Category: Nevin Manimala

Allergy Asthma Clin Immunol. 2024 Feb 15;20(1):14. doi: 10.1186/s13223-024-00876-w.

ABSTRACT

BACKGROUND: Chronic Rhinosinusitis (CRS) is a paranasal sinus inflammatory disease and is divided into two subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays a T helper (Th)2 biased phenotype, and based on sensitivity or tolerance to aspirin or non-steroidal anti-inflammatory drugs (NSAID), is further subdivided into Aspirin-exacerbated respiratory disease (AERD) and non-AERD groups. Considering the challenge of diagnosis and treatment in patients with CRSwNP, particularly the AERD subtype, and the significance of endotyping in these patients, we examined the immune profile and endotyping based on gene expression analysis in the AERD and the non-AERD groups of patients with CRSwNP.

MATERIAL AND METHOD: In this study, 21 patients were enrolled and were categorized into AERD (N = 10) and non-AERD (N = 11) groups based on their sensitivity to aspirin. After the special washing period, nasal polyps were biopsied in both groups, and the infiltration of eosinophils, neutrophils, plasma cells, and lymphocytes was compared between the AERD and the non-AERD groups. Also, gene expression levels of transcription factors including Tbet, GATA3, RoRγt, and FoxP3 and inflammatory cytokines including interleukin (IL)1β, IL1RAP (IL1 receptor accessory protein), IL2, IL4, IL5, IL10, IL13, IL17, TNFα, and IFNγ were investigated by quantitative Real-time PCR (qRT-PCR). Statistical analyses were performed using analytical tests including Kolmogorov-Smirnov, Mann-Whitney, and T-test. A P value less than 0.05 was considered statistically significant.

RESULTS: The mean ± SD age of the studied groups was 37 ± 8.7 years old (21-50) for the AERD, and 40.4 ± 7.7 years old (31-52) for the non-AERD. LMS/EPOS/SNOT scores and pulmonary function tests showed no difference between the two groups. Serum immunoglobulin E (IgE) levels were found to be higher in patients with AERD (p = 0.04), however, the peripheral blood counts of eosinophils were comparable in the two groups. In the histopathologic analysis, the AERD group showed higher percentages of eosinophils (p = 0.04), neutrophils (p = 0.04), and plasma cells (p = 0.04) than the non-AERD group. Additionally, the gene expression levels of GATA3 (p = 0.001), IL4 (p = 0.04), IL5 (p = 0.007), and IL17 (p = 0.03) were significantly higher in the AERD than the non-AERD groups.

CONCLUSION: Higher gene expression levels of GATA3, IL4, IL5, and IL17 were observed in the AERD group compared with the non-AERD group. These findings point to distinct patterns of inflammation in patients with AERD, with a predominance of Th2 inflammation.

PMID:38360807 | DOI:10.1186/s13223-024-00876-w

Nat Commun. 2024 Feb 15;15(1):1390. doi: 10.1038/s41467-024-45547-x.

ABSTRACT

Delaying and slowing antimalarial drug resistance evolution is a priority for malaria-endemic countries. Until novel therapies become available, the mainstay of antimalarial treatment will continue to be artemisinin-based combination therapy (ACT). Deployment of different ACTs can be optimized to minimize evolutionary pressure for drug resistance by deploying them as a set of co-equal multiple first-line therapies (MFT) rather than rotating therapies in and out of use. Here, we consider one potential detriment of MFT policies, namely, that the simultaneous deployment of multiple ACTs could drive the evolution of different resistance alleles concurrently and that these resistance alleles could then be brought together by recombination into double-resistant or triple-resistant parasites. Using an individual-based model, we compare MFT and cycling policies in malaria transmission settings ranging from 0.1% to 50% prevalence. We define a total risk measure for multi-drug resistance (MDR) by summing the area under the genotype-frequency curves (AUC) of double- and triple-resistant genotypes. When prevalence ≥ 1%, total MDR risk ranges from statistically similar to 80% lower under MFT policies than under cycling policies, irrespective of whether resistance is imported or emerges de novo. At 0.1% prevalence, there is little statistical difference in MDR risk between MFT and cycling.

PMID:38360803 | DOI:10.1038/s41467-024-45547-x

BMC Sports Sci Med Rehabil. 2024 Feb 15;16(1):49. doi: 10.1186/s13102-024-00834-4.

ABSTRACT

BACKGROUND: Team management, especially player selection, rotation, and availability, are critical issues when dealing with the high demands of modern training and gameplay. As such, research continuously seeks ways to improve these actions or implement new ideas to gain a competitive advantage through the rotation of players in the starting line-up. The current study aimed to examine the rounds of the 2018 FIFA World Cup Russia in which the most rotations of key players were made and how this affected physical activity.

METHODS: The sample consisted of 110 players from the top eight teams in the 2018 World Cup Russia who played entire matches for up to 90 min in seven consecutive games. All players were divided into key players (KPs, n = 58) and non-key players (NKPs, n = 52). The analysis used data collected by an advanced motion analysis system known as STATS^®, with physical activity variables analyzed, including total distance covered (TDC), distance covered with high intensity over 20 km/h (HIR), and the number of sprints undertaken. In statistical analysis, differences between categories and consecutive matches were calculated using the Kruskal-Wallis H test, and if a significant effect size was found, a multiple comparisons p values test was performed.

RESULTS: The best teams at the 2018 FIFA World Cup Russia used the most KP rotations with NKPs in the third match of the group stage. In addition, this was even more visible among more successful teams than less successful teams. The rotation strategy among the best eight teams allowed them to maintain the physical activity of KPs and NKPs in all rounds of the tournament.

CONCLUSIONS: Coaches and coaching staff should incorporate squad rotation that includes a large group of players in their team management to improve their success. Team management expertise in player rotation during matches played over congested schedules at top tournaments maintains high levels of physical activity indicators (TDC, HIR, and sprints).

PMID:38360783 | DOI:10.1186/s13102-024-00834-4

Eur J Cancer. 2024 Feb 10;201:113914. doi: 10.1016/j.ejca.2024.113914. Online ahead of print.

ABSTRACT

BACKGROUND: CDC37 is a key determinant of client kinase recruitment to the HSP90 chaperoning system. We hypothesized that kinase-specific dependency on CDC37 alters the efficacy of targeted therapies for metastatic colorectal cancer (mCRC).

MATERIAL AND METHODS: Two independent mCRC cohorts were analyzed to compare the survival outcomes between CDC37-high and CDC37-low patients (stratified by the median cutoff values): the CALGB/SWOG 80405 trial (226 and 207 patients receiving first-line bevacizumab- and cetuximab-containing chemotherapies, respectively) and Japanese retrospective (50 refractory patients receiving regorafenib) cohorts. A dataset of specimens submitted to a commercial CLIA-certified laboratory was utilized to characterize molecular profiles of CDC37-high (top quartile, N = 5055) and CDC37-low (bottom quartile, N = 5055) CRCs.

RESULTS: In the bevacizumab-treated group, CDC37-high patients showed significantly better progression-free survival (PFS) (median 13.3 vs 9.6 months, hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.44-0.79, p < 0.01) than CDC37-low patients. In the cetuximab-treated group, CDC37-high and CDC37-low patients had similar outcomes. In the regorafenib-treated group, CDC37-high patients showed significantly better overall survival (median 11.3 vs 6.0 months, HR 0.24, 95% CI 0.11-0.54, p < 0.01) and PFS (median 3.5 vs 1.9 months, HR 0.51, 95% CI 0.28-0.94, p = 0.03). Comprehensive molecular profiling revealed that CDC37-high CRCs were associated with higher VEGFA, FLT1, and KDR expressions and activated hypoxia signature.

CONCLUSIONS: CDC37-high mCRC patients derived more benefit from anti-VEGF therapies, including bevacizumab and regorafenib, but not from cetuximab. Molecular profiles suggested that such tumors were dependent on angiogenesis-relating pathways.

PMID:38359495 | DOI:10.1016/j.ejca.2024.113914

Addict Behav. 2024 Feb 10;152:107982. doi: 10.1016/j.addbeh.2024.107982. Online ahead of print.

ABSTRACT

BACKGROUND: Flavored novel oral nicotine products (ONP), such as pouches, gum, lozenges, tablets, and gummies, have recently entered the US market but have not been authorized for smoking cessation. This study assessed the prevalence and correlates of ONPs in a national sample of youth who smoked little filtered cigars or cigarillos (LCCs) or were susceptible to LCCs.

METHODS: We conducted a national online survey from September-October 2022, as part of a study to develop cigar warnings among youth. Those aged 15-20 years old who reported using (ever or current) or susceptibility to little filtered cigars or cigarillos (LCCs) were eligible. Descriptive statistics and chi-square analyses assessed the prevalence of flavored ONP use and associations with other past 30-day tobacco product use and participant characteristics.

RESULTS: Approximately one-fifth (17.1 %) of the sample (n = 680) reported past month flavored ONP use. Any past month tobacco use was correlated with past month flavored ONP use (ps < 0.001), increasing from 17.1 % in the overall sample to 26.8 % among those reporting e-cigarette use, 41.4 % (LCCs), 47.8 % (waterpipe tobacco), 61.8 % (large cigars), and 69.1 % (smokeless tobacco). The number of products used in the past month was significantly associated with higher odds of ONPs in the past month in a multivariable logistic regression model (aOR2.26; 95 % CI: 1.92, 2.65).

DISCUSSION: Almost one-fifth of participants who use or are susceptible to cigar use in our national sample of youth use ONPs. Dual/poly use of other tobacco products and ONPs among youth suggests that many of these youth may be addicted to nicotine. Additional surveillance and regulation of ONPs that exhibit enticing characteristics, such as flavors, kid-friendly formulations, and targeted marketing/branding may be needed.

PMID:38359494 | DOI:10.1016/j.addbeh.2024.107982

Phys Med Biol. 2024 Feb 15. doi: 10.1088/1361-6560/ad29ba. Online ahead of print.

ABSTRACT

OBJECTIVE: Self-supervised learning methods have been successfully applied for low-dose Computed Tomography (LDCT) denoising, with the advantage of not requiring labeled data. Conventional self-supervised methods operate only in the image domain, ignoring valuable priors in the sinogram domain. Recently proposed dual-domain methods address this limitation but encounter issues with blurring artifacts in the reconstructed image due to the inhomogeneous distribution of noise levels in low-dose sinograms.

APPROACH: To tackle this challenge, this paper proposes SDBDNet, an end-to-end dual-domain self-supervised method for LDCT denoising. With the network designed based on the properties of inhomogeneous noise in low-dose sinograms and the principle of moderate sinogram-domain denoising, SDBDNet achieves effective denoising in dual domains without introducing blurring artifacts. Specifically, we split the sinogram into two subsets based on the positions of detector cells to generate paired training data with high similarity and independent noise. These sub-sinograms are then restored to their original size using 1-D interpolation and learning-based correction. To achieve adaptive and moderate smoothing in the sinogram domain, we integrate Dropblock, a type of convolution layer with regularization, into SDBDNet, and set a weighted average between the denoised sinograms and their noisy counterparts, leading to a well-balanced dual-domain approach.

MAIN RESULTS: Numerical experiments show that our method outperforms popular non-learning and self-supervised learning methods, demonstrating its effectiveness and superior performance.

SIGNIFICANCE: While introducing a novel high-performance dual-domain self-supervised LDCT denoising method, this paper also emphasizes and verifies the importance of appropriate sinogram-domain denoising in dual-domain methods, which might inspire future work.

PMID:38359449 | DOI:10.1088/1361-6560/ad29ba

Arch Cardiol Mex. 2024 Feb 15. doi: 10.24875/ACM.23000126. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: To communicate the experience in an Andean country with the OcclutechTM Duct Occluder device for the closure of patent ductus arteriosus.

METHOD: observational, retrospective, cross-sectional study with basic statistical analysis. Period: December/2014 to December/2022. Data: medical chart, reports of catheterization.

RESULTS: Forty-six patients, female 71.3%, male 28.7%; age: 0.6-38 years-old (median [Me]: 5.2); weight: 6.3-60 kg (Me: 16.5). Origin: Andean 91.3%, coast 8.7%. Types of patent ductus arteriosus: E 54.4%, A 32.6%, D 13%. Minimum ductal diameter: 1.8-11.8 mm (Me: 3.5). Mean pulmonary artery pressure prior to occlusion: 14-67 mmHg (Me: 27). Pulmonary vascular resistance index prior to occlusion: 0.28-4.9 WU/m2 (Me: 1.3). Six of them were classified as hypertensive patent ductus arteriosus. Occlusion rate: 47.8% immediate, 81% at 24 hours, 100% after six months. Fluoroscopy time: 2-13.8 minutes (Me: 4). Complications: a migrated device. Follow-up: 1-6.5 years.

CONCLUSIONS: Occlutech^TM Duct Occluder device was effective and safe for the closure of patent ductus arteriosus type E, A and D in low-altitude and high-altitude dwellers, whether they were children or adults, even when these ductus arteriosus were hypertensive.

PMID:38359430 | DOI:10.24875/ACM.23000126

Appl Neuropsychol Adult. 2024 Feb 15:1-15. doi: 10.1080/23279095.2024.2315555. Online ahead of print.

ABSTRACT

AIM: Given the ever-increasing evidence for the co-occurrence of attention impairments and language disorders in chronic aphasia, this study aimed to compare the effects of two naming treatment programs, one with and one without attention training components, on the naming performance of participants with aphasia.

MATERIALS AND METHODS: This was a single-subject crossover study in which six people with chronic aphasia and different degrees of naming and attention impairments participated. Two treatment programs were implemented for each participant, with the sequence of the treatments with crossover design. Each program consisted of 12 treatment sessions plus pre- and post-treatment assessment sessions (15 weeks for each participant). The visual analysis and WEighted STatistics methods were employed for data analysis.

RESULTS: Based on visual analysis, both treatments improved in comparison to the baseline phase. Statistical analysis revealed that the number of participants with significant naming improvement following combined program (5 participants) was larger than the number of participants showing improvement following completion of the single, program.

CONCLUSION: Although integrating attention training into a conventional treatment for anomia can increase the effect of treatment on naming ability, more studies are required to clarify the role of attention in remediating naming impairments in aphasia.

PMID:38359428 | DOI:10.1080/23279095.2024.2315555

Appl Neuropsychol Child. 2024 Feb 15:1-8. doi: 10.1080/21622965.2024.2311096. Online ahead of print.

ABSTRACT

This study investigates the effectiveness of a computerized cognitive test battery embedded within a video game to assess executive functions (EF) in deaf and hearing children. We evaluated a diverse cohort of 290 elementary school students aged 5 to 13 years (mean age = 8.86, SD = 1.96), comprising 74 sign language users, 14 Spanish-speaking deaf participants, 23 children with mixed communication methods, and 179 typically hearing individuals. Our statistical analysis focused on item discrimination, reliability, and criterion validation of the game-based assessments. The results indicated high reliability and effective discrimination of EF across the game’s three primary stages. External validation was conducted using the Matrices Test, educational attainment, and age as variables. A significant positive correlation (r = 0.377, p < 0.001) was observed between the Matrices Test scores and game-based achievement scores. Furthermore, linear regression analysis revealed education (Standardized Beta = 0.339) and age (Standardized Beta = 0.179) as significant predictors of performance in these scores. This study underscores the value of integrating computerized cognitive assessments within a video game environment for comprehensive neuropsychological evaluations, highlighting its potential in diverse child populations.

PMID:38359416 | DOI:10.1080/21622965.2024.2311096

Prehosp Emerg Care. 2024 Feb 15:1-19. doi: 10.1080/10903127.2024.2319139. Online ahead of print.

ABSTRACT

Background: Emergency Medical Service (EMS) clinicians experience high levels of occupational stress due to long hours, short staffing, and patient deaths, among other factors. While gender has been partially examined, little is known regarding the role of empathy on occupational stress and mental health (MH) outcomes among EMS clinicians. Therefore, the current study examines the moderating role of empathy and, separately, gender on associations between occupational stress and mental health.Methods: A cross-sectional examination of EMS clinician occupational and personal wellbeing was conducted via an anonymous, electronic survey. Information on clinician demographics, and validated measures of occupational stress, burnout, and MH outcomes were collected. Empathy was assessed using the Toronto Empathy Scale (TEQ). Descriptive/bivariate statistics were conducted for variables of interest. Separate multivariable regression models evaluated associations between occupational stress and mental health outcomes. Empathy and gender were examined as potential moderators using interactions.Results: A total of 568 EMS clinicians completed the survey. High levels of mental health difficulties were reported (34.0% anxiety, 29.2% depression, 48.6% burnout). Increased occupational stress was associated with increased anxiety (OR =1.08, 95% CI 1.05-1.10), depression (OR = 1.09, 95% CI 1.06-1.10), and burnout (OR = 1.10, 95% CI 1.07-1.12). No moderation analyses were significant. Greater resilience was associated with lower depression, anxiety, and burnout.Conclusion: EMS clinicians, much like other first responders, experience considerable occupational stress, of which is associated with mental health difficulties and burnout. Findings underscore the need for intervention programs aimed at reducing the impact of occupational stress and the promotion of resilience. Continuing to understand the full scope of EMS mental health, including the role of resilience, is imperative, particularly in light of future public emergencies.

PMID:38359401 | DOI:10.1080/10903127.2024.2319139