tbuckley/cabot-search huggingface dataset:
The efficacy of primary progesterone on survival in early breast cancer: A real world scenario.
Authors: Shalaka Prakash Joshi, Mitchelle Engineer, Vaibhav Vanmali, Shabina Siddique, Rohini W. Hawaldar, Rajendra A. Badwe
Journal: Journal of Clinical Oncology (2024)

e12522 Background: Surgery performed during progestogenic milieu improves survival in breast cancer patients. We previously proved efficacy of pre-operative progesterone in high-risk, operable breast cancer. In another multicenter randomized trial, intra-operative peri-tumoral local anesthetic injection showed 29% reduction in mortality. In this study, several patients had also received progesterone injection since this is adopted as standard of care across some centers including ours. We assessed the effectiveness of pre-operative progesterone in patients who were randomized in the local anesthetic study. Methods: We analyzed 1583 patients randomized on the local anesthetic study during December 2011-October 2018 with respect to receipt of progesterone. All patient who had breast lump of ≥2cm and/or node positive were eligible to receive progesterone injection before surgery. Kaplan Meier curves were plotted along with Cox regression analysis to study factors affecting disease-free and overall survival. Results: Of 1583, 454 patients did not receive, and 1129 patients received progesterone before surgery. The median age of whole cohort was 51 years, median pT size was 3 cm, 45% were node positive, 60% ER/PR+ and 24%TNBC. At median follow-up of 68 (0·5-72) months in surviving patients, there were a total of 292 DFS events (progesterone arm-193, no-progesterone arm-99). The 5-year disease-free survival (DFS) was 86.5% in the progesterone arm and 79.2% in the no-progesterone arm (HR-0.57,0.45-0.73, P&lt;0.001). The 5-year overall survival (OS) was 90.5% in the progesterone arm and 82.8% in the no-progesterone arm (HR-0.47,0.36-0.63,P&lt;0.001). On Cox Regression analysis (Table), administration of progesterone injection was an independent prognostic factor for DFS (HR-0.53,0-41-0.70, p&lt;0.001) and OS (HR-0.44,0-32-0.60, p&lt;0.001) both. Conclusions: The receipt of pre-operative progesterone improved outcomes in the setting of another randomized trial. It should be administered to all high risk (T2/N1) breast cancer patients who are planned for surgery first. [Table: see text]
Hemicircumferential rectal endoscopic submucosal dissection combining multitraction and scope-dependent traction strategies
Authors: Jean Grimaldi, Louis-Jean Masgnaux, Timothée Wallenhorst, Elena De Cristofaro, Jérôme Rivory, Jérémie Jacques, Mathieu Pioche
Journal: Endoscopy (2024)

The development of endoscopic submucosal dissection (ESD) has long been hampered by the difficulty and length of the procedures involved. In recent years, the development of traction strategies has greatly facilitated the practice of ESD [1] [2]. As part of our research into traction, we developed an adaptive multipolar traction strategy using the ATRACT device [3] [4] [5]. We wanted to test combining this strategy with a new endoscopic lifting device, the FlexLifter (Olympus, Japan), which uses forceps to pull the lesion above the plane of the endoscope, thereby enlarging the submucosal plane to be dissected.
Clinical Likelihood Prediction of Hemodynamically Obstructive Coronary Artery Disease in Patients With Stable Chest Pain
Authors: Laust Dupont Rasmussen, Salma Raghad Karim, Jelmer Westra, Louise Nissen, Jonathan Nørtoft Dahl, Gitte Stokvad Brix, Juhani Knuuti, Samuel Emil Schmidt, Niels Ramsing Holm, Evald Høj Christiansen, Ashkan Eftekhari, Morten Bøttcher, Simon Winther
Journal: JACC. Cardiovascular imaging (2024)
Risk factors of breast cancer among patients from a lower- and middle-income country: A case-control study from Nepal.
Authors: Arun Shahi
Journal: Journal of Clinical Oncology (2024)

e12502 Background: Although breast cancer occurs overwhelmingly in high-income countries, there has been a recent increase in the incidence of breast cancer cases in low and middle-income countries. Reports from hospital-based registries showed that breast cancer is second most common cancer in Nepalese women. The study aimed to find the risk factors associated with breast cancer among breast cancer patients at a tertiary care hospital from Nepal. Methods: An Institutional-based 1:1 unmatched case-control study with a sample of 100 women was conducted at Patan Academy of Health Sciences, Patan Hospital, Kathmandu, Nepal, between May to October 2023. Women aged 20-84 years with histologically confirmed breast cancer within the last 4 years of the interview date were identified retrospectively as a study cases. Semi-structured questionnaire was used for data collection. Multivariate logistic regression model was used to calculate the adjusted odds ratio with 95%CI. Results: The significantly associated risk factors included age (41-50yrs: OR 5.03, &gt;50 years: OR31.11), marital status (married: OR9.23), age at menarche (13-15 yrs: OR 3.79), and oral contraception use (OC user: OR 4.26). Conclusions: Emphasizing regular breast cancer screening programs above 40 years of age and adequate counselling and awareness about that risks and benefits of hormonal contraception among high-risk groups might help to mitigate the risk of breast cancer.
Efficacy of a combined diet and exercise intervention in patients with breast cancer undergoing chemotherapy: A meta-analysis of randomized controlled trials.
Authors: Maria Meritxell Roca Mora, Luisa Marin Cunha, Angelina Kozhokar Mikhaylovskaya, Farhan Afzal, Amanda Godoi
Journal: Journal of Clinical Oncology (2024)

e12517 Background: Breast cancer treatment presents challenging side effects that may compromise patients’ health and quality of life (QoL). While exercise programmes have been shown to improve survival, the impact of combined exercise and dietary interventions compared to usual practices alongside chemotherapy remains controversial. Methods: PubMed, Embase, Cochrane Central, and ClinicalTrials.gov were systematically searched up to October 2023. We included randomized controlled trials (RCTs) involving adult breast cancer patients undergoing chemotherapy and comparing combined diet and exercise interventions with usual care. Outcomes of interest included weight change, relative dose intensity (RDI), and Functional Assessment of Cancer Therapy-General scale (FACT-G) score for QoL. Statistical analysis was performed using Review Manager 5.4.1 and RStudio version 4.1.2. The protocol was registered on PROSPERO (ID: CRD42023463543). Results: Seven RCTs with 960 patients undergoing breast cancer therapy were included, of whom 506 (53%) were assigned to combined exercise and dietary interventions. Participants had a mean BMI of 26.6 kg/m 2 , and approximately 52% were postmenopausal. Combined exercise and dietary interventions resulted in significant reductions in weight loss (MD -1.06 kg, 95% CI -1.68 to -0.44; p&lt;0.01), BMI (MD -0.44; 95% CI -1.76 to -0.13; p&lt;0.01), body fat (MD -2.12%; 95% CI -3.99 to -0.26; p=0.03), and FACT-G (MD -3.40; 95% CI -6.25 to -0.55; p=0.02) compared to usual care. No significant differences were observed in waist circumference (p=0.05), RDI (p=0.23), or fatigue levels (p=0.98) between groups. Conclusions: In this meta-analysis of randomized trials, combined exercise and dietary interventions improved weight management in breast cancer patients undergoing chemotherapy but did not significantly impact chemotherapy completion, fatigue levels, and worsened FACT-G score (QoL). Findings can help to further holistic cancer care, taking into account both physical and psychosocial dimensions of patient health.
Exploring factors impacting quality of life in patients with breast cancer undergoing adjuvant hormone therapy: Experience of the Medical Oncology Department-CHU Hassan II-FEZ University Hospital.
Authors: Hafssa El Hilali, Nassiba Bahra, Sanae Guennouni, Chaymae Chbihi, Samia El Hakym, Jihane Chouef, Oumaima Talbi, Hajar Medyouni, Lamiae Amaadour, Karima Oualla, Zineb Benbrahim, Touria Bouhafa, Nawfel Mellas, Samira El Fakir, Samia Arifi
Journal: Journal of Clinical Oncology (2024)

e12507 Background: Considering that the recommended duration of adjuvant hormone therapy in localized breast cancer is at least 5 years, it becomes crucial to investigate the quality of life (QOL) of these patients and the factors influencing it. Objectives: To assess the quality of life (QOL) and identify factors impacting it in patients with localized hormone-sensitive breast cancer receiving adjuvant hormone therapy. Methods: We surveyed 335 patients with localized hormone-sensitive breast cancer undergoing adjuvant hormone therapy using the Moroccan Arabic dialect version of the EORTC QLQ-C30 questionnaire. Written informed consent was obtained from all participants. Confidentiality of participant data was maintained. The study was carried-out with respect to the Moroccan regulation in effect. Results: The overall quality of life (QOL) in our patient population was moderate, with positive scores for social functioning, followed by physical, cognitive, and emotional functioning. Financial difficulties emerged as the most influential factor affecting patients' QOL, followed by fatigue, pain, and other symptoms. Age-related declines in physical functioning were observed, with symptoms more prevalent, especially diarrhea, in patients aged 70 and above (p = 0.009). Urban patients faced a greater financial impact on QOL than rural patients (p = 0.025). Higher education correlated with improved QOL, particularly in physical functioning (p = 0.025). Married individuals demonstrated better overall QOL and fewer symptoms (p = 0.027). Menopausal patients exhibited lower ability and a higher loss of appetite (p = 0.027). No significant correlation was found between UICC stage and QOL. Patey-mastectomy was associated with more pain than tumorectomy (p = 0.024). Previous chemotherapy had no overall QOL impact, but users reported less diarrhea (p = 0.016). Hormone therapy type did not significantly affect overall health status, except for tamoxifen users who demonstrated improved functional roles (p = 0.008). The duration of adjuvant hormone therapy (&lt;5 years or &gt;5 years) showed no significant difference in patient QOL. Associated castration had a significant impact on overall health and role functioning, favoring non-castration (p = 0.034 and p = 0.011). Effective treatment tolerance positively influenced overall QOL, leading to better physical, emotional, and cognitive functioning (p &lt; 0.0001), with fewer pronounced symptoms. Conclusions: Our study indicate that the overall QOL of patients with localized breast cancer under AET was moderate, and several factors were identified as major influences, each affecting the QOL in distinct ways.
Ultra-hypofractionated adjuvant radiation therapy for breast cancer (UK FAST-Forward trial): A real life scenario analysis in a developing country.
Authors: Rennê Bart Aguiar, Ramon Ferrari, Leonardo Oliveira Franco, Carlos Veloso Almeida, Paulo Canary, Daniel Przybysz
Journal: Journal of Clinical Oncology (2024)

e12501 Background: Selected patients showed non-inferior outcomes after conservative surgery for early breast cancer in the FAST-Forward UK (26Gy in 5 fractions) when compared to standard to date treatment. This study triggered an important change in radiation therapy routines across the world. We aimed to establish a pattern of treatment related events at a third-world country cancer center. Methods: We retrospectively analyzed all patients treated with 26Gy in 5 fractions (1 week) from January 2020 to June 2023. All data was exported and analyzed for demographics. A clinical profile was traced, dosimetric parameters and side effects assessed based on individual inquiries to each patient, per and post treatment. A strict medical record was kept in order to understand patterns of side effects and results. Results: 101 individuals were identified. Mean age was 64 years, 48 (47%) patients experienced radiation dermatitis of any grade, 33 (32%) grade 1, 9 (8%) grade 2, 6 grade 3 or 4 (5%). Patients older than 60 years showed to be a significant factor for dermatitis development (34 over a total of 48 - 70%) and 8 (53%) over 15 had grade 2 or higher dermatitis. 27 (26%) developed radiation dermatitis during sessions. 21 (20%) took 7 or less days to heal; 27 (26%) had a recovery longer than one week at an average age of 65 years - being the majority of dermatitis grade 1. Reported toxicities were sharp pain 31 (30%), burning pain 24 (23%), edema 17 (16%) and pruritus 5 (4%). At the time of this study was completed, 3 reported deaths (2%) were reported - with a 97% rate of survival. Conclusions: The FAST-Forward trial regimen has 3 years since its publication. Our study shows that in a selected group of breast cancer patients, this novel model has shown to be a safe alternative for adjuvant radiation therapy following breast conservative surgery, results corroborating with published data. To the best of our knowledge, this is the largest single center group analyzed and published.
Exosome-delivered microRNAs confer adriamycin-resistance through modulating the immune and metabolism-related gene PTEN in HER2-negative breast cancer.
Authors: Sujin Yang, Bei Zhu, Jia-hao Wu, Tian-cheng Cheng, Lin Zheng, Wei-xian Chen
Journal: Journal of Clinical Oncology (2024)

e12500 Background: Anthracycline is widely used in breast cancer (BCa) chemotherapy, but acquired drug resistance remains a challenge. Increasing evidence suggests that changes in the tumour immune microenvironment (TIME) consistently contribute to the development of chemoresistance. Methods: TIME scores and tumor-infiltrating immune cells (TICs) scores were used to investigate the prognosis, characteristics and gene transcriptomic profiling of HER2-negative BCa patients who received anthracycline chemotherapy. Exosomes from MCF/7-ADR (ADR-exos) and MCF/7-S cell lines were characterized. Dysregulated miRNAs were obtained by using miRNA microarray analysis on BCa cells and their corresponding exosomes. Protein profiling was performed to identify differentially expressed proteins in up- and down-regulated miR-222 cells. Ability of ADR-exos to transfer drug-resistance mediated by miR-222 was assessed by immunofluorescence assay and flow cytometry. Conditions to load miR-222 mimic or inhibitor into exosomes were optimized. Influence of miR-222 inhibitor-containing exosomes on the downstream pathway of miR-222 and the potential therapeutic effects were evaluated. Relationship between miR-222/PTEN and drug resistance in circulating exosomes from mice after doxorubicin chemotherapy was investigated. Results: Firstly, we discovered the complicated and heterogeneous TICs subtypes and their unique biological behaviors in HER2-negative BCa. Then, we identified 85 differentially expressed immunologic signature gene sets and 7202 corresponding immune-related genes in three subtypes quantified by gene set variation analysis. We identified 12 up-regulated and 13 down-regulated genes using miRNA microarray analysis in doxorubicin-resistant cells and their exosomes. Mass spectrometry found 45 differentially expressed proteins affected by miR-222. Moreover, we successfully established miRNA mimic/inhibitor-containing exosomes to explore the solo function of exosomal miR-222 in doxorubicin-resistance both in vitro and in vivo. For the first time, we detected the levels of miR-222 and its target gene PTEN in circulating exosomes from mice after doxorubicin-based chemotherapy and explored the potential clinical implications of miR-222/PTEN-containing exosomes in chemotherapy and immune suppression of BCa. Conclusions: Doxorubicin-resistant cells can transmit drug-resistance to sensitive cells via delivering miR-222 by modulating the immune- and metabolism-related gene PTEN without interference from other relevant drug-resistance factors in exosomes. Therefore, miR-222-containing exosomes and their target gene PTEN may be a promising biomarker for predicting chemotherapy efficacy and tumor immunity regulation in BCa patients receiving anthracycline chemotherapy.
3D cell cultures exhibit increased drug resistance, particularly to taxanes.
Authors: Chiara Maestri, Jahanvi Kumar, Rajeshwar Nitiyanandan, Ivan Trus, Ricardo Parker, Brigitte Apfel, Christian Apfel
Journal: Journal of Clinical Oncology (2024)

e12599 Background: Cell culture platforms could be categorized into two main types: 2D and 3D. 3D cell cultures, known for mimicking the physiological cellular environment, are commonly preferred by researchers to assess drug responses as they accurately reproduce aspects of the in vivo cell behavior. We hypothesized that dose-response curves of 2D and 3D platforms may be drug dependent, with some being more sensitive or resistant depending on the platform. Methods: MCF-7 cancer cells were cultured and plated using a 2D flat bottom well plate platform or using a matrix-based and a matrix-free 3D platform. Cells were treated with chemotherapies and targeted therapies for four days and cellular sensitivity was assessed through a viability assay. Four-parameter logistic (4PL) dose response curves were generated and IC 50 values (µM/C max ) were quantified to understand the differences in dose response curves between the 2D and 3D cellular platforms. Results: While the dose-response curves generally correlate between 2D vs. 3D matrix-based (r2=0.82, p&lt;0.001) and 2D vs. 3D matrix-free methods (r2=0.78, p&lt;0.001), noteworthy variations were observed for certain drugs, particularly paclitaxel (2D IC50= 66; 3D matrix-based IC50 = ≥100; 3D matrix-free IC50 = ≥100) and docetaxel (2D IC50 = ≥34; 3D matrix-based IC50 = ≥100; 3D matrix-free IC50 = ≥100). Additionally, a general increase in resistance was evident when cells formed 3D structures compared to the 2D monolayer condition, as indicated by regression analysis (Y-intercept = 0.55, CI95% 0.32 to 0.78; slope = 0.47, CI95% 0.20 to 0.75). Conclusions: Our findings reveal that taxanes such as paclitaxel and docetaxel exhibit distinctive resistance patterns in 3D structures. In addition, a substantial increase in cellular resistance is observed in 3D cellular models when compared to the 2D assay for most drugs. Despite the overall correlation, these drug-specific differences should be considered. Thus, the next generation of an extreme drug resistance assay, aimed at enhancing the quality of life for patients by avoiding ineffective therapies, might preferentially employ a 3D platform to tailor patients’ cancer therapies.
Distinct Comorbidity Clusters in Patients With Acute Heart Failure
Authors: Karla Arevalo Gomez, Jasper Tromp, Sylwia M. Figarska, Iris E. Beldhuis, Gad Cotter, Beth A. Davison, G. Michael Felker, Claudio Gimpelewicz, Barry H. Greenberg, Carolyn S.P. Lam, Adriaan A. Voors, Marco Metra, John R. Teerlink, Peter van der Meer
Journal: JACC Heart Failure (2024)

Multimorbidity frequently occurs in patients with acute heart failure (AHF). The co-occurrence of comorbidities often follows specific patterns.
Electronic Skin: Opportunities and Challenges in Convergence with Machine Learning
Authors: Ja Hoon Koo, Young Joong Lee, Hye Jin Kim, Wojciech Matusik, Dae-Hyeong Kim, Hyoyoung Jeong
Journal: Annual Review of Biomedical Engineering (2024)

Recent advancements in soft electronic skin (e-skin) have led to the development of human-like devices that reproduce the skin's functions and physical attributes. These devices are being explored for applications in robotic prostheses as well as for collecting biopotentials for disease diagnosis and treatment, as exemplified by biomedical e-skins. More recently, machine learning (ML) has been utilized to enhance device control accuracy and data processing efficiency. The convergence of e-skin technologies with ML is promoting their translation into clinical practice, especially in healthcare. This review highlights the latest developments in ML-reinforced e-skin devices for robotic prostheses and biomedical instrumentations. We first describe technological breakthroughs in state-of-the-art e-skin devices, emphasizing technologies that achieve skin-like properties. We then introduce ML methods adopted for control optimization and pattern recognition, followed by practical applications that converge the two technologies. Lastly, we briefly discuss the challenges this interdisciplinary research encounters in its clinical and industrial transition.
Harnessing Immunomodulatory Polymers for Treatment of Autoimmunity, Allergy, and Transplant Rejection
Authors: Allen B. Tu, Gaddam Krishna, Kevin R. Smith, Jamal S. Lewis
Journal: Annual Review of Biomedical Engineering (2024)

Autoimmunity, allergy, and transplant rejection are a collection of chronic diseases that are currently incurable, drastically decrease patient quality of life, and consume considerable health care resources. Underlying each of these diseases is a dysregulated immune system that results in the mounting of an inflammatory response against self or an innocuous antigen. As a consequence, afflicted patients are required to adhere to lifelong regimens of multiple immunomodulatory drugs to control disease and reclaim agency. Unfortunately, current immunomodulatory drugs are associated with a myriad of side effects and adverse events, such as increased risk of cancer and increased risk of serious infection, which negatively impacts patient adherence rates and quality of life. The field of immunoengineering is a new discipline that aims to harness endogenous biological pathways to thwart disease and minimize side effects using novel biomaterial-based strategies. We highlight and discuss polymeric micro/nanoparticles with inherent immunomodulatory properties that are currently under investigation in biomaterial-based therapies for treatment of autoimmunity, allergy, and transplant rejection.
Next-Generation Vaccine Development with Nanomaterials: Recent Advances, Possibilities, and Challenges
Authors: Shamitha Shetty, Pablo Cordero Alvarado, Deleah Pettie, Joel H. Collier
Journal: Annual Review of Biomedical Engineering (2024)

Nanomaterials are becoming important tools for vaccine development owing to their tunable and adaptable nature. Unique properties of nanomaterials afford opportunities to modulate trafficking through various tissues, complement or augment adjuvant activities, and specify antigen valency and display. This versatility has enabled recent work designing nanomaterial vaccines for a broad range of diseases, including cancer, inflammatory diseases, and various infectious diseases. Recent successes of nanoparticle vaccines during the coronavirus disease 2019 (COVID-19) pandemic have fueled enthusiasm further. In this review, the most recent developments in nanovaccines for infectious disease, cancer, inflammatory diseases, allergic diseases, and nanoadjuvants are summarized. Additionally, challenges and opportunities for clinical translation of this unique class of materials are discussed.
Biofabrication of Living Actuators
Authors: Ritu Raman
Journal: Annual Review of Biomedical Engineering (2024)

The impact of tissue engineering has extended beyond a traditional focus in medicine to the rapidly growing realm of biohybrid robotics. Leveraging living actuators as functional components in machines has been a central focus of this field, generating a range of compelling demonstrations of robots capable of muscle-powered swimming, walking, pumping, gripping, and even computation. In this review, we highlight key advances in fabricating tissue-scale cardiac and skeletal muscle actuators for a range of functional applications. We discuss areas for future growth including scalable manufacturing, integrated feedback control, and predictive modeling and also propose methods for ensuring inclusive and bioethics-focused pedagogy in this emerging discipline. We hope this review motivates the next generation of biomedical engineers to advance rational design and practical use of living machines for applications ranging from telesurgery to manufacturing to on- and off-world exploration.