Nevin Manimala

Radiat Oncol. 2022 Nov 7;17(1):176. doi: 10.1186/s13014-022-02147-7.

ABSTRACT

BACKGROUND: To assess the effectiveness and toxicity of radiation dose escalation for locally advanced nasopharyngeal carcinoma (LA-NPC) in patients with local and/or regional residual lesion(s) after standard treatment.

METHODS: From November 2011 to November 2020, 259 LA-NPC patients who had local and/or regional residual lesion(s) after induction chemotherapy followed by concurrent chemoradiotherapy (IC + CCRT) from our hospital were included. The total dose of primary radiotherapy (RT) was 68.1-74.25 Gy (median, 70.4 Gy). The boost doses were 4.0-18.0 Gy (median, 9 Gy), 1.8-2.0 Gy/fraction.

RESULTS: For all patients, the 5-year local relapse-free survival was 90.2%, regional relapse-free survival was 89.1%, locoregional relapse-free survival (LRRFS) was 79.5%, distant metastasis-free survival (DMFS) was 87.9%, failure-free survival (FFS) was 69.0%, and overall survival (OS) was 86.3%. LRRFS, DMFS, FFS, and OS in patients with age ≤ 65 versus > 65, plasma Epstein-Barr virus-deoxyribonucleic acid ≤ 500 versus > 500, T_1-2 versus T_3-4, N_0-1 versus N_2-3, and stage III versus stage IV showed no statistically significant differences. The interval between primary RT and boost was not a prognostic factor for LRRFS, DMFS, FFS, and OS. Males had a lower 3-year FFS rate than females (72.9% vs. 83.7%, P = 0.024). LA-NPCs with locally and regionally residual lesion(s) had the worst 3-year DMFS and OS rates compared with locally or regionally residual lesion(s) (77.7% vs. 98.8% vs. 87.4%, P = 0.014; 75.9% vs. 94.5% vs. 82.4%, P = 0.002).

CONCLUSION: Boost radiation was an option for LA-NPCs with locally and/or regionally residual lesions after receiving IC + CCRT. It warrants further prospective study.

TRIAL REGISTRATION: Retrospectively registered.

PMID:36345003 | DOI:10.1186/s13014-022-02147-7

Breast Cancer Res. 2022 Nov 7;24(1):76. doi: 10.1186/s13058-022-01570-8.

ABSTRACT

BACKGROUND: Breast parenchymal texture features, including grayscale variation (V), capture the patterns of texture variation on a mammogram and are associated with breast cancer risk, independent of mammographic density (MD). However, our knowledge on the genetic basis of these texture features is limited.

METHODS: We conducted a genome-wide association study of V in 7040 European-ancestry women. V assessments were generated from digitized film mammograms. We used linear regression to test the single-nucleotide polymorphism (SNP)-phenotype associations adjusting for age, body mass index (BMI), MD phenotypes, and the top four genetic principal components. We further calculated genetic correlations and performed SNP-set tests of V with MD, breast cancer risk, and other breast cancer risk factors.

RESULTS: We identified three genome-wide significant loci associated with V: rs138141444 (6q24.1) in ECT2L, rs79670367 (8q24.22) in LINC01591, and rs113174754 (12q22) near PGAM1P5. 6q24.1 and 8q24.22 have not previously been associated with MD phenotypes or breast cancer risk, while 12q22 is a known locus for both MD and breast cancer risk. Among known MD and breast cancer risk SNPs, we identified four variants that were associated with V at the Bonferroni-corrected thresholds accounting for the number of SNPs tested: rs335189 (5q23.2) in PRDM6, rs13256025 (8p21.2) in EBF2, rs11836164 (12p12.1) near SSPN, and rs17817449 (16q12.2) in FTO. We observed significant genetic correlations between V and mammographic dense area (r_g = 0.79, P = 5.91 × 10^-5), percent density (r_g = 0.73, P = 1.00 × 10^-4), and adult BMI (r_g = – 0.36, P = 3.88 × 10^-7). Additional significant relationships were observed for non-dense area (z = – 4.14, P = 3.42 × 10^-5), estrogen receptor-positive breast cancer (z = 3.41, P = 6.41 × 10^-4), and childhood body fatness (z = – 4.91, P = 9.05 × 10^-7) from the SNP-set tests.

CONCLUSIONS: These findings provide new insights into the genetic basis of mammographic texture variation and their associations with MD, breast cancer risk, and other breast cancer risk factors.

PMID:36344993 | DOI:10.1186/s13058-022-01570-8

Hum Resour Health. 2022 Nov 7;20(1):78. doi: 10.1186/s12960-022-00774-5.

ABSTRACT

BACKGROUND: Gendered challenges have been shown to persist among health practitioners in countries at all levels of development. Less is known about non-clinical professionals, that is, those who do not deliver services directly but are essential to health systems performance, such as health policy researchers. This national observational study examined gender occupational segregation and wage gaps in the Canadian health policy research workforce using a cross-domain comparative labour market analysis approach.

METHODS: Sourcing data from the 2016 population census, we applied linear regression and Oaxaca-Blinder decomposition techniques to assess wage differentials by sex, traditional human capital measures (e.g., age, education, place of work), and social identity variables intersecting with gender (household head, childcare, migrant status) among health policy researchers aged 25-54. We compared the gender composition and wage gap with seven non-health policy and programme domains, as mapped under the national occupational classification by similarity in the types of work performed.

RESULTS: The health policy research workforce (N = 19 955) was characterized by gender segregation: 74% women, compared with 58% women among non-health policy research occupations (N = 102 555). Women health policy researchers earned on average 4.8% (95% CI 1.5‒8.0%) less than men after adjusting for other professional and personal variables. This gap was wider than among education policy researchers with similar gender composition (75% women; adjusted wage gap of 2.6%). Wages among health policy researchers were 21.1% (95% CI 19.4‒22.8%) lower than their counterparts in the male-dominated economics policy domain, all else being equal. Overall, women’s earnings averaged 3.2% lower than men’s due to factors that remained unexplained by policy domain or other measured predictors.

CONCLUSIONS: This investigation found that the gender inequalities already widely seen among clinical practitioners are replicated among health policy researchers, potentially hindering the competitiveness of the health sector for attracting and retaining talent. Our findings suggest intersectoral actions are necessary to tackle wage gaps and devaluation of female-dominated health professions. Accountability for gender equity in health must extend to the professionals tasked with conducting equity-informative health policy research.

PMID:36344985 | DOI:10.1186/s12960-022-00774-5

Radiat Oncol. 2022 Nov 7;17(1):177. doi: 10.1186/s13014-022-02151-x.

ABSTRACT

BACKGROUND: Based on a previous study on the feasibility of TomoEQA, an exit detector-based patient-specific pre-treatment quality assurance (QA) method for helical tomotherapy, an in-depth clinical evaluation was conducted.

METHODS: Data of one hundred patients were analyzed to evaluate the clinical usefulness of TomoEQA for patient-specific pre-treatment QA in comparison with the conventional phantom-based method. Additional investigations were also performed under unusual measurement conditions to validate the off-axis region. In addition to the clinical evaluation of TomoEQA, a statistical analysis was conducted to determine the plan parameters that affect the pass/failure results of pre-treatment QA.

RESULTS: The average and standard deviations of the gamma passing rate and point dose error for TomoEQA were comparable to those of the conventional QA method. For TomoEQA, the average values of the gamma passing rate and point dose error were 96.32% (standard deviation (1 sigma) = 3.94; 95% confidence interval (CI), 95.55 to 97.09) and – 1.12% (standard deviation (1 sigma) = 1.04; CI, – 1.32 to – 0.92), respectively. For the conventional QA method, the average values of the gamma passing rate and point dose error were 95.95% (standard deviation (1 sigma) = 4.35; 95% confidence interval (CI), 95.10 to 96.80) and – 1.20% (standard deviation (1 sigma) = 1.61; CI, – 1.52 to – 0.88), respectively. Further experiments on the off-axis region demonstrated that TomoEQA can provide accurate results for 3D dose analysis, which is inherently difficult in the conventional QA method. Through a statistical analysis based on the results of TomoEQA, it was validated that the total fraction (Total Fx), monitor units, beam-on-time, leaf-of-time below 100 ms, and planning target volume diameter were statistically significant for the pass/failure of the pre-treatment QA results.

CONCLUSIONS: TomoEQA is a clinically beneficial alternative to the conventional phantom-based QA method.

PMID:36344983 | DOI:10.1186/s13014-022-02151-x

BMC Biol. 2022 Nov 7;20(1):249. doi: 10.1186/s12915-022-01449-2.

ABSTRACT

BACKGROUND: Introgression from extinct Neanderthal and Denisovan human species has been shown to contribute to the genetic pool of modern human populations and their phenotypic spectrum. Evidence of how Neanderthal introgression shaped the genetics of human traits and diseases has been extensively studied in populations of European descent, with signatures of admixture reported for instance in genes associated with pigmentation, immunity, and metabolic traits. However, limited information is currently available about the impact of archaic introgression on other ancestry groups. Additionally, to date, no study has been conducted with respect to the impact of Denisovan introgression on the health and disease of modern populations. Here, we compare the way evolutionary pressures shaped the genetics of complex traits in East Asian and European populations, and provide evidence of the impact of Denisovan introgression on the health of East Asian and Central/South Asian populations.

RESULTS: Leveraging genome-wide association statistics from the Biobank Japan and UK Biobank, we assessed whether Denisovan and Neanderthal introgression together with other evolutionary genomic signatures were enriched for the heritability of physiological and pathological conditions in populations of East Asian and European descent. In EAS, Denisovan-introgressed loci were enriched for coronary artery disease heritability (1.69-fold enrichment, p=0.003). No enrichment for archaic introgression was observed in EUR. We also performed a phenome-wide association study of Denisovan and Neanderthal alleles in six ancestry groups available in the UK Biobank. In EAS, the Denisovan-introgressed SNP rs62391664 in the major histocompatibility complex region was associated with albumin/globulin ratio (beta=-0.17, p=3.57×10^-7). Neanderthal-introgressed alleles were associated with psychiatric and cognitive traits in EAS (e.g., “No Bipolar or Depression”-rs79043717 beta=-1.5, p=1.1×10^-7), and with blood biomarkers (e.g., alkaline phosphatase-rs11244089 beta=0.1, p=3.69×10^-116) and red hair color (rs60733936 beta=-0.86, p=4.49×10^-165) in EUR. In the other ancestry groups, Neanderthal alleles were associated with several traits, also including the use of certain medications (e.g., Central/South East Asia: indapamide – rs732632 beta=-2.38, p=5.22×10^-7).

CONCLUSIONS: Our study provides novel evidence regarding the impact of archaic introgression on the genetics of complex traits in worldwide populations, highlighting the specific contribution of Denisovan introgression in EAS populations.

PMID:36344982 | DOI:10.1186/s12915-022-01449-2

Cardiovasc Diabetol. 2022 Nov 7;21(1):235. doi: 10.1186/s12933-022-01674-7.

ABSTRACT

BACKGROUND: Nephropathy in Diabetes type 2 (NID-2) study is an open-label cluster randomized clinical trial that demonstrated that multifactorial intensive treatment reduces Major Adverse Cardiac Events (MACEs) and overall mortality versus standard of care in type 2 diabetic subjects with albuminuria and no history of cardiovascular disease. Aim of the present post-hoc analysis of NID- 2 study is to evaluate whether the number of risk factors on target associates with patient outcomes.

METHODS: Intervention phase lasted four years and subsequent follow up for survival lasted 10 years. To the aim of this post-hoc analysis, the whole population has been divided into 3 risk groups: 0-1 risk factor (absent/low); 2-3 risk factors (intermediate); 4 risk factors (high). Primary endpoint was a composite of fatal and non-fatal MACEs, the secondary endpoint was all-cause death at the end of the follow-up phase.

RESULTS: Absent/low risk group included 166 patients (52.4%), intermediate risk group 128 (40.4%) and high-risk group 23 (7.3%). Cox model showed a significant higher risk of MACE and death in the high-risk group after adjustment for confounding variables, including treatment arm (HR 1.91, 95% CI 1.04-3.52, P = 0.038 and 1.96, 95%CI 1.02-3.8, P = 0,045, respectively, vs absent/low risk group).

CONCLUSIONS: This post-hoc analysis of the NID-2 trial indicates that the increase in the number of risk factors at target correlates with better cardiovascular-free survival in patients with type 2 diabetes at high CV risk.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925.

PMID:36344978 | DOI:10.1186/s12933-022-01674-7

BMC Public Health. 2022 Nov 7;22(1):2036. doi: 10.1186/s12889-022-14444-7.

ABSTRACT

BACKGROUND: Little research has investigated the associations between proximity to physical activity facilities and behavior-related health and the majority have focused on proximity from home address. We add to the literature by examining proximity of these facilities to work and home address and including a wide range of physical activity facilities. We assess the associations for proximity of physical activity facilities from home and work address with self-reported frequency of exercise and obesity.

METHODS: Our analytical sample of 7358 participants was from the 2018 wave of the Swedish Longitudinal Occupational Survey of Health. We used logistic binomial regression adjusting for age, sex, education, civil status, individual socioeconomic status, neighborhood socioeconomic status, number of children under 12 years of age, work strain, and chronic disease.

RESULTS: Longer distance from home to paid outdoor and paid indoor physical activity facilities was associated with low frequency of exercise (fully adjusted Relative Risk for both 1.01, 95% CI 1.01-1.02). Associations of any or free outdoor facility with low frequency of exercise were not robust. Findings also indicated associations between long distance from workplace to any and paid outdoor facility and low frequency of exercise. Results for obesity were in the similar direction, however, these were not statistically significant.

CONCLUSION: Increased distance of paid outdoor and paid indoor physical activity facilities from home and of paid outdoor facilities from work was associated with low frequency of exercise. Longitudinal and larger studies are needed to confirm our findings, particularly regarding obesity.

PMID:36344975 | DOI:10.1186/s12889-022-14444-7

Cardiovasc Diabetol. 2022 Nov 7;21(1):236. doi: 10.1186/s12933-022-01671-w.

ABSTRACT

BACKGROUND: Even though hyperglycemia is a well-known cardiovascular risk factor, the absolute risk of cardiovascular events varies to a great extent within each glycemic category. The aim of this study is to evaluate whether N-terminal pro-B natriuretic peptide (NT-ProBNP) could help identify subjects at higher cardiovascular risk, independently of blood glucose levels.

METHODS: Serum NT-ProBNP levels were measured in 5502 people aged 45-79 years without heart failure from the general population (3380 with normoglycemia, 1125 with pre-diabetes and 997 with diabetes) that participated in the 1999-2004 cycles of the National Health and Nutrition Examination Survey. We applied Cox and Fine Gray models adjusted for cardiovascular risk factors to evaluate the association between NT-ProBNP levels and all-cause and cardiovascular mortality through December 2015.

RESULTS: After a median follow-up of 13 years, 1509 participants died, 330 of cardiovascular causes. In the multivariable-adjusted models, compared with participants with NT-ProBNP < 100 pg/ml, those with levels 100-300 pg/ml and ≥ 300 pg/ml had a higher incidence of both all-cause mortality (HR 1.61, 95% CI 1.12-2.32, p = 0.012 and HR 2.96, 95% CI 1.75-5.00, p < 0.001, respectively) and cardiovascular mortality (HR 1.57, 95% CI 1.17-2.10, p = 0.011 and HR 2.08, 95% CI 1.47-2.93, p < 0.001, respectively). The association was consistent in subgroup analyses based on glycemic status, obesity, age and sex.

CONCLUSIONS: Elevated NT-ProBNP is independently associated with all-cause and cardiovascular mortality in the general population and could help identify patients at the highest risk. Further studies are needed to evaluate whether intensification of treatment based on biomarker data might lead to improvements in cardiovascular risk reduction.

PMID:36344968 | DOI:10.1186/s12933-022-01671-w

BMC Biol. 2022 Nov 8;20(1):245. doi: 10.1186/s12915-022-01427-8.

ABSTRACT

BACKGROUND: The Nile rat (Avicanthis niloticus) is an important animal model because of its robust diurnal rhythm, a cone-rich retina, and a propensity to develop diet-induced diabetes without chemical or genetic modifications. A closer similarity to humans in these aspects, compared to the widely used Mus musculus and Rattus norvegicus models, holds the promise of better translation of research findings to the clinic.

RESULTS: We report a 2.5 Gb, chromosome-level reference genome assembly with fully resolved parental haplotypes, generated with the Vertebrate Genomes Project (VGP). The assembly is highly contiguous, with contig N50 of 11.1 Mb, scaffold N50 of 83 Mb, and 95.2% of the sequence assigned to chromosomes. We used a novel workflow to identify 3613 segmental duplications and quantify duplicated genes. Comparative analyses revealed unique genomic features of the Nile rat, including some that affect genes associated with type 2 diabetes and metabolic dysfunctions. We discuss 14 genes that are heterozygous in the Nile rat or highly diverged from the house mouse.

CONCLUSIONS: Our findings reflect the exceptional level of genomic resolution present in this assembly, which will greatly expand the potential of the Nile rat as a model organism.

PMID:36344967 | DOI:10.1186/s12915-022-01427-8

BMC Public Health. 2022 Nov 7;22(1):2032. doi: 10.1186/s12889-022-14445-6.

ABSTRACT

BACKGROUND: The migrant elderly following family (MEFF), who migrates to new community to reunite with families, may face challenges of city integration and belonging. This study aims to explore from an elderly service perspective how to improve the sense of city belonging for MEFFs with and without hypertension/diabetes conditions.

METHODS: Data were derived from the 2017 China Migrants Dynamic Survey and China National Statistical Yearbooks in 2017. The study included 882 MEFFs with hypertension or diabetes and 1266 MEFFs without hypertension and diabetes. Hierarchical linear modeling was applied to analyze the effects of individual and provincial elderly services on sense of city belonging among the MEFF with and without hypertension/diabetes.

RESULTS: The MEFFs with hypertension or diabetes exhibited a greater sense of city belonging when they were familiar with a wider range of health education topics (γ = 0.05, p = 0.033) and were in those provinces with a greater number of licensed doctors (γ = 0.39, p < 0.001) and hospitals (p = 0.042). For those MEFFs without hypertension or diabetes, social security cards (γ = 0.57, p < 0.001) and awareness of a wider range of health education topics (γ = 0.07, p = 0.018) may help to improve their sense of city belonging.

CONCLUSION: This study calls for strengthening the accessibility in inclusive elderly services, and minimizing or even eliminating the inequality in elderly services at the individual and provincial levels to increase sense of city belonging among the MEFFs. For the MEFFs with hypertension or diabetes, health managers should focus on improving health information dissemination and increasing the number of doctors per 1000 people as well as and the number of hospitals to enhance the sense of city belonging. Moreover, the government should strengthen social security and health education to facilitate the adaptation and integration of MEFFs without hypertension and diabetes into the host city.

PMID:36344960 | DOI:10.1186/s12889-022-14445-6