Tag: pubmed

Med Phys. 2022 Nov 13. doi: 10.1002/mp.16059. Online ahead of print.

ABSTRACT

Resistance of high grade tumors to treatment involves cancer stem cell features, deregulated cell division, acceleration of genomic errors, and emergence of cellular variants that rely upon diverse signaling pathways. This heterogeneous tumor landscape limits the utility of the focal sampling provided by invasive biopsy when designing strategies for targeted therapies. In this roadmap review paper, we propose and develop methods for enabling mapping of cellular and molecular features in vivo to inform and optimize cancer treatment strategies in the brain. This approach leverages 1) the spatial and temporal advantages of in vivo imaging compared with surgical biopsy, 2) the rapid expansion of meaningful anatomical and functional MR signals, 3) widespread access to cellular and molecular information enabled by next generation sequencing, and 4) the enhanced accuracy and computational efficiency of deep learning techniques. As multiple cellular variants may be present within volumes below the resolution of imaging, we describe a mapping process to decode micro- and even nano-scale properties from the macro-scale data by simultaneously utilizing complimentary multiparametric image signals acquired in routine clinical practice. We outline design protocols for future research efforts that marry revolutionary bioinformation technologies, growing access to increased computational capability, and powerful statistical classification techniques to guide rational treatment selection. This article is protected by copyright. All rights reserved.

PMID:36371678 | DOI:10.1002/mp.16059

J Pathol. 2022 Nov 13. doi: 10.1002/path.6028. Online ahead of print.

ABSTRACT

Esophageal basaloid squamous cell carcinoma (bSCC) is a subtype of squamous cell carcinoma (SCC) with different behavior and poor prognosis. Exploring bSCC’s molecular characteristics and treatment strategies are of great clinical significance. We performed multi-omics analysis of paired bSCC and common SCC (cSCC) using Whole Exome Sequencing and a NanoString nCounter gene expression panel. Immunohistochemistry was used for verification of candidate biomarkers. Different treatment response was analyzed on both patients receiving neoadjuvant treatment and on late-stage patients. The common genetically-clonal origin of bSCC and cSCC was confirmed. No significant differences between their genetic alterations or mutation spectra were observed. Mutation signature 15 (associated with defective DNA damage repair) was less prominent, and TMB was lower in bSCC. bSCC with RNA expression pattern resembling cSCC had better survival than other bSCC. Moreover, bSCC showed significant upregulation of expression of genes associated with angiogenesis response, basement membranes, epithelial-mesenchymal transition, and downregulation of KRT14 (squamous differentiation) and of CCL21 (associated with immune response). Immunohistochemistry for SFRP1 was shown to be highly sensitive and specific for bSCC diagnosis (p<0.001). In addition, bSCC receiving neoadjuvant immuno-chemotherapy had worse pathological response than neoadjuvant chemotherapy (but without statistical significance), even in bSCC positive for PD-L1. Our results demonstrated the molecular characteristics of esophageal bSCC as a subtype with distinct RNA expression pattern and immune characteristics, but no specific genetic mutations. We provided a useful biomarker, SFRP1, for diagnosis. With outcome analysis for 6 bSCCs with neoadjuvant immunotherapy treatment and 4 late-stage bSCCs with immunotherapy, we found that immunotherapy may not be an effective treatment option for most bSCC. This may also provide a clue for the same subtypes of lung and head and neck cancer. Our study highlighted the heterogeneity among bSCC patients, and might explained the conflicting results of bSCC outcomes in existing studies. This article is protected by copyright. All rights reserved.

PMID:36371676 | DOI:10.1002/path.6028

Eur J Neurol. 2022 Nov 12. doi: 10.1111/ene.15632. Online ahead of print.

ABSTRACT

BACKGROUND: Approximately 30% of epilepsy patients develop a drug-refractory epilepsy (DRE), i.e., seizures cannot be controlled with antiepileptic drugs. Surgery has been evaluated as an effective, but costly form of treatment. The aim of this systematic review is to synthesize the available evidence on the cost-effectiveness of surgical treatment compared to medical treatment for these patients.

METHODS: A systematic literature search was performed in MEDLINE, EMBASE, PsycINFO, Cochrane Library, and NHS EED until September 2022. Title, abstract, and full-text screening were conducted by two researchers. We included original studies published in English or German analyzing the cost-effectiveness of surgical compared to medical treatment. Study characteristics, effectiveness measures, costs, and incremental cost-effectiveness ratios (ICERs) were extracted. The quality of studies was assessed using the Drummond checklist.

RESULTS: 14 studies were included. Most studies evaluated surgery as cost-effective: The ICER per patient seizure free ranged from dominant to purchasing power parity US dollars (PPP-USD) 479,275. The ICER per 1% seizure reduction ranged from PPP-USD 227 to PPP-USD 342. The ICER per year without seizures was PPP-USD 4,202 and the ICER per QALY ranged from dominant to PPP-USD 90,874. The studies varied greatly in their methodology and time horizon.

CONCLUSION: Surgical treatment is cost-effective compared to medical treatment, especially when a lifetime horizon is adopted. We conclude that all disease-specific costs should be considered over a long period when assessing the cost-effectiveness of epilepsy treatment. From an economic perspective, efforts should be made to improve access to surgical treatment for patients with DRE.

PMID:36371643 | DOI:10.1111/ene.15632

JPEN J Parenter Enteral Nutr. 2022 Nov 12. doi: 10.1002/jpen.2463. Online ahead of print.

ABSTRACT

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition has been associated with cancer mortality, while the effect is limited and inconsistent. We performed this meta-analysis aiming to assess this relationship in patients with cancer.

METHODS: We systematically searched Embase, PubMed, Web of Science, Cochrane, CINAHL, CNKI, Wanfang and VIP databases from 1 January 2019 to 1 July 2022. Studies evaluating the prognostic effect of GLIM-defined malnutrition on cancer survival were included. A fix-effect model was fitted to estimate the combined hazard ratio (HR) with 95% confidence interval (CI). Heterogeneity of studies was analyzed using the I² statistic. Quality assessment were performed using the Newcastle-Ottawa Scale (NOS) and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool.

RESULTS: The search strategy identified 4378 articles in all databases combined. Nine studies (8829 patients) met the inclusion criteria were included for quantitative analysis. Meta-analysis revealed significant associations between the GLIM-defined pooled malnutrition (HR=1.75, 95%CI=1.43 to 2.15), moderate malnutrition (HR=1.44, 95%CI=1.29 to 1.62) and severe malnutrition (HR=1.79, 95%CI=1.58 to 2.02) with all-cause mortality. Sensitivity analysis supported the robustness of these associations. The between-study heterogeneity was low (all I² < 50 %) and study quality assessed with NOS was high (all scores > 6). The evidence quality by the GRADE tool was very low.

CONCLUSIONS: Our meta-analysis suggests a significant negative association of malnutrition, as defined by the GLIM, with overall survival in patients with cancer. However, definitive conclusions cannot be precluded due to the low quality of the source data. This article is protected by copyright. All rights reserved.

PMID:36371641 | DOI:10.1002/jpen.2463

J Child Adolesc Psychiatr Nurs. 2022 Nov 12. doi: 10.1111/jcap.12401. Online ahead of print.

ABSTRACT

PROBLEM: (1) To identify the factors associated with self-reported smartphone addiction (SRSA) among adolescents in the face of the COVID-19 pandemic; and (2) to analyze the adolescents’ perception of these factors related to SRSA.

METHODS: A mixed-method study with a sequential explanatory design, carried out with Brazilian adolescents aged between 15 and 18 years old.

FINDINGS: The prevalence of SRSA was 56.37%, and the variables that remained in the final model of association were as follows: public schools; longer smartphone use during the COVID-19 pandemic; number of hours connected to the smartphone; preference for sleeping during the day; use of the device immediately after waking up, smartphone use after 9 p.m., amount of sleep less than 8 h a day; and smartphone use during meals. Sequentially, after analyzing the data obtained in the focus groups, it was possible to describe how adolescents perceive the intensification of smartphone uses, its repercussions, and activities carried out on it during the pandemic.

CONCLUSIONS: The pandemic had repercussions on the behavior established with the smartphone, such as time and period of use, being associated with the SRSA. In addition, it was found that such conditions also affect the adolescents’ sleep quality, diet, and studies.

PMID:36371611 | DOI:10.1111/jcap.12401

Sci Rep. 2022 Nov 12;12(1):19394. doi: 10.1038/s41598-022-24123-7.

ABSTRACT

We compared the visual performance of a diffractive bifocal intraocular lens (IOL) with + 4.0 D near addition (ZMB00 [Johnson & Johnson Surgical Vision]) and a rotationally asymmetric refractive IOL with + 1.5 D near addition (LS-313 MF15 [Teleon Surgical BV]) 10 weeks after cataract patients’ last surgery for bilateral ZMB00 or LS-313 MF15 implantation between 2011 and 2020, with the lenses of each eye implanted within 3 months of each other. The ZMB00 and LS-313 MF15 groups comprised 1326 eyes of 663 patients (age: 67.0 ± 7.8 years; females/males, 518/145) and 448 eyes of 224 patients (73.6 ± 7.0 years; females/males, 125/99), respectively. A linear mixed-effects model using data for both eyes, with strict adjustments for sex, age, subjective refraction spherical equivalent, subjective refraction cylinder, corneal astigmatism, axial length, corneal higher-order aberrations, and pupil diameter, ensured statistical validity. Compared to LS-313 MF15, ZMB00 achieved significantly superior uncorrected near visual acuity, reduced higher-order aberrations (ocular/internal, scaled to a 4-mm pupil; Wavefront_4_post_Ocular_Total Higher-Order Aberration/Third/Fourth/Trefoil/Coma/Tetrafoil/Spherical, Wavefront_4_post_Internal_Astigmatism/Total Higher-Order Aberration/Third/Trefoil/Coma/Tetrafoil/Spherical), and superior distance and near spectacle independence (p < 0.00068, Wald test). Contrast sensitivity, measured without (visual angle of the test target: 6.3°/4.0°/2.5°/1.6°/1.0°/0.7°) or with glare (4.0°/2.5°/1.6°/1.0°/0.7°), was significantly better in the LS-313 MF15 than the ZMB00 group (p < 0.00068, Wald test).

PMID:36371596 | DOI:10.1038/s41598-022-24123-7

Sci Rep. 2022 Nov 12;12(1):19383. doi: 10.1038/s41598-022-24153-1.

ABSTRACT

We explored the association between cholesterol levels and dementia risk according to the presence of diabetes and statin use. In this population-based longitudinal cohort study, the Korean National Health Insurance Service datasets (2002-2017) were used. Among individuals aged ≥ 40 years who underwent health examinations in 2009 (N = 6,883,494), the hazard of dementia was evaluated according to cholesterol levels. During a median 8.33 years, 263,185 dementia cases were detected. In statin non-users with or without diabetes, the hazards of all-cause dementia were highest for those in the lowest quartile or quintile of low-density lipoprotein-cholesterol (LDL-C) level, showing an inverted J-shaped relationship. Among statin users with or without diabetes, an advance in LDL-C group was associated with an increase in hazards of all-cause dementia. In statin users with diabetes, even very low LDL-C level was not associated with an increased risk of all-cause dementia. Although there was a seemingly paradoxical association between low LDL-C level and dementia risk in statin non-users, the trend was not observed in statin users and is not likely to be clinically relevant. Rather, an advance in LDL-C levels was associated with an increase in the hazard of all-cause dementia in statin users, regardless of the presence of diabetes.

PMID:36371594 | DOI:10.1038/s41598-022-24153-1

Environ Monit Assess. 2022 Nov 12;195(1):102. doi: 10.1007/s10661-022-10726-0.

ABSTRACT

Aphid (Aphis gossypii) is one of the important pests of papaya crop. In this work, applications of Trichoderma harzianum and Beauveria bassiana (biocontrol agents) and malathion (insecticide) were conducted in vitro and in agrifields for testing their anti-aphid efficacy and compared their efficacy. Furthermore, the enzymatic mechanism of T. harzianum with respect to biocontrolling the pest was unearthed. The LD₅₀ dose of T. harzianum and B. bassiana was 1.2 × 10⁵ spores mL^-1 and 1.0 × 10⁶ spores mL^-1 respectively after 48 h of administration. The LT₅₀ of T. harzianum also exhibited a lower effective time (47.70 h) than B. bassiana (57.53 h) for the same concentration of spores applied (1 × 10⁵ spores mL^-1). The pooled data analysis of two years (2019-2020) showed that the application of T. harzianum spores in agrifields exhibited 31.75 ± 13.00a percentage of reduction of aphid population whereas malathion exhibited 23.93 ± 1.30a%, in comparison to control. The statistical analysis indicated that the application of malathion exhibited the same efficacy as T. harzianum isolate and placed in the same category. In plate detection assay, T. harzianum produced a higher hydrolytic zone for chitinase (8.0 ± 0.4 cm diameter) and protease (7.0 ± 0.4 cm diameter) enzymes, than B. bassiana (1.3 ± 0.2 cm and 1.1 ± 0.2 cm respectively). Quantitative estimation of enzymes exhibited that T. harzianum produced 299 ± 11a μg mL^-1 of chitinase, 519 ± 19a μg mL^-1 of protease, and 65 ± 12a μg mL^-1 of PR1, and on the other hand, B. bassiana yielded 124 ± 12b, 361 ± 23b, and 29 ± 18b μg mL^-1 of chitinase, protease, and PR1 respectively. It indicated that T. harzianum was superior over the B. bassiana in terms of production capacity of all three enzymes. In conclusion, all the above experimental results suggested that T. harzianum showed better aphid-killing efficacy than B. bassiana. It also suggested that T. harzianum should replace hazardous chemical pesticide (malathion) for eco-friendly biocontrol of aphids.

PMID:36371583 | DOI:10.1007/s10661-022-10726-0

Mol Biol Rep. 2022 Nov 12. doi: 10.1007/s11033-022-08027-3. Online ahead of print.

ABSTRACT

BACKGROUND: microRNAs (miRNAs) play key roles in regulating cancer development, including breast cancer. Variation in miRNA genes can associate with the risk of cancer by alterations in the miRNA’s processing and maturation. Therefore, human blood samples and breast cancer cell line (MCF7) were analyzed to study any possible association between the genetic variant (rs2292832) in the miR-149 precursor and breast cancer susceptibility.

METHODS: To study the role of rs2292832 polymorphism in breast cancer, the miR-149 gene variant was genotyped using PCR-RFLP. For evaluating the effect of SNP on function and expression levels of mature miR-149, we inserted pre-miR-149 and flanking region with CC or TT genotype into a pEGFPN1 expression vector, and qPCR was accomplished. Cell survival, proliferation, and migration properties investigated by MTT and wound healing assay. Statistical analysis was carried out for data analysis.

RESULTS: T allele in variant rs2292832 is associated with an increased risk of breast cancer. Such association was also obtained in co-dominant (OR = 2.5) and dominant (OR = 2.016) models. The variant allele led to reduced production of mature miR-149 and resulted in increased cell proliferation and migration of MCF7 cells.

CONCLUSION: These findings suggest that miR-149 suppresses tumor cell proliferation, and the pre-mir-149 polymorphism affects the processing of miR-149, causing an alteration in the abundance of the miRNA mature form, which can regulate tumor progression and metastasis.

PMID:36371555 | DOI:10.1007/s11033-022-08027-3

Commun Biol. 2022 Nov 12;5(1):1234. doi: 10.1038/s42003-022-04197-9.

ABSTRACT

Designing useful functionalities in clinically validated, old antibiotics holds promise to provide the most economical solution for the global lack of effective antibiotics, as undoubtedly a serious health threat. Here we show that using the surface chemistry of the cyclodextrin (βCD) cycle and arginine (arg) as a linker, provides more stable ternary antibiotic complex (βCD-arg-cpx). In contrast to classical less stable inclusion complexes, which only modify antibiotic solubility, here-presented ternary complex is more stable and controls drug release. The components of the complex intensify interactions with bacterial membranes and increase the drug’s availability inside bacterial cells, thereby improving its antimicrobial efficacy and safety profile. Multifunctional antibiotics, formulated as drug delivery systems per se, that take the drug to the site of action, maximize its efficacy, and provide optical detectability are envisaged as the future in fighting against infections. Their role as a tool against multiresistant strains remains as interesting challenge open for further research.

PMID:36371541 | DOI:10.1038/s42003-022-04197-9