Wellcome Open Research最新文献

{"title":"Therapeutic drug monitoring for antimicrobial agents for people living with HIV (TAP).","authors":"Christine Sekaggya-Wiltshire, Eva Agnes Laker Odongpiny, Francis Williams Ojara, Isabella Kyohairwe, Reuben Kiggundu, Hope Mackline, Catriona Waitt, Aida N Kawuma, Allan Kengo, Allan Buzibye, Noela Owarwo, Francis Kakooza, Andrew Kambugu","doi":"10.12688/wellcomeopenres.22707.2","DOIUrl":"10.12688/wellcomeopenres.22707.2","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance (AMR) is a growing health concern, particularly in Africa, and is predicted to become the leading cause of death after cancer by 2050. Factors like overuse or inappropriate use of antibiotics contribute to this crisis. People living with HIV (PLWH) are particularly vulnerable to AMR with potential drug-drug interactions between antiretroviral and antimicrobial agents against common organisms like <i>Mycobacterium tuberculosis.</i> There is limited data on the concentrations of commonly used antimicrobial agents in people living with HIV in resource-limited settings. Therapeutic Drug Monitoring (TDM) offers a promising approach to optimize antibiotic dosing and improve treatment outcomes for those with sub-optimal drug concentrations. TDM has been recommended for PLWH on anti-tuberculosis treatment due to sub-optimal drug concentrations found in a significant proportion of those with TB.</p><p><strong>Objectives: </strong>The main objectives of this study are to determine the concentrations of selected antimicrobial agents in people living with HIV requiring antimicrobial therapy and to assess the utility of therapeutic drug monitoring in achieving therapeutic targets for PLWH receiving rifampicin and isoniazid for the treatment of tuberculosis.</p><p><strong>Methods: </strong>This prospective observational study will enroll adult PLWH receiving amoxicillin, azithromycin, ciprofloxacin, rifampicin, isoniazid, or ceftriaxone. Concentrations of these antibiotics will be measured locally using validated liquid chromatography mass spectrometry methods and high-performance liquid chromatography with ultraviolet detection. TDM with dose adjustment will be performed in a subset of participants on TB treatment. Pharmacokinetic parameters will be estimated using non-linear mixed effects models.</p><p><strong>Results: </strong>This study was reviewed and approved by the research and ethics committee in February 2024. Participant enrolment began in September 2024.</p><p><strong>Conclusions: </strong>We anticipate that the findings from this research will characterize pharmacokinetic and pharmacodynamics relationships to predict treatment response for optimal antimicrobial therapeutic and anti-tuberculosis dosing among people living with HIV (PLWH).</p><p><strong>Clinical registration: </strong>The study is registered with Pan African Clinical Trials Registry, registration number PACTR202409710100607, registration date 07 August 2024, pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=31764.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"9 ","pages":"694"},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms through which exercise reduces symptom severity and/or functional impairment in posttraumatic stress disorder (PTSD): Protocol for a living systematic review of human and non-human studies.","authors":"Simonne Wright, Toshi A Furukawa, Malcolm Macleod, Ouma Simple, Olufisayo Elugbadebo, Virginia Chiocchia, Claire Friedrich, Edoardo G Ostinelli, Jennifer Potts, Fiona J Ramage, Spyridon Siafis, Claire Stainsfield, Francesca Tinsdeall, James Thomas, Andrea Cipriani, Georgia Salanti, Soraya Seedat","doi":"10.12688/wellcomeopenres.19903.3","DOIUrl":"10.12688/wellcomeopenres.19903.3","url":null,"abstract":"<p><strong>Background: </strong>Exercise can play an important role in reducing symptom severity and improving functional impairment in patients with posttraumatic stress disorder (PTSD). However, the precise mechanisms underpinning the effect of exercise in PTSD management are not fully understood. This living systematic review aims to synthesize and triangulate the evidence from non-human and human studies to gain insight into the biopsychosocial mechanisms through which exercise reduces symptom severity and functional impairment.</p><p><strong>Methods: </strong>Independent searches will be conducted in electronic databases to identify eligible studies. Two reviewers will independently conduct the study selection, data extraction, and risk of bias assessment. We will extract outcome data and variables that can act as effect modifiers or as mediators of the effect of exercise. For the non-human studies, outcome data will include the non-human equivalents of PTSD symptom clusters. For human studies, the primary outcome will be PTSD symptom severity. The secondary outcomes will be avoidance symptom severity, reexperiencing symptom severity, hyperarousal symptom severity, negative cognitions and mood severity, functional impairment, loss of PTSD diagnosis, and dropout rates.To explain the biopsychosocial mechanisms through which exercise affects the outcome of interest, we will extract effects that relate to the impact of exercise on potential mediating variables and the effect of the later outcomes. Comparison of within-study direct and indirect effects obtained from mediation analysis, when reported, will provide insight into the importance of the examined mediator.If appropriate, we will synthesize study results using meta-analyses. We will examine potential effect modifiers of the total exercise effect to understand better the impact of exercise on PTSD symptoms and function impairment (when possible). The evidence about the potential mediators of the association between exercise and PTSD-related outcomes will be considered in a consensus meeting when sufficient evidence is available.</p><p><strong>Protocol registration: </strong>PROSPERO-ID: 453615.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"8 ","pages":"494"},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genome sequence of a cluster fly, <i>Pollenia pediculata</i> Macquart, 1834.","authors":"Steven Falk, Liam M Crowley, Olga Sivell","doi":"10.12688/wellcomeopenres.23961.1","DOIUrl":"10.12688/wellcomeopenres.23961.1","url":null,"abstract":"<p><p>We present a genome assembly from a female specimen of <i>Pollenia pediculata</i> (cluster fly; Arthropoda; Insecta; Diptera; Polleniidae). The assembly contains two haplotypes with total lengths of 1,156.86 megabases and 1,222.48 megabases. Most of haplotype 1 (99.79%) is scaffolded into 6 chromosomal pseudomolecules. Haplotype 2 was assembled to scaffold level. The mitochondrial genome has also been assembled, with a length of 15.82 kilobases.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"10 ","pages":"190"},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZC3HC1 has functions distinct from TPR and is dispensable for TPR localisation to the nuclear basket.","authors":"Bethany M Bartlett, Juan Carlos Acosta, Wendy A Bickmore","doi":"10.12688/wellcomeopenres.23711.1","DOIUrl":"10.12688/wellcomeopenres.23711.1","url":null,"abstract":"<p><strong>Background: </strong>The nuclear basket is a 'fishtrap'-like structure on the nucleoplasmic face of the nuclear pore complex which has been implicated in diverse functions including RNA export, heterochromatin organisation, and mitosis. Recently, a novel component of the nuclear basket, ZC3HC1, has been described. The localisation of ZC3HC1 to nuclear pores has been reported to occur reciprocally with TPR, a major structural component of the nuclear basket.</p><p><strong>Methods: </strong>Using siRNA-mediated knock down, immunofluorescence and RNA sequencing we compare the consequences of depleting two proteins of the nuclear pore basket - TPR and ZC3HC1.</p><p><strong>Results: </strong>We show that in human fibroblasts, although ZC3HC1 localisation to nuclear pores is TPR-dependent, TPR localises to pores regardless of the presence of ZC3HC1. We demonstrate that knockdown of TPR and ZC3HC1 produce distinct transcriptional profiles.</p><p><strong>Conclusions: </strong>Our results suggest that there is little overlap in function between these two nuclear basket proteins in human diploid fibroblasts.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"10 ","pages":"188"},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12120416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genome sequence of the short-beaked common dolphin, <i>Delphinus delphis</i> Linnaeus, 1758.","authors":"Nicholas J Davison, Phillip A Morin","doi":"10.12688/wellcomeopenres.23918.1","DOIUrl":"https://doi.org/10.12688/wellcomeopenres.23918.1","url":null,"abstract":"<p><p>We present a genome assembly from a male specimen of <i>Delphinus delphis</i> (short-beaked common dolphin; Chordata; Mammalia; Artiodactyla; Delphinidae). The genome sequence has a total length of 2,663.52 megabases. Most of the assembly (88.76%) is scaffolded into 23 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled, with a length of 16.39 kilobases. Gene annotation of this assembly at Ensembl identified 17,797 protein-coding genes.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"10 ","pages":"178"},"PeriodicalIF":0.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genome sequence of the harbour porpoise, <i>Phocoena phocoena</i> (Linnaeus, 1758).","authors":"Nicholas J Davison, Phillip A Morin","doi":"10.12688/wellcomeopenres.24011.1","DOIUrl":"https://doi.org/10.12688/wellcomeopenres.24011.1","url":null,"abstract":"<p><p>We present a genome assembly from a female specimen of <i>Phocoena phocoena</i> (harbour porpoise; Chordata; Mammalia; Artiodactyla; Phocoenidae). The genome sequence has a total length of 2,512.71 megabases. Most of the assembly (94.41%) is scaffolded into 22 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled, with a length of 16.38 kilobases.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"10 ","pages":"181"},"PeriodicalIF":0.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genome sequence of a snail-killing fly, <i>Dichetophora obliterata</i> (Fabricius, 1805).","authors":"Liam M Crowley, Olga Sivell, Ryan Mitchell, Duncan Sivell","doi":"10.12688/wellcomeopenres.23993.1","DOIUrl":"10.12688/wellcomeopenres.23993.1","url":null,"abstract":"<p><p>We present a genome assembly from a female specimen of <i>Dichetophora obliterata</i> (snail-killing fly; Arthropoda; Insecta; Diptera; Sciomyzidae). The genome sequence has a total length of 1,312.79 megabases. Most of the assembly (99.78%) is scaffolded into 6 chromosomal pseudomolecules. The mitochondrial genome has also been assembled, with a length of 21.36 kilobases. Gene annotation of this assembly on Ensembl identified 15,139 protein-coding genes.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"10 ","pages":"176"},"PeriodicalIF":0.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genome sequence of long-finned pilot whale, <i>Globicephala melas</i> (Traill, 1809).","authors":"Nicholas J Davison, Phillip A Morin","doi":"10.12688/wellcomeopenres.23919.1","DOIUrl":"https://doi.org/10.12688/wellcomeopenres.23919.1","url":null,"abstract":"<p><p>We present a genome assembly from a male specimen of <i>Globicephala melas</i> (long-finned pilot whale; Chordata; Mammalia; Artiodactyla; Delphinidae). The genome sequence has a total length of 2,651.28 megabases. Most of the assembly (89.15%) is scaffolded into 23 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled, with a length of 16.39 kilobases. Gene annotation of this assembly on Ensembl identified 17,911 protein-coding genes.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"10 ","pages":"180"},"PeriodicalIF":0.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genome sequence of the European ground squirrel, <i>Spermophilus citellus</i> (Linnaeus, 1766).","authors":"Dimitra-Lida Rammou, Dionisios Youlatos, Alexandros Triantafyllidis","doi":"10.12688/wellcomeopenres.23974.1","DOIUrl":"10.12688/wellcomeopenres.23974.1","url":null,"abstract":"<p><p>We present a genome assembly from a female <i>Spermophilus citellus</i> (European ground squirrel; Chordata; Mammalia; Rodentia; Sciuridae). The genome sequence has a total length of 3,090.03 megabases. Most of the assembly (95.47%) is scaffolded into 20 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled, with a length of 16.45 kilobases.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"10 ","pages":"184"},"PeriodicalIF":0.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genome sequence of <i>Glossophaga mutica</i> (Chiroptera, Phyllostomidae, Glossophaginae; Merriam, 1898).","authors":"Nancy B Simmons, Melissa R Ingala, Brian P O'Toole, Linelle Abueg, Kirsty McCaffrey, Bonhwang Koo, Giulio Formenti, Erich D Jarvis, Myrtani Pieri, Meike Mai, Larry N Singh, Philge Philip, Laramie L Lindsey, Ning Zhang, Jonathan L Gray, Emma C Teeling, Sonja C Vernes","doi":"10.12688/wellcomeopenres.23611.1","DOIUrl":"10.12688/wellcomeopenres.23611.1","url":null,"abstract":"<p><p>We present a genome assembly from an individual female <i>Glossophaga mutica</i> (Chordata; Mammalia; Chiroptera; Phyllostomidae). The genome sequence is 2.13 in span. The majority of the assembly is scaffolded into 32 chromosomal pseudomolecules, with the X sex chromosome assembled.</p>","PeriodicalId":23677,"journal":{"name":"Wellcome Open Research","volume":"10 ","pages":"174"},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}