Nevin Manimala

Nat Commun. 2022 Jan 17;13(1):342. doi: 10.1038/s41467-022-28034-z.

ABSTRACT

Identifying differentially abundant microbes is a common goal of microbiome studies. Multiple methods are used interchangeably for this purpose in the literature. Yet, there are few large-scale studies systematically exploring the appropriateness of using these tools interchangeably, and the scale and significance of the differences between them. Here, we compare the performance of 14 differential abundance testing methods on 38 16S rRNA gene datasets with two sample groups. We test for differences in amplicon sequence variants and operational taxonomic units (ASVs) between these groups. Our findings confirm that these tools identified drastically different numbers and sets of significant ASVs, and that results depend on data pre-processing. For many tools the number of features identified correlate with aspects of the data, such as sample size, sequencing depth, and effect size of community differences. ALDEx2 and ANCOM-II produce the most consistent results across studies and agree best with the intersect of results from different approaches. Nevertheless, we recommend that researchers should use a consensus approach based on multiple differential abundance methods to help ensure robust biological interpretations.

PMID:35039521 | DOI:10.1038/s41467-022-28034-z

Sci Rep. 2022 Jan 17;12(1):820. doi: 10.1038/s41598-021-04260-1.

ABSTRACT

Despite the structural and functional information contained in the statistical coupling between pairs of residues in a protein, coevolution associated with function is often obscured by artifactual signals such as genetic drift, which shapes a protein’s phylogenetic history and gives rise to concurrent variation between protein sequences that is not driven by selection for function. Here, we introduce a background model for phylogenetic contributions of statistical coupling that separates the coevolution signal due to inter-clade and intra-clade sequence comparisons and demonstrate that coevolution can be measured on multiple phylogenetic timescales within a single protein. Our method, nested coevolution (NC), can be applied as an extension to any coevolution metric. We use NC to demonstrate that poorly conserved residues can nonetheless have important roles in protein function. Moreover, NC improved the structural-contact predictions of several coevolution-based methods, particularly in subsampled alignments with fewer sequences. NC also lowered the noise in detecting functional sectors of collectively coevolving residues. Sectors of coevolving residues identified after application of NC were more spatially compact and phylogenetically distinct from the rest of the protein, and strongly enriched for mutations that disrupt protein activity. Thus, our conceptualization of the phylogenetic separation of coevolution provides the potential to further elucidate relationships among protein evolution, function, and genetic diseases.

PMID:35039514 | DOI:10.1038/s41598-021-04260-1

Nat Commun. 2022 Jan 17;13(1):344. doi: 10.1038/s41467-022-27958-w.

ABSTRACT

Quantum Hall interferometers have been used to probe fractional charge and statistics of quasiparticles. We present measurements of a small Fabry-Perot interferometer in which the electrostatic coupling constants which affect interferometer behavior can be determined experimentally. Near the center of the ν = 1/3 state this device exhibits Aharonov-Bohm interference interrupted by a few discrete phase jumps, and Φ₀ oscillations at higher and lower magnetic fields, consistent with theoretical predictions for detection of anyonic statistics. We estimate the electrostatic parameters K_I and K_IL by two methods: using the ratio of oscillation periods in compressible versus incompressible regions, and from finite-bias conductance measurements. We find that the extracted K_I and K_IL can account for the deviation of the phase jumps from the theoretical anyonic phase θ_a = 2π/3. At integer states, we find that K_I and K_IL can account for the Aharonov-Bohm and Coulomb-dominated behavior of different edge states.

PMID:35039497 | DOI:10.1038/s41467-022-27958-w

Biomed Phys Eng Express. 2022 Jan 17. doi: 10.1088/2057-1976/ac4c2a. Online ahead of print.

ABSTRACT

By using the statistical techniques of ANOVA: mean test and regression, it was found that the N_KRcalibration factor of Standard Imaging (SI) model HDR 1000 plus chambers presents a quadratic dependence with the reference air kerma rateK_R(from 6.9 mGy h^-1to 43.9 mGy h^-1). In order to understand and correct this dependency one model is presented for total recombination:k_s=I₃₀₀/I₁₅₀=1+k_ini+ k_d+k_volI₃₀₀+k_screenI₃₀₀², wherek_iniis the initial recombination,k_dthe thermal diffusion recombination,k_volthe volumetric recombination andk_screenthe screening for the currents/charges collected at the potential differences of 300 and 150 V. In conclusion, the total recombinationk_sis composed by onek_iniwith a constant contribution of 0.019%, onek_dcontribution of 0.017%, onek_volI₃₀₀contribution from 0.022% to 0.138%, and thek_screenI₃₀₀²effects from 0.002% to 0.09% in the range ofK_Rrate above. However, when this model fork_sis applied to try to correct the quadratic dependence of theN_KRvs K_R, explicitly there is no improvement in the variation range of 0.5% of theN_KRvs K_R.Nonetheless, it allows to obtainN_KRvalues consistent with a u_c≤ 0.7 %, which is less than 1.25% reported in the literature by ADCL or SSDL.

PMID:35039465 | DOI:10.1088/2057-1976/ac4c2a

J Clin Pathol. 2022 Jan 17:jclinpath-2021-207556. doi: 10.1136/jclinpath-2021-207556. Online ahead of print.

ABSTRACT

AIMS: To compare specific T-cell responses between laboratory employees in South Africa with and without previously diagnosed SARS-CoV-2 infection.

METHODS: Employees at a private pathology laboratory in South Africa were invited to participate in a nationwide cross-sectional study. T-cell proliferation to SARS-CoV-2 nucleocapsid (N)-proteins and spike (S)-proteins was measured by flow cytometry and compared between participants.

RESULTS: Based on classification according to SARS-CoV-2 reverse transcription (RT)-PCR results, a total of 81% (42/52) of positive participants demonstrated T-cell proliferation to SARS-CoV-2 N-proteins or S-proteins (95% CI 67.5% to 90.4%), while 62% (68/110) of negative participants also had detectable T-cell responses to SARS-CoV-2 proteins (95% CI 52.1% to 70.9%). When classified according to SARS-CoV-2 serology results, 92.6% (50/54) of positive participants demonstrated T-cell proliferation to SARS-CoV-2 proteins (95% CI 82.1 to 97,9 %), while 56% (60/108) of negative participants demonstrated T-cell proliferation (95% CI 45.7% to 65.1%). The magnitude of the T-cell responses as determined by a stimulation index, was significantly higher in the group previously infected by SARS-CoV-2 than in the negative group. A statistically significant difference in T-cell proliferation was noted between high risk and low risk groups for exposure to SARS-CoV-2 within the negative group, but no significant difference in magnitude of the response.

CONCLUSIONS: A significant proportion of South African laboratory employees who were not previously diagnosed with COVID-19 demonstrated T-cell reactivity to SARS-CoV-2 N-proteins and S-proteins. The pre-existing T-cell proliferation responses may be attributable to cross-reactive immune responses to other human coronaviruses, or possibly asymptomatic infection.

PMID:35039453 | DOI:10.1136/jclinpath-2021-207556

J Am Board Fam Med. 2022 Jan-Feb;35(1):140-151. doi: 10.3122/jabfm.2022.01.210273.

ABSTRACT

PURPOSE: Hyperuricemia is associated with increased cardiovascular risk. Because patients with asymptomatic hyperuricemia (AH) experience no immediate discomfort and there are possible side effects of urate-lowering drugs, treatment for AH is controversial. We aimed to perform a network meta-analysis (NMA) to investigate the effects of different urate-lowering therapies (ULTs) on serum uric acid level, renal function, blood pressure (BP), and safety in AH patients.

METHODS: This NMA focused on AH patients. The intervention group (patients receiving urate-lowering drugs) was compared with others using other types of drugs, placebo, or usual care. We undertook a NMA under the frequentist framework by R.

RESULTS: Thirteen eligible trials were identified. The interventions included allopurinol, febuxostat, and benzbromarone, which are not approved in the United States. Benzbromarone and allopurinol had the best efficacy on lowering serum uric acid level in short-term and long-term follow-up (mean difference [MD] = -3.05; 95% CI, -5.19 to -0.91 vs MD = -3.17; 95% CI, -5.19 to -1.15). Patients using allopurinol had significantly higher eGFR than using placebo in both short-term and long-term follow-up (MD = 3.07; 95% CI, 0.18 to 5.95 vs MD = 4.10; 95% CI, 2.66 to 5.54). No difference in BP was found between groups, except for febuxostat to diastolic BP after long-term treatment (MD = -1.47; 95% CI, -2.91 to -0.04). No statistically increased odds of safety events were found with the use of ULT.

CONCLUSIONS: Our result showed that in AH patients, allopurinol has a renoprotective effect. Febuxostat has a significant impact in lowering diastolic BP. ULT does not result in a higher risk of safety events.

PMID:35039419 | DOI:10.3122/jabfm.2022.01.210273

J Neurointerv Surg. 2022 Jan 17:neurintsurg-2021-018353. doi: 10.1136/neurintsurg-2021-018353. Online ahead of print.

ABSTRACT

BACKGROUND: Stent sizing remains a challenging task for flow diverter implantation because of stent foreshortening. In this study, we aimed to quantify the change in length after implantation and assess the error in length prediction using AneuGuide^TM software.

METHODS: In a retrospective cohort of 101 patients with 102 aneurysms undergoing treatment with a pipeline embolization device (PED; Covidien, Irvine, California, USA), we used AneuGuide^TM software to obtain measured lengths (ML) and calculated lengths (CL) after stent implantation. Stent elongation was defined as the ratio of ML-LL to the labeled length (LL). Simulation error was defined as the ratio of the absolute value of CL-ML to ML. The correlation and consistency between ML and LL and between ML and CL were analyzed using Pearson’s correlation test and the Bland-Altman plot. Statistical significance was set at p<0.05.

RESULTS: The mean elongation of ML was 32.6% (range 26.3-109.2%). Moderate consistency was observed between LL and ML (ρ=0.74, p<0.001). With the AneuGuide^TM software, the mean simulation error was 6.6% (range 0.32-21.2%). Pearson’s correlation test and the Bland-Altman plot showed a high correlation and consistency between ML and CL (ρ=0.96, p<0.001).

CONCLUSION: Labeled length provides only a low reference value for predicting the actual length of the flow diverter after implantation. The high consistency between ML and CL obtained from AneuGuide^TM software shows its great potential for the optimization of the flow diverter sizing process.

PMID:35039401 | DOI:10.1136/neurintsurg-2021-018353

BMJ Open. 2022 Jan 17;12(1):e057156. doi: 10.1136/bmjopen-2021-057156.

ABSTRACT

INTRODUCTION: Hand osteoarthritis (OA) is a common joint disorder in the adult population. No cure for hand OA is known yet, but treatment aims to reduce symptoms. Non-surgical and non-pharmacological therapy interventions can include splinting, patient education, and strengthening and range of movement exercises. However, it is still unclear which treatment is most beneficial for which patient. This study aims to identify subgroups of patients with hand OA that benefit most from the different non-surgical and non-pharmacological treatments.

METHODS AND ANALYSIS: We will conduct an individual patient data (IPD) meta-analysis by extracting IPD of eligible published randomised controlled trials (RCTs). A systematic literature search through Embase, Medline and Cochrane was performed on 8 February 2021. The primary outcome will be hand pain, and our secondary outcomes are objective and subjective hand physical functions. Subgroups include age, sex, body mass index, hypermobility and other comorbidities, pain medication, occupation, baseline pain, erosive OA, type and the number of hand joints involved, radiological severity of OA, and duration of symptoms. IPD of RCTs with homogeneous treatment interventions will be pooled and analysed using a two-stage approach to evaluate treatment effect on different subgroups.

ETHICS AND DISSEMINATION: No new data will be collected, so research ethical or governance approval is exempt. Findings will be disseminated via national and international conferences, publications in peer-reviewed journals, and summaries posted on websites accessed by the public and clinicians.

PMID:35039303 | DOI:10.1136/bmjopen-2021-057156

BMJ Open. 2022 Jan 17;12(1):e052376. doi: 10.1136/bmjopen-2021-052376.

ABSTRACT

OBJECTIVES: Colorectal cancer (CRC) is the second-leading cause of cancer deaths globally, with low-income and middle-income countries (LMICs) disproportionately affected. Estimates of CRC rates in LMIC are scarce. We aimed to (1) estimate sex-specific incidence of CRC, (2) estimate temporal trend and (3) determine regional variations of CRC rates on the African continent.

DESIGN: Systematic review and meta-analysis METHODS: PubMed (MEDLINE), OVID (MEDLINE), Scopus and Cochrane Library databases were systematically searched from inception to 12 December 2020. We included population-based studies that reported the incidence or prevalence estimates of CRC in Africa. Studies not conducted in humans or did not directly report the rates of CRC were excluded. Random effects model was used to pool the estimates. The methodological quality of studies was assessed with the Newcastle-Ottawa Scale.

OUTCOME MEASURES: Overall and sex-specific annual age-standardised incidence rates (ASIR) of CRC per 100 000 population.

RESULTS: The meta-analysis included 14 studies consisting of 3365 individuals with CRC (mean age, 58 years, 53% male). The overall ASIR of CRC in Africa per 100 000 population was 5.25 (95% CI 4.08 to 6.75). The rates were slightly higher in males (4.76) than in females (4.18), but not significantly different. Subgroup analysis indicated greater point estimates in North Africa (8.66) compared with sub-Saharan Africa (5.91); and higher estimates in Eastern (8.29) and Northern (8.66) Africa compared with Western (3.55) and Southern (3.57) Africa, but not statistically significant. The overall trend in ASIR has remained constant at nearly 5 per 100 000 population for the last 6 decades.

CONCLUSION: CRC estimates in Africa are heterogeneous and could be underestimated. High-quality data collection systems such as population-based cancer registries may facilitate accurate estimation of country-specific rates and provide critical information which would be lucrative to the consideration of resources needed for screening, early detection, treatment and improving overall patient outcomes.

PMID:35039287 | DOI:10.1136/bmjopen-2021-052376

BMJ Open. 2022 Jan 17;12(1):e052278. doi: 10.1136/bmjopen-2021-052278.

ABSTRACT

OBJECTIVES: Our study aimed to compare the quality of life (QoL) between Chinese developmental dyslexia (DD) and healthy children.

DESIGN: A cross-sectional study.

SETTING: The participants were recruited from grades 3-6 in six primary schools in Tianmen, a city of Hubei Province, China.

PARTICIPANTS: A total of 5679 students were recruited. After excluding children with visual and auditory dysfunction or psychiatric diseases or with a response rate on the scales or questionnaires of less than 90%, 5352 children were finally included in the analysis. DD children were diagnosed according to their clinical symptoms, which were mainly assessed by the Dyslexia Checklist for Chinese Children and the Pupil Rating Scale Revised Screening for Learning Disabilities.

OUTCOME MEASURES: The QoL for DD and healthy children was appraised by the Quality of Life Scale for Children and Adolescents (QLSCA). Outcome measures included its four domain scores (psychosocial function, physiological and mental health, living environment and satisfaction with QoL) and total score.

RESULTS: A total of 186 children were diagnosed with DD. The distribution of DD children in five levels of QoL was statistically different from that of healthy children (χ²=57.63, p<0.001). Compared with healthy children, the proportion of poor or worse QoL in DD was higher, and the proportion of moderate, better or good QoL was lower. The total QLSCA score in DD children was 3.475 lower than that in healthy children (B=-3.475, p=0.006). Psychosocial function, physiological and mental health, living environment and satisfaction with QoL of DD children were also inferior to those of healthy children.

CONCLUSION: The QoL of DD was significantly lower than that of healthy children, prompting more public efforts to improve DD QoL.

PMID:35039286 | DOI:10.1136/bmjopen-2021-052278