bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is there a difference between the incidence of subtypes of tibial plateau fractures between six different level 1, level 2 and level 3 trauma centers in the Netherlands?
Authors: van der Gaast N. , Jaarsma R. L. , Edwards M. J. R. , Doornberg J. N. , Hermans E. ,   the Trauma Platform Collaboration, Huitema Jellina , Assink Nick , IJpma Frank , Meijs Claartje , Duijff Jan , Hekma Edo , Moerbeek Patrick , de Bruin Marcel , Beetz Ivo , van Wijk Bart , Peperkamp Kirsten , Smeeing Diederik 
Published: February 2025

Abstract

Purposes
Tibial plateau fractures can present as different subtypes due to variation in patient characteristics and trauma mechanisms. Insight in the fracture pattern and classification is critical for adequate treatment.This study aims to assess the incidence of tibial plateau fracture subtypes among various levels of trauma centers in the Netherlands, to explore potential variations in fracture patterns and fracture classifications between these centers.

Methods
Over a one-year period data was collected from six Dutch trauma centers representing different levels of trauma care. Fractures were classified using both Schatzker and Luo’s systems. Interobserver agreement was calculated to evaluate the consistency of fracture classification among surgeons.

Results
We included 115 patients treated for a tibial plateau fracture across six different hospitals. The mean patient age was 54 years, ranging from 17 to 85 years. Differences in fracture incidence and mechanisms of injury across trauma centers were revealed; Level 1 trauma centers treated a higher proportion of high-energy trauma cases, predominantly Schatzker 6 fractures, while level 2 and 3 centers dealt with more low-energy traumas, particularly Schatzker 2 fractures. Interobserver agreement for both classification systems was moderate, indicating challenges in classifying tibial plateau fractures accurately.

Conclusion
This study sheds light on the diverse distribution of subtypes of tibial plateau fractures in Dutch trauma centers. Level 1 centers are treating younger, high-energy trauma patients, whereas level 2 and 3 centers handle more low-energy traumas, predominantly Schatzker 2 fractures.

Trial registration
METC Oost-Nederland: 2021–13,184.
Effect of holmium laser prostatectomy on surgical outcomes of primary bladder neck obstruction
Authors: Lee Hyomyoung , Jeong Hyun Ju , Choo Min Soo , Cho Sung Yong , Jeong Seong Jin , Oh Seung-June 
Published: February 2025

Abstract

Background
The purpose of this study is to evaluate the efficacy and safety of holmium laser prostatectomy in patients diagnosed with primary bladder neck obstruction (PBNO), compared with patients with benign prostatic hyperplasia (BPH).

Methods
We analyzed the databases of patients who underwent a holmium laser prostatectomy or enucleation of the prostate for PBNO and BPH between January 2018 and August 2022. PBNO was diagnosed primarily based on cystourethroscopic findings. Patients were followed up according to a regular protocol at 2 weeks, 3 mo, and 6 mo postoperatively.

Results
In total, 28 and 447 patients with PBNO and BPH, respectively, were identified. Preoperative urodynamic studies showed that detrusor underactivity was significantly more prevalent in the PBNO group (78.6%) than in the BPH group (57.5%) (p < 0.01). Both PBNO and BPH groups showed significant improvements in the total International Prostate Symptom Score, Overactive Bladder Symptom Score, and maximum flow rate at 6 mo postoperatively compared with the preoperative values (p < 0.01). Subjective satisfaction 6 mo after operation was not significantly different between the PBNO and BPH groups (p > 0.05). Complications in the PBNO group included recatheterization (n = 1, 3.5%), with no patients requiring blood transfusion or transurethral coagulation.

Conclusions
Holmium laser prostatectomy was effective and safe for patients with PBNO, with elevated subjective patient satisfaction.
Intratumoral microbiome: implications for immune modulation and innovative therapeutic strategies in cancer
Authors: Wang Na , Wu Si , Huang Lanxiang , Hu Yue , He Xin , He Jourong , Hu Ben , Xu Yaqi , Rong Yuan , Yuan Chunhui , Zeng Xiantao , Wang Fubing 
Published: February 2025

Abstract
Recent advancements have revealed the presence of a microbiome within tumor tissues, underscoring the crucial role of the tumor microbiome in the tumor ecosystem. This review delves into the characteristics of the intratumoral microbiome, underscoring its dual role in modulating immune responses and its potential to both suppress and promote tumor growth. We examine state-of-the-art techniques for detecting and analyzing intratumoral bacteria, with a particular focus on their interactions with the immune system and the resulting implications for cancer prognosis and treatment. By elucidating the intricate crosstalk between the intratumoral microbiome and the host immune system, we aim to uncover novel therapeutic strategies that enhance the efficacy of cancer treatments. Additionally, this review addresses the existing challenges and future prospects within this burgeoning field, advocating for the integration of microbiome research into comprehensive cancer therapy frameworks.

Graphical Abstract
EGF receptor in organ development, tissue homeostasis and regeneration
Authors: Tito Claudia , Masciarelli Silvia , Colotti Gianni , Fazi Francesco 
Published: February 2025

Abstract
The epidermal growth factor receptor (EGFR) is a protein embedded in the outer membrane of epithelial and mesenchymal cells, bone cells, blood and immune cells, heart cells, glia and stem neural cells. It belongs to the ErbB family, which includes three other related proteins: HER2/ErbB2/c-neu, HER3/ErbB3, and HER4/ErbB4. EGFR binds to seven known signaling molecules, including epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α). This binding triggers the formation of receptor pairs (dimers), self-phosphorylation of EGFR, and the activation of several signaling pathways within the cell. These pathways influence various cellular processes like proliferation, differentiation, migration, and survival. EGFR plays a critical role in both development and tissue homeostasis, including tissue repair and adult organ regeneration. Altered expression of EGFR is linked to disruption of tissue homeostasis and various diseases, among which cancer. This review focuses on how EGFR contributes to the development of different organs like the placenta, gut, liver, bone, skin, brain, T cell regulation, pancreas, kidneys, mammary glands and lungs along with their associated pathologies. The involvement of EGFR in organ-specific branching morphogenesis process is also discussed. The level of EGFR activity and its impact vary across different organs. Factors as the affinity of its ligands, recycling or degradation processes, and transactivation by other proteins or environmental factors (such as heat stress and smoking) play a role in regulating EGFR activity. Understanding EGFR’s role and regulatory mechanisms holds promise for developing targeted therapeutic strategies.
Comprehensive molecular analysis of 26 newly established human pancreatic ductal adenocarcinoma cell lines reveals two clusters with variating drug sensitivities
Authors: Maeng Ju Eun , Kim Jae-Hyeon , Kim Soon-Chan , Yun Won-Gun , Kwon Wooil , Han Youngmin , Oh Do-Youn , Lee Sang Hyub , Jang Jin-Young , Ku Ja-Lok 
Published: February 2025

Abstract

Background
Pancreatic ductal adenocarcinoma (PDAC) is a malignant form of cancer with the worst survival rate and an extremely low rate of response to treatments. The development and molecular characterization of pancreatic cancer cell lines (PCCLs) are essential for studying the biology of highly aggressive pancreatic adenocarcinoma.

Methods
We applied whole exome sequencing (WES) and RNA-seq to identify molecular characteristics of 26 newly established PCCLs. Eighteen clinically relevant anti-cancer drugs were used to assess highly heterogeneous drug responses across the 26 cell lines.

Results
We confirmed that common driver mutations of PDAC were well retained in our cell lines through WES analysis. Transcriptomic analysis identified two representative clusters that correlated with responses to certain drugs. By using Moffitt’s classification method, the two clusters, C1 and C2, showed comparable expression patterns to “Basal-like” and “Classical” types, respectively. Drug screening results showed varying responses among different cell lines. In our cohort, C2 displayed greater sensitivity to anti-cancer drugs compared to C1. Furthermore, drugs targeting similar molecular pathways exhibited corresponding reactions among cell lines.

Conclusions
Our results underscored that transcriptomic features of pancreatic cancer correlate with drug sensitivity rather than with the effects of targeted drugs. Cell lines are useful in vitro model systems for studying the molecular mechanisms of PDAC.

Graphical Abstract
Making intersectoral stakeholder engagement in medicine quality research work: lessons from the STARmeds study in Indonesia
Authors: Hasnida Amalia , Bal Roland , Manninda Reise , Saputra Stanley , Nugrahani Yunita , Faradiba Faradiba , Kok Maarten Olivier 
Published: February 2025

Abstract

Background
Tackling falsified and substandard medicines requires intersectoral collaboration, impact-oriented research and the effective application of research findings. However, the best way to organize research and involve stakeholders from different sectors to ensure that results are used, remains unclear. We aimed to assess how intersectoral stakeholder engagement in research on medicine quality in Indonesia evolved, influenced the research processes and participants, and affected the uptake of the results.

Methods
For this prospective case study, we adopted an abductive approach inspired by contribution mapping and collaborative governance. We conducted 37 interviews with key informants, observed 24 meetings and analysed 121 documents to systematically map the engagement of stakeholders in a study on medicine quality, focusing on processes, influences and research-related contributions.

Results
From the outset, it proved feasible, but challenging, to effectively engage stakeholders in research into falsified and substandard medicines in Indonesia. After a cautious start and persistent efforts, stakeholders, such as the national medicine regulatory authority, became increasingly involved and developed a shared understanding of the need for intersectoral collaboration to tackle problems with medicine quality. While the research findings did not lead to a different estimate of the magnitude of the problem, the involvement of stakeholders was beneficial. After formalizing the collaboration, stakeholders provided data needed to study potential risk factors, product varieties and sales volumes, and contributed to decisions during the research and interpretation of the findings. Owing to frequent personnel changes and diverging priorities, stakeholder engagement required more effort than anticipated, and necessitated a strategic and adaptive approach. This approach had to account for the varying priorities and interests of stakeholders, the evolving framing of the problem, the implications of the findings and the nature of the field, where regulators must operate cautiously, balance interests and respond to critical incidents.

Conclusions
Intersectoral stakeholder engagement in medicine quality research is challenging but beneficial. Engagement contributed to building trust and relationships between researchers and stakeholders, helped forge an intersectoral network focused on medicine quality, exposed the medicine regulator to new methods, inspired stakeholders to take on new roles and make better use of existing data and furthered a research–policy partnership forum on pharmaceutical topics.
Helping the medicine go down: the role of the healthcare professional in a young person’s experience of achalasia, a rare oesophageal motility disorder
Authors: Capps Geena 
Published: February 2025

Abstract
Young patients can be uniquely vulnerable to the impacts of a rare disease, diagnosed in their critical years of identity formation, social development, and planning for the future. Drawing from my journey as both a rare disease patient and a medical student, this essay explores how the rare disease achalasia has shaped my life, alongside the experiences of another young patient, Isobel. Most importantly, this essay highlights the critical role that individual healthcare professionals play in shaping young patients’ experiences of their condition. Although diagnosing and managing rare diseases can be challenging due to limited research and awareness, my own experiences demonstrate that individual, intentional changes can have profound impacts. By engaging with and believing young patients, individual healthcare providers can reduce misdiagnoses, alleviate isolation and uncertainty, and ultimately, improve healthcare outcomes for young people with rare diseases.
An index of the initial blood pressure response to angiotensin II treatment and its association with clinical outcomes in vasodilatory shock
Authors: Leisman Daniel E. , Wieruszewski Patrick M. , Busse Laurence W. , Chawla Lakhmir S. , Hibbert Kathryn A. , Handisides Damian R. , Khanna Ashish K. , Ostermann Marlies , McCurdy Michael T. , Adams Christopher D. , Hodges Tony N. , Bellomo Rinaldo ,   the ATHOS-3 Investigators
Published: February 2025

Abstract

Background
No standardized index exists to assess cardiovascular responsiveness to angiotensin-II. We hypothesized that a standardized index of initial blood pressure response to angiotensin-II treatment would be associated with clinical outcomes.

Methods
Using data from the Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we developed an Angiotensin-II Initial MAP Response Index of Treatment Effect (AIMRITE) defined as (MAP at hr1 – MAP at baseline)/study drug dose. We assessed AIMRITE continuously and, based on observed distributions, we additionally categorized patients as “responsive” or “resistant”, with responsiveness defined by an AIMRITE ≥ 0.90 mmHg/ng/kg/min. The primary clinical outcome was 28-day mortality. Secondary outcomes included days alive and vasopressor- or ventilator- or renal replacement therapy-free at day-7. Biological outcomes included baseline renin, angiotensin-II, and renin/angiotensin-II ratio, and their change at hr3.

Results
Of 158 placebo patients, as expected, 157 (99%) had AIMRITE < 0.90 mmHg/ng/kg/min (median AIMRITE 0.02; IQR − 0.03–0.10). In contrast, 163 patients assigned to angiotensin-II had a median AIMRITE of 1.43 mmHg/ng/kg/min (IQR 0.35–2.83). Of these, 97 (60%) were responsive (median AIMRITE 2.55; IQR 1.66–4.12) and 66 (40%) were resistant (median AIMRITE 0.24; IQR 0.10–0.52). Each 1.0-unit increase in AIMRITE was associated with a 16% lower hazard of death (HR: 0.84 per-mmHg/ng/kg/min [95% CI 0.74–0.95], p = 0.0062). Responsive patients had half the mortality hazard than resistant patients (HR: 0.50 [95% CI 0.32–0.78], p = 0.0026) and placebo patients (HR 0.58 [95% CI 0.40–0.86], p = 0.0064). Resistant patients had a similar mortality hazard to placebo (HR 1.17 [95% CI 0.80–1.72], p = 0.41). Compared to resistant patients, responsive patients had lower baseline renin and renin/angiotensin-II ratio, but a greater decrease in both at hr3. When stratified by baseline renin level, mortality was highest in placebo patients with high renin (69%) and angiotensin-II resistant patients with low renin (61%).

Conclusions
Among patients with catecholamine-refractory vasodilatory shock treated with angiotensin-II, the AIMRITE was associated with mortality at day-28. Responsive angiotensin-II patients had higher survival versus both angiotensin-II resistant patients and those treated with placebo plus standard vasopressors. This index may serve as a prognostic indicator and early identifier of patients most likely to benefit from angiotensin-II.
Optimal timing of anticoagulation after acute ischaemic stroke with atrial fibrillation (OPTIMAS): statistical analysis plan for a randomised controlled trial
Authors: Ahmed Norin , Dehbi Hakim-Moulay , Freemantle Nick , Best Jonathan , Nash Philip S. , Ruffle James K. , Doig David , Werring David J. 
Published: February 2025

Abstract

Background

Atrial fibrillation causes one-fifth of ischaemic strokes, with a high risk of early recurrence. Although long-term anticoagulation is highly effective for stroke prevention in atrial fibrillation, initiation after stroke can be delayed by concerns over intracranial haemorrhage risk. Direct oral anticoagulants offer a significantly lower risk of intracranial haemorrhage than other anticoagulants, potentially allowing earlier anticoagulation and prevention of ischaemic stroke recurrence, but the safety and efficacy of this approach has not been established. This article describes the statistical analysis plan for the OPTIMAS trial as an update to the published protocol. It was written prior to the end of patient follow-up, before database lock and thus while the outcome of the trial is still unknown.

Aim
The optimal timing of anticoagulation after acute ischaemic stroke with atrial fibrillation (OPTIMAS) trial will investigate whether early treatment with a direct oral anticoagulant within 4 days of stroke onset is as effective as, or better than, delayed initiation at 7 to 14 days from onset.

Methods and design
OPTIMAS is a multicentre randomised controlled trial with blinded outcome adjudication. Participants with acute ischaemic stroke and atrial fibrillation eligible for anticoagulation with a direct oral anticoagulant are randomised 1:1 to early or delayed initiation. Here, we describe in detail the statistical aspects of OPTIMAS, including outcome measures, sample size calculation, general analysis principles, descriptive statistics, statistical models, and planned subgroup analyses.

Study outcomes
The primary outcome is a composite of recurrent stroke (ischaemic stroke or symptomatic intracranial haemorrhage) and systemic arterial embolism within 90 days. Secondary outcomes include each individual component of the composite outcome, major bleeding, functional status assessed by the modified Rankin Scale, ongoing anticoagulation, quality of life, health and social care resource use, and length of hospital stay.

Discussion
OPTIMAS aims to provide high-quality evidence on the safety and efficacy of early direct oral anticoagulant initiation after atrial fibrillation-associated acute ischaemic stroke.

Trial registrations
ISRCTN: 17,896,007; ClinicalTrials.gov: NCT03759938. Registered on November 30 2018.
Comparative effects of selenium-enriched lactobacilli and selenium-enriched yeast on performance, egg selenium enrichment, antioxidant capacity, and ileal microbiota in laying hens
Authors: Zhou Jianmin , Obianwuna Uchechukwu Edna , Zhang Longfei , Liu Yongli , Zhang Haijun , Qiu Kai , Wang Jing , Qi Guanghai , Wu Shugeng 
Published: February 2025

Abstract

Background
Organic selenium (Se) has gained recognition in poultry nutrition as a feed additive to boost production and Se deposition in eggs and tissues, owing to its high bioavailability, efficient tissue accumulation and minimal toxicity. Selenium-enriched yeast (SeY) is a well-established source, while selenium-enriched lactobacilli (SeL), a newer alternative, offers the added benefits of probiotics. This study examined the effects of SeY and SeL on egg quality, antioxidant capacity, Se deposition, and gut health in laying hens. After a two-week pre-treatment with a Se-deficient diet (SeD), 450 Hy-Line Brown laying hens (30-week-old) were assigned into five dietary groups with six replicates of 15 hens each. The groups included a SeD, SeD supplemented with 1.5 mg Se/kg from SeY (SeY15), or 1.5, 3.0, and 6.0 mg Se/kg from SeL (SeL15, SeL30, SeL60). The feeding trial lasted for 12 weeks.

Results
SeY15 and SeL15 improved the feed-to-egg ratio (P < 0.05) in the latter stages. Haugh units were significantly increased (P < 0.05) in the SeY15 and SeL30 groups, while darker yolk color (P < 0.05) was observed in the SeY15, SeL15, and SeL60 groups. All Se-supplemented diets increased Se content in whole eggs, albumen, and yolk (P < 0.05), while SeL groups showed a dose-dependent effect. Antioxidant enzyme activities increased, and MDA content decreased in the serum (P < 0.05), with SeY15 showing the highest GSH-Px levels (P < 0.05). SeL60 increased serum alkaline phosphatase and aspartate transaminase, and distorted the liver architecture (P < 0.05). Se-diets reduced concentrations of reactive oxygen species (ROS) in the ileum and liver (P < 0.05). SeL15 improved the ileal villus height-to-crypt depth ratio (P < 0.05). SeY15 and/or SeL15 up-regulated TXNRD1 and SEPHS1 mRNA while down-regulating SCLY expression in the liver. SeY15 altered ileal microbiota by increasing both beneficial and pathogenic bacteria, whereas SeL15 predominantly boosted beneficial bacteria.

Conclusion
SeL integrates the antioxidant properties of organic Se with the probiotic benefits on gut health, resulting in a performance-enhancing effect comparable to that of SeY. However, high SeL level (6.0 mg Se/kg) compromised productivity and metabolic functions while enhancing Se deposition.
The use of AI in epilepsy and its applications for people with intellectual disabilities: commentary
Authors: Milne-Ives Madison , Brownson-Smith Rosiered , Ananthakrishnan Ananya , Wang Yihan , Cong Cen , Winston Gavin P. , Meinert Edward 
Published: February 2025

Abstract
Epilepsy is one of the most common neurological disorders, affecting more than 50 million people worldwide. Management is particularly complex in individuals with intellectual disabilities, who are at a much higher risk of having severe seizures compared to the general population. People with intellectual disabilities are regularly excluded from epilepsy research, despite having significantly higher risks of negative health outcomes and early mortality. Recent advances in artificial intelligence (AI) have shown great potential in improving the diagnosis, monitoring, and management of epilepsy. Machine learning techniques have been used in analysing electroencephalography data for efficient seizure detection and prediction, as well as individualised treatment, which facilitates timely and customised intervention for individuals with epilepsy. Research and implementation of AI-based solutions for people with intellectual disabilities and epilepsy still remains limited due to a lack of accessible long-term clinical data for model training, difficulties in communicating with people with intellectual disabilities, and ethical challenges in ensuring the safety of the AI systems for this population. This paper presents an overview of recent AI applications in epilepsy and for people with intellectual disabilities, highlighting key challenges and the necessity of including people with intellectual disabilities in research on AI and epilepsy, and potential strategies to promote the development and use of AI applications for this vulnerable population. Given the prevalence and consequences associated with epilepsy in people with intellectual disabilities, the application of AI in epilepsy care has the potential to have a significant positive impact. To achieve this impact and to avoid increasing existing health inequity, there is an urgent need for greater inclusion of people with intellectual disabilities in research around the application of AI to epilepsy care and management.