Tag: nevin manimala

Cytometry A. 2023 Mar 6. doi: 10.1002/cyto.a.24729. Online ahead of print.

ABSTRACT

Highly multiplexed in situ imaging cytometry assays have made it possible to study the spatial organisation of numerous cell types simultaneously. We have addressed the challenge of quantifying complex multi-cellular relationships by proposing a statistical method which clusters local indicators of spatial association. Our approach successfully identifies distinct tissue architectures in datasets generated from three state-of-the-art high-parameter assays demonstrating its value in summarising the information-rich data generated from these technologies.

PMID:36879360 | DOI:10.1002/cyto.a.24729

Allergy Asthma Clin Immunol. 2023 Mar 6;19(1):18. doi: 10.1186/s13223-023-00773-8.

ABSTRACT

BACKGROUND: Results of studies evaluating the relationship between asthma occurrence and early life antibiotic use have been conflicting. The aim of this study was to investigate the relationship between occurrence of asthma in children and systemic antibiotic use in the first year of life based on an incidence density study with careful consideration of the temporal aspects of the determinant-outcome relationship.

METHODS: We conducted an incidence density study nested in a data collection project with information on 1128 mother-child pairs. Systemic antibiotic use in the first year of life was defined as excessive (≥ 4 courses) vs. non-excessive (< 4 courses) use based on information from weekly diaries. Events (cases) were defined as the first parent-reported occurrence of asthma in a child between 1 and 10 years of age. Population time ‘at risk’ was probed by sampling population moments (controls). Missing data were imputed. Multiple logistic regression was used to assess the association between current first asthma occurrence (incidence density) and systemic antibiotic use in the first year of life, to evaluate effect modification and adjust for confounding.

RESULTS: Forty-seven first asthma events and 147 population moments were included. Excessive systemic antibiotic use in the first year of life showed more than twice the incidence density of asthma compared to non-excessive use (adjusted IDR [95% CI]: 2.18 [0.98, 4.87], p = 0.06). The association was more pronounced in children who have had lower respiratory tract infections (LRTIs) in the first year of life compared to children who had no LRTIs in the first year of life (adjusted IDR [95% CI]: 5.17 [1.19, 22.52] versus 1.49 [0.54, 4.14]).

CONCLUSIONS: Excessive use of systemic antibiotics in the first year of life may play a role in the genesis of asthma in children. This effect is modified by the occurrence of LRTIs in the first year of life, with a stronger association observed in children experiencing LRTIs in the first year of life.

PMID:36879341 | DOI:10.1186/s13223-023-00773-8

Adv Rheumatol. 2023 Mar 6;63(1):8. doi: 10.1186/s42358-023-00291-6.

ABSTRACT

OBJECTIVES: BDNF has been implicated in the pathophysiology of systemic lupus erythematosus (SLE), especially its neuropsychiatric symptoms. The purpose of this study was to investigate the profile of blood BDNF levels in patients with SLE.

METHODS: We searched PubMed, EMBASE, and the Cochrane Library for papers that compared BDNF levels in SLE patients and healthy controls (HCs). The Newcastle-Ottawa scale was used to assess the quality of the included publications, and statistical analyses were carried out using R 4.0.4.

RESULTS: The final analysis included eight studies totaling 323 healthy controls and 658 SLE patients. Meta-analysis did not show statistically significant differences in blood BDNF concentrations in SLE patients compared to HCs (SMD 0.08, 95% CI [ – 1.15; 1.32], P value = 0.89). After removing outliers, there was no significant change in the results: SMD -0.3868 (95% CI [ – 1.17; 0.39], P value = 0.33. Univariate meta-regression analysis revealed that sample size, number of males, NOS score, and mean age of the SLE participants accounted for the heterogeneity of the studies (R² were 26.89%, 16.53%, 18.8%, and 49.96%, respectively).

CONCLUSION: In conclusion, our meta-analysis found no significant association between blood BDNF levels and SLE. The potential role and relevance of BDNF in SLE need to be further examined in higher quality studies.

PMID:36879337 | DOI:10.1186/s42358-023-00291-6

Clin Endocrinol (Oxf). 2023 Mar 6. doi: 10.1111/cen.14906. Online ahead of print.

ABSTRACT

OBJECTIVE: There is controversial results about serum kisspeptin, neurokinin-B (NKB), anti-Müllerian hormone (AMH), and inhibin B (INHB) levels in girls with central precocious puberty (CPP). Aim of this study is to evaluate serum levels of these four peptides in patients presented with early pubertal signs, and to evaluate their diagnostic validity in the diagnosis of CPP.

DESIGN: Cross-sectional study PATIENTS: Study included 99 girls (51 CPP, 48 premature thelarche [PT]) whose breast development started before 8 years and 42 age-matched healthy prepubertal girls. Clinical findings, antropometric measurements, laboratory and radiological findings were recorded. Gonadotropin-releasing hormone (GnRH) stimulation test was performed in all cases with early breast development.

MEASUREMENTS: Kisspeptin, NKB, INHB and AMH levels were measured in fasting serum samples using ELISA method.

RESULTS: There was no statistically significant difference between mean ages of girls with CPP (7.1±1.2 years), PT (7.2±1.3 years), and prepubertal controls (7.0±1.0 years). Serum kisspeptin, NKB and INHB levels were higher in CPP group compared to PT and control groups, while serum AMH level was lower in CPP group. Serum kisspeptin, NKB, and INHB were all positively correlated with bone age (BA) advancement, and peak luteinizing hormone (LH) in GnRH test. Multiple stepwise regression analysis revealed that the most important factors used to differentiate CPP from PT were advanced BA, serum kisspeptin, NKB and INHB levels (AUC: 0.819, p<0.001).

CONCLUSIONS: We, firstly showed in the same patients’ group that serum kisspeptin, NKB and INHB were higher in patients with CPP and can be used as alternative parameters to distinguish CPP from PT. This article is protected by copyright. All rights reserved.

PMID:36879296 | DOI:10.1111/cen.14906

J Eat Disord. 2023 Mar 6;11(1):35. doi: 10.1186/s40337-023-00761-8.

ABSTRACT

BACKGROUND: Mostly, visual food stimuli paradigms for functional Magnetic Resonance Imaging are used in studies of eating disorders. However, the optimal contrasts and presentation modes are still under discussion. Therefore, we aimed to create and analyse a visual stimulation paradigm with defined contrast.

METHODS: In this prospective study, a block-design fMRI paradigm with conditions of randomly altering blocks of high- and low-calorie food images and images of fixation cross was established. Food pictures were rated in advance by a group of patients diagnosed with anorexia nervosa to address the dedicated perception of patients with eating disorders. To optimize the scanning procedure and fMRI contrasts we have analysed neural activity differences between high-calorie stimuli versus baseline (H vs. X), low-calorie stimuli versus baseline (L vs. X) and high- versus low-calorie stimuli (H vs. L).

RESULTS: By employing the developed paradigm, we were able to obtain results comparable to other studies and analysed them with different contrasts. Implementation of the contrast H versus X led to increased blood-oxygen-level-dependent signal (BOLD) mainly in unspecific areas, such as the visual cortex, the Broca´s area, bilaterally in the premotor cortex and the supplementary motor area, but also in thalami, insulae, the right dorsolateral prefrontal cortex, the left amygdala, the left putamen (p < .05). When applying the contrast L versus X, an enhancement of the BOLD signal was detected similarly within the visual area, the right temporal pole, the right precentral gyrus, Broca´s area, left insula, left hippocampus, the left parahippocampal gyrus, bilaterally premotor cortex and thalami (p < .05). Comparison of brain reactions regarding visual stimuli (high- versus low-calorie food), assumed to be more relevant in eating disorders, resulted in bilateral enhancement of the BOLD signal in primary, secondary and associative visual cortex (including fusiform gyri), as well as angular gyri (p < .05).

CONCLUSIONS: A carefully designed paradigm, based on the subject’s characteristics, can increase the reliability of the fMRI study, and may reveal specific brain activations elicited by this custom-built stimuli. However, a putative disadvantage of implementing the contrast of high- versus low-calorie stimuli might be the omission of some interesting outcomes due to lower statistical power. Trial registration NCT02980120.

PMID:36879292 | DOI:10.1186/s40337-023-00761-8

J Otolaryngol Head Neck Surg. 2023 Mar 6;52(1):22. doi: 10.1186/s40463-022-00618-1.

ABSTRACT

BACKGROUND: Gender bias is behavior that shows favoritism towards one gender over another. Microaggressions are defined as subtle, often unconscious, discriminatory, or insulting actions that communicate demeaning or negative attitudes. Our objective was to explore how female otolaryngologists experience gender bias and microaggressions in the workplace.

METHODS: Anonymous web-based cross-sectional Canadian survey was distributed to all female otolaryngologists (attendings and trainees) using the Dillman’s Tailored Design Method from July to August of 2021. Quantitative survey included demographic data, validated 44-item Sexist Microaggressions Experiences and Stress Scale (MESS) and validated 10-item General Self-efficacy scale (GSES). Statistical analysis included descriptive and bivariate analysis.

RESULTS: Sixty out of 200 participants (30% response rate) completed the survey (mean age 37 ± 8.3 years, 55.0% white, 41.7% trainee, 50% fellowship-trained, 50% with children, mean 9.2 ± 7.4 years of practice). Participants scored mild to moderate on the Sexist MESS-Frequency (mean ± standard deviation) 55.8 ± 24.2 (42.3% ± 18.3%), Severity 46.0 ± 23.9 (34.8% ± 18.1%), Total 104.5 ± 43.7 (39.6% ± 16.6%) and high on GSES (32.7 ± 5.7). Sexist MESS score was not associated with age, ethnicity, fellowship-training, having children, years of practice, or GSES. In the sexual objectification domain, trainees had higher frequency (p = 0.04), severity (p = 0.02) and total MESS (p = 0.02) scores than attendings.

CONCLUSIONS: This was the first multicenter, Canada-wide study exploring how female otolaryngologists experience gender bias and microaggressions in the workplace. Female otolaryngologists experience mild to moderate gender bias, but have high self-efficacy to manage this issue. Trainees had more severe and frequent microaggressions than attendings in the sexual objectification domain. Future efforts should help develop strategies for all otolaryngologists to manage these experiences, and thereby improve the culture of inclusiveness and diversity in our specialty.

PMID:36879288 | DOI:10.1186/s40463-022-00618-1

BMC Musculoskelet Disord. 2023 Mar 6;24(1):165. doi: 10.1186/s12891-023-06281-5.

ABSTRACT

BACKGROUND: We evaluated the diagnostic efficacy of deep learning radiomics (DLR) and hand-crafted radiomics (HCR) features in differentiating acute and chronic vertebral compression fractures (VCFs).

METHODS: A total of 365 patients with VCFs were retrospectively analysed based on their computed tomography (CT) scan data. All patients completed MRI examination within 2 weeks. There were 315 acute VCFs and 205 chronic VCFs. Deep transfer learning (DTL) features and HCR features were extracted from CT images of patients with VCFs using DLR and traditional radiomics, respectively, and feature fusion was performed to establish the least absolute shrinkage and selection operator. The MRI display of vertebral bone marrow oedema was used as the gold standard for acute VCF, and the model performance was evaluated using the receiver operating characteristic (ROC).To separately evaluate the effectiveness of DLR, traditional radiomics and feature fusion in the differential diagnosis of acute and chronic VCFs, we constructed a nomogram based on the clinical baseline data to visualize the classification evaluation. The predictive power of each model was compared using the Delong test, and the clinical value of the nomogram was evaluated using decision curve analysis (DCA).

RESULTS: Fifty DTL features were obtained from DLR, 41 HCR features were obtained from traditional radiomics, and 77 features fusion were obtained after feature screening and fusion of the two. The area under the curve (AUC) of the DLR model in the training cohort and test cohort were 0.992 (95% confidence interval (CI), 0.983-0.999) and 0.871 (95% CI, 0.805-0.938), respectively. While the AUCs of the conventional radiomics model in the training cohort and test cohort were 0.973 (95% CI, 0.955-0.990) and 0.854 (95% CI, 0.773-0.934), respectively. The AUCs of the features fusion model in the training cohort and test cohort were 0.997 (95% CI, 0.994-0.999) and 0.915 (95% CI, 0.855-0.974), respectively. The AUCs of nomogram constructed by the features fusion in combination with clinical baseline data were 0.998 (95% CI, 0.996-0.999) and 0.946 (95% CI, 0.906-0.987) in the training cohort and test cohort, respectively. The Delong test showed that the differences between the features fusion model and the nomogram in the training cohort and the test cohort were not statistically significant (P values were 0.794 and 0.668, respectively), and the differences in the other prediction models in the training cohort and the test cohort were statistically significant (P < 0.05). DCA showed that the nomogram had high clinical value.

CONCLUSION: The features fusion model can be used for the differential diagnosis of acute and chronic VCFs, and its differential diagnosis ability is improved when compared with that when either radiomics is used alone. At the same time, the nomogram has a high predictive value for acute and chronic VCFs and can be a potential decision-making tool to assist clinicians, especially when a patient is unable to undergo spinal MRI examination.

PMID:36879285 | DOI:10.1186/s12891-023-06281-5

Biomark Res. 2023 Mar 7;11(1):25. doi: 10.1186/s40364-023-00465-w.

ABSTRACT

BACKGROUND: Activated immune cells (IC) in the tumor microenvironment (TME) are critical for anti-tumor efficacy. Greater understanding of the dynamic diversity and crosstalk between IC is needed to clarify their association with immune checkpoint inhibitor efficacy.

METHODS: Patients from three tislelizumab monotherapy trials in solid tumors (NCT02407990, NCT04068519, NCT04004221) were retrospectively divided into subgroups by CD8⁺ T-cell and macrophage (Mφ) levels, assessed via multiplex immunohistochemistry (mIHC; n = 67) or gene expression profiling (GEP; n = 629).

RESULTS: A trend of longer survival was observed in patients with both high CD8⁺ T-cell and Mφ levels versus other subgroups in the mIHC analysis (P = 0.11), which was confirmed with greater statistical significance in the GEP analysis (P = 0.0001). Co-existence of CD8⁺ T cells and Mφ was coupled with elevated CD8⁺ T-cell cytotoxicity, T-cell trafficking, MHC class I antigen presentation signatures/genes, and enrichment of the pro-inflammatory Mφ polarization pathway. Additionally, a high level of pro-inflammatory CD64⁺ Mφ density was associated with an immune-activated TME and survival benefit with tislelizumab (15.2 vs. 5.9 months for low density; P = 0.042). Spatial proximity analysis revealed that closer proximity between CD8⁺ T cells and CD64⁺ Mφ was associated with a survival benefit with tislelizumab (15.2 vs. 5.3 months for low proximity; P = 0.024).

CONCLUSIONS: These findings support the potential role of crosstalk between pro-inflammatory Mφ and cytotoxic T cells in the clinical benefit of tislelizumab.

TRIAL REGISTRATION: NCT02407990, NCT04068519, NCT04004221.

PMID:36879284 | DOI:10.1186/s40364-023-00465-w

Genome Med. 2023 Mar 6;15(1):15. doi: 10.1186/s13073-023-01162-x.

ABSTRACT

BACKGROUND: There has been a growing appreciation recently that mutagenic processes can be studied through the lenses of mutational signatures, which represent characteristic mutation patterns attributed to individual mutagens. However, the causal links between mutagens and observed mutation patterns as well as other types of interactions between mutagenic processes and molecular pathways are not fully understood, limiting the utility of mutational signatures.

METHODS: To gain insights into these relationships, we developed a network-based method, named GENESIGNET that constructs an influence network among genes and mutational signatures. The approach leverages sparse partial correlation among other statistical techniques to uncover dominant influence relations between the activities of network nodes.

RESULTS: Applying GENESIGNET to cancer data sets, we uncovered important relations between mutational signatures and several cellular processes that can shed light on cancer-related processes. Our results are consistent with previous findings, such as the impact of homologous recombination deficiency on clustered APOBEC mutations in breast cancer. The network identified by GENESIGNET also suggest an interaction between APOBEC hypermutation and activation of regulatory T Cells (Tregs), as well as a relation between APOBEC mutations and changes in DNA conformation. GENESIGNET also exposed a possible link between the SBS8 signature of unknown etiology and the Nucleotide Excision Repair (NER) pathway.

CONCLUSIONS: GENESIGNET provides a new and powerful method to reveal the relation between mutational signatures and gene expression. The GENESIGNET method was implemented in python, and installable package, source codes and the data sets used for and generated during this study are available at the Github site https://github.com/ncbi/GeneSigNet.

PMID:36879282 | DOI:10.1186/s13073-023-01162-x

BMC Nurs. 2023 Mar 7;22(1):62. doi: 10.1186/s12912-023-01204-0.

ABSTRACT

BACKGROUND: With today’s complex needs of the population and high demands in quality of care, there will be a continuing need for expanding role of nurses to assume more responsibilities in healthcare. Newly graduated nurses, who possess the competence to function as Registered Nurses, will soon recognize that lecture-based, passive delivery of content is not sufficient to deal with the complex healthcare environment.

AIM: This study aimed to compare the effects of a blended video watching and peer learning program and the usual lecture-based program on the levels of satisfaction and self-confidence in learning, perceptions of peer learning, and academic performance of students enrolled in a master’s nursing program.

METHODS: A quasi-experimental study was conducted. The program was offered to Master of Science in Nursing students during Spring 2021 (intervention group, n = 46), while the usual face-to-face lectures and tutorial classes were provided to students enrolled during Fall 2020 (control group, n = 46).

RESULTS: There was a statistically significant increase in satisfaction, self-confidence in learning, and academic performance in the intervention group after learning in a blended video-watching and peer learning mode.

CONCLUSION: This study fills a knowledge gap to meet the learning needs of time-conscious, part-time students working full time in hospitals.

PMID:36879268 | DOI:10.1186/s12912-023-01204-0