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Insights into potential mechanisms of asthma patients with COVID-19: A study based on the gene expression profiling of bronchoalveolar lavage fluid

Comput Biol Med. 2022 Jul;146:105601. doi: 10.1016/j.compbiomed.2022.105601. Epub 2022 May 19.

ABSTRACT

BACKGROUND: The 2019 novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a major challenge threatening the global healthcare system. Respiratory virus infection is the most common cause of asthma attacks, and thus COVID-19 may contribute to an increase in asthma exacerbations. However, the mechanisms of COVID-19/asthma comorbidity remain unclear.

METHODS: The “Limma” package or “DESeq2” package was used to screen differentially expressed genes (DEGs). Alveolar lavage fluid datasets of COVID-19 and asthma were obtained from the GEO and GSV database. A series of analyses of common host factors for COVID-19 and asthma were conducted, including PPI network construction, module analysis, enrichment analysis, inference of the upstream pathway activity of host factors, tissue-specific analysis and drug candidate prediction. Finally, the key host factors were verified in the GSE152418 and GSE164805 datasets.

RESULTS: 192 overlapping host factors were obtained by analyzing the intersection of asthma and COVID-19. FN1, UBA52, EEF1A1, ITGB1, XPO1, NPM1, EGR1, EIF4E, SRSF1, CCR5, PXN, IRF8 and DDX5 as host factors were tightly connected in the PPI network. Module analysis identified five modules with different biological functions and pathways. According to the degree values ranking in the PPI network, EEF1A1, EGR1, UBA52, DDX5 and IRF8 were considered as the key cohost factors for COVID-19 and asthma. The H2O2, VEGF, IL-1 and Wnt signaling pathways had the strongest activities in the upstream pathways. Tissue-specific enrichment analysis revealed the different expression levels of the five critical host factors. LY294002, wortmannin, PD98059 and heparin might have great potential to evolve into therapeutic drugs for COVID-19 and asthma comorbidity. Finally, the validation dataset confirmed that the expression of five key host factors were statistically significant among COVID-19 groups with different severity and healthy control subjects.

CONCLUSIONS: This study constructed a network of common host factors between asthma and COVID-19 and predicted several drugs with therapeutic potential. Therefore, this study is likely to provide a reference for the management and treatment for COVID-19/asthma comorbidity.

PMID:35751199 | DOI:10.1016/j.compbiomed.2022.105601

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Eight pruning deep learning models for low storage and high-speed COVID-19 computed tomography lung segmentation and heatmap-based lesion localization: A multicenter study using COVLIAS 2.0

Comput Biol Med. 2022 Jul;146:105571. doi: 10.1016/j.compbiomed.2022.105571. Epub 2022 May 21.

ABSTRACT

BACKGROUND: COVLIAS 1.0: an automated lung segmentation was designed for COVID-19 diagnosis. It has issues related to storage space and speed. This study shows that COVLIAS 2.0 uses pruned AI (PAI) networks for improving both storage and speed, wiliest high performance on lung segmentation and lesion localization.

METHOD: ology: The proposed study uses multicenter ∼9,000 CT slices from two different nations, namely, CroMed from Croatia (80 patients, experimental data), and NovMed from Italy (72 patients, validation data). We hypothesize that by using pruning and evolutionary optimization algorithms, the size of the AI models can be reduced significantly, ensuring optimal performance. Eight different pruning techniques (i) differential evolution (DE), (ii) genetic algorithm (GA), (iii) particle swarm optimization algorithm (PSO), and (iv) whale optimization algorithm (WO) in two deep learning frameworks (i) Fully connected network (FCN) and (ii) SegNet were designed. COVLIAS 2.0 was validated using “Unseen NovMed” and benchmarked against MedSeg. Statistical tests for stability and reliability were also conducted.

RESULTS: Pruning algorithms (i) FCN-DE, (ii) FCN-GA, (iii) FCN-PSO, and (iv) FCN-WO showed improvement in storage by 92.4%, 95.3%, 98.7%, and 99.8% respectively when compared against solo FCN, and (v) SegNet-DE, (vi) SegNet-GA, (vii) SegNet-PSO, and (viii) SegNet-WO showed improvement by 97.1%, 97.9%, 98.8%, and 99.2% respectively when compared against solo SegNet. AUC > 0.94 (p < 0.0001) on CroMed and > 0.86 (p < 0.0001) on NovMed data set for all eight EA model. PAI <0.25 s per image. DenseNet-121-based Grad-CAM heatmaps showed validation on glass ground opacity lesions.

CONCLUSIONS: Eight PAI networks that were successfully validated are five times faster, storage efficient, and could be used in clinical settings.

PMID:35751196 | DOI:10.1016/j.compbiomed.2022.105571

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Impact of the Tips from Former Smokers Anti-Smoking Media Campaign on Youth Smoking Behaviors and Anti-Tobacco Attitudes

Nicotine Tob Res. 2022 Jun 24:ntac152. doi: 10.1093/ntr/ntac152. Online ahead of print.

ABSTRACT

INTRODUCTION: Anti-tobacco media campaigns can prevent youth smoking, but there is little research on how adult-targeted campaigns affect youth. We investigated the association between the Tips From Former Smokers (Tips) campaign and youth smoking behaviors and anti-tobacco attitudes, and variation by sex, race/ethnicity, or socioeconomic status (SES).

METHODS: We used data from the Monitoring the Future (MTF) study, a nationally representative survey on 8th, 10th, and 12th graders, from 2013-2015. Quartiles of Tips gross rating points (GRPs) were used to estimate exposure. Youth smoking behavior outcomes included smoking prevalence, initiation, and susceptibility. The anti-tobacco attitude outcomes included the extent that anti-tobacco ads made participants (a) less favorable towards smoking or (b) less likely to smoke cigarettes. Modified Poisson regression models estimated average marginal effects; separate additive interactions between Tips GRP exposure and sex, race/ethnicity, parents’ highest education, and college plans (12th graders only) were used to test for effect modification.

RESULTS: Tips GRPs were not associated with smoking behaviors within any grade. However, 12 th graders in the highest quartile of Tips had a 7.0 percentage point higher probability (95%CI=0.023-0.116) of responding that anti-tobacco ads made them less likely to smoke. Tips GRPs were associated with a lower probability of past 30-day smoking prevalence among 10 th grade females, but not males (joint p-value=0.002). No additional statistically significant interactions were found for any other outcomes for any grade.

CONCLUSIONS: This study revealed the potential for adult-targeted campaigns to increase youth’s anti-smoking attitudes, but campaign exposure was not associated with smoking behaviors.

IMPLICATIONS: Few studies have examined the potential for anti-smoking media campaigns to influence audiences outside their targeted audience. In this study, we show the potential for adult-targeted campaigns to impact youth and suggests that Tips exposure may promote anti-smoking attitudes among youth.

PMID:35749779 | DOI:10.1093/ntr/ntac152

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The Evolution of Extracorporeal Membrane Oxygenation Circuitry and Impact on Clinical Outcomes in Children: A Systematic Review

ASAIO J. 2022 Jun 24. doi: 10.1097/MAT.0000000000001785. Online ahead of print.

ABSTRACT

This systematic review summarizes the major developments in extracorporeal membrane oxygenation (ECMO) circuitry in pediatrics over the past 20 years and demonstrates the impacts of those developments on clinical outcomes. This systematic review followed structured Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 1987 studies were retrieved, of which 82 were included in the final analysis. Over the past 20 years, ECMO pumps have shifted from roller pumps to centrifugal pumps. Silicone and polypropylene hollow fiber membrane oxygenators were initially used but have been replaced by polymethylpentene hollow fiber membrane oxygenators, with other ECMO components poorly reported. Considerable variability in mortality was found across studies and there was no statistical difference in mortality rates across different periods. The duration of ECMO and other outcome measures were inconsistently reported across studies. This systematic review demonstrated technological developments in pumps and oxygenators over the last two decades, although patient mortality rates remained unchanged. This could be because of ECMO support applied to patients in more critical conditions over the years. We also highlighted the limitations of methodology information disclosure and outcome measures in current ECMO studies, showing the need of reporting standardization for future ECMO studies.

PMID:35749749 | DOI:10.1097/MAT.0000000000001785

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Clinical features of UK Biobank subjects carrying protein-truncating variants in genes implicated in schizophrenia pathogenesis

Psychiatr Genet. 2022 Jun 27. doi: 10.1097/YPG.0000000000000318. Online ahead of print.

ABSTRACT

OBJECTIVE: The SCHEMA consortium has identified 10 genes in which protein-truncating variants (PTVs) confer a substantial risk of schizophrenia. This study aimed to determine whether carrying these PTVs was associated with neuropsychiatric impairment in the general population.

METHODS: Phenotype fields of exome-sequenced participants in the UK Biobank who carried PTVs in these genes were studied to determine to what extent they demonstrated features of schizophrenia or had neuropsychiatric impairment.

RESULTS: Following automated quality control and visual inspection of reads, 251 subjects were identified as having well-supported PTVs in one of these genes. The frequency of PTVs in CACNA1G was higher than that had been observed in SCHEMA cases, casting doubt on its role in schizophrenia pathogenesis, but otherwise rates were similar to those observed in SCHEMA controls. Numbers were too small to allow formal statistical analysis but in general carriers of PTVs did not appear to have high rates of psychiatric illness or reduced educational or occupational functioning. One subject with a PTV in SETD1A had a diagnosis of schizophrenia, one with a PTV in HERC1 had psychotic depression and two subjects seemed to have developmental disorders, one with a PTV in GRIN2A and one with a PTV in RBCC1. There seemed to be somewhat increased rates of affective disorders among carriers of PTVs in HERC1 and RB1CC1.

CONCLUSION: Carriers of PTVs did not appear to have subclinical manifestations of schizophrenia. Although PTVs in these genes can substantially increase schizophrenia risk, their effect seems to be dichotomous and most carriers appear psychiatrically well. This research has been conducted using the UK Biobank Resource.

PMID:35749744 | DOI:10.1097/YPG.0000000000000318

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Assessing Efficacy and Use Patterns of Medical Cannabis for Symptom Management in Elderly Cancer Patients

Am J Hosp Palliat Care. 2022 Jun 24:10499091221110217. doi: 10.1177/10499091221110217. Online ahead of print.

ABSTRACT

OBJECTIVES: Our study sought to further characterize patterns of medical cannabis use in elderly cancer patients. Furthermore, we sought to assess efficacy of medical cannabis for the treatment of pain, nausea, anorexia, insomnia and anxiety in elderly cancer patients.

BACKGROUND: Medical cannabis use is growing for symptom management in cancer patients, but limited data exists on the safety or efficacy of use in elderly patients.

METHODS: A retrospective chart review assessing changes in numerical symptom scores reported at clinic visits before and after medical cannabis initiation.

RESULTS: There was no statistically significant difference in pain, nausea, appetite, insomnia or anxiety scores reported before and after initiation of medical cannabis. Oil was the most common form used, followed by vape, and the most common ratios used were high tetrahydrocannabinol (THC) to cannabidiol (CBD) and equal parts THC/CBD products.

CONCLUSION: This study did not find a statistically significant change in symptom scores with medical cannabis use, although further study is warranted given the limitations of the present study. Elderly patients most commonly are using equal parts THC/CBD or high THC ratio products initially.

PMID:35749740 | DOI:10.1177/10499091221110217

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Photobiomodulation Effectiveness in Treating Androgenetic Alopecia

Photobiomodul Photomed Laser Surg. 2022 Jun;40(6):387-394. doi: 10.1089/photob.2022.0011.

ABSTRACT

Background: Androgenetic alopecia (AGA) is a genetically determined condition, which leads to progressive hair loss (HL) of the vertex, affects hair follicles, and promotes partial or total HL. It may be related to important psychological and social distress. Objective: The aim of the study was to evaluate the effects of photobiomodulation (PBM) in patients with AGA. Methods: Twenty-five men 20-54 years of age participated in this study. The irradiations were punctual, in contact mode, with 1 cm between each point covering the entire affected area. A red low-level laser (λ = 660 nm) (Recover®, MMOptics, São Carlos, Brazil) was used with 100 mW, 30 sec, and 3 J per point, twice a week on alternate days for 10 weeks. Evaluations were made by photographic records from the same area before any intervention (T1), after 5 weeks (T2), after 10 weeks (T3). Two blinded evaluators using the ImageJ® software assessed the hair density. Results: The hair density evaluation showed a significant increase in hair count between T1 and T2 (p = 0.0004) and between T1 and T3 (p = 0.0285), however between T2 and T3 no statistical difference was found (p > 0.05). Conclusions: PBM provides a stimulus for hair density in 5 weeks. After this period, we observed that after five extra sessions, it does not increase hair density in the treated region. This study showed that the PBM is effective and promoted safe results with a reduced number of sessions for the AGA treatment.

PMID:35749704 | DOI:10.1089/photob.2022.0011

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Ethics Consultation Requests After Implementation of an Electronic Health Record Order

JCO Oncol Pract. 2022 Jun 24:OP2200174. doi: 10.1200/OP.22.00174. Online ahead of print.

ABSTRACT

PURPOSE: As the role of clinical ethics consultation in health care advances, there are calls to standardize the process of consultation. The Ethics Committee at Memorial Sloan Kettering Cancer Center (MSK) hypothesized that the process of requesting an ethics consultation could be improved by instituting an electronic health record (EHR) order for consultation requests. This report summarizes the impact of adopting an EHR order for ethics consultation requests at MSK.

METHODS: This retrospective review of all clinical ethics consultations requested at a tertiary cancer center from May 2017 to February 2020 spans 17 months before and after implementation of an electronic order for consultation requests. Summary statistics are presented using Pearson chi-square analyses with a significance level of 0.05.

RESULTS: There was a significant increase in the total number of consultation requests placed after implementation of the EHR order (n = 165, 0.08% of total patients) compared with before (n = 108, 0.05% of total patients; P = .007). The number of consults requested by providers from inpatient (P = .02) and outpatient (P = .04) settings significantly increased. The proportion of consults placed by medical versus nonmedical providers remained unchanged (P = .32).

CONCLUSION: In this large single-institution retrospective study, implementation of an EHR order for ethics consultation requests was associated with a significant increase in the number of consultation requests. Implementation of an electronic order may decrease barriers to ethics consultation in diverse practice settings. Further longitudinal, multicenter studies are needed to assess strategies to improve access to clinical ethics consultation for oncology patients.

PMID:35749678 | DOI:10.1200/OP.22.00174

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Defining Essential Childhood Cancer Medicines to Inform Prioritization and Access: Results From an International, Cross-Sectional Survey

JCO Glob Oncol. 2022 Jun;8:e2200034. doi: 10.1200/GO.22.00034.

ABSTRACT

PURPOSE: Access to essential cancer medicines is a major determinant of childhood cancer outcomes globally. The degree to which pediatric oncologists deem medicines listed on WHO’s Model List of Essential Medicines for Children (EMLc) essential is unknown, as is the extent to which such medicines are accessible on the front lines of clinical care.

METHODS: An electronic survey developed was distributed through the International Society of Pediatric Oncology mailing list to members from 87 countries. Respondents were asked to select 10 cancer medicines that would provide the greatest benefit to patients in their context; subsequent questions explored medicine availability and cost. Descriptive and bivariate statistics compared access to medicines between low- and lower-middle-income countries (LMICs), upper-middle-income countries (UMICs), and high-income countries (HICs).

RESULTS: Among 159 respondents from 44 countries, 43 (27%) were from LMICs, 79 (50%) from UMICs, and 37 (23%) from HICs. The top five medicines were methotrexate (75%), vincristine (74%), doxorubicin (74%), cyclophosphamide (69%), and cytarabine (65%). Of the priority medicines identified, 87% (27 of 31) are represented on the 2021 EMLc and 77% (24 of 31) were common to the lists generated by LMIC, UMIC, and HIC respondents. The proportion of respondents indicating universal availability for each of the top medicines ranged from 9% to 46% for LMIC, 25% to 89% for UMIC, and 67% to 100% for HIC. Risk of catastrophic expenditure was more common in LMIC (8%-20%), compared with UMIC (0%-28%) and HIC (0%).

CONCLUSION: Most medicines that oncologists deem essential for childhood cancer treatment are currently included on the EMLc. Barriers remain in access to these medicines, characterized by gaps in availability and risks of catastrophic expenditure for families that are most pronounced in low-income settings but evident across all income contexts.

PMID:35749676 | DOI:10.1200/GO.22.00034

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First report of Diplodia mutila causing wood necrosis in European hazelnut in Chile

Plant Dis. 2022 Jun 24. doi: 10.1094/PDIS-04-22-0869-PDN. Online ahead of print.

ABSTRACT

In Chile, the planted area of European hazelnut (Corylus avellana L.) reaches around 30,000 hectares, mainly concentrated in the central and southern area of the country where climate and soil provide a natural environment well suited to growing this species. Only a few diseases affect this nut tree in Chile. During the spring seasons in 2018 and 2020, European hazelnut plants (6 to 20% of incidence) exhibited wood necrosis and vascular discoloration of branches, with reduced growth, cankers and wilt branches, in orchards located in San Clemente and Curicó, Maule Region, Bulnes and El Carmen, Ñuble Region, Chile (36°45′-36°54′ S; 71°03′-72°26′ W). Symptomatic tissues were surface disinfected using a ~1% commercial sodium hypochlorite solution. Disinfected tissues were cut longitudinally, placed onto potato dextrose agar (PDA, Difco) plates, and incubated at 25 °C in the dark for 48 hours. Fungal hyphal tips were taken and placed on PDA medium. A fungal species was consistently isolated from these lignified tissues. The mycelium was initially translucent (turning white in appearance), while the mature mycelium was aerial, varying in color from pale to dark gray (Munsell color code: colony edge mycelium 6Y-6 4 / 5G and colony center mycelium B6-PB 7 / 5PB). The production of pycnidia and conidia was induced using pine needles in water agar medium and incubated in the dark for 10 days. Hyaline unicellular conidia of 25 ± 1.1 µm (range 23.9 to 26.1 µm) long and 11 ± 0.5 µm (Range 10.5 to 11.5 µm) wide (n = 50) were obtained from black pycnidia. Based on the cultural and morphological characteristics observed, the pathogen was identified as a possible species of the family Botryosphaeriaceae (20 isolates). Molecular techniques were used to identify the species of pathogen, and three isolates (F154, F199, and F167) were analyzed by using Multilocus sequence typing to confirm the identity of the pathogen. Genes ITS (internal transcribed spacer region), tef-1 (translation elongation factor 1-alpha) and β-tub (β-tubulin) were amplified using endpoint PCR, with primers ITS1/ITS4 (White et al., 1990), EF1-728F/EF1-986R (Carbone & Kohn, 1999) and Bt2a/Bt2b (Glass & Donaldson, 1995), respectively. The segments were sequenced using the same primers, deposited in Gen Bank, and the accession numbers for each isolate were OM993582, OM993583, ON003481 for ITS, ON054936, ON054938, ON054937 for tef1 and ON054939, ON054941, ON054940 for β-tub, respectively. A phylogenetic tree was constructed using the maximum likelihood statistical method with the Tamura-Nei model based on a concatenated dataset of ITS region, tef1 and β-tubulin gene using Mega-X, and the three Chilean isolates (F154, F199, and F167) formed a single clade with the reference isolates of Diplodia mutila (Fr.) Mont. BLAST algorithm analyses indicated 100% identity to D. mutila for ITS (accession NR_144906), for tef-1 (accession MK573559), and for β-tubulin (accession MG952719). The pathogenicity of the three isolates was validated through Koch’s postulates. For this purpose, a trial was established in 6-year-old European hazelnut plants cv. Tonda Di Giffoni. Ten healthy branches were individually inoculated using actively growing mycelial discs from each isolate, while a disc of PDA without fungus was used as a control. Holes of 5-mm diameter were inoculated, making sure the mycelium was in contact with the wood. Finally, the wounds were sealed with plastic film to prevent external contamination and improve humidity conditions. After 120 days, each branch was cut longitudinal-sectioned to verify the presence of wood necrosis which arose between 3.0 to 16.2 mm of length around the point of inoculation. No necrosis was observed in the control. To confirm pathogenicity, infected tissues were cut into small pieces with sterile knives and scalpels, and surface disinfected with a 1% sodium hypochlorite solution for 1 min. The disinfected tissues were placed on PDA medium and incubated at 25°C in the dark until fungal growth was observed. Hyphal tips were taken from the mycelia developed from the pieces of wood, and placed on PDA medium in order to obtain pure isolates. The pathogenicity of the D. mutila isolates F154 and F199 was observed in 100% of the inoculated branches, while isolate F167 showed symptoms in 85% of the branches. The reisolated strains showed similar mycelial growth and microscopic fungal structures to those observed in the isolates used for inoculation. This is the first report of D. mutila affecting European hazelnut in Chile. This fungus has been recently reported affecting hazelnut in Oregon, USA (Wiman et al., 2019), causing similar symptoms to those observed in our study. In addition, D. mutila has been reported infecting walnut in Chile (Diaz et al. 2018) and native forest trees, specifically Araucaria araucana in Chile (Besoain et al., 2017). The presence of D. mutila in commercial hazelnut orchards in Chile highlights the need for epidemiological studies in order to understand the characteristics and impact of this pathogen and, based on this, develop adequate phytosanitary programs for its control.

PMID:35749665 | DOI:10.1094/PDIS-04-22-0869-PDN