bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilizing deep learning-based causal inference to explore vancomycin’s impact on continuous kidney replacement therapy necessity in blood culture-positive intensive care unit patients
Authors: Kang Min Woo , Kang Yoonjin
Published: December 2024

Patients with positive blood cultures in the intensive care unit (ICU) are at high risk for septic acute kidney injury requiring continuous kidney replacement therapy (CKRT), especially when treated with vancomycin. This study developed a machine learning model to predict CKRT and examined vancomycin’s impact using deep learning-based causal inference. We analyzed ICU patients with positive blood cultures, utilizing the Medical Information Mart for Intensive Care III data set. The primary outcome was defined as the initiation of CKRT during the ICU stay. The machine learning models were developed to predict the outcome. The deep learning-based causal inference model was utilized to quantitatively demonstrate the impact of vancomycin on the probability of CKRT initiation. Logistic regression was performed to analyze the relationship between the variables and the susceptibility of vancomycin. A total of 1,318 patients were included in the analysis, with 41 requiring CKRT. The Random Forest and Light Gradient Boosting Machine exhibited the best performance, with Area Under Curve of Receiver Operating Characteristic Curve values of 0.905 and 0.886, respectively. The deep learning-based causal inference model demonstrated an average 7.7% increase in the probability of CKRT occurrence when administrating vancomycin in total data set. Additionally, that younger age, lower diastolic blood pressure, higher heart rate, higher baseline creatinine, and lower bicarbonate levels sensitized the probability of CKRT application in response to vancomycin treatment. Deep learning-based causal inference models showed that vancomycin administration increases CKRT risk, identifying specific patient characteristics associated with higher susceptibility.

IMPORTANCE

This study assesses the impact of vancomycin on the risk of continuous kidney replacement therapy (CKRT) in intensive care unit (ICU) patients with blood culture-positive infections. Utilizing deep learning-based causal inference and machine learning models, the research quantifies how vancomycin administration increases CKRT risk by an average of 7.7%. Key variables influencing susceptibility include baseline creatinine, diastolic blood pressure, heart rate, and bicarbonate levels. These findings offer insights into managing vancomycin-induced kidney risk and may inform patient-specific treatment strategies in ICU settings.
How often do parents administer medications to their children in hospital? A prospective direct observational study
Authors: Westbrook Johanna I , Li Ling , Badgery-Parker Tim , Fitzpatrick Erin , Mumford Virginia , Merchant Alison , Raban Magdalena Z
Published: December 2024

Parents and carers play a critical role in supporting their children while in hospital. Multiple qualitative studies have explored parental involvement in the care of hospitalised children. Administration of medication to young children can be difficult and cause anxiety and stress for children. Parents are often willing and able to assist, yet little is known about how often parents are given responsibility for medication administration in hospital.

We analysed data from a prospective direct observational study of nurses administering medication at a major paediatric referral hospital in Australia. Data from observations of 298 nurses preparing and administering 5137 medication doses to children on nine medical and surgical wards between 07:00 and 22:00 were analysed. Details of drugs administered, whether medications were left for parents/carers to administer, and if nurses observed the administration by parents, were recorded.

Parents were at their child’s bedside during 89.7% (n=4610) of observed medication administrations. Parents gave 20.3% (n=1045) of medications. In 14.3% (n=733), medications were left with parents to administer without a nurse present. In 6.1% (n=312) of doses, medications were given to parents, but the administration was observed by a nurse. Parents were most likely to be given medications to administer to young children (1–5 years), and the medications most frequently administered were analgesics and anti-epileptics.

Parents/carers are integrally involved in the administration of many medications to children in hospital. The extent of parents’ role and the impact on medication administration efficiency has been largely absent from the healthcare literature. Given that one in five medication doses is administered by parents, hospitals should recognise this contribution and consider if any additional support for parents is required.
Acute hepatitis of unknown aetiology in children: evidence for and against causal relationships with SARS-CoV-2, HAdv and AAV2
Authors: Gurdasani Deepti , Trent Mallory , Ziauddeen Hisham , Mnatzaganian Emmanuel , Turville Stuart , Chen Xin , Kunasekaran Mohana Priya , Chughtai Abrar Ahmad , Moa Aye , McEniery Julie , Greenhalgh Trisha , MacIntyre Chandini Raina
Published: December 2024

Background

The cause of acute paediatric hepatitis of unknown aetiology (2022) has not been established despite extensive investigation.

Objective

To summarise the evidence for and against a causal role for human adenovirus (HAdv), adeno-associated virus 2 (AAV-2) and SARS-CoV-2 in outbreaks of paediatric hepatitis in 2022.

Methods

We appraised and summarised relevant evidence for each of the Bradford Hill criteria for causality using quantitative (statistical modelling) and qualitative (narrative coherence) approaches. Each team member scored the evidence base for each criterion separately for HAdv, AAV-2 and SARS-CoV-2; differences were resolved by discussion. We additionally examined criteria of strength and temporality by examining the lagged association between SARS-CoV-2 positivity, respiratory HAdv positivity, positive faecal HAdv specimens and excess A&E attendances in 1–4 years for liver conditions in England.

Results

Assessing criteria using the published literature and our modelling: for HAdv three Bradford Hill criteria (strength, consistency and temporality) were partially met; and five criteria (consistency, coherence, experimental manipulation, analogy and temporality) were minimally met. For AAV-2, the strength of association criterion was fully met, five criteria (consistency, temporality, specificity, biological gradient and plausibility) were partially met and three (coherence, analogy and experimental manipulation) were minimally met. For SARS-CoV-2, five criteria (strength of association, plausibility, temporality, coherence and analogy) were fully met; one (consistency) was partially met and three (specificity, biological gradient and experimental manipulation) were minimally met.

Conclusion

Based on the Bradford Hill criteria and modelling, HAdv alone is unlikely to be the cause of the recent increase in hepatitis in children. The causal link between SARS-CoV-2, and to a lesser degree AAV-2, appears substantially stronger but remains unproven. Hepatitis is a known complication of multisystem inflammatory syndrome in children following COVID-19, and SARS-CoV-2 has been linked to increased susceptibility to infection post-COVID-19, which may suggest complex causal pathways including a possible interaction with AAV-2 infection/reactivation in hosts that are genetically susceptible or sensitised to infection.
Prevalence of domestic violence against pregnant women living in rural areas: systematic review and meta-analysis
Authors: Sulaimanova Gulnura , Yamaoka Yui , Bardella Inis Jane , Fujiwara Takeo
Published: December 2024

Background

Many studies have demonstrated that pregnant women living in rural areas are more likely to experience domestic violence (DV). Systematic reviews on the prevalence and risk factors of DV among pregnant women have been conducted mainly in urban areas. Thus, there has been no determination of the global prevalence of DV among rural pregnant women. The objective of this study is to assess the prevalence and types of DV among rural pregnant women globally using systematic review and meta-analysis.

Methods

The Preferred Reporting Items for Systematic Review and Meta-Analysis expanded checklist for 2020 was employed. The Condition-Context-Population framework was used to determine the inclusion criteria. Fifteen studies met the inclusion criteria. The PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature and Scopus databases were searched for published articles through January 2023. Pooled prevalence and types of DV in rural pregnant women were assessed using the random effect model.

Results

DV against rural pregnant women was prevalent at 33.4% (95% CI 20.8 to 47.9%). Psychological violence was the most common with a prevalence of 34.2%, followed by physical violence (14.1%) and sexual violence (13.5%).

Conclusion

One-third of pregnant women in rural areas are victims of DV. In rural pregnant women, the prevalence of DV is higher than overall global estimates. Policymakers, healthcare professionals and researchers must prioritise assessment and prevention of DV against pregnant women who reside in rural areas.
Examining causal relationships between educational attainment and type 2 diabetes using genetic analysis: findings from the EPIC-InterAct study through Mendelian randomisation
Authors: Macciotta Alessandra , Sacerdote Carlotta , Giachino Claudia , Di Girolamo Chiara , Franco Matteo , van der Schouw Yvonne T , Zamora-Ros Raul , Weiderpass Elisabete , Domenighetti Cloé , Elbaz Alexis , Truong Thérèse , Agnoli Claudia , Bendinelli Benedetta , Panico Salvatore , Vineis Paolo , Christakoudi Sofia , Schulze Matthias B , Katzke Verena , Bajracharya Rashmita , Dahm Christina C , Dalton Susanne Oksbjerg , Colorado-Yohar Sandra M , Moreno-Iribas Conchi , Etxezarreta Pilar Amiano , Sanchez María José , Forouhi Nita G , Wareham Nicholas , Ricceri Fulvio
Published: December 2024

Introduction

Observational studies have shown that more educated people are at lower risk of developing type 2 diabetes (T2D). However, robust study designs are needed to investigate the likelihood that such a relationship is causal. This study used genetic instruments for education to estimate the effect of education on T2D using the Mendelian randomisation (MR) approach.

Methods

Analyses have been conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study (more than 20 000 individuals), a case-cohort study of T2D nested in the EPIC cohort. Education was measured as Years of Education and Relative Index of Inequality. Prentice-weighted Cox models were performed to estimate the association between education and T2D. One-sample MR analyses investigated whether genetic predisposition towards longer education was associated with risk of T2D and investigated potential mediators of the association.

Results

MR estimates indicated a risk reduction of about 15% for each year of longer education on the risk of developing T2D, confirming the protective role estimated by observational models (HR 0.96, 95% CI 0.95 to 0.96). MR analyses on putative mediators showed a significant role of education on body mass index, alcohol consumption, adherence to the Mediterranean diet and smoking habits.

Conclusion

The results supported the hypothesis that higher education is a protective factor for the risk of developing T2D. Based on its position in the causal chain, education may be antecedent of other known risk factors for T2D including unhealthy behaviours. These findings reinforce evidence obtained through observational study designs and bridge the gap between correlation and causation.
Cost-related non-adherence to medications among adults with asthma in the USA, 2011–2022
Authors: Hung Chun-Tse , Erickson Steven R , Wu Chung-Hsuen
Published: December 2024

Background

Uncontrolled asthma is possibly caused by medication non-adherence, and financial hardship can be a major contributor to non-adherence. Since economic conditions and asthma management have changed over time, a comprehensive investigation of cost-related medication non-adherence (CRN) among adults with asthma is crucial.

Objective

To evaluate trends, prevalence and determinants of CRN, and its impact on asthma control among US adults with asthma.

Methods

Data from 2011 to 2022 National Health Interview Survey were used. Joinpoint regression analysis was used to evaluate trends in the prevalence of CRN. A multivariable logistic regression model was used to identify factors associated with CRN. Two additional multivariable logistic regression models were used to examine associations between CRN and asthma-related adverse events, including asthma attacks and emergency room (ER) visits for asthma.

Results

A total of 30 793 adults with asthma were included, representing 8.1% (19.38 million) of the US population. From 2011 to 2022, a declining trend in the prevalence of CRN among US adults with asthma was observed. Approximately every one in six adults with asthma was non-adherent to medications due to cost. Several factors, including demographics and comorbidities, were associated with CRN. Adults with asthma who had CRN were at an increased risk of experiencing asthma attacks (adjusted OR, 1.95; 95% CI 1.78 to 2.13) and ER visits for asthma (adjusted OR, 1.63; 95% CI 1.44 to 1.84).

Conclusion

Since asthma is one of the leading chronic diseases, the burden of cost-related non-adherence to medications highlights the need for appropriate policies and social supports to address such problems.
On the photon mass generation in Rarita–Schwinger QED
Authors: Ghasemkhani M. , Soleimani G. , Soto A. , Bufalo R.
Published: December 2024

This work examines the dynamical mass generation for the photon in Rarita–Schwinger QED. We focus our attention on the cases of

$$\omega =2,3$$

ω
=
2
,
3

dimensional spacetime. In these frameworks, it is well known that in the usual QED, the photon field (dynamically) acquires a gauge invariant mass (the Schwinger and Chern–Simons mass, respectively). We wish to scrutinize this phenomenon in terms of the Rarita–Schwinger fields. The presence of higher-derivative terms is shown as the leading contributions to the 1PI function

$$\langle AA \rangle $$

⟨
A
A
⟩

at one-loop order. We study the pole structure of the photon’s complete propagator to unveil the main effects of the Rarita–Schwinger fields on the photon’s mass. In addition, we present some remarks about the renormalizability of this model (in different dimensions) due to the presence of higher-derivative corrections at one-loop.
Geometric Embeddability of Complexes is ∃ℝ-complete
Authors: Abrahamsen Mikkel , Kleist Linda , Miltzow Tillmann
Published: December 2024

We show that the decision problem of determining whether a given (abstract simplicial)
k
-complex has a geometric embedding in ℝ
d
is complete for the Existential Theory of the Reals for all
d
≥ 3 and
k
∈ {
d
-1,
d
} by reducing from pseudoline stretchability. Consequently, the problem is polynomial time equivalent to determining whether a polynomial equation system has a real solution. Moreover, this implies NP-hardness and constitutes the first hardness result for the algorithmic problem of geometrically embedding (abstract simplicial) complexes. This complements recent breakthroughs for the computational complexity of piece-wise linear embeddability [Matoušek, Sedgwick, Tancer, and Wagner, J. ACM 2018, and de Mesmay, Rieck, Sedgwick and Tancer, J. ACM 2020] and establishes connections to computational topology.
Self Data Augmentation for Open Domain Question Answering
Authors: Zhang Qin , Zheng Mengqi , Chen Shangsi , Liu Han , Fang Meng
Published: December 2024

Information Retrieval (IR) constitutes a vital facet of Open Domain Question Answering (ODQA) systems, focusing on the exploration of pertinent information within extensive collections of passages, such as Wikipedia, to facilitate subsequent reader processing. Historically, IR relied on textual overlaps for relevant context retrieval, employing methods like BM25 and TF-IDF, which, however, lacked natural language understanding. The advent of deep learning ushered in a new era, leading to the introduction of Dense Passage Retrievers (DPR), shows superiority over traditional sparse retrievers. These dense retrievers leverage Pre-Trained Language Models (PLMs) to initialize context encoders, enabling the extraction of natural language representations. They utilize the distance between latent vectors of contexts as a metric for assessing similarity. However, DPR methods are heavily reliant on large volumes of meticulously labeled data, such as Natural Questions. The process of data labeling is both costly and time-intensive. In this article, we propose a novel data augmentation methodology Self Data Augmentation (SDA) that employs DPR models to automatically annotate unanswered questions. Specifically, we initiate the process by retrieving relevant pseudo passages for these unlabeled questions. We subsequently introduce three distinct passage selection methods to annotate these pseudo passages. Ultimately, we amalgamate the pseudo-labeled passages with the unanswered questions to create augmented data. Our experimental evaluations conducted on two extensive datasets (Natural Questions and TriviaQA), alongside a relatively small dataset (WebQuestions), utilizing three diverse base models, illustrate the significant enhancement achieved through the incorporation of freshly augmented data. Moreover, our proposed data augmentation method exhibits remarkable flexibility, which is readily adaptable to various dense retrievers. Additionally, we have conducted a comprehensive human study on the augmented data, which further supports our conclusions.
An Evolutionary Algorithm for Expensive Mixed-Integer Black-Box Optimization with Explicit Constraints
Authors: Hong Yuan , Arnold Dirk V.
Published: December 2024

Determining the feasibility of a candidate solution to a constrained black-box optimization problem may be similarly expensive compared to the process of determining its quality, or it may be much cheaper. Constraints that allow obtaining degrees of feasibility or constraint violation without incurring significant computational costs are referred to as explicit. We present an evolutionary algorithm for solving mixed-integer black-box optimization problems where objective function evaluations are expensive but constraints are explicit. We do not assume relaxability of the constraints. The method wraps active-set evolution strategies, an algorithm for solving continuous black-box problems with explicit constraints, in a branching mechanism that allows enforcing integrality constraints. In computer experiments we demonstrate that the algorithm solves a set of mixed-integer problems with significantly fewer objective function evaluations than several algorithms that do not exploit the explicitness of the constraints.
Unified Pressure, Surface Tension and Friction for SPH Fluids
Authors: Probst Timo , Teschner Matthias
Published: December 2024

Fluid droplets behave significantly different from larger fluid bodies. At smaller scales, surface tension and friction between fluids and the boundary play an essential role and are even able to counteract gravitational forces. There are quite a few existing approaches that model surface tension forces within an SPH environment. However, as often as not, physical correctness and simulation stability are still major concerns with many surface tension formulations. We propose a new approach to compute surface tension that is both robust and produces the right amount of surface tension.

Conversely, less attention was given to friction forces at the fluid-boundary interface. Recent experimental research indicates that Coulomb friction can be used to describe the behavior of droplets resting on a slope. Motivated by this, we develop a novel friction force formulation at the fluid-boundary interface following the Coulomb model, which allows us to replicate a new range of well known fluid behavior such as the motion of rain droplets on a window pane.

Both forces are combined with an IISPH variant into one unified solver that is able to simultaneously compute strongly coupled surface tension, friction and pressure forces.
Alterations in Volume and Intrinsic Resting-State Functional Connectivity Detected at Brain MRI in Individuals with Opioid Use Disorder
Authors: Mehta Saloni , Peterson Hannah , Ye Jean , Ibrahim Ahmad , Saeed Gul , Linsky Sarah , Kreinin Iouri , Tsang Sui , Nwanaji-Enwerem Uzoji , Raso Anthony , Arora Jagriti , Tokoglu Fuyuze , Yip Sarah W. , Hahn C. Alice , Lacadie Cheryl , Greene Abigail S. , Jeon Sangchoon , Constable R. Todd , Barry Declan T. , Redeker Nancy S. , Yaggi Henry , Scheinost Dustin
Published: December 2024

T1-weighted MRI and resting-state functional MRI revealed structural and functional brain alterations in opioid receptor–dense regions, such as the thalamus, right medial temporal lobe, cerebellum, and brainstem, in individuals with opioid use disorder compared with healthy controls.
Myonuclear and satellite cell content of the vastus lateralis and soleus with 70 days of simulated microgravity and the NASA SPRINT exercise program
Authors: Skiles Chad M. , Boyd Gerard , Gouw Aaron , Robbins Ethan , Minchev Kiril , Ryder Jeffrey , Ploutz-Snyder Lori , Trappe Todd A. , Trappe Scott
Published: December 2024

This study showed that after 70 days of simulated microgravity, human skeletal muscle does not alter the number of nuclei or satellite cells associated with slow or fast myofibers in the two muscle groups most negatively influenced by microgravity exposure [i.e., quadriceps (vastus lateralis) and triceps surae (soleus)]. Furthermore, the efficacy of exercise countermeasures for maintaining the mass of these muscles does not appear to be related to the myocellular content of nuclei or satellite cells.
Sex differences between postmenopausal women and similar-age men in response to orthostatic stress following 2 wk of bed rest
Authors: Hedge Eric T. , Mastrandrea Carmelo J. , Patterson Courtney A. , Hughson Richard L.
Published: December 2024

Postmenopausal women had lower orthostatic tolerance than similar-age men while standing post-bed rest. Both sexes exhibited lower cerebral blood velocity nadirs upon standing; however, sex-specific interactions of the determinants of cerebral perfusion (i.e., Pco2, cerebrovascular resistance index, and arterial pressure) were observed during prolonged standing after bed rest. These results indicate that postmenopausal women and men have different factors underlying reduced cerebral perfusion while standing after bed rest.
Flow-mediated dilation decreases in women, but not men, following mild acute intermittent hypoxia
Authors: Mascone Sara E. , Limberg Jacqueline K. , Blake Emily F. , Weiner Cynthia M. , Eagan Lauren E. , Khan Shannon E. , Ranadive Sushant M.
Published: December 2024

The present study aimed to investigate the influence of sex on vascular responses to 30 min of acute, mild intermittent hypoxia. Men and women exhibited similar decreases in arterial shear rate and microvascular function after intermittent hypoxia. Although men exhibited increases in blood pressure but no changes in macrovascular function, women exhibited significant decreases in macrovascular function despite no changes in blood pressure. Sex may influence the potential hormetic effects of intermittent hypoxia.
Cells in the Polyaneuploid Cancer Cell State Are Prometastatic
Authors: Mallin Mikaela M. , Rolle Louis T.A. , Schmidt Michael J. , Priyadarsini Nair Shilpa , Zurita Amado J. , Kuhn Peter , Hicks James , Pienta Kenneth J. , Amend Sarah R.
Published: December 2024

Our research aims to understand the adaptive—ergo potentially metastatic—responses of prostate cancer to changing microenvironments. Emerging evidence implicates a role of the polyaneuploid cancer cell (PACC) state in metastasis, positing the PACC state as capable of conferring metastatic competency. Mounting in vitro evidence supports increased metastatic potential of cells in the PACC state. Additionally, our recent retrospective study revealed that PACC presence in patient prostate tumors at the time of radical prostatectomy was predictive of future metastasis. To test for a causative relationship between PACC state biology and metastasis in prostate cancer, we leveraged a novel method designed for flow cytometric detection of circulating tumor cells (CTC) and disseminated tumor cells (DTC) from animal models. This approach provides both quantitative and qualitative information about the number and PACC status of recovered CTCs and DTCs. Specifically, we applied this approach to the analysis of subcutaneous, caudal artery, and intracardiac murine models. Collating data from all models, we found that 74% of recovered CTCs and DTCs were in the PACC state. Furthermore, in vivo colonization assays proved that PACC populations can regain proliferative capacity at metastatic sites. Additional in vitro analyses revealed a PACC-specific partial epithelial-to-mesenchymal transition phenotype and a prometastatic secretory profile, together providing preliminary evidence of prometastatic mechanisms specific to the PACC state.

Implications: Considering that many anticancer agents induce the PACC state, our data position the increased metastatic competency of PACC state cells as an important unforeseen ramification of neoadjuvant regimens, which may help explain clinical correlations between chemotherapy and metastatic progression.
Assessment of Disease Activity in Eosinophilic Esophagitis: Is It Clinically Relevant or Simply an Amusement for Experts?
Authors: Safroneeva Ekaterina , Schoepfer Alain M.
Published: December 2024

Background: Since the first description of eosinophilic esophagitis (EoE) as clinicopathologic syndrome three decades ago, considerable progress has been made to standardize and validate instruments to assess symptom severity, quality of life, endoscopic, and histologic activity for the purpose of randomized controlled trials (RCTs) and observational studies. Standardized assessment of EoE activity is crucial to be able to compare the results of therapeutic interventions and bring much needed therapies to patients. This review focuses on outcome assessment of disease activity in adults with EoE. Summary: The choice of endpoints/instruments to be used depends on the setting, which might be either an RCT, an observational study, or clinical practice. In RCTs, the choice of endpoints further depends on requirements from regional regulatory authorities. Primary endpoints chosen in RCTs typically focused on symptoms and esophageal peak eosinophil counts, although that likely will change, as therapies with new mechanism of action are explored. Validated symptom-based PRO instruments used in RCTs include the Daily Symptom Questionnaire (DSQ), the EoE activity index (EEsAI) PRO instrument, and numeric rating scales for dysphagia and pain. Histologic activity in RCT is assessed using the EoE histologic scoring system (EoEHSS) that takes into account the severity and extent of eight distinct histologic features. Endoscopic activity is assessed using the EREFS (Exudates, Rings, Edema, Furrows, Stricture) grading system. For observational studies, activity assessment is based on EEsAI PRO, epithelial peak eosinophil counts, and EREFS. In daily clinical practice, EoE activity is based on assessment of symptoms using a visual analog scale (VAS, from 0–10), peak eosinophil count, and EREFS. Several other instruments including the I-SEE, dysphagia-free days over a defined period, the dysphagia stress test, and impedance planimetry (EndoFLIP), to assess EoE severity in clinical practice are currently under evaluation. Key Messages: EoE activity assessment based on symptom-based PRO, histology, and endoscopy has become increasingly complex and varies depending on the setting. While more stringent endpoints and daily recall PRO instruments are being used in RCTs, new instruments aimed at broader disease activity assessment and weekly recall PRO instruments are being used in observational studies and daily clinical practice.
De-Stiffening the Aged Aorta with Regular Aerobic Exercise in Humans: Fact or Fallacy?
Authors: Pierce Gary L.
Published: December 2024

Background: Aortic stiffness, quantified by carotid-femoral pulse wave velocity (PWV), is a strong predictor of cardiovascular disease events. In general, dynamic “aerobic” exercise training performed regularly for many years in middle and older age is associated with an attenuated or absence of an age-related increase in aortic stiffness without hypertension. However, cross-sectional studies can be confounded by physiological or lifestyle factors that may contribute in part to the lower aortic stiffness observed, and prospective interventions are often limited by short duration and inadequate exercise frequency to have clinical benefit. Therefore, this review will discuss the evidence for the de-stiffening effects of regular, dynamic aerobic exercise training on aortic stiffness in the presence or absence of hypertension with some discussion on high-intensity interval training (HIIT). Summary: Short-term (3–12 months) aerobic exercise interventions, 2–3 days per week initiated in middle age or older age without hypertension, result in small decreases in carotid-femoral PWV that is likely the result of reductions in distending pressure (i.e., mean arterial pressure) rather than an alteration in structural wall properties. However, cross-sectional data indicate that 4–5 days/week appears to be the minimal frequency that is obligatory for de-stiffening of the aorta among adults who perform regular exercise in middle age and continue into older age. Despite greater improvements in aerobic fitness by high-intensity interval training (HIIT), short-term HIIT 4 days/week does not provide any benefit over moderate-intensity continuous training for de-stiffening the aorta among older adults with or without hypertension. Key Messages: Short-term aerobic exercise interventions 2–3 days/week at moderate intensity initiated in middle age or older age have small or no favorable blood pressure-independent effect on aortic wall stiffness. In contrast, 4–5 days/week appears to be the minimal obligatory dose of aerobic exercise to have some de-stiffening effects if performed during middle age and continuing into older age. Short-term HIIT provides no greater de-stiffening effects on the aged aorta than continuous aerobic exercise training.
Atypical COVID-19-Related Acute Macular Neuroretinopathy with Progression Resulting in Severe Vision Loss
Authors: Weinberger Eva Magdalene , Thangamathesvaran Loka , Arevalo J. Fernando
Published: December 2024

Introduction: We review the clinical course of a patient with decreased vision in the setting of COVID-19 infection consistent with an atypical presentation of acute macular neuroretinopathy (AMN). Case Presentation: A 56-year-old Caucasian woman developed a scotoma in the right eye 3 days after COVID-19 diagnosis and in her left eye on day 5. Baseline exam showed significantly reduced visual acuity bilaterally best corrected visual acuity of 20/60 in the right eye and 20/40 in the left eye from a patient-reported baseline of 20/20 in each eye. Examination of the fundus was remarkable for small flame-shaped hemorrhages in the superior arcade of both eyes. Near-infrared reflectance imaging revealed a singular wedge-shaped lesion in each eye close to the fovea and spectral domain-optical coherence tomography confirmed disruption of the photoreceptor layer and ellipsoid zones. Our leading diagnosis given the presentation was COVID-19-associated AMN. Given no evidence of a clear treatment, observation was selected. Three weeks later, visual acuity deteriorated further to 20/100 OD and 20/80 OS, with persistence of the wedge-shaped lesions. At 3-month follow-up, fundus photographs remained unremarkable; however, visual acuity had dropped further to 20/300 bilaterally, with persistence of the scotomata and outer retinal layer disruptions. 6 months later, treatment with a dexamethasone implant improved vision to 20/125 OD and 20/150 OS. Conclusion: Among COVID-19-induced AMN, our case is remarkable for the severe progression of visual impairment over 3 months of follow-up and improvement with a dexamethasone implant. Furthermore, absence of classical AMN lesions on fundus photography raises the question whether COVID-induced AMN may lead to a clinically distinct, potentially more severe picture than AMN arising from previously identified causes.
Endothelial FUNDC1 Deficiency Drives Pulmonary Hypertension
Authors: Pei Yandong , Ren Dongfeng , Yin Yuanhao , Shi Jiajia , Ai Qianyuan , Hao Wenxin , Luo Xiaofan , Zhang Chenyue , Zhao Yanping , Bai Chenyu , Zhu Lin , Wang Qiong , Li Shuangling , Zhang Yuwei , Lu Jiangtao , Liu Lin , Zhou Lin , Wu Yuli , Weng Yiqi , Jing Yongle , Lu Chengzhi , Cui Yujie , Zheng Hao , Li Yanjun , Chen Guo , Hu Gang , Chen Quan , Liao Xudong
Published: December 2024

BACKGROUND:

Pulmonary hypertension (PH) is associated with endothelial dysfunction. However, the cause of endothelial dysfunction and its impact on PH remain incompletely understood. We aimed to investigate whether the hypoxia-inducible FUNDC1 (FUN14 domain-containing 1)-dependent mitophagy pathway underlies PH pathogenesis and progression.

METHODS:

We first analyzed FUNDC1 protein levels in lung samples from patients with PH and animal models. Using rodent PH models induced by HySu (hypoxia+SU5416) or chronic hypoxia, we further investigated PH pathogenesis and development in response to global and cell-type-specific
Fundc1
loss/gain-of-function. We also investigated the spontaneous PH in mice with inducible loss of endothelial
Fundc1
. In addition, histological, metabolic, and transcriptomic studies were performed to delineate molecular mechanisms. Finally, findings were validated in vivo by compound deficiency of HIF2α (hypoxia-inducible factor 2α;
Epas1
) and pharmacological intervention.

RESULTS:

FUNDC1 protein levels were reduced in PH lung vessels from clinical subjects and animal models. Global
Fundc1
deficiency exacerbated PH, while its overexpression was protective. The effect of FUNDC1 was mediated by endothelial cells rather than smooth muscle cells. Further, inducible loss of endothelial
Fundc1
in postnatal mice was sufficient to cause PH spontaneously, whereas augmenting endothelial
Fundc1
protected against PH before and after the onset of disease. Mechanistically,
Fundc1
deficiency impaired basal mitophagy in endothelial cells, leading to the accumulation of dysfunctional mitochondria, metabolic reprogramming toward aerobic glycolysis, pseudohypoxia, and senescence, likely via a mtROS-HIF2α signaling pathway. Subsequently,
Fundc1
-deficient endothelial cells increased IGFBP2 (insulin-like growth factor-binding protein 2) secretion that drove pulmonary arterial remodeling to instigate PH. Finally, proof-of-principle in vivo studies showed significant efficacy on PH amelioration by targeting endothelial mitophagy, pseudohypoxia, senescence, or IGFBP2.

CONCLUSIONS:

Collectively, we show that FUNDC1-mediated basal mitophagy is critical for endothelial homeostasis, and its disruption instigates PH pathogenesis. Given that similar changes in FUNDC1 and IGFBP2 were observed in PH patients, our findings are of significant clinical relevance and provide novel therapeutic strategies for PH.
Comparing reliability-based measures of functional connectivity between movie and rest: An ROI-based approach
Authors: Shearer Hallee , Eilbott Jeffrey , Vila-Rodriguez Fidel , Noble Stephanie , Xu Ting , Vanderwal Tamara
Published: December 2024

Functional connectivity (FC) has shown promising utility in the field of precision psychiatry. However, to translate from research to clinical use, FC reliability and sensitivity to individual differences still require improvement. Movie watching as an acquisition state offers advantages at the whole-brain level that align with the requirements of FC for individualized measures. However, it is unclear whether these advantages hold in specific brain regions important for precision psychiatry. Here, we compared univariate and multivariate reliability-based measures of movie-watching and resting-state FC data in three psychiatrically relevant brain regions. We found that the reliability of movie-watching FC was comparable with resting-state FC in the dorsolateral prefrontal cortex and presupplementary motor area, and movie-watching FC was more discriminable than resting-state FC in the temporoparietal junction. Rest had higher reliabilities at lower data amounts (e.g., under 5 minutes of scan time). We then expanded this approach to all brain regions and showed that for image intraclass correlation coefficients (I2C2), no parcels were significantly different between movie and rest. For discriminability, 25% (94/379) of parcels were better for movie than for rest, and zero parcels were better for rest. For fingerprinting, 59 parcels were better for movie (mainly in visual and temporal regions, mean improvement in accuracy = 23%) and 4 parcels were better for rest. For researchers interested in cross-state differences in FC reliability, we provide an interactive visualization tool that displays the results for all measures and for all regions in both movie and rest. These findings suggest that movie watching as an acquisition state—even when using different movies across scans—may provide a useful alternative to resting state in research studies that require optimization of FC discriminability.
Pseudo partition-encoded simultaneous multislab (pPRISM) for rapid, navigator-free submillimeter diffusion MRI with reduced slab-boundary signal loss
Authors: Chang Wei-Tang , Liao Congyu , Lee Hong-Hsi
Published: December 2024

The primary aim of this study is to address the challenges in submillimeter diffusion magnetic resonance imaging (dMRI), such as prolonged acquisition time, low signal-to-noise ratio (SNR), and signal attenuation at slab boundary. We introduce a novel 3D Fourier encoding mechanism, PRISM (Partition-encoded Simultaneous Multislab), and a new concept termed “pseudo slab.” The PRISM method allows simultaneous inter-slab and intra-slab Fourier encoding solely using the slice gradient, eliminating the need for RF encoding. The pseudo slab concept not only minimizes inter-slab signal leakage and Gibbs truncation artifacts, but also enables phase scheduling onto intra-slab slices, thus eliminating the need for a phase navigator and time-varying gradient such as variable-rate selective excitation (VERSE). Integrating the pseudo slab with PRISM, the resulting pseudo PRISM (pPRISM) technique achieved rapid acquisition of dMRI with 0.86-mm isotropic resolution and an effective TR of 12 s (TR of 2.4 s per shot). Compared to Generalized Slice Dithered Enhanced Resolution with Simultaneous Multislice (gSlider-SMS), the shortened acquisition time improved the SNR efficiency without aggravating the signal attenuation at slab boundaries. The robustness of pPRISM against field inhomogeneity was also supported by Bloch simulation and empirical data. Furthermore, dMRI was successfully achieved with a 0.76-mm isotropic resolution, an effective TR of 15 s, and b-values of up to 2500 s/mm2. The ultrahigh-resolution results of the proposed pPRISM method demonstrated the anticipated dark bands of fractional anisotropy (FA) at gray-white matter boundaries and yielded more plausible tractography results. Our pPRISM framework paves the way for acquiring ultrahigh-resolution dMRI in clinically feasible times, advancing microstructural research.
Are We Missing Obstructive Sleep Apnea in Patients With Non-traumatic Subglottic Stenosis?
Authors: Lackey Taylor G. , Allen Avery , McCabe Nevan , Clary Matthew , Green Katherine K. , Fink Daniel S.
Published: December 2024

Objective:

To investigate the association between subglottic stenosis (SGS) and obstructive sleep apnea (OSA).

Methods:

This is a cross-sectional pilot cohort study conducted at a single tertiary academic center from 2022 to 2023. Subjects with non-traumatic SGS were recruited for enrollment. All subjects completed a peak expiratory flow (PEF) measurement, validated sleep questionnaires: Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI), and a 1-night home sleep test (HST). Demographic data were summarized. Prevalence was calculated and descriptively compared to a matched population. Partial correlation analysis evaluated the relationship of PEF% and Meyer-Cotton grading, in addition to PEF% and apnea-hypopnea index (AHI). Sleep quality was compared in subjects with and without OSA via a Mann-Whitney U test.

Results:

Twenty subjects participated; all were Caucasian females with a mean age of 48.4 (10.4) years and a body mass index (BMI) of 24.1 (3.8). The majority (80%) had idiopathic SGS, and a mean PEF 288 (71) L/min. OSA was present in 40% of subjects, of which 15% had moderate OSA. PEF% did not correlate to AHI ( P > .05). Poor sleep quality (PSQI ≥ 5) was present in 70% of subjects and 20% had excessive daytime sleepiness (ESS > 9). PSQI and ESS did not differ between subjects with and without OSA ( P > .05).

Conclusion:

OSA prevalence is elevated in a cohort of subjects with SGS. Further study of airway dilation’s impact on OSA is necessary. Screening and surveillance for OSA in patients with subglottic stenosis may need to be considered based on this study’s findings. Level of Evidence: Level 3.
The Mediating Role of Trait Mindfulness in Academic Stress: A Cross-Sectional Study Among Italian University Students
Authors: Ocera Alessandro , Colombo Sofia , de Paz-Cantos Sonia , Frisiello Antonella , Gilotta Silvia , Grazioli Silvia , Michelini Giovanni , Roella Antonella , Gregori Grgič Regina
Published: December 2024

Background: Stress is a significant factor influencing the mental well-being of students, and mindfulness strategies have been associated with reduced academic stress. Nevertheless, there is a limited body of research investigating stress and trait mindfulness in a sample of Italian university students. This study aims to explore the relationship between academic stress, effort-reward imbalance, and trait mindfulness. Methods: Perceived stress, effort-reward imbalance, and trait mindfulness in 442 Italian university students (mean age = 23.37 ± 4.33) were assessed through the Perceived Stress Scale (PSS), Effort-Reward Imbalance – Student Questionnaire (ERI-SQ) and Five Facet Mindfulness Questionnaire (FFMQ). Results: Pearson correlation analysis showed that PSS negatively correlates with FFMQ and it positively correlates with ERI-SQ, while FFMQ negatively correlates with ERI-SQ. Furthermore, mediation analysis revealed that FFMQ partially mediates the effect of ERI-SQ on PSS. Conclusions: This study provides the first examination of the relationships between perceived stress, effort-reward imbalance, and trait mindfulness among Italian students. The findings suggest that trait mindfulness is associated with lower levels of perceived stress and could potentially mediate the relationship between effort-reward imbalance and stress. These insights may inform future research and interventions aimed at reducing academic stress.
Multi-task learning with multi-gate mixture of transformer-based experts for predictive process monitoring in manufacturing
Authors: Wang Jiaojiao , Sui Yao , Liu Chang , Shen Xuewen , Li Zhongjin , Yu Dingguo
Published: December 2024

Manufacturing industries involve both business processes and complex manufacturing processes. Predictive process monitoring techniques are effective for managing process executions by making multi-perspective real-time predictions, preventing issues such as delivery delays. Conventional predictive process monitoring for business processes focuses on predicting the next activity, next event time, and remaining time using single-task learning, which is costly and complex. For complex manufacturing processes, predictive process monitoring primarily aims to predict the remaining time, that is, product cycle time. However, single-task learning methods fail to capture all the variations within the historical process executions. To address them, we propose the multi-gate mixture of transformer-based experts framework, which leverages a transformer network within the multi-gate mixture-of-experts multi-task learning architecture to extract sequential features and employs gated expert networks to model task commonalities and differences. Empirical results demonstrate that multi-gate mixture of transformer-based experts outperforms three alternative architectures across five real-life event logs, highlighting its generalization, effectiveness, and efficiency in predictive process monitoring.
Formation control of multiple VTOL UAVs with global stability subject to switching networks
Authors: Gao Xiangtian , Liu Jinkun , Sun Lin
Published: December 2024

This article investigates the problem of distributed formation control for multiple vertical takeoff and landing (VTOL) unmanned aerial vehicles (UAVs) under a switching network with uniform joint connectivity condition. VTOL UAV, as a representative UAV, combines the VTOL capabilities of rotary-wing aircraft with the forward flight capabilities of fixed-wing aircraft. On the one hand, a novel distributed observer is developed for each VTOL UAV to asymptotically acquire the leader’s desired information. On the other hand, considering the underactuated nature of VTOL UAVs, a hierarchical framework is introduced to achieve position tracking of the desired observation positions and attitude tracking of the commanded attitudes. Compared to existing findings, a notable feature of this study is the allowance for a directed and switching communication network. Specifically, the switching network only requires joint connectivity. Additionally, the introduction of hyperbolic tangent functions ensures the boundedness of control inputs, further guarantees the global asymptotic stability of the entire closed-loop system. Simulation results validate the effectiveness of the algorithm.
Reinforcement of the Anterior Annulus by Overlay Conchal Cartilage in Temporalis Fascia Grafting for Subtotal and Total Perforations
Authors: Yazici Demet
Published: December 2024

Objectives: In this study, the graft success and hearing improvement were compared in patients with subtotal or total tympanic membrane perforations following conchal cartilage-reinforced temporalis fascia graft tympanoplasty (CCRTT) versus traditional tragal island cartilage tympanoplasty (TICT). Material and Methods: Fifty Type 1 tympanoplasties performed for subtotal or total tympanic membrane perforation were classified into 2 groups: CCRTT consisted of 23 patients and TICT consisted of 27 patients. The difference between these 2 groups was analyzed by means of graft success, reperforation, and postoperative hearing gain after 12 months. Results: The graft success rate was 96.3% in TICT group and 91.3% in CCRTT group and there was no statistical difference between 2 groups ( P > .05). Postoperative pure tone average (PTA) gain was 12.9 ± 9 dB for TICT group and 14 ± 8.8 dB for CCRTT group and postoperative air-bone gap (ABG) gain was 11.2 ± 7.7 dB in TCIT group and 11.3 ± 8.5 dB in CCRTT group and again, there was no statistical difference between these 2 study groups considering PTA and ABG gain ( P > .05). Conclusion: Reinforcing tympanic membrane by conchal cartilage in an overlay technique under the anterior tympanic annulus by CCRTT in subtotal and total perforations is as effective as traditional TICT. Considering that graft success is lower in subtotal and total tympanic membrane perforations, both methods can be used interchangeably, depending on the choice of the surgeon.