bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the impact of the COVID-19 pandemic on physician complaint trends in Alberta, Canada
Authors: Hamayeli-Mehrabani Homeira , Kain Nicole , Hurava Iryna , Kumar Kushagr , Hernandez-Ceron Nancy , Ashworth Nigel 
Published: February 2025

Background The COVID-19 pandemic has posed unprecedented challenges to healthcare systems globally. This study aimed to investigate the pandemic's impact on physician complaints in Alberta, Canada, across three periods: pre-, during, and post-pandemic. Methods A cross-sectional study was conducted using the College of Physicians & Surgeons of Alberta (CPSA) complaint database from Q1 2018 to Q4 2023. Complaints were grouped into eight domains, with a detailed analysis of COVID-19-related complaints. A qualitative analysis categorized complaints into thematic domains, and trends were analyzed. The frequency of complaints was compared by using the chi-square test. Results Complaint trends showed stability pre-pandemic, decreasing during the pandemic, and rising post-COVID. Medical reporting complaints decreased during the pandemic but increased post-COVID. Conversely, practice management, third-party involvement, ethical concerns, and systemic issue complaints increased during the pandemic and continued into the post-COVID period. COVID-19-related complaints peaked in Q1 2022, with family physicians receiving most of them. Conclusions Proactive monitoring of complaint trends is essential for healthcare organizations to ensure high-quality, patient-centered care. This study provided insights into the impact of the COVID-19 pandemic on physician complaints in Alberta, emphasizing the necessity for continuous monitoring and intervention.
Experiencing an Early Intervention Programme Targeting Communication and Literacy for Infants Living in a Socially Disadvantaged Community in Ireland
Authors: O’Toole Ciara , Looney Eibhlín , Martin Shirley , Curtin Margaret , Harte Jennifer , Walsh Grace 
Published: February 2025

Background Let’s Grow Together! Infant & Childhood Partnerships (LGT) is a place-based prevention, promotion and intervention programme based in Cork city that supports early childhood development to mitigate the intergenerational impact of poverty. An innovative component of LGT is ‘Babbling Babies’ which offers parents an opportunity to meet a speech and language therapist (SLT) in coordination with their routine 9–11 month developmental check-up with a public health nurse (PHN). The programme explores how parents can support high-quality interaction opportunities to improve communication and early literacy in daily activities. Objective The aim of the study was to establish how feasible it is to measure the efficacy of the ‘ Babbling Babies’. This paper focuses on parental and practitioner views and experiences with the programme. Method A research protocol was co-designed with the LGT team to evaluate the programme. Interviews and focus groups were conducted with families and practitioners to gather their experiences and analysed using reflexive thematic analysis. Results Results indicated that parents found the programme to be acceptable, felt reassured by the information provided and felt empowered to promote their own child’s communication development. The practitioners also valued the programme and the opportunities to collaborate with each other, but indicated a number of structural and systemic barriers that affected successful implementation. Conclusions The programme was acceptable and feasible for families and practitioners and the outcomes will contribute to future research on early interventions aimed to address the inequalities of growing up in socially disadvantaged communities in Ireland.
Mesenchymal stem cells and mesenchymal stem cell-derived exosomes: a promising strategy for treating retinal degenerative diseases
Authors: An Wenjing , Zhang Wenliang , Qi Jia , Xu Weihui , Long Yushan , Qin Huan , Yao Kai 
Published: February 2025

Abstract
Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic strategy in regenerative medicine, demonstrating significant potential for clinical applications. Evidence suggests that MSCs not only exhibit multipotent differentiation potential but also exert critical therapeutic effects in retinal degenerative diseases via robust paracrine mechanisms. MSCs protect retinal cells from degenerative damage by modulating inflammation, inhibiting apoptosis, alleviating oxidative stress, and suppressing cell death pathways. Furthermore, MSCs contribute to retinal structural and functional stability by facilitating vascular remodeling and donating mitochondria to retinal cells. Of particular interest, MSC-derived exosomes have gained widespread attention as a compelling cell-free therapy. Owing to their potent anti-inflammatory, anti-apoptotic, and vascular-stabilizing properties, exosomes show significant promise for the treatment of retinal degenerative diseases.
Freedom of movement and health of nursing home residents with dementia: an exploratory cross-sectional study
Authors: van Liempd Suzan P. , Bolt Sascha R. , Luijkx Katrien G. 
Published: February 2025

Abstract

Background
Having more freedom of movement may relate to better health in nursing home (NH) residents with dementia. Research that tests whether residents in NHs with more freedom of movement are healthier compared to residents in closed NHs is scarce. Also, existing research on freedom of movement does not consider the diverse dimensions of health. This study explored health differences between two groups of nursing home residents with dementia with different levels of freedom of movement.

Methods
We used a quantitative cross-sectional design to investigate differences in health between two groups of NH residents with dementia. One group lived in closed NHs (i.e., with closed unit doors) and the other group in semi-open NHs (i.e., with closed NH entrance doors). A total of 124 residents with dementia were recruited from five NHs in the Netherlands, of whom 61 residents lived in semi-open NHs and 63 residents lived in closed NHs. Data were collected using questionnaires to cover health dimensions according to the concept of Positive Health, including quality of life and participation, mental functioning and perception, daily functioning and bodily functions. An analysis of covariance, adjusted for age, gender and type of dementia, was used to examine differences in residents’ health.

Results
Most included residents had Alzheimer’s or vascular dementia and 68% were female. No significant demographic differences were observed between the two groups in age, gender, type of dementia, length of stay, length of diagnoses and type of care package (p-values ranged from 0.097 to 0.606). After adjusting for multiple comparisons, there were no significant differences in any of the assessed health dimensions between residents of semi-open nursing homes and those of closed nursing homes, with a significance threshold of p <.004 accounting for the correction for multiple testing (p-values ranged from 0.020 to 0.870).

Conclusions
This exploratory study found no significant differences in health between residents with dementia in semi-open and closed NHs. These findings contradict earlier research suggesting that more freedom of movement may enhance overall health in this population. Further research, preferably employing longitudinal designs, is necessary to establish causal pathways and identify the underlying mechanisms.
Understanding the impact of Achilles lipid content on tendon mechanical parameters: a cross-sectional study of people with familial hypercholesterolemia and healthy controls
Authors: Squier Kipling , Waugh Charlie , Callow Joanne , Patola Wayne , Hunt Michael A. , Brunham Liam R. , Jakobi Jennifer , Scott Alexander 
Published: February 2025

Abstract

Background
Familial hypercholesterolemia (FH) is a genetic condition that affects cholesterol metabolism, resulting in life-long elevated serum levels of low-density lipoprotein cholesterol. Systemically elevated cholesterol levels are associated with the onset of tendon injury and potentially lead to impaired mechanical properties. Applying a cross-sectional design, we examined whether FH patients present with altered Achilles biomechanics compared to healthy controls and conducted correlational analyses to determine the relationship between Achilles tendon biomechanics and tendon lipid or water content.

Methods
Patients with FH (n = 33) and healthy controls (n = 31) were recruited from the Greater Vancouver area. Achilles cross sectional area, thickness, lipid and water content was determined using Dixon method magnetic resonance imaging (3.0T). Achilles mechanical properties were determined using synchronized dynamometry, motion capture, ultrasound and electromyography during ramped maximal voluntary isometric contractions, and stiffness and Young’s modulus calculated. Between group differences were assessed with independent t-tests or Mann-Whitney U tests and Pearson’s r or Spearman’s ρ were employed for correlational analyses. Sensitivity analysis was conducted on FH patients diagnosed with Achilles xanthoma and the remaining FH patients.

Results
FH patients had significantly elevated Achilles total water content (p = 0.006), cross-sectional area (p = 0.006), and thickness (p = 0.019). No between-group differences were observed in any of the biomechanical parameters. In patients with FH there were significant positive relationships between tendon lipid or water content and tendon strain (ρ = 0.35, p = 0.046; r = 0.42, p = 0.02, respectively). No significant relationships were observed in control participants. In patients with FH, increased tendon cross-sectional area was associated with reduced stiffness (r=-0.371, p = 0.033) and increased strain (r = 0.48, p = 0.005). The presence of xanthoma was associated with increased Achilles dimensions (p < 0.05), total water content (p = 0.03), strain (p = 0.029), and decreased Young’s modulus (p = 0.001).

Conclusion
Increased Achilles lipid and water content is associated with increased tendon strain in people with FH and the presence of xanthoma might indicate altered tendon mechanics. This study holds relevance for individuals with hypercholesteremia, as best management practices advocate for physical activity as part of a healthy lifestyle.
Assessing lung cancer progression and survival with infrared spectroscopy of blood serum
Authors: Kepesidis Kosmas V. , Stoleriu Mircea-Gabriel , Feiler Nico , Gigou Lea , Fleischmann Frank , Aschauer Jacqueline , Eiselen Sabine , Koch Ina , Reinmuth Niels , Tufman Amanda , Behr Jürgen , Žigman Mihaela 
Published: February 2025

Abstract

Background
Infrared molecular fingerprinting has been identified as a new minimally invasive technological tool for disease diagnosis. While the utility of cross-molecular infrared fingerprints of serum and plasma for in vitro cancer diagnostics has been recently demonstrated, their potential for stratifying and predicting the prognosis of lung cancer remained unexplored. This study investigates the capability of this approach to predict survival and stratify lung cancer patients.

Methods
Molecular fingerprinting through vibrational spectroscopy is employed to probe lung cancer. Fourier-transform infrared (FTIR) spectroscopy is applied to blood sera from 160 therapy-naive lung cancer patients, who were followed for up to 4 years. Machine learning is then utilized to evaluate the prognostic utility of this new approach. Additionally, a case-control study involving 501 individuals is analyzed to investigate the relationship between FTIR spectra and disease progression.

Results
Overall, we establish a strong correlation between the infrared fingerprints and disease progression, specifically in terms of tumor stage. Furthermore, we demonstrate that infrared fingerprinting provides insights into patient survival at performance levels comparable to those of tumor stage and relevant blood-based biomarkers.

Conclusions
Identifying the combined capacity of infrared fingerprinting to complement primary lung cancer diagnostics and to assist in the assessment of lung cancer survival represents the first proof-of-concept study underscoring the potential of this profiling platform. This may provide new avenues for the development of tailored, personalized treatment decision-making.
Association between plasma short-chain fatty acids and inflammation in human immunodeficiency virus-associated neurocognitive disorder: a pilot study
Authors: Chen Xue , Wei Jiaqi , Zhang Ling , Wang Hu , Zhang Yang , Li Zhen , Wang Xia , Liu Lifeng , Zhang Yulin , Zhang Tong 
Published: February 2025

Abstract

Background and aims
Short-chain fatty acids (SCFAs), key metabolites produced by gut microbiota, have neuroprotective effects in neurodegenerative diseases by modulating immune responses. However, their role in human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remains largely unexplored.

Methods
We recruited HAND patients, HIV Control, and healthy controls (HC). Plasma SCFAs and SCFA-producing gut microbiota were quantified via gas chromatography-mass spectrometry and fecal metagenomic analysis. Inflammatory cytokine levels were measured using liquid chromatography. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive accuracy of SCFAs for HAND.

Results
Plasma SCFAs were significantly reduced in HAND patients, correlating with a decrease in SCFA-producing gut bacteria, such as Prevotella and its related species. Reduced SCFAs were positively correlated with pro-inflammatory cytokines and cognitive impairment, while being negatively correlated with anti-inflammatory cytokines. ROC curve analysis demonstrated that several SCFAs exhibited strong predictive accuracy for HAND status.

Conclusions
SCFAs may influence cognitive function by modulating inflammatory responses, and identifies plasma SCFAs as potential biomarkers and therapeutic targets for HAND. Further investigation is needed to delineate the mechanisms that SCFAs influence HAND pathology.
miRNA-503 inhibition exerts anticancer effects and reduces tumor growth in mesothelioma
Authors: Piccioni Miriam , Di Meo Francesco , Valentino Anna , Campani Virginia , Arigoni Maddalena , Tanori Mirella , Mancuso Mariateresa , Cuciniello Rossana , Tomasetti Marco , Monaco Federica , Goteri Gaia , Spugnini Enrico P. , Calogero Raffaele A. , De Rosa Giuseppe , Peluso Gianfranco , Baldi Alfonso , Crispi Stefania 
Published: February 2025

Abstract

Background
Malignant mesothelioma (MM) is a rare and aggressive form of cancer that affects the mesothelial surfaces, associated with exposure to asbestos fibres. To date, no cure is available for MM and therapeutically approved treatments are based on the use of platinum compounds often used in combination with other drugs. We have previously analysed the efficacy of a cisplatin/piroxicam (CDDP/P) combined treatment showing that this treatment was able to reduce in vivo tumor growth. Several studies reported that platinum-drug sensitivity in cancer is connected to modulation of the expression of non-coding RNAs. In this study we analysed if the CDDP/P treatment was able to modulate miRNAs expression in MM.

Methods
miRNA sequencing performed on MSTO-211 H cells treated with CDDP with CDDP/P led us to identify miRNA-503 - downregulated by CDDP/P - as a novel miRNA that acts as an oncomiR in MM. The effect of miRNA-503 inhibition was evaluated in vitro in mesothelioma cells analysing apoptosis induction and reduction of cancer properties. Inhibition of miR-503 expression in vivo, was analysed in ectopic mouse model of MM by using LNP encapsulating anti-mir-503 and miR-503 expression was evaluated in human MM samples.

Results
In vitro and in vivo analysis confirmed miR-503 acts as oncogene in MM since its inhibition was able to reduce cell cancer properties and tumor growth in ectopic mouse model of MM. Its expression was found upregulated in human MM patients compared to normal pleura. Bioinformatic analysis indicated BTG1, CCNG1, EDG1, and TIMP2 as putative target genes of miRNA-503. These genes showed an opposite expression compared to miR-503 levels both in cells and in MM samples. Finally, microarray analysis indicated that miR-503 inhibition affected the expression of the well-known MM biomarkers: CXCL8, SERPINE1 and Osteopontin.

Conclusions
Our study is the first reporting an oncomiR role for miR-503 in MM and suggests that its inactivation could have a clinical value in MM patients. This study reveals that miRNA-503 acts as an oncomiR in MM suggesting that its inhibition, through LNP delivery, has the potential to be considered as a novel therapeutic strategy in MM.
Calcium electroporation induces stress response through upregulation of HSP27, HSP70, aspartate β-hydroxylase, and CD133 in human colon cancer cells
Authors: Szewczyk Anna , Rembiałkowska Nina , Saczko Jolanta , Daczewska Małgorzata , Novickij Vitalij , Kulbacka Julita 
Published: February 2025

Abstract

Background
Electroporation (EP) leverages electric pulses to permeabilize cell membranes, enabling the delivery of therapeutic agents like calcium in cancer treatment. Calcium electroporation (CaEP) induces a rapid influx of calcium ions, disrupting cellular calcium homeostasis and triggering cell death pathways. This study aims to compare the cellular responses between microsecond (µsEP) and nanosecond (nsEP) electroporation, particularly in terms of oxidative stress, immune response activation, and cancer stem cell (CSC) viability in drug-resistant (LoVo Dx) and non-resistant (LoVo) colorectal cancer cell lines.

Results
Both µsEP and nsEP, particularly when combined with Ca2+, significantly reduced the viability of cancer cells, with nsEP showing greater efficacy. Reactive oxygen species (ROS) levels increased 5-fold in malignant cells following nsEP, correlating with decreased ATP production and mitochondrial dysfunction. Nanosecond CaEP (nsCaEP) also induced significant expression of aspartate-β-hydroxylase (ASPH), a protein linked to calcium homeostasis and tumor progression. Moreover, nsEP led to heightened expression of heat shock proteins (HSP27/70), indicating potential immune activation. Interestingly, nsEP without calcium drastically reduced the expression of CD133, a marker for CSCs, while the addition of Ca2+ preserved CD133 expression. The expression of death effector domain-containing DNA binding protein (DEDD), associated with apoptosis, was significantly elevated in treated cancer cells, especially in the nucleus after nsCaEP.

Conclusions
The study confirms that nsEP is more effective than µsEP in disrupting cancer cell viability, enhancing oxidative stress, and triggering immune responses, likely through HSP overexpression and ROS generation. nsEP also appears to reduce CSC viability, offering a promising therapeutic approach. However, preserving CD133 expression in the presence of calcium suggests complex interactions that require further investigation. These findings highlight the potential of nsCaEP as an innovative strategy for targeting both cancer cells and CSCs, potentially improving treatment outcomes in colorectal cancer. Further studies are needed to explore the exact cell death mechanisms and optimize protocols for clinical applications.
Environmental Impact Assessment of Intravenous Versus Subcutaneous Monoclonal Antibodies: A Carbon Footprint Analysis
Authors: Zietse Michiel , Kooijman Thirza , Malmberg Ruben , Spierings Leontine E.A.M.M. , Jager Agnes , Mathijssen Ron H.J. , van Leeuwen Roelof W.F. , Thielen Frederick W. 
Published: February 2025

PURPOSE
The development of subcutaneous (SC) formulations for monoclonal antibodies (mAbs), as an alternative to conventional intravenous (IV) infusion, represents a shift in health care delivery. The relative environmental impact of these two administration methods is not well understood. Minimizing the environmental footprint of health care is crucial due to its substantial contribution to greenhouse gas (GHG) emissions. This study compared the carbon footprint of SC and IV administration using pertuzumab/trastuzumab as a case example.

METHODS

A Life Cycle Assessment was conducted to compare the environmental impacts of IV versus SC administration of pertuzumab/trastuzumab, focusing on climate change impacts expressed in carbon dioxide-equivalents (CO
2
e). The analysis included emissions from single-use medical equipment, drug manufacturing, hospital operations, patient and staff transportation, and waste disposal.

RESULTS

SC pertuzumab/trastuzumab resulted in slightly higher GHG emissions than IV administration, with 47.2 kg CO
2
e for loading doses compared with 45.9 kg CO
2
e, and 33.6 kg CO
2
e for maintenance doses compared with 32.9 kg CO
2
e. This increase was primarily due to the higher dosage required for SC delivery, with mAb production contributing the most to emissions. Nonetheless, SC administration reduced the use of single-use medical equipment and treatment-related energy consumption in health care facilities. Switching to SC pertuzumab/trastuzumab administration in the Netherlands in 2022 would have increased annual CO
2
e emissions by 12.2 tons, equivalent to driving 63,212 km in a petrol-powered car.

CONCLUSION
Both IV and SC administration routes of mAbs have substantial environmental impacts, dominated by mAb production emissions. This research provides a framework for assessing the environmental impact of health care technologies and underscores the importance of integrating environmental considerations into health technology assessments to mitigate the significant contribution of health care to global GHG emissions.
Clinical Effectiveness and Cost-Effectiveness of Multigene Panel Sequencing in Advanced Melanoma: A Population-Level Real-World Target Trial Emulation
Authors: Krebs Emanuel , Weymann Deirdre , Ho Cheryl , Weppler Alison , Bosdet Ian , Karsan Aly , Hanna Timothy P. , Pollard Samantha , Regier Dean A. 
Published: February 2025

PURPOSE

Targeted therapy and immunotherapy promise improved survival in patients with advanced melanoma, yet the effectiveness and cost-effectiveness of multigene panel sequencing compared with single-gene
BRAF
testing to guide therapeutic decisions is unknown.

METHODS

Our population-based quasi-experimental retrospective target trial emulation used comprehensive patient-level data for 364 British Columbia, Canada, adults with an advanced melanoma diagnosis receiving multigene panel sequencing or single-gene
BRAF
testing between September 1, 2016, and December 31, 2018. We 1:1 matched multigene panel patients to controls using genetic algorithm–based matching. Outcomes included 3-year overall survival (OS) and health care costs (2021 Canadian dollars [CAD]) with incremental net monetary benefit for life-years gained (LYG). Outcomes were analyzed using inverse probability of censoring weighted linear regression for the intention-to-treat (ITT) effect. The per-protocol (PP) effect estimation also included stabilized inverse probability of treatment weights. We then used Weibull regression and Kaplan-Meier survival analysis.

RESULTS

We matched 147 multigene panel patients to controls, achieving balance for all covariates. After matching, ITT incremental costs were $19,447 CAD (95% CI, –$18,516 to $76,006) and incremental LYG were 0.22 (95% CI, –0.05 to 0.49). We found uncertainty in differences on OS using Kaplan-Meier (
P
= .11) and Weibull regression (hazard ratio [HR], 0.73 [95% CI, 0.51 to 1.03]) in the ITT. PP incremental costs were $36,367 CAD (95% CI, –$6,653 to $120,216]) and incremental LYG were 0.56 (95% CI, 0.39 to 1.24), with corresponding differences in OS using Kaplan-Meier (
P
= .02) and Weibull regression (HR, 0.56 [95% CI, 0.36 to 0.87]). The probability of multigene panels being cost-effective at $100,000/LYG CAD was 55% for ITT and 65% for PP.

CONCLUSION
The cost-effectiveness of multigene panels was evenly poised at higher thresholds, even when accounting for treatment initiation. Health systems reimbursing multigene panels and expensive therapies may be confronted with a value tradeoff, in which there may be improved survival albeit with a modest change in cost-effectiveness.