1. Lianas are a key component of tropical forests, where they compete intensely with trees, reducing tree recruitment, growth and survival. One of the most important potential outcomes of liana ...competition is the reduction of tree reproduction; however, no previous study has experimentally determined the effects of lianas on tree reproduction beyond a single tree species. 2. We used a large-scale liana removal experiment to quantify the effect of lianas on community-level canopy and understorey tree and palm reproduction. In 2011, we removed lianas from eight 6,400-m² plots (eight plots served as controls) and surveyed understorey tree reproduction in 2012, canopy tree and palm reproduction in 2013, and a second census of all plants in 2016. 3. We found that lianas significantly reduced canopy tree community flowering and fruiting after liana removal. Two years after liana removal, the number of canopy trees with fruits was 173% higher, fruiting individuals had 50% more of their canopy covered by fruits and the number of tree species with fruits was 169% higher than in control plots where lianas were present. Five years after liana removal, the number of canopy trees with fruits was 150% higher, fruiting individuals had 31% more of their canopy covered by fruits and the number of tree species with fruits was 109% higher than in unmanipulated control plots. 4. Liana removal had only a slight positive effect on palms and on understorey tree flower and fruit production, even though understorey light levels had increased 20% following liana cutting. 5. Synthesis. Our findings provide the first experimental demonstration that competition from lianas significantly reduces community-level canopy tree reproduction. Reduced reproduction increases canopy tree seed and dispersal limitations, and may interfere with deterministic mechanisms thought to maintain tropical canopy tree species diversity, as well as reduce food availability to many animal species. Because lianas are increasing in abundance in many neotropical forests, the effects of lianas on tree reproduction will likely increase, and if the effects of lianas on tree reproduction vary with tree species identity, lianas ultimately could have a destabilizing effect on both tree and animal population dynamics.
Background and Aims
We previously identified subsets of patients with NAFLD with different metabolic phenotypes. Here we align metabolomic signatures with cardiovascular disease (CVD) and genetic ...risk factors.
Approach and Results
We analyzed serum metabolome from 1154 individuals with biopsy‐proven NAFLD, and from four mouse models of NAFLD with impaired VLDL‐triglyceride (TG) secretion, and one with normal VLDL‐TG secretion. We identified three metabolic subtypes: A (47%), B (27%), and C (26%). Subtype A phenocopied the metabolome of mice with impaired VLDL‐TG secretion; subtype C phenocopied the metabolome of mice with normal VLDL‐TG; and subtype B showed an intermediate signature. The percent of patients with NASH and fibrosis was comparable among subtypes, although subtypes B and C exhibited higher liver enzymes. Serum VLDL‐TG levels and secretion rate were lower among subtype A compared with subtypes B and C. Subtype A VLDL‐TG and VLDL–apolipoprotein B concentrations were independent of steatosis, whereas subtypes B and C showed an association with these parameters. Serum TG, cholesterol, VLDL, small dense LDL5,6, and remnant lipoprotein cholesterol were lower among subtype A compared with subtypes B and C. The 10‐year high risk of CVD, measured with the Framingham risk score, and the frequency of patatin‐like phospholipase domain‐containing protein 3 NAFLD risk allele were lower in subtype A.
Conclusions
Metabolomic signatures identify three NAFLD subgroups, independent of histological disease severity. These signatures align with known CVD and genetic risk factors, with subtype A exhibiting a lower CVD risk profile. This may account for the variation in hepatic versus cardiovascular outcomes, offering clinically relevant risk stratification.
Endometriosis is a chronic inflammatory disorder characterized by the abnormal growth of endometrial-like tissue outside the uterine cavity, affecting 10–15% of women of reproductive age. Pain is the ...most common symptom. Treatment options include surgery, which has limited effectiveness and high recurrence rates, and pharmacotherapy. Hormonal therapies, commonly used for symptom management, can have side effects and contraceptive outcomes, contributing to the infertility associated with endometriosis, with pain and lesions often reappearing after treatment cessation. Among its etiological factors, immunological and inflammatory dysregulation plays a significant role, representing an interesting target for developing new therapeutic strategies. This review critically analyzes recent studies to provide an updated synthesis of ongoing research into potential new pharmacotherapies focusing on lesion progression, pain relief, and improving quality of life. Immunotherapy, natural anti-inflammatory and antioxidant compounds and drug repurposing show promise in addressing the limitations of current treatments by targeting immunological factors, potentially offering non-invasive solutions for managing pain and infertility in endometriosis. Promising results have been obtained from in vitro and animal model studies, but clinical trials are still limited. More effort is needed to translate these findings into clinical practice to effectively reduce disease progression, alleviate pain symptoms and preserve the reproductive capacity, improving patients’ overall wellbeing.
Lianas are a common plant growth form in tropical forests, where they compete intensely with trees, decreasing tree recruitment, growth, and survival. If the detrimental effects of lianas vary ...significantly with tree species identity, as is often assumed, then lianas may influence tree species diversity and community composition. Furthermore, recent studies have shown that liana abundance and biomass are increasing relative to trees in neotropical forests, which will likely magnify the detrimental effects of lianas and may ultimately alter tree species diversity, relative abundances, and community composition. Few studies, however, have tested the responses of multiple tree species to the presence of lianas in robust, well‐replicated experiments. We tested the hypotheses that lianas reduce tree seedling growth and survival, and that the effect of lianas varies with tree species identity. We used a large‐scale liana removal experiment in Central Panama in which we planted 14 replicate seedlings of 14 different tree species that varied in shade tolerance in each of 16 80 × 80 m plots (eight liana‐removal and eight unmanipulated controls; 3136 total seedlings). Over a nearly two‐yr period, we found that tree seedlings survived 75% more, grew 300% taller, and had twice the aboveground biomass in liana‐removal plots than seedlings in control plots, consistent with strong competition between lianas and tree seedlings. There were no significant differences in the response of tree species to liana competition (i.e., there was no species by treatment interaction), indicating that lianas had a similar negative effect on all 14 tree species. Furthermore, the effect of lianas did not vary with tree species shade tolerance classification, suggesting that the liana effect was not solely based on light. Based on these findings, recently observed increases in liana abundance in neotropical forests will substantially reduce tree regeneration, but will not significantly alter tropical tree species diversity, relative abundance, or community composition.
To analyze trends in urinary tract infection hospitalization (cystitis, pyelonephritis, prostatitis and non-specified UTI) among patients over 65 years in Spain from 2000-2015. We conducted a ...retrospective observational study using the Spanish Hospitalization Minimum Data Set (CMBD), with codifications by the International Classification of Diseases (ICD-9). We collected data on sex, age, type of discharge, main diagnosis, comorbid diagnosis, length of stay, and global cost. All the hospitalizations were grouped by age into three categories: 65-74 years old, 75-84 years old, and 85 years old and above. In the descriptive statistical analysis, crude rates were defined as hospitalizations per 1,000 inhabitants aged greater than or equal to65. To identify trends over time, we performed a Joinpoint regression. From 2000-2015, we found 387,010 hospitalizations coded as UTIs (54,427 pyelonephritis, 15,869 prostatitis, 2643 cystitis and 314,071 non-specified UTI). The crude rate of hospitalization for UTIs between 2000 and 2015 ranged from 2.09 in 2000 to 4.33 in 2015 Rates of hospitalization were higher in men than in women, except with pyelonephritis. By age group, higher rates were observed in patients aged 85 years or older, barring prostatitis-related hospitalizations. Joinpoint analyses showed an average annual percentage increase (AAPC) in incidence rates of 4.9% (95% CI 3.2;6.1) in UTI hospitalizations. We observed two joinpoints, in 2010 and 2013, that found trends of 5.5% between 2000 and 2010 (95% CI 4.7;6.4), 1.5% between 2010 and 2013 (95% CI -6.0;9.6) and 6.8% between 2013 and 2015 (95% CI -0.3;14.4). The urinary infection-related hospitalization rate in Spain doubled during the period 2000-2015. The highest hospitalization rates occurred in men, in the greater than or equal to85 years old age group, and in non-specified UTIs. There were increases in all types of urinary tract infection, with non-specified UTIs having the greatest growth. Understanding these changing trends can be useful for health planning.
Background and aims
Zinc finger E‐box binding homeobox 1 (ZEB1) is a transcription factor that promotes metastatic and stem cell features, which has been associated with poor prognosis in ...cholangiocarcinoma (CCA), a desmoplastic cancer enriched in cancer‐associated fibroblasts (CAFs). We aimed to define ZEB1 regulatory functions in malignant and stromal compartments of CCA.
Approach and Results
Bioinformatic and immunohistochemical analyses were performed to determine correlations between ZEB1 and markers of progressiveness in human intrahepatic CCA (iCCA). Gain‐of‐function and loss‐of‐function models were generated in CCA cells and liver myofibroblasts as a model of CAFs. Conditioned media (CM) was used to unravel tumor–stroma interplay. In vivo experiments were performed using a xenograft CCA model. ZEB1 expression in tumor cells of human iCCA was associated with undifferentiated tumor and vascular invasion. In vitro, ZEB1 promoted epithelial–mesenchymal transition and stemness in tumor cells, leading to cell migration and spheroid formation. In vivo, ZEB1‐overexpressing CCA cells formed larger tumors with more abundant stroma. Expression of cellular communication network factor 2 (CCN2, encoding connective tissue growth factor CTGF) was increased in tumor cells from ZEB1‐overexpressing xenografts and correlated with ZEB1 expression in human tumors. In vitro, CM from ZEB1‐overexpressing tumor cells or recombinant CTGF induced myofibroblast proliferation. ZEB1 was also expressed by CAFs in human CCA, and its expression correlated with CCN2 in myofibroblasts and CCA stroma. In mice, cotransplantation of CCA cells with ZEB1‐depleted myofibroblasts reduced CCA progressiveness compared to CCA cells/ZEB1‐expressing myofibroblasts. Furthermore, ZEB1 controls the expression of paracrine signals (i.e., HGF and IL6) in tumor cells and myofibroblasts.
Conclusions
ZEB1 plays a key role in CCA progression by regulating tumor cell–CAF crosstalk, leading to tumor dedifferentiation and CAF activation.
Objective:
The aim of this study was to validate the Acoustic Voice Quality Index 03.01 (AVQIv3) and the Acoustic Breathiness Index (ABI) in the Spanish language.
Method:
Concatenated voice samples ...of continuous speech (cs) and sustained vowel (sv) from 136 subjects with dysphonia and 47 vocally healthy subjects were perceptually judged for overall voice quality and breathiness severity. First, to reach a higher level of ecological validity, the proportions of cs and sv were equalized regarding the time length of 3 seconds sv part and voiced cs part, respectively. Second, concurrent validity and diagnostic accuracy were verified.
Results:
A moderate reliability of overall voice quality and breathiness severity from 5 experts was used. It was found that 33 syllables as standardization of the cs part, which represents 3 seconds of voiced cs, allows the equalization of both speech tasks. A strong correlation was revealed between AVQIv3 and overall voice quality and ABI and perceived breathiness severity. Additionally, the best diagnostic outcome was identified at a threshold of 2.28 and 3.40 for AVQIv3 and ABI, respectively.
Conclusions:
The AVQIv3 and ABI showed in the Spanish language valid and robust results to quantify abnormal voice qualities regarding overall voice quality and breathiness severity.
The mechanisms governing the progression of non-alcoholic fatty liver disease (NAFLD) towards steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remain elusive. Here, we evaluated the role of ...hsa-miRNA-21-5p in NASH-related hepatocarcinogenesis.
Hepatic hsa-miR-21-5p expression was evaluated in two cohorts of patients with biopsy-proven NAFLD (n = 199) or HCC (n = 366 HCC and n = 11 NAFLD-HCC). Serum/liver metabolomic profiles were correlated with hsa-miR-21-5p in NAFLD obese patients. Wild-type (WT) and Mir21 KO mice were fed a choline-deficient, amino acid-defined (CDAA) diet for 32 and 66 weeks to induce NASH and NASH-HCC, respectively.
In obese individuals, hsa-miR-21-5p expression increased with NAFLD severity and associated with a hepatic lipotoxic profile. CDAA-fed WT mice displayed increased hepatic mmu-miR-21-5p levels and progressively developed NASH and fibrosis, with livers presenting macroscopically discernible pre-neoplastic nodules, hyperplastic foci and deregulated cancer-related pathways. Mir21 KO mice exhibited peroxisome-proliferator-activated receptor α (PPARα) activation, augmented mitochondrial activity, reduced liver injury and NAS below the threshold for NASH diagnosis, with the pro-inflammatory/fibrogenic milieu reversing to baseline levels. In parallel, Mir21 KO mice displayed reduced number of pre-neoplastic nodules, hepatocyte proliferation and activation of oncogenic signalling, being protected from NASH-associated carcinogenesis. The hsa-miRNA-21-5p/PPARα pathway was similarly deregulated in patients with HCC- or NASH-related HCC, correlating with HCC markers and worse prognosis.
Hsa-miR-21-5p is a key inducer of whole-spectrum NAFLD progression, from simple steatosis to NASH and NASH-associated carcinogenesis. The inhibition of hsa-miR-21-5p, leading to a pro-metabolic profile, might constitute an appealing therapeutic approach to ameliorate NASH and prevent progression towards HCC.
The humoral immune response against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants of concern elicited by vaccination was evaluated in COVID‐19 recovered individuals (Rec) ...separated 1–3 months (Rec2m) or 4–12 months (Rec9m) postinfection and compared to the response in naïve participants. Antibody‐mediated immune responses were assessed in 66 participants by three commercial immunoassays and a SARS‐CoV‐2 lentiviral‐based pseudovirus neutralization assay. Immunoglobulin (Ig) levels against SARS‐CoV‐2 spike were lower in naïve participants after two doses than in Rec after a single dose (p < 0.05). After two doses in Rec, levels of total Ig to receptor‐binding domain were significantly increased in Rec9m compared to Rec2m (p < 0.001). The neutralizing potency observed in Rec9m was consistently higher than in Rec2m against variants of concern (VOCs) Alpha, Beta, Delta, and BA.1 sublineage of Omicron with 2.2–2.8‐fold increases. Increasing the interval between SARS‐CoV‐2 infection and the vaccination with messenger RNA‐based vaccines to more than 3 months generates a more efficient heterologous humoral immune response against VOCs by allowing enough time to mount a strong recall memory B cell response.
Cell-free DNA (cfDNA) has recently emerged as a real-time biomarker for diagnosis, monitoring and prediction of therapy response in tumoral disease. Here, we evaluated cfDNA as a prognostic biomarker ...for monitoring muscle-invasive bladder cancer (MIBC) patients at different follow-up time points. Blood samples from 37 MIBC patients who underwent radical cystectomy (RC) were collected at cystectomy and 1, 4, 12 and 24 months later. Plasma cfDNA amount and fragmentation patterns were determined. Four mutations were analyzed in cfDNA to detect circulating tumor DNA (ctDNA) during patient follow-up. During a median follow-up of 36 months, 46% of patients progressed; median time to progression was 10 months. cfDNA levels and ctDNA status four months after RC were identified as independent prognostic biomarkers of tumor progression (HR 5.290; p = 0.033) and cancer-specific survival (HR 4.199; p = 0.038), respectively. Furthermore, ctDNA clearance four months after RC was significantly associated with patients’ clinical outcomes. In conclusion, cfDNA levels and ctDNA status four months after RC have prognostic implications in MIBC patients. In addition, cfDNA monitoring is useful to predict patient outcomes after RC. cfDNA analysis in the clinical setting could greatly improve MIBC patient management.
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