A rapid CAT transformation protocol and nuclear transgene expression tools for metabolic engineering in Cyanidioschyzon merolae 10D.

The eukaryotic red alga Cyanidioschyzon merolae 10D is an emerging algal host for synthetic biology and metabolic engineering. Its small nuclear genome (16.5 Mb; 4775 genes), low intron content (39), stable transgene expression, and capacity for homologous recombination into its nuclear genome make it ideal for genetic and metabolic engineering endeavors.

Perspectives on innovative non-fertilizer applications of sewage sludge for mitigating environmental and health hazards.

As waste production increases and resources become limited, sewage sludge presents a valuable resource with potential beyond traditional land use and incineration. This review emphasizes exploring innovative non-fertilizer applications of sewage sludges and advocates for viewing wastewater treatment plants as sources of valuable feedstock and carbon sequestration. Innovative uses include integrating sewage sludge into construction materials such as asphalt pavements, geopolymer, cementitious composites, and masonry blocks.

Performance of medial pivot, posterior stabilized and rotating platform total knee arthroplasty based on anteroposterior stability and patient-reported outcome measures; a multicentre double-blinded randomized controlled trial of 210 knees.

Background: Despite advancements in total knee arthroplasty (TKA), 10-20% of patients remain dissatisfied after surgery. Improved anteroposterior (AP) stability provided by medial pivot (MP) implants may theoretically lead to higher patient satisfaction.

Methods: AP stability and patient-reported outcome measures (PROMs) at one-year postsurgery were compared between patients who underwent TKA with MP- (n = 121), posterior stabilized (PS; n = 53) and rotating platform (RP; n = 57) implants in a double-blind multicentre randomized controlled trial (Dutch Trial Register: NL6856, 21-02-2018).

A Phase 1/2 Study to Evaluate the Safety and Activity of Nivolumab in Combination With Vorolanib, a Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitor, in Patients With Refractory Thoracic Tumors.

Introduction: Targeting the tumor microenvironment may enhance response to immunotherapy (immune checkpoint inhibitors) and improve outcomes for patients. This study tested the safety and efficacy of vorolanib, a novel tyrosine kinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and c-KIT, in combination with programmed cell death protein 1 blockade using nivolumab for refractory thoracic malignancies.

Methods: This single-arm multicenter study enrolled patients with extensive-stage SCLC, thymic carcinoma, and NSCLC, either naive or had progressed on previous chemotherapy or immune checkpoint inhibitors (either primary or acquired resistance).

Engineered ketocarotenoid biosynthesis in the polyextremophilic red microalga 10D.

The polyextremophilic Cyanidiophyceae are eukaryotic red microalgae with promising biotechnological properties arising from their low pH and elevated temperature requirements which can minimize culture contamination at scale. 10D is a cell wall deficient species with a fully sequenced genome that is amenable to nuclear transgene integration by targeted homologous recombination. maintains a minimal carotenoid profile and here, we sought to determine its capacity for ketocarotenoid accumulation mediated by heterologous expression of a green algal β-carotene ketolase (BKT) and hydroxylase (CHYB).

Assessing Subsoil Conditions with an ASABE Conform Vertical Penetrometer-Development and Evaluation.

Soil is the habitat for soil organisms and associated soil physical and chemical processes. The subsoil is a large reserve of water and nutrients. Soil and subsoil are thus significantly involved in the yield capacity of a site and its resilience in the case of unfavorable weather conditions.

The reckoning: The return of genomic results to 1444 participants across the eMERGE3 Network.

Purpose: The goal of Electronic Medical Records and Genomics (eMERGE) Phase III Network was to return actionable sequence variants to 25,084 consenting participants from 10 different health care institutions across the United States. The purpose of this study was to evaluate system-based issues relating to the return of results (RoR) disclosure process for clinical grade research genomic tests to eMERGE3 participants.

Methods: RoR processes were developed and approved by each eMERGE institution's internal review board.

Enhancing Cancer care of rural dwellers through telehealth and engagement (ENCORE): protocol to evaluate effectiveness of a multi-level telehealth-based intervention to improve rural cancer care delivery.

Background: Despite lower cancer incidence rates, cancer mortality is higher among rural compared to urban dwellers. Patient, provider, and institutional level factors contribute to these disparities. The overarching objective of this study is to leverage the multidisciplinary, multispecialty oncology team from an academic cancer center in order to provide comprehensive cancer care at both the patient and provider levels in rural healthcare centers.

Survival Impact of an Enhanced Multidisciplinary Thoracic Oncology Conference in a Regional Community Health Care System.

Introduction: We compared NSCLC treatment and survival within and outside a multidisciplinary model of care from a large community health care system.

Methods: We implemented a rigorously benchmarked "enhanced" Multidisciplinary Thoracic Oncology Conference (eMTOC) and used Tumor Registry data (2011-2017) to evaluate guideline-concordant care. Because eMTOC was located in metropolitan Memphis, we separated non-MTOC patient by metropolitan and regional location.

Trilaciclib prior to chemotherapy reduces the usage of supportive care interventions for chemotherapy-induced myelosuppression in patients with small cell lung cancer: Pooled analysis of three randomized phase 2 trials.

Background: Supportive care interventions used to manage chemotherapy-induced myelosuppression (CIM), including granulocyte colony-stimulating factors (G-CSFs), erythropoiesis-stimulating agents (ESAs), and red blood cell (RBC) transfusions, are burdensome to patients and associated with greater costs to health care systems. We evaluated the utilization of supportive care interventions and their relationship with the myeloprotective agent, trilaciclib.

Methods: Data were pooled from three independent randomized phase 2 clinical trials of trilaciclib or placebo administered prior to chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC).

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

Background: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.

Patients And Methods: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included.

Increased ease of access to genetic counseling for low-income women with breast cancer using a point of care screening tool.

Increased access to genetic counseling services is of prime importance in minority and underserved populations where genetic testing is currently underutilized. Our study tested a point of care screening tool to identify high-risk low-income patients for genetic counseling in a busy county hospital oncology clinic. Eligible breast patients treated at a "safety-net" hospital, were scored into 'high-risk' (> or = 6) or 'low-risk' (< 6) groups using a screening tool on personal and family history of cancer.

Participant choices for return of genomic results in the eMERGE Network.

Purpose: Secondary findings are typically offered in an all or none fashion when sequencing is used for clinical purposes. This study aims to describe the process of offering categorical and granular choices for results in a large research consortium.

Methods: Within the third phase of the electronic MEdical Records and GEnomics (eMERGE) Network, several sites implemented studies that allowed participants to choose the type of results they wanted to receive from a multigene sequencing panel.

Assessment of Treatment With Sorafenib Plus Doxorubicin vs Sorafenib Alone in Patients With Advanced Hepatocellular Carcinoma: Phase 3 CALGB 80802 Randomized Clinical Trial.

Importance: Previous communication has reported significant improvement in overall survival (OS) when using doxorubicin plus sorafenib in the treatment of advanced hepatocellular cancer (HCC).

Objective: To determine if doxorubicin added to sorafenib therapy improves OS, with stratification for locally advanced and metastatic disease.

Design, Setting, And Participants: This unblinded randomized phase 3 clinical trial was led by Alliance in collaboration with Eastern Cooperative Oncology Group-American College of Radiology Imaging Network, Canadian Cancer Trials Group, and Southwest Oncology Group.

The genomes of polyextremophilic cyanidiales contain 1% horizontally transferred genes with diverse adaptive functions.

The role and extent of horizontal gene transfer (HGT) in eukaryotes are hotly disputed topics that impact our understanding of the origin of metabolic processes and the role of organelles in cellular evolution. We addressed this issue by analyzing 10 novel Cyanidiales genomes and determined that 1% of their gene inventory is HGT-derived. Numerous HGT candidates share a close phylogenetic relationship with prokaryotes that live in similar habitats as the Cyanidiales and encode functions related to polyextremophily.

Bispecific Antibodies in the Treatment of Hematologic Malignancies.

Monoclonal antibody therapies are an important approach for the treatment of hematologic malignancies, but typically show low single-agent activity. Bispecific antibodies, however, redirect immune cells to the tumor for subsequent lysis, and preclinical and accruing clinical data support single-agent efficacy of these agents in hematologic malignancies, presaging an exciting era in the development of novel bispecific formats. This review discusses recent developments in this area, highlighting the challenges in delivering effective immunotherapies for patients.

Extracellular histones are the ligands for the uptake of exosomes and hydroxyapatite-nanoparticles by tumor cells via syndecan-4.

The mechanisms by which exosomes (nano-vesicular messengers of cells) are taken up by recipient cells are poorly understood. We hypothesized that histones associated with these nanoparticles are the ligands which facilitate their interaction with cell surface syndecan-4 (SDC4) to mediate their uptake. We show that the incubation with fetuin-A (exosome-associated proteins) and histones mediates the uptake of exosomes that are normally not endocytosed.

Impact of Fetuin-A (AHSG) on Tumor Progression and Type 2 Diabetes.

Fetuin-A is the protein product of the gene in humans. It is mainly synthesized by the liver in adult humans and is secreted into the blood where its concentration can vary from a low of ~0.2 mg/mL to a high of ~0.

Neoadjuvant PF-05280014 (a potential trastuzumab biosimilar) versus trastuzumab for operable HER2+ breast cancer.

Background: This randomised, double-blind study compared pharmacokinetics, efficacy, safety and immunogenicity of PF-05280014 (potential trastuzumab biosimilar) and trastuzumab reference product (Herceptin) sourced from the European Union (trastuzumab-EU) as neoadjuvant treatment for operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Methods: Patients (N = 226), stratified by primary tumour size and hormone receptor status, were randomised 1:1 to PF-05280014 or trastuzumab-EU (8 mg/kg loading dose; 6 mg/kg thereafter), each with docetaxel and carboplatin, every 3 weeks for six treatment cycles. Primary endpoint was percentage of patients with trough plasma concentration (C) >20 μg/ml at Cycle 5 (Cycle 6 predose).

High salt induces P-glycoprotein mediated treatment resistance in breast cancer cells through store operated calcium influx.

Recent evidence from our laboratory has demonstrated that high salt (Δ0.05 M NaCl) induced inflammatory response and cancer cell proliferation through salt inducible kinase-3 (SIK3) upregulation. As calcium influx is known to effect inflammatory response and drug resistance, we examined the impact of high salt on calcium influx in breast cancer cells.