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Sökning: WFRF:(Leff R.)

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  • Brachi, B., et al. (författare)
  • Plant genetic effects on microbial hubs impact host fitness in repeated field trials
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
  • Tidskriftsartikel (refereegranskat)abstract
    • Although complex interactions between hosts and microbial associates are increasingly well documented, we still know little about how and why hosts shape microbial communities in nature. In addition, host genetic effects on microbial communities vary widely depending on the environment, obscuring conclusions about which microbes are impacted and which plant functions are important. We characterized the leaf microbiota of 200 Arabidopsis thaliana genotypes in eight field experiments and detected consistent host effects on specific, broadly distributed microbial species (operational taxonomic unit [OTUs]). Host genetic effects disproportionately influenced central ecological hubs, with heritability of particular OTUs declining with their distance from the nearest hub within the microbial network. These host effects could reflect either OTUs preferentially associating with specific genotypes or differential microbial success within them. Host genetics associated with microbial hubs explained over 10% of the variation in lifetime seed production among host genotypes across sites and years. We successfully cultured one of these microbial hubs and demonstrated its growth-promoting effects on plants in sterile conditions. Finally, genome-wide association mapping identified many putatively causal genes with small effects on the relative abundance of microbial hubs across sites and years, and these genes were enriched for those involved in the synthesis of specialized metabolites, auxins, and the immune system. Using untargeted metabolomics, we corroborate the consistent association between variation in specialized metabolites and microbial hubs across field sites. Together, our results reveal that host genetic variation impacts the microbial communities in consistent ways across environments and that these effects contribute to fitness variation among host genotypes. 
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  • Brady, MC, et al. (författare)
  • Precision rehabilitation for aphasia by patient age, sex, aphasia severity, and time since stroke? A prespecified, systematic review-based, individual participant data, network, subgroup meta-analysis
  • 2022
  • Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 17:10, s. 1067-1077
  • Tidskriftsartikel (refereegranskat)abstract
    • Stroke rehabilitation interventions are routinely personalized to address individuals’ needs, goals, and challenges based on evidence from aggregated randomized controlled trials (RCT) data and meta-syntheses. Individual participant data (IPD) meta-analyses may better inform the development of precision rehabilitation approaches, quantifying treatment responses while adjusting for confounders and reducing ecological bias. Aim: We explored associations between speech and language therapy (SLT) interventions frequency (days/week), intensity (h/week), and dosage (total SLT-hours) and language outcomes for different age, sex, aphasia severity, and chronicity subgroups by undertaking prespecified subgroup network meta-analyses of the RELEASE database. Methods: MEDLINE, EMBASE, and trial registrations were systematically searched (inception-Sept2015) for RCTs, including ⩾ 10 IPD on stroke-related aphasia. We extracted demographic, stroke, aphasia, SLT, and risk of bias data. Overall-language ability, auditory comprehension, and functional communication outcomes were standardized. A one-stage, random effects, network meta-analysis approach filtered IPD into a single optimal model, examining SLT regimen and language recovery from baseline to first post-intervention follow-up, adjusting for covariates identified a-priori. Data were dichotomized by age (⩽/> 65 years), aphasia severity (mild–moderate/ moderate–severe based on language outcomes’ median value), chronicity (⩽/> 3 months), and sex subgroups. We reported estimates of means and 95% confidence intervals. Where relative variance was high (> 50%), results were reported for completeness. Results: 959 IPD (25 RCTs) were analyzed. For working-age participants, greatest language gains from baseline occurred alongside moderate to high-intensity SLT (functional communication 3-to-4 h/week; overall-language and comprehension > 9 h/week); older participants’ greatest gains occurred alongside low-intensity SLT (⩽ 2 h/week) except for auditory comprehension (> 9 h/week). For both age-groups, SLT-frequency and dosage associated with best language gains were similar. Participants ⩽ 3 months post-onset demonstrated greatest overall-language gains for SLT at low intensity/moderate dosage (⩽ 2 SLT-h/week; 20-to-50 h); for those > 3 months, post-stroke greatest gains were associated with moderate-intensity/high-dosage SLT (3–4 SLT-h/week; ⩾ 50 hours). For moderate–severe participants, 4 SLT-days/week conferred the greatest language gains across outcomes, with auditory comprehension gains only observed for ⩾ 4 SLT-days/week; mild–moderate participants’ greatest functional communication gains were associated with similar frequency (⩾ 4 SLT-days/week) and greatest overall-language gains with higher frequency SLT (⩾ 6 days/weekly). Males’ greatest gains were associated with SLT of moderate (functional communication; 3-to-4 h/weekly) or high intensity (overall-language and auditory comprehension; (> 9 h/weekly) compared to females for whom the greatest gains were associated with lower-intensity SLT (< 2 SLT-h/weekly). Consistencies across subgroups were also evident; greatest overall-language gains were associated with 20-to-50 SLT-h in total; auditory comprehension gains were generally observed when SLT > 9 h over ⩾ 4 days/week. Conclusions: We observed a treatment response in most subgroups’ overall-language, auditory comprehension, and functional communication language gains. For some, the maximum treatment response varied in association with different SLT-frequency, intensity, and dosage. Where differences were observed, working-aged, chronic, mild–moderate, and male subgroups experienced their greatest language gains alongside high-frequency/intensity SLT. In contrast, older, moderate–severely impaired, and female subgroups within 3 months of aphasia onset made their greatest gains for lower-intensity SLT. The acceptability, clinical, and cost effectiveness of precision aphasia rehabilitation approaches based on age, sex, aphasia severity, and chronicity should be evaluated in future clinical RCTs.
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  • Öhlin, Axel, 1990, et al. (författare)
  • Protocol for a multicenter prospective cohort study evaluating arthroscopic and non-surgical treatment for microinstability of the hip joint
  • 2022
  • Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Microinstability of the hip joint is a proposed cause of hip pain and reduced function in young individuals. The underlying mechanism is thought to be extraphysiological hip motion due to bony deficiency and/or soft tissue deficiency or decreased soft tissue function. Recently, the condition has gained increased attention, and despite the fact that treatment today includes both non-surgical and surgical approaches, there is limited evidence on diagnostic specificity and treatment effects. The aim of this study is to evaluate clinical outcomes of both nonsurgical and surgical treatment for microinstability of the hip joint. Methods: A multicenter prospective cohort study is planned to evaluating the outcome of physical therapy aimed at stabilizing the hip joint, as well as arthroscopic plication of the hip joint capsule, if the physical therapy fails. Outcomes will be evaluated using hip-specific patient-reported outcome measures: the short version of the International Hip Outcome Tool and the Copenhagen Hip and Groin Outcome Score, strength and function tests, health-related quality of life as determined using the European Quality of Life-5 Dimensions and the European Quality of Life-Visual Analog Scale, sports activity levels according to the Hip Sport Activity Scale, and reported complications. Patients will be evaluated at 6, 12 and 24 months after each treatment. Discussion: It is important to evaluate the clinical outcomes of both non-surgical and surgical treatment for suspected microinstability of the hip joint, and the planned prospective evaluation will contribute to the understanding of non-surgical as well as surgical treatment outcomes, including complications.
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  • Bates, Scott T., et al. (författare)
  • Meeting Report: Fungal ITS Workshop (October 2012)
  • 2013
  • Ingår i: Standards in Genomic Sciences. - : Springer Science and Business Media LLC. - 1944-3277. ; 8:1, s. 118-123
  • Tidskriftsartikel (refereegranskat)abstract
    • This report summarizes a meeting held in Boulder, CO USA (19–20 October 2012) on fungal community analyses using ultra-high-throughput sequencing of the internal transcribed spacer (ITS) region of the nuclear ribosomal RNA (rRNA) genes. The meeting was organized as a two-day workshop, with the primary goal of supporting collaboration among researchers for improving fungal ITS sequence resources and developing recommendations for standard ITS primers for the research community.
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