bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissemination and outcome reporting bias in clinical malaria intervention trials: a cross-sectional analysis
Authors: Pool Lydia , Ruiz del Portal Luyten Claire , van der Pluijm Rob W. , Soentjens Patrick , Hanscheid Thomas , Grobusch Martin P. , Visser Benjamin J. 
Published: September 2024

Abstract
Background
Dissemination and outcome reporting biases are a significant problem in clinical research, with far-reaching implications for both scientific understanding and clinical decision-making. This study investigates the prevalence of dissemination- and outcome reporting biases in registered interventional malaria research.

Methods
All malaria interventional trials registered on ClinicalTrials.gov from 2010 to 2020 were identified. Subsequently, publications that matched the registration were searched. The primary outcome measures were the percentage of registered studies that resulted in subsequent publication of study results, the concordance between registered outcomes, and reported outcomes. Secondary outcomes were compliance with WHO standards for timely publication (issued in 2017) of summary study results in the respective trial registry (within 12 months of study completion) or peer-reviewed publication (within 24 months of study completion) was evaluated.

Results
A total of 579 trials were identified on ClinicalTrials.gov, of which 544 met the inclusion criteria. Notably, almost 36.6% of these trials (199/544) were registered retrospectively, with 129 (23.7%) registered after the first patient enrolment and 70 (12.9%) following study completion. Publications were identified for 351 out of 544 registered trials (64.5%), involving 1,526,081 study participants. Conversely, publications were not found for 193 of the 544 registrations (35.5%), which aimed to enrol 417,922 study participants. Among these 544 registrations, 444 (81.6%) did not meet the WHO standard to post summary results within 12 months of primary study completion (the last visit of the last subject for collection of data on the primary outcome), while 386 out of 544 registrations (71.0%) failed to publish their results in a peer-reviewed journal within 24 months of primary study completion. Discrepancies were noted in the reported primary outcomes compared to the registered primary outcomes in 47.6% (222/466) of the published trials, and an even higher discordance rate of 73.2% (341/466 publications) for secondary outcomes.

Conclusions
Non-dissemination remains a significant issue in interventional malaria research, with most trials failing to meet WHO standards for timely dissemination of summary results and peer-reviewed journal publications. Additionally, outcome reporting bias is highly prevalent across malaria publications. To address these challenges, it is crucial to implement strategies that enhance the timely reporting of research findings and reduce both non-dissemination and outcome reporting bias.
Revisiting a decade of inequality in healthcare financial burden in Cambodia, 2009–19: trends, determinants and decomposition
Authors: Fernandes Antunes Adélio , Jithitikulchai Theepakorn , Hohmann Juergen , Flessa Steffen 
Published: September 2024

Abstract
Background
Out-of-pocket healthcare expenditure (OOPHE) without adequate social protection often translates to inequitable financial burden and utilization of services. Recent publications highlighted Cambodia’s progress towards Universal Health Coverage (UHC) with reduced incidence of catastrophic health expenditure (CHE) and improvements in its distribution. However, departing from standard CHE measurement methods suggests a different storyline on trends and inequality in the country.

Objective
This study revisits the distribution and impact of OOPHE and its financial burden from 2009–19, employing alternative socio-economic and economic shock metrics. It also identifies determinants of the financial burden and evaluates inequality-contributing and -mitigating factors from 2014–19, including coping mechanisms, free healthcare, and OOPHE financing sources.

Methods
Data from the Cambodian Socio-Economic Surveys of 2009, 2014, and 2019 were utilized. An alternative measure to CHE is proposed: Excessive financial burden (EFB). A household was considered under EFB when its OOPHE surpassed 10% or 25% of total consumption, excluding healthcare costs. A polychoric wealth index was used to rank households and measure EFB inequality using the Erreygers Concentration Index. Inequality shifts from 2014–19 were decomposed using the Recentered Influence Function regression followed by the Oaxaca-Blinder method. Determinants of financial burden levels were assessed through zero-inflated ordered logit regression.

Results
Between 2009–19, EFB incidence increased from 10.95% to 17.92% at the 10% threshold, and from 4.41% to 7.29% at the 25% threshold. EFB was systematically concentrated among the poorest households, with inequality sharply rising over time, and nearly a quarter of the poorest households facing EFB at the 10% threshold. The main determinants of financial burden were geographic location, household size, age and education of household head, social health protection coverage, disease prevalence, hospitalization, and coping strategies. Urbanization, biased disease burdens, and preventive care were key in explaining the evolution of inequality.

Conclusion
More efforts are needed to expand social protection, but monitoring those through standard measures such as CHE has masked inequality and the burden of the poor. The financial burden across the population has risen and become more unequal over the past decade despite expansion and improvements in social health protection schemes. Health Equity funds have, to some extent, mitigated inequality over time. However, their slow expansion and the reduced reliance on coping strategies to finance OOPHE could not outbalance inequality.
European health regulations reduce registry-based research
Authors: Brück Oscar , Sanmark Enni , Ponkilainen Ville , Bützow Alexander , Reito Aleksi , Kauppila Joonas H. , Kuitunen Ilari 
Published: September 2024

Abstract
Background
The European Health Data Space (EHDS) regulation has been proposed to harmonize health data processing. Given its parallels with the Act on Secondary Use of Health and Social Data (Secondary Use Act) implemented in Finland in 2020, this study examines the consequences of heightened privacy constraints on registry-based medical research.

Methods
We collected study permit counts approved by university hospitals in Finland in 2014–2023 and the data authority Findata in 2020‒2023. The changes in the study permit counts were analysed before and after the implementation of the General Data Protection Regulation (GDPR) and the Secondary Use Act. By fitting a linear regression model, we estimated the deficit in study counts following the Secondary Use Act.

Results
Between 2020 and 2023, a median of 5.5% fewer data permits were approved annually by Finnish university hospitals. On the basis of linear regression modelling, we estimated a reduction of 46.9% in new data permits nationally in 2023 compared with the expected count. Similar changes were neither observed after the implementation of the GDPR nor in permit counts of other medical research types, confirming that the deficit was caused by the Secondary Use Act.

Conclusions
This study highlights concerns related to data privacy laws for registry-based medical research and future patient care.
Challenges in the diagnosis of fibrodysplasia ossificans progressiva with the ACVR1 mutation (c.774G > C, p.R258S): a case report and review of literature
Authors: Yang Siqi , Cui Rongrong , Li Jialin , Dai Ruchun 
Published: September 2024

AbstractThe diagnosis of fibrodysplasia ossificans progressiva is missed or delayed because of its insidious precursors, especially in uncharacteristic cases. Fibrodysplasia ossificans progressiva, which mostly displayed the mutation c.617G > A, p.R206H, is characterized by congenital malformation of the great toe and progressive extra-skeletal ossification of ligaments, tendons and muscles. The mutation c.774G > C, p.R258S (HGVS: NC_000002.11:g.158626896 C > G) in activin A receptor type I is an infrequent etiology of fibrodysplasia ossificans progressiva and can present different clinical features. Awareness of these multiple clinical features will help endocrinologists in the early diagnosis of fibrodysplasia ossificans progressiva. We report a case of fibrodysplasia ossificans progressiva with the activin A receptor type I mutation c.774G > C, p.R258S, which was diagnosed before its ossifying period.
Probing the orthogonality and robustness of the mammalian RNA-binding protein Musashi-1 in Escherichia coli
Authors: Dolcemascolo Roswitha , Ruiz Raúl , Baldanta Sara , Goiriz Lucas , Heras-Hernández María , Montagud-Martínez Roser , Rodrigo Guillermo 
Published: September 2024

AbstractRNA recognition motifs (RRMs) are widespread RNA-binding protein domains in eukaryotes, which represent promising synthetic biology tools due to their compact structure and efficient activity. Yet, their use in prokaryotes is limited and their functionality poorly characterized. Recently, we repurposed a mammalian Musashi protein containing two RRMs as a translation regulator in Escherichia coli. Here, employing high-throughput RNA sequencing, we explored the impact of Musashi expression on the transcriptomic and translatomic profiles of E. coli, revealing certain metabolic interference, induction of post-transcriptional regulatory processes, and spurious protein-RNA interactions. Engineered Musashi protein mutants displayed compromised regulatory activity, emphasizing the importance of both RRMs for specific and sensitive RNA binding. We found that a mutation known to impede allosteric regulation led to similar translation control activity. Evolutionary experiments disclosed a loss of function of the synthetic circuit in about 40 generations, with the gene coding for the Musashi protein showing a stability comparable to other heterologous genes. Overall, this work expands our understanding of RRMs for post-transcriptional regulation in prokaryotes and highlight their potential for biotechnological and biomedical applications.
HIF-1α-HPRT1 axis promotes tumorigenesis and gefitinib resistance by enhancing purine metabolism in EGFR-mutant lung adenocarcinoma
Authors: Geng Pengyu , Ye Fei , Dou Peng , Hu Chunxiu , He Jiarui , Zhao Jinhui , Li Qi , Bao Miao , Li Xiangnan , Liu Xinyu , Xu Guowang 
Published: September 2024

Abstract
Background
The mutations of oncogenic epidermal growth factor receptor (EGFR) is an important cause of lung adenocarcinoma (LUAD) malignance. It has been knowm that metabolic reprogramming is an important hallmark of malignant tumors, and purine metabolism is a key metabolic pathway for tumor progression and drug resistance, but its relationship with the EGFR-mutant LUAD is unclear.

Methods
Metabolic reprogramming was studied through capillary electrophoresis-time of flight mass spectrometry (CE-TOF/MS)-based metabolic profiling analysis. Cell proliferation in vitro was evaluated by EdU staining and cell cycle assay. Tumorigenicity in vivo was tested by subcutaneous tumor formation experiment in nude mice. The binding of hypoxia-inducible factor-1 alpha (HIF-1α) and hypoxanthine phosphoribosyltransferase 1 (HPRT1) was detected by DNA pull‑down assay and Chromatin immunoprecipitation (ChIP) assays. HIF-1α, HPRT1, DNA damage and cell apoptosis related genes were examined by western blot. In addition, RNA sequencing, mass spectrometry and bioinformatics analysis were performed.

Results
We found that mutated EGFR (muEGFR) upregulates HPRT1 to promote purine metabolism and tumorigenesis of EGFR-mutant LUAD. Mechanistically, muEGFR increases HIF-1α expression through protein stability. Meanwhile, up-regulated HIF-1α bound to the promoter of HPRT1 and transcriptionally activates HPRT1 expression, enhancing purine metabolism to maintain rapid tumor cell proliferation in EGFR-mutant LUAD. Further, gefitinib inhibited the synthesis of purine nucleotides, and HPRT1 inhibition increased the sensitivity of gefitinib to EGFR-mutant LUAD.

Conclusions
Our study reveals that muEGFR-HIF-1α-HPRT1 axis plays a key role in EGFR-mutant LUAD and provides a new strategy-inhibiting purine metabolism for treating EGFR-mutant LUAD.
Dynamic glycolytic reprogramming effects on dendritic cells in pancreatic ductal adenocarcinoma
Authors: Zhang Bo , Ohuchida Kenoki , Tsutsumi Chikanori , Shimada Yuki , Mochida Yuki , Oyama Koki , Iwamoto Chika , Sheng Nan , Fei Shuang , Shindo Koji , Ikenaga Naoki , Nakata Kohei , Oda Yoshinao , Nakamura Masafumi 
Published: September 2024

Abstract
Background
Pancreatic ductal adenocarcinoma tumors exhibit resistance to chemotherapy, targeted therapies, and even immunotherapy. Dendritic cells use glucose to support their effector functions and play a key role in anti-tumor immunity by promoting cytotoxic CD8+ T cell activity. However, the effects of glucose and lactate levels on dendritic cells in pancreatic ductal adenocarcinoma are unclear. In this study, we aimed to clarify how glucose and lactate can impact the dendritic cell antigen-presenting function and elucidate the relevant mechanisms.

Methods
Glycolytic activity and immune cell infiltration in pancreatic ductal adenocarcinoma were evaluated using patient-derived organoids and resected specimens. Cell lines with increased or decreased glycolysis were established from KPC mice. Flow cytometry and single-cell RNA sequencing were used to evaluate the impacts on the tumor microenvironment. The effects of glucose and lactate on the bone marrow-derived dendritic cell antigen-presenting function were detected by flow cytometry.

Results
The pancreatic ductal adenocarcinoma tumor microenvironment exhibited low glucose and high lactate concentrations from varying levels of glycolytic activity in cancer cells. In mouse transplantation models, tumors with increased glycolysis showed enhanced myeloid-derived suppressor cell infiltration and reduced dendritic cell and CD8+ T cell infiltration, whereas tumors with decreased glycolysis displayed the opposite trends. In three-dimensional co-culture, increased glycolysis in cancer cells suppressed the antigen-presenting function of bone marrow-derived dendritic cells. In addition, low-glucose and high-lactate media inhibited the antigen-presenting and mitochondrial functions of bone marrow-derived dendritic cells.

Conclusions
Our study demonstrates the impact of dynamic glycolytic reprogramming on the composition of immune cells in the tumor microenvironment of pancreatic ductal adenocarcinoma, especially on the antigen-presenting function of dendritic cells.
The epidemiology and outcomes of hospitalized drowning in Thai children: a national data analysis 2015–2019
Authors: Niamsanit Sirapoom , Uppala Rattapon , Sitthikarnkha Phanthila , Techasatian Leelawadee , Saengnipanthkul Suchaorn , Thepsuthammarat Kaewjai , Sutra Sumitr 
Published: September 2024

Abstract
Background
Drowning remains a common cause of death among children. However, the epidemiology and impact of drowning in Thailand was underexplored. This study aimed to analyze the epidemiology and clinical outcomes of pediatric drowning in Thailand and to determine the factors associated with the need for intubation and mortality.

Methods
Data derived from the Thai healthcare delivery system for the period between 2015 and 2019 were used to examine the monthly admissions, mortality rates, length of hospital stay, and the number of patients who received endotracheal intubation. Multivariate logistic regression analysis was employed to identify the risk factors associated with the need for intubation and mortality.

Results
Of the 4,911, 58.8% were under six years old, 63.5% were male, and 31.2% were from the Northeastern region. The majority drowned during April, which is the summer season in Thailand. Among these patients, 28.8% required intubation, with the highest proportion found in the 6-<12 years age group (35.9%). The independent risk factors for intubation were metabolic acidosis (adjusted odd ratio [aOR] 9.74; 95% confidence interval [CI] 7.14–13.29; p < 0.001) and pulmonary edema (aOR 5.82; 95%CI 3.92–8.65; p < 0.001). The overall mortality rate due to drowning was 12.6%. Factors significantly associated with mortality included in-hospital cardiac arrest (aOR 4.43; 95%CI 2.78–7.06; p < 0.001), and the presence of drowning-related complications, particularly renal failure (aOR 7.13; 95%CI 3.93–12.94; p < 0.001).

Conclusion
Drowning admissions and mortality were highest among male children under six years old, occurring mainly during the summer season. Significant factors associated with intubation requirement included metabolic acidosis and pulmonary edema. The mortality was significantly associated with in-hospital cardiac arrest and drowning-related complications, particularly renal failure.

Trial registration
This is an observational study, does not include any intervention, and has therefore not been registered.
Acute exposure to mercury drives changes in gene expression in Drosophila melanogaster
Authors: Sanderson Brian J. , Sims-West Dylan J. , Macdonald Stuart J. 
Published: September 2024

Abstract
Objective
We quantified the effect of acute exposure to a high dosage of inorganic mercury on gene expression in Drosophila melanogaster using RNA-sequencing of whole adult females.

Results
We found 119 genes with higher gene expression following treatment (including all 5 Drosophila metallothionine genes and a number of heat shock protein genes), and 31 with lower expression (several of which are involved in egg formation). Our results highlight biological processes and genetic pathways impacted by exposure to this toxic metal, and provide motivation for future studies to understand the genetic basis of response to mercury.
Identifying SETBP1 haploinsufficiency molecular pathways to improve patient diagnosis using induced pluripotent stem cells and neural disease modelling
Authors: Shaw Nicole C. , Chen Kevin , Farley Kathryn O. , Hedges Mitchell , Forbes Catherine , Baynam Gareth , Lassmann Timo , Fear Vanessa S. 
Published: September 2024

Abstract
Background
SETBP1 Haploinsufficiency Disorder (SETBP1-HD) is characterised by mild to moderate intellectual disability, speech and language impairment, mild motor developmental delay, behavioural issues, hypotonia, mild facial dysmorphisms, and vision impairment. Despite a clear link between SETBP1 mutations and neurodevelopmental disorders the precise role of SETBP1 in neural development remains elusive. We investigate the functional effects of three SETBP1 genetic variants including two pathogenic mutations p.Glu545Ter and SETBP1 p.Tyr1066Ter, resulting in removal of SKI and/or SET domains, and a point mutation p.Thr1387Met in the SET domain.

Methods
Genetic variants were introduced into induced pluripotent stem cells (iPSCs) and subsequently differentiated into neurons to model the disease. We measured changes in cellular differentiation, SETBP1 protein localisation, and gene expression changes.

Results
The data indicated a change in the WNT pathway, RNA polymerase II pathway and identified GATA2 as a central transcription factor in disease perturbation. In addition, the genetic variants altered the expression of gene sets related to neural forebrain development matching characteristics typical of the SETBP1-HD phenotype.

Limitations
The study investigates changes in cellular function in differentiation of iPSC to neural progenitor cells as a human model of SETBP1 HD disorder. Future studies may provide additional information relevant to disease on further neural cell specification, to derive mature neurons, neural forebrain cells, or brain organoids.

Conclusions
We developed a human SETBP1-HD model and identified perturbations to the WNT and POL2RA pathway, genes regulated by GATA2. Strikingly neural cells for both the SETBP1 truncation mutations and the single nucleotide variant displayed a SETBP1-HD-like phenotype.
Assessing abdominal aortic aneurysm growth using radiomic features of perivascular adipose tissue after endovascular repair
Authors: Lv Rui , Hu Ge , Zhang Shenbo , Zhang Zhe , Chen Jin , Wang Kefei , Wang Zhiwei , Jin Zhengyu 
Published: September 2024

Abstract
Objectives
The study aimed to investigate the relationship between the radiomic features of perivascular adipose tissue (PVAT) and abdominal aortic aneurysm (AAA) growth after endovascular aneurysm repair (EVAR).

Methods
Patients with sub-renal AAA who underwent regular follow-up after EVAR between March 2014 and March 2024 were retrospectively collected. Two radiologists segmented aneurysms and PVAT. Patients were categorised into growing and non-growing groups based on volumetric changes observed in two follow-up computed tomography examinations. One hundred seven radiomic features were automatically extracted from the PVAT region. Univariable and multivariable logistic regression was performed to analyse radiomic features and clinical characteristics. Furthermore, the performance of the integrated clinico-radiological model was compared with models using only radiomic features or clinical characteristics separately.

Results
A total of 79 patients (68 ± 9 years, 89% men) were enroled in this study, 19 of whom had a growing aneurysm. Compared to the non-growing group, PVAT of growing AAA showed a higher surface area to volume ratio (non-growing vs growing, 0.63 vs 0.70, p = 0.04), and a trend of low dependence and high dispersion manifested by texture features (p < 0.05). The area under the curve of the integrated clinico-radiological model was 0.78 (95% confidence intervals 0.65–0.91), with a specificity of 87%. The integrated model outperformed models using only radiomic or clinical features separately (0.78 vs 0.69 vs 0.69).

Conclusions
Higher surface area to volume ratio and more heterogeneous texture presentation of PVAT were associated with aneurysm dilation after EVAR. Radiomic features of PVAT have the potential to predict AAA progression.

Clinical relevance statement
Radiomic features of PVAT are associated with AAA progression and can be an independent risk factor for aneurysm dilatation to assist clinicians in postoperative patient surveillance and management.

Key Points

After EVAR for AAA, patients require monitoring for progression.

PVAT surrounding growing AAA after EVAR exhibits a more heterogeneous texture.

Integrating PVAT-related features and clinical features results in better predictive performance.

Graphical Abstract