Tag: nevin manimala

J Natl Cancer Inst. 2022 Feb 21:djac046. doi: 10.1093/jnci/djac046. Online ahead of print.

ABSTRACT

Although indications for immune checkpoint inhibitors (ICIs) have dramatically increased in the past decade, ICIs have been associated with autoinflammatory immune-related adverse events which can resemble autoimmune diseases (ADs). Little is known about the impact of baseline AD on mortality in cancer patients treated with ICIs. Here, we identified 17,497 patients with pre-existing autoimmune diagnoses prior to treatment with anti-PD-1 or anti-PD-L1 therapy and 17,497 matched controls through the TriNetX Diamond network of over 200 million patients across the US and Europe. Using a Cox proportional hazards model, we found that patients with history of AD were not at higher risk of mortality than non-AD controls (HR, 1.03; 95% CI, 1-1.07; p = 0.05). Additionally, history of Hashimoto’s disease (HR, 0.75; 95% CI, 0.62-0.90; p = 0.002) and vitiligo (HR,0.52; 95% CI, 0.34-0.81; p = 0.003) were statistically significantly associated with decreased mortality. This suggests that underlying AD need not be a contraindication to inclusion in clinical trials and administration of ICI for treatment of cancer.

PMID:35188215 | DOI:10.1093/jnci/djac046

J Gerontol B Psychol Sci Soc Sci. 2022 Feb 21:gbab129. doi: 10.1093/geronb/gbab129. Online ahead of print.

ABSTRACT

OBJECTIVES: This study assesses how American life expectancy compares to other high-income countries and identifies key age groups and causes of death responsible for the U.S. life expectancy shortfall.

METHODS: Data from the Human Mortality Database, World Health Organization Mortality Database, and vital statistics agencies for 18 high-income countries are used to examine trends in U.S. life expectancy gaps and how American age-specific death rates compare to other countries. Decomposition is used to estimate the contribution of 19 age groups and 16 causes to the U.S. life expectancy shortfall.

RESULTS: In 2018, life expectancy for American men and women was 5.18 and 5.82 years lower than the world leaders and 3.60 and 3.48 years lower than the average of the comparison countries. Americans aged 25-29 experience death rates nearly three times higher than their counterparts. Together, injuries (drug overdose, firearm-related deaths, motor vehicle accidents, homicide), circulatory diseases, and mental disorders/nervous system diseases (including Alzheimer’s disease) account for 86% and 67% of American men’s and women’s life expectancy shortfall.

DISCUSSION: American life expectancy has fallen far behind its peer countries. The U.S.’s worsening mortality at the prime adult ages and eroding old-age mortality advantage drive its deteriorating performance in international comparisons.

PMID:35188201 | DOI:10.1093/geronb/gbab129

Rheumatology (Oxford). 2022 Feb 21:keac098. doi: 10.1093/rheumatology/keac098. Online ahead of print.

ABSTRACT

OBJECTIVES: Myocarditis in systemic sclerosis (SSc) is associated with a poor prognosis. Cardiac Magnetic Resonance (CMR) is the non-invasive diagnostic modality of choice for SSc-myocarditis. Our study investigates the performance of the mapping techniques, included in the revised Lake Louise Criteria (LLC), for the identification of SSc-myocarditis.

METHODS: CMR data (right and left ventricular function and morphology, early and late gadolinium enhancement [LGE], T2 ratio, and T1 mapping, extra-cellular volume [ECV] and T2 mapping) of SSc patients diagnosed with myocarditis were reviewed. Myocarditis was defined by the presence of symptoms of SSc-heart involvement with increased high-sensitive troponin T(hs-TnT) and/or NT-proBNP and at least an abnormality at 24 h-ECG-Holter and/or echocardiography and/or CMR. A p-value < 0.05 was considered as statistically significant.

RESULTS: 19 patients (median age 54 [46-70] years; females 78.9%; diffuse SSc 52.6%; anti-Scl70 + 52.6%) were identified: 11(57.9%) had echocardiographic, and 8(42.8%) 24 h-ECG Holter abnormalities. All patients had at least one CMR abnormality: LGE in 18(94.7%), increased ECV in 10(52.6%), T2 mapping > 50ms in 15(78.9%). Median T1 and T2 mapping were 1085[1069-1110]ms and 53.1[52-54]ms, respectively. T1 mapping directly correlated with NT-proBNP(r = 0.620; p= 0.005), ESR(r = 0.601; p= 0.008), CRP(r = 0.685; p= 0.001) and skin score(r = 0.507; p= 0.027); ECV correlated with NT-proBNP serum levels(r = 0.702; p= 0.001). No correlations emerged between T2 mapping and other parameters. Ten patients satisfied the 2009 LLC, 17 the 2018 LLC. With the new criteria including T2-mapping, the sensitivity improved from 52.6% to 89.5%.

CONCLUSION: the CMR mapping techniques improve the sensitivity to detect myocardial inflammation in patients with SSc-heart involvement. The evaluation of T2 mapping increases diagnostic accuracy for the recognition of myocardial inflammation in SSc.

PMID:35188182 | DOI:10.1093/rheumatology/keac098

Bioinformatics. 2022 Feb 21:btac110. doi: 10.1093/bioinformatics/btac110. Online ahead of print.

ABSTRACT

MOTIVATION: microRNAs are important post-transcriptional regulators of gene expression, but the identification of functionally relevant targets is still challenging. Recent research has shown improved prediction of microRNA-mediated repression using a biochemical model combined with empirically-derived k-mer affinity predictions, however these findings are not easily applicable.

RESULTS: We translate this approach into a flexible and user-friendly bioconductor package, scanMiR, also available through a web interface. Using lightweight linear models, scanMiR efficiently scans for binding sites, estimates their affinity, and predicts aggregated transcript repression. Moreover, flexible 3′-supplementary alignment enables the prediction of unconventional interactions, such as bindings potentially leading to target-directed microRNA degradation or slicing. We showcase scanMiR through a systematic scan for such unconventional sites on neuronal transcripts, including lncRNAs and circRNAs. Finally, in addition to the main bioconductor package implementing these functions, we provide a user-friendly web application enabling the scanning of sequences, the visualization of predicted bindings, and the browsing of predicted target repression.

AVAILABILITY: scanMiR and companion packages are implemented in R, released under the GPL-3 and accessible on Bioconductor (https://bioconductor.org/packages/release/bioc/html/scanMiR.html) as well as through a shiny web server (https://ethz-ins.org/scanMiR/).

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:35188178 | DOI:10.1093/bioinformatics/btac110

J Vis Exp. 2022 Feb 4;(180). doi: 10.3791/63340.

ABSTRACT

Multiple lines of research provide compelling evidence for a role of the cerebellum in a wide array of cognitive and affective functions, going far beyond its historical association with motor control. Structural and functional neuroimaging studies have further refined understanding of the functional neuroanatomy of the cerebellum beyond its anatomical divisions, highlighting the need for the examination of individual cerebellar subunits in healthy variability and neurological diseases. This paper presents a standardized pipeline for examining cerebellum grey matter morphometry that combines high-resolution, state-of-the-art approaches for optimized and automated cerebellum parcellation (Automatic Cerebellum Anatomical Parcellation using U-Net Locally Constrained Optimization; ACAPULCO) and voxel-based registration of the cerebellum (Spatially Unbiased Infra-tentorial Template; SUIT) for volumetric quantification. The pipeline has broad applicability to a range of neurological diseases and is fully automated, with manual intervention only required for quality control of the outputs. The pipeline is freely available, with substantial accompanying documentation, and can be run on Mac, Windows, and Linux operating systems. The pipeline is applied in a cohort of individuals with Friedreich ataxia (FRDA), and representative results, as well as recommendations on group-level inferential statistical analyses, are provided. This pipeline could facilitate reliability and reproducibility across the field, ultimately providing a powerful methodological approach for characterizing and tracking cerebellar structural changes in neurological diseases.

PMID:35188124 | DOI:10.3791/63340

Elife. 2022 Feb 21;11:e72707. doi: 10.7554/eLife.72707.

ABSTRACT

The prevalence of multicellular organisms is due in part to their ability to form complex structures. How cells pack in these structures is a fundamental biophysical issue, underlying their functional properties. However, much remains unknown about how cell packing geometries arise, and how they are affected by random noise during growth – especially absent developmental programs. Here, we quantify the statistics of cellular neighborhoods of two different multicellular eukaryotes: lab-evolved ‘snowflake’ yeast and the green alga Volvox carteri. We find that despite large differences in cellular organization, the free space associated with individual cells in both organisms closely fits a modified gamma distribution, consistent with maximum entropy predictions originally developed for granular materials. This ‘entropic’ cellular packing ensures a degree of predictability despite noise, facilitating parent-offspring fidelity even in the absence of developmental regulation. Together with simulations of diverse growth morphologies, these results suggest that gamma-distributed cell neighborhood sizes are a general feature of multicellularity, arising from conserved statistics of cellular packing.

PMID:35188101 | DOI:10.7554/eLife.72707

Clin Exp Optom. 2022 Feb 20:1-11. doi: 10.1080/08164622.2022.2033603. Online ahead of print.

ABSTRACT

CLINICAL RELEVANCE: This paper provides eye care practitioners with important information about the potential side effects of 0.01% atropine.

BACKGROUND: Eye care practitioners routinely administer 0.01% atropine eye drops nightly to slow the progression of myopia, but nobody has assessed accommodative lag or facility, near phoria, intraocular pressure or comfort of drop administration.

METHODS: All 21- to 30-year-old adults with no history of accommodative issues or therapy were eligible. During the baseline visit, participants underwent testing related to potential side effects. Participants then administered one drop of 0.01% atropine nightly to both eyes, and all tests were repeated 1 week later.

RESULTS: The average ± standard deviation age of the 31 participants was 23.9 ± 1.6 years, 71% were female, and 81% were Caucasian. The only significant changes were an increase in photopic pupil size from 4.9 ± 0.8 at baseline to 5.1 ± 0.6 mm after 1 week (paired sample t-test, p = 0.002) and an increase of the average intraocular pressure of the two eyes from 15.6 ± 2.7 to 16.7 ± 3.1 mmHg (paired-sample t-test, p = 0.003), but neither of these changes was clinically meaningful. There were no other statistically significant differences before and after 1-week administration of 0.01% atropine for any of the vision, accommodation, reading speed or subjective side effects. When asked how likely they would be to take the atropine drops to delay the onset of myopia on a scale from 1 (definitely not) to 10 (definitely would), participants replied with an average of 8.2 ± 2.0 after taking atropine eye drops for 1 week (paired-sample t-test, p = 0.81).

CONCLUSION: Nightly administration of 0.01% atropine did not result in any clinically meaningful symptoms, so patients would be very likely to take the drops to delay the onset of myopia.

PMID:35188076 | DOI:10.1080/08164622.2022.2033603

J Int Neuropsychol Soc. 2022 Feb 21:1-11. doi: 10.1017/S1355617722000091. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine whether the DCTclock can detect differences across groups of patients seen in the memory clinic for suspected dementia.

METHOD: Patients (n = 123) were classified into the following groups: cognitively normal (CN), subtle cognitive impairment (SbCI), amnestic cognitive impairment (aMCI), and mixed/dysexecutive cognitive impairment (mx/dysMCI). Nine outcome variables included a combined command/copy total score and four command and four copy indices measuring drawing efficiency, simple/complex motor operations, information processing speed, and spatial reasoning.

RESULTS: Total combined command/copy score distinguished between groups in all comparisons with medium to large effects. The mx/dysMCI group had the lowest total combined command/copy scores out of all groups. The mx/dysMCI group scored lower than the CN group on all command indices (p < .050, all analyses); and lower than the SbCI group on drawing efficiency (p = .011). The aMCI group scored lower than the CN group on spatial reasoning (p = .019). Smaller effect sizes were obtained for the four copy indices.

CONCLUSIONS: These results suggest that DCTclock command/copy parameters can dissociate CN, SbCI, and MCI subtypes. The larger effect sizes for command clock indices suggest these metrics are sensitive in detecting early cognitive decline. Additional research with a larger sample is warranted.

PMID:35188095 | DOI:10.1017/S1355617722000091

J Matern Fetal Neonatal Med. 2022 Feb 20:1-8. doi: 10.1080/14767058.2022.2040475. Online ahead of print.

ABSTRACT

PURPOSE: Vitamin D deficiency is common during pregnancy and may cause complications such as preterm labor (PTL). This study was aimed to investigate the effect of the vitamin D-binding protein (VDBP) rs7041 genotype, which has a significant effect on vitamin D metabolism and PTL.

METHODS: This cross-sectional study was conducted with 32 pregnant women who had spontaneous PTL and 54 pregnant women who had no specific findings as a control group. Serum total vitamin D 25-hydroxy vitamin D (25(OH)D) levels were measured using the Elecsys Vitamin D Total Kit. VDBP was measured using a VDBP Quantikine ELISA Kit. The levels of bioavailable 25(OH)D were calculated based on the total 25(OH)D and VDBP concentrations. DNA was extracted using the DNeasy Blood and Tissue Kit. Single nucleotide polymorphisms (rs7041) in GC were analyzed using a TaqMan SNP Genotyping Assay Kit. The unpaired t-test, Chi-squared, and ANCOVA tests were performed. Firth’s penalized logistic regression was applied. The area under the curve (AUC) was calculated and the cutoff value was determined. All statistical analyses were performed using R version 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria).

RESULTS: Total 25(OH)D levels were not significantly different between the two groups. Bioavailable 25(OH)D was significantly decreased in PTL women (p= .011), and VDBP was significantly increased in PTL women (p= .004) compared to the controls. Bioavailable 25(OH)D was lower in women with GT/TG and TT rs7041 genotypes than in those with GG, with statistical significance in women with the TT allele (p= .048). VDBP was higher in women with GT/TG and TT than those with GG, but there was no statistical significance. In PTL prevalence, bioavailable 25(OH)D and VDBP, the odds ratio increased by 1.463 times in GT/TG (p= .728) and increased by 1.675 times in TT compared to the GG allele (p= .640). In receiver operating characteristic (ROC) analysis for bioavailable 25(OH)D and VDBP, the AUC was 0.665 and 0685, respectively. The optimum cutoff of bioavailable 25(OH)D and VDBP levels for the diagnosis of PTL was calculated as 0.6 ng/mL and 523 µg/mL, respectively.

CONCLUSIONS: Pregnant women with the VDBP rs7041(c.1296 T > G) T allele genotype had reduced serum levels of bioavailable 25(OH)D and were more likely to develop PTL. Therefore, if the T allele is found in the VDBP rs7041 SNP genotyping test before or during pregnancy, more careful prenatal care may be required because of the increased risk of PTL.

PMID:35188037 | DOI:10.1080/14767058.2022.2040475

Gynecol Endocrinol. 2022 Feb 21:1-5. doi: 10.1080/09513590.2022.2040474. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the influence of the one-day diabetes mellitus (DM) clinic management model on blood glucose control and prognosis in patients with gestational diabetes mellitus (GDM).

METHODS: A total of 930 patients diagnosed with GDM by oral glucose tolerance test screening at 24-28 weeks of gestation were selected from those who underwent outpatient prenatal checkups at our hospital and were randomly divided into one-day DM clinic group (n = 509) and control group (n = 421). A one-day DM clinic intervention was conducted in the one-day DM clinic group, and individualized dietary interventions and exercise instruction were given in the control group.

RESULTS: The compliance rates of fasting blood glucose and two-hour postprandial blood glucose (2-h PPBG) were higher in the one-day DM clinic group than in the control group (p < .05). The compliance rates of the oral glucose tolerance test and insulin release test were higher in the one-day DM clinic group than in the control group (p < .05). There existed statistically significant differences in fasting blood glucose before delivery, together with the difference between fasting blood glucose at enrollment and before delivery and the difference between glycated hemoglobin at enrollment and before delivery (p < .05).

CONCLUSION: The one-day diabetes mellitus clinic management model is more conducive to blood glucose control in patients with GDM and more conducive to the recovery of blood glucose and islet function in patients with GDM after delivery and to reduce the occurrence of adverse pregnancy outcomes.

PMID:35188053 | DOI:10.1080/09513590.2022.2040474