bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of programmable post-translational switch control platform for on-demand protein secretion in mammalian cells
Authors: Mansouri Maysam , Ray Preetam Guha , Franko Nik , Xue Shuai , Fussenegger Martin 
Published: October 2022

Abstract
The development of novel strategies to program cellular behaviors is a central goal in synthetic biology, and post-translational control mediated by engineered protein circuits is a particularly attractive approach to achieve rapid protein secretion on demand. We have developed a programmable protease-mediated post-translational switch (POSH) control platform composed of a chimeric protein unit that consists of a protein of interest fused via a transmembrane domain to a cleavable ER-retention signal, together with two cytosolic inducer-sensitive split protease components. The protease components combine in the presence of the specific inducer to generate active protease, which cleaves the ER-retention signal, releasing the transmembrane-domain-linked protein for trafficking to the trans-Golgi region. A furin site placed downstream of the protein ensures cleavage and subsequent secretion of the desired protein. We show that stimuli ranging from plant-derived, clinically compatible chemicals to remotely controllable inducers such as light and electrostimulation can program protein secretion in various POSH-engineered designer mammalian cells. As proof-of-concept, an all-in-one POSH control plasmid encoding insulin and abscisic acid-activatable split protease units was hydrodynamically transfected into the liver of type-1 diabetic mice. Induction with abscisic acid attenuated glycemic excursions in glucose-tolerance tests. Increased blood levels of insulin were maintained for 12 days.
TNF or EGFR inhibition equally block AKI-to-CKD transition: opportunities for etanercept treatment
Authors: Abdelmageed Mai M , Kefaloyianni Eirini , Arthanarisami Akshayakeerthi , Komaru Yohei , Atkinson Jeffrey J , Herrlich Andreas 
Published: October 2022

ABSTRACT

Background
Inflammation is a key driver of the transition of acute kidney injury to progressive fibrosis and chronic kidney disease (AKI-to-CKD transition). Blocking a-disintegrin-and-metalloprotease-17 (ADAM17)-dependent ectodomain shedding, in particular of epidermal growth factor receptor (EGFR) ligands and of the type 1 inflammatory cytokine tumor necrosis factor (TNF), reduces pro-inflammatory and pro-fibrotic responses after ischemic AKI or unilateral ureteral obstruction (UUO), a classical fibrosis model. Metalloprotease or EGFR inhibition show significant undesirable side effects in humans. In retrospective studies anti-TNF biologics reduce the incidence and progression of CKD in humans. Whether TNF has a role in AKI-to-CKD transition and how TNF inhibition compares to EGFR inhibition is largely unknown.

Methods
Mice were subjected to bilateral renal ischemia-reperfusion injury or unilateral ureteral obstruction. Kidneys were analyzed by histology, immunohistochemistry, qPCR, western blot, mass cytometry, scRNA sequencing, and cytokine profiling.

Results
Here we show that TNF or EGFR inhibition reduce AKI-to-CKD transition and fibrosis equally by about 25%, while combination has no additional effect. EGFR inhibition reduced kidney TNF expression by about 50% largely by reducing accumulation of TNF expressing immune cells in the kidney early after AKI, while TNF inhibition did not affect EGFR activation or immune cell accumulation. Using scRNAseq data we show that TNF is predominantly expressed by immune cells in AKI but not in proximal tubule cells (PTC), and PTC-TNF knockout did not affect AKI-to-CKD transition in UUO. Thus, the anti-inflammatory and anti-fibrotic effects of the anti-TNF biologic etanercept in AKI-to-CKD transition rely on blocking TNF that is released from immune cells recruited or accumulating in response to PTC-EGFR signals.

Conclusion
Short-term anti-TNF biologics during or after AKI could be helpful in the prevention of AKI-to-CKD transition.
Re-engagement of Low-Income Smokers in Quitline Services: Effects of Incentives and Method of Contact
Authors: Cummins Sharon E , Kirby Carrie A , Wong Shiushing , Anderson Christopher M , Zhu Shu-Hong 
Published: October 2022

AbstractIntroductionFinancial incentives have been shown to improve recruitment of low-income smokers into tobacco quitline services and to improve cessation outcomes. The present study evaluated their use to re-engage low-income smokers who had already used a quitline.Aims and MethodsRandomly selected Medicaid smokers (N = 5200) who had previously enrolled in a quitline were stratified by time since enrollment (3, 6, 9, or 12 months) and randomly assigned in a 2 × 4 factorial design to receive, by mail or telephone, an invitation to reengage, with an offer of no financial incentive or $10, $20, or $40. The primary outcome measure was re-engagement, defined as use of an additional evidence-based quitline service within 90 days. Data were collected from May 2014 to October 2015 and analyzed in 2022.ResultsOf 5200 participants invited to reengage in quitline services, 9.3% did so within 90 days, compared to 6.3% of a randomly selected comparison group (n = 22 614, p &lt; .0001). Letters resulted in greater re-engagement than calls (10.9% vs. 7.8%, respectively, p = .0001). Among letters, there was a dose–response relationship between incentive level and re-engagement rates (p = .003). Re-engagement decreased as time since enrollment increased, from 13.7% at 3 months to 5.7% at 12 months (all p’s &lt; 0.0001).ConclusionsLow-income smokers who previously used quitline services can be motivated to reengage in treatment. Mailed letters and automated calls are effective re-engagement strategies. Financial incentives can increase the effectiveness of re-engagement letters. Inviting Medicaid smokers to re-engage with quitline treatment may help to address socioeconomic health disparities and should be standard practice.ImplicationsNicotine addiction is a chronic relapsing disorder, yet most cessation services are designed to help smokers through only one quit attempt. Smoking is increasingly concentrated in populations with physical and psychological co-morbidities, which can make quitting more difficult and impact whether smokers reach out for additional help following relapse. This study examined whether the timing, method, and content of an offer for further assistance influenced re-engagement rates for a vulnerable population of smokers—Medicaid beneficiaries. Relapsing smokers are responsive to re-engagement offers as early as three months, but there is a closing window of opportunity to reach them.
10 The association between underweight and iron status in early childhood: cross-sectional and prospective study
Authors: Borkhoff Sean , Parkin Patricia , Keown-Stoneman Charles , Birken Catherine , Maguire Jonathon , Macarthur Colin , Borkhoff Cory 
Published: October 2022

Abstract

Background
The American Academy of Pediatrics (AAP) identifies poor growth as a risk factor for iron deficiency (ID). There is limited research to provide evidence of this association.

Objectives
To examine the association between underweight and ID in early childhood.

Design/Methods
We enrolled healthy, young children from primary care practices in Toronto, Canada, and used both a cross-sectional and prospective study design. Underweight was defined as a body mass index z-score (zBMI) &lt;-2. In the cross-sectional cohort, children 12-29 months had concurrent measurement of zBMI and serum ferritin. In the prospective cohort, children 6-14 months had measurement of zBMI and at 15-29 months had measurement of serum ferritin. Multivariable regression models examined serum ferritin as a continuous variable (linear models) and categorical variable with ID defined as &lt;12 µg/L (logistic model), adjusted for pre-specified covariates.

Results
For the cross-sectional cohort (n=1953), the mean age was 18.3 (SD 5.0) months, 51 (2.4%) were underweight, and 269 (13.8%) had ID. There was no association between underweight and serum ferritin (change in median serum ferritin 2.01 µg/L, 95% CI -2.22, 7.01, P=0.37) or underweight and ID (OR 0.98, 95% CI 0.43, 2.21, P= 0.95). In contrast, there was a strong negative association between overweight and serum ferritin (change in median serum ferritin -4.19 µg/L, 95% CI -6.93, -1.04, P=0.01), and a positive association between obesity and ID (OR 3.35, 95% CI 1.10, 10.25, P=0.03). For the prospective cohort (n=672), the mean age at outcome was 21.1 (SD 3.5) months, 34 (5.1%) were underweight, and 104 (15.5%) had ID. There was no association between underweight and serum ferritin or underweight and ID.

Conclusion
Using both a cross-sectional and prospective study design, we found no association between underweight and ID in young children 1 to 2 years of age. In contrast, we found a strong association between overweight/obesity and ID. For risk stratification and targeted screening, overweight/obesity may be more important than underweight as a risk factor for ID in young children.
20 Eat Sleep Console: A Quality Improvement Initiative to Improve the Care of Opioid Exposed Newborns at a Community Hospital
Authors: Hagen Ricki , Trottier-Boucher Marie-Noelle , Stockley Katrina 
Published: October 2022

Abstract

Background
As the opioid crisis continues in B.C., more infants are born to mothers using opioids during pregnancy. Many of these newborns experience neonatal opioid withdrawal syndrome (NOWS) and require specialized medical care and prolonged hospital stays.

Objectives
We sought to improve the care of opioid exposed newborns by replacing the Finnegan Neonatal Abstinence Scoring System (FNASS) with the Eat Sleep Console (ESC) protocol. Our aim was to reduce infant NICU length of stay (LOS) and morphine dosing required for withdrawal management.

Design/Methods
A multi-disciplinary team was formed in 2019 and standard quality improvement methodology was implemented using plan-do-study-act cycles. Interventions included NOWS education for maternity and newborn health care providers, pediatric antenatal consults, introduction of as needed morphine, and implementation of the Eat Sleep Console (ESC) assessment tool. Primary outcomes were number of NICU admission days and cumulative morphine dosing required for NOWS treatment. Data from chart reviews was obtained from 2017 to 2021. Qualitative survey data was collected from nursing staff pre and post ESC implementation.

Results
ESC successfully replaced the FNASS, and nursing staff reported overall satisfaction and confidence with the practice change. Forty-four infants were captured in our data analysis, including 21 from the baseline period (FNASS), 12 from intervention group 1 (PRN morphine and FNASS), and 9 from intervention group 2 (PRN morphine and ESC). Cumulative morphine dose decreased by 55% when comparing the two intervention groups (19.45 mg intervention group 1 vs 10.71 mg intervention group 2). Two infants were managed exclusively with ESC non-pharmacological strategies and did not require any morphine. Although NICU LOS increased over time in our project (10.79 days in the baseline group vs 19.64 in the intervention group 2), there were no differences in the LOS between the two intervention groups (18.49 days vs 19.64 days). Unstable maternal opioid use, defined as illicit opioid use two weeks prior to delivery increased as the project progressed and was unbalanced between groups, possibly affecting our overall outcomes (38% unstable mothers in the baseline period vs 78% intervention group 2). Stratified analysis between stable and unstable mothers showed a trend of increased LOS and morphine requirements for infants born to unstable mothers. In our center, the ability to provide 1:1 care by nurse or parent was the most prominent challenge.

Conclusion
ESC successfully replaced the FNASS at our community hospital and has shown a clinically significant decrease in morphine requirements for infants experiencing opioid withdrawal.
21 Spontaneous resolution of post-hemorrhagic ventricular dilatation in preterm newborns and neurodevelopmental outcomes
Authors: Paquette Mariane , Groulx-Boivin Emilie , Khairy May , Beltempo Marc , Dudley Roy W , Ferrand Amaryllis , Bizgu Victoria , Garfinkle Jarred 
Published: October 2022

Abstract

Background
Post-hemorrhagic ventricular dilatation (PHVD) is a serious complication of intraventricular hemorrhage (IVH) in preterm newborns and is associated with significant impairments. The natural evolution of PHVD and developmental implications of spontaneous resolution are not well established.

Objectives
To investigate the natural evolution of PHVD and compare neurodevelopmental impairments in newborns with (1) spontaneous resolution of PHVD; (2) persistent PHVD and (3) PHVD who underwent neurosurgical intervention.

Design/Methods
We conducted a multicenter retrospective cohort study of 5238 newborns born at ≤34 weeks’ gestational age (GA) admitted to two tertiary Neonatal Intensive Care Units (NICU) between 2012 and 2020. Head ultrasounds (HUS) of 476 newborns with IVH grade ≥2 were reviewed to identify PHVD, defined as ventricular index (VI) &gt;97th centile (p97) for GA and anterior horn width (AHW) &gt;6mm on any HUS in the first 6 weeks of life. Newborns with PHVD were divided into three groups, Group 1: newborns with spontaneous resolution of PHVD, defined as the regression of both lateral ventricles below the VI and AHW thresholds, Group 2: newborns with persistent PHVD absent neurosurgical intervention and Group 3: newborns who underwent any neurosurgical intervention. Neurodevelopmental outcomes at 18 months corrected, obtained through chart review, were compared.

Results
Of 108 newborns with PHVD, 88 survived to NICU discharge (mean GA 28.4 weeks, SD 2.8; median age at PHVD diagnosis 8.0 days, IQR 5.0-12.8). Overall, 34/88 (38.6%) newborns had spontaneous resolution of PHVD (Group 1). The median time between PHVD diagnosis and spontaneous resolution was 14.0 days (IQR 6.8-32.3) (Figure). In Group 3, the median time between PHVD diagnosis and the first neurosurgical intervention was 14.0 days (IQR 7.0-23.0). Group 1 had significantly smaller maximal VI (1.8, 3.4, and 11.1mm above p97, p&lt;0.001) and AHW (7.2, 10.8, and 20.3mm, p&lt;0.001) than Groups 2 and 3, respectively, and were less likely to have bilateral PHVD (OR 0.47, 95% CI 0.33-0.67) than Group 3. Neurodevelopmental outcome data at 18 month were available for 53/88 (60.2%) survivors (Table). Group 1 had lower rates of cerebral palsy (17.4% vs 45.8%; p=0.037), global developmental delay (17.4% vs 50.0%; p=0.018), epilepsy (4.3% vs 29.2%; p=0.048) and involvement of ≥3 allied health professionals (34.8% vs 70.8%; p=0.013) compared to Group 3.

Conclusion
Newborns with PHVD without spontaneous resolution are at higher risk for significant neurodevelopmental impairments despite neurosurgical interventions, which may be due to more prominent ventricular dilatation. Strategies aimed at mitigating the burden of impairments in patients without spontaneous resolution are needed.
33 Evaluation of a Secure Messaging System for Children with Medical Complexity
Authors: Parpia Camilla , Moore Clara , Beatty Madison , Miranda Susan , Adams Sherri , Stinson Jennifer , Desai Arti , Bartlett Leah , Culbert Erin , Cohen Eyal , Orkin Julia 
Published: October 2022

Abstract

Background
The Connecting2gether (C2) platform is a secure online information-sharing tool that aims to improve care for children with medical complexity (CMC) and their families. A key feature of C2 is secure messaging which enables parents to communicate with their child’s care team members (CTMs) in a timely manner.

Objectives
(1) Evaluate the use of a secure messaging system, (2) Examine and compare the content of messages to email and phone calls, and (3) Explore parent and CTMs’ perceptions and experience using secure messaging as a method of communication.

Design/Methods
This study is a sub-study of a larger feasibility evaluation of the C2 platform. Parents of CMC were recruited from a tertiary level complex care program to use the C2 platform for 6 months. Parents could invite CTMs involved in their child’s care to register on the platform. Secure messages were extracted from C2 usage reports, and phone and email documentation from the electronic medical record. Quantitative data from C2 usage reports were analyzed using descriptive statistics. Messaging content codes were iteratively developed through review of the C2 messages. Semi-structured interviews were completed with parents and CTMs. Communication and interview data were analyzed using thematic analysis.

Results
36 parents and 43 care team members, including HCPs and family members, registered on the C2 platform. Participants sent a total of 1853 messages on C2 with parents and nurse practitioners sending a mean of 33.1 and 87.4 messages, respectively. 85.5% of all C2 messages were responded to within 24 hours. Email and phone calls focused primarily on clinical concerns and medications, whereas C2 messaging focused more on education, proactive check-ins, and non-medical aspects of the child’s life (Figure 1). Four themes emerged from the participant interviews related to C2 messaging: Connection to Care Team, Efficient Communication, Clinical Uses of Secure Messaging, and Barriers to Use (Figure 2).

Conclusion
Overall, our study provides valuable insight into the benefits of secure messaging in the care of CMC. Secure messaging provided the opportunity for continued patient education, proactive check-ins from HCPs, and casual conversations about family and child life, which contributed to parents feeling an improved sense of connection with their child’s health care team. Secure messaging can be a beneficial additional communication method to improve communication between parents and their care team, reduce the associated burden of care coordination, and ultimately, improve the experience of care delivery.
34 How online care plans promote partnership, trust, and cohesive care for children with medical complexity
Authors: Adams Sherri , Moore Clara , Beatty Madison , Dharmaraj Blossom , Desai Arti , Bartlett Leah , Culbert Erin , Cohen Eyal , Stinson Jennifer , Orkin Julia 
Published: October 2022

Abstract

Background
Children with medical complexity (CMC) require care coordination across hospital, home, and community settings. The use of a medical care plan supports care coordination; however, the content of the care plan is often controlled by the health care team, limiting the ability of parents to edit in real time. It has been suggested that these limitations could be improved by using online care plans shared between parents of CMC and care team members (CTM).

Objectives
The objective of this study was to explore the perspectives of parents and care team members of children with medical complexity following the use of an online care plan.

Design/Methods
This qualitative study utilized grounded theory (GT) to explore parent and CTM experiences using an online editable medical care plan. Parents of CMC were invited to use a novel online patient-facing platform to coordinate their child’s care and edit/share their child’s care plan. They were also able to invite any of their child’s CTM to use the platform. Parents could make changes to the care plan including adding, editing, or deleting information. After 6 months, parents and CTM participated in semi-structured interviews aimed at exploring their experiences using the online care plan. Consistent with GT, constant comparative analysis was used as data analysis occurred concurrently with interviews, which allowed for theoretical sampling and theory generation.

Results
Thirty-five semi-structured interviews with parents (n=15) and CTM (n=20) were conducted. Interviews revealed three major themes (9 sub-themes): 1) navigation of uncharted roles (trust, role sharing, responsibility), 2) requirements for success (collaborative review, electronic medical record integration, online access), and 3) cohesive care (autonomy, accessibility and convenience, same page). These themes informed the creation of a theory outlining how and why a robust online shared care plan can improve care for CMC. Both parents and CTM identified the uniqueness of this care plan located on the online platform as it promoted collaboration and trust whilst allowing for increased autonomy and convenience.

Conclusion
Online shared care plans, implemented in a safe and thoughtful manner, promote cohesive partnering between parents and care team members while allowing easy access to information. This facilitates care coordination and a cohesive partnering between parents and care team members involved in the care of CMC.
37 Accessible and Specialized COVID-19 Testing for Children and Youth with Medical Complexity
Authors: Dharmaraj Blossom , Bruce-Barrett Cindy , Campigotto Aaron , Science Michelle , Orkin Julia 
Published: October 2022

Abstract

Background
COVID-19 testing for symptomatic individuals is a key public health measure for infection prevention and control. However, COVID-19 testing can be uncomfortable without appropriate supports and can lead to testing hesitancy amongst certain populations such as children with medical complexity (CMC) and those with underlying neurological and respiratory conditions. To support COVID-19 testing, a specialized initiative was developed for CMC and their families onsite at The Hospital for Sick Children to enhance testing uptake, reduce barriers to access, and support a safe and accommodated testing environment for families. Multiple modalities of testing were involved and could be completed in their personal vehicle, with specialized support from nurses and child life if needed.

Objectives
The objectives of our study were to investigate the characteristics of CMC and their families who underwent COVID-19 testing through our program, evaluate indications for testing, and collect case positivity rates.

Design/Methods
Prospective data, including testing and population characteristics, were collected from December 2020-August 2021 through a centralized system, and was analyzed using descriptive methods.

Results
335 children (Table 1) with medical complexity came to the COVID-19 Assessment Center for testing. Of those who were tested 88% (294) had neurodevelopmental conditions with highly challenging behaviours (e.g. autism, developmental delay), and 12% (28) were classified as CMC (i.e. those with active use of medical technology e.g. tracheostomy, G-tube etc.).
Of those tested, 6% (21) tested positive for COVID-19. Sixty percent (199) were tested due to having symptoms consistent with COVID-19, 27% (90) had a COVID-19 exposure, 8% (26) were exposed and tested as part of outbreak management and 5% were of an unknown criteria. The majority of completed tests (74%) were nasopharyngeal (NP) swabs, 18% completed saliva tests and 6% completed anterior nares/throat swab tests. Thirteen percent (43) of families requested additional supports such as extra nurses, child life specialists or other accommodations. All patients had a dedicated paediatric nurse and received testing in their personal vehicle.

Conclusion
CMC and their families face unique barriers to COVID-19 testing. A specialized testing centre for CMC was able to support families by providing unique opportunities for testing, revealing a 6% COVID-19 positivity rate. NP swabs that can be painful were supported through in-vehicle testing with dedicated pediatric nurses. Robust health and safety measures, including a coordinated testing approach, are necessary to ensure accessible testing opportunities for CMC and their families. Further research is needed to be able to support this unique population.