bluuebunny/crossref_metadata_2025_split huggingface dataset:
Klebsiella
phage KP34gp57 capsular depolymerase structure and function: from a serendipitous finding to the design of active mini-enzymes against
K. pneumoniae
Authors: Maciejewska Barbara , Squeglia Flavia , Latka Agnieszka , Privitera Mario , Olejniczak Sebastian , Switala Paulina , Ruggiero Alessia , Marasco Daniela , Kramarska Eliza , Drulis-Kawa Zuzanna , Berisio Rita 
Published: September 2023

ABSTRACT

Virion-associated depolymerases are large trimeric and multi-domain proteins that constitute the phage arsenal to degrade the polysaccharide layers in their bacterial host. Thus, as recombinant proteins, they are endowed with huge potential in biotechnology and medicine. In this study, we elucidated the structural and functional features of the capsular depolymerase KP34gp57 from the
Klebsiella
phage KP34. Based on the crystal structure and site-directed mutagenesis, we localized the key catalytic residues in an intra-subunit deep groove. Moreover, we engineered several N- and C-terminally truncated versions of KP34gp57 to dissect the role of each domain in the enzyme’s stability and catalytic activity. Serendipitously, our studies revealed C-terminally trimmed KP34gp57 variants that did not trimerize and were sufficiently stable to preserve full catalytic activity as monomers. The elaboration of trimmed monomeric and fully active phage depolymerases is innovative in the field, as no previous example exists apart from bacterial enzymes. Mini phage depolymerases can be optionally combined within chimeric enzymes to extend their activity range, facilitating their use in stand-alone treatments. Moreover, the intra-subunit and inter-subunit locations of the catalytic pocket in phage depolymerases might suggest differences in their evolutionary origin.

IMPORTANCE

In this work, we determined the structure of
Klebsiella
phage KP34p57 capsular depolymerase and dissected the role of individual domains in trimerization and functional activity. The crystal structure serendipitously revealed that the enzyme can exist in a monomeric state once deprived of its C-terminal domain. Based on the crystal structure and site-directed mutagenesis, we localized the key catalytic residues in an intra-subunit deep groove. Consistently, we show that C-terminally trimmed KP34p57 variants are monomeric, stable, and fully active. The elaboration of monomeric, fully active phage depolymerases is innovative in the field, as no previous example exists. Indeed, mini phage depolymerases can be combined in chimeric enzymes to extend their activity ranges, allowing their use against multiple serotypes.
Provision of evaluation and management visits by nurse practitioners and physician assistants in the USA from 2013 to 2019: cross-sectional time series study
Authors: Patel Sadiq Y , Auerbach David , Huskamp Haiden A , Frakt Austin , Neprash Hannah , Barnett Michael L , James Hannah O , Smith Laura Barrie , Mehrotra Ateev 
Published: September 2023

Abstract

Objective
To examine the proportion of healthcare visits are delivered by nurse practitioners and physician assistants versus physicians and how this has changed over time and by clinical setting, diagnosis, and patient demographics.

Design
Cross-sectional time series study.

Setting
National data from the traditional Medicare insurance program in the USA.

Participants
Of people using Medicare (ie, those older than 65 years, permanently disabled, and people with end stage renal disease), a 20% random sample was taken.

Main outcome measures
The proportion of physician, nurse practitioner, and physician assistant visits in the outpatient and skilled nursing facility settings delivered by physicians, nurse practitioners, and physician assistants, and how this proportion varies by type of visit and diagnosis.

Results
From 1 January 2013 to 31 December 2019, 276 million visits were included in the sample. The proportion of all visits delivered by nurse practitioners and physician assistants in a year increased from 14.0% (95% confidence interval 14.0% to 14.0%) to 25.6% (25.6% to 25.6%). In 2019, the proportion of visits delivered by a nurse practitioner or physician assistant varied across conditions, ranging from 13.2% for eye disorders and 20.4% for hypertension to 36.7% for anxiety disorders and 41.5% for respiratory infections. Among all patients with at least one visit in 2019, 41.9% had one or more nurse practitioner or physician assistant visits. Compared with patients who had no visits from a nurse practitioner or physician assistant, the likelihood of receiving any care was greatest among patients who were lower income (2.9% greater), rural residents (19.7%), and disabled (5.6%).

Conclusion
The proportion of visits delivered by nurse practitioners and physician assistants in the USA is increasing rapidly and now accounts for a quarter of all healthcare visits.
Measurable and immeasurable spread of knowledge for research impact: a reflection on the validated NutComp tool
Authors: Ball Lauren , Lepre Breanna , Van Dorssen Clare 
Published: September 2023

BackgroundContemporary research now includes effort to generate impact beyond the creation of new knowledge.MethodsThis report provides an illustrative case study of tactful research planning and dissemination for impact and provides an emerging pathway for others to holistically track reach, spread and uptake, to create a nuanced impact narrative.ResultsNutrition Competence Tool (NutComp) is a validated tool that assesses the self-perceived competence of health professionals in providing nutrition care. Since open-access publication in 2015, it has been used by researchers and health professionals in 28 countries across 6 continents. The reach, spread, uptake and impact of NutComp are summarised, including indicators to support impact tracking for knowledge.ConclusionGiven the complex phenomenon of research impact, careful planning is required to capture and attribute research impact.
Effectiveness of music-based interventions to address well-being in people with a vision impairment: a scoping review
Authors: Somani Nurbanu , Beukes Eldre , Street Alexander , Lindsay Rosie , Smith Lee , Allen Peter M 
Published: September 2023

ObjectivesThe objectives of this review were to identify the types of music-based interventions and associated accessibility challenges for people who have visual impairment (VI) and their reported effects on psychological, physiological and social well-being.DesignA scoping review was developed according to the Joanna Briggs Institute methodology and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist and guidelines. A narrative synthesis was conducted to map out the types of music-based interventions undertaken and to compare the therapeutic outcomes. The studies were evaluated according to the music reporting checklist.ResultsIn total 5082 records were identified, 69 full-text articles were screened and 13 studies were included. Eleven studies included younger children and teenagers, two focused on adults with acquired VI. Ten studies involved active music therapy strategies and three used passive music listening. Eleven of the studies focused on social outcomes and two reported mental health. Although the studies reported that music-based intervention strategies improved psychosocial well-being in people with a VI, conclusions could not be drawn as robust outcome measures were not generally used and only four of the studies included any statistical analysis.ConclusionsAlthough potential was evident, details of intervention protocols and training requirements were not sufficiently reported and further, high-quality evidence-based studies are required.
Incidence, characteristics and outcome of post-stroke recrudescence in the Chinese population: a single-centre observational study
Authors: Pu Ming-Jun , Yu Jia-Lun , Hu Xiao , Deng Lan , Chen Chu , Lv Xin-Ni , Li Zuo-Qiao , Wang Zi-Jie , Xie Peng , Li Qi 
Published: September 2023

ObjectivesThe aim of our observational study was to investigate the incidence, clinical characteristics and outcome of post-stroke recrudescence (PSR) in the Chinese population.Design and settingSingle-centre prospective observational study in China.ParticipantsA total of 1114 patients who had a suspected stroke were prospectively screened from October 2020 to February 2022.Outcome measuresThe primary outcome was the proportion of patients with functional independence defined as a score of 0–2 on the modified Rankin Scale (mRS) at 3 months. Secondary outcomes were: early neurological improvement (ENI), defined as a National Institutes of Health Stroke Scale (NIHSS) score of 0 or an improvement of ≥2 points from admission at 24 hours; mortality within 3 months; stroke recurrence within 3 months and length of stay in hospital.ResultsA total of 959 patients with cerebral infarction and 30 patients without an available magnetic resonance imaging (MRI) scan were excluded. Among the 125 included patients, 27 cases of PSR (2.4%), 50 cases of transient ischaemic attack (TIA) (4.5%) and 48 cases of stroke mimics (SMs) (4.3%) were identified. A higher frequency of infection at admission (22.2% vs 2%, p=0.007) was observed in patients with PSR compared with patients with TIA, and a lower proportion of functional independence at 3 months (80% vs 98%, p=0.015) was seen. Patients with TIA had a higher frequency of ENI compared with patients with PSR and SMs (98% vs 59.3%, p<0.001; 98% vs 52.1%, p<0.001). Patients with PSR exhibited a higher frequency of grade 2 Fazekas deep white matter hyperintensity compared with those with SMs (33.3% vs 8.3%, p=0.010).ConclusionsPSR is not uncommon in patients presenting with stroke symptoms and can be distinguished from TIA and SMs based on a combination of clinical features and trigger in the Chinese population. The neurological deficits of patients with PSR often resolve within several days following the resolution of the trigger.
Evaluation of hypofractionated adaptive radiotherapy using the MR Linac in localised pancreatic cancer: protocol summary of the Emerald-Pancreas phase 1/expansion study located at Oxford University Hospital, UK
Authors: Teoh Suliana , Ooms Alexander , George Ben , Owens Rob , Chu Kwun-Ye , Drabble Joe , Robinson Maxwell , Parkes Matthew J , Swan Lynda , Griffiths Lucinda , Nugent Killian , Good James , Maughan Tim , Mukherjee Somnath 
Published: September 2023

IntroductionOnline adaptive MR-guided radiotherapy allows for dose escalation to pancreatic cancer while sparing surrounding critical organs. We seek to evaluate the safety of delivering hypofractionated five-fraction, three-fraction and single-fraction MR-guided stereotactic ablative radiotherapy (SABR) to the pancreas.Methods and analysisThis is a single-centre three-arm phase 1 non-randomised safety study. Patients with localised pancreatic cancer will receive either 50 Gy in five (biological equivalent dose (BED10)=100 Gy), 39 Gy in three (BED10=90 Gy) or 25 Gy in a single fraction (BED10=87.5 Gy) MR-guided daily online adaptive radiotherapy. Each fractionation regimen will be assessed as independent cohorts to determine tolerability, assessed continuously using Bayesian conjugate posterior beta distributions. The primary endpoint of the study is to establish the safety of five-fraction, three-fraction and single-fraction MR-guided hypofractionation SABR in localised pancreatic cancer by assessing dose-limiting toxicities. Secondary endpoints include overall survival, progression-free survival, local control rates, overall control rate, resection rates, long-term toxicities and freedom from second-line chemotherapy. This study plans to also explore imaging and immune biomarkers that may be useful to predict outcome and personalise treatment. The trial will recruit up to 60 patients with a safety run-in.Ethics and disseminationThe trial is approved by the West Midlands—Black Country Research Ethics Committee 22/WM/0122. The results will be disseminated via conference presentations, peer-reviewed scientific journals and submission to regulatory authorities. The data collected for the study, including individual participant data, will be made available to researchers on request to the study team and with appropriate reason, via octo-enquiries@oncology.ox.ac.uk. The shared data will be deidentified participant data and will be available for 3 years following publication of the study. Data will be shared with investigator support, after approval of a proposal and with a signed data access agreement.Trial registration numberISRCTN10557832
Identifying regional disparities of infant mortality rates in Bangladesh: insights from nationwide cross-sectional studies and a statistical modelling approach using linear mixed effects model with temporal variability
Authors: Islam Tarikul , Akter Noor Jahan 
Published: September 2023

ObjectiveThe major objective of this project is to find the best suitable model for district-wise infant mortality rate (IMR) data of Bangladesh over the period 2014–2020 that captures the regional variability and overtime variability of the data.Design, setting and participantsData from seven consecutive cross-sectional surveys that were conducted in Bangladesh between 2014 and 2020 as a part of the Sample Vital Registration System (SVRS) were used in this study. The study included a total of 13 173 (with 390 infant deaths), 17 675 (with 512 infant deaths), 17 965 (with 501 infant deaths), 23 205 (with 556 infant deaths), 23 094 (with 498 infant deaths), 23 090 (with 497 infant deaths) and 23 297 (with 495 infant deaths) complete cases from SVRS datasets for each respective year.MethodA linear mixed effects model (LMM) with a quadratic trend over time in the fixed effects part and a nested random intercept, as well as a nested random slope for a linear trend over time in the part of the random effect, was implemented to describe the situation. This model was selected based on two popular selection criteria: Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC).ResultsThe LMMs analysis results demonstrated statistically significant variations in IMR across different districts and over time. Examining the district-specific area under the logarithm of the IMR curves yielded valuable insights into the disparities in IMR among different districts and regions. Furthermore, a significant inverse relationship was observed between IMR and life expectancy at birth, underscoring the significance of mitigating IMR as a means to enhance population health outcomes.ConclusionThis study accentuates district-wise and temporal variability when modelling IMR data and highlights regional heterogeneity in infant mortality rates in Bangladesh. Area-based programmes should be created for mothers residing in locations with a higher risk of IMR. Further research can examine socioeconomic elements generating these discrepancies.
Neoadjuvant chemoradiation therapy combined with immunotherapy for microsatellite stable ultra-low rectal cancer (CHOICE II): study protocol of a multicentre prospective randomised clinical trial
Authors: Zhou Leqi , Yu Guanyu , Wen Rongbo , Jia Hang , Zhang Tianshuai , Peng Zhiying , Fan Hao , Pan Anfu , Yu Yue , Zhu Xiaoming , Gong Haifeng , Gao Xianhua , Lou Zheng , Zhang Wei 
Published: September 2023

IntroductionNeoadjuvant chemoradiotherapy (nCRT) could bring tumour shrinking and downstaging and increase the probability of organ preservation for patients with low rectal cancer. But for ultra-low rectal cancer, there is little possibility for organ preservation. Immunotherapy has been shown to have significant survival benefits in microsatellite instability-high patients but poor response in microsatellite stable (MSS) patients. Studies have demonstrated that radiotherapy and immunotherapy have synergistic effects in cancer treatment. There is no existing evidence about the clinical efficacy of immunotherapy combined with nCRT for patients with MSS ultra-low rectal cancer.Method and analysisThis trial is an open-labelled multicentre prospective randomised controlled trial (NCT05215379) with two parallel groups and allocation ratio 1:1 (nCRT+immunotherapy vs nCRT group). Eligible participants will be aged 18–75 years, with a desire for anus preservation, confirmed cT1–3aN0–1M0rectal adenocarcinoma, confirmed MSS type, inferior margin of ≤5 cm from the anal verge. The primary endpoint of this trial is complete clinical response (cCR) rate. Immunotherapy is added after 1 week of chemoradiotherapy for two cycles, and then the patients will be administered two cycles of immunotherapy and CAPOX. The evaluations will be carried out after the completion of the whole neoadjuvant therapy. We expect the programme to improve the cCR rate and the quality of life for patients with ultra-low rectal cancer.Ethics and disseminationThis trial was approved by the Ethics committee of Changhai Hospital and other medical centres (Grant number:CHEC2022-118). The results of this study will provide further insight into the clinical efficacy of immunotherapy in combination with nCRT in patients with MSS ultra-low rectal cancer.Trial registration numberNCT05215379.
The role of stress and health behaviour in linking weight discrimination and health: a secondary data analysis in England
Authors: Hackett Ruth A , Jackson Sarah E , Corker Elizabeth , Steptoe Andrew 
Published: September 2023

ObjectiveTo examine the role of stress and health-risk behaviours in relationships between weight discrimination and health and well-being.DesignSecondary data analysis of an observational cohort study.SettingThe English Longitudinal Study of Ageing.ParticipantsData were from 4341 adults (≥50 years) with overweight/obesity.Primary outcome measuresWe tested associations between perceived weight discrimination at baseline (2010/2011) and self-rated health, limiting long-standing illness, depressive symptoms, quality of life and life satisfaction over 4-year follow-up (2010/2011; 2014/2015). Potential mediation by stress exposure (hair cortisol) and health-risk behaviours (smoking, physical inactivity, alcohol consumption) was assessed.ResultsCross-sectionally, perceived weight discrimination was associated with higher odds of fair/poor self-rated health (OR=2.05 (95% CI 1.49 to 2.82)), limiting long-standing illness (OR=1.76 (95% CI 1.29 to 2.41)) and depressive symptoms (OR=2.01 (95% CI 1.41 to 2.85)) and lower quality of life (B=−5.82 (95% CI −7.01 to −4.62)) and life satisfaction (B=−2.36 (95% CI −3.25 to −1.47)). Prospectively, weight discrimination was associated with higher odds of fair/poor self-rated health (OR=1.63 (95% CI 1.10 to 2.40)) and depressive symptoms (OR=2.37 (95% CI 1.57 to 3.60)) adjusting for baseline status. Those who reported discrimination had higher hair cortisol concentrations (B=0.14 (95% CI 0.03 to 0.25)) and higher odds of physical inactivity (OR=1.90 (95% CI 1.18 to 3.05)). These variables did not significantly mediate associations between discrimination and health outcomes.ConclusionsWeight discrimination is associated with poor health and well-being. While this discrimination is associated with stress exposure and physical inactivity, these variables explain little of the association between discrimination and poorer outcomes.
Evaluation of the effectiveness and safety of oral vancomycin versus placebo in the prevention of recurrence ofClostridioides difficileinfection in patients under systemic antibiotic therapy: a phase III, randomised, double-blind clinical trial
Authors: San-Juan Rafael , Origuen Julia , Campion Karen , Fernández-Ruiz Mario , Diaz-Pollan Beatriz , Callejas-Diaz Alejandro , Candela Giancarlo , Orellana Maria Angeles , Lora David , Llorente Muñoz Irene , Garcia Maria Teresa , Martinez-Uña Maite , Ferrari Jose Miguel , Aguado Jose M 
Published: September 2023

IntroductionClostridioides difficileinfection (CDI) is the most prevalent cause of nosocomial bacterial diarrhoea and it is strongly associated with antibiotic use. The recurrence of CDI is a growing medical problem. Data from real-life studies and one open label randomised clinical trial (RCT) suggest that secondary prophylaxis with oral vancomycin (SPV) during subsequent courses of systemic antibiotics is a promising approach for reducing the risk of CDI recurrence. Our aim is to confirm the role of SPV through a double-blind RCT.Methods and analysisWe will perform a phase III, multicentre, placebo-controlled RCT (PREVAN trial) in a 2:1 ratio in favour of SPV (experimental treatment), in four tertiary care hospitals in Spain. Adult patients (≥18 years) with a previous history of CDI in the previous 180 days and with requirement for hospitalisation and systemic antibiotic therapy will be randomly allocated to receive either 125 mg of oral vancomycin or placebo every 6 hours for 10 days. Patients will be followed for 60 days after the end of treatment to verify a reduction in the rate of CDI recurrence in the experimental group. We assume a recurrence rate of 5% in the experimental group versus 25% in the placebo group. Accepting an alpha risk of 0.05 and a beta risk of 0.2 in a two-sided test, 104 subjects will be required in total (68 assigned to the SPV group and 34 to the placebo group).Ethics and disseminationEthical approval has been obtained from the Ethic Committee for Research with medicinal products of the University Hospital ‘12 de Octubre’ (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), which is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders.Trial registration numberNCT05320068.