Category: Statistics

J Biol Inorg Chem. 2022 Oct 8. doi: 10.1007/s00775-022-01966-z. Online ahead of print.

ABSTRACT

LPMOs are enzymes which catalyse the oxidation of a C-H bond within polysaccharides, leading to their oxidative cleavage. To achieve this, LPMOs employ highly reactive oxidising intermediates, the generation of which is likely coupled to substrate binding to the enzyme. The nature of this coupling is unknown. Here we report a statistical comparison for four three-dimensional structures of an AA9 LPMO crystallised in the same space group but in different oxidation and substrate-binding states, to determine which significant structural perturbations occur at the enzyme upon either oxidation state change or the binding of substrate. In a novel step, we determine the global random error associated with the positional coordinates of atoms using the method of moments to ascertain the statistical estimators of Gaussian distributions of pairwise RMS differences between individual atoms in different structures. The results show that a change in the oxidation state of the copper leads to no significant structural changes, and that binding of the substrate leads to a single change in the conformation of a tryptophan residue. This tryptophan has previously been identified as part of a charge transfer pathway between the active site and the external surface of the protein, and the structural change identified herein may be part of the substrate-enzyme coupling mechanism.

PMID:36208326 | DOI:10.1007/s00775-022-01966-z

Pediatr Surg Int. 2022 Oct 8. doi: 10.1007/s00383-022-05257-1. Online ahead of print.

ABSTRACT

PURPOSE: Preterm infants are more susceptible to necrotizing enterocolitis (NEC) than term Queryinfants. This may be due to a relative paucity of Lgr5⁺ or Bmi1⁺-expressing intestinal stem cells (ISCs) which are responsible for promoting intestinal recovery after injury. We hypothesized that the cellular markers of Lgr5⁺ and Bmi1⁺, which represent the two distinct ISC populations, would be lower in younger mice compared to older mice. In addition, we hypothesized that experimental NEC would result in a greater loss of Lgr5⁺ expression compared to Bmi1⁺ expression.

METHODS: Transgenic mice with EGFP-labeled Lgr5 underwent euthanasia at 10 different time points from E15 to P56 (n = 8-11/group). Lgr5⁺-expressing ISCs were quantified by GFP ELISA and Bmi1⁺ was assessed by qPCR. In addition, Lgr5^EGFP mice underwent experimental NEC via formula feeding and hypoxic and hypothermic stress. Additional portions of the intestine underwent immunostaining with anti-GFP or anti-Bmi1⁺ antibodies to confirm ELISA and PCR results. For statistical analysis, p < 0.05 was significant.

RESULTS: Lgr5⁺ and Bmi1⁺expression was lowest in embryonal and early postnatal mice and increased with age in all segments of the intestine. Experimental NEC was associated with loss of Lgr5⁺-expressing ISCs but no significant change in Bmi1⁺ expression.

CONCLUSION: Lgr5⁺ and Bmi1⁺ expression increase with age. Lgr5⁺-expressing ISCs are lower following experimental necrotizing enterocolitis while Bmi1⁺ expression remains relatively unchanged. Developing a targeted medical therapy to protect the low population of ISCs in preterm infants may promote tissue recovery and regeneration after injury from NEC.

PMID:36208323 | DOI:10.1007/s00383-022-05257-1

Eur Spine J. 2022 Oct 8. doi: 10.1007/s00586-022-07415-4. Online ahead of print.

ABSTRACT

PURPOSE: Lumbosacral transitional vertebra (LSTV) is a congenital anomaly of the lumbosacral junction. Its prevalence is variable in the literature such as its association with low back pain. The aim of this study was to identify the prevalence of LSTV in a southern European population, and its correlation with low back pain.

METHODS: A retrospective review of 639 thoraco-abdomino-pelvic consecutive CT-scans between January 2019 and November 2020 was performed. The presence of LSTV was classified into type II, III, IV based on Castellvi’s classification. To investigate the association with low back pain, Oswestry Low Back Disability Questionnaire (ODI) and the EuroQol-5D-3L questionnaire was applied.

RESULTS: The prevalence of LSTV was 24.9% (142 of 571). 37,3% were type IIb, 31,0% were type IIa, 13,4% were type IIIa, 9.9% were type IIIb and 8.5% were type IV. Individuals with LSTV were more likely to report low back pain and have a higher ODI score (OR:0.392, 95% CI:0.192-0.802, p = 0.010), (OR: 1050, 95% CI: 1029-1072, p < 0.01). Castellvi’s type IV showed a significantly higher ODI when compared to type II (OR:1059, 95% CI:1019-1100, p = 0,04). There was no statistical difference in the EuroQol-5D-3L score between two groups (OR:1085, 95% CI: 0.459-2.560, p = 0.852).

CONCLUSION: This population-based study adds to the literature the prevalence of LSTV in a southern European population. LSTV was associated with low back pain. However, this difference did not translate into a loss of quality life. Type IV was associated with higher functional disability when compared with type II.

PMID:36208322 | DOI:10.1007/s00586-022-07415-4

Mil Med. 2022 Oct 8:usac285. doi: 10.1093/milmed/usac285. Online ahead of print.

ABSTRACT

INTRODUCTION: U.S. Navy service members are primarily between the ages of 18 and 30 years and often required to be outside for extended periods of time in geographical locations with increased and often unfamiliar ultraviolet indexes that collectively increase their risk for skin cancer. Skin cancer is the country’s most common form of cancer, yet there is a paucity of skin cancer prevention literature, especially within the U.S. Navy. The purpose of this study was to describe skin cancer risk and skin cancer prevention “cues-to-action” and to determine if skin cancer prevention knowledge was associated with sun-protective attitudes (e.g., prevention perceptions, benefits, threats, barriers, and sun-protective behavior self-efficacy) and sun-protective behaviors (e.g., wearing long sleeve shirts and using sunscreen and not deliberately exposing skin for a tan) in a Navy population.

MATERIALS AND METHODS: A cross-sectional, descriptive, correlational design was utilized, and the study approval was obtained by the Naval Medical Center Portsmouth Institutional Review Board. Two-hundred twenty-nine active duty Navy service members aged 18-30 years who presented to primary care for their periodic health assessment completed the Brief Skin Cancer Risk Assessment and the Skin Cancer Survey. Descriptive statistics were utilized to assess service members’ perceptions and knowledge regarding skin cancer prevention along with sociodemographic characteristics. The Spearman rank-order correlation and the Mann-Whitney U test were used to assess associations. P-values <.05 were used to determine statistical significance.

RESULTS: Skin cancer prevention knowledge was significantly related to sun-protective behavior self-efficacy (r = 0.218, P = .001), benefits (r = 0.271, P ≤ .001), sun protection behaviors (r = 0.152, P = .024), skin cancer risk (r = 0.256, P = .001), current frequency of high-risk sun behavior (r = 0.183, P = .006), past frequency of high-risk sun behavior (r = 0.219, P = .001), sun exposure (U = 4,813.50, P = .005), tanning bed use (U = 3,154.50, P = .031), and training (U = 4,099.50, P = .005).

CONCLUSIONS: Integrating skin cancer education into primary care visits (i.e., periodic health assessments) may improve Navy service members’ modifiable sun-protective attitudes and behaviors and may contribute to lowering future skin cancer rates.

PMID:36208319 | DOI:10.1093/milmed/usac285

Mil Med. 2022 Oct 8:usac291. doi: 10.1093/milmed/usac291. Online ahead of print.

ABSTRACT

INTRODUCTION: This study was a preliminary evaluation of a manualized, brief mindfulness-based intervention (MB-SI) for veterans with suicidal ideation (SI), admitted into an inpatient psychiatric unit (IPU).

MATERIALS AND METHODS: A randomized, controlled pilot study of 20 veterans aged 18-70 years with SI, admitted into a psychiatric unit, assigned to treatment as usual (TAU) or MB-SI groups. Outcome data were collected at three time points: preintervention (beginning of first session), postintervention (end of last session), and 1-month postintervention. Primary outcomes were safety and feasibility. Secondary outcome measures were SI and behavior, mindfulness state and trait, cognitive reappraisal, and emotion regulation. Additionally, psychiatric and emergency department admissions were examined. Data analysis included Generalized Linear Models, Wilcoxon Signed-Rank, Mann-Whitney U, and Fisher’s exact tests for secondary outcomes.

RESULTS: Mindfulness-based intervention for suicidal ideation was feasible to implement on an IPU, and there were no associated adverse effects. Mindfulness-based intervention for suicidal ideation participants experienced statistically significant increase in Toronto Mindfulness Scale curiosity scores 1-month postintervention compared to preintervention and greater Toronto Mindfulness Scale decentering scores 1-month postintervention compared to TAU. Emotion Regulation Questionnaire Reappraisal scores significantly increased for the MB-SI group and significantly decreased for TAU over time. IPU and emergency department admissions were not statistically different between groups or over time. Both TAU and MB-SI participants experienced a significant reduction in Columbia-Suicide Severity Rating Scale-SI scores after the intervention. MB-SI participants experienced a higher increase in Five-Facet Mindfulness Questionnaire scores postintervention compared to TAU.

CONCLUSIONS: Mindfulness-based intervention for suicidal ideation is feasible and safe to implement among veterans during an inpatient psychiatric admission with SI, as it is not associated with increased SI or adverse effects. Preliminary evidence suggests that MB-SI increases veterans’ propensity to view experiences with curiosity while disengaging from experience without emotional overreaction. Further, more rigorous research is warranted to determine efficacy of MB-SI.

TRIAL REGISTRATION: The clinicaltrials.gov registration number is NCT04099173 and dates are July 16, 2019 (initial release) and February 24, 2022 (most recent update).

PMID:36208303 | DOI:10.1093/milmed/usac291

Genome Biol Evol. 2022 Oct 8:evac142. doi: 10.1093/gbe/evac142. Online ahead of print.

ABSTRACT

Trypanosomatids belong to a remarkable group of unicellular, parasitic organisms of the order Kinetoplastida, an early diverging branch of the phylogenetic tree of eukaryotes, exhibiting intriguing biological characteristics affecting gene expression (intronless polycistronic transcription, trans-splicing, and RNA editing), metabolism, surface molecules, and organelles (compartmentalization of glycolysis, variation of the surface molecules, and unique mitochondrial DNA), cell biology and life cycle (phagocytic vacuoles evasion, and intricate patterns of cell morphogenesis). With numerous genomic-scale data of several trypanosomatids becoming available since 2005 (genomes, transcriptomes, and proteomes), the scientific community can further investigate the mechanisms underlying these unusual features and address other unexplored phenomena possibly revealing biological aspects of the early evolution of eukaryotes. One fundamental aspect comprises the processes and mechanisms involved in the acquisition and loss of genes throughout the evolutionary history of these primitive microorganisms. Here, we present a comprehensive in silico analysis of pseudogenes in three major representatives of this group: Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi. Pseudogenes, DNA segments originating from altered genes that lost their original function, are genomic relics that can offer an essential record of the evolutionary history of functional genes, as well as clues about the dynamics and evolution of hosting genomes. Scanning these genomes with functional proteins as proxies to reveal intergenic regions with protein-coding features, relying on a customized threshold to distinguish statistically and biologically significant sequence similarities, and reassembling remnant sequences from their debris, we found thousands of pseudogenes and hundreds of open reading frames (ORFs), with particular characteristics in each trypanosomatid: mutation profile, number, content, density, codon bias, average size, single- or multi-copy gene origin, number and type of mutations, putative primitive function, and transcriptional activity. These features suggest a common process of pseudogene formation, different patterns of pseudogene evolution and extant biological functions, and/or distinct genome organization undertaken by those parasites during evolution, as well as different evolutionary and/or selective pressures acting on distinct lineages.

PMID:36208292 | DOI:10.1093/gbe/evac142

DNA Res. 2022 Oct 8:dsac033. doi: 10.1093/dnares/dsac033. Online ahead of print.

ABSTRACT

A contiguous assembly of the inbred ‘EL10’ sugar beet (Beta vulgaris ssp. vulgaris) genome was constructed using PacBio long read sequencing, BioNano optical mapping, Hi-C scaffolding, and Illumina short read error correction. The EL10.1 assembly was 540 Mb, of which 96.7% was contained in nine chromosome-sized pseudomolecules with lengths from 52 to 65 Mb, and 31 contigs with a median size of 282 kb that remained unassembled. Gene annotation incorporating RNAseq data and curated sequences via the MAKER annotation pipeline generated 24,255 gene models. Results indicated that the EL10.1 genome assembly is a contiguous genome assembly highly congruent with the published sugar beet reference genome. Gross duplicate gene analyses of EL10.1 revealed little large-scale intra-genome duplication. Reduced gene copy number for well-annotated gene families relative to other core eudicots was observed, especially for transcription factors. Variation in genome size in B. vulgaris was investigated by flow cytometry among 50 individuals producing estimates from 633 to 875 Mb/1C. Read depth mapping with short-read whole genome sequences from other sugar beet germplasm suggested that relatively few regions of the sugar beet genome appeared associated with high-copy number variation.

PMID:36208288 | DOI:10.1093/dnares/dsac033

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Oct;30(5):1567-1571. doi: 10.19746/j.cnki.issn.1009-2137.2022.05.041.

ABSTRACT

OBJECTIVE: To observe the efficacy of plasma exchange in the treatment of patients with immune thrombocytopenic purpura (ITP), and to analyze the factors influencing the efficacy of plasma exchange in the treatment of ITP.

METHODS: The medical records of 39 ITP patients who were treated effectively by plasma exchange in Huai’an First People’s Hospital from January 2013 to January 2021 were retrospectively analyzed, and they were set as the effective group. In addition, the medical records of 39 ITP patients who were treated ineffective by plasma exchange during the same period in our hospital were collected, and they were set as the ineffective group. The general data such as sex and age of patients and laboratory indicators on admission were collected and recorded. The possible influencing factors were included, and Logistic regression analysis was used to examine the influencing factors of efficacy of plasma exchange in the treatment of ITP.

RESULTS: The serum levels of IL-6, IL-18 and B lymphocyte activating factor (BAFF) on admission in the ineffective group were significantly higher than those in the effective group, and the proportions of Helicobacter pylori (HP) infection and splenomegaly were significantly higher than those in the effective group (P<0.05). There was no statistical significantly difference in sex, age and other data between the two groups (P>0.05). After single factor analysis, multiple regression model was established, which showed that splenomegaly, HP infection and the over expression of serum IL-6, IL-18 and BAFF on admission might be the influencing factors of ineffective treatment of ITP by plasma exchange (OR>1, P<0.05).

CONCLUSION: The over expression of serum IL-6, IL-18, BAFF, splenomegaly and HP infection on admission may be the influencing factors resulting in the ineffective treatment of plasma exchange in ITP.

PMID:36208267 | DOI:10.19746/j.cnki.issn.1009-2137.2022.05.041

Lasers Surg Med. 2022 Oct 8. doi: 10.1002/lsm.23611. Online ahead of print.

ABSTRACT

OBJECTIVES: The skin aging exposome encompasses internal and external factors that contribute to clinical signs of facial aging. Aging skin can be characterized by distinctive features such as wrinkles, lentigines, elastosis, and roughness. Optical coherence tomography (OCT) is capable of noninvasively measuring skin characteristics. This study aimed to assess bilateral features using OCT to explore temporal skin changes among decades and potential changes in facial skin aging based on laterality.

METHODS: A total of 97 subjects between 20 and 89 years old with Fitzpatrick skin types I to IV were enrolled. VivoSight, a Multi-Beam OCT system intended to gather topographical and histological images of skin, was used to scan the area inferolateral to the lateral canthus, bilaterally. Investigators compared characteristics of skin roughness, attenuation coefficient and blood flow across age groups and based on laterality to determine any differences.

RESULTS: Only data from successful OCT scans were used. Seventy subjects, 10 from each specified decade, had successful bilateral scans and were thus included in the analysis. Chronological aging was characterized by significantly decreased dermal attenuation coefficient with increased age. Skin roughness measurements showed trends of increased roughness with age; however, no statistically significant changes were seen between groups. Qualitative differences amongst scans taken on right and left sides of the face showed no significance regarding roughness, density or blood flow at depths ranging from 0.05 to 0.5 mm.

CONCLUSIONS: OCT is an effective method for evaluating changes in aging skin. Our results illustrate a decline in skin density with chronological age. Additionally, it was illustrated that structural change in the epidermis and dermis does occur, however on a microscopic scale, there are no significant differences based on laterality. OCT holds promise as a noninvasive technique for characterization of aging skin. Its utility and application in the clinical management and treatment of aged skin requires further research; however, the technology has potential to personalize therapies based on objective findings.

PMID:36208115 | DOI:10.1002/lsm.23611

J Magn Reson Imaging. 2022 Oct 8. doi: 10.1002/jmri.28456. Online ahead of print.

ABSTRACT

BACKGROUND: Research suggests that treatment of multiple brain metastases (BMs) with stereotactic radiosurgery shows improvement when metastases are detected early, providing a case for BM detection capabilities on small lesions.

PURPOSE: To demonstrate automatic detection of BM on three MRI datasets using a deep learning-based approach. To improve the performance of the network is iteratively co-trained with datasets from different domains. A systematic approach is proposed to prevent catastrophic forgetting during co-training.

STUDY TYPE: Retrospective.

POPULATION: A total of 156 patients (105 ground truth and 51 pseudo labels) with 1502 BM (BrainMetShare); 121 patients with 722 BM (local); 400 patients with 447 primary gliomas (BrATS). Training/pseudo labels/validation data were distributed 84/51/21 (BrainMetShare). Training/validation data were split: 121/23 (local) and 375/25 (BrATS).

FIELD STRENGTH/SEQUENCE: A 5 T and 3 T/T1 spin-echo postcontrast (T1-gradient echo) (BrainMetShare), 3 T/T1 magnetization prepared rapid acquisition gradient echo postcontrast (T1-MPRAGE) (local), 0.5 T, 1 T, and 1.16 T/T1-weighted-fluid-attenuated inversion recovery (T1-FLAIR) (BrATS).

ASSESSMENT: The ground truth was manually segmented by two (BrainMetShare) and four (BrATS) radiologists and manually annotated by one (local) radiologist. Confidence and volume based domain adaptation (CAVEAT) method of co-training the three datasets on a 3D nonlocal convolutional neural network (CNN) architecture was implemented to detect BM.

STATISTICAL TESTS: The performance was evaluated using sensitivity and false positive rates per patient (FP/patient) and free receiver operating characteristic (FROC) analysis at seven predefined (1/8, 1/4, 1/2, 1, 2, 4, and 8) FPs per scan.

RESULTS: The sensitivity and FP/patient from a held-out set registered 0.811 at 2.952 FP/patient (BrainMetShare), 0.74 at 3.130 (local), and 0.723 at 2.240 (BrATS) using the CAVEAT approach with lesions as small as 1 mm being detected.

DATA CONCLUSION: Improved sensitivities at lower FP can be achieved by co-training datasets via the CAVEAT paradigm to address the problem of data sparsity.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

PMID:36208095 | DOI:10.1002/jmri.28456