bluuebunny/crossref_metadata_2025 huggingface dataset:
Severity of Chronic Kidney Disease as Assessed by the Kidney Failure Risk Equation Is Associated With Incident Acute Ischemic Stroke
Authors: Tan Benjamin Y. Q. , Tan Yong Yi , Lim Sean Shi‐An , Toh Emma M. S. , Tack Reinier W. , Lim Pamela W. N. , Kumari Shikha , Koh Sky W. C. , Khatri Priyanka , Rastogi Shilpa , Yeo Leonard L. L. , Anderson Christopher D. , Chua Horng‐Ruey , Chua Yan Ting , Ngoh Clara L. Y.
Published: February 2025

Aim

Stroke is a leading cause of death and disability, with substantial healthcare implications. Chronic kidney disease (CKD) is similarly impactful, and emerging evidence links CKD to a higher stroke risk. Despite this, stroke risk assessment in CKD patients remains limited. This study explores the kidney failure risk equation (KFRE) as a predictive tool for ischaemic stroke in CKD patients.

Methods

This retrospective cohort study analysed CKD patients from a healthcare registry, excluding those with prior stroke, end‐stage kidney disease, or kidney transplants. Acute ischemic stroke was the primary outcome, with deaths censored. Cox proportional hazards models evaluated associations between the 2‐year and 5‐year 4‐variable KFRE scores and stroke risk.

Results

A total of 14,794 consecutive patients were included, with a median follow‐up of 509 days. The median age of the cohort was 73 years (IQR:14 years), with 6251 females(42.3%), and the majority being of Chinese ethnicity (n = 10 759,73.5%). During the follow‐up period, 155 patients (1.05%) experienced an ischemic stroke event, with a median time to stroke of 265 days (IQR:242 days). The 2‐year (HR: 1.38 per 10% increase, 95% CI: [1.17–1.63], p < 0.001) and 5‐year (HR:1.20 per 10% increase, 95% CI: [1.10–1.31], p < 0.001) 4‐variable KFRE scores were significantly associated with an increased risk of ischemic stroke. These associations remained significant after adjusting for patient demographics, comorbidities, advanced CKD stage, glycated haemoglobin and lipid parameters.

Conclusion

CKD patients at elevated risk of kidney failure also face a significantly increased risk of acute ischaemic stroke. The KFRE could potentially be integrated into CKD management to assess this risk. Future large prospective cohort studies are necessary to validate these findings.
Nur77 Promotes Inflammation in Cisplatin‐Induced Acute Kidney Injury Through Transactivation of SERPINA3 Mediating Wnt/β‐Catenin Pathway
Authors: Zhou Ying , Wan Zhen , Xiong Di , Gong Zhijun , Liu Feiyan
Published: February 2025

Aim

Acute kidney injury (AKI) is the most common complication in the treatment of cisplatin, which is a clinically effective and classical anticancer drug. Orphan Nuclear Receptor Nur77 has been found to promote renal ischaemia–reperfusion injury. In this study, we aim to explore the effects of Nur77 on cisplatin‐induced AKI (CI‐AKI) and its underlying mechanism.

Methods

HK‐2 cells treated with cisplatin were used to construct the CI‐AKI model in vitro. Cell viability and cell proliferation were analysed using CCK‐8 and EdU assays, respectively. Cell apoptosis was analysed by flow cytometry. The inflammation release level was detected using ELISA. Molecular abundance was evaluated using qPCR, Western blot and immunofluorescence. The interaction between Nur77 and SERPINA3 was clarified using ChIP and dual‐luciferase reporter gene assays.

Results

Our works demonstrated that Nur77 and SERPINA3 expression were considerably ascended in cisplatin‐induced HK‐2 cells. The silence of SERPINA3 alleviated cisplatin‐stimulated HK‐2 cell injury, which was characterised by increased cell viability and proliferation, and decreased apoptosis and inflammatory cytokine release. In addition, Nur77 promotes SERPINA3 transcription by binding to the SERPINA3 promoter region (−182 to −175), thereby upregulating SERPINA3 expression and activating the Wnt/β‐catenin pathway. Moreover, HK‐2 cell injury induced by cisplatin was notably inhibited by the knockdown of Nur77. Furthermore, the efficacy of Nur77 downregulation on the cell injury in cisplatin‐stimulated HK‐2 cells was antagonised by SERPINA3 overexpression.

Conclusion

Taken together, our findings revealed that Nur77 knockdown resisted cisplatin‐induced HK‐2 cells injury through lessening the expression of SERPINA3 mediated by transcriptional regulation and inactivating the Wnt/β‐catenin pathway.
Evidence of Holarctic distribution: common frog Rana temporaria eggs in Fennoscandia host photosymbiotic green algae (Oophila sp.)
Authors: Eriksson Pontus F. , Kerney Ryan , Larson-Pollock River , Vickers Elliana , Timenes Laugen Ane
Published: February 2025

Symbiosis is a commonly occurring phenomenon, with most plants and animals being holobionts, comprising of a host and its corresponding symbionts. It is, however, less common to have a symbiont only under a specific life stage and even more so between a photosynthesizing organism and a vertebrate animal. One such relationship is found between the unicellular green algae Oophila amblystomatis and the North American yellow‐spotted salamander Ambystoma maculatum, which is so far the only known endosymbiotic relationship between an alga and a vertebrate. In this study we investigate the possible occurrence of O. amblystomatis in Fennoscandian egg clutches from the genus Rana using citizen science data. We establish that egg capsules of the common frog Rana temporaria in Sweden act as a host species for two subclades of the monophyletic genus Oophila on a microgeographical scale (< 10 km) using a phylogenetic analysis. Furthermore, we investigated a possible endosymbiotic relationship between O. amblystomatis and R. temporaria embryos with fluorescence microscopy, which showed no algal invasion of frog tissue or cells in vivo. The association with a known symbiont Oophila may hold ecological importance for ontogeny, individual fitness, behavior, population dynamics and evolutionary potential of R. temporaria. However, the reciprocal benefits to both partners have not been determined for any Oophila‐bearing ranid. We discuss the possible Holarctic distribution of Oophila and consider the implications of the relationship between R. temporaria and O. amblystomatis.
Ecosystem engineers alter the evolution of seed size by impacting fertility and the understory light environment
Authors: Doughty Christopher E. , Wiebe Benjamin C. , Keany Jenna M. , Gaillard Camille , Abraham Andrew J. , Kristensen Jeppe A.
Published: February 2025

It has been hypothesized that the extinction of the dinosaurs, and later the Pleistocene megafauna, created a darker forest subcanopy benefiting large‐seeded plants. Larger seeds and their fruit, in turn, opened a dietary niche space for animals thus strongly shaping the ecology of the Cenozoic, including our fruit‐eating primate ancestors. In this paper, we develop a mechanistic model where we replicate the conditions of tropical forests of the early Paleocene, with small animal body and small seed size, and the Holocene, with small animal body and large seed size. We first calibrate light levels in our model using stable carbon isotope ratios from fossil leaves and estimate a decrease of understory light of c. 90 μmol m−2 s−1 (a 19% decrease) from the Cretaceous to the Paleocene. Our model predicts a rapid increase in seed size during the Paleocene that eventually plateaued or declined slightly. Specifically, we find a dynamic feedback where increased animal sizes opened the understory causing negative feedback by increasing subcanopy light penetration that limited maximum seed size, matching the actual trend in angiosperm seed sizes in mid/high latitude ecosystems. Adding the ability of larger animals to increase ecosystem fertility to the model, further increased mean animal body size by 17% and mean seed size by 90%. Our model is a drastic simplification and there are many remaining uncertainties, but we show that ecological dynamics can explain seed size trends without adding external factors such as climate change.
A New Allele HLA‐DRB4*01:03:01:22 Identified by HLA‐Targeted Third‐Generation Sequencing
Authors: Zhao Yuanli , Fan Wu , Yang Song , Gao Peng , Wang Liying
Published: February 2025

HLA‐DRB4*01:03:01:22 differs from HLA‐DRB4*01:03:01:06 by one nucleotide change in intron 2.
Characterisation of the Novel HLA‐DQB1*05:355 Allele by Sequencing‐Based Typing
Authors: Pajot Thibault , Elsermans Vincent , Top Isabelle , Labalette Myriam
Published: February 2025

HLA‐DQB1*05:355 differs from HLA‐DQB1*05:01:01:01 by one nucleotide substitution in codon 197 in exon 4.
Characterisation of the Novel HLA‐A*02:1198 Allele by Sequencing‐Based Typing
Authors: Pajot Thibault , Elsermans Vincent , Top Isabelle , Labalette Myriam
Published: February 2025

HLA‐A*02:1198 differs from HLA‐A*02:01:01:01 by one nucleotide substitution in codon −22 in exon 1.
Characterisation of the Novel HLA‐C*05:01:83 Allele by Sequencing‐Based Typing
Authors: Pajot Thibault , Elsermans Vincent , Top Isabelle , Labalette Myriam
Published: February 2025

HLA‐C*05:01:83 differs from HLA‐C*05:01:01:01 by one nucleotide substitution in codon 291 in exon 5.
Red blood cell inventory management: Insights from transfusion laboratory technologists in British Columbia, Canada
Authors: Dhahan Jasdeep , Morrison Douglas , Shih Andrew W. , McDonald Deb , Chen Robby , Hao Lillian , Rosinski Kristin , Buchko Sarah , Blake John , Rutherford Alexander
Published: February 2025

Background and Objectives

There is concern about sustaining the O negative blood supply, especially in areas with many rural/remote hospitals like British Columbia. Red blood cells are perishable, making inventory management challenging. Demand must be met without wasting this precious resource. Inventory management challenges stem from data scarcity and human factors. Transfusion medicine technologists, who manage inventory daily, are key to understanding the human factors in inventory management. We conducted a qualitative study to understand technologists' inventory management perspectives and experiences, particularly for group O negative red blood cells, aiming to inform future inventory modelling to address human factors.

Materials and Methods

We interviewed transfusion laboratory technologists and technical leads from all health authorities and a blood product supplier representative for the Province of British Columbia. Thematic analysis of the interview transcripts was conducted.

Results

We found five themes that influence technologist decision‐making on RBC inventory management, key challenges for O‐negative RBCs, and identified inventory management strategies. We compare the top three inventory practices from our results with literature.

Conclusions

Our findings help bridge the knowledge gap concerning human factors in RBC inventory management, with potential generalizability to other jurisdictions. They hold promise for informing the safeguarding of donors' altruistic contributions.
Evaluation of Complement‐Dependent Cytotoxicity Assays for Gene‐Edited Pig‐to‐Human Xenotransplantation
Authors: Feng Hao , Zhang Man , Xia Qiangbing , Du Jiaxiang , Li Tao , Chen Song , Wang Yi , Pan Dengke , Zhu Lan , Chen Gang
Published: February 2025

Background

Gene‐edited pigs for xenotransplantation usually contain one or more transgenes encoding human complement regulatory proteins (CRPs). Because of species differences, human CRP(s) expressed in gene‐edited pigs may have difficulty inhibiting the activation of exogenous rabbit complement added to a complement‐dependent cytotoxicity (CDC) assay. The use of human complement instead of rabbit complement in CDC experiments may more accurately reflect the actual regulatory activity of human CRP(s).

Methods

Peripheral blood mononuclear cells (PBMCs) were obtained from one GTKO pig and two GTKO/hCD55 pigs with a high or low level of hCD55 expression. After incubation of heat‐inactivated normal human sera (HINHS) with porcine PBMCs, CDC levels were measured after the addition of commercial rabbit complement or human complement. In addition, a modified one‐step CDC method was established using pooled normal human sera (NHS) without the addition of an exogenous complement.

Results

There was no significant difference in the binding of IgM/IgG to PBMCs from the three pigs. Both rabbit and human complement‐mediated a significant cytotoxic effect on GTKO pig PBMCs (98.97% vs. 82.73%). Even the high expression of hCD55 only had a very limited inhibitory effect on rabbit complement‐mediated cytotoxicity (81.70% vs. 98.97%). However, regardless of whether the expression level was high or low, hCD55 had a very remarkable inhibitory effect on human complement‐mediated cytotoxicity (2.94% and 23.83% vs. 82.73%; p < 0.01). Similar results were obtained using the modified one‐step CDC method. In addition, the inhibitory effect of hCD55 on C3c and C5b‐9 deposition on pig PBMCs was positively correlated with the expression level of hCD55.

Conclusion

The use of human complement instead of rabbit complement in CDC assays can better reflect the actual cytotoxic effect of human xenoantibodies against pig PBMCs expressing human CRP(s), and thus may have potential application to gene‐edited pig‐to‐human xenotransplantation.
Sideband Peak Count Technique for Monitoring Bond–Slip Behavior Between Reinforcement Systems and Masonry
Authors: Castellano Anna , Pinchuk Nataliia , Fraddosio Aguinaldo , Martellotta Gianfranco , Piccioni Mario Daniele , Kundu Tribikram
Published: February 2025

The use of Fabric-Reinforced Cementitious Matrix (FRCM) composites has become a cornerstone in strengthening several types of structures, ranging from reinforced concrete structures to historical masonry constructions. It is crucial to experimentally assess the effectiveness of the application of the reinforcing layer. Indeed, the performance of FRCM reinforcing interventions highly depends on the bonding at the matrix–fiber and matrix–substrate interfaces. Therefore, the experimental characterization of FRCM bond behavior is essential for designing and ensuring the durability of reinforcement systems. To address this, we have proposed using an innovative nonlinear ultrasonic method: the Side-band Peak Count (SPC) technique. Specifically, the SPC approach has been applied to analyze ultrasonic test results obtained during Double-Lap Shear Tests (DLT) conducted on masonry specimens reinforced with B-FRCM (basalt fiber textile FRCM). We show that it is possible to correlate nonlinear ultrasonic parameters with the shear stress distribution at the reinforcement–masonry interface. Additionally, a relatively new nonlinear ultrasonic parameter, the SPC index, is shown to be effective in monitoring the evolution of the shear stress–slip relationship at this interface, a crucial aspect for understanding the mechanics of the reinforcement–substrate interaction. The nonlinear ultrasonic results have been compared with the results of DLT debonding tests to validate the proposed methodology. The effectiveness of the SPC technique is investigated and discussed. Finally, we have developed a robust numerical model to analyze the bond behavior between the reinforcement and masonry. The numerical model is valuable for both the design of experimental tests and the validation of the experimental results.
Torsional Vibration of Drill String Induced by Heave Motion in Deepwater Drilling
Authors: Kaneko Tatsuya , Inoue Tomoya , Wada Ryota , Katsui Tokihiro , Hiroyoshi Suzuki
Published: February 2025

Understanding drill-string dynamics is essential to improving drilling efficiency and preventing accidents. Previous studies have mainly focused on self-excited oscillations due to stick-slip and bit-bounce. However, in deepwater drilling, large weight-on-bit fluctuations due to heave motion are a significant concern that can affect torsional dynamics. This paper reports analytical, numerical, and field data investigations on torsional vibrations of a drill string in deepwater drilling. First, we analyzed the field data from deep-sea scientific drilling vessel Chikyu. The field data showed that heave, WOB, and torque oscillated at similar frequencies. This result indicated that the drill string could have forced torsional vibrations due to heave instead of self-excited vibrations due to stick-slip.Second, we analytically and numerically investigated drill-string torsional dynamics. The torsional vibration of the drill string can be described only by self-excited vibration due to stick-slip if WOB is constant. However, when the WOB fluctuates, the forced vibration of the WOB must be considered. The results showed that vibration at the heave frequency had a more significant effect on torsional vibration than the axial self-excited frequency for the same amplitude of WOB variation. In addition, large WOB fluctuations increased the risk of stick-slip and reverse rotation of the drill bit. Numerical experiments with the field data showed that the forced torsional vibration caused by heave motion was predominant in deepwater drilling. These results show the importance of capturing forced torsional vibrations and reducing WOB fluctuations.
Wire Arc Additive Manufacturing With Infrared Image Feedback
Authors: He Honglu , Wen John T.
Published: February 2025

Wire arc additive manufacturing (WAAM) is a metal 3D printing technology that rapidly prototypes by depositing molten metal wire onto a substrate. Traditionally, WAAM has relied on the open-loop control with carefully tuned parameters, a process that can be time-consuming and often results in inconsistent performance. Although laser line scanners and other 3D scanning techniques have been used to ensure geometric fidelity, they typically provide feedback through layer-by-layer scans, leaving imperfections from arc striking and extinguishing. This paper introduces a novel approach that incorporates infrared (IR) camera thermography to achieve more consistent and reliable WAAM printing with real-time feedback. By using IR live streaming to close the loop with in-layer updates, we demonstrate how this feedback mechanism can enhance control over bead width consistency and wire stick-out length, ultimately leading to higher-quality metal 3D-printed structures. Compared with open-loop preset constant welding parameters on a triangular wall geometry, our IR-guided WAAM process achieves 49% bead width variance reduction and 95% wire stick-out length tracking improvement.
Mixed-methods study to develop extensions to the SPIRIT and CONSORT statements for factorial randomised trials: the Reporting Factorial Trials (RAFT) study
Authors: Hall Sophie S , Juszczak Edmund , Birchenall Megan , Elbourne Diana , Beller Elaine , Chan An-Wen , Little Paul , Montgomery Alan A , Kahan Brennan C
Published: February 2025

Background

Extensions to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and Consolidated Standards of Reporting Trials (CONSORT) reporting recommendations specifically for factorial trials have been developed by the Reporting Factorial Trials (RAFT) study group. This article describes the processes and methods used to develop the extensions.

Objective

To develop SPIRIT and CONSORT extensions for factorial trials.

Design and participants

A four-phase, consensus-based approach was used: phase 1: scoping review, phase 2: Delphi survey (n=104 respondents in round 1), phase 3: consensus meeting (n=15 members) and phase 4: checklist finalisation.

Results

In phase 1, the scoping review identified 31 reporting recommendations, which formed a long list of 50 concepts (19 applied to the SPIRIT extension and 31 applied to the CONSORT extension) to include in the guideline development. In phase 2, a three-round Delphi survey resulted in two new concepts being added and ended with 49 concepts (19 applied to SPIRIT and 30 applied to CONSORT) reaching consensus to remain, with only three concepts meeting the exclusion criteria. In phase 3, the concepts were further refined and translated into specific extension item wording, through an extensive review process conducted by the core RAFT team and leading trial experts, who attended a 2-day hybrid meeting. The resulting 9 SPIRIT items and 17 CONSORT items were further evaluated and developed through an iterative process in phase 4, to promote user acceptance and uptake.

Conclusion

Uptake of the CONSORT and SPIRIT extensions will improve the conduct of factorial trials, as well as understanding and interpretation of such trials. By reporting on how these extensions were developed, we promote transparency of this process and share learning experiences to develop best practice when developing reporting guidelines.
How healthcare providers’ IT identity is formed and how it affects the use of telemonitoring: a qualitative interview study in COPD care
Authors: Renting Nienke , Brands Martijn R , Velthausz Emmie A B , Gouw Samantha C
Published: February 2025

Background

Telemonitoring is a promising approach to facilitate patients’ self-management and improve health outcomes, especially among people with chronic health conditions. Yet, many healthcare organisations struggle to implement telemonitoring successfully. IT identity, an individual’s self-identification with an information technology (IT) tool, has been suggested to strongly predict and shape the use of technology. IT identity is related to three emotional responses: emotional energy, dependence and relatedness.

Objective

To explore how healthcare professionals’ IT identity is shaped, and how it affects their attitude towards and intended use of telemonitoring.

Design

Qualitative, semistructured interview study.

Setting

Primary care and hospitals (general and academic) in the Netherlands.

Participants

Sixteen nurses, pulmonologists, general practitioners and researchers working in chronic obstructive pulmonary disease (COPD) care.

Results

Participants expressed varying emotional responses regarding the use of telemonitoring. We associated participants’ responses with the three dimensions of IT identity. Regarding emotional energy, some expressed pride in innovating, while others lacked faith in using telemonitoring. Regarding dependence, different perceived intentions and needs for using telemonitoring were identified: to coach patients, prevent deterioration of health, achieve logistical advantages for patients and preserve the accessibility of healthcare. Regarding relatedness, some participants expressed a strong external but weak internal motivation to use telemonitoring.

Based on emotional responses, we identified five manifestations of IT identity that illustrate how different healthcare professionals use telemonitoring in COPD care: the Scientist, Innovator, Protector, Empowerer and Conversationalist. These manifestations differ in their readiness to innovate and in their beliefs what it means to be a good healthcare provider: to protect or to coach.

Conclusion

Healthcare professionals’ emotional energy, dependence and relatedness regarding telemonitoring in COPD care shaped their IT identity and how they used telemonitoring. Implementation strategies tailored towards the five manifestations of IT identity could help the sustainable implementation of telemonitoring in clinical practice.
Importance of postmortem anthropometric evaluation in defining the role of malnutrition as a cause of infant and child deaths in Sub-Saharan Africa and South Asia: a cohort study
Authors: Das Priya Mehta-Gupta , Madewell Zachary J , Blau Dianna M , Whitney Cynthia G , Ramakrishnan Usha , Stein Aryeh D , Young Melissa F , Suchdev Parminder S
Published: February 2025

Objectives

To evaluate how postmortem anthropometric malnutrition (PAM) measures align with expert panel attribution of malnutrition as a causal or significant condition in under-5 mortality (U5M).

Design

Cohort study using data from the Child Health and Mortality Prevention Surveillance network, incorporating clinical records, postmortem anthropometrics, minimally invasive tissue sampling, clinical abstraction and verbal autopsy to determine multiple causes of death.

Setting/participants

1405 deaths of children aged 1–59 months from six African countries between 2016 and 2023.

Primary and secondary outcome measures

PAM was determined using z-scores from the WHO Child Growth Standards: underweight (weight-for-age<(−2)), wasting (arm circumference-for-age or weight-for-length<(−2)) and stunting (length-for-age <(−2)). Performance metrics (sensitivity (SE), specificity (SP) and positive predictive values (PPV)) were calculated to determine the alignment between PAM and expert panel attribution of malnutrition as a causal or significant condition to death.

Results

Nearly 75% of cases demonstrated moderate-to-severe malnutrition by PAM, while expert panels attributed malnutrition in 41% of cases. Performance metrics varied across anthropometric indices: underweight exhibited the highest SE (89.7%), while wasting based on arm circumference had the highest SP (81.9%) and PPV (76.8%). Discrepancies between PAM classification and expert panel attribution differed significantly by site, age, location of death and preventability of death (p<0.05). Adjusted multivariate regression showed that expert panel attribution was more likely with increasing severity of PAM.

Conclusions

The proportion of U5M attributable to malnutrition ranged between 41% (expert panel attribution) and 74% (PAM). Variability in classification underscores the need for monitoring and quality improvement measures to address discrepancies. Improved alignment between PAM and panel assessments is essential for accurately identifying malnutrition-related deaths and designing effective interventions to reduce U5M.
Patient and family engagement interventions for enhancing patient safety in the perioperative journey: a scoping review
Authors: Seyfulayeva Ayshe , Fonte Bianca Ferreira , Alho Ana Margarida , Shaikh Anum , Nunes Ana Beatriz , Casaca Pedro Gonçalves Carvalho , Leite Andreia , Taha Ayda , Dhingra-Kumar Neelam , Sousa Paulo
Published: February 2025

Background

Surgical procedures present intricate challenges within healthcare delivery, often associated with higher risks of adverse events compared with non-surgical contexts. Patient and family engagement (PFE) throughout the perioperative journey is a possibility to enhance care quality, safety and patient-centredness. However, literature addressing PFE across the entirety of the perioperative journey remains sparse.

Objective

The current scoping review aims to comprehensively map the existing interventions with PFE approach focused on improving patient safety across various types of surgical procedures throughout the perioperative journey. In addition, the review aims to understand the level and type of PFE approach adopted in this context.

Eligibility criteria

Articles published in indexed peer-reviewed journals from 2003 to 2023, written in English, Portuguese or Spanish, that report on interventions with PFE approach targeting adult surgical patients, their families, caregivers, patient advocates and patient champions. The review includes articles reporting on both inpatient and ambulatory surgical patients.

Methods

Following Joanna Briggs Institute guidelines and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews framework, this review systematically searched PubMed, Web of Science, SCOPUS, CINAHL, and PsycINFO for relevant articles. Eligible interventions were categorised using PFE framework regarding the level of engagement and mapped according to the WHO Global Patient Safety Action Plan 2021–2030.

Results

Out of 765 records initially identified, 32 met the eligibility criteria for data extraction and analysis, of which 40% originated from the USA, followed by the UK (18%) and Canada (12%). 47% of the interventions targeted ‘multiple/all types’ of procedures, 19% focused on cardiothoracic surgeries and 9% on gynaecological procedures or organ transplant. The majority of the interventions (88%) focused on PFE at the direct care level, predominantly adopting a consultation-based approach. Furthermore, 81% of eligible interventions emphasised patient information and education, 16% addressed codevelopment of policy and 3% of interventions focused on patient advocacy.

Conclusion

The findings show a predominant focus on PFE interventions targeting patient safety at the direct care level, particularly in the provision of patient information and education. However, interventions at organisational and policy-making levels are notably scarce. Further investment is required to promote interventions engaging patients and families at broader organisational and policy-making levels.
Parental perspectives of trisomy 18: common threads of a life-limiting diagnosis
Authors: Armour Evelyn , MacPherson Melissa J , Mack Cheryl , van Manen Michael
Published: February 2025

There is a narrative told among healthcare providers that the public stories of trisomy 18 do not reflect the experiences of the many families navigating this diagnosis. This is in the context of a recognised paradigm shift occurring in the treatment of children born with trisomy 18 from one focused solely on comfort to one that considers the potential of medical-surgical interventions to afford survival. This study aims to elicit and explore phenomenologically parents’ narratives of trisomy 18. The focus is on the full spectrum of trisomy 18: whether it was diagnosed before or after birth, whether the child’s life was of short or long duration and whether invasive or palliative care was sought. While trisomy 18 was not univocal of the children’s stories, as a focus of this qualitative inquiry unified them. Healthcare providers may benefit from understanding how trisomy 18 may affect a particular diagnosis experience, whether made during pregnancy or the days after birth when parents are still getting to know their child. As parents live with this diagnosis, pregnancy and the life of their child may be shaped by an uncertainty of a life-limiting condition, whereby care is bounded by what is and is not possible. And, we may appreciate how trisomy 18 imparts meanings on ordinary and extraordinary moments for children and their families in a recognisable form. The understandings gained from this research may support healthcare professionals’ reflective clinical practices as they care for children and their families affected by this diagnosis.
Clinical use and impact of mechanical circulatory support for myocardial infarction-related cardiogenic shock in the Netherlands: a registry-based propensity-matched analysis
Authors: Bogerd Margriet , Griffioen Alexander M , Bunge Jeroen J H , Peters Elma J , Ten Berg Sanne , Timmermans Marijke J C , Kraaijeveld Adriaan O , Lipsic Erik , Otterspoor Luuk C , Bleeker Gabe , Montero-Cabezas José M , Sjauw Krischan D , Meuwissen Martijn , Dubois Eric A , van Geuns Robert-Jan M , Henriques José P S
Published: February 2025

Background

Despite limited beneficial evidence, mechanical circulatory support (MCS) is commonly used in patients with acute myocardial infarction-related cardiogenic shock (AMI-CS). In this Dutch registry, we investigated MCS usage, associated patient characteristics and clinical outcomes.

Methods

This real-world, multicentre registry included CS patients undergoing percutaneous coronary intervention between 2017 and 2021 in 14 Dutch hospitals. The impact on clinical outcomes was analysed after 1:1 average propensity-score (aPS) matching.

Results

This AMI-CS registry included 2217 patients with a mean age of 66.4 (±12.3) years and predominantly male (72.8%, n=1613). MCS was deployed in 516 patients (23.3%), of which the intra-aortic balloon pump was used most frequently (n=253, 49.0%). Impella was used in 94 patients (18.2%), extracorporeal membrane oxygenation in 68 patients (13.2%) and 95 patients (18.4%) received multiple devices. Patients receiving MCS were younger (64.2 vs 67.0, p<0.01), presented with lower mean arterial pressures (74.7 vs 78.4 mm Hg, p<0.01), higher heart rates (88.3 vs 81.7 beats per minute, p<0.01) and higher initial lactate levels (6.4 vs 5.4 mmol/L, p<0.01). The percentage of resuscitated patients was comparable among MCS and non-MCS patients (38.6% vs 42.2%, p=0.17). The 30-day mortality rate was higher in MCS patients (55.0% vs 34.7%, p<0.01). After aPS-matching (n=970), 30-day mortality remained higher for MCS patients (53.8% vs 44.7%, p<0.01), with an associated OR of 1.44 (95% CI 1.12 to 1.85, p<0.01).

Conclusions

Despite limited evidence, MCS was used in a fourth of all AMI-CS patients. MCS usage was associated with an increased 30-day mortality in this real-world setting, even after propensity-matching.
Peripandemic outcomes of infants treated for sentinel congenital heart diseases in England and Wales
Authors: Huang Qi , Lawlor Deborah A , Nolan John , Espuny-Pujol Ferran , Caputo Massimo , Pagel Christina , Crowe Sonya , Franklin Rodney CG , Brown Kate L
Published: February 2025

Background

Infants with congenital heart disease (CHD) are clinically vulnerable to cardiac deteriorations and intercurrent infections. We aimed to quantify the impact of health system disruptions during the COVID-19 pandemic, on their clinical outcomes and whether these differed by socioeconomic and ethnic subgroups.

Methods

In this population-based cohort study, we used linked electronic healthcare datasets from England and Wales to identify infants with nine sentinel CHDs born and undergoing intervention in 2018–2022. The outcomes of cardiac intervention timing, infant mortality and hospital care utilisation, were described by birth eras, and risk factors were explored using multivariable regression.

Results

Of 4900 included infants, 1545 (31.5%) were born prepandemic (reference), 1175 (24.0%) in the transition period, 1375 (28.0%) during restrictions and 810 (16.5%) postrestrictions. The casemix was hypoplastic left heart syndrome (195; 3.9%), functionally univentricular heart (180; 3.7%), transposition (610; 13.5%), pulmonary atresia (290; 5.9%), atrioventricular septal defect (590; 12.1%), tetralogy of Fallot (820; 16.7%), aortic stenosis (225; 4.6%), coarctation (740; 15.1%) and ventricular septal defect (1200; 24.5%).

Compared with prepandemic, there was no evidence for delay in treatment procedures in transition, restrictions or postrestrictions eras. Infant mortality increased for those born in the transition period, adjusted OR 1.60 (95% CI 1.06, 2.42) p=0.01, but not in restrictions or postrestrictions. The days spent at home were similar with birth in transition and restrictions, but fewer for postrestrictions, adjusted days difference −2 (95% CI −4, 0), p=0.05.

Outcomes did not vary by pandemic birth era according to social characteristics. There was higher infant mortality in the deprived versus non-deprived binary category (adjusted OR 1.56 (95% CI 1.11, 2.18), p=0.004) and there were fewer days spent at home for the most versus least deprived neighbourhood quintile (adjusted difference −4 (95% CI −6, –2), p<0.001).

Conclusions

Specialist care for infants with CHD during the pandemic, in terms of pathway procedure timing and healthcare contacts, was not compromised. Increased healthcare utilisation postpandemic and heath inequality based on socioeconomic status require further evaluation.
Korean Red Ginseng Marc-Derived Gintonin Improves Alzheimer’s Cognitive Dysfunction by Upregulating LPAR1
Authors: Ha Yujeong , Lee Rami , Jeon Seung Ho , Kim Ji-Hun , Jo Hyo-Sung , Kwon Tae Woo , Hwang Sung-Hee , Lee Jong Kil , Nah Seung-Yeol , Cho Ik-Hyun
Published: February 2025

Ginseng is a well-established functional food for brain health. However, its active ingredients have not yet been identified. Gintonin is a promising compound isolated from white/red ginseng. Its lysophosphatidic acid (LPA) is an exogenous G protein-coupled LPA receptor (LPAR) agonist. Korean red ginseng marc (KRGM) is a by-product after KRG extractions. In a previous study, we demonstrated that KRGM-derived gintonin (KRGM-G) contains LPA C[Formula: see text], a major functional component of both white and red ginseng. [Formula: see text] transgenic mice and SH-SY5Y cells were used to determine molecular mechanisms involved in KRGM-G-mediated anti-Alzheimer’s disease (AD) effects. KRGM-G improved cognition impairment associated with alleviation of amyloid-β accumulation in the brain (hippocampus and cortex) in [Formula: see text] mice. KRGM-G inhibited activation of inflammatory cells (Iba-1-positive microglia and GFAP-positive astrocyte) and expression of pro-inflammatory mediators (IL-1β, IL-6, iNOS, or NO) in the brains of [Formula: see text] mice, increased the viability of H2O2-induced SH-SY5Y cells, and down-regulated the p38 MAPK, NF-κB p65, and STAT3 signaling pathways. KRGM-G also prevented the formation of reactive oxygen species and stimulated the Nrf2-HO-1/4-HNE signaling pathway in the brains of [Formula: see text] mice and SH-SY5Y cells. Interestingly, these positive effects of KRGM-G on AD-related symptoms and immunopathology were associated with up-regulation of LPAR1 in the brains of [Formula: see text] mice. These results suggest that KRGM-G might improve AD-related cognitive dysfunction by stimulating the anti-oxidant pathway (Nrf2) and inhibiting inflammatory pathways (p38/NF-κB/STAT3) through LPAR1.
SARS‐CoV‐2 Infection Among Children in Rondônia, Western Brazilian Amazon
Authors: Mota Amaral Gil Guibson , Sgorlon Gabriella , Batista Ferreira Valcimar , Serrano Batista Flávia , da Silva Soares Farias Luana , Barbagelata Luana Soares , dos Santos Mirleide Cordeiro , da Silva Bedran Rayssa Layana , Souza Vieira Dall’Acqua Deusilene , Benevides Matos Najla
Published: February 2025

We analyzed 364 children symptomatic or asymptomatic for respiratory symptoms, aged 0.1 month–17 years, selected from primary healthcare units of different municipalities of Rondônia from June 2021 to September 2022. Data were collected from medical and electronic records for epidemiological characterization. The positive cohort (n = 96) was quantified using a real‐time (RT) qPCR and sequenced by next‐generation sequencing. Whole‐genome sequences were obtained, SARS‐CoV‐2 strains were classified using the Pango system, and the maximum likelihood method was used for phylogenetic analyses. Among the patients, 59.34% (216/364) were male and 40.66% (148/364) were female. Children aged 10–14 years showed the highest rate of SARS‐CoV‐2 positivity. At the time of collection, 54.12% (197/364) of the patients were not age‐eligible for immunization against COVID‐19. The unvaccinated group accounted for 34.07% (124/364), with the highest proportion in the age groups of 5–9 and 10–14 years. Most patients exhibited mild symptoms. Seventy‐nine high‐quality genomes were obtained: Delta variant of concern (VOC) was the most prevalent (most abundant strain: AY.99.2), Omicron VOC was reported in 26 individuals (most frequent subvariant: BA.1.1), and Gamma VOC with 22 cases (12 cases of P.1 strain). The viral load showed a median of 7.26 log10 copies/mL, with a mean symptom duration of 4 days. Most of the cases were from children who were unvaccinated and age‐ineligible for immunization and were associated with Delta and Omicron VOCs with an increase in subvariants during the study period.
Data from Chromatin Helicase CHD6 Establishes Proinflammatory Enhancers and Is a Synthetic Lethal Target in FH-Deficient Renal Cell Carcinoma
Authors: Jin Juan , Luo Jun , Jin Xiaodong , Lim Kiat Shenq , He Yang , Ding Jiawei , Shen Yan , Hou Yuchen , Liu Hanqing , Zhu Xiaoyu , Zhao Jing , Zhou Wenjie , Huang Hai , Gao Yi , Xiao Jun , He Hongchao , Li Qunyi , Liu Lianxin , Chen Li , He Qiang , Zhang Chuanjie
Published: February 2025

Abstract
Fumarate hydratase (FH) deficiency causes hereditary leiomyomatosis and renal cell carcinoma (RCC). FH-deficient tumors lack effective therapeutic options. Here, we utilized an epigenetic-focused single-guide RNA library to elucidate potential drug targets in FH-deficient tumors. The screen identified chromodomain helicase DNA-binding protein 6 (CHD6) as an essential regulator of the growth of FH-mutated RCC. Mechanically, FH loss induced fumarate-mediated succinylation and inactivation of KEAP1, blocking subsequent ubiquitin–proteasome degradation of CHD6. Stabilized CHD6 formed a complex with p65 to establish proinflammatory enhancers and thereby regulate NF-κB–mediated transcription. Moreover, CHD6 recruited mSWI/SNF ATPases to maintain chromatin accessibility at CHD6-bound enhancers. The PROTAC degrader of SMARCA2/4 AU-15330 effectively abolished structures of cis-regulatory elements bound by CHD6 and suppressed the growth of FH-mutated, but not FH-intact, RCC in vivo. Collectively, these data indicate that CHD6 is a molecular bridge between FH deficiency and proinflammatory enhancer assembly that endows FH-deficient tumors with epigenetic vulnerabilities.

Significance: CHD6 links FH deficiency to aberrant NF-κB activity in renal cell carcinoma, highlighting an epigenetic vulnerability for this rare tumor subtype.
Data from Energy Stress–Induced circEPB41(2) Promotes Lipogenesis in Hepatocellular Carcinoma
Authors: Yang Yang , Luo Jingjing , Wang Zhongyu , Liu Kaiyue , Feng Keyi , Wang Fang , Mei Yide
Published: February 2025

Abstract
The tumor microenvironment plays a pivotal role in the metabolic reprogramming of cancer cells. A better understanding of the underlying mechanisms regulating cancer metabolism could help identify potential therapeutic targets. Here, we identified circEPB41(2) as a metabolically regulated circular RNA that mediates lipid metabolism in hepatocellular carcinoma (HCC). circEPB41(2) was induced in response to glucose deprivation via HNRNPA1-dependent alternative splicing. Upregulation of circEPB41(2) led to enhanced lipogenic gene expression that promoted lipogenesis. Mechanistically, circEPB41(2) cooperated with the N6-methyladenosine demethylase FTO to decrease the mRNA stability of the histone deacetylase sirtuin 6, thereby increasing histone H3 lysine 9 acetylation and histone H3 lysine 27 acetylation levels to activate lipogenic gene expression. Silencing of circEPB41(2) inhibited both in vitro proliferation of HCC cells and in vivo growth of tumor xenografts. Clinically, circEPB41(2) was elevated in HCC, and high circEPB41(2) expression was associated with poor patient prognosis. Overall, this study reveals that circEPB41(2) is an important regulator of lipid metabolic reprogramming and indicates that targeting the circEPB41(2)–FTO–sirtuin 6 axis could represent a promising anticancer strategy for treating HCC.

Significance: circEPB41(2) is induced by glucose deprivation and mediates epigenetic alterations to drive lipogenesis and tumor growth in hepatocellular carcinoma, suggesting circEPB41(2) could be a potential therapeutic target in liver cancer.
Data from Targeting the PREX2/RAC1/PI3Kβ Signaling Axis Confers Sensitivity to Clinically Relevant Therapeutic Approaches in Melanoma
Authors: Ford Catriona A. , Koludrovic Dana , Centeno Patricia P. , Foth Mona , Tsonou Elpida , Vlahov Nikola , Sphyris Nathalie , Gilroy Kathryn , Bull Courtney , Nixon Colin , Serrels Bryan , Munro Alison F. , Dawson John C. , Carragher Neil O. , Pavet Valeria , Hornigold David C. , Dunne Philip D. , Downward Julian , Welch Heidi C.E. , Barry Simon T. , Sansom Owen J. , Campbell Andrew D.
Published: February 2025

Abstract
Metastatic melanoma remains a major clinical challenge. Large-scale genomic sequencing of melanoma has identified bona fide activating mutations in RAC1, which are associated with resistance to BRAF-targeting therapies. Targeting the RAC1-GTPase pathway, including the upstream activator PREX2 and the downstream effector PI3Kβ, could be a potential strategy for overcoming therapeutic resistance, limiting melanoma recurrence, and suppressing metastatic progression. Here, we used genetically engineered mouse models and patient-derived BRAFV600E-driven melanoma cell lines to dissect the role of PREX2 in melanomagenesis and response to therapy. Although PREX2 was dispensable for the initiation and progression of melanoma, its loss conferred sensitivity to clinically relevant therapeutics targeting the MAPK pathway. Importantly, genetic and pharmacologic targeting of PI3Kβ phenocopied PREX2 deficiency, sensitizing model systems to therapy. These data reveal a druggable PREX2/RAC1/PI3Kβ signaling axis in BRAF-mutant melanoma that could be exploited clinically.

Significance: Cotargeting the MAPK and the PREX2/RAC1/PI3Kβ pathways has remarkable efficacy and outperforms monotherapy MAPK inhibition in BRAF-mutant melanoma, supporting the potential of this combination therapy for treating metastatic melanoma.
Data from A Potent, Selective, Small-Molecule Inhibitor of DHX9 Abrogates Proliferation of Microsatellite Instable Cancers with Deficient Mismatch Repair
Authors: Castro Jennifer , Daniels Matthew H. , Brennan David , Johnston Brian , Gotur Deepali , Lee Young-Tae , Knockenhauer Kevin E. , Lu Chuang , Wu Jie , Nayak Sunaina , Collins Cindy , Bansal Rishabh , Buker Shane M. , Case April , Liu Julie , Yao Shihua , Sparling Brian A. , Sickmier E. Allen , Silver Serena J. , Blakemore Stephen J. , Boriack-Sjodin P. Ann , Duncan Kenneth W. , Ribich Scott , Copeland Robert A.
Published: February 2025

Abstract
DHX9 is a multifunctional DExH-box RNA helicase with important roles in the regulation of transcription, translation, and maintenance of genome stability. Elevated expression of DHX9 is evident in multiple cancer types, including colorectal cancer. Microsatellite instable–high (MSI-H) tumors with deficient mismatch repair (dMMR) display a strong dependence on DHX9, making this helicase an attractive target for oncology drug discovery. In this report, we show that DHX9 knockdown increased RNA/DNA secondary structures and replication stress, resulting in cell-cycle arrest and the onset of apoptosis in cancer cells with MSI-H/dMMR. ATX968 was identified as a potent and selective inhibitor of DHX9 helicase activity. Chemical inhibition of DHX9 enzymatic activity elicited similar selective effects on cell proliferation as seen with genetic knockdown. In addition, ATX968 induced robust and durable responses in an MSI-H/dMMR xenograft model but not in a microsatellite stable/proficient MMR model. These preclinical data validate DHX9 as a target for the treatment of patients with MSI-H/dMMR. Additionally, this potent and selective inhibitor of DHX9 provides a valuable tool with which to further explore the effects of inhibition of DHX9 enzymatic activity on the proliferation of cancer cells in vitro and in vivo.

Significance: DHX9 is required in cancer cells with deficient mismatch repair and can be inhibited by ATX968, providing a promising strategy for the development of precision cancer therapeutics.
Supplementary Figure S4 from HMGA2 Expression Predicts Subtype, Survival, and Treatment Outcome in Pancreatic Ductal Adenocarcinoma
Authors: Yamamoto Naomi , Dobersch Stephanie , Loveless Ian , Samraj Annie N. , Jang Gun Ho , Haraguchi Miki , Kang Liang-I. , Ruzinova Marianna B. , Vij Kiran R. , Mudd Jacqueline L. , Walsh Thomas , Safyan Rachael A. , Chiorean Elena Gabriela , Hingorani Sunil R. , Bolton Nathan M. , Li Li , Fields Ryan C. , DeNardo David G. , Notta Faiyaz , Crawford Howard C. , Steele Nina G. , Kugel Sita
Published: February 2025

Supplementary Figure S4. CK5 and CK17 do not predict treatment response or time to recurrence. A) Combining CK5 and GATA6 IHC does not predict overall survival. B) CK17 high, GATA6 low tumors display improved survival compared to CK17 low, GATA6 high tumors. C) Kaplan-Meier survival curves for CK5 positive and negative tumors treated with first-line gemcitabine chemotherapy. D) Kaplan-Meier survival curves for CK17 positive and negative tumors treated with first-line gemcitabine chemotherapy. E) CK5 status does not predict time to recurrence. F) CK17 positive tumors show longer time to recurrence than CK17 negative tumors, the opposite phenotype expected from the basal subtype.