tbuckley/cabot-search huggingface dataset:
LINC00115 promotes chemoresistant breast cancer stem-like cell stemness and metastasis through SETDB1/PLK3/HIF1α signaling
Authors: Fei Luo, Mingda Zhang, Bowen Sun, Chenxin Xu, Yi Yang, Yingwen Zhang, Shanshan Li, Guoyu Chen, Ceshi Chen, Yanxin Li, Haizhong Feng
Journal: Molecular Cancer (2024)

Abstract Background Cancer stem-like cell is a key barrier for therapeutic resistance and metastasis in various cancers, including breast cancer, yet the underlying mechanisms are still elusive. Through a genome-wide lncRNA expression profiling, we identified that LINC00115 is robustly upregulated in chemoresistant breast cancer stem-like cells (BCSCs). Methods LncRNA microarray assay was performed to document abundance changes of lncRNAs in paclitaxel (PTX)-resistant MDA-MB-231 BCSC (ALDH + ) and non-BCSC (ALDH − ). RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to determine the binding proteins of LINC00115. The clinical significance of the LINC00115 pathway was examined in TNBC metastatic lymph node tissues. The biological function of LINC00115 was investigated through gain- and loss-of-function studies. The molecular mechanism was explored through RNA sequencing, mass spectrometry, and the CRISPR/Cas9-knockout system. The therapeutic potential of LINC00115 was examined through xenograft animal models. Results LINC00115 functions as a scaffold lncRNA to link SETDB1 and PLK3, leading to enhanced SETDB1 methylation of PLK3 at both K106 and K200 in drug-resistant BCSC. PLK3 methylation decreases PLK3 phosphorylation of HIF1α and thereby increases HIF1α stability. HIF1α, in turn, upregulates ALKBH5 to reduce m 6 A modification of LINC00115, resulting in attenuated degradation of YTHDF2-dependent m 6 A-modified RNA and enhanced LINC00115 stability. Thus, this positive feedback loop provokes BCSC phenotypes and enhances chemoresistance and metastasis in triple-negative breast cancer. SETDB1 inhibitor TTD-IN with LINC00115 ASO sensitizes PTX-resistant cell response to chemotherapy in a xenograft animal model. Correlative expression of LINC00115, methylation PLK3, SETDB1, and HIF1α are prognostic for clinical triple-negative breast cancers. Conclusions Our findings uncover LINC00115 as a critical regulator of BCSC and highlight targeting LINC00115 and SETDB1 as a potential therapeutic strategy for chemotherapeutic resistant breast cancer.
Avelumab Plus Intermittent Axitinib in Previously Untreated Patients with Metastatic Renal Cell Carcinoma. The Tide-A Phase 2 Study
Authors: Roberto Iacovelli, Chiara Ciccarese, Sebastiano Buti, Paolo Andrea Zucali, Emanuela Fantinel, Davide Bimbatti, Elena Verzoni, Caterina Accettura, Lucia Bonomi, Consuelo Buttigliero, Giuseppe Fornarini, Stefania Pipitone, Francesco Atzori, Cristina Masini, Francesco Massari, Francesca Primi, Alessandro Strusi, Giulia Claire Giudice, Matteo Perrino, Marco Maruzzo, Michele Milella, Diana Giannarelli, Matteo Brunelli, Giuseppe Procopio, Giampaolo Tortora
Journal: European Urology (2024)

Combinations of VEGFR-TKIs plus ICI against PD1/PD-L1 are the standard first-line therapy for patients with mRCC, irrespective of the prognostic class. This study aims to investigate the feasibility and safety of withdrawing the VEGFR-TKI but continuing the anti- PD1/PD-L1 in patients who achieve response to their combination.
A commentary on ‘The efficacy and safety of hydrotherapy in patients with knee osteoarthritis: a meta-analysis of randomized controlled trials’
Authors: Qu Zheng, Yiyan Han, Baoqiang Dong
Journal: International Journal of Surgery (2024)

aCollege of Integrated Traditional Chinese and Western Medicine, Liaoning University of Traditional Chinese Medicine, Liaoning, China, 110847 bAcupuncture and Moxibustion Massage College, Liaoning University of Traditional Chinese Medicine, Liaoning, China, 110847 Qu Zheng and Yiyan Han equally contributed to the study. All data in this comment is available. Fund: National Funded Postdoctoral Researcher Program (GZC20231025);Basic Research Projects of Liaoning Provincial Department of Education (JYTQN2023458); Liaoning University of Traditional Chinese Medicine High Level Talent Launch Fund Support Project (2021LZYGC004) Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Acupuncture and Moxibustion Massage College, Liaoning University of Traditional Chinese Medicine, Liaoning, China. E-mail address: [email protected] (B. Dong). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Intravenous tranexamic acid significantly improved visualization and shortened the operation time in microscopic middle ear surgery: a randomized controlled trial
Authors: Y.P. Zhang, L. Han, W.S. Ding, L. Gao, Y. Feng, H.Y. An
Journal: International Journal of Surgery (2024)

Background: The microscopic middle ear surgery involves a limited operating space and numerous important anatomical structures in which good visualization is crucial, as even a small amount of bleeding can greatly affect the clarity of surgical field. This study aims to investigate whether intravenous 1gram of tranexamic acid can improve surgical visualization and further shorten the operation time in microscopic middle ear surgery. Methods: This study is a prospective, randomized, double-blind, controlled trial conducted from December 2021 to December 2022, enrolling patients who were scheduled for microscopic modified radical mastoidectomy due to chronic otitis media. In addition to standard techniques to optimize the surgical field, participants were randomized into the TXA (tranexamic acid) group (1gram diluted to 20 mL normal saline) and the control group (20 mL normal saline). The primary outcome was assessed based on the clarity of the surgical field using the Modena Bleeding Score. Secondary outcomes included operation time, the surgeon satisfaction with the visual clarity, postoperative 24-hour coagulation parameters, and the incidence of adverse events. Student’s t test, Chi-square test and ANOVA of repeated measures were used for statistical analyses. Results: A total of 28 patients were enrolled in each group using a 1:1 randomized allocation with similar demographic characteristics, including 24 male and 32 female individuals, and the mean age is 45.6±11.9 years. The surgical visualization in the TXA group was significantly better than that of the control group (2.29±0.46 vs. 2.89±0.31, P &lt;0.001) as assessed by the Modena Bleeding Score. Furthermore, the TXA group demonstrated a shorter operation time compared to the control group (88.61±10.9 vs. 105.2±15.9, P &lt;0.001) and higher surgeon satisfaction with surgical field (7.82±0.55 vs. 6.50±0.64, P &lt;0.001). No statistically significant differences were found in postoperative coagulation parameters in the two groups. No TXA-related adverse events or complications occurred during the 12-month follow-up. Conclusion: Intravenous 1gram of TXA can further significantly improve the visual clarity in the microscopic middle ear surgery and shorten the operation time based on other standard measures implemented.
Updates in the management of postoperative pancreatic fistula
Authors: Martina Nebbia, Giovanni Capretti, Gennaro Nappo, Alessandro Zerbi
Journal: International Journal of Surgery (2024)

Postoperative pancreatic fistula (POPF) remains a common and dreaded complication after pancreatic resections and is associated with increased morbidity and mortality. Over the years, several different strategies have been investigated to prevent and mitigate POPF. However, when a POPF occurs, a consensus on the optimal management strategy of grade B and grade C POPF is still lacking, and the current management strategy is often based on local expertise and driven by patient's condition. Nevertheless, whereas the incidence of POPF after pancreatic surgery has remained stable, the overall mortality related to this complication has decreased over the years. This reflects an improvement in the management of this complication, which has become increasingly conservative. The aim of this review is to provide an updated evidence-based overview on the management strategies of POPF for surgeons and physicians in the clinical practice.
Erratum. Our National Approach to Diabetes. Diabetes Care 2023;46:252–254
Authors: Robert M. Califf
Journal: Diabetes Care (2024)

In the Duality of Interest section of the article cited above, it was incorrectly noted, due to a clerical error prior to manuscript submission, that the author served on the board of directors for the Center for Policy Analysis on Trade and Health (CPATH); the correct institution is the Critical Path Institute (C-Path).
ETV2 regulating PHD2-HIF-1α axis controls metabolism reprogramming promotes vascularized bone regeneration
Authors: HaoRan Du, Bang Li, Rui Yu, Xiaoxuan Lu, ChengLin Li, HuiHui Zhang, Fan Yang, RongQuan Zhao, WeiMin Bao, Xuan Yin, YuanYin Wang, Jian Zhou, Jianguang Xu
Journal: Bioactive Materials (2024)

The synchronized development of mineralized bone and blood vessels is a fundamental requirement for successful bone tissue regeneration. Adequate energy production forms the cornerstone supporting new bone formation. ETS variant 2 (ETV2) has been identified as a transcription factor that promotes energy metabolism reprogramming and facilitates the coordination between osteogenesis and angiogenesis. In vitro molecular experiments have demonstrated that ETV2 enhances osteogenic differentiation of dental pulp stem cells (DPSCs) by regulating the ETV2- prolyl hydroxylase 2 (PHD2)- hypoxia-inducible factor-1α (HIF-1α)- vascular endothelial growth factor A (VEGFA) axis. Notably, ETV2 achieves the rapid reprogramming of energy metabolism by simultaneously accelerating mitochondrial aerobic respiration and glycolysis, thus fulfilling the energy requirements essential to expedite osteogenic differentiation. Furthermore, decreased α-ketoglutarate release from ETV2-modified DPSCs contributes to microcirculation reconstruction. Additionally, we engineered hydroxyapatite/chitosan microspheres (HA/CS MS) with biomimetic nanostructures to facilitate multiple ETV2-DPSC functions and further enhanced the osteogenic differentiation. Animal experiments have validated the synergistic effect of ETV2-modified DPSCs and HA/CS MS in promoting the critical-size bone defect regeneration. In summary, this study offers a novel treatment approach for vascularized bone tissue regeneration that relies on energy metabolism activation and the maintenance of a stable local hypoxia signaling state.
ROS-responsive &amp; scavenging NO nanomedicine for vascular diseases treatment by inhibiting endoplasmic reticulum stress and improving NO bioavailability
Authors: Jian Li, Jvhong Zhang, Pengcheng Yu, Han Xu, Meihui Wang, Zhebin Chen, Bo Yu, Jing Gao, Qiao Jin, Fan Jia, Jian Ji, Guosheng Fu
Journal: Bioactive Materials (2024)

Vascular diseases seriously threaten human life and health. Exogenous delivery of nitric oxide (NO) represents an effective approach for maintaining vascular homeostasis during pathological events. However, the overproduction of reactive oxygen species (ROS) at vascular injury sites would react with NO to produce damaging peroxynitrite (ONOO
Targeting inflammation as cancer therapy
Authors: Manni Wang, Siyuan Chen, Xuemei He, Yong Yuan, Xiawei Wei
Journal: Journal of Hematology & Oncology (2024)

Abstract Inflammation has accompanied human beings since the emergence of wounds and infections. In the past decades, numerous efforts have been undertaken to explore the potential role of inflammation in cancer, from tumor development, invasion, and metastasis to the resistance of tumors to treatment. Inflammation-targeted agents not only demonstrate the potential to suppress cancer development, but also to improve the efficacy of other therapeutic modalities. In this review, we describe the highly dynamic and complex inflammatory tumor microenvironment, with discussion on key inflammation mediators in cancer including inflammatory cells, inflammatory cytokines, and their downstream intracellular pathways. In addition, we especially address the role of inflammation in cancer development and highlight the action mechanisms of inflammation-targeted therapies in antitumor response. Finally, we summarize the results from both preclinical and clinical studies up to date to illustrate the translation potential of inflammation-targeted therapies.
Decision-Making Engagement Preferences among Older Adults with CKD
Authors: Kristina M. Gonzales, Susan Koch-Weser, Kristen Kennefick, Mary Lynch, Thalia Porteny, Hocine Tighiouart, John B. Wong, Tamara Isakova, Dena E. Rifkin, Elisa J. Gordon, Ana Rossi, Daniel E. Weiner, Keren Ladin
Journal: Journal of the American Society of Nephrology (2024)

Key Points Clinicians’ uncertainty about the degree to which older patients prefer to engage in decision making remains a key barrier to shared decision making. Most older adults with advanced CKD preferred a collaborative or active role in decision making. Background Older adults with kidney failure face preference-sensitive decisions regarding dialysis initiation. Despite recommendations, few older patients with kidney failure experience shared decision making. Clinician uncertainty about the degree to which older patients prefer to engage in decision making remains a key barrier. Methods This study follows a mixed-methods explanatory, longitudinal, sequential design at four diverse US centers with patients (English-fluent, aged ≥70 years, CKD stages 4–5, nondialysis) from 2018 to 2020. Patient preferences for engagement in decision making were assessed using the Control Preferences Scale, reflecting the degree to which patients want to be involved in their decision making: active (the patient prefers to make the final decision), collaborative (the patient wants to share decision making with the clinician), or passive (the patient wants the clinician to make the final decision) roles. Semistructured interviews about engagement and decision making were conducted in two waves (2019, 2020) with purposively sampled patients and clinicians. Descriptive statistics and ANOVA were used for quantitative analyses; thematic and narrative analyses were used for qualitative data. Results Among 363 patient participants, mean age was 78±6 years, 42% were female, and 21% had a high school education or less. Control Preferences Scale responses reflected that patients preferred to engage actively (48%) or collaboratively (43%) versus passively (8%). Preferred roles remained stable at 3-month follow-up. Seventy-six participants completed interviews (45 patients, 31 clinicians). Four themes emerged: control preference roles reflect levels of decisional engagement; clinicians control information flow, especially about prognosis; adapting a clinical approach to patient preferred roles; and clinicians' responsiveness to patient preferred roles supports patients' satisfaction with shared decision making. Conclusions Most older adults with advanced CKD preferred a collaborative or active role in decision making. Appropriately matched information flow with patient preferences was critical for satisfaction with shared decision making. Clinical Trial registry name and registration number: Decision Aid for Renal Therapy (DART), NCT03522740.
Upfront Neck Dissection for Treatment Selection and Improvement in Quality of Life as a Novel Treatment Paradigm for Deintensification in HPV+ OPSCC
Authors: Paul L. Swiecicki, Emily Bellile, Aleksandar F. Dragovic, Jonathan McHugh, Aaron Udager, Michelle Lynn. Mierzwa, Jennifer Shah, Molly Heft Neal, Andrew Rosko, Kelly M. Malloy, Keith Casper, Steven Bennett. Chinn, Andrew G. Shuman, Chaz Stucken, Douglas B. Chepeha, Gregory T. Wolf, Carol Rossier. Bradford, Avraham Eisbruch, Mark E.P. Prince, Francis P. Worden, Matthew E. Spector
Journal: Clinical Cancer Research (2024)

Locoregionally advanced HPV+ oropharyngeal squamous cell carcinoma (OPSCC) has excellent cure rates, although current treatment regimens are accompanied by acute and long-term toxicities. We designed a phase II deescalation trial for patients with HPV+ OPSCC to evaluate the feasibility of an upfront neck dissection to individualize definitive treatment selection to improve the quality of life without compromising survival.
Defining Roles and Responsibilities of the Health Workforce to Respond to the Climate Crisis
Authors: Cecilia J. Sorensen, Linda P. Fried
Journal: JAMA Network Open (2024)

Importance The adverse effects of climate change are now apparent, disproportionately affecting marginalized and vulnerable populations and resulting in urgent worldwide calls to action. Health professionals occupy a critical position in the response to climate change, including in climate mitigation and adaptation, and their professional expertise and roles as health messengers are currently underused in the society-wide response to this crisis. Observations Clinical and public health professionals have important roles and responsibilities, some of which are shared, that they must fill for society to successfully mitigate the root causes of climate change and build a health system that can reduce morbidity and mortality impacts from climate-related hazards. When viewed through a preventive framework, the unique and synergizing roles and responsibilities provide a blueprint for investment in climate change–related prevention (primary, secondary, and tertiary), capacity building, education, and training of the health workforce. Substantial investment in increasing the competence and collaboration of health professionals is required, which must be undertaken in an urgent, coordinated, and deliberate manner. Conclusions and Relevance Exceptional collaboration, knowledge sharing, and workforce capacity building are essential to tackle the complex ways in which climate change threatens health. This framework serves as a guide for health system leaders, education institutions, policy planners, and others seeking to create a more resilient and just health system.
Enrollment in High-Deductible Health Plans and Incident Diabetes Complications
Authors: Rozalina G. McCoy, Kavya S. Swarna, David H. Jiang, Holly K. Van Houten, Jie Chen, Esa M. Davis, Jeph Herrin
Journal: JAMA Network Open (2024)

Importance Preventing diabetes complications requires monitoring and control of hyperglycemia and cardiovascular risk factors. Switching to high-deductible health plans (HDHPs) has been shown to hinder aspects of diabetes care; however, the association of HDHP enrollment with microvascular and macrovascular diabetes complications is unknown. Objective To examine the association between an employer-required switch to an HDHP and incident complications of diabetes. Design, Setting, and Participants This retrospective cohort study used deidentified administrative claims data for US adults with diabetes enrolled in employer-sponsored health plans between January 1, 2010, and December 31, 2019. Data analysis was performed from May 26, 2022, to January 2, 2024. Exposures Adults with a baseline year of non-HDHP enrollment who had to switch to an HDHP because their employer offered no non-HDHP alternative in that year were compared with adults who were continuously enrolled in a non-HDHP. Main Outcomes and Measures Mixed-effects logistic regression models examined the association between switching to an HDHP and, individually, the odds of myocardial infarction, stroke, hospitalization for heart failure, lower-extremity complication, end-stage kidney disease, proliferative retinopathy, treatment for retinopathy, and blindness. Models were adjusted for demographics, comorbidities, and medications, with inverse propensity score weighting used to account for potential selection bias. Results The study included 42 326 adults who switched to an HDHP (mean [SD] age, 52 [10] years; 19 752 [46.7%] female) and 202 729 adults who did not switch (mean [SD] age, 53 [10] years; 89 828 [44.3%] female). Those who switched to an HDHP had greater odds of experiencing all diabetes complications (odds ratio [OR], 1.11; 95% CI, 1.06-1.16 for myocardial infarction; OR, 1.15; 95% CI, 1.09-1.21 for stroke; OR, 1.35; 95% CI, 1.30-1.41 for hospitalization for heart failure; OR, 2.53; 95% CI, 2.38-2.70 for end-stage kidney disease; OR, 2.23; 95% CI, 2.17-2.29 for lower-extremity complication; OR, 1.17; 95% CI, 1.13-1.21 for proliferative retinopathy; OR, 2.35; 95% CI, 2.18-2.54 for blindness; and OR, 2.28; 95% CI, 2.15-2.41 for retinopathy treatment). Conclusions and Relevance This study found that an employer-driven switch to an HDHP was associated with increased odds of experiencing all diabetes complications. These findings reinforce the potential harm associated with HDHPs for people with diabetes and the importance of affordable and accessible chronic disease management, which is hindered by high out-of-pocket costs incurred by HDHPs.
Telephone-Based Rehabilitation Intervention to Optimize Activity Participation After Breast Cancer
Authors: Kathleen Doyle Lyons, Stephen B. Wechsler, Deborah B. Ejem, Courtney J. Stevens, Andres Azuero, Sarah Khalidi, Mark T. Hegel, Sarah M. dos Anjos, Megan E. Codini, Mary D. Chamberlin, Jamme L. Morency, Jazmine Coffee-Dunning, Karen E. Thorp, Danielle Z. Cloyd, Susan Goedeken, Robin Newman, Colleen Muse, Gabrielle Rocque, Kimberly Keene, Maria Pisu, Jennifer Echols, Marie A. Bakitas
Journal: JAMA Network Open (2024)

Following treatment, breast cancer survivors face challenges participating in valued activities.