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Nevin Manimala Statistics

Evaluation of the mediastinal-thoracic volume ratio on postmortem computed tomography

Int J Legal Med. 2021 Apr 28. doi: 10.1007/s00414-021-02593-0. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to measure the mediastinal-thoracic volume ratio (CTR_VOL) on PMCT as a more accurate version of traditional CTR, in order to assess the terminal positional relationship between the heart and lungs in the different causes of death with regard to age, gender, BMI, cardiomegaly, and lung expansion.

MATERIALS: Two hundred fifty consecutive postmortem cases with pre-autopsy PMCT and full forensic autopsy were retrospectively evaluated. The lungs and the mediastinum were manually segmented on the PMCT data and the correspondent volumes were estimated in situ. CTR_VOL was calculated as the ratio of the mediastinal to the thoracic volume. The volume measurements were repeated by the same rater for the evaluation of the intrarater reliability. Age, gender, body weight and height, heart weight at autopsy, and cause of death were retrieved from the autopsy reports. Presence of lung expansion was radiologically evaluated in situ.

RESULTS: CTR_VOL was positively associated with age and BMI but not with gender and was higher for cardiomegaly compared to normal hearts, lower for asphyxiation-related deaths compared to cardiac deaths and intoxications, and lower for cases with lung expansion. The intrarater reliability was excellent for the calculated volumes of both lungs and mediastinum.

CONCLUSION: The results of the present study support CTR_VOL as a tool to assess the relationship between the heart and lungs in situ, which differs significantly between the studied cause of death categories.

PMID:33909145 | DOI:10.1007/s00414-021-02593-0

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A comparison of transferrin-receptor and epithelial cellular adhesion molecule targeting for microfluidic separation of cancer cells

Biomed Microdevices. 2021 Apr 28;23(2):28. doi: 10.1007/s10544-021-00566-z.

ABSTRACT

Microfluidic, flow cytometry, and immunomagnetic methods for cancer cell isolation have heavily relied on the Epithelial Cellular Adhesion Molecule (EpCAM) for affinity separation. While EpCAM has been used extensively for circulating tumor cell isolation, it cannot be used to isolate non-epithelial cells. The human transferrin receptor (CD71) can also be used for cancer cell isolation and has the advantage that as an affinity target it can separate virtually any cancer cell type, regardless of disease origin. However, direct comparison of the capture ability of EpCAM and CD71 has not been reported previously. In this work, cell capture with both EpCAM and CD71 were studied using a novel higher-throughput herringbone cell separation microfluidic device. Five separation chip models were designed and the one with the highest capture efficiency (average 90 ± 10%) was chosen to compare antigen targets for cell capture. Multiple cancer cell lines including CCRF-CEM, PC-3 and MDA-MB-231 were tested for cell capture performance using both ligands (anti-CD71 and anti-EpCAM) in the optimized chip design. PC-3 and MDA-MB-231 cells were spiked into blood at concentrations ranging from 0.5%-10%. PC-3 cells were separated by anti-CD71 and anti-EpCAM with 32-37% and 31-50% capture purity respectively, while MDA-MB-231 were separated with 35-53% and 33-56% capture purity using anti-CD71 and anti-EpCAM for all concentrations. The enrichment factor for the lowest concentrations of cells in blood ranged from 66-74X. The resulting enrichment of cancer cells shows that anti-CD71 was found to be statistically similar to anti-EpCAM for epithelial cancer cells, while anti-CD71 can be further used for non-epithelial cells, where anti-EpCAM cannot be used.

PMID:33909118 | DOI:10.1007/s10544-021-00566-z

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Experimental freezing of freshwater pennate diatoms from polar habitats

Protoplasma. 2021 Apr 28. doi: 10.1007/s00709-021-01648-8. Online ahead of print.

ABSTRACT

Diatoms are microalgae that thrive in a range of habitats worldwide including polar areas. Remarkably, non-marine pennate diatoms do not create any morphologically distinct dormant stages that could help them to successfully face unfavourable conditions. Their survival is probably connected with the adaptation of vegetative cells to freezing and desiccation. Here we assessed the freezing tolerance of vegetative cells and vegetative-looking resting cells of 12 freshwater strains of benthic pennate diatoms isolated from polar habitats. To test the effect of various environmental factors, the strains were exposed to -20 °C freezing in four differently treated cultures: (1) vegetative cells growing in standard conditions in standard WC medium and (2) resting cells induced by cold and dark acclimation and resting cells, where (3) phosphorus or (4) nitrogen deficiency were used in addition to cold and dark acclimation. Tolerance was evaluated by measurement of basal cell fluorescence of chlorophyll and determination of physiological cell status using a multiparameter fluorescent staining. Four strains out of 12 were able to tolerate freezing in at least some of the treatments. The minority of cells appeared to be active immediately after thawing process, while most cells were inactive, injured or dead. Overall, the results showed a high sensitivity of vegetative and resting cells to freezing stress among strains originating from polar areas. However, the importance of resting cells for survival was emphasized by a slight but statistically significant increase of freezing tolerance of nutrient-depleted cells. Low numbers of surviving cells in our experimental setup could indicate their importance for the overwintering of diatom populations in harsh polar conditions.

PMID:33909137 | DOI:10.1007/s00709-021-01648-8

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The associations of the Palaeolithic diet alone and in combination with lifestyle factors with type 2 diabetes and hypertension risks in women in the E3N prospective cohort

Eur J Nutr. 2021 Apr 28. doi: 10.1007/s00394-021-02565-5. Online ahead of print.

ABSTRACT

PURPOSE: Patterns of change from the traditional Palaeolithic lifestyle to the modern lifestyle may partly explain the epidemic proportions of non-communicable diseases (NCDs). We investigated to what extent adherence to the Palaeolithic diet (PD) and the Palaeolithic-like lifestyle was associated with type 2 diabetes (T2D) and hypertension risks.

METHODS: A study of 70,991 women from the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l’Education Nationale) cohort, followed up for nearly 20 years. There were 3292 incident T2D and 12,504 incident hypertension cases that were validated. Dietary data were collected at baseline in 1993 via a food frequency questionnaire. The PD score and the Palaeolithic-like lifestyle score (PD, physical activity, smoking status, and body mass index [BMI]) were derived and considered in quintiles. Multivariable Cox regression models were employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for incident T2D and hypertension.

RESULTS: In the fully adjusted models, a 1-SD increase of the PD score was associated with 4% and 3% lower risks of T2D and hypertension, respectively. Those in the highest versus the lowest quintile of the score had HR (95% CI) of 0.88 (0.79, 0.98) and 0.91 (0.86, 0.96) for T2D and hypertension, respectively (P-trend < 0.0001). Associations were stronger for the Palaeolithic-like lifestyle score; in the fully adjusted model, a 1-SD increase of the score was associated with 19% and 6% lower risks of T2D and hypertension, respectively. Risks lowered successively with each increase in quintile; those in the highest versus the lowest quintile had HR (95% CI) of 0.58 (0.52, 0.65) and 0.85 (0.80, 0.90) for T2D and hypertension, respectively (P-trend < 0.0001).

CONCLUSIONS: Our data suggest that adhering to a PD based on fruit, vegetables, lean meats, fish, and nuts, and incorporating a Palaeolithic-like lifestyle could be promising options to prevent T2D and hypertension.

PMID:33909140 | DOI:10.1007/s00394-021-02565-5

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A cross-tissue transcriptome-wide association study identifies novel susceptibility genes for lung cancer in Chinese populations

Hum Mol Genet. 2021 Apr 28:ddab119. doi: 10.1093/hmg/ddab119. Online ahead of print.

ABSTRACT

Although dozens of susceptibility loci have been identified for lung cancer in genome-wide association studies (GWASs), the susceptibility genes and underlying mechanisms remain unclear. In this study, we conducted a cross-tissue transcriptome-wide association study (TWAS) with UTMOST based on summary statistics from 13 327 lung cancer cases and 13 328 controls and the genetic-expression matrix over 44 human tissues in the Genotype-Tissue Expression (GTEx) project. After further evaluating the associations in each tissue, we revealed 6 susceptibility genes in known loci and identified 12 novel ones. Among those, five novel genes, including DCAF16 (Pcross-tissue = 2.57 × 10-5, PLung = 2.89 × 10-5), CBL (Pcross-tissue = 5.08 × 10-7, PLung = 1.82 × 10-4), ATR (Pcross-tissue = 1.45 × 10-5, PLung = 9.68 × 10-5), GYPE (Pcross-tissue = 1.45 × 10-5, PLung = 2.17 × 10-3) and PARD3 (Pcross-tissue = 5.79 × 10-6, PLung = 4.05 × 10-3), were significantly associated with the risk of lung cancer in both cross-tissue and lung tissue models. Further colocalization analysis indicated that rs7667864 (C > A) and rs2298650 (G > T) drove the GWAS association signals at 4p15.31-32 (OR = 1.09, 95%CI: 1.04-1.12, PGWAS = 5.54 × 10-5) and 11q23.3 (OR = 1.08, 95%CI: 1.04-1.13, PGWAS = 5.55 × 10-5), as well as the expression of DCAF16 (βGTEx = 0.24, PGTEx = 9.81 × 10-15; βNJLCC = 0.29, PNJLCC = 3.84 × 10-8) and CBL (βGTEx = -0.17, PGTEx = 2.82 × 10-8; βNJLCC = -0.32, PNJLCC = 2.61 × 10-7) in lung tissue. Functional annotations and phenotype assays supported the carcinogenic effect of these novel susceptibility genes in lung carcinogenesis.

PMID:33909040 | DOI:10.1093/hmg/ddab119

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PET/MRI for staging patients with Hodgkin lymphoma: equivalent results with PET/CT in a prospective trial

Ann Hematol. 2021 Apr 28. doi: 10.1007/s00277-021-04537-5. Online ahead of print.

ABSTRACT

To compare FDG-PET/unenhanced MRI and FDG-PET/diagnostic CT in detecting infiltration in patients with newly diagnosed Hodgkin lymphoma (HL). The endpoint was equivalence between PET/MRI and PET/CT in correctly defining the revised Ann Arbor staging system. Seventy consecutive patients with classical-HL were prospectively investigated for nodal and extra-nodal involvement during pretreatment staging with same-day PET/CT and PET/MRI. Findings indicative of malignancy with the imaging procedures were regarded as lymphoma infiltration; in case of discrepancy, positive-biopsy and/or response to treatment were evidenced as lymphoma. Sixty of the 70 (86%) patients were evaluable having completed the staging program. Disease staging based on either PET/MRI or PET/CT was correct for 54 of the 60 patients (90% vs. 90%), with difference between proportions of 0.0 (95% CI, -9 to 9%; P=0.034 for the equivalence test). As compared with reference standard, invasion of lymph nodes was identified with PET/MRI in 100% and with PET/CT in 100%, of the spleen with PET/MRI in 66% and PET/CT in 55%, of the lung with PET/MRI in 60% and PET/CT in 100%, of the liver with PET/MRI in 67% and PET/CT in 100%, and of the bone with PET/MRI in 100% and PET/CT in 50%. The only statistically significant difference between PET/MRI and PET/CT was observed in bony infiltration detection rates. For PET/CT, iodinate contrast medium infusions’ average was 86 mL, and exposure to ionizing radiation was estimated to be 4-fold higher than PET/MRI. PET/MRI is a promising safe new alternative in the care of patients with HL.

PMID:33909101 | DOI:10.1007/s00277-021-04537-5

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Racial/Ethnic Disparities in the Performance of Prediction Models for Death by Suicide After Mental Health Visits

JAMA Psychiatry. 2021 Apr 28. doi: 10.1001/jamapsychiatry.2021.0493. Online ahead of print.

ABSTRACT

IMPORTANCE: Clinical prediction models estimated with health records data may perpetuate inequities.

OBJECTIVE: To evaluate racial/ethnic differences in the performance of statistical models that predict suicide.

DESIGN, SETTING, AND PARTICIPANTS: In this diagnostic/prognostic study, performed from January 1, 2009, to September 30, 2017, with follow-up through December 31, 2017, all outpatient mental health visits to 7 large integrated health care systems by patients 13 years or older were evaluated. Prediction models were estimated using logistic regression with LASSO variable selection and random forest in a training set that contained all visits from a 50% random sample of patients (6 984 184 visits). Performance was evaluated in the remaining 6 996 386 visits, including visits from White (4 031 135 visits), Hispanic (1 664 166 visits), Black (578 508 visits), Asian (313 011 visits), and American Indian/Alaskan Native (48 025 visits) patients and patients without race/ethnicity recorded (274 702 visits). Data analysis was performed from January 1, 2019, to February 1, 2021.

EXPOSURES: Demographic, diagnosis, prescription, and utilization variables and Patient Health Questionnaire 9 responses.

MAIN OUTCOMES AND MEASURES: Suicide death in the 90 days after a visit.

RESULTS: This study included 13 980 570 visits by 1 433 543 patients (64% female; mean [SD] age, 42 [18] years. A total of 768 suicide deaths were observed within 90 days after 3143 visits. Suicide rates were highest for visits by patients with no race/ethnicity recorded (n = 313 visits followed by suicide within 90 days, rate = 5.71 per 10 000 visits), followed by visits by Asian (n = 187 visits followed by suicide within 90 days, rate = 2.99 per 10 000 visits), White (n = 2134 visits followed by suicide within 90 days, rate = 2.65 per 10 000 visits), American Indian/Alaskan Native (n = 21 visits followed by suicide within 90 days, rate = 2.18 per 10 000 visits), Hispanic (n = 392 visits followed by suicide within 90 days, rate = 1.18 per 10 000 visits), and Black (n = 65 visits followed by suicide within 90 days, rate = 0.56 per 10 000 visits) patients. The area under the curve (AUC) and sensitivity of both models were high for White, Hispanic, and Asian patients and poor for Black and American Indian/Alaskan Native patients and patients without race/ethnicity recorded. For example, the AUC for the logistic regression model was 0.828 (95% CI, 0.815-0.840) for White patients compared with 0.640 (95% CI, 0.598-0.681) for patients with unrecorded race/ethnicity and 0.599 (95% CI, 0.513-0.686) for American Indian/Alaskan Native patients. Sensitivity at the 90th percentile was 62.2% (95% CI, 59.2%-65.0%) for White patients compared with 27.5% (95% CI, 21.0%-34.7%) for patients with unrecorded race/ethnicity and 10.0% (95% CI, 0%-23.0%) for Black patients. Results were similar for random forest models, with an AUC of 0.812 (95% CI, 0.800-0.826) for White patients compared with 0.676 (95% CI, 0.638-0.714) for patients with unrecorded race/ethnicity and 0.642 (95% CI, 0.579-0.710) for American Indian/Alaskan Native patients and sensitivities at the 90th percentile of 52.8% (95% CI, 50.0%-55.8%) for White patients, 29.3% (95% CI, 22.8%-36.5%) for patients with unrecorded race/ethnicity, and 6.7% (95% CI, 0%-16.7%) for Black patients.

CONCLUSIONS AND RELEVANCE: These suicide prediction models may provide fewer benefits and more potential harms to American Indian/Alaskan Native or Black patients or those with undrecorded race/ethnicity compared with White, Hispanic, and Asian patients. Improving predictive performance in disadvantaged populations should be prioritized to improve, rather than exacerbate, health disparities.

PMID:33909019 | DOI:10.1001/jamapsychiatry.2021.0493

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IMI 2021 Yearly Digest

Invest Ophthalmol Vis Sci. 2021 Apr 28;62(5):7. doi: 10.1167/iovs.62.5.7.

ABSTRACT

PURPOSE: The International Myopia Institute (IMI) Yearly Digest highlights new research considered to be of importance since the publication of the first series of IMI white papers.

METHODS: A literature search was conducted for articles on myopia between 2019 and mid-2020 to inform definitions and classifications, experimental models, genetics, interventions, clinical trials, and clinical management. Conference abstracts from key meetings in the same period were also considered.

RESULTS: One thousand articles on myopia have been published between 2019 and mid-2020. Key advances include the use of the definition of premyopia in studies currently under way to test interventions in myopia, new definitions in the field of pathologic myopia, the role of new pharmacologic treatments in experimental models such as intraocular pressure-lowering latanoprost, a large meta-analysis of refractive error identifying 336 new genetic loci, new clinical interventions such as the defocus incorporated multisegment spectacles and combination therapy with low-dose atropine and orthokeratology (OK), normative standards in refractive error, the ethical dilemma of a placebo control group when myopia control treatments are established, reporting the physical metric of myopia reduction versus a percentage reduction, comparison of the risk of pediatric OK wear with risk of vision impairment in myopia, the justification of preventing myopic and axial length increase versus quality of life, and future vision loss.

CONCLUSIONS: Large amounts of research in myopia have been published since the IMI 2019 white papers were released. The yearly digest serves to highlight the latest research and advances in myopia.

PMID:33909031 | DOI:10.1167/iovs.62.5.7

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IMI Risk Factors for Myopia

Invest Ophthalmol Vis Sci. 2021 Apr 28;62(5):3. doi: 10.1167/iovs.62.5.3.

ABSTRACT

Risk factor analysis provides an important basis for developing interventions for any condition. In the case of myopia, evidence for a large number of risk factors has been presented, but they have not been systematically tested for confounding. To be useful for designing preventive interventions, risk factor analysis ideally needs to be carried through to demonstration of a causal connection, with a defined mechanism. Statistical analysis is often complicated by covariation of variables, and demonstration of a causal relationship between a factor and myopia using Mendelian randomization or in a randomized clinical trial should be aimed for. When strict analysis of this kind is applied, associations between various measures of educational pressure and myopia are consistently observed. However, associations between more nearwork and more myopia are generally weak and inconsistent, but have been supported by meta-analysis. Associations between time outdoors and less myopia are stronger and more consistently observed, including by meta-analysis. Measurement of nearwork and time outdoors has traditionally been performed with questionnaires, but is increasingly being pursued with wearable objective devices. A causal link between increased years of education and more myopia has been confirmed by Mendelian randomization, whereas the protective effect of increased time outdoors from the development of myopia has been confirmed in randomized clinical trials. Other proposed risk factors need to be tested to see if they modulate these variables. The evidence linking increased screen time to myopia is weak and inconsistent, although limitations on screen time are increasingly under consideration as interventions to control the epidemic of myopia.

PMID:33909035 | DOI:10.1167/iovs.62.5.3

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Impact of photobiomodulation and low-intensity pulsed ultrasound adjunctive interventions on orthodontic treatment duration during clear aligner therapy: A retrospective study

Angle Orthod. 2021 Apr 28. doi: 10.2319/112420-956.1. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the efficiency of low-intensity pulsed ultrasound (LIPUS) and photobiomodulation (PBM) interventions in accelerating orthodontic tooth movement during clear aligner therapy (CAT).

MATERIALS AND METHODS: This retrospective study was carried out on the records of 84 subjects who were treated using CAT. Twenty-eight patients were treated using CAT with a daily use of LIPUS for 20 minutes, 28 patients were treated using CAT with a daily use of PBM for 10 minutes, and 28 patients were treated using CAT alone. The total duration of treatment was recorded for all patients. One-way analysis of variance and post hoc Tukey test were used to assess whether there was any significant difference in total treatment duration among the three groups (P < .05).

RESULTS: The mean treatment durations in days were 719 ± 220, 533 ± 242, and 528 ± 323 for the control, LIPUS, and PBM groups, respectively. The LIPUS group showed a 26% reduction, on average, in treatment duration when compared with the control group, whereas the PBM group showed an average 26.6% reduction in the treatment duration when compared with the control group. The results showed that there were statistically significant differences among the groups (P = .011). Treatment durations were significantly reduced in the LIPUS and PBM groups as compared with the control (P = .027 and P = .023, respectively), with no statistically significant differences between the LIPUS and PBM groups (P = .998).

CONCLUSIONS: Daily use of LIPUS or PBM as adjunctive interventions during CAT could reduce the duration of orthodontic treatment.

PMID:33909012 | DOI:10.2319/112420-956.1