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| 2. |
- Mulder, Renée L., et al.
(författare)
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Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer : recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group
- 2021
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 22:2, s. 68-80
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Forskningsöversikt (refereegranskat)abstract
- Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.
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| 3. |
- Milham, Michael P., et al.
(författare)
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An Open Resource for Non-human Primate Imaging
- 2018
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 100:1, s. 61-74
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Tidskriftsartikel (refereegranskat)abstract
- Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets.
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| 4. |
- Aleksandrova, Elena V, et al.
(författare)
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Structural basis of Cfr-mediated antimicrobial resistance and mechanisms for its evasion
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The ribosome is an essential drug target as many classes of clinically important antibiotics bind and inhibit its functional centers. The catalytic peptidyl transferase center (PTC) is targeted by the broadest array of inhibitors belonging to several chemical classes. One of the most abundant and clinically prevalent mechanisms of resistance to PTC-acting drugs is C8-methylation of the universally conserved adenine residue 2503 (A2503) of the 23S rRNA by the methyltransferase Cfr. Despite its clinical significance, a sufficient understanding of the molecular mechanisms underlying Cfr-mediated resistance is currently lacking. In this work, we developed a method to express a functionally-active Cfr-methyltransferase in the thermophilic bacterium Thermus thermophilus and report a set of high-resolution structures of the Cfr-modified 70S ribosome containing aminoacyl- and peptidyl-tRNAs. Our structures reveal that an allosteric rearrangement of nucleotide A2062 upon Cfr-methylation of A2503 is likely responsible for the inability of some PTC inhibitors to bind to the ribosome, providing additional insights into the Cfr resistance mechanism. Lastly, by determining the structures of the Cfr-methylated ribosome in complex with the antibiotics iboxamycin and tylosin, we provide the structural bases behind two distinct mechanisms of evading Cfr-mediated resistance.
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| 5. |
- Aleksandrova, Elena V., et al.
(författare)
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Structural basis of Cfr-mediated antimicrobial resistance and mechanisms to evade it
- 2024
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Ingår i: Nature Chemical Biology. - : Springer Nature. - 1552-4450 .- 1552-4469.
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Tidskriftsartikel (refereegranskat)abstract
- The bacterial ribosome is an essential drug target as many clinically important antibiotics bind and inhibit its functional centers. The catalytic peptidyl transferase center (PTC) is targeted by the broadest array of inhibitors belonging to several chemical classes. One of the most abundant and clinically prevalent resistance mechanisms to PTC-acting drugs in Gram-positive bacteria is C8-methylation of the universally conserved A2503 nucleobase by Cfr methylase in 23S ribosomal RNA. Despite its clinical importance, a sufficient understanding of the molecular mechanisms underlying Cfr-mediated resistance is currently lacking. Here, we report a set of high-resolution structures of the Cfr-modified 70S ribosome containing aminoacyl- and peptidyl-transfer RNAs. These structures reveal an allosteric rearrangement of nucleotide A2062 upon Cfr-mediated methylation of A2503 that likely contributes to the reduced potency of some PTC inhibitors. Additionally, we provide the structural bases behind two distinct mechanisms of engaging the Cfr-methylated ribosome by the antibiotics iboxamycin and tylosin.
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| 7. |
- Field, Dawn, et al.
(författare)
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The minimum information about a genome sequence (MIGS) specification.
- 2008
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Ingår i: Nature biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 26:5, s. 541-7
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Tidskriftsartikel (refereegranskat)abstract
- With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the 'transparency' of the information contained in existing genomic databases.
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| 8. |
- Kelvin, Elizabeth A., et al.
(författare)
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Evaluating effect modification by HIV testing history to understand the mechanisms behind the impact of announcing HIV self-testing availability in a clinic system in Kenya
- 2023
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Ingår i: Frontiers in Public Health. - : Frontiers Media SA. - 2296-2565. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: In sub-Saharan Africa, truckers and female sex workers (FSWs) have high HIV risk and face challenges accessing HIV testing. Adding HIV self-testing (HIVST) to standard of care (SOC) programs increases testing rates. However, the underlying mechanisms are not fully understood. HIVST may decrease barriers (inconvenient clinic hours, confidentiality concerns) and thus we would expect a greater impact among those not accessing SOC testing (barriers prevented previous testing). As a new biomedical technology, HIVST may also be a cue to action (the novelty of a new product motivates people to try it), in which case we might expect the impact to be similar by testing history. Methods: We used data from two randomized controlled trials evaluating the announcement of HIVST availability via text-message to male truckers (n = 2,260) and FSWs (n = 2,196) in Kenya. Log binomial regression was used to estimate the risk ratio (RR) for testing ≤ 2 months post-announcement in the intervention vs. SOC overall and by having tested in the previous 12-months (12m-tested); and we assessed interaction between the intervention and 12m-tested. We also estimated risk differences (RD) per 100 and tested additive interaction using linear binomial regression. Results: We found no evidence that 12m-tested modified the HIVST impact. Among truckers, those in the intervention were 3.1 times more likely to test than the SOC (p < 0.001). Although testing was slightly higher among those not 12m-tested (RR = 3.5, p = 0.001 vs. RR = 2.7, p = 0.020), the interaction was not significant (p = 0.683). Among FSWs, results were similar (unstratified RR = 2.6, p < 0.001; 12m-tested: RR = 2.7, p < 0.001; not 12m-tested: RR = 2.5, p < 0.001; interaction p = 0.795). We also did not find significant interaction on the additive scale (truckers: unstratified RD = 2.8, p < 0.001; 12m-tested RD = 3.8, p = 0.037; not 12m-tested RD = 2.5, p = 0.003; interaction p = 0.496. FSWs: unstratified RD = 9.7, p < 0.001; 12m-tested RD = 10.7, p < 0.001, not 12m-tested RD = 9.1, p < 0.001; interaction p = 0.615). Conclusion: The impact of HIVST was not significantly modified by 12m-tested among truckers and FSWs on the multiplicative or additive scales. Announcing the availability of HIVST likely served primarily as a cue to action and testing clinics might maximize the HIVST benefits by holding periodic HIVST events to maintain the cue to action impact rather than making HIVST continually available.
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| 9. |
- Mantell, Joanne E., et al.
(författare)
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Preferences, beliefs, and attitudes about oral fluid and blood-based HIV self-testing among truck drivers in Kenya choosing not to test for HIV
- 2022
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Ingår i: Frontiers in Public Health. - : Frontiers Media SA. - 2296-2565. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Clinical trials in sub-Saharan Africa support that HIV self-testing (HIVST) can increase testing rates in difficult-to-reach populations. However, trials mostly evaluate oral fluid HIVST only. We describe preferences for oral fluid vs. blood-based HIVST to elucidate prior trial results and inform testing programs. Methods: Participants were recruited from a HIVST randomized controlled trial in Nakuru County, Kenya, which aimed to test the effect of choice between oral HIVST and facility-based testing compared to standard-of-care on HIV testing among truck drivers. We conducted in-depth interviews (IDIs) with purposively sampled trial participants who declined HIV testing at baseline or who were offered access to oral fluid HIVST and chose not to pick up the kit during follow-up. IDIs were conducted with all consenting participants. We first describe IDI participants compared to the other study participants, assessing the statistical significance of differences in characteristics between the two samples and then describe preferences, beliefs, and attitudes about HIVST biospecimen type expressed in the IDIs. Results: The final sample consisted of 16 men who refused HIV testing at baseline and 8 men who did not test during follow-up. All IDI participants had tested prior to study participation; mean number of years since last HIV test was 1.55, vs. 0.98 among non-IDI participants (p = 0.093). Of the 14 participants who answered the question about preferred type of HIVST, nine preferred blood-based HIVST, and five, oral HIVST. Preference varied by study arm with four of five participants who answered this question in the Choice arm and five of nine in the SOC arm preferring blood-based HIVST. Six key themes characterized truckers' views about test type: (1) Rapidity of return of test results. (2) Pain and fear associated with finger prick. (3) Ease of use. (4) Trust in test results; (5) fear of infection by contamination; and (6) Concerns about HIVST kit storage and disposal. Conclusion: We found no general pattern in the themes for preference for oral or blood-based HIVST, but if blood-based HIVST had been offered, some participants in the Choice arm might have chosen to self-test. Offering choices for HIVST could increase testing uptake.
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| 10. |
- Wang, Fang, et al.
(författare)
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Emerging contaminants: A One Health perspective
- 2024
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Ingår i: Innovation. - 2666-6758. ; 5
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Forskningsöversikt (refereegranskat)abstract
- Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.
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