Web-CONEXS: an inroad to theoretical X-ray absorption spectroscopy.

Accurate analysis of the rich information contained within X-ray spectra usually calls for detailed electronic structure theory simulations. However, density functional theory (DFT), time-dependent DFT and many-body perturbation theory calculations increasingly require the use of advanced codes running on high-performance computing (HPC) facilities. Consequently, many researchers who would like to augment their experimental work with such simulations are hampered by the compounding of nontrivial knowledge requirements, specialist training and significant time investment. To this end, we present Web-CONEXS, an intuitive graphical web application for democratizing electronic structure theory simulations. Web-CONEXS generates and submits simulation workflows for theoretical X-ray absorption and X-ray emission spectroscopy to a remote computing cluster. In the present form, Web-CONEXS interfaces with three software packages: ORCA, FDMNES and Quantum ESPRESSO, and an extensive materials database courtesy of the Materials Project API. These software packages have been selected to model diverse materials and properties. Web-CONEXS has been conceived with the novice user in mind; job submission is limited to a subset of simulation parameters. This ensures that much of the simulation complexity is lifted and preliminary theoretical results are generated faster. Web-CONEXS can be leveraged to support beam time proposals and serve as a platform for preliminary analysis of experimental data.

How to: assess patient suitability for unlicensed phage therapy in the United Kingdom.

BACKGROUND: Bacteriophage (phage) therapy is a promising alternative antimicrobial approach which has the potential to transform the way we treat bacterial infections. The antibiotic resistance crisis is driving renewed interest in phage therapy. There are currently no licenced phage therapy medicinal products and phage therapy is used in small but growing patient numbers on an unlicensed basis. OBJECTIVES: This article provides guidelines on the assessment of patient suitability for unlicensed phage therapy for clinicians in the United Kingdom. SOURCES: This article builds on Health Improvement Scotland's recommendation for the consideration of phage therapy in difficult-to-treat infection and the experience of the author group who have collectively assessed the suitability of 30 patients for phage therapy. CONTENT: In the UK, unlicensed medicines, including phages, may be considered to meet special clinical needs. The use of unlicensed medicines is governed by national legislation and local NHS Trust policies. Phages can be used in any NHS Trust and decisions about suitability should be made via existing local clinical management pathways. This article sets out guidelines to support local clinical teams in the assessment of patient suitability for phage therapy. Clinical and microbiological considerations are presented, including allergy and pregnancy.

Effect of parenteral lipids on essential fatty acid deficiency in pediatric intestinal failure: A retrospective cohort study.

BACKGROUND: Pediatric patients with intestinal failure require long-term parenteral nutrition owing to impaired enteral nutrition absorption. A potential complication is essential fatty acid deficiency (EFAD), resulting from decreased linoleic and α-linolenic acid concentrations and defined by an increased triene:tetraene ratio (TTR; Mead acid:arachidonic acid). Historically, soybean oil lipid emulsion (SOLE) was the only commercially available parenteral lipid in the United States. Recently, a composite lipid emulsion (CLE) and fish oil lipid emulsion (FOLE) received US Food and Drug Administration approval. This study investigated whether lipid emulsion regimen impacts EFAD incidence in pediatric patients with intestinal failure. METHODS: This study was a 10-year retrospective cohort study of pediatric patients with intestinal failure who received parenteral SOLE, CLE, or FOLE. The primary outcome was EFAD incidence, defined as a TTR ≥ 0.2. Secondary outcomes included TTR ≥ 0.05, cholestasis incidence, lipid dose effect on EFAD incidence, and fatty acid parameter differences. RESULTS: A total of 144 fatty acid profiles from 47 patients were reviewed. EFAD did not occur in any lipid emulsion group. There were no differences in the incidence of TTR ≥ 0.05 or cholestasis. The effect of dose could not be evaluated because of no EFAD incidence. Lastly, although each group had varied fatty acid parameters, none saw decreased essential fatty acid levels. CONCLUSION: This study found that, with close monitoring, the lipid emulsion regimen did not impact EFAD incidence. This suggests that FOLE and CLE do not increase EFAD risk compared with SOLE in pediatric patients with intestinal failure.

Comparison of Clinical Outcomes After Medial Patellofemoral Ligament Reconstruction With Allograft Versus Autograft: A Matched-Cohort Analysis.

Background: Disruption of the medial patellofemoral ligament (MPFL) may lead to recurrent lateral patellar dislocation and patellofemoral chondral injury. Despite significant previous work investigating numerous performance parameters, the optimal graft choice for MPFL reconstruction for patellar instability remains unclear. Purpose: To compare functional outcomes scores, subjective recurrent instability, and revision rates between autograft and allograft in MPFL reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent MPFL reconstruction with autograft between 2013 and 2018 were identified. A 2:1 comparison group of patients who underwent MPFL reconstruction with allograft was matched by sex, age (±3 years), and body mass index (BMI) (±3 kg/m2). Patient characteristics, preoperative radiograph measurements, and intraoperative data were compared between the groups, as were patient-reported outcome measures, including International Knee Documentation Committee (IKDC) score, Lysholm score, Single Assessment Numerical Evaluation (SANE), and visual analog scale (VAS) for pain. Subjective recurrent instability and revision rate were also compared between groups. Results: The autograft group was composed of 30 patients (13 male, 17 female) with a mean age of 24.4 years and mean BMI of 25.0 kg/m2, and the allograft group was composed of 60 matched patients (25 male, 35 female) with a mean age of 24.1 years and mean BMI of 25.1 kg/m2. The autograft and allograft groups reported similar IKDC scores (73.0 vs 73.7; P = .678), Lysholm scores (77.5 vs 80.7; P = .514), SANE (72.0 vs 75.8; P = .236), and VAS pain (30.7 vs 26.6; P = .482), as well as similar rates of postoperative patellar subluxations (20.0% vs 19.3%; P = .867) and dislocations (10.0% vs 15.0%; P = .805). Conclusion: Both allograft and autograft were found to be viable options for MPFL reconstruction. There were no significant group differences in failure rates, patient-reported outcomes, pain, or complications between autograft and allograft MPFL reconstruction in this series.

Telomere length and clonal chromosomal alterations in peripheral blood of patients with severe aplastic anaemia.

Severe aplastic anaemia (SAA) is a rare and life-threatening bone marrow failure disorder. We used data from the transplant outcomes in aplastic anaemia study to characterize mosaic chromosomal alterations (mCAs) in the peripheral blood of 738 patients with acquired SAA and evaluate their associations with telomere length (TL) and survival post-haematopoietic cell transplant (HCT). The median age at HCT was 20.4 years (range = 0.2-77.4). Patients with SAA had shorter TL than expected for their age (median TL percentile for age: 35.7th; range <1-99.99). mCAs were detected in 211 patients (28.6%), with chr6p copy-neutral loss of heterozygosity (6p-CNLOH) in 15.9% and chr7 loss in 3.0% of the patients; chrX loss was detected in 4.1% of female patients. Negative correlations between mCA cell fraction and measured TL (r = -0.14, p = 0.0002), and possibly genetically predicted TL (r = -0.07, p = 0.06) were noted. The post-HCT 3-year survival probability was low in patients with chr7 loss (39% vs. 72% in patients with chr6-CNLOH, 60% in patients with other mCAs and 70% in patients with no mCAs; p-log rank = 0.001). In multivariable analysis, short TL (p = 0.01), but not chr7 loss (p = 0.29), was associated with worse post-HCT survival. TL may guide clinical decisions in patients with SAA.

Dissemination of health content through social networks: YouTube and opioid use disorders.

INTRODUCTION: Most Americans now access social media platforms, including YouTube, to obtain health information. However, few studies have evaluated the quality of YouTube content related to opioid use disorder (OUD), including medications for OUD (MOUD; buprenorphine) and harm reduction resources (e.g., naloxone). The purpose of this cross-sectional analysis was to assess the quality, accuracy, and reliability of MOUD and harm reduction-related video content available on YouTube. METHODS: The study team conducted a YouTube search between June 2022 and July 2022 using key words related to MOUD and harm reduction content (e.g., "suboxone," "methadone," "Narcan"). The 5 most viewed videos from each search term were analyzed for quality (i.e., Global Quality Scale; GQS), accuracy (i.e., JAMA Benchmark Criteria), and reliability (i.e., DISCERN). Videos that were non-English, duplicate, or that did not directly mention OUD, MOUD, or harm reduction were excluded from the review (N = 6). RESULTS: YouTube videos (N = 70) were mostly produced by medical professionals (27.1 %), independent nonmedical users (21.4 %; e.g., vloggers, individuals documenting their experiences), medical organizations (17.1 %; e.g., hospitals, treatment programs), and/or media (14.3 %; e.g., news agencies). The target audience was primarily the general public (65.7 %), people who use opioids (20.0 %), and healthcare providers (10.0 %). Videos containing MOUD content (N = 64, 61.4 %) mostly focused on suboxone (25.0 %), methadone (23.4 %), Sublocade (14.1 %), and subutex/buprenorphine (14.1 %). The median quality score was 2 based on the GQS with 3 videos receiving the highest quality rating (5). Two videos were highly rated for accuracy per all three JAMA Benchmark criteria. Videos produced by nonmedical educational channels had the highest overall reliability scores on the DISCERN criteria (median 4), followed by medical professionals (median 3), and medical organizations (median 2.5). CONCLUSION: The overall quality, accuracy, and reliability of MOUD and harm reduction related content posted on YouTube is poor. The lack of evidence-based content posted on YouTube reinforces the need for public health expert involvement in disseminating guideline-based content on social media.

Transcriptomics and epigenetic data integration learning module on Google Cloud.

Multi-omics (genomics, transcriptomics, epigenomics, proteomics, metabolomics, etc.) research approaches are vital for understanding the hierarchical complexity of human biology and have proven to be extremely valuable in cancer research and precision medicine. Emerging scientific advances in recent years have made high-throughput genome-wide sequencing a central focus in molecular research by allowing for the collective analysis of various kinds of molecular biological data from different types of specimens in a single tissue or even at the level of a single cell. Additionally, with the help of improved computational resources and data mining, researchers are able to integrate data from different multi-omics regimes to identify new prognostic, diagnostic, or predictive biomarkers, uncover novel therapeutic targets, and develop more personalized treatment protocols for patients. For the research community to parse the scientifically and clinically meaningful information out of all the biological data being generated each day more efficiently with less wasted resources, being familiar with and comfortable using advanced analytical tools, such as Google Cloud Platform becomes imperative. This project is an interdisciplinary, cross-organizational effort to provide a guided learning module for integrating transcriptomics and epigenetics data analysis protocols into a comprehensive analysis pipeline for users to implement in their own work, utilizing the cloud computing infrastructure on Google Cloud. The learning module consists of three submodules that guide the user through tutorial examples that illustrate the analysis of RNA-sequence and Reduced-Representation Bisulfite Sequencing data. The examples are in the form of breast cancer case studies, and the data sets were procured from the public repository Gene Expression Omnibus. The first submodule is devoted to transcriptomics analysis with the RNA sequencing data, the second submodule focuses on epigenetics analysis using the DNA methylation data, and the third submodule integrates the two methods for a deeper biological understanding. The modules begin with data collection and preprocessing, with further downstream analysis performed in a Vertex AI Jupyter notebook instance with an R kernel. Analysis results are returned to Google Cloud buckets for storage and visualization, removing the computational strain from local resources. The final product is a start-to-finish tutorial for the researchers with limited experience in multi-omics to integrate transcriptomics and epigenetics data analysis into a comprehensive pipeline to perform their own biological research.This manuscript describes the development of a resource module that is part of a learning platform named ``NIGMS Sandbox for Cloud-based Learning'' https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox [16] at the beginning of this Supplement. This module delivers learning materials on the analysis of bulk and single-cell ATAC-seq data in an interactive format that uses appropriate cloud resources for data access and analyses.

The Military Medicine Leadership Life Cycle: A Model for Longitudinal Leadership Development for Staff Physicians.

Leadership development is a challenge for all health care systems. Military Medicine has unique challenges with increased frequency of physician turnover and more junior leaders taking on positions of leadership earlier in their careers. Military medical corps officers are also challenged with leading in clinical, academic, and operational settings. Effective leadership within the Military Healthcare System requires an intentional and ongoing leadership development process across the careers of military medical corps officers. This article describes the leadership lifecycle of military medical corps officers, highlighting existing leadership development opportunities and providing an example of a leadership lifecycle from junior staff to senior executive for other organizations. The article concludes with specific recommendations that will allow military medicine to continue to strengthen the leadership skills of its officers to meet ever growing challenges.

Management of Postprocedural Conduction Disturbances Using a Prespecified Algorithm in the Optimize PRO Study.

Background: Lack of standardization in posttranscatheter aortic valve replacement (TAVR) conduction disturbance (CD) identification and treatment may affect permanent pacemaker implantation (PPI) rates and clinical outcomes. The safety and efficacy of a standardized TAVR CD algorithm has not been analyzed. This study analyzes the Optimize PRO post-TAVR CD management algorithm with Evolut PRO/PRO+ valves. Methods: Optimize PRO is a prospective, postmarket study implementing 2 strategies to reduce pacemaker rates: TAVR with cusp overlap technique and a post-TAVR CD algorithm. The 2-hour postprocedural electrocardiogram (ECG) stratified patients to early discharge in the absence of new ECG changes or to CD algorithms for (1) ECG changes with preexisting right or left bundle branch block (LBBB), interventricular conduction delay or first-degree atrioventricular block, (2) new LBBB, or (3) high-degree atrioventricular block (HAVB). Results: The interim analysis of the CD cohort consisted of 125/400 TAVR recipients. In the CD cohort, the 30-day new PPI rate was higher (28.1% vs 1.5%; P <.001), and 60 (48%) patients were discharged with a 30-day continuous ECG monitor. At 30 days, 90% of patients discharged with a monitor did not require PPI. Clinical outcomes, including mortality, stroke, bleeding, and reintervention, were similar in patients with and without CDs. No patient experienced sudden cardiac death. Conclusions: Effective management of CDs using a standard algorithm following Evolut TAVR provides similar 30-day safety outcomes to patients without CDs who undergo routine next day discharge. The CD algorithm may provide an effective strategy to recognize arrhythmias early, improve PPI utilization, and facilitate safe monitoring of patients after discharge.

Diagnostic Performances of an in-House Immunochromatography Test Based on the Monoclonal Antibody 18B7 to Glucuronoxylomannan for Clinical Suspected Cryptococcosis: a Large-Scale Prototype Evaluation in Northern Thailand.

OBJECTIVE: Cryptococcosis predominantly presents as a meningoencephalitis in Thailand. Early and expeditious diagnosis is essential for reducing both mortality and morbidity associated with cryptococcal meningitis. We aim to define and establish the diagnostic performances between the benchmark commercially available diagnostic kit (CrAg® LFA) and the large-scale prototype of an inexpensive in-house immunochromatographic test (ICT) based on monoclonal antibody (MAb) 18B7. METHODS: We have developed the large-scale prototype for the rapid detection of cryptococcal polysaccharide antigens by utilizing a single antibody sandwich ICT format employing MAb 18B7, which is highly specific to Cryptococcus neoformans glucuronoxylomannan (GXM) antigens. An in-house MAb18B7 ICT was manufactured in accordance with industry standards under the control of the International Organization for Standardization (ISO) 13485. RESULTS: The diagnostic sensitivity, specificity, and accuracy for the in-house MAb 18B7 ICT were 99.10%, 97.61%, and 97.83%, respectively. The agreement kappa (κ) coefficient was 0.968 based on the retrospective evaluation of 580 specimens from patients living in northern Thailand with clinically suspected cryptococcosis. CONCLUSION: The data suggest that this in-house MAb 18B7 ICT will be highly beneficial for addressing the issue of cryptococcal infection in Thailand. Moreover, it is anticipated that this inexpensive ICT can play a pivotal role in various global strategies aimed at eradicating cryptococcal meningitis among individuals living with HIV by 2030.

Risk of Suicidal Ideation and Behavior Following Early-Onset Idiopathic Restless Legs Syndrome Treatment.

PURPOSE: To estimate incidence rates of suicidal ideation and behavior following treatment initiation with gabapentinoids or dopamine agonists (DAs) in patients with newly diagnosed early-onset idiopathic restless legs syndrome (RLS) and to examine suicidal behavior risk, comparing between those receiving gabapentinoids and DAs. METHODS: A new user retrospective cohort study using MarketScan claims data from 2012 to 2019 was conducted. Exposures were monotherapy gabapentinoids or DAs initiated within 60 days of new RLS diagnosis. Three varying outcome measures of suicidality were examined and incidence rates were calculated for each. A log-binomial regression model the estimated relative risk (RR) of the outcomes with gabapentinoids. Propensity score weighting adjusted for baseline covariates, including age, substance use disorders, hyperlipidemia, antipsychotic use, hypnotic/sedative use, and mood stabilizer use, which were most imbalanced before weighting. RESULTS: The cohort included 6672 patients, with 4986 (74.7%) initiating a DA and 1686 (25.3%) initiating a gabapentinoid. Incidence rates for all outcome measures were higher in the gabapentinoid group (suicidality: 21.6 vs. 10.7 per 1000 person-years; suicidality with self-harm: 23.0 vs. 11.1 per 1000 person-years; overdose- and suicide-related events: 30.0 vs. 15.5 person-years). Associated risk of suicidality (adjusted RR, 1.27 [95% CI, 0.86-1.88]); suicidality with self-harm (adjusted RR, 1.30 [95% CI, 0.89-1.90]); or overdose- and suicide-related events (adjusted RR, 1.30 [95% CI, 0.93-1.80]) was not significant with gabapentinoids. CONCLUSIONS: Incidence rates for suicidal ideation and behavior were higher among the gabapentinoid group, although increased risk was not detected after adjustment. A possible signal cannot be ruled out given limitations of the data and rarity of the outcome.

Incidence of Acute Cystoid Macular Edema After Starting a Prostaglandin Analog Compared With Other Classes of Glaucoma Medications.

PURPOSE: There is a longstanding belief that prostaglandin analogs (PGAs) may predispose patients with glaucoma to develop acute cystoid macular edema (CME). However, there is little solid evidence supporting this notion. The purpose of this study is to compare CME incidence rates among patients initiating treatment with different glaucoma medication classes. DESIGN: Database study. PARTICIPANTS: 39948 patients who were newly prescribed glaucoma medications METHODS: Using data from 10 health systems contributing data to the Sight Outcomes Research Collaborative (SOURCE) Ophthalmology Data Repository, we identified all adults with glaucoma who had been newly started on a topical glaucoma medication. Patients with pre-existing documentation of macular edema were excluded. We assessed the incidence of CME among patients with glaucoma who were newly started on PGAs, topical beta blockers (BBs), alpha agonists (AAs), and carbonic anhydrase inhibitors (CAIs). Using multivariable logistic regression, and adjusting for sociodemographic factors, we assessed the odds of developing CME among patients prescribed each of the 4 glaucoma medication classes. We also performed a subset regression analysis including lens status as a co-variate. MAIN OUTCOME MEASURES: Incidence of CME within 3 months of initiating therapy with different topical glaucoma medications. RESULTS: Among the 39,948 patients were newly treated with a topical glaucoma medication, 139 (0.35%) developed CME. The incidence of CME was 0.13%, 0.65%, 0.55%, 1.76% for users of PGAs, BBs, alpha agonists (AAs) and carbonic anhydrase inhibitors (CAIs), respectively. After adjusting for sociodemographic factors, users of topical BBs, AAs and CAIs had substantially higher odds of developing CME compared with PGA users (P<0.001 for all comparisons). The subset analysis also showed higher odds ratio of the non-PGA medication classes in association with CME. CONCLUSIONS: Clinicians should reconsider the notion that PGAs carry a higher risk of CME versus other glaucoma medication classes. If additional studies support the findings of these analyses, clinicians may feel more comfortable prescribing PGAs to patients with glaucoma without fear they will predispose patients to CME.

One fish, two fish, three fish, more: novel resighting method produces precise and cost-effective estimates of abundance.

Estimates of abundance are essential to manage and conserve marine species. Numerous methods are available to determine population size, but the suitability of methods for schooling fishes and the associated precision can vary depending on the species and system. Here, we developed and compared three mark-recapture/resight methods to assess the most robust method to estimate the abundance of silver trevally (Pseudocaranx georgianus). While the recapture rate was similar across the methods, the swim pass method (resighting) recorded the largest number of individuals (mean ± standard error 211 ± 14.9) and had the lowest coefficient of variation (CV; 4.5%-12%) compared to 360-video (resighting, 45 ± 2.1 individuals surveyed, 14.8%-22.2% CV) and large-scale capture methods (recapture, 30 ± 3.8 individuals surveyed, 17.3%-26.5% CV). The inclusion of individual identification into the abundance estimator models for large-scale capture did not change the abundance estimates and showed similar resolution between the models (CV 18.2%-26.7%). We showed that the swim pass method is logistically easy to implement and generates precise estimates of silver trevally abundance. This new method provides a low-cost, time-efficient resighting method that can be adapted to suit similar aggregating pelagic species interacting with wildlife tourism operations, enabling researchers to rapidly estimate the abundance of species that have been previously difficult to count.

End-of-Life Healthcare Utilization in Lewy Body Dementia.

Background: Lewy body dementia (LBD) is the second most common neurodegenerative dementia in the US, presenting unique end-of-life challenges. Objective: This study examined healthcare utilization and care continuity in the last year of life in LBD. Methods: Medicare claims for enrollees with LBD, continuously enrolled in the year preceding death, were examined from 2011-2018. We assessed hospital stays, emergency department (ED) visits, intensive care unit (ICU) admissions, life-extending procedures, medications, and care continuity. Results: We identified 45,762 LBD decedents, predominantly female (51.8%), White (85.9%), with average age of 84.1 years (SD 7.5). There was a median of 2 ED visits (IQR 1-5) and 1 inpatient stay (IQR 0-2). Higher age was inversely associated with ICU stays (Odds Ratio [OR] 0.96; 95% Confidence Interval [CI] 0.96-0.97) and life-extending procedures (OR 0.96; 95% CI 0.95-0.96). Black and Hispanic patients experienced higher rates of ED visits, inpatient hospitalizations, ICU admissions, life-extending procedures, and in-hospital deaths relative to White patients. On average, 15 (7.5) medications were prescribed in the last year. Enhanced care continuity correlated with reduced hospital (OR 0.72; 95% CI 0.70-0.74) and ED visits (OR 0.71; 95% CI 0.69-0.87) and fewer life-extending procedures (OR 0.71; 95% CI 0.64-0.79). Conclusions: This study underscored the complex healthcare needs of people with LBD during their final year, which was influenced by age and race. Care continuity may reduce hospital and ED visits and life-extending procedures.

Comparing research attitudes in Down syndrome and non-Down syndrome research decision-makers.

INTRODUCTION: Recruitment challenges in people with and without Down syndrome (DS) can delay research progress and risk sample bias. This study identified and quantified differences in research attitudes across populations of research enrollment decision-makers for individuals with and without DS. METHODS: We performed analyses using data from two registries: the University of California, Irvine Consent-to-Contact (C2C) Registry and DS-Connect. The former represented a sample of non-DS decision-makers (N = 4818), while for the latter, we excluded individuals with DS, leaving a population of DS family decision-makers (N = 976). We assessed scores on the Research Attitudes Questionnaire (RAQ) between DS and non-DS decision-makers. We compared total RAQ scores using linear regression and assessed item-level RAQ differences using proportional odds regression. RESULTS: Mean total RAQ scores were not statistically different between decision-makers in the two registries, after adjusting for age, sex, race and ethnicity, education, and the coronavirus disease 2019 (COVID-19) time frame (Est. Diff = 0.11, 95% confidence interval [CI]: -0.22, 0.43; p = 0.531). However, in a pre-specified analysis, we did find evidence of differential attitudes on item-level RAQ scores. Specifically, decision-makers for participants with DS had increased odds of a more favorable response to the question of responsibility to help others (DS vs. non-DS: odds ratio [OR] = 1.26, 95% CI: 1.08, 1.48) and decreased odds of a more favorable response to the question regarding the belief that medical research would find cures for major diseases during their lifetime (DS vs. non-DS: OR = 0.77, 95% CI: 0.66, 0.90). DISCUSSION: Our findings provide insights for researchers to develop strategies for recruiting individuals with and without DS into clinical research. The observed item-level differences warrant further investigation to instruct precise recruitment strategies. Highlights: Research attitudes between decision-makers for individuals with Down syndrome (DS) and decision-makers without DS were observed to be similar on average.Item-level differences in research attitudes were observed to differ for DS and non-DS decision-makers.These results can help facilitate precise recruitment strategies for populations with DS.

Assessing and harnessing updated polyketide synthase modules through combinatorial engineering.

The modular nature of polyketide assembly lines and the significance of their products make them prime targets for combinatorial engineering. The recently updated module boundary has been successful for engineering short synthases, yet larger synthases constructed using the updated boundary have not been investigated. Here we describe our design and implementation of a BioBricks-like platform to rapidly construct 5 triketide, 25 tetraketide, and 125 pentaketide synthases to test every module combination of the pikromycin synthase. Anticipated products are detected from 60% of the triketide synthases, 32% of the tetraketide synthases, and 6.4% of the pentaketide synthases. We determine ketosynthase gatekeeping and module-skipping are the principal impediments to obtaining functional synthases. The platform is also employed to construct active hybrid synthases by incorporating modules from the erythromycin, spinosyn, and rapamycin assembly lines. The relaxed gatekeeping of a ketosynthase in the rapamycin synthase is especially encouraging in the quest to produce designer polyketides.

MAMS: matrix and analysis metadata standards to facilitate harmonization and reproducibility of single-cell data.

Many datasets are being produced by consortia that seek to characterize healthy and disease tissues at single-cell resolution. While biospecimen and experimental information is often captured, detailed metadata standards related to data matrices and analysis workflows are currently lacking. To address this, we develop the matrix and analysis metadata standards (MAMS) to serve as a resource for data centers, repositories, and tool developers. We define metadata fields for matrices and parameters commonly utilized in analytical workflows and developed the rmams package to extract MAMS from single-cell objects. Overall, MAMS promotes the harmonization, integration, and reproducibility of single-cell data across platforms.