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Nevin Manimala Statistics

coupleCoC+: An information-theoretic co-clustering-based transfer learning framework for the integrative analysis of single-cell genomic data

PLoS Comput Biol. 2021 Jun 2;17(6):e1009064. doi: 10.1371/journal.pcbi.1009064. Online ahead of print.

ABSTRACT

Technological advances have enabled us to profile multiple molecular layers at unprecedented single-cell resolution and the available datasets from multiple samples or domains are growing. These datasets, including scRNA-seq data, scATAC-seq data and sc-methylation data, usually have different powers in identifying the unknown cell types through clustering. So, methods that integrate multiple datasets can potentially lead to a better clustering performance. Here we propose coupleCoC+ for the integrative analysis of single-cell genomic data. coupleCoC+ is a transfer learning method based on the information-theoretic co-clustering framework. In coupleCoC+, we utilize the information in one dataset, the source data, to facilitate the analysis of another dataset, the target data. coupleCoC+ uses the linked features in the two datasets for effective knowledge transfer, and it also uses the information of the features in the target data that are unlinked with the source data. In addition, coupleCoC+ matches similar cell types across the source data and the target data. By applying coupleCoC+ to the integrative clustering of mouse cortex scATAC-seq data and scRNA-seq data, mouse and human scRNA-seq data, mouse cortex sc-methylation and scRNA-seq data, and human blood dendritic cells scRNA-seq data from two batches, we demonstrate that coupleCoC+ improves the overall clustering performance and matches the cell subpopulations across multimodal single-cell genomic datasets. coupleCoC+ has fast convergence and it is computationally efficient. The software is available at https://github.com/cuhklinlab/coupleCoC_plus.

PMID:34077420 | DOI:10.1371/journal.pcbi.1009064

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Nevin Manimala Statistics

The epistemic roles of clinical expertise: An empirical study of how Swedish healthcare professionals understand proven experience

PLoS One. 2021 Jun 2;16(6):e0252160. doi: 10.1371/journal.pone.0252160. eCollection 2021.

ABSTRACT

Clinical expertise has since 1891 a Swedish counterpart in proven experience. This study aims to increase our understanding of clinicians’ views of their professional expertise, both as a source or body of knowledge and as a skill or quality. We examine how Swedish healthcare personnel view their expertise as captured by the (legally and culturally relevant) Swedish concept of “proven experience,” through a survey administered to a simple random sample of Swedish physicians and nurses (2018, n = 560). This study is the first empirical attempt to analyse the notion of proven experience as it is understood by Swedish physicians and nurses. Using statistical techniques for data dimensionality reduction (confirmatory factor analysis and multidimensional scaling), the study provides evidence that the proven experience concept is multidimensional and that a model consisting of three dimensions-for brevity referred to as “test/evidence”, “practice”, and “being an experienced/competent person”-describes the survey responses well. In addition, our results cannot corroborate the widely held assumption in evidence-based medicine that an important component of clinical expertise consists of experience of patients’ preferences.

PMID:34077421 | DOI:10.1371/journal.pone.0252160

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Nevin Manimala Statistics

Carmines (E120) in coloured yoghurts: a case-study contribution for human risk assessment

Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2021 Jun 2:1-8. doi: 10.1080/19440049.2021.1923820. Online ahead of print.

ABSTRACT

Carmines (E120) are used worldwide as natural food colouring agents of animal origin, with a widespread application, including yoghurts. Despite being considered safe for human health, carmines are known to cause allergic reactions. Our goal was to evaluate the presence of carmines in different yoghurts with a label declaration of E120, purchased in Portugal, and, for the first time, to assess the human risk. The analytical methodology, recommended by JECFA, was based on acid hydrolysis of the samples followed by spectrophotometric UV-Vis analysis at 494 nm. This methodology allowed for a limit of quantification (LOQ) of 39.0 mg/kg and recovery rates higher than 97.7%. All the samples had carmines at levels above the LOQ, ranging between 43.8 and 193.8 mg/kg, with an average of 125.2 ± 34.5 mg/kg. In total, 8 (26.7%) samples exceeded the European Union (EU) maximum permitted level (MPL) established for carmines in this foodstuff, 150 mg/kg. Solid yoghurts presented higher average levels, 137.2 mg/kg, when compared to liquid samples, 107.2 mg/kg, with a significant statistical difference (p= 0.0236) being observed. No significant statistical difference was observed between white and private labels, whose average levels were very similar, 125.4 vs 125 mg/kg, respectively. Although some samples were above the allowable values, the estimated daily intake (EDI), designed for the different scenarios of different yoghurt types, did not exceed the established ADI, 5 mg/kg bw/day. According to the obtained results, carmine ingestion through the consumption of yoghurt poses low risk to the Portuguese consumers. However, children were the most vulnerable population group with a calculated risk value of up to 10% considering the mean content scenario. These first findings point out the need to reinforce surveillance programmes and monitoring studies, contributing to an increased awareness regarding carmine exposure, however it must be emphasised that yoghurt has evident nutritional benefits depending on a healthful consumer choice.

PMID:34077331 | DOI:10.1080/19440049.2021.1923820

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Nevin Manimala Statistics

What Matters Most to Residency and Intern Selection Committees in Veterinary Medicine?

J Vet Med Educ. 2021 Jun 2:e20200098. doi: 10.3138/jvme-2020-0098. Online ahead of print.

ABSTRACT

A recent survey of members of residency selection committees for the American College of Veterinary Internal Medicine and American College of Veterinary Surgeons boards found letters of recommendation to be the most important factor when reviewing a resident’s application followed by class rank as the second most important factor. These statistics indicate an interesting, but possibly troubling trend. This Letter to The Editor discusses the major problems concerning these findings and what residency program committees might consider as an alternative.

PMID:34077333 | DOI:10.3138/jvme-2020-0098

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Nevin Manimala Statistics

A half marathon shifts the mediolateral force distribution at the tibiofemoral joint

Eur J Sport Sci. 2021 Jun 2:1-23. doi: 10.1080/17461391.2021.1938690. Online ahead of print.

ABSTRACT

AbstractRunners’ gait patterns vary during a half marathon and influence the knee joint mechanics. Joint contact force is a better estimate of the net joint loadings than external joint moments and closely correlates to injury risks. This study explored the changes of lower limb joint kinematics, muscle activities, and knee joint loading in runners across the running mileages of a half marathon. Fourteen runners completed a half marathon on an instrumented treadmill where motion capture was conducted every 2 km (from 2 km to 20 km). A musculoskeletal model incorporating medial/lateral tibiofemoral compartments was used to process the movement data and report outcome variables at the selected distance checkpoints. Statistics showed no changes in joint angles, muscle co-contraction index, ground reaction force variables, and medial tibiofemoral contact force (p > 0.05). Knee adduction moment at 18 km was significantly lower than those at 2 km (p = 0.002, γ = 0.813) and 6 km (p = 0.001, γ = 0.663). Compared to that at 2 km, lateral tibiofemoral contact force was reduced at 18 km (p = 0.030, Hedges’ g = 0.690), 16 km (p < 0.001, Hedges’ g = 0.782), 14 km (p = 0.045, Hedges’ g = 0.859), and 10 km (p < 0.001, Hedges’ g = 0.771) respectively. Mechanical realignment of the lower limb may be the cause of the altered knee loadings and possibly led to reduced running economy in response to a prolonged run. The injury potential of the redistributed tibiofemoral forces warranted further studies.

PMID:34077303 | DOI:10.1080/17461391.2021.1938690

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Nevin Manimala Statistics

Clinical Study Evaluating the Efficacy of Ivermectin in COVID-19 Treatment: A Randomized Controlled Study

J Med Virol. 2021 Jun 2. doi: 10.1002/jmv.27122. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Researchers around the world are working at record speed to find the best ways to treat and prevent COVID-19. This study aimed to evaluate the efficacy of ivermectin for the treatment of hospitalized mild to moderate COVID-19 infected patients.

METHODS: This was a randomized open-label controlled study which included 164 COVID-19 patients. Patients were randomized into two groups where group1 (Ivermectin group) included patients who received ivermectin12mg once daily for 3 days with standard care and group 2 (control group) included patients who received standard protocol of treatment alone for 14 days. The main outcomes were mortality, the length of hospital stay and the need for mechanical ventilation. All patients were followed up for one month.

RESULTS: Overall, 82 individuals were randomised to receive ivermectin plus standard of care and 82 to receive standard of care alone. Patients in the ivermectin group had shorter length of hospital stay (8.82± 4.94 days) than the control group (10.97 ± 5.28 days), but this was not statistically significant (P= 0.085). Three patients (3.7%) in each group required mechanical ventilation (P= 1.00). The death rate was three patients in the ivermectin group (3.7%) versus four patients (4.9%) in the control group without any significant difference between the two groups (P= 1.00).

CONCLUSION: Whereas there was no statistically significant difference in any endpoints by ivermectin doses (12 mg/day for 3 days); there was an observed trend to reducing hospital stay in the ivermectin treated group. This article is protected by copyright. All rights reserved.

PMID:34076901 | DOI:10.1002/jmv.27122

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ActiPso: Definition of activity types for psoriasis disease. A novel marker for an advanced disease classification

J Eur Acad Dermatol Venereol. 2021 Jun 2. doi: 10.1111/jdv.17434. Online ahead of print.

ABSTRACT

BACKGROUND: Assessment of psoriasis is exclusively done measuring severity using somatic scores such as the psoriasis area and severity index (PASI) or patient-reported outcomes such as the dermatology life quality index (DLQI). There is no established tool to measure a patient’s individual psoriasis activity over time.

OBJECTIVES: Development of a new tool to classify psoriasis activity types.

METHODS: Open patient interviews were performed and adapted in several steps and by using different groups of patients. Wording of the tool’s axis and description how to use it was optimized with the input of patients. The final ActiPso tool was used in a prospective study in psoriasis patients.

RESULTS: Four activity types could be identified describing psoriasis intensity (eg. severity, itch, pain) over one typical year and an event/trigger type describing flares. In the study in 586 psoriasis patients of the 536 patients eligible for analysis 40.9% self-classified as type 1 (“stable”), 22.6 % as type 2 (“unstable”), 30.6 % as type 3 (“winter-type”), and 6.0 % as type 4 (“summer-type”), respectively. Flares of psoriasis as identified by the event/trigger type were reported in 36.1 % of patients with activity type 1, 67.8 % with type 2, 73.8 % of type 3, and 59.4 % of type 4, respectively.

LIMITATIONS: In regions with no seasonal variations ActiPso types 3 and 4 may not apply.

CONCLUSIONS: Interviewed patients were able to describe their course of psoriasis disease and to name potential triggering factors. By doing so activity types of psoriasis were defined for the first time and the importance of events/triggers for flares described and integrated into ActiPso types as a basis for advanced patient-centric management.

PMID:34076926 | DOI:10.1111/jdv.17434

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Utility of interim blood tests for cancer screening in Li-Fraumeni syndrome

Fam Cancer. 2021 Jun 2. doi: 10.1007/s10689-021-00265-x. Online ahead of print.

ABSTRACT

Comprehensive annual screening reduces cancer-related mortality in Li-Fraumeni syndrome (LFS), a cancer-prone disorder caused by pathogenic germline TP53 variants. Blood tests at months 4 and 8 between annual screening are recommended but their effectiveness in early cancer detection has not been established. Interim blood counts and inflammatory biomarkers were evaluated in 132 individuals with LFS (112 adults, 87 female, median age 36 years [range 3-68], median follow-up 37 months [range 2-70]) and test abnormalities were observed in 225 (35%). Thirteen cancers in 12 individuals were diagnosed between annual screenings but only one cancer (colorectal adenocarcinoma) was diagnosed due to an abnormal interim blood test. Fisher’s exact test and generalized estimating equation models found no statistical associations between cancer diagnoses and any test abnormality. Four- and 8-monthly interim screening blood tests may not be of independent benefit for cancer detection in LFS, but annual cancer screening and personalized follow-up remain essential.

PMID:34076823 | DOI:10.1007/s10689-021-00265-x

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Combined effects of PNPLA3, TM6SF2 and HSD17B13 variants on severity of biopsy-proven non-alcoholic fatty liver disease

Hepatol Int. 2021 Jun 2. doi: 10.1007/s12072-021-10200-y. Online ahead of print.

ABSTRACT

OBJECTIVE: Several single-nucleotide polymorphisms have been identified to be disadvantageous or protective in regard to disease severity in patients with non-alcoholic fatty liver disease (NAFLD). However, it is unclear, whether including genetic risk factor(s) either alone or combined into risk stratification algorithms for NAFLD actually provides incremental benefit over clinical risk factors.

DESIGN: Patients with biopsy-proven NAFLD were genotyped for the PNPLA3-rs738409(minor allele:G), TM6SF2-rs58542926(minor allele:T) and HSD17B13- rs72613567 (minor allele:TA) variants. The NAFLD activity score (NAS) and fibrosis stage (F0-F4) were used to grade and stage all liver biopsy samples. Patients from seven centers throughout Central Europe were considered for the study.

RESULTS: 703 patients were included: NAS ≥ 5:173(24.6%); Fibrosis: F3-4:81(11.5%). PNPLA3 G/G genotype was associated with a NAS ≥ 5(aOR 2.23, p = 0.007) and advanced fibrosis (aOR-3.48, p < 0.001).TM6SF2 T/- was associated with advanced fibrosis (aOR 1.99, p = 0.023). HSD17B13 TA/- was associated with a lower probability of NAS ≥ 5(TA/T: aOR 0.65, p = 0.041, TA/TA: aOR 0.40, p = 0.033). Regarding the predictive capability for NAS ≥ 5, well-known risk factors (age, sex, BMI, diabetes, and ALT; baseline model) had an AUC of 0.758, Addition of PNPLA3(AUC 0.766), HSB17B13(AUC 0.766), and their combination(AUC 0.775), but not of TM6SF2(AUC 0.762), resulted in a higher diagnostic accuracy of the model. Addition of genetic markers for the prediction of advanced fibrosis (baseline model: age, sex, BMI, diabetes: AUC 0.777) resulted in a higher AUC if PNPLA3(AUC 0.789), and TM6SF2(AUC 0.786) but not if HSD17B13(0.777) were added.

CONCLUSION: In biopsy-proven NAFLD, PNPLA3 G/-, TM6SF2 T/- and HSD17B13 TA/- carriage are associated with severity of NAFLD. Incorporating these genetic risk factors into risk stratification models might improve their predictive accuracy for severity of NAFLD and/or advanced fibrosis on liver biopsy.

PMID:34076851 | DOI:10.1007/s12072-021-10200-y

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Nevin Manimala Statistics

Is pyoderma gangrenosum associated with solid malignancies? Insights from a population-based cohort study

Australas J Dermatol. 2021 Jun 2. doi: 10.1111/ajd.13631. Online ahead of print.

ABSTRACT

BACKGROUND: The question of whether solid malignancies (SMs) are associated with pyoderma gangrenosum (PG) remains to be conclusively answered.

OBJECTIVE: To evaluate the risk of SM among patients with PG and the odds of PG after a diagnosis of SM.

METHODS: A population-based retrospective cohort study was conducted to study the risk for SM in patients with PG (n = 302) as compared with age-, sex- and ethnicity-matched control subjects (n = 1799). A case-control design was used to estimate the odds of PG in those with a preexisting history of SM.

RESULTS: The prevalence of a preexisting SM was comparable in patients with PG and controls (7.5% vs. 8.8%, respectively; P = 0.490). The odds of having PG following a diagnosis of a SM was not statistically increased (OR, 0.85; 95% CI, 0.53-1.36). The incidence of SM was 6.8 (95% CI, 3.5-12.2) and 7.9 (95% CI, 6.1-10.1) per 1000 person-years among patients with PG and controls, respectively. Patients with PG were not more likely to develop SM as compared to controls (HR, 0.86; 95% CI, 0.44-1.69). Patients with a dual diagnosis of PG and SM were older and had more frequent comorbid conditions and increased mortality.

CONCLUSIONS: SM is not associated with provoking PG, and patients with PG are not at an increased risk of developing SM. A thorough routine screening for SM in patients with new-onset PG is an unnecessary approach based on the study findings.

PMID:34076886 | DOI:10.1111/ajd.13631