Search

In humans, AMPylation of cellular proteins is carried out by Huntingtin yeast-interacting protein E (HYPE), activated under conditions of endoplasmic reticulum stress, such as in cancer cells. Extracts of the human chronic lymphocytic leukemia cell line, OSU-CLL, were fractionated using immuno-precipitation with antibodies against adenosine-phosphate and then AMP-Tyr. The proteins isolated were modified with AMP, the 'AMPylome.' AMP-labelled peptides isolated from HYPE wild-type (WT) and HYPE knock-out (KO) cells were identified using tandem mass spectrometry. A total of 213 proteins were identified from WT cell extracts, while only 23 of these were pulled down from KO cells, consistent with the presence of another AMPylator, besides HYPE. The KO cells were more sensitive to fludarabine nucleoside (2-FaraA) than WT cells. Ingenuity Pathway Analysis of the AMPylated proteins identified in WT cells clustered actin binding proteins of the cytoskeleton, and proteins of the RHO GTPase pathway that would jointly stimulate cell proliferation. [ABSTRACT FROM AUTHOR]

Triple combination FCR (fludarabine, cyclophosphamide and rituximab) is often used as front-line treatment for chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma. Results from our laboratory indicate that 2-FaraAMP (fludarabine) has multiple mechanisms of cytotoxicity that include accumulation of isoforms and phosphorylated derivatives of p53, and induction of the unfolded protein response (UPR). Using protein pull-downs with Dynabeads coated with p53 antibody, we have found that 2-FaraA (fludarabine nucleoside) induces major changes in the p53 interactome in human Raji lymphoma and IM9 multiple myeloma cells. These changes are likely driven by DNA strand breaks induced by 2-FaraA that activate protein kinases such as ATM, ATR and Chk1. [ABSTRACT FROM AUTHOR]

The lymph node and bone marrow microenvironments promote the survival and proliferation of CLL cells. Defining the immunophenotype of CLL cells from the tumor microenvironment may help to better understand the mechanisms of action of current therapies and identify novel drug targets. Significant changes in the levels of 25 CD antigens were identified using the DotScan™ antibody microarray following CLL-cell culture with CD40L-expressing fibroblasts. Ibrutinib or idelalisib countered the change in expression of 11 of these antigens (CD23, CD27, CD53, CD58, CD71, CD80, CD84, CD97, CD126, CD150, and FMC7), which have known roles in cell activation and adhesion. The immunophenotypic changes identified may provide further insight into the mechanisms by which CLL cells interact with the tumor microenvironment and better define how ibrutinib and idelalisib release CLL cells from the lymph nodes and bone marrow. [ABSTRACT FROM AUTHOR]

Microenvironments within the lymph node and bone marrow promote proliferation and drug resistance in chronic lymphocytic leukemia (CLL). Successful treatment of CLL must therefore target the leukemic cells within these compartments. A better understanding of the interaction between CLL cells and the tumor microenvironment has led to the development ofin vitromodels that mimic the mechanisms that support leukemic cell survival and proliferationin vivo. Employing these models as part of the pre-clinical evaluation of novel therapeutic agents enables a better approximation of their potential clinical efficacy. In this review we summarize the current literature describing how different aspects of the tumor microenvironment have been modeledin vitroand detail how these models have been employed to study the biology of the disease and potential efficacy of novel therapeutic agents. [ABSTRACT FROM AUTHOR]

Patients with a stable chronic lymphocytic leukemia (CLL) double their blood lymphocyte count in >5 years, but may develop progressive disease with lymphocytes doubling in <12 months. To identify a protein signature for progressive CLL, whole cell extracts of peripheral blood mononuclear cells from patients with CLL (n = 27) were screened using iTRAQ (isobaric tags for relative and absolute quantification) analysis. A total of 84 differentially abundant proteins were identified from patients with stable and progressive CLL. Subsequently, 32 of these proteins were quantified by SRM (selected reaction monitoring) using extracts of purified CD19+CLL cells from patients (n = 50). Hierarchical clustering of these protein profiles showed two clusters of patients that correlated with progressive and stable CLL, providing signatures that should be useful for triaging patients. Some of the proteins in the progressive cluster have not been linked with CLL, for example, glutamate dehydrogenase 1 and transcription intermediary factor 1-beta. [ABSTRACT FROM PUBLISHER]

Chronic lymphocytic leukaemia ( CLL) occurs rarely with pregnancy and monoclonal B-Lymphocytosis ( MBL) has not previously been described in this setting. CLL is predominantly a disease of the elderly and affects men twice as often as women and hence only an estimated 2% of patients are females of childbearing age. We identified only five reported cases of CLL in pregnancy in the literature. We describe two additional cases, plus three other women with CLL dealing with pregnancy-related decisions. We review the literature and discuss proposals for management and issues that arise in this relatively uncommon occurrence. In contrast to many other haematological malignancies where longer remissions are typically associated with a lower risk of relapse, most patients with CLL who require treatment will ultimately relapse with current therapy. This complex setting requires careful consideration and well informed patients to assist with decisions related to pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: The Chinese community constitutes the largest demographic and faces the highest rates of cancer incidence in Singapore. Given this, palliative care plays a crucial role in supporting individuals, particularly those nearing the end of life, with family serving as their primary source of support. Many Chinese family caregivers in Singapore reported significant unmet needs in cancer care provision, with studies indicating that they often bear the brunt of caregiving responsibilities. Despite this, there has been a lack of research exploring the needs and perspectives of Chinese Singaporean family caregivers caring for terminally ill cancer patients at home. Thus, this study seeks to address this gap by investigating the lived experiences of Chinese Singaporean family caregivers providing end-of-life cancer care in a home setting., Methods: This study employed a hermeneutic phenomenological approach, guided by the framework developed by van Manen (1990), to uncover the essential meaning of each participant's lived experience. In-depth, semi-structured virtual interviews were conducted face-to-face with ten Chinese Singaporean family caregivers. These caregivers shared their personal journeys of caring for a loved one with advanced cancer during their final stage of life at home. The interviews were audio recorded, and open-ended questions were used to facilitate discussion. Each interview lasted between 30 and 60 min. The principal investigator manually transcribed all audio recordings. Additionally, an external transcriber translated the interviews into written form to ensure accuracy and authenticity. The interview texts were then analyzed and interpreted using the philosophical underpinnings rooted in phenomenology., Results: The attempts to identify meanings and make sense of the Chinese Singaporean's lived experience led to the development of two main themes and eight sub-themes. Under the primary theme of "experiences from caregiving" comprises the sub-themes "being a caregiver," "suffering," and "well-being," and the major theme of "expectations in caregiving" encompasses the sub-themes "caregiving support," "decision-making," "communication," "spirituality," and "being a Chinese Singaporean"., Conclusion: In conclusion, addressing family caregivers' needs requires culturally sensitive nursing education, peer support initiatives, public awareness campaigns, and enhanced training for domestic helpers. These measures, coupled with further research into diverse cultural caregiving needs and male caregivers' experiences, will improve support systems and empower caregivers in their essential roles., Competing Interests: Declarations. Ethics approval: Ethical approval was obtained from both the University of Southern Queensland Research Ethics Committee (H20REA101) and the Agency for Integrated Care Institutional Review Board (2020–002). The procedures used in this study adhere to the tenets of the Declaration of Helsinki. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Planetary Health emphasizes the interconnectedness of human health and the natural environment. Despite this, human-induced destruction of ecosystems threatens planetary stability. Understanding planetary empathy may offer insights into how healthcare professionals can better live and work with nature., Purpose: This paper presents a concept analysis of planetary empathy, exploring its impact on healthcare and the roles of healthcare professionals., Methods: The Walker and Avant eight-stage approach for concept analysis informed this paper. Data were obtained from literature searches, dictionaries, encyclopedias, and relevant international organization websites., Discussion: Planetary empathy is a cyclical process involving reflection, reciprocal relationships with nature, recognition of biases, responsibility for future generations, and behavioral responses to protect planetary health., Conclusion: Planetary empathy catalyzes prosocial environmental behaviors. Healthcare professionals who embody this empathy are more likely to be engaged in creating a healthier, more equitable world for all people and ecosystems., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The objective of this article is to compare outcomes of robotic-assisted partial nephrectomy (RAPN) versus laparoscopic partial nephrectomy (LPN) for surgical management of renal tumours by performing a systematic review., Materials and Methods: Prospective randomised controlled trials comparing robotic to laparoscopic partial nephrectomy were included in this analysis. No date or language restriction was imposed. Studies on paediatric patients (<16 years old) were excluded. No specific outcomes were required for inclusion in the analysis. The authors independently extracted data and assessed the risk of bias using the risk of bias tool (RoB 1). Meta-analysis was performed using ReviewManager (RevMan) Software (Cochrane Collaboration, London, United Kingdom)., Results: Two prospective randomised controlled trials involving 190 participants were included. A comparative analysis of 190 patients undergoing partial nephrectomy showed no significant difference in overall complication rates. However, RAPN was associated with a reduced risk of minor complications (Clavien-Dindo grade 1-2). Operatively, LPN demonstrated a marginally shorter duration; whereas, RAPN showed a slight advantage in warm ischemia time. Regarding renal function, RAPN resulted in a less pronounced increase in serum creatinine levels six months postoperatively. In contrast, changes in estimated glomerular filtration rate did not significantly differ between the groups. Length of hospital stay and positive surgical margin rates were comparable between approaches., Conclusion: There is limited low-quality evidence in small-scale trials that may indicate robotic partial nephrectomy is comparable to laparoscopic partial nephrectomy. RAPN has lower minor complication rates, with potential advantages in warm ischemia time and complication rates.

Background: Climate Change is causing frequent and sever extreme weather events globally, impacting human health and well-being. Primary healthcare (PHC) nurses' are at the forefront of addressing these challenges and must be prepared., Purpose: This scoping revieww explored literature on the preparedness of the PHC nursing workforce for extreme weather events and identify gaps in knowledge and practice., Methods: Using Arksey and O'Malley's framework, a comprehensive search was conducted across PubMed, Scopus, CINHAL, Web of Sciences, and ProQuest, on studies from 2014-2024, addressing PHC nurses' preparedness., Discussion: Nine studies were identified and highlighted a need for preparedness training and facility-based preparedness plans. Key themes included prioritizing regional networks, clinical leadership, service delivery, health information, health workforce, medical products and technologies, and financing., Conclusion: Strengthening PHC nurses' resilience against extreme weather requires targeted professional development, mental health support, comprehensive planning, and collaborative efforts. Future strategies should enhance PHC nurses' capacity through training, support, and policy development., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)