Forecasting daily COVID-19 cases with gradient boosted regression trees and other methods: evidence from U.S. cities.

Introduction: There is a vast literature on the performance of different short-term forecasting models for country specific COVID-19 cases, but much less research with respect to city level cases. This paper employs daily case counts for 25 Metropolitan Statistical Areas (MSAs) in the U.S.

The impact of JUUL market entry on cigarette sales: evidence from a major chain retailer in Canada.

Background: Electronic nicotine delivery systems (ENDS), such as the JUUL system, are nicotine products for adults who currently smoke cigarettes but are looking for an alternative to combustible cigarettes. Sales of ENDS products were legislatively acknowledged and authorized federally in Canada with the Royal Assent of the Tobacco and Vaping Products Act in 2018.

Methods: With the unique dataset from a major chain retailer in Canada, we evaluated the impacts of JUUL market entry on cigarette sales across Canada from January 2017 to August 2019 using two-way fixed effects panel regression models by leveraging on the entry time variation at the city level.

Do more stringent policies reduce daily COVID-19 case counts? Evidence from Canadian provinces.

The enactment of COVID-19 policies in Canada falls under provincial jurisdiction. This study exploits time-series variation across four Canadian provinces to evaluate the effects of stricter COVID-19 policies on daily case counts. Employing data from this time-period allows an evaluation of the efficacy of policies independent of vaccine impacts.

Extracellular fluid viscosity enhances cell migration and cancer dissemination.

Cells respond to physical stimuli, such as stiffness, fluid shear stress and hydraulic pressure. Extracellular fluid viscosity is a key physical cue that varies under physiological and pathological conditions, such as cancer. However, its influence on cancer biology and the mechanism by which cells sense and respond to changes in viscosity are unknown.

Estimating the Effects of Non-Pharmaceutical Interventions and Population Mobility on Daily COVID-19 Cases: Evidence from Ontario.

This study uses coronavirus disease 2019 (COVID-19) case counts and Google mobility data for 12 of Ontario's largest Public Health Units from Spring 2020 until the end of January 2021 to evaluate the effects of non-pharmaceutical interventions (NPIs; policy restrictions on business operations and social gatherings) and population mobility on daily cases. Instrumental variables (IV) estimation is used to account for potential simultaneity bias, because both daily COVID-19 cases and NPIs are dependent on lagged case numbers. IV estimates based on differences in lag lengths to infer causal estimates imply that the implementation of stricter NPIs and indoor mask mandates are associated with reductions in COVID-19 cases.

Discovery of Phospholipase D Inhibitors with Improved Drug-like Properties and Central Nervous System Penetrance.

Phospholipase D (PLD) is a phospholipase enzyme responsible for hydrolyzing phosphatidylcholine into the lipid signaling molecule, phosphatidic acid, and choline. From a therapeutic perspective, PLD has been implicated in human cancer progression as well as a target for neurodegenerative diseases, including Alzheimer's. Moreover, knockdown of PLD rescues the ALS phenotype in multiple models of ALS (amyotrophic lateral sclerosis) and displays modest motor benefits in an SOD1 ALS mouse model.

Identifying the Socioeconomic, Demographic, and Political Determinants of Social Mobility and Their Effects on COVID-19 Cases and Deaths: Evidence From US Counties.

Background: The spread of COVID-19 at the local level is significantly impacted by population mobility. The U.S.

Amyotrophic Lateral Sclerosis Modifiers in Reveal the Phospholipase D Pathway as a Potential Therapeutic Target.

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a devastating neurodegenerative disorder lacking effective treatments. ALS pathology is linked to mutations in >20 different genes indicating a complex underlying genetic architecture that is effectively unknown. Here, in an attempt to identify genes and pathways for potential therapeutic intervention and explore the genetic circuitry underlying models of ALS, we carry out two independent genome-wide screens for modifiers of degenerative phenotypes associated with the expression of transgenic constructs carrying familial ALS-causing alleles of FUS (hFUS) and TDP-43 (hTDP-43).

PINK1/Parkin Influences Cell Cycle by Sequestering TBK1 at Damaged Mitochondria, Inhibiting Mitosis.

PINK1 and Parkin are established mediators of mitophagy, the selective removal of damaged mitochondria by autophagy. PINK1 and Parkin have been proposed to act as tumor suppressors, as loss-of-function mutations are correlated with enhanced tumorigenesis. However, it is unclear how PINK1 and Parkin act in coordination during mitophagy to influence the cell cycle.

Context-Dependent and Disease-Specific Diversity in Protein Interactions within Stress Granules.

Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form during cellular stress and are increasingly implicated in human neurodegeneration. To study the proteome and compositional diversity of SGs in different cell types and in the context of neurodegeneration-linked mutations, we used ascorbate peroxidase (APEX) proximity labeling, mass spectrometry, and immunofluorescence to identify ∼150 previously unknown human SG components. A highly integrated, pre-existing SG protein interaction network in unstressed cells facilitates rapid coalescence into larger SGs.

Evaluation of intrarenal oxygenation in iodinated contrast-induced acute kidney injury-susceptible rats by blood oxygen level-dependent magnetic resonance imaging.

Objectives: The objectives of this study were to evaluate differences in intrarenal oxygenation as assessed by blood oxygen level-dependent (BOLD) magnetic resonance imaging in contrast-induced acute kidney injury (CIAKI)-susceptible rats when using 4 contrast media with different physicochemical properties and to demonstrate the feasibility of acquiring urinary neutrophil gelatinase-associated lipocalin (NGAL) levels as a marker of CIAKI in this model.

Materials And Methods: Our institutional animal care and use committee approved the study. Sixty-six Sprague-Dawley rats were divided into CIAKI-susceptible groups (received nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester [10 mg/kg] and cycloxygenase inhibitor indomethacin [10mg/kg]) and control groups (received saline instead).

Genetic circuitry modulating notch signals through endosomal trafficking.

Genetic modifier screens offer a powerful, indeed a uniquely powerful tool for the analysis and identification of elements capable of modulating specific cellular functions in development. Here, we describe the methodology that allowed us to explore the genetic circuitry that affects a Notch mutant phenotype caused by the abnormal endosomal trafficking of the Notch receptor. Endosomal trafficking events are increasingly appreciated to play a major role in controlling Notch signaling in development.

Genetic circuitry of Survival motor neuron, the gene underlying spinal muscular atrophy.

The clinical severity of the neurodegenerative disorder spinal muscular atrophy (SMA) is dependent on the levels of functional Survival Motor Neuron (SMN) protein. Consequently, current strategies for developing treatments for SMA generally focus on augmenting SMN levels. To identify additional potential therapeutic avenues and achieve a greater understanding of SMN, we applied in vivo, in vitro, and in silico approaches to identify genetic and biochemical interactors of the Drosophila SMN homolog.

Notch signaling at a glance.

Cell-cell interactions define a quintessential aspect of multicellular development. Metazoan morphogenesis depends on a handful of fundamental, conserved cellular interaction mechanisms, one of which is defined by the Notch signaling pathway. Signals transmitted through the Notch surface receptor have a unique developmental role: Notch signaling links the fate of one cell with that of a cellular neighbor through physical interactions between the Notch receptor and the membrane-bound ligands that are expressed in an apposing cell.

An extracellular region of Serrate is essential for ligand-induced cis-inhibition of Notch signaling.

Cell-to-cell communication via the Notch pathway is mediated between the membrane-bound Notch receptor and either of its canonical membrane-bound ligands Delta or Serrate. Notch ligands mediate receptor transactivation between cells and also mediate receptor cis-inhibition when Notch and ligand are co-expressed on the same cell. We demonstrate in Drosophila that removal of any of the EGF-like repeats (ELRs) 4, 5 or 6 results in a Serrate molecule capable of transactivating Notch but exhibiting little or no Notch cis-inhibition capacity.

Regulation of ligand-independent Notch signal through intracellular trafficking.

Notch signaling is an evolutionarily conserved mechanism that defines a key cell fate control mechanism in metazoans. Notch signaling relies on the surface interaction between the Notch receptor and membrane bound ligands in an apposing cell. In our recent study,(22) we uncover a non-canonical receptor activation path that relies on a ligand-independent, intracellular activation of the receptor as it travels through the endosomal compartments.

Synergy between the ESCRT-III complex and Deltex defines a ligand-independent Notch signal.

The Notch signaling pathway defines a conserved mechanism that regulates cell fate decisions in metazoans. Signaling is modulated by a broad and multifaceted genetic circuitry, including members of the endocytic machinery. Several individual steps in the endocytic pathway have been linked to the positive or negative regulation of the Notch receptor.

Estimating the effects of cigarette taxes on birth outcomes.

Employing provincial data from 1979 to 2004 allows us to exploit the significant (45 percent to 60 percent) reduction in excise taxes in Eastern Canada enacted in February 1994 to estimate the impacts of cigarette taxes on birth outcomes. Empirical estimates suggest that an increase in cigarette taxes is significantly associated with lower infant mortalities. However, we also find some evidence of a counter-intuitive positive correlation between taxes and fetal deaths.

Modeling spinal muscular atrophy in Drosophila links Smn to FGF signaling.

Spinal muscular atrophy (SMA), a devastating neurodegenerative disorder characterized by motor neuron loss and muscle atrophy, has been linked to mutations in the Survival Motor Neuron (SMN) gene. Based on an SMA model we developed in Drosophila, which displays features that are analogous to the human pathology and vertebrate SMA models, we functionally linked the fibroblast growth factor (FGF) signaling pathway to the Drosophila homologue of SMN, Smn. Here, we characterize this relationship and demonstrate that Smn activity regulates the expression of FGF signaling components and thus FGF signaling.

SCALE-PWI: A pulse sequence for absolute quantitative cerebral perfusion imaging.

The Bookend technique is a magnetic resonance imaging (MRI) dynamic susceptibility contrast method that provides reliable quantitative measurement of cerebral blood flow (CBF) and cerebral blood volume (CBV). The quantification is patient specific, is derived from a steady-state measurement of CBV, and is obtained from T(1) changes in the white matter and the blood pool after contrast agent injection. In the current implementation, the Bookend technique consists of three scanning steps requiring a cumulative scan time of 3 minutes 47 seconds, a well-trained technologist, and extra time for offline image reconstruction.