Category: Statistics

Life Sci Alliance. 2021 Oct 8;4(12):e202101126. doi: 10.26508/lsa.202101126. Print 2021 Dec.

ABSTRACT

The yeast chromatin protein Set4 is a member of the Set3-subfamily of SET domain proteins which play critical roles in the regulation of gene expression in diverse developmental and environmental contexts. We previously reported that Set4 promotes survival during oxidative stress and regulates expression of stress response genes via stress-dependent chromatin localization. In this study, global gene expression analysis and investigation of histone modification status identified a role for Set4 in maintaining gene repressive mechanisms within yeast subtelomeres under both normal and stress conditions. We show that Set4 works in a partially overlapping pathway to the SIR complex and the histone deacetylase Rpd3 to maintain proper levels of histone acetylation and expression of stress response genes encoded in subtelomeres. This role for Set4 is particularly critical for cells under hypoxic conditions, where the loss of Set4 decreases cell fitness and cell wall integrity. These findings uncover a new regulator of subtelomeric chromatin that is key to stress defense pathways and demonstrate a function for Set4 in regulating repressive, heterochromatin-like environments.

PMID:34625508 | DOI:10.26508/lsa.202101126

BMJ. 2021 Oct 8;375:n2368. doi: 10.1136/bmj.n2368.

ABSTRACT

OBJECTIVE: To investigate the association between changes in long term residential exposure to ambient fine particulate matter (PM_2.5) and premature mortality in Canada.

DESIGN: Population based quasi-experimental study.

SETTING: Canada.

PARTICIPANTS: 663 100 respondents to the 1996, 2001, and 2006 Canadian censuses aged 25-89 years who had consistently lived in areas with either high or low PM_2.5 levels over five years preceding census day and moved during the ensuing five years.

INTERVENTIONS: Changes in long term exposure to PM_2.5 arising from residential mobility.

MAIN OUTCOME MEASURES: The primary outcome was deaths from natural causes. Secondary outcomes were deaths from any cardiometabolic cause, any respiratory cause, and any cancer cause. All outcomes were obtained from the national vital statistics database.

RESULTS: Using a propensity score matching technique with numerous personal, socioeconomic, health, and environment related covariates, each participant who moved to a different PM_2.5 area was matched with up to three participants who moved within the same PM_2.5 area. In the matched groups that moved from high to intermediate or low PM_2.5 areas, residential mobility was associated with a decline in annual PM_2.5 exposure from 10.6 μg/m³ to 7.4 and 5.0 μg/m³, respectively. Conversely, in the matched groups that moved from low to intermediate or high PM_2.5 areas, annual PM_2.5 increased from 4.6 μg/m³ to 6.7 and 9.2 μg/m³. Five years after moving, individuals who experienced a reduction in exposure to PM_2.5 from high to intermediate levels showed a 6.8% (95% confidence interval 1.7% to 11.7%) reduction in mortality (2510 deaths in 56 025 v 4925 deaths in 101 960). A greater decline in mortality occurred among those exposed to a larger reduction in PM_2.5. Increased mortality was found with exposure to PM_2.5 from low to high levels, and to a lesser degree from low to intermediate levels. Furthermore, the decreases in PM_2.5 exposure were most strongly associated with reductions in cardiometabolic deaths, whereas the increases in PM_2.5 exposure were mostly related to respiratory deaths. No strong evidence was found for the changes in PM_2.5 exposure with cancer related deaths.

CONCLUSIONS: In Canada, decreases in PM_2.5 were associated with lower mortality, whereas increases in PM_2.5 were associated with higher mortality. These results were observed at PM_2.5 levels considerably lower than many other countries, providing support for continuously improving air quality.

PMID:34625469 | DOI:10.1136/bmj.n2368

Proc Natl Acad Sci U S A. 2021 Oct 12;118(41):e2102166118. doi: 10.1073/pnas.2102166118.

ABSTRACT

Highly resolved spatial data of complex systems encode rich and nonlinear information. Quantification of heterogeneous and noisy data-often with outliers, artifacts, and mislabeled points-such as those from tissues, remains a challenge. The mathematical field that extracts information from the shape of data, topological data analysis (TDA), has expanded its capability for analyzing real-world datasets in recent years by extending theory, statistics, and computation. An extension to the standard theory to handle heterogeneous data is multiparameter persistent homology (MPH). Here we provide an application of MPH landscapes, a statistical tool with theoretical underpinnings. MPH landscapes, computed for (noisy) data from agent-based model simulations of immune cells infiltrating into a spheroid, are shown to surpass existing spatial statistics and one-parameter persistent homology. We then apply MPH landscapes to study immune cell location in digital histology images from head and neck cancer. We quantify intratumoral immune cells and find that infiltrating regulatory T cells have more prominent voids in their spatial patterns than macrophages. Finally, we consider how TDA can integrate and interrogate data of different types and scales, e.g., immune cell locations and regions with differing levels of oxygenation. This work highlights the power of MPH landscapes for quantifying, characterizing, and comparing features within the tumor microenvironment in synthetic and real datasets.

PMID:34625491 | DOI:10.1073/pnas.2102166118

Int J Spine Surg. 2021 Oct 8:8127. doi: 10.14444/8127. Online ahead of print.

ABSTRACT

BACKGROUND: Single and multilevel lumbar arthroplasty has had excellent results, but the L5-S1 level frequently has pathology that precludes arthroplasty. This study evaluated clinical outcomes and sagittal range of motion (ROM) of operated levels and adjacent motion segments in single- and multiple-level ProDisc-L above a simultaneous L5-S1 fusion (hybrid) after a 2- to 6-year follow-up.

METHODS: In this prospective cohort study, 46 patients underwent simultaneous lumbar total disc replacement (TDR) at one to three levels and anterior lumbar interbody fusion (ALIF) at L5-S1. Twenty-three patients had L5-S1 ALIF + L4-5 TDR, 19 patients had L5-S1 ALIF + two-level TDR, and 4 patients had L5-S1 ALIF + three-level TDR. Oswestry disability index (ODI) and visual analog scores (VAS) of patient satisfaction (VAS-S) and pain (VAS-P) were recorded. Sagittal motion on pre- and postoperative lumbar radiographs at each operative segment and adjacent segment was acquired. Patients were evaluated preoperatively and at 6 weeks, 3 months, 6 months, and annually for 24 to 72 months postoperatively.

RESULTS: For clinical results, there were no differences among the groups for age, gender, body mass index, tobacco use, or worker’s compensation status. At 2-6 years postoperation, all patients had significant reductions in ODI and VAS scores. For radiographic results, at the nonsurgical level adjacent to the TDR + ALIF constructs, the mean preoperative ROM was 9.40 ± 1.80° compared with 10.50 ± 2.25° postoperatively. The mean preoperative ROM at levels undergoing TDR was 10.4 ± 2.71° versus 12.6 ± 2.25° postoperatively. There was no statistically significant difference in ROM at each prosthetic motion segment between patients receiving one-, two-, or three-level TDR. The mean preoperative ROM at the L5-S1 segment to undergo fusion was 2.4 ± 2.44°, with all patients having a postoperative ROM of 0.00°.

CONCLUSIONS: Multilevel TDR above an L5-S1 ALIF (hybrid procedure) preserves ROM at the individual TDR levels and does not reduce the fusion rate of the L5-S1 fused level. Most significantly, the nonoperative adjacent level maintains its preoperative ROM at 2-6 years postoperatively.

PMID:34625452 | DOI:10.14444/8127

BMJ Glob Health. 2021 Oct;6(10):e006660. doi: 10.1136/bmjgh-2021-006660.

ABSTRACT

INTRODUCTION: Recent studies suggest that more male than female deaths are registered and a higher proportion of female deaths are certified as ‘garbage’ causes (ie, vague or ill-defined causes of limited policy value). This can reduce the utility of sex-specific mortality statistics for governments to address health problems. To assess whether there are sex differences in completeness and quality of data from civil registration and vital statistics systems, we analysed available global death registration and cause of death data.

METHODS: Completeness of death registration for females and males was compared in 112 countries, and in subsets of countries with incomplete death registration. For 64 countries with medical certificate of cause of death data, the level, severity and type of garbage causes was compared between females and males, standardised for the older age distribution and different cause composition of female compared with male deaths.

RESULTS: For 42 countries with completeness of less than 95% (both sexes), average female completeness was 1.2 percentage points (p.p.) lower (95% uncertainty interval (UI) -2.5 to -0.2 p.p.) than for males. Aggregate female completeness for these countries was 7.1 p.p. lower (95% UI -12.2 to -2.0 p.p.; female 72.9%, male 80.1%), due to much higher male completeness in nine countries including India. Garbage causes were higher for females than males in 58 of 64 countries (statistically significant in 48 countries), but only by an average 1.4 p.p. (1.3-1.6 p.p.); results were consistent by severity and type of garbage.

CONCLUSION: Although in most countries analysed there was no clear bias against females in death registration, there was clear evidence in a few countries of systematic undercounting of female deaths which substantially reduces the utility of mortality data. In countries with cause of death data, it was only of marginally poorer quality for females than males.

PMID:34625458 | DOI:10.1136/bmjgh-2021-006660

Cancer Res. 2021 Oct 8:canres.0899.2021. doi: 10.1158/0008-5472.CAN-21-0899. Online ahead of print.

ABSTRACT

Mutational signatures are patterns of somatic alterations in the genome caused by carcinogenic exposures or aberrant cellular processes. To provide a comprehensive workflow for preprocessing, analysis, and visualization of mutational signatures, we created the Mutational Signature Comprehensive Analysis Toolkit (musicatk) package. musicatk enables users to select different schemas for counting mutation types and easily combine count tables from different schemas. Multiple distinct methods are available to deconvolute signatures and exposures or to predict exposures in individual samples given a pre-existing set of signatures. Additional exploratory features include the ability to compare signatures to the COSMIC database, embed tumors in two dimensions with UMAP, cluster tumors into subgroups based on exposure frequencies, identify differentially active exposures between tumor subgroups, and plot exposure distributions across user-defined annotations such as tumor type. Overall, musicatk will enable users to gain novel insights into the patterns of mutational signatures observed in cancer cohorts.

PMID:34625425 | DOI:10.1158/0008-5472.CAN-21-0899

Br J Ophthalmol. 2021 Jun 18:bjophthalmol-2020-317793. doi: 10.1136/bjophthalmol-2020-317793. Online ahead of print.

ABSTRACT

AIMS: To evaluate visual acuity (VA) outcomes of cataract surgery, and factors associated with good visual outcomes, among a population with diabetes.

METHODS: Participants with type 2 diabetes enrolled in The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and ACCORD-eye substudy. 1136 eyes of 784 ACCORD participants receiving cataract surgery during follow-up (2001-2014) were included. Of these, 362 eyes had fundus photographs gradable for diabetic retinopathy. The main outcome measure was the achievement of postoperative VA of 20/40 or better.

RESULTS: In the sample of 1136 eyes, 762 eyes (67.1%) achieved good visual outcome of 20/40 or better. Factors predictive of good visual outcome were higher level of educational attainment (college vs some high school, OR 2.35 (95% CI 1.44 to 3.82)), bilateral cataract surgery (OR 1.55 (1.14 to 2.10)) and preoperative VA (20/20 or better vs worse than 20/200, OR 10.59 (4.07 to 27.54)). Factors not significantly associated (p>0.05) included age, sex, race, smoking, diabetes duration, blood pressure, lipid levels and haemoglobin A1C (HbA1C). In the subsample of 362 eyes, absence of diabetic retinopathy was associated with good visual outcome (OR 1.73 (1.02 to 2.94)).

CONCLUSION: Among individuals with diabetes, two-thirds of eyes achieved good visual outcome after cataract surgery. Notable factors associated with visual outcome included preoperative VA and diabetic retinopathy, but not HbA1C, underscoring that while certain ocular measures may help evaluate visual potential, systemic parameters may not be as valuable. Sociodemographic factors might also be important considerations. Although the current visual prognosis after cataract surgery is usually favourable, certain factors still limit the visual potential in those with diabetes.

PMID:34625432 | DOI:10.1136/bjophthalmol-2020-317793

Disabil Health J. 2021 Oct 4:101219. doi: 10.1016/j.dhjo.2021.101219. Online ahead of print.

ABSTRACT

BACKGROUND: Recent evidence suggests that many adults with intellectual and developmental disabilities (IDD) do not adequately manage hypertension (HTN) medication. Known risk factors for insufficient prescription filling include age, residential placement, and lack of caregiver support. This is a first report of a randomized intervention trial designed to analyze the relationship of a brief educational intervention with increased knowledge about HTN and improvement in prescription filling for anti-hypertensive medication.

OBJECTIVE/HYPOTHESIS: The objective was to test whether an educational flyer and regular messages about HTN and the importance of refilling medication would improve scores on knowledge surveys. Participants were Medicaid members with HTN and IDD (Member) or caregivers (Helpers) who chose to participate on behalf of a Member.

METHODS: Recruitment letters explained that either the Member or their Helper could participate (not both). Participants were randomly assigned to the Case or Comparison group, and both were comprised of Members and Helpers. Only Case participants received a flyer and monthly HTN education messages for one year, but all participants completed knowledge surveys at baseline, six, and 12 months. Linear regression and log-binomial models were used to compare responses between groups.

RESULTS: Case Helpers had statistically significant improvements on HTN knowledge from baseline through the first year, compared to Comparison Members and Comparison Helpers. Regardless of group assignment, Helpers scored better on surveys than did Members.

CONCLUSIONS: This study suggests that it is beneficial to explicitly include Helpers in health care instruction and in management of chronic disease for adults with IDD.

PMID:34625396 | DOI:10.1016/j.dhjo.2021.101219

BMJ Open. 2021 Oct 8;11(10):e045871. doi: 10.1136/bmjopen-2020-045871.

ABSTRACT

OBJECTIVES: To investigate the association between shingles and dementia, and between Zostavax vaccination and dementia.

DESIGN: Nested case-control study.

SETTINGS: Data were drawn from the UK Biobank cohort study with a total of 228 223 participants with Hospital Episodes Statistics and primary care linkage health records.

PARTICIPANTS: The analyses included 2378 incident dementia cases and 225 845 controls. Inclusion criteria for incident cases were a dementia diagnosis 3 years or more after the first assessment date derived from all sources including International Classification of Diseases (ICD)-10, ICD-9, self-report and primary care linkage records. Subjects with no dementia code from all sources were coded as controls. Both shingles and Zostavax vaccination were investigated for their association with dementia risk.

RESULTS: There was a small but non-significant increase in the risk of dementia in subjects with shingles diagnosed 3 years or more prior to dementia diagnosis (OR: 1.088 with 95% CI: 0.978 to 1.211). In those subjects who had had Zostavax vaccination, the risk of dementia significantly decreased (OR: 0.808 with 95% CI: 0.657 to 0.993).

CONCLUSION: A history of shingles was not associated with an increased risk of dementia. In subjects who were eligible for the immunisation and vaccinated with Zostavax, we saw reduced risk of developing dementia.

PMID:34625411 | DOI:10.1136/bmjopen-2020-045871

Nutr Metab Cardiovasc Dis. 2021 Aug 12:S0939-4753(21)00395-1. doi: 10.1016/j.numecd.2021.08.026. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Triglyceride-Glucose (TyG) index is an accurate biomarker of insulin resistance, which is potentially associated with adverse cardiovascular events. We aimed to assess the dose-response relationship between Triglyceride-Glucose (TyG) Index and Major Adverse Cardiovascular Events (MACE) in patients with Acute Coronary Syndrome (ACS).

METHODS AND RESULTS: A systematic literature search was performed using PubMed, Scopus, and Embase for records published from the inception up until 7 February 2021. Studies that fulfilled all of these criteria were included: 1) prospective or retrospective observational studies reporting patients with ACS and 2) assessing the impact of TyG index on MACE with at least three quantitative classifications. The outcome of interest is MACE across the TyG index intervals. MACE was a composite of all-cause mortality, myocardial infarction, unstable angina pectoris, target vessel revascularization, cerebrovascular accidents, and heart failure. The effect estimates were reported as relative risks (RRs). There are 13,684 subjects from 4 studies included in this meta-analysis. This meta-analysis showed that the highest category of TyG index was associated with twofold MACE (RR 2.09 [1.59, 2.76], p < 0.001; I²: 68.4%, p = 0.02) compared to the lowest category in patients with ACS. Dose-response meta-analysis showed that the relationship between TyG index and MACE was non-linear (p < 0.001), with statistical significance reached around TyG index 8.9 and increased non-linearly. The dose-response curve became significantly steeper after TyG index of 9.1-9.2.

CONCLUSION: TyG index was associated with MACE in patients with ACS in a non-linear fashion.

PROSPERO: CRD42021235765.

PMID:34625361 | DOI:10.1016/j.numecd.2021.08.026