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Nevin Manimala Statistics

Using proteomics for stratification and risk prediction in patients with solid tumors

Pathologie (Heidelb). 2023 Nov 24. doi: 10.1007/s00292-023-01261-x. Online ahead of print.

ABSTRACT

Proteomics, the study of proteins and their functions, has greatly evolved due to advances in analytical chemistry and computational biology. Unlike genomics or transcriptomics, proteomics captures the dynamic and diverse nature of proteins, which play crucial roles in cellular processes. This is exemplified in cancer, where genomic and transcriptomic information often falls short in reflecting actual protein expression and interactions. Liquid chromatography-mass spectrometry (LC-MS) is pivotal in proteomic data generation, enabling high-throughput analysis of protein samples. The MS-based workflow involves protein digestion, chromatographic separation, ionization, and fragmentation, leading to peptide identification and quantification. Computational biostatistics, particularly using tools in R (R Foundation for Statistical Computing, Vienna, Austria; www.R-project.org ), aid in data analysis, revealing protein expression patterns and correlations with clinical variables. Proteomic studies can be explorative, aiming to characterize entire proteomes, or targeted, focusing on specific proteins of interest. The integration of proteomics with genomics addresses database limitations and enhances peptide identification. Case studies in intrahepatic cholangiocarcinoma, glioblastoma multiforme, and pancreatic ductal adenocarcinoma highlight proteomics’ clinical applications, from subtyping cancers to identifying diagnostic markers. Moreover, proteomic data augment molecular tumor boards by providing deeper insights into pathway activities and genomic mutations, supporting personalized treatment decisions. Overall, proteomics contributes significantly to advancing our understanding of cellular biology and improving clinical care.

PMID:37999758 | DOI:10.1007/s00292-023-01261-x

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Nevin Manimala Statistics

Prospective Randomized Controlled Trial Comparing Absorbable and Nonabsorbable Sutures in A1 Pulley Release

Hand (N Y). 2023 Nov 24:15589447231210332. doi: 10.1177/15589447231210332. Online ahead of print.

ABSTRACT

BACKGROUND: Both absorbable and nonabsorbable sutures are used to correct palmar incisions or lacerations. Nonabsorbable sutures have been used without complications but require removal at a follow-up appointment. Alternatively, the use of absorbable sutures has increased in popularity as postoperative suture removal is not required but is associated with local immunological and inflammatory responses. In this study, we compared the scar quality and outcomes of nonabsorbable and absorbable sutures in A1 pulley release.

METHODS: Patients who underwent A1 pulley release were randomized to 1 of 2 suture materials. The Patient Scar Assessment Scale, Observer Scar Assessment Scale, Visual Analogue Scale, and Disabilities of the Arm, Shoulder, and Hand scores were collected at 2, 6, and 12 weeks postoperatively. Among the 41 patients included in the study, 23 were randomized to the nonabsorbable suture group, and 18 to the absorbable suture group.

RESULTS: There were no significant differences between the two suture groups in the aforementioned assessments. Complication rates were higher in the nonabsorbable suture group, but the difference was not statistically significant. Notably, 1 case in the absorbable suture group had uncontrolled postoperative bleeding and required reoperation.

CONCLUSION: We found no significant difference between the two materials in terms of the Patient or Observer Scar Assessment Scales, overall complication rates, symptom scores, or pain scores. Therefore, the choice using absorbable or nonabsorbable can be guided by other factors such as physician or patient preference, availability, and cost.

PMID:37997760 | DOI:10.1177/15589447231210332

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Nevin Manimala Statistics

The utility of the Necessity-Concerns Framework (NCF) in explaining adherence and parental beliefs about controller medication in Saudi Arabian children with asthma

J Asthma. 2023 Nov 24:1-12. doi: 10.1080/02770903.2023.2288320. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to assess beliefs about asthma controller medications among parents of Saudi Arabian children with asthma and the association between these beliefs and medication adherence using the Necessity-Concerns Framework.

METHODS: A cross-sectional survey was provided to parents of children with asthma when they brought their children to routine appointments at local public clinics between May 16 and July 10, 2018. Participants electronically filled out validated Arabic versions of the Medication Adherence Reported Scale (MARS) and Beliefs About Medications Questionnaire (BMQ). Descriptive statistics were used to characterize the study participants, while hierarchical linear regression analysis assessed associations between parental beliefs about controller medications and medication adherence.

RESULTS: A total of 381 parents of children with asthma completed the study survey. The vast majority (89%) of study participants were non-adherent to their children’s prescribed medications while only 11% were adherent. Additionally, our study revealed a significantly positive association between adherence and parents’ beliefs in the necessity of the medication (p < .001), with concerns about the adverse effects of medication being negatively associated with parental adherence. A higher mean score for medication adherence was reported among the ambivalent groups compared to the accepting, indifferent, and skeptical groups.

CONCLUSIONS: Medication adherence among parents of children with asthma was relatively low. In addition, necessity beliefs were significantly associated with parental adherence to controller medications for their children with asthma. Further studies are warranted to investigate potential factors contributing to poor parental adherence and develop tailored interventions that support parental medication adherence for their asthmatic children.

PMID:37997759 | DOI:10.1080/02770903.2023.2288320

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Efficacy of tyrosine-kinase-2 and phosphodiesterase-4 inhibitors for scalp psoriasis: a systematic review and meta-analysis

Curr Med Res Opin. 2023 Nov 24:1-17. doi: 10.1080/03007995.2023.2288280. Online ahead of print.

ABSTRACT

OBJECTIVES: Psoriasis of the scalp is challenging to manage. The only approved oral tyrosine kinase 2 and phosphodiesterase 4 inhibitors for psoriasis are deucravacitinib and apremilast. The aim of this study was to explore their efficacy for scalp psoriasis utilizing data from randomized controlled trials.

METHODS: We searched Medline, Scopus, Web of Science, CENTRAL and ClinicalTrials.gov up to 4th of August 2023. To determine risk of bias, the revised Risk of Bias assessment tool 2.0 was used. Inverse variance random effects meta-analyses were executed. Heterogeneity was assessed utilizing Q and I2 statistics. Pre-determined outcomes included the proportion of participants with cleared scalp skin (Scalp Physician’s Global Assessment [ScPGA] of 0/1), mean change in Psoriasis Scalp Severity Index (PSSI), and mean improvement in Dermatology Life Quality Index (DLQI).

RESULTS: Ten RCTs fulfilled inclusion criteria. Both apremilast (RR 2.41, 95% CI 2.08 to 2.79, Tau2=0, I2=0) and deucravacitinib (RR 3.86, 95% CI 3.02 to 4.94, Tau2=0, I2=0) were more effective in inducing ScPGA of 0/1 at 16 weeks compared to placebo. Furthermore, deucravacitinib was more effective than apremilast (RR 1.70, 95% CI 1.44 to 2.00, Tau2=0, I2=0). An analysis could not be executed for the rest of the outcomes.

CONCLUSIONS: Apremilast and deucravacitinib are effective for scalp psoriasis. Deucravacitinib may be more efficient in clearing the scalp.

PMID:37997745 | DOI:10.1080/03007995.2023.2288280

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Nevin Manimala Statistics

Association between Dried Fruit Intake and DNA Methylation: A Multivariable Mendelian Randomization Analysis

J Nutr Health Aging. 2023;27(11):1132-1139. doi: 10.1007/s12603-023-2030-x.

ABSTRACT

OBJECTIVES: Observational studies have reported associations between dried fruit intake and DNA methylation(DNAm). However, inherent flaws in observational study designs make them susceptible to confounding and reverse causality bias. Consequently, it is unclear whether a causal association exists. In the present study, we aimed to investigate the causal associations between dried fruit intake and DNAm.

METHODS: We performed two-sample Mendelian randomization (MR) using the IEU Open GWAS database aggregated data. Forty-three single nucleotide polymorphisms (SNPs) associated with dried fruit intake as instrumental variables (IVs) were selected as exposure. DNAm outcomes include Gran (estimated granulocyte proportions); AgeAccelGrim(GrimAge acceleration); Hannum (Hannum age acceleration); IEAA(Intrinsic epigenetic age acceleration), AgeAccelPheno( PhenoAge acceleration), and DNAmPAIadjAge (DNAm-estimated plasminogen activator inhibitor-1 levels). We used the MR pleiotropy residual sum and outlier test (MRPRESSO) and Radial-MR test to identify any level of multi-effect outliers and assessed the causal effect estimates(after removing outliers). The primary causal effects were estimated using inverse-variance weighted (IVW) method and undertook sensitivity analyses using MR methods robust to horizontal pleiotropy.The direct effects of dried fruit intake on DNAm were estimated using multivariable mendelian randomization (MVMR).

RESULTS: Leveraging two-sample MR analysis, we observed statistically significant associations between dried fruit intake with a lower AgeAccelGrim(β=-1.365, 95% confidence intervals [CI] -2.266 to -0.464, PIVW=2.985×10-3) and AgeAccelPheno (β= -1.933, 95% CI -3.068 to -0.798, PIVW=8.371×10-4). By contrast, the effects level on Gran (β=0.008, PIVW=0.430), Hannum(β=-0.430, PIVW=0.357), IEAA(β=-0.184, PIVW=0.700), and DNAmPAIadjAge (β=-1.861, PIVW=0.093) were not statistically significant. MVMR results adjusting for the potential effects of confounders showed that the causal relationship between dried fruit intake and AgeAccelGrim(β= -1.315, 95% CI -2.373 to -0.258, PIVW=1.480×10-2) and AgeAccelPheno(β= -1.595, 95% CI -2.987 to -0.202, PIVW=2.483×10-2) persisted. No significant horizontal polymorphism was found in the sensitivity analysis.

CONCLUSION: Our MR study suggested that increased dried fruit intake is associated with slower AgeAccelGrim and AgeAccelPheno. It can providing a promising avenue for exploring the beneficial effects of dried fruit intake on lifespan extension.

PMID:37997736 | DOI:10.1007/s12603-023-2030-x

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Nevin Manimala Statistics

The Joint Effect of Body Mass Index and Serum Lipid Levels on Incident Dementia among Community-Dwelling Older Adults

J Nutr Health Aging. 2023;27(11):1118-1126. doi: 10.1007/s12603-023-2027-5.

ABSTRACT

OBJECTIVES: This study aimed to explore the joint effect of body mass index (BMI) and serum lipids levels on incident dementia.

METHODS: We prospectively followed up with 1,627 dementia-free community residents aged ≥60 for 5.7 years on average. At baseline, weight, and height were measured, and total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were detected in serum. Demographic characteristics were collected through questionnaires. Dementia was based on consensus diagnosis of neurologists and neuropsychologists using DSM-IV criteria. Additive Cox proportional model was used to assess the exposure-response relationship between BMI and serum lipid levels and dementia risk. Interactions and further classifications of BMI and serum lipid levels were further presented by bivariate surface models and decision-tree models.

RESULTS: The joint effects of TC with BMI, TG with BMI, and LDL-C with BMI on the risk of incident dementia shared a similar pattern, different from their independent exposure-response curves. The joint effect of HDL-C with BMI showed an S-surface but without statistical significance. Participants with TC<5.4 mmol/L and BMI<21 kg/m2 (Hazard Ratio(HR) 1.93, 95% Confidence Interval (CI) 1.05-3.53), TC<5.4 mmol/L and BMI≥21 kg/m2 (HR 1.73, 95% CI 1.09-2.72), and TC≥5.4 mmol/L and BMI<21 kg/m2 (HR 4.02, 95% CI 2.10-7.71) were identified to have the increased risk of incident dementia compared to those with TC≥5.4 mmol/L and BMI≥21 kg/m2. Participants with TG<1.7 mmol/L and BMI<21 kg/m2 had an increased risk of incident dementia compared to those with TG≥1.7 mmol/L and BMI≥21 kg/m2 (HR 1.98, 95%CI 1.17-3.3). Participants with LDL-C≥3.3 mmol/L and BMI<21 kg/m2 were identified to have an increased risk of incident dementia compared to those with LDL-C≥3.3 mmol/L and BMI≥21 kg/m2 (HR 3.33, 95%CI 1.64-6.78).

CONCLUSIONS: Our study showed that low BMI combined with low or high levels of serum lipids may increase the risk of dementia among older adults. This finding suggests the potential impacts of these two metabolic indexes on the risk of dementia.

PMID:37997734 | DOI:10.1007/s12603-023-2027-5

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Adherence to Healthy and Sustainable Dietary Patterns and Long-Term Chronic Inflammation: Data from the EPIC-Potsdam Cohort

J Nutr Health Aging. 2023;27(11):1109-1117. doi: 10.1007/s12603-023-2010-1.

ABSTRACT

OBJECTIVES: We explored the prospective associations between adherence to a priori chosen dietary patterns, including EAT-Lancet (EAT-L) and Mediterranean (tMDS) diet with long-term inflammatory responses in a German population sample.

DESIGN AND SETTING: Prospective cohort study.

PARTICIPANTS: A subsample of 636 predominantly healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study who were on average 51-years old at baseline.

MEASUREMENTS: Data was collected repeatedly between 1994/1998 – 2013. At baseline (1994/1998) and 6.8-years later (2001/2005), EAT-L and tMDS scores were derived from available food frequency questionnaires. Stable high, stable low, increasing, and decreasing adherence to EAT-L and tMDS were defined as scoring above/below baseline median at baseline and 6.8-years later. Long-term chronic inflammation was assessed based on the average values of repeated measurements of two inflammatory biomarkers – chemerin and high-sensitivity C-reactive protein (hs-CRP) – in plasma samples collected between 2010/2012 and 2013. Multivariable linear regression analysis adjusted for socio-demographic and lifestyle factors at baseline and in 2010/2012 was used to assess the association between diet adherence and long-term hs-CRP and chemerin concentrations.

RESULTS: Stable high or increasing adherence to EAT-L diet compared to stable low adherence was associated with slight reduction of long-term chemerin concentrations on the long run (stable high: -4.4%; increasing: -4.0%), not reaching statistical significance. Increasing adherence to tMDS compared to stable low adherence was also associated with a minor reduction in chemerin concentrations (-3.6%). Decreasing adherence to tMDS compared stable high adherence was associated with 2.7% higher chemerin. The associations were even less pronounced when hs-CRP was used as an outcome.

CONCLUSIONS: Adherence to healthy and sustainable dietary patterns defined using existing definitions for EAT-L and tMDS were associated with minor and not statistically significant reduction in the concentrations of inflammatory biomarkers on the long run. More research is needed to explore whether following these diets may represent a suitable approach for targeted prevention in the general population.

PMID:37997733 | DOI:10.1007/s12603-023-2010-1

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Nevin Manimala Statistics

Association between Reduction of Muscle Mass and Faster Declines in Global Cognition among Older People: A 4-Year Prospective Cohort Study

J Nutr Health Aging. 2023;27(11):932-939. doi: 10.1007/s12603-023-2007-9.

ABSTRACT

OBJECTIVES: A few studies reported that both decrease and increase in body mass index (BMI) were associated with the development of dementia in later life. However, it is unclear what changes in body composition are associated with cognitive decline. This study investigated the longitudinal influences of changes in body composition on cognitive function among community-dwelling adults.

DESIGN, SETTING AND PARTICIPANTS: This longitudinal study included older adults aged ≥60 years without cognitive impairment who participated in National Institute for Longevity Sciences – Longitudinal Study of Aging.

MEASUREMENTS: Cognitive function was assessed using the MMSE. Body composition was measured by a dual-energy X-ray absorptiometry system. Then, BMI, fat mass index (FMI), fat-free mass index (FFMI), and muscle mass index (MMI) were calculated. The changes in body composition over 6 years (second wave to fifth wave) were calculated, and three groups were created: decreased group, decrease of >5%; stable group, change within 5%, and increased group, increase of >5%. In statistical analysis, a linear mixed model was applied by sex to investigate the influences of body composition changes on cognitive function over 4 years (fifth wave to seventh wave).

RESULTS: This study analyzed 515 participants (mean age, 67.05 years; 53.4% men). Men with decreased group in FFMI and MMI exhibited faster declines in MMSE scores than those with stable group (β [95% CI]: FFMI, -0.293 [-0.719 to -0.020]; MMI, -0.472 [-0.884 to -0.059]). In women, there was no significant association between body composition changes and cognitive functions.

CONCLUSIONS: Decrease in fat-free mass and muscle mass is associated with faster cognitive declines in men. These results suggest the importance of continuous monitoring of muscle mass to prevent cognitive decline in later life.

PMID:37997712 | DOI:10.1007/s12603-023-2007-9

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Nevin Manimala Statistics

Raising the U.S. Army Height-Weight (Body Mass Index) Standards: Quantifying Metabolic Risk

Mil Med. 2023 Nov 23:usad450. doi: 10.1093/milmed/usad450. Online ahead of print.

ABSTRACT

BACKGROUND & OBJECTIVES: The U.S. Army fell 25% short of its recruitment goal in 2022 and therefore, increasing the eligibility pool for potential recruits is of interest. Raising the body mass index (BMI) standards for eligibility presents a path to increase the recruitable population; however, there may be additional costs incurred due to attendant health risks that may be present in individuals with higher BMI.

METHODS: We filtered the 2017-2020 National Health and Nutrition Examination Survey by age (17-25 years) and BMI (up to 30 kg/m2). A k-means cluster analysis was performed on the filtered dataset for the variables used to determine metabolic syndrome. Metabolic syndrome Clusters were characterized through summary statistics and compared over clinical measurements and questionnaire responses.

RESULTS: Five distinct clusters were identified and mean BMI in two clusters (Clusters1 and 3) exceeded the current U.S. Army BMI thresholds. Of these two clusters, Cluster 1 members had metabolic syndrome. Cluster 3 members were at higher risk for metabolic syndrome compared to members of Clusters 2, 4, and 5. Mean waist circumference was slightly lower in Cluster 3 compared to Cluster 1. None of the clusters had significant differences in depression scores, poverty index, or frequency of dental visits.

CONCLUSIONS: Potential recruits from Cluster 1 have excessive health risk and may incur substantial cost to the U.S. Army if enlisted. However, potential recruits from Cluster 3 appear to add little risk and offer an opportunity to increase the pool for recruiting.

PMID:37997687 | DOI:10.1093/milmed/usad450

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Comparing fracture resistance on bovine incisors restored by tooth fragment reattachment versus direct composite restoration techniques

Dent Traumatol. 2023 Nov 24. doi: 10.1111/edt.12909. Online ahead of print.

ABSTRACT

BACKGROUND/AIM: Anterior teeth are prone to traumatic dental injuries (TDIs). Although a number of techniques ranging from original tooth fragment reattachment (TFR) to direct composite restoration (DCR) can be used to restore uncomplicated crown fractures, there is no consensus on which method is best. The purpose of this study was to investigate the fracture resistance of bovine incisors restored by two different techniques (TFR and DCR) in three different fracture models.

MATERIALS AND METHODS: Sixty extracted bovine lower incisors were randomly divided into three groups (n = 20). Angle, oblique, or transverse sections of all the teeth in a group were prepared by using a disk. The cut surfaces were scanned, and the cross-sectional areas (CSA) of the enamel and dentin were measured. Half the teeth in each group were restored by DCR (n = 10) and the other half by TFR (n = 10). The forces required to fracture the restored teeth were then measured using a Universal testing machine, and the fracture modes were analyzed (cohesive, adhesive, or mixed).

RESULTS: No statistically significant differences between the TFR and DCR restorations were detected for total and enamel CSAs in any of the restoration shapes (p > .067). The fracture forces required to break DCT angle and transverse restorations were significantly greater than for the corresponding shapes restored with TFR (p < .033). However, the difference in the forces needed to fracture oblique section restorations by DCR or TFR was not statistically significant (p = .239), despite a similar trend (143.4 ± 51 N and 120.9 ± 25 N, respectively).

CONCLUSION: This study revealed that a greater force is required to fracture teeth restored by the DCT than by the TFR technique, especially for a transverse section. This demonstrates that restoring a fractured tooth provides a superior outcome compared to reattaching the fractured fragment.

PMID:37997669 | DOI:10.1111/edt.12909