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Nevin Manimala Statistics

Dealing with missing values in proteomics data

Proteomics. 2022 Nov 9:e2200092. doi: 10.1002/pmic.202200092. Online ahead of print.

ABSTRACT

Proteomics data are often plagued with missingness issues. These missing values (MVs) threaten the integrity of subsequent statistical analyses by reduction of statistical power, introduction of bias, and failure to represent the true sample. Over the years, several categories of missing value imputation (MVI) methods have been developed and adapted for proteomics data. These MVI methods perform their tasks based on different prior assumptions (e.g., data is normally or independently distributed) and operating principles (e.g., the algorithm is built to address random missingness only), resulting in varying levels of performance even when dealing with the same dataset. Thus, to achieve a satisfactory outcome, a suitable MVI method must be selected. To guide decision making on suitable MVI method, we provide a decision chart which facilitates strategic considerations on datasets presenting different characteristics. We also bring attention to other issues that can impact proper MVI such as the presence of confounders (e.g., batch effects) which can influence MVI performance. Thus, these too, should be considered during or before MVI. This article is protected by copyright. All rights reserved.

PMID:36349819 | DOI:10.1002/pmic.202200092

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Nevin Manimala Statistics

Mass spectrometry-based high-throughput proteomics and its role in biomedical studies and systems biology

Proteomics. 2022 Nov 9:e2200013. doi: 10.1002/pmic.202200013. Online ahead of print.

ABSTRACT

There are multiple reasons why the next generation of biological and medical studies require increasing numbers of samples. First, many conditions need to be considered to produce generalisable results. For example, biological systems are dynamic, and the effect of a perturbation depends on the genetic background and environment. Moreover, human population and clinical studies only reach sufficient statistical power if conducted at scale and with precise measurement methods. Finally, many proteins remain without sufficient functional annotations, because they have not been systematically studied under a broad range of conditions. In this review, we discuss the latest technical developments in mass spectrometry-based proteomics that facilitate large-scale studies by fast and efficient chromatography, fast scanning mass spectrometers, data-independent acquisition (DIA), and new software. We further highlight recent studies which demonstrate how high-throughput proteomics can be applied to capture biological diversity, annotate gene functions or to generate predictive and prognostic models for human disease. This article is protected by copyright. All rights reserved.

PMID:36349817 | DOI:10.1002/pmic.202200013

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Nevin Manimala Statistics

Fusional vergence dysfunctions in acute acquired concomitant esotropia of adulthood with myopia

Ophthalmic Res. 2022 Nov 7. doi: 10.1159/000527884. Online ahead of print.

ABSTRACT

INTRODUCTION: Acute acquired concomitant esotropia (AACE) has been increased dramatically in myopia. To clarify whether fusional vergence dysfunctions exist in AACE with myopia, and to explore the relationship between fusional vergence and myopia in AACE Methods: A prospective clinical study. Adult AACE patients as well as controls (aged ≥18 years) both with myopia were prospectively recruited from October 2016 to August 2021. Refractive error and fusional divergence and convergence amplitude at distance were measured, as determined with a comprehensive refractor. The main outcome measures were the real value of the fusional divergence amplitude (calculated by subtracting the break point value from the angle of deviation) and the real value of the fusional convergence amplitude (calculated by subtracting the angle of deviation from the break point value). Two-sided p value of less than 0.05 was considered to indicate statistical significance.

RESULTS: Fusional vergence consisting of fusional divergence and fusional convergence in patients with AACE of adulthood were different from the controls (p<0.001), with fusional convergence decreased and fusional divergence increased. In the linear regression analysis, spherical equivalents were significantly negatively correlated with fusional convergence (right eyes, p<0.001; left eyes, p<0.001) in patients with AACE of adulthood but not in controls. There was a significant difference in fusional convergence amplitude among different degrees of spherical equivalents (p<0.001).

CONCLUSIONS: Fusional vergence dysfunction exist in AACE of adulthood, which may be attributed to self-adaptation based on concomitant esotropia to maintain fusion in AACE. Fusional convergence was associated with degrees of myopia, implying the adaption would be weakened as the degree of myopia becomes serious.

PMID:36349785 | DOI:10.1159/000527884

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Nevin Manimala Statistics

Dietary Protein and Fiber Affect Gut Microbiome and Treg/Th17 Commitment in Chronic Kidney Disease Mice

Am J Nephrol. 2022 Nov 7:1-6. doi: 10.1159/000526957. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with chronic kidney disease (CKD) have dysbiosis, dysmetabolism, and immune dysregulation. Gut microbiome plays an important role shaping the immune system which is an important modulator of CKD progression.

METHODS: We compared the effect of a diet low in protein and high in fiber (LP-HF; n = 7) to that of diet rich in protein, but low in fiber (HP-LF; n = 7) on gut microbiome and T-cell commitment in male CKD (Alb/TGF-β1) mice. The gut microbiomes of these mice were subjected to 16S rRNA taxonomic profiling at baseline, 6 weeks and 12 weeks of the study.

RESULTS: The LP-HF diet was associated with an increase in Butyricicoccus pullicaecorum BT, a taxon whose functions include those closely related to butyric acid synthesis (Kendall’s W statistic = 180 in analysis of microbiome composition). HP-LF diet was associated with increased abundance of two predominantly proteolytic bacterial strains related to Parabacteroides distasonis (W statistic = 173), Mucispirillum schaedleri, and Bacteroides dorei (W statistic = 192). Pathway analysis suggested that the LP-HF diet induced carbohydrate, lipid, and butyrate metabolism. As compared with HP-LF mice, LP-HF mice had 1.7-fold increase in CD4+Foxp3+Treg cells in spleen and 2.4-fold increase of these cells in peripheral blood. There was an 87% decrease in percentage of CD4+ Th17 + cells in spleen and an 85% decrease in peripheral blood, respectively, in LP-HF mice compared to the HP-LF mice.

CONCLUSION: The LP-HF diet promotes the proliferation of saccharolytic bacteria and favors T-cell commitment toward Treg cells in a CKD mouse of model. Clinical significance of the finding needs to be further investigated.

PMID:36349783 | DOI:10.1159/000526957

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Nevin Manimala Statistics

Effects of modified Baizhu Shaoyao San on postoperative diarrhea in colorectal cancer patients: a single-blind, randomised controlled trial

Complement Med Res. 2022 Nov 7. doi: 10.1159/000527706. Online ahead of print.

ABSTRACT

INTRODUCTION: Postoperative gastrointestinal tract dysfunction is considered a common complication affecting patients undergoing intestinal surgery. This research aims to provide evidence to assess the efficacy and safety of Baizhu Shaoyao San (BSS) or modified BSS in treating postoperative diarrhea of colorectal cancer patients.

METHODS: Eighty patients with colorectal cancer were randomized within two weeks after surgery to receive either modified BSS or Loperamide combined with the respective dummy. The curative effect was evaluated with the traditional Chinese medicine (TCM) syndrome score. Determination of motilin and gastrin in plasma was conducted utilizing ELISA.

RESULTS: Compared with Loperamide therapy, the efficacy of modified BSS was statistically significant, the traditional Chinese medicine syndrome score decreased, and the total effective rate increased. Levels of motilin and gastrin in plasma decreased.

CONCLUSION: The curative effect and safety of modified BSS were statistically significant.

PMID:36349756 | DOI:10.1159/000527706

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Nevin Manimala Statistics

Evaluation of X chromosome inactivation in endemic Tunisian pemphigus foliaceus

Mol Genet Genomic Med. 2022 Nov 9:e2080. doi: 10.1002/mgg3.2080. Online ahead of print.

ABSTRACT

BACKGROUND: Almost 5% of the world’s population develops an autoimmune disease (AID), it is considered the fourth leading cause of disability for women, who represent 78% of cases. The sex ratio when it comes to the most prevalent AID varies from 9:1 in systemic lupus erythematosus (SLE) to 13:1 in endemic Tunisian pemphigus foliaceus (PF).

METHODS: To test the potential involvement of skewed x-inactivation in the pathogenesis of Tunisian PF, we analyzed the methylation status of a highly polymorphic CAG repeat in the androgen receptor gene and evaluated the x chromosome inactivation (XCI) patterns in peripheral blood-leukocyte-derived DNA samples of female patients with PF (n = 98) compared to healthy control (HC) subjects (n = 150), as well as female patients with SLE (n = 98) were enrolled as a reference group.

RESULTS: XCI status was informative for 50 of the 98 PF patients (51%) and 70 of the 150 HC women (47%). Extremely skewed XCI patterns were more frequent in PF and SLEwomen than HC, but the difference was statistically significant only in women with SLE. No statistical difference was observed in XCI patterns between PF and SLE patients. PF phenotype-XCI correlation analysis revealed that (i) skewed XCI patterns may be involved in the disease’s subtype and (ii) it was more pronounced in the endemic group than the sporadic one. Furthermore, preferential XCI showed an increase in heterozygote genotypes of PF’s susceptibility polymorphisms in immunity-related X genes (FOXP3, AR, and TLR7) in PF patients compared to HC.

CONCLUSION: Our results suggest that skewed XCI could lead to hemizygosity of X-linked alleles that might unmask X-linked deleterious alleles.

PMID:36349750 | DOI:10.1002/mgg3.2080

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Nevin Manimala Statistics

Functional loss and worsening geriatric assessment parameters are more common in dementia with Lewy bodies than Alzheimer’s disease

Psychogeriatrics. 2022 Nov 9. doi: 10.1111/psyg.12905. Online ahead of print.

ABSTRACT

BACKGROUND: The main aim of this study was to compare older patients with Alzheimer’s disease (AD) to those with dementia with Lewy bodies (DLB) according to their dependency in daily living activities and comprehensive geriatric assessment parameters.

METHOD: A total of 227 AD and 123 DLB patients underwent a geriatric assessment that included comorbidities, number of drugs used, falls, urinary incontinence, hand grip strength, Mini-Nutritional Assessment (MNA), Tinetti Performance Oriented Mobility Assessment Scale, Insomnia Severity Index (ISI), and Epworth Sleepiness Scale. Basic and instrumental activities of daily living were assessed by the Barthel Index and the Lawton scale, respectively.

RESULTS: The mean age of the participants was 83.4 years, and 73% were female. There were no statistically significant differences between AD and DLB patients in age, gender, cognitive function, or comorbidities except for coronary artery disease (P < 0.05). The number of falls, drugs used, and ISI and Epworth scores were higher in patients with DLB than patients with AD (P < 0.05). DLB patients had lower MNA, Tinetti scale, and hand grip strength scores than AD patients. The ratio of patients highly dependent in basic daily activities as a whole was significantly greater in DLB than in AD (P < 0.05), but there was no significant difference in the overall levels of dependency in instrumental activities.

CONCLUSION: DLB patients are more dependent on their caregivers than AD patients. Nutritional deterioration, sleep disorders, falls, balance and gait problems, decreased muscle strength, and multiple drug use are more common in those with DLB compared to those with AD. The management of older patients with DLB may be more difficult than older patients with AD.

PMID:36349708 | DOI:10.1111/psyg.12905

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Nevin Manimala Statistics

Interpretation bias in health anxiety: a systematic review and meta-analysis

Psychol Med. 2022 Nov 9:1-12. doi: 10.1017/S0033291722003427. Online ahead of print.

ABSTRACT

Interpretation bias (i.e. the selective negative interpretation of ambiguous stimuli) may contribute to the development and maintenance of health anxiety. However, the strength of the empirical evidence for this association remains a topic of debate. This study aimed to estimate the association between health anxiety and interpretation bias and to identify potential moderators of this association. Chinese-language databases (CNKI, VIP, and Wanfang), English-language databases (Web of Science, PubMed, PsycINFO, and Scopus), and German-language databases (Psyndex and PubPsych) were searched for relevant studies. There were 36 articles (39 studies) identified by this search (N = 8984), of which 32 articles (34 studies) were included in the meta-analysis (N = 8602). Results revealed a medium overall effect size (g = 0.67). Statistically equivalent effect sizes were observed for patients diagnosed with clinical health anxiety (g = 0.58) and subclinical health anxiety (g = 0.72). The effect sizes for threat stimuli that were health related (g = 0.68) and not health related (g = 0.63) did not differ significantly. The effect size for studies using an offline paradigm (g = 0.75) was significantly higher than that for studies using an online paradigm (g = 0.50). It is concluded that health anxiety is significantly and robustly associated with interpretation bias. These findings are of central importance for the advancement of models and treatment of health anxiety.

PMID:36349699 | DOI:10.1017/S0033291722003427

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Nevin Manimala Statistics

Reliability and Validity of the Tinnitus Handicap Inventory: A Clinical Study of Questionnaires

J Int Adv Otol. 2022 Nov;18(6):522-529. doi: 10.5152/iao.2022.21503.

ABSTRACT

BACKGROUND: The aim of this study is to observe the application of the Chinese version of Tinnitus Handicap Inventory-China in Tinnitus patients and verify its reliability and validity.

METHODS: About 1129 patients with tinnitus as the first complaint were selected as subjects. The patients were randomly divided into 2 groups: exploration group (n = 565), whose data were analyzed with reliability analysis method using Statistical Package for the Social Sciences software 19.0, validation group (n = 564), whose data were analyzed with validity analysis method using AMOS21.0.

RESULTS: (1) Reliability test: The Cronbach’s α coefficients of the Tinnitus Handicap Inventory-China scale in both groups were 0.94, among which, the Cronbach’s α coefficients of functional factor (F), emotion factor (E), and catastrophic factor (C) in group E were 0.87, 0.90, and 0.78, respectively. The half-reliability of the 2 components is 0.87. The correlation coefficient between items and the scale in group E and group V is 0.36-0.78 and 0.33-0.77, respectively. (2) Content validity: The Kaiser-Meyer-Olkin value of group E is 0.96, a total of 4 common factors were extracted, and the cumulative interpretation rate is 57.844%. The number of factors with load less than 0.4 on the 4 common factors is only 1 (F24), suggesting that this factor had little significance; the number of factors with load more than 0.4 on the 2 common factors is 8 (F1, E6, F9, C11, F15, E21, E22, and C23), suggesting that patients had different understandings of these 8 questions. (3) Structural validity: The root mean square error of approximation value of the AMOS structural model in group V is 0.065, and the root mean square residual value is 0.114, indicating low fitness; the NC value is 3.353, indicating good fitness of the scale, but it still needed to be simplified.

CONCLUSION: The Chinese version of Tinnitus Handicap Inventory-China has a high reliability when applied in China, but the content validity and structure validity are not high, and the clinical practicability needs to be improved.

PMID:36349675 | DOI:10.5152/iao.2022.21503

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Nevin Manimala Statistics

Optimizing the Measurement of 0.5-kHz Cubic Distortion Product Otoacoustic Emission

J Int Adv Otol. 2022 Nov;18(6):471-477. doi: 10.5152/iao.2022.21639.

ABSTRACT

BACKGROUND: The measurement of low-frequency cubic distortion product otoacoustic emission, for example, 0.5-kHz cubic distortion product otoacoustic emission, is often severely affected by background noise, and currently 0.5-kHz cubic distortion product otoacoustic emission is not commonly applicable in clinical setting.

METHODS: The fundamental part of current study was the optimization of recording technology to reduce noise interference with the measurement of 0.5-kHz cubic distortion product otoacoustic emission and to establish the response patterns of cubic distortion product otoacoustic emission across speech frequencies from 0.5 to 8kHz in the presence of normal hearing and noise-induced hearing loss.

RESULTS: After a series of optimization, a clinically applicable technology of measuring 0.5-kHz cubic distortion product otoacoustic emission was successfully completed via animal model. Cubic distortion product otoacoustic emission was recorded in 6 guinea pigs across speech frequencies from 0.5 to 8kHz before and after exposure to white bandnoise between 0.5 and 2 kHz. After noise exposure, significant reduction in the signal-to-noise ratio of cubic distortion product otoacoustic emission was found at 0.5 and 2 kHz, indicating our recording technology was sensitive and accurate. Other interesting finding was the reduction in cubic distortion product otoacoustic emiss ion-s ignal -to-n oise ratio at 4 and 6 kHz although the reduction was not statistically significant probably because of short exposure time. The result implied that the damaging effect induced by low-frequency noise exposure might spread upward to high-frequency region.

CONCLUSIONS: Our recording technology was stable and reliable and had the great potentiality to be used in clinical setting.

PMID:36349667 | DOI:10.5152/iao.2022.21639