bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 290: Early Monitoring Of Neurological Recovery Using Poincare Analysis Index Of Heart Rate Variability - A Potential Biomarker For Asphyxial Cardiac Arrest Related Brain Injury
Authors: Agarwal Prachi , Geocadin Romergryko , Thakor Nitish 
Published: June 2023

Heart rate variability (HRV) is influenced by autonomic nervous system including subcortical structures such as brainstem. We hypothesized that HRV would reflect graded response to hypoxic ischemic brain injury after cardiac arrest (CA). We investigated HRV based on the Poincare analysis method during the hyperacute recovery period after resuscitation to define its role in assessing neurologic recovery.
Adult male Wistar rats (360±20g) were subjected to either 5 /7-min of asphyxial CA and grouped based on neurologic recovery - good (n=17) and bad (n=16), assessed at 4 hr post resuscitation using a standardized Neurological Deficit Scale (NDS). A good outcome (GO) was defined as a NDS sub score (arousal+brainstem) of 36-40 and bad outcome (BO) as 23-35, with 40 as good and 0 as brain dead. A Poincare plot showing successive heart rate intervals was developed and analysed on 5-min ECG segments (first 1 hr) owing to the nonstationary HRV patterns during early recovery period. Several machine learning models were trained to assess the results from the standard deviations (SD1, SD2), to decipher the parasympathetic and sympathetic activities, and evaluated by the area under receiver operating characteristic curve (AUC). GO group demonstrated an NDS of 39.65±0.99, while the BO group had an NDS of (30±2.65) showing a statistical difference between groups (p<0.01). GO group exhibited an immediate increase post resuscitation in SD1 (0.55±0.23) and SD2 (0.67±0.29) with a gradual decrease ~1 hr, SD1 (0.20±0.12) and SD2 (0.13±0.09). No significant differences in initial SD1 (0.30±0.14) and SD2 (0.28±0.16) vs after 1 hr of recovery (SD1 (0.29±0.08), SD2 (0.30±0.16)) were observed across BO group. For GO, all parameters indicated a faster return to baseline values- SD1 (0.21±0.08) SD2 (0.15±0.16), showing a better recovery of the cardiac autonomic control, in agreement with the evolution of NDS. Logistic regression and naïve bayes performed best with SD2, giving an accuracy of 72% (AUC: 0.75) and 75% (AUC: 0.88) for recovery prognostication in 5-fold cross validation. Unlike previous studies to find biomarkers for CA related brain injury focused on cortical assessment, our results indicate that the novel HRV method can fill the gap in assessing subcortical injury after CA.
Static and dynamic fMRI-derived functional connectomes represent largely similar information
Authors: Matkovič Andraž , Anticevic Alan , Murray John D. , Repovš Grega 
Published: June 2023

Abstract
Functional connectivity (FC) of blood oxygen level-dependent (BOLD) fMRI time series can be estimated using methods that differ in sensitivity to the temporal order of time points (static vs. dynamic) and the number of regions considered in estimating a single edge (bivariate vs. multivariate). Previous research suggests that dynamic FC explains variability in FC fluctuations and behavior beyond static FC. Our aim was to systematically compare methods on both dimensions. We compared five FC methods: Pearson’s/full correlation (static, bivariate), lagged correlation (dynamic, bivariate), partial correlation (static, multivariate), and multivariate AR model with and without self-connections (dynamic, multivariate). We compared these methods by (i) assessing similarities between FC matrices, (ii) by comparing node centrality measures, and (iii) by comparing the patterns of brain-behavior associations. Although FC estimates did not differ as a function of sensitivity to temporal order, we observed differences between the multivariate and bivariate FC methods. The dynamic FC estimates were highly correlated with the static FC estimates, especially when comparing group-level FC matrices. Similarly, there were high correlations between the patterns of brain-behavior associations obtained using the dynamic and static FC methods. We conclude that the dynamic FC estimates represent information largely similar to that of the static FC.
Understanding and Detecting Hallucinations in Neural Machine Translation via Model Introspection
Authors: Xu Weijia , Agrawal Sweta , Briakou Eleftheria , Martindale Marianna J. , Carpuat Marine 
Published: June 2023

AbstractNeural sequence generation models are known to “hallucinate”, by producing outputs that are unrelated to the source text. These hallucinations are potentially harmful, yet it remains unclear in what conditions they arise and how to mitigate their impact. In this work, we first identify internal model symptoms of hallucinations by analyzing the relative token contributions to the generation in contrastive hallucinated vs. non-hallucinated outputs generated via source perturbations. We then show that these symptoms are reliable indicators of natural hallucinations, by using them to design a lightweight hallucination detector which outperforms both model-free baselines and strong classifiers based on quality estimation or large pre-trained models on manually annotated English-Chinese and German-English translation test beds.
Idolatry and Mystery
Authors: Mannen Sara 
Published: June 2023

Abstract
This article contrasts the accounts of mystery used to combat idolatry found in the theology of Karl Barth and in contemporary apophatic theology. It describes Barth’s account of mystery as distinctly Protestant in its soteriological nature and basis in contrast to recent apophatic accounts of mystery based on the doctrine of creatio ex nihilo. These divergent theologies of mystery—as either light or darkness based on different dogmatic res—ultimately reveal contrasting commitments in the doctrine of God. For both, Jesus Christ is the light of God’s gracious revelation. However, the movement in apophatic theology is from the light of Christ to the mystery of divine darkness, while in Barth’s theology Jesus Christ is the luminous mystery of God that dispels the Deus absconditus. This article argues that idolatry is better counteracted by Barth’s positive concept that mystery is grace and filled with content in Jesus Christ.
Philosophical and Philological Debates on Kulliyyāt I.1.ii of Ibn Sīnā’s Qānūn: From Faḫr al-Dīn al-Rāzī to Quṭb al-Dīn al-Šīrāzī
Authors: Eshera Osama 
Published: June 2023

Abstract
The debates on Kulliyyāt I.1.ii of Ibn Sīnā’s Qānūn (“on the subjects of medicine”) were initiated by Faḫr al-Dīn al-Rāzī and continued by Afḍal al-Dīn al-Ḫūnaǧī, Naǧm al-Dīn al-Naḫǧawānī, Yaʿqūb ibn Ġanāʾim al-Sāmirī, Rafīʿ al-Dīn al-Ǧīlī, Ibn al-Nafīs, and Ibn al-Quff al-Masīḥī. In his own commentary, entitled al-Tuḥfa al-saʿdiyya, Quṭb al-Dīn al-Šīrāzī preserved and scrutinized his predecessors’ commentaries, in order to offer what he believed to be more conclusive interpretations of Ibn Sīnā. Focusing on the introductory part of Kulliyyāt I.1.ii, we show that the commentators were divided not only on philosophical issues, but also on the very text that should be attributed to Ibn Sīnā.
Palliative Care Knowledge Following an Interdisciplinary Palliative Care Seminar
Authors: Mollman Sarah , Gierach Michelle , Sedlacek Amanda 
Published: June 2023

Background The COVID-19 pandemic created a unique opportunity to evolve an interdisciplinary palliative care seminar (IPC) into a virtual platform. This seminar provides foundational palliative and hospice concepts, introductions into palliative care disciplines, integration of teamwork, and incorporates interdisciplinary student led patient encounters. Traditionally, this experience had been in person, however during the COVID-19 pandemic, healthcare restrictions transitioned the educational delivery to a virtual platform. Methods To assess the knowledge gained from this novel experience, the Palliative Care Knowledge Test (PCKT) was administered before and after the IPC Seminar. A 1-year follow up survey was also administered to evaluate how the IPC Seminar was applicable to the students’ clinical experiences and practice. Results The virtual didactics and virtual student led patient encounters significantly improved learners understanding of palliative and hospice care. This gain of knowledge was noted across undergraduate and graduate programs, which highlights the need for and benefit from foundational concepts. Furthermore, a 1-year follow up survey noted the IPC seminar was applicable to their practices and suggests that this experience will impact future patients. Discussion Many of the students practice in rural areas where access to palliative care services is limited or non-existent. This experience exponentially impacts the growth of palliative and hospice care understanding and access to care across the region. Conclusion Evolving our IPC Seminar has shown to significantly improve knowledge, foster collaboration of student led interdisciplinary teams, and increases capacity to meet the needs of more learners.
Effects of Deep Venous Thrombosis Treatments on Early and Long-term Quality of Life: Medical Therapy vs. Systemic Thrombolysis vs. Pharmacomechanical Thrombolysis
Authors: Yıldız Ziya , Kayğın Mehmet A. , Özkara Taha , Limandal Hüsnü K. , Diler Mevriye S. , Çüçen Dayı Hatice I. , Ergün Servet , Dağ Özgür 
Published: June 2023

Objectives The present study aimed to compare the effects of medical therapy (MT), systemic thrombolysis (ST), and pharmacomechanical thrombolysis (PMT) methods used in our clinic for the treatment of deep venous thrombosis (DVT) on symptom reduction, the incidence of post-thrombotic syndrome (PTS) development, and quality of life. Methods Data from160 patients diagnosed with acute DVT between January 2012 and May 2021 and treated and followed up in our clinic were retrospectively analyzed. The patients were divided into three groups according to treatment method. The patients who received MT treatment were defined as Group 1, anticoagulant treatment after ST as Group 2, and anticoagulant treatment after PMT as Group 3. The patients were called to the outpatient clinic, informed consent was obtained, EuroQol-5D-3 L (EQ-5D-3 L) scoring and Villalta scoring were performed, and anamnesis was taken. Results A total of 160 patients were included, with 71 (44.4%) patients in Group 1, 45 (28.1%) in Group 2, and 44 (27.5%) in Group 3. The mean age was 48.9 ± 14.9 years for Group 1, 42.2 ± 10.8 for Group 2, and 29.0 ± 7.2 for Group 3. When the time to return to normal life and the EQ-5D-3 L score index were compared, the differences between Groups 1 and 2 and between Groups 1 and 3 were statistically significant ( P = .000 and P = .000, respectively). However, the differences between Groups 2 and 3 were statistically insignificant ( P = .213 and p = .074, respectively). When Villalta scores and EQ Visual Analogue Scale (EQ-VAS) scores were compared between groups, the difference between all groups was statistically significant ( P = .000). Conclusions The medical treatment alone was observed to be insufficient in terms of symptomatic improvement, development of PTS, quality of life, and long-term complications. When the ST and PMT groups were compared, it was determined that PMT treatment was more advantageous in terms of EQ-VAS score and PTS development, although there was no statistical difference regarding complications, such as return to normal life and long-term quality of life, the incidence of recurrent DVT development, and pulmonary thromboembolism incidence.
Evaluating surveillance definitions of HIV viral suppression 2015–2019: Which definition best detected barriers to care?
Authors: Erly Steven , Campos Leticia , Buskin Susan , Reuer Jennifer 
Published: June 2023

Background: People living with HIV (PLWH) who have not achieved or maintained viral suppression post-diagnosis likely face multiple barriers to HIV care. To identify these barriers a universally accepted definition of viral suppression is needed. The most common definition, the Center for Disease Control and Prevention (CDC) definition, contains simplifying assumptions that may misclassify individuals and attenuate associations. In this study, we evaluated alternative definitions of viral suppression on their ability to identify barriers to care. Design and methods: We used HIV surveillance data to classify participants of the 2015–2019 Washington Medical Monitoring Project (MMP) as virally suppressed or not using the CDC definition and two definitions that assess viral suppression over a longer period (“Enriched” and “Durable”). We identified barriers to suppression from literature (unstable housing, illicit drug use, poor mental health, heavy drinking, recent incarceration, racism, and poverty) and measured them using interview questions from MMP. We compared the rate ratios (RR) of being not virally suppressed using each definition for each barrier. Results: There were 858 PLWH in our study. All viral suppression definitions classified a similar proportion of people as suppressed (85%–89%). The durable viral suppression definition consistently yielded the largest rate ratios (e.g. unstable housing: CDC RR = 1.3, 95% CI 0.9–1.8; Enriched 1.5, 95% CI 1.0–2.2; Durable 2.2, 95% CI 1.6–3.1) and reclassified 10% of the population relative to the CDC definition. Conclusions: Longitudinal definitions for viral suppression may yield less misclassification and serve as superior tools for identifying and curtailing barriers to HIV care.
Translational predictions of phase 2a first-in-patient efficacy studies for antituberculosis drugs
Authors: Ernest Jacqueline P. , Goh Janice Jia Ni , Strydom Natasha , Wang Qianwen , van Wijk Rob C. , Zhang Nan , Deitchman Amelia , Nuermberger Eric , Savic Rada M. 
Published: June 2023

Background:Phase 2a trials in tuberculosis typically use early bactericidal activity (EBA), the decline in sputum CFU over 14 days, as the primary end-point for testing the efficacy of drugs as monotherapy. However, the cost of phase 2a trials can range from USD 7 million to USD 19.6 million on average, while >30% of drugs fail to progress to phase 3. Better utilising pre-clinical data to predict and prioritise the most likely drugs to succeed will thus help to accelerate drug development and reduce costs. We aim to predict clinical EBA using pre-clinicalin vivopharmacokinetic (PK)-pharmacodynamic (PD) data and a model-based translational pharmacology approach.Methods and findings:First, mouse PK, PD and clinical PK models were compiled. Second, mouse PK-PD models were built to derive an exposure–response relationship. Third, translational prediction of clinical EBA studies was performed using mouse PK-PD relationships and informed by clinical PK models and species-specific protein binding. Presence or absence of clinical efficacy was accurately predicted from the mouse model. Predicted daily decreases of CFU in the first 2 days of treatment and between day 2 and day 14 were consistent with clinical observations.Conclusion:This platform provides an innovative solution to inform or even replace phase 2a EBA trials, to bridge the gap between mouse efficacy studies and phase 2b and phase 3 trials, and to substantially accelerate drug development.
Nasal airway microRNA profiling of infants with severe bronchiolitis and risk of childhood asthma: a multicentre prospective study
Authors: Zhu Zhaozhong , Freishtat Robert J. , Harmon Brennan , Hahn Andrea , Teach Stephen J. , Pérez-Losada Marcos , Hasegawa Kohei , Camargo Carlos A. 
Published: June 2023

BackgroundSevere bronchiolitis (i.e.bronchiolitis requiring hospitalisation) during infancy is a major risk factor for childhood asthma. However, the exact mechanism linking these common conditions remains unclear. We examined the longitudinal relationship between nasal airway miRNAs during severe bronchiolitis and the risk of developing asthma.MethodsIn a 17-centre prospective cohort study of infants with severe bronchiolitis, we sequenced their nasal microRNA at hospitalisation. First, we identified differentially expressed microRNAs (DEmiRNAs) associated with the risk of developing asthma by age 6 years. Second, we characterised the DEmiRNAs based on their association with asthma-related clinical features, and expression level by tissue and cell types. Third, we conducted pathway and network analyses by integrating DEmiRNAs and their mRNA targets. Finally, we investigated the association of DEmiRNAs and nasal cytokines.ResultsIn 575 infants (median age 3 months), we identified 23 DEmiRNAs associated with asthma development (e.g.hsa-miR-29a-3p; false discovery rate (FDR) <0.10), particularly in infants with respiratory syncytial virus infection (FDR for the interaction <0.05). These DEmiRNAs were associated with 16 asthma-related clinical features (FDR <0.05),e.g.infant eczema and corticosteroid use during hospitalisation. In addition, these DEmiRNAs were highly expressed in lung tissue and immune cells (e.g.T-helper cells, neutrophils). Third, DEmiRNAs were negatively correlated with their mRNA targets (e.g.hsa-miR-324-3p/IL13), which were enriched in asthma-related pathways (FDR <0.05),e.g.toll-like receptor, PI3K-Akt and FcɛR signalling pathways, and validated by cytokine data.ConclusionIn a multicentre cohort of infants with severe bronchiolitis, we identified nasal miRNAs during illness that were associated with major asthma-related clinical features, immune response, and risk of asthma development.
Causal analysis between gastro-oesophageal reflux disease and obstructive sleep apnoea
Authors: Chen Gui , Gong Xin , Liu Shenrong , Xie Junyang , Wang Yingqi , Guo Wucheng , Liao Wenjing , Song Lijuan , Zhang Xiaowen 
Published: June 2023

BackgroundBased on evidence from existing observational research, clarifying the causal relationship between gastro-oesophageal reflux disease (GORD) and obstructive sleep apnoea (OSA) is challenging. Here, Mendelian randomisation, a method based on genetics, was used to provide new evidence for causality.MethodsSummary statistics from two publicly available genome-wide association studies were used to evaluate the causal relationship between GORD and OSA (the GORD database was used as an exposure variable and the OSA database as an outcome). Inverse variance weighting was used as the main analytical tool in Mendelian randomisation to estimate causal effects. The robustness of the results was evaluated by sensitivity analysis. Possible mediators were evaluated using multivariate Mendelian randomisation.ResultsA statistically significant causal relationship was observed between GORD and OSA (OR 1.597, 95% CI 1.401–1.821, p<0.001), and similar results were observed in weighted median and Mendelian randomisation–Egger regression analyses. No bias was found in the sensitivity analysis of Mendelian randomisation estimation. Multivariate Mendelian randomisation showed that GORD significantly increased the risk of developing OSA, even when the possible mediator was excluded (OR 1.107, 95% CI 1.101–1.212, p<0.001).ConclusionOur study confirmed a causal relationship between GORD and OSA and suggests that intervention measures should be taken for patients with GORD to prevent the occurrence of OSA.
Modified-release morphine or placebo for chronic breathlessness: the MABEL trial protocol
Authors: Date Kathryn , Williams Bronwen , Cohen Judith , Chaudhuri Nazia , Bajwah Sabrina , Pearson Mark , Higginson Irene , Norrie John , Keerie Catriona , Tuck Sharon , Hall Peter , Currow David , Fallon Marie , Johnson Miriam 
Published: June 2023

Chronic breathlessness, a persistent and disabling symptom despite optimal treatment of underlying causes, is a frightening symptom with serious and widespread impact on patients and their carers. Clinical guidelines support the use of morphine for the relief of chronic breathlessness in common long-term conditions, but questions remain around clinical effectiveness, safety and longer term (>7 days) administration. This trial will evaluate the effectiveness of low-dose oral modified-release morphine in chronic breathlessness.This is a multicentre, parallel group, double-blind, randomised, placebo-controlled trial. Participants (n=158) will be opioid-naïve with chronic breathlessness due to heart or lung disease, cancer or post-coronavirus disease 2019. Participants will be randomised 1:1 to 5 mg oral modified-release morphine/placebo twice daily and docusate/placebo 100 mg twice daily for 56 days. Non-responders at Day 7 will dose escalate to 10 mg morphine/placebo twice daily at Day 15.The primary end-point (Day 28) measure will be worst breathlessness severity (previous 24 h). Secondary outcome measures include worst cough, distress, pain, functional status, physical activity, quality of life, and early identification and management of morphine-related side-effects. At Day 56, participants may opt to take open-label, oral modified-release morphine as part of usual care and complete quarterly breathlessness and toxicity questionnaires.The study is powered to be able to reject the null hypothesis and an embedded normalisation process theory-informed qualitative substudy will explore the adoption of morphine as a first-line pharmacological treatment for chronic breathlessness in clinical practice if effective.
Mental health: the new frontier for labour economics
Authors: Layard Richard 
Published: June 2023

AbstractThis lecture argues that mental health is a major factor of production. It is the biggest single influence on life satisfaction, with mental health eight years earlier a more powerful explanatory factor than current income. Mental health also affects earnings and educational success. But, most strikingly, it affects employment and physical health.In advanced countries mental health problems are the main illness of working age – amounting to 40% of all illness under 65. They account for over one third of disability and absenteeism in advanced countries. They can also cause or exacerbate physical illness. It is estimated that in the absence of mental illness, the costs of physical healthcare for chronic diseases would be one third lower.The good news is that cost-effective treatments for the most common mental illnesses now exist (both drugs and psychological therapy). But only a quarter of those who suffer are in treatment. Yet psychological therapy, such as cognitive behavioural therapy, if more widely available would pay for itself in savings on benefits and lost taxes.The lecture ends by illustrating how rational policy can be made using life-course models of wellbeing. Such policies should include a much greater role for the treatment and prevention of mental illness.
Jel codes
I30, J30