Risk factors and health behaviors associated with loneliness among cancer survivors during the COVID-19 pandemic.

Loneliness may exacerbate poor health outcomes particularly among cancer survivors during the COVID-19 pandemic. Little is known about the risk factors of loneliness among cancer survivors. We evaluated the risk factors of loneliness in the context of COVID-19 pandemic-related prevention behaviors and lifestyle/psychosocial factors among cancer survivors. Cancer survivors (n = 1471) seen at Huntsman Cancer Institute completed a survey between August-September 2020 evaluating health behaviors, medical care, and psychosocial factors including loneliness during COVID-19 pandemic. Participants were classified into two groups: 'lonely' (sometimes, usually, or always felt lonely in past month) and 'non-lonely' (never or rarely felt lonely in past month). 33% of cancer survivors reported feeling lonely in the past month. Multivariable logistic regression showed female sex, not living with a spouse/partner, poor health status, COVID-19 pandemic-associated lifestyle factors including increased alcohol consumption and marijuana/CBD oil use, and psychosocial stressors such as disruptions in daily life, less social interaction, and higher perceived stress and financial stress were associated with feeling lonely as compared to being non-lonely (all p < 0.05). A significant proportion of participants reported loneliness, which is a serious health risk among vulnerable populations, particularly cancer survivors. Modifiable risk factors such as unhealthy lifestyle behaviors and psychosocial stress were associated with loneliness. These results highlight the need to screen for unhealthy lifestyle factors and psychosocial stressors to identify cancer survivors at increased risk of loneliness and to develop effective management strategies.

Exercise and lung cancer surgery: A systematic review of randomized-controlled trials.

Lung cancer patients undergoing surgery are often left physically deconditioned and/or with functional deficits. Exercise interventions may improve pulmonary and physical function before and after lung resection. We conducted a systematic review of randomized-controlled trials (RCTs) testing the impact of pre-, post-, and combined pre-and-post surgery exercise interventions on physical and pulmonary function in lung cancer patients. Exercise pre-surgery seems to substantially improve physical and pulmonary function, which are factors associated with improved ability to undergo surgery while reducing post-surgery complications. Evidence is inconsistent for post-surgery interventions, reporting no or moderate effects. Results from pre-and-post surgery interventions are limited to one study. In conclusion, pre- and post-surgery exercise interventions, individually, have shown beneficial effects for lung cancer patients undergoing surgery. The impact of interventions combining both pre- and post-surgery exercise programs remains unknown. More evidence is needed on the ideal exercise setting, and timing across the lung cancer care continuum.

Generating high quality libraries for DIA MS with empirically corrected peptide predictions.

Data-independent acquisition approaches typically rely on experiment-specific spectrum libraries, requiring offline fractionation and tens to hundreds of injections. We demonstrate a library generation workflow that leverages fragmentation and retention time prediction to build libraries containing every peptide in a proteome, and then refines those libraries with empirical data. Our method specifically enables rapid, experiment-specific library generation for non-model organisms, which we demonstrate using the malaria parasite Plasmodium falciparum, and non-canonical databases, which we show by detecting missense variants in HeLa.

Clinically Integrated Physical Therapist Practice in Cancer Care: A New Comprehensive Approach.

Best practice recommendations in cancer care increasingly call for integrated rehabilitation services to address physical impairments and disability. These recommendations have languished primarily due to a lack of pragmatic, generalizable intervention models. This perspective paper proposes a clinically integrated physical therapist (CI-PT) model that enables flexible and scalable services for screening, triage, and intervention addressing functional mobility. The model is based on (1) a CI-PT embedded in cancer care provider clinics, and (2) rehabilitation across the care continuum determined by the patient's level of functional mobility. The CI-PT model includes regular screening of functional mobility in provider clinics via a patient-reported mobility measure-the Activity Measure for Post-Acute Care, a brief physical therapy evaluation tailored to the specific functional needs of the individual-and a tailored, skilled physical therapist intervention based on functional level. The CI-PT model provides a pragmatic, barrier-free, patient-centric, data-driven approach to integrating rehabilitation as part of standard care for survivors of cancer. The model standardizes CI-PT practice and may be sufficiently agile to provide targeted interventions in widely varying cancer settings and populations. Therefore, it may be ideal for wide implementation among outpatient oncological settings. Implementation of this model requires a shared approach to care that includes physical therapists, rehabilitation administrators, cancer care providers, and cancer center administrators.

Precision-Exercise-Prescription in patients with lung cancer undergoing surgery: rationale and design of the PEP study trial.

INTRODUCTION: Lung cancer is a significant burden on societies worldwide, and the most common cause of death in patients with cancer overall. Exercise intervention studies in patients with lung cancer have consistently shown benefits with respect to physical and emotional functioning. However, to date, exercise training has not been consistently implemented into clinical practice given that interventions have been costly and not aligned with clinical care. METHODS/DESIGN: The Precision-Exercise-Prescription (PEP) study is a prospective randomised controlled trial comparing the effectiveness and feasibility of a personalised intervention exercise programme among patients with lung cancer undergoing surgery. Two-hundred patients who are diagnosed with stage primary or secondary lung cancer and are eligible to undergo surgical treatment at Huntsman Cancer Institute comprise the target population. Patients are randomised to either the (1) outpatient precision-exercise intervention group or (2) delayed intervention group. The intervention approach uses Motivation and Problem Solving, a hybrid behavioural treatment based on motivational interviewing and practical problem solving. The dosage of the exercise intervention is personalised based on the individual's Activity Measure for Post-Acute-Care outpatient basic mobility score, and incorporates four exercise modes: mobility, callisthenics, aerobic and resistance. Exercise is implemented by physical therapists at study visits from presurgery until 6 months postsurgery. The primary endpoint is the level of physical function assessed by 6 min walk distance at 2 months postsurgery. Secondary outcomes include patient-reported outcomes (eg, quality of life, fatigue and self-efficacy) and other clinical outcomes, including length of stay, complications, readmission, pulmonary function and treatment-related costs up to 6 months postsurgery. ETHICS/DISSEMINATION: The PEP study will test the clinical effectiveness and feasibility of a personalised exercise intervention in patients with lung cancer undergoing surgery. Outcomes of this clinical trial will be presented at national and international conferences and symposia and will be published in international, peer-reviewed journals. Ethics approval was obtained at the University of Utah (IRB 00104671). TRIAL REGISTRATION NUMBER: NCT03306992.

Characterization of the chondrocyte secretome in photoclickable poly(ethylene glycol) hydrogels.

Poly(ethylene glycol) (PEG) hydrogels are highly tunable platforms that are promising cell delivery vehicles for chondrocytes and cartilage tissue engineering. In addition to characterizing the type of extracellular matrix (ECM) that forms, understanding the types of proteins that are secreted by encapsulated cells may be important. Thus, the objectives for this study were to characterize the secretome of chondrocytes encapsulated in PEG hydrogels and determine whether the secretome varies as a function of hydrogel stiffness and culture condition. Bovine chondrocytes were encapsulated in photoclickable PEG hydrogels with a compressive modulus of 8 and 46 kPa and cultured under free swelling or dynamic compressive loading conditions. Cartilage ECM deposition was assessed by biochemical assays and immunohistochemistry. The conditioned medium was analyzed by liquid chromatography-tandem mass spectrometry. Chondrocytes maintained their phenotype within the hydrogels and deposited cartilage-specific ECM that increased over time and included aggrecan and collagens II and VI. Analysis of the secretome revealed a total of 64 proteins, which were largely similar among all experimental conditions. The identified proteins have diverse functions such as biological regulation, response to stress, and collagen fibril organization. Notably, many of the proteins important to the assembly of a collagen-rich cartilage ECM were identified and included collagen types II(α1), VI (α1, α2, and α3), IX (α1), XI (α1 and α2), and biglycan. In addition, many of the other identified proteins have been reported to be present within cell-secreted exosomes. In summary, chondrocytes encapsulated within photoclickable PEG hydrogels secrete many types of proteins that diffuse out of the hydrogel and which have diverse functions, but which are largely preserved across different hydrogel culture environments. Biotechnol. Bioeng. 2017;114: 2096-2108. © 2017 Wiley Periodicals, Inc.

CRL4(WDR23)-Mediated SLBP Ubiquitylation Ensures Histone Supply during DNA Replication.

To maintain genome integrity and epigenetic information, mammalian cells must carefully coordinate the supply and deposition of histones during DNA replication. Here we report that the CUL4 E3 ubiquitin ligase complex CRL4(WDR23) directly regulates the stem-loop binding protein (SLBP), which orchestrates the life cycle of histone transcripts including their stability, maturation, and translation. Lack of CRL4(WDR23) activity is characterized by depletion of histones resulting in inhibited DNA replication and a severe slowdown of growth in human cells. Detailed analysis revealed that CRL4(WDR23) is required for efficient histone mRNA 3' end processing to produce mature histone mRNAs for translation. CRL4(WDR23) binds and ubiquitylates SLBP in vitro and in vivo, and this modification activates SLBP function in histone mRNA 3' end processing without affecting its protein levels. Together, these results establish a mechanism by which CUL4 regulates DNA replication and possible additional chromatin transactions by controlling the concerted expression of core histones.

Linking the foreign body response and protein adsorption to PEG-based hydrogels using proteomics.

Poly(ethylene glycol) (PEG) hydrogels with their highly tunable properties are promising implantable materials, but as with all non-biological materials, they elicit a foreign body response (FBR). Recent studies, however, have shown that incorporating the oligopeptide RGD into PEG hydrogels reduces the FBR. To better understand the mechanisms involved and the role of RGD in mediating the FBR, PEG, PEG-RGD and PEG-RDG hydrogels were investigated. After a 28-day subcutaneous implantation in mice, a thinner and less dense fibrous capsule formed around PEG-RGD hydrogels, while PEG and PEG-RDG hydrogels exhibited stronger, but similar FBRs. Protein adsorption to the hydrogels, which is considered the first step in the FBR, was also characterized. In vitro experiments confirmed that serum proteins adsorbed to PEG-based hydrogels and were necessary to promote macrophage adhesion to PEG and PEG-RDG, but not PEG-RGD hydrogels. Proteins adsorbed to the hydrogels in vivo were identified using liquid chromatography-tandem mass spectrometry. The majority (245) of the total proteins (≥300) that were identified was present on all hydrogels with many proteins being associated with wounding and acute inflammation. These findings suggest that the FBR to PEG hydrogels may be mediated by the presence of inflammatory-related proteins adsorbed to the surface, but that macrophages appear to sense the underlying chemistry, which for RGD improves the FBR.

The development of a culturally relevant, theoretically driven HPV prevention intervention for urban adolescent females and their parents/guardians.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States, accounting for the large majority of cervical cancer and anogenital warts cases. Two HPV vaccines are currently licensed and recommended for women and girls. However, vaccination rates have been suboptimal, with evidence of disparities influencing both uptake and series completion among African American and Hispanic adolescents. There has been a dearth of theory-based, behavioral interventions targeted to prevent HPV infection and increase HPV vaccine uptake among urban adolescents. This article describes the development of two skills-based intervention curricula aimed to increase HPV prevention and vaccination among low-income urban adolescent females 9 to 18 years old. Guided by the theory of planned behavior, elicitation research was conducted to elucidate the social psychological factors that underlie HPV vaccination intentions (N = 141). The findings were subsequently used to identify theoretical mediators of behavioral change to drive the intervention. Culturally relevant strategies to promote HPV vaccination were translated into the curricula content. Both curricula were designed to motivate and empower participants to reduce risk of being infected with HPV. Targeting theoretical mediators of behavioral change, derived from the voices of the community, may prove to be successful in increasing HPV vaccination and preventing HPV.

Identifying individual cell types in heterogeneous cultures using secondary ion mass spectrometry imaging with C60 etching and multivariate analysis.

Tissue engineering approaches fabricate and subsequently implant cell-seeded and unseeded scaffold biomaterials. Once in the body, these biomaterials are repopulated with somatic cells of various phenotypes whose identification upon explantation can be expensive and time-consuming. We show that imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS) can be used to distinguish mammalian cell types in heterogeneous cultures. Primary rat esophageal epithelial cells (REEC) were cultured with NIH 3T3 mouse fibroblasts on tissue culture polystyrene and freeze-dried before TOF-SIMS imaging. Results show that a short etching sequence with C(60)(+) ions can be used to clean the sample surface and improve the TOF-SIMS image quality. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were used to identify peaks whose contributions to the total variance in the multivariate model were due to either the two cell types or the substrate. Using PLS-DA, unknown regions of cellularity that were otherwise unidentifiable by SIMS could be classified. From the loadings in the PLS-DA model, peaks were selected that were indicative of the two cell types and TOF-SIMS images were created and overlaid that showed the ability of this method to distinguish features visually.