Olaparib as treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis.

Background: LIGHT (oLaparib In HRD-Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive non-BRCAm, and HRD-negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression-free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS).

Coexisting Calcific Aortic Stenosis and Transthyretin Cardiac Amyloidosis: Real-World Evaluation of Clinical Characteristics and Outcomes.

Background: The coexistence of transthyretin cardiac amyloidosis (ATTR-CA) and aortic stenosis (AS) is increasingly recognized, but the clinical consequences are unclear. We aimed to characterize clinical outcomes in AS plus ATTR-CA compared with only AS or ATTR-CA.

Methods And Results: In a retrospective cohort study, patients with AS only, ATTR-CA only, or AS plus ATTR-CA were identified using all-payer claims data (2015-2021).

A Phase 1 Randomized Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Escalating Oral Doses of Dordaviprone and the Effects of Food on the Bioavailability of Dordaviprone in Healthy Adult Subjects.

Dordaviprone (ONC201) is a novel, small molecule imipridone with antitumor effects in glioma patients. This study evaluated the pharmacokinetics and safety of dordaviprone following single escalating doses (Part A), as a capsule content mixed with applesauce or Gatorade (sports drink) [Part B1]), and with or without food [Part B2]. The most common treatment-emergent adverse events pooled across study parts (Parts A, B1, and B2) were headache, dizziness, and headache, respectively; all were mild.

Lessons learned from 5 years of pegvaliase in US clinics: A case series.

Objective: To provide insights and strategies for pegvaliase management in challenging cases with phenylketonuria (PKU) based on the first 5 years of experience with pegvaliase in real-world clinical practice.

Methods: Twelve PKU experts gathered during a one-day, in-person meeting to discuss clinical cases illustrating important lessons from their experiences treating patients with pegvaliase in real-world clinical practice. Challenges with pegvaliase experienced prior to and during treatment and corresponding strategies to overcome them were discussed.

Prevalence of co-occurring conditions among youths receiving treatment with primary anxiety, ADHD, or depressive disorder diagnoses.

Introduction: Anxiety disorders, depressive disorders, and attention-deficit/hyperactivity disorder (ADHD) are some of the most common conditions that youths (<18 years old) receive mental health treatment for. These conditions are associated with high-risk substance use or substance use disorders (SUDs). This study sought to identify the proportion of youths (<18 years old) with anxiety disorders, depressive disorders, or ADHD as a primary diagnosis in community mental health centers (CMHCs) having co-occurring high-risk substance use or a SUD.

First-line pembrolizumab-axitinib versus sunitinib in metastatic RCC: subgroup analysis of patients enrolled in the phase 3 KEYNOTE-426 in Eastern Asia.

Background: The phase 3 open-label KEYNOTE-426 study demonstrated that first-line pembrolizumab plus axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC) in a global population. This subgroup analysis investigated the efficacy and safety of pembrolizumab-axitinib versus sunitinib in patients enrolled in KEYNOTE-426 in East Asia (Japan, South Korea, and Taiwan).

Methods: Adults with clear cell mRCC were randomly assigned 1:1 to receive intravenous pembrolizumab 200 mg every 3 weeks with oral axitinib 5 mg twice daily or oral sunitinib 50 mg once daily (4 weeks on/2 weeks off).

Broadband highly efficient source of collimated terahertz radiation driven by an ultrafast optical oscillator.

We demonstrate experimentally an efficient terahertz emitter that consists of a 20 µm thick layer of LiNbO clamped between a fused silica substrate and a Si semicone. A focused laser beam from an ultrafast optical oscillator propagates in the LiNbO layer and emits a Cherenkov cone of terahertz radiation to the Si semicone. The radiation is totally internally reflected by the semicone's convex surface and escapes the semicone through its base as a collimated beam.

Observation of complete energy transfer by orthogonally polarized Raman scattering in a high-birefringence fiber.

This study reports the observation of complete orthogonally polarized Raman scattering (OPRS) in a 1.0-km high-birefringence fiber (HBF). An incident pump pulse at 1560 nm with an energy of 2.

A conceptual model for advanced/metastatic gastric or gastroesophageal junction cancer: a review of qualitative studies and results from patient interviews.

Background: Despite approvals of new first-line immunotherapies for advanced/metastatic gastric cancer/gastroesophageal junction cancer (aGC/GEJC), patients' median survival is around 14 months and their health-related quality of life (HRQoL) is affected by disease-related symptoms and treatment-related side effects. Using a targeted literature review (TLR) and patient interviews, this study identified disease- and treatment-related concepts that are important to patients with aGC/GEJC and their HRQoL.

Methods: A TLR was conducted to identify primary qualitative studies from 2018 to 2021 on patients' experiences with aGC/GEJC.

Resolving tissue complexity by multimodal spatial omics modeling with MISO.

Spatial molecular profiling has provided biomedical researchers valuable opportunities to better understand the relationship between cellular localization and tissue function. Effectively modeling multimodal spatial omics data is crucial for understanding tissue complexity and underlying biology. Furthermore, improvements in spatial resolution have led to the advent of technologies that can generate spatial molecular data with subcellular resolution, requiring the development of computationally efficient methods that can handle the resulting large-scale datasets.

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study.

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.

Ancient DNA reveals reproductive barrier despite shared Avar-period culture.

After a long-distance migration, Avars with Eastern Asian ancestry arrived in Eastern Central Europe in 567 to 568 CE and encountered groups with very different European ancestry. We used ancient genome-wide data of 722 individuals and fine-grained interdisciplinary analysis of large seventh- to eighth-century CE neighbouring cemeteries south of Vienna (Austria) to address the centuries-long impact of this encounter. We found that even 200 years after immigration, the ancestry at one site (Leobersdorf) remained dominantly East Asian-like, whereas the other site (Mödling) shows local, European-like ancestry.

Antibacterial and antioxidant potentials, detection of host origin compounds, and metabolic profiling of endophytic Bacillus spp. isolated from Rauvolfia serpentina (L.) Benth. ex Kurz.

The research highlights the importance of exploring endophytic microbiomes of medicinal plants to uncover their potential for secondary metabolite production and their role in the biosynthesis of host-derived compounds. This study was aimed to isolate leaf endophytic bacteria of Rauvolfia serpentina, investigate their antibacterial, antioxidant potentials and detect host-origin compound reserpine using Reverse Phase High-Performance Liquid Chromatography (RPHPLC). Untargeted analysis via Ultra High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry (UHPLC-HRMS/MS) was conducted for profiling main phytochemicals in the leaves and to explore potential bioactive compounds in bacterial extracts.

Machine learning analysis of cervical balance in early-onset scoliosis post-growing rod surgery: a case-control study.

We aimed to analyze the cervical sagittal alignment change following the growing rod treatment in early-onset scoliosis (EOS) and identify the risk factors of sagittal cervical imbalance after growing-rod surgery of machine learning. EOS patients from our centre between 2007 and 2019 were retrospectively reviewed. Radiographic parameters include the cervical lordosis (CL), T1 slope, C2-C7 sagittal vertical axis (C2-7 SVA), primary curve Cobb angle, thoracic kyphosis (TK), C7-S1 sagittal vertical axis (C7-S1 SVA) and proximal junctional angle (PJA) were evaluated preoperatively, postoperatively and at the final follow-up.

Auditory decision-making deficits after permanent noise-induced hearing loss.

Loud noise exposure is one of the leading causes of permanent hearing loss. Individuals with noise-induced hearing loss (NIHL) suffer from speech comprehension deficits and experience impairments to cognitive functions such as attention and decision-making. Here, we investigate the specific underlying cognitive processes during auditory perceptual decision-making that are impacted by NIHL.

Association between abatacept exposure levels and infection occurrence in patients with rheumatoid arthritis: post hoc analysis of the AVERT-2 study.

Objective: To determine if higher serum exposure during subcutaneous (SC) abatacept treatment was associated with an increased infection risk in adult patients with early rheumatoid arthritis (RA).

Methods: Data from AVERT-2 (Assessing Very Early Rheumatoid arthritis Treatment-2, NCT02504268), a randomized, placebo-controlled study in anticitrullinated protein antibody- positive patients with early RA, were analyzed. A post hoc population pharmacokinetic (PPK) analysis was performed.

Change in management for digital subtraction angiography-identified false-positive traumatic vertebral artery injury.

Background: For patients with suspected traumatic vertebral artery injury (TVAI), CT angiography (CTA) is the first-line screening modality. Digital subtraction angiography (DSA) serves as the confirmatory diagnostic imaging, and is the gold standard for cerebrovascular injury assessment, due to its higher sensitivity and specificity. Among patients with TVAI based on CTA who have undergone follow-up DSA, this study aims to investigate how diagnostic information with additional imaging affects clinical management.

Open Chrono-Morph Viewer: visualize big bioimage time series containing heterogeneous volumes.

Summary: Time-lapse 3D imaging is fundamental for studying biological processes but requires software able to handle terabytes of voxel data. Although many multidimensional viewing applications exist, they mostly lack support for heterogeneous voxel counts, datatypes, and modalities in a single timeline. Open Chrono-Morph Viewer provides a straightforward graphical user interface to quickly investigate multi-timescale datasets represented as separate volume files in the common NRRD format for compatibility between toolchains.

Spatially programmed alignment and actuation in printed liquid crystal elastomers.

Liquid crystal elastomers (LCEs) exhibit reversible shape morphing behavior when cycled above their nematic-to-isotropic transition temperature. During extrusion-based 3D printing, LCE inks are subjected to coupled shear and extensional flows that can be harnessed to spatially control the alignment of their nematic director along prescribed print paths. Here, we combine experiment and modeling to elucidate the effects of ink composition, nozzle geometry, and printing parameters on director alignment.

A histochemical approach to activity-based copper sensing reveals cuproplasia-dependent vulnerabilities in cancer.

Copper is an essential nutrient for sustaining vital cellular processes spanning respiration, metabolism, and proliferation. However, loss of copper homeostasis, particularly misregulation of loosely bound copper ions which are defined as the labile copper pool, occurs in major diseases such as cancer, where tumor growth and metastasis have a heightened requirement for this metal. To help decipher the role of copper in the etiology of cancer, we report a histochemical activity-based sensing approach that enables systematic, high-throughput profiling of labile copper status across many cell lines in parallel.