Real-world outcomes of first-line maintenance niraparib monotherapy in patients with epithelial ovarian cancer.

Aims: To assess real-world progression-free survival (rwPFS) and time to next treatment (rwTTNT) among patients with epithelial ovarian cancer (EOC) who received first-line maintenance (1LM) niraparib monotherapy.

Patients & Methods: In this US-nationwide, electronic health record-derived, deidentified database study, eligible patients with EOC initiated 1LM niraparib monotherapy (1 January 2017-1 December 2022) following first-line platinum-based chemotherapy. Median rwPFS and rwTTNT were estimated with Kaplan-Meier methodology overall and in a homologous recombination-deficient (HRd) subgroup (further stratified as wild-type [wt] or -mutated [m]).

Niraparib as First-Line Maintenance Therapy in Patients with Stage III Ovarian Cancer and No Visible Residual Disease: AR1ZE Real-World Study.

Introduction: Niraparib was approved for first-line (1L) maintenance (1LM) treatment of patients with advanced epithelial ovarian cancer (EOC) following the PRIMA/ENGOT-OV26/GOG-3012 (PRIMA) trial. PRIMA was restricted to patients at higher risk of progression (excluded stage III EOC with no visible residual disease [NVRD] after primary cytoreductive surgery [PCS]). This retrospective study evaluated the potential impact of excluding stage III EOC with NVRD from PRIMA by assessing real-world treatment outcomes following 1LM niraparib monotherapy in this patient population.

Ovarian Cancer Retrospective European (O'CaRE) study: first-line outcomes by number of risk factors for progression.

The Ovarian Cancer Retrospective European (O'CaRE) study assessed the cumulative impact of high-risk factors on progression-free survival (PFS) and overall survival (OS) following first-line treatment in patients diagnosed with advanced ovarian cancer. Medical records were collected from five European countries (2014 and 2015). Patients were grouped by number of high-risk factors: stage IV diagnosis, no known , interval debulking surgery or no surgery, or visible residual disease.

Characteristics and real-world outcomes of patients with epithelial ovarian cancer who received niraparib plus bevacizumab first-line maintenance therapy in the COMB1NE study.

Objective: In the phase 2 OVARIO trial (NCT03326193) investigating niraparib-bevacizumab first-line maintenance, median progression-free survival was 14.2 months (95% confidence interval (CI) 8.6 to 16.

Patient Characteristics Associated with Time to Next Treatment in Patients with Ovarian Cancer Treated with Niraparib: The PRED1CT Real-World Study.

Introduction: Niraparib first-line maintenance (1LM) therapy has demonstrated clinical benefit for patients with ovarian cancer (OC) in clinical trial and real-world settings, but data on factors associated with real-world patient outcomes remain limited. This analysis identified patient characteristics associated with time to next treatment (TTNT), a proxy for real-world progression-free survival, in patients with OC treated with 1LM niraparib monotherapy.

Methods: This retrospective observational study used a USA nationwide electronic health record-derived deidentified database and included adult patients diagnosed with OC who initiated 1LM niraparib monotherapy after first-line platinum-based chemotherapy.

Real-World First-Line Maintenance Niraparib Monotherapy Use Following Chemotherapy Plus Bevacizumab: The SW1TCH Study.

Introduction: Clinical trials have demonstrated prolonged survival associated with niraparib first-line maintenance (1LM) therapy, compared with placebo, for patients with ovarian cancer (OC). However, data are limited on real-world 1LM niraparib monotherapy use, particularly as switch 1LM, following first-line (1L) combination chemotherapy plus bevacizumab. This real-world study aimed to describe patient demographics, clinical characteristics, and clinical outcomes of patients with OC receiving 1LM niraparib monotherapy following 1L combination chemotherapy plus bevacizumab.

Major declines in NE Atlantic plankton contrast with more stable populations in the rapidly warming North Sea.

Plankton form the base of marine food webs, making them important indicators of ecosystem status. Changes in the abundance of plankton functional groups, or lifeforms, can affect higher trophic levels and can indicate important shifts in ecosystem functioning. Here, we extend this knowledge by combining data from Continuous Plankton Recorder and fixed-point stations to provide the most comprehensive analysis of plankton time-series for the North-East Atlantic and North-West European shelf to date.

Clinical and Biological Activity of Chemoimmunotherapy in Advanced Endometrial Adenocarcinoma: A Phase II Trial of the Big Ten Cancer Research Consortium.

Purpose: The objective of this study was to assess the efficacy and safety of pembrolizumab in combination with standard carboplatin/paclitaxel in patients with advanced endometrial cancer (EC).

Patients And Methods: This single-arm, open-label, multi-center phase II study enrolled patients with RECIST measurable advanced EC. Patients could have received < 1 prior platinum-based regimen and < one non-platinum chemotherapy.

Allochthony, fatty acid and mercury trends in muscle of Eurasian perch (Perca fluviatilis) along boreal environmental gradients.

Environmental change, including joint effects of increasing dissolved organic carbon (DOC) and total phosphorus (TP) in boreal northern lakes may affect food web energy sources and the biochemical composition of organisms. These environmental stressors are enhanced by anthropogenic land-use and can decrease the quality of polyunsaturated fatty acids (PUFAs) in seston and zooplankton, and therefore, possibly cascading up to fish. In contrast, the content of mercury in fish increases with lake browning potentially amplified by intensive forestry practises.

Tumor collection/processing under physioxia uncovers highly relevant signaling networks and drug sensitivity.

Preclinical studies of primary cancer cells are typically done after tumors are removed from patients or animals at ambient atmospheric oxygen (O, ~21%). However, O concentrations in organs are in the ~3 to 10% range, with most tumors in a hypoxic or 1 to 2% O environment in vivo. Although effects of O tension on tumor cell characteristics in vitro have been studied, these studies are done only after tumors are first collected and processed in ambient air.

A Novel Use of Laryngoscope for Difficult Papanicolaou Smear Collection.

The prevalence of cervical cancer has dropped significantly since introduction of the Papanicolaou (Pap) screen. The greatest risk factor for cervical cancer is inadequate screening. Altered pelvic anatomy can limit the ability to collect a Pap smear.

Carbon Budget and Molecular Structure of Natural Organic Matter in Bank Infiltrated Groundwater.

Managed aquifer recharge (MAR) provides means to remove natural organic matter (NOM) from surface waters. Recent studies have explored the degree of NOM removal in groundwater. In this study, we further elaborate the NOM removal at a lakeside natural bank infiltration site that functions as a surrogate for MAR.

The Transient Complex of Cytochrome c and Cytochrome c Peroxidase: Insights into the Encounter Complex from Multifrequency EPR and NMR Spectroscopy.

We present a novel approach to study transient protein-protein complexes with standard, 9 GHz, and high-field, 95 GHz, electron paramagnetic resonance (EPR) and paramagnetic NMR at ambient temperatures and in solution. We apply it to the complex of yeast mitochondrial iso-1-cytochrome c (Cc) with cytochrome c peroxidase (CcP) with the spin label [1-oxyl-2,2,5,5-tetramethyl-Δ3-pyrroline-3-methyl)-methanethiosulfonate] attached at position 81 of Cc (SL-Cc). A dissociation constant K of 20±4×10  M (EPR and NMR) and an equal amount of stereo-specific and encounter complex (NMR) are found.

Cell Origins of High-Grade Serous Ovarian Cancer.

High-grade serous ovarian cancer, also known as high-grade serous carcinoma (HGSC), is the most common and deadliest type of ovarian cancer. HGSC appears to arise from the ovary, fallopian tube, or peritoneum. As most HGSC cases present with widespread peritoneal metastases, it is often not clear where HGSC truly originates.

Randomized phase II trial of bevacizumab plus everolimus versus bevacizumab alone for recurrent or persistent ovarian, fallopian tube or peritoneal carcinoma: An NRG oncology/gynecologic oncology group study.

Purpose: Bevacizumab (BV) monotherapy leads to compensatory upregulation of multiple signaling pathways, resulting in mTOR activation. We evaluated combining BV and everolimus (EV), an mTOR kinase inhibitor, to circumvent BV-resistance in women with recurrent or persistent ovarian, fallopian tube or primary peritoneal cancer (OC).

Patients And Methods: Eligible OC patients had measurable (RECIST1.

On the use of absolute interface coordinates in the floating frame of reference formulation for flexible multibody dynamics.

In this work a new formulation for flexible multibody systems is presented based on the floating frame formulation. In this method, the absolute interface coordinates are used as degrees of freedom. To this end, a coordinate transformation is established from the absolute floating frame coordinates and the local interface coordinates to the absolute interface coordinates.

Trophic state changes can affect the importance of methane-derived carbon in aquatic food webs.

Methane-derived carbon, incorporated by methane-oxidizing bacteria, has been identified as a significant source of carbon in food webs of many lakes. By measuring the stable carbon isotopic composition (δC values) of particulate organic matter, Chironomidae and spp. and their resting eggs (ephippia), we show that methane-derived carbon presently plays a relevant role in the food web of hypertrophic Lake De Waay, The Netherlands.

The terminology of akinesia, bradykinesia and hypokinesia: Past, present and future.

Akinesia, hypokinesia, and bradykinesia are extensively used to describe motor execution disturbances, but are applied inconsistently and cover more conditions than their Greek translations would suggest. We investigated the origins and changes in meaning of these terms over time, particularly in relation to Parkinson's disease (PD). We searched the literature from 1817 to 2015 for use and interpretation of the words akinesia, bradykinesia, hypokinesia, and PD.

Weak self-association of cytochrome c peroxidase molecules observed by paramagnetic NMR.

There is growing experimental evidence that many proteins exhibit a tendency for (ultra)weak homo- or hetero- oligomerization interactions. With the development of paramagnetic relaxation enhancement NMR spectroscopy it has become possible to characterize weak complexes experimentally and even detect complexes with affinities in the 1-25 mM range. We present evidence for a weak complex between cytochrome c peroxidase (CcP) molecules.

Randomized Phase II Evaluation of Bevacizumab Versus Bevacizumab Plus Fosbretabulin in Recurrent Ovarian, Tubal, or Peritoneal Carcinoma: An NRG Oncology/Gynecologic Oncology Group Study.

Purpose: The vascular disrupting agent fosbretabulin tromethamine selectively targets pre-existing tumor vasculature, which causes vascular shutdown and leads to cancer cell death and necrosis. Antiangiogenesis agents such as bevacizumab, a humanized antivascular endothelial growth factor monoclonal antibody, might prevent revascularization during and after treatment with a vascular disrupting agent.

Patients And Methods: Patients with recurrent or persistent epithelial ovarian, tubal, or peritoneal carcinoma, measurable or detectable disease, and three or fewer prior regimens were randomly assigned to bevacizumab (15 mg/kg intravenously once every 3 weeks) or the combination of bevacizumab (15 mg/kg) plus fosbretabulin (60 mg/m(2)) intravenously once every 3 weeks until disease progression or toxicity.

The Effectiveness of an Intervention to Promote Awareness and Reduce Online Risk Behavior in Early Adolescence.

The current study explored the effect of a school-based intervention on online risk awareness and behavior in order to shed light on a relatively unexplored field with high practical relevance. More than 800 Belgium primary school children (grade 4 and 6) were assessed at two measurements (n T1 = 812, 51.2 % female; n T2 = 819, 51.

Protein docking using an ensemble of spin labels optimized by intra-molecular paramagnetic relaxation enhancement.

Paramagnetic NMR is a useful technique to study proteins and protein complexes and the use of paramagnetic relaxation enhancement (PRE) for this purpose has become wide-spread. PREs are commonly generated using paramagnetic spin labels (SLs) that contain an unpaired electron in the form of a nitroxide radical, with 1-oxyl-2,2,5,5-tetramethyl-2,5-dihydropyrrol-3-ylmethyl methane thiosulfonate (MTSL) being the most popular tag. The inherent flexibility of the SL causes sampling of several conformations in solution, which can be problematic as over- or underestimation of the spatial distribution of the unpaired electron in structural calculations will lead to errors in the distance restraints.