Assessing Elevated Blood Glucose Levels Through Blood Glucose Evaluation and Monitoring Using Machine Learning and Wearable Photoplethysmography Sensors: Algorithm Development and Validation.

Background: Diabetes mellitus is the most challenging and fastest-growing global public health concern. Approximately 10.5% of the global adult population is affected by diabetes, and almost half of them are undiagnosed.

Format-tuning of in vivo-launched bispecific T cell engager enhances efficacy against renal cell carcinoma.

Background: Advanced clear cell renal cell carcinoma (ccRCC) is a prevalent kidney cancer for which long-term survival rates are abysmal, though immunotherapies are showing potential. Not yet clinically vetted are bispecific T cell engagers (BTEs) that activate T cell-mediated cancer killing through intercellular synapsing. Multiple BTE formats exist, however, with limited cross-characterizations to help optimize new drug design.

Patterns of use of symptomatic treatments for Alzheimer's disease dementia (AD).

Background: Symptomatic treatment for Alzheimer's disease (AD) dementia could temporarily slow symptom worsening and improve the quality of life for both AD dementia patients and their caregivers. A comprehensive evaluation of symptomatic treatment patterns using recent data for newly diagnosed AD dementia has not been performed and compared across different countries.

Methods: The drug name, time to the first therapy, duration, discontinuation or switches were described in newly diagnosed AD dementia patients in two databases (a major U.

Generate Analysis-Ready Data for Real-world Evidence: Tutorial for Harnessing Electronic Health Records With Advanced Informatic Technologies.

Although randomized controlled trials (RCTs) are the gold standard for establishing the efficacy and safety of a medical treatment, real-world evidence (RWE) generated from real-world data has been vital in postapproval monitoring and is being promoted for the regulatory process of experimental therapies. An emerging source of real-world data is electronic health records (EHRs), which contain detailed information on patient care in both structured (eg, diagnosis codes) and unstructured (eg, clinical notes and images) forms. Despite the granularity of the data available in EHRs, the critical variables required to reliably assess the relationship between a treatment and clinical outcome are challenging to extract.

Contribution of Comorbid Conditions to the Diagnosis of Insomnia: A Database Study in a Commercially Insured Population.

Insomnia is a common sleep disorder characterized as dissatisfaction with sleep quantity or quality resulting in distress or impairment of social, occupational, or other daily functioning. It is unknown if there are medical conditions that have strong associations with insomnia but are unrecognized in previous literature. In this cross-sectional study based on IBM Marketscan Research Databases, we measured insomnia and 78 medical conditions in patients with 2-year continuous enrollment during 2018-2019.

Multivalent delivery of DNA-encoded bispecific T cell engagers effectively controls heterogeneous GBM tumors and mitigates immune escape.

Glioblastoma multiforme (GBM) is among the most difficult cancers to treat with a 5-year survival rate less than 5%. An immunotherapeutic vaccine approach targeting GBM-specific antigen, EGFRvIII, previously demonstrated important clinical impact. However, immune escape variants were reported in the trial, suggesting that multivalent approaches targeting GBM-associated antigens may be of importance.

Engineered antibody cytokine chimera synergizes with DNA-launched nanoparticle vaccines to potentiate melanoma suppression .

Cancer immunotherapy has demonstrated great promise with several checkpoint inhibitors being approved as the first-line therapy for some types of cancer, and new engineered cytokines such as Neo2/15 now being evaluated in many studies. In this work, we designed antibody-cytokine chimera (ACC) scaffolding cytokine mimetics on a full-length tumor-specific antibody. We characterized the pharmacokinetic (PK) and pharmacodynamic (PD) properties of first-generation ACC TA99-Neo2/15, which synergized with DLnano-vaccines to suppress melanoma proliferation and induced significant systemic cytokine activation.

A mAb against surface-expressed FSHR engineered to engage adaptive immunity for ovarian cancer immunotherapy.

Despite advances in ovarian cancer (OC) therapy, recurrent OC remains a poor-prognosis disease. Because of the close interaction between OC cells and the tumor microenvironment (TME), it is important to develop strategies that target tumor cells and engage components of the TME. A major obstacle in the development of OC therapies is the identification of targets with expression limited to tumor surface to avoid off-target interactions.

A Study Protocol of Realist Evaluation of Palliative Home Care Program for Non-Cancer Patients in Singapore.

Introduction: Violet Program (ViP) was developed address the current home palliative service gap for individuals with life limiting non-cancer conditions residing in the Eastern part of Singapore. While its basic principles and processes have been planned and implemented, how ViP works, for whom and in what circumstances are not yet well understood. Therefore, we propose for a realist evaluation (RE) - a theory-based evaluation, to address the current knowledge gaps.

DNA-launched bispecific T cell engager targeting IL-13Rα2 controls tumor growth in an animal model of glioblastoma multiforme.

Glioblastoma is an aggressive tumor with poor survival rates. Bispecific T cell engagers (BTEs) against different cancers are in various stages of clinical development. Toxicity resulting from cytokine release syndrome and the short half-life of BTEs, which necessitates continuous infusion, complicating delivery and increasing costs, are major challenges in the field.

Temporal Trends in Clinical Evidence of 5-Year Survival Within Electronic Health Records Among Patients With Early-Stage Colon Cancer Managed With Laparoscopy-Assisted Colectomy vs Open Colectomy.

Importance: Temporal shifts in clinical knowledge and practice need to be adjusted for in treatment outcome assessment in clinical evidence.

Objective: To use electronic health record (EHR) data to (1) assess the temporal trends in treatment decisions and patient outcomes and (2) emulate a randomized clinical trial (RCT) using EHR data with proper adjustment for temporal trends.

Design, Setting, And Participants: The Clinical Outcomes of Surgical Therapy (COST) Study Group Trial assessing overall survival of patients with stages I to III early-stage colon cancer was chosen as the target trial.

Holding Space for Facilitated Dialogues on Antiracism in Academic Medicine.

The year 2020 brought unprecedented challenges and renewed focus on racial disparities and inequities in the United States. For racial and ethnic minority groups, and in particular African Americans, racial disparities have been a constant presence and threat from the time of slavery through the present day. These racial disparities, sanctioned and maintained by institutional racism, manifest in all aspects of life for African Americans-segregated and unequal education and housing systems, health and mental health care disparities, disproportionally elevated incarceration rates, and, as painfully highlighted this past year, continued vulnerability to acts of violence at the hands of law enforcement.

Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drives rapid and potent immunogenicity capable of single-dose protection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may target epitopes that reduce durability or increase the potential for escape from vaccine-induced immunity. Using synthetic vaccinology, we have developed rationally immune-focused SARS-CoV-2 Spike-based vaccines. Glycans can be employed to alter antibody responses to infection and vaccines.

DNA immunotherapy targeting BARF1 induces potent anti-tumor responses against Epstein-Barr-virus-associated carcinomas.

Latent Epstein-Barr virus (EBV) infection is associated with several types of cancer. Several clinical studies have targeted EBV antigens as immune therapeutic targets with limited efficacy of EBV malignancies, suggesting that additional targets might be important. HI-A rightward frame 1 (BARF1) is an EBV antigen that is highly expressed in EBV nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinoma (EBVaGC).

DNA mismatch repair and microsatellite instability in colorectal tumors: an observational study in the Veterans Affairs Health Care System.

Challenges in identifying microsatellite instability (MSI)/mismatch repair (MMR)-tested colorectal carcinoma (CRC) patients in electronic health records have led to gaps in the understanding of MSI-high/deficient mismatch repair prevalence. An algorithm to identify MSI-/MMR-tested Veterans Affairs patients was developed and an observational study of adult CRC patients with MSI/MMR testing from 2010 to 2018 was undertaken. An optimized model to identify MSI-/MMR-tested patients yielded high positive predictive value (89.

Dendrimer-2PMPA Delays Muscle Function Loss and Denervation in a Murine Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease where muscle weakness and neuromuscular junction (NMJ) denervation precede motor neuron cell death. Although acetylcholine is the canonical neurotransmitter at the mammalian NMJ synapse, glutamate has recently been identified as a critical neurotransmitter for NMJ development and maintenance. One source of glutamate is through the catabolism of N-acetyl-aspartyl-glutamate (NAAG), which is found in mM concentrations in mammalian motoneurons, where it is released upon stimulation and hydrolyzed to glutamate by the glial enzyme glutamate carboxypeptidase II (GCPII).

Immunothrombosis Biomarkers for Distinguishing Coronavirus Disease 2019 Patients From Noncoronavirus Disease Septic Patients With Pneumonia and for Predicting ICU Mortality.

Importance: Coronavirus disease 2019 patients have an increased risk of thrombotic complications that may reflect immunothrombosis, a process characterized by blood clotting, endothelial dysfunction, and the release of neutrophil extracellular traps. To date, few studies have investigated longitudinal changes in immunothrombosis biomarkers in these patients. Furthermore, how these longitudinal changes differ between coronavirus disease 2019 patients and noncoronavirus disease septic patients with pneumonia are unknown.

Dendrimer-2PMPA selectively blocks upregulated microglial GCPII activity and improves cognition in a mouse model of multiple sclerosis.

Cognitive impairment is a common aspect of multiple sclerosis (MS) for which there are no treatments. Reduced brain -acetylaspartylglutamate (NAAG) levels are linked to impaired cognition in various neurological diseases, including MS. NAAG levels are regulated by glutamate carboxypeptidase II (GCPII), which hydrolyzes the neuropeptide to -acetyl-aspartate and glutamate.

ssDNA nanotubes for selective targeting of glioblastoma and delivery of doxorubicin for enhanced survival.

Effective treatment of glioblastoma remains a daunting challenge. One of the major hurdles in the development of therapeutics is their inability to cross the blood-brain tumor barrier (BBTB). Local delivery is an alternative approach that can still suffer from toxicity in the absence of target selectivity.

Epidemiology of Treatment-Resistant Depression in the United States.

The prevalence of treatment-resistant depression (TRD) among patients with pharmaceutically treated depression (PTD) varies greatly in publications. The aim of this study is to estimate the prevalence of TRD using 2 large claims databases in the US. This cross-sectional study used data from the Humana and Optum databases.

Replication of Oncology Randomized Trial Results using Swedish Registry Real World-Data: A Feasibility Study.

Nationwide healthcare registries are potential important real-world data (RWD) sources for assessing drug effectiveness in oncology. However, it is unclear whether registry-derived RWD are suitable for clinical development. In this study, we replicate results from the comparator arm of two previously published oncology randomized controlled trials (RCTs) using RWD from Swedish nationwide healthcare registries.