bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adversarial regularized autoencoder graph neural network for microbe-disease associations prediction
Authors: He Limuxuan , Zou Quan , Dai Qi , Cheng Shuang , Wang Yansu 
Published: November 2024

Abstract

Background
Microorganisms inhabit various regions of the human body and significantly contribute to numerous diseases. Predicting the associations between microbes and diseases is crucial for understanding pathogenic mechanisms and informing prevention and treatment strategies. Biological experiments to determine these associations are time-consuming and costly. Therefore, integrating deep learning with biological networks can efficiently identify potential microbe-disease associations on a large scale.

Methods
We propose an adversarial regularized autoencoder graph neural network algorithm, named Stacked Adversarial Regularization for Microbe-Disease Associations Prediction (SARMDA), for predicting associations between microbes and diseases. First, we integrate topological structural similarity and functional similarity metrics of microbes and diseases to construct a heterogeneous network. Then, utilizing an autoencoder based on GraphSAGE, we learn both the topological and attribute representations of nodes within the constructed network. Finally, we introduce an adversarial regularized autoencoder graph neural network embedding model to address the inherent limitations of traditional GraphSAGE autoencoders in capturing global information.

Results
Under the five-fold cross-validation on microbe-disease pairs, SARMDA was compared with eight advanced methods using the Human Microbe-Disease Association Database (HMDAD) and Disbiome databases. The best area under the ROC curve (AUC) achieved by SARMDA on HMDAD was 0.9891$\pm$0.0057, and the best area under the precision-recall curve (AUPR) was 0.9902$\pm$0.0128. On the Disbiome dataset, the AUC was 0.9328$\pm$0.0072, and the best AUPR was 0.9233$\pm$0.0089, outperforming the other eight MDAs prediction methods. Furthermore, the effectiveness of our model was demonstrated through a detailed analysis of asthma and inflammatory bowel disease cases.
Unveiling novel regulatory mechanisms of miR-5195-3p in pelvic organ prolapse pathogenesis
Authors: Zhang Hao , Wang Xinlu , Dong Meng , Wang Jie , Ren Weidong 
Published: November 2024

Abstract
Pelvic organ prolapse is a condition that significantly affects women’s quality of life. The pathological mechanism of pelvic organ prolapse is not yet fully understood, and its pathogenesis is often caused by multiple factors, including the metabolic imbalance of the extracellular matrix. This study aims to investigate the role of miR-5195-3p, a microRNA, in the pathology of pelvic organ prolapse and its regulatory mechanism. Using various molecular biology techniques such as real-time reverse transcription Polymerase Chain Reaction (PCR), fluorescence in situ hybridization, immunohistochemistry, and Western blot, miR-5195-3p expression was examined in vaginal wall tissues obtained from pelvic organ prolapse patients. Results revealed an up-regulation of miR-5195-3p expression in these tissues, showing a negative correlation with the expression of extracellular matrix–related proteins. Further analysis using bioinformatics tools identified Lipoxygenase (LOX) as a potential target in pelvic organ prolapse. Dual luciferase reporter gene experiments confirmed LOX as a direct target of miR-5195-3p. Interestingly, regulating the expression of LOX also influenced the transforming growth factor β1 signaling pathway and had an impact on extracellular matrix metabolism. This finding suggests that miR-5195-3p controls extracellular matrix metabolism by targeting LOX and modulating the TGF-β1 signaling pathway. In conclusion, this study unveils the involvement of miR-5195-3p in the pathological mechanism of pelvic organ prolapse by regulating extracellular matrix metabolism through the LOX/TGF-β1 axis. These findings reveal new mechanisms in the pathogenesis of pelvic organ prolapse, providing a theoretical foundation and therapeutic targets for further research on pelvic organ prolapse treatment.
Bayesian pathway analysis over brain network mediators for survival data
Authors: Tian Xinyuan , Li Fan , Shen Li , Esserman Denise , Zhao Yize 
Published: November 2024

ABSTRACT
Technological advancements in noninvasive imaging facilitate the construction of whole brain interconnected networks, known as brain connectivity. Existing approaches to analyze brain connectivity frequently disaggregate the entire network into a vector of unique edges or summary measures, leading to a substantial loss of information. Motivated by the need to explore the effect mechanism among genetic exposure, brain connectivity, and time to disease onset with maximum information extraction, we propose a Bayesian approach to model the effect pathway between each of these components while quantifying the mediating role of brain networks. To accommodate the biological architectures of brain connectivity constructed along white matter fiber tracts, we develop a structural model which includes a symmetric matrix-variate accelerated failure time model for disease onset and a symmetric matrix response regression for the network-variate mediator. We further impose within-graph sparsity and between-graph shrinkage to identify informative network configurations and eliminate the interference of noisy components. Simulations are carried out to confirm the advantages of our proposed method over existing alternatives. By applying the proposed method to the landmark Alzheimer’s Disease Neuroimaging Initiative study, we obtain neurobiologically plausible insights that may inform future intervention strategies.
Minimizing preparation time for repeated prolonged deep-inspiration breath holds during breast cancer irradiation using pre-oxygenation with high-flow nasal oxygen and voluntary hyperventilation
Authors: Vakaet Vincent , Van Hulle Hans , De Noyette Renée , Schoepen Max , Deseyne Pieter , Huybrechts Vincent , Van Caelenberg Els , Van Greveling Annick , Monten Chris , De Baerdemaeker Luc , De Neve Wilfried , Coppens Marc , Veldeman Liv 
Published: November 2024

Abstract

Objectives
Deep inspiration breath-holds (DIBHs) reduce heart and lung toxicity during breast cancer radiotherapy. Consecutive DIBHs are stressful, time-consuming, and leads to position changes. To facilitate the introduction of pre-oxygenation using high-flow nasal oxygen (HFNO) and hyperventilation to prolong DIBHs (L-DIBHs), we examined the effect of hyperventilation time on the duration of L-DIBHs. Additionally, to minimize total treatment time, the feasibility of several successive L-DIBHs was examined.

Methods
Our previous protocol imposed 3 min of hyperventilation at 16 breaths per minute with pre-oxygenation using HFNO, in prone position. In the first phase, the effect of hyperventilation time on the length of the L-DIBH was investigated. The aim of the second phase was to investigate the feasibility of shorter preparation times before the second and third L-DIBH in the case of 3 consecutive L-DIBHs of at least 2 minutes.

Results
There is a positive but weak correlation between preparation time and L-DIBH duration. With either 3 minutes 30 seconds or 6 minutes 20 seconds (depending on fitness) of voluntary hyperventilation duration, 93% of subjects could hold 3 consecutive L-DIBHs for over 2 minutes. The median duration of the third and last L-DIBH was 3 minutes 17 seconds (SD 1 min 4 seconds).

Conclusion
A weak relationship exists between the hyperventilation time and L-DIBH duration. Repeating L-DIBHs with shorter preparations is achievable, resulting in a shorter total treatment time required.

Advances in knowledge
It is possible to perform repeated L-DIBHs for breast cancer irradiation using HFNO and hyperventilation.
Shared orbitofrontal dynamics to a drug-themed movie track craving and recovery in heroin addiction
Authors: Kronberg Greg , Ceceli Ahmet O , Huang Yuefeng , Gaudreault Pierre-Olivier , King Sarah G , McClain Natalie , Alia-Klein Nelly , Goldstein Rita Z 
Published: November 2024

Abstract
Movies captivate groups of individuals (the audience), especially if they contain themes of common motivational interest to the group. In drug addiction, a key mechanism is maladaptive motivational salience attribution whereby drug cues outcompete other reinforcers within the same environment or context. We predicted that while watching a drug-themed movie, where cues for drugs and other stimuli share a continuous narrative context, functional MRI responses in individuals with heroin use disorder (iHUD) will preferentially synchronize during drug scenes.
Thirty inpatient iHUD (24 male) and 25 healthy controls (16 male) watched a drug-themed movie at baseline and at follow-up after 15 weeks.
Results revealed such drug-biased synchronization in the orbitofrontal cortex (OFC), ventromedial and ventrolateral prefrontal cortex, and insula. After 15 weeks during ongoing inpatient treatment, there was a significant reduction in this drug-biased shared response in the OFC, which correlated with a concomitant reduction in dynamically-measured craving, suggesting synchronized OFC responses to a drug-themed movie as a neural marker of craving and recovery in iHUD.
Adsorption behavior of zirconium metal–organic frameworks in multicomponent metal-ion solutions
Authors: Rani Reetu , Ueda Takahiro , Saeki Kentaro , Toda Kei , Ohira Shin-Ichi 
Published: November 2024

Abstract
In this study, the adsorptive behavior of zirconium metal–organic frameworks (Zr-MOFs) was investigated for the adsorption of alkali and alkaline earth metal ions from multi-element aqueous solutions. Zr-MOFs exhibit high water stability, notable surface area, and a significant pore volume, all of which contribute to their enhanced adsorption capacity. Three Zr-MOFs, namely bare UiO-66, amine-functionalized NH2-UiO-66, and carboxyl-functionalized UiO-66-(COOH)2, were tested for the adsorption of alkali and alkaline earth metal ions. Among the 3 MOFs that were tested, only the carboxyl group-functionalized Zr-MOF showed significant adsorption capacity toward divalent metal ions. Further, a thorough investigation was conducted to understand how the pH, initial concentration of the solution, and Zr-MOF dosage impact the adsorption properties of UiO-66-(COOH)2. At the natural pH (6.5) of the solution, UiO-66-(COOH)2 exhibited a superior adsorption capacity toward Sr2+ (15.3 mg g−1) and Ca2+ (7.9 mg g−1), which was attributable to the stronger electrostatic attraction of these ions relative to monovalent ions. The kinetic study results indicated that the preferred mechanism of adsorption was chemisorption for divalent metal ions. Additionally, the adsorption behavior of UiO-66-(COOH)2 for 24 elements was evaluated and the MOF showed significant adsorption of Sr2+ and Ca2+ alongside other divalent and trivalent metal ions. The experimental findings of the present study suggest that carboxylic-functionalized Zr-MOF holds significant potential toward the preparation of suitable sorbents for the extraction of higher-valence metal ions.
Development of triggerable peroxidase-tagged primers for colorimetric DNA detection applicable to various DNA polymerases
Authors: Munakata Hironao , Sohma Yuri , Utsumi Kaito , Ohno Rinka , Ishida Kotaro , Morita Eiji , Sato Shin-ichi , Hagihara Masaki 
Published: November 2024

Abstract
To meet the demand for more cost-effective rapid and sensitive nucleic acid detection methods to benefit various applications, we introduce a novel technique that uses a modified triggerable guanine quadruplex-based peroxidase (POD)-tagged primer. This technique allows sensitive colorimetric detection by activating an inactive POD tag during polymerase chain reaction amplification, which, importantly, functions independently of the type of DNA polymerase used.
Long-Acting Cabotegravir Plus Rilpivirine in People With Human Immunodeficiency Virus With Adherence Challenges and Viremia: Current Data and Future Directions
Authors: Davis Jennifer M , Rana Aadia , Sax Paul E , Bares Sara H 
Published: November 2024

Abstract
Long-acting injectable cabotegravir plus rilpivirine (LA CAB/RPV) is currently US Food and Drug Administration approved and Human Immunodeficiency Virus (HIV) treatment guideline endorsed as a switch strategy for patients with HIV (PWH) who are virologically suppressed on oral antiretroviral therapy without a history of treatment failure. Recent changes to the International Antiviral Society–USA and US Department of Health and Human Services’ Panel on Antiretroviral Guidelines recommend the consideration of LA CAB/RPV in select PWH with viremia who are unable to achieve suppression with oral antiretroviral therapy due to suboptimal medication adherence. In this article, we review the existing data on this off-label use of LA CAB/RPV, discuss the motivations and specific caveats implicit in the guideline change, and propose next steps in exploring this novel treatment in a vulnerable patient population.
Drug use and acute kidney injury: a Drug-Wide Association Study (DWAS) in Denmark and Sweden
Authors: Bosi Alessandro , Lund Lars Christian , Mahalingasivam Viyaasan , Mazhar Faizan , Christiansen Christian Fynbo , Sjölander Arvid , Pottegård Anton , Carrero Juan Jesus 
Published: November 2024

ABSTRACT

Background
Knowledge of which medications may lead to acute kidney injury (AKI) is limited, relying mostly on spontaneous reporting in pharmacovigilance systems. We here conducted an exploratory drug-wide association study (DWAS) to screen for associations between dispensed drugs and AKI risk.

Methods
Using two large Danish and Swedish data linkages, we identified AKI hospitalizations occurring between April 1997 and December 2021 in Denmark and between March 2007 and December 2021 in Sweden. We used a case-time control design comparing drug dispensing in the 3 months prior to the AKI with earlier periods for the same patient. Odds ratios (ORs) for the association between each drug and AKI were estimated using conditional logistic regression and adjusting for the presence of comorbidities. We sought replication of signals in both health systems and explored the plausibility of findings through pharmacovigilance system analysis in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, appearance in the RESCUE list of medications that report AKI as a side effect, PubMed evidence review and causality assessment through direct acyclic graphs.

Results
We included 20 622 adults in Denmark and 13 852 in Sweden hospitalized for AKI. In total, 16 unique medications were identified in both cohorts as associated to increased AKI occurrence. Of these, 10 medications had higher reporting ORs in the FAERS database, 9 were listed by RESCUE, and 7 appearing in PubMed. This analysis identified some medications with known AKI risks (i.e. likely true positives such as furosemide, penicillin, spironolactone and omeprazole), medications that may have initiated in response to conditions that lead to AKI (i.e. false positives like metoclopramide provided to treat nausea/vomiting) and other candidates (e.g. opioids) that warrant further evaluation in subsequent studies.

Conclusions
This hypothesis-generating study identifies medications with potential involvement in AKI that require confirmation and validation.
Long-term outcomes after stress echocardiography in real-world practice: a 5-year follow-up of the UK EVAREST study
Authors: Woodward William , Johnson Casey L , Krasner Samuel , O’Driscoll Jamie , McCourt Annabelle , Dockerill Cameron , Balkhausen Katrin , Chandrasekaran Badrinathan , Firoozan Soroosh , Kardos Attila , Sabharwal Nikant , Sarwar Rizwan , Senior Roxy , Sharma Rajan , Wong Kenneth , Augustine Daniel X , Leeson Paul 
Published: November 2024

Abstract

Aims
Stress echocardiography is widely used to assess patients with chest pain. The clinical value of a positive or negative test result to inform on likely longer-term outcomes when applied in real-world practice across a healthcare system has not been previously reported.

Methods and results
Five thousand five hundred and three patients recruited across 32 UK NHS hospitals between 2018 and 2022, participating in the EVAREST/BSE-NSTEP prospective cohort study, with data on medical outcomes up to 2023 available from NHS England were included in the analysis. Stress echocardiography results were related to outcomes, including death, procedures, hospital admissions, and relevant cardiovascular diagnoses, based on Kaplan–Meier analysis and Cox proportional hazard ratios (HRs). Median follow-up was 829 days (interquartile range 224–1434). A positive stress echocardiogram was associated with a greater risk of myocardial infarction [HR 2.71, 95% confidence interval (CI) 1.73–4.24, P &lt; 0.001] and a composite endpoint of cardiac-related mortality and myocardial infarction (HR 2.03, 95% CI 1.41–2.93, P &lt; 0.001). Hazard ratios increased with ischaemic burden. A negative stress echocardiogram identified an event-free ‘warranty period’ of at least 5 years in patients with no prior history of coronary artery disease and 4 years for those with disease.

Conclusion
In real-world practice, the degree of myocardial ischaemia recorded by clinicians at stress echocardiography correctly categorizes risk of future events over the next 5 years. Reporting a stress echocardiogram as negative correctly identifies patients with no greater than a background risk of cardiovascular events over a similar time period.
Multicentre retrospective analysis of physician-modified fenestrated/inner-branched endovascular repair for complex aortic aneurysms
Authors: Shibata Tsuyoshi , Iba Yutaka , Yasuhara Kiyomitsu , Kuwada Noriaki , Katada Yoshiaki , Hashiguchi Hitoki , Uzuka Takeshi , Hosaka Itaru , Nakajima Tomohiro , Kawaharada Nobuyoshi 
Published: November 2024

Abstract

OBJECTIVES
In this multicentre retrospective observational study, we present the early outcomes of physician-modified fenestrated/inner-branched endovascular repair for pararenal and thoracoabdominal aortic aneurysms in patients at high risk for open surgical repair.

METHODS
We comprehensively reviewed the clinical data and outcomes of consecutive patients treated with physician-modified fenestrated/inner-branched endovascular repair for pararenal or thoracoabdominal aortic aneurysms at 6 centres between December 2020 and December 2021. Primary end-points included technical success, in-hospital mortality rates, major adverse events.

RESULTS
Seven and 31 patients (median age, 80.5 years) had pararenal and thoracoabdominal aortic aneurysms, respectively, involving 93 renal-mesenteric arteries incorporated through 10 fenestrations or 83 inner branches. Seven patients (18.4%) were treated non-elective conditions. The technical success rate was 89.5%. The median operative time was 334.5 min. Ten patients (26.3%) experienced major adverse events, including in-hospital mortality in 6 patients (15.8%), acute kidney injury in 3 patients (7.9%), respiratory failure in 3 patients (7.9%), bowel ischaemia in 1 patient (2.6%), stroke in 1 patient (2.6%) and paraplegia in 1 patient (2.6%). Among elective cases, in-hospital deaths occurred in 3 patients (9.7%), while in non-elective cases, the mortality rate was higher, with 3 patients (42.9%) succumbing. The median follow-up duration was 14 months.

CONCLUSIONS
Physician-modified fenestrated/inner-branched endovascular repair is a viable treatment for pararenal or thoracoabdominal aortic aneurysms in patients at high risk for open surgical repair. It provides customization without location constraints or production delays, but further validation is needed to ensure long-term reliability.
Variants in LPA are associated with familial hypercholesterolaemia: whole genome sequencing analysis in the 100 000 Genomes Project
Authors: Bird Martin , Rimbert Antoine , Pittman Alan Michael , Humphries Steve Eric , Futema Marta 
Published: November 2024

Abstract

Aims
Familial hypercholesterolaemia (FH) is an inherited disease of high LDL cholesterol (LDL-C) caused by defects in LDLR, APOB, APOE, and PCSK9 genes. A pathogenic variant cannot be found in ∼60% of clinical FH patients. Using whole genome sequencing (WGS), we examined genetic determinants of FH.

Methods and results
Whole genome sequencing data generated by the 100 000 Genomes Project (100KGP) included 536 FH patients diagnosed using the FH Simon–Broome criteria. Rare variants in known FH genes were analysed. Genome-wide association study between 443 FH variant-negative unrelated FH cases and 77 275 control participants of the 100KGP was run using high-coverage WGS data. Polygenic risk scores for LDL-C (LDL PRS) and lipoprotein(a) (Lp(a) PRS) were computed. An FH-causing variant was found in 17.4% of FH cases. Genome-wide association study identified the LPA gene locus being significantly associated (P &lt; 1 × 10−8). Familial hypercholesterolaemia variant-negative participants had higher LDL and Lp(a) PRSs in comparison with the controls (P &lt; 1.0 × 10−16 and P &lt; 4.09 × 10−6, respectively). Similar associations were found in the monogenic FH with both LDL and Lp(a) PRSs being higher than in controls (P &lt; 4.03 × 10−4 and P &lt; 3.01 × 10−3, respectively). High LDL PRS was observed in 36.4% of FH variant-negative cases, whereas high Lp(a) PRS in 18.5%, with 7.0% having both high LDL and Lp(a) PRSs.

Conclusion
This genome-wide analysis of monogenic and polygenic FH causes confirms a complex and heterogeneous architecture of hypercholesterolaemia, with the LPA gene playing a significant role. Both Lp(a) and LDL-C should be measured for precision FH diagnosis. Specific therapies to lower Lp(a) should be targeted to those who will benefit most.
The impact of reminders on representativeness and survey estimates among web-mode invited in the Danish National Health Survey
Authors: Jezek Andrea Huber , Ekholm Ola , Thygesen Lau Caspar , Christensen Anne Illemann 
Published: November 2024

Abstract
Declining response proportions in health surveys may lead to increased non-response bias. Multiple reminders are often used to increase response proportions, and, thus, we aimed to determine if the use of reminders decreased the magnitude of non-response bias among web-mode invited in the Danish National Health Survey 2023. In the Danish National Health Survey 2023, a national random sample of 23 467 individuals (aged ≥16 years) with residence in Denmark were invited by a secure electronic mail service. Invited individuals received up to five inquiries: (i) web invitation, (ii) web reminder, (iii) paper invitation including a questionnaire and a prepaid return envelope, (iv) paper reminder, and (v) paper reminder including a questionnaire and a prepaid return envelope. The cumulative response proportions after first-, second-, third-, fourth-, and fifth inquiries were 19.1%, 28.9%, 37.2%, 39.3%, and 42.0%, respectively. In general, third, fourth, and fifth mailing respondents were more often men, at younger ages, with non-Western backgrounds, and unmarried compared to first mailing respondents. Furthermore, third, fourth, and fifth mailing respondents were in general found to have less favorable health behavior than first mailing respondents, but also a lower prevalence of fair or poor self-rated health and long-standing health problems. In conlusion, reminders are an effective way to increase the response proportion. Furthermore, the use of reminders was found to decrease the magnitude of non-response bias; however, the decrease was small due to the low number of individuals responding after fourth and fifth inquiries.