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  • Oxford University Press (OUP)  (6)
  • 1
    Online Resource
    Online Resource
    Compassionate Use of Bacteriophages for Failed Persistent Infections During the First 5 Years of the Israeli Phage Therapy Center
    Oxford University Press (OUP) ; 2023
    In:  Open Forum Infectious Diseases Vol. 10, No. 5 ( 2023-05-03)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 10, No. 5 ( 2023-05-03)
    Abstract: The use of bacteriophages (phages) is reemerging as a potential treatment option for antibiotic-resistant or nonresolving bacterial infections. Phages are bacteria-specific viruses that may serve as a personalized therapeutic option with minimal collateral damage to the patient or the microbiome. In 2018 we established the Israeli Phage Therapy Center (IPTC) as a shared initiative of the Hadassah Medical Center and the Hebrew University of Jerusalem, aiming to conduct all of the steps required for phage-based solutions, from phage isolation and characterization to treatments, for nonresolving bacterial infections. So far, a total of 159 requests for phage therapy arrived to the IPTC; 145 of them were from Israel and the rest from other countries. This number of registered requests is growing annually. Multidrug-resistant bacteria accounted for 38% of all phage requests. Respiratory and bone infections were the most prevalent among clinical indications and accounted for 51% of the requests. To date, 20 phage therapy courses were given to 18 patients by the IPTC. In 77.7% (n = 14) of the cases, a favorable clinical outcome of infection remission or recovery was seen. Clearly, establishing an Israeli phage center has led to an increased demand for compassionate use of phages with favorable outcomes for many previously failed infections. As clinical trials are still lacking, publishing patient data from cohort studies is pertinent to establish clinical indications, protocols, and success and failure rates. Last, workflow processes and bottlenecks should be shared to enable faster availability and authorization of phages for clinical use.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofad221
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2757767-3
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  • 2
    Online Resource
    Online Resource
    The multi-allelic APRR2 gene is associated with fruit pigment accumulation in melon and watermelon
    Oxford University Press (OUP) ; 2019
    In:  Journal of Experimental Botany Vol. 70, No. 15 ( 2019-08-07), p. 3781-3794
    Details
    In: Journal of Experimental Botany, Oxford University Press (OUP), Vol. 70, No. 15 ( 2019-08-07), p. 3781-3794
    Abstract: Color and pigment contents are important aspects of fruit quality and consumer acceptance of cucurbit crops. Here, we describe the independent mapping and cloning of a common causative APRR2 gene regulating pigment accumulation in melon and watermelon. We initially show that the APRR2 transcription factor is causative for the qualitative difference between dark and light green rind in both crops. Further analyses establish the link between sequence or expression level variations in the CmAPRR2 gene and pigment content in the rind and flesh of mature melon fruits. A genome-wide association study (GWAS) of young fruit rind color in a panel composed of 177 diverse melon accessions did not result in any significant association, leading to an earlier assumption that multiple genes are involved in shaping the overall phenotypic variation in this trait. Through resequencing of 25 representative accessions and allelism tests between light rind accessions, we show that multiple independent single nucleotide polymorphisms in the CmAPRR2 gene are causative of the light rind phenotype. The multi-haplotypic nature of this gene explains the lack of detection power obtained through genotyping by sequencing-based GWAS and confirms the pivotal role of this gene in shaping fruit color variation in melon. This study demonstrates the power of combining bi- and multi-allelic designs with deep sequencing, to resolve lack of power due to high haplotypic diversity and low allele frequencies. Due to its central role and broad effect on pigment accumulation in fruits, the APRR2 gene is an attractive target for carotenoid bio-fortification of cucurbit crops.
    Type of Medium: Online Resource
    ISSN: 0022-0957 , 1460-2431
    URL: Article
    DOI: 10.1093/jxb/erz182
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1466717-4
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Post-Selection Estimation and Testing Following Aggregate Association Tests
    Oxford University Press (OUP) ; 2019
    In:  Journal of the Royal Statistical Society Series B: Statistical Methodology Vol. 81, No. 3 ( 2019-07-01), p. 547-573
    Details
    In: Journal of the Royal Statistical Society Series B: Statistical Methodology, Oxford University Press (OUP), Vol. 81, No. 3 ( 2019-07-01), p. 547-573
    Abstract: The practice of pooling several individual test statistics to form aggregate tests is common in many statistical applications where individual tests may be underpowered. Although selection by aggregate tests can serve to increase power, the selection process invalidates inference based on the individual test statistics, making it difficult to identify those that drive the signal in follow-up inference. Here, we develop a general approach for valid inference following selection by aggregate testing. We present novel powerful post-selection tests for the individual null hypotheses which are exact for the normal model and asymptotically justified otherwise. Our approach relies on the ability to characterize the distribution of the individual test statistics after conditioning on the event of selection. We provide efficient algorithms for computation of the post-selection maximum likelihood estimates and suggest confidence intervals which rely on a novel switching regime for good coverage guarantees. We validate our methods via comprehensive simulation studies and apply them to data from the Dallas Heart Study, demonstrating that single-variant association discovery following selection by an aggregate test is indeed possible in practice.
    Type of Medium: Online Resource
    ISSN: 1369-7412 , 1467-9868
    URL: Article
    DOI: 10.1111/rssb.12318
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 204795-0
    detail.hit.zdb_id: 1490719-7
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  • 4
    Online Resource
    Online Resource
    Underground heterosis for yield improvement in melon
    Oxford University Press (OUP) ; 2021
    In:  Journal of Experimental Botany Vol. 72, No. 18 ( 2021-09-30), p. 6205-6218
    Details
    In: Journal of Experimental Botany, Oxford University Press (OUP), Vol. 72, No. 18 ( 2021-09-30), p. 6205-6218
    Abstract: Heterosis, the superiority of hybrids over their parents, is a major genetic force associated with plant fitness and crop yield enhancement. We investigated root-mediated yield heterosis in melons (Cucumis melo) by characterizing a common variety grafted onto 190 hybrid rootstocks, resulting from crossing 20 diverse inbreds in a diallel-mating scheme. Hybrid rootstocks improved yield by more than 40% compared with their parents, and the best hybrid yield outperformed the reference commercial variety by 65% under both optimal and minimal irrigation treatments. To characterize the genetics of underground heterosis we conducted whole genome re-sequencing of the 20 founder lines, and showed that parental genetic distance was no predictor for the level of heterosis. Through inference of the 190 hybrid genotypes from their parental genomes, followed by genome-wide association analysis, we mapped multiple quantitative trait loci for root-mediated yield. Yield enhancement of the four best-performing hybrid rootstocks was validated in multiple experiments with four different scion varieties. Our grafting approach is complementary to the common roots genetic approach that focuses mainly on variation in root system architecture, and is a step towards discovery of candidate genes involved in root function and yield enhancement.
    Type of Medium: Online Resource
    ISSN: 0022-0957 , 1460-2431
    URL: Article
    DOI: 10.1093/jxb/erab219
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1466717-4
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Management and outcome of patients with non-ST elevation myocardial infarction and intercurrent non-coronary precipitating events
    Oxford University Press (OUP) ; 2022
    In:  European Heart Journal. Acute Cardiovascular Care Vol. 11, No. 12 ( 2022-12-27), p. 922-930
    Details
    In: European Heart Journal. Acute Cardiovascular Care, Oxford University Press (OUP), Vol. 11, No. 12 ( 2022-12-27), p. 922-930
    Abstract: To evaluate the effect of an intercurrent non-coronary illness on the management and outcome of patients with non-ST-segment elevation myocardial infarction (NSTEMI). Methods and results Consecutive hospitalized patients with a primary diagnosis of NSTEMI between August 2008 and December 2019 at Sheba Medical Center. All patients’ records were reviewed for the presence of a non-coronary precipitating event (NCPE): a major intercurrent acute non-coronary illness or condition, either cardiac or non-cardiac. The primary outcome was all-cause mortality. Cox regression with interaction analysis was applied. Final study population comprised 6491 patients, of whom 2621 (40%) had NCPEs. Patients with NCPEs were older (77 vs. 69 years) and more likely to have comorbidities. The most prevalent event was infection (35%, n = 922). During a median follow-up of 30 months, 2529 patients died. Patients with NCPEs were 43% more likely to die during follow-up in a multivariable model (95% CI: 1.31–1.55). Invasive strategy was associated with a 55% lower mortality among patients without NCPE and only 44% among patients with NCPE (P for interaction & lt; 0.001). Dual antiplatelet therapy (DAPT) was associated with a 20% lower mortality in patients without NCEP and a non-significant mortality difference among patients with NCPE (P for interaction = 0.014). Sub-analysis by the specific NCPE showed the highest mortality risk among patients with infectious precipitant. The lower mortality associated with invasive strategy was not observed in this subgroup. Conclusion Among NSTEMI patients, the presence of an NCPE is associated with poor survival and modifies the effect of management strategies.
    Type of Medium: Online Resource
    ISSN: 2048-8726 , 2048-8734
    URL: Article
    DOI: 10.1093/ehjacc/zuac134
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2663340-1
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  • 6
    Online Resource
    Online Resource
    A Kelch domain-containing F-box coding gene negatively regulates flavonoid accumulation in Cucumis melo L.
    Oxford University Press (OUP) ; 2015
    In:  Plant Physiology
    Details
    In: Plant Physiology, Oxford University Press (OUP)
    Type of Medium: Online Resource
    ISSN: 0032-0889 , 1532-2548
    URL: Article
    DOI: 10.1104/pp.15.01008
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 2004346-6
    detail.hit.zdb_id: 208914-2
    SSG: 12
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