Nevin Manimala

Nucleic Acids Res. 2021 May 21:gkab340. doi: 10.1093/nar/gkab340. Online ahead of print.

ABSTRACT

RNA-RNA inter- and intramolecular interactions are fundamental for numerous biological processes. While there are reasonable approaches to map RNA secondary structures genome-wide, understanding how different RNAs interact to carry out their regulatory functions requires mapping of intermolecular base pairs. Recently, different strategies to detect RNA-RNA duplexes in living cells, so called direct duplex detection (DDD) methods, have been developed. Common to all is the Psoralen-mediated in vivo RNA crosslinking followed by RNA Proximity Ligation to join the two interacting RNA strands. Sequencing of the RNA via classical RNA-seq and subsequent specialised bioinformatic analyses the result in the prediction of inter- and intramolecular RNA-RNA interactions. Existing approaches adapt standard RNA-seq analysis pipelines, but often neglect inherent features of RNA-RNA interactions that are useful for filtering and statistical assessment. Here we present RNAnue, a general pipeline for the inference of RNA-RNA interactions from DDD experiments that takes into account hybridisation potential and statistical significance to improve prediction accuracy. We applied RNAnue to data from different DDD studies and compared our results to those of the original methods. This showed that RNAnue performs better in terms of quantity and quality of predictions.

PMID:34019662 | DOI:10.1093/nar/gkab340

Transl Vis Sci Technol. 2021 May 3;10(6):28. doi: 10.1167/tvst.10.6.28.

ABSTRACT

PURPOSE: To assess the structure-function relationship in glaucoma using Humphrey visual field (HVF) perimetry and a three-dimensional neuroretinal rim parameter derived from spectral domain optical coherence tomography (SD-OCT) volume scans.

METHODS: Structure-function correlation was analyzed globally and regionally (four quadrants and four sectors). Structural data included peripapillary retinal nerve fiber layer (RNFL) thickness and minimum distance band (MDB) neuroretinal rim thickness, defined as the shortest distance between the inner cup surface and the outer retinal pigment epithelium/Bruch’s membrane complex. Logarithmic regression analyses were performed and Pearson correlation coefficients determined to assess relationship strength.

RESULTS: The study consisted of 102 open-angle glaucoma patients and 58 healthy subjects. The Pearson correlation coefficient for global MDB thickness (R = 0.585) was higher than for global RNFL thickness (R = 0.492), but the difference was not statistically significant (P = 0.18). The correlation coefficients for regional MDB thicknesses and corresponding HVF sensitivities were higher than those for regional RNFL thicknesses and HVF in six out of eight regions (P = 0.08 to 0.47). In the remaining two out of eight regions, the correlation coefficients were higher for RNFL thickness than for MDB thickness (P = 0.15 to 0.20).

CONCLUSIONS: Three-dimensional MDB neuroretinal rim thickness relates to visual function as strongly as the most commonly used SD-OCT parameter for glaucoma, two-dimensional peripapillary RNFL thickness.

TRANSLATIONAL RELEVANCE: This paper illustrates the potential for 3D OCT algorithms to improve in vivo imaging in glaucoma.

PMID:34019635 | DOI:10.1167/tvst.10.6.28

Arch Pathol Lab Med. 2021 May 21. doi: 10.5858/arpa.2020-0413-OA. Online ahead of print.

ABSTRACT

CONTEXT.—: Active surveillance of small renal masses highlights the need for accurate prognostication of biopsies.

OBJECTIVE.—: To comprehensively evaluate the accuracy of biopsies in assessing known prognostic parameters including histologic subtype by comparison with subsequent nephrectomy samples.

DESIGN.—: We retrospectively identified patients at University of Texas Southwestern Medical Center, Dallas, Texas, who had a biopsy for a renal mass between 2004-2018. Biopsy samples were evaluated for known prognostic factors such as tumor grade, necrosis, sarcomatoid/rhabdoid change, and BRCA1-associated protein-1 (BAP1) status, which we previously showed is an independent prognostic factor for clear cell renal cell carcinoma. Accuracy was determined by comparison with subsequent analyses of nephrectomy specimens. Statistical analyses were performed to assess biopsy accuracy and correlation with tumor size and pathologic stage.

RESULTS.—: From 805 biopsies with a diagnosis of renal neoplasm, 178 had subsequent resection of the biopsied tumor. Concordance rate for histologic subtype was 96.9% (κ [w], 0.90; 95% CI, 0.82-0.99) and excellent for small renal masses (98.8%; κ [w], 0.97; 95% CI, 0.90-1). Amongst the prognostic variables evaluated, BAP1 immunohistochemistry in clear cell renal cell carcinoma had the highest agreement (94.8%; κ [w], 0.83; 95% CI, 0.66-0.99). The presence of 1 or more aggressive features (grade 3-4, tumor necrosis, BAP1 loss, sarcomatoid/rhabdoid change) in a biopsy significantly correlated with pT stage (P = .004).

CONCLUSIONS.—: Biopsy analyses showed high accuracy for subtyping renal tumors, but it underestimated several poor prognostic features. Addition of BAP1 for clear cell renal cell carcinoma may increase prognostic accuracy. If validated, routine incorporation of BAP1 immunohistochemistry in clear cell renal cell carcinoma biopsies may refine prognosis and aid in the selection of patients for active surveillance.

PMID:34019633 | DOI:10.5858/arpa.2020-0413-OA

Adv Nutr. 2021 May 21:nmab058. doi: 10.1093/advances/nmab058. Online ahead of print.

ABSTRACT

Mobile dietary record apps have been increasingly validated by studies with various study designs. This review aims to evaluate the overall accuracy of dietary record apps in measuring the intake of energy, macro- and micronutrients, and food groups in real-life settings and the designs of validation studies. We systematically searched mobile dietary record validation studies published during the period from 2013 to 2019. We identified 14 studies for the systematic review, of which 11 studies were suitable for meta-analyses on energy intake and 8 studies on macronutrient intake. Mean differences and SDs of nutrient estimations between the app and the reference method from studies were pooled using a random-effects model. All apps underestimated energy intake when compared with their reference methods, with a pooled effect of -202 kcal/d (95% CI: -319, -85 kcal/d); the heterogeneity of studies was 72%. After stratification, studies that used the same food-composition table for both the app and the reference method had a lower level of heterogeneity (0%) and a pooled effect of -57 kcal/d (95% CI: -116, 2 kcal/d). The heterogeneity of studies in the differences in carbohydrate, fat, and protein intake was 54%, 73%, and 80%, with the pooled effect of -18.8 g/d, -12.7 g/d, and -12.2 g/d, respectively, after excluding outliers. The intakes of micronutrients and food groups were statistically nonsignificantly underestimated by the apps in most cases. In conclusion, dietary record apps underestimated food consumption compared with traditional dietary assessment methods. Moreover, varying study designs have been found across studies. Recommended practices for conducting validation studies were formulated including considering biomarkers as the reference, testing in a larger and more representative study population for a longer period, avoiding the learning effect of each method, and comparing food group or food item consumption in addition to comparing energy and nutrient intakes.

PMID:34019624 | DOI:10.1093/advances/nmab058

PLoS One. 2021 May 21;16(5):e0252068. doi: 10.1371/journal.pone.0252068. eCollection 2021.

ABSTRACT

Donor-Recipient (D-R) matching is one of the main challenges to be fulfilled nowadays. Due to the increasing number of recipients and the small amount of donors in liver transplantation, the allocation method is crucial. In this paper, to establish a fair comparison, the United Network for Organ Sharing database was used with 4 different end-points (3 months, and 1, 2 and 5 years), with a total of 39, 189 D-R pairs and 28 donor and recipient variables. Modelling techniques were divided into two groups: 1) classical statistical methods, including Logistic Regression (LR) and Naïve Bayes (NB), and 2) standard machine learning techniques, including Multilayer Perceptron (MLP), Random Forest (RF), Gradient Boosting (GB) or Support Vector Machines (SVM), among others. The methods were compared with standard scores, MELD, SOFT and BAR. For the 5-years end-point, LR (AUC = 0.654) outperformed several machine learning techniques, such as MLP (AUC = 0.599), GB (AUC = 0.600), SVM (AUC = 0.624) or RF (AUC = 0.644), among others. Moreover, LR also outperformed standard scores. The same pattern was reproduced for the others 3 end-points. Complex machine learning methods were not able to improve the performance of liver allocation, probably due to the implicit limitations associated to the collection process of the database.

PMID:34019601 | DOI:10.1371/journal.pone.0252068

PLoS One. 2021 May 21;16(5):e0252019. doi: 10.1371/journal.pone.0252019. eCollection 2021.

ABSTRACT

Against the current COVID-19 pandemic, governments worldwide have devised a variety of non-pharmaceutical interventions to mitigate it. However, it is generally difficult to estimate the joint impact of different control strategies. In this paper, we tackle this question with an extended epidemic SEIR model, informed by a socio-political classification of different interventions. First, we inquire the conceptual effect of mitigation parameters on the infection curve. Then, we illustrate the potential of our model to reproduce and explain empirical data from a number of countries, to perform cross-country comparisons. This gives information on the best synergies of interventions to control epidemic outbreaks while minimising impact on socio-economic needs. For instance, our results suggest that, while rapid and strong lockdown is an effective pandemic mitigation measure, a combination of social distancing and early contact tracing can achieve similar mitigation synergistically, while keeping lower isolation rates. This quantitative understanding can support the establishment of mid- and long-term interventions, to prepare containment strategies against further outbreaks. This paper also provides an online tool that allows researchers and decision makers to interactively simulate diverse scenarios with our model.

PMID:34019589 | DOI:10.1371/journal.pone.0252019

PLoS One. 2021 May 21;16(5):e0252144. doi: 10.1371/journal.pone.0252144. eCollection 2021.

ABSTRACT

BACKGROUND: Antiretroviral therapy has significantly improved prognosis in treatment against HIV infection, however, prolonged exposure is associated to cardiovascular diseases, lipodystrophy, type 2 diabetes, insulin resistance, metabolic alteration, as obesity which includes the accumulation of oxidative stress in adipose tissue. FGF21 is a peptide hormone that is known to regulate glucose and lipid metabolism. FGF21 is expressed and secreted primarily in the liver and adipose tissue, promoting oxidation of glucose/fatty acids and insulin sensitivity. Alterations in FGF21 may be associated with the development of insulin resistance, metabolic syndrome and cardiovascular disease. We hypothesized that FGF21 protein levels are associated with metabolic abnormalities, placing special attention to the alterations in relation to the concurrence of overweight/obesity in people living with HIV (PLWH).

DESIGN: Serum FGF21 was analyzed in 241 subjects, 160 PLWH and 81 unrelated HIV-uninfected subjects as a control group. Clinical records were consulted to obtain CD4+ cell counting and number of viral RNA copies. Serum FGF21 levels were tested for correlation with anthropometric and metabolic parameters; glucose, cholesterol, HDL, LDL, VLDL, triglycerides, insulin and indexes of atherogenesis and insulin resistance (HOMA).

RESULTS: The participants were classified into four groups: (i) PLWH with normal weight, (ii) PLWH with overweight/obesity, (iii) HIV-uninfected with normal weight, and (iv) HIV-uninfected with overweight/obesity. Insulin levels were higher in normal-weight PLWH than in the HIV-uninfected group but not statistically significant, however, for the overweight/obesity PLWH group, insulin levels were significantly higher in comparison with the other three groups (p<0.0001). For FGF21, serum levels were slightly higher in the overweight/obesity groups in both patients and controls. In HIV-infected subjects, FGF21 levels showed a strong positive correlation with triglycerides, insulin levels and insulin resistance with a p-value <0.0001. In the seronegative group, FGF21 was only correlated with weight and waist circumference, showing an important association of FGF21 levels with the degree of obesity of the individuals.

CONCLUSION: Insulin resistance and FGF21 elevations were observed in overweight-obese PLWH. FGF21 elevation could be viewed as a compensation mechanism as, in the control group, FGF21 correlations appeared to be confined to weight and waist circumference. This can be explained based on the action of FGF21 promoting the uptake of glucose in adipose tissue. In PLWH, FGF21 was low, possibly as a result of a change in adiposity leading to a metabolic disruption.

PMID:34019585 | DOI:10.1371/journal.pone.0252144

PLoS One. 2021 May 21;16(5):e0251345. doi: 10.1371/journal.pone.0251345. eCollection 2021.

ABSTRACT

OBJECTIVE: China has a high cesarean delivery (CD) and low labor epidural analgesia (LEA) rate. This online survey was conducted to explore the reasons behind this phenomenon and potential solutions.

METHODS: A voluntary, anonymous survey was distributed via both WeChat and professional websites for 4 months amongst groups of Chinese perinatal professionals. Data was collected and analyzed using a Chi-square test and presented as percentages of respondents.

RESULTS: 1412 respondents were recorded (43% anesthesiologists, 35% obstetricians, 15.5% midwives or labor and delivery nurses, and 6.5% others), and 1320 respondents were care providers. It was found that 82.7% (1092/1320) of the provider respondents used CD per patient request in fear of lawsuits or yinao/yibao and 63.4% (837/1320) used CD for respecting superstitious culture. The number one reason (noted by 60.2% (795/1320) of all the three specialties) for low LEA use was lack of anesthesia manpower without statistical difference among specialties. The most recommended solution was increasing the anesthesia workforce, proposed by 79.8% (1053/1320) of the three specialties. However, the top solution provided by the two non-anesthesia specialties is different from the one proposed by anesthesiologists. The later (83%, 504/606) suggested increasing the incentive to provide the service is more effective. The answers to questions related to medical knowledge about CD and LEA, and unwillingness of anesthesiologists, parturients and their family members to LEA were similar for the most part, while the opinions regarding low LEA use related to poor experiences and unwillingness of obstetricians and hospital administrators were significantly divided among the three specialties. In the providers’ point of view, the unwillingness to LEA from parturient’s family members was the most salient (26.1%, 345/1320), which is more than all care providers, hospital administrators, and parturients themselves (16.8%, 222/1320).

CONCLUSION: The reasons for high CD rate and low LEA use are multifactorial. The sociological issues (fear of yinao/yibao and superstitious culture) were the top two contributing factors for the high CD rate in China, while lack of anesthesia manpower was the top response for the low LEA use, which contributes to its being the most recommended solution overall from the three specialties. An incentive approach to providers is a short-term solution while training more perinatal care providers (especially among anesthesiologists and midwives), improving billing systems, and reforming legal systems are 3 systemic approaches to tackling this problem in the long-term.

PMID:34019570 | DOI:10.1371/journal.pone.0251345

PLoS One. 2021 May 21;16(5):e0251849. doi: 10.1371/journal.pone.0251849. eCollection 2021.

ABSTRACT

We investigated the feasibility aspects of two choice reaction time tasks designed to assess implicit sequence learning and dual task ability in individuals with mild to moderate Parkinson’s disease in comparison to healthy individuals. Twelve individuals with mild to moderate Parkinson’s disease and 12 healthy individuals, all ≥ 60 years of age, were included. A serial reaction time task was used as a measure of implicit sequence learning and a similar task but with the addition of a simple counting task, was used as a measure of dual task ability. We have present thorough descriptive statistics of the data but we have refrained from any inferential statistics due to the small sample size. All participants understood the task instructions and the difficulty level of both tasks was deemed acceptable. There were indications of task fatigue that demand careful choices for how best to analyse the data from such tasks in future trials. Ceiling effects were present in several accuracy outcomes, but not in the reaction time outcomes. Overall, we found both tasks to be feasible to use in samples of individuals with mild to moderate Parkinson’s disease and healthy older individuals.

PMID:34019565 | DOI:10.1371/journal.pone.0251849

PLoS One. 2021 May 21;16(5):e0250824. doi: 10.1371/journal.pone.0250824. eCollection 2021.

ABSTRACT

The aim of our study was to quantify sex-specific patterns of smoking prevalence and initiation in 10-year birth cohorts from 1910 to 1989 in Australia. We combined individual data of 385,810 participants from 33 cross-sectional surveys conducted between 1962 and 2018. We found that age-specific smoking prevalence varied considerably between men and women within birth cohorts born before 1960. The largest difference was observed in the earliest cohort (1910-1919), with up to 37.7% point greater proportion of current smokers in men than in women. In subsequent cohorts, the proportion decreased among men, but increased among women, until there was no more than 7.4% point difference in the 1960-69 birth cohort. In the 1970-79 and 1980-89 cohorts, smoking among men marginally increased, but the proportion was at most ~11.0% points higher than women. Our analysis of initiation indicated that many women born before the 1930s who smoked commenced smoking after age 25 years (e.g., ~27% born in 1910-19); compared to at most 8% of men in any birth cohort. The earliest birth cohort (1910-1919) had the greatest difference in age at initiation between sexes; 26.6 years in women versus 19.0 in men. In later cohorts, male and female smokers initiated increasingly earlier, converging in the 1960-69 cohort (17.6 and 17.8 years, respectively). While 22.9% of men and 8.4% of women initiated smoking aged < = 15 in the 1910-1919 cohort, in the latest cohort (1980-89) the reverse was true (21.4% and 28.8% for men and women, respectively). Marked differences in smoking prevalence and age at initiation existed between birth cohorts of Australian men and women born before 1960; after this, sex-specific trends in prevalence and initiation were similar. Understanding these patterns may inform the evaluation of tobacco control policies and the targeting of potential interventions for exposed populations such as lung cancer screening.

PMID:34019558 | DOI:10.1371/journal.pone.0250824