COVID-19 vaccinated children, adolescents, and young adults with acute lymphoblastic leukemia show spike reactive antibodies and multifunctional T-cells.

Little is known about the efficacy of COVID-19 vaccines during acute lymphoblastic leukemia therapy (ALL); data for COVID-19 vaccine immune responses in pediatric leukemia remain sparse. We conducted a single center study of patients aged 5-25 years undergoing ALL chemotherapy who received COVID-19 vaccination. Twenty-one patients were enrolled; efficacy was evaluable in 20.

Low Literacy Levels Among U.S. Adults and Difficult Ballot Propositions.

High-level literacy skills are required for full participation in the democratic process through voting. Consequently, adults with low-level literacy skills are at a disadvantage. This work investigated the disparity between the readability of U.

Indoximod-based chemo-immunotherapy for pediatric brain tumors: A first-in-children phase I trial.

Background: Recurrent brain tumors are the leading cause of cancer death in children. Indoleamine 2,3-dioxygenase (IDO) is a targetable metabolic checkpoint that, in preclinical models, inhibits anti-tumor immunity following chemotherapy.

Methods: We conducted a phase I trial (NCT02502708) of the oral IDO-pathway inhibitor indoximod in children with recurrent brain tumors or newly diagnosed diffuse intrinsic pontine glioma (DIPG).

Method validation of multi-element panel in whole blood by inductively coupled plasma mass spectrometry (ICP-MS).

Background: Analytical methods to measure trace and toxic elements are essential to evaluate exposure and nutritional status. A ten-element panel was developed and validated for clinical testing in whole blood. Retrospective data analysis was conducted on patient samples performed at ARUP Laboratories.

Malpractice Cases Arising From Telephone Based Telemedicine Triage in Ophthalmology.

Purpose: To determine the allegation, precipitating medical issue, and outcome of telephone triage focused malpractice litigation among ophthalmologists.

Methods: The WestLaw Edge database was reviewed using terms pertaining to ophthalmology and telemedicine. The search ranged from 4/7/30 to 1/25/22.

COVID-19 outcomes in children, adolescents and young adults with cancer.

Pediatric oncology patients are at risk for poor outcomes with respiratory viral infections. Outcome data for COVID-19 in children and young adults with cancer are needed; data are sparse for obese/overweight and adolescent and young adult subgroups. We conducted a single center cohort study of COVID-19 outcomes in patients younger than 25 years with cancer.

Have you caught that outlier yet? Evaluate the utility of repeat testing in nutritional and toxic element assessment.

Repeat testing is routinely required by regulatory bodies as a measure to rule out contamination in trace elements and heavy metal analysis, especially when the initial analysis result is outside the reference interval. However, its clinical utilities in detecting analytical measurement outliers have not been systematically evaluated in different clinical testing scenarios. In this study, we present an extensive evaluation of repeat testing and its comparison with the initial analysis in four serum and plasma trace element assays performed by inductively coupled plasma mass spectrometry.

IAP and HDAC inhibitors interact synergistically in myeloma cells through noncanonical NF-κB- and caspase-8-dependent mechanisms.

Interactions between the inhibitor of apoptosis protein antagonist LCL161 and the histone deacetylase inhibitor panobinostat (LBH589) were examined in human multiple myeloma (MM) cells. LCL161 and panobinostat interacted synergistically to induce apoptosis in diverse MM cell lines, including those resistant to bortezomib (PS-R). Similar interactions were observed with other histone deacetylase inhibitors (MS-275) or inhibitors of apoptosis protein antagonists (birinapant).

Inhibition and Reading Comprehension in Adolescents with and without Histories of Language Difficulties.

This study sought to determine if the inhibitory construct of executive function (EF) and self-regulation (SR) contributes unique variance to reading comprehension (RC) beyond word recognition/decoding (WR/D) and language comprehension (LC), and if the contribution differs according to language history. Thirty-two sixth, seventh, and eighth grade students participated in this study. Seventeen students had language difficulties (LD) and fifteen students had typical language histories (LH).

The level of oncogenic Ras determines the malignant transformation of Lkb1 mutant tissue in vivo.

The genetic and metabolic heterogeneity of RAS-driven cancers has confounded therapeutic strategies in the clinic. To address this, rapid and genetically tractable animal models are needed that recapitulate the heterogeneity of RAS-driven cancers in vivo. Here, we generate a Drosophila melanogaster model of Ras/Lkb1 mutant carcinoma.

Does acupressure help reduce nausea and vomiting in palliative care patients? A double blind randomised controlled trial.

Introduction: Nausea and vomiting are common symptoms for patients with advanced cancer. While there is evidence for acupuncture point stimulation for treatment of these symptoms for patients having anticancer treatment, there is little for when they are not related to such treatment.

Objective: To determine whether acupressure at the pericardium 6 site can help in the treatment of nausea and vomiting suffered by palliative care patients with advanced cancer.

Method validation for a multi-element panel in serum by inductively coupled plasma mass spectrometry (ICP-MS).

Background: Laboratory testing for trace and toxic elements is important to diagnose metal toxicity and nutritional deficiency. There are several essential elements that are necessary for biological function and non-essential elements that can pose risk from exposure. Both essential and nonessential elements can be toxic if concentrations exceed a certain threshold.

Managing and Measuring Emergency Department Care: Results of the Fourth Emergency Department Benchmarking Definitions Summit.

Background: A shared language and vocabulary are essential for managing emergency department (ED) operations. This Fourth Emergency Department Benchmarking Alliance (EDBA) Summit brought together experts in the field to review, update, and add to key definitions and metrics of ED operations.

Objective: Summit objectives were to review and revise existing definitions, define and characterize new practices related to ED operations, and introduce financial and regulatory definitions affecting ED reimbursement.

Correction: Synergistic interactions between PLK1 and HDAC inhibitors in non-Hodgkin's lymphoma cells occur and and proceed through multiple mechanisms.

[This corrects the article DOI: 10.18632/oncotarget.15649.

Data-Driven Construction of Antitumor Agents with Controlled Polypharmacology.

Controlling which particular members of a large protein family are targeted by a drug is key to achieving a desired therapeutic response. In this study, we report a rational data-driven strategy for achieving restricted polypharmacology in the design of antitumor agents selectively targeting the TYRO3, AXL, and MERTK (TAM) family tyrosine kinases. Our computational approach, based on the concept of fragments in structural environments (FRASE), distills relevant chemical information from structural and chemogenomic databases to assemble a three-dimensional inhibitor structure directly in the protein pocket.

Inductively coupled plasma mass spectrometry assay for quantification of free infliximab in serum.

TNF antagonists such as infliximab are effective for the treatment of several inflammatory and autoimmune diseases. Recent clinical studies have advocated the importance of measuring trough infliximab levels to guide treatment decisions. We have developed a novel assay for measuring serum free infliximab levels using inductively coupled plasma-mass spectrometry (ICP-MS).

Homoharringtonine interacts synergistically with bortezomib in NHL cells through MCL-1 and NOXA-dependent mechanisms.

Background: Interactions between the protein synthesis inhibitor homoharringtonine (HHT) and the proteasome inhibitor bortezomib were investigated in DLBCL and mantle cell lymphoma cells (MCL).

Methods: Various DLBCL and MCL cells were exposed to HHT and bortezomib alone or together after which apoptosis and signaling pathway perturbations were monitored by flow cytometry and Western blot analysis. Xenograft mouse models were used to assess tumor growth and animal survival.

MERTK inhibition alters the PD-1 axis and promotes anti-leukemia immunity.

MERTK is ectopically expressed and promotes survival in acute lymphoblastic leukemia (ALL) cells and is thus a potential therapeutic target. Here we demonstrate both direct therapeutic effects of MERTK inhibition on leukemia cells and induction of anti-leukemia immunity via suppression of the coinhibitory PD-1 axis. A MERTK-selective tyrosine kinase inhibitor, MRX-2843, mediated therapeutic anti-leukemia effects in immunocompromised mice bearing a MERTK-expressing human leukemia xenograft.

Highly Selective MERTK Inhibitors Achieved by a Single Methyl Group.

Although all kinases share the same ATP binding pocket, subtle differences in the residues that form the pocket differentiate individual kinases' affinity for ATP competitive inhibitors. We have found that by introducing a single methyl group, the selectivity of our MERTK inhibitors over another target, FLT3, was increased up to 1000-fold (compound 31). Compound 19 was identified as an in vivo tool compound with subnanomolar activity against MERTK and 38-fold selectivity over FLT3 in vitro.

MERTK Promotes Resistance to Irreversible EGFR Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancers Expressing Wild-type Family Members.

Purpose: Lung cancer is the leading cause of cancer-related death. Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers and over 60% express wild-type (); however, EGFR tyrosine kinase inhibitors (TKIs) have limited effect in most patients with tumors. We previously identified MERTK tyrosine kinase as a potential therapeutic target in NSCLC and developed MRX-2843, a novel MERTK-selective inhibitor with favorable properties for clinical translation.

MERTK Mediates Intrinsic and Adaptive Resistance to AXL-targeting Agents.

The TAM (TYRO3, AXL, MERTK) family receptor tyrosine kinases (RTK) play an important role in promoting growth, survival, and metastatic spread of several tumor types. AXL and MERTK are overexpressed in head and neck squamous cell carcinoma (HNSCC), triple-negative breast cancer (TNBC), and non-small cell lung cancer (NSCLC), malignancies that are highly metastatic and lethal. AXL is the most well-characterized TAM receptor and mediates resistance to both conventional and targeted cancer therapies.

Pollen sleuthing for terrestrial plant surveys: Locating plant populations by exploiting pollen movement.

Premise Of The Study: We present an innovative technique for sampling, identifying, and locating plant populations that release pollen, without extensive ground surveys. This method (1) samples pollen at random locations within the target species' habitat, (2) detects species' presence using morphological pollen analysis, and (3) uses kriging to predict likely locations of populations to focus future search efforts.

Methods: To demonstrate, we applied the pollen sleuthing system to search for artificially constructed populations of in an old field.