tbuckley/cabot-search huggingface dataset:
Continuous iontronic chemotherapy reduces brain tumor growth in embryonic avian in vivo models
Authors: Verena Handl, Linda Waldherr, Theresia Arbring Sjöström, Tobias Abrahamsson, Maria Seitanidou, Sabine Erschen, Astrid Gorischek, Iwona Bernacka-Wojcik, Helena Saarela, Tamara Tomin, Sophie Elisabeth Honeder, Joachim Distl, Waltraud Huber, Martin Asslaber, Ruth Birner-Grünberger, Ute Schäfer, Magnus Berggren, Rainer Schindl, Silke Patz, Daniel T. Simon, Nassim Ghaffari-Tabrizi-Wizsy
Journal: Journal of Controlled Release (2024)

Local and long-lasting administration of potent chemotherapeutics is a promising therapeutic intervention to increase the efficiency of chemotherapy of hard-to-treat tumors such as the most lethal brain tumors, glioblastomas (GBM). However, despite high toxicity for GBM cells, potent chemotherapeutics such as gemcitabine (Gem) cannot be widely implemented as they do not efficiently cross the blood brain barrier (BBB). As an alternative method for continuous administration of Gem, we here operate freestanding iontronic pumps – "GemIPs" – equipped with a custom-synthesized ion exchange membrane (IEM) to treat a GBM tumor in an avian embryonic in vivo system. We compare GemIP treatment effects with a topical metronomic treatment and observe that a remarkable growth inhibition was only achieved with steady dosing via GemIPs. Daily topical drug administration (at the maximum dosage that was not lethal for the embryonic host organism) did not decrease tumor sizes, while both treatment regimes caused S-phase cell cycle arrest and apoptosis. We hypothesize that the pharmacodynamic effects generate different intratumoral drug concentration profiles for each technique, which causes this difference in outcome. We created a digital model of the experiment, which proposes a fast decay in the local drug concentration for the topical daily treatment, but a long-lasting high local concentration of Gem close to the tumor area with GemIPs. Continuous chemotherapy with iontronic devices opens new possibilities in cancer treatment: the long-lasting and highly local dosing of clinically available, potent chemotherapeutics to greatly enhance treatment efficiency without systemic side-effects. Iontronic pumps (GemIPs) provide continuous and localized administration of the chemotherapeutic gemcitabine (Gem) for treating glioblastoma in vivo. By generating high and constant drug concentrations near the vascularized growing tumor, GemIPs offer an efficient and less harmful alternative to systemic administration. Continuous GemIP dosing resulted in remarkable growth inhibition, superior to daily topical Gem application at higher doses. Our digital modelling shows the advantages of iontronic chemotherapy in overcoming limitations of burst release and transient concentration profiles, and providing precise control over dosing profiles and local distribution. This technology holds promise for future implants, could revolutionize treatment strategies, and offers a new platform for studying the influence of timing and dosing dependencies of already-established drugs in the fight against hard-to-treat tumors.
Comparative efficacy of carfilzomib, lenalidomide, and dexamethasone (<scp>KRd</scp>) versus bortezomib, lenalidomide, and dexamethasone (<scp>VRd</scp>) in newly‐diagnosed multiple myeloma: A systematic review and meta‐analysis
Authors: Bruno Almeida Costa, Thomaz Alexandre Costa, Kevin Pak, Aesha Patel, Nicole Felix, Tarek H. Mouhieddine, Joshua Richter
Journal: American Journal of Hematology (2024)

In view of the increasing data evaluating carfilzomib-based induction for newly-diagnosed multiple myeloma (NDMM), we conducted a systematic review and meta-analysis comparing the efficacy of carfilzomib/lenalidomide/dexamethasone (KRd) versus bortezomib/lenalidomide/dexamethasone (VRd). Three studies totaling 1597 patients (50% KRd-treated, 50% VRd-treated) were included. Despite similar survival outcomes and overall response rate compared with the VRd arm, KRd-treated subjects showed higher odds of achieving complete responses and measurable residual disease negativity. Among patients with high-risk cytogenetics (n = 348), KRd was associated with significant improvement in progression-free survival (HR = 0.70; 95% CI = 0.50-0.97; p = .03; I
Mechanosensitive protein polycystin-1 promotes periosteal stem/progenitor cells osteochondral differentiation in fracture healing
Authors: Ran Liu, Yu-Rui Jiao, Mei Huang, Nan-Yu Zou, Chen He, Min Huang, Kai-Xuan Chen, Wen-Zhen He, Ling Liu, Yu-Chen Sun, Zhu-Ying Xia, L Darryl Quarles, Hai-Lin Yang, Wei-Shan Wang, Zhou-Sheng Xiao, Xiang-Hang Luo, Chang-Jun Li
Journal: Theranostics (2024)

Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive.
Exploring the role of combined external beam radiotherapy and targeted radioligand therapy with [<sup>177</sup>Lu]Lu-PSMA-617 for prostate cancer - from bench to bedside
Authors: Daria Arbuznikova, Aikaterini Klotsotyra, Lisa Uhlmann, Lisa-Charlotte Domogalla, Nils Steinacker, Michael Mix, Gabriele Niedermann, Simon K B Spohn, Martin T Freitag, Anca L Grosu, Philipp T Meyer, Christian Gratzke, Matthias Eder, Constantinos Zamboglou, Ann-Christin Eder
Journal: Theranostics (2024)

Management of prostate cancer (PC) might be improved by combining external beam radiotherapy (EBRT) and prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with lutetium-177 (
IL4 receptor targeting enables nab-paclitaxel to enhance reprogramming of M2-type macrophages into M1-like phenotype via ROS-HMGB1-TLR4 axis and inhibition of tumor growth and metastasis
Authors: Sri Murugan Poongkavithai Vadevoo, Yeoul Kang, Gowri Rangaswamy Gunassekaran, Seok-Min Lee, Min-Sung Park, Dong Gyun Jo, Sang-Kyun Kim, Ho Lee, Won Jong Kim, Byungheon Lee
Journal: Theranostics (2024)

Nab-paclitaxel (Abx) is widely employed in malignant tumor therapy. In tumor cells and pro-tumoral M2-type macrophages, the IL4 receptor (IL4R) is upregulated. This study aimed to elucidate the selective delivery of Abx to M2-type macrophages by targeting IL4R and reprogramming them into an anti-tumoral M1-type.
Basic processes and clinical applications of mental imagery in worry: A systematic review
Authors: Lauren Stavropoulos, David D.J. Cooper, Sophie M. Champion, Luke Keevers, Jill M. Newby, Jessica R. Grisham
Journal: Clinical Psychology Review (2024)

In this systematic review, we aimed to synthesise existing research on the phenomenology of mental imagery among high worriers compared to healthy individuals, and to characterise the nature and effectiveness of existing imagery-related interventions in treatment of worry.
The evolving posology and administration of immune checkpoint inhibitors: subcutaneous formulations
Authors: Matthew J. Hadfield, David J. Benjamin, Jonathan Krell, Jeremy Warner, Mark P. Lythgoe
Journal: Trends in cancer (2024)

Immune checkpoint inhibitors (ICIs) have transformed cancer care. Recently, atezolizumab gained its first global approval in a subcutaneous (SC) formulation by the UK medicines regulator, being notable as the first time an FDA- and/or European Medicines Agency (EMA)-approved ICI has been licensed via this administration route. Here, we discuss this approval, other SC ICIs in development, and the benefits and challenges of this administration route, including potential implications for patient care.
Correction: Rescue technique after endoscopic ultrasound-guided hepaticogastrostomy stent dislocation
Authors: Takeshi Ogura, Taro Iwatsubo, Atsushi Okuda, Saori Ueno, Hiroki Nishikawa
Journal: Endoscopy (2023)

Correction to: Rescue technique after endoscopic ultrasound-guided hepaticogastrostomy stent dislocationEndoscopy 2023; 55(S 01): E1236-E1237DOI: 10.1055/a-2213-1149
Re: Bertrand Tombal, Sean Collins, Alicia K. Morgans, et al. Impact of Relugolix Versus Leuprolide on the Quality of Life of Men with Advanced Prostate Cancer: Results from the Phase 3 HERO Study. Eur Urol 2023;84:579–87
Authors: Hannah L. Rush, Duncan C. Gilbert, Ruth E. Langley
Journal: European Urology (2024)
Endoscopic ultrasound-guided pancreatic duct drainage with a two-step puncture technique for a non-dilated pancreatic duct
Authors: Shunsuke Horitani, Masaaki Shimatani, Masataka Kano, Toshiyuki Mitsuyama, Tsukasa Ikeura, Shuntaro Mukai, Takao Itoi
Journal: Endoscopy (2024)

Endoscopic ultrasound-guided pancreatic duct drainage (EUS-PD) has emerged as an option in patients with failure of standard transpapillary endoscopic retrograde access to the pancreatic duct (PD) or surgically altered anatomy [1]. The ductal pressure of a non-dilated PD is often low and the duct can be easily compressed by the tip of the needle, thus requiring a technical tip to handle this situation [2]. We describe successful EUS-PD with a two-step puncture technique for a non-dilated PD after pancreaticoduodenectomy as a result of solid pseudopapillary neoplasm ([Video 1]).
FUME-TCRseq Enables Sensitive and Accurate Sequencing of the T-cell Receptor from Limited Input of Degraded RNA
Authors: Ann-Marie Baker, Gayathri Nageswaran, Pablo Nenclares, Tahel Ronel, Kane Smith, Christopher Kimberley, Miangela M. Laclé, Shreerang Bhide, Kevin J. Harrington, Alan Melcher, Manuel Rodriguez-Justo, Benny Chain, Trevor A. Graham
Journal: Cancer Research (2024)

Abstract Genomic analysis of the T-cell receptor (TCR) reveals the strength, breadth, and clonal dynamics of the adaptive immune response to pathogens or cancer. The diversity of the TCR repertoire, however, means that sequencing is technically challenging, particularly for samples with low-quality, degraded nucleic acids. Here, we developed and validated FUME-TCRseq, a robust and sensitive RNA-based TCR sequencing methodology that is suitable for formalin-fixed paraffin-embedded samples and low amounts of input material. FUME-TCRseq incorporates unique molecular identifiers into each molecule of cDNA, allowing correction for sequencing errors and PCR bias. Using RNA extracted from colorectal and head and neck cancers to benchmark the accuracy and sensitivity of FUME-TCRseq against existing methods demonstrated excellent concordance between the datasets. Furthermore, FUME-TCRseq detected more clonotypes than a commercial RNA-based alternative, with shorter library preparation time and significantly lower cost. The high sensitivity and the ability to sequence RNA of poor quality and limited amount enabled quantitative analysis of small numbers of cells from archival tissue sections, which is not possible with other methods. Spatially resolved FUME-TCRseq analysis of colorectal cancers using macrodissected archival samples revealed the shifting T-cell landscapes at the transition to an invasive phenotype and between tumor subclones containing distinct driver alterations. In summary, FUME-TCRseq represents an accurate, sensitive, and low-cost tool for the characterization of T-cell repertoires, particularly in samples with low-quality RNA that have not been accessible using existing methodology. Significance: FUME-TCRseq is a TCR sequencing methodology that supports sensitive and spatially resolved detection of TCR clones in archival clinical specimens, which can facilitate longitudinal tracking of immune responses through disease course and treatment.
Factors Associated With Racial and Ethnic Disparities in Locally Advanced Rectal Cancer Outcomes
Authors: Rebecca M. Shulman, Mengying Deng, Elizabeth A. Handorf, Joshua E. Meyer, Shannon M. Lynch, Sanjeevani Arora
Journal: JAMA Network Open (2024)

Importance Hispanic and non-Hispanic Black patients receiving neoadjuvant therapy and surgery for locally advanced rectal cancer (LARC) achieve less favorable clinical outcomes than non-Hispanic White patients, but the source of this disparity is incompletely understood. Objective To assess whether racial and ethnic disparities in treatment outcomes among patients with LARC could be accounted for by social determinants of health and demographic, clinical, and pathologic factors known to be associated with treatment response. Design, Setting, and Participants The National Cancer Database was interrogated to identify patients with T3 to T4 or N1 to N2 LARC treated with neoadjuvant therapy and surgery. Patients were diagnosed between January 1, 2004, and December 31, 2017. Data were culled from the National Cancer Database from July 1, 2022, through December 31, 2023. Exposure Neoadjuvant therapy for rectal cancer followed by surgical resection. Main Outcomes and Measures The primary outcome was the rate of pathologic complete response (pCR) following neoadjuvant therapy. Secondary outcomes were rate of tumor downstaging and achievement of pN0 status. Results A total of 34 500 patient records were reviewed; 21 679 of the patients (62.8%) were men and 12 821 (37.2%) were women. The mean (SD) age at diagnosis was 59.7 (12.0) years. In terms of race and ethnicity, 2217 patients (6.4%) were Hispanic, 2843 (8.2%) were non-Hispanic Black, and 29 440 (85.3%) were non-Hispanic White. Hispanic patients achieved tumor downstaging (48.9% vs 51.8%; P = .01) and pN0 status (66.8% vs 68.8%; P = .02) less often than non-Hispanic White patients. Non-Hispanic Black race, but not Hispanic ethnicity, was associated with less tumor downstaging (odds ratio [OR], 0.86 [95% CI, 0.78-0.94]), less frequent pN0 status (OR, 0.91 [95% CI, 0.83-0.99]), and less frequent pCR (OR, 0.81 [95% CI, 0.72-0.92]). Other factors associated with reduced rate of pCR included rural location (OR, 0.80 [95% CI, 0.69-0.93]), lack of or inadequate insurance (OR for Medicaid, 0.86 [95% CI, 0.76-0.98]; OR for no insurance, 0.65 [95% CI, 0.54-0.78]), and treatment in a low-volume center (OR for first quartile, 0.73 [95% CI, 0.62-0.87]; OR for second quartile, 0.79 [95% CI, 0.70-0.90]; OR for third quartile, 0.86 [95% CI, 0.78-0.94]). Clinical and pathologic variables associated with a decreased pCR included higher tumor grade (OR, 0.58 [95% CI, 0.49-0.70]), advanced tumor stage (OR for T3, 0.56 [95% CI, 0.42-0.76]; OR for T4, 0.30 [95% CI, 0.22-0.42]), and lymph node–positive disease (OR for N1, 0.83 [95% CI, 0.77-0.89]; OR for N2, 0.73 [95% CI, 0.65-0.82]). Conclusions and Relevance The findings of this cohort study suggest that disparate treatment outcomes for Hispanic and non-Hispanic Black patients are likely multifactorial in origin. Future investigation into additional social determinants of health and biological variables is warranted.
Electronic Patient-Reported Outcome–Based Symptom Management Versus Usual Care After Lung Cancer Surgery: Long-Term Results of a Multicenter, Randomized, Controlled Trial
Authors: Wei Dai, Yaqin Wang, Jia Liao, Xing Wei, Zhen Dai, Wei Xu, Yangjun Liu, Xin Shelley Wang, Cecilia Pompili, Hongfan Yu, Yang Pu, Yuqian Zhao, Bangrong Cao, Qifeng Wang, Wenhong Feng, Yuanqiang Zhang, Fang Liu, Yuanle Deng, Jin Zhou, Juan Li, Shaohua Xie, Run Xiang, Xiang Wang, Bo Tian, Xiaozun Yang, Bin Hu, Xiaoqin Liu, Tianpeng Xie, Xiaojun Yang, Xiang Zhuang, Guibin Qiao, Qiang Li, Qiuling Shi
Journal: Journal of Clinical Oncology (2024)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We previously reported superior symptom control of electronic patient-reported outcome (ePRO)–based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where patients were assigned 1:1 to receive postoperative ePRO-based symptom management or usual care daily postsurgery, twice weekly postdischarge until 1 month, and at 3, 6, 9, and 12 months postdischarge. Long-term patient-reported outcomes were assessed with MD Anderson Symptom Inventory-Lung Cancer module. Per-protocol analyses were performed with 55 patients in the ePRO group and 57 in the usual care group. At 12 months postdischarge, the ePRO group reported significantly fewer symptom threshold events (any of the five target symptom scored ≥4; median [IQR], 0 [0-0] v 0 [0-1]; P = .040) than the usual care group. From 1 to 12 months postdischarge, the ePRO group consistently reported significantly lower composite scores for physical interference (estimate, –0.86 [95% CI, –1.32 to –0.39]) and affective interference (estimate, –0.70 [95% CI, –1.14 to –0.26]). Early intensive ePRO-based symptom management after lung cancer surgery reduced symptom burden and improved functional status for up to 1 year postdischarge, supporting its integration into standard care.
Transpapillary biliary drainage using a forward-viewing endoscope for distal malignant biliary obstruction after placement of a duodenal stent for type I duodenal stenosis
Authors: Yuichi Hirata, Takahiro Oribe, Kosuke Sugihara, Mizuka Yonezawa, Daisuke Orita, Yoshihiro Okabe
Journal: Endoscopy (2024)

Transpapillary biliary drainage using a side-viewing duodenoscope is widely performed for patients with obstructive jaundice. In patients with pancreaticobiliary cancer, both distal malignant biliary obstruction (MBO) and duodenal stenosis may be complicated ([Fig. 1]) [1], and it is often difficult to insert the duodenoscope in patients with duodenal stenosis on the oral side of the major papilla, especially. Endoscopic ultrasound-guided biliary drainage and percutaneous transhepatic biliary drainage are useful as alternative procedures; however, the presence of ascites or collateral flow makes it impossible to perform these procedures. We report a case of transpapillary biliary drainage for MBO using a forward-viewing endoscope after placement of a duodenal stent for type I duodenal stenosis.
Novel technique of additional anchor plastic stent placement during endoscopic ultrasound-guided gallbladder drainage
Authors: Toji Murabayashi, Ryutaro Matsushima, Shinya Sugimoto
Journal: Endoscopy (2024)

A fully covered self-expanding metal stent (FCSEMS) is frequently used for endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) in some countries where the use of lumen-apposing metal stent for EUS-GBD is not approved [1] [2]. Coaxial placement of a double-pigtail plastic stent (DPPS) as an anchor within the FCSEMS for EUS-GBD is preferred to prevent food impaction, delayed bleeding, and stent migration [2] [3]. However, placing the additional stent through the distal end of the FCSEMS can be challenging and risky, as the pushing force of the DPPS may be transmitted to an inappropriate axis on the bent portion of the long FCSEMS ([Fig. 1] a). We developed a novel technique to overcome these technical difficulties ([Fig. 1] b).
Author Correction: Efferocytosis reprograms the tumor microenvironment to promote pancreatic cancer liver metastasis
Authors: Yuliana Astuti, Meirion Raymant, Valeria Quaranta, Kim Clarke, Maidinaimu Abudula, Olivia Smith, Gaia Bellomo, Vatshala Chandran-Gorner, Craig Nourse, Christopher Halloran, Paula Ghaneh, Daniel Palmer, Robert P. Jones, Fiona Campbell, Jeffrey W. Pollard, Jennifer P. Morton, Ainhoa Mielgo, Michael C. Schmid
Journal: Nature Cancer (2024)
Investigation of the Dysfunction Caused by High Glucose, Advanced Glycation End Products, and Interleukin‐1 Beta and the Effects of Therapeutic Agents on the Microphysiological Artery Model
Authors: Ungsig Nam, Jaesang Kim, Hee‐gyeong Yi, Jessie S. Jeon
Journal: Advanced Healthcare Materials (2024)

Diabetes mellitus (DM) has substantial global implications and contributes to vascular inflammation and the onset of atherosclerotic cardiovascular diseases. However, translating the findings from animal models to humans has inherent limitations, necessitating a novel platform. Therefore, herein, an arterial model is established using a microphysiological system. This model successfully replicates the stratified characteristics of human arteries by integrating collagen, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs). Perfusion via a peristaltic pump shows dynamic characteristics distinct from those of static culture models. High glucose, advanced glycation end products (AGEs), and interleukin-1 beta are employed to stimulate diabetic conditions, resulting in notable cellular changes and different levels of cytokines and nitric oxide. Additionally, the interactions between the disease models and oxidized low-density lipoproteins (LDL) are examined. Finally, the potential therapeutic effects of metformin, atorvastatin, and diphenyleneiodonium are investigated. Metformin and diphenyleneiodonium mitigate high-glucose- and AGE-associated pathological changes, whereas atorvastatin affects only the morphology of ECs. Altogether, the arterial model represents a pivotal advancement, offering a robust and insightful platform for investigating cardiovascular diseases and their corresponding drug development.
A novel peptide-drug conjugate for glioma-targeted drug delivery
Authors: Jianfen Zhou, Nana Meng, Linwei Lu, Jiasheng Lu, Sunyi Wu, Yuan Ding, Shuai Wu, Yanning Bao, Qianzhu Xu, Ruohan Chen, Jun Wang, Cao Xie, Jinsong Wu, Weiyue Lu
Journal: Journal of Controlled Release (2024)
The Role of Reactive Oxygen Species in Alzheimer's Disease:from Mechanism to Biomaterials Therapy
Authors: Zhuohang Yu, Feng Luo
Journal: Advanced Healthcare Materials (2024)

Alzheimer's disease (AD) is a chronic, insidious, and progressive neurodegenerative disease that remains a clinical challenge for society. The fully approved drug lecanemab exhibits the prospect of therapy against the pathological processes, while debatable adverse events conflict with the drug concentration required for the anticipated therapeutic effects. Reactive oxygen species (ROS) are involved in the pathological progression of AD, as has been demonstrated in much research regarding oxidative stress (OS). The contradiction between anticipated dosage and adverse event may be resolved through targeted transport by biomaterials and get therapeutic effects through pathological progression via regulation of ROS. Besides, biomaterials fix delivery issues by promoting the penetration of drugs across the blood-brain barrier (BBB), protecting the drug from peripheral degradation, and elevating bioavailability. The goal is to comprehensively understand the mechanisms of ROS in the progression of AD disease and the potential of ROS-related biomaterials in the treatment of AD. This review focuses on OS and its connection with AD and novel biomaterials in recent years against AD via OS to inspire novel biomaterial development. Revisiting these biomaterials and mechanisms associated with OS in AD via thorough investigations presents a considerable potential and bright future for improving effective interventions for AD.
Heterojunction‐Mediated Co‐Adjustment of Band Structure and Valence State for Achieving Selective Regulation of Semiconductor Nanozymes
Authors: Jiahao Huang, Xiaodan Jia, Yue Wang, Yue Qiao, Xiue Jiang
Journal: Advanced Healthcare Materials (2024)

Improving reaction selectivity is the next target for nanozymes to mimic natural enzymes. Currently, the majority of strategies in this field are exclusively applicable to metal-organic-based or organic-based nanozymes, while limited in regulating metal oxide-based semiconductor nanozymes. Herein, taking semiconductor Co