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Purpose: The aim of this study is to describe our clinical experience with tyrosine kinase inhibitors (TKIs) and to evaluate their efficacy and tolerability in patients with iodine-refractory differentiated thyroid cancer (DTC).Methods: There were 17 patients (47.1% women, mean age: 65.7) with DTC iodine-refractory (9 papillary, 2 follicular and 3 Hürthle cell), treated with TKIs: 16 with sorafenib and 1 with lenvatinib as first-line treatment; 7 required second-line treatment (4 lenvatinib and 3 axitinib). Primary endpoints were progression-free survival (PFS) and radiographic response (determinate at 3, 6, 12, 18, and 24 months after the initiation of treatment) and second endpoints were determining differences in baseline characteristics depending on clinical course and describing toxicities and tolerability.Results: Median PFS was 18 months. During the first 24 months of treatment with TKIs PR rate was 35.3% (only 5.8% ≥ 6 months) and SD ≥ 6 months was observed in 58.8%. There were no significant differences in baseline characteristics between patients with good and poor evolution. Adverse events (AEs) were present in 100% of patients, but most of them were grade 1 and 2.Conclusions: In our population of patients with iodine-refractory DTC, treatment with sorafenib, lenvatinib, and axitinib allows the stabilization of the disease in a high percentage of cases, with acceptable tolerability. [ABSTRACT FROM AUTHOR]

Objectives Atrial anastomosis in lung transplantation (LT) can present significant technical difficulties, especially when there is a very posterior left inferior pulmonary vein, in donor-recipient disproportion or excessive separation of the receptor's pulmonary veins owing to atrial dilatation; hence, its implementation requires excessive heart handling and longer ischemia time, which result in increased perioperative complications. This technique, which uses the recipient's superior pulmonary vein, avoids these problems, although it is not applicable in all cases because no pressure gradient at the suture level is required. Therefore, the suture diameter must be equal or greater than the sum of both graft pulmonary veins diameters. Methods This retrospective study recorded the age/gender (donor and recipient), preoperative morbidity, type of surgery, perioperative, vascular complications, mortality, and postoperative stay. Descriptive and inferential statistical study was made by SPSS. Results We performed 82 LTs between January 2009 and June 2012, 18 with the new technique (14 men/4 women; 52 ± 15 years). There were 14 single lung and 4 double lung transplants. The new technique does not increase the ischemic times when compared with the classic technique. No vascular dehiscence, fistulas, or thrombosis were found. There were observed fewer vascular complications ( P = .042). Early mortality was presented in 4 cases (22.2%). Conclusions This new technique achieves the objectives described (no increases in ischemic time, fewer vascular complications). However, an absolute confirmation requires a study comparing similar technical LT given that the new resource was only used in highly complex procedures. [ABSTRACT FROM AUTHOR]

High early mortality after lung transplantation (LT) for idiopathic pulmonary fibrosis (IPF) is still not well controlled, and some aspects remain debated. The aim of this study was to evaluate our experience to identify factors that might improve the early outcomes. Among the 427 patients transplanted from October 1993 to December 2014, 117 IPF patients underwent LT at our department. There was an increasing age of transplant recipients, and the overall early (1-mo_ mortality was 25/117 (21.4%) with a progressive decrease over the years. Logistic regression analysis for early mortality was performed, and multivariate analysis identified recipient age <55 years ( P = .042; odds ratio [OR], 2.98), single-lung transplants ( P = .001; OR, 5.226), and previous corticosteroid treatment ( P = .05; OR, 5.128) as independent risk factors for development of early mortality. In conclusion, despite the increasing age of transplant recipients, we observed a decrease in mortality to almost one-half compared with our initial results. According to our results, the mortality risk in patients <55 years old is independent from the type of transplant (single or double), being higher with a single transplant. In addition, corticosteroid treatment should be reduced to achieve lower early mortality. [ABSTRACT FROM AUTHOR]

Abstract: The postoperative period following lung transplantation remains critical because of several complications. Infection, primary graft failure, acute rejection, and surgical complications are risk factors for mortality and morbidity. The recognition and early treatment of these complications is important to optimize outcomes. This article provides an overview of postoperative complications observed in our center during the last year. We were particularly interested in the influence of variables, such as inotrope usage and Acute Physiology and Chronic Health Evaluation (APACHE II) score, a well-known, and validated mortality prediction model for general intensive care unit (ICU) patients only infrequently reported in the transplantation literature. High APACHE II scores were significantly associated with prolonged mechanical ventilation (P = 0.041) and a tracheostomy requirement (P = .035). The factors significantly associated with an early postoperative death were older donor age (P = .005), prolonged donor ICU period (P = .004), need for cardiopulmonary bypass (CB; P = .005), and high inotrope requirements in the ICU (P = .034). CB data were biased because we selected the worst case patients. Donor age and high inotrope requirements in the ICU have been reported previously to be prognostic factors for poor graft function. We believe that control of these variables may improve outcomes. [Copyright &y& Elsevier]

(1) Background: Accurate body composition assessment in CCR patients is crucial due to the high prevalence of malnutrition, sarcopenia, and cachexia affecting survival. This study evaluates the correlation between body composition assessed by CT imaging as a reference technique, BIVA, nutritional ultrasound, and handgrip strength in CCR patients. (2) Methods: This retrospective study included CCR patients assessed by the Endocrinology and Nutrition Services of Virgen de la Victoria in Malaga and Vall d'Hebron in Barcelona from October 2018 to July 2023. Assessments included anthropometry, BIVA, NU, HGS, and AI-assisted CT analysis at the L3 level for body composition. Pearson's analysis determined the correlation of CT-derived variables with BIVA, NU, and HGS. (3) Results: A total of 267 CCR patients (mean age 68.2 ± 10.9 years, 61.8% men) were studied. Significant gender differences were found in body composition and strength. CT-SMI showed strong correlations with body cell mass (r = 0.65), rectus femoris cross-sectional area (r = 0.56), and handgrip strength (r = 0.55), with a Cronbach's alpha of 0.789. CT-based adipose tissue measurements showed significant correlations with fat mass (r = 0.56), BMI (r = 0.78), A-SAT (r = 0.49), and L-SAT (r = 0.66). Regression analysis indicated a high predictive power for CT-SMI, explaining approximately 80% of its variance (R 2 = 0.796). (4) Conclusions: Comprehensive screening of colorectal cancer patients through BIVA, NU, HGS, and CT optimizes the results of the evaluation. These methods complement each other in assessing muscle mass, fat distribution, and nutritional status in CCR. When CT is unavailable or bedside assessment is needed, HGS, BIVA, and NU provide an accurate assessment of body composition.

Early bolting is a major breeding objective for globe artichoke ( Cynara cardunculus var. scolymus L.). It has been suggested that globe artichoke bolting time is linked to a vernalization requirement, although environmental conditions under which vernalized plants and controls have been grown may not always allow for proper comparison. Here, we defined morphological markers to monitor the vegetative-to-reproductive phase transition at the shoot apex and linked these to expression changes of homologs of key Arabidopsis flowering regulators SOC1 , FUL , and AP1 . Importantly, we developed an experimental setup where control and vernalized plants grow under comparable conditions. These tools together allowed for comparison of the vegetative-to-reproductive phase transition between early- and late-bolting genotypes and how they respond to vernalization. Our results show that vernalization requirement is significantly lower in early-bolting genotypes, supporting the hypothesis that the early-bolting trait is at least partly underlain by alterations in the network controlling vernalization response., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Monocarpic plants have a single reproductive phase in their life. Therefore, flower and fruit production are restricted to the length of this period. This reproductive strategy involves the regulation of flowering cessation by a coordinated arrest of the growth of the inflorescence meristems, optimizing resource allocation to ensure seed filling. Flowering cessation appears to be a regulated phenomenon in all monocarpic plants. Early studies in several species identified seed production as a major factor triggering inflorescence proliferative arrest. Recently, genetic factors controlling inflorescence arrest, in parallel to the putative signals elicited by seed production, have started to be uncovered in Arabidopsis, with the MADS-box gene FRUITFULL (FUL) playing a central role in the process. However, whether the genetic network regulating arrest is also at play in other species is completely unknown. Here, we show that this role of FUL is not restricted to Arabidopsis but is conserved in another monocarpic species with a different inflorescence structure, field pea, strongly suggesting that the network controlling the end of flowering is common to other plants. Moreover, field trials with lines carrying mutations in pea FUL genes show that they could be used to boost crop yield., Competing Interests: Competing interests statement:The authors declare no competing interest.

Primary cutaneous B-cell lymphomas (PCBCLs) are B-cell lymphomas that can occur in the skin without evidence of extracutaneous involvement. The 2005 WHO/EORTC classification of cutaneous lymphomas and its 2018 update have distinguished three main categories based on clinicopathological, immunohistochemical, and genetic characteristics: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT). PCMZL and PCFCL are clinically indolent, while PCDLBCL-LT is an aggressive lymphoma. Due to its low incidence and lack of prospective studies, it is difficult to establish a standard treatment for each subgroup. The objective of our study was to describe the clinical and pathological characteristics of 103 patients with cutaneous B-cell lymphoma from 12 centres belonging to the Spanish Lymphoma Oncology Group. The median age was 53 years (40-65). According to skin extension, 62% had single-site lymphoma, 17% had regional lymphoma, and 20% had multifocal lymphoma. Histology: 66% had PCMZL, 26% had PCFCL, and 8% had PCDLBCL-LT. Twenty-three percent of the patients were treated exclusively with surgery, 26% with radiotherapy only, 21% with surgery plus radiotherapy, 10% with polychemotherapy, and 5% with rituximab monotherapy. Overall, 96% of patients achieved a complete response, and 44% subsequently relapsed, most of them relapsing either locally or regionally. The 10-year OS was 94.5% for the entire cohort, 98% for the PCMZL cohort, 95% for the PCFCL cohort, and 85.7% for the PCDLBCL-LT cohort. Our data are comparable to those of other published series, except for the high frequency of PCMZL. The expected heterogeneity in therapeutic management has been observed.

Background: The value of the phase angle (PhA), measured via bioelectrical impedance analysis (BIA), could be considered a good marker of the cell mass and the cell damage of a patient; however, there are new techniques, such as muscle ultrasonography, that allow the quantity and quality of muscle to be assessed in a minimally invasive way. The aim of this study is to determine the prognostic value of morphofunctional techniques in the prognosis of mortality in patients with idiopathic pulmonary fibrosis (IPF)., Methods: This multicenter, cross-sectional study included 86 patients with idiopathic pulmonary fibrosis with a mean age of 71 years, 82.7% of whom were male. The nutritional risk of the patients was assessed by means of questionnaires, such as the Subjective Global Assessment (SGA), and non-invasive functional techniques, including BIA, nutritional ultrasound, and hand grip strength (HGS). Statistical analysis of the sample was performed using JAMOVI version 2.3.22., Results: Correlations were made between the RF-CSA techniques with PhA (r = 0.48, p < 0.001), BCM (r = 0.70, p < 0.001), SMI (r = 0.64, p < 0.001), and HGS (r = 0.54, p < 0.001). The cut-off points for 12-month mortality were PhA = 4.5° (AUC = 0.722, sensitivity of 72.7% and specificity of 66.6%), BCM = 28.8 kg (AUC = 0.609, sensitivity of 32.4% and specificity of 100.0%), RF-CSA = 3.00 cm 2 (AUC = 0.857, sensitivity of 64.4% and specificity of 100.0%), 6MMW = 420 m (AUC = 0.830, sensitivity of 63.27% and specificity of 100.0%), and TUG = 7.2 s (AUC = 0.771, sensitivity of 100.0% and specificity of 56.67%). In addition, a multivariate analysis was performed with RF-CSA, HR = 8.11 (1.39-47.16, p = 0.020), and PhA of 6.35 (1.29-31.15, p = 0.023), taking into account age, sex, and BMI to determine mortality. Finally, a Kaplan-Meier survival analysis was conducted with low or normal values for classical parameters (GAP and T6MM) and new parameters (PhA, BCM, RF-CSA, and TUG)., Conclusion: RF-CSA and PhA were shown to be good prognostic markers of 12-month mortality and could, therefore, be useful screening tools to complement the nutritional assessment of IPF patients.

Muscle-invasive urothelial carcinoma represents 20% of newly diagnosed cases of bladder cancer, and most cases show aggressive biological behavior with a poor prognosis. It is necessary to identify biomarkers that can be used as prognostic and predictive factors in daily clinical practice. In our study, we analyzed different antibodies in selected cases of muscle-invasive urinary bladder carcinoma and lymph node metastasis to identify immunohistochemical types and their value as possible prognostic factors. A total of 38 patients were included, 87% men and 13% women, with a mean age of 67.8 years. The most frequent histopathological type was urothelial carcinoma. In the primary lesion, the mixed type was the most common. In unilateral metastasis, the mixed type was the most frequently found. In cases of primary lesions and bilateral metastasis, the luminal and mixed types were observed. The luminal subtype was the most stable in immunohistochemical expression across primary tumors and metastases. The basal type showed a better prognosis in terms of disease-free survival. In conclusion, immunohistochemical studies are useful in assessing primary and metastatic lesions in patients with urothelial carcinoma. Immunohistochemical classification can typify muscle-invasive urothelial carcinoma, and the immunophenotype seems to have prognostic implications.

Liquid biopsy has improved significantly over the last decade and is attracting attention as a tool that can complement tissue biopsy to evaluate the genetic landscape of solid tumors. In the present study, we evaluated the usefulness of liquid biopsy in daily oncology practice in different clinical contexts. We studied ctDNA and tissue biopsy to investigate EGFR , KRAS , NRAS , and BRAF mutations from 199 cancer patients between January 2016 and March 2021. The study included 114 male and 85 female patients with a median age of 68 years. A total of 122 cases were lung carcinoma, 53 were colorectal carcinoma, and 24 were melanoma. Liquid biopsy was positive for a potentially druggable driver mutation in 14 lung and colorectal carcinoma where tissue biopsy was not performed, and in two (3%) lung carcinoma patients whose tissue biopsy was negative. Liquid biopsy identified nine (45%) de novo EGFR-T790M mutations during TKI-treatment follow-up in lung carcinoma. BRAF-V600 mutation resurgence was detected in three (12.5%) melanoma patients during follow-up. Our results confirm the value of liquid biopsy in routine clinical oncologic practice for targeted therapy, diagnosis of resistance to treatment, and cancer follow-up.

LEAFY plant-specific transcription factors, which are key regulators of flower meristem identity and floral patterning, also contribute to meristem activity. Notably, in some legumes, LFY orthologs such as Medicago truncatula SINGLE LEAFLET (SGL1) are essential in maintaining an undifferentiated and proliferating fate required for leaflet formation. This function contrasts with most other species, in which leaf dissection depends on the reactivation of KNOTTED-like class I homeobox genes (KNOXI). KNOXI and SGL1 genes appear to induce leaf complexity through conserved downstream genes such as the meristematic and boundary CUP-SHAPED COTYLEDON genes. Here, we compare in M. truncatula the function of SGL1 with that of the Arabidopsis thaliana KNOXI gene, SHOOT MERISTEMLESS (AtSTM). Our data show that AtSTM can substitute for SGL1 to form complex leaves when ectopically expressed in M. truncatula. The shared function between AtSTM and SGL1 extended to the major contribution of SGL1 during floral development as ectopic AtSTM expression could promote floral organ identity gene expression in sgl1 flowers and restore sepal shape and petal formation. Together, our work reveals a function for AtSTM in floral organ identity and a higher level of interchangeability between meristematic and floral identity functions for the AtSTM and SGL1 transcription factors than previously thought.

Inflorescence architecture contributes to essential plant traits. It determines plant shape, contributing to morphological diversity, and also determines the position and number of flowers and fruits produced by the plant, thus influencing seed yield. Most legumes have compound inflorescences, where flowers are produced in secondary inflorescences (I2), formed at the flanks of the main primary inflorescence (I1), in contrast to simple inflorescences of plants like Arabidopsis, in which flowers are directly formed on the I1. The pea VEGETATIVE1/FULc ( VEG1 ) gene, and its homologs in other legumes, specify the formation of the I2 meristem, a function apparently restricted to legumes. To understand the control of I2 development, it is important to identify the genes working downstream of VEG1 . In this study, we adopted a novel strategy to identify genes expressed in the I2 meristem, as potential regulatory targets of VEG1. To identify pea I2-meristem genes, we compared the transcriptomes of inflorescence apices from wild-type and mutants affected in I2 development, such as proliferating inflorescence meristems ( pim , with more I2 meristems), and veg1 and vegetative2 (both without I2 meristems). Analysis of the differentially expressed genes using Arabidopsis genome databases combined with RT-qPCR expression analysis in pea allowed the selection of genes expressed in the pea inflorescence apex. In situ hybridization of four of these genes showed that all four genes are expressed in the I2 meristem, proving our approach to identify I2-meristem genes was successful. Finally, analysis by VIGS (virus-induced gene silencing) in pea identified one gene, PsDAO1 , whose silencing leads to small plants, and another gene, PsHUP54 , whose silencing leads to plants with very large stubs, meaning that this gene controls the activity of the I2 meristem. PsHUP54- VIGS plants are also large and, more importantly, produce large pods with almost double the seeds as the control. Our study shows a new useful strategy to isolate I2-meristem genes and identifies a novel gene, PsHUP54 , which seems to be a promising tool to improve yield in pea and in other legumes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Serra-Picó, Hecht, Weller, Benlloch and Madueño.)

Legumes usually have compound inflorescences, where flowers/pods develop from secondary inflorescences (I2), formed laterally at the primary inflorescence (I1). Number of flowers per I2, characteristic of each legume species, has important ecological and evolutionary relevance as it determines diversity in inflorescence architecture; moreover, it is also agronomically important for its potential impact on yield. Nevertheless, the genetic network controlling the number of flowers per I2 is virtually unknown. Chickpea (Cicer arietinum) typically produces one flower per I2 but single flower (sfl) mutants produce two (double-pod phenotype). We isolated the SFL gene by mapping the sfl-d mutation and identifying and characterising a second mutant allele. We analysed the effect of sfl on chickpea inflorescence ontogeny with scanning electron microscopy and studied the expression of SFL and meristem identity genes by RNA in situ hybridisation. We show that SFL corresponds to CaRAX1/2a, which codes a MYB transcription factor specifically expressed in the I2 meristem. Our findings reveal SFL as a central factor controlling chickpea inflorescence architecture, acting in the I2 meristem to regulate the length of the period for which it remains active, and therefore determining the number of floral meristems that it can produce., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Redox homeostasis has been linked to proper anther and pollen development. Accordingly, plant cells have developed several Reactive Oxygen Species (ROS)-scavenging mechanisms to maintain the redox balance. Hemopexins constitute one of these mechanisms preventing heme-associated oxidative stress in animals, fungi, and plants. Pisum sativum ENDOTHECIUM 1 (PsEND1 ) is a pea anther-specific gene that encodes a protein containing four hemopexin domains. We report the functional characterization of PsEND1 and the identification in its promoter region of cis -regulatory elements that are essential for the specific expression in anthers. PsEND1 promoter deletion analysis revealed that a putative CArG-like regulatory motif is necessary to confer promoter activity in developing anthers. Our data suggest that PsEND1 might be a hemopexin regulated by a MADS-box protein. PsEND1 gene silencing in pea, and its overexpression in heterologous systems, result in similar defects in the anthers consisting of precocious tapetum degradation and the impairment of pollen development. Such alterations were associated to the production of superoxide anion and altered activity of ROS-scavenging enzymes. Our findings demonstrate that PsEND1 is essential for pollen development by modulating ROS levels during the differentiation of the anther tissues surrounding the microsporocytes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hamza, Roque, Gómez-Mena, Madueño, Beltrán and Cañas.)

Throughout development, plant meristems regularly produce organs in defined spiral, opposite, or whorl patterns. Cauliflowers present an unusual organ arrangement with a multitude of spirals nested over a wide range of scales. How such a fractal, self-similar organization emerges from developmental mechanisms has remained elusive. Combining experimental analyses in an Arabidopsis thaliana cauliflower-like mutant with modeling, we found that curd self-similarity arises because the meristems fail to form flowers but keep the "memory" of their transient passage in a floral state. Additional mutations affecting meristem growth can induce the production of conical structures reminiscent of the conspicuous fractal Romanesco shape. This study reveals how fractal-like forms may emerge from the combination of key, defined perturbations of floral developmental programs and growth dynamics., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The specified floral meristem will develop a pre-established number of floral organs and, thus, terminate the floral meristematic cells. The floral meristematic pool of cells is controlled, among some others, by WUSCHEL (WUS) and AGAMOUS (AG) transcription factors (TFs). Here, we demonstrate that the SCI1 ( Stigma/style cell-cycle inhibitor 1 ) gene, a cell proliferation regulator, starts to be expressed since the floral meristem specification of Nicotiana tabacum and is expressed in all floral meristematic cells. Its expression is higher in the floral meristem and the organs being specified, and then it decreases from outside to inside whorls when the organs are differentiating. SCI1 is co-expressed with N. tabacum WUSCHEL ( NtWUS ) in the floral meristem and the whorl primordia at very early developmental stages. Later in development, SCI1 is co-expressed with NAG1 ( N. tabacum AG ) in the floral meristem and specialized tissues of the pistil. In silico analyses identified cis -regulatory elements for these TFs in the SCI1 genomic sequence. Yeast one-hybrid and electrophoresis mobility shift assay demonstrated that both TFs interact with the SCI1 promoter sequence. Additionally, the luciferase activity assay showed that NAG1 clearly activates SCI1 expression, while NtWUS could not do so. Taken together, our results suggest that during floral development, the spatiotemporal regulation of SCI1 by NtWUS and NAG1 may result in the maintenance or termination of proliferative cells in the floral meristem, respectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cruz, San Martin, Lubini, Strini, Sobral, Pinoti, Ferreira, Thomé, Quiapim, Dornelas, Pranchevicius, Madueño, Costa and Goldman.)