Proteolysis and Contractility Regulate Tissue Opening and Wound Healing by Lung Fibroblasts in 3D Microenvironments.

Damage and repair are recurring processes in tissues, with fibroblasts playing key roles by remodeling extracellular matrices (ECM) through protein synthesis, proteolysis, and cell contractility. Dysregulation of fibroblasts can lead to fibrosis and tissue damage, as seen in idiopathic pulmonary fibrosis (IPF). In advanced IPF, tissue damage manifests as honeycombing, or voids in the lungs. This study explores how transforming growth factor-beta (TGF-ß), a crucial factor in IPF, induces lung fibroblast spheroids to create voids in reconstituted collagen through proteolysis and cell contractility, a process is termed as hole formation. These voids reduce when proteases are blocked. Spheroids mimic fibroblast foci observed in IPF. Results indicate that cell contractility mediates tissue opening by stretching fractures in the collagen meshwork. Matrix metalloproteinases (MMPs), including MMP1 and MT1-MMP, are essential for hole formation, with invadopodia playing a significant role. Blocking MMPs reduces hole size and promotes wound healing. This study shows how TGF-ß induces excessive tissue destruction and how blocking proteolysis can reverse damage, offering insights into IPF pathology and potential therapeutic interventions.

Newcastle disease virus vector-based SARS-CoV-2 vaccine candidate AVX/COVID-12 activates T cells and is recognized by antibodies from COVID-19 patients and vaccinated individuals.

Introduction: Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system. Methods: This study aims to analyze the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations. Results: Our findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-γ) in both CD4+ and CD8+ T-cells. Discussion: The AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.

Diagnostic approach and treatment of ventricular septal defect associated with PDA, coarctation of aorta, hypoplastic aortic arch and multiple valvular heart disease in a tertiary center: An infrequent association.

Ventricular septal defect is the most common congenital heart disease in children and is associated with patent ductus arteriosus in 1%-7% of cases. The coexistence of both malformities with hypoplastic aortic arch and aortic coarctation is even rarer. We present the case of a 6-year-old girl referred to our hospital because of dyspnea on feeding, recurrent respiratory infections, poor weight gain, and a heart murmur. The image studies revealed a ventricular septal defect, patent ductus arteriosus, severe hypoplasia of the aortic arch with critical stenosis of the proximal portion, severe dilatation of the pulmonary artery and pulmonary, mitral, tricuspid, and aortic regurgitation. We will discuss the diagnostic approach and treatment in a tertiary reference center for patients with cardiovascular diseases.

Phage display identification of high-affinity ligands for human TSG101-UEV: A structural and thermodynamic study of PTAP recognition.

The ubiquitin E2 variant domain of TSG101 (TSG101-UEV) plays a pivotal role in protein sorting and virus budding by recognizing PTAP motifs within ubiquitinated proteins. Disrupting TSG101-UEV/PTAP interactions has emerged as a promising strategy for the development of novel host-oriented antivirals with a broad spectrum of action. Nonetheless, finding inhibitors with good properties as therapeutic agents remains a challenge since the key determinants of binding affinity and specificity are still poorly understood. Here we present a detailed thermodynamic, structural, and dynamic characterization viral PTAP Late domain recognition by TSG101-UEV, combining isothermal titration calorimetry, X-ray diffraction structural studies, molecular dynamics simulations, and computational analysis of intramolecular communication pathways. Our analysis highlights key contributions from conserved hydrophobic contacts and water-mediated hydrogen bonds at the PTAP binding interface. We have identified additional electrostatic hotspots adjacent to the core motif that modulate affinity. Using competitive phage display screening we have improved affinity by 1-2 orders of magnitude, producing novel peptides with low micromolar affinities that combine critical elements found in the best natural binders. Molecular dynamics simulations revealed that optimized peptides engage new pockets on the UEV domain surface. This study provides a comprehensive view of the molecular forces directing TSG101-UEV recognition of PTAP motifs, revealing that binding is governed by conserved structural elements yet tuneable through targeted optimization. These insights open new venues to design inhibitors targeting TSG101-dependent pathways with potential application as novel broad-spectrum antivirals.

Healthcare and Epidemiological Surveillance Costs of Hepatitis A Outbreaks in Spain in Regions with and without Universal Hepatitis A Vaccination of Children during 2010-2018.

The aim of this study was to evaluate and compare hepatitis A outbreak-associated healthcare and epidemiological surveillance costs in Spain in two types of autonomous regions during 2010-2018: (1) regions with a prevention strategy based on universal hepatitis A vaccination of children and vaccination of high-risk population groups (Catalonia) and (2) regions with a prevention strategy based on vaccinating high-risk population groups (Castile and Leon, Murcia, Navarra, Community of Madrid, Community of Valencia). Healthcare costs were determined based on the resources used to treat hepatitis A outbreak-associated cases and hospitalizations. Epidemiological surveillance costs were calculated from the resources used during surveillance activities. The ratios for total, healthcare and epidemiological surveillance costs (regions without universal hepatitis A vaccination of children vs. Catalonia) were used to compare the two hepatitis A prevention strategies. From 2010 to 2018, the total, healthcare and epidemiological surveillance costs per million population were 1.75 times (EUR 101,671 vs. EUR 58,032), 1.96 times (EUR 75,500 vs. EUR 38,516) and 1.34 times greater (EUR 26,171 vs. EUR 19,515) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. The ratios tended to increase over time during 2010-2018. In 2015-2018, total, healthcare and epidemiological surveillance costs per million population were 2.68 times (EUR 69,993 vs. EUR 26,158), 2.86 times (EUR 53,807 vs. EUR 18,825) and 2.21 times greater (EUR 16,186 vs. EUR 7333) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. These findings suggest that universal hepatitis A vaccination of children could reduce hepatitis A outbreak-associated costs.

Comparison Between Corticocancellous Allograft and Bovine Xenograft for Sinus Augmentation: A Radiographic, Histologic, and Histomorphometric Clinical Study.

Sinus floor augmentation is one of the most common approaches to obtain sufficient bone availability for placing implants in cases with severe bone atrophy in the posterior maxilla. Several bone substitutes are indicated for sinus augmentation, but they may achieve different clinical outcomes. This study aims to compare bovine bone mineral (BBM) with freeze-dried bone allograft (FDBA) in a two-stage lateral window sinus grafting approach. Twenty patients received a lateral window sinus elevation with either FDBA or BBM. Postoperative graft height was measured with CBCT. Implants were placed 6 months later, at which time biopsy samples were taken for histologic analysis and new CBCT scans were performed to measure graft height. The mean height reduction at 6 months was 20.27% ± 4.94% for FDBA samples and 5.36% ± 2.41% for BBM samples. The histologic analysis revealed a mean ratio of newly formed bone of 43.70% ± 5.29% for the FDBA group and 38.11% ± 4.03% for the BBM group. The FDBA group also showed a higher amount of residual biomaterial (17.25% ± 10.10%) and connective tissue (14.63% ± 4.38%) compared to the BBM group (15.53% ± 5.42% and 13.11% ± 4.42%, respectively). The differences between groups were statistically significant for the height reduction and newly formed bone (P ≤ .05) but not for the amounts of residual biomaterial and nonmineralized connective tissue (P ≥ .05). Six months after performing a lateral window sinus elevation, the percentage of newly formed bone was significantly higher when using FDBA than when using BBM, although the graft height reduction was also significantly higher for the FDBA group.

Monastrol suppresses invasion and metastasis in human colorectal cancer cells by targeting fascin independent of kinesin-Eg5 pathway.

Rearrangement of the actin cytoskeleton is a prerequisite for carcinoma cells to develop cellular protrusions, which are required for migration, invasion, and metastasis. Fascin is a key protein involved in actin bundling and is expressed in aggressive and invasive carcinomas. Additionally, fascin appears to be involved in tubulin-binding and microtubule rearrangement. Pharmacophoric-based in silico screening was performed to identify compounds with better fascin inhibitory properties than migrastatin, a gold-standard fascin inhibitor. We hypothesized that monastrol displays anti-migratory and anti-invasive properties via fascin blocking in colorectal cancer cell lines. Biophysical (thermofluor and ligand titration followed by fluorescence spectroscopy), biochemical (NMR), and cellular assays (MTT, invasion of human tissue), as well as animal model studies (zebrafish invasion) were performed to characterize the inhibitory effect of monastrol on fascin activity. In silico analysis revealed that monastrol is a potential fascin-binding compound. Biophysical and biochemical assays demonstrated that monastrol binds to fascin and interferes with its actin-bundling activity. Cell culture studies, including a 3D human myoma disc model, showed that monastrol inhibited fascin-driven cytoplasmic protrusions as well as invasion. In silico, confocal microscopy, and immunoprecipitation assays demonstrated that monastrol disrupted fascin-tubulin interactions. These anti-invasive effects were confirmed in vivo. In silico confocal microscopy and immunoprecipitation assays were carried out to test whether monastrol disrupted the fascin-tubulin interaction. This study reports, for the first time, the in vitro and in vivo anti-invasive properties of monastrol in colorectal tumor cells. The number and types of interactions suggest potential binding of monastrol across actin and tubulin sites on fascin, which could be valuable for the development of antitumor therapies.

The three-dimensional structure of DapE from Enterococcus faecium reveals new insights into DapE/ArgE subfamily ligand specificity.

DapE is a Zn2+-metallohydrolase recognized as a drug target for bacterial control. It is a homodimer that requires the exchange of interface strands by an induced fit essential for catalysis. Identifying novel anti-DapE agents requires greater structural details. Most of the characterized DapEs are from the Gram-negative group. Here, two high-resolution DapE crystal structures from Enterococcus faecium are presented for the first time with novel aspects. A loosened enzyme intermediate between the open and closed conformations is observed. Substrates may bind to loose state, subsequently it closes, where hydrolysis occurs, and finally, the change to the open state leads to the release of the products. Mutation of His352 suggests a role, along with His194, in the oxyanion stabilization in the mono-metalated Zn2+ isoform, while in the di-metalated isoform, the metal center 2 complements it function. An aromatic-π box potentially involved in the interaction of DapE with other proteins, and a peptide flip could determine the specificity in the Gram-positive ArgE/DapE group. Finally, details of two extra-catalytic cavities whose geometry changes depending on the conformational state of the enzyme are presented. These cavities could be a target for developing non-competitive agents that trap the enzyme in an inactive state.

Enhancing MD simulations: ASGARD's automated analysis for GROMACS.

Molecular Dynamics (MD) simulations are essential in analyzing the physical movement of molecules, with GROMACS being a widely recognized open-source package for this purpose. However, conducting analyses individually in GROMACS can take excessive time and effort. Addressing this challenge, we introduce ASGARD, an innovative workflow designed to streamline and automate the analysis of MD simulation of protein or protein-ligand complex. Unlike the traditional, manual approach, ASGARD enables researchers to generate comprehensive analyses with a single command line, significantly accelerating the research process and avoiding the laborious task of manual report generation. This tool automatically performs a range of analyses post-simulation, including system stability and flexibility assessments through RMSD Fluctuation and Distribution calculations. It further provides dynamic analysis using SASA, DSSP method graphs, and various interaction analyses. A key feature of ASGARD is its user-friendly design; it requires no additional installations or dependencies, making it highly accessible for researchers. In conclusion, ASGARD simplifies the MD simulation analysis process and substantially enhances efficiency and productivity in molecular research by providing an integrated, one-command analysis solution.Communicated by Ramaswamy H. Sarma.

A metabolomics perspective on the effect of environmental micro and nanoplastics on living organisms: A review.

The increasing trend regarding the use of plastics has arisen an exponential concern on the fate of their derived products to the environment. Among these derivatives, microplastics and nanoplastics (MNPs) have been featured for their associated environmental impact due to their low molecular size and high surface area, which has prompted their ubiquitous transference among all environmental interfaces. Due to the heterogenous chemical composition of MNPs, the study of these particles has focused a high number of studies, as a result of the myriad of associated physicochemical properties that contribute to the co-transference of a wide range of contaminants, thus becoming a major challenge for the scientific community. In this sense, both primary and secondary MNPs are well-known to be adscribed to industrial and urbanized areas, from which they are massively released to the environment through a multiscale level, involving the atmosphere, hydrosphere, and lithosphere. Consequently, much research has been conducted on the understanding of the interconnection between those interfaces, that motivate the spread of these contaminants to biological systems, being mostly represented by the biosphere, especially phytosphere and, finally, the anthroposphere. These findings have highlighted the potential hazardous risk for human health through different mechanisms from the environment, requiring a much deeper approach to define the real risk of MNPs exposure. As a result, there is a gap of knowledge regarding the environmental impact of MNPs from a high-throughput perspective. In this review, a metabolomics-based overview on the impact of MNPs to all environmental interfaces was proposed, considering this technology a highly valuable tool to decipher the real impact of MNPs on biological systems, thus opening a novel perspective on the study of these contaminants.

Design and Validation of Primer Sets for the Detection and Quantification of Antibiotic Resistance Genes in Environmental Samples by Quantitative PCR.

The high prevalence of antibiotic resistant bacteria (ARB) in several environments is a great concern threatening human health. Particularly, wastewater treatment plants (WWTP) become important contributors to the dissemination of ARB to receiving water bodies, due to the inefficient management or treatment of highly antibiotic-concentrated wastewaters. Hence, it is vital to develop molecular tools that allow proper monitoring of the genes encoding resistances to these important therapeutic compounds (antibiotic resistant genes, ARGs). For an accurate quantification of ARGs, there is a need for sensitive and robust qPCR assays supported by a good design of primers and validated protocols. In this study, eleven relevant ARGs were selected as targets, including aadA and aadB (conferring resistance to aminoglycosides); ampC, blaTEM, blaSHV, and mecA (resistance to beta-lactams); dfrA1 (resistance to trimethoprim); ermB (resistance to macrolides); fosA (resistance to fosfomycin); qnrS (resistance to quinolones); and tetA(A) (resistance to tetracyclines). The in silico design of the new primer sets was performed based on the alignment of all the sequences of the target ARGs (orthology grade > 70%) deposited in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, allowing higher coverages of the ARGs' biodiversity than those of several primers described to date. The adequate design and performance of the new molecular tools were validated in six samples, retrieved from both natural and engineered environments related to wastewater treatment. The hallmarks of the optimized qPCR assays were high amplification efficiency (> 90%), good linearity of the standard curve (R2 > 0.980), repeatability and reproducibility across experiments, and a wide linear dynamic range. The new primer sets and methodology described here are valuable tools to upgrade the monitorization of the abundance and emergence of the targeted ARGs by qPCR in WWTPs and related environments.

Effect of Applying 1% Metformin on Guided Bone Regeneration Processes with Bovine-Derived Xenografts.

Background: Although xenografts have shown successful results in GBR procedures due to their osteoconductive properties, many authors have opted to add co-adjuvant drugs to favor osteogenesis and differentiate cells into an osteoblastic lineage. Metformin has been shown to have bone-protective properties, regulating osteoclast differentiation, as well as the ability to promote osteoblast mineralization and differentiation. The present study aimed to evaluate the effect of the local application of a 1% metformin solution on bone neoformation in the treatment of an experimental bone defect in a guided bone regeneration animal model with a particulated bovine hydroxyapatite xenograft with hyaluronate. Methods: With this purpose in mind, two critical defects with 8 mm diameter and 0.5 mm depth were created in eight male New Zealand rabbit calvarias. Titanium cylinders were fixed in each defect and filled with particulate hydroxyapatite of bovine origin and sodium hyaluronate, with sterile injectable saline added to the control group and sterile 1% metformin solution added to the test group. At 6 weeks, the animals were euthanized, and samples were obtained and prepared for histomorphometric analysis. Results: A higher percentage of new bone formation was observed in the metformin samples than in the control samples, both in the region closest to the animal's calvaria and in the most distal region analyzed. A higher average bone-biomaterial contact percentage was observed in the samples, with metformin in both the proximal and distal regions. There was no statistically significant difference in the mean value in either region in both parameters. Conclusion: The local application of a 1% metformin solution in an animal model of guided bone regeneration with particulate bovine hydroxyapatite and hyaluronate resulted in greater bone neoformation and xenograft osseointegration than in the control group.

Biomechanical Effects of Ti-Base Abutment Height on the Dental Implant System: A Finite Element Analysis.

This study aims to analyse, using a finite element analysis, the effects of Ti-base abutment height on the distribution and magnitude of transferred load and the resulting bone microstrain in the bone-implant system. A three-dimensional bone model of the mandibular premolar section was created with an implant placed in a juxta-osseous position. Three prosthetic models were designed: a 1 mm-high titanium-base (Ti-base) abutment with an 8 mm-high cemented monolithic zirconia crown was designed for model A, a 2 mm-high Ti-base abutment with a 7 mm-high crown for model B, and a 3 mm-high abutment with a 6 mm-high crown for model C. A static load of 150 N was applied to the central fossa at a six-degree angle with respect to the axial axis of the implant to evaluate the magnitude and distribution of load transfer and microstrain. The results showed a trend towards a direct linear association between the increase in the height of the Ti-base abutments and the increase in the transferred stress and the resulting microstrain to both the prosthetic elements and the bone/implant system. An increase in transferred stress and deformation of all elements of the system, within physiological ranges, was observed as the size of the Ti-base abutment increased.

Weak effect of urbanization on bdelloid rotifers living in lichens.

Human activities have an overwhelming impact on the natural environment, leading to a deep biodiversity crisis whose effects range from genes to ecosystems. Here, we analysed the effect of such anthropogenic impacts on bdelloid rotifers (Rotifera Bdelloidea), for whom these effects are poorly understood. We targeted bdelloid rotifers living in lichen patches across urbanization gradients in Flanders and Brussels (Belgium). Urbanization was measured as the percentage of built-up area (BU) across different spatial scales, at circles from 50 to 3200 m of radius around the lichen. Urbanization effects on biodiversity were assessed on abundance, species richness and community-weighted mean body size of bdelloid rotifers, as well as on genetic diversity of a mitochondrial marker (cytochrome c oxidase subunit I) of one of the most common and widespread bdelloid species, Adineta vaga. Overall, no negative effect of urbanization was found at any diversity level and any spatial scale. Counterintuitively, the BU area quantified at the largest spatial scale had a positive effect on abundance. These results leave open the question of whether negative effects of urbanization are present for bdelloid rotifers, if they are mediated by other unexplored drivers, or if such effects are only visible at even larger spatial scales.

Hepatopathy secondary to infiltration by malignant melanoma: diagnostic value of liver biopsy.

We present the case of a 61-year-old male with no relevant history of interest who was admitted to hospital due to constitutional syndrome and discomfort in the right hypochondrium. On admission, abdominal ultrasound was performed with findings of chronic liver disease and innumerable well-defined hypoechogenic lesions of small size. Although the study was extended with other imaging tests, they did not provide more information than what was available at the time. Subsequently, an ultrasound-guided liver biopsy was performed with pathological anatomy compatible with infiltration by malignant melanoma. Subsequently, a search for the primary origin of the melanoma was performed and it was found in the right thigh. Hepatic involvement by melanoma is infrequent and both the symptoms and the findings in the complementary tests are non-specific, characteristics that make diagnosis difficult. Therefore, in these cases liver biopsy plays a fundamental role in the diagnosis.

Recommendations and good practices for dissolved organic carbon (DOC) analyses at low concentrations.

Numerous protocols for dissolved organic carbon (DOC) measurements on natural water are used in the literature. An ISO protocol for the determination of DOC exists since 2018, but it is certified for DOC values ≥ 1 mg L-1, while many publications report DOC values much lower. In addition, this ISO protocol does not include indications on vials cleaning, filtering material, and type of caps and septa to be used. The purpose of this study was to evaluate protocols for measurements of low DOC concentrations (≤ 1 mg L-1). The effect of the sample container, type of septum, filtration material, nature of acid used for storage, and matrix effects on DOC concentration were evaluated.•The use of glass vials decontaminated at 450 °C or 500 °C for at least 1 h, 0.45 µm hydrophilic polytetrafluoroethylene (PTFE) membranes previously rinsed with 20 mL ultra-pure water and HCl acidification gives the lowest DOC contamination,•Sulfides (ΣH2S), sodium (Na+) or calcium (Ca2+) do not induce high matrix effect for the analysis (≤ 10%),•At low DOC concentrations (≤ 1 mg L-1), the use of pierced PTFE septa with acidified samples induce slight DOC contamination after storage at 4 °C, and dramatic contamination after storage at -18 °C.

Microbial Ecology of Granular Biofilm Technologies for Wastewater Treatment: A Review.

Nowadays, the discharge of wastewater is a global concern due to the damage caused to human and environmental health. Wastewater treatment has progressed to provide environmentally and economically sustainable technologies. The biological treatment of wastewater is one of the fundamental bases of this field, and the employment of new technologies based on granular biofilm systems is demonstrating success in tackling the environmental issues derived from the discharge of wastewater. The granular-conforming microorganisms must be evaluated as functional entities because their activities and functions for removing pollutants are interconnected with the surrounding microbiota. The deep knowledge of microbial communities allows for the improvement in system operation, as the proliferation of microorganisms in charge of metabolic roles could be modified by adjustments to operational conditions. This is why engineering must consider the intrinsic microbiological aspects of biological wastewater treatment systems to obtain the most effective performance. This review provides an extensive view of the microbial ecology of biological wastewater treatment technologies based on granular biofilms for mitigating water pollution.

Synthesis and Raman Detection of 5-Amino-2-mercaptobenzimidazole Self-Assembled Monolayers in Nanoparticle-on-a-Mirror Plasmonic Cavity Driven by Dielectric Waveguides.

Functionalization of metallic surfaces by molecular monolayers is a key process in fields such as nanophotonics or biotechnology. To strongly enhance light-matter interaction in such monolayers, nanoparticle-on-a-mirror (NPoM) cavities can be formed by placing metal nanoparticles on such chemically functionalized metallic monolayers. In this work, we present a novel functionalization process of gold surfaces using 5-amino-2-mercaptobenzimidazole (5-A-2MBI) molecules, which can be used for upconversion from THz to visible frequencies. The synthesized surfaces and NPoM cavities are characterized by Raman spectroscopy, atomic force microscopy (AFM), and advancing-receding contact angle measurements. Moreover, we show that NPoM cavities can be efficiently integrated on a silicon-based photonic chip performing pump injection and Raman-signal extraction via silicon nitride waveguides. Our results open the way for the use of 5-A-2MBI monolayers in different applications, showing that NPoM cavities can be effectively integrated with photonic waveguides, enabling on-chip enhanced Raman spectroscopy or detection of infrared and THz radiation.

An international worldwide retrospective cohort observational study comparing primary cytoreductive surgery with neoadjuvant chemotherapy and interval cytoreductive surgery in patients with carcinoma of the ovary, fallopian tubes, and peritoneum (SUROVA trial).

BACKGROUND: Currently, a lively debate exists within the scientific community regarding the most suitable procedure for treating stages IIIB-IVB carcinoma of the ovary, fallopian tubes, and peritoneum. The options under most consideration are primary cytoreductive surgery or neoadjuvant chemotherapy followed by interval cytoreductive surgery. PRIMARY OBJECTIVE: To compare overall survival at 5 years in patients who underwent primary cytoreductive surgery versus neoadjuvant chemotherapy and interval cytoreductive surgery for stage IIIB-IVB ovarian cancer STUDY HYPOTHESIS: The treatment with primary cytoreductive surgery results in superior patient survival compared with neoadjuvant chemotherapy followed by interval cytoreductive surgery. TRIAL DESIGN: This is a multicenter, retrospective cohort observational study. Data will be collected from patients undergoing surgery in hospitals worldwide. Two arms will be compared: primary cytoreductive surgery and neoadjuvant chemotherapy followed by interval cytoreductive surgery. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients must have suspected or histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stages IIIB-IVB ovarian, peritoneal, or fallopian tube cancers. They must have undergone primary surgery or first course of neoadjuvant chemotherapy between January 1, 2018 and December 31, 2019. Based on all available information before the surgery (primary or interval), the patient must have been considered completely resectable. PRIMARY ENDPOINT: Overall survival at 5 years from the first treatment (chemotherapy in the case of neoadjuvant chemotherapy and cytoreduction in the case of primary cytoreductive surgery). SAMPLE SIZE: An estimated total of 5000 patients will be enrolled in the study. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: March 2025 TRIAL REGISTRATION: NCT06223763.