Nevin Manimala

Nat Commun. 2021 Oct 18;12(1):6073. doi: 10.1038/s41467-021-26246-3.

ABSTRACT

Large-scale profiling of intact glycopeptides is critical but challenging in glycoproteomics. Data independent acquisition (DIA) is an emerging technology with deep proteome coverage and accurate quantitative capability in proteomics studies, but is still in the early stage of development in the field of glycoproteomics. We propose GproDIA, a framework for the proteome-wide characterization of intact glycopeptides from DIA data with comprehensive statistical control by a 2-dimentional false discovery rate approach and a glycoform inference algorithm, enabling accurate identification of intact glycopeptides using wide isolation windows. We further utilize a semi-empirical spectrum prediction strategy to expand the coverage of spectral libraries of glycopeptides. We benchmark our method for N-glycopeptide profiling on DIA data of yeast and human serum samples, demonstrating that DIA with GproDIA outperforms the data-dependent acquisition-based methods for glycoproteomics in terms of capacity and data completeness of identification, as well as accuracy and precision of quantification. We expect that this work can provide a powerful tool for glycoproteomic studies.

PMID:34663801 | DOI:10.1038/s41467-021-26246-3

Nutr Diabetes. 2021 Oct 18;11(1):32. doi: 10.1038/s41387-021-00170-3.

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a strong risk factor for liver fibrosis in non-alcoholic fatty liver disease (NAFLD). It remains uncertain why T2DM increases the risk of liver fibrosis. It has been suggested that growth differentiation factor-15 (GDF-15) concentrations increase the risk of liver fibrosis. We aimed to investigate (a) whether GDF-15 concentrations were associated with liver fibrosis and involved in the relationship between T2DM and liver fibrosis and (b) what factors linked with T2DM are associated with increased GDF-15 concentrations.

METHODS: Ninety-nine patients with NAFLD (61% men, 42.4% T2DM) were studied. Serum GDF-15 concentrations were measured by electro-chemiluminescence immunoassay. Vibration-controlled transient elastography (VCTE)-validated thresholds were used to assess liver fibrosis. Regression modelling, receiver operator characteristic curve analysis and Sobel test statistics were used to test associations, risk predictors and the involvement of GDF-15 in the relationship between T2DM and liver fibrosis, respectively.

RESULTS: Patients with NAFLD and T2DM (n = 42) had higher serum GDF-15 concentrations [mean (SD): 1271.0 (902.1) vs. 640.3 (332.5) pg/ml, p < 0.0001], and a higher proportion had VCTE assessed ≥F2 fibrosis (48.8 vs. 23.2%, p = 0.01) than those without T2DM. GDF-15 was independently associated with liver fibrosis (p = 0.001), and GDF-15 was the most important single factor predicting ≥F2 or ≥F3 fibrosis (≥F2 fibrosis AUROC 0.75, (95% CI 0.63-0.86), p < 0.001, with sensitivity, specificity, positive predictive (PPV) and negative predictive (NPV) values of 56.3%, 86.9%, 69.2% and 79.1%, respectively). GDF-15 was involved in the association between T2DM and ≥F2 fibrosis (Sobel test statistic 2.90, p = 0.004). Other factors associated with T2DM explained 60% of the variance in GDF-15 concentrations (p < 0.0001). HbA1c concentrations alone explained 30% of the variance (p < 0.0001).

CONCLUSIONS: GDF-15 concentrations are a predictor of liver fibrosis and potentially involved in the association between T2DM and liver fibrosis in NAFLD. HbA1c concentrations explain a large proportion of the variance in GDF-15 concentrations.

PMID:34663793 | DOI:10.1038/s41387-021-00170-3

Uisahak. 2021 Aug;30(2):355-392. doi: 10.13081/kjmh.2021.30.355.

ABSTRACT

The anti-cholera measures of 1969-70 represent one of the most unsuccessful quarantine cases in modern Korea. The military government, which overthrew the democratic government in 1961, tried to amend the Constitution aiming for a long-term seizure of power, and had to overcome the cholera crisis of 1969-70. Previous scholarship has emphasized the limitation of the state power when it came to controlling the cholera epidemic or the poor sanitation system of 1969-70. However, it is undeniable that the military government did have organizations, facilities, and human capital available. When a cholera epidemic broke out in 1963-64, the military government defended its people against cholera as part of the Revolutionary Tasks. Furthermore, it took counsel from a team of medical professionals knowledgeable in microbiology. In 1969, the possibility of bacteriological warfare by North Korea emerged while the government responded to cholera. To avoid this crisis, Park Chŏng-hŭi’s military government, which had been preparing for longterm rule, had to provide successful model in the cholera defense. For the military government, the concealment and distortion of infectious disease information was inevitable. Many other medical professionals trusted the activities of international organizations more than they did the government bodies, and the media accused the government of fabricating cholera death statistics. As the government failed to prevent the cholera crisis, it tightened its secrecy by concealing facts and controlling information.

PMID:34663775 | DOI:10.13081/kjmh.2021.30.355

Uisahak. 2021 Aug;30(2):221-275. doi: 10.13081/kjmh.2021.30.221.

ABSTRACT

Uiyeokju Palsebo is a genealogy record that contains the eighth generation of patrilineal ancestors, maternal grandfathers, and fathers-in-law of technical officials who worked in three fields: medicine, linguistics, and mathematics. This book covers members of influential families who monopolized the positions of technical officers. In that respect, it seems to have had an effect like a kind of ‘white list’. This paper identifies the range of families based on common ancestors above eight generations according to the editing method of this book, attempting various statistical analysis. The results of the analysis shows that it is possible to determine the size of the medical families, which varied according to the number of medical bureaucrats and the distance of kinship between them. Most of the families had workers in the three fields of medicine, linguistics, and mathematics, but there were also ‘families more specialized in medicine’ that produced a large number of medical figures. The ancestors of medical figures were mainly engaged in the three fields of medicine, linguistics, and mathematics, but there were also a small number of officials in charge of “unhak(including astronomy, geography, and fortune-telling),” law, art, and transcription. For distant ancestors from common ancestors to the fifth generation, the proportion of technical officers was small, but for relatively close ancestors, the proportion of technical officers, especially medical officers, increased. It can be seen that the status as a medical officer tends to be hereditary further down the generations. The fields of activity of the maternal grandfathers and fathers-in-law of medical figures were more concentrated in the medical field. This can be the result of confirming the influence of the marital relationship network that was formed in the close period with the medical persons being investigated. In this paper, only medical figures were considered as primary research subjects, but their macroscopic networks were relatively evenly spread out in the three fields of medicine, linguistics, and mathematics. In this network, Uiyeokju Palsebo contained homogeneous hierarchies that could continuously dominate a specific field of government office.

PMID:34663772 | DOI:10.13081/kjmh.2021.30.221

Phys Med Biol. 2021 Oct 18. doi: 10.1088/1361-6560/ac30a1. Online ahead of print.

ABSTRACT

Gliomas are the most common type of primary brain tumors and have different grades. Accurate grading of a glioma is therefore significant for its clinical treatment planning and prognostic assessment with multiple-modality magnetic resonance imaging (MRI). In this study, we developed a noninvasive deep-learning method based on multimodal MRI for grading gliomas by focusing on effective multimodal fusion via leveraging collaborative and diverse high-order statistical information. Specifically, a novel high-order multimodal interaction module was designed to promote interactive learning of multimodal knowledge for more efficient fusion. For more powerful feature expression and feature correlation learning, the high-order attention mechanism is embedded in the interaction module for modeling complex and high-order statistical information to enhance the classification capability of the network. Moreover, we applied increasing orders at different levels to hierarchically recalibrate each modality stream through diverse-order attention statistics, thus encouraging all-sided attention knowledge with lesser parameters. To evaluate the effectiveness of the proposed scheme, extensive experiments were conducted on The Cancer Imaging Archive (TCIA) and Multimodal Brain Tumor Image Segmentation Benchmark 2017 (BraTS2017) datasets with five-fold cross validation to demonstrate that the proposed method can achieve high prediction performance, with area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity values of 95.2%, 94.28%, 95.24%, and 92.00% on the BraTS2017 and 93.50%, 92.86%, 97.14%, and 90.48% on TCIA datasets, respectively.

PMID:34663762 | DOI:10.1088/1361-6560/ac30a1

Proc Natl Acad Sci U S A. 2021 Oct 26;118(43):e2114679118. doi: 10.1073/pnas.2114679118.

ABSTRACT

An important idea underlying a plausible dynamical theory of circulation in three-dimensional turbulence is the so-called area rule, according to which the probability density function (PDF) of the circulation around closed loops depends only on the minimal area of the loop, not its shape. We assess the robustness of the area rule, for both planar and nonplanar loops, using high-resolution data from direct numerical simulations. For planar loops, the circulation moments for rectangular shapes match those for the square with only small differences, these differences being larger when the aspect ratio is farther from unity and when the moment order increases. The differences do not exceed about 5% for any condition examined here. The aspect ratio dependence observed for the second-order moment is indistinguishable from results for the Gaussian random field (GRF) with the same two-point correlation function (for which the results are order-independent by construction). When normalized by the SD of the PDF, the aspect ratio dependence is even smaller ( < 2%) but does not vanish unlike for the GRF. We obtain circulation statistics around minimal area loops in three dimensions and compare them to those of a planar loop circumscribing equivalent areas, and we find that circulation statistics match in the two cases only when normalized by an internal variable such as the SD. This work highlights the hitherto unknown connection between minimal surfaces and turbulence.

PMID:34663734 | DOI:10.1073/pnas.2114679118

Proc Natl Acad Sci U S A. 2021 Oct 26;118(43):e2105666118. doi: 10.1073/pnas.2105666118.

ABSTRACT

Fire is a common ecosystem process in forests and grasslands worldwide. Increasingly, ignitions are controlled by human activities either through suppression of wildfires or intentional ignition of prescribed fires. The southeastern United States leads the nation in prescribed fire, burning ca. 80% of the country’s extent annually. The COVID-19 pandemic radically changed human behavior as workplaces implemented social-distancing guidelines and provided an opportunity to evaluate relationships between humans and fire as fire management plans were postponed or cancelled. Using active fire data from satellite-based observations, we found that in the southeastern United States, COVID-19 led to a 21% reduction in fire activity compared to the 2003 to 2019 average. The reduction was more pronounced for federally managed lands, up to 41% below average compared to the past 20 y (38% below average compared to the past decade). Declines in fire activity were partly affected by an unusually wet February before the COVID-19 shutdown began in mid-March 2020. Despite the wet spring, the predicted number of active fire detections was still lower than expected, confirming a COVID-19 signal on ignitions. In addition, prescribed fire management statistics reported by US federal agencies confirmed the satellite observations and showed that, following the wet February and before the mid-March COVID-19 shutdown, cumulative burned area was approaching record highs across the region. With fire return intervals in the southeastern United States as frequent as 1 to 2 y, COVID-19 fire impacts will contribute to an increasing backlog in necessary fire management activities, affecting biodiversity and future fire danger.

PMID:34663728 | DOI:10.1073/pnas.2105666118

Neurosciences (Riyadh). 2021 Oct;26(4):366-371. doi: 10.17712/nsj.2021.4.20210070.

ABSTRACT

OBJECTIVES: To assess depression and its relation with different factors among people with epilepsy in wider range of ages.

METHODS: A cross-sectional study was conducted in Taif city. The sample size was 150; the inclusion criteria were ≥18-year-old patients diagnosed with epilepsy. The data were collected by interviewing patients following up from rural and urban areas of Taif in neurology clinics at King Faisal Medical Complex (KFMC) and King Abdul-Aziz Specialist Hospital (KAASH). The PHQ-9 score was used to screen for depression.

RESULTS: Our study showed that approximately 76.7% (n=115) of the patients had some form of depression. A severe form of depression was identified in 8.7% (n=13) of the patients, and a moderately severe form was observed in 13.3% (n=20) of the patients. There was no significant association between depression and gender, duration of epilepsy, type of epilepsy, and medications for epilepsy, while there was a statistical association between depression and age, stress level, and employment status (p<0.044, p<0.001, p<0.008, respectively).

CONCLUSION: Depression is common in people with epilepsy. Regular screening for depression is recommended in people with epilepsy for early detection and treatment.

PMID:34663709 | DOI:10.17712/nsj.2021.4.20210070

Neurosciences (Riyadh). 2021 Oct;26(4):357-365. doi: 10.17712/nsj.2021.4.20210075.

ABSTRACT

OBJECTIVES: To evaluate the efficacy of valproic acid (VPA) in a cohort of children below 2 years of age. We also aim to review the characteristics of such patients and the role and safety of VPA for this age group.

METHODS: A retrospective chart review conducted at King Abdulaziz University Hospital, Jeddah, Kingdome of Saudi Arabia, for children below 2 years of age diagnosed with epilepsy and treated with valproic acid from January 2016 to January 2020.

RESULTS: The cohort for this study includes 50 children below the age of 2 years (25 males, 25 females). Aged 3 months to 23 months at commencing valproic acid. The mean age of seizure onset was 9 months and the mean age of starting valproic acid was 16 months. Thirty-two patients (64%) had more than 50% seizure improvement after valproic acid. Eleven patients (22%) were seizure-free. No statistical significance abnormalities in blood count indices and ammonia were seen during the treatment period. Two patients had dose-related lethargy that improved after decreasing their dosage. Asymptomatic mild elevation in glutamate dehydrogenase was noticed in 18% of patients.

CONCLUSION: Using valproic acid in infants and children below the age of 2 years can be considered as a safe and effective treatment option for epilepsy in this age group.

PMID:34663708 | DOI:10.17712/nsj.2021.4.20210075

Neurosciences (Riyadh). 2021 Oct;26(4):346-356. doi: 10.17712/nsj.2021.4.20200050.

ABSTRACT

OBJECTIVES: To investigate the association between mannose-binding lectin 2 (MBL2) codon 54 polymorphism and clinical features of patients diagnosed with schizophrenia (SCZ) or bipolar disorder (BD).

METHODS: One hundred and eighteen patients with SCZ, 100 patients with BD, and 100 healthy volunteers were included in the case-control study. The patients consecutively admitted to the outpatient clinic in December 2017-May 2018 and were evaluated with some scales for clinical parameters. Polymerase chain reaction and RFLP were used to determine MBL2 polymorphism in DNA material.

RESULTS: The MBL2 gene polymorphism distributions in SCZ or BD patients were significantly different from the control group. The heterozygous genotype percentages were significantly higher in the control group than in the SCZ or BD patients (OR: 0.450; 95% Cl: 0.243-0.830; p=0.010; OR: 0.532; 95%Cl: 0.284-0.995; p=0.047, respectively), and there were statistically significant differences in the MBL2 polymorphism distributions between treatment-responsive SCZ or BD patients and treatment-resistant patients diagnosed with SCZ or BD. The heterozygous genotype percentages were also significantly higher in the treatment-responsive group than in the treatment-resistant group in SCZ or BD patients (OR: 7.857; 95% Cl: 1.006-61.363; p=0.023; OR: 8.782; 95% Cl: 1.114-69.197; p=0.016, respectively).

CONCLUSION: The presence of a heterozygous MBL2 genotype seems to be favorable both in terms of the absence of SCZ and BD in the healthy population and treatment response for Turkish patients.

PMID:34663707 | DOI:10.17712/nsj.2021.4.20200050