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Role of Immunotherapy in Stage IV Large Cell Neuroendocrine Carcinoma of the Lung

Asian Pac J Cancer Prev. 2021 Feb 1;22(2):365-370. doi: 10.31557/APJCP.2021.22.2.365.

ABSTRACT

BACKGROUND: Despite approvals of immune checkpoint inhibitors in both small cell and non-small cell lung cancers, the role of immunotherapy in large cell neuroendocrine carcinoma (LCNEC) in lung is undefined.

METHODS: Using the National Cancer Database (NCDB), Stage IV lung LCNEC cases diagnosed from 2014 to 2016 were analyzed. Information regarding cancer treatment was limited to first course of therapy, including surgery for primary lesion, radiation, chemotherapy, and immunotherapy. Survival analysis was performed using Kaplan-Meier curves and Log-rank tests. Cox proportional hazard model was used for multivariate analysis.

RESULTS: Among 661 eligible cases, 37 patients were treated with immunotherapy. No significant association between use of immunotherapy and clinical demographics was observed except for use of chemotherapy (p=0.0008). Chemotherapy was administered in 34 (92%) and 406 (65%) in immunotherapy and non-immunotherapy groups, respectively. Use of immunotherapy was associated with improved overall survival (Log-rank p=0.0018). Landmark analysis in the immunotherapy group showed 12 and 18-month survivals of 34.0% and 29.1%, respectively, whereas those in the non-immunotherapy group were 24.1% and 15.0%, respectively. Multivariate analysis demonstrated that female sex (HR=0.79, p=0.0063), liver metastases (HR=0.75, p=.0392), surgery (HR= 0.50, p <0.0001) use of chemotherapy (HR= 0.44, p <0.0001), and use of immunotherapy (HR=0.64, p=0.0164) had statistical significance. Propensity score matching in overall survival analysis showed a nonsignificant trend (p=0.0733) in favor of immunotherapy treatment.

CONCLUSION: This retrospective study using NCDB suggests that use of immunotherapy may improve survival of LCNEC patients.

PMID:33639649 | DOI:10.31557/APJCP.2021.22.2.365

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How Well Have Projected Lung Cancer Rates Predicted the Actual Observed Rates?

Asian Pac J Cancer Prev. 2021 Feb 1;22(2):437-445. doi: 10.31557/APJCP.2021.22.2.437.

ABSTRACT

BACKGROUND: While many past studies have constructed projections of future lung cancer rates, little is known about their consistency with the corresponding observed data for the time period covered by the projections. The aim of this study was to assess the agreement between previously published lung cancer incidence and/or mortality rate projections and observed rates.

METHODS: Published studies were included in the current study if they projected future lung cancer rates for at least 10 years beyond the period for which rates were used to obtain the projections, and if more recent observed rates for comparison covered a minimum of 10 years from the beginning of the projection period. Projected lung cancer incidence and/or mortality rates from these included studies were extracted from the publications. Observed rates were obtained from cancer registries or the World Health Organization’s Mortality Database. Agreement between projected and observed rates was assessed and the relative difference (RD) for each projected rate was calculated as the percentage difference between the projected and observed rates.

RESULTS: A total of 59 projections reported in 14 studies were included. Nine studies provided projections for 20 years or more. RDs were higher for those projections in which the lung cancer rates peaked during the projection period, and RDs increased substantially with the length of the projection period. When lung cancer rates peaked during the projection period, methods incorporating smoking data were generally more successful at predicting the trend reversal than those which did not incorporate smoking data. Mean RDs for 15-year projections comparing methods with or without smoking data were 12.7% versus 48.0% for males and 8.2% versus 42.3% for females.

CONCLUSIONS: The agreement between projected and observed lung cancer rates is dependent on the trends in the observed rates and characteristics of the population, particularly trends in smoking.

PMID:33639658 | DOI:10.31557/APJCP.2021.22.2.437

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AI identifies social bias trends in Bollywood, Hollywood movies

An automated computer analysis method designed by Carnegie Mellon University computer scientists makes it possible to track social biases across decades of Bollywood and Hollywood movies.
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Timing of mortality in mothers with recurrent convictions for driving under the influence of alcohol and their children, from childbirth to child age 17

Drug Alcohol Depend. 2021 Feb 16;221:108620. doi: 10.1016/j.drugalcdep.2021.108620. Online ahead of print.

ABSTRACT

BACKGROUND: We tested variation in the timing of child and maternal mortality associated with severe maternal AUD, as represented by recurrent arrests for driving under the influence of alcohol (rDUI).

METHODS: rDUI mothers (N = 1614) and Controls with no alcohol-related driving offenses (N = 109,928) who gave birth in Missouri from 2000 to 2004 were identified using vital records. Propensity score matching adjusted for birth record measures including delayed prenatal care, smoking during pregnancy, relationship with reproductive partner [married/unmarried, paternity acknowledged/unacknowledged], partner DUI status from driving records, and for socioeconomic characteristics of maternal residential census tract at birth derived from census data. Survival analysis was used to test months from childbirth to child or maternal death as a function of lifetime rDUI status.

RESULTS: Maternal rDUIs were associated with a consistently elevated probability of child mortality from birth through child age 17 after propensity score-adjustment (Hazard Ratio [HR] = 1.70, 95 % CI = 1.17-2.47). Maternal mortality was not elevated, relative to Controls, until child age 6-11 (HR = 1.58, 95 % CI = 1.05-2.35) and increased again from child age 12-17 (HR = 4.12, 95 % CI = 3.04-5.86).

CONCLUSIONS: Severe maternal AUD, as characterized by rDUI, increases the risk for child mortality over that of Controls through age 17. Delays in rDUI maternal mortality until child age 6 may indicate a period when maternal referral for intervention to reduce harm to child and mother is likely to be especially effective.

PMID:33639571 | DOI:10.1016/j.drugalcdep.2021.108620

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Nevin Manimala Statistics

Changes in SARS CoV-2 Seroprevalence Over Time in Ten Sites in the United States, March – August, 2020

Clin Infect Dis. 2021 Feb 26:ciab185. doi: 10.1093/cid/ciab185. Online ahead of print.

ABSTRACT

BACKGROUND: Monitoring of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody prevalence can complement case reporting to inform more accurate estimates of SARS-CoV-2 infection burden, but few studies have undertaken repeated sampling over time on a broad geographic scale.

METHODS: We performed serologic testing on a convenience sample of residual sera obtained from persons of all ages, at ten sites in the United States from March 23 through August 14, 2020, from routine clinical testing at commercial laboratories. We age-sex-standardized our seroprevalence rates using census population projections and adjusted for laboratory assay performance. Confidence intervals were generated with a two-stage bootstrap. We used Bayesian modeling to test whether seroprevalence changes over time were statistically significant.

RESULTS: Seroprevalence remained below 10% at all sites except New York and Florida, where it reached 23.2% and 13.3%, respectively. Statistically significant increases in seroprevalence followed peaks in reported cases in New York, South Florida, Utah, Missouri and Louisiana. In the absence of such peaks, some significant decreases were observed over time in New York, Missouri, Utah, and Western Washington. The estimated cumulative number of infections with detectable antibody response continued to exceed reported cases in all sites.

CONCLUSIONS: Estimated seroprevalence was low in most sites, indicating that most people in the U.S. have not been infected with SARS-CoV-2 as of July 2020. The majority of infections are likely not reported. Decreases in seroprevalence may be related to changes in healthcare-seeking behavior, or evidence of waning of detectable anti-SARS CoV-2 antibody levels at the population level. Thus, seroprevalence estimates may underestimate the cumulative incidence of infection.

PMID:33639620 | DOI:10.1093/cid/ciab185

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Metabolomic profiling reveals plasma GlycA and GlycB as a potential biomarkers for treatment efficiency in rheumatoid arthritis

J Pharm Biomed Anal. 2021 Feb 17;197:113971. doi: 10.1016/j.jpba.2021.113971. Online ahead of print.

ABSTRACT

In this pilot study, we carried out metabolic profiling of patients with rheumatoid arthritis (RA) starting therapy with biological disease-modifying antirheumatic drugs (bDMARDs). The main aim of the study was to assess the occurring metabolic changes associated with therapy success and metabolic pathways involved. In particular, the potential of the metabolomics profiles was evaluated as therapeutically valuable prognostic indicators of the effectiveness of bDMARD treatment to identify responders versus non-responders prior to implementing treatment. Plasma metabolomic profiles of twenty-five patients with RA prior bDMARD treatment and after three months of therapy were obtained by 1H NMR, liquid chromatography – mass spectrometry, and gas chromatography – mass spectrometry and evaluated by statistical and multivariate analyses. In the group of responders, significant differences in their metabolic patterns were seen after three months of the bDMARD therapy compared with profiles prior to treatment. We identified 24 metabolites that differed significantly between these two-time points mainly belonging to amino acid metabolism, peptides, lipids, cofactors, and vitamins and xenobiotics. Eleven metabolites differentiated responders versus non-responders before treatment. Additionally, N-acetylglucosamine and N-acetylgalactosamine (GlycA) and N-acetylneuraminic acid (GlycB) persisted significant in comparison responders to non-responders after three months of therapy. Moreover, those two metabolites indicated prediction of response potential by results of receiver-operating characteristic (ROC) curve analysis. The applied analysis provides novel insights into the metabolic pathways involved in RA patient’s response to bDMARD and therapy effectiveness. GlycA and GlycB are promising biomarkers to identify responding patients prior onset of bDMARD therapy.

PMID:33639525 | DOI:10.1016/j.jpba.2021.113971

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Application of ultrasonication at different microbial growth stages during apple juice fermentation by Lactobacillus plantarum: Investigation on the metabolic response

Ultrason Sonochem. 2021 Feb 4;73:105486. doi: 10.1016/j.ultsonch.2021.105486. Online ahead of print.

ABSTRACT

In this work, low-intensity ultrasonication (58.3 and 93.6 W/L) was performed at lag, logarithmic and stationary growth phases of Lactobacillus plantarum in apple juice fermentation, separately. Microbial responses to sonication, including microbial growth, profiles of organic acids profile, amino acids, phenolics, and antioxidant capacity, were examined. The results revealed that obvious responses were made by Lactobacillus plantarum to ultrasonication at lag and logarithmic phases, whereas sonication at stationary phase had a negligible impact. Sonication at lag and logarithmic phases promoted microbial growth and intensified biotransformation of malic acid to lactic acid. For example, after sonication at lag phase for 0.5 h, microbial count and lactic acid content in the ultrasound-treated samples at 58.3 W/L reached 7.91 ± 0.01 Log CFU/mL and 133.70 ± 7.39 mg/L, which were significantly higher than that in the non-sonicated samples. However, the ultrasonic effect on microbial growth and metabolism of organic acids attenuated with fermentation. Moreover, ultrasonication at lag and logarithmic phases had complex influences on the metabolism of apple phenolics such as chlorogenic acid, caffeic acid, procyanidin B2, catechin and gallic acid. Ultrasound could positively affect the hydrolysis of chlorogenic acid to caffeic acid, the transformation of procyanidin B2 and decarboxylation of gallic acid. The metabolism of organic acids and free amino acids in the sonicated samples was statistically correlated with phenolic metabolism, implying that ultrasound may benefit phenolic derivation by improving the microbial metabolism of organic acids and amino acids.

PMID:33639530 | DOI:10.1016/j.ultsonch.2021.105486

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Racial/ethnic differences in positive childhood experiences across a national sample

Child Abuse Negl. 2021 Feb 24;115:105012. doi: 10.1016/j.chiabu.2021.105012. Online ahead of print.

ABSTRACT

BACKGROUND: Examination of racial/ethnic differences in positive childhood experiences (PCEs) is needed, as the absence of supportive factors may hinder children from healthy processing and mitigation of adversity.

OBJECTIVE: The purpose of this study was to examine the prevalence of PCEs in a nationally representative sample of children and determine whether PCE exposure differed across race and ethnic groups.

PARTICIPANTS AND SETTING: Data were drawn from the nationally representative 2017-2018 National Survey of Children’s Health (NSCH) (n = 33,747).

METHODS: Descriptive statistics and bivariate analyses were used in order to calculate frequencies, proportions, and unadjusted associations for each variable. Multivariable regression models were used to examine the association between race/ethnicity and PCEs.

RESULTS: All racial-ethnic minority groups of children had a lower likelihood of mentorship, living in a safe neighborhood, or living in a supportive neighborhood, than their Non-Hispanic White counterparts. Non-Hispanic Black children had a lower likelihood of having a mentor for advice or guidance (aOR 0.50; 95 % CI 0.38-0.62), living in a safe neighborhood (aOR 0.62; 95 % CI 0.52-0.73), and living in a supportive neighborhood (aOR 0.75; 95 % CI 0.64-0.87) than Non-Hispanic white children.

CONCLUSIONS: The information from this study highlights the negative disparities borne by racial/ethnic minority populations. Findings can be used to inform policymakers, program developers, and stakeholders on where to target interventions and how to bring together families and communities to not only confront adversity in childhood, but also to leverage community and family-level assets to create PCEs for all children.

PMID:33639558 | DOI:10.1016/j.chiabu.2021.105012

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Random forest model based fine scale spatiotemporal O3 trends in the Beijing-Tianjin-Hebei region in China, 2010 to 2017

Environ Pollut. 2021 Feb 2;276:116635. doi: 10.1016/j.envpol.2021.116635. Online ahead of print.

ABSTRACT

Ambient ozone (O3) concentrations have shown an upward trend in China and its health hazards have also been recognized in recent years. High-resolution exposure data based on statistical models are needed. Our study aimed to build high-performance random forest (RF) models based on training data from 2013 to 2017 in the Beijing-Tianjin-Hebei (BTH) region in China at a 0.01 ° × 0.01 ° resolution, and estimated daily maximum 8h average O3 (O3-8hmax) concentration, daily average O3 (O3-mean) concentration, and daily maximum 1h O3 (O3-1hmax) concentration from 2010 to 2017. Model features included meteorological variables, chemical transport model output variables, geographic variables, and population data. The test-R2 of sample-based O3-8hmax, O3-mean and O3-1hmax models were all greater than 0.80, while the R2 of site-based and date-based model were 0.68-0.87. From 2010 to 2017, O3-8hmax, O3-mean, and O3-1hmax concentrations in the BTH region increased by 4.18 μg/m3, 0.11 μg/m3, and 4.71 μg/m3, especially in more developed regions. Due to the influence of weather conditions, which showed high contribution to the model, the long-term spatial distribution of O3 concentrations indicated a similar pattern as altitude, where high concentration levels were distributed in regions with higher altitude.

PMID:33639490 | DOI:10.1016/j.envpol.2021.116635

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Qualitative characterization of breast tumors with diffusion-weighted imaging has comparable accuracy to quantitative analysis

Clin Imaging. 2021 Feb 23;77:17-24. doi: 10.1016/j.clinimag.2021.02.025. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the applicability and accuracy of a new qualitative diffusion-weighted imaging (DWI) assessment method in the characterization of breast tumors compared to quantitative ADC measurement and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI).

MATERIALS AND METHODS: After review board approval, MRIs of 216 consecutive women with final diagnoses (131 malignant, 85 benign) were retrospectively analyzed. Two radiologists independently scored DWI and dynamic contrast-enhanced MRI (DCE-MRI) according to malignancy probability. Qualitative assessments were performed by combined analysis of tumor morphology and diffusion signal. Quantitative data was obtained from apparent diffusion coefficient (ADC) measurements. Lastly, descriptive DWI features were evaluated and recorded. Cohen’s kappa, receiver operating characteristic and multivariate analyzes were applied.

RESULTS: Of malignant tumors, 97% were visible on DWI. Qualitative and quantitative DWI assessments provided comparable sensitivities of 89-94% and 88-92% and specificities of 51-61% and 59-67%, respectively. There was no statistical difference between the accuracies of qualitative and quantitative DWI (p ≥ 0.105). Best diagnostic values were obtained with DCE-MRI (sensitivity, 99-100%; specificity, 69-71%). Inter-reader agreement was moderate (kappa = 0.597) for qualitative DWI and substantial (kappa = 0.689) for DCE-MRI (p < 0.001). Agreement between qualitative DWI and DCE-MRI scores was moderate (kappa = 0.536 and 0.442). Visual diffusion signal, mass margin and shape were the most predictive features of malignancy on multivariate analysis of qualitative assessment.

CONCLUSION: Qualitative characterization of breast tumors on DWI has comparable accuracy to quantitative ADC analysis. This method might be used to make DWI more widely available with eliminating the need to a predetermined ADC threshold in tumor characterization. However, lower accuracy and inter-reader agreement of it compared to DCE-MRI should be considered.

PMID:33639496 | DOI:10.1016/j.clinimag.2021.02.025