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Single (375 mg/m2) vs. double dose of rituximab along with mycophenolate mofetil for children with steroid-dependent/frequently relapsing nephrotic syndrome: a multicentre open-label randomized controlled trial

Pediatr Nephrol. 2024 Dec 27. doi: 10.1007/s00467-024-06619-8. Online ahead of print.

ABSTRACT

BACKGROUND: Optimal dosing of rituximab when given with mycophenolate mofetil (MMF) for frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome (FRNS/SDNS) remains uncertain.

METHODS: This was a prospective, non-inferiority, open-label randomized controlled multicentre study. Children (2-18 years old) with difficult FRNS/SDNS were randomized to group A (rituximab 375 mg/m2 once) or group B (rituximab 375 mg/m2 twice; 7-14 days apart) followed by continuous MMF and 3 months of tapered steroids. Primary outcome at an 18-month follow-up was time to first relapse. Secondary outcomes included post rituximab time to CD19 repopulation, sustained remission and significant adverse events (SAEs).

RESULTS: Ninety-six children (median age 8.6 years; IQR 6.4 to 11.3 years, 72% male) were randomized, 48 per arm. CD19 depletion (< 1%) was achieved in both groups. Three from single dose and two from double dose arm were lost to follow-up or withdrew. After 18 months, although non-inferiority could not be demonstrated, there was no difference in primary outcome either by intention-to-treat or per-protocol analysis. The restricted mean time to first relapse was 14.5 months (95% CI 13.1-15.9) in group A and 14.8 months (95% CI 13.5-16.1) in group B (p = 0.69). Relapse rate was similar between group A (19/45; 42%) and group B (16/46; 35%) (p = 0.53, hazard ratio 0.86 (95% CI 0.46-1.6)). Secondary outcomes were also similar between the groups.

CONCLUSIONS: Among children with FRNS/SDNS although non-inferiority could not be demonstrated, no statistically significant difference in outcome was found between 375 and 750 mg/m2 rituximab when accompanied with MMF.

PMID:39729126 | DOI:10.1007/s00467-024-06619-8

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ASYMPTOMATIC INFLAMMATORY BOWEL DISEASE DIAGNOSED DURING COLORECTAL CANCER POPULATION SCREENING IN CATALONIA: CHARACTERISTICS AND NATURAL HISTORY

Clin Transl Gastroenterol. 2024 Dec 26. doi: 10.14309/ctg.0000000000000740. Online ahead of print.

ABSTRACT

INTRODUCTION: Inflammatory bowel disease (IBD) is usually diagnosed when symptomatic. Prognosis and evolution of preclinical IBD is largely unknown. However, colorectal cancer screening programs (CRCSP) detect a subset of IBD patients with no symptoms. The aim of this study is to describe the natural history of asymptomatic IBD diagnosed through CRCSP.

METHODS: An observational, longitudinal and retrospective study was performed at 22 centres in Catalonia between January 2010 and December 2019 including patients with asymptomatic IBD detected in the CRCSP. Demographic data and IBD characteristics, evolution and treatment were recorded. Descriptive statistics and Kaplan-Meier analysis were used for the analysis. Data were given separately for IBD, Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU).

RESULTS: One hundred and eighty-eight patients were included: 103 UC (54.8%), 60 CD (31.9%) and 25 IBDU (13.3%). Sixty-six (35.1%) were women and the average age was 59.9 ± 5.9 years. Sixty-four patients (34.0%) developed symptoms after a median follow-up of 35.6 months. Diarrhoea was the most frequent symptom for CD and IBDU (25.4% and 11.5% respectively) and blood in stools for UC (21.4%). Median time to first symptom was 11.6 months. Treatment was prescribed in 135 patients (72.2%); mesalazine was the most prescribed drug (123 patients; 65.4%). Thirteen patients (6.9%) required biological treatment. None underwent surgery.

CONCLUSION: Around one-third of asymptomatic IBD patients developed symptoms after a medium follow-up of 3 years. Only 6.9% required biological treatment and none required surgery. Overall, prognosis of asymptomatic IBD seems better.

PMID:39729123 | DOI:10.14309/ctg.0000000000000740

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Fire and seed dormancy: A global meta-analysis

Ann Bot. 2024 Dec 27:mcae229. doi: 10.1093/aob/mcae229. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Fire-released seed dormancy (SD) is a key trait for successful germination and plant persistence in many fire-prone ecosystems. Many local studies have shown that fire-released SD depends on heat and exposure time, dose of smoke-derived compounds, SD class, plant lineage and the fire regime. However, a global quantitative analysis of fire-released SD is lacking. We hypothesized that fire-released SD is more prevalent in fire-prone than in non-fire-prone ecosystems, and in crown-fire compared to surface-fire ecosystems. Additionally, uncovering patterns in the relationship between fire cues and SD classes at the global scale that mirror those identified in local or regional studies was expected.

METHODS: Totally, 246 published germination studies during 1970-2022, encompassing 1782 species from 128 families was used in our meta-analysis. Meta-analysis moderators included different fire cues, smoke application methods, smoke exposure duration and concentration, smoke compounds, fire-proneness, fire regimes, and ecosystem types.

KEY RESULTS: Heat released physical, and smoke released physiological and morphophysiological dormancies. For SD release, heat and smoke acted synergistically, and KAR1 was the most effective smoke compound. Fire-released SD was more prevalent in fire-prone than non-fire-prone regions; and particularly under crown fire regimes. Fire-released SD occurred mainly in Mediterranean ecosystems, temperate dry forests, and temperate warm ecosystems, whereas species from savannas and tropical grasslands, temperate grasslands, and tropical rainforests generally responded negatively to fire.

CONCLUSIONS: Fire-released SD is strongly influenced by fire regimes the latter with significant role in shaping SD and germination patterns on a global scale. The synergistic effect of heat and smoke in dormancy release reveals more intricate interactions between fire cues than previously understood. Understanding these patterns is crucial in the context of shifting fire regimes driven by climate change, as they may disrupt plant life cycles, alter ecosystem functions, biodiversity, and community composition and provide key insights for biodiversity conservation and ecological restoration in fire-prone ecosystems.

PMID:39727142 | DOI:10.1093/aob/mcae229

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Spatiotemporal dynamics of forest cover and its response to climate change in Shandong Province, China during 2000-2022.

Ying Yong Sheng Tai Xue Bao. 2024 Oct;35(10):2803-2812. doi: 10.13287/j.1001-9332.202410.024.

ABSTRACT

Accurately capturing the spatiotemporal dynamics of regional forest cover and its response to climate change is of great significance for forest resource management and ecological environment protection. We used statistical methods such us linear regression and correlation analysis, as well as remote sensing change monitoring to investigate the spatiotemporal dynamics of forest cover and its response to climate change from 2000 to 2022 in Shandong Province based on MODIS VCF products and meteorological data. The results showed that the forest co-verage and forest area in Shandong Province increased from 43.0% and 197.06×104 hm2 in 2000 to 43.1% and 326.08×104 hm2 in 2022, respectively. Spatially, forest coverage grew stepwise from the southwest and northwest to the center and east of Shandong. 90.6% of the forest area of Shandong Province experienced a relative increase in forest cover during 2000-2022. Most of the increased area was concentrated in the central southern mountains and hills and the eastern low mountains and hills. The area expansion of forest cover was primarily located in the lowland areas of Liaocheng, Dezhou, Heze, Jining, and Binzhou, which accounted for 52.3% of the provincial forest area. There was a positive correlation between forest coverage and air temperature, but a negative correlation between forest coverage and precipitation. Air temperature was the main climatic factor influencing the shift in forest coverage during the study period.

PMID:39727127 | DOI:10.13287/j.1001-9332.202410.024

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Perivascular Invasion: A Promising Prognostic Parameter for Breast Cancer

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

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Smoking, Genetic Susceptibility and Early Menopause: Unveiling Biological Mechanisms and Potential Therapy Targets

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

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Impact of Bifurcation Lesions on Outcomes After FFR-Guided PCI or CABG

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 (Pinteraction=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

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Predicting phage-host interactions via feature augmentation and regional graph convolution

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

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The Utility of Secondary Data Analysis in Breastfeeding Research: Opportunities and Challenges

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

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Recovery Following Recurrent Fires Across Mediterranean Ecosystems

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