bluuebunny/crossref_metadata_2025_split huggingface dataset:
DeepGSEA: explainable deep gene set enrichment analysis for single-cell transcriptomic data
Authors: Xiong Guangzhi , LeRoy Nathan J , Bekiranov Stefan , Sheffield Nathan C , Zhang Aidong 
Published: July 2024

Abstract

Motivation
Gene set enrichment (GSE) analysis allows for an interpretation of gene expression through pre-defined gene set databases and is a critical step in understanding different phenotypes. With the rapid development of single-cell RNA sequencing (scRNA-seq) technology, GSE analysis can be performed on fine-grained gene expression data to gain a nuanced understanding of phenotypes of interest. However, with the cellular heterogeneity in single-cell gene profiles, current statistical GSE analysis methods sometimes fail to identify enriched gene sets. Meanwhile, deep learning has gained traction in applications like clustering and trajectory inference in single-cell studies due to its prowess in capturing complex data patterns. However, its use in GSE analysis remains limited, due to interpretability challenges.

Results
In this paper, we present DeepGSEA, an explainable deep gene set enrichment analysis approach which leverages the expressiveness of interpretable, prototype-based neural networks to provide an in-depth analysis of GSE. DeepGSEA learns the ability to capture GSE information through our designed classification tasks, and significance tests can be performed on each gene set, enabling the identification of enriched sets. The underlying distribution of a gene set learned by DeepGSEA can be explicitly visualized using the encoded cell and cellular prototype embeddings. We demonstrate the performance of DeepGSEA over commonly used GSE analysis methods by examining their sensitivity and specificity with four simulation studies. In addition, we test our model on three real scRNA-seq datasets and illustrate the interpretability of DeepGSEA by showing how its results can be explained.

Availability and implementation
https://github.com/Teddy-XiongGZ/DeepGSEA
Toward acid- and heparin-free dialysis: the regional anticoagulation approach
Authors: Lefevre Flora , Vial Romain , Grellier Sophie , Bujon Solène , Bouchouareb Dammar , Brunet Philippe , Scarfoglière Violaine , Robert Thomas 
Published: July 2024

ABSTRACT

Background
In chronic intermittent hemodialysis, heparin is the standard anticoagulant as is the use of acid-containing dialysate. Regional anticoagulation (RA) with a calcium-free, citrate-containing dialysate has been developed. We compared RA using a calcium-free, citrate-free dialysate, routinely used in our center, versus systemic heparinization.

Methods
In a retrospective, observational, single-center, crossover study, we examined 15 patients undergoing chronic hemodialysis who were at high risk of bleeding and temporarily unable to use heparin. These patients received temporary treatment with RA involving calcium-free and citrate-free dialysate. We compared the dialysis session success rates during two distinct periods: standard heparinization and RA procedure with a calcium-free and citrate-free dialysate.

Results
In our study of 15 patients on chronic hemodialysis which compared 30 RA sessions versus 28 heparin-based anticoagulation session, we observed a 100% success rate with a median session duration of 240 min in both RA and heparin groups. No early extracorporeal circulation (ECC) loss was reported. However, we noted significant differences in the post-dialysis ECC thrombosis scores, with higher Global Thrombosis Index (GTI) and higher membrane coagulation scores in the RA group (P &lt; .007 and P &lt; .02, respectively). No hypocalcaemia or hypercalcemia symptoms occurred. Median post-filter ionized calcium levels were 0.32 (0.29–0.39) mmol/L at 30 min and median patient ionized calcium levels was 1.19 (1.135–1.28) mmol/L at 60 min. No significant difference in per-dialysis arterial blood pressure was observed between groups.

Conclusion
Our study evaluated the RA approach using a calcium-free, citrate-free acetate dialysate in a chronic hemodialysis center and found it effective. Although an acid-free dialysate was not used in this study, our findings suggest it could be the next frontier in the evolution of advanced dialysis techniques.
Parity, infertility, age at first birth, and risk of atrial fibrillation: data from the HUNT study
Authors: Morooka Hikaru , Haug Eirin B , Malmo Vegard , Loennechen Jan Pål , Mukamal Kenneth J , Sen Abhijit , Janszky Imre , Horn Julie 
Published: July 2024

Abstract

Aims
Although parity, infertility, and age at first birth are important for later development of cardiovascular disease, research on their association with atrial fibrillation (AF) is limited.

Methods and results
We linked data from the population-based HUNT study and the Medical Birth Registry of Norway (MBRN) and validated medical records from local hospitals. A total of 24 015 women aged 45 years or older were followed for verified incident AF. Parity and age at first birth were retrieved from the MBRN or from self-reported questionnaires in the HUNT study. A history of infertility was self-reported on the HUNT questionnaire. Cox proportional hazards models were used to calculate hazard ratios (HRs) for the multivariable-adjusted associations of parity, infertility, and age at first birth with risk of AF. During a median follow-up of 12.8 years, 1448 (6.0%) participants developed AF. Women with higher parity (four or more births vs. two births) were at 21% higher risk of AF [HR 1.21, 95% confidence interval (CI) 1.05–1.39]. A history of infertility was also associated with the risk of AF (HR 1.20, 95% CI 1.02–1.42). Among parous women, younger age at first birth (&lt;20 vs. 20–29 years) was associated with a 20% higher risk of AF (HR 1.20, 95% CI 1.03–1.40).

Conclusion
Women with four or more births, or a history of infertility, or younger age at first birth have approximately a 20% higher risk of AF among women over 45 years old.
A pilot clinical risk model to predict polymyxin-induced nephrotoxicity: a real-world, retrospective cohort study
Authors: Song Mong-Hsiu , Xiang Bi-Xiao , Yang Chien-Yi , Lee Chou-Hsi , Yan Yu-Xuan , Yang Qin-Jie , Yin Wen-Jun , Zhou Yangang , Zuo Xiao-Cong , Xie Yue-Liang 
Published: July 2024

Abstract

Objectives
Polymyxin-induced nephrotoxicity (PIN) is a major safety concern and challenge in clinical practice, which limits the clinical use of polymyxins. This study aims to investigate the risk factors and to develop a scoring tool for the early prediction of PIN.

Methods
Data on critically ill patients who received intravenous polymyxin B or colistin sulfate for over 24 h were collected. Logistic regression with the least absolute shrinkage and selection operator (LASSO) was used to identify variables that are associated with outcomes. The eXtreme Gradient Boosting (XGB) classifier algorithm was used to further visualize factors with significant differences. A prediction model for PIN was developed through binary logistic regression analysis and the model was assessed by temporal validation and external validation. Finally, a risk-scoring system was developed based on the prediction model.

Results
Of 508 patients, 161 (31.6%) patients developed PIN. Polymyxin type, loading dose, septic shock, concomitant vasopressors and baseline blood urea nitrogen (BUN) level were identified as significant predictors of PIN. All validation exhibited great discrimination, with the AUC of 0.742 (95% CI: 0.696–0.787) for internal validation, of 0.708 (95% CI: 0.605–0.810) for temporal validation and of 0.874 (95% CI: 0.759–0.989) for external validation, respectively. A simple risk-scoring tool was developed with a total risk score ranging from −3 to 4, corresponding to a risk of PIN from 0.79% to 81.24%.

Conclusions
This study established a prediction model for PIN. Before using polymyxins, the simple risk-scoring tool can effectively identify patients at risk of developing PIN within a range of 7% to 65%.
Molecular characterization of macrolide resistance in Haemophilus influenzae and Haemophilus parainfluenzae strains (2018–21)
Authors: Cadenas-Jiménez Irene , Saiz-Escobedo Lucía , Carrera-Salinas Anna , Camprubí-Márquez Xenia , Calvo-Silveria Sara , Camps-Massa Paula , Berbel Dàmaris , Tubau Fe , Santos Salud , Domínguez M Angeles , González-Díaz Aida , Ardanuy Carmen , Martí Sara 
Published: July 2024

Abstract

Objectives
This study aimed to explore the prevalence of macrolide resistance and the underlying resistance mechanisms in Haemophilus influenzae (n = 2556) and Haemophilus parainfluenzae (n = 510) collected between 2018 and 2021 from Bellvitge University Hospital, Spain.

Methods
Antimicrobial susceptibility was tested by microdilution. Whole-genome sequencing was performed using Illumina MiSeq and Oxford Nanopore technologies, and sequences were examined for macrolide resistance determinants and mobile genetic structures.

Results
Macrolide resistance was detected in 67 H. influenzae (2.6%) and 52 (10.2%) H. parainfluenzae strains and associated with resistance to other antimicrobials (co-trimoxazole, chloramphenicol, tetracycline). Differences in macrolide resistance existed between the two species. Acquired resistance genes were more prevalent in H. parainfluenzae (35/52; 67.3%) than in H. influenzae (12/67; 17.9%). Gene mutations and amino acid substitutions were more common in H. influenzae (57/67; 85%) than in H. parainfluenzae (16/52; 30.8%). Substitutions in L22 and in 23S rRNA were only detected in H. influenzae (34.3% and 29.0%, respectively), while substitutions in L4 and AcrAB/AcrR were observed in both species. The MEGA element was identified in 35 (67.3%) H. parainfluenzae strains, five located in an integrative and conjugative element (ICE); by contrast, 11 (16.4%) H. influenzae strains contained the MEGA element (all in an ICE). A new ICEHpaHUB8 was described in H. parainfluenzae.

Conclusions
Macrolide resistance was higher in H. parainfluenzae than in H. influenzae, with differences in the underlying mechanisms. H. parainfluenzae exhibits co-resistance to other antimicrobials, often leading to an extensively drug-resistant phenotype. This highlights the importance of conducting antimicrobial resistance surveillance.
Completeness and readability of GPT-4-generated multilingual discharge instructions in the pediatric emergency department
Authors: Gimeno Alex , Krause Kevin , D’Souza Starina , Walsh Colin G 
Published: July 2024

Abstract

Objectives
The aim of this study was to assess the completeness and readability of generative pre-trained transformer-4 (GPT-4)-generated discharge instructions at prespecified reading levels for common pediatric emergency room complaints.

Materials and Methods
The outputs for 6 discharge scenarios stratified by reading level (fifth or eighth grade) and language (English, Spanish) were generated fivefold using GPT-4. Specifically, 120 discharge instructions were produced and analyzed (6 scenarios: 60 in English, 60 in Spanish; 60 at a fifth-grade reading level, 60 at an eighth-grade reading level) and compared for completeness and readability (between language, between reading level, and stratified by group and reading level). Completeness was defined as the proportion of literature-derived key points included in discharge instructions. Readability was quantified using Flesch-Kincaid (English) and Fernandez-Huerta (Spanish) readability scores.

Results
English-language GPT-generated discharge instructions contained a significantly higher proportion of must-include discharge instructions than those in Spanish (English: mean (standard error of the mean) = 62% (3%), Spanish: 53% (3%), P = .02). In the fifth-grade and eighth-grade level conditions, there was no significant difference between English and Spanish outputs in completeness. Readability did not differ across languages.

Discussion
GPT-4 produced readable discharge instructions in English and Spanish while modulating document reading level. Discharge instructions in English tended to have higher completeness than those in Spanish.

Conclusion
Future research in prompt engineering and GPT-4 performance, both generally and in multiple languages, is needed to reduce potential for health disparities by language and reading level.
Modification to the Jeans criterion by external tides: anisotropic fragmentation and formation of filaments
Authors: Li Guang-Xing 
Published: July 2024

ABSTRACT
The Jeans criterion sets the foundation of our understanding of gravitational collapse. Jog studied the fragmentation of gas under external tides and derived a dispersion relation $l^{\prime } = l_{\rm Jeans} \frac{1}{(1 + \lambda _0^{\prime } / 4 \pi G \rho _0)^{1/2}} \,\,.$ She further concludes that the Jeans mass is $m_{\rm incorrect}^{\prime }=m_{\rm Jeans} [1/(1 + \lambda _0^{\prime } / 4 \pi G \rho _0)^{3/2}]$. We clarify that due to the inhomogeneous nature of tides, this characteristic mass is incorrect. Under weak tides, the mass is $m \approx \rho \, l_1 l_2 l_3$, where the modifications to Jeans lengths along all three dimensions need to be considered; when the tide is strong enough, collapse can only occur once 1 or 2 dimensions. In the latter case, tides can stretch the gas, leading to the formation of filaments.
Velcrin molecular glues induce apoptosis in glioblastomas with high PDE3A and SLFN12 expression
Authors: Aquilanti Elisa , Goldoni Silvia , Baker Andrew , Kotynkova Kristyna , Andersen Sawyer , Bozinov Vincent , Gao Galen F , Cherniack Andrew D , Lange Martin , Lesche Ralf , Kopitz Charlotte , Lienau Philip , Lewis Timothy A , Garrido Marine , Gradl Stefan , Seidel Henrik , Tseng Yuen-Yi , Ligon Keith L , Wen Patrick Y , Meyerson Matthew , Greulich Heidi 
Published: July 2024

Abstract

Background
Velcrins are molecular glues that kill cells by inducing the formation of a protein complex between the RNase SLFN12 and the phosphodiesterase PDE3A. Formation of the complex activates SLFN12, which cleaves tRNALeu(TAA) and induces apoptosis. Velcrins such as the clinical investigational compound, BAY 2666605, were found to have activity across multiple solid tumor cell lines from the cancer cell line encyclopedia, including glioblastoma cell lines. We therefore aim to characterize velcrins as novel therapeutic agents in glioblastoma.

Materials and Methods
PDE3A and SLFN12 expression levels were measured in glioblastoma cell lines, the Cancer Genome Atlas (TCGA) tumor samples, and tumor neurospheres. Velcrin-treated cells were assayed for viability, induction of apoptosis, cell cycle phases, and global changes in translation. Transcriptional profiling of the cells was obtained. Xenograft-harboring mice treated with velcrins were also monitored for survival.

Results
We identified several velcrin-sensitive glioblastoma cell lines and 4 velcrin-sensitive glioblastoma patient-derived models. We determined that BAY 2666605 crosses the blood-brain barrier and elicits full tumor regression in an orthotopic xenograft model of GB1 cells. We also determined that the velcrins BAY 2666605 and BRD3800 induce tumor regression in subcutaneous glioblastoma PDX models.

Conclusions
Velcrins have antitumor activity in preclinical models of glioblastoma, warranting further investigation as potential therapeutic agents.
Enhanced radiation sensitivity, decreased DNA damage repair, and differentiation defects in airway stem cells derived from patients with chronic obstructive pulmonary disease
Authors: Giuranno Lorena , Piepers Jolanda A F , Korsten Evelien , Borman Reitske , van de Kamp Gerarda , De Ruysscher Dirk , Essers Jeroen , Vooijs Marc A 
Published: July 2024

Abstract
Radiation therapy (RT) is a common treatment for lung cancer. Still, it can lead to irreversible loss of pulmonary function and a significant reduction in quality of life for one-third of patients. Preexisting comorbidities, such as chronic obstructive pulmonary disease (COPD), are frequent in patients with lung cancer and further increase the risk of complications. Because lung stem cells are crucial for the regeneration of lung tissue following injury, we hypothesized that airway stem cells from patients with COPD with lung cancer might contribute to increased radiation sensitivity. We used the air-liquid interface model, a three-dimensional (3D) culture system, to compare the radiation response of primary human airway stem cells from healthy and patients with COPD. We found that COPD-derived airway stem cells, compared to healthy airway stem cell cultures, exhibited disproportionate pathological mucociliary differentiation, aberrant cell cycle checkpoints, residual DNA damage, reduced survival of stem cells and self-renewal, and terminally differentiated cells post-irradiation, which could be reversed by blocking the Notch pathway using small-molecule γ-secretase inhibitors. Our findings shed light on the mechanisms underlying the increased radiation sensitivity of COPD and suggest that airway stem cells reflect part of the pathological remodeling seen in lung tissue from patients with lung cancer receiving thoracic RT.
Integrating Genomics and Biogeography to Unravel the Origin of a Mountain Biota: The Case of a Reptile Endemicity Hotspot in Arabia
Authors: Burriel-Carranza Bernat , Tejero-Cicuéndez Héctor , Carné Albert , Mochales-Riaño Gabriel , Talavera Adrián , Al Saadi Saleh , Els Johannes , Šmíd Jiří , Tamar Karin , Tarroso Pedro , Carranza Salvador 
Published: July 2024

Abstract
Advances in genomics have greatly enhanced our understanding of mountain biodiversity, providing new insights into the complex and dynamic mechanisms that drive the formation of mountain biotas. These span from broad biogeographic patterns to population dynamics and adaptations to these environments. However, significant challenges remain in integrating large-scale and fine-scale findings to develop a comprehensive understanding of mountain biodiversity. One significant challenge is the lack of genomic data, especially in historically understudied arid regions where reptiles are a particularly diverse vertebrate group. In the present study, we assembled a de novo genome-wide SNP dataset for the complete endemic reptile fauna of a mountain range (19 described species with more than 600 specimens sequenced), and integrated state-of-the-art biogeographic analyses at the population, species, and community level. Thus, we provide a holistic integration of how a whole endemic reptile community has originated, diversified and dispersed through a mountain system. Our results show that reptiles independently colonized the Hajar Mountains of southeastern Arabia 11 times. After colonization, species delimitation methods suggest high levels of within-mountain diversification, supporting up to 49 deep lineages. This diversity is strongly structured following local topography, with the highest peaks acting as a broad barrier to gene flow among the entire community. Interestingly, orogenic events do not seem key drivers of the biogeographic history of reptiles in this system. Instead, past climatic events seem to have had a major role in this community assemblage. We observe an increase of vicariant events from Late Pliocene onwards, coinciding with an unstable climatic period of rapid shifts between hyper-arid and semiarid conditions that led to the ongoing desertification of Arabia. We conclude that paleoclimate, and particularly extreme aridification, acted as a main driver of diversification in arid mountain systems which is tangled with the generation of highly adapted endemicity. Overall, our study does not only provide a valuable contribution to understanding the evolution of mountain biodiversity, but also offers a flexible and scalable approach that can be reproduced into any taxonomic group and at any discrete environment.
Czech Republic: Czech private foundations and trusts in the light of recent discussions and case law
Authors: Pihera Vlastimil , Ronovská Kateřina 
Published: July 2024

Abstract
This article aims to summarize, in the context of recent court decisions (case law), the development of the views and concepts with which private foundations and trusts have been viewed in Czech law over the last 10 years. In this respect, the authors believe that Czech law can serve as a kind of (albeit imperfect) laboratory for exploring the general difficulties encountered by traditional civil law jurisdictions in introducing these wealth management instruments institutes into traditional civil law systems.
LncRNA HILPDA promotes contrast-induced acute kidney injury by recruiting eIF4B to upregulate XPO1 expression
Authors: Wei Haiyan , Tilakezi Tuersun , Feng Wei , Yang Heyin , Yang Shujun 
Published: July 2024

Abstract

Background
Contrast-induced acute kidney injury (CI-AKI) is a serious and common complication following the use of iodinated contrast media, with a 20% fatality rate. The function of long non-coding RNA HILPDA (lnc-HILPDA) in CI-AKI development was investigated in this study.

Methods
CI-AKI models were constructed by iopromide treatment. Kidney pathological changes were analyzed by HE staining. TUNEL labeling and flow cytometry were used to examine cell apoptosis. CCK-8 assay was used to determine cell viability. The interactions between lnc-HILPDA, eIF4B, and XPO1 were verified by RIP or Co-IP assay.

Results
Lnc-HILPDA was upregulated in CI-AKI, and its knockdown decreased contrast-trigged oxidative stress and apoptosis in HK-2 cells. Mechanically, lnc-HILPDA activated the NF-κB pathway by upregulating XPO1 through interacting with eIF4B. Moreover, the inhibitory effect of lnc-HILPDA downregulation on contrast-induced oxidative stress and apoptosis in HK-2 cells was weakened by XPO1 overexpression.

Conclusion
Lnc-HILPDA accelerated CI-AKI progression by elevating XPO1 expression through eIF4B to activate NF-κB pathway.
Return to Work After Surgery for Lumbar Disk Herniation
Authors: Hara Sozaburo , Aasdahl Lene , Salvesen Øyvind , Solberg Tore , Gulati Sasha , Hara Karen Walseth 
Published: July 2024

Study Design.
An observational registry-based study.

Objective.
We investigated the long-term patterns of sick leave among patients undergoing surgery for lumbar disk herniation using two nationwide databases to study the achievement of post-surgery return to work (RTW).

Summary of Background Data.
The ability to RTW is increasingly recognized as an essential outcome measure for spine surgery.

Methods.
The study included 13,698 patients aged 18 to 60 on sick leave undergoing surgery for lumbar disk herniation from January 2007 through January 2019. Data from the Norwegian Registry for Spine Surgery (NORspine) and the Norwegian Labour and Welfare Administration (NAV) were linked. Certified sick leave around the time of surgery was assessed. The patients were further categorized according to the length of pre-surgery sick leave, and the rate of sustainable RTW for the different groups was compared using survival analysis. The association between successful surgical outcomes, defined by a 30% improvement in Oswestry Disability Index score, and achievement of sustainable RTW was analyzed using a logistic regression model.

Results.
Two years after surgery, 76% of the patients had returned to work. Shorter pre-surgery sick leave was associated with a higher proportion and rate of achieved sustainable RTW: Among patients with sick leave of less than 30 days, a total of 99% achieved sustainable RTW (median 46 d); only 40% of patients with longer-lasting work assessment allowance achieved the same goal within two years. Successful surgical outcomes were associated with sustainable RTW for all patient groups, but the impact of surgical success on RTW declined as sick leave extended beyond 180 days.

Conclusion.
Most patients had returned to work two years after lumbar disk herniation surgery. Shorter pre-surgery sick leave was associated with achieving faster and more sustainable RTW. Successful surgical outcomes had less impact on patients with extended sick leave.

Level of Evidence
III