Ensembl 2024.

Ensembl (https://www.ensembl.org) is a freely available genomic resource that has produced high-quality annotations, tools, and services for vertebrates and model organisms for more than two decades. In recent years, there has been a dramatic shift in the genomic landscape, with a large increase in the number and phylogenetic breadth of high-quality reference genomes, alongside major advances in the pan-genome representations of higher species. In order to support these efforts and accelerate downstream research, Ensembl continues to focus on scaling for the rapid annotation of new genome assemblies, developing new methods for comparative analysis, and expanding the depth and quality of our genome annotations. This year we have continued our expansion to support global biodiversity research, doubling the number of annotated genomes we support on our Rapid Release site to over 1700, driven by our close collaboration with biodiversity projects such as Darwin Tree of Life. We have also strengthened support for key agricultural species, including the first regulatory builds for farmed animals, and have updated key tools and resources that support the global scientific community, notably the Ensembl Variant Effect Predictor. Ensembl data, software, and tools are freely available.

Effectiveness of Mepolizumab in Patients with Severe Eosinophilic Asthma with/without Nasal Polyposis: A Real-Life Study.

INTRODUCTION: Asthma is one of the most common chronic diseases and affects around 334 million people worldwide. The estimated prevalence of severe asthma is 3-10% of the asthmatic population. Mepolizumab has demonstrated efficacy in reducing exacerbations, oral corticosteroid use, and improving quality of life, asthma control, and lung function in patients with severe eosinophilic asthma (SEA). Our study aimed to check the response to mepolizumab in a series of severe asthma patients regarding exacerbations, oral corticosteroid use, asthma control, quality of life, and lung function and to compare the response between patients with and without nasal polyps. METHOD: This is a retrospective, multicenter study of RE-ASGRAMUR (Register of Severe Asthma of the Region of Murcia) performed in eight hospitals of the Region of Murcia (Spain) under routine clinical practice conditions. We included patients diagnosed with SEA who completed at least 1 year of treatment with mepolizumab. We analyzed clinical characteristics, drug tolerance, and effectiveness: exacerbations, ACT, miniAQLQ, forced expiratory volume in 1 s (FEV1), and use of oral corticosteroids. We also compared the results between patients with and without nasal polyps. RESULTS: The median of exacerbations before treatment was 3 and decreased to 0 after treatment (mean decrease of 77.4%). The median diary oral prednisone intake was 15 mg before treatment and 5 mg after treatment (mean 56% reduction). We have obtained a significant improvement in other variables: ED visits and hospitalizations, asthma control (ACT), quality of life (miniAQLQ), and lung function (FEV1). Thirty-four out of 70 patients (48.57%) fulfilled the criteria of super-responder, and 17 out of 70 (24.29%) had a complete response. More patients in the group with nasal polyps fulfilled the criteria of super-responder and complete response to mepolizumab. CONCLUSIONS: Mepolizumab is a safe and effective treatment for SEA patients, improving exacerbations, oral corticosteroid intake, asthma control, quality of life, and lung function. In patients with associated nasal polyposis, there is a statistically significant higher proportion of super-responders and complete responders.

Advanced Myocardial MRI Tissue Characterization Combining Contrast Agent-Free T1-Rho Mapping With Fully Automated Analysis.

BACKGROUND: Myocardial T1-rho (T1ρ) mapping is a promising method for identifying and quantifying myocardial injuries without contrast agents, but its clinical use is hindered by the lack of dedicated analysis tools. PURPOSE: To explore the feasibility of clinically integrated artificial intelligence-driven analysis for efficient and automated myocardial T1ρ mapping. STUDY TYPE: Retrospective. POPULATION: Five hundred seventy-three patients divided into a training (N = 500) and a test set (N = 73) including ischemic and nonischemic cases. FIELD STRENGTH/SEQUENCE: Single-shot bSSFP T1ρ mapping sequence at 1.5 T. ASSESSMENT: The automated process included: left ventricular (LV) wall segmentation, right ventricular insertion point detection and creation of a 16-segment model for segmental T1ρ value analysis. Two radiologists (20 and 7 years of MRI experience) provided ground truth annotations. Interobserver variability and segmentation quality were assessed using the Dice coefficient with manual segmentation as reference standard. Global and segmental T1ρ values were compared. Processing times were measured. STATISTICAL TESTS: Intraclass correlation coefficients (ICCs) and Bland-Altman analysis (bias ±2SD); Paired Student's t-tests and one-way ANOVA. A P value <0.05 was considered significant. RESULTS: The automated approach significantly reduced processing time (3 seconds vs. 1 minute 51 seconds ± 22 seconds). In the test set, automated LV wall segmentation closely matched manual results (Dice 81.9% ± 9.0) and closely aligned with interobserver segmentation (Dice 82.2% ± 6.5). Excellent ICCs were achieved on a patient basis (0.94 [95% CI: 0.91 to 0.96]) with bias of -0.93 cm2 ± 6.60. There was no significant difference in global T1ρ values between manual (54.9 msec ± 4.6; 95% CI: 53.8 to 56.0 msec, range: 46.6-70.9 msec) and automated processing (55.4 msec ± 5.1; 95% CI: 54.2 to 56.6 msec; range: 46.4-75.1 msec; P = 0.099). The pipeline demonstrated a high level of agreement with manual-derived T1ρ values at the patient level (ICC = 0.85; bias +0.52 msec ± 5.18). No significant differences in myocardial T1ρ values were found between methods across the 16 segments (P = 0.75). DATA CONCLUSION: Automated myocardial T1ρ mapping shows promise for the rapid and noninvasive assessment of heart disease. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Laparoscopic versus open approach for interval cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced epithelial ovarian cancer: a matched comparative study.

BACKGROUND: The use of the laparoscopic approach for the treatment of carcinomatosis from epithelial ovarian cancer (EOC) is controversial. The aim of this study was to compare the short-term outcomes of both laparoscopic and open approach for interval CRS+HIPEC in a matched cohort of patients with advanced EOC. METHODS: A retrospective analysis of a prospectively maintained database including 254 patients treated with interval CRS-HIPEC between January 2016 and December 2021 was performed. Patients with primary disease and limited carcinomatosis (PCI ≤ 10) were selected. A comparative analysis of patients treated by either open (O-CRS-HIPEC) or the laparoscopic (L-CRS-HIPEC) approach was conducted. Overall survival (OS), disease-free survival (DFS), and perioperative outcomes were analysed. RESULTS: Fifty-three patients were finally selected and enrolled into two comparable groups in this study. Of these, 14 patients were treated by interval L-CRS-HIPEC and 39 by interval O-CRS-HIPEC. The L-CRS-HIPEC group had a shorter hospital stay (5.6 ± 1.9 vs. 9.7 ± 9.8 days; p < 0.001) and a shorter time to return to systemic chemotherapy (4.3 ± 1.9 vs. 10.3 ± 16.8 weeks; p = 0.003). There were no significant differences in postoperative complications between both groups. The 2-year OS and DFS was 100% and 62% in the L-CRS-HIPEC group versus 92% and 60% in the O-CRS-HIPEC group, respectively (p = 0.96; p = 0.786). CONCLUSION: This study suggests that the use of interval L-CRS-HIPEC for primary advanced EOC is associated with shorter hospital stay and return to systemic treatment while obtaining similar oncological results compared to the open approach. Further prospective research is needed to recommend this new approach for these strictly selected patients.

The RIN4-like/NOI proteins NOI10 and NOI11 modulate the response to biotic stresses mediated by RIN4 in Arabidopsis.

KEY MESSAGE: NOI10 and NOI11 are two RIN4-like/NOI proteins that participate in the immune response of the Arabidopsis plant and affect the RIN4-regulated mechanisms involving the R-proteins RPM1 and RPS2. The immune response in plants depends on the regulation of signaling pathways triggered by pathogens and herbivores. RIN4, a protein of the RIN4-like/NOI family, is considered to be a central immune signal in the interactions of plants and pathogens. In Arabidopsis thaliana, four of the 15 members of the RIN4-like/NOI family (NOI3, NOI5, NOI10, and NOI11) were induced in response to the plant herbivore Tetranychus urticae. While overexpressing NOI10 and NOI11 plants did not affect mite performance, opposite callose accumulation patterns were observed when compared to RIN4 overexpressing plants. In vitro and in vivo analyses demonstrated the interaction of NOI10 and NOI11 with the RIN4 interactors RPM1, RPS2, and RIPK, suggesting a role in the context of the RIN4-regulated immune response. Transient expression experiments in Nicotiana benthamiana evidenced that NOI10 and NOI11 differed from RIN4 in their functionality. Furthermore, overexpressing NOI10 and NOI11 plants had significant differences in susceptibility with WT and overexpressing RIN4 plants when challenged with Pseudomonas syringae bacteria expressing the AvrRpt2 or the AvrRpm1 effectors. These results demonstrate the participation of NOI10 and NOI11 in the RIN4-mediated pathway. Whereas RIN4 is considered a guardee protein, NOI10 and NOI11 could act as decoys to modulate the concerted activity of effectors and R-proteins.

The beating heart: artificial intelligence for cardiovascular application in the clinic.

Artificial intelligence (AI) integration in cardiac magnetic resonance imaging presents new and exciting avenues for advancing patient care, automating post-processing tasks, and enhancing diagnostic precision and outcomes. The use of AI significantly streamlines the examination workflow through the reduction of acquisition and postprocessing durations, coupled with the automation of scan planning and acquisition parameters selection. This has led to a notable improvement in examination workflow efficiency, a reduction in operator variability, and an enhancement in overall image quality. Importantly, AI unlocks new possibilities to achieve spatial resolutions that were previously unattainable in patients. Furthermore, the potential for low-dose and contrast-agent-free imaging represents a stride toward safer and more patient-friendly diagnostic procedures. Beyond these benefits, AI facilitates precise risk stratification and prognosis evaluation by adeptly analysing extensive datasets. This comprehensive review article explores recent applications of AI in the realm of cardiac magnetic resonance imaging, offering insights into its transformative potential in the field.

PHI-base in 2022: a multi-species phenotype database for Pathogen-Host Interactions.

Since 2005, the Pathogen-Host Interactions Database (PHI-base) has manually curated experimentally verified pathogenicity, virulence and effector genes from fungal, bacterial and protist pathogens, which infect animal, plant, fish, insect and/or fungal hosts. PHI-base (www.phi-base.org) is devoted to the identification and presentation of phenotype information on pathogenicity and effector genes and their host interactions. Specific gene alterations that did not alter the in host interaction phenotype are also presented. PHI-base is invaluable for comparative analyses and for the discovery of candidate targets in medically and agronomically important species for intervention. Version 4.12 (September 2021) contains 4387 references, and provides information on 8411 genes from 279 pathogens, tested on 228 hosts in 18, 190 interactions. This provides a 24% increase in gene content since Version 4.8 (September 2019). Bacterial and fungal pathogens represent the majority of the interaction data, with a 54:46 split of entries, whilst protists, protozoa, nematodes and insects represent 3.6% of entries. Host species consist of approximately 54% plants and 46% others of medical, veterinary and/or environmental importance. PHI-base data is disseminated to UniProtKB, FungiDB and Ensembl Genomes. PHI-base will migrate to a new gene-centric version (version 5.0) in early 2022. This major development is briefly described.

Ensembl Genomes 2022: an expanding genome resource for non-vertebrates.

Ensembl Genomes (https://www.ensemblgenomes.org) provides access to non-vertebrate genomes and analysis complementing vertebrate resources developed by the Ensembl project (https://www.ensembl.org). The two resources collectively present genome annotation through a consistent set of interfaces spanning the tree of life presenting genome sequence, annotation, variation, transcriptomic data and comparative analysis. Here, we present our largest increase in plant, metazoan and fungal genomes since the project's inception creating one of the world's most comprehensive genomic resources and describe our efforts to reduce genome redundancy in our Bacteria portal. We detail our new efforts in gene annotation, our emerging support for pangenome analysis, our efforts to accelerate data dissemination through the Ensembl Rapid Release resource and our new AlphaFold visualization. Finally, we present details of our future plans including updates on our integration with Ensembl, and how we plan to improve our support for the microbial research community. Software and data are made available without restriction via our website, online tools platform and programmatic interfaces (available under an Apache 2.0 license). Data updates are synchronised with Ensembl's release cycle.

Size Control of Chiral Nanospheres Obtained via Nanoprecipitation of Helical Poly(phenylacetylene)s in the Absence of Surfactants.

Nanostructuration of dynamic helical polymers such as poly(phenylacetylene)s (PPAs) depends on the secondary structure adopted by the polymer and the functional group used to connect the chiral pendant to the PPA backbone. Thus, while PPAs with dynamic and flexible scaffolds (para- and meta-substituted, ω1< 165º) generate by nanoprecipitation low polydisperse nanospheres with controllable size at different acetone/water mixtures, those with a quasi-static behavior and the presence of an extended, almost planar structure (ortho-substituted, ω1> 165º), aggregate into a mixture of spherical and oval nanostructures whose size is not controlled. Photostability studies show that poly(phenylacetylene) particles are more stable to light irradiation than when dissolved macromolecularly. Moreover, the photostability of the particle depends on the secondary structure of the PPA and its screw sense excess. This fact, in combination with the encapsulation ability of these polymer particles, allows the creation of light stimuli-responsive nanocarriers, whose cargo can be delivered by light irradiation.

Changing patterns of nest predation and predator communities along a tropical elevation gradient.

Tropical montane communities host the world's highest beta diversity of birds, a phenomenon usually attributed to community turnover caused by changes in biotic and abiotic factors along elevation gradients. Yet, empirical data on most biotic factors are lacking. Nest predation is thought to be especially important because it appears to be common and can change selective pressures underlying life history traits, which can alter competitive interactions. We monitored 2538 nests, 338 of which had known nest predators, to evaluate if nest predation changes along a tropical elevational gradient. We found that nest predation decreased with elevation, reflecting the loss of lowland predators that do not tolerate colder climates. We found different "super" nest predators at each elevation that accounted for a high percentage of events, suggesting that selection pressures exerted by nest predator communities may be less diffuse than has been hypothesized, at least for birds nesting in the understory.

Respiratory and allergic outcomes among 5-year-old children exposed to pesticides.

BACKGROUND: Little is known about the effects of pesticides on children's respiratory and allergic outcomes. We evaluated associations of prenatal and current pesticide exposures with respiratory and allergic outcomes in children from the Infants' Environmental Health Study in Costa Rica. METHODS: Among 5-year-old children (n=303), we measured prenatal and current specific gravity-corrected urinary metabolite concentrations of insecticides (chlorpyrifos, pyrethroids), fungicides (mancozeb, pyrimethanil, thiabendazole) and 2,4-D. We collected information from caregivers on respiratory (ever doctor-diagnosed asthma and lower respiratory tract infections (LRTI), wheeze and cough during last 12 months) and allergic (nasal allergies, itchy rash, ever eczema) outcomes. We fitted separate multivariable logistic regression models for high (≥75th percentile (P75)) vs low (

Hydroxynitrile lyase defends Arabidopsis against Tetranychus urticae.

Plant-pest interactions involve multifaceted processes encompassing a complex crosstalk of pathways, molecules, and regulators aimed at overcoming defenses developed by each interacting organism. Among plant defensive compounds against phytophagous arthropods, cyanide-derived products are toxic molecules that directly target pest physiology. Here, we identified the Arabidopsis (Arabidopsis thaliana) gene encoding hydroxynitrile lyase (AtHNL, At5g10300) as one gene induced in response to spider mite (Tetranychus urticae) infestation. AtHNL catalyzes the reversible interconversion between cyanohydrins and derived carbonyl compounds with free cyanide. AtHNL loss- and gain-of-function Arabidopsis plants showed that specific activity of AtHNL using mandelonitrile as substrate was higher in the overexpressing lines than in wild-type (WT) and mutant lines. Concomitantly, mandelonitrile accumulated at higher levels in mutant lines than in WT plants and was significantly reduced in the AtHNL overexpressing lines. After mite infestation, mandelonitrile content increased in WT and overexpressing plants but not in mutant lines, while hydrogen cyanide (HCN) accumulated in the three infested Arabidopsis genotypes. Feeding bioassays demonstrated that the AtHNL gene participated in Arabidopsis defense against T. urticae. The reduced leaf damage detected in the AtHNL overexpressing lines reflected the mite's reduced ability to feed on leaves, which consequently restricted mite fecundity. In turn, mites upregulated TuCAS1 encoding ß-cyanoalanine synthase to avoid the respiratory damage produced by HCN. This detoxification effect was functionally demonstrated by reduced mite fecundity observed when dsRNA-TuCAS-treated mites fed on WT plants and hnl1 mutant lines. These findings add more players in the Arabidopsis-T. urticae interplay to overcome mutual defenses.

Dynamic Invasive Hemodynamic Congestion Profile Impacts Acute Myocardial Infarction Complicated by Cardiogenic Shock Outcomes: A Real-World Single-Center Study.

BACKGROUND: Cardiogenic shock (CS) commonly complicates the management of acute myocardial infarction (AMI), and it results in high mortality rates. Pulmonary artery catheter (PAC) monitoring can be valuable for personalizing critical-care interventions. We hypothesized that patients with AMI-CS experiencing persistent congestion measures during the first 24 hours of the PAC installment would exhibit worse in-hospital survival rates. METHODS AND RESULTS: We studied 295 patients with AMI-CS between January 2006 and December 2021. The first 24-hour PAC-derived hemodynamic measures were divided by the congestion profiling and the proposed 2022 Cardiovascular Angiography and Interventions (SCAI) classification. Biventricular congestion was the most common profile and was associated with the highest patient mortality rates at all time points (mean 56.6%). A persistent congestive profile was associated with increased mortality rates (hazard ratio [HR] = 1.85; P = 0.002) compared with patients who achieved decongestive profiles. Patients with SCAI stages D/E had higher levels of right atrial pressure (RAP): 14-15 mmHg) and pulmonary capillary wedge pressure (PCWP): 18-20 mmHg) compared with stage C (RAP, 10-11 mmHg, mean difference 3-5 mmHg; P < 0.001; PCWP 14-17 mmHg; mean difference 1.56-4 mmHg; P = 0.011). In SCAI stages D/E, the pulmonary artery pulsatility index (0.8-1.19) was lower than in those with grade C (1.29-1.63; mean difference 0.21-0.73; P < 0.001). CONCLUSIONS: Continuous congestion profiling using the SCAI classification matched the grade of hemodynamic severity and the increased risk of in-hospital death. Early decongestion appears to be an important prognostic and therapeutic goal in patients with AMI-CS and warrants further study.

Steric hindrance, ligand ejection and associated photocytotoxic properties of ruthenium(II) polypyridyl complexes.

Two ruthenium(II) polypyridyl complexes were prepared with the {Ru(phen)2}2+ moiety and a third sterically non-hindering bidentate ligand, namely 2,2'-dipyridylamine (dpa) and N-benzyl-2,2'-dipyridylamine (Bndpa). Hence, complexes [Ru(phen)2(dpa)](PF6)2 (1) and [Ru(phen)2(Bndpa)](PF6)2 (2) were characterized and their photochemical behaviour in solution (acetonitrile and water) was subsequently investigated. Compounds 1 and 2, which do not exhibit notably distorted octahedral coordination environments, contrarily to the homoleptic "parent" compound [Ru(phen)3](PF6)2, experience two-step photoejection of the dpa and Bndpa ligand upon irradiation (1050-430 nm) for several hours. DNA-binding studies revealed that compounds 1 and 2 affect the biomolecule differently upon irradiation; while 2 solely modifies its electrophoretic mobility, complex 1 is also capable of cleaving it. In vitro cytotoxicity studies with two cancer-cell lines, namely A549 (lung adenocarcinoma) and A375 (melanoma), showed that both 1 and 2 are not toxic in the dark, while only 1 is significantly cytotoxic if irradiated, 2 remaining non-toxic under these conditions. Light irradiation of the complex cation [Ru(phen)2(dpa)]2+ leads to the generation of transient Ru species that is present in the solution medium for several hours, and that is significantly cytotoxic, ultimately producing non-toxic free dpa and [Ru(phen)(OH2)2]2+.

Dark-field and directional dark-field on low-coherence x ray sources with random mask modulations: validation with SAXS anisotropy measurements.

Phase-contrast imaging, dark-field, and directional dark-field imaging are recent x ray imaging modalities that have been demonstrated to reveal different information and contrast from those provided by conventional x ray imaging. Access to these new types of images is currently limited because the acquisitions require coherent sources such as synchrotron radiation or complicated optical setups. This Letter demonstrates the possibility of efficiently performing phase-contrast, dark-field, and directional dark-field imaging on a low-coherence laboratory system equipped with a conventional x ray tube, using a simple, fast, and robust single-mask technique.

Kinetico-Mechanistic Studies on a Reactive Organocopper(II) Complex: Cu-C Bond Homolysis versus Heterolysis.

Organocopper(II) reagents are an unexplored frontier of copper catalysis. Despite being proposed as reactive intermediates, an understanding of the stability and reactivity of the CuII-C bond has remained elusive. Two main pathways can be considered for the cleavage mode of a CuII-C bond: homolysis and heterolysis. We recently showed how organocopper(II) reagents can react with alkenes via radical addition, a homolytic pathway. In this work, the decomposition of the complex [CuIILR]+ [L = tris(2- dimethylaminoethyl)amine, Me6tren, R = NCCH2-] in the absence and presence of an initiator (RX, X = Cl, Br) was evaluated. When no initiator was present, first-order CuII-C bond homolysis occurred producing [CuIL]+ and succinonitrile, via radical termination. When an excess of the initiator was present, a subsequent formation of [CuIILX]+ via a second-order reaction was found, which results from the reaction of [CuIL]+ with RX following homolysis. However, when Brønsted acids (R'-OH: R' = H, Me, Ph, PhCO) were present, heterolytic cleavage of the CuII-C bond produced [CuIIL(OR')]+ and MeCN. Kinetic studies were undertaken to obtain the thermal (ΔH⧧, ΔS⧧) and pressure (ΔV⧧) activation parameters and deuterium kinetic isotopic effects, which provided an understanding of the strength of the CuII-C bond and the nature of the transition state for the reactions involved. These results reveal possible reaction pathways for organocopper(II) complexes relevant to their applications as catalysts in C-C bond forming reactions.

Pulse arrival time variation as a non-invasive marker of acute response to cardiac resynchronization therapy.

AIMS: Successful cardiac resynchronization therapy (CRT) shortens the pre-ejection period (PEP) which is prolonged in the left bundle branch block (LBBB). In a combined animal and patient study, we investigated if changes in the pulse arrival time (PAT) could be used to measure acute changes in PEP during CRT implantation and hence be used to evaluate acute CRT response non-invasively and in real time. METHODS AND RESULTS: In six canines, a pulse transducer was attached to a lower limb and PAT was measured together with left ventricular (LV) pressure by micromanometer at baseline, after induction of LBBB and during biventricular pacing. Time-to-peak LV dP/dt (Td) was used as a surrogate for PEP. In twelve LBBB patients during implantation of CRT, LV and femoral pressures were measured at baseline and during five different pacing configurations. PAT increased from baseline (277 ± 9 ms) to LBBB (313 ± 16 ms, P < 0.05) and shortened with biventricular pacing (290 ± 16 ms, P < 0.05) in animals. There was a strong relationship between changes in PAT and Td in patients (r2 = 0.91). Two patients were classified as non-responders at 6 months follow-up. CRT decreased PAT from 320 ± 41 to 298 ± 39 ms (P < 0.05) in the responders, while PAT increased by 5 and 8 ms in the two non-responders. CONCLUSION: This proof-of-concept study indicates that PAT can be used as a simple, non-invasive method to assess the acute effects of CRT in real time with the potential to identify long-term response in patients.

Home-based prehabilitation improves physical conditions measured by ergospirometry and 6MWT in colorectal cancer patients: a randomized controlled pilot study.

PURPOSE/BACKGROUND: Prehabilitation aims to improve physical condition in the preoperative period and, therefore, decrease the loss of cardiopulmonary capacity postoperatively, with the aim of reducing complications and promoting an early recovery. This study aims to evaluate the impact of home-based prehabilitation on the physical condition of patients treated surgically for colorectal cancer. METHODS: A prospective and randomized clinical study was conducted on 60 patients during two periods from October 2018 to February 2019 and from September 2019 to September 2020, in a single university hospital. Patients were randomized into two study groups (30 per group): prehabilitation vs. standard care. Changes in physical condition, measured at diagnosis, the day before surgery, and at 6-8 weeks after surgery using the cardiopulmonary exercise testing (CPET) and the 6-minute walk test (6MWT) were evaluated. RESULTS: Prehabilitation reduced postoperative complications (17.4% vs. 33.3%, p = 0.22) and hospital stay (5.74 vs. 6.67 days, p = 0.30). 6MWT showed a significant improvement in the prehabilitation group (+78.9 m). Six weeks after surgery, prehabilitation showed a significant improvement in the 6MWT (+68.9 m vs. -27.2 m, p = 0.01). Significant differences were also observed in the ergospirometry between the diagnosis and postoperative study (+0.79 METs vs. -0.84 METs, p = 0.001). A strong correlation was observed between CPET and 6MWT (0.767 (p < 0.001)). CONCLUSION: Home prehabilitation achieved lower overall postoperative complications than standard care and reached significant improvements in 6MWT and CET. A strong correlation was observed between CET and 6MWT, which allows validation of 6MWT as a valid and reliable measure of functional exercise capacity in colorectal patients when other, more specific and expensive tests are not available. TRIAL REGISTRATION: Registered in ClinicalTrials.gov in August 2018 with registration number https://clinicaltrials.gov/study/NCT03618329?cond=Prehabilitation%20cancer&term=arroyo&distance=50&rank=1  (NCT03618329). Initial results published in Supportive Care in Cancer: Effect of home-based prehabilitation in an enhanced recovery after surgery program for patients undergoing colorectal cancer surgery during the COVID-19 pandemic. DOI: https://doi.org/10.1007/s00520-021-06343-1 .

A cross-sectional analysis of medical conditions and environmental factors associated with fractional exhaled nitric oxide (FeNO) in women and children from the ISA birth cohort, Costa Rica.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a marker of airway inflammation. Elevated FeNO has been associated with environmental exposures, however, studies from tropical countries are limited. Using data from the Infants' Environmental Health Study (ISA) birth cohort, we evaluated medical conditions and environmental exposures' association with elevated FeNO. METHODS: We performed a cross-sectional analysis of 277 women and 293 8-year old children who participated in the 8-year post-partum visit in 2019. We measured FeNO and collected information on medical conditions and environmental exposures including smoke from waste burning, work in banana plantations, and home pesticide use. We defined elevated FeNO as >25 ppb for women and >20 ppb for children. To evaluate factors associated with elevated FeNO, we used logistic regression models adjusted for obesity in women and unadjusted in children. RESULTS: Overall elevated FeNO was common (20% of women, 13% of children). Rhinitis diagnosis was significantly associated with elevated FeNO in both women (odds ratio (OR): 3.67 95% Confidence Interval (CI): 1.81,7.35) and children (OR: 8.18 95%CI: 3.15, 21.22); wheeze was associated with elevated FeNO in women (OR: 4.50 95% CI: 2.25, 8.99). Environmental exposures were associated with elevated FeNO, but not significantly. Waste burning was associated with elevated FeNO in both women (OR: 1.58 95%CI 0.68, 4.15) and children (OR: 2.49 95%CI:0.82, 10.79). Para-occupational pesticide exposures were associated with elevated FeNO in women and children. For women, having a partner working in agriculture was associated with elevated FeNO (OR: 1.61 95%CI:0.77, 3.58) and for children, maternal work in agriculture was associated with elevated FeNO. (OR 2.08 95%CI 0.86, 4.67) CONCLUSION: Rhinitis and wheeze were associated with elevated FeNO in this rural, agricultural population. Smoke from waste burning as well as para-occupational pesticide exposure may contribute to elevated FeNO in rural communities.

Learning curve for minimal invasive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) procedures.

PURPOSE: The benefits of the minimally invasive approach for performing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (L-CRS + HIPEC) have been described previously, associating an early recovery with similar oncologic outcomes in patients with limited peritoneal carcinomatosis. Currently, no studies are focusing on the learning curve for this emerging procedure. This study aimed to evaluate the L-CRS + HIPEC learning curve and its knock-on effect on the perioperative outcomes. METHODS: We identified all consecutive unselected patients who underwent L-CRS + HIPEC by a single surgeon between April 2016 and January 2022 (n = 51). Patients who underwent risk-reducing CRS + HIPEC (PCI = 0) or initial conversion due to an intraoperative PCI > 10 were excluded from the final analysis. To evaluate the learning curve, perioperative data were analysed using the cumulative sum (CUSUM) analysis. RESULTS: Twenty-six patients were included in the final analysis. Major morbidity occurred in one patient (3.8%). The difficulty of the L-CRS + HIPEC procedures was categorised as low in 23.1% (n = 6), intermediate in 19.2% (n = 5), and advanced in 57.7% (n = 15). The mean length of hospital stay was 5.4 ± 1.5 days. No patient had a conversion to open surgery. The learning curve was divided into two distinct phases: the learning phase (1-14) and the consolidation phase (15-26). A significant decrease in the operative time (375 ± 103.1 vs 239.2 ± 63.6 min) was observed with no differences in complexity, the number of peritonectomy procedures, or morbidity. CONCLUSION: L-CRS + HIPEC is a complex procedure that must be performed in a high-volume and experienced oncologic unit, requiring a learning curve to achieve the consolidation condition, which could be established after 14 procedures.