tbuckley/cabot-search huggingface dataset:
Programmable DNA Hydrogel Assisting Microcrystal Formulations for Sustained Locoregional Drug Delivery in Surgical Residual Tumor Lesions and Lymph Node Metastasis
Authors: Zi‐jie Zhang, Yi Zhou, Huan Tong, Xi‐cheng Sun, Zi‐cheng Lv, June‐kong Yong, Yi‐chi Wu, Xue‐lin Xiang, Fei Ding, Xiao‐lei Zuo, Fan Li, Qiang Xia, Hao Feng, Chun‐hai Fan
Journal: Advanced Healthcare Materials (2023)

Abstract Surgical residual tumor lesions (R1 resection of surgical procedures (e.g., liver cancer infiltrating the diaphragm, surgical residual breast cancer, postoperative residual ovarian cancer) or boundary residual after ablation) and lymph node metastasis that cannot be surgically resected (retroperitoneal lymph nodes) significantly affect postoperative survival of tumor patients. This clinical conundrum poses three challenges for local drug delivery systems: stable and continuous delivery, good biocompatibility, and the ability to package new targeted drugs that can synergize with other treatments. Here, a drug‐laden hydrogel generated from pure DNA strands and highly programmable in adjusting its mesh size is reported. Meanwhile, the DNA hydrogel can assist the microcrystallization of novel radiosensitizing drugs, ataxia telangiectasia and rad3‐related protein (ATR) inhibitor (Elimusertib), further facilitating its long‐term release. When applied to the tumor site, the hydrogel system demonstrates significant antitumor activity, minimized systemic toxicity, and has a modulatory effect on the tumor‐immune cell interface. This drug‐loaded DNA‐hydrogel platform represents a novel modality for adjuvant therapy in patients with surgical residual tumor lesions and lymph node metastasis.
INX-315, a Selective CDK2 Inhibitor, Induces Cell Cycle Arrest and Senescence in Solid Tumors
Authors: Catherine Dietrich, Alec Trub, Antonio Ahn, Michael Taylor, Krutika Ambani, Keefe T. Chan, Kun-Hui Lu, Christabella A. Mahendra, Catherine Blyth, Rhiannon Coulson, Susanne Ramm, April C. Watt, Sunil Kumar Matsa, John Bisi, Jay Strum, Patrick Roberts, Shom Goel
Journal: Cancer Discovery (2023)

Cyclin-dependent kinase 2 (CDK2) is thought to play an important role in driving proliferation of certain cancers, including those harboring CCNE1 amplification and breast cancers that have acquired resistance to CDK4/6 inhibitors (CDK4/6i). The precise impact of pharmacologic inhibition of CDK2 is not known due to the lack of selective CDK2 inhibitors. Here we describe INX-315, a novel and potent CDK2 inhibitor with high selectivity over other CDK family members. Using cell-based assays, patient-derived xenografts (PDX), and transgenic mouse models, we show that INX-315 (i) promotes retinoblastoma protein hypophosphorylation and therapy-induced senescence (TIS) in CCNE1-amplified tumors, leading to durable control of tumor growth; (ii) overcomes breast cancer resistance to CDK4/6i, restoring cell cycle control while reinstating the chromatin architecture of CDK4/6i-induced TIS; and (iii) delays the onset of CDK4/6i resistance in breast cancer by driving deeper suppression of E2F targets. Our results support the clinical development of selective CDK2 inhibitors. INX-315 is a novel, selective inhibitor of CDK2. Our preclinical studies demonstrate activity for INX-315 in both CCNE1-amplified cancers and CDK4/6i-resistant breast cancer. In each case, CDK2 inhibition induces cell cycle arrest and a phenotype resembling cellular senescence. Our data support the development of selective CDK2 inhibitors in clinical trials. See related commentary by Watts and Spencer, p. 386. This article is featured in Selected Articles from This Issue, p. 384.
A novel piwi-interacting RNA associates with type 2–high asthma phenotypes
Authors: Jiang Li, Xiaoning Hong, Mingye Jiang, Alvin T. Kho, Anshul Tiwari, Alberta L. Wang, Robert P. Chase, Juan C. Celedón, Scott T. Weiss, Michael J. McGeachie, Kelan G. Tantisira
Journal: Journal of Allergy and Clinical Immunology (2023)
Integrated transcriptomics, proteomics, and functional analysis to characterize the tissue‐specific small extracellular vesicle network of breast cancer
Authors: Lesang Shen, Huanhuan Huang, Zichen Wei, Wuzhen Chen, Jiaxin Li, Yao Yao, Jun Zhou, Jian Liu, Shanshan Sun, Wenjie Xia, Ting Zhang, Xiuyan Yu, Jun Shen, Weilan Wang, Jingxin Jiang, Jian Huang, Ming Jiang, Chao Ni
Journal: MedComm (2023)

Abstract Small extracellular vesicles (sEVs) are essential mediators of intercellular communication within the tumor microenvironment (TME). Although the biological features of sEVs have been characterized based on in vitro culture models, recent evidence indicates significant differences between sEVs derived from tissue and those derived from in vitro models in terms of both content and biological function. However, comprehensive comparisons and functional analyses are still limited. Here, we collected sEVs from breast cancer tissues (T‐sEVs), paired normal tissues (N‐sEVs), corresponding plasma (B‐sEVs), and tumor organoids (O‐sEVs) to characterize their transcriptomic and proteomic profiles. We identified the actual cancer‐specific sEV signatures characterized by enriched cell adhesion and immunomodulatory molecules. Furthermore, we revealed the significant contribution of cancer‐associated fibroblasts in the sEV network within the TME. In vitro model‐derived sEVs did not entirely inherit the extracellular matrix‐ and immunity regulation‐related features of T‐sEVs. Also, we demonstrated the greater immunostimulatory ability of T‐sEVs on macrophages and CD8+ T cells compared to O‐sEVs. Moreover, certain sEV biomarkers derived from noncancer cells in the circulation exhibited promising diagnostic potential. This study provides valuable insights into the functional characteristics of tumor tissue‐derived sEVs, highlighting their potential as diagnostic markers and therapeutic agents for breast cancer.
The first population size estimation of transgender and non-binary people in Georgia
Authors: Maksym Kasianczuk, Beka Gabadadze, Vitaly Djuma, Lana Miruashvili
Journal: International Journal of Transgender Health (2023)

Accurate data on the number of transgender and non-binary people are essential for the effectiveness of planning and implementation of transgender services, as well as for advocacy, but these data are insufficient. Our goal in this study was to estimate the number of transgender people in Georgia and compare it with estimations in other Eastern European and Central Asian (EECA) countries.
Author Correction: Liquid biopsy epigenomic profiling for cancer subtyping
Authors: Sylvan C. Baca, Ji-Heui Seo, Matthew P. Davidsohn, Brad Fortunato, Karl Semaan, Shahabbedin Sotudian, Gitanjali Lakshminarayanan, Miklos Diossy, Xintao Qiu, Talal El Zarif, Hunter Savignano, John Canniff, Ikenna Madueke, Renee Maria Saliby, Ziwei Zhang, Rong Li, Yijia Jiang, Len Taing, Mark Awad, Cindy H. Chau, James A. DeCaprio, William D. Figg, Tim F. Greten, Aaron N. Hata, F. Stephen Hodi, Melissa E. Hughes, Keith L. Ligon, Nancy Lin, Kimmie Ng, Matthew G. Oser, Catherine Meador, Heather A. Parsons, Mark M. Pomerantz, Arun Rajan, Jerome Ritz, Manisha Thakuria, Sara M. Tolaney, Patrick Y. Wen, Henry Long, Jacob E. Berchuck, Zoltan Szallasi, Toni K. Choueiri, Matthew L. Freedman
Journal: Nature Medicine (2023)
Natural Targeting Potent ROS‐Eliminating Tungsten‐Based Polyoxometalate Nanodots for Efficient Treatment of Pulmonary Hypertension
Authors: Hong Liu, Shuya Wang, Qiaohui Chen, Xiaoyue Ge, Huang Ning, Yanzi Guo, Di Wang, Kelong Ai, Changping Hu
Journal: Advanced Healthcare Materials (2023)

Adv. Healthcare Mater. 2023, 12, 2300252 https://doi.org/10.1002/adhm.202300252 In the originally published version of this article, the scale bars in Figures 4I and S10I are incorrectly written as 25 µm. These scale bars should both be 50 µm. The correct figures are displayed below. These corrections do not impact the overall findings and conclusions of the article. The authors sincerely apologize for any confusion that these errors may have caused.
An Integrated Therapeutic and Preventive Nanozyme‐Based Microneedle for Biofilm‐Infected Diabetic Wound Healing (Adv. Healthcare Mater. 30/2023)
Authors: Caixia Sun, Xinyu Zhou, Cong Liu, Shuyue Deng, Yuhan Song, Jun Yang, Jianjun Dai, Yanmin Ju
Journal: Advanced Healthcare Materials (2023)
Long-term mortality burden trends attributed to black carbon and PM2·5 from wildfire emissions across the continental USA from 2000 to 2020: a deep learning modelling study
Authors: Jing Wei, Jun Wang, Zhanqing Li, Shobha Kondragunta, Susan Anenberg, Yi Wang, Huanxin Zhang, David Diner, Jenny Hand, Alexei Lyapustin, Ralph Kahn, Peter Colarco, Arlindo da Silva, Charles Ichoku
Journal: The Lancet Planetary Health (2023)

Long-term improvements in air quality and public health in the continental USA were disrupted over the past decade by increased fire emissions that potentially offset the decrease in anthropogenic emissions. This study aims to estimate trends in black carbon and PM
In symptomatic adults undergoing high-resolution manometry, long-term opioid use was linked to esophageal dysmotility
Authors: James Kim
Journal: Annals of Internal Medicine (2023)

Source Citation Niu C, Zhang J, Bapaye J, et al. Systematic review with meta-analysis: chronic opioid use is associated with esophageal dysmotility in symptomatic patients. Am J Gastroenterol. 18 Aug 2023. [Epub ahead of print]. 37463432
NSAIDs and hormonal contraceptives are linked to VTE in women with no previous thrombotic disease
Authors: Anna L. Parks, Scott M. Stevens
Journal: Annals of Internal Medicine (2023)

Source Citation Meaidi A, Mascolo A, Sessa M, et al. Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study. BMJ. 2023;382:e074450. 37673431
Mendelian randomization analyses suggest a causal role for circulating GIP and IL-1RA levels in homeostatic model assessment-derived measures of β-cell function and insulin sensitivity in Africans without type 2 diabetes
Authors: Karlijn A. C. Meeks, Amy R. Bentley, Themistocles L. Assimes, Nora Franceschini, Adebowale A. Adeyemo, Charles N. Rotimi, Ayo P. Doumatey
Journal: Genome Medicine (2023)

In vitro and in vivo studies have shown that certain cytokines and hormones may play a role in the development and progression of type 2 diabetes (T2D). However, studies on their role in T2D in humans are scarce. We evaluated associations between 11 circulating cytokines and hormones with T2D among a population of sub-Saharan Africans and tested for causal relationships using Mendelian randomization (MR) analyses. We used logistic regression analysis adjusted for age, sex, body mass index, and recruitment country to regress levels of 11 cytokines and hormones (adipsin, leptin, visfatin, PAI-1, GIP, GLP-1, ghrelin, resistin, IL-6, IL-10, IL-1RA) on T2D among Ghanaians, Nigerians, and Kenyans from the Africa America Diabetes Mellitus study including 2276 individuals with T2D and 2790 non-T2D individuals. Similar linear regression models were fitted with homeostatic modelling assessments of insulin sensitivity (HOMA-S) and β-cell function (HOMA-B) as dependent variables among non-T2D individuals (n = 2790). We used 35 genetic variants previously associated with at least one of these 11 cytokines and hormones among non-T2D individuals as instrumental variables in univariable and multivariable MR analyses. Statistical significance was set at 0.0045 (0.05/11 cytokines and hormones). Circulating GIP and IL-1RA levels were associated with T2D. Nine of the 11 cytokines and hormones (exceptions GLP-1 and IL-6) were associated with HOMA-S, HOMA-B, or both among non-T2D individuals. Two-stage least squares MR analysis provided evidence for a causal effect of GIP and IL-RA on HOMA-S and HOMA-B in multivariable analyses (GIP ~ HOMA-S β = - 0.67, P-value = 1.88 × 10-6 and HOMA-B β = 0.59, P-value = 1.88 × 10-5; IL-1RA ~ HOMA-S β = - 0.51, P-value = 8.49 × 10-5 and HOMA-B β = 0.48, P-value = 5.71 × 10-4). IL-RA was partly mediated via BMI (30-34%), but GIP was not. Inverse variance weighted MR analysis provided evidence for a causal effect of adipsin on T2D (multivariable OR = 1.83, P-value = 9.79 × 10-6), though these associations were not consistent in all sensitivity analyses. The findings of this comprehensive MR analysis indicate that circulating GIP and IL-1RA levels are causal for reduced insulin sensitivity and increased β-cell function. GIP's effect being independent of BMI suggests that circulating levels of GIP could be a promising early biomarker for T2D risk. Our MR analyses do not provide conclusive evidence for a causal role of other circulating cytokines in T2D among sub-Saharan Africans.
A dual-receptor T-cell platform with Ab-TCR and costimulatory receptor achieves specificity and potency against AML
Authors: Tao Dao, Guangyan Xiong, Sung Soo Mun, Jeremy Meyerberg, Tatyana Korontsvit, Jingyi Xiang, Ziyou Cui, Aaron Y. Chang, Casey Jarvis, Winson Cai, Hanzhi Luo, Aspen Pierson, Anthony Daniyan, Sarah Yoo, Sumiko Takao, Michael Kharas, Alex Kentsis, Cheng Liu, David A. Scheinberg
Journal: Blood (2023)
CSF1R inhibition promotes neuroinflammation and behavioral deficits during graft-versus-host disease in mice
Authors: Rachael C. Adams, Dylan Carter-Cusack, Genesis T. Llanes, Christopher R. Hunter, Janaki Manoja Vinnakota, Marc J. Ruitenberg, Jana Vukovic, Patrick Bertolino, Kirat K. Chand, Julie A. Wixey, Samuel P. Nayler, Geoffrey R. Hill, Scott N. Furlan, Robert Zeiser, Kelli P. A. MacDonald
Journal: Blood (2023)
Let’s make poor reporting of early phase dose finding clinical trials a thing of the past
Authors: Christina Yap
Journal: BMJ (2023)

Let's make poor reporting of early phase dose finding clinical trials a thing of the past Christina Yap professor of clinical trials biostatisticsIn 2017, I was drafting the first manuscript for a phase I clinical trial.I was familiar with the consolidated standards of reporting trials (Consort) for randomised parallel group trials, so I was surprised by the absence of Consort reporting guidance tailored for early phase dose finding trials.
In patients with HFpEF and obesity, semaglutide increased weight loss and reduced symptoms and physical limitations at 52 wk
Authors: Hyeon-Ju Ali, Anita Deswal
Journal: Annals of Internal Medicine (2023)

Source Citation Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al; STEP-HFpEF Trial Committees and Investigators. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389:1069-1084. 37622681
Spontaneous Remission of High-Grade Non-Hodgkin Lymphoma After SARS-CoV-2 Infection
Authors: Rita Teixeira Ferreira, Inês Cardoso Ferreira, Susana Carmona, Ana Montalvão, Ana Isabel Santos
Journal: Clinical Nuclear Medicine (2023)

Abstract Despite extensive research into COVID-19 since its emergence in late 2019, there is still much not fully understood about its long-term effects. When infected with SARS-CoV-2, cancer patients have been reported to be at higher risk for unfavorable outcomes. Nevertheless, evidence suggests that viruses may exhibit an antitumor effect in some cases, which has recently been anecdotally reported with SARS-CoV-2. We present the case of a patient with a recent high-grade non-Hodgkin lymphoma diagnosis and without any cancer-specific therapy, in whom a complete metabolic response on 2-[ 18 F]FDG PET/CT was observed after COVID-19.
Second-Line Chimeric Antigen Receptor T-Cell Therapy in Diffuse Large B-Cell Lymphoma
Authors: Amar H. Kelkar, Edward R. Scheffer Cliff, Caron A. Jacobson, Gregory A. Abel, Stijntje W. Dijk, Eline M. Krijkamp, Robert Redd, Joanna C. Zurko, Mehdi Hamadani, M.G. Myriam Hunink, Corey Cutler
Journal: Annals of Internal Medicine (2023)

First-line treatment of diffuse large B-cell lymphoma (DLBCL) achieves durable remission in approximately 60% of patients. In relapsed or refractory disease, only about 20% achieve durable remission with salvage chemoimmunotherapy and consolidative autologous stem cell transplantation (ASCT). The ZUMA-7 (axicabtagene ciloleucel [axi-cel]) and TRANSFORM (lisocabtagene maraleucel [liso-cel]) trials demonstrated superior event-free survival (and, in ZUMA-7, overall survival) in primary-refractory or early-relapsed (high-risk) DLBCL with chimeric antigen receptor T-cell therapy (CAR-T) compared with salvage chemoimmunotherapy and consolidative ASCT; however, list prices for CAR-T exceed $400 000 per infusion.
Predictors of unsustained measurable residual disease negativity in transplant-eligible patients with multiple myeloma
Authors: Camila Guerrero, Noemi Puig, María-Teresa Cedena, María-José Calasanz, Norma C. Gutierrez, Manuela Fernandez, Albert Oriol, Rafael Ríos-Tamayo, Miguel-Teodoro Hernandez, Rafael Martínez-Martínez, Joan Bargay, Felipe de Arriba, Luis Palomera, Ana Pilar Gonzalez-Rodriguez, Marta-Sonia Gonzalez Perez, Alberto Orfao, María-Victoria Mateos, Joaquin Martinez-Lopez, Laura Rosiñol, Joan Bladé, Juan-Jose Lahuerta, Jesus F. San-Miguel, Bruno Paiva
Journal: Blood (2023)
18F-FDG PET/MRI for Diagnosis and Treatment Efficacy Evaluation of Spinal Sarcoidosis
Authors: Ashjan Kaseb, Darejan Bessac, Lea Frantzen, Mathilde Herber, Vincent Poindron, Alessio Imperiale
Journal: Clinical Nuclear Medicine (2023)

Spinal cord sarcoidosis (SCS) is an uncommon disease with estimated incidence of 0.4% in patients with systemic sarcoidosis. Spinal cord sarcoidosis typically manifests late in the disease course and significantly contributes to patient morbidity. Therefore, early SCS diagnosis and prompt initiation of therapy are crucial. Herein, we report the case of a 51-year-old man with symptomatic SCS managed by 18 F-FDG PET/MRI, allowing diagnosis and treatment efficacy evaluation of spine involvement. We believe that the increasing clinical availability of hybrid PET/MRI devices will offer new opportunities for optimal management of patients with uncommon severe sarcoidosis localizations, such as nervous system.
Zanubrutinib in Waldenström Macroglobulinemia
Authors: Yuan-bin Song, Jing-bo Xu, Robert Peter Gale, Yang Liang
Journal: Journal of Clinical Oncology (2023)

The unblinded multicenter phase III ASPEN study (ClinicalTrials.govidentifier: NCT03053440) compared the safety and efficacy of zanubrutinib with that of ibrutinib in advanced Waldenstr öm macroglobulinemia. 1 We raise some concerns regarding the recently published 44-month ASPEN follow-up, which we hope the authors might address.The first concern is the changing ibrutinib response rates in consecutive studies.2][3] We admit it is inappropriate to compare results from different studies when one cannot adjust for latent and unknowable predictive covariates or for chance.However, we note that the median number of prior therapies of patients receiving ibrutinib in the PCYC-1118 study was 2 (1-9), and 43% received ≥3, whereas the median number of prior therapies of patients receiving ibrutinib in the ASPEN study was 1 (0-6), and only 25% received ≥3.In patients in the MYD88 mut /CXCR4 WT cohort in the PCYC-1118E study, the ≥VGPR rate was 44% (28%-62%) compared with 31% (20%-42%) in seemingly similar patients receiving ibrutinib in the ASPEN study.
FDG PET/CT in Solitary Isolated Renal Metastasis From Squamous Cell Lung Cancer
Authors: Jun Zhang, Aisheng Dong, Yang Wang
Journal: Clinical Nuclear Medicine (2023)

We describe FDG PET/CT findings in a patient with a solitary isolated renal metastasis from squamous cell lung cancer. The renal metastasis appeared as a small focus of activity at the renal cortex on FDG PET/CT at initial staging of the lung tumor, misinterpreted as cortical tracer retention, and was significantly enlarged on the second FDG PET/CT performed 4 months after the first PET/CT. This case demonstrates the usefulness of FDG PET/CT in identifying unexpected extrathoracic metastasis from lung cancer. Focal FDG uptake in the renal cortical region in a cancer patient should be evaluated carefully to avoid misdiagnosis.
Associations Between Postdischarge Care and Cognitive Impairment–Related Hospital Readmissions for Ketoacidosis and Severe Hypoglycemia in Adults With Diabetes
Authors: Yehua Wang, Tianze Jiao, Matthew R. Muschett, Joshua D. Brown, Serena Jingchuan Guo, Ambar Kulshreshtha, Yongkang Zhang, Almut G. Winterstein, Hui Shao
Journal: Diabetes Care (2023)

OBJECTIVE Patients with severe hypoglycemia (SH) or diabetic ketoacidosis (DKA) experience high hospital readmission after being discharged. Cognitive impairment (CI) may further increase the risk, especially in those experiencing an interruption of medical care after discharge. This study examined the effect modification role of postdischarge care (PDC) on CI-associated readmission risk among U.S. adults with diabetes initially admitted for DKA or SH. RESEARCH DESIGN AND METHODS We used the Nationwide Readmissions Database (NRD) (2016–2018) to identify individuals hospitalized with a diagnosis of DKA or SH. Multivariate Cox regression was used to compare the all-cause readmission risk at 30 days between those with and without CI identified during the initial hospitalization. We assessed the CI-associated readmission risk in the patients with and without PDC, an effect modifier with the CI status. RESULTS We identified 23,775 SH patients (53.3% women, mean age 65.9 ± 15.3 years) and 140,490 DKA patients (45.8% women, mean age 40.3 ± 15.4 years), and 2,675 (11.2%) and 1,261 (0.9%), respectively, had a CI diagnosis during their index hospitalization. For SH and DKA patients discharged without PDC, CI was associated with a higher readmission risk of 23% (adjusted hazard ratio [aHR] 1.23, 95% confidence interval 1.08–1.40) and 35% (aHR 1.35, 95% confidence interval 1.08–1.70), respectively. However, when patients were discharged with PDC, we found PDC was an effect modifier to mitigate CI-associated readmission risk for both SH and DKA patients (P &amp;lt; 0.05 for all). CONCLUSIONS Our results suggest that PDC can potentially mitigate the excessive readmission risk associated with CI, emphasizing the importance of postdischarge continuity of care for medically complex patients with comorbid diabetes and CI.
Apixaban for Prevention of Thromboembolism in Pediatric Heart Disease
Authors: R. Mark Payne, Kristin M. Burns, Andrew C. Glatz, Christoph Male, Andrea Donti, Leonardo R. Brandão, Gunter Balling, Christina J. VanderPluym, Frances Bu’Lock, Lazaros K. Kochilas, Brigitte Stiller, James F. Cnota, Otto Rahkonen, Asra Khan, Rachele Adorisio, Serban Stoica, Lindsay May, Jane C. Burns, Jose Francisco K. Saraiva, Kimberly E. McHugh, John S. Kim, Agustin Rubio, Nadia G. Chía-Vazquez, Marcie R. Meador, Joshua L. Dyme, Alison M. Reedy, Toni Ajavon-Hartmann, Praneeth Jarugula, Lauren E. Carlson-Taneja, Donna Mills, Olivia Wheaton, Paul Monagle
Journal: Journal of the American College of Cardiology (2023)
Disparities in Diagnosis, Treatment, and Outcomes of Peripheral Artery Disease
Authors: Mary M. McDermott, Karen J. Ho, Olamide Alabi, Michael H. Criqui, Philip Goodney, Naomi Hamburg, Demetria M. McNeal, Amy Pollak, Kim G. Smolderen, Marc Bonaca
Journal: Journal of the American College of Cardiology (2023)