Tag: pubmed

High-resolution population-specific recombination rates and their effect on phasing and genotype imputation.

Eur J Hum Genet. 2020 Nov 28;:

Authors: Hassan S, Surakka I, Taskinen MR, Salomaa V, Palotie A, Wessman M, Tukiainen T, Pirinen M, Palta P, Ripatti S

Abstract
Previous research has shown that using population-specific reference panels has a significant effect on downstream population genomic analyses like haplotype phasing, genotype imputation, and association, especially in the context of population isolates. Here, we developed a high-resolution recombination rate mapping at 10 and 50 kb scale using high-coverage (20-30×) whole-genome sequenced data of 55 family trios from Finland and compared it to recombination rates of non-Finnish Europeans (NFE). We tested the downstream effects of the population-specific recombination rates in statistical phasing and genotype imputation in Finns as compared to the same analyses performed by using the NFE-based recombination rates. We found that Finnish recombination rates have a moderately high correlation (Spearman’s ρ = 0.67-0.79) with NFE, although on average (across all autosomal chromosomes), Finnish rates (2.268 ± 0.4209 cM/Mb) are 12-14% lower than NFE (2.641 ± 0.5032 cM/Mb). Finnish recombination map was found to have no significant effect in haplotype phasing accuracy (switch error rates ~2%) and average imputation concordance rates (97-98% for common, 92-96% for low frequency and 78-90% for rare variants). Our results suggest that haplotype phasing and genotype imputation mostly depend on population-specific contexts like appropriate reference panels and their sample size, but not on population-specific recombination maps. Even though recombination rate estimates had some differences between the Finnish and NFE populations, haplotyping and imputation had not been noticeably affected by the recombination map used. Therefore, the currently available HapMap recombination maps seem robust for population-specific phasing and imputation pipelines, even in the context of relatively isolated populations like Finland.

PMID: 33249422 [PubMed – as supplied by publisher]

Impact of preconception, pregnancy, and postpartum culinary nutrition education interventions: a systematic review.

Nutr Rev. 2020 Nov 29;:

Authors: Taylor RM, Wolfson JA, Lavelle F, Dean M, Frawley J, Hutchesson MJ, Collins CE, Shrewsbury VA

Abstract
CONTEXT: Frequent consumption of home-prepared meals is associated with higher diet quality in children and adults. Therefore, increasing the culinary skills of women and couples during their childbearing years may be an effective strategy for the prevention of overweight and obesity.
OBJECTIVE: To determine the impact of culinary nutrition-education interventions for women with or without their partners during preconception, pregnancy, or postpartum (PPP) on parental cooking skills, nutrition knowledge, parent/child diet quality, or health outcomes.
DATA SOURCES: Eligibility criteria were defined using a PICOS framework. A systematic search strategy was developed to identify eligible studies and was implemented in 11 electronic databases. Reference lists of selected systematic reviews were manually searched for additional studies.
DATA EXTRACTION: Study characteristics and outcomes were extracted from eligible studies by 1 reviewer and checked by a second reviewer.
DATA ANALYSIS: A narrative synthesis of the findings of eligible studies was prepared including descriptive statistics. Reporting was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and Synthesis Without Meta-Analysis in systematic reviews reporting guideline.
RESULTS: A total of 6951 articles were identified from the search strategy and 31 studies during pregnancy or postpartum were included. By category, the number of studies with a favorable outcome per total number of studies measuring outcome were as follows: parental food/cooking skills (n = 5 of 5), nutrition knowledge (n = 6 of 11), parent/child diet quality (n = 10 of 19), infant feeding (n = 6 of 11), eating behavior (n = 2 of 5), maternal (n = 2 of 5) and child anthropometry (n = 6 of 10), mental health and development n = (2 of 3), and clinical indictors (n = 1 of 1).
CONCLUSIONS: Culinary nutrition-education interventions during pregnancy and the postpartum period show promise in improving cooking skills, diet quality, and a variety of health-related outcomes. The precise effect of these interventions during PPP is limited by the quality and heterogeneity of study designs to date.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42020154966.

PMID: 33249446 [PubMed – as supplied by publisher]

Onyx versus coil embolization for the treatment of type II endoleaks.

J Vasc Surg. 2020 Nov 26;:

Authors: Scallan O, Kribs S, Power AH, DeRose G, Duncan A, Dubois L

Abstract
OBJECTIVE: There is little evidence supporting the optimal treatment of type II endoleaks associated with aortic sac growth. Previous studies have lacked comparisons between treatment methods and long-term follow-up. The purpose of this study was to review our center’s experience with the treatment of type II endoleaks comparing Onyx (a liquid embolization agent consisting of ethylene vinyl alcohol) embolization with coil embolization.
METHODS: A retrospective review of a prospectively collected vascular surgery database was performed to identify all patients who underwent embolization of a type II endoleak for aortic sac growth after EVAR between 2005 and 2018. Onyx and coil embolization groups were compared using univariate statistics.
RESULTS: In total, 58 patients underwent 77 embolizations for type II endoleaks with either Onyx (27 patients, 37 procedures) or coils (31 patients, 40 procedures). The average aneurysm size at the time of embolization was larger in the Onyx group (77.9mm±15.1) compared to coil embolization (73.4mm±11.9). Mean follow-up was 57 months in the Onyx group and 74 months in the coil embolization group. Among the 27 patients undergoing Onyx embolization, two patients (7.4%) required graft explantation compared to five patients (16.1%) among the 31 patients undergoing coil embolization (p=.33). Based on per-patient analysis, the coil embolization group had a significantly higher rate of need for further reinterventions compared to the Onyx group (55% vs 19%, p<.01). Clinical success was observed in 13 (48%) of the Onyx embolization group compared to 10 (32%) of the coil embolization group (p=0.04). Two patients in each group presented with secondary rupture of the aneurysm sac following attempted embolization.
CONCLUSIONS: Type II endoleaks associated with sac growth treated with Onyx are less likely to require further reinterventions than with coil embolization, and there is a trend towards greater need for EVAR explant following coil embolization. With a high rate of further reintervention and potential for sac rupture, diligent follow-up is required after attempted type II embolization regardless of technique.

PMID: 33249208 [PubMed – as supplied by publisher]

The prognostic value of the tumor-stroma ratio in squamous cell lung cancer, a cohort study.

Cancer Treat Res Commun. 2020 Nov 21;25:100247

Authors: Smit MA, Philipsen MW, Postmus PE, Putter H, Tollenaar RA, Cohen D, Mesker WE

Abstract
OBJECTIVES: The tumor-stroma ratio (TSR) is based on the relative amount of stroma in the primary tumor and has proven to be an independent prognostic factor in various solid tumors. The prognosis of patients and adjuvant treatment decision making in lung squamous cell carcinomas (SqCC) is based on the TNM classification. Currently, no other prognostic biomarkers are available. In this study we evaluated the prognostic value of the TSR in lung SqCC.
MATERIAL AND METHODS: Patients undergoing lung surgery because of lung SqCC between 2000 and 2018 at the Leiden University Medical Center were included. The TSR was scored on hematoxylin & eosin stained tissue sections. Based on the amount of tumor-stroma, two groups were defined: ≤50% was classified as a stroma-low tumor and >50% as stroma-high. The prognostic value of the TSR was determined with survival analysis.
RESULTS: A total of 174 stage I-III patients were included. Of them, 79 (45%) were stroma-low and 95 (55%) stroma-high. Separately analyzed for tumor stages, the TSR showed to be an independent prognostic biomarker in stage II (n = 68) for 5-year overall survival (HR=3.0; 95% CI, 1.1-8.6; p = 0.035) and 5-year disease free survival (DFS) (HR=3.6; 95% CI, 1.3-9.9; p = 0.014). Patients with a stroma-high tumor had a worse 5-year DFS in the whole cohort (HR 1.6; 95% CI, 1.0-2.4; p = 0.048), but no independent prognostic value was found.
CONCLUSION: In stage II lung SqCC patients, stroma-low tumors have a better prognosis compared to stroma-high tumors. Moreover, adjuvant chemotherapy could be spared for these stroma-low patients.

PMID: 33249210 [PubMed – as supplied by publisher]

Grain analysis of atomic force microscopy images via persistent homology.

Ultramicroscopy. 2020 Nov 21;220:113176

Authors: Duman AN

Abstract
Atomic force microscopy (AFM) is an established technique in nanoscale grain analysis due to its accuracy in producing 3-dimensional images. Even though height threshold and watershed algorithms are commonly used to determine the grain size and number of grains, they mostly require image processing that result in the change of topographical features of the surface that generates misleading conclusions. In this study, we use persistent homology, a method of representing topological features, to obtain more accurate information about the granular surfaces from unprocessed AFM images than the conventional methods. The method is also useful as a robust alternative to common parameters describing the topography of the AFM images. Most of these parameters such as arithmetic roughness and root-mean-squared roughness are represented by a single number which results in uncertainty in characterization of different surfaces. Persistent homology provides more precise summary about surface properties than a single parameter.

PMID: 33249346 [PubMed – as supplied by publisher]

Predictors of treatment decisions made by adult orthodontic patients presenting with unerupted permanent teeth.

Int Orthod. 2020 Nov 25;:

Authors: Liu C, Wong L, Hameed O, Pandis N, Seehra J

Abstract
OBJECTIVE: Unerupted permanent teeth are amongst the most commonly occurring dental anomalies in adults and present unique treatment challenges. The aim of this retrospective study was to (1) identify the prevalence of adult patients with unerupted teeth attending a multidisciplinary clinic and (2) to identify predictors (age, gender, incisor and skeletal classification) which influence the patients treatment decision.
MATERIAL AND METHODS: Consecutive adult patients with unerupted permanent teeth attending the Joint Orthodontic-Restorative clinic were identified. Study variables were collected using a prespecified data collection form. Descriptive statistics were employed; Fisher’s exact test was used to detect associations between variables and treatment decision outcome. Ordinal logistic regression derived multinomial regression relative risk ratios (RRR) and 95% confidence intervals (CI) were calculated for the effect of age, gender, incisor and skeletal classification on treatment decision/outcome.
RESULTS: Sixty-six patients with impacted teeth were identified from a sample of 483. The prevalence of adults with unerupted teeth was 13.7%. The mean age was 30.7 years (SD 11.2). The majority of the sample had a Class I incisor relationship (54.6%) or Class I skeletal base relationship (54.6%), and the most common distribution of impacted teeth was a single unerupted upper right canine (34.9%). Orthodontic treatment (non-extraction or extraction basis incorporating the alignment or removal of impacted teeth) and restorative treatment only were equally favoured. Factors including age, gender, incisor and skeletal classification did not appear to influence or predict the final treatment decision.
CONCLUSIONS: In this sample, adults presenting with impacted teeth favoured certain treatment modalities: orthodontic treatment only and restorative treatment only. Factors such as age, gender, incisor and skeletal classification did not influence the outcome.

PMID: 33248909 [PubMed – as supplied by publisher]

Randomized Trial of Scrambler Therapy for Chemotherapy-Induced Peripheral Neuropathy: Crossover Analysis.

J Pain Symptom Manage. 2020 Nov 26;:

Authors: Childs DS, Le-Rademacher JG, McMurray R, Bendel M, O’Neill C, Smith TJ, Loprinzi CL

Abstract
BACKGROUND: Preliminary trials report that Scrambler Therapy, a form of electroanalgesia, may improve discomfort from chemotherapy-induced peripheral neuropathy (CIPN). The objective of this phase II, randomized controlled trial was to evaluate the efficacy of Scrambler Therapy versus Transcutaneous Electrical Nerve Stimulation (TENS) in treating CIPN.
METHODS: Fifty patients were accrued for the first half of this two-part, crossover trial consisting of a 2-week treatment period with either Scrambler or TENS, followed by an 8-week observation period, and then crossover treatment. Twenty-two patients proceeded to the crossover phase. The primary means of assessment was patient reported outcomes, including symptom severity scales and Global Impression of Change questionnaires. Symptoms were assessed daily during the treatment period and weekly during an 8-week observation period.
RESULTS: A 50% or greater reduction in primary symptom (pain or tingling) score on the last day of treatment was achieved by 6 of 10 Scrambler-treated patients (60%) and 3 of 12 TENS-treated patients (25%) following crossover (p=0.11). By day 4 of treatment, the two arms diverged with respect to mean change in primary symptom score; this effect was largely carried through to the end of the two-week treatment period. Similarly, Scrambler Therapy appeared better than TENS when assessed by Global Impression of Change for neuropathy, pain, and overall quality of life.
CONCLUSIONS: Similar findings from the initial randomization and crossover phases of this study support further evaluation of the efficacy of Scrambler Therapy in alleviating CIPN symptoms. Evaluation in a larger, randomized controlled trial with standardized treatment is warranted.

PMID: 33249081 [PubMed – as supplied by publisher]

An integrated metagenomics and metabolomics approach implicates the microbiota-gut-brain axis in the pathogenesis of Huntington’s disease.

Neurobiol Dis. 2020 Nov 26;:105199

Authors: Kong G, Ellul S, Narayana VK, Kanojia K, Ha HTT, Li S, Renoir T, Cao KL, Hannan AJ

Abstract
BACKGROUND: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder with onset and severity of symptoms influenced by various environmental factors. Recent discoveries have highlighted the importance of the gastrointestinal microbiome in mediating the gut-brain-axis bidirectional communication via circulating factors. Using shotgun sequencing, we investigated the gut microbiome composition in the R6/1 transgenic mouse model of HD from 4 to 12 weeks of age (early adolescent through to adult stages). Targeted metabolomics was also performed on the blood plasma of these mice (n = 9 per group) at 12 weeks of age to investigate potential effects of gut dysbiosis on the plasma metabolome profile.
RESULTS: Modelled time profiles of each species, KEGG Orthologs and bacterial genes, revealed heightened volatility in the R6/1 mice, indicating potential early effects of HD mutation in the gut. In addition to gut dysbiosis in R6/1 mice at 12 weeks of age, gut microbiome function was perturbed. In particular, the butanoate metabolism pathway was elevated, suggesting increased production of the protective SCFA, butyrate, in the gut. No significant alterations were found in the plasma butyrate and propionate levels in the R6/1 mice at 12 weeks of age. The statistical integration of the metagenomics and metabolomics unraveled several Bacteroides species that were negatively correlated with ATP and pipecolic acid in the plasma.
CONCLUSIONS: The present study revealed the instability of the HD gut microbiome during the pre-motor symptomatic stage of the disease which may have dire consequences on the host’s health. Perturbation of the HD gut microbiome function prior to significant cognitive and motor dysfunction suggest the potential role of the gut in modulating the pathogenesis of HD, potentially via specific altered plasma metabolites which mediate gut-brain signaling.

PMID: 33249136 [PubMed – as supplied by publisher]

A non-invasive tool for early detection of acute leukemia in children using a paper-based optoelectronic nose based on an array of metallic nanoparticles.

Anal Chim Acta. 2021 Jan 02;1141:28-35

Authors: Bordbar MM, Barzegar H, Tashkhourian J, Bordbar M, Hemmateenejad B

Abstract
Volatile organic compounds (VOCs) in blood samples can be used as useful biomarkers to diagnose various human diseases. This study describes the potential of a paper-based sensor array for detecting leukemia using blood VOCs. Blood samples were collected from 59 new leukemia cases and 47 healthy cases as a control group. Each blood sample was divided into two parts; one for a laboratory test and the other was used in our study. Samples were mixed with heparin and then transferred to a sterile container, and a sensor was stacked on its cap. This sensor array contains 16 nanoparticles deposited on a sheet of hydrophobic paper in a 4 × 4 array format. Containers were stored in an oven at 60 °C for 4.5 h. Then, the image of sensors was recorded by a scanner and compared to the image before exposing the blood vapor. The sensor responses were subjected to different multivariate statistical methods to develop models that discriminate between control and leukemia samples. The interaction of nanoparticles with the volatile metabolome of blood caused aggregation and consequently changing in the color of nanoparticles. The color changes resulted in a specific pattern for blood samples with leukemia, which is different from those obtained from healthy specimens. The discrimination analysis was approved by pattern recognition methods such as principal component analysis with 97% accuracy. Among 59 patients, the mean age was 6.02 ± 4.55 years (range 1-16 y). The mean total response was 652.83 ± 117.02. The rock curve showed an accuracy of 96% for classifying patients from the control group. The logistic regression model showed that 93.6% of healthy and 93.2% of patients were classified correctly by using this method. These statistics agree with the classification results obtained by principal component analysis. For every 5000-unit increase in platelet count, the chance of leukemia decreased by 9%. Additionally, the chance of being categorized as a patient decreased by 10% for every 20-unit increase in total response. The electronic nose using VOC’s of blood is a non-invasive and inexpensive tool for detecting new cases of leukemia with high sensitivity and specificity. Platelet count is an essential para-clinical parameter determining the total response of the sensors. Follow up studies with a larger sample size are warranted to elucidate its clinical applicability.

PMID: 33248659 [PubMed – as supplied by publisher]

Prospectively Assigned AAST Grade versus Modified Hinchey Class and Acute Diverticulitis Outcomes.

J Surg Res. 2020 Nov 25;:

Authors: Choi J, Bessoff K, Bromley-Dulfano R, Li Z, Gupta A, Taylor K, Wadhwa H, Seltzer R, Spain DA, Knowlton LM

Abstract
BACKGROUND: The American Association for the Surgery of Trauma (AAST) recently developed a classification system to standardize outcomes analyses for several emergency general surgery conditions. To highlight this system’s full potential, we conducted a study integrating prospective AAST grade assignment within the electronic medical record.
METHODS: Our institution integrated AAST grade assignment into our clinical workflow in July 2018. Patients with acute diverticulitis were prospectively assigned AAST grades and modified Hinchey classes at the time of surgical consultation. Support vector machine-a machine learning algorithm attuned for small sample sizes-was used to compare the associations between the two classification systems and decision to operate and incidence of complications.
RESULTS: 67 patients were included (median age of 62 y, 40% male) for analysis. The decision for operative management, hospital length of stay, intensive care unit admission, and intensive care unit length of stay were associated with both increasing AAST grade and increasing modified Hinchey class (all P < 0.001). AAST grade additionally showed a correlation with complication severity (P = 0.02). Compared with modified Hinchey class, AAST grade better predicted decision to operate (88.2% versus 82.4%).
CONCLUSIONS: This study showed the feasibility of electronic medical record integration to support the full potential of AAST classification system’s utility as a clinical decision-making tool. Prospectively assigned AAST grade may be an accurate and pragmatic method to find associations with outcomes, yet validation requires further study.

PMID: 33248670 [PubMed – as supplied by publisher]