qian Chen, Shuwei Ren, Chunhong Lan, Nengtai Ouyang, Jianwei Liao, Yongsheng Huang, Jinsong Li
Journal: Drug Resistance Updates (2024)
Cerebrospinal fluid galactomannan detection for the diagnosis of central nervous system aspergillosis: a diagnostic test accuracy systematic review and meta-analysis
Authors: Adam S. Komorowski, Clayton W. Hall, Sukhreet Atwal, Rochelle Johnstone, Robert Walker, Dominik Mertz, Eva A. Piessens, Deborah Yamamura, Ekkehard M. Kasper
Journal: Clinical Microbiology and Infection (2024)
Targeting senescent cells to reshape the tumor microenvironment and improve anticancer efficacy
Authors: Birong Jiang, Wei Zhang, Xuguang Zhang, Yu Sun
Journal: Seminars in Cancer Biology (2024)

Cancer is daunting pathology with remarkable breadth and scope, spanning genetics, epigenetics, proteomics, metalobomics and cell biology. Cellular senescence represents a stress-induced and essentially irreversible cell fate associated with aging and various age-related diseases, including malignancies. Senescent cells are characterized of morphologic alterations and metabolic reprogramming, and develop a highly active secretome termed as the senescence-associated secretory phenotype (SASP). Since the first discovery, senescence has been understood as an important barrier to tumor progression, as its induction in pre-neoplastic cells limits carcinogenesis. Paradoxically, senescent cells arising in the tumor microenvironment (TME) contribute to tumor progression, including augmented therapeutic resistance. In this article, we define typical forms of senescent cells commonly observed within the TME and how senescent cells functionally remodel their surrounding niche, affect immune responses and promote cancer evolution. Furthermore, we highlight the recently emerging pipelines of senotherapies particularly senolytics, which can selectively deplete senescent cells from affected organs in vivo and impede tumor progression by restoring therapeutic responses and securing anticancer efficacies. Together, co-targeting cancer cells and their normal but senescent counterparts in the TME holds the potential to achieve increased therapeutic benefits and restrained disease relapse in future clinical oncology.