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Carielle Joy Rio,1 Taichi Goto,1 Chao-Pin Hsiao,2 Alexander LR Ross,1 Leorey N Saligan2 1National Institute of Nursing Research, Division of Intramural Research, National Institutes of Health, Bethesda, MD, USA; 2Case Western Reserve University School of Nursing, Cleveland, OH, USACorrespondence: Leorey N Saligan, National Institute of Nursing Research, Division of Intramural Research, National Institutes of Health, Building 3, Room 5E14, 3 Center Drive, Bethesda, MD, 20892, USA, Tel/Fax +1 301-451-1685, Email saliganl@mail.nih.govPurpose: Prostate cancer and its treatment may affect patients’ sexual function and social wellbeing. This study investigated the relationship between social/family wellbeing and sexual health in patients with prostate cancer. Additionally, the moderating effect of clinical characteristics on this relationship was also explored.Patients and Methods: This is a descriptive correlational study using baseline data of a longitudinal study enrolling 137 patients with prostate cancer. Sexual Function (SF) and Sexual Function Distress (SFD) data were collected using the Symptom Index questionnaire. Demographic data were obtained during study intake and clinical data were obtained from chart review. Bivariate correlation determined the correlations among continuous demographic/clinical data, social/family wellbeing, and sexual health. Moderated regression analysis determined the moderating effects of clinical characteristics on the relationship of social/family wellbeing and sexual health.Results: Moderate positive correlation was found between social/family wellbeing and SF, whereas a weak negative correlation was noted between social/family wellbeing and SFD. Depression was significantly correlated with social/family wellbeing and SFD. Both sexual health domains were significantly correlated with Gleason score. A significant difference was noted in the social/family wellbeing and both SF and SFD in participants receiving androgen deprivation therapy (ADT) compared to those not receiving ADT. Concomitant ADT use was the only clinical characteristic found to be a significant moderator of the relationship between social/family wellbeing and SFD, but none of the clinical characteristics was found to have a moderating effect on the relationship of social/family wellbeing and SF. Among patients who were not receiving ADT, high social/family wellbeing was associated with low SFD. Patients who were receiving ADT reported slightly higher SFD despite having higher social/family wellbeing.Conclusion: Ensuring sexual health in patients with prostate cancer requires a comprehensive approach to address factors contributing to sexual health such as side effects of treatment and family wellbeing.Keywords: sexual function, sexual function distress, family health, male reproductive health

Nada Lukkahatai,1 Brian Walitt,2 Enrique J Deandrés-Galiana,3 Juan Luis Fernández-Martínez,3 Leorey N Saligan2 1Acute and Chronic Care, Johns Hopkins School of Nursing, Baltimore, MD, USA; 2Symptoms Biology Unit, National Institute of Nursing Research (NINR), Bethesda, MD, USA; 3Group of Inverse Problems, Optimization and Machine Learning, Applied Mathematics, University of Oviedo, Oviedo, Spain Objectives: Fibromyalgia syndrome (FMS) is a chronic and often debilitating condition that is characterized by persistent fatigue, pain, bowel abnormalities, and sleep disturbances. Currently, there are no definitive prognostic or diagnostic biomarkers for FMS. This study attempted to utilize a novel predictive algorithm to identify a group of genes whose differential expression discriminated individuals with FMS diagnosis from healthy controls. Methods: Secondary analysis of gene expression data from 28 women with FMS and 19 age- and race-matched healthy women. Expression of discriminatory genes were identified using fold-change differential and Fisher’s ratio (FR). Discriminatory accuracy of the differential expression of these genes was determined using leave-one-out-cross-validation. Functional networks of the discriminating genes were described from the Ingenuity’s Knowledge Base. Results: The small-scale signature contained 57 genes whose expressions were highly discriminatory of the FMS diagnosis. The combination of these high discriminatory genes with FR higher than 1.45 provided a leave-one-out-cross-validation accuracy for the FMS diagnosis of 85.11%. The discriminatory genes were associated with 3 canonical pathways: hepatic stellate cell activation, oxidative phosphorylation, and airway pathology related to COPD. Conclusion: The discriminating genes, especially the 2 with the highest accuracy, are associated with mitochondrial function or oxidative phosphorylation and glutamate signaling. Further validation of the clinical utility of this finding is warranted. Keywords: chronic pain, machine learning, medically unexplained symptoms, microarray

Posttraumatic stress disorder (PTSD) commonly occurs in primary care patients. Although these symptoms are often observed by NPs and other primary care providers, PTSD is not routinely assessed in primary care. [ABSTRACT FROM AUTHOR]

Seasonal affective disorder is characterized by an onset of recurrent major depressive episodes during the fall or winter, followed by a full remission or hypomanic/manic episode in the spring or summer. It is essential to determine the time of onset and remission of depressive episodes, including a confirmation that symptoms follow a seasonal pattern for at least 2 years. [ABSTRACT FROM AUTHOR]

Ocular hyperemia, or red eye, is a common complaint of patients evaluated in a primary care clinic. The condition can be attributed to multiple causes; however, a thorough evaluation consisting of a history and focused physical examination can provide valuable clues to assist in the diagnosis of this sometimes complex problem. [ABSTRACT FROM AUTHOR]

Objectives: Cancer-related cognitive impairment (CRCI) is a highly prevalent and debilitating symptom reported by breast cancer survivors (BCS). The etiology of CRCI remains unclear, leading to poor symptom management. Building from prior studies, BCS with the C/C genotype of apolipoprotein E (APOE) rs7412 and the T/T genotype of brain-derived neurotrophic factor (BDNF) rs6265 were hypothesized to experience more severe CRCI. Therefore, we investigated the relationships between the severity of CRCI and polymorphisms of APOE and BDNF among BCS., Methods: This was a subanalysis of data from a larger descriptive, correlational, and cross-sectional study. Subjective and objective CRCI were measured using the Patient-Reported Outcomes Measurement Information System and CANTAB Cambridge Cognitive assessment, respectively. Buccal swab samples were collected to evaluate the single nucleotide polymorphisms. Multivariable generalized linear regression models were used to analyze data., Results: APOE rs7412 and BDNF rs6265 were significantly associated with lower self-reported cognitive abilities in a total of 353 BCS. Age was positively associated with self-reported cognitive scores, indicating that younger BCS perceived lower cognitive abilities. Individuals carrying genotype of C/T for APOE with the C/C or C/T for BDNF showed positive associations with cognitive abilities., Conclusions: Younger BCS with the C/C genotype for APOE rs7412 and the T/T genotype for BDNF rs6265 may be at risk for CRCI. Knowledge regarding predictive markers for CRCI symptoms is essential for precision symptom management. Further investigation with a longitudinal and translational design is necessary to explore the etiologies for CRCI., Implications for Nursing Practice: Integrating genetic phenotyping into routine clinical practice will provide nurses with unique opportunities to understand individual susceptibilities, and how symptoms may trigger other symptoms. Further, findings from these innovative investigations will provide symptom interventionists and implementation scientists with critical data to optimize individualized strategies for symptom prevention, detection, and management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose of Review: This focused, narrative review mostly describes our team's investigations into the potential inflammatory mechanisms that contribute to the development of cancer-related gastrointestinal (GI) mucositis and its associated symptoms. This review summarizes details of our clinical and preclinical findings to test the role of inflammation in the development and occurrence of these cancer-related conditions., Recent Findings: GI mucositis (GIM) is a common, distressing condition reported by cancer patients. GIM is often clustered with other behaviors including fatigue, pain, anorexia, depression, and diarrhea. It is hypothesized that there is a common biologic mechanism underpinning this symptom cluster. Our multi-platform investigations revealed that GIM and its associated cluster of behaviors may be triggered by local inflammation spreading systemically causing pro-inflammatory-mediated toxicities, leading to alterations in immune, metabolic, and nervous system functions and activities. For example, behavioral toxicities related to local irradiation for non-metastatic cancer may be triggered by mGluR5 activation influencing prolonged T cell as well as NF-κB transcription factor activities. Thus, interventions targeting inflammation and associated pathways may be a reasonable strategy to alleviate GIM and its symptom cluster., Summary: GIM may be a sign of a broader systemic inflammatory response triggered by cancer or its treatment. Addressing GIM and its associated symptoms primarily involves supportive care strategies focused on relieving symptoms, promoting healing, and preventing complications., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: This study examined the relationships between a single-nucleotide polymorphism (SNP) of brain-derived neurotrophic factor (BDNF) rs6265 and psychoneurological (PN) symptoms in female cancer survivors., Methods: This secondary analysis examined 393 study participants. In addition to demographic variables, self-reported PN symptom scores (anxiety, bodily pain, depression, fatigue, neuropathic pain, and sleep disturbance) were collected using the Patient-Reported Outcomes Measurement Information System and 36-Item Short-Form Health Survey. Buccal swab samples were collected to obtain genotypes for BDNF rs6265 (Val/Val, Val/Met, or Met/Met). The PN symptom scores were compared across genotypes, and the relationships were examined using a regression model. We also explored correlations between different symptoms within each genotype., Results: Participants with the Met/Met genotype reported significantly worse cancer-related fatigue and neuropathic pain, which was confirmed by rank-based regression analysis. In addition, cancer-related fatigue was correlated with other PN symptoms, particularly depression. These correlations were stronger in study participants with the Met/Met genotype than those with other genotypes., Conclusion: Our study suggests that female cancer survivors with the Met/Met genotype of BDNF rs6265 are likely to experience worse cancer-related fatigue and neuropathic pain and that cancer-related fatigue is a good predictor of co-occurring PN symptoms in this population., Implications for Cancer Survivors: Our findings advance the scientific community's understanding of cancer-related PN symptoms experienced by female cancer survivors, especially the unique role of BDNF rs6265 polymorphism in these symptoms. Our findings offer valuable insights for clinical practice that the symptom experience among female cancer survivors may vary based on BDNF genotypes., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Fatigue is a multidimensional, highly individualized symptom experience perceived by people, regardless of health status. It is the most common complaint among those seeking primary care, yet, despite being a frequently reported symptom, it remains poorly understood., Methods: This is an exploratory study utilizing a qualitative descriptive approach that aims to explore the description of fatigue from the personal experiences of 16 participants living with chronic fatigue. Themes were generated from transcripts of in-depth interviews that focused on a central question: "how would you describe your fatigue from your own experience?", Results: Analysis of the participants' interview transcripts revealed three themes. The first theme focused on fatigue as a unique personal experience, which included experiential descriptions or measures of fatigue that the participants used to describe their symptoms. The second theme focused on fatigue as an experience beyond self, which highlighted the consequences of fatigue on interpersonal interactions and the performance of social roles, as well as the potential of utilizing social support to cope with the limitations caused by this condition. The last theme was on living with fatigue, which focused on ways participants attempted to discern their condition and manage the consequences of fatigue., Discussion: Experiences of chronic fatigue have patterns and personal meanings that vary between individuals. Caring for persons experiencing chronic fatigue requires acknowledgment of unique personal experiences and coping strategies. Due to the nature of the method, the results of this study are not generalizable and only reflect the experiences of the participants., 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 © 2024 Rio, Gehling, Blumhorst, Ross and Saligan.)

Background: Older cancer survivors in general are at greater risk for cancer-related cognitive impairment (CRCI), yet few studies have explored its association with health outcomes. This study examined the association between subjective and objective measures of cognitive function and physical function, frailty, and quality of life (QoL) among older breast cancer survivors., Materials and Methods: Older breast cancer survivors who reported cognitive concerns completed surveys on patient-reported cognitive function, physical function, frailty, and QoL as well as objective tests of visuospatial working memory and sustained attention. Data were analyzed using descriptive statistics and separate linear regression models., Results: A total of 219 female breast cancer survivors completed the study. Perceived cognitive abilities were associated with better physical function, frailty, and QoL ( p ≤ 0.001) while cognitive concerns were negatively related with these metrics ( p ≤ 0.001). Poorer visuospatial working memory and sustained attention were linked to increased frailty ( p ≤ 0.001-0.01), whereas poorer sustained attention was associated with poorer physical function ( p < 0.01)., Conclusions: Older breast cancer survivors with perceived cognitive impairment and poorer cognitive performance reported poorer physical functioning, increased frailty, and poorer QoL. These findings underscore the importance of assessing cognitive concerns and their associated outcomes in older breast cancer survivors.

Purpose: Cancer-related fatigue (CRF) is challenging to diagnose and manage due to a lack of consensus on its definition and assessment. The objective of this scoping review is to summarize how CRF has been defined and assessed in adult patients with cancer worldwide., Methods: Four databases (PubMed, Embase, CINAHL Plus, PsycNet) were searched to identify eligible original research articles published in English over a 10-year span (2010-2020); CRF was required to be a primary outcome and described as a dimensional construct. Each review phase was piloted: title and abstract screening, full-text screening, and data extraction. Then, two independent reviewers participated in each review phase, and discrepancies were resolved by a third party., Results: 2923 articles were screened, and 150 were included. Only 68% of articles provided a definition for CRF, of which 90% described CRF as a multidimensional construct, and 41% were identical to the National Comprehensive Cancer Network definition. Studies were primarily conducted in the United States (19%) and the majority employed longitudinal (67%), quantitative (93%), and observational (57%) study designs with sample sizes ≥ 100 people (57%). Participant age and race were often not reported (31% and 82%, respectively). The most common cancer diagnosis and treatment were breast cancer (79%) and chemotherapy (80%; n = 86), respectively. CRF measures were predominantly multidimensional (97%, n = 139), with the Multidimensional Fatigue Inventory (MFI-20) (26%) as the most common CRF measure and "Physical" (76%) as the most common CRF dimension., Conclusion: This review confirms the need for a universally agreed-upon definition and standardized assessment battery for CRF., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Cancer-related cognitive impairment (CRCI) is a prevalent condition that significantly impacts the quality of life of individuals who receive cancer treatment. Clinical management of CRCI presents challenges due to the absence of a standardized assessment. This study identified clinically relevant phenotypic clusters of CRCI based on subjective and objective cognitive function scores., Methods: In this cross-sectional study, participants were clustered using the VARCLUS™ based on subjective cognitive impairment assessed through the PROMIS® version 1.0 short-form subscales of cognitive abilities and cognitive concerns and the CANTAB Cambridge Cognition® scores, which included measures of visuospatial working memory capacity, visual episodic memory, new learning, working memory, executive function, and sustained attention. Each cluster's characteristics were described using demographics, physical and psychosocial factors (physical function, affect, optimism, and social support), and psychoneurological symptoms (anxiety, depression, fatigue, neuropathic pain, and sleep disturbance)., Results: We obtained five clusters from a total of 414 participants, where 99% were female, and 93% were self-reported white. Clusters 4 and 5 showed the highest PROMIS® cognitive abilities and the lowest measures of cognitive concern, while Clusters 1 and 2 showed the lowest cognitive abilities and the highest cognitive concerns. Clusters 4 and 5 had higher education, income, employment, and higher scores in physical function, positive affect, optimism, and social support. Additionally, individuals in these clusters were less prone to experience severe cancer-related psychoneurological symptoms., Conclusion: Our clustering approach, combining subjective and objective cognitive function information, shows promise in identifying phenotypes that hold clinical relevance for categorizing patient presentation of CRCI and facilitating individualized management strategies., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Patient self-reporting of health-specific information, including symptoms, allows healthcare providers to provide more timely, personalized, and patient-centered care to meet their needs. It is critical to acknowledge that symptom reporting draws from the individual's unique sociocultural background influencing how one perceives health and illness. This scoping review will explore whether racial groups with 4 chronic diseases (cardiovascular diseases, respiratory diseases, cancers, and diabetes) differ in self-reporting of psychoneurophysical (PNP) symptoms. The PNP symptoms of interest include depressive symptoms, fatigue, anxiety, pain, cognitive impairment, sleep impairment, mood impairment, irritability, and shortness of breath., Methods: Four databases will be searched by a biomedical librarian: CINAHL Plus (EBSCOhost), Embase (Elsevier), PubMed (NLM), Web of Science: Core Collection (Clarivate Analytics), and limited to publications written in the English language. Two independent reviewers will screen the records' title, abstract, and then full text and extract the data from included articles using Covidence. A third reviewer will be used for resolving disagreements. Included articles must comprise adult patients with at least one of the specified chronic diseases who self-report at least one of the specified PNP symptoms. Studies that used clinician-administered questionnaires or obtained symptom responses from primary caregiver or patient designee will be excluded. Articles on patient-reported functionality or perceived quality of life will also be excluded from the review. Two reviewers will independently extract data (e.g., demographics, study design, racial group, chronic disease, measure/scale used for self-report) from each included article using Covidence and Microsoft Excel for data cleaning and analyses., Discussion: This scoping review may potentially identify the relevant and practical implications related to clinical decision-making and health outcomes for patients experiencing the psychoneurophysical symptoms included in this study. The authors will present how the results can be utilized in clinical practice, health policy, and research planning., Systematic Review Registration: The protocol was registered on Open Science Framework (OSF) at: https://osf.io/ps7aw., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Cancer survivors are at risk of frailty because of cancer and its treatment. Understanding the factors that increase the risk of frailty is an important aspect of cancer care for the development of interventions to prevent or manage frailty, thus improving cancer survival and overall quality of life of cancer survivors. This study aimed to identify demographic, clinical, and psychosocial correlates of frailty in older, female cancer survivors., Materials and Methods: This is a sub-study focusing on the exploratory aim of a larger cross-sectional study (NURS-IIR-IUSCC-0748). A total of 213 female cancer survivors aged 59-87 years old were included from the parent study in the current analysis. Frailty, the primary outcome, was measured using the Tilburg Frailty Indicator scale. The independent variables were age, relationship status, clinical stage of cancer, treatment type, comorbidity, depression, affect, optimism, stress, and social support. Stepwise linear regression modeling identified the independent variables that were significantly associated with frailty., Results: The final regression model revealed that high patient-reported stress and depression, comorbidity, not being married or living with a partner, and low positive affect were significantly associated with worsening frailty in this population., Discussion: Understanding the context of frailty is important for the design of interventions that target factors known to be associated with frailty in older cancer survivors. Further validation with a larger and a more diverse sample from a broad spectrum of sociodemographic and clinical population would fully account for the multiple independent variables influencing frailty in cancer survivors., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare or any financial interest to report., (Published by Elsevier Ltd.)

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: Cancer-related fatigue (CRF) is a highly prevalent and debilitating symptom reported by breast cancer survivors (BCS). CRF has been associated with the co-occurrence of anxiety, depression, poor sleep quality, cognitive impairment, which are collectively termed as psychoneurophysiological (PNP) symptoms. CRF and these PNP symptoms are often reported during and after treatment with long-lasting distress. It is unclear how CRF and these PNP symptoms influence each other. This study aimed to explore predictive factors (i.e., PNP symptoms and social-demographic factors) of CRF, and test exploratory path models of the relationships of CRF with PNP symptoms (depression, anxiety, sleep disturbance, pain, and cognitive function) in BCS., Methods: This paper is part of a larger descriptive, correlational, and cross-sectional study. Validated and reliable instruments assessed CRF, depression, anxiety, sleep disturbance, pain, and cognitive function. Descriptive statistics, Pearson correlation, multiple linear regression models, and path analysis were employed., Results: Patients (N = 373) who reported less bodily pain had worst CRF (r = -0.45, p < .01). Significant predictors of CRF included depression, sleep disorder, bodily pain, perceived cognitive ability, and dispositional (state) optimism. Depression alone accounted for 31% of the variance in CRF. An integrative path model with bodily pain, neuropathic pain, CRF, and depression showed a good fit across different indices (CFI = 0.993, RMSEA = 0.047, 90% CI 0-0.12, SRMR = 0.027)., Conclusions: This study identified significant predictors of CRF and revealed a good fit mediation model with significant pathways for CRF, suggesting that a common etiology may underpin the co-occurrence of CRF with PNP symptoms (pain and depression). However, further investigation with longitudinal design is necessary to explore the causal relationships of these symptoms. Evidence-based strategies/interventions are needed to reduce or eliminate the burden of these symptoms on the lives of BCS., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Physical impairments following cancer treatment have been linked with the toxic effects of these treatments on muscle mass and strength, through their deleterious effects on skeletal muscle mitochondrial oxidative capacity. Accordingly, we designed the present study to explore relationships of skeletal muscle mitochondrial oxidative capacity with physical performance and perceived cancer-related psychosocial experiences of cancer survivors. We assessed skeletal muscle mitochondrial oxidative capacity using in vivo phosphorus-31 magnetic resonance spectroscopy ( 31 P MRS), measuring the postexercise phosphocreatine resynthesis time constant, τPCr, in 11 post-chemotherapy participants aged 34-70 years. During the MRS procedure, participants performed rapid ballistic knee extension exercise to deplete phosphocreatine (PCr); hence, measuring the primary study outcome, which was the recovery rate of PCr (τPCr). Patient-reported outcomes of psychosocial symptoms and well-being were assessed using the Patient-Reported Outcomes Measurement Information System and the 36-Item Short Form health survey (SF-36). Rapid bioenergetic recovery, reflected through a smaller value of τPCr was associated with worse depression (rho ρ = - 0.69, p = 0.018, and Cohen's d = - 1.104), anxiety (ρ = - 0.61, p = .046, d = - 0.677), and overall mental health (ρ = 0.74, p = 0.010, d = 2.198) scores, but better resilience (ρ = 0.65, p = 0.029), and coping-self efficacy (ρ = 0.63, p = 0.04) scores. This is the first study to link skeletal muscle mitochondrial oxidative capacity with subjective reports of cancer-related behavioral toxicities. Further investigations are warranted to confirm these findings probing into the role of disease status and personal attributes in these preliminary results., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Breast cancer survivors (BCS) often complain of cancer-related cognitive impairment (CRCI) during and even months after completing primary cancer treatments, particularly chemotherapy. The etiology of CRCI is unknown, but associations of CRCI with germline genetic polymorphisms have been reported, including Brain-Derived Neurotrophic Factor (BDNF) rs6265 polymorphism. The current study investigated the associations of specific BDNF rs6265 with CRCI., Methods: Cancer-related cognitive impairment was assessed using subjective reports of cognitive symptoms (the version 1.0, 8-item short-forms of the Patient-Reported Outcomes Measurement Information System®) and computerized objective cognitive function scores (CANTAB®). BDNF rs6265 genotypes were determined from buccal swabs. The associations of specific BDNF rs6265 with CRCI were examined by either one-way analysis of variance or the Kruskal-Wallis test followed by post hoc tests and rank-based regression analysis., Results: We examined 356 female BCS. The mean (SD) age was 55.6 (9.8) years old, the median (IQR) years since cancer diagnosis were 4.0 (6.0), and 331 (92.7%) were self-described as White. BCS carrying the Met/Met genotype showed poorer results on 'visual episodic memory and new learning' and 'spatial working memory and executive function.' This relationship was observed regardless of prior chemotherapy., Conclusion: Our findings suggest that carrying the BDNF rs6265 Met/Met genotype increases the risk for CRCI in BCS. These results are foundational in nature and provide important information to identify mechanisms underpinning CRCI., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Wound care management for unhoused individuals is challenging due to the lack of healthcare infrastructure to handle the unique needs of this population. Therefore, we aimed to obtain insights for best practices and to establish a care clinic that is low threshold, community-based and meets the needs of unhoused people. We employed two approaches: (1) conduct a targeted narrative review of the literature of existing or proposed community-based program models that can address the wound care needs of unhoused individuals, and (2) assess cost-effectiveness and describe the results of a survey administered to unhoused clients and their health care providers at a community-based wound care program in Honolulu, Hawai'i. The literature search and screening yielded 11 articles relevant to the topic. Per the literature, existing community-based healthcare programs were successful when: (1) wound care services were incorporated into a broader social/health program, (2) cost-effective, and (3) comprehensive services were provided. Survey results in Honolulu found that the wound care program matched the needs of the targeted population and was cost-effective. Difficulty in following clients until wound closure and the sustainability of the program, particularly the lack of insurance reimbursement for street-based services, were perceived challenges. Additionally, the lack of insurance reimbursement for street-based wound care services continues to impact sustainability. Community-based programs can be successful in addressing the wound care needs of unhoused individuals if they address complex fundamental issues. This paper highlights existing gaps in logistics and policies that must be addressed to meet the specific medical needs of these vulnerable individuals., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

This study aims to examine the feasibility of DNA methylation age as a biomarker for symptoms and resilience in cancer survivors with multiple chronic conditions (MCCs). We included ten participants from our parent study, an ongoing randomized control trial study. Participants' symptoms and resilience were assessed, and peripheral blood was collected. DNA methylation age calculation was performed using DNAge ® analysis. Data were analyzed using Spearman's correlation analysis and the Mann-Whitney U test. Participants in the intervention group tended to have a decrease in DNA methylation age and age acceleration after completing an exercise program (mean difference = -0.83 ± 1.26). The change in DNA methylation age was significantly correlated with the change in resilience score (r = -0.897, p = 0.015). The preliminary results suggest that DNA methylation age can be a potential biomarker for improving resilience in cancer survivors with multiple chronic conditions. This finding is limited by the small sample size, and a larger study is needed.

This paper aims to emphasize the need to acknowledge unique cultural and contextual meanings of physical activity to improve health outcomes in different communities. Leininger's Sunrise Model was used as the theoretical base to understand the complex cultural and contextual factors that influence physical activity. Beliefs and practices surrounding physical activity are influenced by a variety of cultural and contextual factors. Providing culturally relevant contexts to the meaning of physical activity allows opportunities for improving policies or programs that would engage individuals and communities in physical activity in culturally meaningful ways. Incorporating cultural and contextual factors is critical to promote physical activity, especially in minority and vulnerable communities., 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 Rio and Saligan.)

This scoping review was designed to synthesize the extant literature on associations between subjective and/or objective measures of cancer-related cognitive impairment (CRCI) and blood-based biomarkers in adults with non-central nervous system cancers. The literature search was done for studies published from the start of each database searched (i.e., MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, grey literature) through to October 20, 2021. A total of 95 studies are included in this review. Of note, a wide variety of biomarkers were evaluated. Most studies evaluated patients with breast cancer. A variety of cognitive assessment measures were used. The most consistent significant findings were with various subjective and objective measures of CRCI and levels of interleukin-6 and tumor necrosis factor. Overall, biomarker research is in an exploratory phase. However, this review synthesizes findings and proposes directions for future research., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Cancer-related fatigue is a prevalent, debilitating, and persistent condition. Mitochondrial dysfunction is a putative contributor to cancer-related fatigue, but relationships between mitochondrial function and cancer-related fatigue are not well understood., Objectives: We investigated the relationships between mitochondrial DNA (mtDNA) gene expression and cancer-related fatigue, as well as the effects of fish and soybean oil supplementation on these relationships., Methods: A secondary analysis was performed on data from a randomized controlled trial of breast cancer survivors 4-36 months posttreatment with moderate-severe cancer-related fatigue. Participants were randomized to take 6 g fish oil, 6 g soybean oil, or 3 g each daily for 6 weeks. At pre- and postintervention, participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire and provided whole blood for assessment of mtDNA gene expression. The expression of 12 protein-encoding genes was reduced to a single dimension using principal component analysis for use in regression analysis. Relationships between mtDNA expression and cancer-related fatigue were assessed using linear regression., Results: Among 68 participants, cancer-related fatigue improved and expression of all mtDNA genes decreased over 6 weeks with no effect of treatment group on either outcome. Participants with lower baseline mtDNA gene expression had greater improvements in cancer-related fatigue. No significant associations were observed between mtDNA gene expression and cancer-related fatigue at baseline or changes in mtDNA gene expression and changes in cancer-related fatigue., Discussion: Data from this exploratory study add to the growing literature that mitochondrial dysfunction may contribute to the etiology and pathophysiology of cancer-related fatigue., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Fatigue is a persistent and debilitating symptom following cancer treatments such as chemotherapy. Recent clinical studies have suggested a common single-nucleotide polymorphism of brain-derived neurotrophic factor (BDNF), Val66Met (rs6265), may be related to the severity of fatigue following cancer treatment. In this study, we tested transgenic mice homozygous for the human Val66Met BDNF gene and wild-type controls. We injected three doses of 5-fluorouracil (5FU) as a model of chemotherapy treatment, and we used changes in voluntary wheel running activity (VWRA) as a measure of fatigue-like behavior. Prior to 5FU injection, we found that during the baseline wheel-running period, the Val66Met mice lost more weight than WT controls. We next administered 5FU and saw a robust fatigue-like phenotype that lasted about 2 weeks. During the first week, the fatigue-like phenotype was less severe in the Val66Met mice and unrelated to the age of the mice. In contrast, during the second week after 5FU treatment, the fatigue-like phenotype was unrelated to the BDNF genotype but was more severe in middle aged mice compared to young mice. We conclude that the BDNF polymorphism may play a direct, protective role against chemotherapy-induced fatigue., 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 © 2022 Wolff, Allen, Feng and Saligan.)

Background: The role of alterations in gut microbiota composition (termed dysbiosis) has been implicated in the pathobiology of depressive symptoms; however, evidence remains limited. This cross-sectional pilot study is aimed at exploring whether depressive symptom scores changed during neoadjuvant chemotherapy and radiation therapy to treat rectal cancer, and if gut microbial taxa abundances and predicted functional pathways correlate with depressive symptoms at the end of chemotherapy and radiation therapy., Methods: 40 newly diagnosed rectal cancer patients (ages 28-81; 23 males) were assessed for depressive symptoms using the Hamilton Rating Scale for Depression (HAM-D) and provided stool samples for 16S rRNA sequencing. Gut microbiome data were analyzed using QIIME2, and correlations and regression analyses were performed in R., Results: Participants had significantly higher depressive symptoms at the end as compared to before CRT. The relative abundances of Gemella , Bacillales Family XI , Actinomyces , Streptococcus , Lactococcus , Weissella , and Leuconostocaceae were positively correlated (Spearman's rho = 0.42 to 0.32), while Coprobacter , Intestinibacter , Intestimonas , Lachnospiraceae , Phascolarctobacterium , Ruminiclostridium , Ruminococcaceae (UCG-005 and uncultured) , Tyzzerella , and Parasutterella (Spearman's rho = -0.43 to - 0.31) were negatively correlated with HAM-D scores. Of the 14 predicted MetaCyc pathways that correlated with depressive symptom scores at the end of CRT, 11 (79%) were associated with biosynthetic pathways., Conclusions: Significant bacterial taxa and predicted functional pathways correlated with depressive symptoms at the end of chemotherapy and radiation therapy for rectal cancer which warrants further examination and replication of our findings., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Velda J. Gonzalez-Mercado et al.)

Limited information is available regarding clinical and biological properties of fatigue in patients with chronic graft-versus-host disease (cGvHD). Patients with moderate-to-severe cGvHD per NIH criteria were enrolled on a cross-sectional study and categorized as "fatigued" if SF-36 vitality score was <40. Clinical and laboratory parameters of fatigued (n = 109) and nonfatigued patients (n = 72) were compared. In univariate analysis, walk velocity, NIH joint-fascia score, human activity profile, and SF-36 physical and mental health self-report scales were correlates of fatigue. No cGvHD biomarkers were associated with fatigue. NIH joint score, Lee sleep and depression questions, and PG-SGA activities and function score jointly predicted fatigue. Though higher rates of depression and insomnia were reported in the fatigued group, antidepressant or sleep aid use did not differ between groups. Survival ratio was not significantly different by fatigue status. Pathophysiology of fatigue in patients with cGvHD is complex and may involve mechanisms unrelated to disease activity. Patients with cGvHD experiencing fatigue had higher rates of untreated depression and insomnia, highlighting the need to focus clinical management of these conditions to improve health-related quality of life., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Postoperative pain and delayed healing in surgical wounds, which require complex management strategies have understudied complicated mechanisms. Here we investigated temporal changes in behavior, tissue structure, and transcriptomic profiles in a rat model of a surgical incision, using hyperalgesic behavioral tests, histological analyses, and next-generation RNA sequencing, respectively. The most rapidly (1 hour) expressed genes were the chemokines, Cxcl1 and Cxcl2. Consequently, infiltrating leukocytes were abundantly observed starting at 6 and peaking at 24 hours after incising which was supported by histological analysis and appearance of the neutrophil markers, S100a8 and S100a9. At this time, hyperalgesia was at a peak and overall transcriptional activity was most highly activated. At the 1-day timepoint, Nppb, coding for natriuretic peptide precursor B, was the most strongly upregulated gene and was localized by in situ hybridization to the epidermal keratinocytes at the margins of the incision. Nppb was basically unaffected in a peripheral inflammation model transcriptomic dataset. At the late phase of wound healing, five secreted, incision-specific peptidases, Mmp2, Aebp1, Mmp23, Adamts7, and Adamtsl1, showed increased expression, supporting the idea of a sustained tissue remodeling process. Transcripts that are specifically upregulated at each timepoint in the incision model may be potential candidates for either biomarkers or therapeutic targets for wound pain and wound healing. This study incorporates the examination of longitudinal temporal molecular responses, corresponding anatomical localization, and hyperalgesic behavioral alterations in the surgical incision model that together provide important and novel foundational knowledge to understand mechanisms of wound pain and wound healing., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Context: Although microbial-mediated disturbance of intestinal mucosal homeostasis (dysbiosis) is believed to contribute to the pathogenesis of chemotherapy and radiotherapy (CRT)-related fatigue, potential differences in the gut microbial diversity and in the abundance of gut microbial taxa between fatigued and non-fatigued patients have not been adequately examined, particularly in the rectal cancer population., Purpose: In this cross-sectional study, we aim to examine the differences in (a) gut microbial diversity and gut microbial abundances and (b) predicted functional pathways of the gut microbiome between rectal cancer participants with and without fatigue at the end of CRT., Methods: Rectal cancer patients (n = 50) provided stool samples for 16S rRNA gene sequencing and symptom ratings for fatigue at the end of CRT. Gut microbiome data were analyzed using QIIME2, LEfSe, and the R statistical package., Results: Fatigued (n = 35) participants showed enriched bacterial abundances of Eubacterium, Streptococcus, Adlercreutzia, and Actinomyces, as well as enriched abundances of the microbial sucrose degradation pathway, compared to non-fatigued patients at the end of CRT (n = 15)., Conclusions: Differentially abundant microbial taxa were identified in fatigued and non-fatigued rectal cancer participants at the end of CRT. However, the exact role of these taxa (and identification of species) in the biology of CRT-related fatigue remains to be examined.

Background: Epigenetic age acceleration has been studied as a promising biomarker of age-related conditions, including cognitive aging. This pilot study aims to explore potential cognitive aging-related biomarkers by investigating the relationship of epigenetic age acceleration and cognitive function and by examining the epigenetic age acceleration differences between successful cognitive aging (SCA) and normal cognitive aging (NCA) among Korean community-dwelling older adults (CDOAs)., Methods: We used data and blood samples of Korean CDOAs from the Korean Frailty and Aging Cohort Study. The participants were classified into two groups, SCA (above the 50th percentile in all domains of cognitive function) and NCA. The genome-wide DNA methylation profiling array using Illumina Infinium MethylationEPIC BeadChip was used to calculate the following: the DNA methylation age, universal epigenetic age acceleration, intrinsic epigenetic age acceleration (IEAA), and extrinsic epigenetic age acceleration (EEAA). We also used Pearson correlation analysis and independent t -tests to analyze the data., Results: Universal age acceleration correlated with the Frontal Assessment Battery test results ( r = -0.42, p = 0.025); the EEAA correlated with the Word List Recognition test results ( r = -0.41, p = 0.027). There was a significant difference between SCA and NCA groups in IEAA ( p = 0.041, Cohen's d = 0.82) and EEAA ( p = 0.042, Cohen's d = 0.78)., Conclusions: Epigenetic age acceleration can be used as a biomarker for early detection of cognitive decline in Korean community-dwelling older adults. Large longitudinal studies are warranted.

Purpose: The Doctor of Nursing Practice (DNP) programs have grown exponentially for the last 10 years across the United States. However, the intra-professional collaboration among DNP and PhD scholars is not clearly demonstrated in the literature as it relates to frequency, training models, and the outcomes of these collaborations on translation. The purposes of this paper are to: (1) examine the role for DNP nurses in symptom science research and (2) describe training models to cultivate the PhD-DNP collaboration to strengthen the translation of discoveries from nursing research, to facilitate implementation of discoveries, and to improve clinical practice of nurses., Methods: A targeted review of the literature was conducted to identify, (1) the role of the DNP, (2) examples of PhD-DNP collaborations, (3) training models that support collaborations, and (4) the outcomes of these intra-professional collaborations., Results: Two articles reported on PhD-DNP collaboration within a university setting; however, they did not address how the partnership was modeled. One additional article described an academic-hospital partnership model aimed at MSN-prepared advanced practice nurses (APRN) by which outcomes were measured. No examples were found outside of academic settings. The National Institute of Nursing Research (NINR) has established the Symptom Science Center (SSC) with an interest in training the next generation of symptom scientists. By developing a training curriculum through the NINR SSC, DNP-prepared students and practitioners can be exposed to the research enterprise and potentially develop early partnerships with PhD-prepared students and scholars that lead to research translation., Conclusion: The NINR Department of Intramural Research (DIR) and National Institutes of Health Clinical Center are dedicated to building stronger ties between PhD- and DNP-prepared scientists. The SSC can serve as an optimal platform to promote the collaboration of PhD and DNP nurses to advance symptom science translation., Clinical Relevance: Nurses have a remarkable role in early detection of disease progression. Training opportunities to cultivate the PhD-DNP collaboration have significant relevance for expediting the translation of nursing science to nursing practice., (Published by Elsevier Inc.)

Introduction: Fatigue is a prevalent and potentially debilitating symptom that impacts the health-related quality-of-life of individuals diagnosed with acute and chronic medical conditions. Yet, its etiologic mechanism is not fully understood. Additionally, the assessment and determination of the clinical meaning of fatigue and its multidimensionality may vary by medical condition., Methods: A scoping literature review was conducted to investigate how fatigue is defined and measured, including its dimensions, in non-oncologic medical conditions. The PubMed database was searched using keywords., Results: Overall, 8376 articles were screened at the title/abstract levels, where 293 articles were chosen for full-text review that mentioned fatigue or included fatigue measures. The review of the full text excluded 246 articles that did not assess at least one fatigue dimension using validated questionnaires and clinical tests. The final set included 47 articles. Physical fatigue was the most assessed fatigue dimension and the Multidimensional Fatigue Inventory was the most widely used questionnaire to assess fatigue in this review., Limitations: This review was limited by including only English-language publications and using PubMed as the sole database for the search., Conclusions: This review affirms that fatigue is a multidimensional construct, agnostic of medical condition, and that individual fatigue dimensions can be measured by validated clinical measures. Future research should focus on expanding the repertoire of clinical measures to assess specific fatigue dimensions., Competing Interests: There are no conflicts of interest to report.

Fatigue is a persistent and debilitating symptom following radiation therapy for prostate cancer. However, it is not well-understood how radiation targeted to a small region of the body can lead to broad changes in behavior. In this study, we used targeted pelvic irradiation of healthy male mice to test whether inflammatory signaling mediates changes in voluntary physical activity levels. First, we tested the relationship between radiation dose, blood cell counts, and fatigue-like behavior measured as voluntary wheel-running activity. Next, we used oral minocycline treatments to reduce inflammation and found that minocycline reduces, but does not eliminate, the fatigue-like behavioral changes induced by radiation. We also used a strain of mice lacking the MyD88 adaptor protein and found that these mice also showed less fatigue-like behavior than the wild-type controls. Finally, using serum and brain tissue samples, we determined changes in inflammatory signaling induced by irradiation in wild-type, minocycline treated, and MyD88 knockout mice. We found that irradiation increased serum levels of IL-6, a change that was partially reversed in mice treated with minocycline or lacking MyD88. Overall, our results suggest that inflammation plays a causal role in radiation-induced fatigue and that IL-6 may be an important mediator., Competing Interests: There are no conflicts of interest to report.

Practicing in unprecedented working environment and fighting against the COVID-19 crisis influenced the image of nursing in the general population, as well as among nurses themselves. This study aimed to describe the sense of professional identity among Chinese nursing students during the COVID-19 outbreak and to explore the relationship between psychological resilience and the sense of professional identity in this cohort. A nationwide online cross-sectional survey was conducted. Nursing students were recruited from 18 Chinese universities. The 10-item Connor-Davidson resilience scale (CD-RISC-10) evaluated psychological resilience and professional identity was assessed by the Professional Identity Questionnaire for Nursing Students (PIQNS). A total of 6348 respondents had a moderate level of professional identity to nursing (average PIQNS score at 62.02 ± 12.02). About 86% of respondents attributed the response to the COVID-19 pandemic in elevating the nursing image. Psychological resilience was the strongest contributor to professional identity (β = 0.371, P < 0.001). There was a high level of professional identity among Chinese nursing students during the COVID-19 crisis. Policy support and courses to enhance psychological resilience are critical to sustain professional identity among nursing students., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Metabolomics is the newest -omics methodology and allows for a functional snapshot of the biochemical activity and cellular state. The goal of this study is to characterize metabolomic profiles associated with cancer-related fatigue, a debilitating symptom commonly reported by oncology patients., Methods: Untargeted ultrahigh performance liquid chromatography/mass spectrometry metabolomics approach was used to identify metabolites in plasma samples collected from a total of 197 participants with or without cancer. Partial least squares-discriminant analysis (PLS-DA) was used to identify discriminant metabolite features, and diagnostic performance of selected classifiers was quantified using area under the receiver operating characteristics (AUROC) curve analysis. Pathway enrichment analysis was performed using Fisher's exact test and the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway database., Findings: The global metabolomics approach yielded a total of 1120 compounds of known identity. Significant metabolic pathways unique to fatigued cancer versus control groups included sphingolipid metabolism, histidine metabolism, and cysteine and methionine metabolism. Significant pathways unique to non-fatigued cancer versus control groups included inositol phosphate metabolism, primary bile acid biosynthesis, ascorbate and aldarate metabolism, starch and sucrose metabolism, and pentose and glucuronate interconversions. Pathways shared between the two comparisons included caffeine metabolism, tyrosine metabolism, steroid hormone biosynthesis, sulfur metabolism, and phenylalanine metabolism., Conclusions: We found significant metabolomic profile differences associated with cancer-related fatigue. By comparing metabolic signatures unique to fatigued cancer patients with metabolites associated with, but not unique to, fatigued cancer individuals (overlap pathways) and metabolites associated with cancer but not fatigue, we provided a broad view of the metabolic phenotype of cancer-related fatigue., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Radiotherapy treatment-induced intestinal injury and gut microbial perturbation/dysbiosis have been implicated in the pathobiology of cancer-related fatigue. The objective of this brief review was to explore the available evidence of the relationship between intestinal injury and self-reported fatigue, especially among cancer patients. The scientific evidence-including our own-linking gut mucosal barrier dysfunction and gut microbial perturbation/dysbiosis induced by cancer treatment with worsening of cancer related fatigue (perhaps through the gut-brain axis) is limited but promising. Emerging data suggest that lifestyle interventions and the administration of specific probiotics may favorably modulate the gut microbiota and potentially mediate beneficial effects leading to improvements in fatigue.

Pain is a common but potentially debilitating symptom, often requiring complex management strategies. To understand the molecular dynamics of peripheral inflammation and nociceptive pain, we investigated longitudinal changes in behavior, tissue structure, and transcriptomic profiles in the rat carrageenan-induced peripheral inflammation model. Sequential changes in the number of differentially expressed genes are consistent with temporal recruitment of key leukocyte populations, mainly neutrophils and macrophages with each wave being preceded by upregulation of the cell-specific chemoattractants, Cxcl1 and Cxcl2, and Ccl2 and Ccl7, respectively. We defined 12 temporal gene clusters based on expression pattern. Within the patterns we extracted genes comprising the inflammatory secretome and others related to nociceptive tissue remodeling and to sensory perception of pain. Structural tissue changes, involving upregulation of multiple collagens occurred as soon as 1-hour postinjection, consistent with inflammatory tissue remodeling. Inflammatory expression profiling revealed a broad-spectrum, temporally orchestrated molecular and cellular recruitment process. The results provide numerous potential targets for modulation of pain and inflammation. PERSPECTIVE: This study investigates the highly orchestrated biological response during tissue inflammation with precise assessment of molecular dynamics at the transcriptional level. The results identify transcriptional changes that define an evolving inflammatory state in rats. This study provides foundational data for identifying markers of, and potential treatments for, inflammation and pain in patients., (Published by Elsevier Inc.)

Older adults suffer from multiple symptoms, which negatively affects their health-related quality of life. The single-symptom management approach has been less than effective. The data of 2362 Korean community-dwelling older adults aged 70 and above were analyzed in the Korean Frailty and Aging Cohort Study (KFACS) study. A cluster analysis, correlation analysis, and logistic regression were used to analyze the data. We found three symptom clusters: high symptom burden (HSB, n = 1032); pain and fatigue group (PAF, n = 566); and the sleep deprivation group (SDP, n = 764). Participants in the HSB group are more likely to be of old age (OR = 1.1), be female (OR = 2.4), live in a rural area (OR = 1.4), have low physical activity (OR = 0.9), and have multiple chronic conditions (OR = 1.5). The clinical blood markers analysis showed a negative relationship among the physical health, free T4 ( r = -0.083, p < 0.01) and insulin ( r = -0.084, p < 0.01). The sex-specific blood markers analysis showed differences among three clusters. While free testosterone (male: r = 0.124, female: r = 0.110, p < 0.05) and dehydroepiandrosterone (DHEA) (male: r = 0.352 and female: r = 0.134, p < 0.05) were associated with physical health in the HSB group, only free testosterone was associated with mental health (male: r = -0.093, and female: r = -0.116, p < 0.05) in the SDP group. These findings suggest the potential role of the patient's sex and sex hormones in symptoms of Korean community-dwelling older adults. Understanding the symptom profiles and impact of biopsychosocial factors may enhance precision symptom management.

Purpose: To examine a) whether there are significant differences in the severity of symptoms of fatigue, sleep disturbance, or depression between patients with rectal cancer who develop co-occurring symptoms and those with no symptoms before and at the end of chemotherapy and radiation therapy (CRT); b) differences in gut microbial diversity between those with co-occurring symptoms and those with no symptoms; and c) whether before-treatment diversity measurements and taxa abundances can predict co-occurrence of symptoms., Methods: Stool samples and symptom ratings were collected from 31 patients with rectal cancer prior to and at the end of (24-28 treatments) CRT. Descriptive statistics were computed and the Mann-Whitney U test was performed for symptoms. Gut microbiome data were analyzed using R's vegan package software., Results: Participants with co-occurring symptoms reported greater severity of fatigue at the end of CRT than those with no symptoms. Bacteroides and Blautia2 abundances differed between participants with co-occurring symptoms and those with no symptoms. Our random forest classification (unsupervised learning algorithm) predicted participants who developed co-occurring symptoms with 74% accuracy, using specific phylum, family, and genera abundances as predictors., Conclusion: Our preliminary results point to an association between the gut microbiota and co-occurring symptoms in rectal cancer patients and serves as a first step in potential identification of a microbiota-based classifier.

Purpose: Effective management of wound pain is essential for optimal wound healing. Nevertheless, the outcomes of wound pain interventions are based on subjective measures, which can prove problematic in patients with cognitive impairment. Identification of biomarkers associated with wound pain and wound healing can be used to more objectively estimate wound pain and contribute to the development of precise management options to reduce wound pain and promote wound healing. This scoping review aimed to identify wound pain and wound healing biomarkers from wound exudates and to describe different wound collection methods to identify these biomarkers., Methods: We searched the literature (PROSPERO database registration number: CRD42018103843) via a scoping review., Search Strategy: The PubMed database was searched for articles that explored relationships between cutaneous wound pain, wound healing, and biomolecules. Inclusion criteria were articles that reported original data, used adult human samples, and were published in English., Findings: Twenty-one articles were retrieved: 17 investigated molecules from wound exudate associated with wound healing status, and 4 reported molecules associated with wound pain. The most frequently observed wound pain biomarkers were proinflammatory cytokines; the most frequently observed wound healing biomarkers were proteases including those in the matrix metalloproteinase family. Six wound exudate collection methods were identified to extract potential wound pain and wound healing biomarkers from wound exudate., Implications: The results can guide future wound exudate research to validate these wound pain and wound healing biomarkers and to develop therapies targeting these biomarkers to reduce wound pain and promote wound healing.

Cancer-related fatigue is an extremely common and debilitating psychiatric symptom that affects up to 80% of cancer patients. Despite its negative impact on the patient's quality of life, there is no well-established biomarker or mechanisms associated with this debilitating condition. The functional brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism (SNP) has been associated with a variety of psychiatric illnesses. We hypothesized that Val66Met may influence the risk for developing cancer-related fatigue. BDNF Val66Met was analyzed by polymerase chain reaction in 180 patients with confirmed cancer diagnoses. Fatigue was measured using the Functional Assessment of Cancer Therapy-Fatigue (FACIT-Fatigue) questionnaire. Depression was measured using the Hamilton Depression Scale (HAM-D). Data were transformed when necessary and regression models were constructed to access the association between genotype and symptom severity. Participants carrying the Met allele reported significantly less fatigue compared to the Val/Val genotype group. The presence of the Met allele did not influence depression levels. The results suggest that the BDNF Val66Met polymorphism confers protective advantage against cancer-related fatigue; whereas having the Val/Val genotype may be a genetic risk factor. Findings from this study not only provide clues to the neural basis of cancer-related fatigue, but also allow for symptom severity prediction and patient education with the goal to improve symptom management.

Fatigue and anhedonia are commonly reported, co-occurring clinical symptoms associated with chronic illnesses. Fatigue is a multidimensional construct that is defined as a distressing, persistent, subjective sense of physical, cognitive, or emotional tiredness that interferes with usual functioning. Anhedonia is a component of depressive disorders and other psychiatric conditions, such as schizophrenia, and is defined by the reduced ability to experience pleasure. Both symptoms greatly affect the health-related quality of life of patients with chronic illnesses. Although fatigue and anhedonia are commonly associated with each other, understanding the differences between the two constructs is necessary for diagnosis and clinical treatment. A scoping review was conducted based on published guidance, starting with a comprehensive search of existing literature to understand the similarities and differences between fatigue and anhedonia. An initial search of PubMed using fatigue and anhedonia as medical subject headings yielded a total of 5254 articles. A complete full-text review of the final 21 articles was conducted to find articles that treated both constructs similarly and articles that presented fatigue and anhedonia as distinct constructs. About 60% of the reviewed articles consider both constructs as distinct, but a considerable number of the reviewed articles found these constructs indistinguishable. Nomenclature and biology were two themes from the reviewed articles supporting the idea that anhedonia and fatigue are indistinguishable constructs. The information generated from this review is clinically relevant to optimize the management of fatigue related to anhedonia from other fatigue subtypes.

Fatigue and cognitive deficits are often co-occurring symptoms reported by patients after radiation therapy for prostate cancer. In this study, we induced fatigue-like behavior in mice using targeted pelvic irradiation to mimic the clinical treatment regimen and assess cognitive behavioral changes. We observed that pelvic irradiation produced a robust fatigue phenotype, a reduced rate of spontaneous alternation in a Y-maze test, and no behavioral change in an open field test. We found that reversal learning for fatigued mice was slower with respect to time, but not with respect to effort put into the test, suggesting that fatigue may impact the ability or motivation to work at a cognitive task without impairing cognitive capabilities. In addition, we found that mice undergoing pelvic irradiation show lower whole-brain levels of mature BDNF, and that whole-brain proBDNF levels also correlate with spontaneous alternation in a Y-maze test. These results suggest that changes in BDNF levels could be both a cause and an effect of fatigue-related changes in behavior., Competing Interests: The authors have declared that no competing interests exist.

Following the publication of the article, the authors realized that they have overlooked acknowledging the assistance they received from the Murine Phenotyping Core at NHLBI. Therefore, the Acknowledgements section of the Declarations should also have stated the following: 'We would like to thank the Murine Phenotyping Core at NHLBI for all their help with the mouse experiments, including Dr Danielle Springer, Audrey Noguchi, Michele Allen, Heather Potts and Morteza Peiravi.' The authors regret their oversight in failing to include this information in the Acknowledgements section of their paper. [the original article was published in International Journal of Molecular Medicine 45: 485‑496, 2020; DOI: 10.3892/ijmm.2019.4435].

Introduction: Limited studies have examined potential risk factors associated with the fatigue experience of a sample of Puerto Rican men treated with radiotherapy for non-metastatic prostate cancer. Identifying these factors may provide initial information about targets for individualized interventions, leading to more effective management of fatigue in this population., Purpose: To examine the relationship of age, body max index, depressive symptoms, physical activity, and sleep disturbance with fatigue during radiotherapy for prostate cancer., Methods: Twenty six participants completed five inventories: demographic intake, health form, the Functional Assessment of Cancer-Therapy-fatigue, Patient-Reported Outcome Measures Information System-Sleep disturbance, and the International Physical Activity Questionnaire-Short Form before, middle/days 19-21 and completion/days 38-42 of radiotherapy. The principal investigator rated the Hamilton depression scale. Descriptive statistics were performed. Interactions and influence of variables on fatigue were assessed using bivariate correlation and multiple linear regression, respectively., Results: At each study time point, sleep disturbance and depressive symptoms were strongly correlated with each other and fatigue. The linear combination of sleep disturbance and depressive symptoms was significantly related to fatigue., Conclusion: Given the high association of sleep disturbance and depressive symptoms with fatigue, clinicians should assess and develop interventions to manage these symptoms altogether., Competing Interests: The authors have no conflicts of interest to report.

Background: Phenotype prediction problems are usually considered ill-posed, as the amount of samples is very limited with respect to the scrutinized genetic probes. This fact complicates the sampling of the defective genetic pathways due to the high number of possible discriminatory genetic networks involved. In this research, we outline three novel sampling algorithms utilized to identify, classify and characterize the defective pathways in phenotype prediction problems, such as the Fisher's ratio sampler, the Holdout sampler and the Random sampler, and apply each one to the analysis of genetic pathways involved in tumor behavior and outcomes of triple negative breast cancers (TNBC). Altered biological pathways are identified using the most frequently sampled genes and are compared to those obtained via Bayesian Networks (BNs)., Results: Random, Fisher's ratio and Holdout samplers were more accurate and robust than BNs, while providing comparable insights about disease genomics., Conclusions: The three samplers tested are good alternatives to Bayesian Networks since they are less computationally demanding algorithms. Importantly, this analysis confirms the concept of "biological invariance" since the altered pathways should be independent of the sampling methodology and the classifier used for their inference. Nevertheless, still some modifications are needed in the Bayesian networks to be able to sample correctly the uncertainty space in phenotype prediction problems, since the probabilistic parameterization of the uncertainty space is not unique and the use of the optimum network might falsify the pathways analysis.

Purpose: This article aims to provide perspectives on the establishment of a consortium for nurse scientists with similar career trajectories interested in cancer-related symptoms (CRS) research. Hereby, we describe the development of and recent outcomes from the CRS consortium, the lessons learned in establishing the consortium, and future directions to advance the science of CRS., Model and Methods: New and innovative strategies are needed to address the complexity of CRS research. A CRS consortium was created to allow a mechanism for oncology nurse scientists with varying expertise to collaborate to advance CRS research. The National Institutes of Health (NIH) Symptom Science Model (SSM) guides the research of the CRS Consortium., Discussion and Conclusions: A need for improved CRS assessment and management has been identified. The CRS consortium was created as a collaborative think tank to begin to address this need. Guided by the NIH SSM, CRS consortium members have worked to define symptom phenotypes, enhance understanding of the biologic mechanisms that can contribute to symptom phenotypes, and develop tailored interventions to improve symptom management. Dissemination of the CRS consortium efforts involve publications and presentations., Clinical Implications: Nurse scientists interested in symptom science and biobehavorial research face many challenges on how to initiate and sustain independent programs of research. Through the formation of a CRS consortium, oncology nurse scientists can work together to address identified issues in symptom measurement and management., (© 2019 Sigma Theta Tau International.)

Background: The objective of this study was to investigate the dynamic brain activity following auricular point acupressure (APA) in chemotherapy-induced neuropathy (CIN)., Methods: Participants received 4 weeks of APA in an open-pilot trial with repeated observation. Along with the clinical self-reported CIN outcomes, objective outcomes were measured over the course of the treatment by physiological changes in pain sensory thresholds from quantitative sensory testing (QST) and repeated functional magnetic resonance imaging scans., Results: After 4 weeks of APA, participants had reported clinically significant improvements (ie, ≥30%) in a reduction of CIN symptoms (including pain, numbness, tingling, and stiffness) in lower extremity stiffness (32%), reduced foot sensitivity (13%), and higher pain threshold (13%). Across the 11 intrinsic brain networks examined, there was a trend toward significance of the connectivity of the basal ganglia network (BGN) to the salience network (SAL), which was decreased pre-APA versus immediate-APA (effect size [ES] = 1.04, P  = .07). The BGN also demonstrated decreased connectivity with the language network pre-APA versus delayed imaging post-APA (ES = -0.92, P  = .07). Furthermore, there was increased executive control network (ECN) and SAL within-network connectivity comparing pre-APA to delayed imaging post-APA, trending toward significance (ES = 0.41, P  = .09 and ES = 0.17, P  = .09, respectively)., Conclusion: The changes in connectivity and activity within or between the ECN, SAL, and BGN from pre- to post-APA suggest ongoing alterations in brain functional connectivity following APA, particularly in the insula, anterior cingulate, and dorsolateral prefrontal cortices, which play significant roles in pain, memory, and cognitive function., (© The Author(s) 2020.)

Objectives: The objectives of this proof of concept study were to (a) examine the temporal changes in fatigue and diversity of the gut microbiome over the course of chemoradiotherapy (CRT) in adults with rectal cancers; (b) investigate whether there are differences in diversity of the gut microbiome between fatigued and nonfatigued participants at the middle and at the end of CRT; and (c) investigate whether there are differences in the relative abundance of fecal microbiota at the phylum and genus levels between fatigued and nonfatigued participants at the middle and at the end of CRT., Methods: Stool samples and symptom ratings were collected prior to the inception of CRT, at the middle (after 12-16 treatments) and at the end (after 24-28 treatments) of the CRT. Descriptive statistics and Mann-Whitney U test were computed for fatigue. Gut microbiome data were analyzed using the QIIME2 software., Results: Participants ( N  = 29) ranged in age from 37 to 80 years. The median fatigue score significantly changed at the end of CRT (median = 23.0) compared with the median score before the initiation of CRT for the total sample (median = 17.0; p ≤ 0.05). At the middle of CRT, the alpha diversity (abundance of Operational Taxonomic Units) was lower for fatigued participants (149.30 ± 53.1) than for nonfatigued participants (189.15 ± 44.18, t (23) = 2.08, p ≤ 0.05). At the middle of CRT, the alpha diversity (abundance of Operational Taxonomic Units) was lower for fatigued participants (149.30 ± 53.1) than for nonfatigued participants (189.15 ± 44.18, Proteobacteria , Firmicutes , and Bacteroidetes were the dominant phyla for fatigued participants, and Escherichia , Bacteroides , Faecalibacterium , and Oscillospira were the most abundant genera for fatigued participants., Conclusion: CRT-associated perturbation of the gut microbiome composition may contribute to fatigue., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Velda J. González-Mercado et al.)

Combined androgen deprivation therapy (ADT) and radiation therapy (RT) is the standard of care treatment for non‑metastatic prostate cancer (NMPC). Despite the efficacy, treatment‑related symptoms including fatigue greatly reduce the quality of life of cancer patients. The goal of the study is to examine the influence of combined ADT/RT on fatigue and understand its underlying mechanisms. A total of 64 participants with NMPC were enrolled. Fatigue was assessed using the Functional Assessment of Cancer Therapy‑Fatigue. Mitochondrial function parameters were measured as oxygen consumption from peripheral blood mononuclear cells (PBMCs) extracted from participants' whole blood. An ADT/RT‑induced fatigue mouse model was developed, with fatigue measured as a reduction in voluntary wheel‑running activity (VWRA) in 54 mice. Mitochondrial function was assessed in the ADT/RT mouse brains using western blot analysis of glucose transporter 4 (GLUT4) and transcription factor A, mitochondrial (TFAM). The results demonstrated that fatigue in the ADT group was exacerbated during RT compared with the non‑ADT group. This effect was specific to fatigue, as depressive symptoms were unaffected. PBMCs of fatigued subjects exhibited decreased ATP coupling efficiency compared to non‑fatigued subjects, indicative of mitochondrial dysfunction. The ADT/RT mice demonstrated the synergistic effect of ADT and RT in decreasing VWRA. Brain tissues of ADT/RT mice exhibited decreased levels of GLUT4 and TFAM suggesting that impaired neuronal metabolic homeostasis may contribute to fatigue pathogenesis. In conclusion, these findings suggest that fatigue induced by ADT/RT may be attributable to mitochondrial dysfunction both peripherally and in the central nervous system (CNS). The synergistic effect of ADT/RT is behaviorally reproducible in a mouse model and its mechanism may be related to bioenergetics in the CNS.