Nevin Manimala

Medeni Med J. 2024 Dec 27;39(4):302-308. doi: 10.4274/MMJ.galenos.2024.66169.

ABSTRACT

OBJECTIVE: Angiotropism/perivascular invasion (PVI) is an emerging topic in various types of cancer, with studies primarily focusing on melanoma. However, limited data are available on the significance of PVI in breast cancer. This study aimed to assess the prognostic significance of PVI in breast cancer and its correlation with traditional clinicopathological prognostic parameters.

METHODS: A total of 150 patients with breast cancer diagnosed between July 2020 and January 2022 were included. Clinicopathological data were retrieved from the hospital records. The presence of PVI was evaluated on hematoxylin&eosin stained slides, and the association between PVI and clinicopathological parameters was statistically analyzed. A p-value of <0.05 was regarded as statistically significant.

RESULTS: All patients were female. The mean age was 54.0±13.6 years (range 26-97 years). PVI was significantly more common in patients with ≥2.5 cm tumors and the absence of PVI showed a significant correlation with a lower histologic grade (p=0.004 and p=0.040, respectively). Lymphovascular invasion (LVI) and perineural invasion (PNI) were also significantly more frequent in tumors with PVI (p=0.001 and 0.02, respectively). There was a statistically significant association between the absence of both PVI and extranodal extension (ENE) (p=0.035).

CONCLUSIONS: The specific role of PVI in different types of cancer has not yet been clarified. Our findings showed that PVI was significantly associated with tumor size, histological grade, LVI, PNI, and ENE, all of which are well-known negative prognostic factors in breast cancer. The presence of PVI is a promising topic in breast cancer research, and the PVI status in pathology reports may help oncologists perform better risk assessments for patients with breast carcinoma.

PMID:39727072 | DOI:10.4274/MMJ.galenos.2024.66169

BJOG. 2024 Dec 27. doi: 10.1111/1471-0528.18052. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the association between smoking, genetic susceptibility and early menopause (EM) and clarify the potential mechanisms underlying this relationship.

DESIGN: An observational and Transcriptome-wide association analysis (TWAS) study.

SETTING: UK Biobank and public summary statistics.

POPULATION: 139 869 women with full baseline and menopause data, and no gynaecological surgery history.

METHODS: Adjusted modified Poisson regression models were developed to determine the smoking and genetic risk effects on EM. TWAS was used to identify gene expression between smoking and EM, with Mendelian randomisation (MR) to infer causality. Enrichment analysis explored regulatory networks of transcription factors, microRNAs and potential therapeutic targets. Small molecule drugs were predicted using drug-gene interaction analysis.

MAIN OUTCOME MEASURES: EM prevalence and common gene expression patterns.

RESULTS: Women with over 30 pack-years of smoking had about 1.5 times higher EM risk, with RRs of 1.39 (95%CI, 1.23-1.56), 1.45 (1.33-1.59) and 1.45 (1.36-1.55) in the low, intermediate and high genetic risk groups. TWAS identified hub genes such as IMMP2L, BMPR2 and HMGN1. MR confirmed daily cigarette consumption as a causal factor in early menopause. Several potential therapeutic targets (e.g., SP600125, INCB18424 and ruxolitinib) were identified.

CONCLUSIONS: Smoking reduction significantly lowered the risk of EM. Hub genes and therapeutic targets identified provided new avenues for mitigating harmful effects of smoking.

PMID:39727065 | DOI:10.1111/1471-0528.18052

Circ Cardiovasc Interv. 2024 Dec 27:e014610. doi: 10.1161/CIRCINTERVENTIONS.124.014610. Online ahead of print.

ABSTRACT

BACKGROUND: In the era of first-generation drug-eluting stents and angiography-guided percutaneous coronary intervention (PCI), the presence of a bifurcation lesion was associated with adverse outcomes after PCI. In contrast, the presence of a bifurcation lesion had no impact on outcomes following coronary artery bypass grafting (CABG). Therefore, the presence of a coronary bifurcation lesion requires special attention when choosing between CABG and PCI. The aim of this study is to assess whether the presence of a bifurcation lesion still influences clinical outcomes after contemporary PCI using second-generation drug-eluting stent and fractional flow reserve (FFR) guidance versus CABG.

METHODS: The randomized FAME 3 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) compared FFR-guided PCI using current drug-eluting stents with CABG in patients with 3-vessel coronary artery disease. The prespecified key end point at 3-year follow-up was the composite of death, myocardial infarction, or stroke. In this substudy, the impact of bifurcation lesions on outcomes after FFR-guided PCI and CABG was investigated.

RESULTS: The FAME 3 trial enrolled 1500 patients and 653 (45.2%) patients had at least 1 true bifurcation lesion. There was no difference in the composite of death, myocardial infarction, or stroke at the 3-year follow-up between patients with or without at least 1 true bifurcation lesion (11.6% versus 10.0%; hazard ratio, 1.17 [95% CI, 0.86-1.61]; P=0.32), regardless of revascularization strategy. The composite end point was not statistically different between FFR-guided PCI and CABG in patients with at least 1 true bifurcation lesion (hazard ratio, 1.27 [95% CI, 0.80-2.00]) or without a true bifurcation lesion (hazard ratio, 1.36 [95% CI, 0.87-2.12]), with no significant interaction (P_interaction=0.81).

CONCLUSIONS: In patients with 3-vessel coronary artery disease, the presence of a true bifurcation lesion was not associated with a different treatment effect after FFR-guided PCI with contemporary drug-eluting stent versus CABG.

PMID:39727036 | DOI:10.1161/CIRCINTERVENTIONS.124.014610

Brief Bioinform. 2024 Nov 22;26(1):bbae672. doi: 10.1093/bib/bbae672.

ABSTRACT

Identifying phage-host interactions (PHIs) is a crucial step in developing phage therapy, which is the promising solution to addressing the issue of antibiotic resistance in superbugs. However, the lifestyle of phages, which strongly depends on their host for life activities, limits their cultivability, making the study of predicting PHIs time-consuming and labor-intensive for traditional wet lab experiments. Although many deep learning (DL) approaches have been applied to PHIs prediction, most DL methods are predominantly based on sequence information, failing to comprehensively model the intricate relationships within PHIs. Moreover, most existing approaches are limited for sub-optimal performance, due to the potential risk of overfitting induced by the highly data sparsity in the task of PHIs prediction. In this study, we propose a novel approach called MI-RGC, which introduces mutual information for feature augmentation and employs regional graph convolution to learn meaningful representations. Specifically, MI-RGC treats the presence status of phages in environmental samples as random variables, and derives the mutual information between these random variables as the dependency relationships among phages. Consequently, a mutual information-based heterogeneous network is construted as feature augmentation for sequence information of phages, which is utilized for building a sequence information-based heterogeneous network. By considering the different contributions of neighboring nodes at varying distances, a regional graph convolutional model is designed, in which the neighboring nodes are segmented into different regions and a regional-level attention mechanism is employed to derive node embeddings. Finally, the embeddings learned from these two networks are aggregated through an attention mechanism, on which the prediction of PHIs is condcuted accordingly. Experimental results on three benchmark datasets demonstrate that MI-RGC derives superior performance over other methods on the task of PHIs prediction.

PMID:39727002 | DOI:10.1093/bib/bbae672

J Hum Lact. 2024 Dec 27:8903344241304623. doi: 10.1177/08903344241304623. Online ahead of print.

ABSTRACT

Secondary data analysis has emerged as an important approach for researchers seeking to explore new research questions using existing datasets. These datasets often comprise large and diverse, as well as longitudinal data, enabling comprehensive analyses that might be impractical through primary data collection alone. This paper discusses the importance of secondary data analysis in breastfeeding research, provides examples of publicly available and restricted datasets containing breastfeeding variables, outlines the methodological steps in conducting secondary data analysis, and discusses common limitations associated with this approach. By emphasizing both the utility and challenges of secondary data analysis, the paper aims to encourage informed use of secondary data analysis to advance knowledge and address important research questions in breastfeeding.

PMID:39726998 | DOI:10.1177/08903344241304623

Glob Chang Biol. 2024 Dec;30(12):e70013. doi: 10.1111/gcb.70013.

ABSTRACT

In fire-prone regions such as the Mediterranean biome, fire seasons are becoming longer, and fires are becoming more frequent and severe. Post-fire recovery dynamics is a key component of ecosystem resilience and stability. Even though Mediterranean ecosystems can tolerate high exposure to extreme temperatures and recover from fire, changes in climate conditions and fire intensity or frequency might contribute to loss of ecosystem resilience and increase the potential for irreversible changes in vegetation communities. In this study, we assess the recovery rates of burned vegetation after recurrent fires across Mediterranean regions globally, based on remotely sensed Enhanced Vegetation Index (EVI) data, a proxy for vegetation status, from 2001 to 2022. Recovery rates are quantified through a statistical model of EVI time-series. This approach allows resolving recovery dynamics in time and space, overcoming the limitations of space-for-time approaches typically used to study recovery dynamics through remote sensing. We focus on pixels burning repeatedly over the study period and evaluate how fire severity, pre-fire vegetation greenness, and post-fire climate conditions modulate vegetation recovery rates of different vegetation types. We detect large contrasts between recovery rates, mostly explained by regional differences in vegetation type. Particularly, needle-leaved forests tend to recover faster following the second event, contrasting with shrublands that tend to recover faster from the first event. Our results also show that fire severity can promote a faster recovery across forested ecosystems. An important modulating role of pre-fire fuel conditions on fire severity is also detected, with pixels with higher EVI before the fire resulting in stronger relative greenness loss. In addition, post-fire climate conditions, particularly air temperature and precipitation, were found to modulate recovery speed across all regions, highlighting how direct impacts of fire can compound with impacts from climate anomalies in time and likely destabilise ecosystems under changing climate conditions.

PMID:39726993 | DOI:10.1111/gcb.70013

Front Microbiol. 2024 Dec 12;15:1504742. doi: 10.3389/fmicb.2024.1504742. eCollection 2024.

ABSTRACT

This study aimed to screen native methionine gamma-lyase (L-methioninase) producing bacteria from soil samples and optimize the culture media for enhanced enzyme production using statistical design. Three bacteria, Pseudomonas mosselii, Ralstonia solanacearum, and Cytobacillus kochii, were identified as novel L-methioninase producers, which alternative source of L-methioninase for cancer treatment could be utilized alongside other therapeutic agents. The bacteria were isolated from various garden soils and cultured on a modified M9 medium and screened by Nessler reagent. According to Bergey’s manual of systematic bacteriology, identification tests determined the morphological, physiological, and biochemical characterizations. Further identification was performed using the analysis of the 16 s rDNA gene sequences using PCR and universal bacterial primers. The optimization of medium constituents for L-methioninase production was performed in two steps using Response Surface Methodology (RSM). The first step used the “one factor at a time” method to screen and identify critical medium components for L-methioninase production. The second step used the Box-Behnken design to assess quadratic effects and two-way interactions between variables and determine the response’s nonlinear nature. The study found that three isolates produced L-methioninase, namely Pseudomonas mosselii spp.MN02 (GenBank PP431975), Ralstonia solanacearum spp.MN02 (GenBank PP431636), and Cytobacillus kochii spp.MN02 (GenBank PP432622). Among these, Pseudomonas mosselii spp.MN02 produced the highest amount of L-methioninase and was therefore chosen for enzyme production optimization process. The maximum L-methioninase production of 1.5 ± 0.1 U/mL was obtained at a pH 6, and the best nitrogen source was yeast extract (1% concentration). The influence of different carbon sources revealed that glucose was the best carbon source for L-methioninase production (3.25 ± 0.1 U/mL). The optimization experiments using the Box-Behnken design predicted that L-methioninase would have an activity of 12.56 U/mL under optimal conditions, including 2% glucose, 2% yeast extract, pH 6, and temperature at 30°C. In conclusion, this study presents a promising new methods for identifying potential L-methioninase producers and optimizing the culture medium for more enzyme production by microbial fermentation. This could pave the way for developing a drug that assists in human cancers treatment.

PMID:39726960 | PMC:PMC11669666 | DOI:10.3389/fmicb.2024.1504742

Front Microbiol. 2024 Dec 11;15:1491551. doi: 10.3389/fmicb.2024.1491551. eCollection 2024.

ABSTRACT

Yak (Bos grunniens) is a large ruminant endemic to the Tibetan plateau. The addition of enzyme complexes to feed can significantly improve their growth performance. Therefore, studying the effects of ruminant compound enzyme preparations dosage on yak rumen microorganisms and production performance is crucial to promoting the development of the yak industry. This study aimed to determine the effects of feeding yaks with different doses of ruminant enzyme compounds on the performance, meat quality, and rumen microorganisms of yaks. Three kinds of experimental diets with doses of 0.5 g/kg (LE group), 1 g/kg (ME group), and 2 g/kg (HE group) were selected to determine the growth index, meat quality, serum biochemical indexes, rumen fluid pH and other indexes of the three experimental groups. Metagenomics studies were used to investigate the differences in rumen microbial composition and function among yak groups, and transcriptome sequencing of the longest dorsal muscle was performed to reveal the expression of differential genes among different groups. It was determined that the levels of dietary enzyme complexes significantly affected growth performance, rumen fluid pH, and serum biochemical indices. At the phylum level, the dominant phylum in all three treatment groups was Bacteroidota, Bacillota, Kiritimatiellota, and Pseudomonadota. At the genus level, Prevotella, Methanobrevibacter, Oscillibacter. Fibrobacter showed statistically significant differences in abundance (p < 0.05). CAZymes family analysis revealed significant differences in GHs, CTs, and CEs among the three groups. Genome-wide differential gene expression in the longest muscle of the yak back was analyzed by RNA-seq between the three experimental groups. Some DEGs were found to be enriched in the ECM, PI3K-Akt, PPAR, and protein digestion and absorption receptor pathways. Combined metagenomics and transcriptomics analyses revealed that some microorganisms were significantly associated with the genes COL11A1, POSTN, and PTHLH, which are involved in growth metabolism. In summary, this study investigated the effects and interrelationships of ruminant complex enzymes on yak performance, meat quality, and rumen environment. The results of this study provide a scientific basis for adding ruminant enzymes to yaks.

PMID:39726957 | PMC:PMC11670318 | DOI:10.3389/fmicb.2024.1491551

Front Genet. 2024 Dec 12;15:1488425. doi: 10.3389/fgene.2024.1488425. eCollection 2024.

ABSTRACT

BACKGROUND: Noonan syndrome (NS) is a rare group of autosomal genetic disorders. In recent years, with the exploration and development of molecular diagnostic techniques, more and more researchers have begun to pay attention to NS. However, there is still a lack of reports on the bibliometric analysis of NS worldwide. This study aims to assess the current research status and development trend of NS, to explore the research hotspots and emerging topics, and to point out the direction for future scientific research.

METHODS: Web of Science Core Collection was selected as the search database for bibliometric analysis of NS-related publications from 1998 to 2023. Statistical and visual analysis of the number of publications, countries, institutions, authors, journals, keywords, and references were analyzed using Citespace, VOSviewer, Scimago Graphica, and BibliometrixR.

RESULTS: A total of 2041 articles were included in this study. The United States had the highest number of publications, and Istituto Superiore di Sanità, Italy, was the institution with the highest number of publications. TARTAGLIA M was the scientist with the highest number of publications and citations. Among the journals, AMERICAN JOURNAL OF MEDICAL GENETICS PART A has the highest output, and Nature Genetics is the most frequently cited. The reference with the highest outburst intensity is Roberts AE, LANCET, 2013. the cluster diagram divides all the keywords into seven categories, with the most vigorous outburst being “of function mutations.”

CONCLUSION: Research hotspots in the field of NS focus on the correspondence between NS genotype and phenotype and the precise diagnosis of NS. Future research efforts will explore more deeply from the perspective of long-term intervention strategies for NS. There is an urgent need to rely on significant research countries, institutions, journals, and authors to lead the construction of a more robust global collaborative network that will enhance research efficacy.

PMID:39726952 | PMC:PMC11669677 | DOI:10.3389/fgene.2024.1488425

Front Cardiovasc Med. 2024 Dec 12;11:1475483. doi: 10.3389/fcvm.2024.1475483. eCollection 2024.

ABSTRACT

BACKGROUND AND OBJECTIVES: The optimal timing for complete revascularization (CR) in patients with acute myocardial infarction (AMI) and multivessel disease (MVD) remain uncertain.

METHODS: This post-hoc analysis of the FRAME-AMI trial included AMI patients with MVD (n = 549). They were classified into immediate (n = 329) and staged CR (n = 220) groups. All percutaneous coronary interventions were performed during inex hospitalization. The primary endpoint was a composite of all-cause death, acute myocardial infarction, and repeated revascularization. Secondary endpoints included each component of the primary endpoint. Additional comparisons for the outcomes in ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) were also performed.

RESULTS: The incidence of the primary endpoint was not significantly different in any of the AMI patients [12.7% [immediate CR] vs. 17.4% [staged CR], p = 0.905, adjusted hazard ratio [HR] of staged CR = 0.81, 95% confidence interval = 0.43-1.53, p = 0.528]. Other secondary endpoints were also not significantly different. Analyses of STEMI and Neither the primary or secondary endpoints of NSTEMI patients were significantly different.

CONCLUSIONS: In this post-hoc analysis of the FRAME-AMI trial, no significant difference in clinical outcomes was observed between the immediate and staged CR strategies for AMI with MVD and the subgroups, such as STEMI or NSTEMI. However, the results should be interpreted carefully because of the many limitations, including a limited sample size and a lack of statistical power. Trial Registration: FRAME-AMI clinicaltrials.gov, identifier (NCT02715518).

PMID:39726942 | PMC:PMC11669547 | DOI:10.3389/fcvm.2024.1475483