Search

Abstract Medulloblastomas (MBs) are malignant pediatric brain tumors that are molecularly and clinically heterogenous. The application of omics technologies—mainly studying nucleic acids—has significantly improved MB classification and stratification, but treatment options are still unsatisfactory. The proteome and their N-glycans hold the potential to discover clinically relevant phenotypes and targetable pathways. We compile a harmonized proteome dataset of 167 MBs and integrate findings with DNA methylome, transcriptome and N-glycome data. We show six proteome MB subtypes, that can be assigned to two main molecular programs: transcription/translation (pSHHt, pWNT and pG3myc), and synapses/immunological processes (pSHHs, pG3 and pG4). Multiomic analysis reveals different conservation levels of proteome features across MB subtypes at the DNA methylome level. Aggressive pGroup3myc MBs and favorable pWNT MBs are most similar in cluster hierarchies concerning overall proteome patterns but show different protein abundances of the vincristine resistance-associated multiprotein complex TriC/CCT and of N-glycan turnover-associated factors. The N-glycome reflects proteome subtypes and complex-bisecting N-glycans characterize pGroup3myc tumors. Our results shed light on targetable alterations in MB and set a foundation for potential immunotherapies targeting glycan structures.

Abstract Pediatric high-grade gliomas of the subclass MYCN (HGG-MYCN) are highly aggressive tumors frequently carrying MYCN amplifications, TP53 mutations, or both alterations. Due to their rarity, such tumors have only recently been identified as a distinct entity, and biological as well as clinical characteristics have not been addressed specifically. To gain insights into tumorigenesis and molecular profiles of these tumors, and to ultimately suggest alternative treatment options, we generated a genetically engineered mouse model by breeding hGFAP-cre::Trp53 Fl/Fl ::lsl-MYCN mice. All mice developed aggressive forebrain tumors early in their lifetime that mimic human HGG-MYCN regarding histology, DNA methylation, and gene expression. Single-cell RNA sequencing revealed a high intratumoral heterogeneity with neuronal and oligodendroglial lineage signatures. High-throughput drug screening using both mouse and human tumor cells finally indicated high efficacy of Doxorubicin, Irinotecan, and Etoposide as possible therapy options that children with HGG-MYCN might benefit from.

Abstract To date, several studies on genomic events underlying medulloblastoma (MB) biology have expanded our understanding of this tumour entity and led to its division into four groups—WNT, SHH, group 3 (G3) and group 4 (G4). However, there is little information about the relevance of pathogenic mitochondrial DNA (mtDNA) mutations and their consequences across these. In this report, we describe the case of a female patient with MB and a mitochondriopathy, followed by a study of mtDNA variants in MB groups. After being diagnosed with G4 MB, the index patient was treated in line with the HIT 2000 protocol with no indications of relapse after five years. Long-term side effects of treatment were complemented by additional neurological symptoms and elevated lactate levels ten years later, resulting in suspected mitochondrial disease. This was confirmed by identifying a mutation in the MT-TS1 gene which appeared homoplasmic in patient tissue and heteroplasmic in the patient’s mother. Motivated by this case, we explored mtDNA mutations across 444 patients from ICGC and HIT cohorts. While there was no statistically significant enrichment of mutations in one MB group, both cohorts encompassed a small group of patients harbouring potentially deleterious mtDNA variants. The case presented here highlights the possible similarities between sequelae caused by MB treatment and neurological symptoms of mitochondrial dysfunction, which may apply to patients across all MB groups. In the context of the current advances in characterising and interpreting mtDNA aberrations, recognising affected patients could enhance our future knowledge regarding the mutations’ impact on carcinogenesis and cancer treatment.

Abstract Background Cancer metabolism influences multiple aspects of tumorigenesis and causes diversity across malignancies. Although comprehensive research has extended our knowledge of molecular subgroups in medulloblastoma (MB), discrete analysis of metabolic heterogeneity is currently lacking. This study seeks to improve our understanding of metabolic phenotypes in MB and their impact on patients’ outcomes. Methods Data from four independent MB cohorts encompassing 1,288 patients were analysed. We explored metabolic characteristics of 902 patients (ICGC and MAGIC cohorts) on bulk RNA level. Moreover, data from 491 patients (ICGC cohort) were searched for DNA alterations in genes regulating cell metabolism. To determine the role of intratumoral metabolic differences, we examined single-cell RNA-sequencing (scRNA-seq) data from 34 additional patients. Findings on metabolic heterogeneity were correlated to clinical data. Results Established MB groups exhibit substantial differences in metabolic gene expression. By employing unsupervised analyses, we identified three clusters of group 3 and 4 samples with distinct metabolic features in ICGC and MAGIC cohorts. Analysis of scRNA-seq data confirmed our results of intertumoral heterogeneity underlying the according differences in metabolic gene expression. On DNA level, we discovered clear associations between altered regulatory genes involved in MB development and lipid metabolism. Additionally, we determined the prognostic value of metabolic gene expression in MB and showed that expression of genes involved in metabolism of inositol phosphates and nucleotides correlates with patient survival. Conclusion Our research underlines the biological and clinical relevance of metabolic alterations in MB. Thus, distinct metabolic signatures presented here might be the first step towards future metabolism-targeted therapeutic options. Graphical Abstract

Abstract Background The gene of the Epidermal growth factor receptor (EGFR) is one of the most frequently altered genes in glioblastoma (GBM), with deletions of exons 2–7 (EGFRvIII) being amongst the most common genomic mutations. EGFRvIII is heterogeneously expressed in GBM. We already showed that EGFRvIII expression has an impact on chemosensitivity, replication stress, and the DNA damage response. Wee1 kinase is a major regulator of the DNA damage induced G2 checkpoint. It is highly expressed in GBM and its overexpression is associated with poor prognosis. Since Wee1 inhibition can lead to radiosensitization of EGFRvIII-negative (EGFRvIII−) GBM cells, we asked, if Wee1 inhibition is sufficient to radiosensitize also EGFRvIII-positive (EGFRvIII+) GBM cells. Methods We used the clinically relevant Wee1 inhibitor adavosertib and two pairs of isogenetic GBM cell lines with and without endogenous EGFRvIII expression exhibiting different TP53 status. Moreover, human GBM samples displaying heterogenous EGFRvIII expression were analyzed. Expression of Wee1 was assessed by Western blot and respectively immunohistochemistry. The impact of Wee1 inhibition in combination with irradiation on cell cycle and cell survival was analyzed by flow cytometry and colony formation assay. Results Analysis of GBM cells and patient samples revealed a higher expression of Wee1 in EGFRvIII+ cells compared to their EGFRvIII− counterparts. Downregulation of EGFRvIII expression by siRNA resulted in a strong decrease in Wee1 expression. Wee1 inhibition efficiently abrogated radiation-induced G2-arrest and caused radiosensitization, without obvious differences between EGFRvIII− and EGFRvIII+ GBM cells. Conclusion We conclude that the inhibition of Wee1 is an effective targeting approach for the radiosensitization of both EGFRvIII− and EGFRvIII+ GBM cells and may therefore represent a promising new therapeutic option to increase response to radiotherapy.

Background: The COVID-19 pandemic has had a significant impact on delivery of NHS care. We have developed the OpenSAFELY Service Restoration Observatory (SRO) to develop key measures of primary care activity and describe the trends in these measures throughout the COVID-19 pandemic. Methods: With the approval of NHS England, we developed an open source software framework for data management and analysis to describe trends and variation in clinical activity across primary care electronic health record (EHR) data on 48 million adults. Results: We produced 11 measures reflective of clinical activity in general practice. A substantial drop in activity was observed in all measures at the outset of the COVID-19 pandemic. By April 2021, the median rate had recovered to within 15% of the median rate in April 2019 in six measures. The remaining measures showed a sustained drop, ranging from a 18.5% reduction in medication reviews to a 42.0% reduction in blood pressure monitoring. Three measures continued to show a sustained drop by December 2021. Conclusions: The COVID-19 pandemic was associated with a substantial change in primary care activity across the measures we developed, with recovery in most measures. We delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. We will continue to expand the set of key measures to be routinely monitored using our publicly available NHS OpenSAFELY SRO dashboards with near real-time data. Funding: This research used data assets made available as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058).The OpenSAFELY Platform is supported by grants from the Wellcome Trust (222097/Z/20/Z); MRC (MR/V015757/1, MC_PC-20059, MR/W016729/1); NIHR (NIHR135559, COV-LT2-0073), and Health Data Research UK (HDRUK2021.000, 2021.0157).

Sarcomas are morphologically heterogeneous tumours rendering their classification challenging. Here the authors developed a classifier using DNA methylation data from several soft tissue and bone sarcoma subtypes, which has the potential to improve classification for research and clinical purposes.

Objectives We sought to investigate if duplicate faecal immunochemical testing (FIT) sampling improves the negative and positive predictive value of patients thought to be at risk of colorectal cancer (CRC). Specifically, we aimed to investigate whether the proportion of FIT-negative CRC missed by a single FIT test in symptomatic patients could be reduced by duplicate FIT testing.Design A retrospective service evaluation cohort study of the diagnostic accuracy of duplicate FIT testing.Setting Patients referred from primary care with suspected CRC to four secondary care trusts in North-West England.Participants 28 622 patients over 18-years-old with lower gastrointestinal symptoms suggestive of CRC who completed two FIT samples.Primary and secondary outcome measures The performance of duplicate FIT for detecting CRC at a threshold of 10 µgHb/g.Results The sensitivity if either test was >10 µgHb/g was 0.978 (0.955–0.989), specificity was 0.662 (0.657–0.668), positive predictive value 0.031 (0.028–0.035) and negative predictive value 1.00 (0.999–1.00). Despite two-thirds of patients (18952) being negative following two tests, at this threshold only seven CRC were missed over a 26-month period. All seven patients had other high-risk features which should have prompted investigation.Conclusions This study suggests that in routine NHS practice, a duplicate FIT sample strategy together with clinical evaluation for evidence of anaemia and weight loss is superior to a single FIT sample alone and would allow symptomatic patients to be managed in primary care without the need for urgent referral to secondary care for urgent colonic imaging.

Introduction. Several reports have described the use of amantadine for managing symptoms in Marchiafava–Bignami disease (MBD); however, amantadine’s role for the treatment of MBD symptoms is unclear. Here, we describe 2 patients with MBD who were treated with amantadine and hypothesize a potential mechanism responsible for clinical benefit. Case 1. A 38-year-old woman with excessive wine drinking presented with agitation, impaired speech, and a minimally conscious state. MRI revealed lesions in the splenium and genu. After being diagnosed with MBD, she was treated with intravenous thiamine, multivitamins, and 100 mg of amantadine twice a day for 2 weeks. She recovered to near baseline after 3 weeks. Case 2. A 54-year-old woman with years of heavy alcohol use presented with sudden bradyphrenia, acalculia, disinhibited behavior, weakness, and urinary incontinence. MRI revealed a large anterior callosal lesion. Two years after initial recovery from MBD, she noted that consuming “energy drinks” resulted in a transient, near-complete resolution of her residual behavioral, fatigue, and language symptoms. 100 mg of amantadine twice a day was trialled. After noted improvement, a further escalation to 200 mgs 3 times a day resulted in significant improvement in language and behavioral symptoms. Conclusion. Amantadine in addition to vitamins may be beneficial in the treatment of MBD. It is possible that the dopaminergic effect of amantadine leads to improved recovery and function in dopamine-mediated pathways, including mesocortical and mesolimbic pathways during initial recovery, as well as improved speech, behavior, and fatigue in the following months. The role of amantadine in the treatment of MBD warrants further study.

Gorlin syndrome is a genetic condition associated with the occurrence of SHH activated medulloblastoma, basal cell carcinoma, macrocephaly and other congenital anomalies. It is caused by heterozygous pathogenic variants in PTCH1 or SUFU. In this study we included 16 patients from the HIT2000, HIT2000interim, I-HIT-MED, observation registry and older registries such as HIT-SKK87, HIT-SKK92 (1987 – 2020) with genetically confirmed Gorlin syndrome, harboring 10 PTCH1 and 6 SUFU mutations. Nine patients presented with desmoplastic medulloblastomas (DMB), 6 with medulloblastomas with extensive nodularity (MBEN) and one patient with classic medulloblastoma (CMB); all tumors affected the cerebellum, vermis or the fourth ventricle. SHH activation was present in all investigated tumors (14/16); DNA methylation analysis (when available) classified 3 tumors as iSHH-I and 4 tumors as iSHH-II. Age at diagnosis ranged from 0.65 to 3.41 years. All but one patient received chemotherapy according to the HIT-SKK protocol. Ten patients were in complete remission after completion of primary therapy; four subsequently presented with PD. No patient received radiotherapy during initial treatment. Five patients acquired additional neoplasms, namely basal cell carcinomas, odontogenic tumors, ovarian fibromas and meningioma. Developmental delay was documented in 5/16 patients. Overall survival (OS) and progression-free survival (PFS) between patients with PTCH1 or SUFU mutations did not differ statistically (10y-OS 90% vs. 100%, p=0.414; 5y-PFS 88.9% ± 10.5% vs. 41.7% ± 22.2%, p=0.139). Comparing the Gorlin patients to all young, SHH activated MBs in the registries (10y-OS 93.3% ± 6.4% vs. 92.5% ± 3.3%, p=0.738; 10y-PFS 64.9%+-16.7% vs. 83.8%+-4.5%, p=0.228) as well as comparing Gorlin M0 SKK-treated patients to all young, SHH activated, M0, SKK-treated MBs in the HIT-MED database did not reveal significantly different clinical outcomes (10y-OS 88.9% ± 10.5% vs. 88% ± 4%, p=0.812; 5y-PFS 87.5% ± 11.7% vs. 77.7% ± 5.1%, p=0.746). Gorlin syndrome should be considered in young children with SHH activated medulloblastoma, especially DMB and MBEN but cannot be ruled out for CMB. Survival did not differ to patients with SHH-activated medulloblastoma with unknown germline status or between PTCH1 and SUFU mutated patients. Additional neoplasms, especially basal cell carcinomas, need to be expected and screened for. Genetic counselling should be provided for families with young medulloblastoma patients with SHH activation.

Abstract Introduction Risk stratification of children with ependymomas of the posterior fossa in current therapeutic protocols is mainly based on clinical criteria. We aimed to identify independent outcome predictors for this disease entity by a systematic integrated analysis of clinical, histological and genetic information in a defined cohort of patients treated according to the German HIT protocols. Methods Tumor samples of 134 patients aged 0.2–15.9 years treated between 1999 and 2010 according to HIT protocols were analyzed for histological features including mitotic activity, necrosis and vascular proliferation and genomic alterations by SNP and molecular inversion probe analysis. Survival analysis was performed by Kaplan-Meier method with log rank test and multivariate Cox regression analysis. Results Residual tumor after surgery, chromosome 1q gain and structural genomic alterations were identified as predictors of significantly shorter event-free (EFS) and overall survival (OS). Furthermore, specific histological features including vascular proliferation, necrosis and high mitotic activity were predictive for shorter OS. Multivariate Cox regression revealed residual tumor, chromosome 1q gain and mitotic activity as independent predictors of both EFS and OS. Using these independent predictors of outcome, we were able to build a 3-tiered risk stratification model that separates patients with standard, intermediate and high risk, and which outperforms current stratification procedures. Conclusion The integration of defined clinical, histological and genetic parameters led to an improved risk-stratification model for posterior fossa ependymoma of childhood. After validation in independent cohorts this model may provide the basis for risk-adapted treatment of children with ependymomas of the posterior fossa.

This essay explores the material production of a single work of art, The Disgrace of Wolsey by Henry Monro (1791–1814), in the collection of Tate, in order to provide an historical perspective on the issues of artistic labour and art-educational access, which have been at the fore of contemporary cultural debates. It combines art history, sociology, and technical analysis to provide a case study in the social economics of artistic labour. Although he died young, Monro has a well-established biography and many of his works and associated documentation have been preserved. Most remarkably, there is a detailed work diary, which provides, among other things, a daily record of the production of The Disgrace of Wolsey. From this diary, we can deduce with some precision the people and materials, the time and the locations involved in the making of this painting. In its level of chronological detail, the work diary provides an exceptional insight into the working methods of a young artist in the early nineteenth century. The essay considers the social and economic factors involved, and provides a detailed commentary checking the textual record of the diary against the physical evidence of the painting itself. Technical analysis including X-radiograph, cross-sections, and surface examination are compared to technical painting treatises of the period. The essay concentrates on the compositional areas worked each day, recording a chronological account of activities. It gives insight into how the composition was built, developed, revisited, and adjusted, and suggests some of the wider lessons to be drawn from this unique documentary record about the practice of art in the early nineteenth century.

Objective: While self-efficacy plays an important role in physical activity, relatively little research has examined this construct in minorities. This study identified theoretical correlates associated with self-efficacy among insufficiently active, hypertensive Black women.Methods: Correlates of self-efficacy to: (1) overcoming barriers to physical activity; (2) making time for activity; and (3) "sticking with" physical activity were studied.Results: Sixty-one women (M=50.48+/-4.2 years) participated. We accounted for 32% of the variance in confidence in overcoming barriers. Women confident in overcoming barriers reported less worry about physical activity. The TTM processes of change were also in the model: consciousness raising, environmental reevaluation, counter conditioning, and self-liberation. We accounted for 16% of the variance in "making time" self-efficacy. An aversiveness barrier (e.g., physical activity is boring, physical activity is hard work) was the dominant variable in the model. Confidence to 'stick with' physical activity was associated with self-reevaluation (i.e., reflection on how personal values correspond to behavior). Social support and competing demands were not associated with self-efficacy.Conclusions: Consistent with Social Cognitive Theory, results suggest that self-efficacy is behavior specific and each measure likely provides unique information.Practice Implications: Interventions should be tailored to address specific self-efficacy types. [ABSTRACT FROM AUTHOR]

Background: African American women are more likely to be diagnosed at later stages of breast cancer. Methods: A total of 15 residents participated in a program to increase their self-efficacy in communication skills relevant to understanding and responding to African American cultural issues associated with mammography screening. Results: Physicians reported increasing confidence in their ability to elicit barriers to mammography; assess cultural beliefs and norms; assess perceived health benefits and emotional adjustment; engage in emotional talk; motivate; and negotiate and build partnerships with patients. Conclusions: A brief program can increase physician communication skills to meet the needs of a diverse population. [ABSTRACT FROM AUTHOR]

From 1808 the British Museum in London began regularly to open its newly established Townley Gallery so that art students could draw from the ancient sculptures housed there. This article documents and comments on this development in art education, based on an analysis of the 165 individuals recorded in the surviving register of attendance at the Museum, covering the period 1809–17. The register is presented as a photographic record, with a transcription and biographical directory. The accompanying essay situates the opening of the Museum’s sculpture rooms to students within a far-reaching set of historical shifts. It argues that this new museum access contributed to the early nineteenth-century emergence of a liberal state. But if the rhetoric surrounding this development emphasized freedom and general public benefit in the spirit of liberalization, the evidence suggests that this new level of access actually served to further entrench the “middle-classification” of art education at this historical juncture.

The review considers Andrei Pop’s Antiquity, Theatre & The Painting of Henry Fuseli. This argues for the history painter and writer Fuseli as an exemplary ‘Neopagan’, a term coined by Pop to refer to the new sense of cultural pluralism and historical relativism which emerged in Europe after the discovery of the remains of Pompeii and Herculaneum in 1748. While this perspective offers a fresh view of the artist, relating him to the emergence of modernity, and illuminates some important aspects of his work, the reviewer also suggests that the monographic focus risks re-asserting a sense of Fuseli’s exceptionalism.

Patients after solid organ transplantation (SOT) carry a substantially increased risk to develop malignant lymphomas. This is in part due to the immunosuppression required to maintain the function of the organ graft. Depending on the transplanted organ, up to 15% of pediatric transplant recipients acquire posttransplant lymphoproliferative disease (PTLD), and eventually 20% of those succumb to the disease. Early diagnosis of PTLD is often hampered by the unspecific symptoms and the difficult differential diagnosis, which includes atypical infections as well as graft rejection. Treatment of PTLD is limited by the high vulnerability towards antineoplastic chemotherapy in transplanted children. However, new treatment strategies and especially the introduction of the monoclonal anti-CD20 antibody rituximab have dramatically improved outcomes of PTLD. This review discusses risk factors for the development of PTLD in children, summarizes current approaches to therapy, and gives an outlook on developing new treatment modalities like targeted therapy with virus-specific T cells. Finally, monitoring strategies are evaluated.

Between 1990 and 2017 the four central eastern European countries (CEECs), Czechia, Hungary, Poland and Slovakia narrowed the gap in economic levels with the EU average. The key driver in most of this period was inward foreign direct investment (FDI) by multinational companies (MNCs), which brought success for export-oriented manufacturing activities. This justifies a characterisation of the resulting variety of capitalism as “dependent”, following theories of dependent development used for Latin America. However, this development brought rapid growth only for a time, still leaving a substantial lag relative to western Europe. The potential for further growth is investigated with an analysis of the strategies pursued in CEECs by those MNCs, using data on the products they export. The fact of lower wages gives them good reasons for not transferring their most advanced products and processes to CEECs and the transfer of less advanced activities in turn helps keep wage levels below those of western Europe. The implication is that CEECs may not catch up with western Europe without a change in their growth model.

This text was published in social media in January 2017 in a series of improvised, spontaneous tweets, which reached 3 million views within one month. Their common element was their trademark signature, “- With love, your Eastern European friends”, and the accompanying hashtag #LearnFromEurope. Excerpts and summaries were published by various on-line media, but this is the first time it is published as a whole.

When can we expect the European Commission to launch an infringement action against the “muzzle law”? When will the European Commission act to sanction Polish authorities’ refusal to comply with the Court of Justice’s A. K. preliminary ruling of 19 November 2019? When will the European Commission apply for financial sanctions following Polish authorities’ public refusal to immediately and fully comply with the Court of Justice’s interim relief order of 8 April 2020 in respect of the so-called “disciplinary chamber”? When will the European Commission launch an infringement action in respect of the unlawful actions of the so-called “Constitutional Tribunal”?

Die EU-Kommission hat bekannt gegeben, Polen wegen des sog. „Maulkorbgesetzes“ gegen die unabhängige Justiz mit einem Vertragsverletzungsverfahren zu überziehen – endlich, wie viele sagen würden. Ob das reicht, ob das zu spät kommt angesichts der gnadenlosen Politik der geschaffenen Fakten, die die polnische Regierung an den Tag legt, darüber spricht Max Steinbeis in der heutigen Folge unseres Krisenpodcasts mit dem Demokratie-Aktivisten MARTIN MYCIELSKI von der Open Dialogue Foundation.

Background Health Melas are community-led public health events held in the North West of England that provide health information and free health checks. This descriptive observational study evaluates whether Health Melas are able to identify undiagnosed cardiovascular disease (CVD) risk factors in hard-to-reach communities and encourage individuals to make lifestyle changes.Methods Attendees ≥18 years at three separate Health Melas in 2016–2017 were invited to participate in screening and counselling for CVD risk factors as part of a Health MOT. Information was collected about demographics, CVD risk factors, blood pressure, total cholesterol, blood sugar and attendees’ feedback. QRISK2 scoring system was used to estimate CVD risk.Results 375 attendees completed a questionnaire. The highest proportion (36.9%) of attendees were from areas of the lowest Index of Health Deprivation and Disability quintile; 38.8% were of South Asian ethnicity. Of the attendees who were eligible for a free National Health Service Health Check, 9.1% had received one. Overall, 57.5% of all attendees had a QRISK2 score ≥10% (of whom 56.9% were not on statins), 92.2% of attendees believed the Health Mela will help them to make lifestyle changes, 98.2% said they had improved their understanding of their health, and 99.6% thought the Health Mela was useful. 73.6% of those who had received a previous Health MOT reported making lifestyle changes. There was a positive correlation between South Asian ethnicity and QRISK2 score.Conclusion This study suggests the Health Melas successfully involve South Asian populations and people from a lower Index of Health Deprivation and Disability. Attendees felt the events were useful, improved understanding of their health needs and encouraged them to make lifestyle changes. High rates of modifiable CVD risk factors were newly identified and a high proportion of attendees were found to be at intermediate to high risk of CVD.

Background: Kikuchi-Fujimoto lymphadenitis (or histiocytic necrotising lymphadenitis) is a rare disease that is usually benign and self-limiting. A higher prevalence is reported amongst East Asian populations. No clear etiology has been identified although it has been associated with some viruses, rarely the Human Immunodeficiency Virus (HIV) and autoimmune pathologies. To date, there has only been a handful of cases reported globally in association with HIV, and this association is even rarer in the Asian context., Case Presentation: A 20-year-old Asian ethnic Malay male, with no past medical history, presented with daily fevers and chills for 2 weeks associated with constitutional symptoms and bilateral non-tender cervical, axillary and inguinal lymphadenopathy. Full blood count showed lymphocytosis with large granular lymphocytes. HIV viral load returned positive at >10 million copies/mL. His absolute CD4 T helper cell count was 375 cells/uL (7%). The rest of the infective and autoimmune workup were negative. Excision biopsy of an enlarged left cervical lymph node revealed Kikuchi lymphadenitis in the proliferative phase, with no evidence of lymphoproliferative disease. He was started on anti-retroviral therapy with resolution of the lymphadenopathy in 3 months., Conclusion: We present a case of Kikuchi lymphadenitis associated with HIV. This highlights that Kikuchi lymphadenitis may mimic sinister pathologies (such as tuberculosis and lymphoma) and that it needs to be considered in the differential diagnosis before empirical treatment for tuberculosis or invasive investigations for lymphoma are done., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Obesity continues to be a significant public health challenge. While weight loss medications have been studied and available for several years, the newest generation of highly effective anti-obesity medications (AOMs) will shift how behavioral science professionals approach obesity treatment and research. With the unique skill set of behavioral science professionals, this commentary suggests ways to integrate behavioral science into the rapidly evolving landscape of AOM use to accelerate better obesity care and generate new lines of research. The goal of this commentary is to stimulate discussion and encourage responsive and relevant action to improve population health., (© Society of Behavioral Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In this paper, we present a novel approach for the optimal camera selection in video games. The new approach explores the use of information theoretic metrics f-divergences, to measure the correlation between the objects as viewed in camera frustum and the ideal or target view. The f-divergences considered are the Kullback-Leibler divergence or relative entropy, the total variation and the χ2 divergence. Shannon entropy is also used for comparison purposes. The visibility is measured using the differential form factors from the camera to objects and is computed by casting rays with importance sampling Monte Carlo. Our method allows a very fast dynamic selection of the best viewpoints, which can take into account changes in the scene, in the ideal or target view, and in the objectives of the game. Our prototype is implemented in Unity engine, and our results show an efficient selection of the camera and an improved visual quality. The most discriminating results are obtained with the use of Kullback-Leibler divergence.

Purpose: Adjuvant endocrine therapy (AET) increases sexual health challenges for women with early-stage breast cancer. Black women are more likely than women of other racial/ethnic groups to report adverse symptoms and least likely to initiate and maintain AET. Little is known about how sexual health challenges influence patient-clinician communication and treatment adherence. This study explores facilitators of and barriers to patient-clinician communication about sexual health and how those factors might affect AET adherence among Black women with early-stage breast cancer., Methods: We conducted 32 semi-structured, in-depth interviews among Black women with early-stage breast cancer in the U.S. Mid-South region. Participants completed an online questionnaire prior to interviews. Data were analyzed using thematic analysis., Results: Participants' median age was 59 (range 40-78 years, SD = 9.0). Adverse sexual symptoms hindered participants' AET adherence. Facilitators of patient-clinician communication about sexual health included female clinicians and peer support. Barriers included perceptions of male oncologists' disinterest in Black women's sexual health, perceptions of male oncologists' biased beliefs about sexual activity among older Black women, cultural norms of sexual silence among Southern Black women, and medical mistrust., Conclusions: Adverse sexual symptoms and poor patient-clinician communication about sexual health contribute to lower AET adherence among Black women with early-stage breast cancer. New interventions using peer support models and female clinicians trained to discuss sexual health could ameliorate communication barriers and improve treatment adherence., Implications for Cancer Survivors: Black women with early-stage breast cancer in the U.S. Mid-South may require additional resources to address sociocultural and psychosocial implications of cancer survivorship to enable candid discussions with oncologists., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The Emotional Well-Being and Economic Burden (EMOT-ECON) Research Network is one of six research networks funded by the National Institutes of Health (NIH) to advance research about emotional well-being (EWB), and the only one that focuses on addressing how economic burden due to disease or illness affects EWB. The network convened researchers, patients, patient advocates, health care providers and other stakeholders from across the US to discuss the significance of addressing the impact of the economic burden of disease on EWB, the complexity of this prevalent problem for patients and families, and the research gaps that still need to be studied to ultimately develop strategies to reduce the impact of economic burden of disease on EWB and health. Participants identified some important future areas of research as those investigating: (i) prevalent and relevant emotions for patients experiencing economic burden of disease and financial hardship, and how their broader outlook on life is impacted; (ii) constructs and contexts that influence whether the economic burden is stressful; (iii) strategies to deal and cope and their positive or negative effects on EWB and health; and (iv) multi-level and multi-stakeholder interventions to address economic factors (e.g., costs, ability to pay), administrative burdens, education and training, and especially patients' emotional as well as financial status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pisu, Liang, Pressman, Ryff, Patel, Hussein, Williams, Henrikson, Schoenberger, Pracht, Bradshaw, Carpenter, Matthis, Schwartz and Martin.)

Objective: To facilitate replication and future intervention design of web-based multibehavior lifestyle interventions, we describe the rationale, development, and content of the A i M , P lan, and act on LIF est Y les (AMPLIFY) Survivor Health intervention which provides healthy eating and exercise behavior change support for older cancer survivors. The intervention promotes weight loss, improvements in diet quality, and meeting exercise recommendations., Methods: The Template for Intervention Description and Replication (TIDieR) checklist was used to provide a comprehensive description of the AMPLIFY intervention, consistent with CONSORT recommendations., Results: A social cognitive theory web-based intervention founded on the core components of efficacious print and in-person interventions was conceptualized and developed through an iterative collaboration involving cancer survivors, web design experts, and a multidisciplinary investigative team. The intervention includes the AMPLIFY website, text and/or email messaging, and a private Facebook group. The website consists of: (1) Sessions (weekly interactive e-learning tutorials); (2) My Progress (logging current behavior, receiving feedback, setting goals); (3) Tools (additional information and resources); (4) Support (social support resources, frequently asked questions); and (5) Home page. Algorithms were used to generate fresh content daily and weekly, tailor information, and personalize goal recommendations. An a priori rubric was used to facilitate intervention delivery as healthy eating only (24 weeks), exercise only (24 weeks), or both behaviors concurrently over 48 weeks., Conclusions: Our TIDieR-guided AMPLIFY description provides pragmatic information helpful for researchers designing multibehavior web-based interventions and enhances potential opportunities to improve such interventions., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Symptom burden differences may contribute to racial disparities in breast cancer survival. We compared symptom changes from before to during chemotherapy among women with breast cancer., Methods: This observational study followed a cohort of Black and White women diagnosed with Stage I-III, hormone receptor-positive breast cancer from a large cancer center in 2007 to 2015, and reported symptoms before and during chemotherapy. We identified patients who experienced a one-standard deviation (SD) increase in symptom burden after starting chemotherapy using four validated composite scores (General Physical Symptoms, Treatment Side Effects, Acute Distress, and Despair). Kitagawa-Blinder-Oaxaca decomposition was used to quantify race differences in symptom changes explained by baseline characteristics (sociodemographic, baseline scores, cancer stage) and first-line chemotherapy regimens., Results: Among 1,273 patients, Black women (n = 405, 31.8%) were more likely to report one-SD increase in General Physical Symptoms (55.6% vs. 48.2%, P = 0.015), Treatment Side Effects (74.0% vs. 63.4%, P < 0.001), and Acute Distress (27.4% vs. 20.0%, P = 0.010) than White women. Baseline characteristics and first-line chemotherapy regimens explained a large and significant proportion of the difference in Acute Distress changes (93.7%, P = 0.001), but not General Physical Symptoms (25.7%, P = 0.25) or Treatment Side Effects (16.4%, P = 0.28)., Conclusions: Black women with early-stage breast cancer were more likely to experience significant increases in physical and psychological symptom burden during chemotherapy. Most of the difference in physical symptom changes remained unexplained by baseline characteristics, which suggests inadequate symptom management among Black women., Impact: Future studies should identify strategies to improve symptom management among Black women and reduce differences in symptom burden. See related commentary by Rosenzweig and Mazanec, p. 157., (©2022 American Association for Cancer Research.)

Introduction: Cancer remains a substantial burden on society. Our objective was to update projections on the number of new cancer diagnoses in the United States by age, race, ethnicity, and sex through 2040., Materials and Methods: Population-based cancer incidence data were obtained using Surveillance, Epidemiology, and End Results (SEER) data. Population estimates were made using the 2010 US Census data population projections to calculate future cancer incidence. Trends in age-adjusted incidence rates for 23 cancer types along with total cancers were calculated and incorporated into a second projection model., Results: If cancer incidence remains stable, annual cancer diagnoses are projected to increase by 29.5% from 1.86 million to 2.4 million between 2020 and 2040. This increase outpaces the projected US population growth of 12.3% over the same period. The population of older adults is projected to represent an increasing proportion of total cancer diagnoses with patients ≥65 years old comprising 69% of all new cancer diagnoses and patients ≥85 years old representing 13% of new diagnoses by 2040. Cancer diagnoses are projected to increase in racial minority groups, with a projected 44% increase in Black Americans (from 222,000 to 320,000 annually), and 86% in Hispanic Americans (from 175,000 to 326,000 annually)., Discussion: The landscape of cancer care will continue to change over the next several decades. The burden of disease will remain substantial, and the growing proportion of older and minority patients with cancer remains of particular interest. These projections should help guide future health policy and research priorities., Competing Interests: Declaration of Competing Interest There are no conflicts of interest related to this study. Disclosures include: Benjamin D. Smith is supported by a grant from the Cancer Prevention and Research Institute of Texas (RP160674) and the NIHR01 CA207216-01 and is an Andrew Sabin Family Fellow. He has an equity interest in Oncora Medical and received prior research funding from Varian Medical Systems, both unrelated to the current submission. Grant R. Williams received honorium from Carevive Systems unrelated to the current submission. Yuefeng Wang is a consultant for MASEP and on the advisory board for Novocure unrelated to this submission. Matthew T. Ballo is a consultant for Novocure unrelated to this submission. Noam A. VanderWalde is a consultant and advisory board member for Concerto Health AI unrelated to this submission., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: This scoping review of reviews aims to describe the current landscape of measures of emotional well-being (EWB)., Methods: Following established practices for scoping reviews, we searched the PsycInfo, ERIC, Scopus and PubMed databases in June and July 2021 for reviews of measures of EWB that described their review methods and psychometric properties of included measures. From each eligible article, two coders independently extracted the authors' (1) definition of EWB, (2) purpose for the review, (3) methods (eg, search terms, inclusion and exclusion criteria), (4) identified measures (including any noted adaptations) and (5) the scope of psychometric information presented. Descriptive and content analyses were used to examine data., Results: Forty-nine reviews were included in this scoping review. Reviews included anywhere between 1 and 34 measures of EWB and 135 unique EWB measures were captured across all reviews. We found that there was no consistent definition of EWB, identified measures varied widely and reviews were published in a range of disciplines. Psychometric evidence varied as did authors' purposes for conducting the reviews., Conclusions: Overall, these reviews suggest that literature on EWB measurement is disjointed and diffuse. Conceptual integration and harmonisation of measures is needed to advance knowledge of EWB and its measurement., Trial Registration Numbers: 10.17605/OSF.IO/BQDS7 and 10.17605/OSF.IO/WV8PF., Competing Interests: Competing interests: CDW-M has served as a consultant to the non-profit organisation Healthy Minds Innovations., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Our target article (Park et al., this issue) described the process of developing a provisional conceptualization of emotional well-being (EWB). In that article, we considered strengths and gaps in current perspectives on a variety of related concepts and ways that the proposed conceptualization of EWB informs our evaluation of measures and methods of assessment and identification of its causes and consequences. We concluded with recommendations for moving the framework and the field forward. Eight rich, thoughtful, and highly engaged commentaries addressed the target article. Collectively, these commentaries illustrate both points of consensus and areas of substantial disagreement, providing a potential roadmap for continued work. In this response, we summarize key issues raised and highlight those points raised by multiple commentators or that we considered seminal to advancing future discussion and research., Competing Interests: Conflicts of InterestNone to disclose., (© The Society for Affective Science 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Assess the feasibility, acceptability, and preliminary efficacy of a healthy lifestyle website, SurvivorSHINE ( www.survivorshine.org ), for cancer survivors using a mixed-methods approach. Formative research included a comprehensive literature review and four focus groups on website preferences with diagnosis-diverse cancer survivors (N = 17). Their feedback informed a web adaptation of a telephone counseling and mailed-print lifestyle intervention previously found effective for cancer survivors. The resulting web-based intervention was examined in a 3-week, single-arm trial among 41 cancer survivors. Assessments of physical activity, diet, body weight, and knowledge related to exercise and diet guidelines for cancer survivors occurred at baseline and 3 weeks later, along with exit interviews. Themes from focus groups indicated cancer survivors' desire for easy-to-use, interactive web-based platforms to access credible diet and exercise information. The study sample was recruited within 12 months, and study retention was high (85.4%). Participants showed significant pre- to post-test improvements in diet and exercise knowledge (t = 5.31, p < .0001) and physical activity (t = 2.40, p = .02). Improvements in body weight and some dietary components (red meat, alcohol) were observed, but did not reach statistical significance. Results support the feasibility and acceptability of SurvivorSHINE. The significant increases in healthy lifestyle knowledge and physical activity found in the current study are promising, but a larger, randomized-controlled trial is needed to determine efficacy., (© 2021. American Association for Cancer Education.)

Psychological aspects of well-being are increasingly recognized and studied as fundamental components of healthy human functioning. However, this body of work is fragmented, with many different conceptualizations and terms being used (e.g., subjective well-being, psychological well-being). We describe the development of a provisional conceptualization of this form of well-being, here termed emotional well-being (EWB), leveraging prior conceptual and theoretical approaches. Our developmental process included review of related concepts and definitions from multiple disciplines, engagement with subject matter experts, consideration of essential properties across definitions, and concept mapping. Our conceptualization provides insight into key strengths and gaps in existing perspectives on this form of well-being, setting a foundation for evaluating assessment approaches, enhancing our understanding of the causes and consequences of EWB, and, ultimately, developing effective intervention strategies that promote EWB. We argue that this foundation is essential for developing a more cohesive and informative body of work on EWB., Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-022-00163-0., Competing Interests: Conflict of InterestNot applicable., (© The Society for Affective Science 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: Prior cancer research is limited by inconsistencies in defining rurality. The purpose of this study was to describe the prevalence of cancer risk factors and cancer screening behaviors across various county-based rural classification codes, including measures reflecting a continuum, to inform our understanding of cancer disparities according to the extent of rurality., Methods: Using an ecological cross-sectional design, we examined differences in cancer risk factors and cancer screening behaviors from the Behavioral Risk Factor Surveillance System and National Health Interview Survey (2008-2013) across rural counties and between rural and urban counties using four rural-urban classification codes for counties and county-equivalents in 2013: U.S. Office of Management and Budget, National Center for Health Statistics, USDA Economic Research Service's rural-urban continuum codes, and Urban Influence Codes., Results: Although a rural-to-urban gradient was not consistently evident across all classification codes, the prevalence of smoking, obesity, physical inactivity, and binge alcohol use increased (all p trend  < 0.03), while colorectal, cervical and breast cancer screening decreased (all p trend  < 0.001) with increasing rurality. Differences in the prevalence of risk factors and screening behaviors across rural areas were greater than differences between rural and urban counties for obesity (2.4% vs. 1.5%), physical activity (2.9% vs. 2.5%), binge alcohol use (3.4% vs. 0.4%), cervical cancer screening (6.8% vs. 4.0%), and colorectal cancer screening (4.4% vs. 3.8%)., Conclusions: Rural cancer disparities persist across multiple rural-urban classification codes, with marked variation in cancer risk factors and screening evident within rural regions. Focusing only on a rural-urban dichotomy may not sufficiently capture subpopulations of rural residents at greater risk for cancer and cancer-related mortality., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Importance: Adjuvant endocrine therapy (AET) reduces breast cancer recurrence, but symptom burden is a key barrier to adherence. Black women have lower AET adherence and worse health outcomes than White women., Objective: To investigate the association between symptom burden and AET adherence differences by race., Design, Setting, and Participants: A retrospective cohort study using electronic health records with patient-reported data from a large cancer center in the US. Patients included Black and White women initiating AET therapy for early-stage breast cancer from August 2007 to December 2015 who were followed for 1 year from AET initiation. Sixty symptoms classified into 7 physical and 2 psychological symptom clusters were evaluated. For each cluster, the number of symptoms with moderate severity at baseline, and symptoms with 3-point or greater increases during AET were counted. Adherence was measured as the proportion of days covered by AET during the first-year follow-up. Multivariable regressions for patients' adherence adjusting for race, symptom measures, sociodemographic characteristics, and clinical characteristics were conducted. Kitagawa-Blinder-Oaxaca decomposition was used to quantify racial differences in adherence explained by symptoms and patient characteristics. Analyses were conducted from July 2021 to January 2022., Exposures: Physical and psychological symptoms at baseline and changes during AET., Results: Among 559 patients (168 [30.1%] Black and 391 [69.9%] White; mean [SD] age 65.5 [12.1] years), Black women received diagnoses younger (mean [SD] age at diagnosis, 58.7 [13.7] vs 68.5 [10.0] years old) than White women, with more advanced stages (30 Black participants [17.9%] vs 31 White participants [7.9%] had stage III disease at diagnosis), and lived in areas with fewer adults attaining high school education (mean [SD], 78.8% [7.8%] vs 84.0% [9.3%]). AET adherence in the first year was 78.8% for Black and 82.3% for White women. Black women reported higher severity in most symptom clusters than White women. Neuropsychological, vasomotor, musculoskeletal, cardiorespiratory, distress, and despair symptoms at baseline and increases during the follow-up were associated with 1.2 to 2.6 percentage points decreases in adherence, which corresponds to 4 to 9 missed days receiving AET in the first year. After adjusting for psychological symptoms, being Black was associated with 6.5 percentage points higher adherence than being White., Conclusions and Relevance: In this cohort study, severe symptoms were associated with lower AET adherence. Black women had lower adherence rates that were explained by their higher symptom burden and baseline characteristics. These findings suggest that better symptom management with a focus on psychological symptoms could improve AET adherence and reduce racial disparities in cancer outcomes.

Purpose: Though lay navigation programs have proven beneficial for individuals during cancer treatment, little is known about the effects of lay navigation on health care utilization and Medicare spending among older adults during cancer survivorship., Methods: This retrospective cohort study used administrative claims data to evaluate a lay navigation program implemented from 2012 to 2015 at 12 academic and community cancer centers in the Southeast. Medicare beneficiaries age ≥65 years navigated during survivorship were compared to propensity score-matched, non-navigated cancer survivors. Quarterly trends in Medicare spending were estimated using repeated measures mixed models. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated using repeated measures generalized linear models for quarterly emergency room (ER) visits and hospitalizations., Results: Medicare spending for navigated (n = 3255) versus non-navigated older cancer survivors (n = 3255) was initially higher but declined faster by $513 per patient per quarter (95% CI -$616, -$410). Per patient per quarter risk of ER visits decreased by 11% (RR 0.89, 95% CI 0.86, 0.92) and hospitalizations decreased by 16% (RR 0.84, 95% CI 0.81, 0.88) over time comparing navigated versus non-navigated patients. Similar results were seen for patients enrolled in navigation post-treatment (N = 1893)., Conclusions: In older cancer survivors receiving care in the Deep South, patients receiving lay navigation compared to those non-navigated had significant reductions in Medicare spending, hospitalizations, and ER visits., Implications for Cancer Survivors: Though much emphasis has been placed on lay navigation during initial cancer treatment, navigation is needed throughout survivorship due to the high costs and health care utilization that persist post-treatment., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Radiation treatment interruption associated with unplanned hospitalization remains understudied. The intent of this study was to benchmark the frequency of hospitalization-associated radiation therapy interruptions (HARTI), characterize disease processes causing hospitalization during radiation, identify factors predictive for HARTI, and localize neighborhood environments associated with HARTI at our academic referral center., Methods and Materials: This retrospective review of electronic health records provided descriptive statistics of HARTI event rates at our institutional practice. Uni- and multivariable logistic regression models were developed to identify significant factors predictive for HARTI. Causes of hospitalization were established from primary discharge diagnoses. HARTI rates were mapped according to patient residence addresses., Results: Between January 1, 2015, and December 31, 2017, 197 HARTI events (5.3%) were captured across 3729 patients with 727 total missed treatments. The 3 most common causes of hospitalization were malnutrition/dehydration (n = 28; 17.7%), respiratory distress/infection (n = 24; 13.7%), and fever/sepsis (n = 17; 9.7%). Factors predictive for HARTI included African-American race (odds ratio [OR]: 1.48; 95% confidence interval [CI], 1.07-2.06; P  = .018), Medicaid/uninsured status (OR: 2.05; 95% CI, 1.32-3.15; P  = .0013), Medicare coverage (OR: 1.7; 95% CI, 1.21-2.39; P  = .0022), lung (OR: 5.97; 95% CI, 3.22-11.44; P < .0001), and head and neck (OR: 5.6; 95% CI, 2.96-10.93; P < .0001) malignancies, and prescriptions >20 fractions (OR: 2.23; 95% CI, 1.51-3.34; P < .0001). HARTI events clustered among Medicaid/uninsured patients living in urban, low-income, majority African-American neighborhoods, and patients from middle-income suburban communities, independent of race and insurance status. Only the wealthiest residential areas demonstrated low HARTI rates., Conclusions: HARTI disproportionately affected socioeconomically disadvantaged urban patients facing a high treatment burden in our catchment population. A complementary geospatial analysis also captured the risk experienced by middle-income suburban patients independent of race or insurance status. Confirmatory studies are warranted to provide scale and context to guide intervention strategies to equitably reduce HARTI events., (© 2022 The Authors.)

Background: Scalable, multiple behavior change interventions are needed to address poor diet, inactivity, and excess adiposity among the rising number of cancer survivors. Efficacy-tested diet (RENEW) and exercise (BEAT Cancer) programs were adapted for web delivery among middle-aged and older cancer survivors for the AMPLIFI study, a National Cancer Institute-funded, multi-site, program project., Methods: Throughout the continental U.S., survivors of several obesity-related cancers are being recruited for three interconnected randomized controlled trials (RCTs). Projects 1 and 2 test 6-month diet or exercise interventions versus a wait-list control condition. Upon completion of the 6-month study period, the intervention participants receive the next behavior change sequence (i.e., diet receives exercise, exercise receives diet) and the wait-list control arm initiates a 12-month combined diet and exercise intervention. Project 3 tests the efficacy of the sequential versus simultaneous interventions. Assessments occur at baseline and semi-annually for up to 2-years and include: body mass index, health behaviors (diet quality, accelerometry-assessed physical activity/sleep), waist circumference, D3 creatine-assessed muscle mass, physical performance, potential mediators/moderators of treatment efficacy, biomarkers of inflammation and metabolic regulation, health care utilization, cost, and overall health. Four shared resources support AMPLIFI RCTs: 1) Administrative; 2) Adaptation, Dissemination and Implementation; 3) Recruitment and Retention; and 4) Assessment and Analysis., Discussion: Representing a new generation of RCTs, AMPLIFI will exclusively use remote technologies to recruit, intervene and assess the efficacy of the newly-adapted, web-based diet and exercise interventions and determine whether sequential or combined delivery works best for at-risk (older, rural, racial minority) cancer survivors., Trial Registration: ClinicalTrials.gov , NCT04000880 . Registered 27 June 2019., (© 2022. The Author(s).)