Withdrawal of drug therapy in responders to cardiac resynchronization therapy: rationale and design of the REMOVE trial.

Introduction and objectives Cardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients. Methods The REMOVE trial (NCT05151861) is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF > 10% (provided the LVEF is < 50%); b) a reduction in LVEF > 10% accompanied by an increase > 15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted. Conclusions The results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients.

Deep Ordinal Classification in Forest Areas Using Light Detection and Ranging Point Clouds.

Recent advances in Deep Learning and aerial Light Detection And Ranging (LiDAR) have offered the possibility of refining the classification and segmentation of 3D point clouds to contribute to the monitoring of complex environments. In this context, the present study focuses on developing an ordinal classification model in forest areas where LiDAR point clouds can be classified into four distinct ordinal classes: ground, low vegetation, medium vegetation, and high vegetation. To do so, an effective soft labeling technique based on a novel proposed generalized exponential function (CE-GE) is applied to the PointNet network architecture. Statistical analyses based on Kolmogorov-Smirnov and Student's t-test reveal that the CE-GE method achieves the best results for all the evaluation metrics compared to other methodologies. Regarding the confusion matrices of the best alternative conceived and the standard categorical cross-entropy method, the smoothed ordinal classification obtains a more consistent classification compared to the nominal approach. Thus, the proposed methodology significantly improves the point-by-point classification of PointNet, reducing the errors in distinguishing between the middle classes (low vegetation and medium vegetation).

Exploring the electronic and steric effects on the dimerization of intramolecular frustrated Lewis pairs: a comparison between aminoboranes and aminoalanes.

The dimerization of intramolecular aminoborane and aminoalane frustrated Lewis pairs was investigated using density functional theory. We systematically varied the substituents to gradually increase their bulkiness, including H, CH3, t-Bu, Ph, and Mes groups. Starting from the most stable conformer of the monomers, a frustrated Lewis pair or classic Lewis adduct, we studied the dimerization process for all systems, revealing significant variations in the Gibbs free energy. Dimerization was favored in four aminoboranes and six aminoalanes, depending on the specific combinations of substituents. Applying an energy decomposition analysis, we found that the preparation energy of the monomers and the non-orbital interactions between them are the primary contributors to the observed energetic differences, showing a clear linear relationship. Additionally, we analyzed the electronic effects by increasing the acidity of the Lewis acid, observing a shift toward endergonic and exergonic directions in aminoboranes and aminoalanes, respectively. This shift was attributed to the stabilization of a classic Lewis adduct. This study underscores three crucial factors influencing dimer formation: (i) substituent size, (ii) stabilization of the classic Lewis adduct conformation, and (iii) covalent radii of the Lewis centers. Understanding these factors is essential for designing FLPs and preventing unwanted dimerization that could affect their catalytic performance in H2 activation processes.

Substitution Effects in Aryl Halides and Amides into the Reaction Mechanism of Ullmann-Type Coupling Reactions.

In this article, we present a comprehensive computational investigation into the reaction mechanism of N-arylation of substituted aryl halides through Ullmann-type coupling reactions. Our computational findings, obtained through DFT ωB97X-D/6-311G(d,p) and ωB97X-D/LanL2DZ calculations, reveal a direct relation between the previously reported experimental reaction yields and the activation energy of haloarene activation, which constitutes the rate-limiting step in the overall coupling process. A detailed analysis of the reaction mechanism employing the Activation Strain Model indicates that the strain in the substituted iodoanilines is the primary contributor to the energy barrier, representing an average of 80% of the total strain energy. Additional analysis based on conceptual Density Functional Theory (DFT) suggests that the nucleophilicity of the nitrogen in the lactam is directly linked to the activation energies. These results provide valuable insights into the factors influencing energetic barriers and, consequently, reaction yields. These insights enable the rational modification of reactants to optimize the N-arylation process.

Flexible gold standards for transcription factor regulatory interactions in Escherichia coli K-12: architecture of evidence types.

Post-genomic implementations have expanded the experimental strategies to identify elements involved in the regulation of transcription initiation. Here, we present for the first time a detailed analysis of the sources of knowledge supporting the collection of transcriptional regulatory interactions (RIs) of Escherichia coli K-12. An RI groups the transcription factor, its effect (positive or negative) and the regulated target, a promoter, a gene or transcription unit. We improved the evidence codes so that specific methods are incorporated and classified into independent groups. On this basis we updated the computation of confidence levels, weak, strong, or confirmed, for the collection of RIs. These updates enabled us to map the RI set to the current collection of HT TF-binding datasets from ChIP-seq, ChIP-exo, gSELEX and DAP-seq in RegulonDB, enriching in this way the evidence of close to one-quarter (1329) of RIs from the current total 5446 RIs. Based on the new computational capabilities of our improved annotation of evidence sources, we can now analyze the internal architecture of evidence, their categories (experimental, classical, HT, computational), and confidence levels. This is how we know that the joint contribution of HT and computational methods increase the overall fraction of reliable RIs (the sum of confirmed and strong evidence) from 49% to 71%. Thus, the current collection has 3912 reliable RIs, with 2718 or 70% of them with classical evidence which can be used to benchmark novel HT methods. Users can selectively exclude the method they want to benchmark, or keep for instance only the confirmed interactions. The recovery of regulatory sites in RegulonDB by the different HT methods ranges between 33% by ChIP-exo to 76% by ChIP-seq although as discussed, many potential confounding factors limit their interpretation. The collection of improvements reported here provides a solid foundation to incorporate new methods and data, and to further integrate the diverse sources of knowledge of the different components of the transcriptional regulatory network. There is no other genomic database that offers this comprehensive high-quality architecture of knowledge supporting a corpus of transcriptional regulatory interactions.

A memetic dynamic coral reef optimisation algorithm for simultaneous training, design, and optimisation of artificial neural networks.

Artificial Neural Networks (ANNs) have been used in a multitude of real-world applications given their predictive capabilities, and algorithms based on gradient descent, such as Backpropagation (BP) and variants, are usually considered for their optimisation. However, these algorithms have been shown to get stuck at local optima, and they require a cautious design of the architecture of the model. This paper proposes a novel memetic training method for simultaneously learning the ANNs structure and weights based on the Coral Reef Optimisation algorithms (CROs), a global-search metaheuristic based on corals' biology and coral reef formation. Three versions based on the original CRO combined with a Local Search procedure are developed: (1) the basic one, called Memetic CRO; (2) a statistically guided version called Memetic SCRO (M-SCRO) that adjusts the algorithm parameters based on the population fitness; (3) and, finally, an improved Dynamic Statistically-driven version called Memetic Dynamic SCRO (M-DSCRO). M-DSCRO is designed with the idea of improving the M-SCRO version in the evolutionary process, evaluating whether the fitness distribution of the population of ANNs is normal to automatically decide the statistic to be used for assigning the algorithm parameters. Furthermore, all algorithms are adapted to the design of ANNs by means of the most suitable operators. The performance of the different algorithms is evaluated with 40 classification datasets, showing that the proposed M-DSCRO algorithm outperforms the other two versions on most of the datasets. In the final analysis, M-DSCRO is compared against four state-of-the-art methods, demonstrating its superior efficacy in terms of overall accuracy and minority class performance.

Learning Ordinal-Hierarchical Constraints for Deep Learning Classifiers.

Real-world classification problems may disclose different hierarchical levels where the categories are displayed in an ordinal structure. However, no specific deep learning (DL) models simultaneously learn hierarchical and ordinal constraints while improving generalization performance. To fill this gap, we propose the introduction of two novel ordinal-hierarchical DL methodologies, namely, the hierarchical cumulative link model (HCLM) and hierarchical-ordinal binary decomposition (HOBD), which are able to model the ordinal structure within different hierarchical levels of the labels. In particular, we decompose the hierarchical-ordinal problem into local and global graph paths that may encode an ordinal constraint for each hierarchical level. Thus, we frame this problem as simultaneously minimizing global and local losses. Furthermore, the ordinal constraints are set by two approaches ordinal binary decomposition (OBD) and cumulative link model (CLM) within each global and local function. The effectiveness of the proposed approach is measured on four real-use case datasets concerning industrial, biomedical, computer vision, and financial domains. The extracted results demonstrate a statistically significant improvement to state-of-the-art nominal, ordinal, and hierarchical approaches.

Harnessing Non-Thermal Plasma to Supercharge Recovery in Abdominal Surgeries: A Pilot Study.

(1) Background: This study aims to evaluate the efficacy and safety of non-thermal plasma (NTP) therapy in accelerating wound healing in patients who have undergone laparoscopic and open surgeries. (2) Methods: NTP was applied using a needle-type reactor with an irradiance of 0.5 W/cm2 on the surgical wounds of fifty patients after obtaining informed consent. Three NTP treatments, each lasting three minutes, were administered hourly. (3) Results: The pilot study showed that NTP-treated surgical wounds healed completely without any signs of infection, dehiscence, pain, or itching. Notably, patients reported minimal pain after the NTP treatment. Visual assessments conducted twenty-four hours after surgery revealed no redness or fluid discharge. Comparisons with traditionally sutured wounds indicated that NTP-treated wounds healed at a rate equivalent to seven days. (4) Conclusions: The application of NTP in laparoscopic and open wounds proved safe and effective, expediting the wound healing process and eliminating clinical risks post-surgery. Significantly, NTP facilitated a healing rate within twenty-four hours, equivalent to seven days for suture-treated wounds, significantly reducing the hospitalization time to a single day. These findings highlight the potential of NTP to be a transformative approach for promoting postoperative recovery.

RegulonDB v12.0: a comprehensive resource of transcriptional regulation in E. coli K-12.

RegulonDB is a database that contains the most comprehensive corpus of knowledge of the regulation of transcription initiation of Escherichia coli K-12, including data from both classical molecular biology and high-throughput methodologies. Here, we describe biological advances since our last NAR paper of 2019. We explain the changes to satisfy FAIR requirements. We also present a full reconstruction of the RegulonDB computational infrastructure, which has significantly improved data storage, retrieval and accessibility and thus supports a more intuitive and user-friendly experience. The integration of graphical tools provides clear visual representations of genetic regulation data, facilitating data interpretation and knowledge integration. RegulonDB version 12.0 can be accessed at https://regulondb.ccg.unam.mx.

Design of the Global Health chemical diversity library v2 for screening against infectious diseases.

There is a need for novel chemical matter for phenotypic and target-based screens to find starting points for drug discovery programmes in neglected infectious diseases and non-hormonal contraceptives that disproportionately affect Low- and Middle-Income Countries (LMICs). In some disease areas multiple screens of corporate and other libraries have been carried out, giving rise to some valuable starting points and leading to preclinical candidates. Whilst in other disease areas, little screening has been carried out. Much screening against pathogens has been conducted phenotypically as there are few robustly validated protein targets. However, many of the active compound series identified share the same molecular targets. To address the need for new chemical material, in this article we describe the design of a new library, designed for screening in drug discovery programmes for neglected infectious diseases. The compounds have been selected from the Enamine REAL (REadily AccessibLe) library, a virtual library which contains approximately 4.5 billion molecules. The molecules theoretically can be synthesized quickly using commercially available intermediates and building blocks. The vast majority of these have not been prepared before, so this is a source of novel compounds. In this paper we describe the design of a diverse library of 30,000 compounds from this collection (graphical abstract). The new library will be made available to laboratories working in neglected infectious diseases, subject to a review process. The project has been supported by the Bill & Melinda Gates Foundation and the Wellcome Trust (Wellcome).

New insights into H2 activation by intramolecular frustrated Lewis pairs based on aminoboranes: the local electrophilicity index of boron as a suitable indicator to tune the reversibility of the process.

A large set of intramolecular aminoborane-based FLPs was studied employing density functional theory in the H2 activation process to analyze how the acidity and basicity of boron and nitrogen atoms, respectively, affect the reversibility of the process. Three different linkers were employed, keeping the C-C nature in the connection between both Lewis centers: -CH2-CH2-, -CH[double bond, length as m-dash]CH-, and -C6H4-. The results show that significant differences in the Gibbs free energy of the process are found by considering all the combinations of substituents. Of the 75 systems studied, only 9 showed the ability to carry out the process reversibly (ΔGH2 in the range of -3.5 to 2.0 kcal mol-1), where combinations of alkyl/aryl or aryl/alkyl in boron/nitrogen generate systems capable of reaching reversibility. If the alkyl/alkyl or aryl/aryl combination is employed, highly exergonic (non-reversible H2 activation) and endergonic (unfeasible H2 activation) reactions are found, respectively. No appreciable differences in the linker were found, allowing us to continue the analysis with the most entropically favorable linker, the -C6H4- linker. From this, 25 different FLP systems of type 2-[bis(X)boryl]-(Y)aniline (X: H, CF3, C6F5, PFtB, FMes and Y: H, CH3, t-but, Ph, Mes) can be formed. By analyzing the electronic properties of each system, we have found that the condensed-to-boron electrophilicity index ωB+ is inversely related to the ΔGH2. Interestingly, two relationships were found; the first is for alkyl groups (Y: CH3 and t-but) and the second for aryl groups (Y: H, Ph, and Mes), which is intimately related to the proton affinity of each aniline. In addition, it is quite interesting when the frustration degree, given by B⋯N distance dB-N, is brought together with ωB+, since the quotient has unit energy/length corresponding to unit force; concomitantly, a measure of the FLP strength in H-H bond activation can be defined. With this finding, a rational design of this kind of FLP can be performed by analyzing the acidity of boron through condensed-to-boron electrophilicity and knowing the nature of the substituent of nitrogen according to whether the Y is alkyl or aryl, optimizing the H2 reversible activation in a rational way, which is crucial to improve the catalytic performance.

Dynamics of the Microbiota and Its Relationship with Post-COVID-19 Syndrome.

Coronavirus disease (COVID-19) is an infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be asymptomatic or present with multiple organ dysfunction. Many infected individuals have chronic alterations associated with neuropsychiatric, endocrine, gastrointestinal, and musculoskeletal symptoms, even several months after disease onset, developing long-COVID or post-acute COVID-19 syndrome (PACS). Microbiota dysbiosis contributes to the onset and progression of many viral diseases, including COVID-19 and post-COVID-19 manifestations, which could serve as potential diagnostic and prognostic biomarkers. This review aimed to discuss the most recent findings on gut microbiota dysbiosis and its relationship with the sequelae of PACS. Elucidating these mechanisms could help develop personalized and non-invasive clinical strategies to identify individuals at a higher risk of experiencing severe disease progression or complications associated with PACS. Moreover, the review highlights the importance of targeting the gut microbiota composition to avoid dysbiosis and to develop possible prophylactic and therapeutic measures against COVID-19 and PACS in future studies.

Experiencia inicial en nuestro centro con la embolización preventiva de la arteria mesentérica inferior en el tratamiento endovascular de los aneurismas de aorta abdominal / Early experience with preventive embolization of the inferior mesenteric artery in the endovascular treatment of abdominal aortic aneurysms

Introducción: la endofuga de tipo II (EFT2) es la más frecuente tras la reparación endovascular de aneurismas de aorta abdominal (EVAR). Objetivos: analizar la presencia de endofugas de tipo II durante el seguimiento, la regresión del saco aneurismático, la tasa de reintervención debido a EFT2, el análisis de los resultados en nuestra serie de casos tratados con embolización de la AMI antes del implante de la endoprótesis aórtica como método útil para disminuir las EFT2 durante el seguimiento. Material y métodos: análisis retrospectivo de los pacientes tratados en nuestro centro con embolización de la AMI previa al EVAR en el periodo 2019-2021. Los criterios utilizados para la embolización de la AMI fueron: diámetro > 3 mm y AL con diámetro > 2 mm o aneurismas aortoilíacos. Se incluyeron 7 pacientes varones (edad media: 72,1 años). El 42 % presentaba aneurismas aortoilíacos. En dos casos se llevó a cabo la embolización de la AMI en un primer tiempo y posteriormente el EVAR; en los restantes se realizó en el mismo procedimiento. El diámetro medio de la AMI fue 5,02 ± 0,9 mm. Todos los pacientes presentaban, al menos, dos AL enfrentadas al origen de la AMI con un diámetro > 2 mm. Resultados: el éxito técnico fue del 100 %. La mediana de seguimiento, 20,7 meses. En los angio TAC al mes y a los 12 meses se objetivó una correcta embolización de la AMI. No hubo fugas de tipo II durante el seguimiento. En todos los casos se visualizó una disminución en el diámetro del saco aneurismático (mediana de regresión: 5,08 mm). No hubo reintervenciones relacionadas con la patología aórtica. Conclusiones: la embolización de la AMI previa al EVAR en pacientes con un diámetro > 3 mm y al menos dos AL con diámetro > 2 mm o aneurismas aortoilíacos parece proteger frente al desarrollo de EFT2 a los 12 meses, a la espera de poder confirmar los resultados a medio y largo plazo. Alto éxito técnico y aceptable regresión del saco aneurismático.(AU)

Introduction: type II endoleak (T2EL), through the inferior mesenteric artery (IMA) or lumbar arteries (LA), is themost common endoleak after endovascular abdominal aortic aneurysm repair (EVAR). Objectives: the primary endpoint was the presence of type II endoleak at follow-up. Secondary endpoints includedaneurysm sac regression and reoperation rate due to T2EL, as well as the analysis of the results in our series of casestreated with IMA embolization prior to the endovascular procedure as a useful method to reduce T2EL at follow-up. Material and methods: this was a retrospective analysis of patients treated at our unit with IMA embolizationprior to EVAR from 2019 through 2021. The criteria used for IMA embolization were IMA diameter > 3 mm, presenceof LA with a diameter > 2 mm, or aortoiliac aneurysms. A total of 7 male patients were included with a mean age of72.1 years. A total of 42 % had aortoiliac aneurysms. In 2 of the cases, IMA embolization was performed initiallyfollowed by EVAR while in the remaining cases it was performed within the same procedure. The mean diameterof IMA was 5.02 mm ± 0.9 mm. All patients had at least 2 LAs facing the origin of the IMA with a diameter > 2 mm.Results: technical success was 100 %. The median follow-up was 20.7 months. In the CCTA performed 1 monthand 12 months postoperatively, correct IMA embolization was observed. There were no type II leaks at follow-up.In all cases, a decrease in the diameter of the aneurysmal sac was observed with a mean regression of 5.08 mm. There were no subsequent reinterventions associated with aortic valve disease. Conclusions: IMA embolization prior to EVAR in patients with a diameters > 3 mm and the presence of at least2 ALs with diameters > 2 mm and/or aortoiliac aneurysms seems to protect against the development of T2EL at12 months, waiting to be able to confirm the results in the mid- and long-term...(AU)

Validación de técnica de ganglio centinela en cáncer de endometrio en el Hospital de Talca / Validation of sentinel lymph node technique in endometrial cancer at the Hospital de Talca

Objetivo: Validar la técnica de ganglio centinela utilizando verde de indocianina en la estadificación del cáncer de endometrio. Método: Realizamos un estudio prospectivo entre enero y diciembre de 2021. Se incluyeron todas las pacientes portadoras de cáncer de endometrio clínicamente en etapa 1, de todos los grados de diferenciación e histologías. Todas las pacientes fueron sometidas a una estadificación laparoscópica. Se inició el procedimiento con identificación de ganglio centinela utilizando verde de indocianina. Posteriormente, se completó la cirugía de estadiaje estándar en todas las pacientes. Los ganglios centinelas fueron procesados con técnica de ultraestadiaje. Resultados: Se incluyeron 33 pacientes. El 81% presentaron histología endometrioide. El 100% fueron sometida además a una linfadenectomía pelviana estándar y el 20% a una linfadenectomía paraaórtica simultáneamente. Se detectó al menos un ganglio centinela en el 100% de los casos. La detección bilateral ocurrió en el 90,9%. La localización más frecuente fue la fosa obturatriz y la arteria hipogástrica. Obtuvimos una sensibilidad del 90% para detectar enfermedad ganglionar y un valor predictivo negativo del 95,8%. Conclusiones: La técnica de ganglio centinela utilizando verde de indocianina es replicable. Los resultados de nuestra serie nos permiten realizar procedimientos menos agresivos al estadificar el cáncer de endometrio.

Objective: To validate sentinel node mapping using indocyanine green in endometrial cancer staging. Method: A prospective study was conducted between January and December 2021. All patients with clinically stage 1 endometrial cancer, of all grades and histologies were included. All patients underwent laparoscopic staging. The procedure began with identification of the sentinel node using indocyanine green. Subsequently, standard staging surgery was completed in all patients. Sentinel nodes were processed using ultrastaging technique. Results: Thirty-three patients were enrolled. 81% of cases had endometrioid histology. All patients also underwent a standard pelvic lymphadenectomy and in 20% of cases a para-aortic lymphadenectomy. At least one sentinel node was detected in 100% of the cases. Bilateral detection occurred in 90.9%. The most frequent location was obturator fossa and hypogastric artery. Sensitivity to detect lymph node disease was 90% and negative predictive value 95.8%. Conclusions: Sentinel lymph node mapping using indocyanine green is a replicable technique. Our results allows us to perform less aggressive procedures in endometrial cancer staging.

A Gold Standard for Transcription Factor Regulatory Interactions in Escherichia coli K-12: Architecture of Evidence Types.

Post-genomic implementations have expanded the experimental strategies to identify elements involved in the regulation of transcription initiation. As new methodologies emerge, a natural step is to compare their results with those from established methodologies, such as the classic methods of molecular biology used to characterize transcription factor binding sites, promoters, or transcription units. In the case of Escherichia coli K-12, the best-studied microorganism, for the last 30 years we have continuously gathered such knowledge from original scientific publications, and have organized it in two databases, RegulonDB and EcoCyc. Furthermore, since RegulonDB version 11.0 (1), we offer comprehensive datasets of binding sites from chromatin immunoprecipitation combined with sequencing (ChIP-seq), ChIP combined with exonuclease digestion and next-generation sequencing (ChIP-exo), genomic SELEX screening (gSELEX), and DNA affinity purification sequencing (DAP-seq) HT technologies, as well as additional datasets for transcription start sites, transcription units and RNA sequencing (RNA-seq) expression profiles. Here, we present for the first time an analysis of the sources of knowledge supporting the collection of transcriptional regulatory interactions (RIs) of E. coli K-12. An RI is formed by the transcription factor, its positive or negative effect on a promoter, a gene or transcription unit. We improved the evidence codes so that the specific methods are described, and we classified them into seven independent groups. This is the basis for our updated computation of confidence levels, weak, strong, or confirmed, for the collection of RIs. We compare the confidence levels of the RI collection before and after adding HT evidence illustrating how knowledge will change as more HT data and methods appear in the future. Users can generate subsets filtering out the method they want to benchmark and avoid circularity, or keep for instance only the confirmed interactions. The comparison of different HT methods with the available datasets indicate that ChIP-seq recovers the highest fraction (>70%) of binding sites present in RegulonDB followed by gSELEX, DAP-seq and ChIP-exo. There is no other genomic database that offers this comprehensive high-quality anatomy of evidence supporting a corpus of transcriptional regulatory interactions.

Impact of dapagliflozin on cardiac remodelling in patients with chronic heart failure: The DAPA-MODA study.

AIMS: Dapagliflozin improves the prognosis of patients with heart failure (HF), regardless of left ventricular ejection fraction (LVEF). However, its effect on cardiac remodelling parameters, specifically left atrial (LA) remodelling, is not well established. METHODS AND RESULTS: The DAPA-MODA trial (NCT04707352) is a multicentre, single-arm, open-label, prospective and interventional study that aimed to evaluate the effect of dapagliflozin on cardiac remodelling parameters over 6 months. Patients with stable chronic HF receiving optimized guideline-directed therapy, except for any sodium-glucose cotransporter 2 inhibitor, were included. Echocardiography was performed at baseline, 30 and 180 days, and analysed by a central core-lab in a blinded manner to both patient and time. The primary endpoint was the change in maximal LA volume index (LAVI). A total of 162 patients (64.2% men, 70.5 ± 10.6 years, 52% LVEF >40%) were included in the study. At baseline, LA dilatation was observed (LAVI 48.1 ± 22.6 ml/m2 ) and LA parameters were similar between LVEF-based phenotypes (≤40% vs. >40%). LAVI showed a significant reduction at 180 days (-6.6% [95% confidence interval -11.1, -1.8], p = 0.008), primarily due to a decrease in reservoir volume (-13.8% [95% confidence interval -22.5, -4], p = 0.007). Left ventricular geometry improved with significant reductions in left ventricular mass index (-13.9% [95% confidence interval -18.7, -8.7], p < 0.001), end-diastolic volume (-8.0% [95% confidence interval -11.6, -4.2], p < 0.001) and end-systolic volume (-11.9% [95% confidence interval -16.7, -6.8], p < 0.001) at 180 days. N-terminal pro-B-type natriuretic peptide (NT-proBNP) showed a significant reduction at 180 days (-18.2% [95% confidence interval -27.1, -8.2], p < 0.001), without changes in filling Doppler measures. CONCLUSION: Dapagliflozin administration in stable out-setting patients with chronic HF and optimized therapy results in global reverse remodelling of cardiac structure, including reductions in LA volumes and improvement in left ventricular geometry and NT-proBNP concentrations.

The EcoCyc Database (2023).

EcoCyc is a bioinformatics database available online at EcoCyc.org that describes the genome and the biochemical machinery of Escherichia coli K-12 MG1655. The long-term goal of the project is to describe the complete molecular catalog of the E. coli cell, as well as the functions of each of its molecular parts, to facilitate a system-level understanding of E. coli. EcoCyc is an electronic reference source for E. coli biologists and for biologists who work with related microorganisms. The database includes information pages on each E. coli gene product, metabolite, reaction, operon, and metabolic pathway. The database also includes information on the regulation of gene expression, E. coli gene essentiality, and nutrient conditions that do or do not support the growth of E. coli. The website and downloadable software contain tools for the analysis of high-throughput data sets. In addition, a steady-state metabolic flux model is generated from each new version of EcoCyc and can be executed online. The model can predict metabolic flux rates, nutrient uptake rates, and growth rates for different gene knockouts and nutrient conditions. Data generated from a whole-cell model that is parameterized from the latest data on EcoCyc are also available. This review outlines the data content of EcoCyc and of the procedures by which this content is generated.