Biomechanical analysis using finite element analysis of orbital floor fractures reproduced in a realistic experimental environment with an anatomical model.

Introduction: In this study, we attempted to demonstrate the actual process of orbital floor fracture visually and computationally in anatomically reconstructed structures and to investigate them using finite element analysis. Methods: A finite element model of the skull and cervical vertebrae was reconstructed from computed tomography data, and an eyeball surrounded by extraocular adipose was modeled in the orbital cavity. Three-dimensional volume mesh was generated using 173,894 of the 4-node hexahedral solid elements. Results: For the cases where the impactor hit the infraorbital foramen, buckling occurred at the orbital bone as a result of the compressive force, and the von Mises stress exceeded 150 MPa. The range of stress components included inferior orbital rim and orbital floor. For the cases where the impactor hit the eyeball first, the orbital bone experienced less stress and the range of stress components limited in orbital floor. The critical speeds for blowout fracture were 4 m/s and 6 m/s for buckling and hydraulic mechanism. Conclusion: Each mechanism has its own fracture inducing energy and its transmission process, type of force causing the fracture, and fracture pattern. It is possible to determine the mechanism of the fracture based on whether an orbital rim fracture is present.

Effect of dentin surface conditions and curing mode of resin cement on the dentin bond strength.

This study investigates the effects of dentin's drying time, roughness, and curing modes of resin cement on bond strength. Forty human teeth were divided into eight groups based on three experimental factors: dentin's roughness by 240-or 600-grit SiC paper (coarse or fine), dentin wetness with air-drying time (5-s or 10-s), and Single Bond Universal adhesive's curing mode by co-curing with RelyX Ultimate cement or light-curing separately (co-curing or light-curing). The micro-tensile bond strength of fifteen resin-dentin stikcs per groups was measured. Failure mode and adhesive layers were observed using stereoscopic and confocal laser scanning microscopy, respectively. The curing mode of the adhesive layer affected the bond strength of the dentin-resin cement (p<0.05). In particular, the light-curing mode exhibited a significantly higher bond strength than the co-curing one (p<0.05). The bond strength between the resin cement and dentin was improved in the 5-s drying groups than in the 10-s drying groups.

The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation.

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/ß-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/ß-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.

VSTM2L is a promising therapeutic target and a prognostic soluble-biomarker in cholangiocarcinoma.

The aim of the present study is to provide a rational background for silencing the V-set and transmembrane domain containing 2 like (VSTM2L) in consort with recognising soluble VSTM2L against cholangiocarcinoma. A therapeutic target against cholangiocarcinoma was selected using iterative patient partitioning (IPP) calculation, and it was verified by in vitro and in silico analyses. VSTM2L was selected as a potential therapeutic target against cholangiocarcinoma. Silencing the VSTM2L expression significantly attenuated the viability and survival of cholangiocarcinoma cells through blockade of the intracellular signalling pathway. In silico analysis showed that VSTM2L affected the positive regulation of cell growth in cholangiocarcinoma. Liptak's z value revealed that the expression of VSTM2L worsened the prognosis of cholangiocarcinoma patients. In addition, soluble VSTM2L was significantly detected in the whole blood of cholangiocarcinoma patients compared with that of healthy donors. Our report reveals that VSTM2L might be the potential therapeutic target and a soluble prognostic biomarker against cholangiocarcinoma.

Current treatment strategies for ovarian cancer in the East Asian Gynecologic Oncology Trial Group (EAGOT).

Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors. The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT's multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia.

Context-dependent genomic locus effects on antibody production in recombinant Chinese hamster ovary cells generated through random integration.

High-yield production of therapeutic protein using Chinese hamster ovary (CHO) cells requires stable cell line development (CLD). CLD typically uses random integration of transgenes; however, this results in clonal variation and subsequent laborious clone screening. Therefore, site-specific integration of a protein expression cassette into a desired chromosomal locus showing high transcriptional activity and stability, referred to as a hot spot, is emerging. Although positional effects are important for therapeutic protein expression, the sequence-specific mechanisms by which hotspots work are not well understood. In this study, we performed whole-genome sequencing (WGS) to locate randomly inserted vectors in the genome of recombinant CHO cells expressing high levels of monoclonal antibodies (mAbs) and experimentally validated these locations and vector compositions. The integration site was characterized by active histone marks and potential enhancer activities, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) mediated indel mutations in the region upstream of the integration site led to a significant reduction in specific antibody productivity by up to 30%. Notably, the integration site and its core region did not function equivalently outside the native genomic context, showing a minimal effect on the increase in exogenous protein expression in the host cell line. We also observed a superior production capacity of the mAb expressing cell line compared to that of the host cell line. Collectively, this study demonstrates that developing recombinant CHO cell lines to produce therapeutic proteins at high levels requires a balance of factors including transgene configuration, genomic locus landscape, and host cell properties.

All-dielectric polarization-sensitive metasurface for terahertz polarimetric imaging.

Terahertz polarimetric imaging, capable of capturing not only intensity profiles but also the polarization states of the incident pattern, is an essential technique with promising applications such as security scans and medical diagnoses. Recently, a novel approach for terahertz imaging has been proposed using a metasurface absorber that converts terahertz light into a temperature profile. However, polarization remains indistinguishable in the imaging process due to the isotropic geometry of the metasurface. To address this issue, this study introduces an all-dielectric, polarization-sensitive metasurface absorber and showcases its suitability for terahertz polarimetric imaging. Optical and thermal simulations confirm that the polarization dependence of our metasurface is translated into the thermal domain, allowing us to distinguish both intensity and polarization states in the incoming image. Additionally, we demonstrate that polarimetric imaging under general, elliptical polarization is attainable. This metasurface facilitates terahertz polarimetric imaging, eliminating the need for complex setups or bulky components, thereby reducing the form factor and enabling widespread use.

Genetic Characterization and Phylogeographic Analysis of the First H13N6 Avian Influenza Virus Isolated from Vega Gull in South Korea.

Avian influenza virus (AIV) is a pathogen with zoonotic and pandemic potential. Migratory birds are natural reservoirs of all known subtypes of AIVs, except for H17N10 and H18N11, and they have been implicated in previous highly pathogenic avian influenza outbreaks worldwide. This study identified and characterized the first isolate of the H13N6 subtype from a Vega gull (Larus vegae mongolicus) in South Korea. The amino acid sequence of hemagglutinin gene showed a low pathogenic AIV subtype and various amino acid substitutions were found in the sequence compared to the reference sequence and known H13 isolates. High sequence homology with other H13N6 isolates was found in HA, NA, PB1, and PA genes, but not for PB2, NP, M, and NS genes. Interestingly, various point amino acid mutations were found on all gene segments, and some are linked to an increased binding to human-type receptors, resistance to antivirals, and virulence. Evolutionary and phylogenetic analyses showed that all gene segments are gull-adapted, with a phylogeographic origin of mostly Eurasian, except for PB2, PA, and M. Findings from this study support the evidence that reassortment of AIVs continuously occurs in nature, and migratory birds are vital in the intercontinental spread of avian influenza viruses.

Serum Lipidome Profiling Reveals a Distinct Signature of Ovarian Cancer in Korean Women.

BACKGROUND: Distinguishing ovarian cancer from other gynecological malignancies is crucial for patient survival yet hindered by non-specific symptoms and limited understanding of ovarian cancer pathogenesis. Accumulating evidence suggests a link between ovarian cancer and deregulated lipid metabolism. Most studies have small sample sizes, especially for early-stage cases, and lack racial/ethnic diversity, necessitating more inclusive research for improved ovarian cancer diagnosis and prevention. METHODS: Here, we profiled the serum lipidome of 208 ovarian cancer, including 93 early-stage patients with ovarian cancer and 117 nonovarian cancer (other gynecological malignancies) patients of Korean descent. Serum samples were analyzed with a high-coverage liquid chromatography high-resolution mass spectrometry platform, and lipidome alterations were investigated via statistical and machine learning (ML) approaches. RESULTS: We found that lipidome alterations unique to ovarian cancer were present in Korean women as early as when the cancer is localized, and those changes increase in magnitude as the diseases progresses. Analysis of relative lipid abundances revealed specific patterns for various lipid classes, with most classes showing decreased abundance in ovarian cancer in comparison with other gynecological diseases. ML methods selected a panel of 17 lipids that discriminated ovarian cancer from nonovarian cancer cases with an AUC value of 0.85 for an independent test set. CONCLUSIONS: This study provides a systemic analysis of lipidome alterations in human ovarian cancer, specifically in Korean women. IMPACT: Here, we show the potential of circulating lipids in distinguishing ovarian cancer from nonovarian cancer conditions.

Comparative Analysis of Autophagy and Apoptosis in Disc Degeneration: Understanding the Dynamics of Temporary-Compression-Induced Early Autophagy and Sustained-Compression-Triggered Apoptosis.

The purpose of this study was to investigate the initiation of autophagy activation and apoptosis in nucleus pulposus cells under temporary compression (TC) and sustained compression (SC) to identify ideal research approaches in intervertebral disc degeneration. Various techniques were used: radiography (X-ray), magnetic resonance imaging (MRI), transmission electron microscope (TEM), H&E staining, Masson's trichrome staining, immunohistochemistry (IHC) (LC3, beclin-1, and cleaved caspase-3), and real-time polymerase chain reaction (RT-qPCR) for autophagy-related (beclin-1, LC3, and P62) and apoptosis-related (caspase-3 and PARP) gene expression analysis. X-ray and MRI revealed varying degrees of disc degeneration, ranging from moderate to severe in both groups. The severity was directly linked to compression duration, with SC resulting in notably severe central NP cell degeneration. Surprisingly, TC also caused similar, though less severe, degeneration. Elevated expression of LC3 and beclin-1 was identified after 6 weeks, but it notably declined after 12 weeks. Central NP cells in both groups exhibited increased expression of cleaved caspase-3 that was positively correlated with the duration of SC. TC showed fewer apoptotic markers compared to SC. LC3, beclin-1, and P62 mRNA expression peaked after 6 weeks and declined after 12 weeks in both groups. Cleaved caspase-3 and PARP expression peaked in SC, positively correlating with longer compression duration, while TC showed lower levels of apoptosis gene expression. Furthermore, TEM results revealed different events of the autophagic degradation process after 2 weeks of compression. TCmay be ideal for studying early triggered autophagy-mediated degeneration, while SC may be ideal for studying late or slower-triggered apoptosis-mediated degeneration.

Comparison of the stress distribution in base materials and thicknesses in composite resin restorations.

Resin-based composite materials are commonly used for restorations, but their dimensional changes during the polymerization could cause various clinical problems. This study evaluated the influence of a base of different materials and thicknesses on the stress magnitude and distribution in a second maxillary premolar with an MOD resin composite restoration using three-dimensional finite element analysis. A sound tooth without cavity was considered as the control group (ST), and another group was restored with composite resin without applying a base material in a MOD cavity (CR). The other three groups were restored with composite resin along with the following base materials: glass ionomer cement, low-viscosity resin, and tricalcium silicate, respectively (CR-GIC, CR-LR, and CR-TS). These three groups were further divided into two subgroups according to the thickness of the base layer: thin (0.5 mm) and thick (1.0 mm). The stress distribution was compared using the maximum principal stress after polymerization shrinkage and vertical loading with 600 N on the occlusal surface. Group ST showed the lowest stress value, and its stress propagation was confined to outer enamel surfaces only. Group CR demonstrated the highest stress distribution in the tooth-restoration interface with increased failure risk on marginal areas. The thin and thick subgroups of the three groups with a base layer had lower stress levels than Group CR. The base materials reduced the marginal stress caused by polymerization shrinkage of composite resin in MOD cavities. Different base materials and thicknesses did not affect the stress distribution.

Anti-inflammatory effects of immature Citrus unshiu fruit extracts via suppression of NF-κB and MAPK signal pathways in LPS-induced RAW264.7 macrophage cells.

This study examined the anti-inflammatory effects of 70% ethanol crude extract of immature Citrus unshiu fruits (ICE) and its solvent fractions in LPS-stimulated RAW 264.7 cells. In addition, we analyzed the active compounds related to suppression of inflammation. It was found that the ethyl acetate (EtOAc) fraction showed the highest level of inhibition of NO production, and this inhibitory activity was concentration-dependent. Moreover, the EtOAc fraction not only inhibited TNF-α and IL-6 production but also inhibited iNOS and COX-2 protein expression. Furthermore, inhibition of NF-κB activity and MAPK phosphorylation was also observed. In addition, ß-sitosterol, campesterol and isoferulic acid were identified as major anti-inflammatory components in the EtOAc fraction. These results suggested that the EtOAc fraction of immature C. unshiu fruit extract exerts anti-inflammatory effects by inhibiting NF-κB and MAPK signaling pathways, and that this fruit could be used as a natural anti-inflammatory material.

Skin-whitening effects of Spergularia marina by suppressing MITF translocation.

Spergularia marina is a plant that grows in salty regions along the coastline and exerts radical-scavenging and anti-inflammatory effects. In this study, we investigated the skin-whitening effects of S. marina extract (SME) in B16F10 melanoma cells. SME was found to exert radical-scavenging effects. It suppressed α-melanocyte-stimulating hormone-induced melanogenesis and tyrosinase activity. We also assessed the melanin production signaling pathway to identify the inhibitory action mechanism of SME on melanogenesis. SME decreased the protein expression levels of tyrosinase-related protein (TRP)-1, TRP-2, and tyrosinase, which play important roles in melanogenesis. Furthermore, western blotting revealed that SME inhibited the nuclear translocation of melanocyte inducing transcription factor (MITF), which is a transcription factor for TRP-1, TRP-2, and tyrosinase, suggesting that SME exerts its skin-whitening effect by inhibiting MITF nuclear translocation. Therefore, SME may potentially be used in skin-whitening medicines and cosmetics.

Comparison of Adverse Events Between PARP Inhibitors in Patients with Epithelial Ovarian Cancer: A Nationwide Propensity Score Matched Cohort Study.

BACKGROUND: Despite improvement in progression-free survival (PFS) with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) as maintenance treatment for patients with epithelial ovarian cancer (EOC), a comparative analysis of clinical events of interest (CEIs) of different PARPi is scarce. OBJECTIVE: This study aimed to compare the safety of different PARPi in patients with EOC. PATIENTS AND METHODS: Through analyzing the Korean National Health Insurance Service from January 2009 to January 2022, this study involved BRCA-mutated, platinum-sensitive patients with EOC treated with olaparib (tablet), niraparib, and olaparib (capsule) as first-line or second-line maintenance treatment. CEIs were identified using International Statistical Classification of Diseases (ICD) 9/10 codes, with additional outcomes being dose modification and persistence. RESULTS: In the first-line maintenance treatment [118 niraparib, 104 olaparib (tablet) patients], no significant differences were noted in CEIs, dose reduction, or 6-month discontinuation rate. For second-line maintenance treatment [303 niraparib, 126 olaparib (tablet), and 675 olaparib (capsule) patients], niraparib was associated with a higher risk of hematologic CEIs, particularly anemia, compared with olaparib (tablet) (0.51 [0.26-0.98] and 0.09 [0.01-0.74], respectively), and higher rate of discontinuation rate at 6 months. Of note, patients over 60 years old showed an increased risk of CEIs with niraparib, as indicated by the hazard ratio divergence in restricted cubic spline plots. CONCLUSIONS: No differences were observed among the PARPi during first-line maintenance treatment. However, in the second-line maintenance treatment, significant differences were observed in the risk of experiencing CEIs, dose alteration possibilities, and discontinuation of PARPi between niraparib and olaparib (tablets). Moreover, our findings suggest that an age of 60 years may be a critical factor in selecting PARPi to reduce CEI incidence.

Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial).

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.

Amelioration of Astrocyte-Mediated Neuroinflammation by EI-16004 Confers Neuroprotection in an MPTP-induced Parkinson's Disease Model.

Parkinson's disease (PD) is a neurodegenerative disorder that results in motor impairment due to dopaminergic neuronal loss. The pathology of PD is closely associated with neuroinflammation, which can be characterized by astrocyte activation. Thus, targeting the inflammatory response in astrocytes might provide a novel therapeutic approach. We conducted a luciferase assay on an in-house chemical library to identify compounds with anti-inflammatory effects capable of reducing MPP+-induced NF-κB activity in astrocytes. Among the compounds identified, EI-16004, a novel 3-benzyl-N-phenyl-1H-pyrazole-5-carboxamides, exhibited a significant anti-inflammatory effect by significantly reducing MPP+-induced astrocyte activation. Biochemical analysis and docking simulation indicated that EI-16004 inhibited the MPP+-induced phosphorylation of p65 by attenuating ERK phosphorylation, and EI-16004 reduced pro-inflammatory cytokine and chemokine levels in astrocytes. In vivo studies on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in male C57BL/6 mice showed that EI-16004 ameliorated motor impairment and protected against dopaminergic neuronal loss, and EI-16004 effectively mitigated the MPTP-induced astrocyte activation in striatum (STR) and substantia nigra (SN). These results indicate EI-16004 is a potential neuroprotective agent for the prevention and treatment of astrocyte-mediated neuroinflammatory conditions in PD.

Malignant peripheral nerve sheath tumor in the kidney of a dog.

A 12-year-old castrated male poodle presented with vomiting and diarrhea. Ultrasonography and computed tomography revealed a protruding mass at the caudal pole of the left kidney. Grossly, the poorly circumscribed abnormal mass was 1.6 × 1.8 × 1.9 cm in size and had multifocal dark-red foci. Microscopically, it was composed of densely or loosely packed variable-sized short spindle or ovoid cells. These neoplastic cells showed high pleomorphism, mitotic figures, and invasive tendency to the adjacent tissue. Immunohistochemically, the neoplastic spindle cells expressed vimentin, S100, neuron-specific enolase, nerve growth factor receptor, and laminin. Therefore, the mass was diagnosed as a malignant peripheral nerve sheath tumor (MPNST). To our knowledge, this is the first report of primary renal MPNST in a dog.

Lugol's Solution Reduces Positive Margins and Residual Disease After the Large Loop Excision of Transformation Zone.

OBJECTIVE: This study aimed to examine whether the intraoperative use of Lugol's solution reduces the proportion of positive resection margins (RMs) using the data of women who underwent large loop excision of the transformation zone (LLETZ). MATERIALS AND METHODS: A total of 1,751 consecutive women with cervical intraepithelial neoplasia (CIN) who underwent LLETZ with or without Lugol's solution were retrospectively retrieved from each database of 3 university hospitals in South Korea. Outcomes included positive RMs and residual disease pathologically confirmed within 6 months after LLETZ. RESULTS: Positive RMs were noted in 345 cases (19.7%). Among 1,507 women followed up, residual disease was diagnosed in 100 cases (6.6%) (69/308 cases with positive RMs; 31/1,199 cases with negative RMs). The Lugol's solution group was less likely to have positive RMs (11.8% vs 25.5%, p < .01), to require additional surgical intervention (5.4% vs 10.2%, p < .01), and to have residual disease (4.9% vs 8.0%, p = .02). On multiple logistic regression analysis, Lugol's solution reduced the proportion of positive RMs (adjusted odds ratio [aOR], 0.31). Age (50 years or older; aOR, 1.64), preconization cervical cytology (aOR, 1.53), high-risk human papillomavirus (aOR, 1.75), and CIN 2 or 3 (aOR, 2.65) were independent risk factors for margin positivity ( p < .01 for all except high-risk human papillomavirus of p = .05). CONCLUSIONS: Lugol's solution optimizes CIN treatment by reducing the proportion of positive RMs and residual disease after LLETZ.

Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naïve Platinum-Sensitive Relapsed Ovarian Cancer: A Phase II Multi-Cohort Study.

PURPOSE: Early results from the phase II MEDIOLA study (NCT02734004) in germline BRCA1- and/or BRCA2-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) showed promising efficacy and safety with olaparib plus durvalumab. We report efficacy and safety of olaparib plus durvalumab in an expansion cohort of women with gBRCAm PSROC (gBRCAm expansion doublet cohort) and two cohorts with non-gBRCAm PSROC, one of which also received bevacizumab (non-gBRCAm doublet and triplet cohorts). PATIENTS AND METHODS: In this open-label, multicenter study, PARP inhibitor-naïve patients received olaparib plus durvalumab treatment until disease progression; the non-gBRCAm triplet cohort also received bevacizumab. Primary endpoints were objective response rate (ORR; gBRCAm expansion doublet cohort), disease control rate (DCR) at 24 weeks (non-gBRCAm cohorts), and safety (all cohorts). RESULTS: The full analysis and safety analysis sets comprised 51, 32, and 31 patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively. ORR was 92.2% [95% confidence interval (CI), 81.1-97.8] in the gBRCAm expansion doublet cohort (primary endpoint); DCR at 24 weeks was 28.1% (90% CI, 15.5-43.9) in the non-gBRCAm doublet cohort (primary endpoint) and 74.2% (90% CI, 58.2-86.5) in the non-gBRCAm triplet cohort (primary endpoint). Grade ≥ 3 adverse events were reported in 47.1%, 65.6%, and 61.3% of patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively, most commonly anemia. CONCLUSIONS: Olaparib plus durvalumab continued to show notable clinical activity in women with gBRCAm PSROC. Olaparib plus durvalumab with bevacizumab demonstrated encouraging clinical activity in women with non-gBRCAm PSROC. No new safety signals were identified.