re3data - Indexing the Global Research Data Repository Landscape Since 2012.

For more than ten years, re3data, a global registry of research data repositories (RDRs), has been helping scientists, funding agencies, libraries, and data centers with finding, identifying, and referencing RDRs. As the world's largest directory of RDRs, re3data currently describes over 3,000 RDRs on the basis of a comprehensive metadata schema. The service allows searching for RDRs of any type and from all disciplines, and users can filter results based on a wide range of characteristics. The re3data RDR descriptions are available as Open Data accessible through an API and are utilized by numerous Open Science services. re3data is engaged in various initiatives and projects concerning data management and is mentioned in the policies of many scientific institutions, funding organizations, and publishers. This article reflects on the ten-year experience of running re3data and discusses ten key issues related to the management of an Open Science service that caters to RDRs worldwide.

Risk factors for developing subglottic and tracheal stenosis from the medical intensive care unit.

Objective: Endotracheal intubation is a common procedure in the medical intensive care unit (MICU), but it carries risk of complications including, but not limited to, subglottic stenosis (SGS) and tracheal stenosis (TS). Current literature suggests identifiable risk factors for the development of airway complications. This study is a comprehensive evaluation of potential risk factors in patients who developed SGS and TS following endotracheal intubation in our MICU. Methods: Patients intubated in our MICU were identified from 2013 to 2019. Diagnoses of SGS or TS within 1 year of MICU admission were identified. Data extracted included age, sex, body measurements, comorbidities, bronchoscopies, endotracheal tube size, tracheostomy, social history, and medications. Patients with prior diagnosis of airway complication, tracheostomy, or head and neck cancer were excluded. Univariate and multivariate logistic regressions were performed. Results: A total of 136 patients with TS or SGS were identified out of a sample of 6603 patients intubated in the MICU. Cases were matched to controls who did not develop airway stenosis based on identical Charlson Comorbidity Index scores. Eighty six controls were identified with a complete record of endotracheal/tracheostomy tube size, airway procedures, sociodemographic data, and medical diagnosis. Regression analysis showed that SGS or TS were associated with tracheostomy, bronchoscopy, chronic obstructive pulmonary disease, current tobacco use, gastroesophageal reflux disease, systemic lupus erythematosus, pneumonia, bronchitis, and numerous medication classes. Conclusion: Various conditions, procedures, and medications are associated with an increased risk of developing SGS or TS. Level of evidence: 4.

Healthcare disparities for the development of airway stenosis from the medical intensive care unit.

Objectives/hypothesis: To identify sociodemographic factors associated with the development of airway stenosis (AS) among intubated medical intensive care unit (MICU) patients. Study design: Retrospective cohort study. Methods: A retrospective review of adult MICU intubated patients from 2013 to 2019 at a single academic institution was performed. Univariate and multivariate analysis with logistic regression examined associations between the development of AS and subsite abnormalities such as posterior glottic stenosis (PGS), subglottic stenosis (SGS), tracheal stenosis (TS), vocal fold immobility (VFI), and posterior glottic granuloma (PGG) with age, body mass index (BMI), height, weight, race, ethnicity, sex, rurality, Appalachian status, length of admission, distance to hospital, and median household income. Results: Of an overall sample of 6603 MICU patients, 449 intubated patients were included in the study, and 204 patients were found to have AS. AS was statistically associated with decreased driving distance to the hospital and increases in BMI. PGS was statistically associated with increases in age. TS was statistically associated with increases in admission duration and not having residence status in Appalachia. VFI was statistically associated with decreases in driving distance to the hospital and not having residence status in Appalachia. Additionally, black patients had a higher odds of developing VFI compared to Caucasian patients. Conclusion: AS is associated with sociodemographic factors such as age, BMI, shorter distance to hospital, admission duration, and no Appalachian status. These data demonstrate the need to further investigate the impact of social determinants of health on airway pathology and outcomes. Level of evidence: 4.

Physical Activity Opportunities in US Early Child Care Programs.

BACKGROUND AND OBJECTIVES: Physical activity provides health and developmental benefits to young children. The Study of Nutrition and Activity in Child Care Settings describes physical activity opportunities and sedentary occasions for children aged 1 to 5 years at programs participating in the US Department of Agriculture Child and Adult Care Food Program. METHODS: The Study of Nutrition and Activity in Child Care Settings obtained a nationally representative sample of classrooms within Child and Adult Care Food Program-participating Head Start and child care centers via multistage cluster sampling. For 1 observation day, an observer in each classroom tallied designated outdoor and indoor playspaces; minutes children spent in playspaces; barriers and facilitators to physical activity; and classroom time when most children were physically active (eg, walking, dancing), sedentary (seated, lying down), or neither. Weighted descriptive tabulations by program type compared outdoor physical activity opportunity counts and total physical activity opportunity durations to national guidelines. Multivariate regression analysis investigated association of barriers with physical activity opportunity duration. RESULTS: The sample included 227 classrooms, 96 in child care centers and 131 in Head Start programs. All had sedentary occasions outside meals, snacks, and naps; virtually all offered opportunities for physical activity. Seventy-four percent of programs met national guidance on sufficient number of outdoor opportunities, weather permitting. Just 50% met guidance of ≥60 to 90 minutes of physical activity, whereas only 43% met both sets of guidance. Weather and staff not joining in outdoor play were associated with 74 and 31 fewer minutes devoted to physical activity, respectively. CONCLUSIONS: Findings suggest ample room for improvement in provision of physical activity opportunities during child care.

Foods Served in Child Care Programs Participating in the Child and Adult Care Food Program and Alignment with Program Meal Patterns.

OBJECTIVE: Assess Child and Adult Care Food Program (CACFP) program compliance with meal component requirements for children aged 3-5 years by program type, and describe foods and beverages most commonly served. DESIGN: Cross-sectional analysis of 1-week menu surveys during winter/spring 2017. SETTING: US CACFP-participating child care programs. PARTICIPANTS: Nationally representative multistage cluster sample of 664 programs: 222 child care centers, 247 Head Start programs, 195 family child care homes. MAIN OUTCOME MEASURE(S): Percentage of meals including required components; frequently served foods and beverages. ANALYSIS: Mean percentages; 2-tailed t tests; alpha = 0.05 significance level. RESULTS: Most breakfasts (97%), lunches (88%), and afternoon snacks (97%) included all required CACFP meal components. Most breakfasts included fruits (96%), but not vegetables; 16% included a meat/meat alternate. Most lunches (81%) included both fruits and vegetables. Afternoon snacks were mostly grains/breads (80%) and fruits (57%). Most frequently served foods included 1% unflavored milk and fresh fruits such as apples and bananas. Most menus limited juice, offered low-sugar cereal, and did not include flavored milk; very few menus included noncreditable foods with added sugar. CONCLUSIONS AND IMPLICATIONS: Most CACFP meals provided required components, but there is room for improvement, particularly for increasing vegetables served and limiting foods high in added sugar and fat.

National Database Outcomes of Esophageal Dilations.

OBJECTIVES/HYPOTHESIS: To better assess rates of postoperative complications and mortality following esophageal dilation, and to identify factors associated with adverse outcomes. STUDY DESIGN: Observational, retrospective cohort study. METHODS: We queried a national database of insurance claims for Current Procedural Terminology (CPT) codes representing esophageal dilation performed between 2011 and 2017. Patients aged 18 to 100 who were continuously enrolled with their insurance provider were included. Demographic information, additional CPT codes, concomitant diagnoses, and anticoagulant medication data were collected for all patients included. Postoperative mortality was assessed and International Classification of Diseases (ICD)9/10 codes for complications, including esophageal perforation, hemorrhage, mediastinitis, and sepsis were flagged. RESULTS: We identified 202,965 encounters for esophageal dilation. Of these procedures, 193 were performed on a patient who underwent percutaneous endoscopic gastrostomy (PEG) during the study period and was analyzed separately. Another 244 dilations were excluded due to repeat entries. Of the remaining 202,528 procedures remaining, 42,310 were repeat dilations in the same patient. Data analysis was confined to each patient's initial dilation. 160,218 initial dilations remained. Of these, 62,107 were performed on male patients and 98,111 were performed on female patients. The average age was 57.7 years. There were 12 mortalities within 30 days postoperatively, representing 0.0075% of all dilations. Esophageal perforation and esophageal hemorrhage were the most common reported complications, with 139 and 110 occurrences, respectively. The overall per-dilation complication rate was 0.215%. CONCLUSIONS: Evidence from a national insurance claim database suggests that esophageal dilation is a safe procedure with a low rate of serious complications and a 30-day all-cause mortality rate of less than 1 per 10,000 dilations. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2436-2440, 2021.

Evaluation of camera-based freehand SPECT in preoperative sentinel lymph node mapping for melanoma patients.

BACKGROUND: Assessment of lymphatic status via sentinel lymph node (SLN) biopsy is an integral and crucial part of melanoma surgical oncology. The most common technique for sentinel node mapping is preoperative planar scintigraphy of an injected gamma-emitting lymphatic tracer followed by intraoperative node localization using a non-imaging gamma probe with auditory feedback. In recent years, intraoperative visualization of SLNs in 3D has become possible by coupling the probe to an external system capable of tracking its location and orientation as it is read out, thereby enabling computation of the 3D distribution of the tracer (freehand SPECT). In this project, the non-imaging probe of the fhSPECT system was replaced by a unique handheld gamma camera containing an array of sodium iodide crystals optically coupled to an array of silicon photomultipliers (SiPMs). A feasibility study was performed in which preoperative SLN mapping was performed using camera fhSPECT and the number of detected nodes was compared to that visualized by lymphoscintigraphy, probe fhSPECT, and to the number ultimately excised under non-imaging probe guidance. RESULTS: Among five subjects, SLNs were detected in nine lymphatic basins, with one to five SLNs detected per basin. A basin-by-basin comparison showed that the number of SLNs detected using camera fhSPECT exceeded that using lymphoscintigraphy and probe fhSPECT in seven of nine basins and five of five basins, respectively. (Probe fhSPECT scans were not performed for four basins.) It exceeded the number excised under non-imaging probe guidance for seven of nine basins and equaled the number excised for the other two basins. CONCLUSIONS: Freehand SPECT using a prototype SiPM-based gamma camera demonstrates high sensitivity for detection of SLNs in a preoperative setting. Camera fhSPECT is a potential means for efficiently obtaining real-time 3D activity distribution maps in applications such as image-guided percutaneous biopsy, and surgical SLN biopsy or radioguided tumor excision.

Towards Interoperability in Clinical Research - Enabling FHIR on the Open-Source Research Platform XNAT.

This paper presents an approach to enable interoperability of the research data management system XNAT by the implementation of the HL7 standards framework Fast Healthcare Interoperability Resources (FHIR). The FHIR implementation is realized as an XNAT plugin (Source code: https://github.com/somnonetz/xnat-fhir-plugin ), that allows easy adoption in arbitrary XNAT instances. The approach is demonstrated on patient data exchange between a FHIR reference implementation and XNAT.

Multi-Level Data-Security and Data-Protection in a Distributed Search Infrastructure for Digital Medical Samples.

Human sample data is stored in biobanks with software managing digital derived sample data. When these stand-alone components are connected and a search infrastructure is employed users become able to collect required research data from different data sources. Data protection, patient rights, data heterogeneity and access control are major challenges for such an infrastructure. This dissertation will investigate concepts for a multi-level security architecture to comply with these requirements.

The thyroid receptor modulator KB3495 reduces atherosclerosis independently of total cholesterol in the circulation in ApoE deficient mice.

BACKGROUND: Thyroid hormones (TH) regulate cholesterol metabolism but their use as lipid-lowering drugs is restricted due to negative cardiac effects. TH mimetic compounds modulating TH receptor ß (THRß) have been designed as potential drugs, reducing serum cholesterol levels while avoiding apparent deleterious cardiac effects. OBJECTIVE: Using ApoE deficient mice, we examined whether KB3495, a TH mimetic compound, reduces atherosclerosis and if there is a synergistic effect with atorvastatin. The effect of KB3495 was investigated after 10 and 25 weeks. RESULTS: KB3495 treatment reduced atherosclerotic plaque formation in aorta and decreased the cholesteryl ester (CE) content by 57%. Treatment with KB3495 was also associated with a reduction of macrophage content in the atherosclerotic plaques and reduced serum levels of IL-1ß, TNFalpha, IL-6, Interferon γ, MCP-1 and M-CSF. Serum lipoprotein analysis showed no change in total cholesterol levels in ApoB-containing lipoproteins. KB3495 alone increased fecal BA excretion by 90%. The excretion of neutral sterols increased in all groups, with the largest increase in the combination group (350%). After 25 weeks, the animals treated with KB3495 showed 50% lower CE levels in the skin and even further reductions were observed in the combination group where the CE levels were reduced by almost 95% as compared to controls. CONCLUSION: KB3495 treatment reduced atherosclerosis independently of total cholesterol levels in ApoB-containing lipoproteins likely by stimulation of sterol excretion from the body and by inhibition of the inflammatory response.

3D pancreatic carcinoma spheroids induce a matrix-rich, chemoresistant phenotype offering a better model for drug testing.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer related death. It is lethal in nearly all patients, due to an almost complete chemoresistance. Most if not all drugs that pass preclinical tests successfully, fail miserably in the patient. This raises the question whether traditional 2D cell culture is the correct tool for drug screening. The objective of this study is to develop a simple, high-throughput 3D model of human PDAC cell lines, and to explore mechanisms underlying the transition from 2D to 3D that might be responsible for chemoresistance. METHODS: Several established human PDAC and a KPC mouse cell lines were tested, whereby Panc-1 was studied in more detail. 3D spheroid formation was facilitated with methylcellulose. Spheroids were studied morphologically, electron microscopically and by qRT-PCR for selected matrix genes, related factors and miRNA. Metabolic studies were performed, and a panel of novel drugs was tested against gemcitabine. RESULTS: Comparing 3D to 2D cell culture, matrix proteins were significantly increased as were lumican, SNED1, DARP32, and miR-146a. Cell metabolism in 3D was shifted towards glycolysis. All drugs tested were less effective in 3D, except for allicin, MT100 and AX, which demonstrated effect. CONCLUSIONS: We developed a high-throughput 3D cell culture drug screening system for pancreatic cancer, which displays a strongly increased chemoresistance. Features associated to the 3D cell model are increased expression of matrix proteins and miRNA as well as stromal markers such as PPP1R1B and SNED1. This is supporting the concept of cell adhesion mediated drug resistance.

Modulation of diazepam-insensitive GABA(A) receptors by micromolar concentrations of thyroxine and related compounds in vitro.

The effects of thyroxine and its related compounds on the benzodiazepine-insensitive γ-aminobutyric acid type A (GABA(A)) receptors were studied. Thyroxine at micromolar concentrations potentiated the (3)H-Ro15-4513 binding to rat brain membranes in-vitro in the thalamus, striatum, cortex and hippocampus, but not in cerebellum. In the thalamus, the rank order of potency was the following: 3,3',5,5'-tetraiodothyroacetic acid (TETRAC)>L-thyroxine>3,5-diiodo-l-thyronine (3,5-T2). TETRAC induced a slight potentiation of flumazenil binding to diazepam-sensitive GABA(A) receptors in the thalamus and striatum while no effect was found in cortex and hippocampus. Consequently, we examined whether these compounds could exert their modulatory effect on the currents mediated by benzodiazepine-insensitive GABA(A) receptors. The diazepam-insensitive GABA(A) receptor-mediated currents were recorded from acutely isolated rat ventrobasal thalamic neurons by applying low concentrations of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). TETRAC and thyroxine at low µM concentrations potentiated the THIP-evoked currents, although 3,5-T2 had no effect on the THIP-induced currents. Ethanol had no effect on the enhancing effects of TETRAC. TETRAC itself evoked GABA(A) receptor-mediated currents at high concentrations beyond 30 µM. Although the effects of TETRAC and thyroxine were observed at non-physiological concentrations of hormones, the present results might lead to new lead structures with specificity to diazepam-insensitive GABA(A) receptor subtypes.

Data sharing, small science and institutional repositories.

Results are presented from the Data Curation Profiles project research, on who is willing to share what data with whom and when. Emerging from scientists' discussions on sharing are several dimensions suggestive of the variation in both what it means 'to share' and how these processes are carried out. This research indicates that data curation services will need to accommodate a wide range of subdisciplinary data characteristics and sharing practices. As part of a larger set of strategies emerging across academic institutions, institutional repositories (IRs) will contribute to the stewardship and mobilization of scientific research data for e-Research and learning. There will be particular types of data that can be managed well in an IR context when characteristics and practices are well understood. Findings from this study elucidate scientists' views on 'sharable' forms of data-the particular representation that they view as most valued for reuse by others within their own research areas-and the anticipated duration for such reuse. Reported sharing incidents that provide insights into barriers to sharing and related concerns on data misuse are included.

Gastric artery apoplexy presenting as an acute abdomen in an adolescent.

Nontraumatic abdominal apoplexy, which is the occurrence of hemorrhage into the peritoneal cavity, is uncommon in the pediatric literature. Adult case reports of nontraumatic abdominal apoplexy include visceral artery aneurysms from the aorta, splenic, celiac, hepatic, gastric, and gastroepiploic arteries as well as gynecologic pathology. We identified 2 case reports of spontaneous abdominal apoplexy due to injury of the short gastric arteries in adult patients with histories of vomiting after alcohol consumption. This is the first reported case of nontraumatic abdominal apoplexy due to injury to the short gastric arteries in a pediatric patient.

Involvement of corepressor complex subunit GPS2 in transcriptional pathways governing human bile acid biosynthesis.

Coordinated regulation of bile acid biosynthesis, the predominant pathway for hepatic cholesterol catabolism, is mediated by few key nuclear receptors including the orphan receptors liver receptor homolog 1 (LRH-1), hepatocyte nuclear factor 4alpha (HNF4alpha), small heterodimer partner (SHP), and the bile acid receptor FXR (farnesoid X receptor). Activation of FXR initiates a feedback regulatory loop via induction of SHP, which suppresses LRH-1- and HNF4alpha-dependent expression of cholesterol 7alpha hydroxylase (CYP7A1) and sterol 12alpha hydroxylase (CYP8B1), the two major pathway enzymes. Here we dissect the transcriptional network governing bile acid biosynthesis in human liver by identifying GPS2, a stoichiometric subunit of a conserved corepressor complex, as a differential coregulator of CYP7A1 and CYP8B1 expression. Direct interactions of GPS2 with SHP, LRH-1, HNF4alpha, and FXR indicate alternative coregulator recruitment strategies to cause differential transcriptional outcomes. In addition, species-specific differences in the regulation of bile acid biosynthesis were uncovered by identifying human CYP8B1 as a direct FXR target gene, which has implications for therapeutic approaches in bile acid-related human disorders.

Aqueous phosphoric acid as a mild reagent for deprotection of tert-butyl carbamates, esters, and ethers.

Aqueous phosphoric acid (85 wt %) is an effective, environmentally benign reagent for the deprotection of tert-butyl carbamates, tert-butyl esters, and tert-butyl ethers. The reaction conditions are mild and offer good selectivity in the presence of other acid-sensitive groups, including CBZ carbamates, azetidine, benzyl and methyl esters, TBDMS, and methyl phenyl ethers. The mildness of the reaction is further demonstrated in the synthesis of clarithromycin derivative, in which a tert-butyl ester is removed in the presence of cyclic carbamate, lactone, ketal, acetate ester, and epimerizable methyl ketone functionalities. The reaction preserves the stereochemical integrity of the substrates. The reactions are high yielding, and the workup is convenient.