bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prenatal diagnosis of 18p deletion and 8p trisomy syndrome: literature review and report of a novel case
Authors: Papamichail Maria , Eleftheriades Anna , Manolakos Emmanouil , Papamichail Adamantia , Christopoulos Panagiotis , Manegold-Brauer Gwendolin , Eleftheriades Makarios 
Published: April 2024

Abstract18p deletion syndrome constitutes one of the most frequent autosomal terminal deletion syndromes, affecting one in 50,000 live births. The syndrome has un-specific clinical features which vary significantly between patients and may overlap with other genetic conditions. Its prenatal description is extremely rare as the fetal phenotype is often not present during pregnancy. Trisomy 8p Syndrome is characterized by heterogenous phenotype, with the most frequent components to be cardiac malformation, developmental and intellectual delay. Its prenatal diagnosis is very rare due to the unspecific sonographic features of the affected fetuses. We present a very rare case of a fetus with multiple anomalies diagnosed during the second trimester whose genomic analysis revealed a 18p Deletion and 8p trisomy Syndrome. This is the first case where this combination of DNA mutations has been described prenatally and the second case in general. The presentation of this case, as well as the detailed review of all described cases, aim to expand the existing knowledge regarding this rare condition facilitating its diagnosis in the future.
Validating the knowledge represented by a self-organizing map with an expert-derived knowledge structure
Authors: Amos Andrew James , Lee Kyungmi , Gupta Tarun Sen , Malau-Aduli Bunmi S. 
Published: April 2024

Abstract
Background
Professionals are reluctant to make use of machine learning results for tasks like curriculum development if they do not understand how the results were generated and what they mean. Visualizations of peer reviewed medical literature can summarize enormous amounts of information but are difficult to interpret. This article reports the validation of the meaning of a self-organizing map derived from the Medline/PubMed index of peer reviewed medical literature by its capacity to coherently summarize the references of a core psychiatric textbook.

Methods
Reference lists from ten editions of Kaplan and Sadock's Comprehensive Textbook of Psychiatry were projected onto a self-organizing map trained on Medical Subject Headings annotating the complete set of peer reviewed medical research articles indexed in the Medline/PubMed database (MedSOM). K-means clustering was applied to references from every edition to examine the ability of the self-organizing map to coherently summarize the knowledge contained within the textbook.

Results
MedSOM coherently clustered references into six psychiatric knowledge domains across ten editions (1967–2017). Clustering occurred at the abstract level of broad psychiatric practice including General/adult psychiatry, Child psychiatry, and Administrative psychiatry.

Conclusions
The uptake of visualizations of published medical literature by medical experts for purposes like curriculum development depends upon validation of the meaning of the visualizations. The current research demonstrates that a self-organizing map (MedSOM) can validate the stability and coherence of the references used to support the knowledge claims of a standard psychiatric textbook, linking the products of machine learning to a widely accepted standard of knowledge.
Pan-inhibition of the three H2S synthesizing enzymes restrains tumor progression and immunosuppression in breast cancer
Authors: Dawoud Alyaa , Youness Rana A. , Nafea Heba , Manie Tamer , Bourquin Carole , Szabo Csaba , Abdel-Kader Reham M. , Gad Mohamed Z. 
Published: April 2024

Abstract
Background
Hydrogen sulfide (H2S) is a significant endogenous mediator that has been implicated in the progression of various forms of cancer including breast cancer (BC). Cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) are the three principal mammalian enzymes responsible for H2S production. Overexpression of CBS, CSE and 3MST was found to be associated with poor prognosis of BC patients. Moreover, H2S was linked to an immune-suppressive tumor microenvironment in BC. Recently it was observed that BC cells, in response to single or dual inhibition of H2S synthesizing enzymes, develop an escape mechanism by overexpressing alternative sources of H2S generation. Thus, the aim of this work is to escape the H2S compensatory mechanism by pan repressing the three enzymes using microRNAs (miRNAs) and to investigate their impact on the oncogenic and immunogenic profile of BC cells.

Methods
BC female patients (n = 25) were recruited. In-silico analysis was used to identify miRNAs targeting CBS, CSE, and 3MST. MDA-MB-231 cells were cultured and transfected using oligonucleotides. Total RNA was extracted using Biazol, reverse transcribed and quantified using qRT-PCR. H2S levels were measured using AzMc assay. BC hallmarks were assessed using trans-well migration, wound healing, MTT, and colony forming assays.

Results
miR-193a and miR-548c were validated by eight different bioinformatics software to simultaneously target CBS, CSE and 3MST. MiR-193a and miR-548c were significantly downregulated in BC tissues compared to their non-cancerous counterparts. Ectopic expression of miR-193a and miR-548c in MDA-MB-231 TNBC cells resulted in a marked repression of CBS, CSE, and 3MST transcript and protein levels, a significant decrease in H2S levels, reduction in cellular viability, inhibition of migration and colony forming ability, repression of immune-suppressor proteins GAL3 GAL9, and CD155 and upregulation of the immunostimulatory MICA and MICB proteins.

Conclusion
This study sheds the light onto miR-193a and miR-548c as potential pan-repressors of the H2S synthesizing enzymes. and identifies them as novel tumor suppressor and immunomodulatory miRNAs in TNBC.
A novel immunogenic cell death-related classification indicates the immune landscape and predicts clinical outcome and treatment response in acute myeloid leukemia
Authors: Zhong Fangmin , He Shuyang , Guo Ni , Shi Luyi , Zhang Linlin , Jin Hua , Kong Guangyao 
Published: April 2024

Abstract
Background
Immunogenic cell death (ICD) is closely related to anti-tumor therapy and regulates the tumor microenvironment (TME). This study aims to explore the molecular characteristics of ICD in acute myeloid leukemia (AML) and to analyze the value of ICD-related biomarkers in TME indication, prognosis prediction, and treatment response evaluation in AML.

Methods
Single-sample gene set enrichment analysis was used to calculate the ICD score. LASSO regression was used to construct a prognostic risk score model. We also analyzed differences in clinical characteristics, immune landscape, immunotherapy response, and chemotherapy sensitivity between high-risk and low-risk patients.

Results
This study identified two ICD-related subtypes and found significant heterogeneity in clinical prognosis, TME, and immune landscape between different ICD subtypes. Subsequently, a novel ICD-related prognostic risk score model was developed, which accurately predicted the prognosis of AML patients and was validated in nine AML cohorts. Moreover, there were significant correlations between risk scores and clinicopathological factors, somatic mutations, TME characteristics, immune cell infiltration, immunotherapy response, and chemosensitivity. We further validated the model gene expression in a clinically real-world cohort.

Conclusions
The novel ICD-related signatures identified and validated by us can serve as promising biomarkers for predicting clinical outcomes, chemotherapy sensitivity, and immunotherapy response in AML patients, guiding the establishment of personalized and accurate treatment strategies for AML.

Graphical Abstract
All-cause, cardiovascular disease and cancer mortality in the population of a large Italian area contaminated by perfluoroalkyl and polyfluoroalkyl substances (1980–2018)
Authors: Biggeri Annibale , Stoppa Giorgia , Facciolo Laura , Fin Giuliano , Mancini Silvia , Manno Valerio , Minelli Giada , Zamagni Federica , Zamboni Michela , Catelan Dolores , Bucchi Lauro 
Published: April 2024

Abstract
Background
Per- and polyfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. An evident association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (northern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018.

Methods
The Italian National Institute of Health pre-processed and made available anonymous data from the Italian National Institute of Statistics death certificate archives for residents of the provinces of Vicenza, Padua and Verona (males, n = 29,629; females, n = 29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardised mortality ratios using the total population of the three provinces in the same calendar period as reference. The birth cohort analysis was performed using 20–84 years cumulative standardised mortality ratios. Exposure was defined as being resident in one of the 30 municipalities of the Red area, where the aqueduct supplying drinking water was fed by the contaminated groundwater.

Results
During the 34 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of availability of cause-specific mortality data), in the resident population of the Red area we observed 51,621 deaths vs. 47,731 expected (age- and sex-SMR: 108; 90% CI: 107–109). We found evidence of raised mortality from cardiovascular disease (in particular, heart diseases and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer.

Conclusions
For the first time, an association of PFAS exposure with mortality from cardiovascular disease was formally demonstrated. The evidence regarding kidney cancer and testicular cancer is consistent with previously reported data.
Ambient long-term exposure to organophosphorus pesticides and the human gut microbiome: an observational study
Authors: Zhang Keren , Paul Kimberly , Jacobs Jonathan P. , Cockburn Myles G. , Bronstein Jeff M. , del Rosario Irish , Ritz Beate 
Published: April 2024

Abstract
Background
Organophosphorus pesticides (OP) have been associated with various human health conditions. Animal experiments and in-vitro models suggested that OP may also affect the gut microbiota. We examined associations between ambient chronic exposure to OP and gut microbial changes in humans.

Methods
We recruited 190 participants from a community-based epidemiologic study of Parkinson’s disease living in a region known for heavy agricultural pesticide use in California. Of these, 61% of participants had Parkinson’s disease and their mean age was 72 years. Microbiome and predicted metagenome data were generated by 16S rRNA gene sequencing of fecal samples. Ambient long-term OP exposures were assessed using pesticide application records combined with residential addresses in a geographic information system. We examined gut microbiome differences due to OP exposures, specifically differences in microbial diversity based on the Shannon index and Bray–Curtis dissimilarities, and differential taxa abundance and predicted Metacyc pathway expression relying on regression models and adjusting for potential confounders.

Results
OP exposure was not associated with alpha or beta diversity of the gut microbiome. However, the predicted metagenome was sparser and less evenly expressed among those highly exposed to OP (p = 0.04). Additionally, we found that the abundance of two bacterial families, 22 genera, and the predicted expression of 34 Metacyc pathways were associated with long-term OP exposure. These pathways included perturbed processes related to cellular respiration, increased biosynthesis and degradation of compounds related to bacterial wall structure, increased biosynthesis of RNA/DNA precursors, and decreased synthesis of Vitamin B1 and B6.

Conclusion
In support of previous animal studies and in-vitro findings, our results suggest that ambient chronic OP pesticide exposure alters gut microbiome composition and its predicted metabolism in humans.
LXR agonism for CNS diseases: promises and challenges
Authors: Zhang Ruiyi , Wuerch Emily , Yong V. Wee , Xue Mengzhou 
Published: April 2024

AbstractThe unfavorable prognosis of many neurological conditions could be attributed to limited tissue regeneration in central nervous system (CNS) and overwhelming inflammation, while liver X receptor (LXR) may regulate both processes due to its pivotal role in cholesterol metabolism and inflammatory response, and thus receives increasing attentions from neuroscientists and clinicians. Here, we summarize the signal transduction of LXR pathway, discuss the therapeutic potentials of LXR agonists based on preclinical data using different disease models, and analyze the dilemma and possible resolutions for clinical translation to encourage further investigations of LXR related therapies in CNS disorders.
Graphical Abstract
Privatisation of government services in Australia: what is known about health and equity impacts
Authors: Anaf Julia , Freeman Toby , Baum Fran 
Published: April 2024

Abstract
Background
Historically in Australia, all levels of government created collective wealth by owning and operating infrastructure, and managing natural assets, key public goods and essential services while being answerable to the public. This strong state tradition was challenged in the 1980s when privatisation became a widespread government approach globally. Privatisation involves displacing the public sector through modes of financing, ownership, management and product or service delivery. The Australian literature shows that negative effects from privatisation are not spread equitably, and the health and equity impacts appear to be under-researched. This narrative overview aims to address a gap in the literature by answering research questions on what evidence exists for positive and negative outcomes of privatisation; how well societal impacts are evaluated, and the implications for health and equity.

Methods
Database and grey literature were searched by keywords, with inclusion criteria of items limited to Australia, published between 1990 and 2022, relating to any industry or government sector, including an evaluative aspect, or identifying positive or negative aspects from privatisation, contracting out, or outsourcing. Thematic analysis was aided by NVivo qualitative data software and guided by an a-priori coding frame.

Results
No items explicitly reflected on the relationship between privatisation and health. Main themes identified were the public cost of privatisation, loss of government control and expertise, lack of accountability and transparency, constraints to accessing social determinants of health, and benefits accruing to the private sector.

Discussion
Our results supported the view that privatisation is more than asset-stripping the public sector. It is a comprehensive strategy for restructuring public services in the interests of capital, with privatisation therefore both a political and commercial determinant of health. There is growing discussion on the need for re-nationalisation of certain public assets, including by the Victorian government.

Conclusion
Privatisation of public services is likely to have had an adverse impact on population health and contributed to the increase in inequities. This review suggests that there is little evidence for the benefits of privatisation, with a need for greater attention to political and commercial determinants of health in policy formation and in research.
Management of embolic splenic abscess secondary to aortic valve endocarditis – case report and review of literature
Authors: Nunez-Ordonez Nicolas , Luna Juan Sebastián , Mackenzie Jaime Camacho , Jiménez Andrés Felipe , González Alejandro , Pico Andrea J. , Román Carlos F. , Rivera Paulo A. Cabrera , Hincapié Carlos A. Villa 
Published: April 2024

Abstract
Background
Splenic abscess is a serious complication associated with infective endocarditis. There is still contradicting evidence regarding the optimal treatment pathway including timing of valve intervention and the approach for managing splenic foci.

Case presentation
We present a case of a hybrid staged approach in which we successfully performed a laparoscopic splenectomy following percutaneous abscess drainage and a delayed aortic valve replacement.

Conclusions
A multidisciplinary teamwork is fundamental in providing optimal care for patients with distant complications associated with infective endocarditis. Our hybrid approach seems safe and feasible.
Effect of intra-arrest transport, extracorporeal cardiopulmonary resuscitation and immediate invasive assessment in refractory out-of-hospital cardiac arrest: a long-term follow-up of the Prague OHCA trial
Authors: Rob Daniel , Farkasovska Klaudia , Kreckova Marketa , Smid Ondrej , Kavalkova Petra , Macoun Jaromir , Huptych Michal , Havrankova Petra , Gallo Juraj , Pudil Jan , Dusik Milan , Havranek Stepan , Linhart Ales , Belohlavek Jan 
Published: April 2024

Abstract
Background
Randomized data evaluating the impact of the extracorporeal cardiopulmonary resuscitation (ECPR) approach on long-term clinical outcomes in patients with refractory out-of-hospital cardiac arrest (OHCA) are lacking. The objective of this follow-up study was to assess the long-term clinical outcomes of the ECPR-based versus CCPR approach.

Methods
The Prague OHCA trial was a single-center, randomized, open-label trial. Patients with witnessed refractory OHCA of presumed cardiac origin, without return of spontaneous circulation, were randomized during ongoing resuscitation on scene to conventional CPR (CCPR) or an ECPR-based approach (intra-arrest transport, ECPR if ROSC is not achieved prehospital and immediate invasive assessment).

Results
From March 2013 to October 2020, 264 patients were randomized during ongoing resuscitation on scene, and 256 patients were enrolled. Long-term follow-up was performed 5.3 (interquartile range 3.8–7.2) years after initial randomization and was completed in 255 of 256 patients (99.6%). In total, 34/123 (27.6%) patients in the ECPR-based group and 26/132 (19.7%) in the CCPR group were alive (log-rank P = 0.01). There were no significant differences between the treatment groups in the neurological outcome, survival after hospital discharge, risk of hospitalization, major cardiovascular events and quality of life. Of long-term survivors, 1/34 (2.9%) in the ECPR-based arm and 1/26 (3.8%) in the CCPR arm had poor neurological outcome (both patients had a cerebral performance category score of 3).

Conclusions
Among patients with refractory OHCA, the ECPR-based approach significantly improved long-term survival. There were no differences in the neurological outcome, major cardiovascular events and quality of life between the groups, but the trial was possibly underpowered to detect a clinically relevant difference in these outcomes.
Trial registration ClinicalTrials.gov Identifier: NCT01511666, Registered 19 January 2012.
A methodological review of randomised n-of-1 trials
Authors: Hawksworth Olivia , Chatters Robin , Julious Steven , Cook Andrew , Biggs Katie , Solaiman Kiera , Quah Michael C. H. , Cheong Sxe Chang 
Published: April 2024

Abstract
Background
n-of-1 trials are a type of crossover trial designed to optimise the evaluation of health technologies in individual patients. This trial design may be considered for the evaluation of health technologies in rare conditions where fewer patients are available to take part in research. This review describes the characteristics of randomised n-of-1 trials conducted over the span of 12 years, including how the n-of-1 design has been employed to study both rare and non-rare conditions.

Methods
Databases and clinical trials registries were searched for articles including “n-of-1” in the title between 2011 and 2023. The reference lists of reviews identified by the searches were searched for any additional eligible articles. Randomised n-of-1 trials were selected for inclusion and data were extracted on a range of design, population, and analysis characteristics. Descriptive statistics were produced for all variables.

Results
We identified 74 studies meeting our eligibility criteria, 13 of which (17.6%) were conducted in rare conditions. They were conducted in a range of clinical areas with the most common being neurological conditions (n = 16, 21.6%). The median (Q1, Q3) number of participants randomised was 9 (4, 20) and 12 trials (16.2%) involved a single patient only. Forty-six (62.2%) trials evaluated pharmaceutical interventions and 49 (66.2%) trials were placebo controlled. Trials had a median (Q1, Q3) of six (4, 8) periods and 61 (82.4%) compared two health technologies. Fifty-seven (77.0%) trials incorporated blinding and 32 (43.2%) had a washout period. Forty-nine trials (66.2%) used patient-reported outcome measures (PROMs) to assess the primary outcome. Trials used a range of approaches to analysis and 48 (64.9%) combined data from multiple patients. The characteristics of the n-of-1 trials conducted in rare conditions were generally consistent with those in non-rare conditions.

Conclusions
n-of-1 trials are still underused and the application of the n-of-1 design for the evaluation of health technologies for rare diseases has been particularly limited. We have summarised the characteristics of randomised n-of-1 trials in rare and non-rare conditions. We hope that it can inform researchers in the design of future n-of-1 studies. Further work is required to provide guidance on specific design considerations, implementation, and statistical analysis of these studies.

Trial registration
Not applicable.
PheSeq, a Bayesian deep learning model to enhance and interpret the gene-disease association studies
Authors: Yao Xinzhi , Ouyang Sizhuo , Lian Yulong , Peng Qianqian , Zhou Xionghui , Huang Feier , Hu Xuehai , Shi Feng , Xia Jingbo 
Published: April 2024

AbstractDespite the abundance of genotype-phenotype association studies, the resulting association outcomes often lack robustness and interpretations. To address these challenges, we introduce PheSeq, a Bayesian deep learning model that enhances and interprets association studies through the integration and perception of phenotype descriptions. By implementing the PheSeq model in three case studies on Alzheimer’s disease, breast cancer, and lung cancer, we identify 1024 priority genes for Alzheimer’s disease and 818 and 566 genes for breast cancer and lung cancer, respectively. Benefiting from data fusion, these findings represent moderate positive rates, high recall rates, and interpretation in gene-disease association studies.