Category: Statistics

mSystems. 2022 Jul 12:e0034822. doi: 10.1128/msystems.00348-22. Online ahead of print.

ABSTRACT

Microbial tolerance to organic solvents such as ionic liquids (ILs) is a robust phenotype beneficial for novel biotransformation. While most microbes become inhibited in 1% to 5% (vol/vol) IL (e.g., 1-ethyl-3-methylimidazolium acetate), we engineered a robust Yarrowia lipolytica strain (YlCW001) that tolerates a record high of 18% (vol/vol) IL via adaptive laboratory evolution. Yet, genotypes conferring high IL tolerance in YlCW001 remain to be discovered. In this study, we shed light on the underlying cellular processes that enable robust Y. lipolytica to thrive in inhibitory ILs. By using dynamic transcriptome sequencing (RNA-Seq) data, we introduced Gene Coexpression Connectivity (GeCCo) as a metric to discover genotypes conferring desirable phenotypes that might not be found by the conventional differential expression (DE) approaches. GeCCo selects genes based on their number of coexpressed genes in a subnetwork of upregulated genes by the target phenotype. We experimentally validated GeCCo by reverse engineering a high-IL-tolerance phenotype in wild-type Y. lipolytica. We found that gene targets selected by both DE and GeCCo exhibited the best statistical chance at increasing IL tolerance when individually overexpressed. Remarkably, the best combination of dual-overexpression genes was genes selected by GeCCo alone. This nonintuitive combination of genes, BRN1 and OYE2, is involved in guiding/regulating mitotic cell division, chromatin segregation/condensation, microtubule and cytoskeletal organization, and Golgi vesicle transport. IMPORTANCE Cellular robustness to cope with stressors is an important phenotype. Y. lipolytica is an industrial robust oleaginous yeast that has recently been discovered to tolerate record high concentrations of ILs, beneficial for novel biotransformation in organic solvents. However, genotypes that link to IL tolerance in Y. lipolytica are largely unknown. Due to the complex IL-tolerant phenotype, conventional gene discovery and validation based on differential gene expression approaches are time-consuming due to a large search space and might encounter a high false-discovery rate. Here, using the developed Gene Coexpression Connectivity (GeCCo) method, we identified and validated a subset of most promising gene targets conferring the IL-tolerant phenotypes and shed light on their potential mechanisms. We anticipate GeCCo being a useful method to discover the genotype-to-phenotype link.

PMID:35862814 | DOI:10.1128/msystems.00348-22

mSystems. 2022 Jul 18:e0012022. doi: 10.1128/msystems.00120-22. Online ahead of print.

ABSTRACT

Pathogenic fungal infections in plants may, in some cases, lead to downstream systematic impacts on the plant metabolome and microbiome that may either alleviate or exacerbate the effects of the fungal pathogen. While Sphaerulina musiva is a well-characterized fungal pathogen which infects Populus tree species, an important wood fiber and biofuel feedstock, little is known about its systematic effects on the metabolome and microbiome of Populus. Here, we investigated the metabolome of Populus trichocarpa and Populus deltoides leaves and roots and the microbiome of the leaf and root endospheres, phylloplane, and rhizosphere to understand the systematic impacts of S. musiva abundance and infection on Populus species in a common garden field setting. We found that S. musiva is indeed present in both P. deltoides and P. trichocarpa, but S. musiva abundance was not statistically related to stem canker onset. We also found that the leaf and root metabolomes significantly differ between the two Populus species and that certain leaf metabolites, particularly the phenolic glycosides salirepin and salireposide, are diminished in canker-infected P. trichocarpa trees compared to their uninfected counterparts. Furthermore, we found significant associations between the metabolome, S. musiva abundance, and microbiome composition and α-diversity, particularly in P. trichocarpa leaves. Our results show that S. musiva colonizes both resistant and susceptible hosts and that the effects of S. musiva on susceptible trees are not confined to the site of canker infection. IMPORTANCE Poplar (Populus spp.) trees are ecologically and economically important trees throughout North America. However, many western North American poplar plantations are at risk due to the introduction of the nonnative fungal pathogen Sphaerulina musiva, which causes leaf spot and cankers, limiting their production. To better understand the interactions among the pathogen S. musiva, the poplar metabolome, and the poplar microbiome, we collected leaf, root, and rhizosphere samples from poplar trees consisting of 10 genotypes and two species with differential resistance to S. musiva in a common garden experiment. Here, we outline the nuanced relationships between the poplar metabolome, microbiome, and S. musiva, showing that S. musiva may affect poplar trees in tissues distal to the site of infection (i.e., stem). Our research contributes to improving the fundamental understanding of S. musiva and Populus sp. ecology and the utility of a holobiont approach in understanding plant disease.

PMID:35862808 | DOI:10.1128/msystems.00120-22

Am J Bot. 2022 Jul 21. doi: 10.1002/ajb2.16040. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Antheridiogen systems are a set of pheromonal mechanisms that control sex expression in fern gametophytes. However, antheridiogen has rarely been studied outside of the laboratory and little is known about its function in natural settings. Combining predictions based on field and laboratory study, we test if the sexual structure of tree fern gametophyte colonies is attributable to antheridiogen.

METHODS: Gametophyte colonies of the antheridiogen-producing tree fern species Cyathea multiflora were collected at La Selva Biological Station in Costa Rica in January 2019. The sex of each gametophyte was determined, mapped, and spatial statistic approaches were used to examine the distribution of sex in each colony.

KEY RESULTS: In all gametophyte colonies, males were most common, representing 62%-68% of individuals. No hermaphroditic gametophytes were identified in any colony. A quadrat-based method showed female gametophytes were not clustered in each colony while male gametophytes were clustered. In two of the colonies, the K(r) test statistic for males was greater than expected compared to random simulations of sex, indicating male sex expression was spatially associated with females.

CONCLUSIONS: This study provides the first documentation of spatial sex expression in natural gametophyte settings of an antheridiogen-producing tree fern species. The profound impact of antheridiogen on gametophyte sex expression in field settings suggests this system is intimately tied to mating system, fitness, and genetic diversity in Cyathea multiflora. This article is protected by copyright. All rights reserved.

PMID:35862812 | DOI:10.1002/ajb2.16040

mSphere. 2022 Jul 11:e0029422. doi: 10.1128/msphere.00294-22. Online ahead of print.

NO ABSTRACT

PMID:35862806 | DOI:10.1128/msphere.00294-22

Antimicrob Agents Chemother. 2022 Jul 6:e0224421. doi: 10.1128/aac.02244-21. Online ahead of print.

ABSTRACT

Reduction of Clostridioides difficile infection (CDI) recurrence is an essential endpoint for CDI-directed antibiotic development that is often not evaluated until Phase III trials. The purpose of this project was to use a functional and metagenomic approach to predict the potential anti-CDI recurrence effect of ibezapolstat, a DNA polymerase IIIC inhibitor, in clinical development for CDI. As part of the Phase I ibezapolstat clinical study, stool samples were collected from 22 healthy volunteers, who were given either ibezapolstat or vancomycin. Stool samples were evaluated for microbiome changes and bile acid concentrations. Ibezapolstat 450 mg and vancomycin, but not ibezapolstat 300 mg, showed statistically significant changes in alpha diversity over time compared to that of a placebo. Beta diversity changes confirmed that microbiota were significantly different between study groups. Vancomycin had a more wide-ranging effect on the microbiome, characterized by an increased proportion of Gammaproteobacteria. Ibezapolstat demonstrated an increased proportion of Actinobacteria, including the Bifidobacteriaceae family. Using a linear regression analysis, vancomycin was associated with significant increases in primary bile acids as well as primary:secondary bile acid ratios. An overabundance of Enterobacteriaceae was most highly correlated with primary bile acid concentrations (r = 0.63; P < 0.0001). Using Phase I healthy volunteer samples, beneficial changes suggestive of a lower risk of CDI recurrence were associated with ibezapolstat compared to vancomycin. This novel omics approach may allow for better and earlier prediction of anti-CDI recurrence effects for antibiotics in the clinical development pipeline.

PMID:35862742 | DOI:10.1128/aac.02244-21

Am J Sports Med. 2022 Jul 21:3635465221108975. doi: 10.1177/03635465221108975. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with femoroacetabular impingement syndrome (FAIS) may frequently have co-existing sacroiliac joint (SIJ) pain. It is known that patients with lower back pain undergoing total hip arthroplasty (THA) have inferior outcomes; however, it is unclear what the effect of SIJ pain is on outcomes after hip arthroscopy.

PURPOSE: To determine whether patients undergoing hip arthroscopy with SIJ pain either subjectively or on physical examination achieve similar postoperative improvement in patient-reported outcomes (PROs) compared with patients without SIJ pain at 2-year follow-up.

STUDY DESIGN: Cohort study; Level of evidence, 3.

METHODS: Patients with a minimum 2-year follow-up who underwent primary hip arthroscopy for FAIS with SIJ pain were matched in a 1:2 ratio to controls without SIJ pain. Baseline demographics, as well as postoperative PROs and rates of achievement of the minimal clinically important difference (MCID) or Patient Acceptable Symptom State (PASS) at 2-year follow-up were compared between the 2 groups.

RESULTS: A total of 73 patients (75 hips) with SIJ pain were matched to 150 control patients (150 hips) without SIJ pain. Both groups demonstrated statistically significant improvement in all PROs at 2 years (P < .05 for all). Patients with SIJ pain had significantly lower postoperative PRO scores for the Hip Outcome Score-Activities of Daily Living (HOS-ADL) (SIJ pain: 80.4 ± 22.4 vs no SIJ pain: 88.0 ± 15.1; P = .006), modified Harris Hip Score (mHHS) (SIJ pain: 73.2 ± 22.8 vs no SIJ pain: 80.0 ± 17.3; P < .001), and International Hip Outcome Tool-12 questionnaire (iHOT-12) (SIJ pain: 61.7 ± 25.9 vs no SIJ pain: 73.7 ± 23.7; P = .008). There were no statistically significant differences in improvement (delta) in PRO scores between the 2 groups (P > .05 for all). The SIJ pain group had significantly lower achievement of MCID for the HOS-ADL (SIJ pain: 65.2% vs no SIJ pain: 80.5%; P = .044) but not HOS-SS, mHHS, or iHOT-12 (P > .05 for all). The SIJ pain group had significantly lower achievement of PASS for the mHHS (SIJ pain: 27.5% vs no SIJ pain: 45.3%; P = .030) and iHOT-12 (SIJ pain: 31.0% vs no SIJ pain: 56.0%; P = .010) but not the HOS-ADL and HOS-SS (P > .05 for both). Only 4.1% of patients with SIJ pain and 2.4% of controls required revision surgery or converted to THA at the time of final follow-up (P = .69).

CONCLUSION: Patients with FAIS and SIJ pain on history or physical examination experience significant improvement in PROs at 2 years after hip arthroscopy. However, they may be less likely to achieve the MCID or PASS and have significantly lower postoperative PROs compared with a matched cohort of patients without SIJ pain. Overall rates of revision and conversion to THA were similarly low in both groups.

PMID:35862645 | DOI:10.1177/03635465221108975

J Physician Assist Educ. 2022 Jul 20. doi: 10.1097/JPA.0000000000000454. Online ahead of print.

ABSTRACT

INTRODUCTION: The purpose of this study was to conduct an innovative seminar that was developed by using clips from the television program ER to teach/reinforce key concepts of effective communication for didactic phase physician assistant (PA) students.

METHODS: Interactive, 2-hour, small group seminars were conducted as part of the PA curriculum. Demographic data, as well as information about prior exposure to medical-related television shows and interest in specific medical disciplines, were collected at baseline. The evaluation of this unconventional teaching strategy was completed via a post-activity self-administered, electronic survey. Descriptive statistics were calculated for closed-ended questions, and a thematic analysis approach was used to examine open-ended questions.

RESULTS: Approximately two-thirds (n = 49) of the students who attended the seminars completed both the baseline and post-activity surveys. The seminars were well-received, with 94% of respondents indicating they would like to participate in similar trainings in the future. The primary suggestion was to use clips from multiple television programs.

DISCUSSION: The results suggest that this instructional format was highly acceptable to modern PA students, who yearn for an amalgamation of education and entertainment. Future work could examine the influence of the seminar on students’ communication in clinical environments.

PMID:35862632 | DOI:10.1097/JPA.0000000000000454

Am J Sports Med. 2022 Jul 21:3635465221107371. doi: 10.1177/03635465221107371. Online ahead of print.

ABSTRACT

BACKGROUND: Arthroscopic rotator cuff repair is an effective procedure through which to decrease pain and increase strength, with favorable long-term outcomes demonstrated in older patient populations with full-thickness rotator cuff tears. The long-term outcomes after this procedure in younger, higher-demand patients, however, is not as clearly defined.

PURPOSE: To report on the long-term outcomes after arthroscopic rotator cuff repair of traumatic full-thickness rotator cuff tears in active duty military patients under the age of 40 years at the time of surgery.

STUDY DESIGN: Case series; Level of evidence, 4.

METHODS: Preoperative, midterm, and final evaluations were collected, including scores on the visual analog scale for pain, Single Assessment Numeric Evaluation, and American Shoulder and Elbow Surgeons shoulder form. A total of 42 patients were screened for inclusion: 3 underwent additional surgical procedures on the operative shoulder and 2 were lost to follow-up, leaving 37 patients with mean follow-up of 104.51 months available for analysis. A subgroup analysis was performed comparing outcomes between patients with Southern California Orthopaedic Institute grade 1 or 2 tears and those with grade 3 or 4 tears.

RESULTS: At final follow-up, pain per the visual analog scale decreased to 1.16 from 8.03 (P < .0001); the Single Assessment Numeric Evaluation score increased to 87.32 from 48.24 (P < .0001); and the American Shoulder and Elbow Surgeons score increased to 88.68 from 41.00 (P < .0001). There was no statistically significant difference in outcome scores or range of motion between midterm and final follow-up. Improvement in outcome scores and range of motion at final follow-up did not vary between patients with small and large tears. Of 42 patients, 37 (88.1%) were able to return to full unrestricted active duty and sporting activity, while 5 (11.9%) were medically separated from the military.

CONCLUSION: Active duty military patients under the age of 40 years with traumatic full-thickness rotator cuff tears had statistically and clinically significant increases in outcome scores and decreases in pain after arthroscopic rotator cuff repair at long-term follow-up.

PMID:35862618 | DOI:10.1177/03635465221107371

J Asthma. 2022 Jul 21:1-20. doi: 10.1080/02770903.2022.2103429. Online ahead of print.

ABSTRACT

Objective: The aim of this study is to review the effects of aerobic exercise on asthma control and quality of life in adult patient populations.:Data Sources: Randomized controlled trials and prospective studies published between January 2012 and April 2022 were searched in Scopus, Web of Science, and PubMed databases.:Study Selections: We followed pre-specified inclusion criteria and excluded manuscripts that studied pediatric populations and those that did not study asthma control or quality of life. We included ten randomized controlled trials and four prospective studies from a combined 2286 search results.:Results: Of the included studies, all but three studies found significant improvement in asthma control and quality of life after aerobic intervention. The method of measuring aerobic intervention varied among the studies. Statistical significance was consistent among studies that used maximal heart rate and peak power output to measure intervention.Conclusion: Aerobic exercise intervention can improve asthma control and quality of life in both the acute and chronic response phase. Aerobic activity can be measured by various methods, but in this review, there were no significant adverse events with activity. Higher quality studies are necessary to confirm these results.

PMID:35862617 | DOI:10.1080/02770903.2022.2103429

Am J Nurs. 2022 Aug 1;122(8):24-33. doi: 10.1097/01.NAJ.0000854488.48801.59.

ABSTRACT

BACKGROUND: Treatment-resistant schizophrenia (TRS) comes with significant medical comorbidities, including heart disease, liver disease, and diabetes-all of which contribute to higher mortality rates and shortened life expectancy. Second-generation antipsychotic medications do not consistently alleviate psychotic symptoms, especially among patients with TRS. Clozapine, the gold standard of pharmacological treatment for TRS, offers only partial relief for many patients. Additional treatment approaches, which include cognitive behavioral therapy (CBT), are often necessary.

PURPOSE: The aim of this integrative review was to assess the efficacy of CBT as an adjunctive treatment for TRS in various study populations.

METHODS: The Johns Hopkins Nursing Evidence-Based Practice Model and Guidelines were used to guide the review. A literature search of PubMed, CINAHL, Scopus, and PsycInfo was conducted, and a total of 66 articles were identified. Strong inclusion and exclusion criteria were applied to ensure that only high-quality studies were included for analysis.

RESULTS: Of the eight studies that met the eligibility criteria, five indicated that CBT has statistically significant efficacy in reducing positive psychotic symptoms of TRS. There was also evidence that in implementing CBT, a follow-up period of at least six months helps to sustain improvements.

CONCLUSIONS: CBT can be a safe and effective adjunctive treatment for patients with this illness. We recommend that nurses who work in psychiatric settings, EDs, and home health or community care settings obtain training in CBT.

PMID:35862601 | DOI:10.1097/01.NAJ.0000854488.48801.59