Publications by authors named "John Shepherd"

376 Publications

Emergence of the obesity epidemic: six decade visualization with humanoid avatars.

Am J Clin Nutr 2022 Jan 14. Epub 2022 Jan 14.

Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.

Background: Visualizations of the emerging obesity epidemic, such as with serial United States (US) color prevalence maps, provide graphic images that extend informative public health messages beyond those in written communications. Advances in low-cost 3D optical technology now allows for development of large image databases that include participants varying in race/ethnicity, body mass, height, age, and circumferences. When combined with contemporary statistical methods, these data sets can be used to create humanoid avatar images with pre-specified anthropometric features.

Objective: The current study aimed to develop a humanoid avatar series with characteristics of representative US adults extending over the past six decades.

Methods: 3D optical scans were conducted on a demographically diverse sample of 570 healthy adults. Image data was converted to principal components and manifold regression equations were then developed with body mass, height, age, and waist circumference as covariates. Humanoid avatars were generated for representative adults with these four characteristics as reported in Center for Disease Control surveys beginning in 1960-62 up to 2015-18.

Results: There was a curvilinear increase in adult US population body mass, waist circumference, and body mass index (BMI) in males and females across the nine surveys spanning six decades. A small increase in average adult population age was present between 1960 and 2018; height changes were inconsistent. A series of four avatars developed at approximately 20-year intervals for representative males and females reveal the changes in body size and shape consistent with the emergence of the obesity epidemic. An additional series of developed avatars portray the shapes and sizes of males and females at key BMI cut points.

Conclusions: New mathematical approaches and accessible 3D optical technology combined with increasingly available large and diverse data sets across the lifespan now makes unique visualization of body size and shape possible on a previously unattainable scale. The study is registered at: https://clinicaltrials.gov/ct2/show/NCT03637855.
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http://dx.doi.org/10.1093/ajcn/nqac005DOI Listing
January 2022

Reproducibility and flexibility of monoclonal antibody production with .

MAbs 2022 Jan-Dec;14(1):2013594

Kentucky BioProcessing, Inc, Owensboro, KY, USA.

The ongoing SARS-CoV-2 coronavirus pandemic of 2020-2021 underscores the need for manufacturing platforms that can rapidly produce monoclonal antibody (mAb) therapies. As reported here, a platform based on produced mAb therapeutics with high batch-to-batch reproducibility and flexibility, enabling production of 19 different mAbs of sufficient purity and safety for clinical application(s). With a single manufacturing run, impurities were effectively removed for a representative mAb product (the ZMapp component c4G7). Our results show for the first time the reproducibility of the platform for production of multiple batches of clinical-grade mAb, manufactured under current Good Manufacturing Practices, from . The flexibility of the system was confirmed by the results of release testing of 19 different mAbs generated with the platform. The process from plant infection to product can be completed within 10 days. Therefore, with a constant supply of plants, response to the outbreak of an infectious disease could be initiated within a matter of weeks. Thus, these data demonstrated that this platform represents a reproducible, flexible system for rapid production of mAb therapeutics to support clinical development.
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http://dx.doi.org/10.1080/19420862.2021.2013594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744878PMC
January 2022

Sugar-sweetened beverage consumption and breast composition in a longitudinal study of Chilean girls.

Breast Cancer Res 2022 Jan 8;24(1). Epub 2022 Jan 8.

Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, 650 Charles Young Drive South, Los Angeles, CA, 90095, USA.

Background: Frequent sugar-sweetened beverage (SSB) intake has been associated with indirect markers of breast cancer risk, such as weight gain in adolescents and early menarche. How SSB intake relates to breast composition in adolescent girls has not been explored.

Methods: We evaluated the association between prospective intake of SSB and breast density in a cohort of 374 adolescent girls participating in the Growth and Obesity Cohort Study in Santiago, Chile. Multivariable linear regression models were used to analyze the association between average daily SSB intake quartiles and breast composition (absolute fibroglandular volume [aFGV], percent fibroglandular volume [%FGV], total breast volume [tBV]). Models were adjusted for potential confounding by BMI Z-score, age, daily energy intake (g/day), maternal education, hours of daily television watching after school, dairy intake (g/day), meat intake (g/day), waist circumference, and menarche. To examine the sensitivity of the association to the number of dietary recalls for each girl, analyses were further stratified by girls with one dietary recall and girls with > one dietary recall.

Results: A total of 881 dietary recalls were available for 374 girls prior to the breast density assessment. More than 60% of the cohort had > one dietary recall available. In multivariable analyses, we found no association between SSB intake quartile and aFGV (Q2 vs Q1 β: - 5.4, 95% CI - 15.1, 4.4; Q3 vs Q1 β: 1.3, 95% CI - 8.6, 11.3; Q4 vs Q1 β: 3.0, 95% CI - 7.1, 13). No associations were noted for %FGV and tBV. Among girls with at least one dietary recall, we found no significant associations between SSB intake quartiles and %FGV, aFGV, or tBV.

Conclusion: Overall, we observed no evidence that SSB intake was associated with breast density in adolescent Chilean girls.
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http://dx.doi.org/10.1186/s13058-021-01495-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742361PMC
January 2022

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

PLoS Med 2021 12 20;18(12):e1003872. Epub 2021 Dec 20.

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.

Background: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma.

Methods And Findings: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects.

Conclusions: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease.

Trial Registration: ClinicalTrials.gov NCT#: NCT04338360.
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http://dx.doi.org/10.1371/journal.pmed.1003872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8730442PMC
December 2021

Assessment of clinical measures of total and regional body composition from a commercial 3-dimensional optical body scanner.

Clin Nutr 2022 Jan 7;41(1):211-218. Epub 2021 Dec 7.

Graduate Program in Human Nutrition, University of Hawai'i Manoa, Agricultural Science Building, 1955 East-West Rd, Honolulu, HI, 96822, USA; Department of Epidemiology, University of Hawai'i Cancer Center, 701 Ilalo St, Honolulu, HI, 96813, USA.

Background: The accurate assessment of total body and regional body circumferences, volumes, and compositions are critical to monitor physical activity and dietary interventions, as well as accurate disease classifications including obesity, metabolic syndrome, sarcopenia, and lymphedema. We assessed body composition and anthropometry estimates provided by a commercial 3-dimensional optical (3DO) imaging system compared to criterion measures.

Methods: Participants of the Shape Up! Adults study were recruited for similar sized stratifications by sex, age (18-40, 40-60, >60 years), BMI (under, normal, overweight, obese), and across five ethnicities (non-Hispanic [NH] Black, NH White, Hispanic, Asian, Native Hawaiian/Pacific Islander). All participants received manual anthropometry assessments, duplicate whole-body 3DO (Styku S100), and dual-energy X-ray absorptiometry (DXA) scans. 3DO estimates provided by the manufacturer for anthropometry and body composition were compared to the criterion measures using concordance correlation coefficient (CCC) and Bland-Altman analysis. Test-retest precision was assessed by root mean square error (RMSE) and coefficient of variation.

Results: A total of 188 (102 female) participants were included. The overall fat free mass (FFM) as measured by DXA (54.1 ± 15.2 kg) and 3DO (55.3 ± 15.0 kg) showed a small mean difference of 1.2 ± 3.4 kg (95% limits of agreement -7.0 to +5.6) and the CCC was 0.97 (95% CI: 0.96-0.98). The CCC for FM was 0.95 (95% CI: 0.94-0.97) and the mean difference of 1.3 ± 3.4 kg (95% CI: -5.5 to +8.1) reflected the difference in FFM measures. 3DO anthropometry and body composition measurements showed high test-retest precision for whole body volume (1.1 L), fat mass (0.41 kg), percent fat (0.60%), arm and leg volumes, (0.11 and 0.21 L, respectively), and waist and hip circumferences (all <0.60 cm). No group differences were observed when stratified by body mass index, sex, or race/ethnicity.

Conclusions: The anthropometric and body composition estimates provided by the 3DO scanner are precise and accurate to criterion methods if offsets are considered. This method offers a rapid, broadly available, and automated method of body composition assessment regardless of body size. Further studies are recommended to examine the relationship between measurements obtained by 3DO scans and metabolic health in healthy and clinical populations.
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http://dx.doi.org/10.1016/j.clnu.2021.11.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727542PMC
January 2022

Associations of the Dietary Inflammatory Index with total adiposity and ectopic fat through the gut microbiota, lipopolysaccharides, and C-reactive protein in the Multiethnic Cohort-Adiposity Phenotype Study.

Am J Clin Nutr 2021 Dec 6. Epub 2021 Dec 6.

Fred Hutchinson Cancer Research Center.

Background Mechanisms linking a pro-inflammatory diet to obesity remain under investigation. The ability of diet to influence the gut microbiome (GM) in creating chronic low-grade systemic inflammation provides a plausible connection to adiposity.

Methods: In the cross-sectional Multiethnic Cohort Adiposity Phenotype Study (812 men, 843 women, 60 to 77 years) we tested whether associations between the energy-adjusted Dietary Inflammatory Index (E-DIITM) score and total adiposity, visceral adipose tissue (VAT), and liver fat (% volume) function through the GM, lipopolysaccharides (LPS), and high-sensitivity C-reactive protein (hs-CRP). Dual energy X-ray absorptiometry (DXA)-derived total fat mass, MRI-measured VAT, and MRI-based liver fat were measured. Participants provided stool and fasting blood samples and completed a food frequency questionnaire (FFQ). Stool bacterial DNA was amplified and the 16S rRNA gene was sequenced at the V1-V3 region. E-DII score was computed from FFQ data, with a higher E-DII representing a more pro-inflammatory diet. The associations between E-DII score, GM (10 phyla, 28 genera, alpha diversity), and adiposity phenotypes were examined using linear regression and mediation analyses, adjusting for confounders.

Results: There were positive total effects (c) between E-DII and total fat mass (c = 0.68; 95% CI = 0.47, 0.90), VAT (c = 4.61; 95% CI = 2.95, 6.27), and liver fat (c = 0.40; 95% CI = 0.27, 0.53). The association between E-DII score and total fat mass was mediated by LPS, Flavonifractor, [Ruminococcus] gnavus group, and Tyzzerella. The association between E-DII score and ectopic fat occurred indirectly through Fusobacteria, Christensenellaceae R-7 group, Coprococcus 2, Escherichia- Shigella, [Eubacterium] xylanophilum group, Flavonifractor, Lachnoclostridium, [Ruminococcus] gnavus group, Tyzzerella, [Ruminococcus] gnavus group (VAT only), and alpha diversity (liver fat only). There was no significant association between E-DII score and adiposity phenotype through hs-CRP.

Conclusion: Associations found between E-DII and adiposity phenotypes occurred through the GM and LPS.
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http://dx.doi.org/10.1093/ajcn/nqab398DOI Listing
December 2021

Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle.

Vaccines (Basel) 2021 Nov 17;9(11). Epub 2021 Nov 17.

Kentucky BioProcessing, Inc., Owensboro, KY 42301, USA.

Stable, effective, easy-to-manufacture vaccines are critical to stopping the COVID-19 pandemic resulting from the coronavirus SARS-CoV-2. We constructed a vaccine candidate CoV-RBD121-NP, which is comprised of the SARS-CoV-2 receptor-binding domain (RBD) of the spike glycoprotein (S) fused to a human IgG1 Fc domain (CoV-RBD121) and conjugated to a modified tobacco mosaic virus (TMV) nanoparticle. In vitro, CoV-RBD121 bound to the host virus receptor ACE2 and to the monoclonal antibody CR3022, a neutralizing antibody that blocks S binding to ACE2. The CoV-RBD121-NP vaccine candidate retained key SARS-CoV-2 spike protein epitopes, had consistent manufacturing release properties of safety, identity, and strength, and displayed stable potency when stored for 12 months at 2-8 °C or 22-28 °C. Immunogenicity studies revealed strong antibody responses in C57BL/6 mice with non-adjuvanted or adjuvanted (7909 CpG) formulations. The non-adjuvanted vaccine induced a balanced Th1/Th2 response and antibodies that recognized both the S1 domain and full S protein from SARS2-CoV-2, whereas the adjuvanted vaccine induced a Th1-biased response. Both adjuvanted and non-adjuvanted vaccines induced virus neutralizing titers as measured by three different assays. Collectively, these data showed the production of a stable candidate vaccine for COVID-19 through the association of the SARS-CoV-2 RBD with the TMV-like nanoparticle.
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http://dx.doi.org/10.3390/vaccines9111347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619098PMC
November 2021

CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated Immunopathology.

Vaccines (Basel) 2021 Nov 17;9(11). Epub 2021 Nov 17.

Kentucky BioProcessing, Inc., Owensboro, KY 42301, USA.

We developed a SARS-CoV-2 vaccine candidate (CoV-RBD121-NP) comprised of a tobacco mosaic virus-like nanoparticle conjugated to the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is stable for up to 12 months at 2-8 or 22-28 °C. Here, we showed that this vaccine induces a strong neutralizing antibody response in K18-hACE2 mice. Furthermore, we demonstrated that immunization protects mice from virus-associated mortality and symptomatic disease. Our data indicated that a sufficient pre-existing pool of neutralizing antibodies is required to restrict SARS-CoV-2 replication upon exposure and prevent induction of inflammatory mediators associated with severe disease. Finally, we identified a potential role for CXCL5 as a protective cytokine in SARS-CoV-2 infection. Our results suggested that disruption of the CXCL5 and CXCL1/2 axis may be important early components of the inflammatory dysregulation that is characteristic of severe cases of COVID-19.
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http://dx.doi.org/10.3390/vaccines9111346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618284PMC
November 2021

Changes in Bone Mineral Density Following Conventional Oral Phosphonate Treatment of Hypophosphatemic Osteomalacia: A Non-Randomized Controlled Study.

Int J Gen Med 2021 8;14:7925-7931. Epub 2021 Nov 8.

National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People's Republic of China.

Purpose: There are limited clinical studies aimed at solving the problem of the efficiency of conventional treatment with oral phosphate and calcitriol in adults with hypophosphatemic osteomalacia (HO). In addition, there still had no good non-hazardous markers to evaluate the severity of bone loss of osteomalacia before and after treatment. Therefore, the purpose of this study was to assess the efficacy of conventional treatment with a self-blended phosphate supplementation and calcitriol on patients with HO and whether bone mineral density (BMD) can be helpful for monitoring the efficacy.

Patients And Methods: A total of 21 HO patients and 105 healthy controls were enrolled. All patients were tested for serum biomarkers and BMD of the lumbar spine (L1-L4), femoral neck, and total left hip. After three years of treatment, 11 of 21 HO patients were recalled for BMD measurement. According to the administration of drugs, HO patients with calcium and calcitriol were divided into three phosphate treatment groups: patients in group A (n = 3) received continuous phosphate supplementation, patients in group B (n = 5) received intermittent phosphate supplementation and patients in group C (n = 3) received no phosphate supplementation.

Results: The diagnoses of 21 HO patients were 5 cases of hereditary hypophosphatemic rickets, 4 cases of Fanconi syndrome with the features of renal tubular acidosis and vitamin D deficiency, and 12 cases of hereditary vitamin D abnormality. The average initial serum phosphorus level of the patient group was approximately 50% lower than that of the control group. Lower BMD was significantly observed in the HO group than the control group at the lumbar spine and total hip. Continuous treatment with the phosphate supplement could increase BMD in the lumbar spine and total hip by 33.4-52.3% and in the femoral neck increased by 43.2-79.3% compared with baseline, and the effect appears to be continued once treatment is discontinued.

Conclusion: These findings suggest that conventional therapy can improve bone mineral defects in patients with HO, especially in the femoral neck. Detection of BMD in HO patients is a good tool to assess the extent of bone defects and the therapeutic effect.

Trial Registration: Chinese Clinical Trial Registry, ChiCTR-OOC-16010095. Registered 7 December 2016. Retrospectively registered.
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http://dx.doi.org/10.2147/IJGM.S332534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593346PMC
November 2021

Use of Dual-Energy X-Ray Absorptiometry to Assess Soft Tissue Composition in Breast Cancer Survivors With and Without Lymphedema.

Lymphat Res Biol 2021 Nov 18. Epub 2021 Nov 18.

School of Medicine, University of California San Francisco, San Francisco, California, USA.

In patients with lymphedema (LE), in addition to hand dominance, between-group comparisons of interlimb soft tissue differences need to account for differences in whole-body adiposity, measured directly by dual energy X-ray absorptiometry (DXA) or indirectly by body mass index. No study has evaluated the effects of hand dominance and whole-body adiposity on limb composition in patients with LE. This study's purpose was to compare soft tissue composition of affected and unaffected limbs of women with breast cancer, who did and did not have LE, controlling for dominance and percent body fat. Whole-body DXA scans were acquired and included measures of percent body fat, upper limb total mass, upper limb fat mass, and upper limb fat-free mass. Participants were classified into one of three groups: women without LE; women with only subjective LE; and women with objective signs of LE at the time of assessment. Differences among the LE groups were evaluated using analysis of variance (ANOVA) and Chi-square analyses. Analysis of covariance (ANCOVA) was used to control for percent body fat and for the affected limb dominance. Compared to women without LE, women with objective signs of LE have greater total limb mass, fat mass, and fat-free mass in their affected limbs, independent of affected side dominance and percent body fat. In addition, the interlimb differences in total mass, fat mass, and fat-free mass were greater for the women with objective signs of LE, compared to the other two groups. DXA is useful in identifying soft tissue changes in patients with LE. Given that limb circumferences measure only changes in limb volume and that bioimpedance provides estimates of extracellular fluid, DXA has the advantage of being able to estimate the volumes of specific tissues in the limb.
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http://dx.doi.org/10.1089/lrb.2021.0030DOI Listing
November 2021

Identifying cases of spinal cord injury or disease in a primary care electronic medical record database.

J Spinal Cord Med 2021 ;44(sup1):S28-S39

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.

Objective: To identify cases of spinal cord injury or disease (SCI/D) in an Ontario database of primary care electronic medical records (EMR).

Design: A reference standard of cases of chronic SCI/D was established via manual review of EMRs; this reference standard was used to evaluate potential case identification algorithms for use in the same database.

Setting: Electronic Medical Records Primary Care (EMRPC) Database, Ontario, Canada.

Participants: A sample of 48,000 adult patients was randomly selected from 213,887 eligible patients in the EMRPC database.

Interventions: N/A.

Main Outcome Measure(s): Candidate algorithms were evaluated using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F-score.

Results: 126 cases of chronic SCI/D were identified, forming the reference standard. Of these, 57 were cases of traumatic spinal cord injury (TSCI), and 67 were cases of non-traumatic spinal cord injury (NTSCI). The optimal case identification algorithm used free-text keyword searches and a physician billing code, and had 70.6% sensitivity (61.9-78.4), 98.5% specificity (97.3-99.3), 89.9% PPV (82.2-95.0), 94.7% NPV (92.8-96.3), and an F-score of 79.1.

Conclusions: Identifying cases of chronic SCI/D from a database of primary care EMRs using free-text entries is feasible, relying on a comprehensive case definition. Identifying a cohort of patients with SCI/D will allow for future study of the epidemiology and health service utilization of these patients.
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http://dx.doi.org/10.1080/10790268.2021.1971357DOI Listing
December 2021

CYP11B1 variants influence skeletal maturation via alternative splicing.

Commun Biol 2021 11 9;4(1):1274. Epub 2021 Nov 9.

Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Dr Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.

We performed genome-wide association study meta-analysis to identify genetic determinants of skeletal age (SA) deviating in multiple growth disorders. The joint meta-analysis (N = 4557) in two multiethnic cohorts of school-aged children identified one locus, CYP11B1 (expression confined to the adrenal gland), robustly associated with SA (rs6471570-A; β = 0.14; P = 6.2 × 10). rs6410 (a synonymous variant in the first exon of CYP11B1 in high LD with rs6471570), was prioritized for functional follow-up being second most significant and the one closest to the first intron-exon boundary. In 208 adrenal RNA-seq samples from GTEx, C-allele of rs6410 was associated with intron 3 retention (P = 8.11 × 10), exon 4 inclusion (P = 4.29 × 10), and decreased exon 3 and 5 splicing (P = 7.85 × 10), replicated using RT-PCR in 15 adrenal samples. As CYP11B1 encodes 11-β-hydroxylase, involved in adrenal glucocorticoid and mineralocorticoid biosynthesis, our findings highlight the role of adrenal steroidogenesis in SA in healthy children, suggesting alternative splicing as a likely underlying mechanism.
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http://dx.doi.org/10.1038/s42003-021-02774-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578655PMC
November 2021

Mammary collagen architecture and its association with mammographic density and lesion severity among women undergoing image-guided breast biopsy.

Breast Cancer Res 2021 11 9;23(1):105. Epub 2021 Nov 9.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr., Rm 7-E238, Bethesda, MD, 20892, USA.

Background: Elevated mammographic breast density is a strong breast cancer risk factor with poorly understood etiology. Increased deposition of collagen, one of the main fibrous proteins present in breast stroma, has been associated with increased mammographic density. Collagen fiber architecture has been linked to poor outcomes in breast cancer. However, relationships of quantitative collagen fiber features assessed in diagnostic biopsies with mammographic density and lesion severity are not well-established.

Methods: Clinically indicated breast biopsies from 65 in situ or invasive breast cancer cases and 73 frequency matched-controls with a benign biopsy result were used to measure collagen fiber features (length, straightness, width, alignment, orientation and density (fibers/µm)) using second harmonic generation microscopy in up to three regions of interest (ROIs) per biopsy: normal, benign breast disease, and cancer. Local and global mammographic density volumes were quantified in the ipsilateral breast in pre-biopsy full-field digital mammograms. Associations of fibrillar collagen features with mammographic density and severity of biopsy diagnosis were evaluated using generalized estimating equation models with an independent correlation structure to account for multiple ROIs within each biopsy section.

Results: Collagen fiber density was positively associated with the proportion of stroma on the biopsy slide (p < 0.001) and with local percent mammographic density volume at both the biopsy target (p = 0.035) and within a 2 mm perilesional ring (p = 0.02), but not with global mammographic density measures. As severity of the breast biopsy diagnosis increased at the ROI level, collagen fibers tended to be less dense, shorter, straighter, thinner, and more aligned with one another (p < 0.05).

Conclusions: Collagen fiber density was positively associated with local, but not global, mammographic density, suggesting that collagen microarchitecture may not translate into macroscopic mammographic features. However, collagen fiber features may be markers of cancer risk and/or progression among women referred for biopsy based on abnormal breast imaging.
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http://dx.doi.org/10.1186/s13058-021-01482-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579610PMC
November 2021

The potential of using artificial intelligence to improve skin cancer diagnoses in Hawai'i's multiethnic population.

Melanoma Res 2021 12;31(6):504-514

Population Sciences in the Pacific Program, University of Hawai'i Cancer Center, Honolulu, Hawai'i, USA.

Skin cancer remains the most commonly diagnosed cancer in the USA with more than 1 million new cases each year. Melanomas account for about 1% of all skin cancers and most skin cancer deaths. Multiethnic individuals whose skin is pigmented underestimate their risk for skin cancers and melanomas and may delay seeking a diagnosis. The use of artificial intelligence may help improve the diagnostic precision of dermatologists/physicians to identify malignant lesions. To validate our artificial intelligence's efficiency in distinguishing between images, we utilized 50 images obtained from our International Skin Imaging Collaboration dataset (n = 25) and pathologically confirmed lesions (n = 25). We compared the ability of our artificial intelligence to visually diagnose these 50 skin cancer lesions with a panel of three dermatologists. The artificial intelligence model better differentiated between melanoma vs. nonmelanoma with an area under the curve of 0.948. The three-panel member dermatologists correctly diagnosed a similar number of images (n = 35) as the artificial intelligence program (n = 34). Fleiss' kappa (ĸ) score for the raters and artificial intelligence indicated fair (0.247) agreement. However, the combined result of the dermatologists panel with the artificial intelligence assessments correctly identified 100% of the images from the test data set. Our artificial intelligence platform was able to utilize visual images to discriminate melanoma from nonmelanoma, using de-identified images. The combined results of the artificial intelligence with those of the dermatologists support the use of artificial intelligence as an efficient lesion assessment strategy to reduce time and expense in diagnoses to reduce delays in treatment.
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http://dx.doi.org/10.1097/CMR.0000000000000779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580213PMC
December 2021

Manufacturing plant-made monoclonal antibodies for research or therapeutic applications.

Methods Enzymol 2021 24;660:239-263. Epub 2021 Jun 24.

Kentucky BioProcessing, Inc., Owensboro, KY, United States.

Monoclonal antibodies (mAbs) hold great promise for treating diseases ranging from cancer to infectious disease. Manufacture of mAbs is challenging, expensive, and time-consuming using mammalian systems. We describe detailed methods used by Kentucky BioProcessing (KBP), a subsidiary of British American Tobacco, for producing high quality mAbs in a Nicotiana benthamiana host. Using this process, mAbs that meet GMP standards can be produced in as little as 10 days. Guidance for using individual plants, as well as detailed methods for large-scale production, are described. These procedures enable flexible, robust, and consistent production of research and therapeutic mAbs.
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http://dx.doi.org/10.1016/bs.mie.2021.05.011DOI Listing
June 2021

The impact of nutritional risk factors and sarcopenia on survival in patients treated with pelvic exenteration for recurrent gynaecological malignancy: a retrospective cohort study.

Arch Gynecol Obstet 2021 Nov 3. Epub 2021 Nov 3.

Department of Gynaecological Oncology, The Royal Marsden NHS Foundation Trust, 203 Fulham Road, Chelsea, London, SW3 6JJ, UK.

Purpose: The aim of the present study is to investigate the prognostic significance of nutritional risk factors and sarcopenia on the outcome of patients with recurrent gynaecological malignancies treated by pelvic exenteration.

Methods: We retrospectively evaluated muscle body composite measurements based on pre-operative CT scans, nutritional risk factors as assessed by a validated pre-operative questionnaire, and clinical-pathological parameters in 65 consecutive patients with recurrent gynaecological malignancies, excluding ovarian cancer, treated by pelvic exenteration at the Royal Marsden Hospital London. Predictive value for postoperative morbidity was investigated by logistic regression analyses. Relevant parameters were included in uni- and multivariate survival analyses.

Results: We found only (1) low muscle attenuation (MA)-an established factor for muscle depletion-and (2) moderate risk for malnutrition to be independently associated with shorter overall survival (p = 0.006 and p = 0.008, respectively). MA was significantly lower in overweight and obese patients (p = 0.04). Muscle body composite measurements were not predictive for post-operative morbidity.

Conclusion: The study suggests that pre-operative low MA and moderate risk for malnutrition are associated with shorter survival in patients with recurrent gynaecological malignancies treated with pelvic exenteration. Further studies are needed to validate these findings in larger cohorts.
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http://dx.doi.org/10.1007/s00404-021-06273-7DOI Listing
November 2021

Diet and Liver Adiposity in Older Adults: The Multiethnic Cohort Adiposity Phenotype Study.

J Nutr 2021 Nov;151(11):3579-3587

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: Diet plays a key role in the pathogenesis of nonalcoholic fatty liver disease. Limited data exist regarding specific nutrients and food groups and liver fat continuously, particularly among different ethnicities.

Objectives: We aimed to determine the relationship between usual dietary intake and accurately measured liver fat content in a multiethnic population.

Methods: Participants from the Multiethnic Cohort were recruited into the cross-sectional Adiposity Phenotype Study including women and men aged 60-77 y and 5 race/ethnic groups (African American, Japanese American, Latino, Native Hawaiian, and white). They filled out a detailed FFQ and underwent abdominal MRI for liver fat quantification and whole-body DXA for total adiposity. Intake of a priori-selected dietary factors (total and macronutrient energy, specific micronutrients, and food groups) was analyzed in relation to liver fat by estimating the mean percentage liver fat for quartiles of each dietary factor in a general linear model that adjusted for age, sex, race/ethnicity, percentage body fat, and daily energy intake (kcal/d).

Results: In total, 1682 participants (mean age: 69.2 y; 51% female) were included. Mean ± SD liver fat percentage was 5.7 ± 4.6. A significant positive association with liver fat was found across quartiles of percentage energy from fat, saturated fat, cholesterol, total red meat, red meat excluding processed red meat, and coffee (Bonferroni-adjusted P-trend < 0.05). A significant inverse association was observed for dietary fiber, vitamin C, and vitamin E (Bonferroni-adjusted P-trend < 0.05).

Conclusions: This study of ethnically diverse older adults shows that certain dietary factors, in particular red meat and saturated fat from red meat, were strongly associated with liver fat, whereas dietary fiber was inversely associated with liver fat, replicating some of the previous studies conducted mostly in whites.
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http://dx.doi.org/10.1093/jn/nxab300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564699PMC
November 2021

A pose-independent method for accurate and precise body composition from 3D optical scans.

Obesity (Silver Spring) 2021 11 21;29(11):1835-1847. Epub 2021 Sep 21.

Graduate Program in Human Nutrition, University of Hawai'i Manoa, Honolulu, Hawaii, USA.

Objective: The aim of this study was to investigate whether digitally re-posing three-dimensional optical (3DO) whole-body scans to a standardized pose would improve body composition accuracy and precision regardless of the initial pose.

Methods: Healthy adults (n = 540), stratified by sex, BMI, and age, completed whole-body 3DO and dual-energy X-ray absorptiometry (DXA) scans in the Shape Up! Adults study. The 3DO mesh vertices were represented with standardized templates and a low-dimensional space by principal component analysis (stratified by sex). The total sample was split into a training (80%) and test (20%) set for both males and females. Stepwise linear regression was used to build prediction models for body composition and anthropometry outputs using 3DO principal components (PCs).

Results: The analysis included 472 participants after exclusions. After re-posing, three PCs described 95% of the shape variance in the male and female training sets. 3DO body composition accuracy compared with DXA was as follows: fat mass R = 0.91 male, 0.94 female; fat-free mass R = 0.95 male, 0.92 female; visceral fat mass R = 0.77 male, 0.79 female.

Conclusions: Re-posed 3DO body shape PCs produced more accurate and precise body composition models that may be used in clinical or nonclinical settings when DXA is unavailable or when frequent ionizing radiation exposure is unwanted.
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http://dx.doi.org/10.1002/oby.23256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570991PMC
November 2021

Associations of the gut microbiome with hepatic adiposity in the Multiethnic Cohort Adiposity Phenotype Study.

Gut Microbes 2021 Jan-Dec;13(1):1965463

Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, U.S.A.

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for liver cancer and prevalence varies by ethnicity. Along with genetic and lifestyle factors, the gut microbiome (GM) may contribute to NAFLD and its progression to advanced liver disease. Our cross-sectional analysis assessed the association of the GM with hepatic adiposity among African American, Japanese American, White, Latino, and Native Hawaiian participants in the Multiethnic Cohort. We used MRI to measure liver fat and determine nonalcoholic fatty liver disease (NAFLD) status (n = 511 cases) in 1,544 participants, aged 60-77 years, with 12-53% overall adiposity (BMI of 17.8-46.2 kg/m). The GM was measured by 16S rRNA gene sequencing and, on a subset, by metagenomic sequencing. Alpha diversity was lower overall with NAFLD and in certain ethnicities (African Americans, Whites, and Latinos). In models regressing genus on NAFLD status, 62 of 149 genera (40%) exhibited a significant interaction between NAFLD and ethnicity stratified analysis found 69 genera significantly associated with NAFLD in at least one ethnic group. No single genus was significantly associated with NAFLD across all ethnicities. In contrast, the same bacterial metabolic pathways were over-represented in participants with NAFLD regardless of ethnicity. Imputed secondary bile acid and carbohydrate pathways were associated with NAFLD, the latter of which was corroborated by metagenomics, although different genera in different ethnicities were associated with these pathways. Overall, we found that NAFLD was associated with altered bacterial composition and metabolism, and that bacterial endotoxin, assessed by plasma lipopolysaccharide binding protein (LBP), may mediate liver fat-associated systemic inflammation in a manner that seems to vary by ethnicity.
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http://dx.doi.org/10.1080/19490976.2021.1965463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425768PMC
January 2022

Deep Learning Predicts Interval and Screening-detected Cancer from Screening Mammograms: A Case-Case-Control Study in 6369 Women.

Radiology 2021 12 7;301(3):550-558. Epub 2021 Sep 7.

From the Department of Epidemiology, University of Hawaii Cancer Center, 701 Ilalo St, Suite 522, Honolulu, HI 96813 (X.Z., T.K.W., L.L., J.A.S.); Department of Information and Computer Sciences, University of Hawaii at Manoa, Honolulu, Hawaii (L.L., P.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, Minn (M.J., C.S., S.W., C.V.); and Departments of Medicine and Epidemiology/Biostatistics, University of California, San Francisco, San Francisco, Calif (K.K.).

Background The ability of deep learning (DL) models to classify women as at risk for either screening mammography-detected or interval cancer (not detected at mammography) has not yet been explored in the literature. Purpose To examine the ability of DL models to estimate the risk of interval and screening-detected breast cancers with and without clinical risk factors. Materials and Methods This study was performed on 25 096 digital screening mammograms obtained from January 2006 to December 2013. The mammograms were obtained in 6369 women without breast cancer, 1609 of whom developed screening-detected breast cancer and 351 of whom developed interval invasive breast cancer. A DL model was trained on the negative mammograms to classify women into those who did not develop cancer and those who developed screening-detected cancer or interval invasive cancer. Model effectiveness was evaluated as a matched concordance statistic (C statistic) in a held-out 26% (1669 of 6369) test set of the mammograms. Results The C statistics and odds ratios for comparing patients with screening-detected cancer versus matched controls were 0.66 (95% CI: 0.63, 0.69) and 1.25 (95% CI: 1.17, 1.33), respectively, for the DL model, 0.62 (95% CI: 0.59, 0.65) and 2.14 (95% CI: 1.32, 3.45) for the clinical risk factors with the Breast Imaging Reporting and Data System (BI-RADS) density model, and 0.66 (95% CI: 0.63, 0.69) and 1.21 (95% CI: 1.13, 1.30) for the combined DL and clinical risk factors model. For comparing patients with interval cancer versus controls, the C statistics and odds ratios were 0.64 (95% CI: 0.58, 0.71) and 1.26 (95% CI: 1.10, 1.45), respectively, for the DL model, 0.71 (95% CI: 0.65, 0.77) and 7.25 (95% CI: 2.94, 17.9) for the risk factors with BI-RADS density (b rated vs non-b rated) model, and 0.72 (95% CI: 0.66, 0.78) and 1.10 (95% CI: 0.94, 1.29) for the combined DL and clinical risk factors model. The values between the DL, BI-RADS, and combined model's ability to detect screen and interval cancer were .99, .002, and .03, respectively. Conclusion The deep learning model outperformed in determining screening-detected cancer risk but underperformed for interval cancer risk when compared with clinical risk factors including breast density. © RSNA, 2021 See also the editorial by Bae and Kim in this issue.
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http://dx.doi.org/10.1148/radiol.2021203758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630596PMC
December 2021

Using an integrated knowledge translation approach to inform a pilot feasibility randomized controlled trial on peer support for individuals with traumatic brain injury: A qualitative descriptive study.

PLoS One 2021 24;16(8):e0256650. Epub 2021 Aug 24.

Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, Canada.

Introduction: Traumatic brain injury (TBI) is estimated to affect 10 million people annually, making it a leading cause of morbidity and mortality worldwide. One cost-effective intervention that has been shown to minimize some of the negative sequelae after TBI is peer support. However, the evidence supporting the benefits of peer support for individuals with TBI is sparse and of low quality. Integrated knowledge translation (iKT) may be one approach to optimizing the evaluation of peer support programs among individuals with TBI. Therefore, the objectives are: (1) To understand key informants' perspectives of the barriers and facilitators of participating in peer support research and programs among individuals with TBI; (2) to understand key informants' perspectives on the perceived impacts of peer support programs on individuals with TBI; and, (3) to demonstrate how an iKT approach can inform the development and implementation of a pilot feasibility randomized controlled trial (RCT).

Methods: A qualitative descriptive approach using one-on-one semi-structured interviews was used. Purposive sampling of 22 key informants included 8 peer support mentors, 4 individuals with TBI who received peer support, 3 caregivers of individuals with TBI, 4 peer support program staff, and 3 academics in peer support and/or TBI.

Results: There were five main themes related to the barriers and facilitators to participating in peer support research and programs: knowledge, awareness, and communication; logistics of participating; readiness and motivation to participate; need for clear expectations; and matching. There were three main themes related to the perceived impact of peer support: acceptance, community, social experiences; vicarious experience/learning through others: shared experiences, role-modelling, encouragement; and "I feel better." Discussions with our Research Partner led to several significant adaptations to our trial protocol, including removing the twice/week intervention arm, shortening of the length of trial, and changing the measure for the community integration outcome.

Discussion/conclusion: This is the first study to use an iKT approach to inform a trial protocol and the first to assess the barriers and facilitators to participating in peer support research.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256650PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384186PMC
December 2021

Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors.

Nat Commun 2021 08 11;12(1):4864. Epub 2021 Aug 11.

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA.

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.
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http://dx.doi.org/10.1038/s41467-021-25113-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357797PMC
August 2021

Genome-wide association study of pancreatic fat: The Multiethnic Cohort Adiposity Phenotype Study.

PLoS One 2021 30;16(7):e0249615. Epub 2021 Jul 30.

University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, Hawaii, United States of America.

Several studies have found associations between higher pancreatic fat content and adverse health outcomes, such as diabetes and the metabolic syndrome, but investigations into the genetic contributions to pancreatic fat are limited. This genome-wide association study, comprised of 804 participants with MRI-assessed pancreatic fat measurements, was conducted in the ethnically diverse Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS). Two genetic variants reaching genome-wide significance, rs73449607 on chromosome 13q21.2 (Beta = -0.67, P = 4.50x10-8) and rs7996760 on chromosome 6q14 (Beta = -0.90, P = 4.91x10-8) were associated with percent pancreatic fat on the log scale. Rs73449607 was most common in the African American population (13%) and rs79967607 was most common in the European American population (6%). Rs73449607 was also associated with lower risk of type 2 diabetes (OR = 0.95, 95% CI = 0.89-1.00, P = 0.047) in the Population Architecture Genomics and Epidemiology (PAGE) Study and the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM), which included substantial numbers of non-European ancestry participants (53,102 cases and 193,679 controls). Rs73449607 is located in an intergenic region between GSX1 and PLUTO, and rs79967607 is in intron 1 of EPM2A. PLUTO, a lncRNA, regulates transcription of an adjacent gene, PDX1, that controls beta-cell function in the mature pancreas, and EPM2A encodes the protein laforin, which plays a critical role in regulating glycogen production. If validated, these variants may suggest a genetic component for pancreatic fat and a common etiologic link between pancreatic fat and type 2 diabetes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249615PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323875PMC
October 2021

Biomarker-based visceral adiposity score and incident type 2 diabetes in the multiethnic cohort.

Ann Epidemiol 2021 11 21;63:29-34. Epub 2021 Jul 21.

University of Hawaii Cancer Center, Honolulu, HI. Electronic address:

Purpose: Visceral adipose tissue (VAT) may be more important than subcutaneous fat in type 2 diabetes (T2D) etiology. We examined a VAT score developed in reference to MRI measurement of VAT in the Multiethnic Cohort (MEC) as a risk factor for incident T2D.

Methods: Two nested case-control studies of cancer allowed calculation of the VAT score based on anthropometric measures and 8 biomarkers among 2,556 participants without T2D. Incident cases were identified from Medicare linkages and self-reports after blood draws in 2001-2006. Cox regression with age as time metric was applied to estimate the association of the VAT score with T2D.

Results: During 10.1 ± 2.4 years, 355 incident T2D cases were identified. VAT scores were higher in T2D cases than among those without disease (5.06±0.43 vs. 4.95±0.41; P<0.0001) and significantly associated with T2D (HR = 2.70; 95%CI 1.60, 4.58 per unit) with similar values in men (HR = 2.99; 95%CI 1.03, 8.73) and women (HR = 2.61; 95%CI 1.39, 4.91). A significant association was observed in all five ethnic groups but only statistically significant among Japanese Americans (HR = 6.24; 95%CI 2.34, 16.68).

Conclusion: These findings support that VAT as estimated by a biomarker-based score predicts T2D incidence beyond BMI in particular among older adults of Japanese ancestry.
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http://dx.doi.org/10.1016/j.annepidem.2021.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500936PMC
November 2021

The Gut Microbiome Is Associated with Circulating Dietary Biomarkers of Fruit and Vegetable Intake in a Multiethnic Cohort.

J Acad Nutr Diet 2022 Jan 3;122(1):78-98. Epub 2021 Jul 3.

Fred Hutchinson Cancer Research Center, Seattle, WA. Electronic address:

Background: Results from observational studies suggest high diet quality favorably influences the human gut microbiome. Fruit and vegetable consumption is often a key contributor to high diet quality.

Objective: To evaluate measures of gut bacterial diversity and abundance in relation to serum biomarkers of fruit and vegetable intake.

Design: Secondary analysis of cross-sectional data.

Participants And Setting: Men and women from Los Angeles, CA, and Hawai'i who participated in the Multiethnic Cohort-Adiposity Phenotype Study from 2013 to 2016 (N = 1,709).

Main Outcome Measures: Gut microbiome diversity and composition in relation to dietary biomarkers.

Statistical Analysis: Carotenoid (beta carotene, alpha carotene, cryptoxanthins, lutein, lycopene, and zeaxanthin), tocopherol (α, β + γ, and δ), and retinol concentrations were assessed in serum. The α and β diversity and composition of the gut microbiome were classified based on 16S rRNA gene sequencing of bacterial DNA from self-collected fecal samples. Global differences in microbial community profiles in relation dietary biomarkers were evaluated using multivariable permutational analysis of variance. Associations of α diversity (Shannon index), β diversity (weighted and unweighted UniFrac) with center log-ratio-transformed phyla and genera abundances were evaluated using linear regression, adjusted for covariates.

Results: Increasing total carotenoid, beta carotene, alpha carotene, cryptoxanthin, and lycopene concentrations were associated with higher gut bacterial diversity (Shannon Index) (P < 0.001). Total tocopherol, α-tocopherol, and δ-tocopherol concentrations contributed significantly to more than 1% of the microbiome variation in gut bacterial community: total tocopherol: 1.74%; α-tocopherol: 1.70%; and δ-tocopherol: 1.16% (P < 0.001). Higher total carotenoid was associated with greater abundance of some genera relevant for microbial macronutrient metabolism (P < 0.001).

Conclusions: Objective biomarkers of fruit and vegetable intake, particularly carotenoids, were favorably associated with gut bacterial composition and diversity in this multiethnic population. These observations provide supportive evidence that fruit and vegetable intake is related to gut bacterial composition; more work is needed to elucidate how this influences host health.
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http://dx.doi.org/10.1016/j.jand.2021.05.023DOI Listing
January 2022

A Pilot Feasibility Randomized Controlled Trial on the Ontario Brain Injury Association Peer Support Program.

J Clin Med 2021 Jun 29;10(13). Epub 2021 Jun 29.

Toronto Rehabilitation Institute, University Health Network, Toronto, ON M5G 2A2, Canada.

Background: The long-term consequences of traumatic brain injury can create major barriers to community integration. Peer support represents a sustainable model of support across this transition. The objective of the current study was to determine the feasibility of conducting a randomized controlled trial on the Ontario Brain Injury Association Peer Support Program and the preliminary effectiveness of the program on community integration, mood, health-related quality of life, and self-efficacy; Methods: A pilot feasibility randomized controlled trial with an embedded qualitative component was conducted. Mentees with moderate-to-severe traumatic brain injury (n = 13) were randomized to a weekly intervention or waitlist control group. Interviews were conducted with a subset of mentees and peer mentors (n = 10). Integration of the quantitative and qualitative data was completed using a joint display approach; Results: No statistically significant results were found for community integration, mood, or self-efficacy; however, changes in these outcomes were accompanied by moderate-to-large effect sizes. Within health-related quality of life, the mean pain score of the intervention group was significantly lower than that of the control group at the two-month timepoint but not at completion. Interviews revealed proximal improvements in knowledge, skills, and goals, and identified two domains related to trial acceptability: (1) environmental context and resources, and (2) reinforcement; Conclusions: Given the conceivable importance of proximal improvements in domains such as knowledge, skills, and/or goals for the attainment of more distal outcomes, modifications to the existing Peer Support Program may be warranted. The introduction of program recommendations which promote discussion around particular domains may help facilitate long-term improvements in health outcomes.
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http://dx.doi.org/10.3390/jcm10132913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269307PMC
June 2021

Mammographic Variation Measures, Breast Density, and Breast Cancer Risk.

AJR Am J Roentgenol 2021 08 23;217(2):326-335. Epub 2021 Jun 23.

Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905.

Our previous work showed that variation measures, which represent breast architecture derived from mammograms, were significantly associated with breast cancer. For replication purposes, we examined the association of three variation measures (variation [V], which is measured in the image domain, and P and p [a normalized version of P], which are derived from restricted regions in the Fourier domain) with breast cancer risk in an independent population. We also compared these measures to volumetric density measures (volumetric percent density [VPD] and dense volume [DV]) from a commercial product. We examined 514 patients with breast cancer and 1377 control patients from a screening practice who were matched for age, date of examination, mammography unit, facility, and state of residence. Spearman rank-order correlation was used to evaluate the monotonic association between measures. Breast cancer associations were estimated using conditional logistic regression, after adjustment for age and body mass index. Odds ratios were calculated per SD increment in mammographic measure. These variation measures were strongly correlated with VPD (correlation, 0.68-0.80) but not with DV (correlation, 0.31-0.48). Similar to previous findings, all variation measures were significantly associated with breast cancer (odds ratio per SD: 1.30 [95% CI, 1.16-1.46] for V, 1.55 [95% CI, 1.35-1.77] for P, and 1.51 [95% CI, 1.33-1.72] for p). Associations of volumetric density measures with breast cancer were similar (odds ratio per SD: 1.54 [95% CI, 1.33-1.78] for VPD and 1.34 [95% CI, 1.20-1.50] for DV). When DV was included with each variation measure in the same model, all measures retained significance. Variation measures were significantly associated with breast cancer risk (comparable to the volumetric density measures) but were independent of the DV.
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http://dx.doi.org/10.2214/AJR.20.22794DOI Listing
August 2021

Multicomponent density models for body composition: Review of the dual energy X-ray absorptiometry volume approach.

Obes Rev 2021 08 7;22(8):e13274. Epub 2021 Jun 7.

Cancer Center, University of Hawaii Cancer Center, Honolulu, HI, USA.

Accurate and precise body composition estimates, notably of total body adiposity, are a vital component of in vivo physiology and metabolic studies. The reference against which other body composition approaches are usually validated or calibrated is the family of methods referred to as multicomponent "body density" models. These models quantify three to six components by combining measurements of body mass, body volume, total body water, and osseous mineral mass. Body mass is measured with calibrated scales, volume with underwater weighing or air-displacement plethysmography, total body water with isotope dilution, and osseous mineral mass by dual-energy X-ray absorptiometry. Body density is then calculated for use in model as body mass/volume. Studies over the past decade introduced a new approach to quantifying body volume that relies on dual-energy X-ray absorptiometry measurements, an advance that simplifies multicomponent density model development by eliminating the need for underwater weighing or air-displacement plethysmography systems when these technologies are unavailable and makes these methods more accessible to research and clinical programs. This review critically examines these new dual-energy X-ray approaches for quantifying body volume and density, explores their shortcomings, suggests alternative derivation approaches, and introduces ideas for potential future research studies.
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http://dx.doi.org/10.1111/obr.13274DOI Listing
August 2021

Digital anthropometric evaluation of young children: comparison to results acquired with conventional anthropometry.

Eur J Clin Nutr 2021 May 26. Epub 2021 May 26.

Pennington Biomedical Research Center, LSU System, Baton Rouge, LA, USA.

Objective: Three-dimensional optical (3DO) imaging devices for acquiring anthropometric measurements are proliferating in healthcare facilities, although applicability in young children has not been evaluated; small body size and movement may limit device accuracy. The current study aim was to critically test three commercial 3DO devices in young children.

Methods: The number of successful scans and circumference measurements at six anatomic sites were quantified with the 3DO devices in 64 children, ages 5-8 years. Of the scans available for processing, 3DO and flexible tape-measure measurements made by a trained anthropometrist were compared.

Results: Sixty of 181 scans (33.1%) could not be processed for technical reasons. Of processed scans, mean 3DO-tape circumference differences tended to be small (~1-9%) and varied across systems; correlations and bias estimates also varied in strength across anatomic sites and systems (e.g., regression Rs, 0.54-0.97, all p < 0.01). Overall findings differed across devices; best results were for a multi-camera stationary system and less so for two rotating single- or dual-camera systems.

Conclusions: Available 3DO devices for quantifying anthropometric dimensions in adults vary in applicability in young children according to instrument design. These findings suggest the need for 3DO devices designed specifically for small and/or young children.
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http://dx.doi.org/10.1038/s41430-021-00938-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617044PMC
May 2021

Web-Based Peer Support Interventions for Adults Living With Chronic Conditions: Scoping Review.

JMIR Rehabil Assist Technol 2021 May 25;8(2):e14321. Epub 2021 May 25.

Toronto Rehabilitation Institute - Rumsey Centre, University Health Network, Toronto, ON, Canada.

Background: Globally, 1 in 3 adults live with multiple chronic conditions. Thus, effective interventions are needed to prevent and manage these chronic conditions and to reduce the associated health care costs. Teaching effective self-management practices to people with chronic diseases is one strategy to address the burden of chronic conditions. With the increasing availability of and access to the internet, the implementation of web-based peer support programs has become increasingly common.

Objective: The purpose of this scoping review is to synthesize existing literature and key characteristics of web-based peer support programs for persons with chronic conditions.

Methods: This scoping review follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) extension for scoping reviews guidelines. Studies were identified by searching MEDLINE, CINAHL, Embase, PsycINFO, and the Physiotherapy Evidence Database. Chronic diseases identified by the Public Health Agency of Canada were included. Our review was limited to peer support interventions delivered on the web. Peers providing support had to have the chronic condition that they were providing support for. The information abstracted included the year of publication, country of study, purpose of the study, participant population, key characteristics of the intervention, outcome measures, and results.

Results: After duplicates were removed, 12,641 articles were screened. Data abstraction was completed for 41 articles. There was a lack of participant diversity in the included studies, specifically with respect to the conditions studied. There was a lack of studies with older participants aged ≥70 years. There was inconsistency in how the interventions were described in terms of the duration and frequency of the interventions. Informational, emotional, and appraisal support were implemented in the studied interventions. Few studies used a randomized controlled trial design. A total of 4 of the 6 randomized controlled trials reported positive and significant results, including decreased emotional distress and increased health service navigation, self-efficacy, social participation, and constructive attitudes and approaches. Among the qualitative studies included in this review, there were several positive experiences related to participating in a web-based peer support intervention, including increased compassion and improved attitudes toward the individual's chronic condition, access to information, and empowerment.

Conclusions: There is limited recent, high-level evidence on web-based peer support interventions. Where evidence exists, significant improvements in social participation, self-efficacy, and health-directed activity were demonstrated. Some studies incorporated a theoretical framework, and all forms of peer support-emotional, informational, and appraisal support-were identified in the studies included in this review. We recommend further research on web-based peer support in more diverse patient groups (eg, for older adults and chronic conditions outside of cancer, cardiovascular disease, and HIV or AIDS). Key gaps in the area of web-based peer support will serve to inform the development and implementation of future programs.
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http://dx.doi.org/10.2196/14321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188320PMC
May 2021
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