Category: Nevin Manimala

PLoS One. 2021 Aug 3;16(8):e0255579. doi: 10.1371/journal.pone.0255579. eCollection 2021.

ABSTRACT

Multi-omic analyses that integrate many high-dimensional datasets often present significant deficiencies in statistical power and require time consuming computations to execute the analytical methods. We present SuMO-Fil to remedy against these issues which is a pre-processing method for Supervised Multi-Omic Filtering that removes variables or features considered to be irrelevant noise. SuMO-Fil is intended to be performed prior to downstream analyses that detect supervised gene networks in sparse settings. We accomplish this by implementing variable filters based on low similarity across the datasets in conjunction with low similarity with the outcome. This approach can improve accuracy, as well as reduce run times for a variety of computationally expensive downstream analyses. This method has applications in a setting where the downstream analysis may include sparse canonical correlation analysis. Filtering methods specifically for cluster and network analysis are introduced and compared by simulating modular networks with known statistical properties. The SuMO-Fil method performs favorably by eliminating non-network features while maintaining important biological signal under a variety of different signal settings as compared to popular filtering techniques based on low means or low variances. We show that the speed and accuracy of methods such as supervised sparse canonical correlation are increased after using SuMO-Fil, thus greatly improving the scalability of these approaches.

PMID:34343218 | DOI:10.1371/journal.pone.0255579

PLoS One. 2021 Aug 3;16(8):e0255164. doi: 10.1371/journal.pone.0255164. eCollection 2021.

ABSTRACT

Glutamate plays diverse roles in neuronal cells, affecting cell energetics and reactive oxygen species (ROS) generation. These roles are especially vital for neuronal cells, which deal with high amounts of glutamate as a neurotransmitter. Our analysis explored neuronal glutamate implication in cellular energy metabolism and ROS generation, using a kinetic model that simulates electron transport details in respiratory complexes, linked ROS generation and metabolic reactions. The analysis focused on the fact that glutamate attenuates complex II inhibition by oxaloacetate, stimulating the latter’s transformation into aspartate. Such a mechanism of complex II activation by glutamate could cause almost complete reduction of ubiquinone and deficiency of oxidized form (Q), which closes the main stream of electron transport and opens a way to massive ROS generating transfer in complex III from semiquinone radicals to molecular oxygen. In this way, under low workload, glutamate triggers the respiratory chain (RC) into a different steady state characterized by high ROS generation rate. The observed stepwise dependence of ROS generation on glutamate concentration experimentally validated this prediction. However, glutamate’s attenuation of oxaloacetate’s inhibition accelerates electron transport under high workload. Glutamate-oxaloacetate interaction in complex II regulation underlies the observed effects of uncouplers and inhibitors and acceleration of Ca2+ uptake. Thus, this theoretical analysis uncovered the previously unknown roles of oxaloacetate as a regulator of ROS generation and glutamate as a modifier of this regulation. The model predicted that this mechanism of complex II activation by glutamate might be operative in situ and responsible for excitotoxicity. Spatial-time gradients of synthesized hydrogen peroxide concentration, calculated in the reaction-diffusion model with convection under a non-uniform local approximation of nervous tissue, have shown that overproduction of H2O2 in a cell causes excess of its level in neighbor cells.

PMID:34343196 | DOI:10.1371/journal.pone.0255164

PLoS One. 2021 Aug 3;16(8):e0255527. doi: 10.1371/journal.pone.0255527. eCollection 2021.

ABSTRACT

The objective of this study was to explore the effects of time, seasons, and total carbon (TC) on Copper (Cu) and Zinc (Zn) deposition in the surface sediments. This study was performed at the H-02 constructed wetland on the Savannah River Site (Aiken, SC, USA). Covering both warm (April-September) and cool (October-March) seasons, several sediment cores were collected twice a year from the H-02 constructed wetland cells from 2007 to 2013. Total concentrations of Cu and Zn were measured in the sediments. Concentrations of Cu and Zn (mean ± standard deviation) in the surface sediments over 7 years of operation increased from 6.0 ± 2.8 and 14.6 ± 4.5 mg kg-1 to 139.6 ± 87.7 and 279.3 ± 202.9 mg kg-1 dry weight, respectively. The linear regression model explained the behavior and the variability of Cu deposition in the sediments. On the other hand, using the generalized least squares extension with the linear regression model allowed for unequal variance and thus produced a model that explained the variance properly, and as a result, was more successful in explaining the pattern of Zn deposition. Total carbon significantly affected both Cu (p = 0.047) and Zn (p < 0.001). Time effect on Cu deposition was statistically significant (p = 0.013), whereas Zn was significantly affected by the season (p = 0.009).

PMID:34343201 | DOI:10.1371/journal.pone.0255527

PLoS One. 2021 Aug 3;16(8):e0255368. doi: 10.1371/journal.pone.0255368. eCollection 2021.

ABSTRACT

Most of our knowledge on reproductive biology of gray whales dates back to scientific research conducted during commercial whaling in the late 1950s and 1960s. The goal of the present study was to provide updated insights on reproductive physiology of gray whales, using progesterone and testosterone as biomarkers. We measured hormone concentrations using enzyme immunoassay (EIA) techniques in blubber biopsies collected from 106 individual whales from March to November over a span of 12 years (2004-2016) between California and Alaska. We found testosterone concentrations in males to increase significantly with age (P = 0.03). Adult males showed significantly elevated testosterone concentrations when sampled in the fall compared to the summer (P = 0.01), likely indicating physiological preparation for mating. We measured testosterone concentrations in females of different age classes, but no statistical differences were found. We found significantly higher progesterone concentrations in pregnant females compared to non-pregnant females and adult males (P< 0.001), indicating progesterone is a valid biomarker for pregnancy in gray whales. Both female and male calves had elevated progesterone concentrations, suggesting maternal transfer via lactation. We fit a mixture of two normal distributions to progesterone data from all non-calf females to identify clusters of high and low progesterone and estimated the probability of being pregnant for whales of unknown reproductive status. With this approach we identified likely pregnant and non-pregnant animals. This study represents an important milestone on reproductive profiles in this population, that can be used to estimate more accurate and precise reproductive parameters to be used for better understanding population dynamics of gray whales.

PMID:34343192 | DOI:10.1371/journal.pone.0255368

PLoS One. 2021 Aug 3;16(8):e0255473. doi: 10.1371/journal.pone.0255473. eCollection 2021.

ABSTRACT

BACKGROUND: Applicability of totally implantable venous access port (TIVAP) and peripherally inserted central venous catheter (PICC) in non-hematological malignancies patients remains controversial.

METHODS: A systematic studies search in the public databases PubMed, EMBASE, Wan Fang, CNKI (China National Knowledge Infrastructure), the Cochrane Library and Google Scholar (updated to May 1, 2020) was performed to identify eligible researches. All statistical tests in this meta-analysis were performed using Stata 12.0 software (Stata Corp, College Station, TX). A P value less than 0.05 was considered statistically significant.

RESULTS: Thirteen studies were included in this final meta-analysis. The pooled data showed that compared with PICC, TIVAP was associated with a higher first-puncture success rate (OR:2.028, 95%CI:1.25-3.289, P<0.05), a lower accidental removal rate (OR:0.447, 95%CI:0.225-0.889, P<0.05) and lower complication rates, including infection (OR:0.570, 95%CI: 0.383-0.850, P<0.05), occlusion (OR:0.172, 95%CI:0.092-0.324, P<0.05), malposition (OR:0.279, 95%CI:0.128-0.608, P<0.05), thrombosis (OR:0.191, 95%CI, 0.111-0.329, P<0.05), phlebitis (OR:0.102, 95%CI, 0.038-0.273, P<0.05), allergy (OR:0.155, 95%CI:0.035-0.696, P<0.05). However, no difference was found in catheter life span (P>0.05) and extravasation (P>0.05). Moreover, TIVAP is more expensive compared with PICC in six-month use (weighted mean difference:3.132, 95%CI:2.434-3.83, P<0.05), but is much similar in 12 months use (P>0.05).

CONCLUSION: For the patients with non-hematological malignancies, TIVAP was superior to PICC in the data related to placement and the incidence of complications. Meanwhile, TIVAP is more expensive compared with PICC in six-month use, but it is much similar in twelve-month use.

PMID:34343193 | DOI:10.1371/journal.pone.0255473

PLoS One. 2021 Aug 3;16(8):e0254702. doi: 10.1371/journal.pone.0254702. eCollection 2021.

ABSTRACT

Thermal variables are crucial drivers of biological processes in lakes and ponds. In the current context of climate change, determining which factors better constrain their variation within lake districts become of paramount importance for understanding species distribution and their conservation. In this study, we describe the regional and short-term interannual variability in surface water temperature of high mountain lakes and ponds of the Pyrenees. And, we use mixed regression models to identify key environmental factors and to infer mean and maximum summer temperature, accumulated degree-days, diel temperature ranges and three-days’ oscillation. The study is based on 59 lake-temperature series measured from 2001 to 2014. We found that altitude was the primary explicative factor for accumulated degree-days and mean and maximum temperature. In contrast, lake area showed the most relevant effect on the diel temperature range and temperature oscillations, although diel temperature range was also found to decline with altitude. Furthermore, the morphology of the catchment significantly affected accumulated degree-days and maximum and mean water temperatures. The statistical models developed here were applied to upscale spatially the current thermic conditions across the whole set of lakes and ponds of the Pyrenees.

PMID:34343195 | DOI:10.1371/journal.pone.0254702

J Hypertens. 2021 Aug 2. doi: 10.1097/HJH.0000000000002944. Online ahead of print.

ABSTRACT

BACKGROUND: Orthostatic hypotension is an independent risk factor for cardiovascular morbidity and mortality. Arterial stiffness has been shown to be a pathophysiological mechanism linking orthostatic hypotension and increased cardiovascular risk. This study aims to evaluate the relationship between arterial stiffness, orthostatic hypotension and subendocardial viability ratio (SEVR) and moreover to identify the main predictors of orthostatic hypotension, carotid-femoral pulse wave velocity (PWV-cf) and SEVR.

METHODS: Seventy-five patients were enrolled (mean age 82.95 ± 6.45) in Verona’s AOUI Geriatric ward. They underwent blood pressure, heart rate, body weight measurements and also comorbidity, arterial stiffness (PWV-cf measured by applanation tonometry), SEVR and biochemical indexes.

RESULTS: Prevalence of orthostatic hypotension was 46.6%. Even after adjustment for age, sex, glomerular filtration rate and mean arterial pressure, SEVR values corrected for arterial oxygen and haemoglobin content were statistically lower in orthostatic hypotension patients (P = 0.05) and PWV-cf values were statistically higher in orthostatic hypotension individuals (P = 0.042). In a binary logistic regression, PWV-cf was the only significant predictor of orthostatic hypotension (odds ratio 1.123; P = 0.039; confidence interval = 1.006–1.17).In a backward logistic regression model sex, creatinine clearance and orthostatic hypotension were significant predictors of SEVR corrected for O2 content. Mean arterial pressure, creatinine clearance and orthostatic hypotension were significant predictors of PWV-cf.

CONCLUSION: This study shows that orthostatic hypotension is related to increased arterial stiffness, confirming its higher prevalence in elderly patients. Orthostatic hypotension was also associated with reduced values of corrected SEVR, showing a relevant consequence of orthostatic hypotension on subendocardial perfusion impairment.

PMID:34343144 | DOI:10.1097/HJH.0000000000002944

PLoS One. 2021 Aug 3;16(8):e0254955. doi: 10.1371/journal.pone.0254955. eCollection 2021.

ABSTRACT

PURPOSE: To investigate the impact of large choroidal vessels (LCV) on Choriocapillaris (CC) flow deficit (FD) analyses with swept-source optical coherence tomography angiography (SS-OCTA).

DESIGN: Prospective, cross-sectional study.

METHODS: Macular 6x6mm SS-OCTA scans were obtained from intermediate age-related macular degeneration (iAMD) and healthy eyes. Images were captured and processed according to most common standards and analyzed for percentage of flow-deficits (FD%) within four 1x1mm squares at the corners of each image. Choroidal thickness (CT), iris color and refraction error were considered as potential influential factors for LCV visibility. A linear mixed model and logistic regression models were calculated for statistical evaluation.

RESULTS: Sixty-nine iAMD and 49 age-matched healthy eyes were enrolled. LCV were visible in at least one sector in 52% of iAMD and 47% of healthy eyes. Within the iAMD group FD% were significantly lower in areas containing LCV (p = 0.0029). Increasing CT resulted in an odds ratio decrease of LCV (OR: 0.94, p<0.0001). Below a CT value of ≤118μm LCV could be expected with a sensitivity of 86% and a specificity of 85%.

CONCLUSIONS: LCV can significantly affect CC FD analyses of SS-OCTA images. Their visibility is negatively associated with CT. The impact of LCV should be taken into account when performing CC FD assessments, especially in patients where reduced CT is to be expected and inclusion of affected areas should be considered carefully.

PMID:34343177 | DOI:10.1371/journal.pone.0254955

Curr Opin Neurol. 2021 Aug 2. doi: 10.1097/WCO.0000000000000986. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is an archetypal complex disease wherein disease risk and severity are, for the majority of patients, the product of interaction between multiple genetic and environmental factors. We are in a period of unprecedented discovery with new large-scale genome-wide association study (GWAS) and accelerating discovery of risk genes. However, much of the observed heritability of ALS is undiscovered and we are not yet approaching elucidation of the total genetic architecture, which will be necessary for comprehensive disease subclassification.

RECENT FINDINGS: We summarize recent developments and discuss the future. New machine learning models will help to address nonlinear genetic interactions. Statistical power for genetic discovery may be boosted by reducing the search-space using cell-specific epigenetic profiles and expanding our scope to include genetically correlated phenotypes. Structural variation, somatic heterogeneity and consideration of environmental modifiers represent significant challenges which will require integration of multiple technologies and a multidisciplinary approach, including clinicians, geneticists and pathologists.

SUMMARY: The move away from fully penetrant Mendelian risk genes necessitates new experimental designs and new standards for validation. The challenges are significant, but the potential reward for successful disease subclassification is large-scale and effective personalized medicine.

PMID:34343141 | DOI:10.1097/WCO.0000000000000986

Clin Exp Dermatol. 2021 Aug 3. doi: 10.1111/ced.14870. Online ahead of print.

ABSTRACT

BACKGROUND: Although MDA-5 autoantibodies are widely explored in dermatomyositis (DM), most studies relied on MDA-5 autoantibody testing performed in research settings and not with the now-available commercial laboratory tests.

OBJECTIVE: To characterize the clinical and histopathologic data in patients with DM and circulating MDA5-autoantibodies, as defined by commercial-based testing.

METHODS: Retrospective review of patients with DM who underwent MDA-5 antibody testing. All available skin biopsy slides were reviewed.

RESULTS: Cutaneous features more prevalent in MDA-5 positive DM included Raynaud syndrome (p <0.0001), cutaneous ulcerations (p=0.013), mechanic hands (p=0.0164), palmar papules (p=0.004), oral ulcers (p=0.024) and alopecia (p= 0.027). Joint and pulmonary involvement were more frequently in patients with MDA-5 positive DM (both p<0.0001) as was dysphagia (p=0.0029). Myopathy (p=0.404) and malignancy (p=0.342) were not statistically different between the cohorts. Vasculopathy was more frequent in MDA-5 positive DM (p=0.005), while spongiosis was less (p=0.016).

CONCLUSIONS: This study not only confirmed some known associations between disease manifestations and MDA-5 autoantibody status, as determined by commercially-available testing, but also identified new associations, including Raynaud syndrome and dysphagia.

PMID:34342883 | DOI:10.1111/ced.14870