Blocking tumor-intrinsic MNK1 kinase restricts metabolic adaptation and diminishes liver metastasis.

Dysregulation of the mitogen-activated protein kinase interacting kinases 1/2 (MNK1/2)-eukaryotic initiation factor 4E (eIF4E) signaling axis promotes breast cancer progression. MNK1 is known to influence cancer stem cells (CSCs); self-renewing populations that support metastasis, recurrence, and chemotherapeutic resistance, making them a clinically relevant target. The precise function of MNK1 in regulating CSCs, however, remains unexplored.

Mitochondrial Phosphopantetheinylation is Required for Oxidative Function.

4'-phosphopantetheinyl (4'PP) groups are essential co-factors added to target proteins by p hospho p antetheinyl transferase (PPTase) enzymes. Although mitochondrial 4'PP-modified proteins have been described for decades, a mitochondrially-localized PPTase has never been found in mammals. We discovered that the cytoplasmic PPTase a mino a dipate s emialdehyde d ehydrogenase p hospho p antetheinyl t ransferase (AASDHPPT) is required for mitochondrial respiration and oxidative metabolism.

A comparative study of CARE 2D and N2V 2D for tissue-specific denoising in second harmonic generation imaging.

This study explored the application of deep learning in second harmonic generation (SHG) microscopy, a rapidly growing area. This study focuses on the impact of glycerol concentration on image noise in SHG microscopy and compares two image restoration techniques: Noise-to-Void 2D (N2V 2D, no reference image restoration) and content-aware image restoration (CARE 2D, full reference image restoration). We demonstrated that N2V 2D effectively restored the images affected by high glycerol concentrations.

Tunable PhenoCycler imaging of the murine pre-clinical tumour microenvironments.

Background: The tumour microenvironment (TME) consists of tumour-supportive immune cells, endothelial cells, and fibroblasts. PhenoCycler, a high-plex single cell spatial biology imaging platform, is used to characterize the complexity of the TME. Researchers worldwide harvest and bank tissues from mouse models which are employed to model a plethora of human disease.

Excess natural-cause mortality in US counties and its association with reported COVID-19 deaths.

In the United States, estimates of excess deaths attributable to the COVID-19 pandemic have consistently surpassed reported COVID-19 death counts. Excess deaths reported to non-COVID-19 natural causes may represent unrecognized COVID-19 deaths, deaths caused by pandemic health care interruptions, and/or deaths from the pandemic's socioeconomic impacts. The geographic and temporal distribution of these deaths may help to evaluate which explanation is most plausible.

COVID-19 and All-Cause Mortality by Race, Ethnicity, and Age Across Five Periods of the Pandemic in the United States.

Racial/ethnic and age disparities in COVID-19 and all-cause mortality during 2020 are well documented, but less is known about their evolution over time. We examine changes in age-specific mortality across five pandemic periods in the United States from March 2020 to December 2022 among four racial/ethnic groups (non-Hispanic White, non-Hispanic Black, Hispanic, and non-Hispanic Asian) for ages 35+. We fit Gompertz models to all-cause and COVID-19 death rates by 5-year age groups and construct age-specific racial/ethnic mortality ratios across an Initial peak (Mar-Aug 2020), Winter peak (Nov 2020-Feb 2021), Delta peak (Aug-Oct 2021), Omicron peak (Nov 2021-Feb 2022), and Endemic period (Mar-Dec 2022).

Monthly excess mortality across counties in the United States during the COVID-19 pandemic, March 2020 to February 2022.

Excess mortality is the difference between expected and observed mortality in a given period and has emerged as a leading measure of the COVID-19 pandemic's mortality impact. Spatially and temporally granular estimates of excess mortality are needed to understand which areas have been most impacted by the pandemic, evaluate exacerbating factors, and inform response efforts. We estimated all-cause excess mortality for the United States from March 2020 through February 2022 by county and month using a Bayesian hierarchical model trained on data from 2015 to 2019.

Nonlinear microscopy and deep learning classification for mammary gland microenvironment studies.

Tumors, their microenvironment, and the mechanisms by which collagen morphology changes throughout cancer progression have recently been a topic of interest. Second harmonic generation (SHG) and polarization second harmonic (P-SHG) microscopy are label-free, hallmark methods that can highlight this alteration in the extracellular matrix (ECM). This article uses automated sample scanning SHG and P-SHG microscopy to investigate ECM deposition associated with tumors residing in the mammary gland.

COVID-19 Mortality by Race and Ethnicity in US Metropolitan and Nonmetropolitan Areas, March 2020 to February 2022.

Importance: Prior research has established that Hispanic and non-Hispanic Black residents in the US experienced substantially higher COVID-19 mortality rates in 2020 than non-Hispanic White residents owing to structural racism. In 2021, these disparities decreased.

Objective: To assess to what extent national decreases in racial and ethnic disparities in COVID-19 mortality between the initial pandemic wave and subsequent Omicron wave reflect reductions in mortality vs other factors, such as the pandemic's changing geography.

Associations between mortality from COVID-19 and other causes: A state-level analysis.

Background: During the COVID-19 pandemic, the high death toll from COVID-19 was accompanied by a rise in mortality from other causes of death. The objective of this study was to identify the relationship between mortality from COVID-19 and changes in mortality from specific causes of death by exploiting spatial variation in these relationships across US states.

Methods: We use cause-specific mortality data from CDC Wonder and population estimates from the US Census Bureau to examine relationships at the state level between mortality from COVID-19 and changes in mortality from other causes of death.

Differences Between Reported COVID-19 Deaths and Estimated Excess Deaths in Counties Across the United States, March 2020 to February 2022.

Accurate and timely tracking of COVID-19 deaths is essential to a well-functioning public health surveillance system. The extent to which official COVID-19 death tallies have captured the true toll of the pandemic in the United States is unknown. In the current study, we develop a Bayesian hierarchical model to estimate monthly excess mortality in each county over the first two years of the pandemic and compare these estimates to the number of deaths officially attributed to Covid-19 on death certificates.

Proteomic Assessment of the Murine Mammary Gland Extracellular Matrix.

The extracellular matrix (ECM) is a molecular scaffold mainly comprising fibrous proteins, glycoproteins, proteoglycans, and polysaccharides. Aside from acting as a structural support, the ECM's composition dictates cell-matrix interactions at the biochemical and biophysical level. In the context of cancer, the ECM is a critical component of the tumor microenvironment (TME) and dysregulation of its deposition and remodelling has been shown to promote tumor onset, progression, and metastasis.

Phosphorylation of eIF4E in the stroma drives the production and spatial organisation of collagen type I in the mammary gland.

The extracellular matrix (ECM) plays critical roles in breast cancer development. Whether ECM composition is regulated by the phosphorylation of eIF4E on serine 209, an event required for tumorigenesis, has not been explored. Herein, we used proteomics and mouse modeling to investigate the impact of mutating serine 209 to alanine on eIF4E (i.

Evaluation of Age Patterns of COVID-19 Mortality by Race and Ethnicity From March 2020 to October 2021 in the US.

This cross-sectional study examines age-specific COVID-19 mortality rates in the US from March 2020 to October 2021 by sex and race and ethnicity.

Monthly excess mortality across counties in the United States during the Covid-19 pandemic, March 2020 to February 2022.

Excess mortality is the difference between expected and observed mortality in a given period and has emerged as a leading measure of the overall impact of the Covid-19 pandemic that is not biased by differences in testing or cause-of-death assignment. Spatially and temporally granular estimates of excess mortality are needed to understand which areas have been most impacted by the pandemic, evaluate exacerbating and mitigating factors, and inform response efforts, including allocating resources to affected communities. We estimated all-cause excess mortality for the United States from March 2020 through February 2022 by county and month using a Bayesian hierarchical model trained on data from 2015 to 2019.

A Non-Hazardous Deparaffinization Protocol Enables Quantitative Proteomics of Core Needle Biopsy-Sized Formalin-Fixed and Paraffin-Embedded (FFPE) Tissue Specimens.

Most human tumor tissues that are obtained for pathology and diagnostic purposes are formalin-fixed and paraffin-embedded (FFPE). To perform quantitative proteomics of FFPE samples, paraffin has to be removed and formalin-induced crosslinks have to be reversed prior to proteolytic digestion. A central component of almost all deparaffinization protocols is xylene, a toxic and highly flammable solvent that has been reported to negatively affect protein extraction and quantitative proteome analysis.

Self-care and Wellness Checks in Emergency Field Hospitals During COVID-19 Pandemic: A New Self-check Tool for Military Personnel and Civilians.

The authors explore the impact of cumulative stress on United States (US) military service members (SM), including soldiers and medical personnel, deployed to serve in New York City (NYC) communities. Their mission was to assist in establishing emergency field hospitals during the COVID-19 pandemic. Causative biopsychosocial factors are presented, as well as the impact of wellness checks, which were utilized to monitor the mood and morale of frontline healthcare providers, military personnel, and infected patients in a 2,500-bed emergency field hospital and a 1,000-bed Naval hospital ship operating in the metropolitan NYC area.

PRMT7 ablation stimulates anti-tumor immunity and sensitizes melanoma to immune checkpoint blockade.

Despite the success of immune checkpoint inhibitor (ICI) therapy for cancer, resistance and relapse are frequent. Combination therapies are expected to enhance response rates and overcome this resistance. Herein, we report that combining PRMT7 inhibition with ICI therapy induces a strong anti-tumor T cell immunity and restrains tumor growth in vivo by increasing immune cell infiltration.

Acquired Resistance to EZH2 Inhibitor GSK343 Promotes the Differentiation of Human DLBCL Cell Lines toward an ABC-Like Phenotype.

Diffuse large B-cell lymphoma (DLBCL) accounts for 40% of non-Hodgkin lymphoma, and 30% to 40% of patients will succumb to relapsed/refractory disease (rrDLBCL). Patients with rrDLBCL generally have low long-term survival rates due to a lack of efficient salvage therapies. Small-molecule inhibitors targeting the histone methyltransferase EZH2 represent an emerging group of novel therapeutics that show promising clinical efficacy in patients with rrDLBCL.

County-level estimates of excess mortality associated with COVID-19 in the United States.

The COVID-19 pandemic in the U.S. has been largely monitored using death certificates containing reference to COVID-19.

The unequal burden of the Covid-19 pandemic: Capturing racial/ethnic disparities in US cause-specific mortality.

Despite a growing body of literature focused on racial/ethnic disparities in Covid-19 mortality, few previous studies have examined the pandemic's impact on 2020 cause-specific mortality by race and ethnicity. This paper documents changes in mortality by underlying cause of death and race/ethnicity between 2019 and 2020. Using age-standardized death rates, we attribute changes for Black, Hispanic, and White populations to various underlying causes of death and show how these racial and ethnic patterns vary by age and sex.

Association of Health Care Factors With Excess Deaths Not Assigned to COVID-19 in the US.

This cross-sectional study assesses health care factors associated with excess deaths not assigned to COVID-19 in US counties in 2020.