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The generation of lineage-specific gene expression programmes that alter proliferation capacity, metabolic profile and cell type-specific functions during differentiation from multipotent stem cells to specialised cell types is crucial for development. During differentiation gene expression programmes are dynamically modulated by a complex interplay between sequence-specific transcription factors, associated cofactors and epigenetic regulators. Here, we study U-shaped (Ush), a multi-zinc finger protein that maintains the multipotency of stem cell-like hemocyte progenitors during Drosophila hematopoiesis. Using genomewide approaches we reveal that Ush binds to promoters and enhancers and that it controls the expression of three gene classes that encode proteins relevant to stem cell-like functions and differentiation: cell cycle regulators, key metabolic enzymes and proteins conferring specific functions of differentiated hemocytes. We employ complementary biochemical approaches to characterise the molecular mechanisms of Ush-mediated gene regulation. We uncover distinct Ush isoforms one of which binds the Nucleosome Remodeling and Deacetylation (NuRD) complex using an evolutionary conserved peptide motif. Remarkably, the Ush/NuRD complex specifically contributes to the repression of lineage-specific genes but does not impact the expression of cell cycle regulators or metabolic genes. This reveals a mechanism that enables specific and concerted modulation of functionally related portions of a wider gene expression programme. Finally, we use genetic assays to demonstrate that Ush and NuRD regulate enhancer activity during hemocyte differentiation in vivo and that both cooperate to suppress the differentiation of lamellocytes, a highly specialised blood cell type. Our findings reveal that Ush coordinates proliferation, metabolism and cell type-specific activities by isoform-specific cooperation with an epigenetic regulator.

Objective: Understanding patients' wishes and preferences during hospitalisation is a crucial component of care. We identified a gap related to documentation of advance directives and patient preferences for care and focused on ensuring appropriate goals of care discussions were occurring and documented. Our aim was to improve the documentation of advance care planning notes to include 80% of targeted hospitalised patients., Patients and Methods: Hospitalised patients in two community hospitals were included. We performed serial Plan-Do-Measure-Act cycles. The first intervention introduced the 'surprise question' during an afternoon huddle. Intervention 2 emphasised documentation of the advance care planning note. The third intervention used a structured approach led by administrators at daily multidisciplinary huddles and identified patients with an Elderly Risk Assessment score of 16 or greater as targets for advance care planning documentation., Results: From a baseline performance under 10%, we increased to greater than 80% of patients with Elderly Risk Assessment scores of 16 or higher having documented advance care planning. We were able to sustain this performance over subsequent years., Conclusion: A structured approach that identifies a targeted population at higher risk of mortality, and implementation of a checklist at a daily multidisciplinary huddle provided sustained improvement in advance care planning documentation. This provides the opportunity for improved patient care that is aligned with their values and preferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Introduction: Nasal symptoms are frequently reported by patients undergoing chemotherapy., Methods: Eligible patients planning to receive paclitaxel, docetaxel, nab-paclitaxel, bevacizumab without a concomitant taxane, or "other" (non-taxane, non-bevacizumab) chemotherapy regimens were invited to participate in this prospective study. Patients reported nasal symptoms prior to each dose of chemotherapy., Results: The percentage of patients (95% CI) who reported nasal symptoms was the same for patients who received bevacizumab or nab-paclitaxel, 82.6% (61.2%, 95.1%). There were no significant differences among the proportions of patients experiencing nasal symptoms within the paclitaxel, nab-paclitaxel, and bevacizumab cohorts. Patients in the nab-paclitaxel cohort were more likely to experience symptoms than those in the non-taxane non-bevacizumab cohort or docetaxel cohort (p = 0.001, p = 0.001). Patients in the bevacizumab cohort were more likely to experience nasal symptoms than those in the non-taxane non-bevacizumab cohort (p = 0.03)., Conclusion: Nasal vestibulitis symptoms are common in patients receiving chemotherapy, especially those receiving paclitaxel, docetaxel, and bevacizumab. Further investigations into treatments of this symptom complex are warranted., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Although the benefits of surveillance mammography for older breast cancer survivors have not been quantified prospectively, it is unlikely that mammography provides substantial benefit (and possible that mammography is harmful) to women with limited life expectancy and a low risk for in-breast cancer events., Materials and Methods: We identified 1268 women aged 77 and older with a history of Stage I-III breast cancer, who did not undergo bilateral mastectomy, were diagnosed with cancer at least three years prior to study entry, and who had consented to be surveyed as part of the Mayo Clinic Breast Disease Registry. We mailed them a one-time survey asking about their experiences with surveillance mammography. Women with metastatic disease were excluded. The primary endpoint was whether or not women reported at least one mammogram since breast cancer surgery., Results: Eight hundred forty-six of 1268 (67%) returned the survey, 734 of whom were eligible for analysis. The median age at the time of survey was 82, and the median time since cancer diagnosis was 12 years. Ninety-three percent reported having had at least one mammogram since their initial breast cancer surgery. Seventy-nine percent reported that they had surveillance mammography annually over the prior three years, including 76% of the 491 aged 80+ and 64% of the 189 aged 85 + ., Discussion: Most older breast cancer survivors who have residual breast tissue are undergoing annual mammograms. Additional educational materials may be beneficial for patients and clinicians to better individualize plans for surveillance mammography in older breast cancer survivors., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: To describe the natural history of nasal vestibulitis in patients receiving taxane chemotherapy, including incidence, severity, and associated symptoms., Methods: Eligible patients with minimal or no baseline nasal symptoms were enrolled in this natural history study at initiation of a new chemotherapy regimen. Patients completed nasal symptom logs each time they received a chemotherapy dose. This manuscript reports upon the patients who received paclitaxel, docetaxel, or non-taxane non-bevacizumab chemotherapy. The proportions of patients within each cohort reporting any treatment-emergent nasal symptoms were estimated, with corresponding exact 95% confidence intervals. A cumulative incidence function was estimated within the chemotherapy cohorts to calculate the cumulative incidence rate of treatment-emergent nasal vestibulitis, treating death and disease progression as competing risks., Results: Of the 81 evaluable patients, nasal symptoms were reported by 76.5% (58.8%, 89.3%) receiving paclitaxel, 54.2% (32.8%, 74.5%) receiving docetaxel, and 47.8% (26.8%, 69.4%) receiving non-taxane and non-bevacizumab chemotherapy. Of the three pairwise chemotherapy group comparisons, both the tests comparing the cumulative incidence function between the paclitaxel and non-taxane non-bevacizumab chemotherapy cohorts and between the paclitaxel and docetaxel cohorts achieved statistical significance at the 5% level with a higher incidence of treatment-emergent nasal vestibulitis in the paclitaxel cohort in both comparisons (P = 0.026 and P = 0.035, respectively). These significant differences were retained in the cumulative incidence function regression analysis controlling for age, smoking history, allergies, and asthma. Most patients in the paclitaxel cohort reported nasal symptoms as moderate or severe (56%)., Conclusion: Patients receiving paclitaxel chemotherapy experience a high incidence of nasal symptoms., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/objective: Nummular headache (NH) is a primary headache disorder characterised by intermittent or continuous scalp pain, affecting a small circumscribed area of the scalp. As there are limited data in the literature on NH, we conducted this review to evaluate demographic characteristics and factors associated with complete resolution of the headache, and effectiveness of treatment options., Methods: We performed a systematic review of cases reported through PubMed database, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and 'nummular headache', 'coin-shaped headache' and 'coin-shaped cephalalgia' keywords. Analysis was performed by using χ 2 test and Wilcoxon rank-sum test. For individual interventions, the response rate (RR%) of the treatment was calculated., Results: We analysed a total of 110 NH cases, with median age 47 years and age of pain onset 42 years. Median duration to make correct diagnosis was 18 months after first attack. The median intensity of each attack was 5/10 on verbal rating scale over 4 cm diameter with duration of attack <30 min. Patients with NH had median three attacks per day with frequency of 9.5 days per month. 40 (57.97%) patients had complete resolution of the headache after treatment. Patients with complete resolution were younger, more likely to be female, and were more likely to have diagnosis within year. Patients with complete resolution more likely to have received treatment with onabotulinum toxin A (botulinum toxin type A (BoNT-A)), and gabapentin compared with patients without complete resolution. Most effective interventions were gabapentin (n=34; RR=67.7%), non-steroidal anti-inflammatory drugs (NSAIDs) (n=32; RR=65.6%), BoNT-A (n=12; RR=100%) and tricyclic antidepressant (n=9; RR=44.4%)., Conclusion: Younger patients, female sex and early diagnosis were associated with complete resolution. NSAIDs, gabapentin and BoNT-A were most commonly used medications, with significant RRs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Male breast cancer (MBC) is a rare disease for which there is limited understanding of treatment patterns and prognostic factors., Methods: Men with TNM stage I to stage III breast cancer diagnosed between 2004 and 2014 in the National Cancer Data Base were included. Trends in treatment modalities were described using the average annual percentage change (AAPC) and estimated using Joinpoint software for the analysis of trends. Kaplan-Meier curves and the multivariate Cox proportional hazards regression model were used to compare survival between subgroups and to identify prognostic factors., Results: A total of 10,873 MBC cases were included, with a median age at diagnosis of 64 years. Breast-conserving surgery was performed in 24% of patients, and 70% of patients undergoing breast conservation received radiotherapy. Approximately 44% of patients received chemotherapy, and 62% of patients with estrogen receptor-positive disease received endocrine therapy. Oncotype DX was ordered in 35% of patients with lymph node-negative, estrogen receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. During the study period, there was a significant increase in the rates of total mastectomy, contralateral prophylactic mastectomy, radiotherapy after breast conservation, ordering of Oncotype DX, and the use of endocrine therapy (P < .05). On multivariate analysis, factors found to be associated with worse overall survival were older age, black race, higher Charlson Comorbidity Index, high tumor grade and stage of disease, and undergoing total mastectomy. Residing in a higher income area; having progesterone receptor-positive tumors; and receipt of chemotherapy, radiotherapy, and endocrine therapy were associated with better overall survival., Conclusions: Despite the lack of prospective randomized trials in patients with MBC, the results of the current study demonstrated that the treatment of this disease has evolved over the years. These findings further the understanding of the modern treatment and prognosis of MBC, and identify several areas for further research., (© 2019 American Cancer Society.)

Objective: To examine the effect of HLP, defined as having a pre-existing or a new in-hospital diagnosis based on low density lipoprotein cholesterol (LDL-C) level ≥100 mg/dL during index hospitalisation or within the preceding 6 months, on all-cause mortality after hospitalisation for acute myocardial infarction (AMI) or acute decompensated heart failure (ADHF) and to determine whether HLP modifies mortality associations of other competing comorbidities. A systematic review and meta-analysis to place the current findings in the context of published literature., Design: Retrospective study, 1:1 propensity-score matching cohorts; a meta-analysis., Setting: Large academic centre, 1996-2015., Participants: Hospitalised patients with AMI or ADHF., Main Outcomes and Measures: All-cause mortality and meta-analysis of relative risks (RR)., Results: Unmatched cohorts: 13 680 patients with AMI (age (mean) 68.5 ± (SD) 13.7 years; 7894 (58%) with HLP) and 9717 patients with ADHF (age, 73.1±13.7 years; 3668 (38%) with HLP). In matched cohorts, the mortality was lower in AMI patients (n=4348 pairs) with HLP versus no HLP, 5.9 versus 8.6/100 person-years of follow-up, respectively (HR 0.76, 95% CI 0.72 to 0.80). A similar mortality reduction occurred in matched ADHF patients (n=2879 pairs) with or without HLP (12.4 vs 16.3 deaths/100 person-years; HR 0.80, 95% CI 0.75 to 0.86). HRs showed modest reductions when HLP occurred concurrently with other comorbidities. Meta-analyses of nine observational studies showed that HLP was associated with a lower mortality at ≥2 years after incident AMI or ADHF (AMI: RR 0.72, 95% CI 0.69 to 0.76; heart failure (HF): RR 0.67, 95% CI 0.55 to 0.81)., Conclusions: Among matched AMI and ADHF cohorts, concurrent HLP, compared with no HLP, was associated with a lower mortality and attenuation of mortality associations with other competing comorbidities. These findings were supported by a systematic review and meta-analysis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Between 2009 and 2014, nearly 3% of US children (age ≤ 17 years) lived in households with at least 1 parent with substance use disorder. The present systematic review aimed to evaluate effects of parental opioid use disorder on the parent-child relationship and child developmental and behavioral outcomes., Methods: Several databases were comprehensively searched for studies published from January 1980 through February 2018 that reviewed effects of parental opioid addiction on parent-child relationships and outcomes of children (age, 0-16 years)., Results: Of 304 unique studies, 12 evaluated effects of parental opioid addiction on the parent-child relationship as the primary outcome and on children's outcomes, including behaviors and development. Observation of mother-child interaction showed that mothers with opioid use disorders are more irritable, ambivalent, and disinterested while showing greater difficulty interpreting children's cues compared with the control group. Children of parents with opioid use disorders showed greater disorganized attachment; they were less likely to seek contact and more avoidant than children in the control group. The children also had increased risk of emotional and behavioral issues, poor academic performance, and poor social skills. Younger children had increased risk of abuse or neglect, or both, that later in life may lead to such difficulties as unemployment, legal issues, and substance abuse., Conclusions: Current evidence shows association between parental opioid addiction and poorer mother-child attachment and suboptimal child developmental and behavioral outcomes. Further research and treatment targeting children and families with parental opioid use are needed to prevent difficulties later in life.