bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methodological challenges using routine clinical care data for real-world evidence: a rapid review utilizing a systematic literature search and focus group discussion
Authors: Pfaffenlehner Michelle , Behrens Max , Zöller Daniela , Ungethüm Kathrin , Günther Kai , Rücker Viktoria , Reese Jens-Peter , Heuschmann Peter , Kesselmeier Miriam , Remo Flavia , Scherag André , Binder Harald , Binder Nadine ,   for the EVA4MII project
Published: January 2025

Abstract

Background
The integration of real-world evidence (RWE) from real-world data (RWD) in clinical research is crucial for bridging the gap between clinical trial results and real-world outcomes. Analyzing routinely collected data to generate clinical evidence faces methodological concerns like confounding and bias, similar to prospectively documented observational studies. This study focuses on additional limitations frequently reported in the literature, providing an overview of the challenges and biases inherent to analyzing routine clinical care data, including health claims data (hereafter: routine data).

Methods
We conducted a literature search on routine data studies in four high-impact journals based on the Journal Citation Reports (JCR) category “Medicine, General & Internal” as of 2022 and three oncology journals, covering articles published from January 2018 to October 2023. Articles were screened and categorized into three scenarios based on their potential to provide meaningful RWE: (1) Burden of Disease, (2) Safety and Risk Group Analysis, and (3) Treatment Comparison. Limitations of this type of data cited in the discussion sections were extracted and classified according to different bias types: main bias categories in non-randomized studies (information bias, reporting bias, selection bias, confounding) and additional routine data-specific challenges (i.e., operationalization, coding, follow-up, missing data, validation, and data quality). These classifications were then ranked by relevance in a focus group meeting of methodological experts. The search was pre-specified and registered in PROSPERO (CRD42023477616).

Results
In October 2023, 227 articles were identified, 69 were assessed for eligibility, and 39 were included in the review: 11 on the burden of disease, 17 on safety and risk group analysis, and 11 on treatment comparison. Besides typical biases in observational studies, we identified additional challenges specific to RWE frequently mentioned in the discussion sections. The focus group had varied opinions on the limitations of Safety and Risk Group Analysis and Treatment Comparison but agreed on the essential limitations for the Burden of Disease category.

Conclusion
This review provides a comprehensive overview of potential limitations and biases in analyzing routine data reported in recent high-impact journals. We highlighted key challenges that have high potential to impact analysis results, emphasizing the need for thorough consideration and discussion for meaningful inferences.
Microalgae-based bioremediation of refractory pollutants: an approach towards environmental sustainability
Authors: El-Sheekh Mostafa M. , El-Kassas Hala Y. , Ali Sameh S. 
Published: January 2025

Abstract
Extensive anthropogenic activity has led to the accumulation of organic and inorganic contaminants in diverse ecosystems, which presents significant challenges for the environment and its inhabitants. Utilizing microalgae as a bioremediation tool can present a potential solution to these challenges. Microalgae have gained significant attention as a promising biotechnological solution for detoxifying environmental pollutants. This is due to their advantages, such as rapid growth rate, cost-effectiveness, high oil-rich biomass production, and ease of implementation. Moreover, microalgae-based remediation is more environmentally sustainable for not generating additional waste sludge, capturing atmospheric CO2, and being efficient for nutrient recycling and sustainable algal biomass production for biofuels and high-value-added products generation. Hence, microalgae can achieve sustainability's three main pillars (environmental, economic, and social). Microalgal biomass can mediate contaminated wastewater effectively through accumulation, adsorption, and metabolism. These mechanisms enable the microalgae to reduce the concentration of heavy metals and organic contaminants to levels that are considered non-toxic. However, several factors, such as microalgal strain, cultivation technique, and the type of pollutants, limit the understanding of the microalgal removal mechanism and efficiency. Furthermore, adopting novel technological advancements (e.g., nanotechnology) may serve as a viable approach to address the challenge of refractory pollutants and bioremediation process sustainability. Therefore, this review discusses the mechanism and the ability of different microalgal species to mitigate persistent refractory pollutants, such as industrial effluents, dyes, pesticides, and pharmaceuticals. Also, this review paper provided insight into the production of nanomaterials, nanoparticles, and nanoparticle-based biosensors from microalgae and the immobilization of microalgae on nanomaterials to enhance bioremediation process efficiency. This review may open a new avenue for future advancing research regarding a sustainable biodegradation process of refractory pollutants.
Gains and pains: a qualitative study on the implications of value-based health care for professionals
Authors: van Engen Veerle , Bonfrer Igna , Mieris Fabio , Ensink Malou , Stiggelbout Anne , Ahaus Kees , Buljac-Samardzic Martina 
Published: January 2025

Abstract

Background
While aiming to optimize patient value, the shift towards Value-Based Health Care (VBHC) in hospitals worldwide has been argued to benefit healthcare professionals as well. However, robust evidence regarding VBHC’s workforce implications is lacking. This gap is problematic, as the motivation and health of healthcare professionals are central to the quality of care and crucial amidst contemporary workforce challenges. This study aims to qualitatively examine the implications of VBHC for healthcare professionals’ motivation, job strain, and ongoing participation in VBHC. In addition, it explores how these outcomes are regulated at both the individual and organizational levels.

Methods
Semi-structured interviews were conducted with 26 healthcare professionals across six Dutch hospitals. Interviewees engaged in three VBHC activities: (1) value-based outpatient consultations and/or; (2) value-based quality improvement activities; as well as in; (3) VBHC implementation. Interview questions and data analysis were guided by the Job Demands–Resources model.

Results
VBHC interacts with four themes perceived to affect professional’s motivation (perception of making a positive impact, enjoyability of job activities, personal development, and sense of community and support) and three themes perceived to affect job strain (workload, cognitive demands, and confidence). VBHC creates both gains (primarily increasing motivation; occasionally reducing strain) and pains (primarily increasing strain; sometimes reducing motivation). The perceived impact of VBHC depends on the fit between the individual, one’s activities in VBHC, the working conditions, and the pace of VBHC implementation. An observation that warrants attention is that healthcare professionals with a 'do-er' mentality and high ambitions to optimize patient value can become demotivated to continue advancing VBHC with the same intensity, particularly due to perceived slow progress.

Conclusions
While VBHC is centered around patients, this study emphasizes that the needs, experiences and changing role identities of healthcare professionals cannot be overlooked in this transition. VBHC currently presents as a double-edged sword for healthcare professionals: resulting in both gains and pains. In the move to VBHC, it is crucial to maintain alignment between the individual, their job activities, the work environment, and the pace at which VBHC unfolds. This is essential for fostering and retaining motivated individuals, who are not only vital to the workforce but also pivotal in advancing VBHC.
A study to identify individuals at risk to be affected by late-onset Pompe disease who had previously been given a non-specific or tentative diagnosis for their muscle weakness (Pompe PURSUE)
Authors: Laney Dawn A. , Banks Kayla A. , Botha Eleanor G. , Keever Maria , Long Valynne , Foley Allison L. 
Published: January 2025

Abstract

Background
Late-onset Pompe disease (LOPD) is an autosomal recessive lysosomal storage disorder that results in severe progressive proximal muscle weakness. Over time, reductions in muscle strength result in respiratory failure and a loss of ambulation. Delayed diagnosis of LOPD deprives patients of treatments that can enhance quality of life and potentially slow disease progression. The objective of this study is to determine if patients with a nonspecific diagnosis, such as muscle weakness, may be at risk for LOPD using retrospective chart review of patients seen at two centers: an academic center and a community health system.

Results
Initial data pulls identified 80,070 patients with one of the ICD-10 codes of interest. Chart review found 551 of these patients also had at least one lab value commonly abnormal in individuals with LOPD and of these 110 scored as “at-risk”. After removing phenocopies/other confirmed unrelated diagnoses, 46 individuals were contacted either directly or through their healthcare provider for genetic counseling. Three patients had pretest genetic counseling and were tested for decreased levels of acid-α-glucosidase. One patient was found to have deficient acid-α-glucosidase. Additionally, a physician educated through the program ordered LOPD testing for their patient and diagnosed them with LOPD.

Conclusion
This study confirms that a symptom-based scoring tool and chart review combined with provider education can identify patients who are at increased likelihood to have a missed LOPD diagnosis.
Alternative 3′ UTR polyadenylation is disrupted in the rNLS8 mouse model of ALS/FTLD
Authors: Eck Randall J. , Valdmanis Paul N. , Liachko Nicole F. , Kraemer Brian C. 
Published: January 2025

Abstract
Recent research has highlighted widespread dysregulation of alternative polyadenylation in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Here, we identify significant disruptions to 3` UTR polyadenylation in the ALS/FTLD-TDP mouse model rNLS8 that correlate with changes in gene expression and protein levels through the re-analysis of published RNA sequencing and proteomic data. A subset of these changes are shared with TDP-43 knock-down mice suggesting depletion of endogenous mouse TDP-43 is a contributor to polyadenylation dysfunction in rNLS8 mice. Some conservation exists between alternative polyadenylation in rNLS8 mice and human disease models including in disease relevant genes and biological pathways. Together, these findings support both TDP-43 loss and toxic gain-of-function phenotypes as contributors to the neurodegeneration in rNLS8 mice, nominating its continued utility as a preclinical model for investigating mechanisms of neurodegeneration in ALS/FTLD-TDP.
18F−Prostate−Specific Membrane Antigen PET/CT imaging for potentially resectable pancreatic cancer (PANSCAN−2): a phase I/II study
Authors: Puik Jisce R. , Poels Thomas T. , Hooijer Gerrit K. J. , Cysouw Matthijs C. F. , Verheij Joanne , Wilmink Johanna W. , Giovannetti Elisa , Kazemier Geert , Sarasqueta Arantza Farina , Oprea-Lager Daniela E. , Swijnenburg Rutger-Jan 
Published: January 2025

Abstract

Background
Current diagnostic imaging modalities have limited ability to differentiate between malignant and benign pancreaticobiliary disease, and lack accuracy in detecting lymph node metastases. 18F-Prostate-Specific Membrane Antigen (PSMA) PET/CT is an imaging modality used for staging of prostate cancer, but has incidentally also identified PSMA-avid pancreatic lesions, histologically characterized as pancreatic ductal adenocarcinoma (PDAC). This phase I/II study aimed to assess the feasibility of 18F-PSMA PET/CT to detect PDAC.

Methods
Seventeen patients with clinically resectable PDAC underwent 18F-PSMA PET/CT prior to surgical resection. Images were analyzed both visually and (semi)quantitatively by deriving the maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR). TBR was defined as the ratio between SUVmax of the primary tumor divided by SUVmax of the aortic blood pool. Finally, tracer uptake on PET was correlated to tissue expression of PSMA in surgical specimens.

Results
Out of 17 PSMA PET/CT scans, 13 scans demonstrated positive PSMA tracer uptake, with a mean SUVmax of 5.0 ± 1.3. The suspected primary tumor was detectable (TBR ≥ 2) with a mean TBR of 3.3 ± 1.3. For histologically confirmed PDAC, mean SUVmax and mean TBR were 4.9 ± 1.2 and 3.3 ± 1.5, respectively. Although eight patients had histologically confirmed regional lymph node metastases and two patients had distant metastases, none of these metastases demonstrated 18F-PSMA uptake. There was no correlation between 18F-PSMA PET/CT SUVmax and tissue expression of PSMA in surgical specimens.

Conclusions

18F-PSMA PET/CT was able to detect several pancreaticobiliary cancers, including PDAC. However, uptake was generally low, not specific to PDAC and no tracer uptake was observed in lymph node or distant metastases. The added value of PSMA PET in this setting appears to be limited.

Trial registration
The trial is registered as PANSCAN-2 in the European Clinical Trials Database (EudraCT number: 2020–002185-14).

Graphical Abstract
Does a non-performing assets disposal fund help control systemic risk? Evidence from an interbank financial network in China
Authors: Song Lei , Chen Yu 
Published: January 2025

Abstract
The COVID-19 pandemic precipitated a surge in the non-performing assets held by financial institutions, elevating systemic risk in financial networks. Therefore, developing strategies to alleviate this risk, with a focus on non-performing assets, has become a research area of interest. Supported by policies related to the Chinese insurance market, this study proposes the establishment of a non-performing assets disposal fund backed by insurance capital. This fund will invest in the non-performing assets of financial institutions with the aim of mitigating systemic risk. Using a linear threshold model, we identify an asymptotically optimal scheme for disposing of non-performing assets. Additionally, we construct a payment model integrated with non-performing assets, from which we derive an optimal payment and clearing strategy. Our research also proposes a robust set of criteria to assist regulators in determining whether to use the non-performing assets disposal fund. To demonstrate the efficacy of the fund in reducing systemic risk, we conduct simulations and analyze data from the Chinese interbank financial network. Through this rigorous analysis, we confirm the role of the fund in enhancing the stability of the financial system.
Personalized fund recommendation with dynamic utility learning
Authors: Wei Jiaxin , Liu Jia 
Published: January 2025

Abstract
This study introduces a fund recommendation system based on the

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-greedy algorithm and an incremental learning framework. This model simulates the interaction process when customers browse the web-pages of fund products. Customers click on their preferred fund products when visiting a fund recommendation web-page. The system collects customer click sequences to continually estimate and update their utility function. The system generates product lists using the

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-greedy algorithm, where each product on the list has the probability of 1-

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of being selected as an exploitation strategy, and the probability of

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is chosen as the exploration strategy. We perform a series of numerical tests to evaluate the estimation performance with different values of

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.
When is synthetic sufficient? Ethical considerations and alternatives in simulation-based ultrasound education
Authors: Doyle Andrea J. , Condron Claire M. 
Published: January 2025

Abstract
Simulation-based education (SBE) has become an integral part of training in health professions education, offering a safe environment for learners to acquire and refine clinical skills. As a non-ionising imaging modality, ultrasound is a domain of health professions education that is particularly supported by SBE. Central to many simulation programs is the use of animal models, tissues, or body parts to replicate human anatomy and physiology. However, along with its educational benefits, the use of animals in SBE generates a considerable amount of waste, raising important environmental and ethical concerns. Although research indicates that animal models yield comparable educational outcomes to synthetic models, animal models continue to be preferred in surgical and medical training. In response to these challenges, the principles of Replacement, Reduction, and Refinement (the 3Rs) have emerged as guiding standards to minimise the impact of animal use in research and education. Furthermore, synthetic models align with 3R principles, addressing ethical and environmental issues by reducing animal dependence and waste generation. Synthetic models offer key educational benefits over animal models by closely mimicking human anatomy and pathophysiology, providing consistent and anatomically accurate training. Unlike animal models, they eliminate variability in tissue properties, ensuring standardised and reliable experiences. Moreover, synthetic models can simulate specific pathologies, enabling targeted learning that may be difficult with animal tissue. Resistance related to clinical relevance and preference for animal-based SBE is a persisting challenge that might be overcome through the development of clinically and anatomically relevant tissue-mimicking materials, like those previously developed for other applications such as quality assurance phantoms in diagnostic imaging. The involvement of knowledge or end-user engagement, along with evidence-based design solutions, is crucial to catalyse a paradigm shift in a discipline deeply entrenched in tradition. The combined expertise, skills, and perspectives of medical professionals, educators, academic researchers, and industry specialists could collaboratively develop alternative methods to simulate live animal scenarios, replacing and reducing animal tissue dependence in SBE.
Implications of cytokine genes polymorphisms in Jordanian patients with obsessive compulsive disorder
Authors: Khalil Ahmad M. , Khrais Manal W. , Al-Qaoud Khaled M. , Al Ta’any Mohamad Y. 
Published: January 2025

Abstract

Background
Obsessive–compulsive disorder (OCD) is a common and often highly debilitating chronic neuropsychiatric condition. There is substantial evidence that immune system and genetic changes are involved in OCD pathogenesis. Only a few studies have been encountered in the literature in this field. We aimed at providing experimental evidence for single nucleotide polymorphisms (SNPs) in candidate cytokine genes for the etiology of OCD.

Methods
A total of 52 OCD patients and 54 healthy controls were randomly recruited from the Jordanian population. Age ranged between 16 and 55 years (35.5 ± 13.72 and 33.5 ± 10.48 years) for patients and controls, respectively. Five polymorphic positions in four interleukin genes (IL-1β; rs16944 and rs1143634, IL-6; rs1800795, IL-10; rs1800896 and rs1800795) were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. The tumor necrosis factor-α (TNF-α) SNP (rs1800629) DNA was sequenced by the Sanger method. The obtained data were analyzed using the GraphPad Prism method.

Results
There were no statistically significant differences between the alleles and genotypes in opposite groups. However, there was a positive association between the incidence of the studied SNP cytokine genes in OCD patients and non-OCD individuals. The alleles of two SNPs (IL-1β + 3954 C > T and TNF-α-308 G > A) were more predominant and more positively correlated with a higher risk in OCD women. In contrast, the link between the gender and the occurrence of the mutant alleles of the other four SNPs IL-1β (− 511 C > T); IL-6 (− 174 G > C); IL-10 (− 1082 A > G); and IL-10 (− 819 C > T was more robust in the males OCD patients than the corresponding females.

Conclusion
The observed differences between the alleles in different groups may be due to an association in the tested samples rather than a true association. But, the possibility of a critical effect still exists. One might want to explore this further by repeating the study with a larger sample size.
Abatement by Alhagi maurorum of lead-induced nephrotoxicity in rats: emphasis on Nrf2/HO-1
Authors: Algandaby Mardi M. 
Published: January 2025

Abstract

Background
Lead (Pb) is a heavy metal with extreme toxicity and numerous industrial uses. It produces nephrotoxicity with notable changes in renal architecture and function. The Alhagi maurorum (AM) belongs to the family Fabaceae and is native to the Middle East area. In the present study, the potential nephroprotective effects of AM in Pb-intoxicated rats were evaluated.

Results
AM methanolic extract was standardized in reference to its main phenolic compounds orientin, rutin, and quercetin. Acute oral toxicity studies indicated that the extract is safe for animals. Rats were allocated into five groups and treated for 28 days as follows: control, AM (200 mg/kg, orally), Pb (15 mg/kg, orally), Pb + AM (100 mg/kg), and Pb + AM (200 mg/kg). Pb administration markedly increased serum cystatin C, urea, creatinine levels, and urinary NAG. Pb also caused renal histopathological alterations. However, AM o-treatment ameliorated such pathological changes. In addition, AM treatment prevented Pb-induced accumulation of malondialdehyde (MDA), attenuated glutathione (GSH) depletion, and catalase (CAT) and superoxide dismutase (SOD) exhaustion. AM guarded against Pb-induced enhanced the protein expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB). Further, AM significantly prevented Pb-induced upregulation of mRNA levels of Bax and downregulation of Bcl-2. These effects were associated with increased levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in renal tissue.

Conclusion
AM guards against Pb-induced nephrotoxicity in rats that involve, at least partly, the antioxidant, anti-inflammatory, and anti-apoptotic activities as well as the modulation of HO-1 and Nrf2 expression.