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Sequential epigenetic therapy in AML
Experiences of rehabilitation one year after breast cancer diagnosis–A focus group study from the ReScreen randomized controlled trial
Background Treatment for breast cancer poses major challenges and leads to a variety of side-effects and problems that affect life for a long time. Experiences and symptoms vary, and research indicates a lack of structures for ensuring individualized rehabilitation. This qualitative focus group study aims to explore the experience of women with BC after participating in a complex randomized controlled trial (RCT) (Clinicaltrials.gov NCT03434717) focusing on cancer rehabilitation from a comprehensive perspective. Method Nine semi-structured focus group interviews with women (n = 30) who participated in the Rescreen RCT were conducted. The women were interviewed divided into three RCT groups (intervention, control, or observation group). Data were initially analyzed inductively using conventional content analysis, followed by a deductive approach, guided by the result from the inductive analysis. Results The inductive analysis resulted in two categories and four sub-categories and showed a great variation in experiences and needs. Some women described a well-functioning process, while others described lack of individualized information, continuity with healthcare providers, and clear pathways for support. After the deductive analysis, a variation between the groups appeared. Women in the intervention group expressed that a proactive and individualized approach facilitated rehabilitation and they experienced a feeling of being recognized as a person, which they highlighted as important. On the contrary, women from the control group described feelings of being abandoned from healthcare, hindering rehabilitation. The observation group expressed that their needs had been fulfilled within the healthcare system. Conclusions This study adds important knowledge to the evaluation of the ReScreen model and contributes to existing research on how individualized rehabilitation after breast cancer can be applied in clinical practice. A proactive, person-centered approach in rehabilitation, aimed at those with extended needs, would potentially optimize rehabilitation and facilitate the recovery process after breast cancer treatment.
Ferroptosis regulates hemolysis in stored murine and human red blood cells
Abstract Red blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. However, the genetic underpinnings of RBC metabolic heterogeneity and extravascular hemolysis at population scale are incompletely understood. On the basis of the breeding of 8 founder strains with extreme genetic diversity, the Jackson Laboratory diversity outbred population can capture the impact of genetic heterogeneity in like manner to population-based studies. RBCs from 350 outbred mice, either fresh or stored for 7 days, were tested for posttransfusion recovery, as well as metabolomics and lipidomics analyses. Metabolite and lipid quantitative trait loci (QTL) mapped >400 gene-metabolite associations, which we collated into an online interactive portal. Relevant to RBC storage, we identified a QTL hotspot on chromosome 1, mapping on the region coding for the ferrireductase 6-transmembrane epithelial antigen of the prostate 3 (Steap3), a transcriptional target to p53. Steap3 regulated posttransfusion recovery, contributing to a ferroptosis-like process of lipid peroxidation, as validated via genetic manipulation in mice. Translational validation of murine findings in humans, STEAP3 polymorphisms were associated with RBC iron content, lipid peroxidation, and in vitro hemolysis in 13 091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. QTL analyses in humans identified a network of gene products (fatty acid desaturases 1 and 2, epoxide hydrolase 2, lysophosphatidylcholine acetyl-transferase 3, solute carrier family 22 member 16, glucose 6-phosphate dehydrogenase, very long chain fatty acid elongase, and phospholipase A2 group VI) associated with altered levels of oxylipins. These polymorphisms were prevalent in donors of African descent and were linked to allele frequency of hemolysis-linked polymorphisms for Steap3 or p53. These genetic variants were also associated with lower hemoglobin increments in thousands of single-unit transfusion recipients from the vein-to-vein database.
Sickness absenteeism among nurses after the COVID-19 pandemic: A study protocol
Introduction Sickness absenteeism among the nurses in Malaysia is not fully understood. Complicated with the increase in workload and mental stress during the COVID-19 pandemic and the manifestation of long COVID-19 symptoms, there is a need for an updated insight on the prevalence and the risk factors of sickness absenteeism among nurses in Malaysia. As such, we designed a study protocol that assess the prevalence and risk factors of sickness absenteeism among nurses in Malaysia in the post-COVID-19 pandemic era. Materials and methods This is a correlational cross-sectional study. The sociodemographic and clinical questionnaire, sickness absenteeism questionnaire, job characteristics questionnaire, Demand-Control-Support Questionnaire (DCSQ), Work-Related Strain Inventory (WRSI), Work and Family Conflict Scale (WAFCS), the COVID-19-related workplace worries questionnaire, as well as the Depression, Anxiety, and Stress (DASS-21) questionnaire will be randomly distributed to 166 nurses from October 2024 to May 2025. Discussion While physical illnesses, psychological disorders, job-related factors, and sociodemographic factors have been identified as risk factors to sickness absenteeism among healthcare professionals in general, the role of these risk factors in causing sickness absenteeism among the nurses remains unclear. Additionally, the increased stress and workload faced by nurses during the COVID-19 pandemic, as well as post-acute COVID-19 syndrome, may have further impacted sickness absenteeism. Conclusion By examining the various risk factors of sickness absenteeism, especially in the post-COVID-19 pandemic era, this research will inform future targeted interventions to reduce sickness absenteeism among Malaysian nurses and its associated consequences.
Mosunetuzumab next up to bat … is it a home run?
From larva to adult: In vitro rearing protocol for honey bee (Apis mellifera) drones
Development of a successful in vitro rearing protocol has been essential for pesticide safety assessment of immature honey bee workers under laboratory conditions. In contrast, pesticide safety testing of honey bee drones is limited, in part due to the lack of successful laboratory rearing protocols for this reproductive caste. Considering that healthy drones are essential for successful mating and reproduction of the honey bee queen, a standardized in vitro rearing protocol for honey bee drones is necessary to support reproductive safety studies, as well as to gain a deeper understanding of honey bee drone development. Using the established in vitro rearing protocol for honey bee workers, we modified the days of grafting and pupal transfer, as well as the diet volume, pupation plate orientation, and absorbent tissue in the pupal wells to successfully rear honey bee drones in vitro. In vitro-reared drones were evaluated for gross wing abnormalities, body weight, testes weight, and abdominal area, and compared with age-matched drones reared in field colonies. We found that honey bee drones reared in a vertically oriented pupation plate containing WypAll® absorbent tissue in each well had a mean survival to adulthood of 74 ± 3.5% (SEM) until adulthood. In contrast, drones reared in a horizontally oriented pupation plate containing Kimwipe® absorbent tissue in each well had significantly lower survival (5.5 ± 2.3%) and demonstrated gross wing abnormalities. All in vitro-reared drones had significantly lower body weight, testes weight and abdominal area relative to colony-reared control drones. Accordingly, we successfully developed an in vitro rearing protocol for honey bee drones which has the potential to improve future reproductive safety assessment of pesticides for honey bees.
Heme fuels venetoclax resistance in multiple myeloma
Investigating the safety of physical rehabilitation with critically ill patients receiving vasoactive drugs: An exploratory observational feasibility study
Background Physical rehabilitation of critically ill patients may improve physical outcomes; however, the relative benefits and risks with patients requiring vasoactive drugs is currently unknown. A feasibility study is needed to inform the design of a future trial required to address this issue. Methods A two-phase exploratory observational feasibility study was carried out: A retrospective study to clarify the current practice of rehabilitation with patients receiving vasoactive drugs to inform future trial interventions and design. A prospective study exploring recruitment and outcome measurement. Intensive care patients receiving vasoactive drugs were recruited and asked about the acceptability of a future trial. The feasibility of using an adverse event tool was measured during rehabilitation. Patients were followed up after 60 days to describe the feasibility of measuring outcomes for a future trial. Results Retrospective study (n = 78): Twenty-one percent of patients took part in physical rehabilitation whilst receiving vasoactive drugs. Of 321 days with vasoactive drugs administered, physical rehabilitation occurred on 27 days (8%). Prospective study (n = 40): Eighty-one percent of participants indicated acceptability of being recruited into a future trial (n = 37). Eighty-eight percent of clinicians found it acceptable to randomise patients into either early rehabilitation or standard care. The adverse event tool was implemented by researchers with 2% loss of information. Finally, a 100% follow-up rate at day 60 was achieved for mortality outcomes. Follow-up rates were 70% for the EQ-5D (5 level), 65% for the World Health Organisation’s Disability Assessment Schedule 2.0 and RAND 36-item Health Survey 1.0 and 26% for the 6-minute walk test. Conclusions This study found a low frequency of physical rehabilitation occurring with intensive care patients receiving vasoactive drugs. A high proportion of clinicians and patients found a future RCT within this patient group acceptable. Mortality and patient-reported outcomes were the most feasible to measure.
Unraveling MCL biology to understand resistance and identify vulnerabilities
Abstract Mantle cell lymphoma (MCL) is a rare (5%-7%), aggressive B-cell non-Hodgkin lymphoma with well-defined hallmarks (eg, cyclin D1, SOX11), and its expansion is highly dependent on the tumor microenvironment (TME). Parallel drastic progress in the understanding of lymphomagenesis and improved treatments led to a paradigm shift in this B-cell malignancy with now prolonged disease-free survival after intensive chemotherapy and anti-CD20-based maintenance. However, this toxic strategy is not applicable in frail or older patients, and a small but significant part of the cases present a refractory disease representing unmet medical needs. Importantly, the field has recently seen the rapid emergence of targeted and immune-based strategies with effective combinations relying on biological rationales to overcome malignant plasticity and intratumor heterogeneity. In this review, we expose how unraveling the biology of MCL allows to better understand the therapeutic resistances and to identify neo-vulnerabilities in tumors, which are essential to offer efficient novel strategies for high-risk patients. We first highlight the tumor intrinsic resistance mechanisms and associated Achilles heels within various pathways, such as NF-κB, mitochondrial apoptosis, DNA repair, and epigenetic regulators. We then place the tumor in its complex ecosystem to decipher the dialog with the multiple TME components and show how the resulting protumoral signals could be disrupted with innovative therapeutic strategies. Finally, we discuss how these progresses could be integrated into a personalized approach in MCL.
The impact of carbohydrate quality on gut health: Insights from the NHANES
Background High- and low-quality carbohydrate diets are linked to gut health. However, their specific relationship with constipation or diarrhea is unclear. This study uses 2005–2010 NHANES data to examine the relationship between carbohydrate quality and constipation and diarrhea, and to identify suitable populations for different carbohydrate diets. Methods Chronic constipation was defined as BSFS types 1 and 2, and chronic diarrhea as types 6 and 7. Dietary intake data were provided by the FPED, using data from the NHANES database. Subjects recalled foods and beverages consumed in the past 24 hours, and intake was averaged and divided into quartiles (Q). After adjusting for covariates, associations between high- and low-quality carbohydrate diets and constipation or diarrhea were assessed using weighted RCS curves and multivariate logistic regression. Results were expressed as weighted ORs and 95% CIs, with subgroup analyses performed. Results A total of 11,355 people participated, with 10,488 in the constipation group and 10,516 in the diarrhea group. Multiple regression showed that high-quality carbohydrates were negatively associated with constipation (OR: 0.852, 95% CI: 0.796–0.912, P = 0.0001). Low-quality carbohydrates were positively associated with constipation (OR: 1.010, 95% CI: 1.002–1.018, P = 0.0295). There was no significant direct association between carbohydrate quality and diarrhoea (P = 0.5189, P = 0.8278). Segmented regression results showed a non-significant association between low quality carbohydrate intake above 40.65 servings/day and constipation, while quality carbohydrate intake above 3.84 servings/day was not significantly associated with diarrhoea. Subgroup analyses showed differences in carbohydrate quality and constipation or diarrhoea across populations. Conclusions High-quality carbohydrates lowered constipation risk by 33.7% and reduced diarrhea risk with intake up to 3.84 servings/day. In contrast, low-quality carbohydrates increased constipation risk by 83.4%, with risk stabilizing beyond 40.65 servings/day. These effects varied across groups, suggesting that better carbohydrate quality supports gut health, especially in sensitive individuals.
Frontline management of mantle cell lymphoma
Abstract Despite many recent therapeutic advances, mantle cell lymphoma (MCL) remains a largely incurable disease. Treatments for patients with relapsed/refractory (R/R) disease are limited in number and in response durability. Therefore, improving the efficacy of frontline (1L) treatment, and specifically maximizing the duration of first remission, remains of critical importance to obtain favorable long-term outcomes. As 1L treatments become more effective, improving tolerability is also becoming an increasingly realistic goal. Targeted agents, which are now mainstays of treatment in R/R MCL, are establishing new, paradigm-changing roles in frontline treatment. Here, we review data supporting current standard-of-care approaches and explore 6 main areas of possible focus for advancement of 1L management: optimizing the chemoimmunotherapy (CIT) backbone, adding targeted agents to CIT, redefining the role of autologous stem cell transplantation, improving maintenance therapy, using targeted agent combinations with omission of CIT, and using measurable residual disease–guided therapy. We highlight several ongoing phase 3 trials that may soon impact frontline MCL management, and outline some areas of necessary investigation as the field continues to strive toward a cure for this disease.
Dozens of new obesity drugs are coming: these are the ones to watch
Design of quinoline SARS-CoV-2 papain-like protease inhibitors as oral antiviral drug candidates
Exploring the underlying mechanisms of customers’ intention to adopt product recommendations from live streamers: A moderated mediation approach
Live streaming has emerged as one of the indispensable channels for product information dissemination. Product recommendations from live streamers play an increasingly important role in customers’ purchasing decisions. Our study aims to understand the mechanism behind individuals’ intention to adopt product recommendations in live streaming. To that end, we implemented a moderated mediation model to test the direct and indirect effects of perceived value on customers’ intention to adopt product recommendations from live streamers, the mediating role of perceived credibility in the relationship between perceived value and adoption intention, the moderating role of sense of telepresence in the link between perceived value and perceived credibility, and the moderating role of self-identification in the association between perceived credibility and adoption intention. Results show that perceived credibility plays a partial intermediary role in the link between perceived value and adoption intention, sense of telepresence can positively predict perceived credibility but cannot significantly moderate the relationship between perceived value and adoption intention, and self-identification can positively buffer the association between perceived credibility and adoption intention, but negatively moderate the relationship between perceived value and adoption intention. This study advances theoretical research on product recommendations in the live-streaming context and provides practical inspiration for live streamers and managers of social commerce companies.
QTLs unlock RBC storage hemolysis secrets
An optoelectrochemical synapse based on a single-component n-type mixed conductor
Understanding the aliya pulsed electric field dose-response relationship: Implications for ablation size, thermal load, and immune response in an orthotopic murine breast cancer model
Aliya®Pulsed Electric Field (PEF) technology is an emerging strategy in the field of cancer treatment, offering a novel approach to ablation therapy that does not rely on thermal mechanisms. By employing a multi-stage experimental setup, including potato tuber, porcine liver, and murine breast cancer models, we explored the dose-response relationship on ablation and immune modulation by varying the pulse packets delivered from 20 to 100. The biologic response observed with 60 packets represented a minimum effective dose yielding reproducible ablation parameters, immune response, and efficacy which could be augmented with immune checkpoint blockade. This pre-clinical analysis provides a first step toward understanding the therapeutic index for PEF technology beyond ablation, a consideration that will require robust clinical validation in well-designed prospective studies.
High-risk MCL: recognition and treatment
Abstract Significant progress in determining the molecular origins and resistance mechanisms of mantle cell lymphoma (MCL) has improved our understanding of the disease’s clinical diversity. These factors greatly impact the prognosis of patients with MCL. Given the dynamic alterations in MCL clones and disease evolution, it is crucial to recognize high-risk prognostic factors at diagnosis and relapse. Clinical factors include a high MCL International Prognostic Index score with a high Ki-67 proliferation index, early disease progression within 24 months of first-line treatment, >3 previous lines of therapy at relapse, and an aggressive (blastoid or pleomorphic) histology. Molecular aberrations include dysregulated cyclin D1, an aberrant SOX11-CD70 axis, upregulated Musashi-2, MYC rearrangement, metabolic reprogramming, and epigenetic changes. Other factors that contribute to high-risk MCL include an immune-depleted microenvironment and clone adaptability with complex chromosomal anomalies and somatic mutations in TP53, NSD2, CCND1, CDKN2A, BIRC3, SP140, KMT2D, NFkBIE, SMARCA4, and NOTCH2. Ultra-high-risk MCL is indicated by the coexistence of multiple high-risk prognostic factors in the relapse setting and can portend very short progression-free survival. As MCL treatments advance toward cellular therapies, resistance to anti-CD19 chimeric antigen receptor T-cell therapy is also observed. These findings necessitate revisiting the prognostic impact of high-risk factors, current management strategies, new bi- and trispecific T-cell engagers, combination therapies, novel therapeutic targets, and next-generation clinical trials for patients with high-risk MCL. This article provides a comprehensive update on recognizing and managing high-risk MCL and encompass current practices and future directions.