Sentinel lymph node biopsy before and after neoadjuvant chemotherapy in cN0 breast cancer patients: impact on axillary morbidity and survival-a propensity score cohort study.

PURPOSE: In patients with clinically lymph node-negative (cN0) breast cancer, performing sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NACT) has been preferentially embraced in comparison to before NACT. However, survival outcomes associated with both strategies remain understudied. We aimed to compare the axillary lymphadenectomy (ALND) rate, disease-free survival (DFS), and overall survival (OS), between two strategies. METHODS: We included 310 patients in a retrospective observational study. SNLB was performed before NACT from December 2006 to April 2014 (107 cases) and after NACT from May 2014 to May 2020 (203 patients). An inverse probability of treatment weighting (IPTW) method was applied to homogenize both groups. Hazard ratios (HR) and odd ratios (OR) are reported with 95% confidence intervals (95%CI). RESULTS: The lymphadenectomy rate was 29.9% before NACT and 7.4% after NACT (p < 0.001), with an OR of 5.35 95%CI (2.7-10.4); p = .002. After 4 years of follow-up, SLNB after NACT was associated with lower risk for DFS, HR 0.42 95%CI (0.17-1.06); p = 0.066 and better OS, HR 0.21 CI 95% (0.07-0.67); p = 0.009 than SLNB before NACT. After multivariate analysis, independent adverse prognostic factors for OS included SLNB before NACT, HR 3.095 95%CI (2.323-4.123), clinical nonresponse to NACT, HR 1.702 95% CI (1.012-2.861), and small tumors (cT1) with high proliferation index, HR 1.889 95% (1.195-2.985). CONCLUSION: Performing SLNB before NACT results in more ALND and has no benefit for patient survival. These findings support discontinuing the practice of SLNB before NACT in patients with cN0 breast cancer.

Effects of grazing on soil properties in mediterranean forests (Central-Eastern Spain).

Traditional management practices, such as grazing, can have adverse impact on soils. Despite an extensive body of literature exploring the effects of grazing on soil and plants worldwide, there is a notable lack of research on its impacts in Mediterranean forests within the Iberian Peninsula Furthermore, there is a knowledge gap on the enzymatic activities and basal respiration of soil in forest after grazing. To address these gaps, this study aimed to investigate the impact of grazing on various important physicochemical and biological soil properties along with vegetation richness in a Mediterranean forest located in Castilla-La Mancha (Central Eastern Spain). Relative to undisturbed sites, grazing significantly reduced soil water content (-53%) and available water (-59%). However, soil hydraulic conductivity remained unaffected by animal trampling and the soil water repellency observed in ungrazed sites disappeared. Grazed soils experienced a slight increase in pH (+18%). Among the biochemical properties studied, only dehydrogenase showed a significant increase (+100%) while basal respiration exhibited a notable decrease (-24%). Grazing resulted in a reduction of plant species richness (-34%) indicating a loss of biodiversity in grazed areas. The observed significant alterations in key soil and plant properties due to livestock activity suggest that grazing has the potential to modify the overall soil quality of these sites. Certain variables that exhibited noteworthy differences between grazed and ungrazed sites could serve as indicators of grazing impacts in Mediterranean forests. These indicators may be considered proxies for establishing effective land management strategies to mitigate degradation in the Mediterranean forest ecosystem.

Management of the axilla in postmenopausal patients with cN0 hormone receptor-positive/HER2-negative breast cancer treated with neoadjuvant endocrine therapy and its prognostic impact.

PURPOSE: To evaluate the differences in nodal positivity if the sentinel lymph node biopsy (SLNB) is performed before or after neoadjuvant endocrine therapy (NET) in breast cancer patients, and its impact on prognosis. METHODS: A retrospective cohort study was performed in a single center including 91 postmenopausal cases with clinically node-negative and hormone receptor-positive/HER2-negative (HR + /HER2-) breast cancer, treated with NET and SLNB. SLNB was done pre-NET until 2014, and post-NET thereafter. Axillary lymph node dissection (ALND) was indicated only in SLNB macrometastasis, although in selected elderly patients, it was omitted. Kaplan-Meier survival curves were estimated in relation to the status of the axilla, and the differences assessed using the log-rank test. RESULTS: Between December 2006 and March 2022, SLNB was performed pre-NET in 14 cases and post-NET in 77. Both groups were similar in baseline tumor and patient characteristics. SLNB positivity was similar regardless of whether SLNB was performed before (5/14, 35.7%) or after NET (27/77, 37%), with 2/14 SLN macrometastases in the pre-NET cohort and 17/77 in the post-NET cohort. Only three patients (18.7%) with SLN macrometastasis had > 3 positive nodes following ALND. The 5-year overall survival and distant disease-free survival were 92.4% and 94.8%, respectively, with no significant differences according to SLNB status (p 0.5 and 0.8, respectively). CONCLUSION: SLN positivity did not differ according to its timing (before or after NET). Therefore, NET has no effect on lymph node clearance. Furthermore, the prognosis is good regardless of the axillary involvement. Therefore, factors other than axillary involvement may affect the prognosis in these patients.

Organic amendments from recycled waste promote short-term carbon sequestration of restored soils in drylands.

Soils are considered as a major reservoir for terrestrial carbon and it can act as a source or sink depending upon the land management activities. In semi-arid areas, the natural recovery of soils degraded by mining activities is complicated. A possible solution to recover soil quality and functionality, plant cover and carbon sequestration capacity could be the application of organic amendments. This work focuses on a restoration carried out in 2018 by applying with different composted organic amendments (stabilized sludge, gardening and greenhouse waste) in a limestone quarry under semi-arid climate (SE Spain). The objective was to evaluate the effects of different organic amendments on net CO2 exchange in two microcosms: soil-Stipa tenacissima and soil-spontaneous vegetation. Soil physical and chemical properties, environmental and ecological variables and their interrelationship were studied in amended and unamended soils. The results obtained under soil-forming factors in the study area showed an increase in soil organic carbon and nitrogen content, improved moisture and plant growth, and plant canopy development in amended soils. Soil moisture, soil temperature and plant cover significantly influenced net CO2 exchange. In general, microcosms with S. tenacissima showed higher carbon sequestration rates than soils with only spontaneous plant cover. Soils treated with a vegetable-only amendments showed higher plant cover and CO2 fixation rates after significant rainfall. On the other hand, the plots treated with sludge compost presented more soil respiration than photosynthesis, especially in the wet seasons. Soils with sludge and greenhouse compost mixed had higher CO2 fixation rates than soils restored with a mixture of sludge and garden compost. Soils with greenhouse waste compost showed CO2 fixation in the microcosm with plants in all campaigns, being the best treatment to promote atmospheric CO2 sequestration in soil restoration.

The SINGLE FLOWER (SFL) gene encodes a MYB transcription factor that regulates the number of flowers produced by the inflorescence of chickpea.

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.

Genetic analysis of early phenology in lentil identifies distinct loci controlling component traits.

Modern-day domesticated lentil germplasm is generally considered to form three broad adaptation groups: Mediterranean, South Asian, and northern temperate, which correspond to the major global production environments. Reproductive phenology plays a key role in lentil adaptation to this diverse ecogeographic variation. Here, we dissect the characteristic earliness of the pilosae ecotype, suited to the typically short cropping season of South Asian environments. We identified two loci, DTF6a and DTF6b, at which dominant alleles confer early flowering, and we show that DTF6a alone is sufficient to confer early flowering under extremely short photoperiods. Genomic synteny confirmed the presence of a conserved cluster of three florigen (FT) gene orthologues among potential candidate genes, and expression analysis in near-isogenic material showed that the early allele is associated with a strong derepression of the FTa1 gene in particular. Sequence analysis revealed a 7.4 kb deletion in the FTa1-FTa2 intergenic region in the pilosae parent, and a wide survey of >350 accessions with diverse origin showed that the dtf6a allele is predominant in South Asian material. Collectively, these results contribute to understanding the molecular basis of global adaptation in lentil, and further emphasize the importance of this conserved genomic region for adaptation in temperate legumes generally.

The effect of omitting axillary dissection and the impact of radiotherapy on patients with breast cancer sentinel node macrometastases: a cohort study following the ACOSOG Z0011 and AMAROS trials.

PURPOSE: To report the outcomes of implementing the ACOSOG Z0011 and AMAROS trials relevant to clinical practice, and to define target groups in whom to avoid or recommend axillary radiotherapy (ART). We also aimed to analyse the reduction in morbidity when axillary lymph node dissection (ALND) was omitted. METHODS: A retrospective cohort study of T1-T2 patients with macrometastases at sentinel lymph node (SLN) who were treated between 2011 and 2020. Breast surgery included either lumpectomy or mastectomy. Patients with ≤ 2 positive SLN were divided into two cohorts by whether they received ART or not. Survival outcomes and morbidity were analysed by Kaplan-Meyer curves and Cox-regression, respectively. RESULTS: 260 pN1a patients were included and ALND was avoided in 167 (64.2%). According the Z0011 results, 72 (43.1%) received no further ART; and based on AMAROS criteria 95 (56.9%) received ART. Median follow-up was 54 months. The 5-year overall survival was 96.8% in the non-RT cohort and 93.4% in the RT cohort (p = 0.19), while the respective 5-year disease-free survivals were 100% and 92.3% (p = 1.06). Lymphedema developed in 3.6% of patients after SLNB versus 43% after ALND (OR 20.25; 95%CI 8.13-50.43). Decreased upper-extremity range of motion appeared in 8.4% of patients after SLNB versus 31.2% after ALND (OR 4.95; 95%CI 2.45-9.98%). CONCLUSIONS: Our study confirms that omitting ALND is safe and has high survival rates in patients with T1-T2 tumours and ≤ 2 positive SLNs. Adding ART could be a treatment option for patients who present other risk factors. Avoiding ALND with or without ART was associated with significantly less arm morbidity.

Can we avoid axillary lymph node dissection in N2 breast cancer patients with chemo-sensitive tumours such as HER2 and TNBC?

PURPOSE: To find a group of cN2 patients or patients with high axillary burden who become ypN0 after neoadjuvant chemotherapy (NACT) and who may benefit from avoiding a lymphadenectomy. METHODS: A retrospective observational cohort study was conducted with 221 clinically staged N2 patients or patients with at least 3 suspicious lymph nodes found by ultrasound at diagnosis. The predictive factors for ypN0 analysed were age, MRI-determined tumour size, histological subtype, the Nottingham histologic grade, surrogate molecular subtype, ki-67 and vascular invasion when present. Clinical and radiological responses after NACT were also evaluated. Univariate and multivariate analyses by logistic regression were performed. Distant disease-free survival (DDFS) was calculated in relation to the status of the axillary lymph nodes after NACT. RESULTS: After NACT, 89 patients (40.3%) had axillary pathologic complete response (pCR) (ypN0) and 132 (59.7%) had residual axillary disease (ypN+). Molecular surrogate subtype, Ki-67 expression, and the clinical and radiological responses to NACT were the only independent factors associated with ypN0. Axillary pCR was observed more often in HER2-positive and triple-negative tumours than in luminal ones (OR 7.5 and 3.6, respectively). DDFS was 88.7% (95% CI 80.7-96.7%) for ypN0 and 56.2% (95% CI 32.1-80.3%) for ypN+ (p = 0.09). CONCLUSIONS: In HER2-positive and triple-negative breast cancer patients staged as cN2 or with high axillary burden before NACT, a sentinel lymph node biopsy after NACT could be recommended if there is a clinical and radiological response.

Analysis of the performance of machine learning and deep learning methods for sex estimation of infant individuals from the analysis of 2D images of the ilium.

Reducing the subjectivity of the methods used for biological profile estimation is, at present, a priority research line in forensic anthropology. To achieve this, artificial intelligence (AI) techniques can be a valuable tool yet to be exploited in this discipline. The goal of this study is to compare the effectiveness of different machine learning (ML) methods with the visual assessment of an expert to estimate the sex of infant skeletons from images of the ilium. Photographs of the ilium of 135 individuals, age between 5 months of gestation and 6 years, from the collection of identified infant skeletons of the University of Granada have been used, and classic ML and deep learning (DL) techniques have been applied to develop prediction algorithms. To assess their effectiveness, the results have been compared with those obtained by a forensic expert, who has estimated the sex from each photograph through direct observation and subjective assessment following the criteria described by Schutkowsky in 1993. The results show that the algorithms obtained using DL techniques offer an accuracy of 59%, very close to the 61% obtained by the expert, and 10 percentual points better than classic ML techniques. This study offers promising results and represents the first AI-based approach for estimating sex in infant individuals using photographs of the ilium.

Highly Discriminative Physiological Parameters for Thermal Pattern Classification.

Infrared Thermography (IRT) is a non-contact, non-intrusive, and non-ionizing radiation tool used for detecting breast lesions. This paper analyzes the surface temperature distribution (STD) on an optimal Region of Interest (RoI) for extraction of suitable internal heat source parameters. The physiological parameters are estimated through the inverse solution of the bio-heat equation and the STD of suspicious areas related to the hottest spots of the RoI. To reach these values, the STD is analyzed by means: the Depth-Intensity-Radius (D-I-R) measurement model and the fitting method of Lorentz curve. A highly discriminative pattern vector composed of the extracted physiological parameters is proposed to classify normal and abnormal breast thermograms. A well-defined RoI is delimited at a radial distance, determined by the Support Vector Machines (SVM). Nevertheless, this distance is less than or equal to 1.8 cm due to the maximum temperature location close to the boundary image. The methodology is applied to 87 breast thermograms that belong to the Database for Mastology Research with Infrared Image (DMR-IR). This methodology does not apply any image enhancements or normalization of input data. At an optimal position, the three-dimensional scattergrams show a correct separation between normal and abnormal thermograms. In other cases, the feature vectors are highly correlated. According to our experimental results, the proposed pattern vector extracted at optimal position a=1.6 cm reaches the highest sensitivity, specificity, and accuracy. Even more, the proposed technique utilizes a reduced number of physiological parameters to obtain a Correct Rate Classification (CRC) of 100%. The precision assessment confirms the performance superiority of the proposed method compared with other techniques for the breast thermogram classification of the DMR-IR.

Structure-Function Correlation: Engineering High Quantum Yields in Down-Shifting Nanophosphors.

Lanthanides are routinely incorporated into quantum dots to act as down-shifting and up-converting phosphors in display and lighting applications due to their high photoluminescence quantum yields (PLQY). Recent efforts in the field have demonstrated that trivalent lanthanide, Ln(III), incorporated into ZnAl2O4 spinel nanocrystals can achieve PLQYs of 50% for down-shifting nanophosphors using earth abundant materials. The high PLQY is surprising as the Al(III) site in a spinel is centrosymmetric, which should lead to poor performance for these nanophosphors. However, spinels are prone to formation of an admixture of inverse and normal spinel lattices when the cation size ratio is not optimal. Such behavior can produce local cation disorder that can influence the phosphor performance. Herein, we describe the use of Tb(III) as an optical probe to evaluate the fractional population of the inverse and normal spinel structures within TbxZnAl2-xO4. The experimental data exhibits a Tb(III) concentration dependent change in the fractional population that results in a maximum PLQY of 37% with 3.56% Tb(III) incorporation. A decrease in the degree of inversion (cation disorder) leads to larger amounts of the cubic Fd3m phase resulting in the observed photoluminescence behavior. The correlation of NMR, pXRD, and optical methods provides direct insight into the high PLQY behavior for this class of nanophosphor.

Study of breast cancer incidence in patients of lymphangioleiomyomatosis.

Molecular evidence has linked the pathophysiology of lymphangioleiomyomatosis (LAM) to that of metastatic breast cancer. Following on this observation, we assessed the association between LAM and subsequent breast cancer. An epidemiological study was carried out using three LAM country cohorts, from Japan, Spain, and the United Kingdom. The number of incident breast cancer cases observed in these cohorts was compared with the number expected on the basis of the country-specific incidence rates for the period 2000-2014. Immunohistochemical studies and exome sequence analysis were performed in two and one tumors, respectively. All cohorts revealed breast cancer standardized incidence ratios (SIRs) ≥ 2.25. The combined analysis of all cases or restricted to pre-menopausal age groups revealed significantly higher incidence of breast cancer: SIR = 2.81, 95 % confidence interval (CI) = 1.32-5.57, P = 0.009; and SIR = 4.88, 95 % CI = 2.29-9.99, P = 0.0007, respectively. Immunohistochemical analyses showed positivity for known markers of lung metastatic potential. This study suggests the existence of increased breast cancer risk among LAM patients. Prospective studies may be warranted to corroborate this result, which may be particularly relevant for pre-menopausal women with LAM.

Compositional and functional analysis of the bacterial community of Mediterranean Leptosols under livestock grazing.

The composition and functioning of soil bacterial communities, as well as their responses to multiple perturbations, are not well understood in the terrestrial ecosystems. Our study focuses on the bacterial community of erosive and poorly developed soils (Haplic Leptosols) in Mediterranean rangelands of Extremadura (W Spain) with different grazing intensities. Leptosols from similar natural conditions were selected and sampled at two depths to determine the soil properties as well as the structure and activity of bacterial communities. As grazing intensified, the soil C and N content increased, as did the number and diversity of bacteria, mainly of fast-growing lineages. Aridibacter, Acidobacteria Gp6 and Gp10, Gemmatimonas, and Segetibacter increased their abundance along the grazing-intensity gradient. Firmicutes such as Romboutsia and Turicibacter from livestock microbiome also increased. In functional terms, the KEGG pathways enriched in the soils with moderate and high grazing intensity were ABC transporters, DNA repair and recombination proteins, the two-component system, and the degradation of xenobiotics. All of these proved to be related to stronger cell division and response mechanisms to environmental stressors such as drought, warming, toxic substances, and nutrient deprivation. Consequently, the bacterial community was affected by grazing, but appeared to adapt and counteract the effects of a high grazing intensity. Therefore, a clearly detrimental effect of grazing was not detected in the bacterial community of the soils studied.

avidaR: an R library to perform complex queries on an ontology-based database of digital organisms.

Digital evolution is a branch of artificial life in which self-replicating computer programs-digital organisms-mutate and evolve within a user-defined computational environment. In spite of its value in biology, we still lack an up-to-date and comprehensive database on digital organisms resulting from evolution experiments. Therefore, we have developed an ontology-based semantic database-avidaDB-and an R package-avidaR-that provides users of the R programming language with an easy-to-use tool for performing complex queries without specific knowledge of SPARQL or RDF. avidaR can be used to do research on robustness, evolvability, complexity, phenotypic plasticity, gene regulatory networks, and genomic architecture by retrieving the genomes, phenotypes, and transcriptomes of more than a million digital organisms available on avidaDB. avidaR is already accepted on CRAN (i.e., a comprehensive collection of R packages contributed by the R community) and will make biologists better equipped to embrace the field of digital evolution.

Ontology for the Avida digital evolution platform.

The Ontology for Avida (OntoAvida) aims to develop an integrated vocabulary for the description of Avida, the most widely used computational approach for performing experimental evolution using digital organisms-self-replicating computer programs that evolve within a user-defined computational environment. The lack of a clearly defined vocabulary makes some biologists feel reluctant to embrace the field of digital evolution. This integrated framework empowers biologists by equipping them with the necessary tools to explore and analyze the field of digital evolution more effectively. By leveraging the vocabulary of Avida, researchers can gain deeper insights into the evolutionary processes and dynamics of digital organisms. In addition, OntoAvida allows researchers to make inference based on certain rules and constraints, facilitate the reproducibility of in silico evolution experiments and trace the provenance of the data stored in avidaDB-an RDF database containing the genomes, transcriptomes, and phenotypes of more than a million digital organisms. OntoAvida is part of the Open Biological and Biomedical Ontologies (OBO Foundry) and is available at http://www.obofoundry.org/ontology/ontoavida.html .

Altitudinal Gradient and Soil Depth as Sources of Variations in Fungal Communities Revealed by Culture-Dependent and Culture-Independent Methods in the Negev Desert, Israel.

We examined fungal communities in soil profiles of 0-10 cm depth along the altitudinal gradient of 250-530-990 m.a.s.l. at the Central Negev Desert, Israel, which benefit from similar annual precipitation (95 mm). In the soil samples collected in the summer of 2020, a mycobiota accounting for 169 species was revealed by both culture-dependent and culture-independent (DNA-based) methodologies. The impact of soil depth on the variations in fungal communities was stronger than the impact of altitude. Both methodologies displayed a similar tendency in the composition of fungal communities: the prevalence of melanin-containing species with many-celled large spores (mainly Alternaria spp.) in the uppermost layers and the depth-wise increase in the proportion of light-colored species producing a high amount of small one-celled spores. The culturable and the DNA-based fungal communities had only 13 species in common. The differences were attributed to the pros and cons of each method. Nevertheless, despite the drawbacks, the employment of both methodologies has an advantage in providing a more comprehensive picture of fungal diversity in soils.

Short-term effects of post-fire soil mulching with wheat straw and wood chips on the enzymatic activities in a Mediterranean pine forest.

Soils of Mediterranean forests can be severely degraded due to wildfire. However, post-fire management techniques, such as soil mulching with vegetal residues, can limit degradation and increase functionality of burned soils. The effects of post-fire mulching on soil functionality have been little studied in Mediterranean forests, and it is still unclear whether the application of straw or wood residues is beneficial. This study explores the changes in important soil chemical and biochemical properties in a pine forest of Central Eastern Spain after a wildfire and post-fire mulching with straw or wood chips. Only basal soil respiration (BSR), dehydrogenase activity (DHA), pH and water field capacity (WFC) significantly changed after the fire and mulching. In contrast, the other enzymatic activities - urease (UA), alkaline phosphatase (Alk-PA) and ß-glucosidase (BGA), - total organic carbon (TOC) and electrical conductivity (EC) were not influenced by these soil disturbances. Time from fire and soil conditions (due to burning and management) were significant variability factors for BSR, pH, BGA, UA, TOC, EC. Mulching increased BSR compared to burned areas, especially in soils with straw (+30 %), thanks to addition of fresh organic residues, quickly incorporated in the soil. Soil pH showed a low variability among the four soil conditions, and TOC was higher in mulched soils (on average + 20 % compared to the burned soils), and this was correlated to the increased BSR. The role of mulching was essential with reference to WFC, as the post-fire management limited its reduction after the fire (on average from -30 % to -20 %). Finally, the Principal Component Analysis coupled to the Analytical Hierarchical Cluster Analysis confirmed the significant influence of the post-fire management on some enzymatic activities, although a sharp discrimination among the four soil conditions was only evident between unburned and burned sites, regardless of the management. Overall, it has been shown that mulching promotes conservation of fragile Mediterranean soils, indicating its effectiveness at preserving soil functionality in areas affected by forest fires.

Intensive vegetable production under plastic mulch: A field study on soil plastic and pesticide residues and their effects on the soil microbiome.

Intensive agriculture relies on external inputs to reach high productivity and profitability. Plastic mulch, mainly in the form of Low-Density Polyethylene (LDPE), is widely used in agriculture to decrease evaporation, increase soil temperature and prevent weeds. The incomplete removal of LDPE mulch after use causes plastic contamination in agricultural soils. In conventional agriculture, the use of pesticides also leaves residues accumulating in soils. Thus, the objective of this study was to measure plastic and pesticide residues in agricultural soils and their effects on the soil microbiome. For this, we sampled soil (0-10 cm and 10-30 cm) from 18 parcels from 6 vegetable farms in SE Spain. The farms were under either organic or conventional management, where plastic mulch had been used for >25 years. We measured the macro- and micro-light density plastic debris contents, the pesticide residue levels, and a range of physiochemical properties. We also carried out DNA sequencing on the soil fungal and bacterial communities. Plastic debris (>100 µm) was found in all samples with an average number of 2 × 103 particles kg-1 and area of 60 cm2 kg-1. We found 4-10 different pesticide residues in all conventional soils, for an average of 140 µg kg-1. Overall, pesticide content was ∼100 times lower in organic farms. The soil microbiomes were farm-specific and related to different soil physicochemical parameters and contaminants. Regarding contaminants, bacterial communities responded to the total pesticide residues, the fungicide Azoxystrobin and the insecticide Chlorantraniliprole as well as the plastic area. The fungicide Boscalid was the only contaminant to influence the fungal community. The wide spread of plastic and pesticide residues in agricultural soil and their effects on soil microbial communities may impact crop production and other environmental services. More studies are required to evaluate the total costs of intensive agriculture.

Axillary lymph node dissection versus radiotherapy in breast cancer with positive sentinel nodes after neoadjuvant therapy (ADARNAT trial).

Introduction: Breast cancer surgery currently focuses on de-escalating treatment without compromising patient survival. Axillary radiotherapy (ART) now replaces axillary lymph node dissection (ALND) in patients with limited sentinel lymph node (SLN) involvement during the primary surgery, and this has significantly reduced the incidence of lymphedema without worsening the prognosis. However, patients treated with neoadjuvant systemic treatment (NST) cannot benefit from this option despite the low incidence of residual disease in the armpit in most cases. Data regarding the use of radiotherapy instead of ALND in this population are lacking. This study will assess whether ART is non-inferior to ALND in terms of recurrence and overall survival in patients with positive SLN after NST, including whether it reduces surgery-related adverse effects. Methods and analyses: This multicenter, randomized, open-label, phase 3 trial will enroll 1660 patients with breast cancer and positive SLNs following NST in approximately 50 Spanish centers over 3 years. Patients will be stratified by NST regimen and nodal involvement (isolated tumoral cells or micrometastasis versus macrometastasis) and randomly assigned 1:1 to ART without ALND (study arm) or ALND alone (control arm). Level 3 and supraclavicular radiotherapy will be added in both arms. The primary outcome is the 5-year axillary recurrence determined by clinical and radiological examination. The secondary outcomes include lymphedema or arm dysfunction, quality of life based (EORTC QLQ-C30 and QLQ-BR23 questionnaires), disease-free survival, and overall survival. Discussion: This study aims to provide data to confirm the efficacy and safety of ART over ALND in patients with a positive SLN after NST, together with the impact on morbidity. Ethics and dissemination: The Research Ethics Committee of Bellvitge University Hospital approved this trial (Protocol Record PR148/21, version 3, 1/2/2022) and all patients must provide written informed consent. The involvement of around 50 centers across Spain will facilitate the dissemination of our results. Trial registration: ClinicalTrials.gov, identifier number NCT04889924.

Oral Sodium Chloride in the Prevention of Contrast-Associated Acute Kidney Injury in Elderly Outpatients: The PNIC-Na Randomized Non-Inferiority Trial.

OBJECTIVE: We aimed to test the non-inferiority of oral versus intravenous hydration in the incidence of contrast-associated acute kidney injury (CA-AKI) in elderly outpatients undergoing a contrast-enhanced computed tomography (CE-CT) scan. METHODS: PNIC-Na (NCT03476460) is a phase-2, single-center, randomized, open-label, non-inferiority trial. We included outpatients undergoing a CE-CT scan, >65 years having at least one risk factor for CA-AKI, such as diabetes, heart failure, or an estimated glomerular filtration rate (eGFR) of 30-59 mL/min/1.73 m². Participants were randomized (1:1) to oral sodium-chloride capsules or intravenous hydration. The primary outcome was an increase in serum creatinine >0.3 mg/dL or a reduction in eGFR >25% within 48 h. The non-inferiority margin was set at 5%. RESULTS: A total of 271 subjects (mean age 74 years, 66% male) were randomized, and 252 were considered for the main analysis (per-protocol). A total of 123 received oral hydration and 129 intravenous. CA-AKI occurred in 9 (3.6%) of 252 patients and 5/123 (4.1%) in the oral-hydration group vs. 4/129 (3.1%) in the intravenous-hydration group. The absolute difference between the groups was 1.0% (95% CI -4.8% to 7.0%), and the upper limit of the 95% CI exceeded the pre-established non-inferiority margin. No major safety concerns were observed. CONCLUSION: The incidence of CA-AKI was lower than expected. Although both regimens showed similar incidences of CA-AKI, the non-inferiority was not shown.