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The document discusses the impact of climate change on young children and their families, as presented at the World Forum on Early Care and Education conference in Vancouver, Canada. The conference highlighted the need for research, practice, and pedagogy to support young children and families in adapting to and developing resilience in the face of climate change. Stories from practitioners and researchers showcased initiatives such as food systems journeys, emergency programs for children affected by natural disasters, and children's voices advocating for learning for sustainability. The document emphasizes the importance of intercultural and interdisciplinary knowledge exchange in addressing climate change challenges in early childhood settings. [Extracted from the article]

Massive transfusion, crystalloid resuscitation, persistent coagulopathy, and damage control surgery (DCS) are the most significant risk factors for uROR. Minimizing crystalloid and ongoing balanced resuscitation, particularly during DCS, is essential.

Right ventricular outflow dysfunction, manifesting as stenosis, regurgitation, or both, is nearly universal in patients with repaired tetralogy of Fallot, precipitating a complex pathophysiological cascade that leads to increasing rates of morbidity and mortality with advancing age. As the number of adolescent and adult patients with repaired tetralogy of Fallot continues to grow as a result of excellent survival during infancy, the need to improve late outcomes has become an urgent priority. This American Heart Association scientific statement provides an update on the current state of knowledge of the pathophysiology, methods of surveillance, risk stratification, and latest available therapies, including transcatheter and surgical pulmonary valve replacement strategies, as well as management of life-threatening arrhythmias. It reviews emerging evidence on the roles of comorbidities and patient-reported outcomes and their impact on quality of life. In addition, this scientific statement explores contemporary evidence for clinical choices such as transcatheter or surgical pulmonary valve replacement, discusses criteria and options for intervention for failing implanted bioprosthetic pulmonary valves, and considers a new approach to determining optimal timing and indications for pulmonary valve replacement.

Objectives Patients with dextro-transposition of the great arteries (d-TGA) frequently undergo balloon atrial septostomy (BAS) prior to the arterial switch operation (ASO) to promote atrial-level mixing. Balloon atrial septostomy has inherent risks as an invasive procedure and may not always be necessary. This study revisits the routine utilization of BAS prior to ASO.Methods Single-center, retrospective review of d-TGA patients undergoing the ASO from July 2018 to March 2023. Preoperative patient characteristics, pulse oximetry oxygen saturations (SpO2), cerebral/renal near-infrared spectroscopy (NIRS) readings along with prostaglandin status at the time of the ASO were analyzed with descriptive and univariate statistics.Results Thirty patients underwent the ASO. Of these, 7 (23%) were female, 25 (83%) were white, and median weight at ASO was 3.2 kg (range 0.8-4.2). Twenty-two (73%) patients underwent BAS. There were no demographic differences between BAS and no-BAS patients. Of those who underwent BAS, there was a significant increase in SpO2(median 83% [range 54-92] to median 87% [range 72-95], P= .007); however, there was no change in NIRS from pre-to-post BAS. Six (27%) patients in the BAS group were prostaglandin-free at ASO. Balloon atrial septostomy patients underwent the ASO later compared with no-BAS patients (median 8 [range 3-32] vs 4 [range 2-10] days old, P= .016) and had a longer hospital length of stay (median 13 [range 7-43] vs 10 [range 8-131] days, P= .108).Conclusions While BAS is an accepted preoperative procedure in d-TGA patients to improve oxygen saturations, it is also an additional invasive procedure, does not guarantee prostaglandin-free status at the time of ASO, and may increase the interval to ASO. Birth to direct early ASO, with prostaglandin support, should be revisited as an alternative, potentially more expeditious strategy.

Near-field tides prediction for tsunami detection in the coastal area is a significant problem of the cable-based tsunami meter system in north Sipora, Indonesia. The problem is caused by its shallow water condition and the unavailability of an applicable model or research for tsunami detection in this area. The problem foundation of shallow water area is its ambient noise level-dependent property that requires preprocessing to improve its feature representation. Moreover, because this shallow water is close to the land area, we must consider a model that can accommodate low prediction time for a Tsunami Early Warning System. Therefore, we propose a recurrent neural network (RNN) model because of its reliable performance for time series forecasting. Our report evaluates variants of the RNN model (the vanilla RNN, LSTM and GRU models) in tides prediction and z-score analysis for tsunami identification. The GRU model overwhelms the other two variants in error scores and time processed (training and prediction). It can achieve median error score distribution of 7.8×10-5on the L1000-P250 configuration with time prediction under 0.1 s. This lower-time prediction is necessary to ensure the early warning system is going well. Moreover, the GRU model can identify all synthetic tsunami tide spikes (compared with the ground truth result) from magnitude 7.2–8.2 by applying a z-score on the GRU’s prediction.

The article offers information on understanding the dynamics of soil microbiomes to ensure sustainable winter agriculture. Topics discussed include the impact of human exploitation and climate change on soil health; the increasing threat of fusarium wilt on lettuce fields in Yuma, Arizona; the importance of soil microbiomes in supporting food production; and ongoing research aimed at combating this disease by studying the soil microbiome.

•Surgery residents reported a lack of space, resources, and dedicated time for pumping.•67% of survey respondents stated that they did not have adequate time for pumping.•2/3 of breastfeeding mothers reported a reduction in milk supply after return to work.•These challenges contribute to shorter breastfeeding duration.•It is crucial to provide well equipped lactation rooms and to foster a supportive culture.

Value creation assessment is a fundamental topic for the literature deepening on business incubation. However, it must be oriented to a value approach beyond the economic outlook and from an alternative angle to the value creation processes. To this end, the study investigates the value outcomes of incubation, first by applying the laddering technique as a decision process-tracing method to observe the value outcomes of incubators in terms of sustainability dimensions; second by developing a framework - considering strategic target users, innovation objects and sustainability dimensions - applied to incubatees to reveal how they perceive their value outcomes according to those framework elements. The findings show a significant asymmetry of managerial views between incubators and incubatees. For incubators, value outcomes of an economic nature still prevail over other dimensions, whilst incubated companies reveal more concern in positively impacting further sustainability dimensions with their innovation offering.

The second edition of Applied Behavior Analysis Advanced Guidebook: A Manual for Professional Practice(Luiselli, 2023) covers 17 chapters on topics that are relevant to applied behavior analysis practitioners. In this review, we discuss the purpose and intended audience of the Guidebook, briefly summarize the contents of the Guidebook, and critically evaluate the contents with respect to breadth and depth, audience fit, organization, and cohesion. In addition, we discuss emerging areas that are highlighted in the Guidebook (i.e., technology and telehealth, diversity and multiculturism, and practice‐oriented research).

Active tectonics in an area includes ongoing or recent geologic events. This paper investigates the tectonic influence on the subsidence, uplift and tilt of western Saurashtra through morphotectonic analysis of ten watersheds along with characteristics of relief and drainage orientation. Watersheds 7–9 to the north (N) are tectonically active, which can be linked with the North Kathiawar Fault System (NKFS) and followed by watersheds 6, 10, 1, 4 and 5. Stream-length gradient index and sinuosity index indicate the effect of tectonic events along the master streams in watersheds 6–9. Higher R2values of the linear curve fit for watershed 7 indicate its master stream is much more tectonically active than the others. The R2curve fitting model and earthquake magnitude/depth analysis confirm the region to be active. The reactivation of the NKFS most likely led to the vertical movement of western Saurashtra.

Le panorama des sarcomes utérins se complexifie de plus en plus avec la description de nouvelles entités associées à des altérations moléculaires récurrentes. Les léiomyosarcomes et les sarcomes utérins indifférenciés sont des sarcomes à génomique complexe. Les sarcomes du stroma endométrial de bas grade et de haut grade, d’autres sarcomes associés aux transcrits de fusion (tels que NTRK, PDGFB, ALK, RET ROS1) et le sarcome utérin déficient en SMARCA4 sont des sarcomes à génomique simple. Le léiomyosarcome est le sarcome utérin le plus fréquent suivi par les sarcomes du stroma endométrial. Il existe trois différents sous-types histologiques de léiomyosarcome (fusiforme, myxoïde, épithélioïde), les léiomyosarcomes myxoïde et épithélioïde étant plus agressifs que le léiomyosarcome fusiforme. La distinction entre un sarcome du stroma endométrial de bas grade et de haut grade est tout d’abord morphologique et immunohistochimique. La mise en évidence des transcrits de fusions aide au diagnostic. Définitivement reconnu comme entité distincte parmi les tumeurs mésenchymateuses gynécologiques, le PECome utérin fait partie des tumeurs rares. Grâce à des algorithmes d’évaluation du risque, les PEComes utérins sont différentiés en borderlineet en malins. Le rhabdomyosarcome embryonnaire du col utérin survient typiquement chez l’enfant, mais peut s’observer également chez la femme adulte. Le rhabdomyosarcome embryonnaire du col utérin est presque toujours DICER1 muté, à la différence de celui du vagin qui est DICER1 sauvage, et de l’adénosarcome qui peut être DICER1 muté mais en moindre fréquence. Parmi les entités émergentes, les sarcomes associés aux transcrits de fusion impliquant les gènes NTRK, ALK, PDGFBbénéficient d’une thérapeutique ciblée. L’intégration des données moléculaires avec l’histologie et la clinique permet de mieux identifier les sarcomes utérins afin de mieux les traiter.

Innovations to enhance residency training in interpersonal and communication skills are needed and a resident-led strategy has not been well-described. In this study, we explored a resident-led comprehensive communication skills curriculum for internal medicine residents. Residents and faculty prepared the curriculum as part of an Accreditation Council for Graduate Medical Education (ACGME) Back to Bedside Project and with “The language of caring guide for physicians.” Employing active learning techniques, three residents led 43 internal medicine residents in seven 1 h sessions from 2019 to 2020. Using a 35-question survey, we assessed pre and post self-reported competence in: mindful practice, collaboration and teamwork, effective openings and closing, communicating with empathy, effective explanations, engaging patients and families as partners, and hard conversations. A Wilcoxon signed rank test was employed to explore differences in median scores after matching each person’s pretest and posttest score. The median score for aggregate communication and the scores for all seven competencies assessed improved from pre to post (p < 0.05). This indicates that residents reported higher incidences of performing patient-centered communication skills after the curriculum compared to before. Using a five-point Likert scale, 100% of participants agreed the program improved their communication skills and improved confidence in bedside patient-centered communications. A resident-led comprehensive communication skills curriculum for internal medicine residents was implemented showing improvement in skills over the course of the curriculum. The curriculum was well-accepted by post-survey evaluation and was feasible with motivated resident-leaders, use of an existing guide to communication, and reserved didactic time to implement the program.

AbstractIntroduction:Hypoplastic Left Heart Syndrome accounts for a significant proportion of CHD morbidity and mortality, despite improvements in care and improved survival. This study evaluates number of, reasons for, and trends in discharges of patients with hypoplastic left heart syndrome over 11 years in Texas.Methods:The Texas Inpatient Discharge Dataset Public Use File captures almost all discharges in Texas and was reviewed from 2009 to 2019. Discharges of patients ≥5 years of age and diagnosis codes for Hypoplastic Left Heart Syndrome were included. The admitting and principle diagnoses were categorised and all discharges were evaluated for procedures performed. Descriptive and univariate statistical analyses were performed.Results:A total of 1024 discharges were identified with a 16.9% annual increase over the study period. Median length of stay was 4 [IQR: 2–8] and there were 17 (1.7%) in-hospital mortalities with no differences across age groups. Seven (17.1%) discharges of patients 25+ years were uninsured, higher than other age groups (p < 0.001). The most common admitting diagnosis was CHD and 224 (21.9%) of discharges included a procedure, including 23 heart transplants. Discharges occurred from 67 different hospitals with 4 (6.0%) representing 71.4% of all discharges.Conclusions:Discharges of Hypoplastic Left Heart Syndrome have increased rapidly, particularly in the older age groups and were spread over a large number of hospitals. Further work is needed to understand the interplay between Hypoplastic Left Heart Syndrome and other conditions and care experiences that occur within the general population, which will become more common as this population ages and grows.

AbstractIntroduction:With advances in care, an increasing number of individuals with single-ventricle CHD are surviving into adulthood. Partners of individuals with chronic illness have unique experiences and challenges. The goal of this pilot qualitative research study was to explore the lived experiences of partners of individuals with single-ventricle CHD.Methods:Partners of patients ≥18 years with single-ventricle CHD were recruited and participated in Experience Group sessions and 1:1 interviews. Experience Group sessions are lightly moderated groups that bring together individuals with similar circumstances to discuss their lived experiences, centreing them as the experts. Formal inductive qualitative coding was performed to identify salient themes.Results:Six partners of patients participated. Of these, four were males and four were married; all were partners of someone of the opposite sex. Themes identified included uncertainty about their partners’ future health and mortality, becoming a lay CHD specialist, balancing multiple roles, and providing positivity and optimism. Over time, they took on a role as advocates for their partners and as repositories of medical history to help navigate the health system. Despite the uncertainties, participants described championing positivity and optimism for the future.Conclusions:In this first-of-its-kind pilot study, partners of individuals with single-ventricle CHD expressed unique challenges and experiences in their lives. There is a tacit need to design strategies to help partners cope with those challenges. Further larger-scale research is required to better understand the experiences of this unique population.

Drug resistance and cancer relapse represent significant therapeutic challenges after chemotherapy or immunotherapy, and a major limiting factor for long-term cancer survival. Netrin-1 was initially identified as a neuronal navigation cue but has more recently emerged as an interesting target for cancer therapy, which is currently clinically investigated. We show here that netrin-1 is an independent prognostic marker for clinical progression of breast and ovary cancers. Cancer stem cells (CSCs)/Tumor initiating cells (TICs) are hypothesized to be involved in clinical progression, tumor relapse and resistance. We found a significant correlation between netrin-1 expression and cancer stem cell (CSC) markers levels. We also show in different mice models of resistance to chemotherapies that netrin-1 interference using a therapeutic netrin-1 blocking antibody alleviates resistance to chemotherapy and triggers an efficient delay in tumor relapse and this effect is associated with CSCs loss. We also demonstrate that netrin-1 interference limits tumor resistance to immune checkpoint inhibitor and provide evidence linking this enhanced anti-tumor efficacy to a decreased recruitment of a subtype of myeloid-derived suppressor cells (MDSCs) called polymorphonuclear (PMN)-MDSCs. We have functionally demonstrated that these immune cells promote CSCs features and, consequently, resistance to anti-cancer treatments. Together, these data support the view of both a direct and indirect contribution of netrin-1 to cancer stemness and we propose that this may lead to therapeutic opportunities by combining conventional chemotherapies and immunotherapies with netrin-1 interfering drugs.

When I taught undergraduate education courses, I had to design lesson plans to engage students at all levels with different learning styles. But the concept of learning styles, like visual [...]

Neonatal congenital atrioventricular block (nCAVB) is rare, causes bradycardia, confers high mortality, and frequently requires pacing. In-hospital outcomes and pacemaker management in nCAVB are limited.

In this report, high-frequency electric impedance spectroscopy was performed to investigate ionic transport through nanochannels. Special attention was focused on (i) conductance behaviors depending on the role of cation valence in three background electrolytes (XCln): monovalent 1-1 (K+and Cl–), divalent 2-1 (Mg2+and 2Cl–), and trivalent 3-1 (La3+and 3Cl–), (ii) the effects of proton and bicarbonate ions on bulk and surface conductance, and (iii) the connected microchannel dimension (surface/height ratio aspect) within the nanochannel apparent conductance. The results highlight a net quantitative increase in surface silanol density and a strong decrease in surface ionization degree when lanthanum cations are employed. The results also demonstrate that La3+strongly interacts with the silica surface, leading to negative values of standard free energy for ion-site interactions and chemical potential for ion–ion correlations in the Stern layer of −0.8 and −10.2 kT, respectively. We ascribed the evolution of surface charge density to the balance between the mole ratios of water molecules and adsorbed cations at equilibrium. We found that La3+behaves as an acidic cation (Lewis conceptualization) that neutralizes the negative silica surface accompanying water molecule expulsion due to steric hindrance. This study constitutes a new contribution to ion-site interactions and to ion–ion correlation phenomena on the planar silica surface to explain charge inversion observation in micro-nanofluidic devices.

ABSTRACTLeachate from landfills can be a significant challenge to manage and treat due to conventional contaminants. The addition of emerging contaminants such as per- and polyfluorinatedalkyl substances (PFASs) makes treatment even more complex. PFASs enter landfills through consumer waste and have been detected in landfill leachates at varying concentrations. The design and decision-making on leachate treatment require essential information since it depends on local factors, e.g. climate, proximity to wastewater treatment plants, and waste type. This study conducted a survey on actively operated public municipal solid waste (MSW) landfills in the Eastern and Northwestern regions of the US to understand the current leachate treatment practices and views from public MSW landfill managers on PFAS treatment. The survey aims to explore the possible adaptations from the industry to the pending regulatory guidelines for the potential PFASs treatment. Results show the majority of the landfills are currently using off-site disposal (72% of the responses), followed by complete onsite treatment (18% of the responses) and pre-treatment onsite and off-site disposal methods (10% of the responses). The factors that guided the selection of treatment methods included climate, economics, and future regulations. Evaporation and recirculation were the most prevalent onsite treatment technologies for public landfills, which reduced the leachate quantity for treatment. The public landfills expressed awareness of the potential impact of PFASs on the changes in leachate treatment. The current state-level regulation, potential federal PFAS regulation, and treatment costs are raising awareness of the onsite treatment for PFASs. The results of this study will benefit the improvement of PFAS awareness and provide critical information that will directly affect the leachate treatment process for PFASs.Implications: This study presents a survey on the current leachate treatment process in the public municipal solid waste landfills in the eastern and northwestern U.S. and their potential process improvement on the impact of PFASs. This study is relevant to the topic of the JA&WMA because the research falls directly within the scope of this journal, and it documents the leachate treatment of landfills, and the results of this study will immediately contribute to our understanding of the waste treatment, benefiting the improvement of PFASs awareness, and providing critical information that will directly affect the leachate treatment process.

During the last decades, several hospitals stopped service due to severe seismic damage to nonstructural components and medical equipment. This article investigates the dynamic behavior of medical equipment deployed in a full-scale, five-story building with two different support conditions, base isolated (BI) and fixed to the base (FB). Two nonlinear mathematical models, namely, rolling and toppling, are used to simulate the observed experimental responses using recorded data and the camera projection technique (CPT). CPT generated the possibility of measuring equipment horizontal displacements, slips, rotations, rocking, and toppling responses. The Euler–Lagrange formulation, along with the Stribeck friction model, was used to numerically model the rolling and in-plane rotation behavior of a four-wheel mobile cart (4WMC), which is considered to represent the trajectory of equipment supported on caster wheels. Besides, a simple two-dimensional (2D) rigid block model was used to describe the rocking and toppling behavior of locked and free-standing equipment. It was found that the 4WMC model was sensitive to the platform and wheels’ initial orientation angles, as well as the static and kinetic friction coefficients. As it should be, the toppling model was sensitive to the block dimensions and the intensity of the shaking. It was concluded that both numerical models successfully predicted the equipment rolling, in-plane rotation, rocking, and toppling behavior, as long as neither severe lateral impacts nor significant changes in the equipment mass occur during the motion.

Les patients de 65ans et plus représenteraient 10 % des patients atteints de DA, dont l’origine serait liée à une perte de fonction barrière cutanée et à une immunosénescence (effet pro-inflammatoire et orientation Th2). Le concept de DA du sujet âgé étant récent, il existe un manque de données concernant ses particularités notamment par rapport à la DA de l’adulte jeune. L’objectif de l’étude est de décrire les caractéristiques cliniques, thérapeutiques et le fardeau de la DA après 65ans en comparaison aux adultes jeunes<30ans.

Trois traitements sont proposés, souvent hors AMM, en 1ère ligne du traitement systémique du psoriasis sévère de l’enfant : acitrétine, méthotrexate, et ciclosporine. Si le méthotrexate est préféré dans le nord de l’Europe et aux États-Unis, l’acitrétine est plus régulièrement utilisée dans le sud de l’Europe. Il n’existe pas d’algorithme, ni d’essais comparatifs permettant de définir les critères qui font choisir un de ces traitements.

Trois traitements dits conventionnels sont prescrits dans la prise en charge du psoriasis sévère de l’enfant, bien que n’ayant pas tous une AMM dans cette population : acitrétine, méthotrexate et ciclosporine. Si ces molécules semblent efficaces et relativement bien tolérées chez l’enfant, il n’existe pas d’étude comparative du taux de maintien de ces traitements chez les enfants souffrant de psoriasis.

Recent behavior analytic studies have examined behavioral skills training to teach adults to arrange safe infant sleeping environments. These studies were conducted in an analogue environment and with all training components delivered by an expert staff trainer. The purpose of the current study was to replicate and extend this literature by substituting video‐based training for behavioral skills training. We assessed whether expectant caregivers could arrange safe infant sleeping environments following video‐based training. The results suggested that video‐based training alone resulted in positive outcomes for a portion of participants, whereas a subset of participants required feedback to reach mastery criteria. The social validity data suggest that the participants found the training procedures favorable.

Sleep‐related infant deaths are one of the top causes of infant mortality in the United States. A few behavior analytic studies have examined behavioral skills training to teach adults to arrange safe infant sleeping environments. These studies were conducted in an analogue environment, and no data were collected outside the training setting. The purpose of the current study was to replicate and extend the extant literature. We taught caregivers to arrange safe infant sleeping environments in a community‐based organization. Thereafter, we assessed the feasibility and effectiveness of a technology‐based contingency management procedure to examine caregivers' adherence with arrangement of a safe sleeping environment for their newborns across a 2‐week period. As in previous studies, behavioral skills training resulted in positive outcomes, and follow‐up data suggested that the technology‐based contingency management procedure may be a promising approach to promoting adherence with infant sleeping environment recommendations.

The aim of this case series was to assess the safety and effectiveness of peripheral nerve stimulation (PNS) of the brachial plexus performed using a low invasive percutaneous approach with ultrasound guide.

Background:Pericardial effusion (PCE) is a significant complication after pediatric cardiac surgery. This study investigates PCE development after the arterial switch operation (ASO) and its short-term and longitudinal impacts. Methods:A retrospective review of the Pediatric Health Information System database. Patients with dextro-transposition of the great arteries who underwent ASO from January 1, 2004, to March 31, 2022, were identified. Patients with and without PCE were analyzed with descriptive, univariate, and multivariable regression statistics. Results:There were 4896 patients identified with 300 (6.1%) diagnosed with PCE. Thirty-five (11.7%) with PCE underwent pericardiocentesis. There were no differences in background demographics or concomitant procedures between those who developed PCE and those who did not. Patients who developed PCE more frequently had acute renal failure (N = 56 (18.7%) vs N = 603(13.1%), P= .006), pleural effusions (N = 46 (15.3%) vs N = 441 (9.6%), P= .001), mechanical circulatory support (N = 26 (8.7%) vs N = 199 (4.3%), P< .001), and had longer postoperative length of stay (15 [11-24.5] vs 13 [IQR: 9-20] days). After adjustment for additional factors, pleural effusions (OR = 1.7 [95% CI: 1.2-2.4]), and mechanical circulatory support (OR = 1.81 [95% CI: 1.15-2.85]) conferred higher odds of PCE. There were 2298 total readmissions, of which 46 (2%) had PCE, with no difference in median readmission rate for patients diagnosed with PCE at index hospitalization (median 0 [IQR: 0-1] vs 0 [IQR: 0-0], P= .208). Conclusions:PCE occurred after 6.1% of ASO and was associated with pleural effusions and mechanical circulatory support. PCE is associated with morbidity and prolonged length of stay; however, there was no association with in-hospital mortality or readmissions.

Purpose: This paper aims to identify and classify the parameters that construct the input, processes, output, productivity and outcome variables that affect performance. These parameters are used in the evaluation model to measure research performance in universities so that they can be used as the basis for making leadership policies both at the national and institutional levels. Design/methodology/approach: The design of this research is a quantitative research method using a survey questionnaire that was sent to the heads of research institutions at universities in Indonesia. To obtain these parameters, a test for determining the value of the loading factor was used. Findings: The authors found that input variable parameters consisted of 10 parameters; process variable consisted of 22 parameters; output variable parameters consisted of 8 parameters; productivity variable consisted of 4 parameters; and outcome variable parameters consisted of 10 parameters. Originality/value: One approach to obtain parameters is through systems theory, where every element that makes up the organization contributes to the achievement of goals. This study attempted to develop parameters in the performance appraisal model of systems theory-based research institutions that are adapted to trends in the direction of research in universities. These parameters are based on aspects of input, process, output, productivity and outcome.

Netrin-1 is upregulated in cancers as a protumoural mechanism1. Here we describe netrin-1 upregulation in a majority of human endometrial carcinomas (ECs) and demonstrate that netrin-1 blockade, using an anti-netrin-1 antibody (NP137), is effective in reduction of tumour progression in an EC mouse model. We next examined the efficacy of NP137, as a first-in-class single agent, in a Phase I trial comprising 14 patients with advanced EC. As best response we observed 8 stable disease (8 out of 14, 57.1%) and 1 objective response as RECIST v.1.1 (partial response, 1 out of 14 (7.1%), 51.16% reduction in target lesions at 6 weeks and up to 54.65% reduction during the following 6 months). To evaluate the NP137 mechanism of action, mouse tumour gene profiling was performed, and we observed, in addition to cell death induction, that NP137 inhibited epithelial-to-mesenchymal transition (EMT). By performing bulk RNA sequencing (RNA-seq), spatial transcriptomics and single-cell RNA-seq on paired pre- and on-treatment biopsies from patients with EC from the NP137 trial, we noted a net reduction in tumour EMT. This was associated with changes in immune infiltrate and increased interactions between cancer cells and the tumour microenvironment. Given the importance of EMT in resistance to current standards of care2, we show in the EC mouse model that a combination of NP137 with carboplatin-paclitaxel outperformed carboplatin-paclitaxel alone. Our results identify netrin-1 blockade as a clinical strategy triggering both tumour debulking and EMT inhibition, thus potentially alleviating resistance to standard treatments.