Spectral matching of MS
fragmentation spectra has become a popular method for characterizing natural products libraries but identification remains challenging due to differences in MS
fragmentation ...properties between instruments and the low coverage of current spectral reference libraries. To address this bottleneck we present Structural similarity Network Annotation Platform for Mass Spectrometry (SNAP-MS) which matches chemical similarity grouping in the Natural Products Atlas to grouping of mass spectrometry features from molecular networking. This approach assigns compound families to molecular networking subnetworks without the need for experimental or calculated reference spectra. We demonstrate SNAP-MS can accurately annotate subnetworks built from both reference spectra and an in-house microbial extract library, and correctly predict compound families from published molecular networks acquired on a range of MS instrumentation. Compound family annotations for the microbial extract library are validated by co-injection of standards or isolation and spectroscopic analysis. SNAP-MS is freely available at www.npatlas.org/discover/snapms .
Abstract
Within the natural products field there is an increasing emphasis on the study of compounds from microbial sources. This has been fuelled by interest in the central role that microorganisms ...play in mediating both interspecies interactions and host-microbe relationships. To support the study of natural products chemistry produced by microorganisms we released the Natural Products Atlas, a database of known microbial natural products structures, in 2019. This paper reports the release of a new version of the database which includes a full RESTful application programming interface (API), a new website framework, and an expanded database that includes 8128 new compounds, bringing the total to 32 552. In addition to these structural and content changes we have added full taxonomic descriptions for all microbial taxa and have added chemical ontology terms from both NP Classifier and ClassyFire. We have also performed manual curation to review all entries with incomplete configurational assignments and have integrated data from external resources, including CyanoMetDB. Finally, we have improved the user experience by updating the Overview dashboard and creating a dashboard for taxonomic origin. The database can be accessed via the new interactive website at https://www.npatlas.org.
Vascular access in hypotensive trauma patients is challenging. Little evidence exists on the time required and success rates of vascular access types. We hypothesized that intraosseous (IO) access ...would be faster and more successful than peripheral intravenous (PIV) and central venous catheter (CVC) access in hypotensive patients.
An EAST prospective multicenter trial was performed; 19 centers provided data. Trauma video review was used to evaluate the resuscitations of hypotensive (systolic blood pressure ≤90 mm Hg) trauma patients. Highly granular data from video recordings were abstracted. Data collected included vascular access attempt type, location, success rate, and procedural time. Demographic and injury-specific variables were obtained from the medical record. Success rates, procedural durations, and time to resuscitation were compared among access strategies (IO vs. PIV vs. CVC).
There were 1,410 access attempts that occurred in 581 patients with a median age of 40 years (27-59 years) and an Injury Severity Score of 22 10-34. Nine hundred thirty-two PIV, 204 IO, and 249 CVC were attempted. Seventy percent of access attempts were successful but were significantly less likely to be successful in females (64% vs. 71%, p = 0.01). Median time to any access was 5.0 minutes (3.2-8.0 minutes). Intraosseous had higher success rates than PIV or CVC (93% vs. 67% vs. 59%, p < 0.001) and remained higher after subsequent failures (second attempt, 85% vs. 59% vs. 69%, p = 0.08; third attempt, 100% vs. 33% vs. 67%, p = 0.002). Duration varied by access type (IO, 36 23-60 seconds; PIV, 44 31-61 seconds; CVC 171 105-298seconds) and was significantly different between IO versus CVC ( p < 0.001) and PIV versus CVC ( p < 0.001) but not PIV versus IO. Time to resuscitation initiation was shorter in patients whose initial access attempt was IO, 5.8 minutes versus 6.7 minutes ( p = 0.015). This was more pronounced in patients arriving to the hospital with no established access (5.7 minutes vs. 7.5 minutes, p = 0.001).
Intraosseous is as fast as PIV and more likely to be successful compared with other access strategies in hypotensive trauma patients. Patients whose initial access attempt was IO were resuscitated more expeditiously. Intraosseous access should be considered a first line therapy in hypotensive trauma patients.
Therapeutic/Care Management; Level II.
Defining the complex role of the microbiome in colorectal cancer and the discovery of novel, protumorigenic microbes are areas of active investigation. In the present study, culturing and ...reassociation experiments revealed that toxigenic strains of Clostridioides difficile drove the tumorigenic phenotype of a subset of colorectal cancer patient-derived mucosal slurries in germ-free ApcMin/+ mice. Tumorigenesis was dependent on the C. difficile toxin TcdB and was associated with induction of Wnt signaling, reactive oxygen species, and protumorigenic mucosal immune responses marked by the infiltration of activated myeloid cells and IL17-producing lymphoid and innate lymphoid cell subsets. These findings suggest that chronic colonization with toxigenic C. difficile is a potential driver of colorectal cancer in patients.
Colorectal cancer is a leading cause of cancer and cancer-related deaths worldwide, with a multifactorial etiology that likely includes procarcinogenic bacteria. Using human colon cancer specimens, culturing, and murine models, we demonstrate that chronic infection with the enteric pathogen C. difficile is a previously unrecognized contributor to colonic tumorigenesis. See related commentary by Jain and Dudeja, p. 1838. This article is highlighted in the In This Issue feature, p. 1825.
Minutes matter for trauma patients in hemorrhagic shock. How trauma team function impacts time to the next phase of care has not been rigorously evaluated. We hypothesized better team performance ...scores to be associated with decreased time to the next phase of trauma care.
This retrospective secondary analysis of a prospective multicenter observational study included hypotensive trauma patients at 19 centers. Using trauma video review, we analyzed team performance with the validated Non-Technical Skills for Trauma scale: leadership, cooperation and resource management, communication, assessment/decision making, and situational awareness. The primary outcome was minutes from patient arrival to next phase of care; deaths in the bay were excluded. Secondary outcomes included time to initiation and completion of first unit of blood and inpatient mortality. Associations between team dynamics and outcomes were assessed with a linear mixed-effects model adjusting for Injury Severity Score, mechanism, initial blood pressure and heart rate, number of team members, and trauma team lead training level and sex.
A total of 441 patients were included. The median Injury Severity Score was 22 (interquartile range, 10-34), and most (61%) sustained blunt trauma. The median time to next phase of care was 23.5 minutes (interquartile range, 17-35 minutes). Better leadership, communication, assessment/decision making, and situational awareness scores were associated with faster times to next phase of care (all p < 0.05). Each 1-point worsening in the Non-Technical Skills for Trauma scale score (scale, 5-15) was associated with 1.6 minutes more in the bay. The median resuscitation team size was 12 (interquartile range, 10-15), and larger teams were slower ( p < 0.05). Better situational awareness was associated with faster completion of first unit of blood by 4 to 5 minutes ( p < 0.05).
Better team performance is associated with faster transitions to next phase of care in hypotensive trauma patients, and larger teams are slower. Trauma team training should focus on optimizing team performance to facilitate faster hemorrhage control.
Therapeutic/Care Management; Level III.
Traditionally, breast cancer is staged using TNM criteria: tumor size (T), nodal status (N), and metastasis (M). The Oncotype DX assay provides a recurrence score (RS) based on genomics that predicts ...the likelihood of distant recurrence in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-)/lymph node-negative (LN-) tumors.
We retrospectively reviewed the medical records of patients with ER+/HER2-/LN- breast cancer tumors who were evaluated between 2007 and 2017 with Oncotype DX RS. We compared the RS to tumor size, patient age, progesterone receptor (PR) status, and LN immunohistochemistry to assess for factors that may independently predict recurrence risk. We also compared tumor size to tumor grade.
The data set included 296 tumors: 248 ER+/PR-positive (PR+)/HER2- and 48 ER+/PR-negative (PR-)/HER2-. RS ranged from 0 to 66, patient age ranged from 33 to 77 years, and tumor size ranged from 1 to 65 mm. No significant correlation was found between age and RS (
=-0.073,
=0.208). PR- tumors had a significantly higher RS regardless of size (PR- mean RS 30.8 ± 12.7; PR+ mean RS 16.3
7.3;
(53)=7.6,
<0.0001). No significant correlation was seen between tumor size and RS for all tumors (
=-0.028,
=0.635), and this finding remained true for the PR+ tumor subgroup (
=0.114,
=0.072). However, a significant negative correlation was seen between tumor size and RS in the PR- subgroup (
=-0.343,
=0.017). Further analysis to ensure that differences in tumor grade did not account for this correlation showed equal distribution of well differentiated, moderately differentiated, and poorly differentiated tumors with no significant correlation between tumor size and grade.
Increasing tumor size may not be associated with increasing biological aggressiveness. Traditionally, smaller tumors are thought to be lower risk and larger tumors higher risk, with a tendency to use chemotherapy with large tumors. However, our data showed a negative correlation between tumor size and RS in the PR- subgroup. A tumor with PR negativity that reaches a large size without metastasizing may suggest a favorable tumor biology. These tumors may not receive as much benefit from chemotherapy as previously thought. Also, the higher RS seen in smaller PR- tumors may demonstrate PR- status as a predictor for higher risk of distant recurrence. We propose that all tumors meeting the ER+/PR-/LN- criteria, regardless of size, should be considered for genotyping, with the RS used to guide chemotherapy benefit.
An American political scientist and a Russian geographer, specialists in postCommunist political reform and Russian regional politics, respectively, adopt a subnational approach to democratization, ...measuring democracy in a standard fashion across 57 regions of Russia. They rate levels of democracy in Russia's oblasts, krays, and federal cities based on the results of a survey they administered to experts on Russian provincial politics. The article presents the ranking of the regions, evaluates the survey as a means of measuring provincial democracy, and examines five possible explanations for subnational variation in democracy. Journal of Economic Literature, Classification Numbers: H11, H77, P16, P26. 3 figures, 4 tables, 79 references, 2 appendices.
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