Impact of COVID-19-related experiences on health-related quality of life in cancer survivors in the United States.

OBJECTIVE: Little evidence exists on the impact of the COVID-19 pandemic on cancer survivors, limiting recommendations to improve health-related quality of life (HRQoL) in this population. We describe survivors' pandemic experiences and examine associations between COVID-19-related exposures, psychosocial experiences, and HRQoL. METHODS: Between May 2020-April 2021, survivors completed cross-sectional questionnaires capturing COVID-19-related exposures (e.g., exposure to virus, job loss); psychosocial experiences (i.e., COVID-19-related anxiety/depression, disruptions to health care and daily activities/social interactions, satisfaction with providers' response to COVID, financial hardship, perceived benefits of the pandemic, social support, and perceived stress management ability); and HRQoL. RESULTS: Data were collected from N = 11,325 survivors in the United States. Participants were mostly female (58%), White (89%) and non-Hispanic (88%), and age 63 on average. Breast cancer was the most common diagnosis (23%). Eight percent of participants reported being exposed to COVID-19; 1% tested positive. About 6% of participants lost their jobs, while 24% lost household income. Nearly 30% avoided attending in-person oncology appointments because of the pandemic. Poorer HRQoL was associated with demographic (younger age; female; non-Hispanic White), clinical (Medicare; stage IV disease; hematologic/digestive/respiratory system cancer), and psychosocial factors (low perceived benefits and stress management ability; more disruption to health care and daily activities/social interactions; financial hardship). CONCLUSIONS: COVID-19-related stressors were associated with various psychosocial experiences in cancer survivors, and these psychosocial experiences were associated with HRQoL above and beyond demographic and clinical factors.

Effects of the Brief Simha Kriya Breathing Practice for Health Care Workers During the COVID-19 Pandemic.

Introduction: During the COVID-19 pandemic, health care workers (HCWs) experienced increased anxiety, depression, loneliness, and other mental health issues. HCWs need additional resources to cope with the mental health impact of their work. Yoga techniques could be helpful strategies to manage different stressors during times of uncertainty. Methods: This prospective, single-arm, trial examined the effects of a brief pranayama yoga practice on the wellbeing of HCWs during the height of COVID-19. HCWs were recruited through announcements and institutional websites at a large major cancer center in the southern United States. A short, prerecorded, 5-min breathwork video intervention called "Simha Kriya" was provided to participants, and they were encouraged to practice one to two times daily for 4 weeks. Participants completed self-report instruments at baseline and weeks 1 and 4, including: (1) Perceived Stress Scale (PSS); (2) Brief Resilient Coping Scale (BRCS); and (3) a questionnaire assessing the experience of COVID-19 among HCWs that had five subscales. HCWs also conducted a measure of breath holding time. Paired sample t-tests and mixed-effects analysis of variance models examined changes over time. Results: One hundred participants consented to the study, with 88 female, 60 white, 39 worked remotely, and 27 were clinical staff. Sixty-nine participants provided data at week 1 and 56 at week 4. Participants' adherence to the breathing exercises between weeks 1 and 4 was similar, with a mean of six times per week. At week 4, there were significant decreases in the COVID-19 Distress score (p < 0.0001) and COVID-19 Disruption (p = 0.013), yet no changes in the PSS. There were also significant increases in COVID-19 Stress Management (p = 0.0001) and BRCS scores (p = 0.012), but no changes in Perceived Benefits of COVID-19 and no changes in breath holding time. Discussion: Brief yoga-based breathing practices helped reduce pandemic-specific stress, improved resilience, and stress management skills in HCWs. Trial Registration Number: NCT04482647.

Development and initial psychometric evaluation of a COVID-related psychosocial experiences questionnaire for cancer survivors.

BACKGROUND: Cancer survivors are at elevated risk of psychological problems related to COVID-19, yet no published measure adequately assesses their psychosocial experiences during the pandemic. PURPOSE: Describe the development and factor structure of a comprehensive, self-report measure (COVID-19 Practical and Psychosocial Experiences questionnaire [COVID-PPE]) assessing the pandemic's impact on US cancer survivors. METHODS: The sample (n = 10,584) was divided into three groups to assess COVID-PPE factor structure by conducting: (1) initial calibration/exploratory analysis of the factor structure of 37 items (n = 5070), (2) confirmatory factor analysis of the best-fitting model (36 items after item removal; n = 5140), and (3) post-hoc confirmatory analysis with an additional six items not collected in the first two groups (42 items; n = 374). RESULTS: The final COVID-PPE was divided into two sets of subscales, conceptualized as Risk Factors and Protective Factors. The five Risk Factors subscales were labeled Anxiety Symptoms, Depression Symptoms, Health Care Disruptions, Disruptions to Daily Activities and Social Interactions, and Financial Hardship. The four Protective Factors subscales were labeled Perceived Benefits, Provider Satisfaction, Perceived Stress Management Skills, and Social Support. Internal consistency was acceptable for seven subscales (αs = 0.726-0.895; ωs = 0.802-0.895) but poor or questionable for the remaining two subscales (αs = 0.599-0.681; ωs = 0.586-0.692). CONCLUSIONS: To our knowledge, this is the first published self-report measure comprehensively capturing psychosocial impact-both positive and negative-of the pandemic on cancer survivors. Future work should evaluate predictive utility of COVID-PPE subscales, particularly as the pandemic evolves, which may inform recommendations for cancer survivors and facilitate identification of survivors most in need of intervention.

Understanding the Link between Sugar and Cancer: An Examination of the Preclinical and Clinical Evidence.

Per capita sugar consumption has increased in the United States to over 45 kg per year. The average person in the US currently consumes significantly more added sugar in their diet than the World Health Organization's, the American Cancer Society's, and the American Heart Association's recommendations for daily sugar consumption. Evidence from epidemiologic and preclinical studies demonstrates that excess sugar consumption can lead to development of cancer and progression of disease for those with cancer independent of the association between sugar and obesity. Human epidemiologic studies and mechanistic preclinical studies in multiple cancers support a causal link between excess sugar and cancer. Preclinical studies show that high-sucrose or high-fructose diets activate several mechanistic pathways, including inflammation, glucose, and lipid metabolic pathways. Although human studies are limited, compelling human and primate studies have explored the link between added sugar and metabolic syndrome (MetS), a risk factor for cancer. Substantial evidence suggests a causal link between MetS and added sugar, indicating important implications in the association between excess sugar consumption and cancer. Human clinical trials are needed to determine whether sugar increases cancer development and progression independently of its established role in causing obesity as well as for further exploration of the mechanisms involved.

Managing and Mentoring: Experiences of Assistant Professors in Working with Research Assistants.

Support from research assistants (RAs) is often framed as a resource to facilitate faculty research productivity, yet most assistant professors have received minimal training on how to effectively make use of this resource. This study collected data from a national sample of assistant professors to examine tasks RAs are asked to perform, satisfaction with RA work, challenges in working with RAs, and lessons learned to be successful. Authors used a sequential mixed-methods design, first conducting a Web-based survey with 109 assistant professors in social work schools with doctoral programs, then qualitative interviews with a subset of 13 respondents who volunteered to talk more about their experiences. Evidence indicated low levels of satisfaction regarding the preparation of students for RA work, particularly among those assistant professors working with first-year doctoral students. Primary challenges included lack of student skills and commitment and sufficient time to supervise and train students. Recommendations include careful assessment of student skills at the start of the relationship and setting clear expectations. Social work programs can improve faculty-RA relationships by training new assistant professors on how to support and manage RAs and training incoming students on basic research skills for their work as RAs.

Cancer survivorship care-planning: Practice, research, and policy implications for social work.

Increasing numbers of cancer survivors are living longer than 5 years from their diagnosis date. This has resulted in a growing population of cancer survivors, expected to reach 19 million by 2024. Survivors frequently experience late effects caused by cancer and its treatment, reducing survivors' quality of life in multiple domains. Survivorship care-plans may aid the many physical, psychosocial, and financial needs that emerge posttreatment. However, the lack of reimbursement mechanisms, the limited amount of effectiveness research, and minimal guidelines for content and delivery are barriers to the widespread provision of survivorship care-plans. Challenges and opportunities for social work practice, research, and policy are identified and discussed.

Design, synthesis and selection of DNA-encoded small-molecule libraries.

Biochemical combinatorial techniques such as phage display, RNA display and oligonucleotide aptamers have proven to be reliable methods for generation of ligands to protein targets. Adapting these techniques to small synthetic molecules has been a long-sought goal. We report the synthesis and interrogation of an 800-million-member DNA-encoded library in which small molecules are covalently attached to an encoding oligonucleotide. The library was assembled by a combination of chemical and enzymatic synthesis, and interrogated by affinity selection. We describe methods for the selection and deconvolution of the chemical display library, and the discovery of inhibitors for two enzymes: Aurora A kinase and p38 MAP kinase.

Directed evolution of high-affinity antibody mimics using mRNA display.

We constructed a library of >10(12) unique, covalently coupled mRNA-protein molecules by randomizing three exposed loops of an immunoglobulin-like protein, the tenth fibronectin type III domain (10Fn3). The antibody mimics that bound TNF-alpha were isolated from the library using mRNA display. Ten rounds of selection produced 10Fn3 variants that bound TNF-alpha with dissociation constants (K(d)) between 1 and 24 nM. After affinity maturation, the lowest K(d) measured was 20 pM. Selected antibody mimics were shown to capture TNF-alpha when immobilized in a protein microarray. 10Fn3-based scaffold libraries and mRNA-display allow the isolation of high-affinity, specific antigen binding proteins; potential applications of such binding proteins include diagnostic protein microarrays and protein therapeutics.

Identification of epitope-like consensus motifs using mRNA display.

The mRNA display approach to in vitro protein selection is based upon the puromycin-mediated formation of a covalent bond between an mRNA and its gene product. This technique can be used to identify peptide sequences involved in macromolecular recognition, including those identical or homologous to natural ligand epitopes. To demonstrate this approach, we determined the peptide sequences recognized by the trypsin active site, and by the anti-c-Myc antibody, 9E10. Here we describe the use of two peptide libraries of different diversities, one a constrained library based on the trypsin inhibitor EETI-II, where only the six residues in the first loop were randomized (6.4 x 10(7) possible sequences, 6.0 x 10(11) sequences in the library), the other a linear-peptide library with 27 randomized amino acids (1.3 x 10(35) possible sequences, 2 x 10(13) sequences in the library). The constrained library was screened against the natural target of wild-type EETI, bovine trypsin, and the linear library was screened against the anti-c-myc antibody, 9E10. The analysis of selected sequences revealed minimal consensus sequences of PR(I,L,V)L for the first loop of EETI-II and LISE for the 9E10 epitope. The wild-type sequences, PRILMR for the first loop of EETI-II and QKLISE for the 9E10 epitope, were selected with the highest frequency, and in each case the complete wild-type epitope was selected from the library.

Weakly coupled molecular photonic wires: synthesis and excited-state energy-transfer dynamics.

Molecular photonic wires, which absorb light and undergo excited-state energy transfer, are of interest as biomimetic models for photosynthetic light-harvesting systems and as molecular devices with potential applications in materials chemistry. We describe the stepwise synthesis of four molecular photonic wires. Each wire consists of an input unit, transmission element, and output unit. The input unit consists of a boron-dipyrrin dye or a perylene-monoimide dye (linked either at the N-imide or the C9 position); the transmission element consists of one or three zinc porphyrins affording short or long wires, respectively; and the output unit consists of a free base (Fb) porphyrin. The components in the arrays are joined in a linear architecture via diarylethyne linkers (an ethynylphenyl linker is attached to the C9-linked perylene). The wires have been examined by static absorption, static fluorescence, and time-resolved absorption spectroscopy. Each wire (with the exception of the C9-linked perylene wire) exhibits a visible absorption spectrum that is the sum of the spectra of the component parts, indicating the relatively weak electronic coupling between the components. Excitation of each wire at the wavelength where the input unit absorbs preferentially (typically 480-520 nm) results in emission almost exclusively from the Fb porphyrin. The static emission and time-resolved data indicate that the overall rate constants and quantum efficiencies for end-to-end (i.e., input to output) energy transfer are as follows: perylene-(N-imide)-linked short wire, (33 ps)(-1) and >99%; perylene-(C9)-linked short wire, (26 ps)(-1) and >99%; boron-dipyrrin-based long wire, (190 ps)(-1) and 81%; perylene-(N-imide)-linked long wire, (175 ps)(-1) and 86%. Collectively, the studies provide valuable insight into the singlet-singlet excited-state energy-transfer properties in weakly coupled molecular photonic wires.

Generating addressable protein microarrays with PROfusion covalent mRNA-protein fusion technology.

An mRNA-protein fusion consists of a polypeptide covalently linked to its corresponding mRNA. These species, prepared individually or en masse by in vitro translation with a modified mRNA conjugate (the PROfusion process), link phenotype to genotype and enable powerful directed evolution schemes. We have exploited the informational content of the nucleic acid component of the mRNA-protein fusion to create an addressable protein microarray that self-assembles via hybridization to surface-bound DNA capture probes. The nucleic acid component not only directs the mRNA-protein fusion to the proper coordinate of the microarray, but also positions the protein in a uniform orientation. We demonstrate the feasibility of this protein chip concept with several mRNA-protein fusions, each possessing a unique peptide epitope sequence. These addressable proteins could be visualized on the microarray both by autoradiography and highly specific monoclonal antibody binding. The anchoring of the protein to the chip surface is surprisingly robust, and the system is sensitive enough to detect sub-attomole quantities of displayed protein without signal amplification. Such protein arrays should be useful for functional screening in massively parallel formats, as well as other applications involving immobilized peptides and proteins.

Synthesis of Linear Amphipathic Porphyrin Dimers and Trimers: An Approach to Bilayer Lipid Membrane Spanning Porphyrin Arrays.

A modular building-block approach has been developed for the construction of linear amphipathic porphyrin arrays. The reaction of meso-(trifluoromethyl)dipyrromethane and an aldehyde under the conditions of the two-step room temperature porphyrin synthesis affords the trans-substituted porphyrin (13-56% yields). A similar reaction with two different aldehydes provides access to porphyrins bearing two different functional groups. An ethyne porphyrin and an iodo porphyrin (either free base or zinc) are selectively joined via Pd(0)-catalyzed coupling reactions, affording a linear array with porphyrins in defined metalation states. Coupling of a zinc-porphyrin bearing iodo and ester groups with a free base porphyrin bearing ethyne and ester groups yielded the zinc-free base porphyrin dimer. Coupling of a bis-ethyne porphyrin with a porphyrin bearing iodo and ester groups afforded the porphyrin trimer. Cleavage of the esters yielded the amphipathic porphyrin dimer and trimer arrays. The arrays with adjacent zinc and free base porphyrins undergo efficient electronic energy transfer. Both amphipathic porphyrin arrays have been incorporated into L-alpha-phosphatidylcholine vesicles. This versatile synthetic strategy provides access to a family of porphyrin arrays for studies of photophysical processes in supramolecular assemblies.