SACCHARIS v2: Streamlining Prediction of Carbohydrate-Active Enzyme Specificities Within Large Datasets.

Carbohydrates are chemically and structurally diverse, composed of a wide array of monosaccharides, stereochemical linkages, substituent groups, and intermolecular associations with other biological molecules. A large repertoire of carbohydrate-active enzymes (CAZymes) and enzymatic activities are required to form, dismantle, and metabolize these complex molecules. The software SACCHARIS (Sequence Analysis and Clustering of CarboHydrate Active enzymes for Rapid Informed prediction of Specificity) provides a rapid, easy-to-use pipeline for the prediction of potential CAZyme function in new datasets. We have updated SACCHARIS to (i) simplify its installation by re-writing in Python and packaging for Conda; (ii) enhance its usability through a new (optional) interactive GUI; and (iii) enable semi-automated annotation of phylogenetic tree output via a new R package or the commonly-used webserver iTOL. Significantly, SACCHARIS v2 has been developed with high-throughput omics in mind, with pipeline automation geared toward complex (meta)genome and (meta)transcriptome datasets to reveal the total CAZyme content ("CAZome") of an organism or community. Here, we outline the development and use of SACCHARIS v2 to discover and annotate CAZymes and provide insight into complex carbohydrate metabolisms in individual organisms and communities.

Research to classrooms: a co-designed curriculum brings All of Us data to secondary schools.

OBJECTIVES: We describe new curriculum materials for engaging secondary school students in exploring the "big data" in the NIH All of Us Research Program's Public Data Browser and the co-design processes used to collaboratively develop the materials. We also describe the methods used to develop and validate assessment items for studying the efficacy of the materials for student learning as well as preliminary findings from these studies. MATERIALS AND METHODS: Secondary-level biology teachers from across the United States participated in a 2.5-day Co-design Summer Institute. After learning about the All of Us Research Program and its Data Browser, they collaboratively developed learning objectives and initial ideas for learning experiences related to exploring the Data Browser and big data. The Genetic Science Learning Center team at the University of Utah further developed the educators' ideas. Additional teachers and their students participated in classroom pilot studies to validate a 22-item instrument that assesses students' knowledge. Educators completed surveys about the materials and their experiences. RESULTS: The "Exploring Big Data with the All of Us Data Browser" curriculum module includes 3 data exploration guides that engage students in using the Data Browser, 3 related multimedia pieces, and teacher support materials. Pilot testing showed substantial growth in students' understanding of key big data concepts and research applications. DISCUSSION AND CONCLUSION: Our co-design process provides a model for educator engagement. The new curriculum module serves as a model for introducing secondary students to big data and precision medicine research by exploring diverse real-world datasets.

Establishing Silphids in the invertebrate DNA toolbox: a proof of concept.

Environmental DNA (eDNA) analyses are an increasingly popular tool for assessing biodiversity. eDNA sampling that uses invertebrates, or invertebrate DNA (iDNA), has become a more common method in mammal biodiversity studies where biodiversity is assessed via diet analysis of different coprophagous or hematophagous invertebrates. The carrion feeding family of beetles (Silphidae: Coleoptera, Latreille (1807)), have not yet been established as a viable iDNA source in primary scientific literature, yet could be useful indicators for tracking biodiversity in forested ecosystems. Silphids find carcasses of varying size for both food and reproduction, with some species having host preference for small mammals; therefore, iDNA Silphid studies could potentially target small mammal communities. To establish the first valid use of iDNA methods to detect Silphid diets, we conducted a study with the objective of testing the validity of iDNA methods applied to Silphids using both Sanger sequencing and high throughput Illumina sequencing. Beetles were collected using inexpensive pitfall traps in Alberta, Michigan in 2019 and 2022. We successfully sequenced diet DNA and environmental DNA from externally swabbed Silphid samples and diet DNA from gut dissections, confirming their potential as an iDNA tool in mammalian studies. Our results demonstrate the usefulness of Silphids for iDNA research where we detected species from the genera Anaxyrus, Blarina, Procyon, Condylura, Peromyscus, Canis, and Bos. Our results highlight the potential for Silphid iDNA to be used in future wildlife surveys.

Operative Treatment of Acromial and Scapular Spine Fracture Nonunions Complicating Reverse Total Shoulder Arthroplasty.

BACKGROUND: Fractures of the acromion and spine can have a major impact on the outcome of reverse shoulder arthroplasty (RSA) with respect to pain, motion, and function. Reports on internal fixation for these fractures are isolated to small series or case reports with variable outcomes. The purpose of this study was to report on the outcome of open reduction and internal fixation (ORIF) of acromion or spine fractures encountered before or after RSA and describe our evolution of fixation techniques. METHODS: Between 2011 and 2023, 22 fractures or nonunions of the acromion or spine of the scapula underwent ORIF at a single institution and were followed for a minimum of 1 year. In 16 shoulders, fractures occurred after RSA, whereas 5 shoulders underwent ORIF prior to RSA. One shoulder had undergone prior failed ORIF elsewhere and revision ORIF was performed at our institution. There were 10 males and 12 females with a mean age of 67 (SD=15.1) years. Fixation strategies included single (n=11) and double plate fixation (n=11). Kruskal-Wallis one-way analyses of variance were used to analyze continuous variables and Chi-square tests employed for categorical variables. RESULTS: Of the 5 fractures treated with ORIF pre-RSA, 1 shoulder suffered an additional fracture medial to the hardware and 1 required additional bone grafting for incomplete union at the time of RSA. These 5 shoulders all underwent RSA uneventfully, but one fracture experienced late displacement of the scapular spine nonunion, leading to plate removal. Of the 16 post-RSA ORIF shoulders, radiographic union was confirmed in 14 and substantial residual inferior angulation identified in 3. New fractures occurred after ORIF in 5 shoulders. For patients who underwent ORIF after RSA, pain scores improved from a mean of 8 to 1.9 points, with more modest elevation gains (58.2° to 91.3° pre- and postoperatively, respectively). CONCLUSIONS: ORIF of acromion and scapular spine fractures or nonunions in the setting of RSA have the potential to lead to union. When these fractures and nonunions are encountered prior to RSA, ORIF allows for uneventful RSA implantation, but secondary displacement may occur. ORIF seems to lead to improvements in pain, but more modest improvements in motion and function. Our fixation strategy has evolved to (1) dual plating, (2) spanning the whole length of the spine with one of the plates, (3) use of hook features under the acromion or os trigonum if possible, and (4) liberal use of bone graft.

Pilot study of humanized glypican-3-targeted zirconium-89 immuno-positron emission tomography for hepatocellular carcinoma.

Purpose: Glypican-3 (GPC3)-targeted radioisotope immuno-positron emission tomography (immunoPET) may lead to earlier and more accurate diagnosis of hepatocellular carcinoma (HCC), thus facilitating curative treatment, decreasing early recurrence, and enhancing patient survival. We previously demonstrated reliable HCC detection using a zirconium-89-labeled murine anti-GPC3 antibody (89Zr-αGPC3M) for immunoPET. This study evaluated the efficacy of the humanized antibody successor (αGPC3H) to further clinical translation of a GPC3-based theranostic for HCC. Methods: In vitro αGPC3 binding to HepG2 cells was assessed by flow cytometry. In vivo 89Zr-αGPC3H and 89Zr-αGPC3M tumor uptake was evaluated by PET/CT and biodistribution studies in an orthotopic xenograft mouse model of HCC. Results: αGPC3H maintained binding to GPC3 in vitro and 89Zr-αGPC3H immunoPET identified liver tumors in vivo. PET/CT and biodistribution analyses demonstrated high 89Zr-αGPC3H tumor uptake and tumor-to-liver ratios, with no difference between groups. Conclusion: Humanized αGPC3 successfully targeted GPC3 in vitro and in vivo. 89Zr-αGPC3H immunoPET had comparable tumor detection to 89Zr-αGPC3M, with highly specific tumor uptake, making it a promising strategy to improve HCC detection.

Discovery of disease-adapted bacterial lineages in inflammatory bowel diseases.

Gut bacteria are implicated in inflammatory bowel disease (IBD), but the strains driving these associations are unknown. Large-scale studies of microbiome evolution could reveal the imprint of disease on gut bacteria, thus pinpointing the strains and genes that may underlie inflammation. Here, we use stool metagenomes of thousands of IBD patients and healthy controls to reconstruct 140,000 strain genotypes, revealing hundreds of lineages enriched in IBD. We demonstrate that these strains are ancient, taxonomically diverse, and ubiquitous in humans. Moreover, disease-associated strains outcompete their healthy counterparts during inflammation, implying long-term adaptation to disease. Strain genetic differences map onto known axes of inflammation, including oxidative stress, nutrient biosynthesis, and immune evasion. Lastly, the loss of health-associated strains of Eggerthella lenta was predictive of fecal calprotectin, a biomarker of disease severity. Our work identifies reservoirs of strain diversity that may impact inflammatory disease and can be extended to other microbiome-associated diseases.

A fast and sensitive size-exclusion chromatography method for plasma extracellular vesicle proteomic analysis.

Extracellular vesicles (EVs) carry diverse biomolecules derived from their parental cells, making their components excellent biomarker candidates. However, purifying EVs is a major hurdle in biomarker discovery since current methods require large amounts of samples, are time-consuming and typically have poor reproducibility. Here we describe a simple, fast, and sensitive EV fractionation method using size exclusion chromatography (SEC) on a fast protein liquid chromatography (FPLC) system. Our method uses a Superose 6 Increase 5/150, which has a bed volume of 2.9 mL. The FPLC system and small column size enable reproducible separation of only 50 µL of human plasma in 15 min. To demonstrate the utility of our method, we used longitudinal samples from a group of individuals who underwent intense exercise. A total of 838 proteins were identified, of which, 261 were previously characterized as EV proteins, including classical markers, such as cluster of differentiation (CD)9 and CD81. Quantitative analysis showed low technical variability with correlation coefficients greater than 0.9 between replicates. The analysis captured differences in relevant EV proteins involved in response to physical activity. Our method enables fast and sensitive fractionation of plasma EVs with low variability, which will facilitate biomarker studies in large clinical cohorts.

Communicating Alzheimer's biomarker results to cognitively unimpaired research participants: Satisfaction, utility, and impact on research attitudes.

Introduction: Recruitment and retention pose a significant challenge to Alzheimer's disease (AD) research. Returning AD biomarker results to participants has been proposed as a means to improve recruitment and retention. We present findings related to participant satisfaction, utility, and impact on research attitudes from the amyloid positron emission tomography (PET) disclosure sub-study within the Wisconsin Registry for Alzheimer's Prevention (WRAP). Methods: Ninety-nine cognitively unimpaired WRAP participants learned their amyloid PET results (mean age ± SD = 72.0 ± 4.8). Measures of reasons for wanting to learn results, study comprehension, result utility, visit satisfaction, research attitudes, and future study enrollment willingness were collected. Between-group, chi-squared analysis was conducted to determine differences by result type (elevated vs. not elevated amyloid PET result) in study comprehension, result utility, and visit satisfaction. Linear mixed-effects modeling was used to evaluate changes in research attitudes and enrollment willingness as a function of time, amyloid result type (elevated/not elevated), and their interaction. Results: The reasons most frequently endorsed for wanting to learn amyloid PET result was a "desire to contribute to research on Alzheimer's disease dementia" and "to inform preventative measures [one] might take (e.g., change diet, exercise, or other lifestyle changes)." Overall, participants reported understanding the results and found learning them useful. Satisfaction with the study visits was overwhelmingly high, with over 80% agreeing with visit usefulness and their satisfaction. Few differences were found between participants who learned an elevated and not elevated result. Over the course of the study, participants who learned an elevated amyloid PET result reported higher willingness to enroll in drug trials (beta: 0.12, p = 0.01) and lifestyle interventions (beta: 0.10, p = 0.02) compared to participants who learned a not elevated result. Discussion: Formal incorporation of disclosure practices may encourage participant recruitment and retention within AD research. Highlights: Participants wanted to learn their amyloid results to contribute to research.Satisfaction with disclosure and post-disclosure visits was high overall.Returning AD biomarkers can increase willingness to participate in research.

Targeting Patient-Derived Orthotopic Gastric Cancers with a Fluorescent Humanized Anti-CEA Antibody.

BACKGROUND: Gastric cancer poses a major diagnostic and therapeutic challenge as surgical resection provides the only opportunity for a cure. Specific labeling of gastric cancer could distinguish resectable and nonresectable disease and facilitate an R0 resection, which could improve survival. METHODS: Two patient-derived gastric cancer lines, KG8 and KG10, were established from surgical specimens of two patients who underwent gastrectomy for gastric adenocarcinoma. Harvested tumor fragments were implanted into the greater curvature of the stomach to establish patient-derived orthotopic xenograft (PDOX) models. M5A (humanized anti-CEA antibody) or IgG control antibodies were conjugated with the near-infrared dye IRDye800CW. Mice received 50 µg of M5A-IR800 or 50 µg of IgG-IR800 intravenously and were imaged after 72 hr. Fluorescence imaging was performed by using the LI-COR Pearl Imaging System. A tumor-to-background ratio (TBR) was calculated by dividing the mean fluorescence intensity of the tumor versus adjacent stomach tissue. RESULTS: M5A-IR800 administration resulted in bright labeling of both KG8 and K10 tumors. In the KG8 PDOX models, the TBR for M5A-IR800 was 5.85 (SE ± 1.64) compared with IgG-IR800 at 0.70 (SE ± 0.17). The K10 PDOX models had a TBR of 3.71 (SE ± 0.73) for M5A-IR800 compared with 0.66 (SE ± 0.12) for IgG-IR800. CONCLUSIONS: Humanized anti-CEA (M5A) antibodies conjugated to fluorescent dyes provide bright and specific labeling of gastric cancer PDOX models. This tumor-specific fluorescent antibody is a promising potential clinical tool to detect the extent of disease for the determination of resectability as well as to visualize tumor margins during gastric cancer resection.

Living with wolves: A worldwide systematic review of attitudes.

This systematic review of peer reviewed articles on attitudes towards gray wolves (Canis lupus), shows that attitudes are mainly measured either by mean values of attitudes or by proportional differences in attitudes. This may impact on how attitudes are perceived and interpreted across studies and areas. However, independent of method used, we found that people living in areas where wolves always have existed, are more negative towards wolves compared to people living in areas where there are no wolves, or where wolves have recovered after years of absence. People who express fear, or being directly affected by having wolves, such as farmers and hunters, report more negative attitudes compared to other groups of respondents. For wolf conservation we recommend politicians and management authorities to prepare local societies of the different consequences of living in wolf areas. We recommend using dialogues and conflict management methods to minimize the level of conflicts.

Implementation of a Multidisciplinary Team to Improve the Quality of Care for Older Surgical Patients at a Rural Academic Medical Center.

For the first time in history, people age older than 65 years make up >20% of the non-metro population, compared with 16% of the metro population. From 2010 to 2020 the nonmetro population age older than 65 years grew by 22%, while the working-age population declined by 4.9%, and the population aged under 18 years declined by 5.7%.1,2 Multidisciplinary geriatric surgical programs are an increasingly recognized approach to the care of older surgical patients and preliminary data suggest they can reduce length of stay. Although rural areas have the greatest proportion of patients age older than 65 years, implementation of such programs faces special challenges in rural settings with limited resources. Dartmouth-Hitchcock Medical Center is one of the most rural academic centers in the United States. Challenges include a shortage of geriatric-trained providers, long distances to access primary care and subspecialists, and extremely limited postacute care options and skilled nursing facility beds. To address the unique needs of our provider and patient population we began with a development period where we conducted stakeholder interviews. Using these data, we mapped out a workflow and developed pilot projects to address different portions of the workflow, such as preoperative screening for frailty and cognitive impairment, interdisciplinary weekly case conferences, proactive case management, delirium and geriatric surgery postoperative pathway order sets, and a variety of tools for reorientation and delirium management. Herein we describe the process of development and pragmatic clinical implementation of geriatric-focused care for older surgical patients in our rural tertiary center, including some of the main challenges we faced and the strategies we undertook to overcome them, and some of our early patient centered and clinical outcomes. This information may assist other institutions as they design geriatric-focused surgical programs to address the growing population of older adults and the need for compliance with state legislation. The clinical program described is not a research study, and the outcome data we report is for the purpose of description, and should not be interpreted as a rigorous research investigation of the effect of our intervention.

Disparities in hepatocellular carcinoma incidence among Hispanic and non-Hispanic adults in Arizona: Trends between 2009-2017.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly lethal cancer with few treatment options available to patients. Most HCC cases in Arizona, a state with a high proportion of Hispanic adults, have not been included in recent reports of HCC incidence. This study describes trends in HCC incidence and stage at diagnosis among Arizona residents between 2009-2017 and reports on racial and ethnic disparities for these outcomes. METHODS: The Arizona Cancer Registry was used to identify Arizonans aged 19 or older diagnosed with liver cell carcinoma diagnosed between 2009-2017. A total of 5043 cases were examined. Adjusted annual and 3-year HCC incidence rates (per 100,000) were examined for non-Hispanic White (NHW) and Hispanic adults. RESULTS: The total age-adjusted HCC incidence rate increased significantly between 2009-2012 and then declined significantly between 2012-2017. Across nearly all years, age-adjusted HCC incidence in Hispanic adults was twice that of NHW adults. Hispanic adults were more likely to be diagnosed at a later stage across all time periods. The disparity in 3-year age-adjusted HCC incidence rate between NHW and Hispanic adults decreased between 2009-2017. CONCLUSION: Whe total age-adjusted HCC incidence rate increased significantly between 2009-2012 and then declined significantly between 2012-2017. Across nearly all years, age-adjusted HCC incidence in Hispanic adults was twice that of NHW adults. Hispanic adults were more likely to be diagnosed at a later stage across all time periods. The disparity in 3-year age-adjusted HCC incidence rate between NHW and Hispanic adults decreased between 2009-2017.

Evaluation of Timing of Antimicrobial Surgical Prophylaxis on Rates of Surgical Site Infections.

Background: Surgical site infections (SSIs) are common healthcare-associated infections, and national guidelines recommend that antimicrobial prophylaxis (AP) be administered 60 min prior to incision. However, there are limited data regarding the "most optimal" time for administration within the 60-min window. Patients and Methods: This was a multicenter, retrospective study of adult (≥18-year-old) patients that underwent an abdominal hysterectomy, colorectal surgery, or craniotomy and received AP within 60 min of incision. Incidence of SSI was compared between patients who received AP 0-30 versus 31-60 min of incision. In addition, a predefined subgroup analysis evaluated incidence of SSI for 15-min intervals within the 60-min timeframe. Results: Of the 277 patients included in the primary analysis, 233 (84.1%) and 44 (15.9%) received AP 0-30 min and 31-60 min prior to incision, respectively. SSIs were documented in 6.0% (14/233) versus 4.5% (2/44) of patients in the primary analysis (p = 0.703). In the secondary analysis, 137 (49.5%), 95 (34.3%), 34 (12.3%), and 11 (4.0%) patients received AP 0-15, 16-30, 31-45, and 46-60 min prior to incision, respectively. There was no difference in incidence of SSIs among the 15-min intervals (4.4% vs. 8.4% vs. 2.9% vs. 9.1%, p = 0.487). Of the 16 patients in this study that incurred a SSI, 5 patients had positive cultures, of which 3 contained bacteria that proved to be resistant to the antibiotic used for AP. Conclusions: The results of our analysis support current national guidelines. Future investigation of different intervals (e.g., AP 15-45 min prior to incision) may be beneficial on the basis of pharmacokinetics of routinely prescribed AP.

High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats.

Obesity, associated with the intake of a high-fat diet (HFD), and anxiety are common among those living in modern urban societies. Recent studies suggest a role of microbiome-gut-brain axis signaling, including a role for brain serotonergic systems in the relationship between HFD and anxiety. Evidence suggests the gut microbiome and the serotonergic brain system together may play an important role in this response. Here we conducted a nine-week HFD protocol in male rats, followed by an analysis of the gut microbiome diversity and community composition, brainstem serotonergic gene expression (tph2, htr1a, and slc6a4), and anxiety-related defensive behavioral responses. We show that HFD intake decreased alpha diversity and altered the community composition of the gut microbiome in association with obesity, increased brainstem tph2, htr1a and slc6a4 mRNA expression, including in the caudal part of the dorsomedial dorsal raphe nucleus (cDRD), a subregion previously associated with stress- and anxiety-related behavioral responses, and, finally, increased anxiety-related defensive behavioral responses. The HFD increased the Firmicutes/Bacteroidetes ratio relative to control diet, as well as higher relative abundances of Blautia, and decreases in Prevotella. We found that tph2, htr1a and slc6a4 mRNA expression were increased in subregions of the dorsal raphe nucleus in the HFD, relative to control diet. Specific bacterial taxa were associated with increased serotonergic gene expression in the cDRD. Thus, we propose that HFD-induced obesity is associated with altered microbiome-gut-serotonergic brain axis signaling, leading to increased anxiety-related defensive behavioral responses in rats.

Exoskeleton-based exercises for overground gait and balance rehabilitation in spinal cord injury: a systematic review of dose and dosage parameters.

BACKGROUND: Exoskeletons are increasingly applied during overground gait and balance rehabilitation following neurological impairment, although optimal parameters for specific indications are yet to be established. OBJECTIVE: This systematic review aimed to identify dose and dosage of exoskeleton-based therapy protocols for overground locomotor training in spinal cord injury/disease. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items Systematic Reviews and Meta-Analyses guidelines. A literature search was performed using the CINAHL Complete, Embase, Emcare Nursing, Medline ALL, and Web of Science databases. Studies in adults with subacute and/or chronic spinal cord injury/disease were included if they reported (1) dose (e.g., single session duration and total number of sessions) and dosage (e.g., frequency of sessions/week and total duration of intervention) parameters, and (2) at least one gait and/or balance outcome measure. RESULTS: Of 2,108 studies identified, after removing duplicates and filtering for inclusion, 19 were selected and dose, dosage and efficacy were abstracted. Data revealed a great heterogeneity in dose, dosage, and indications, with overall recommendation of 60-min sessions delivered 3 times a week, for 9 weeks in 27 sessions. Specific protocols were also identified for functional restoration (60-min, 3 times a week, for 8 weeks/24 sessions) and cardiorespiratory rehabilitation (60-min, 3 times a week, for 12 weeks/36 sessions). CONCLUSION: This review provides evidence-based best practice recommendations for overground exoskeleton training among individuals with spinal cord injury/disease based on individual therapeutic goals - functional restoration or cardiorespiratory rehabilitation. There is a need for structured exoskeleton clinical translation studies based on standardized methods and common therapeutic outcomes.

Maternal age effects on offspring lifespan and reproduction vary within a species.

Across diverse taxa, offspring from older mothers have decreased lifespan and fitness. Little is known about the extent to which maternal age effects vary among genotypes for a given species, however, except for studies of a few arthropod species. To investigate the presence and degree of intraspecific variability in maternal age effects, we compared lifespan, reproductive schedule, and lifetime reproductive output of offspring produced by young, middle-aged, and old mothers in four strains of rotifers in the Brachionus plicatilis species complex. We found significant variability among strains in the magnitude and direction of maternal age effects on offspring life history traits. In one strain, offspring of young mothers lived 20% longer than offspring of old mothers, whereas there were no significant effects of maternal age on lifespan for other strains. Depending on strain, advanced maternal age had positive effects, negative effects, or no effect on lifetime reproductive output. Across strains, older mothers produced offspring that had higher maximum daily reproduction early in life. The effects of maternal age on offspring vital rates could not be explained by changes in trade-offs between lifespan and reproduction. This study documents intraspecific variability in maternal age effects in an additional clade. Investigating intraspecific variability is critical for understanding the ubiquity of maternal age effects and their role in the evolution of life history and aging.

Are extra locking bolts or fibular plating more important in extreme nailing of distal tibia fractures? A cadaveric biomechanical analysis.

OBJECTIVES: In far-distal extra-articular tibia fracture "extreme" nailing, debate surrounds the relative biomechanical performance of plating the fibula compared with extra distal interlocks. This study aimed to evaluate several constructs for extreme nailing including one interlock (one medial-lateral interlock), one interlock + plate (one medial-lateral interlock with lateral fibula compression plating), and two interlocks (one medial-lateral interlock and one anterior-posterior interlock). METHODS: Fifteen pairs of fresh cadaver legs were instrumented with a tibial nail to the physeal scar. A 1 cm segment of bone was resected from the distal tibia 3.5 cm from the joint and an oblique osteotomy was made in the distal fibula. We loaded specimens with three different distal fixation constructs (one interlock, one interlock + plate, and two interlocks) through 10,000 cycles form 100N-700 N of axial loading. Load to failure (Newtons), angulation and displacement were also measured. RESULTS: Mean load to failure was 2092 N (one interlock), 1917 N (one interlock + plate), and 2545 N (two interlocks). Linear mixed effects modeling demonstrated that two interlocks had a load to failure 578 N higher than one interlock alone (95 % CI, 74N-1082 N; P = 0.02), but demonstrated no significant difference between one interlock and one interlock + plate. No statistically significant difference in rates or timing of displacement >2 mm or angulation >10° were demonstrated. CONCLUSIONS: When nailing far-distal extra-articular tibia and fibula fractures, adding a second interlock provides more stability than adding a fibular plate. Distal fibula plating may have minimal biomechanical effect in extreme nailing.

A compendium of multi-omics data illuminating host responses to lethal human virus infections.

Human infections caused by viral pathogens trigger a complex gamut of host responses that limit disease, resolve infection, generate immunity, and contribute to severe disease or death. Here, we present experimental methods and multi-omics data capture approaches representing the global host response to infection generated from 45 individual experiments involving human viruses from the Orthomyxoviridae, Filoviridae, Flaviviridae, and Coronaviridae families. Analogous experimental designs were implemented across human or mouse host model systems, longitudinal samples were collected over defined time courses, and global multi-omics data (transcriptomics, proteomics, metabolomics, and lipidomics) were acquired by microarray, RNA sequencing, or mass spectrometry analyses. For comparison, we have included transcriptomics datasets from cells treated with type I and type II human interferon. Raw multi-omics data and metadata were deposited in public repositories, and we provide a central location linking the raw data with experimental metadata and ready-to-use, quality-controlled, statistically processed multi-omics datasets not previously available in any public repository. This compendium of infection-induced host response data for reuse will be useful for those endeavouring to understand viral disease pathophysiology and network biology.