Category: Statistics

J Med Radiat Sci. 2022 Jun 18. doi: 10.1002/jmrs.602. Online ahead of print.

ABSTRACT

INTRODUCTION: The magnitude and impact of rotational error is unclear in rectal cancer radiation therapy. This study evaluates rotational errors in rectal cancer patients, and investigates the feasibility of planning target volume (PTV) margin reduction to decrease organs at risk (OAR) irradiation.

METHODS: In this study, 10 patients with rectal cancer were retrospectively selected. Rotational errors were assessed through image registration of daily cone beam computed tomography (CBCT) and planning CT scans. Two reference treatment plans (TP_R ) with PTV margins of 5 mm and 10 mm were generated for each patient. Pre-determined rotational errors (±1°, ±3°, ±5°) were simulated to produce six manipulated treatment plans (TP_M ) from each TP_R . Differences in evaluated dose-volume metrics between TP_R and TP_M of each rotation were compared using Wilcoxon Signed-Rank Test. Clinical compliance was investigated for statistically significant dose-volume metrics.

RESULTS: Mean rotational errors in pitch, roll and yaw were -0.72 ± 1.81°, -0.04 ± 1.36° and 0.38 ± 0.96° respectively. Pitch resulted in the largest potential circumferential displacement of clinical target volume (CTV) at 1.42 ± 1.06 mm. Pre-determined rotational errors resulted in statistically significant differences in CTV, small bowel, femoral heads and iliac crests (P < 0.05). Only small bowel and iliac crests failed clinical compliance, with majority in the PTV 10 mm margin group.

CONCLUSION: Rotational errors affected clinical compliance for OAR dose but exerted minimal impact on CTV coverage even with reduced PTV margins. Both PTV margin reduction and rotational correction decreased irradiated volume of OAR. PTV margin reduction to 5 mm is feasible, and rotational corrections are recommended in rectal patients to further minimise OAR irradiation.

PMID:35715996 | DOI:10.1002/jmrs.602

Obesity (Silver Spring). 2022 Jun 17. doi: 10.1002/oby.23453. Online ahead of print.

ABSTRACT

OBJECTIVE: Metabolic bariatric procedures are potentially efficacious treatment options in patients with type 2 diabetes mellitus (T2DM). Previous meta-analyses focused on individual operative approaches rather than the mechanistic pathways behind different bariatric procedures. This updated network meta-analysis aimed to synthesize new evidence and comparatively evaluate the efficacy of metabolic surgery against restrictive procedures and standard first-line treatment for patients with T2DM.

METHODS: Embase, MEDLINE, and trial registries were searched for randomized controlled trials on bariatric surgeries in patients with T2DM on September 3, 2021. A Bayesian network meta-analysis was conducted. The primary outcome was T2DM remission. Secondary outcomes included changes in BMI, lipoprotein levels, and blood pressure.

RESULTS: Thirty-two articles were included. Metabolic surgery was statistically superior to restrictive procedures (risk ratio [RR]: 2.57, 95% credibility intervals [CrI]: 1.36-5.43), medical therapy (RR: 35.29, 95% Crl: 10.56-183.23), and lifestyle intervention (RR: 40.51, 95% Crl: 5.32-402.59) in T2DM remission. Metabolic surgery significantly lowered BMI and blood pressure compared with other interventions. Restrictive procedures significantly increased high-density lipoprotein compared with metabolic surgery. Lifestyle intervention and metabolic surgery were statistically superior to restrictive procedures in reducing low-density lipoprotein.

CONCLUSIONS: The superiority in diabetes remission and favorable metabolic profile support the choice of metabolic surgery over restrictive bariatric procedures.

PMID:35715979 | DOI:10.1002/oby.23453

Health Soc Care Community. 2022 Jun 17. doi: 10.1111/hsc.13862. Online ahead of print.

ABSTRACT

As behavioural health occupations have diversified, more specialists such as social workers and counsellors are involved in providing substance use disorder treatment services. This study examined the association between changes in the number of different types of behavioural health professionals and changes in drug and opioid overdose deaths in the United States. Using publicly available state-level data from 2008 to 2017, we constructed multivariate linear regression models with state- and year fixed-effects to examine the effect of changes in the number of different types of behavioural health professionals (i.e. psychiatrists, psychologists, social workers and counsellors) on changes in drug and opioid overdose deaths at the state level, controlling for state population characteristics and other state-level factors. After controlling for confounding factors, a 1% increase in the number of social workers and counsellors at the state level was significantly associated with a 0.215% reduction in drug overdose deaths per 100,000 state population and with a 0.358% reduction in opioid overdose deaths per 100,000 state population. We did not find statistically significant associations between changes in drug overdose death rates and increases in the number of psychiatrists or psychologists alone. Our findings suggest efforts to facilitate a prepared and skilled workforce, such as expanding the capacity of social workers and counsellors, to maximise access to substance use disorder treatment services.

PMID:35715970 | DOI:10.1111/hsc.13862

Biophys J. 2022 Jun 16:S0006-3495(22)00477-5. doi: 10.1016/j.bpj.2022.06.018. Online ahead of print.

ABSTRACT

Missense mutations that compromise the plasma membrane expression (PME) of integral membrane proteins are the root cause of numerous genetic diseases. Differentiation of this class of mutations from those that specifically modify the activity of the folded protein has proven useful for the development and targeting of precision therapeutics. Nevertheless, it remains challenging to predict the effects of mutations on the stability and/ or expression of membrane proteins. In this work, we utilize deep mutational scanning data to train a series of artificial neural networks to predict the PME of transmembrane domain variants of G-protein coupled receptors (GPCRs) from structural and/ or evolutionary features. We show that our best performing network, which we term PMEpred, can recapitulate mutagenic trends within rhodopsin and can differentiate pathogenic transmembrane domain variants that cause it to misfold from those that compromise its’ signaling. This network also generates statistically significant predictions for the relative PME of transmembrane domain variants for another class A GPCR (β₂ adrenergic receptor) but not for an unrelated voltage-gated potassium channel (KCNQ1). Notably, our analyses of these networks suggest structural features alone are generally sufficient to recapitulate the observed mutagenic trends. Moreover, our findings imply that networks trained in this manner may be generalizable to proteins that share a common fold. Implications of our findings for the design of mechanistically specific genetic predictors are discussed.

PMID:35715957 | DOI:10.1016/j.bpj.2022.06.018

Ann Noninvasive Electrocardiol. 2022 Jun 17:e12977. doi: 10.1111/anec.12977. Online ahead of print.

ABSTRACT

OBJECTIVE: To analyze the efficacy and safety of antiplatelet drugs combined with new oral anticoagulants (noac) in the treatment of coronary atherosclerotic heart disease (CAD).

METHODS: The randomized controlled trials of noac combined with antiplatelet therapy in Cochrane, CNKI, PubMed, EMBASE, Wanfang, Google Scholar, and Baidu library were searched using the literature database. Two researchers independently searched and screened to ensure the consistency of the results, and the literature was summarized and analyzed by Revman 5.3 software.

RESULTS: Five research results were included. The results showed that the incidence of mace [95% CI 0.75-0.95, or = 0.84,p = .04], the incidence of major and minor bleeding [95% CI 1.25-5.16, or = 2.54,p = .01], the mortality of cardiovascular disease [95% CI 0.78-0.96, or = 0.86, p = .05], the total mortality [95% CI 0.79-0.95, or = 0.87, p = .003], and the incidence of myocardial infarction in patients with CAD treated with noac and antiplatelet drugs [95% CI 0.77-0.95, or = 0.85, p = .004] was lower than that treated with antiplatelet drugs alone, and the difference was statistically significant (p < .05); the incidence of fatal bleeding [95% CI 0.81-2.08, or = 1.30, p = .28], the incidence of stroke [95% CI 0.50-1.03, or = 0.71, p = .07], and the incidence of intracranial hemorrhage [95% CI 1.02-2.56, or = 1.61, p = .06]. There was no significant difference with antiplatelet drugs alone (p > .05).

CONCLUSION: Noac combined with antiplatelet drugs can reduce mace, total mortality, the incidence of myocardial infarction, and cardiovascular mortality in patients with CAD, but may increase the risk of bleeding.

PMID:35715952 | DOI:10.1111/anec.12977

Vet Med Sci. 2022 Jun 17. doi: 10.1002/vms3.841. Online ahead of print.

ABSTRACT

BACKGROUND: Heat stress (HS) is a major environmental effect on sheep production. Hereby, we estimated the genetic (co)variance component of HS on the pre-weaning performance of 19,022 Merino lambs by analysing the climatological index of temperature and relative humidity (recorded 30 days before lambing and after lambing) using transversal and longitudinal mixed linear models.

METHODS AND RESULTS: The global impact of HS during the last 30 days of pregnancy was -17% for birthweight and ranged between -4% and -8% for live weight at 15, 30 days of age (W30), and average daily gain from birth at 30 days. The results from both statistical approaches showed very similar heritabilities (h² ), ranging from 0.192 to 0.237 for the direct genetic (D) effects and from 0.072 to 0.082 for the maternal genetic (M) effects, but the antagonism between (D) and (M) was higher when a longitudinal model was used. A significant genotype-environmental effect was also found regardless of whether the climatological covariables were considered in the model. In addition, we employed D and M breeding values for W30 as an example to create a new subjacent index by first using a principal component analysis and employing the leading eigenvalues as a weighted factor that provides the information needed to identify those genotypes that maximise the response for both genetic effects over a wide range of climate-environment levels.

CONCLUSIONS: Our study revealed that the HS indexes of the mother during the gestation period have a significant effect on the growth of the lambs during the early stages of life.

PMID:35715950 | DOI:10.1002/vms3.841

Clin Cardiol. 2022 Jun 17. doi: 10.1002/clc.23844. Online ahead of print.

ABSTRACT

BACKGROUND: Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) assessed the cardiovascular (CV) safety of sitagliptin versus placebo on CV outcomes in patients with type 2 diabetes and CV disease and found sitagliptin noninferior to placebo. Subsequently, based on feedback from FDA, the Sponsor of the trial, Merck & Co., Inc., engaged a separate academic research organization, the TIMI Study Group, to re-adjudicate a prespecified set of originally adjudicated events.

METHODS: TIMI adjudicated in a blinded fashion all potential hospitalization for heart failure (HHF) events, all potential MACE+ events previously adjudicated as not an endpoint event, and a random subset (~10%) of MACE+ events previously adjudicated as an endpoint event. An updated study-level meta-analysis of four randomized, placebo-controlled, CV outcomes trials with dipeptidyl peptidase 4 (DPP-4) inhibitors was then performed.

RESULTS: After re-adjudication of potential HHF events in the intent-to-treat population, there were 224 patients with a confirmed event in the sitagliptin arm (1.05/100 person-years) and 239 patients in the placebo arm (1.13/100 person-years), corresponding to a hazard ratio (HR) of 0.94 (95% confidence interval [95% CI]: 0.78-1.13, p = .49). Concordance between the outcome of the original adjudication and the re-adjudication for HHF events was 82.7%. The meta-analysis of CV outcomes trials with DPP-4 inhibitors with placebo and involving 43 522 patients yielded an HR of 1.07 (95% CI: 0.83-1.39), with moderate heterogeneity (p = .45, I² = 62.07%).

CONCLUSION: The results of this independent re-adjudication process and analyses of CV outcomes from TECOS were consistent with the original adjudication results and overall study findings. An updated study-level meta-analysis showed no overall significant risk for HHF with DPP-4 inhibitors, but with statistical heterogeneity.

PMID:35715946 | DOI:10.1002/clc.23844

J Biomed Nanotechnol. 2022 Mar 1;18(3):718-728. doi: 10.1166/jbn.2022.3303.

ABSTRACT

In this manuscript we constructed a dual-responsive nano-drug delivery system for matrix metalloproteinases and ATP in ovarian cancer microenvironment. The nanomicelle PCL-DNA/DOX-Peptide-PEG was prepared by intercalating doxorubicin hydrochloride between C and G base pairs of DNA double helix structure. Another ATP-responsive nanomicelle PCL-DNA/DOX-PEG was prepared. Then we analyzed the characterization of nanomicelles (particle size, potential, surface morphology, etc.) and drug loading binding and drug release behavior. In addition, the effect of nanomicelles on the viability of mouse ovarian epithelial tumor cell ID-8 was detected by CCK-8 method. CCK-8 assay detected that different concentrations of carrier had no difference on the proliferation of ID-8 cells, and the survival rate of ID-8 cells by different concentrations of DOX preparations was statistically significant and the same results were observed in cytotoxicity comparison. Confocal microscopy showed that DOX in the drug-loaded micelle group was concentrated in the nucleus, while free DOX was concentrated in the cytoplasm. ID-8 cells took up the drug-loaded micelles faster. The semi-quantitative analysis of the DOX uptake of ID-8 cells with different treatments showed extremely significant statistical differences. In conclusion, the prepared self-assembled dual-responsive nanomicelle PCL-DNA/DOX-Peptide-PEG is novel anti-tumor agent, and is expected to have good tumor tissue penetration ability with a low toxicity.

PMID:35715904 | DOI:10.1166/jbn.2022.3303

Yeast. 2022 Jun 17. doi: 10.1002/yea.3804. Online ahead of print.

ABSTRACT

The plant phyllosphere is one of the largest sources of microorganisms, including yeasts. In bromeliads, the knowledge of yeasts is dispersed and still incipient. To understand the extent of our knowledge on the subject, this review proposes to compile and synthesize existing knowledge, elucidating possible patterns, biotechnological and taxonomic potentials, bringing to light new knowledge, and identifying information gaps. For such, we systematically review scientific production on yeasts in bromeliads using various databases. The results indicated that the plant compartments flowers, fruits, leaves, and water tank (phytotelma) have been studied when focusing on the yeast community in the bromeliad phyllosphere. More than 180 species of yeasts and yeast-like fungi were recorded from the phyllosphere, 70% were exclusively found in one of these four compartments and only 2% were shared among all. In addition, most of the community had a low frequency of occurrence, and approximately half of the species had a single record. Variables such as bromeliad subfamilies and functional types, as well as plant compartments, were statistically significant, though inconclusive and with low explanatory power. At least 50 yeast species with some biotechnological potentials have been isolated from bromeliads. More than 90% of these species were able to produce extracellular enzymes. In addition, other biotechnological applications have also been recorded. Moreover, new species have been described, though yeasts were only exploited in approximately 1% of the existing bromeliads species, which highlights that there is still much to be explored. Nevertheless, it appears that we are still far from recovering the completeness of the diversity of yeasts in this host. Furthermore, bromeliads proved to be a good ecological model for prospecting new yeasts and for studies on the interaction between plants and yeasts. In addition, the yeast community diverged among plant compartments, establishing bromeliads as a microbiologically complex and heterogeneous mosaic. This article is protected by copyright. All rights reserved.

PMID:35715939 | DOI:10.1002/yea.3804

J Magn Reson Imaging. 2022 Jun 17. doi: 10.1002/jmri.28306. Online ahead of print.

ABSTRACT

BACKGROUND: Obesity is highly prevalent in patients with hypertrophic cardiomyopathy (HCM) and believed to influence its phenotype.

PURPOSE: To explore the effects of obesity on left ventricular (LV) remodeling and long-term clinical course in Chinese patients with HCM.

STUDY TYPE: Longitudinal.

POPULATION: A total of 247 patients with HCM classified according to body mass index (BMI) (normal weight: BMI = 18.0-22.9 kg/m² [N = 90]; overweight: BMI = 23.0-24.9 kg/m² [N = 58]; and obese: BMI ≥ 25 kg/m² [N = 99]).

FIELD STRENGTH/SEQUENCE: 3.0 T/Balanced steady-state free precession sequence and phase-sensitive inversion recovery late gadolinium enhancement (LGE) sequence.

ASSESSMENT: LV function and geometry were measured. LV peak strain analysis was performed. The presence and percentage of LGE in the LV were recorded. The endpoints including heart failure, sudden cardiac death, and overall composite outcome were assessed during a median follow-up of 4.1 years (interquartile range, 3.0-6.2 years).

STATISTICAL TESTS: One-way analysis of variance, Kruskal-Wallis test, or chi-square test; Pearson correlation coefficient (r); multivariable linear regression analysis; Kaplan-Meier survival analysis; and Cox proportional hazards model analysis were conducted. A two-tailed P-value < 0.05 was considered statistically significant.

RESULTS: Obese patients exhibited a significant progressive increase in LV mass compared with normal-weight patients. The magnitude of all LV strain indices gradually and significantly decreased as BMI increased, whereas LV ejection fraction was not significantly different among BMI groups (P = 0.364). Multivariable linear regression analysis showed that obesity had a significant association with impaired strain indices as well as with indexed LV mass. Multivariable Cox model analysis retained obesity as an independent marker for future endpoints, and conveyed a > 3-fold increase in risk compared with patients with normal weight (hazard ratio, 3.04; 95% confidence interval, 1.07-6.57).

DATA CONCLUSION: Obesity is an important environmental modifier that is associated with adverse LV remodeling and is independently associated with future clinical outcomes in Chinese patients with HCM.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

PMID:35715897 | DOI:10.1002/jmri.28306