A Machine Vision Perspective on Droplet-Based Microfluidics.

Microfluidic droplets, with their unique properties and broad applications, are essential in in chemical, biological, and materials synthesis research. Despite the flourishing studies on artificial intelligence-accelerated microfluidics, most research efforts have focused on the upstream design phase of microfluidic systems. Generating user-desired microfluidic droplets still remains laborious, inefficient, and time-consuming.

Operando Decoding Ion-Conductive Switch in Stimuli-Responsive Hydrogel by Nanodiamond-Based Quantum Sensing.

Thermal-responsive hydrogels are developed as ion-conductive switchs for energy storage devices, however, the molecule mechanism of switch on/off remains unclear. Here, poly(N-isopropylacrylamide-co-acrylamide) hydrogel is synthesized as a model material and nanodiamond (ND) based quantum sensing for phase change study is developed. First, micro-scale phase separation with cross-linked mesh structure after sol-gel transition is visualized in situ and water molecules are trapped by polymer chains and on a chemically "frozen" state.

Non-small cell lung cancer with amplification: review of epidemiology, associated disease characteristics, testing procedures, burden, and treatments.

Introduction: Mesenchymal-epidermal transition factor gene amplification (amp) is being investigated as a therapeutic target in advanced non-small cell lung cancer (NSCLC). We reviewed the epidemiology and disease characteristics associated with primary and secondary amp, as well as the testing procedures used to identify amp, in advanced NSCLC. Economic and humanistic burdens, and the practice patterns and treatments under investigation for amp were also examined.

In situ mycoremediation of acid rain and heavy metals co-contaminated soil through microbial inoculation with Pleurotus ostreatus.

The combined pollution of acid rain and heavy metals in soil is a pressing environmental problem, especially in the regions with large-scale heavy industrial production activities. Low remediation efficiency and weak long-lasting stability are major challenges when disposing the heavy metals contaminated soil in acid rain polluted sites. Herein, a specific microbe, strain CT13 was isolated and domesticated to exhibit high tolerance to both acid rain and cadmium (Cd).

Evaluating Oncologists' Practice Patterns and Decision-Making in Locally Advanced or Metastatic Urothelial Carcinoma: The US Physician PARADIGM Study.

Background: The treatment landscape for locally advanced/metastatic urothelial carcinoma (la/mUC) has evolved. This study examined US prescribing patterns and clinical decision-making for first-line (1L) and first-line maintenance (1LM) treatment.

Materials And Methods: US-based oncologists (N = 150) completed an online survey on patient demographics, practice patterns, and important factors considered in 1L/1LM selection.

Clinical and Economic Outcomes in Patients With Metastatic Urothelial Carcinoma Receiving First-Line Systemic Treatment (the IMPACT UC I Study).

Background: The IMPACT UC I study assessed real-world treatment patterns, outcomes, healthcare resource utilization (HCRU), and costs in patients with metastatic urothelial carcinoma (mUC) receiving first-line (1L) systemic treatment after the FDA approval of 1L immune checkpoint inhibitor (ICI) monotherapy.

Patients And Methods: This retrospective study used 100% Medicare fee-for-service claims from 1/1/2015 to 6/30/2019 to identify patients aged ≥18 years diagnosed with UC with evidence of metastatic disease, continuously enrolled for 6 months before and after initial diagnosis. Patients were grouped by 1L treatment: cisplatin-containing chemotherapy, carboplatin-containing chemotherapy, ICI monotherapy, or nonplatinum-containing therapy.

Recent progress in nucleic acid detection with CRISPR.

Recent advances in CRISPR-based biotechnologies have greatly expanded our capabilities to repurpose CRISPR for the development of molecular diagnostic systems. The key attribute that allows CRISPR to be widely utilized is its programmable and highly specific nature. In this review, we first illustrate the principle of the class 2 CRISPR nucleases for molecular diagnostics which originates from their immunologic defence systems.

Isothermal Background-Free Nucleic Acid Quantification by a One-Pot Cas13a Assay Using Droplet Microfluidics.

High sensitivity and specificity nucleic acid detection has been achieved by the Cas13a collateral effect in combination with a separate recombinase polymerase amplification (RPA). However, these emerging methods cannot provide accurate quantification of nucleic acids because the two-step assay performance may be compromised if the RPA and Cas13a reactions are simply unified in a single step. In this work, we first addressed the challenges associated with enzymatic incompatibility and the macromolecular crowding effect in the one-pot assay development, making the consolidated RPA-Cas13a assay a facile and robust diagnostic tool.

Droplet digital recombinase polymerase amplification (ddRPA) reaction unlocking via picoinjection.

Recombinase polymerase amplification (RPA) has been recognized as a promising isothermal amplification method for nucleic acid detection. However, the digital format of RPA is still challenging to implement due to its MgOAc-initiated reaction feature and the inherent non-specific amplification. Here we develop a Picoinjection Aided Digital reaction unLOCKing (PADLOCK) approach utilizing droplet microfluidics to achieve droplet digital RPA (ddRPA) for absolute nucleic acid quantification.

Diagnostic and economic value of biomarker testing for targetable mutations in non-small-cell lung cancer: a literature review.

We aimed to assess the diagnostic and economic value of next-generation sequencing (NGS) versus single-gene testing, and of liquid biopsy (LBx) versus tissue biopsy (TBx) in non-small-cell lung cancer biomarker testing through literature review. Embase and MEDLINE were searched to identify relevant studies (n = 43) from 2015 to 2020 in adults with advanced non-small-cell lung cancer. For NGS versus single-gene testing, concordance was 70-99% and sensitivity was 86-100%.

Effects of early vs delayed progression on clinical and economic outcomes in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors as first-line therapy: results from the IMPACT RCC claims data analysis.

A key therapeutic goal of metastatic renal cell carcinoma (mRCC) treatment is delayed disease progression. The degree to which early therapeutic success affects downstream outcomes is not well established. To assess the clinical and economic impact of early vs delayed disease progression in patients with mRCC treated with first-line (1L) tyrosine kinase inhibitors (TKIs) followed by second-line (2L) therapy in the US Veterans Health Administration (VHA) database.

Budget impact of tepotinib in the treatment of adult patients with metastatic non-small cell lung cancer harboring ex14 skipping alterations in the United States.

Aims: To estimate the budget impact of adding tepotinib to United States (US) health plans for treating adult patients with metastatic non-small cell lung cancer (mNSCLC) harboring mesenchymal-epithelial transition exon 14 (ex14) skipping alterations.

Methods: The base-case analysis was conducted from the perspective of a hypothetical Medicare plan of 1 million members. Scenarios were analysed for other US health plans.

Real-World Clinical Outcomes in Patients with Locally Advanced or Metastatic Merkel Cell Carcinoma Treated in U.S. Oncology Clinical Practices: Results from SPEAR-Merkel.

Background: Immunotherapy (IO) has been associated with improved outcomes in patients with locally advanced Merkel cell carcinoma (laMCC) and metastatic Merkel cell carcinoma (mMCC). The primary objective of SPEAR-Merkel was to explore treatment patterns, clinical outcomes, and health care resource utilization (HCRU) in patients with laMCC or mMCC initiating first-line (1L) treatment with avelumab, non-avelumab IO, or chemotherapy in a U.S.

The Impact of Adverse Events on Health Care Resource Utilization, Costs, and Mortality Among Patients Treated with Immune Checkpoint Inhibitors.

Background: We investigated the association between adverse events (AEs) suspected to be immune-related and health care resource utilization, costs, and mortality among patients receiving programmed cell death 1/programmed cell death ligand 1 immune checkpoint inhibitor (ICI) monotherapy for urothelial carcinoma, renal cell carcinoma, non-small cell lung cancer, or Merkel cell carcinoma.

Patients And Methods: We conducted a retrospective cohort study using medical and pharmacy claims and enrollment information from U.S.

Real-world clinical outcomes with first-line avelumab in locally advanced/metastatic Merkel cell carcinoma in the USA: SPEAR-Merkel.

To assess clinical outcomes in patients with locally advanced (la) or metastatic (m) Merkel cell carcinoma (MCC) initiating first-line (1L) avelumab in a USA community oncology setting. Adults with laMCC or mMCC initiating 1L avelumab were identified from The US Oncology Network electronic health record database and chart review. Median overall survival and progression-free survival were not reached in laMCC (n = 9) vs 20.

Real-world symptoms, disease burden, resource use and quality of life in US patients with advanced renal cell cancer.

To assess symptoms, healthcare resource utilization and health-related quality of life in advanced renal cell carcinoma (aRCC) clinical practice. The USA point-in-time survey of physicians and patients was conducted between February and September 2019. Data were available for 227 patients.

Treatment patterns, outcomes and clinical characteristics in advanced renal cell carcinoma: a real-world US study.

Assessing treatment patterns, outcomes and clinical characteristics in advanced renal cell carcinoma clinical practice. A US cross-sectional physician survey conducted February-September 2019. Surveyed physicians reported first-line treatment of 445 patients involving tyrosine kinase inhibitor monotherapy (51.

Health-related quality of life (QoL) in patients with advanced melanoma receiving immunotherapies in real-world clinical practice settings.

Background: Pembrolizumab (PEMBRO) and ipilimumab + nivolumab (IPI + NIVO) are approved advanced melanoma (AM) immunotherapies. To address limited health-related quality of life (QoL) real-world evidence with immunotherapies in AM, we compared QoL in AM patients receiving either treatment in clinical practice.

Methods: A prospective US observational study enrolled adult AM patients initiating first-line PEMBRO or IPI + NIVO between June 2017 and March 2018.

Hospitalization and emergency department utilization in patients with advanced melanoma receiving pembrolizumab versus ipilimumab plus nivolumab in US academic centers.

Both pembrolizumab (PEMBRO) and ipilimumab + nivolumab (IPI + NIVO) are FDA-approved immunotherapy regimens for advanced melanoma (AM). Each regimen has different toxicity profiles potentially impacting healthcare resource utilization (HCRU). This study compared real-world hospitalization and emergency department (ED) utilization within 12 months of therapy initiation of each regimen.

An indirect treatment comparison of the efficacy of pembrolizumab versus competing regimens for the adjuvant treatment of stage III melanoma.

To determine the efficacy of pembrolizumab relative to other treatments used in stage III melanoma by conducting a systematic literature review (SLR) and network meta-analysis (NMA). A SLR was conducted to identify randomized clinical trials (RCTs) evaluating approved adjuvant treatments including interferon-containing regimens, BRAF-inhibitors, and PD-L1 inhibitors in stage III melanoma patients. Relative treatment effects for recurrence-free survival (RFS) were synthesized with Bayesian NMA models that allowed for hazard ratios (HRs) to vary over time.

Real-world experience with pembrolizumab in patients with advanced melanoma: A large retrospective observational study.

Pembrolizumab has been approved in the United States for treating advanced melanoma for >4 years. We examined real-world pembrolizumab use and associated outcomes in US oncology clinical practices, including patients who would not be eligible for clinical trials.Flatiron Health longitudinal database was used to identify adult patients with advanced melanoma initiating ≥1 dose of pembrolizumab from September 4, 2014, through December 31, 2016, with follow-up through December 31, 2017.

Real-world treatment patterns and clinical outcomes among patients with advanced melanoma: A retrospective, community oncology-based cohort study (A STROBE-compliant article).

Recently, the effectiveness of novel immune checkpoint inhibitors and BRAF-directed therapies has been demonstrated in advanced melanoma trial populations. Limited research, however, has evaluated the impact of these therapies in a real-world setting. The aim of this study was to evaluate treatment patterns and clinical outcomes among advanced melanoma patients treated with modern therapies within community oncology clinics.

Cost-effectiveness of pembrolizumab for the adjuvant treatment of resected high-risk stage III melanoma in the United States.

To evaluate the cost-effectiveness of adjuvant pembrolizumab relative to observation alone following complete resection of high-risk stage III melanoma with lymph node involvement, from a US health system perspective. A Markov cohort model with four health states (recurrence-free, locoregional recurrence, distant metastases, and death) was developed to estimate costs, life-years, and quality-adjusted life-years (QALYs) associated with pembrolizumab vs observation over a lifetime (46-year) horizon. Using a parametric multi-state modeling approach, transition probabilities starting from recurrence-free were estimated based on patient-level data from KEYNOTE-054 (NCT02362594), a direct head-to-head phase 3 trial.

Health Care Resource Utilization and Costs in First-Line Treatments for Patients with Metastatic Melanoma in the United States.

Background: The treatment landscape for patients with metastatic melanoma has changed dramatically with the introduction of novel therapies, such as targeted therapies and immunotherapies, in recent years. Health care resource utilization (HCRU) and cost data are needed to further evaluate these treatments in a value-based health care system.

Objective: To examine HCRU and total cost of care among U.