bluuebunny/crossref_metadata_2025 huggingface dataset:
The Surprising Truth About Attitudes of Tourism Students Toward Statistics
Authors: Suherlan Herlan , Hidayah Nurdin
Published: February 2025

The study investigates the influence of various components on tourism students’ attitudes toward statistics, and the causal relationship between these components. A total of 435 students were asked to fill out a questionnaire on the Survey of Attitudes Toward Statistics (SATS). The main data analysis in this study uses exploratory factor analysis (EFA) or principal component analysis (PCA) to look for interdependence relationships between variables in order to identify the dimensions or factors that shape attitudes. Our results show that students’ attitudes toward statistics before and after the learning process tend to be positive, where attitudes toward statistics before learning for each group of student backgrounds show a linear relationship with attitudes toward statistics after learning, except for groups based on work experience. The results of the study also show that the original 4-factor structure, namely, cognitive, affective, difficulty, and value, according to conditions in Indonesia, especially for tourism students, produces four components, namely, value, affect, interest, and difficulty components. For stakeholders, the results of this study have broad implications for the development of a tourism education curriculum, as tourism students increasingly need to be given statistical literacy skills.
Does High-Speed Rail Promote Residents’ Subjective Well-Being? Evidence From China
Authors: Wang Yunmin , Dong Jie , Wang Jingjing
Published: February 2025

Although the impact of high-speed railway (HSR) on economic development has received extensive attention, few studies explore how HSR influences individuals’ daily life. Using the pooled cross-section data from China Labor-force Dynamic Survey (CLDS), we examine the relationship between HSR services and subjective well-being (SWB). The baseline result indicates that HSR project bring a significant and positive improvement on individuals’ SWB in the cities it serves. Evidence from a variety of identification strategies suggests that the relationship is robust. Mechanism analysis shows that HSR services increase residents’ SWB by improving household income, inducing tourism, and promoting health status. Moreover, our evidence finds urban residents, young residents, and high-income residents benefit more from HSR services. Our study reveals the potential value of HSR services from the perspective of SWB, which is growingly concerned in the policymakers concerning route planning and cost-benefit analysis of HSR projects.

JEL Classification: I15, I31, R21, R40, R42, Z32
Impact of Entrepreneurial Leadership, Talent Management, Social Media, Artificial Intelligence and Digital Technology on Business Performance in Handicraft Industry: An Analysis of Innovation as Moderating Construct
Authors: Yadav Uma Shankar , Rena Ravinder
Published: February 2025

This article aims to analyse the impact of digital technology (DT), entrepreneurial leadership (EL), social media (SM) and artificial intelligence (AI) on business performance (BP). This study also analyses the mediating impact of talent management (TM), strategic resilience (SR) and entrepreneurial orientation (EO) and the moderating impact of innovation (INO) for TM and BP. We used the SMART partial least square method (SMART PLS-SEM) software to analyse the valid data. Data were collected by the survey method through a random sampling procedure from 410 related handicraft artisans. The study’s findings prove EL, TM and DT and that SM significantly impacts BP, but AI has an insignificant effect on BP. This study explores artisans’ formal EL style, but the role of AI, DT, SM and TM has remained unexplored. This research shows that craft business owners and managers must allocate more resources to talent management. The most effective business methods in the arts and crafts sector can be implemented with excellent talent management. This study is unique because the dynamic capability theory and resource-based view used for supporting variables will be extended.
Leveraging the Shift in the Geocultural Landscape Towards Internationalizing Cultural Entrepreneurship
Authors: Aljanova Nurlykhan , Shakti Sneh , Bokebayev Bakyt
Published: February 2025

This article examines how geocultural shifts provide new opportunities for internationalizing cultural entrepreneurship, using the case study of a unique international action company from Kazakhstan. Founded in 2000, Nomad Stunts has risen to international prominence, collaborating with leading studios across Hollywood, Bollywood and other major film industries. This study investigates how could geocultural shifts influence creative entrepreneurship and its internationalization? The findings highlight how geocultural changes—such as shifting production hubs and expanding global networks—enabled the company to transform local expertise in equestrian stunts, acrobatics and other disciplines into an internationally recognized brand. The research also reveals the critical role of discipline, resilience and versatility in the company’s growth and underscores the significance of combining cultural authenticity with global standards. This study contributes to understanding how creative enterprises can capitalize on geocultural changes to enhance their competitive advantage and international presence.
Cephalomedullary Nail Fixation for Prophylactic Treatment of Incomplete Femoral Neck Stress Fractures in Athletes
Authors: McMellen Christopher J. , Sinkler Margaret A. , Winter Ethan , Fanaeian Elika , Strony John T. , Williams Austin D. , Wetzel Robert J.
Published: February 2025

Background:

The traditional management of femoral neck stress fractures (FNSFs)—such as cannulated screw fixation—requires a period of protected weightbearing and does not provide fixed angle stability.

Purpose:

To report the technique and outcomes of a single surgeon's case series of prophylactic fixation of incomplete FNSFs using cephalomedullary nailing (CMN) followed by immediate weightbearing.

Study Design:

Case series; Level of evidence, 4.

Methods:

A retrospective review of 17 FNSFs treated using CMN by a single surgeon over 7 years was conducted. descriptive, injury, and treatment-related data were collected. Perioperative complications and recovery courses were included for each case. Descriptive statistics were used to summarize the characteristics, clinical presentation, diagnostic imaging findings, treatment details, and follow-up outcomes of the study population.

Results:

There were no perioperative complications across the 17 injuries. The mean intraoperative blood loss was 67 mL (range, 20-150 mL). In all 17 cases, immediate full weightbearing was recommended. All patients were able to initiate a return to running by 6 weeks postoperatively. Time until completion of narcotic use was noted for 15 cases, with narcotic medications no longer required at 2 weeks for 12 injuries (71%), at 6 weeks for 2 injuries (12%), and at 3 months for 1 injury (5.9%). Patients had a mean of 12.4 months of follow-up (range, 6-48 months). At the final follow-up, 5 cases (29%) had persistent pain—1 from gluteus medius tendinosis and 4 from painful distal interlocking screws. Two patients underwent the removal of symptomatic hardware.

Conclusion:

This study demonstrated that prophylactic fixation of FNSFs with CMN in endurance athletes is a safe and effective construct that permits early return to baseline impact activity because of the inherent stability of the construct, with a favorable complication profile—although with a 30% rate of persistent pain from the surgical site.
Systematic Video Analysis of ACL Injuries in Male Professional English Soccer Players: A Study of 124 Cases
Authors: Della Villa Francesco , Stride Matthew , Bortolami Antonio , Williams Andy , Davison Michael , Buckthorpe Matthew
Published: February 2025

Background:

Improving our understanding of the situations and biomechanics that result in anterior cruciate ligament (ACL) injury will support the design of effective injury risk mitigation programs. A few video analyses have been published in recent years, but not specifically involving English soccer.

Purpose:

To describe the mechanisms, situational patterns, and biomechanics (kinematics) of ACL injuries of players involved in matches involving teams in the top 2 tiers of professional English soccer (the Premier League and the Championship).

Study Design:

Case series; Level of evidence, 4.

Methods:

We identified 148 consecutive ACL injuries across 11 seasons of professional English soccer. Overall, 124 (84%) injury videos were analyzed for mechanism and situational patterns, while biomechanical analysis was possible in 91 injuries. Three independent reviewers evaluated each video. ACL injury epidemiology (month, timing within the match, and location on the playing field at the time of injury) was also reported.

Results:

More injuries occurred in defensive (n = 79; 64%) than offensive (n = 45; 36%) playing situations; 24 (19%) injuries were direct contact, 52 (42%) indirect contact, and 47 (38%) noncontact. Of the indirect and non-contact ACL injuries (n = 100), most (91%) occurred during 4 main situational patterns: (1) pressing/tackling (n = 50; 50%); (2) being tackled (n = 18; 18%), (3) landing from a jump (n = 13; 13%), and (4) regaining balance after kicking (n = 10; 10%). These injuries generally involved a knee flexion strategy (with minimal hip/trunk flexion and reduced plantarflexion) in the sagittal plane and appearance of knee valgus in most cases (70%; 96% of identifiable cases). More (n = 71; 57%) injuries occurred in the first half of matches than in the second half ( P < .01).

Conclusion:

Indirect contact rather than noncontact was the main ACL injury mechanism in male elite English soccer players. Four main situational patterns were described, with pressing/tackling and being tackled accounting for two-thirds of all indirect and noncontact injuries. Biomechanical analysis confirmed a multiplanar mechanism, with knee loading patterning in the sagittal plane accompanied with dynamic valgus. More injuries occurred in the first half of matches.
Developing the Digital Communication Acceptance Scale (DICAS) for Measuring Employee Acceptance of Digital Communication Technologies in the Workplace
Authors: Tkalac Verčič Ana , Einwiller Sabine , Tench Ralph , Verčič Dejan
Published: February 2025

The study explores the impact of Digital Communication Technologies (DCT) on internal communication within organizations, focusing on employee acceptance. It introduces the Digital Communication Acceptance Scale (DICAS) to fill the gap in existing technology acceptance models, such as the Technology Acceptance Model (TAM) and the Unified Theory of Acceptance and Use of Technology (UTAUT), which don’t consider factors critical in the context of internal communication. The research was conducted in three phases: item creation and expert review, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA). Results showed a six-factor model—Interaction Facilitation, Apprehension, Effort Expectancy, Performance Expectancy, Facilitating Conditions, and Social Influence—explaining 79.5% of the variance. Reliability of the scale was confirmed with high internal consistency (α = .918). DICAS allows organizations to assess employee attitudes toward DCT, offering practical insights for improving communication strategies and facilitating smoother digital transformations. The scale also addresses privacy concerns, social dynamics, and organizational support, providing a comprehensive framework to guide future research and practice in digital workplace communication.
Pediatric Surgical Nurses and Trauma-Informed Care
Authors: Binford Leslie , Ellison Deborah , Wilson Debra Rose
Published: February 2025

Adverse childhood experiences profoundly impact the development and overall health of children that carry into adulthood, affecting immune function, inflammation, and mental well-being. Medical procedures can be traumatic. Trauma-informed care is an essential framework utilized in a variety of healthcare settings to address early trauma, utilizing supportive interventions to mitigate long-term health consequences. The implementation of trauma-informed care principles such as safety, trust, and collaboration work to address the complex needs of children and families effectively. Pediatric surgical nurses are encouraged to utilize interventions aimed at establishing an environment of care that prioritizes autonomy, safety, active listening, and shared decision-making to avoid re-traumatization and promote healing. These principles profoundly affect patients and families by promoting healing.
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.
Outcomes of the COVID-19 pandemic in chronic lymphocytic leukemia: Focus on the very early period and Omicron era
Authors: Hedberg Pontus , Blixt Lisa , Eketorp Sylvan Sandra , Killander Möller Isabela , Lindahl Hannes , Kahn Fredrik M , Nilsdotter-Augustinsson Åsa , Fredriksson Mats , Nyström Sofia , Bergman Peter , Carlander Christina , Aleman Soo , Nauclér Pontus , Osterborg Anders , Hansson Lotta
Published: February 2025

Individuals with chronic lymphocytic leukemia (CLL) face increased risk of severe COVID-19. This study from Sweden, a country with few mandatory restrictions at the onset of the pandemic, used 10 nationwide registers to compare risks of severe COVID-19 outcomes of PCR-verified SARS-CoV-2 infections through February 2023 in individuals with vs without CLL. From a population of 8,275,839 (6,653 CLL) individuals born 1930-2003, 2,088,163 first infections (1,289 CLL) were included. The 90-day all-cause mortality rate and adjusted relative risk (aRR [95% CI]) for individuals with CLL vs the general population was 24.8% (1.95 [1.58-2.41)) during Wild-type, 17.2% (2.38 [1.58-3.57)) during Alpha, 4.1% (0.71 [0.24-2.08]) during Delta, and 12.6% (1.49 [1.24-1.78]) during Omicron. Their mortality during Omicron was 0.6% (<65 years), 5.4% (65-74 years), and 19.7% (>75 years). Small molecule inhibitors (1.56 [1.03-2.37]) and corticosteroid usage (1.45 [1.04-2.02]) was associated with increased mortality. Next, we analyzed the all-cause mortality in the capital (Stockholm), widely affected by SARS-CoV-2 at the onset of the pandemic. Mortality in individuals with CLL increased by 55% during the first 6 months of 2020 vs 2019 and age- and sex aRR by June 30 was 1.53 [1.09-2.15] for individuals with CLL (P=.02) and 1.29 [1.25-1.33] for the general population (P<.001). Collectively, a significantly increased risk of severe COVID-19 and death was observed among individuals with CLL in Sweden, particularly at the onset of the pandemic when few national protective measures were introduced, but also after Omicron emerged, emphasizing the need for a more pro-active pandemic strategy for CLL.
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

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

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

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

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

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

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

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.
Probing Visual Literacy Skills Reveals Unexpected Student Conceptions of Chromosomes
Authors: Uminski Crystal , Newman Dina L. , Wright L. Kate
Published: February 2025

We explored undergraduate students' visual literacy by asking them to draw and interpret images of chromosomes and found that most students held incorrect or incomplete conceptions about chromosome structure and function. These findings stress the importance of teaching visual literacy skills in biology courses.
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.
Art Spiegelman’s Bounding Boxes: Mishkan, Midrash, Maus
Authors: Waldman Emmy
Published: February 2025

As vexing questions of Jewish identity and Holocaust memory loom large, this essay asks what it would mean to read Maus as a Jewish text. Thinking, with Hillary Chute’s landmark 2006 essay, “The Shadow of a Past Time:, History and Graphic Representation in Maus,” it uses Spiegelman’s (slippery), metaphor of comics panels as built boxes to link the book to Jewish traditions, surrounding the material preservation and transmission of historical texts., Reconsidering Maus through and as “boxes,” whether humble cardboard or, wooden coffin, reveals Spiegelman’s survivor’s “tale” as a text, commentary, object, memorial, testimony, even a kind of secular phylactery or reliquary, through which the son of survivors negotiates his parents’ trauma and the, push-pull of his own Jewish identity. Ultimately, the essay offers boxes as a, way (back) into Maus as a signal text both for Jewish identity today and for, the reparative work that the comics form can do in approaching the traumas, of history.
Life During Wartime: Domestic Surrealism in Jonathan Lethem’s Chronic City
Authors: Cohen Samuel
Published: February 2025

This essay argues that Jonathan Lethem’s 2009 novel Chronic City is the product of 1) the author’s anti-Bloomian relationship to literary influence, as seen in his 2007 essay “Ecstasy of Influence: A Plagiarism” (and elsewhere) and as worked out in his use of genre and the modes of realism and the fantastic, and 2) anxieties about the future characteristic of the author’s time. The result is an approach to representation the essay calls “domestic surrealism” and demonstrates this at work in the novel’s presentation of an unreal-feeling, spectacular New York City. At stake in Chronic City, the essay argues, is the question of whether the city’s/the world’s condition is chronic or terminal or if a time can be imagined that might be different from the current “wartime” and the dark future toward which we seem to be inevitably headed and, if it can be imagined, whether it is possible.
The correlation between the ultrasound examination parameters and the pathological characteristics of papillary thyroid carcinomas
Authors: Yang Lei , Luo Yang , Li Zhiyong
Published: February 2025

Objective: To evaluate the correlation between ultrasound (US) examination parameters and pathological characteristics of papillary thyroid carcinomas (PTC).
Methods: A retrospective analysis was conducted using clinical data from 89 patients with PTC (malignant group) and 89 patients with benign thyroid nodules (benign group) who underwent US at Chengdu Shuangliu Hospital of Traditional Chinese Medicine between February 2021 to February 2023. The correlation between ultrasound parameters and pathological features of PTC was analyzed.
Results: Ultrasound parameters in the malignant group were significantly different from those in the benign group (P<0.05). Peak systolic blood flow velocity (PSV), pulsation index (PI), and resistance index (RI) were significantly higher in patients with malignant lymph node metastasis (LNM) and stage III-IV PTC. In contrast, peak intensity (Peak), mean transit time (MTT), time to peak (TTP), and area under curve (AUC) were significantly lower than those in patients without LNM and stage I-II (P<0.05). Spearman’s analysis revealed significant correlations between ultrasound parameters, LNM, disease staging, and gene mutations (P<0.05). Of the 89 PTC patients, 27 had disease recurrence, and five died during the follow-up. The poor prognosis group had significantly higher PSV, PI, and RI and lower Peak, MTT, TTP, and AUC compared to the good prognosis group (P<0.05).
Conclusions: Ultrasound is a valuable tool for diagnosing and evaluating papillary thyroid carcinoma (PTC). It shows strong correlations between ultrasound parameters and pathological features, including lymph node metastasis and disease staging, aiding early diagnosis and prognosis prediction.
doi: https://doi.org/10.12669/pjms.41.3.10566
How to cite this: Yang L, Luo Y, Li Z. The correlation between the ultrasound examination parameters and the pathological characteristics of papillary thyroid carcinomas. Pak J Med Sci. 2025;41(3):848-855-. doi: https://doi.org/10.12669/pjms.41.3.10566
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Digital Health Literacy: A systematic review of interventions and their influence on healthcare access and sustainable development Goal-3 (SDG-3)
Authors: Mukhtar Tehreem , Muhammad Naveed Babur  , Roohi Abbas  , Asima Irshad  , Qurba Kiran
Published: February 2025

This study explores how interventions focused on digital health literacy (DHL) can improve access to healthcare and contribute to achieving Sustainable Development Goal-3 (SDG- 3). We scrutinized information from PubMed (MEDLINE), Scopus, and Web of Science released search articles from March 1, 2020 to January 31, 2024. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the review concentrated only on experimental studies that assessed how DHL initiatives have influenced enhancing patient health outcomes and access to healthcare. Research that did not cover DHL or the availability of healthcare, was not included. The analysis was primarily qualitative, focusing on thematic patterns and insights rather than statistical outcomes. Our results showed that DHL interventions typically result in enhanced health literacy, improved medication adherence, and higher self-confidence, particularly benefiting marginalized communities. Limitations to safe & accessible healthcare underscore the need for more focused and culturally appropriate strategies. This review shows that interventions by DHL can greatly enhance healthcare results, highlighting the need to tackle inequalities to ensure marginalized communities also benefit.
doi: https://doi.org/10.12669/pjms.41.3.10639
How to cite this: Mukhtar T, Babur MN, Abbas R, Irshad A, Kiran Q. Digital Health Literacy: A systematic review of interventions and their influence on healthcare access and sustainable development Goal-3 (SDG-3). Pak J Med Sci. 2025;41(3):910-918.  doi: https://doi.org/10.12669/pjms.41.3.10639
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.