bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering meropenem persistence in
Acinetobacter baumannii
facilitates discovery of anti-persister activity of thymol
Authors: Hussain Arsalan , Bhando Timsy , Casius Ananth , Gupta Rinki , Pathania Ranjana 
Published: February 2025

ABSTRACT

Decades of antibiotic misuse have accelerated the emergence of multi- and extensively drug-resistant bacteria. Bacterial pathogens employ several strategies such as antibiotic resistance, tolerance, and biofilm formation in response to extreme environments and antibiotic stress. Another crucial survival mechanism involves the stochastic generation of bacterial subpopulations known as persisters, which can endure high concentrations of antibiotics. Upon removal of antibiotic stress, these subpopulations revert back to their original phenotype which links them to the relapse and recalcitrance of chronic infections, a significant problem in clinical settings. Persistent infections are particularly notable in
Acinetobacter baumannii
, a top-priority ESKAPE pathogen, where carbapenems serve as last-resort antibiotics. Several reports indicate the rising therapeutic failure of carbapenems due to persistence, underscoring the importance of developing anti-persister therapeutics. In this study, we explored the mechanisms of transient persister formation in
A. baumannii
against meropenem. Our investigation revealed significant changes in membrane properties and energetics in meropenem persisters of
A. baumannii
, including a noteworthy increase in tolerance to other antibiotics. This understanding guided the evaluation of an in-house collection of GRAS status compounds for their potential anti-persister activity. The compound thymol demonstrated remarkable inhibitory activity against meropenem persisters of
A. baumannii
and other ESKAPE pathogens. Further investigation revealed its impact on persister cell physiology, including efflux pump inhibition and disruption of cellular respiration. Given our results, we propose a compelling strategy where thymol could be employed either as a monotherapy or in combination with meropenem in anti-persister therapeutics.
A CURE lab in an introductory biology course has minimal impact on student outcomes, self-confidence, and preferences compared to a traditional lab
Authors: Mashintonio Andrew F. , Heineman Richard H. 
Published: February 2025

ABSTRACT

Course-based undergraduate research experiences (CUREs) have grown in popularity, particularly within introductory biology courses, to provide more students with authentic research experiences. CUREs have been shown to have many of the same positive effects as conventional research experiences; however, most assessments of CUREs lack an appropriate comparison group to evaluate their effectiveness. Here, we introduced a CURE into an introductory biology lab at a regional public university but maintained a traditional, “cookie-cutter” lab in half the lab sections over a 3-year period. We compared changes in test scores and survey responses, final lab and lecture scores, and D, F, withdrawal, and incomplete (DFWI) and retention rates between non-honors biology students in each group. While both groups showed significant improvement in test scores, only transfer students had significantly greater improvement in the CURE vs traditional lab. Students in both groups showed significant increases in self-confidence in some lab-related tasks, but differences in these changes were generally not significant between groups. There were no significant differences in final lecture score, lab score, DFWI rate, or retention rate. Factors affecting the lack of measured CURE success may include the type of CURE chosen, student career interests, and COVID-19; other positive impacts of the CURE may not have been captured by our measurements. This study demonstrates the importance of carefully choosing a CURE to match the student population, as well as assessing the CURE’s impact against a comparison group.
Large-scale genomic analysis reveals significant role of insertion sequences in antimicrobial resistance of
Acinetobacter baumannii
Authors: Xie Fei , Wang Lifeng , Li Song , Hu Long , Wen Yanhua , Li Xuming , Ye Kun , Duan Zhimei , Wang Qi , Guan Yuanlin , Zhang Ye , Shi Qiqi , Yang Jiyong , Xia Han , Xie Lixin 
Published: February 2025

ABSTRACT

Acinetobacter baumannii
, a prominent nosocomial pathogen renowned for its extensive resistance to antimicrobial agents, poses a significant challenge in the accurate prediction of antimicrobial resistance (AMR) from genomic data. Despite thorough researches on the molecular mechanisms of AMR, gaps remain in our understanding of key contributors. This study utilized rule-based and three machine learning models to predict AMR phenotypes, aiming to decipher key genomic factors associated with AMR. Genomes and antibiotic resistance phenotypes from 1,012 public isolates were employed for model construction and training. To validate the models, a data set comprising 164 self-collected strains underwent next-generation sequencing, nanopore long-read sequencing, and antimicrobial susceptibility testing using the broth dilution method. It was found that the presence of antibiotic resistance genes (ARGs) alone was insufficient to accurately predict AMR phenotype for the majority of antibiotics (90%, 18 out of 20) in the public data set. Conversely, it was observed that combining ARGs with insertion sequence (IS) elements significantly enhanced predictive performance. The Random Forest model was found to outperform the support vector machine (SVM), logistic regression model, and rule-based method across all 20 antibiotics, with accuracies ranging from 83.80% to 97.70%. In the validation data set, even higher accuracies were achieved, ranging from 85.63% to 99.31%. Furthermore, conserved sequence patterns between IS elements and ARGs were validated using self-collected long-read sequencing data, substantially enhancing the accuracy of AMR prediction in
A. baumannii
. This study underscores the pivotal role of IS elements in AMR.

IMPORTANCE

The interplay between insertion sequences (ISs) and antibiotic resistance genes (ARGs) in
Acinetobacter baumannii
contributes to resistance against specific antibiotics. Conventionally, genetic variations and ARGs have been utilized for predicting resistance phenotypes, with the potential pivotal role of IS elements largely overlooked. Our study advances this approach by integrating both rule-based and machine learning models to predict AMR in
A. baumannii
. This significantly enhances the accuracy of AMR prediction, emphasizing the pivotal function of IS elements in antibiotic resistance. Notably, we uncover a series of conserved sequence patterns linking IS elements and ARGs, which outperform ARGs alone in phenotypic prediction. Our findings are crucial for bioinformatics strategies aimed at studying and tracking AMR, offering novel insights into combating the escalating AMR challenge.
Cross-laboratory replication of pseudomyxoma peritonei tumor microbiome reveals reproducible microbial signatures
Authors: Nieciecki Victoria F. , Blum Faith C. , Johnson Ryan C. , Testerman Traci L. , McAvoy Tom J. , King Mary Caitlin , Gushchin Vadim , Whitmire Jeannette M. , Frey Kenneth G. , Glang Lindsay , Peña-Gomez Dessiree , Bishop-Lilly Kimberly A. , Sardi Armando , Merrell D. Scott , Metcalf Jessica L. 
Published: February 2025

ABSTRACT

Recent work has demonstrated that cancer-specific microbial communities often colonize tumor tissues. However, untangling low-biomass signals from environmental contamination makes this research technically challenging. We utilize pseudomyxoma peritonei (PMP), a cancer characterized by the spread of mucus-secreting cells throughout the peritoneal cavity, to develop a robust workflow for identifying reproducible tumor microbiomes. Typically originating from the rupture of an appendiceal tumor into the peritoneal cavity, metastasized tumors have been previously shown to harbor a core set of microbes. However, that work did not control for the potential contamination of these low microbial biomass samples. We expand upon these prior findings by characterizing the microbiome of 70 additional PMP tumors and six normal peritoneal control tissues along with appropriate laboratory controls. Additionally, DNA from a subset of 25 tissues was extracted and sequenced at an independent laboratory. We found evidence of reproducible microbial signatures between the replicates of six different PMP tumors that include a set of core taxa that may be introduced from surgical contamination, as well as patient-specific taxa that are also commonly implicated in colorectal cancer. In addition, preoperative chemotherapy treatment was found to reduce tumor microbiome diversity. Our findings demonstrate how independent sample replication can be a powerful approach to investigate low-biomass microbial communities associated with tumor tissues that will improve low microbial biomass research.

IMPORTANCE
Recent work has demonstrated that microbial communities colonize over 30 different types of tumor tissues. The origin of these communities and their possible involvement in carcinogenesis or cancer treatment outcomes remains an unclear, yet important area of research. A current major challenge in characterizing low-biomass, tumor-associated microbiomes is the introduction of environmental contamination during collection, handling, DNA extraction, PCR, and sequencing. Here, we provide a framework for replicating low-biomass tumor microbiome samples to help identify tumors with robust microbial signals and low background contamination. Using this replication approach, we show that pseudomyxoma peritonei (PMP) tumors host reproducible microbial communities, including organisms that have previously been associated with colorectal cancer. Incorporating sample replication into future tumor microbiome studies is a promising approach that will help identify robust signals and increase reproducibility in the field.
Exploring the value Australian community leaders see in a system dynamics model calibrated with local data: social norms and childhood obesity
Authors: Crielaard Loes , Brown Andrew D , Nicolaou Mary , Hayward Joshua , Stronks Karien , Allender Steven 
Published: February 2025

ObjectivesSystems approaches (SAs) seek to understand the dynamics behind system behaviour and formulate effective actions given these dynamics. In public health, SAs often rely on qualitative systems maps visualising factors and their interconnections, frequently developed through group model building. Quantitative system dynamics models (SDMs) can offer additional insights: SDMs can simulate how system behaviour would change if we were to make an adjustment to the system, in what-if scenarios. We explored what (added) value Australian community leaders involved in SAs see in an SDM for understanding a system and its behaviour.SettingThe Whole of Systems Trial of Prevention Strategies for Childhood Obesity (WHOSTOPS), a community-level collaboration between researchers and community leaders in South-Western Victoria, Australia.DesignWe calibrated an existing small and high-level SDM with local data from the WHOSTOPS communities, so that the simulations pertained to their local context. The SDM was developed to simulate potential interventions addressing either social norms regarding body weight or individual weight-related behaviour. We presented the SDM to the community leaders via an interactive interface in an online workshop.ParticipantsWe calibrated the SDM using WHOSTOPS’ baseline measurement (2015), with an 80% participation rate among eligible children (1792/2516). 11 community leaders participated in the workshop.ResultsThe community leaders’ first impression of the SDM was that it could be a valuable additional tool, particularly because of its ability to compare what-if scenarios resembling individual vs systems perspectives, intuitive presentation of simulation results, and use of local data.ConclusionsOur preliminary exploration showed that the small and high-level SDM, using what-if scenarios reflecting interventions on different system levels, could contribute to the understanding and communication of (community-based) SAs.
Efficacy of psychotherapy versus pharmacotherapy, or their combination, in chronic depression: study protocol for a systematic review and network meta-analysis using aggregated and individual patient data
Authors: Schramm Elisabeth , Elsaesser Moritz , Müller Julia , Kwarteng Nana-Adjoa , Evrenoglou Theodoros , Cuijpers Pim , Orestis Efthimiou , Klein Daniel N , Keller Martin B , Furukawa Toshi A , Nikolakopoulou Adriani 
Published: February 2025

IntroductionChronic depression represents a common and highly disabling disorder. Several randomised controlled trials (RCTs) investigated the effectiveness of psychological, pharmacological and combined treatments for chronic depression. This is the first overarching systematic review and network meta-analysis (NMA) based on aggregated and individual patient data comparing the efficacy and acceptability of various treatment options for all subtypes of chronic depression. Furthermore, individual demographic and clinical characteristics that predict or moderate therapy outcomes will be investigated.Methods and analysisA systematic literature search of the Cochrane Library, MEDLINE via Ovid, PsycINFO, Web of Science and metapsy databases will be conducted from database inception without language restrictions to include all available samples from RCTs that investigated the efficacy of psychotherapy versus pharmacotherapy, or their combination in adult inpatients or outpatients with a primary diagnosis of chronic depression. Exclusively internet-based treatment studies will be excluded. The main outcome is depression severity measured on a continuous observer-rated scale for depression at 6 months post-treatment (range 3–12 months). Two reviewers will independently screen and select eligible studies based on the predefined inclusion and exclusion criteria. Risk of bias will be assessed using version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2). Individual patient data (IPD) will be requested and incorporated in the network when provided, as it is the gold standard of evidence. For studies which do not provide IPD, aggregate data (AD) will be extracted and incorporated in lieu of IPD for the NMA, strengthening the evidence base and leveraging all existing evidence regardless of data availability restrictions. An NMA comparing psychotherapies and a network meta-regression estimating individualised treatment effects of psychotherapy will be implemented assuming a Bayesian framework. All models will be fitted in R with calls to JAGS. Empirical informative prior distributions will be used for model parameters where available, and non-informative priors will be used in cases where empirical priors are not available.Ethics and disseminationThis IPD-NMA requires no ethical approval. All results will be disseminated as peer-reviewed publication in a leading journal in this field and presented at (inter)national scientific conferences.PROSPERO registration numberCRD42024526755.
Contemporary European practice in left atrial appendage closure: results from a survey focusing on planning, techniques and post-implantation management
Authors: Garot Philippe , Nielsen-Kudsk Jens-Erik , Freixa Xavier , Berti Sergio , Wunderlich Nina , Cruz-Gonzalez Ignacio , Räber Lorenz , Aminian Adel , De Backer Ole 
Published: February 2025

ObjectivesThe purpose of this European survey was to describe current preprocedural planning, procedure techniques and post-implantation management of left atrial appendage closure (LAAC).DesignProspective survey regarding current practice for LAAC between March and August 2023.Setting357 participating European LAAC centres in 14 countries.ResultsIn 2022, the participating centres performed a total number of 9447 LAAC procedures, with a mean of 26 LAAC cases per centre (median 20; IQR 10–35). Preprocedure planning was performed with transoesophageal echocardiography (TOE) in 63% of centres, cardiac CT in 16%, or both in 21%. LAAC procedures were performed under general anaesthesia (59%), conscious sedation (36%) or with local anaesthesia only (5%). Device implantation was guided by conventional TOE (94%), intracardiac echocardiography (6%), miniaturised TOE probes (4%) or CT/fluoroscopy fusion (2%). The standard post-procedural antithrombotic regimen was dual antiplatelet therapy (73%), followed by single antiplatelet therapy (18%), conventional dose direct oral anticoagulant (DOAC) (7%) or half dose DOAC (1%), and no antithrombotic treatment (1%). There was a large heterogeneity between regions in terms of procedure volumes, hospital organisation, preprocedural planning, as well as procedural techniques and post-procedure management.ConclusionsThe present survey indicates that LAAC has become a widespread procedure in Europe. The findings highlight considerable heterogeneity among European countries in terms of preprocedural planning, procedural techniques including guidance and the post-procedural antithrombotic regimen. There is a need to evaluate the outcomes of different practices.
Telephonic verbal autopsies among adults in South Africa: a feasibility and acceptability pilot study
Authors: Sant Fruchtman Carmen , Neethling Ian , Bradshaw Debbie , Cobos Muñoz Daniel , Morof Diane , Ngobeni Sizzy , Ngwenya Xolani , Edwards Anita , Glass Tracy , Kahn Kathleen , Herbst Kobus , Morden Erna , Zinyakatira Nesbert , Groenewald Pamela 
Published: February 2025

ObjectiveThis pilot study explores the feasibility and acceptability of using telephonic verbal autopsies (teleVAs) in South Africa to collect information on causes of death.DesignQuantitative and qualitative data collection methods were used to evaluate the feasibility and acceptability of these telephonic interviews.SettingThe teleVA pilot was conducted in South Africa’s Western Cape province. The qualitative component also included two rural South African Population Research Infrastructure Network nodes (Africa Health Research Institute in KwaZulu-Natal and Agincourt in Mpumalanga), which had transitioned to teleVAs during COVID-19, allowing exploration of teleVA’s feasibility in both urban and rural settings.ParticipantsWe recruited 229 respondents to participate in a pilot teleVA. After each VA, VA interviewers filled in a survey to assess their perceptions and discern if they experienced any technical challenges. We also conducted 18 in-depth interviews with both interviewers (n=6) and respondents (n=12) to explore their views on the acceptability of the teleVA. We conducted a thematic analysis of these interviews.InterventionsVA was piloted over the phone, instead of face-to-face.Primary and secondary outcome measuresPrimary outcomes focused on the feasibility and acceptability of phone VAs among both interviewers and respondents. Secondary outcomes evaluated the quality of teleVAs.ResultsParticipants expressed willingness to participate in teleVAs, considering them valuable for public health planning and decision-making. The feasibility of collecting next-of-kin information proved challenging, with incomplete or incorrect contact details posing future logistic issues. Only one question out of 76, showed a statistically significant difference in the proportions of non-informative teleVA compared with face-to-face VA.ConclusionsThe study offers valuable insights into using teleVAs to gather cause of death information in resource-limited settings. It highlights the feasibility and acceptability of teleVAs while emphasising the need for comprehensive planning, integration with the civil registration and vital statistics system and community participation enhancement.
Implementation of decarbonisation actions in general practice: a systematic review and narrative synthesis
Authors: Nunes Ana Raquel , Karaba Florence , Geddes Olivia , Bickerton Abi , Atherton Helen , Dahlmann Frederik , Eccles Abi , Gregg Michael , Spencer Rachel , Twohig Helen , Dale Jeremy 
Published: February 2025

ObjectivesTo summarise and synthesise existing literature on the implementation of decarbonisation actions in general practice, to outline the actions being implemented, factors influencing decarbonisation, identify evidence gaps and questions for future research.DesignA systematic review and narrative synthesis.Data sourcesMEDLINE, Embase, CINAHL, Web of Science and ProQuest (grey literature) were searched for literature published up to 29 March 2024.Eligibility criteria for selecting studiesStudies of any design investigating the implementation of decarbonisation actions in general practice.Data extraction and synthesisTwo reviewers extracted data and conducted quality assessments using a mixed methods appraisal tool. Narrative synthesis was used to analyse findings.ResultsFifteen studies were included. Studies were primarily from the UK (n=5), followed by Australia (n=3), USA (n=2), Germany (n=2) and one each from France, Switzerland and Israel. Study designs were qualitative (n=7), quantitative (n=7) and one mixed methods. Participants included healthcare staff (n=7), patients (n=5), health stakeholders (n=2) and the general public (n=1). There was evidence of general practices adopting decarbonisation actions such as resource reuse, improved waste management, energy-efficient systems and preventive care to reduce overmedication, with strong leadership and institutional support being crucial for their success. However, barriers such as high costs, resource constraints and limited awareness among clinicians and patients highlighted the need for enhanced communication, education and the structured promotion of initiatives to improve patient and community engagement.ConclusionsThere is limited evidence on the implementation of decarbonisation actions in general practice. A range of factors may impact on the extent to which implementation occurs. Addressing these will be crucial for effectively promoting and scaling decarbonisation actions in general practice. Future research should focus on understanding the role of institutional context, evaluating the real-world impact of interventions on greenhouse gas emissions and exploring patient and community involvement.PROSPERO registration numberCRD42023470889.
School participation, supports and barriers of children with and without attention deficit hyperactivity disorder
Authors: Kara Koray , Kaya Kara Ozgun , Kose Barkin , Doğan Mert , Cetin Sebahat Yaprak , Sahin Sedef , Anaby Dana 
Published: February 2025

ObjectivesTo investigate the differences in participation patterns, environmental barriers and supports across specific activities typically done at school between children with attention deficit hyperactivity disorder (ADHD) and without ADHD.DesignProspective cross-sectional study.SettingThe children and adolescents with ADHD were selected from those routinely referred to the Health Sciences University Research and Training Hospital’s child and adolescent psychiatry department, which is a reference centre for the region.ParticipantsA total of 365 children (nchildren with ADHD=175, nchildren without ADHD=190, mean age 11.66 years, SD 2.96 years) and their primary caregivers were included in the study.Primary outcome measuresParticipation and Environment Measure for Children and Youth was used to evaluate children.ResultsThe mean frequency of participation in five different school activities was significantly lower in children with ADHD than in children without ADHD, with moderate to large effect sizes. Children with ADHD were less likely to be involved in any activity type than children without ADHD, with moderate to large effect sizes. The characteristics of the school environment typically made it more challenging for children with ADHD to participate than for children without ADHD, with moderate effect sizes.ConclusionsChildren with ADHD have challenges in classroom activities and with socialising with peers outside class, cognitive demands, sensorial qualities and safety. Relationships with friends, cultural acceptance and support could improve the school participation of children with ADHD.