bluuebunny/crossref_metadata_2025_split huggingface dataset:
The first established microsatellite markers to distinguish
Candida orthopsilosis
isolates and detection of a nosocomial outbreak in China
Authors: Luo Zhengyu , Ning Yating , Yu Shuying , Xiao Meng , Dai Rongchen , Chen Xinfei , Wang Yao , Kang Wei , Jiang Yan , Yu Hua , Liang Hongjie , Xu Yingchun , Sun Tianshu , Zhang Li 
Published: October 2023

ABSTRACT

The infection proportion of
Candida orthopsilosis
, a member of the
C. parapsilosis
complex, has increased globally in recent years, and nosocomial outbreaks have been reported in several countries. This study aimed to establish microsatellite loci-based typing method that was able to effectively distinguish among
C. orthopsilosis
isolates. Three reference
C. orthopsilosis
genome sequences were analyzed to identify repeat loci. DNA sequences containing over eight bi- or more nucleotide repeats were selected. A total of 51 loci were initially identified, and locus-specific primers were designed and tested with 20 epidemiologically unrelated isolates. Four loci with excellent reproducibility, specificity, and resolution for molecular typing purposes were identified, and the combined discriminatory power (DP, based on 20 epidemiologically unrelated isolates) of these four loci was 1.0. Reproducibility was demonstrated by consistently testing three strains each in triplicate, and stability, demonstrated by testing 10 successive passages. Then, we collected 48
C
.
orthopsilosis
non-duplicate clinical isolates from the China Hospital Invasive Fungal Surveillance Net study to compare the DP of the microsatellite-based typing with internal transcribed spacer (ITS) and amplified fragment length polymorphism (AFLP) typing analyses, using ATCC 96139 as a reference strain. These 49 isolates were subdivided into 12 microsatellite types (COMT1–12), six AFLP types, and three ITS types, while all the isolates with the same COMT belonged to consistent AFLP and ITS type, demonstrating the high DP of our microsatellite-type method. According to our results, COMT12 was found to be the predominant type in China, and COMT5 was the second largest and responsible for causing a nosocomial outbreak. This microsatellite-type method is a valuable tool for the differentiation of
C. orthopsilosis
and could be vital for epidemiological studies to determine strain relatedness and monitor transmission.
Developing scientific literacy with a cyclic independent study assisted CURE detecting SARS-CoV-2 in wastewater
Authors: Dye Kristine 
Published: October 2023

ABSTRACT
The COVID-19 pandemic has exposed a high level of scientific illiteracy and mistrust that pervades the scientific and medical communities. This finding has proven the necessity of updating current methods used to expose undergraduates to research. The research in traditional course-based undergraduate research experiences (CUREs) is limited by undergraduate time constraints, skill level, and course structure, and consequently it does not attain the learning objectives or the high-impact, relevant studies achieved in graduate-level laboratories using a cyclic trainee/trainer model. Although undergraduate independent study (ISY) research more closely matches the structure and learning objectives of graduate-level research, they are uncommon as professors and universities typically view them as a significant time and resource burden with limited return. Cyclic independent study-assisted CUREs (CIS-CUREs) combine many positive aspects of ISY graduate-level research, and CUREs by pre-training ISY research lead to facilitate CURE proposal and project semesters in a cyclic model. The CIS-CURE approach allowed undergraduate students at Stetson University to perform and disseminate more rigorous, involved, long-term, and challenging research projects, such as the surveillance of SARS-CoV-2 in wastewater. In doing so, all students would have the opportunity to participate in a high-impact research project and consequently gain a more comprehensive training, reach higher levels of research dissemination, and increase their competitiveness after graduating. Together, CIS-CUREs generate graduates with higher scientific literacy and thus combat scientific mistrust in communities.
The protein phosphatase PPKL is a key regulator of daughter parasite development in
Toxoplasma gondii
Authors: Yang Chunlin , Doud Emma H. , Sampson Emily , Arrizabalaga Gustavo 
Published: October 2023

ABSTRACT

Apicomplexan parasites, including
Toxoplasma gondii
, encode many plant-like proteins, which play significant roles and present attractive targets for drug development. In this study, we have characterized the plant-like protein phosphatase PPKL, which is unique to the parasite and absent in its mammalian host. We have shown that its localization changes as the parasite divides. In non-dividing parasites, it is present in the cytoplasm, nucleus, and preconoidal region. As the parasite begins division, PPKL is enriched in the preconoidal region and the cortical cytoskeleton of nascent parasites. Later in the division, PPKL is present in the basal complex ring. Conditional knockdown of PPKL showed that it is essential for parasite propagation. Moreover, parasites lacking PPKL exhibit uncoupling of division, with normal DNA duplication but severe defects in forming daughter parasites. While PPKL depletion does not impair the duplication of centrosomes, it affects the stability of cortical microtubules. Both co-immunoprecipitation and proximity labeling identified the kinase DYRK1 as a potential functional partner of PPKL. Complete knockout of
DYRK1
causes parasites to exhibit division defects with predominantly asynchronous divisions. Global phosphoproteomics analysis revealed a significant increase in phosphorylation of the microtubule-associated protein SPM1 in PPKL-depleted parasites, suggesting that PPKL regulates cortical microtubules by mediating the phosphorylation state of SPM1. More importantly, the phosphorylation of cell cycle-associated kinase Crk1, a known regulator of daughter cell assembly, is altered in PPKL-depleted parasites. Thus, we propose that PPKL regulates daughter parasite development by influencing the Crk1-dependent signaling pathway.

IMPORTANCE

Toxoplasma gondii
can cause severe disease in immunocompromised or immunosuppressed patients and during congenital infections. Treating toxoplasmosis presents enormous challenges since the parasite shares many biological processes with its mammalian hosts, which results in significant side effects with current therapies. Consequently, proteins that are essential and unique to the parasite represent favorable targets for drug development. Interestingly,
Toxoplasma
, like other members of the phylum Apicomplexa, has numerous plant-like proteins, many of which play crucial roles and do not have equivalents in the mammalian host. In this study, we found that the plant-like protein phosphatase PPKL appears to be a key regulator of daughter parasite development. With the depletion of PPKL, the parasite shows severe defects in forming daughter parasites. This study provides novel insights into the understanding of parasite division and offers a new potential target for the development of antiparasitic drugs.
Count Me In: an inclusive approach towards patient recruitment for clinical research studies in the NHS
Authors: Hinze Verena , Henshall Catherine , Smith Tanya , Littlejohns Jemima , Collett Zoe , Jones Helen , Maughan Daniel , Ede Roger , Moll Deborah , Marlowe Karl , Broughton Nick , Geddes John , Cipriani Andrea 
Published: October 2023

BackgroundParticipation in clinical research is associated with better patient outcomes and higher staff retention and satisfaction rates. Nevertheless, patient recruitment to mental health studies is challenging due to a reliance on clinician or patient referrals (standard approach). To empower patients and make healthcare research more equitable, we explored a novel researcher-led approach, called ‘Count Me In’ (CMI).ObjectiveTo evaluate a 12-month implementation of CMI in a routine clinical setting.MethodsCMI was launched in August 2021 in a mental health National Health Service (NHS) Trust in England. Patients (aged 18+) learnt about CMI at their initial clinical appointment. Unless they opted out, they became contactable for research (via research informatics searches).FindingsAfter 12 months, 368 patients opted out and 22 741 became contactable through CMI, including 2716 through the standard approach and 20 025 through electronic searches (637% increase). Of those identified via electronic searches, 738 were contacted about specific studies and 270 consented to participate. Five themes were identified based on patient and staff experiences of CMI: ‘level of awareness and accessibility of CMI’, ‘perceptions of research and perceived engagement with CMI’, ‘inclusive research practice’, ‘engagement and incentives for research participation’, and ‘relationships between clinical and research settings’.ConclusionsCMI (vs standard) led to a larger and diverse patient cohort and was favoured by patients and staff. Yet a shift in the NHS research culture is needed to ensure that this diversity translates to actual research participation.Clinical implicationsThrough collaboration with other NHS Trusts and services, key funders (National Institute for Health and Care Research) and new national initiatives (Office for Life Sciences Mental Health Mission), CMI has the potential to address recruitment challenges through rapid patient recruitment into time-sensitive country-wide studies.
Plant-based diets and the incidence of cardiovascular disease: the Million Veteran Program
Authors: Li Yanping , Wang Dong D , Nguyen Xuan-Mai T , Song Rebecca J , Ho Yuk-Lam , Hu Frank B , Willett Walter C , Wilson Peter W F , Cho Kelly , Gaziano John Michael , Djousse Luc 
Published: October 2023

BackgroundA healthful plant-based diet was associated with lower risks of coronary heart disease and type 2 diabetes, and a favourable profile of adiposity-associated biomarkers, while an unhealthful plant-based diet was associated with elevated risk of cardiometabolic disease in health professional populations. However, little is known about the associations between plant-based dietary patterns and risk of cardiovascular disease (CVD) in US veterans.MethodsThe study population consisted of 148 506 participants who were free of diabetes, CVD and cancer at baseline in the Veterans Affairs (VA) Million Veteran Program. Diet was assessed using a Food Frequency Questionnaire at baseline. We calculated an overall Plant-Based Diet Index (PDI), a healthful PDI (hPDI) and an unhealthful PDI (uPDI). The CVD endpoints included non-fatal myocardial infarction (MI) and acute ischaemic stroke (AIS) identified through high-throughput phenotyping algorithms approach and fatal CVD events identified by searching the National Death Index.ResultsWith up to 8 years of follow-up, we documented 5025 CVD cases. After adjustment for confounding factors, a higher PDI was significantly associated with a lower risk of CVD (HR comparing extreme quintiles=0.75, 95% CI 0.68 to 0.82, Ptrend<0.0001). We observed an inverse association between hPDI and the risk of CVD (HR comparing extreme quintiles=0.71, 95% CI 0.64 to 0.78, Ptrend<0.001), whereas uPDI was positively associated with the risk of CVD (HR comparing extreme quintiles=1.12, 95% CI 1.02 to 1.24, Ptrend<0.001). We found similar associations of hPDI with subtypes of CVD; a 10-unit increment in hPDI was associated with HRs (95% CI) of 0.81 (0.75 to 0.87) for fatal CVD, 0.86 (0.79 to 0.94) for non-fatal MI and 0.86 (0.78 to 0.95) for non-fatal AIS.ConclusionsPlant-based dietary pattern enriched with healthier plant foods was associated with a substantially lower CVD risk in US veterans.
Efficacy and safety of therapeutic HPV vaccines to treat CIN 2/CIN 3 lesions: a systematic review and meta-analysis of phase II/III clinical trials
Authors: Ibrahim Khalil Ahmadaye , Zhang Li , Muwonge Richard , Sauvaget Catherine , Basu Partha 
Published: October 2023

ObjectivesWe aim to assess the efficacy and safety of therapeutic human papillomavirus (HPV) vaccines to treat cervical intraepithelial neoplasia of grade 2 or 3 (CIN 2/3).DesignSystematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.Data sourcesPubMed, Embase, Web of Science, Global Index Medicus and CENTRAL Cochrane were searched up to 31 January 2022.Eligibility criteriaPhase II/III randomised controlled trials (RCTs) and single-arm studies reporting the efficacy of therapeutic vaccines to achieve regression of CIN 2/3 lesions were included. Studies evaluating only safety and side effects of the vaccine were excluded.Data extraction and synthesisTwo independent reviewers extracted data and evaluated study quality. A random-effect model was used to pool the proportions of regression and/or HPV clearance.Results12 trials met the inclusion criteria. Out of 734 women (all studies considered) receiving therapeutic HPV vaccine for CIN 2/3, 414 regressed to normal/CIN 1 with an overall proportion of regression of 0.54 (95% CI 0.39 to 0.69) for vaccinated group; 166 women (from five RCTs) receiving placebo only achieving a pooled normal/CIN 1 regression of 0.27 (95% CI 0.20 to 0.34). When including only the five two-arm studies, the regression proportion for the 410 vaccine group participants was higher than that of the 166 control group participants (relative risk (RR) 1.52; 95% CI 1.14 to 2.04). The pooled proportion of high-risk human papillomavirus (hrHPV) clearance was 0.42 (95% CI 0.32 to 0.52) in the vaccine group (six studies with a total of 357 participants) and 0.17 (95% CI 0.11 to 0.26) in the control group (three RCTs with a total of 104 participants). Based on these three RCTs, the hrHPV clearance was significantly higher in the vaccinated group (250 participants) compared with the control group (RR 2.03; 95% CI 1.30 to 3.16). Similar results were found regarding HPV 16/18 clearance. No significant unsolicited adverse events have been consistently reported.ConclusionsThe efficacy of the therapeutic vaccines in the treatment of CIN 2/3 was modest. Implementation issues such as feasibility, acceptability, adoption and cost-effectiveness need to be further studied.PROSPERO registration numberCRD42022307418.
Evaluation of the safety status of intrahospital transfer of critically ill patients from the perspective of emergency and ICU nurses: a cross-sectional study in Iran
Authors: Hashemian Maryam , Salami Zahra , Azizpour Islam , Mirzaei Alireza 
Published: October 2023

ObjectiveCritically ill patients often require intrahospital transfer (IHT) for diagnostic and therapeutic procedures. However, this process carries potential risks and can harm the patient’s safety. This study aimed to assess the safety of IHT for critically ill patients by gathering feedback from emergency and intensive care unit (ICU) nurses.DesignA cross-sectional study.SettingA study was conducted in Ardabil City, Iran’s educational and medical hospitals. The study involved 288 emergency and ICU nurses. The data were collected through a paper-based form, which included demographic and work-related characteristics and an IHT safety scale.ResultsThe mean score of IHT was 75.2±15.53. The results of multiple regression analysis showed that work experience (B=0.291, p=0.011), perception of IHT safety (B=0.196, p=0.003), education level (B=−0.123, p=0.038) and equipment checker (B=−0.121, p=0.045), variables were the predictors of IHT safety.ConclusionThe study found that the safety level during the interhospital transfer (IHT) was low. Hospitals aim to create a safe environment that minimises the risks associated with IHT. Therefore, they must identify potential risks during the transfer process and take necessary measures to mitigate them. Practical strategies that can be employed include using experienced nursing staff, conducting equipment checks, ensuring a complete understanding of the tools and technologies involved in the transfer process, and increasing awareness of IHT safety.
A qualitative study exploring experiences of the safetxt digital health intervention to reduce sexually transmitted infections in young people in the UK
Authors: Berendes Sima , Gubijev Anasztazia , French Rebecca , Hickson Ford Colin Ian , Free Caroline 
Published: October 2023

ObjectivesPeople aged 16–24 are more likely than other age groups to acquire sexually transmitted infections (STI). Safetxt was a randomised controlled trial of a theory-based digital health intervention to reduce STIs among 16–24 year-old people in the UK. We report results of qualitative research regarding participants’ perceptions and experiences of the intervention and trial participation.DesignQualitative thematic analysis following a critical realist paradigm of written open feedback comments provided in the 12-month follow-up questionnaire and semistructured interviews.SettingSafetxt trial participants were recruited from UK sexual health clinics.ParticipantsTrial inclusion criteria: people aged 16–24 diagnosed with or treated for chlamydia, gonorrhoea or non-specific urethritis. Optional open feedback provided by 3526 of 6248 safetxt participants at 12 months and interviews with a purposive sample of 18 participants after the trial.ResultsWe summarise and report results in seven broad themes. According to recipients, the safetxt intervention increased awareness of the importance of avoiding STIs and ways to prevent them. Participants reported improved confidence, agency, sexual well-being and communication about sexual health with partners, friends and family. Recipients attributed increased condom use, increased STI testing after (rather than before) sex with new partners, and more confident partner notification to the intervention. Recipients described a reduced sense of isolation and stigma in having an STI. Control group participants reported that having had an STI and receiving control texts asking them to report any changes in contact details acted as reminders to use condoms and get tested. We also summarise participant recommendations for future interventions and studies.ConclusionsWhile control group participants reported precautionary behaviours were ‘triggered’ by trial participation, intervention recipients reported additional benefits of the intervention in increasing precautionary behaviours and in broader aspects of sexual health such as confidence, communication, emotional well-being and agency.Trial registrationISRCTN registryISRCTN64390461.
Exploring older care recipients’ sleep status as a predictor for informal carer distress: evidence from New Zealand’s interRAI home care assessment data
Authors: Gibson Rosemary , Abey-Nesbit Rebecca , Gander Philippa , Parsons Matthew 
Published: October 2023

ObjectivesUnderstanding factors affecting informal carers’ well-being is important to support healthy ageing at home. Sleep disturbances of care recipients are increasingly recognised as affecting the well-being of both parties. This research assesses the relationship between indicators of care recipients’ sleep status and carer distress, as well as carer distress with subsequent admission to residential aged care, using prospectively collected Home Care International Residential Assessment Instrument (interRAI-HC) assessment data.ParticipantsData were sourced from 127 832 assessments conducted between 2012 and 2019 for people aged 55 years or older who had support from at least one informal carer. The majority (59.4%) of care recipients were female and 59.1% were defined as having cognitive impairment or dementia (CIoD).SettingNew Zealand.DesignLogistic regression modelling was used to assess the independent relationships between indicators of care recipients’ sleep status (difficulty sleeping and fatigue) and primary caregivers’ distress (feeling overwhelmed or distressed). Kaplan meier curves illustrated the subsequent relationship between caregiver distress and care recipients’ transitions to aged residential care.ResultsCare recipients’ sleeping difficulty (32.4%) and moderate–severe fatigue (46.6%) were independently associated with caregiver distress after controlling for key demographic and health factors included in the assessment. Distress was reported by 39.9% of informal caregivers and was three times more likely among those supporting someone with a CIoD. Caregiver distress was significantly associated with care recipients’ earlier admission into aged residential care.ConclusionsIndicators of sleep disturbance among care recipients are associated with increased likelihood of carer distress. This has implications for managing the overall home-care situation and long-term care needs, as well as the well-being of both parties. Findings will inform research and development of measures, services and interventions to improve the sleep and waking health of older people, including those with CIoD and family caregivers.
Clinical decision support tools for paediatric sepsis in resource-poor settings: an international qualitative study
Authors: Jimenez-Zambrano Andrea , Ritger Carly , Rebull Margaret , Wiens Matthew O , Kabajaasi Olive , Jaramillo-Bustamante Juan Camilo , Argent Andrew C , Kissoon Niranjan , Schlapbach Luregn J , Sorce Lauren R , Watson R Scott , Dorsey Holliman Brooke , Sanchez-Pinto Lazaro N , Bennett Tellen D 
Published: October 2023

ObjectiveNew paediatric sepsis criteria are being developed by an international task force. However, it remains unknown what type of clinical decision support (CDS) tools will be most useful for dissemination of those criteria in resource-poor settings. We sought to design effective CDS tools by identifying the paediatric sepsis-related decisional needs of multidisciplinary clinicians and health system administrators in resource-poor settings.DesignSemistructured qualitative focus groups and interviews with 35 clinicians (8 nurses, 27 physicians) and 5 administrators at health systems that regularly provide care for children with sepsis, April–May 2022.SettingHealth systems in Africa, Asia and Latin America, where sepsis has a large impact on child health and healthcare resources may be limited.ParticipantsParticipants had a mean age of 45 years, a mean of 15 years of experience, and were 45% female.ResultsEmergent themes were related to the decisional needs of clinicians caring for children with sepsis and to the needs of health system administrators as they make decisions about which CDS tools to implement. Themes included variation across regions and institutions in infectious aetiologies of sepsis and available clinical resources, the need for CDS tools to be flexible and customisable in order for implementation to be successful, and proposed features and format of an ideal paediatric sepsis CDS tool.ConclusionFindings from this study will directly contribute to the design and implementation of CDS tools to increase the uptake and impact of the new paediatric sepsis criteria in resource-poor settings.