Treasure (Hunt for) Your Health! Addressing Pediatric Social Determinants of Health Through Child-Friendly Community Engagement Events.

Social determinants of health (SDoH), including factors such as education level, housing, poverty, racism, and food insecurity and their impact on health outcomes have been well documented. The "Wayne Pediatrics Health and Nutrition Expo" held at Detroit's Eastern Market was an activity-based health and nutrition event addressing pediatric SDoH. Partnering with community organizations, the event had 10 stations addressing SDoH: access to a primary-care pediatrician; HIV-care and prevention; childhood literacy; clothing & winter coats; mental health and childhood development; nutrition; staying active; vaccination; and food insecurity.

T1-Weighted, Dynamic Contrast-Enhanced MR Perfusion Imaging Can Differentiate between Treatment Success and Failure in Spine Metastases Undergoing Radiation Therapy.

Background And Purpose: Current imaging techniques have difficulty differentiating treatment success and failure in spinal metastases undergoing radiation therapy. This study investigated the correlation between changes in dynamic contrast-enhanced MR imaging perfusion parameters and clinical outcomes following radiation therapy for spinal metastases. We hypothesized that perfusion parameters will outperform traditional size measurements in discriminating treatment success and failure.

Influence of socioeconomic factors on discharge disposition following traumatic cervicothoracic spinal cord injury at level I and II trauma centers in the United States.

Background: Discharge to acute rehabilitation is strongly correlated with functional recovery after traumatic injury, including spinal cord injury (SCI). However, services such as acute care rehabilitation and Skilled Nursing Facilities (SNF) are expensive. Our objective was to understand if high-cost, resource-intensive post-discharge rehabilitation or alternative care facilities are utilized at disparate rates across socioeconomic groups after SCI.

A Computational Platform Integrating a Mechanistic Model of Crohn's Disease for Predicting Temporal Progression of Mucosal Damage and Healing.

Introduction: Physicians are often required to make treatment decisions for patients with Crohn's disease on the basis of limited objective information about the state of the patient's gastrointestinal tissue while aiming to achieve mucosal healing. Tools to predict changes in mucosal health with treatment are needed. We evaluated a computational approach integrating a mechanistic model of Crohn's disease with a responder classifier to predict temporal changes in mucosal health.

Food intake and weight loss of surviving inpatients in the course of COVID-19 infection: A longitudinal study of the multicenter NutriCoviD30 cohort.

Objectives: NutriCoviD30 is a longitudinal multicenter cohort study that aimed to provide nutritional objective data of inpatients during COVID-19 infection. The aims of this study were to describe the nutritional effects of COVID-19 infection on adult inpatients on the short- to mid-term (≤30 d after hospital discharge), using food intake and weight measurements and to identify factors associated with a decrease in food intake and weight.

Methods: Food intake and weight trajectories, as well as clinical signs of the disease, preexisting chronic diseases, and nutritional strategies were collected and analyzed during the course of the disease.

Dramatic Response to Pembrolizumab Monotherapy in a Patient With ARID1A-Mutant Lung Adenocarcinoma: Case Report.

Immunotherapy based on immune checkpoint inhibitors (ICIs) either alone or in combination with platinum-based chemotherapy has dramatically changed the therapeutic scenario in non-small cell lung cancer. However, only a subset of patients derives clinical benefits. Although programmed death-ligand 1 (PD-L1) and tumor mutational burden (TMB) are known to be prognostic and demonstrated utility in selecting patients for immunotherapy response, they are imperfect biomarkers.

SARS-CoV-2 testing for asymptomatic adult cancer patients before initiating systemic treatments: a systematic review.

Introduction: Cancer patients may have a higher risk of severe events and unfavourable outcomes in the setting of COVID-19. This review addresses the question of whether to test asymptomatic cancer patients before initiating systemic cancer treatments.

Methods: This systematic review was conducted based on the PRISMA framework.

The effects of IKK-beta inhibition on early NF-kappa-B activation and transcription of downstream genes.

Small molecule approaches targeting the nuclear factor kappa B (NF-kB) pathway, a regulator of inflammation, have thus far proven unsuccessful in the clinic in part due to the complex pleiotropic nature of this network. Downstream effects depend on multiple factors including stimulus-specific temporal patterns of NF-kB activity. Despite considerable advances, genome-level impact of changes in temporal NF-kB activity caused by inhibitors and their stimulus dependency remains unexplored.

Entropic Control of Receptor Recycling Using Engineered Ligands.

Receptor internalization by endocytosis regulates diverse cellular processes, from the rate of nutrient uptake to the timescale of essential signaling events. The established view is that internalization is tightly controlled by specific protein-binding interactions. However, recent work suggests that physical aspects of receptors influence the process in ways that cannot be explained by biochemistry alone.

Oscillation dynamics underlie functional switching of NF-κB for B-cell activation.

Transcription factor nuclear factor kappa B (NF-κB) shows cooperative switch-like activation followed by prolonged oscillatory nuclear translocation in response to extracellular stimuli. These dynamics are important for activation of the NF-κB transcriptional machinery, however, NF-κB activity regulated by coordinated actions of these dynamics has not been elucidated at the system level. Using a variety of B cells with artificially rewired NF-κB signaling networks, we show that oscillations and switch-like activation of NF-κB can be dissected and that, under some conditions, these two behaviors are separated upon antigen receptor activation.

Iterative Modeling Reveals Evidence of Sequential Transcriptional Control Mechanisms.

Combinatorial control of gene expression is presumed to be mediated by molecular interactions between coincident transcription factors (TFs). While information on the genome-wide locations of TFs is available, the genes they regulate and whether they function combinatorially often remain open questions. Here, we developed a mechanistic, rather than statistical, modeling approach to elucidate TF control logic from gene expression data.

Persistence with Insulin Therapy in Patients with Type 2 Diabetes in France: An Insurance Claims Study.

Introduction: The objective of this study was to document the initiation of insulin therapy in patients with type 2 diabetes mellitus (T2DM) and its maintenance as a function of time after initiation in a French nationwide representative cohort.

Methods: A retrospective cohort study was conducted on a random sample of ~600,000 beneficiaries registered in the French national health insurance database. Newly insulin treated T2DM patients were selected.

Anatomy of a negative feedback loop: the case of IκBα.

The magnitude, duration and oscillation of cellular signalling pathway responses are often limited by negative feedback loops, defined as an 'activator-induced inhibitor' regulatory motif. Within the NFκB signalling pathway, a key negative feedback regulator is IκBα. We show here that, contrary to current understanding, NFκB-inducible expression is not sufficient for providing effective negative feedback.

Topology, dynamics, and heterogeneity in immune signaling.

Development and function of the immune system depends on cells exchanging information between themselves and with their environment. This information is processed and integrated by complex signal transduction and gene regulatory networks with rich temporal dynamics. A growing body of evidence points to a combination of network topology and temporal dynamics as a fundamental link between stimulus and function.

Is ultrasound a better target than clinical disease activity scores in rheumatoid arthritis with fibromyalgia? A case-control study.

Objectives: Our goal is to study the correlations among gray-scale seven-joint ultrasound score (GS-US7), power Doppler seven-joint ultrasound score (PD-US7), disease activity score-28 joints (DAS28), simplified disease activity index (SDAI) and clinical disease activity index (CDAI) in patients with and without fibromyalgia (FM).

Methods: A matched case-control study included all patients consecutively seen in the Rheumatoid Arthritis (RA) Clinic. Participants were allocated into one of two groups: RA with FM and RA without FM.

Energy deposition of H and He ion beams in hydroxyapatite films: a study with implications for ion-beam cancer therapy.

Ion-beam cancer therapy is a promising technique to treat deep-seated tumors; however, for an accurate treatment planning, the energy deposition by the ions must be well known both in soft and hard human tissues. Although the energy loss of ions in water and other organic and biological materials is fairly well known, scarce information is available for the hard tissues (i.e.

Positive feedback within a kinase signaling complex functions as a switch mechanism for NF-κB activation.

A switchlike response in nuclear factor-κB (NF-κB) activity implies the existence of a threshold in the NF-κB signaling module. We show that the CARD-containing MAGUK protein 1 (CARMA1, also called CARD11)-TAK1 (MAP3K7)-inhibitor of NF-κB (IκB) kinase-β (IKKβ) module is a switch mechanism for NF-κB activation in B cell receptor (BCR) signaling. Experimental and mathematical modeling analyses showed that IKK activity is regulated by positive feedback from IKKβ to TAK1, generating a steep dose response to BCR stimulation.

The dynamics of signaling as a pharmacological target.

Highly networked signaling hubs are often associated with disease, but targeting them pharmacologically has largely been unsuccessful in the clinic because of their functional pleiotropy. Motivated by the hypothesis that a dynamic signaling code confers functional specificity, we investigated whether dynamic features may be targeted pharmacologically to achieve therapeutic specificity. With a virtual screen, we identified combinations of signaling hub topologies and dynamic signal profiles that are amenable to selective inhibition.

Analysis of the RelA:CBP/p300 interaction reveals its involvement in NF-κB-driven transcription.

NF-κB plays a vital role in cellular immune and inflammatory response, survival, and proliferation by regulating the transcription of various genes involved in these processes. To activate transcription, RelA (a prominent NF-κB family member) interacts with transcriptional co-activators like CREB-binding protein (CBP) and its paralog p300 in addition to its cognate κB sites on the promoter/enhancer regions of DNA. The RelA:CBP/p300 complex is comprised of two components--first, DNA binding domain of RelA interacts with the KIX domain of CBP/p300, and second, the transcriptional activation domain (TAD) of RelA binds to the TAZ1 domain of CBP/p300.

Tunable signal processing through a kinase control cycle: the IKK signaling node.

The transcription factor NFκB, a key component of the immune system, shows intricate stimulus-specific temporal dynamics. Those dynamics are thought to play a role in controlling the physiological response to cytokines and pathogens. Biochemical evidence suggests that the NFκB inducing kinase, IKK, a signaling hub onto which many signaling pathways converge, is regulated via a regulatory cycle comprising a poised, an active, and an inactive state.

NEMO ensures signaling specificity of the pleiotropic IKKβ by directing its kinase activity toward IκBα.

Besides activating NFκB by phosphorylating IκBs, IKKα/IKKβ kinases are also involved in regulating metabolic insulin signaling, the mTOR pathway, Wnt signaling, and autophagy. How IKKβ enzymatic activity is targeted to stimulus-specific substrates has remained unclear. We show here that NEMO, known to be essential for IKKβ activation by inflammatory stimuli, is also a specificity factor that directs IKKβ activity toward IκBα.

Lessons from mathematically modeling the NF-κB pathway.

Mathematical modeling has proved to be a critically important approach in the study of many complex networks and dynamic systems in physics, engineering, chemistry, and biology. The nuclear factor κB (NF-κB) system consists of more than 50 proteins and protein complexes and is both a highly networked and dynamic system. To date, mathematical modeling has only addressed a small fraction of the molecular species and their regulation, but when employed in conjunction with experimental analysis has already led to important insights.

Yeast dynamically modify their environment to achieve better mating efficiency.

The maintenance and detection of signaling gradients are critical for proper development and cell migration. In single-cell organisms, gradient detection allows cells to orient toward a distant mating partner or nutrient source. Budding yeast expand their growth toward mating pheromone gradients through a process known as chemotropic growth.