bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cu- and Ag-mediated inactivation of
L. pneumophila
in bench- and pilot-scale drinking water systems
Authors: Hintz Chelsea L. , Morris Brian , Witt Sue , Sojda Nicole , Buse Helen Y. 
Published: December 2024

ABSTRACT

Legionella pneumophila
(Lp) is an opportunistic drinking water pathogen that can cause infections through the inhalation of Lp-containing aerosols and can occur in premise plumbing systems. In this work, the use of copper (Cu) and silver (Ag) ions was evaluated at the bench and pilot scale to determine (i) the effective independent concentrations of copper and silver that are efficacious in inactivating Lp, (ii) the impact of various water quality parameters on the efficaciousness of copper and silver ions, and (iii) the effectiveness and practicality of using dissociation to produce ions at the pilot scale. At the bench scale, it was determined that 0.3 ppm and 0.03 ppm of Cu and Ag, respectively, achieved 6-log inactivation of Lp in 5 h in experimental buffer. But, in dechlorinated filter-sterilized tap water, the same concentrations of Cu were not effective, and the effectiveness of Ag was slower. pH and dissolved inorganic carbon content were found to be important parameters in determining if the use of Cu and Ag ions is appropriate. At the pilot scale, dissociation was successfully used to produce Cu and Ag ions. Target levels of ions were met at the pilot scale but were difficult to achieve, and no impact was observed on Lp concentrations. Results from this study suggest that there are important caveats in the application of this technology when applied in a drinking water matrix and prior understanding of a system’s water chemistry may be important to determine the effectiveness of Lp disinfection using Cu and Ag.

IMPORTANCE

This work sheds light on the effectiveness of using Cu and Ag ions to inactivate (or kill)
Legionella pneumophila. Legionella
is an opportunistic drinking water pathogen of public health concern. This work demonstrates that there are important caveats in the application of using Cu and Ag ions to inactivate
Legionella pneumophila
.
A newly developed oral infection mouse model of shigellosis for immunogenicity and protective efficacy studies of a candidate vaccine
Authors: Haldar Risha , Halder Prolay , Koley Hemanta , Miyoshi Shin-ichi , Das Santasabuj 
Published: December 2024

ABSTRACT

Shigella
infection poses a significant public health challenge in the developing world. However, lack of a widely available mouse model that replicates human shigellosis creates a major bottleneck to better understanding of disease pathogenesis and development of newer drugs and vaccines. BALB/c mice pre-treated with streptomycin and iron (FeCl
3
) plus desferrioxamine intraperitoneally followed by oral infection with virulent
Shigella flexneri 2a
resulted in diarrhea, loss of body weight, bacterial colonization and progressive colitis characterized by disruption of epithelial lining, loss of crypt architecture with goblet cell depletion, increased polymorphonuclear infiltration into the mucosa, submucosal swelling (edema), and raised proinflammatory cytokines and chemokines in the large intestine. To evaluate the usefulness of the model for vaccine efficacy studies, mice were immunized intranasally with a recombinant protein vaccine containing
Shigella
invasion protein invasion plasmid antigen B (IpaB). Vaccinated mice conferred protection against
Shigella
, indicating that the model is suitable for testing of vaccine candidates. To protect both
Shigella
and
Salmonella
, a chimeric recombinant vaccine (rIpaB–T2544) was developed by fusing IpaB with
Salmonella
outer membrane protein T2544. Vaccinated mice developed antigen-specific serum IgG and IgA antibodies and a balanced Th1/Th2 response and were protected against oral challenge with
Shigella
(
S. flexneri 2a
,
Shigella dysenteriae
, and
Shigella sonnei
) using our present mouse model and
Salmonella
(
Salmonella
Typhi and Paratyphi) using an iron overload mouse model. We describe here the development of an oral S
higella
infection model in wild-type mouse. This model was successfully used to demonstrate the immunogenicity and protective efficacy of a candidate protein subunit vaccine against
Shigella
.
DDO-adjuvanted influenza A virus nucleoprotein mRNA vaccine induces robust humoral and cellular type 1 immune responses and protects mice from challenge
Authors: Gnazzo Victoria , Saleh Hanaa , Castro Ítalo A. , Boon Adrianus C. M. , Pinto Amelia K. , Brien James D. , López Carolina B. 
Published: December 2024

ABSTRACT

A challenge in viral vaccine development is to produce vaccines that generate both neutralizing antibodies to prevent infection and cytotoxic CD8
+
T-cells that target conserved viral proteins and can eliminate infected cells to control virus spread. mRNA technology offers an opportunity to design vaccines based on conserved CD8-targeting epitopes, but achieving robust antigen-specific CD8
+
T-cells remains a challenge. Here, we tested the viral-derived oligonucleotide DDO268 as an adjuvant in the context of a model influenza A virus (IAV) nucleoprotein (NP) mRNA vaccine in C57BL/6 mice. DDO268 when co-packaged with mRNA in lipid nanoparticles is sensed by RIG I-like receptors and safely induces local type I interferon (IFN) production followed by dendritic cells type 1 activation and migration to the draining lymph nodes. This early response triggered by DDO268 improved the generation of IgG2c antibodies and antigen-specific Th1 CD4
+
and CD8
+
T-cells (IFNγ
+
TNFα
+
IL2
+
) that provided enhanced protection against lethal IAV challenge. In addition, the inclusion of DDO268 reduced the antigen dose required to achieve protection. These results highlight the potential of DDO268 as an effective mRNA vaccine adjuvant and show that an IAV NP mRNA/DDO268 vaccine is a promising approach for generating protective immunity against conserved internal IAV epitopes.

IMPORTANCE

Vaccines that generate neutralizing antibodies and cytotoxic CD8
+
T-cells targeting conserved epitopes are ideal for effective protection against viruses. mRNA vaccines combined with the right adjuvant offer a promising solution to this challenge. We show that the virus-derived oligonucleotide DDO268 enhances antibody and T-cell responses to an influenza A virus (IAV) nucleoprotein mRNA vaccine in mice. DDO268 safely induces local type I interferon production and stimulates dendritic cell activation providing enhanced protection against IAV challenge. In addition, the adjuvant activity of DDO268 allows for the use of lower antigen doses during vaccination.
Effect of heated mittens on physical hand function in people with hand osteoarthritis: randomised controlled trial
Authors: Bartholdy Cecilie , Døssing Anna , Stisen Zara R , Nielsen Sabrina M , Christensen Robin , Danneskiold-Samsøe Bente , Bliddal Henning , Henriksen Marius , Ellegaard Karen 
Published: December 2024

Abstract

Objective
To assess the effect of electrically heated mittens on physical hand function in people with osteoarthritis of the hands compared with control mittens.

Design
Randomised controlled trial.

Setting
Osteoarthritis outpatient clinic, Copenhagen, Denmark.

Participants
200 people with hand osteoarthritis aged 42-90 years. 100 participants were assigned to the intervention group and 100 to the control group.

Interventions
Electrically heated mittens or control mittens (heating elements disconnected) worn for at least 15 minutes daily for six weeks.

Main outcome measures
The primary outcome was change in hand function measured on the function subscale of the Australian/Canadian hand osteoarthritis index (AUSCAN; score 0-100 points) at six weeks. Key secondary outcomes included changes in the AUSCAN hand pain subscale (score 0-100 points), global rating of hand osteoarthritis related problems (0-100 visual analogue scale), and grip strength (newtons) at six weeks. Analysis of secondary outcomes was performed using a hierarchical gatekeeping approach.

Results
91 participants in the intervention group and 95 in the control group completed the trial. The mean age of participants was 71 years, 87% (n=173) were women, and mean body mass index was 24.9 (SD 4.4). Median disease duration was 10 years (interquartile range 5-15 years). The between group difference for change in AUSCAN function at week 6 was 3.0 points (95% confidence interval (CI) −0.4 to 6.3; P=0.09) in favour of heated mittens. For the key secondary outcome, change in AUSCAN hand pain score from baseline, a group difference was observed of 5.9 points (95% CI 2.2 to 9.5) in favour of heated mittens. Changes in global rating of hand osteoarthritis related problems and grip strength did not differ between the groups with an observed difference between groups of 2.8 points (95% CI −3.7 to 9.2) and 2.3 newtons (95% CI −16.3 to 21.0) in favour of heated mittens, respectively.

Conclusion
Use of electrically heated mittens for six weeks was not related to a positive change in physical hand function compared with control mittens. Heated mittens provided no additional benefits on global rating of hand osteoarthritis related problems and grip strength. A small benefit was detected for hand pain, but this could have been overestimated.

Trial registration

ClinicalTrials.gov
NCT04576403
Antigen-specific immune therapy (CNP-106) for treatment of generalised myasthenia gravis: rationale and design of first-in-human randomised controlled trial
Authors: G Brew Samantha , Frey Molly , P McCarthy Derrick , Elhofy Adam , Nowak Richard J 
Published: December 2024

IntroductionMyasthenia gravis (MG) is a T cell-dependent B cell-mediated autoimmune disease with pathogenic antibodies directed against components of the acetylcholine receptor (AChR). Current therapies do not address the root cause of the disease (autoimmune recognition of AChR) and are associated with possible serious side effects. Therefore, new therapeutic options targeting antigen-specific autoimmunity are needed. COUR nanoparticle (CNP-106) is an antigen-specific immune tolerance therapy directed to the AChR to stop the pathogenic driver of MG. Data from experimental models suggest the potential benefit of CNP-106 to patients by reprogramming the immune system to AChR and stopping the progression of the disease. The aim of this study is to determine the safety and preliminary efficacy of CNP-106 in AChR antibody-positive generalised MG subjects.Methods and analysisThe outlined study is a multicentre Phase 1b/2a double-blind, randomised, placebo-controlled trial with an enrolment target of 54 AChR antibody-positive generalised MG subjects. The primary endpoint is safety and tolerability. Exploratory and secondary endpoints include disease-specific clinical scores, measures of quality of life and activities of daily living, antigen-specific T cells and AChR antibodies. Trial enrolment is anticipated to start in 2024.Ethics and disseminationThe trial has ethical approval from the Central Institutional Review Boards and has clinical trial authorisation from the Food and Drug Administration. Trial results will be communicated to participants, presented at national and international meetings and published in peer-reviewed journals.Trial registration numberNCT06106672.
Patients' and clinicians’ perspectives on virtual phone consultation in vascular surgery
Authors: Yahya Muhammad Syafwan , Tang Lilian , Healy Donagh 
Published: December 2024

IntroductionThe pandemic limited our capacity for face-to-face (F2F) outpatient clinics and therefore we set up virtual phone consultation clinics (VPC). Our study evaluated patients' and clinicians’ perspectives on our VPC and identified areas for improvement.MethodsWe designed a questionnaire for patients and a questionnaire for clinicians. These included questions on satisfaction with VPC, practical aspects of VPC and suggestions for improvement. Between December 2021 and February 2022, one hundred patients and 11 clinicians completed these questionnaires.ResultsThe average satisfaction score for the patients’ last VPC attendance was 4.42/5 (SD 0.90). The main benefits of VPC from the perspective of patients were: reduced risk of infection, the convenience of not needing to travel and increased efficiency. A large proportion of the patients were unaware that an F2F clinic attendance could be requested instead of a VPC. 3 patients suggested that we could do video calls. 52 patients indicated that they would prefer an F2F attendance for their next review.The average satisfaction score for our clinicians was 4.19 (SD 0.98). Our clinicians believed that the advantages of VPC were increased efficiency, reduced risk of infection and lower cost. Clinicians felt that patients who needed to be told about normal scan results and patients who could not travel were most suitable for VPC. The most notable disadvantage of VPC was the inability to perform a physical examination and our clinicians felt that this could delay treatment. Some clinicians felt that giving patients a written summary of the VPC would be beneficial.ConclusionOur patients and staff were satisfied with our VPC programme and understand its advantages. Our study provided justification for the continued use of VPC.
Bundled de-implementation of recurring hospital orders with a novel electronic medical record order set
Authors: Murphy Caleb J , Narala Vanshika , Katiki Aishwarya , Martinez Maylyn S , Cerasale Matthew T , Nguyen Khanh T 
Published: December 2024

IntroductionHigh-frequency recurring orders placed through the electronic medical record (EMR) may contribute to unnecessary care in hospitalised patients. This quality initiative sought to develop and pilot test a hospital order set for bundled review and de-implementation of common recurring orders.MethodsA voluntary-use EMR order set was developed to display low-frequency order alternatives for common hospital care components. The order set was introduced to hospitalists at a large academic hospital from February to June 2023. Orders for overnight vital signs, tubes/tethers (a composite of telemetry, continuous pulse oximetry and Foley catheter) and daily labs (a composite of complete blood counts and metabolic panels) were monitored twice weekly in hospitalised patients at low risk for clinical decompensation from December 2022 through June 2023. Paired t-test was used to assess for differences in order frequency before and after order set introduction.ResultsThe order set was used in 48 unique encounters to place 80 de-implementation orders, most commonly for discontinuation of overnight vital signs (n=37). Two or more de-implementation orders were placed during 44% of order set encounters. Mean (SD) total high-frequency orders decreased by 0.22 per patient day (95% CI −0.39 to −0.06; p=0.010) after order set introduction, driven by a reduction in overnight vital sign orders of 0.17 per patient day (95% CI −0.23 to −0.12; p<0.001). There was no statistically significant difference in orders for tubes/tethers or daily labs before and after order set introduction.DiscussionIntroduction of a novel order set for bundled review and de-implementation of recurring orders was associated with reduced high-frequency recurring orders in hospitalised patients, driven by a reduction in overnight vital signs. Nearly half of order set use was for two or more de-implementation orders, suggesting that bundling de-implementation orders may be an efficient way to reduce unnecessary orders.
Prevalence of anxiety and depression in former elite athletes: a systematic review and meta-analysis
Authors: Runacres Adam , Marshall Zoe A 
Published: December 2024

ObjectivesTo summarise the evidence regarding the prevalence of anxiety and depression in former elite athletes compared with the general population.DesignSystematic review and meta-analysis.Data sourcesFive electronic databases (Web of Science, PubMed, MEDLINE, Scopus and SPORTDiscus) were searched from 1970 to 2023.Eligibility criteriaStudies were included in the meta-analysis if they: (1) were written in English; (2) included male or female elite athletes that had been retired ≥1 year; (3) included a control grouporpopulation reference values; (4) reported the time-point prevalence of anxiety and/or depression; and (5) were of a retrospective, longitudinal or prospective, methodological design. A modified version of the Downs and Black tool was used to determine risk of bias.Results37 unique studies including 24 732 former athletes (2% female) were included in the meta-analysis. The time-point prevalence of anxiety (prevalence ratio (PR): 2.08 (95% CI 1.57 to 2.60)) and depression (PR: 2.58 (95% CI 2.04 to 3.12)) in former athletes was over twice that of the general population. Subgroup analyses revealed former American football players and jockeys had the highest time-point prevalence of both anxiety and depression (PR: 2.24–2.88), whereas the time-point prevalence of depression and anxiety was not significantly different to the general population for former rugby players (PR: 1.13–1.30).ConclusionOur meta-analyses demonstrated the time-point prevalence of anxiety and depression in former elite athletes could be over twice that of the general population, with sport-specific differences evident.PROSPERO registration numberCRD42022347359.
Impact of telehealth-based therapeutic exercise on pain, functional performance and dynamic knee valgus in young adult females with patellofemoral pain: a randomised controlled trial
Authors: Nilmart Patcharin , Vongsirinavarat Mantana , Khawsuwan Pimpaka , Chumthong Kiatrada , Tadein Russareeta , Komalasari Dwi Rosella 
Published: December 2024

ObjectivesThis study aimed to evaluate the effectiveness of a telehealth-based therapeutic exercise (TTE) programme with real-time video conference supervision for young adult females with patellofemoral pain (PFP).MethodsThe study design was a randomised controlled trial. Forty-two participants with PFP were allocated to either the TTE group or the control (C) group. The TTE group received a 4-week telehealth-based exercise programme supervised through real-time video conferencing, while the C group followed a self-guided stretching exercise. Pain intensity was assessed using the Visual Analogue Scale, while functional performance was evaluated with hop tests and the step-down test. Dynamic knee valgus was measured by the frontal plane projection angle during a single-leg squat. In addition, the study used a specific health questionnaire which evaluated knee pain and function, including the self-administered Kujala Patellofemoral Questionnaire (KPQ). All outcomes were assessed both before and after the intervention.ResultsAfter the 4-week interventions, the results showed a significant interaction between the group and the time of pain intensity, functional performance and dynamic knee valgus (p<0.001). The TTE group demonstrated significant pain reduction (p<0.001) and improved KPQ score (p<0.001), while the C group showed no significant changes. TTE participants also exhibited improved functional performance in the hop and step-down tests. Additionally, dynamic knee valgus was significantly decreased in the TTE group.ConclusionThe telehealth-based exercise programmes offer a convenient and effective alternative for managing PFP symptoms, providing remotely accessible and specialised care.
Outcomes of tricuspid valve surgery in patients with significant tricuspid regurgitation and low to intermediate risk
Authors: Gwak Seo-Yeon , Kim Kyu , Lee Hyun-Jung , Cho Iksung , Hong Geu-Ru , Ha Jong-Won , Shim Chi Young 
Published: December 2024

BackgroundIn patients with tricuspid regurgitation (TR), delayed surgical intervention is associated with poor outcomes, particularly in advanced stages. This study aimed to assess whether earlier tricuspid valve (TV) surgery provides a survival benefit in patients with moderate to severe TR who are considered at low to intermediate risk of adverse clinical or surgical outcomes.MethodsThis retrospective cohort study included 10 016 patients diagnosed with moderate to severe TR between 2008 and 2020. Patients were stratified using the the Tricuspid Regurgitation Impact on Outcomes (TRIO) Score (for general health risk) and TRI-SCORE (for perioperative risk). We focused on patients deemed at low or intermediate risk by these scores, comparing the all-cause mortality of those who underwent TV surgery to those managed medically.ResultsAmong 8874 patients categorised as low or intermediate risk, 871 (9.8%) underwent TV surgery. Patients in the surgical group were younger and had a higher prevalence of RV enlargement and RV dysfunction compared to those in the medical treatment group. During a mean follow-up of 5.2 years, surgical patients had a lower risk of death (HR 0.38, 95% CI 0.29 to 0.50) compared with medically managed patients after adjusting for confounders. This association persisted in patients who underwent isolated TV surgery. However, the potential for residual confounding in this non-randomised analysis should be considered.ConclusionsTV surgery was associated with higher survival rates in patients with moderate to severe TR and low to intermediate prognostic risk. However, the observational nature of the study means that uncontrolled confounding cannot be excluded. These findings warrant further investigation in randomised studies.
Evaluation of immune checkpoint inhibitor efficacy for solid tumors withCD274(PD-L1 gene) amplification identified by comprehensive genomic profiling: retrospective study based on a nationwide database
Authors: Nakayama Tomohiro , Takahama Takayuki , Chiba Yasutaka , Shiraishi Naoki , Kawakami Hisato , Yonesaka Kimio , Nakagawa Kazuhiko , Hayashi Hidetoshi 
Published: December 2024

BackgroundAmplification of the programmed cell death-ligand 1 gene (CD274) is highly prevalent and associated with a high response rate to immune checkpoint inhibitors (ICIs) in lymphomas, and is also a potential biomarker for ICI treatment of solid tumors. However, the efficacy of ICIs for solid tumors withCD274amplification identified by comprehensive genomic profiling (CGP) has been unclear. We here examined ICI efficacy for solid tumors withCD274amplification identified by CGP in a national database.MethodsWe retrospectively analyzed data from the Center for Cancer Genomics and Advanced Therapeutics database containing 60,155 CGP test results for individuals with solid tumors. Only clinical data from patients treated with ICIs alone (not those undergoing concomitant therapy with molecularly targeted or cytotoxic chemotherapeutic agents) were evaluated. We matched 48 patients in theCD274amplification-positive group with 170 patients in theCD274amplification-negative group in a 1:4 ratio based on tumor type, histology, treatment, and age. Overall survival (OS), time to next treatment (TTNT), and response rate were evaluated as treatment outcomes in the two groups.ResultsOS was similar in theCD274-amplified and matchedCD274-non-amplified groups (median of 22.1 vs 26.3 months, respectively; HR of 0.92 with a 95% CI of 0.55 to 1.54; p=0.075). TTNT tended to be longer in theCD274-amplified group than in the matchedCD274-non-amplified group (median of 16.5 vs 14.0 months; HR of 0.63 with a 95% CI of 0.37 to 1.08; p=0.091). The objective response rate was 33.3% and 18.4% (difference of 14.9%, with a 95% CI of –0.2% to 31.6%), and the disease control rate was 63.9% and 41.1% (difference of 22.8%, with a 95% CI of 5.1% to 40.4%), in theCD274-amplified and matchedCD274-non-amplified groups, respectively.ConclusionsThe number of patients with solid tumors positive forCD274amplification in this analysis is the largest to date, and our results suggest that such gene amplification may be associated with the outcome of ICI treatment in such individuals.CD274amplification identified by CGP may therefore be a predictor of ICI efficacy for solid tumors.Trial registration numberUMIN000029779.