tbuckley/cabot-search huggingface dataset:
Trends in New Use of Disease‐Modifying Antirheumatic Drugs in Juvenile Idiopathic Arthritis Among Commercially Insured Children in the United States from 2001‐2022
Authors: Priyanka Yalamanchili, Lydia Y. Lee, Greta Bushnell, Melissa L. Mannion, Chintan V. Dave, Daniel B. Horton
Journal: Arthritis & Rheumatology (2024)

Objective To describe recent trends in DMARD use for children with juvenile idiopathic arthritis (JIA) in the US. Methods We used commercial claims data (2000‐2022) to perform a serial cross‐sectional utilization study of children ages 1‐18 diagnosed with JIA. Initiations of conventional synthetic (cs), biologic (b), or targeted synthetic (ts) DMARDs were identified after a ≥12‐month baseline and expressed as percentage of all new DMARD initiations per year, by category, class, and individual agent. Trends were evaluated using linear regression. Secondarily, we examined first b/tsDMARDs initiated after csDMARD monotherapy. Results We identified 20,258 new DMARD use episodes among 13,696 individuals (median age 14 years, 67.5% female). csDMARDs, while most commonly used overall, declined from 89.5% of new use episodes to 43.2% (2001‐2022, p&lt;0.001 for trend). In contrast, bDMARD use increased (10.5‐50.0%, p&lt;0.001). For tumor necrosis factor inhibitors (TNFi), etanercept peaked at 28.3% (2006) and declined to 4.2% (2022) (p=0.002). Meanwhile, adalimumab use doubled (7.0‐14.0%, 2007‐2008) after JIA approval, increasing further following a less painful formulation release (20.5%, 2022, p&lt;0.001). However, overall TNFi use has declined with increasing use of other b/tsDMARDs, particularly ustekinumab, secukinumab, and tofacitinib. By 2022, adalimumab was the most common b/tsDMARD initiated first after csDMARDs (77.8%). Conclusion Among commercially insured children with JIA in the US, new b/tsDMARD use is rising while new csDMARD use declines. For b/tsDMARDs, adalimumab is most used and the predominant b/tsDMARD initiated first after csDMARDs. Patterns in DMARD use for JIA have evolved relative to multiple factors, including regulatory approvals and tolerability.
Preventing postsurgical colorectal cancer relapse: A hemostatic hydrogel loaded with METTL3 inhibitor for CAR-NK cell therapy
Authors: Zilin Tan, Liangjie Tian, Yang Luo, Kexin Ai, Xuehua Zhang, Haitao Yuan, Jinfan Zhou, Guangyao Ye, Shuofei Yang, Ming Zhong, Gaohua Li, Yanan Wang
Journal: Bioactive Materials (2024)
Not just a “lifestyle disease”
Authors: Ian T Gilmore
Journal: BMJ (2008)

The growing problem of binge drinking among young women is one that must be dealt with at a societal level, says <b>Ian Gilmore</b>. Nevertheless, doctors can make a difference at an individual level, and <b>Brenda Reiss-Brennan and colleagues</b> (doi: 10.1136/bmj.39520.730370.94) describe one US quality improvement intervention in primary care
Robust anti-myeloma effect of TAS0612, an RSK/AKT/S6K inhibitor, with venetoclax regardless of cytogenetic abnormalities
Authors: Haruya Okamoto, Shinsuke Mizutani, Taku Tsukamoto, Yoko Katsuragawa-Taminishi, Yuka Kawaji-Kanayama, Kentaro Mizuhara, Ayako Muramatsu, Reiko Isa, Takahiro Fujino, Yuji Shimura, Koji Ichikawa, Junya Kuroda
Journal: Leukemia (2024)
METTL16 inhibits pancreatic cancer proliferation and metastasis by promoting MROH8 RNA stability and inhibiting CAPN2 expression
Authors: Tingzhuang Yi, Chunming Wang, Xia Ye, Jie Lin, Chen Lin, Fengzhen Qin, Wanlin Yang, Yulu Ye, Dengchong Ning, Jinyan Lan, Huafu Li, Chunying Luo, Jian Ma, Zhongheng Wei
Journal: International Journal of Surgery (2024)

Background: N6-methyladenosine (m6A) modification plays a crucial role in the progression of various cancers, including pancreatic cancer, by regulating gene expression. However, the specific mechanisms by which m6A affects pancreatic cancer metastasis remain unclear. This study aims to elucidate the role of METTL16, an m6A writer gene, in regulating core genes such as CAPN2 and MROH8, influencing tumor growth and metastasis. Materials and methods: Transcriptomic data from pancreatic cancer patients in The Cancer Genome Atlas (TCGA) were analyzed to identify m6A-related genes. We performed correlation and survival analyses to uncover core genes influenced by m6A expression. Functional assays, including METTL16 knockdown and overexpression experiments, were conducted in pancreatic cancer cell lines, patient-derived organoids, and animal models. Immunofluorescence, co-immunoprecipitation (Co-IP), and m6A-specific quantitative PCR were used to validate protein interactions and m6A modifications. Chromatin immunoprecipitation (ChIP) analysis was utilized to investigate transcription factor binding at gene promoter regions. Results: METTL16 and METTL3 were identified as key m6A regulators associated with improved prognosis in pancreatic cancer patients ( P &lt;0.05). CAPN2, CHMP2B, ITGA3, ITGA6, ITPR1, and RAC1 were identified as core genes linked to m6A expression, all significantly correlated with patient prognosis ( P &lt;0.05). METTL16 overexpression significantly inhibited tumor growth and metastasis ( P &lt;0.001) by downregulating CAPN2 through an indirect mechanism involving the transcription factor TBP and the gene MROH8. MROH8 negatively regulated CAPN2 by promoting TBP degradation, with METTL16 enhancing MROH8 mRNA stability through m6A modifications ( P &lt;0.01). Functional assays demonstrated that METTL16 and YTHDC2 (an m6A reader) collaboratively enhanced MROH8 mRNA stability, thereby inhibiting CAPN2 expression and reducing tumor proliferation and metastasis ( P &lt;0.001). Conclusion: This study reveals a novel regulatory axis involving METTL16, MROH8, and TBP that modulates CAPN2 expression, contributing to the suppression of pancreatic cancer progression. The METTL16-MROH8-TBP-CAPN2 pathway offers potential therapeutic targets for pancreatic cancer treatment, highlighting the significance of m6A modifications in tumor regulation. Further clinical validation is needed to confirm these findings in human patients.
Current trends in Site-Specific lymph node dissection for upper tract urothelial carcinoma: precise staging and survival
Authors: Yige Jia, Kan Wu, Xiang Li
Journal: International Journal of Surgery (2024)

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China Re: Birtle AJ, Jones R, Chester J, et al. Improved Disease-Free Survival With Adjuvant Chemotherapy After Nephroureterectomy for Upper Tract Urothelial Cancer: Final Results of the POUT Trial. J Clin Oncol. 2024;42(13):1466-1471. doi:10.1200/JCO.23.01659 Sponsorships or competing interests that may be relevant to content are disclosed at the end of this articles. Published online ■ ■ *Corresponding author. Address: Department of Urology, Institute of Urology, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041, China. Tel.: +028-85120376. E-mail: [email protected] (X. Li). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Indocyanine Green Fluorescence Angiography (ICG-FA) in the management of intestinal injuries following penetrating abdominal trauma: a case-control study comparing postoperative outcomes
Authors: Mohamed Q. Patel, Jens TF Osterkamp, Johan JP Buitendag, Timothy R. Forgan, Elmin Steyn
Journal: International Journal of Surgery (2024)

The surgical management of penetrating hollow visceral injuries includes primary repair or exteriorization. Tissue perfusion at the site of gastrointestinal suture repair may be challenging to assess and is vulnerable to local energy transfer-related injury, micro- or macro-circulatory insufficiency, or splanchnic vasoconstriction for various reasons. Breakdown of suture lines can lead to potentially life-threatening complications. The intraoperative use of Indocyanine Green Fluorescence Angiography (ICG-FA) may reduce the risk of postoperative morbidity and mortality by ensuring optimal tissue perfusion at the chosen site of suture repair.
Iron and siRNA co-encapsulated ferritin nanocages induce ferroptosis synergistically for cancer therapy
Authors: Danni Liu, Yaoqi Wang, Qi Sun, Dong Mei, Xiaoling Wang, Yan Su, Jie Zhang, Ran Huo, Yang Tian, Siyu Liu, Shuang Zhang, Chunying Cui
Journal: Acta Pharmaceutica Sinica B (2024)

Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.
Amplifying Glioblastoma Immunotherapy: T Cell Shielding through Nitric Oxide/Reactive Oxygen Species Scavenging Nanoparticles Potentiates anti-PD-1
Authors: Jihye Lee, Yeoul Kang, Hyori Lee, Gurusamy Saravanakumar, Soon A Park, Stephen Ahn, Won Jong Kim
Journal: Biomaterials (2024)
Outcomes of Down-Titration in Patients with Severe Scalp Alopecia Areata Initially Treated with Baricitinib 4-mg: Week 152 data from BRAVE-AA2
Authors: Brett King, Manabu Ohyama, Maryanne Senna, Jerry Shapiro, Yves Dutronc, Frederick Durand, Chunyuan Liu, Guanglei Yu, Jill Kolodsick, Chiara Chiasserini, Najwa Somani, Bianca Maria Piraccini
Journal: Journal of the American Academy of Dermatology (2024)
Long‐term outcome of 2‐year survivors after allogeneic hematopoietic cell transplantation for acute leukemia
Authors: Marion Larue, Myriam Labopin, Thomas Schroeder, Xiao‐jun Huang, Igor W. Blau, Johannes Schetelig, Arnold Ganser, Rose‐Marie Hamladji, Wolfgang Bethge, Nicolaus Kröger, Gerard Socié, Urpu Salmenniemi, Henrik Sengeloev, Bhagirathbhai Dholaria, Bipin N. Savani, Arnon Nagler, Fabio Ciceri, Mohamad Mohty
Journal: HemaSphere (2024)

Abstract Information on late complications in patients with acute leukemia who have undergone allogeneic hematopoietic cell transplantation (HCT) is limited. We performed a left‐truncated analysis of long‐term survival in patients with acute leukemia who were alive and disease‐free 2 years after HCT. We included 2701 patients with acute lymphoblastic leukemia (ALL) and 9027 patients with acute myeloid leukemia (AML) who underwent HCT between 2005 and 2012. The 10‐year overall survival (OS) rate was 81.3% for ALL and 76.2% for AML, with the main causes of late mortality being relapse (ALL‐33.9%, AML‐44.9%) and chronic graft‐versus‐host disease (ALL‐29%, AML‐18%). At 10 years, HCT‐related mortality was 16.8% and 20.4%, respectively. Older age and unrelated donor transplantation were associated with a worse prognosis for both types of leukemia. In addition, transplantation in the second or third complete remission and peripheral blood HSC for ALL are associated with worse outcomes. Similarly, adverse cytogenetics, female donor to male patient combination, and reduced intensity conditioning in AML contribute to poor prognosis. We conclude that 2‐year survival in remission after HCT for acute leukemia is encouraging, with OS of nearly 80% at 10 years. However, the long‐term mortality risk of HCT survivors remains significantly higher than that of the age‐matched general population. These findings underscore the importance of tailoring transplantation strategies to improve long‐term outcomes in patients with acute leukemia undergoing HCT.
In Vitro Sonodynamic Therapy Using a High Throughput 3D Glioblastoma Spheroid Model with 5‐ALA and TMZ Sonosensitizers
Authors: Priyankan Datta, Nan Sook Lee, Sreejesh Moolayadukkam, Rakesh P. Sahu, Xi Yu, Tianze Guo, Qifa Zhou, Y. Wang, Ishwar K. Puri
Journal: Advanced Healthcare Materials (2024)

Abstract Sonodynamic therapy (SDT) administered using low‐intensity pulsed ultrasound and sonosensitizers is an emerging, minimally invasive, targeted deep‐tissue therapy for solid tumors such as glioblastoma multiforme (GBM). Initial clinical trials show promising outcomes for SDT treatments of GBM. A crucial aspect of SDT is the sonosensitizer that interacts with ultrasound, facilitating energy transfer to the tumor, thus inducing therapeutic efficacy. Current in vitro methods for determining the therapeutic efficacies of sonosensitizers are time‐consuming and expensive. A novel high‐throughput magnetically printed 3D GBM model is used to overcome this challenge. The hypothesis is that the use of two sonosensitizers, one a chemotherapeutic drug, enhances SDT efficacy through their additive chemical interactions. The GBM model is used to evaluate the effectiveness of two sonosensitizer molecules, 5‐aminolevulinic acid (5‐ALA) and theU.S. Food and Drug Administration (FDA)‐approved chemotherapeutic drug Temozolomide (TMZ). It is confirmed that implement high‐throughput GBM models to evaluate sonosensitizer combinations and their efficacies is feasible and, for the first time, show that the combined effect of both sensitizers, 5‐ALA and TMZ, is superior for preventing spheroid growth than employing each molecule separately. This finding is relevant for future clinical trials of GBM treatment with SDT.
Artificial Internalizing Receptors: Intracellular Delivery of Cargo Through Bio‐Orthogonal Recognition
Authors: Ane Bretschneider Søgaard, Rikke Fabech Hansson, Anne Selch Tvilum, Alexander N. Zelikin
Journal: Advanced Healthcare Materials (2024)

Abstract Drug targeting is a methodology that helps to overcome the side effects of therapeutic molecules. However, insufficient targeting specificity and the on‐target/off‐site delivery leave much room for improvement in the targeting endeavors. One approach to enhance the specificity of drug targeting is to engineer artificial receptors with recognition ligands not observed in nature. To this end, artificial internalizing receptors that feature cholesterylamine as the artificial pull‐in mechanism, and an anti‐fluorescein antibody as the exofacial recognition and capture tool are developed. Fluorescein labeling is among the most routine techniques in biochemistry and can readily provide a way to make cognate derivatives for receptor‐mediated endocytosis using these artificial receptors. Herein, the synthesis and the structure‐activity relationship for these artificial receptors are detailed, their potency and efficacy in mediating drug delivery for the antibody‐drug conjugates are illustrated, and the scope and limitations of targeting the chemically engineered cells via artificial receptors are investigated. Taken together, the presented data explore an innovative approach to drug targeting and contribute to the development of techniques in cell engineering using the tools of chemistry.
Evaluating Biparametric Versus Multiparametric Magnetic Resonance Imaging for Diagnosing Clinically Significant Prostate Cancer: An International, Paired, Noninferiority, Confirmatory Observer Study
Authors: Jasper J Twilt, Anindo Saha, Joeran S Bosma, Bram van Ginneken, Anders Bjartell, Anwar R Padhani, David Bonekamp, Geert Villeirs, Georg Salomon, Gianluca Giannarini, Jayashree Kalpathy-Cramer, Jelle Barentsz, Klaus H Maier-Hein, Mirabela Rusu, Olivier Rouvière, Roderick van den Bergh, Valeria Panebianco, Veeru Kasivisvanathan, Nancy A Obuchowski, Derya Yakar, Mattijs Elschot, Jeroen Veltman, Jurgen J Fütterer, Henkjan Huisman, Maarten de Rooij
Journal: European Urology (2024)
International expert guidance for defining and monitoring small bowel strictures in Crohn's disease on intestinal ultrasound: a consensus statement
Authors: Cathy Lu, Ryan Rosentreter, Claire E Parker, Julie Remillard, Stephanie R Wilson, Mark E Baker, Gauraang Bhatnagar, Jakob Begun, David H Bruining, Robert V Bryant, Britt Christensen, Brian G Feagan, Joel G Fletcher, Ilyssa Gordon, Gaylyn Henderson, Vipul Jairath, John Knudsen, Torsten Kucharzik, Kyle Lesack, Christian Maaser, Giovanni Maconi, Kerri Novak, Jordi Rimola, Stuart A Taylor, Rune Wilkens, Florian Rieder
Journal: The Lancet. Gastroenterology & hepatology (2024)
An objective comparison of methods for augmented reality in laparoscopic liver resection by preoperative-to-intraoperative image fusion from the MICCAI2022 challenge
Authors: Sharib Ali, Yamid Espinel, Yueming Jin, Peng Liu, Bianca Güttner, Xukun Zhang, Lihua Zhang, Tom Dowrick, Matthew J Clarkson, Shiting Xiao, Yifan Wu, Yijun Yang, Lei Zhu, Dai Sun, Lan Li, Micha Pfeiffer, Shahid Farid, Lena Maier-Hein, Emmanuel Buc, Adrien Bartoli
Journal: Medical Image Analysis (2024)
Molybdenum nanodots act as antioxidants for photothermal therapy osteoarthritis
Authors: Guang Shi, Shenghui Lan, Qi Zhang, Junwu Wang, Feihong Shu, Zhuowen Hao, Tianhong Chen, Mengyue Zhu, Renxin Chen, Jiayao Chen, Zijian Wu, Bo Wu, Zhenwei Zou, Jingfeng Li
Journal: Biomaterials (2024)
Omnidirectional improvement of mitochondrial health in Alzheimer's disease by multi-targeting engineered activated neutrophil exosomes
Authors: Lei Zhang, Jiaquan Lin, Kai Xiang, Tianshu Shi, Baosheng Guo
Journal: Journal of Controlled Release (2024)

Alzheimer's disease (AD) is one kind of devasting neurodegenerative disorders affecting over 50 million people worldwide. Multi-targeted therapy has emerged as a new treatment for diagnosing and alleviating the pathogenesis process of AD; however, the current strategy is limited by its unsatisfactory efficiency. In our study, engineered activated neutrophil-derived exosomes (MP@Cur-MExo) were developed to improve the mitochondrial function in neurons by targeting and alleviating Aβ-induced neurotoxicity. MP@Cur-MExo are exosomes derived from IL-8-stimulated neutrophils decorated with mitochondria targeting ligand and Aβ targeted ligand modified SPION. Engineered exosomes can be cleaved by matrix metallopeptidase-2, which is overexpressed in the AD brain. Consequently, the released SPION and Curcumin-loaded engineered exosomes collaboratively protected neuron cells against Aβ-induced mitochondrial deficiency. In addition, MP@Cur-MExo effectively accumulated in the inflamed region of AD brain at an early stage, allowing early diagnosis of AD through bimodal (MRI/IVIS) imaging. Importantly, in a mouse model at an early stage of AD, intravenously injected MP@Cur-MExo restored mitochondrial function and reduced Aβ-induced mitochondrial damage, thereby attenuating AD progression. In conclusion, our designed engineered exosomes demonstrated that omnidirectional improvement of mitochondrial function can serve as a novel and practical approach for the diagnosis and treatment of neurodegenerative diseases. This study also reveals a promising therapeutic agent for impeding AD progression for future clinical applications.
Deep learning improves test–retest reproducibility of regional strain in echocardiography
Authors: John Nyberg, Andreas Østvik, Ivar M Salte, Sindre Olaisen, Sigve Karlsen, Thomas Dahlslett, Erik Smistad, Torfinn Eriksen-Volnes, Harald Brunvand, Thor Edvardsen, Kristina H Haugaa, Lasse Lovstakken, Havard Dalen, Bjørnar Grenne
Journal:  (2024)

Abstract Aims The clinical utility of regional strain measurements in echocardiography is challenged by suboptimal reproducibility. In this study, we aimed to evaluate the test–retest reproducibility of regional longitudinal strain (RLS) per coronary artery perfusion territory (RLSTerritory) and basal-to-apical level of the left ventricle (RLSLevel), measured by a novel fully automated deep learning (DL) method based on point tracking. Methods and results We measured strain in a dual-centre test–retest data set that included 40 controls and 40 patients with suspected non-ST elevation acute coronary syndrome. Two consecutive echocardiograms per subject were recorded by different operators. The reproducibility of RLSTerritory and RLSLevel measured by the DL method and by three experienced observers using semi-automatic software (2D Strain, EchoPAC, GE HealthCare) was evaluated as minimal detectable change (MDC). The DL method had MDC for RLSTerritory and RLSLevel ranging from 3.6 to 4.3%, corresponding to a 33–35% improved reproducibility compared with the inter- and intraobserver scenarios (MDC 5.5–6.4% and 4.9–5.4%). Furthermore, the DL method had a lower variance of test–retest differences for both RLSTerritory and RLSLevel compared with inter- and intraobserver scenarios (all P &amp;lt; 0.001). Bland–Altman analyses demonstrated superior reproducibility by the DL method for the whole range of strain values compared with the best observer scenarios. The feasibility of the DL method was 93% and measurement time was only 1 s per echocardiogram. Conclusion The novel DL method provided fully automated measurements of RLS, with improved test–retest reproducibility compared with semi-automatic measurements by experienced observers. RLS measured by the DL method has the potential to advance patient care through a more detailed, more efficient, and less user-dependent clinical assessment of myocardial function.