mpactR: an R adaptation of the metabolomics peak analysis computational tool (MPACT) for use in reproducible data analysis pipelines.

mpactR automates pre-processing of liquid chromatography-tandem mass spectrometry (LC-MS/MS) data from microbiological samples to correct mispicked peaks, resolve inter-sample variation in abundance across technical replicates, account for in-source ion fragmentation, and remove background noise to yield high-quality mass spectrometry features. The package is available through CRAN and GitHub.

Increased functional potency of multi-edited CAR-T cells manufactured by a non-viral transfection system.

Chimeric antigen receptor (CAR)-T cell therapy represents a breakthrough for the treatment of hematological malignancies. However, to treat solid tumors and certain hematologic cancers, next-generation CAR-T cells require further genetic modifications to overcome some of the current limitations. Improving manufacturing processes to preserve cell health and function of edited T cells is equally critical.

Optical Coherence Tomography Angiography in Patients With the Boston Keratoprosthesis Type 1.

Purpose: To report on optical coherence tomography angiography (OCTA) in patients with a type 1 Boston keratoprosthesis (KPro) and determine its feasibility through assessment of imaging artifacts.

Methods: KPro and non-KPro subjects were matched for age, gender, and glaucoma diagnosis. OCTA images of the peripapillary optic nerve were obtained, reviewed by 2 readers masked to the diagnosis for artifacts and usability, and used for microvascular measurements.

One BAG doesn't fit all: the differences and similarities of BAG family members in mediating CNS homeostasis.

There is an increasing awareness that B-cell lymphoma 2 (Bcl-2)-associated athanogene (BAG) proteins play critical roles in maintaining neural homeostasis, and that their dysregulation contributes to neurological disorders. This protein family of nine members is evolutionarily conserved, with each member having at least one BAG domain that binds to the nucleotide-binding domains of Heat Shock Protein (Hsp) 70 family members. Collectively, these proteins are essential for the proper functioning of the central nervous system (CNS).

The A to Z of Peroral Endoscopic Myotomy.

Peroral endoscopic myotomy (POEM) is a novel technique within the field of third space endoscopy. The overarching principal is creation of a mucosal incision, careful dissection of the submucosal space using an electrosurgical knife to reach the muscularis (ie, tunneling), performing a controlled myotomy, and finally, closure of the mucosal incision. POEM was first developed for the management of achalasia, and now a decade of evidence shows the procedure is safe, effective, and highly reproducible.

Pharmacological Inhibition of Astrocytic Transglutaminase 2 Facilitates the Expression of a Neurosupportive Astrocyte Reactive Phenotype in Association with Increased Histone Acetylation.

Astrocytes play critical roles in supporting structural and metabolic homeostasis in the central nervous system (CNS). CNS injury leads to the development of a range of reactive phenotypes in astrocytes whose molecular determinants are poorly understood. Finding ways to modulate astrocytic injury responses and leverage a pro-recovery phenotype holds promise in treating CNS injury.

Critical comparison of BMD and TD methods for the calculation of acceptable intakes for N-nitroso compounds.

The tumorigenic dose 50 (TD) is a widely used measure of carcinogenic potency which has historically been used to determine acceptable intake limits for carcinogenic compounds. Although broadly used, the TD model was not designed to account for important biological factors such as DNA repair and cell compensatory mechanisms, changes in absorption, etc., leading to the development of benchmark dose (BMD) approaches, which use more flexible dose-response models that are better able to account for these processes.

Canine synovial lipomatosis: Clinicopathologic findings and HGMA2 immunohistochemistry in 4 cases.

Synovial lipomatosis is an uncommon, intra-articular, fat-containing, proliferative lesion with unknown etiology that is rarely reported in dogs. A retrospective study spanning 13 years was conducted to search for cases of canine synovial lipomatosis. Among 188 synovial biopsies of major diarthrodial joints (ie, shoulder, elbow, carpus, hip, stifle, and tarsus) from 186 dogs, 4 cases (2.

Closure of Earth's Global Seasonal Cycle of Energy Storage.

The global seasonal cycle of energy in Earth's climate system is quantified using observations and reanalyses. After removing long-term trends, net energy entering and exiting the climate system at the top of the atmosphere (TOA) should agree with the sum of energy entering and exiting the ocean, atmosphere, land, and ice over the course of an average year. Achieving such a balanced budget with observations has been challenging.

Observational Assessment of Changes in Earth's Energy Imbalance Since 2000.

Satellite observations from the Clouds and the Earth's Radiant Energy System show that Earth's energy imbalance has doubled from 0.5 ± 0.2 Wm during the first 10 years of this century to 1.

North Atlantic Heat Transport Convergence Derived from a Regional Energy Budget Using Different Ocean Heat Content Estimates.

This study uses an oceanic energy budget to estimate the ocean heat transport convergence in the North Atlantic during 2005-2018. The horizontal convergence of the ocean heat transport is estimated using ocean heat content tendency primarily derived from satellite altimetry combined with space gravimetry. The net surface energy fluxes are inferred from mass-corrected divergence of atmospheric energy transport and tendency of the ECMWF ERA5 reanalysis combined with top-of-the-atmosphere radiative fluxes from the clouds and the Earth's radiant energy system project.

The equity inventory planning process: A pilot program promoting racial justice in early care and education organizations.

Leaders undertaking the effort to dismantle structural inqualities at the organizational level often find traditional professional development on diversity, equity, and inclusion to be limited in scope, rarely leading to meaningful organizational change. The Racial Equity, Diversity, and Inclusion (REDI) Movement was developed in 2020 by associates within a Midwest university research center to increase efforts toward the pursuit of a holistic, systems-level approach to equity, social justice, and inclusion. REDI now includes several interventions that prepare associates and their teams to advance racial justice and equity across four levels of the REDI Framework: Intrapersonal, Interpersonal, Institutional, and Societal.

Monitoring, Modeling, and Statistical Analysis in Metal Additive Manufacturing: A Review.

Despite the significant advances made involving the additive manufacturing (AM) of metals, including those related to both materials and processes, challenges remain in regard to the rapid qualification and insertion of such materials into applications. In general, understanding the process-microstructure-property interrelationships is essential. To successfully understand these interrelationships on a process-by-process basis and exploit such knowledge in practice, leveraging monitoring, modeling, and statistical analysis is necessary.

Photoluminescence Switching in Quantum Dots Connected with Carboxylic Acid and Thiocarboxylic Acid End-Group Diarylethene Molecules.

We contrast the switching of photoluminescence (PL) of PbS quantum dots (QDs) cross-linked with photochromic diarylethene molecules with different end groups, 4,4'-(1-cyclopentene-1,2-diyl)bis[5-methyl-2-thiophenecarboxylic acid] () and 4,4'-(1-cyclopentene-1,2-diyl)bis[5-methyl-2-thiophenethiocarboxylic acid] (). Our results show that the QDs cross-linked with the carboxylic acid end group molecules () exhibit a greater amount of switching in photoluminescence intensity compared to QDs cross-linked with the thiocarboxylic acid end group (). We also demonstrate that regardless of the molecule used, greater switching amounts are observed for smaller quantum dots.

Phase II study of MEK inhibitor trametinib alone and in combination with AKT inhibitor GSK2141795/uprosertib in patients with metastatic triple negative breast cancer.

Purpose: While MEK inhibitors demonstrated activity in metastatic triple negative breast cancer (mTNBC) preclinical studies, preclinical, and clinical studies implicate rapid development of resistance limiting clinical benefit. The purpose of this study was to determine response rate for Trametinib alone and in combination with Uprosertib in patients with mTNBC previously treated with chemotherapy.

Methods: This was an open-label, two-part, phase II, single-arm, multicenter study.

Tumor-intrinsic kinome landscape of pancreatic cancer reveals new therapeutic approaches.

Effective therapies for pancreatic ductal adenocarcinoma (PDAC) have been largely elusive. Here, we perform Multiplexed kinase Inhibitor Bead Mass Spectrometry on 102 patient derived xenografts derived from 14 unique primary PDAC to define the tumor-intrinsic kinome landscape. Our findings uncover three kinome subgroups making up two tumor-intrinsic kinome subtypes that we call kinotypes.

In-field prostate cancer recurrence following radical prostatectomy and salvage radiation.

Objective: To define the natural history, patterns of recurrence and treatment modalities for local prostate cancer (PCa) recurrence following radical prostatectomy (RP) and radiation therapy (RT), and to investigate factors that could predict metastasis-free survival (MFS) in this unique patient population.

Methods: We queried a prospectively maintained PCa registry to identify men developing in-field recurrence (IFR) following RP and RT from 2008 to 2021 at a single institution. IFR was defined as biopsy-proven recurrent PCa or the presence of persistent positron emission tomography-avid lesions in the prior radiation field without evidence of metastasis.

Ever Use of Telehealth in Nebraska by March 2021: Cross-Sectional Analysis.

Background: Nationally, COVID-19 spurred the uptake of telehealth to facilitate patients' access to medical care, especially among individuals living in geographically isolated areas. Despite the potential benefits of telehealth to address health care access barriers and enhance health outcomes, there are still disparities in the accessibility and utilization of telehealth services. Hence, identifying facilitators and barriers to telehealth should be prioritized to ensure that disparities are mitigated rather than exacerbated.

Deletion Variant in Basenji Dogs with Fanconi Syndrome.

Fanconi syndrome is a disorder of renal proximal tubule transport characterized by metabolic acidosis, amino aciduria, glucosuria, and phosphaturia. There are acquired and hereditary forms of this disorder. A late-onset form of Fanconi syndrome in Basenjis was first described in 1976 and is now recognized as an inherited disease in these dogs.

Canine Multiple System Degeneration Associated with Sequence Variants in .

Canine multiple system degeneration (CMSD) is an early onset, progressive movement disorder affecting Kerry Blue Terriers and Chinese Crested dogs. The associated pathologic lesions include degeneration of the cerebellum, caudate nucleus, and substantia nigra. CMSD is inherited as an autosomal recessive trait in both dog breeds.

Mitochondrial Quality Control in Alzheimer's Disease: Insights from Models.

Alzheimer's disease (AD) is a complex neurodegenerative disorder that is classically defined by the extracellular deposition of senile plaques rich in amyloid-beta (Aβ) protein and the intracellular accumulation of neurofibrillary tangles (NFTs) that are rich in aberrantly modified tau protein. In addition to aggregative and proteostatic abnormalities, neurons affected by AD also frequently possess dysfunctional mitochondria and disrupted mitochondrial maintenance, such as the inability to eliminate damaged mitochondria via mitophagy. Decades have been spent interrogating the etiopathogenesis of AD, and contributions from model organism research have aided in developing a more fundamental understanding of molecular dysfunction caused by Aβ and toxic tau aggregates.