Outbreak.info: A standardized, searchable platform to discover and explore COVID-19 resources and data

To combat the ongoing COVID-19 pandemic, scientists have been conducting research at breakneck speeds, producing over 52,000 peer-reviewed articles within the first year. To address the challenge in tracking the vast amount of new research located in separate repositories, we developed outbreak.info Research Library, a standardized, searchable interface of COVID-19 and SARS-CoV-2 resources. Unifying metadata from sixteen repositories, we assembled a collection of over 350,000 publications, clinical trials, datasets, protocols, and other resources as of October 2022. We used a rigorous schema to enforce consistency across different sources and resource types and linked related resources. Researchers can quickly search the latest research across data repositories, regardless of resource type or repository location, via a search interface, public API, and R package. Finally, we discuss the challenges inherent in combining metadata from scattered and heterogeneous resources and provide recommendations to streamline this process to aid scientific research.

Persistent increases of PKMζ in memory-activated neurons trace LTP maintenance during spatial long-term memory storage.

PKMζ is an autonomously active PKC isoform crucial for the maintenance of synaptic long-term potentiation (LTP) and long-term memory. Unlike other kinases that are transiently stimulated by second messengers, PKMζ is persistently activated through sustained increases in protein expression of the kinase. Therefore, visualizing increases in PKMζ expression during long-term memory storage might reveal the sites of its persistent action and thus the location of memory-associated LTP maintenance in the brain. Using quantitative immunohistochemistry validated by the lack of staining in PKMζ-null mice, we examined the amount and distribution of PKMζ in subregions of the hippocampal formation of wild-type mice during LTP maintenance and spatial long-term memory storage. During LTP maintenance in hippocampal slices, PKMζ increases in the pyramidal cell body and stimulated dendritic layers of CA1 for at least 2 hr. During spatial memory storage, PKMζ increases in CA1 pyramidal cells for at least 1 month, paralleling the persistence of the memory. During the initial expression of the memory, we tagged principal cells with immediate-early gene Arc promoter-driven transcription of fluorescent proteins. The subset of memory-tagged CA1 cells selectively increases expression of PKMζ during memory storage, and the increase persists in dendritic compartments within stratum radiatum for 1 month, indicating long-term storage of information in the CA3-to-CA1 pathway. We conclude that persistent increases in PKMζ trace the molecular mechanism of LTP maintenance and thus the sites of information storage within brain circuitry during long-term memory.

A comprehensive program for preterm infants with patent ductus arteriosus.

OBJECTIVES: Patent ductus arteriosus (PDA) is a common finding in preterm infants. A hemodynamically significant PDA may require intervention for closure. This article aims to describe a transcatheter PDA closure (TCPC) program for preterm infants and the components of a comprehensive outpatient follow-up strategy. SETTING: A multidisciplinary team approach including neonatology, cardiology, anesthesiology, medical transport team, pulmonology, cardiac surgery, neurodevelopmental specialist, nutrition, speech therapy, social work, research collaborators, and other health care specialists is integral to the dedicated care and promotion of wellness of extremely low birth weight (ELBW) infants. PATIENTS: To date, we have performed TCPC on 134 ELBW infants weighing <2 kg at the time of the procedure, 54 of whom were <1 kg with the smallest weighing 640 g with a median gestation age of 25 weeks (range 23-27 weeks). INTERVENTIONS: A comprehensive follow-up strategy with the creation of the Memphis PDA Clinic was implemented. OUTCOME MEASURES: Respiratory support, tolerance of enteral feeds, growth, and neurodevelopmental progress are indicators of favorable outcomes. RESULTS: TCPC has benefited ELBW infants with faster weaning off the ventilator, increase in enteral feedings, and somatic growth with the overall shortening of the hospital length of stay. The Memphis PDA Clinic has ensured optimal postdischarge follow-up to improve long-term outcomes. CONCLUSIONS: TCPC is a safe and effective alternative to manage ELBW infants with a hemodynamically significant PDA. Comprehensive follow-up after discharge provided in a multispecialty clinic developed specifically for this unique population has been successful in improving outcomes.

New Patent Ductus Arteriosus Closure Devices and Techniques.

Patent ductus arteriosus (PDA) in extremely low-birth-weight infants puts this vulnerable population at high risks of morbidity and mortality. Inclusion of a multidisciplinary team and newly available transcatheter PDA occlusion devices in the management of these infants can mitigate those risks and promote better long-term outcomes. It is important that specific techniques with venous-only approach outlined in this article be followed to achieve optimal results.

Acute and long-term effects of endovascular debanding of pulmonary arteries in a swine model.

OBJECTIVES: The primary objective of this study was to demonstrate that pulmonary artery (PA) debanding via cardiac catheterization using balloon angioplasty is feasible and safe in swine. The secondary objectives were to determine the acute and long-term effects of this therapy. DESIGN: This is a chronic survival experimental study in newborn swine. BACKGROUND: PA bands are used in infants for transient palliation of congenital heart defects with excessive pulmonary blood flow. Although rare, if these defects should close spontaneously or become hemodynamically insignificant, a sternotomy and occasionally cardiopulmonary bypass may still be required for band removal. Alternatively, debanding could be accomplished through less invasive methods. INTERVENTIONS: The main pulmonary artery was banded in three piglets, and the left pulmonary artery in five piglets via mini-thoracotomy at a mean weight of 2.5 kg. Following a threefold increase in weight, the piglets underwent PA debanding via balloon angioplasty. Four piglets were sacrificed to evaluate the acute effects. The remainder were followed to evaluate long-term effects. Histopathology was performed on all piglets. OUTCOME MEASURES: Reintervention rates. Histopathologic consequences of high pressure balloon angioplasty used for PA debanding acutely and after reinterventions. RESULTS: Debanding was performed at a mean weight of 8.1 ± 2.23 kg. The median preintervention gradient across the band was 18 mm Hg. Debanding was successful in all piglets. The median postintervention gradient was 3.5 mm Hg. All piglets in the long-term model required re-interventions for recurrent stenosis at mean weights of 26 ± 1.6 and 61 ± 3.2 kg. Histopathology demonstrated vessel wall injury in only one piglet. CONCLUSIONS: Endovascular PA debanding can be safely achieved in a swine model. Angioplasty following debanding may be necessary for recurrent stenosis. This catheter-based therapy may provide a less-invasive alternative to surgery.

Compensation for PKMζ in long-term potentiation and spatial long-term memory in mutant mice.

PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice.

Unzipping of small diameter stents: an in vitro study.

OBJECTIVE: The purpose of this study was to determine if small-diameter stents can be unzipped in vitro. BACKGROUND: Small-diameter stents can relieve stenosis in infant blood vessels. As the child grows, refractory stenosis may result. If an implanted stent can be intentionally fractured along its length-"unzipped," it can be redilated to the eventual adult vessel diameter. METHODS: Stents of diameters ≤6 mm were dilated using angioplasty balloons until they fractured. The change in length-diameter (dL/dD ratio), and the yield-point-force (σy ) for each stent was calculated. RESULTS: Thirty-four coronary (CS), 11 biliary, and 10 nitinol peripheral stents (median diameter = 4, 5, and 6 mm; range = 2.75-4.5, 4-6, 6 mm, respectively) were tested. Stainless-steel (SS) CS unzipped predictably at twice their nominal diameter with minimal shortening (n = 24, median dL/dD = 0.4). Nitinol stents fractured in a disorganized fashion. The remaining stents unzipped, had disorganized fractures, and shortened significantly (dL/dD>1). A dL/dD ratio of<1 had a strong, positive correlation with the ability to unzip (Pearson rho = 0.94). By multivariate regression analysis, SS alloy, and closed-cell design were found to be significant predictors (P < 0.05) for unzipping. Optimal cut-off points for stents to unzip included, strut-thickness = 112 µm, alloy-density = 7.7 g/cm(3) , dL/dD ratio = 0.12 and σy = 108Mpa (Youden's index = 0.8, 0.4, 0.8, and 0.5, respectively). CONCLUSIONS: Stainless-steel, coronary stents of a closed-cell design unzip at twice their nominal diameter without significant shortening when serially dilated. This study may encourage the implantation of small stents in infant blood vessels and aid in selection of appropriate stent type.