tbuckley/cabot-search huggingface dataset:
Breaking Barriers; Phytoestrogens in the Fight Against Triple‐Negative Breast Cancer: A Comprehensive Review
Authors: Md Sohel
Journal: Medicinal Research Reviews (2025)

ABSTRACT The development of standard drugs for some unusual cancers, including estrogen‐nonresponsive breast cancer, is somewhat difficult within a very short time. So, considering the current situation, phytoestrogen may be a potential candidate for unraveling chemotherapeutics agents. The reason for this review article is to manifest overall information regarding the effects of phytoestrogen on triple‐negative breast cancer (TNBC), along with its related cellular and molecular pathways in different TNBC models. Data was retrieved by systematic searches according to PRISMA guidelines, and commonly used tools and servers are BioRender, ChemDraw professional 16.0, Schrodinger, and ADMETlab 2.0. TNBC may be caused due to dysregulation of several signaling mechanisms such as Wnt/β‐catenin, hedgehog, MAPK, notch, PI3K/AKT/mTOR, hippo, NF‐κB, and JAK/STAT signaling cascades. Among all phytoestrogens ( n = 150), 48 compounds are therapeutically effective on TNBC in some in vitro and preclinical models. Chemotherapeutics activities are regulated through varieties of mechanisms, including targeting signaling pathways such as phosphor‐Akt, PI3K/AKT/mTOR, NF‐κB, TNF‐α; apoptosis such as FASL, Bcl2, Bax, Bak, Bad, apfa1, ASK1, Capase, and PARP; metastasis such as MMPs (1,2,3,9), Wnt/‐β catenin, angiogenesis (E&amp;N Cadherin, Vimentin), cell proliferation (cyclins‐A, B1, D1, E1, and CDKs 1, 6,7), inflammatory molecules (TNF‐α, NF‐κB, IL‐1β, IL‐8), regulating tumor suppressor genes (p21, p27, p51, p53) and some nonspecific pathways like DNA damage and repair (γH2AX, RAD51, and surviving), autophagy (mTOR, ULK1, and cathepsin B), epigenetic (HDAC1, DNMT1, telomerase production) and metabolism regulation (glucose regulation‐GLUT1 and GLUT4), showing antioxidant and many other pathways. Some selective phytoestrogens exert synergistic activities with conventional cancer drugs as well radiotherapy like as conventional mechanism and reverse drug resistance through regulation of the EMT process, signaling pathways, drug sensitizing, miRNA regulation, and improving drug uptake. Nano‐based phytoestrogen can target TNBC cells, stimulate drug accumulation, and improve drug efficacies, making phytoestrogens more effective agents in treating TNBC. Additionally, an in‐silico pharmacokinetics study reveals that phytoestrogen possesses suitable pharmacokinetic characteristics with minor toxicity. So, phytoestrogen can be a potential candidate drug against TNBC until standard and fully effective pharma drugs are available at markets.
Danshensu Derivatives: A Series of Promising Drugs With Protective Effects Against Cardiocerebrovascular Diseases and Cancers
Authors: Yang Yang, Luyang Du, Huadong Zhao, Ye Zhao, Sha Liao, Zhe Zhang, Shaofei Zhang, Yajun Bai, Xiaohui Zheng
Journal: Medicinal Research Reviews (2025)

ABSTRACT Salvia miltiorrhiza (Danshen in Chinese) is a traditional medicinal plant with an extensive range of cardiocerebrovascular protective effects widely used in China and other Asian countries. Danshensu (DSS) is the most important water‐soluble component of Danshen and has significant antioxidant, anti‐inflammatory, antiplatelet aggregation, antitumor, and other pharmacological activities. However, DSS has poor fat solubility and is unstable due to its o ‐phenol hydroxyl and α‐hydroxy carboxylic acids. Therefore, it is necessary to develop new DSS derivatives through reasonable structural modifications to obtain new drugs with better activity, preferable stability, and higher bioavailability. Our team has previously investigated the effect of Danshen on chronic diseases. Through nearly two decades of research, we have made considerable research progress on the impact of DSS derivatives on cardiocerebrovascular diseases. Based on the published literature and our previous work, it was confirmed that DSS derivatives have a wide range of cardiocerebrovascular protective and other pharmacological effects. Here, this review summarized recent research progress on DSS derivatives in terms of design, synthesis, pharmacological effects, and molecular mechanisms to provide new insights for further research.
Immune Dysfunction and Consequences in Chronic Lymphocytic Leukemia
Authors: Mayur Narkhede, Chaitra S. Ujjani
Journal: Journal of the National Comprehensive Cancer Network (2025)

Infectious complications are among the leading causes of mortality in chronic lymphocytic leukemia (CLL). Over the past decade, several advances have been made in treating CLL through inhibition of Bruton tyrosine kinase and the antiapoptotic protein BCL-2. As mortality from CLL progression is expected to decline in the next several years, mortality from severe infections is anticipated to increase. Therefore, understanding the nature of immune defects in CLL and developing strategies to augment the impaired immune system are needed to keep pace with advancements in treatment. This review article summarizes the available data on immune dysfunctions, their clinical consequences, therapeutic implications, and current strategies to enhance immune function in patients with CLL.
Pediatric Central Nervous System Cancers, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology
Authors: Amar Gajjar, Anita Mahajan, Tejus Bale, Daniel C. Bowers, Liz Canan, Susan Chi, Andrew Cluster, Kenneth Cohen, Bonnie Cole, Scott Coven, Wendy Darlington, Kathleen Dorris, Jennifer Elster, Ralph Ermoian, Andrea Franson, Elizabeth George, Jeffrey Helgager, Daniel Landi, Chi Lin, Laura Metrock, Ronica Nanda, Joshua Palmer, Sonia Partap, Ashley Plant, Sumit Pruthi, Renee Reynolds, Duncan Stearns, Phillip Storm, Anthony Wang, Leo D. Wang, Nicholas Whipple, Wafik Zaky, Nicole McMillian, Swathi Ramakrishnan
Journal: Journal of the National Comprehensive Cancer Network (2025)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Central Nervous System Cancers provide multidisciplinary diagnostic workup, staging, and treatment recommendations for diffuse high-grade gliomas and medulloblastomas in children and adolescents. This article summarizes the studies and panel discussion that serve as the rationale for comprehensive care recommendations included in the NCCN Guidelines for Pediatric Central Nervous System Cancers.
Monoallelic expression in human immune cells: linking genotype to phenotype
Authors: Lennart Hammarström, Qiang Pan-Hammarström
Journal: Trends in Immunology (2025)

Patients with an inborn error of immunity (IEI) often show a complete penetrance of their disease-causing mutation, whereas other forms of IEI show a family pattern where many family members carrying the same mutation remain unaffected. The underlying mechanism, differential allele-specific expression, was recently and elegantly demonstrated by Stewart et al.
NCCN Guidelines® Insights: Myelodysplastic Syndromes, Version 2.2025
Authors: Peter L. Greenberg, Richard M. Stone, Yasmin Abaza, Aref Al-Kali, Sarah Anand, Brian Ball, John M. Bennett, Uma Borate, Andrew M. Brunner, Wanxing Chai-Ho, Peter Curtin, Amy E. DeZern, Karin Gaensler, Zhubin Gahvari, Guillermo Garcia-Manero, Elizabeth A. Griffiths, Tamanna Haque, Meagan Jacoby, Brian A. Jonas, Sioban Keel, Rashmi Khanal, Ashwin Kishtagari, Yazan Madanat, Lori J. Maness, Shannon R. McCurdy, Christine McMahon, Olatoyosi Odenike, Afaf Osman, Vishnu V. Reddy, David A. Sallman, Hamid Sayar, Rory Shallis, Abhay Singh, Tiffany Tanaka, Swapna Thota, Emily Kovach, Jamie Nguyen, Cindy Hochstetler
Journal: Journal of the National Comprehensive Cancer Network (2025)

The NCCN Guidelines for Myelodysplastic Syndromes (MDS) provide recommendations for the evaluation, diagnosis, and comprehensive care of patients with MDS based on a review of recent clinical evidence that has led to important advances in treatment or has yielded new information on biologic factors that may have prognostic significance in MDS. The multidisciplinary panel of MDS experts is convened at least on an annual basis. During the annual meeting, the panel evaluates new and emerging data to inform their recommendations. These NCCN Guidelines Insights review the recent updates, including treatment recommendations both for lower-risk and higher-risk MDS, preference stratification of therapeutic agents, and emerging data on novel therapeutics.
Dynamics of replication timing during mammalian development
Authors: Tsunetoshi Nakatani
Journal: Trends in Genetics (2025)

Recent developments in low-input genomics techniques have greatly advanced the analysis of the order in which DNA is replicated in the genome - that is, replication timing (RT) - and its interrelationships with other processes. RT correlates or anticorrelates with genomic-specific parameters such as gene expression, chromatin accessibility, histone modifications, and the 3D structure of the genome, but the significance of how they influence each other and how they relate to biological processes remains unclear. In this review I discuss the results of recent analyses of RT, the time at which it is remodeled and consolidated during embryogenesis, how it influences development and differentiation, and the regulatory mechanisms and factors involved.
A Multicenter Feasibility Study of a Novel Curriculum for Oncology Trainees Regarding Medical Cannabis
Authors: Rushad Patell, Poorva Bindal, Jason Freed, Laura E. Dodge, Gayathri Nagaraj, Ann S. LaCasce, Jacob Elkon, Anne Im, Sakiko Suzuki, Nina Yedavalli, Jerome D. Winegarden, Mary K. Buss, Mara A. Schonberg, Ilana M. Braun, Deepa Rangachari
Journal: Journal of the National Comprehensive Cancer Network (2025)

Background: Oncology providers often lack the confidence to make clinical recommendations about medical cannabis (MC). This study aimed to develop and evaluate the feasibility of implementing an educational curriculum on the use of MC in patient care for oncology trainees. Methods: A multidisciplinary team designed an educational curriculum for MC use in oncology. The curriculum was piloted as a 1-hour interactive webinar across 8 United States–based hematology/oncology fellowship programs between 2022 and 2023. Incentivized surveys measuring feasibility outcomes, including cultural attitudes/norms, acceptability, compatibility, and self-efficacy (a composite index of self-confidence in discussing MC efficacy, risks, modes of use, and role in symptom management), were distributed before, immediately after, and 12 weeks post-webinar. Results: Of 103 trainees, 75 (72.8%) completed the pretraining survey and 66 (64.1%) completed the posttraining survey. Most respondents believed discussions about the role of MC in symptom management were valuable (n=56; 74.7%), though few (14.7%) believed trainees were expected to engage in such discussions. Most participants rated the curriculum as helpful (92.4%), beneficial for oncology trainees (84.8%), and likely to be recommended to colleagues (87.9%). Post-webinar, 78.8% of participants reported an increased likelihood of initiating discussions with patients regarding MC. There were significant improvements in the composite self-confidence index from pre- to post-webinar (2.7% vs 65.2%; P &lt;.001), which persisted in the follow-up surveys (n=36; response rate, 34.9%). Conclusions: This multisite study demonstrates the feasibility of implementing a novel curriculum focused on MC for oncology trainees. These findings can guide the design of a prospective, multi-institutional study to evaluate knowledge expansion, retention, and behavioral changes resulting from the intervention.
Gut microbiome-driven regulation of sex hormone homeostasis: a potential neuroendocrine connection
Authors: Anna Clapp Organski, Bartek Rajwa, Anjali Reddivari, Joan S. Jorgensen, Tzu-Wen L. Cross
Journal: Gut Microbes (2025)

The gut microbiome is known to have a bidirectional relationship with sex hormone homeostasis; however, its role in mediating interactions between the primary regulatory axes of sex hormones and their productions is yet to be fully understood. We utilized both conventionally raised and gnotobiotic mouse models to investigate the regulatory role of the gut microbiome on the hypothalamic-pituitary-gonadal (HPG) axis. Male and female conventionally raised mice underwent surgical modifications as follows: (1) hormonally intact controls; (2) gonadectomized males and females; (3) gonadectomized males and females supplemented with testosterone and estrogen, respectively. Fecal samples from these mice were used to colonize sex-matched, intact, germ-free recipient mice through fecal microbiota transplant (FMT). Serum gonadotropins, gonadal sex hormones, cecal microbiota, and the serum global metabolome were assessed. FMT recipients of gonadectomized-associated microbiota showed lower circulating gonadotropin levels than recipients of intact-associated microbiota, opposite to that of FMT donors. FMT recipients of gonadectomized-associated microbiota also had greater testicular weights compared to recipients of intact-associated microbiota. The gut microbiota composition of recipient mice differed significantly based on the FMT received, with the male microbiota having a more concerted impact in response to changes in the HPG axis. Network analyses showed that multiple metabolically unrelated pathways may be involved in driving differences in serum metabolites due to sex and microbiome received in the recipient mice. In sum, our findings indicate that the gut microbiome responds to the HPG axis and subsequently modulates its feedback mechanisms. A deeper understanding of interactions between the gut microbiota and the neuroendocrine-gonadal system may contribute to the development of therapies for sexually dimorphic diseases.
Leveraging space innovations for cancer breakthroughs on Earth
Authors: Hossein Akbarialiabad, Parnian Jamshidi, Zahra Aminzade, Narges Azizi, Seyed Reza Taha, Najmeh Sadeghian, Lydia Johnson Kolaparambil Varghese, Mohsen Farjoud Kouhanjani, Nafise Niknam, Dora Babocs, Fatima El-Assaad, Thais Russomano, Dedee F. Murrell, Shahram Paydar, Christopher G. Bunick, Rowena Christiansen, M. Mark Melin
Journal: Trends in cancer (2025)
Clinical Phenotype and Prognostic Significance of Frailty in Transthyretin Cardiac Amyloidosis
Authors: Carlo Fumagalli, Adam Ioannou, Francesco Cappelli, Mathew S Maurer, Yousuf Razvi, Aldostefano Porcari, Mattia Zampieri, Federico Perfetto, Muhammad U Rauf, Ana Martinez-Naharro, Lucia Venneri, Aviva Petrie, Carol Whelan, Ashutosh Wechalekar, Helen Lachmann, Philip N Hawkins, Iacopo Olivotto, Raffaele Marfella, Andrea Ungar, Niccolò Marchionni, Julian D Gillmore, Marianna Fontana
Journal: JACC CardioOncology (2025)

The prevalence and clinical impact of frailty in transthyretin cardiac amyloidosis (ATTR-CA) remains poorly characterized. This study aimed to evaluate the prevalence, clinical determinants, and prognostic significance of frailty in a large cohort of patients with ATTR-CA. Frailty was assessed in 880 patients with ATTR-CA (median age 80 years [Q1-Q3: 75-84 years], 719 [81.7%] male) using the Clinical Frailty Scale (CFS). Frailty was analyzed as a continuous variable and categorized as CFS 1 to 3, CFS 4 or 5, CFS 6 or 7, and CFS 8 or 9. Frailty was observed in 502 (57.1%) patients (CFS 4 or 5: 364 [41.4%]; CFS 6 or 7: 129 [14.7%]; CFS 8 or 9: 9 [1.0%]). Independent predictors of worsening frailty included older age, female sex, non-p.(V142I) hereditary ATTR-CA variants, and National Amyloidosis Centre stage 3 disease. Mortality rates increased incrementally with frailty severity (deaths per 100 person-years: 2.9 vs 11.0 vs 21.1 vs 40.9; log-rank P < 0.001). Frailty was independently associated with higher mortality risk across all age groups, genotypes, and disease stages. Frailty is common in ATTR-CA and is independently linked to increased mortality risk. Incorporating frailty assessment alongside traditional markers enhances prognostication across genotypes and disease severities, particularly for short-term risk estimation.
Acute Effect of Moderate-Intensity Interval Intradialytic Exercise on Cerebral Oxygenation in Hemodialysis Patients
Authors: Sho Kojima, Naoto Usui, Akimi Uehata, Akihito Inatsu, Yasuo Chiba, Hisadome Hideki, Yusuke Suzuki, Junichiro Nakata, Atsuhiro Tsubaki
Journal: Journal of the American Society of Nephrology (2025)

Background Cognitive dysfunction in hemodialysis (HD) patients is associated with decreased regional cerebral oxygenation (rSO 2 ). Intradialytic exercise improves cognitive function; nonetheless, the acute effect of intradialytic exercise on cerebral circulation remains unknown. This study aimed to evaluate the acute effect of intradialytic exercise on rSO 2 during HD. Methods This single-center, open-label, randomized crossover trial included 20 HD patients. Patients received the control condition as usual care and the intradialytic exercise condition in random order. The intradialytic exercise condition involved the performance of anaerobic threshold-intensity interval exercise for 35 min. Cerebral oxygenation (rSO 2 , oxygenated hemoglobin, deoxygenated hemoglobin, and total hemoglobin) in the prefrontal cortex was measured using near-infrared spectroscopy during HD. Cardiovascular responses, including the heart rate, cardiac index, mean arterial pressure, and blood gas, were also assessed. The two conditions were compared using two-way repeated-measures analysis of variance. Results The analysis included 16 patients, four of whom were excluded because of artifacts in the cerebral oxygenation data. The rSO 2 ( P &lt;0.001), oxygenated hemoglobin ( P &lt;0.001), and total hemoglobin ( P =0.004) showed significant interactions and were significantly increased at end of exercise (rSO 2 1.3%, 95%CI [0.5, 2.1]; oxygenated hemoglobin 0.01 mM, 95%CI [0.00, 0.02]; total hemoglobin 0.01 mM, 95%CI [0.00, 0.03]) and 15-min after exercise (rSO 2 1.1%, 95%CI [0.2, 2.0]; oxygenated hemoglobin 0.01 mM, 95%CI [0.00, 0.03]; total hemoglobin 0.02 mM, 95%CI [0.00, 0.03]) in the intradialytic exercise condition compared with the control condition. The rSO 2 at the end of HD in the control condition was significantly decreased compared with that during pre-HD (-1.5%, 95%CI [-2.7, -0.3]), but not in the intradialytic exercise condition (-1.2%, 95%CI [-2.8, 0.5]). Conclusions Intradialytic exercise significantly increased rSO 2 during and after exercise and improved rSO 2 to the same extent as pre-dialysis.
Impact of Donor Age and Donor Cytomegalovirus Serostatus on Outcomes After Related Donor Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Rohtesh S. Mehta, Hannah Choe, Jennifer Saultz, Zimu Gong, Prashant Sharma, Taha Al‐Juhaishi, Gabriela S. Petitto, Aleksandr Lazaryan, Anurag Singh, Elisabetta Xue, Dimana Dimitrova, Mustafa Hyder, Shannon McCurdy, Annie Im, Bryan Huber, Yosra M. Aljawai, Jennifer Kanakry, Filippo Milano, Christopher G. Kanakry
Journal: American Journal of Hematology (2025)

ABSTRACT Cytomegalovirus (CMV) infection post‐hematopoietic cell transplantation (HCT) remains a significant cause of morbidity and mortality. While letermovir prophylaxis is available for CMV‐seropositive recipients, optimal donor selection for CMV‐seronegative recipients remains unclear, with donor age often prioritized over CMV serostatus. We investigated the relative impact of donor age and CMV serostatus in CMV‐seronegative recipients ( n = 1013) with either CMV‐seropositive ( n = 318) or CMV‐seronegative donors ( n = 695), who underwent HCT with HLA‐matched sibling donors with calcineurin inhibitor‐based or post‐transplant cyclophosphamide (PTCy)‐based graft‐versus‐host disease prophylaxis, or haploidentical donors with PTCy. Multiple conventional and machine‐learning approaches were employed to account for confounding factors. Across all analyses, CMV‐seropositive donor status was consistently associated with significantly inferior overall survival (OS) and disease‐free survival, primarily driven by increased non‐relapse mortality (NRM). Older donor age showed a statistically significant association with OS and DFS in some but not all models, and its effect size was small (about 1% increased hazard per year in Cox proportional hazard model) compared to the substantial impact of CMV‐seropositive donors (about 27%–33% increased hazards for worse OS, approximately 50%–60% higher NRM in Cox proportional hazard model). However, our machine learning model revealed a more nuanced and complex non‐linear effect of donor age, further demonstrating the adverse impact of donor CMV serostatus. Our findings suggest that prioritizing a CMV‐seronegative donor may be associated with improved outcomes in CMV‐seronegative recipients. Further research is needed to validate these findings and explore underlying mechanisms.
Quality of life in heart failure. The heart of the matter. A scientific statement of the Heart Failure Association and the <scp>European Association of Preventive Cardiology</scp> of the <scp>European Society of Cardiology</scp>
Authors: Maurizio Volterrani, Geza Halasz, Stamatis Adamopoulos, Pier Giuseppe Agostoni, Javed Butler, Andrew J.S. Coats, Alan Cohen‐Solal, Wolfram Doehner, Gerasimos Filippatos, Ewa Jankowska, Carolyn S.P. Lam, Ekaterini Lambrinou, Lars H. Lund, Giuseppe Rosano, Marco Metra, Stefania Paolillo, Pasquale Perrone Filardi, Amina Rakisheva, Gianluigi Savarese, Petar Seferovic, Carlo Gabriele Tocchetti, Massimo Piepoli
Journal: European Journal of Heart Failure (2025)

For most patients with chronic, progressive illnesses, maintaining good quality of life (QoL), with preserved functional capacity, is just as crucial as prolonging survival. Patients with heart failure (HF) experience much worse QoL and effort intolerance than both the general population and people with other chronic conditions, since they present a range of physical and psychological symptoms, including shortness of breath, chest discomfort, fatigue, fluid congestion, trouble with sleeping, and depression. These symptoms reduce patients' capacity for daily social and physical activity. Usual endpoints of large‐scale trials in chronic HF have mostly been defined to evaluate treatments regarding hospitalizations and mortality, but more recently, patients' priorities and needs expressed with QoL are gaining more awareness and are being more extensively evaluated. This scientific statement aims at discussing the importance of QoL in HF, summarizing the most largely adopted questionnaires in HF care, and providing an overview on their application in trials and the potential for their transition to clinical practice. Finally, by discussing the reasons limiting their application in daily clinical routine and the strategies that may promote their implementation, this statement aims at fostering the systematic integration of the patient's standpoint in HF care.