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The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) maintains a database of extremely preterm infants known as the Generic Database (GDB). Begun in 1987, this database now includes more than 91,000 infants, most of whom are extremely preterm (29 weeks gestation). The GDB has been the backbone of the NRN, providing high quality, prospectively collected data to study the changing epidemiology of extreme prematurity and its outcomes over time. In addition, GDB data have been used to generate hypotheses for prospective studies and to develop new clinical trials by providing information about the numbers and characteristics of available subjects and the expected event rates for conditions and complications to be studied. Since its inception, the GDB has been the basis of more than 200 publications in peer-reviewed journals, many of which have had a significant impact on the field of neonatology.

Background: Metastatic bone pain is very difficult to treat and challenging to manage for health care professionals. Kyphoplasty or vertebroplasty has been used to reinstate the height of a compressed fractured vertebral body. OsteoCoolTM radiofrequency ablation (RFA) is a relatively new ablation technique and at present, current literature only supports its role for thoracic and lumbar vertebral metastases. Case Report: In the present case report, we utilized OsteoCoolTM RFA using anterolateral cervical kyphoplasty for cervical spinal metastasis with intractable pain and limited range of motion. Discussion: A successful palliative treatment was provided with a combination of kyphoplasty and OsteoCoolTM RFA. The patient has had great relief of pain and an increased range of motion of the cervical spine post procedure. Conclusion: Anterolateral balloon kyphoplasty provides stability to fractured vertebrae and when combined with OsteoCoolTM RFA, it potentially can provide effective pain relief in patients who have failed radiation and for whom surgery is contraindicated. Key words: Cervical kyphoplasty, cervical vertebral metastasis, kyphoplasty, OsteoCoolTM

Background: Obesity is increasing at an alarming rate worldwide, with some estimates at a 40% rise in prevalence between 2000 and 2018. Recent data indicates that 42.2% of adults in the United States are obese. Obesity can increase morbidity and mortality as a consequence of complex physiologic changes, and as a result, has many consequences for health care delivery and management of these patients. Patients who are obese often need interventional pain procedures; however, perception of higher risk can lead to less opportunity for these often very needed procedures. Case Report: The present case report reviews technical aspects, safety, and efficacy of successful kyphoplasty in a morbidly obese patient. Discussion: This case helps expand the current knowledge base of kyphoplasty in the morbidly obese. Conclusion: Morbidly obese patients, in general, should have access to kyphoplasty similar to normal body mass index patients. Key words: Kyphoplasty, morbidly obese, obstructive sleep apnea, sedation, super-super obesity, vertebral fractures

Methicillin-resistant

The ability to freely move across the landscape to track the emergence of nutritious spring green-up (termed 'green-wave surfing') is key to the foraging strategy of migratory ungulates. Across the vast landscapes traversed by many migratory herds, habitats are being altered by development with unknown consequences for surfing. Using a unique long-term tracking dataset, we found that when energy development occurs within mule deer (Odocoileus hemionus) migration corridors, migrating animals become decoupled from the green wave. During the early phases of a coalbed natural gas development, deer synchronized their movements with peak green-up. But faced with increasing disturbance as development expanded, deer altered their movements by holding up at the edge of the gas field and letting the green wave pass them by. Development often modified only a small portion of the migration corridor but had far-reaching effects on behaviour before and after migrating deer encountered it, thus reducing surfing along the entire route by 38.65% over the 14-year study period. Our study suggests that industrial development within migratory corridors can change the behaviour of migrating ungulates and diminish the benefits of migration. Such disruptions to migratory behaviour present a common mechanism whereby corridors become unprofitable and could ultimately be lost on highly developed landscapes.

The tricolored blackbird, Agelaius tricolor, is a gregarious species that forms enormous breeding and foraging colonies in wetland and agricultural habitats, primarily in California, USA. Once extremely abundant, species numbers have declined dramatically in the past century, largely due to losses of breeding and foraging habitats. Tricolored blackbirds are currently listed as Endangered by the IUCN, and Threatened under the California Endangered Species Act. Increased genetic information is needed to detail the evolutionary consequences of a species-wide bottleneck and inform conservation management. Here, we present a contiguous tricolored blackbird reference genome, assembled with PacBio HiFi long reads and Dovetail Omni-C data to generate a scaffold-level assembly containing multiple chromosome-length scaffolds. This genome adds a valuable resource for important evolutionary and conservation research on tricolored blackbirds and related species.

Context Rural populations experience both a higher prevalence of and risk for premature death from chronic conditions than do their urban counterparts. Yet barriers to implement community-based chronic disease self-management programs persist. Program The Living Well program, a multi-sector collaboration between a rural health care system and a network of community-based organizations, has offered the 6-week evidence-based Chronic Disease Self-Management and Diabetes Self-Management workshops since 2017. The program was a response to a quality improvement initiative to improve hypertension and diabetes outcomes throughout the health care system. Implementation Using the rapid cycling quality improvement process, Living Well developed a self-management program recruitment, referral, and coordinating office for a six-county region. Through continuous capacity-building efforts with community partners, as well as leveraging key health care system assets such as the electronic health record and provider detailing, program reach and adoption was increased. Evaluation The Reach, Effectiveness, Adoption, Implementation, and Maintenance framework was used for the process evaluation. During 3 years, more than 750 individuals engaged with the program, with nearly 600 completing a workshop. The region saw increased engagement by primary care clinicians to refer, and structural changes were embedded into the health care system to facilitate clinic–community partnerships. Discussion A coordinated, multi-sector approach is necessary to develop solutions to complex, chronic health problems. A regional coordinating hub is an effective strategy for implementing community-based programs in rural areas. However, low health care system engagement and fragmented funding remain as barriers to optimal implementation.

There is limited information on pulseless electrical activity (PEA)/asystolic cardiac arrest (CA) in the infant population. The aim is to describe the incidence and factors associated with outcomes in infants with PEA/asystolic CA.Single-center retrospective chart review study of infants less than one year of age who suffer in-hospital PEA/asystolic CA from January 1 2011 to June 30 2019. The primary outcome was the return of spontaneous circulation. The secondary outcome was survival to discharge.CA occurred in 148 infants and PEA/asystolic was found in 38 (26%). Of those 29 (76%) achieved ROSC, and 12 (32%) survived to discharge. Infants on inotrope support or receiving longer duration of chest compressions and epinephrine had increase mortality. All infants with respiratory etiology of arrest survived to hospital discharge.PEA/asystolic CAs are uncommon. Poor prognostic indicators include the need for pre-arrest inotrope support and increased duration of chest compressions.

The evidence-based Diabetes Self-Management Program (DSMP) has been shown to improve a variety of health-related outcomes, but the program has been challenging to implement in rural areas, and rural dissemination has been low. The purpose of this project was to evaluate the effect of implementing the DSMP on self-reported outcomes in a rural region. Through a collaboration with multiple partners, the Living Well program delivered 28 DSMP workshops from 2017 to 2019. Data were collected to determine whether there were post-intervention changes in patient-reported outcomes on measures of diabetes distress, self-management, and patient activation. In addition, secondary analysis of A1C was abstracted from the medical records of participants with type 2 diabetes who completed at least four sessions of a DSMP workshop between 2017 and 2019 and whose medical records had an A1C value in the year before the program and at least one A1C value >3 months after the program. Statistically significant improvements were seen for the Diabetes Distress Scale (P = 0.0017), the Diabetes Self-Management Questionnaire (P

Supplementary Figure S5. Mena isoform expression does not affect Integrin alphav, beta1 or FAK levels.

Supplementary Figure S2. MenaINV drives haptotaxis at high FN concentrations.

Supplementary Figure S3. TCGA analysis supplementary analysis and characterization of MenaINV-specific monoclonal antibody.

Supplementary Figure S1. Effects on haptotaxis are independent of effects on cell velocity.

Supplementary Figure Legends

Supplementary Figure Legends

Supplementary Figure S6. MenaINV-driven ECM reorganization in vitro and in vivo.

Supplementary Figure S4. Deletion of LERER in MenaINV affects tumor growth in a xenograft model.

Supplementary Figures S1-S2 from ERBB1 and ERBB2 Have Distinct Functions in Tumor Cell Invasion and Intravasation

Purpose: The epidermal growth factor receptor (ERBB1) and related family member HER-2/neu (ERBB2) are often overexpressed in aggressive breast cancers and their overexpression is correlated with poor prognosis. Clinical studies using ERBB inhibitors have focused on tumor growth effects, but ERBBs can contribute to malignancy independent of their effects on tumor growth. Our studies were designed to evaluate the effect of ERBB inhibition on tumor cell motility and intravasation in vivo using clinically relevant small-molecule inhibitors.Experimental Design: Using in vivo mouse models of breast cancer, we test the effects of ERBB1 and ERBB2 inhibitors AC480 and lapatinib, ERBB1 inhibitor gefitinib, and ERBB2 inhibitor AG825 on in vivo tumor cell invasive properties in mammary fat pad tumors.Results: ERBB1 and ERBB2 inhibition rapidly (within 3 h) inhibits both tumor cell motility and intravasation. Using gefitinib, ERBB1 inhibition rapidly inhibits tumor cell motility and invasion but not intravasation, whereas ERBB2 inhibition by AG825 rapidly blocks intravasation.Conclusions: ERBB1 and ERBB2 inhibition can rapidly block tumor cell invasive properties. In addition, we differentiate for the first time the contributions of ERBB1 and ERBB2 to the key metastatic properties of in vivo tumor cell invasion and intravasation. These experiments temporally and molecularly separate two key stages in tumor cell entry into blood vessels: invasion and intravasation. These results indicate that ERBB inhibition should be considered for blocking other tumor cell malignant properties besides growth.

Supplementary Movie S2 from ERBB1 and ERBB2 Have Distinct Functions in Tumor Cell Invasion and Intravasation

Supplementary Movie S1 from ERBB1 and ERBB2 Have Distinct Functions in Tumor Cell Invasion and Intravasation

Tumor accumulation of AS750 after PEG-NR heat exposure with varying delta T (S1); Diminished window of tumor transport after re-exposure to PEG-NR heating (S2); Animal weights during PEG-NR and doxorubicin liposome therapeutic trial (S3); Transvascular transport in tumors after single exposure and re-exposure to PEGNR heating (S4); Vascular endothelial growth factor (VEGF) expression in PEG-NR heated tumors (S5); Endothelial cell F-Actin dynamics during heat exposure and recovery (S6); Visualizing PEG-NRs in the tumor microenvironment using multiphoton microscopy (S7); Cargo accumulation in tumors with Hsf1+/+ and Hsf1-/- vasculature after single exposure to PEG-NR heating (S8); HSF1 expression in tumor-associated vasculature following PEG-NR heating (S9); Size-dependent macromolecular extravasation from the unheated vasculature (S10).

Supplementary Table 1 from Breast Cancer Cells Isolated by Chemotaxis from Primary Tumors Show Increased Survival and Resistance to Chemotherapy

Supplementary Movie 3 from Coordinated Regulation of Pathways for Enhanced Cell Motility and Chemotaxis Is Conserved in Rat and Mouse Mammary Tumors

Supplementary Figure Legends 1-2 from Differential Enhancement of Breast Cancer Cell Motility and Metastasis by Helical and Kinase Domain Mutations of Class IA Phosphoinositide 3-Kinase

Supplementary Figure 3 from Invasion of Human Breast Cancer Cells In vivo Requires Both Paracrine and Autocrine Loops Involving the Colony-Stimulating Factor-1 Receptor

Supplementary Movie 2 from Direct Visualization of Macrophage-Assisted Tumor Cell Intravasation in Mammary Tumors

Legends to Supplementary Figures & Movies from Direct Visualization of Macrophage-Assisted Tumor Cell Intravasation in Mammary Tumors

Supplementary Movie from Epidermal Growth Factor Receptor Overexpression Results in Increased Tumor Cell Motility In vivo Coordinately with Enhanced Intravasation and Metastasis

Supplementary Table 1 from Coordinated Regulation of Pathways for Enhanced Cell Motility and Chemotaxis Is Conserved in Rat and Mouse Mammary Tumors

Supplementary Movie 1 from Differential Enhancement of Breast Cancer Cell Motility and Metastasis by Helical and Kinase Domain Mutations of Class IA Phosphoinositide 3-Kinase

Supplementary Movie 4 from Direct Visualization of Macrophage-Assisted Tumor Cell Intravasation in Mammary Tumors

Supplementary Table 4 from Identification and Testing of a Gene Expression Signature of Invasive Carcinoma Cells within Primary Mammary Tumors

Supplementary Figure 3 from Direct Visualization of Macrophage-Assisted Tumor Cell Intravasation in Mammary Tumors

Supplementary Table 2 from Coordinated Regulation of Pathways for Enhanced Cell Motility and Chemotaxis Is Conserved in Rat and Mouse Mammary Tumors

An important step in the process of metastasis from the primary tumor is invasive spread into the surrounding stroma. Using an in vivo invasion assay, we have previously shown that imposed gradients of epidermal growth factor (EGF) or colony-stimulating factor-1 (CSF-1) can induce invasion through an EGF/CSF-1 paracrine loop between cancer cells and macrophages. We now report that invasion induced by other ligands also relies on this EGF/CSF-1 paracrine invasive loop. Using an in vivo invasion assay, we show that MTLn3 breast cancer cells overexpressing ErbB3 exhibit enhanced invasion compared with control MTLn3 cells in response to the ErbB3 ligand HRG-β1. The invasive response of both MTLn3-ErbB3 and transgenic MMTV-Neu tumors to HRG-β1 is inhibited by blocking EGF receptor, CSF-1 receptor, or macrophage function, indicating that invasiveness to HRG-β1 is dependent on the EGF/CSF-1 paracrine loop. Furthermore, we show that CXCL12 also triggers in vivo invasion of transgenic MMTV-PyMT tumors in an EGF/CSF-1–dependent manner. Although the invasion induced by HRG-β1 or CXCL12 is dependent on the EGF/CSF-1 paracrine loop, invasion induced by EGF is not dependent on HRG-β1 or CXCL12 signaling, showing an asymmetrical relationship between different ligand/receptor systems in driving invasion. Our results identify a stromal/tumor interaction that acts as an engine underlying invasion induced by multiple ligands. [Cancer Res 2009;69(7):3221–7]

Supplementary Figure 1 from Differential Enhancement of Breast Cancer Cell Motility and Metastasis by Helical and Kinase Domain Mutations of Class IA Phosphoinositide 3-Kinase

Supplementary Movie 1 from Direct Visualization of Macrophage-Assisted Tumor Cell Intravasation in Mammary Tumors

Supplementary Figure 2 from Differential Enhancement of Breast Cancer Cell Motility and Metastasis by Helical and Kinase Domain Mutations of Class IA Phosphoinositide 3-Kinase