bluuebunny/crossref_metadata_2025 huggingface dataset:
Rate-Limiting Enzymes in Cardiometabolic Health and Aging in Humans
Authors: Parnell Laurence D. , McCaffrey Kira S. , Brooks Athena W. , Smith Caren E. , Lai Chao-Qiang , Christensen Jacob J. , Wiley Christopher D. , Ordovas Jose M.
Published: July 2023

Introduction: Rate-limiting enzymes (RLEs) are innate slow points in metabolic pathways, and many function in bio-processes related to nutrient sensing. Many RLEs carry causal mutations relevant to inherited metabolic disorders. Because the activity of RLEs in cardiovascular health is poorly characterized, our objective was to assess their involvement in cardiometabolic health and disease and where altered biophysical and biochemical functions can promote disease. Methods: A dataset of 380 human RLEs was compared to protein and gene datasets for factors likely to contribute to cardiometabolic disease, including proteins showing significant age-related altered expression in blood and genetic loci with variants that associate with common cardiometabolic phenotypes. The biochemical reactions catalyzed by RLEs were evaluated for metabolites enriched in RLE subsets associating with various cardiometabolic phenotypes. Most significance tests were based on Z-score enrichment converted to p values with a normal distribution function. Results: Of 380 RLEs analyzed, 112 function in mitochondria, and 53 are assigned to inherited metabolic disorders. There was a depletion of RLE proteins known as aging biomarkers. At the gene level, RLEs were assessed for common genetic variants that associated with important cardiometabolic traits of LDL-cholesterol or any of the five outcomes pertinent to metabolic syndrome. This revealed several RLEs with links to cardiometabolic traits, from a minimum of 26 for HDL-cholesterol to a maximum of 45 for plasma glucose. Analysis of these GWAS-linked RLEs for enrichment of the molecular constituents of the catalyzed reactions disclosed a number of significant phenotype-metabolite links. These included blood pressure with acetate (p = 2.2 × 10−4) and NADP+ (p = 0.0091), plasma HDL-cholesterol and triglyceride with diacylglycerol (p = 2.6 × 10−5, 6.4 × 10−5, respectively) and diolein (p = 2.2 × 10−6, 5.9 × 10−6), and waist circumference with d-glucosamine-6-phosphate (p = 1.8 × 10−4). Conclusion: In the context of cardiometabolic health, aging, and disease, these results highlight key diet-derived metabolites that are central to specific rate-limited processes that are linked to cardiometabolic health. These metabolites include acetate and diacylglycerol, pertinent to blood pressure and triglycerides, respectively, as well as diacylglycerol and HDL-cholesterol.
Distribution of the Retinal Microcirculation Based on the Morphology of Peripapillary Atrophy in High Myopia
Authors: Tang Wenquan , Ouyang Junyi , Luo YuLin
Published: July 2023

Introduction: The objective of this study was to evaluate the retinal microvasculature of the optic nerve head and macula in high myopia (HM), investigate the association between the vascular parameters and peripapillary atrophy (PPA) deformation, and assess and identify the PPA morphology changes during the development of HM. Methods: One hundred sixty-seven right eyes from 167 HM patients were enrolled in this cross-sectional study. Using the optical coherence tomography angiography (OCTA) and fundus camera, we evaluated the following parameters: radian and type of PPA, intrapapillary vascular density (IVD), peripapillary vascular density (PVD), macular vascular density (MVD), and foveal avascular zone (FAZ). Based on the PPA radian, subjects were divided into four groups: the non-PPA, temporal PPA, advanced PPA, and annular PPA. At the same time, the above parameters were compared between the groups using analysis of variance (ANOVA) and least significant difference test. Results: Total enrolled patients were divided into the non-PPA group (22 eyes), temporal-PPA group (70 eyes), advanced-PPA group (60 eyes), and annular-PPA group (15 eyes). The results showed that the PVD in the annular-PPA group was smaller than that in the non-PPA group, especially in the superonasal, nasosuperior, nasoinferior, inferotemporal, temporoinferior, and superotemporal directions (F = 4.059, 5.014, 2.830, 4.798, 5.892, 3.439; p < 0.05). Notably, the PVD showcased the highest value in temporal, followed by that in superior and inferior, and the lowest in the nasal. Concerning the fovea deep macular vascular density, FAZ area, and subfoveal choroidal thickness in the annular-PPA group, they were less than those of the rest of the groups (p < 0.05). Conclusion: The retinal microvasculature differed significantly in HM according to the PPA morphology. In addition to PVD and SFCT, the PPA can also affect FAZ. Finally, we speculated that PVD demonstrated better predictability of myopic progression than MVD.
Coarctation of the Aorta: Modern Paradigms Across the Lifespan
Authors: Salciccioli Katherine B. , Zachariah Justin P.
Published: July 2023

While coarctation of the aorta varies greatly in both severity and age at presentation, all patients are at increased risk of hypertension both before and after repair. Despite advances in knowledge about genetic etiologies, pathophysiologic mechanisms, and optimal repair strategies, patients with repaired coarctation of the aorta remain at increased risk of acquired cardiovascular disease. The aims of this review are to describe the management of coarctation of the aorta at all ages before and after repair, highlight pathophysiologic mechanisms of hypertension, and review long-term follow-up considerations.
Global and Regional Estimate of HIV-Associated Stroke Burden: A Meta-Analysis and Population Attributable Modeling Study
Authors: Yang Yumei , Yao Xiaoqin , Liu Yuping , Zhao Jianhui , Sun Ping , Zhang Yixuan , Li Kangning , Chen Yan , Zheng Jinxin , Deng Ling , Fan Song , Ma Xiaoxiang , Guo Shujin , Shuai Ping , Wan Zhengwei
Published: July 2023

BACKGROUND:

This study aimed to determine the correlation between human-immunodeficiency-virus (HIV) infection and stroke, as well as to estimate the global, regional, and national burden of HIV-associated stroke.

METHODS:

A registered meta-analysis was performed by searching PubMed, Embase, and Web of Science for relevant literature up to October 31, 2022. The pooled relative risk of stroke in HIV-infected people was calculated using a random-effects model. HIV prevalence and disability-adjusted life years (DALYs) datasets were obtained from the Joint United Nations Program on HIV and AIDS, and the Global Health Data Exchange, respectively. The population attributable fraction was estimated and delivered to calculate the HIV-associated DALYs of stroke from 1990 to 2019, at the global, regional, and national levels. Pearson correlation analysis were conducted to assess the correlation between the age-standardized rate or estimated annual percentage changes and the sociodemographic index.

RESULTS:

Out of 10 080 identified studies, 11 were included in this meta-analysis. Compared with individuals without HIV-infection, the pooled relative risk of stroke in HIV-infected individuals was 1.40 (95% CI, 1.18–1.65). From 1990 to 2019, the global population attributable fraction of HIV-associated stroke increased almost 3-fold, while the HIV-associated DALYs increased from 18 595 (95% CI, 7485–31 196) in 1990 to 60 684 (95% CI, 24 281–101 894) in 2019. Meanwhile, HIV-associated DALYs varied by region, with Eastern and Southern Africa having the highest value of 126 160 in 2019. Moreover, countries with middle social development index were shouldering the highest increase trend of the HIV-associated DALYs age-standardized rates.

CONCLUSIONS:

HIV-infected individuals face a significantly higher risk of stroke, and the global burden of HIV-associated stroke has increased over the past 3 decades, showing regional variations. Eastern and Southern Africa bear the highest burden, while Eastern Europe and Central Asia have seen significant growth. Health care providers, researchers, and decision-makers should give increased attention to stroke prevention and management in HIV-endemic areas.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: CRD42022367450.
Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders
Authors: Eratne Dhamidhu , Kang Matthew , Malpas Charles , Simpson-Yap Steve , Lewis Courtney , Dang Christa , Grewal Jasleen , Coe Amy , Dobson Hannah , Keem Michael , Chiu Wei-Hsuan , Kalincik Tomas , Ooi Suyi , Darby David , Brodtmann Amy , Hansson Oskar , Janelidze Shorena , Blennow Kaj , Zetterberg Henrik , Walker Adam , Dean Olivia , Berk Michael , Wannan Cassandra , Pantelis Christos , Loi Samantha M , Walterfang Mark , Berkovic Samuel F , Santillo Alexander F , Velakoulis Dennis
Published: July 2023

Objective:

Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models.

Methods:

Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD ( n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models).

Results:

Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS.

Conclusions:

This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings.
Networked Movements and Bureaucratic Unions: The Structure of the 2018 #RedForEd Teachers’ Strikes
Authors: Tarlau Rebecca
Published: July 2023

How do digitally enabled movements of workers reshape, replace, or reinforce the role of unions? Based on a comparative case study of the 2018 #RedForEd teachers’ strikes in West Virginia, Oklahoma, and Arizona, this article argues that despite the hierarchical and bureaucratic character of statewide teachers’ unions, the infrastructure they provided to organize, connect, and legitimize teachers’ actions was critical for statewide strikes. Facebook provided a forum for teachers to express frustrations, scale participation, and in some cases, organize actions. However, the unions’ coordinating capacities were also central. These findings show how combining the mobilizing capacities of social media with existing movement infrastructure can facilitate collective action. In contrast to predictions of digitally enabled activism ushering in an era of “organizing without organizations,” these findings suggest that 21st-century labor movements must meld old and new organizational forms, and not discard the century-and-a-half accumulation of labor infrastructure won by previous generations.
Body Perception From Connected Speech: Speaker Height Discrimination from Natural Sentences and Sine-Wave Replicas with and without Pitch
Authors: González-Alvarez Julio , Sos-Peña Rosa
Published: July 2023

In addition to language, the human voice carries information about the physical characteristics of speakers, including their body size (height and weight). The fundamental speaking frequency, perceived as voice pitch, and the formant frequencies, or resonators of the vocal tract, are the acoustic speech parameters that have been most intensely studied for perceiving a speaker’s body size. In this study, we created sine-wave (SW) replicas of connected speech (sentences) uttered by 20 male and 20 female speakers, consisting of three time-varying sinusoidal waves matching the frequency pattern of the first three formants of each sentence. These stimuli only provide information about the formant frequencies of a speech signal. We also created a new experimental condition by adding a sinusoidal replica of the voice pitch of each sentence. Results obtained from a binary discrimination task revealed that (a) our SW replicas provided sufficient useful information to accurately judge the speakers’ body height at an above chance level; (b) adding the sinusoidal replica about the voice pitch did not significantly increase accuracy; and (c) stimuli from female speakers were more informative for body height detection and allowed higher perceptual accuracy, due to a stronger correlation between formant frequencies and actual body height than stimuli from male speakers.
Clio's Stepchildren: Anne of Cyprus, Louis of Savoy, and the Politics of Historiography
Authors: Kügle Karl
Published: July 2023

The historiographical image of Anne of Cyprus (1418–1462), Duchess of Savoy, and her husband, Duke Louis of Savoy (1413–1465), is overwhelmingly negative. The couple undoubtedly encountered serious political difficulties during their reign, but the ‘black legend’ circulating about Anne and Louis since the seventeenth century appears far from justified. It originated with the so-called Chronica Latina Sabaudiae, a text completed shortly after 1487 and probably written by Étienne Morel (c. 1440–1499), a high-ranking cleric who was a supporter of the estranged son of Anne and Louis, Philippe of Savoy (1438–1497). Morel's narrative, its historical and literary context, and its reception in early-modern and modern historiography are examined against the background of contemporaneous Sabaudian and European politics. Morel's polemics seem inspired by the Commentarii genre of historiography cultivated by fifteenth-century humanists such as Enea Silvio Piccolomini. Both the genesis and the reception of Morel's text demonstrate the shifting but unshakeable alliance of historiography and dynastic politics, exemplifying historiography's role in the fabric of power.
Dearth of Media reportage of environmental issues in Nigeria: Need for innovation and adoption of green culture to curb environmental decay
Authors: Ogadimma Emenyeonu C , Raza Syed Hassan , Khan Sanan Waheed , Mohamad Bahtiar
Published: July 2023

Environmental degradation has become a significant challenge of our time, from the rising temperature emanating from the depletion of the Ozone layer, shrinking of forest reserves, flooding, and pollution, to man-made disasters that affect the environment. The world, especially the global south, including Africa (Nigeria), has continued to experience multiple consequences emanating from exacerbated environmental woes. The media plays a massive role in mounting surveillance on the environment for proper environmental management. The media is also seen as the driving force behind adopting pro-environmental behavior among citizens. How the media reports and persuades citizens to be environmentally correct will determine the robustness of the environment. It, therefore, becomes pertinent to gauge how much surveillance the media – the watchdog of society - mounts on the environment. This study employed content analysis to assess how much attention and the quality of attention the media pays to environmental issues. The study utilized the media production frame to understand and explain what influences (environmental) content creation in the media. The study finds that both the quantum and quality of media attention to environmental issues are dismal. The results revealed that only 754 stories were reported by the four newspapers analyzed within the two-year study period, and of the 754 stories reported, only eight were editorials. This study argues that it takes more than the media to create awareness about environmental sustainability. This research addressed this gap by recommending a national system of innovation and adaptation of green culture - where all the environmental stakeholders – the public and private sectors, and the media would synergistically address environmental challenges through mitigation and adaptation measures that will bring about the right policies, perception, attitude, and support to the sustenance of the environment.
Factors influencing perceived stress in middle leaders of education
Authors: Lambert Steve
Published: July 2023

The role of middle leaders, that is, those who report to a member of the organisation's senior leadership, in bringing about improvements to schools is well documented. Yet middle leadership is often considered one of the most challenging roles within educational leadership, often under-conceptualised and theorised. Before we can look at the literature on resilience and any potential role it has in mediating against stress within the workplace, we need to know what stressors middle leaders in education experience. This paper outlines some initial findings from a study of 62 middle leaders, in England, exploring the key stressors they experience in their role. All participants were asked to complete a short online survey where they could enter free text when asked to identify the 5 stressors they most commonly experienced. Participants felt that staffing issues, followed by a lack of time and increasing workloads as the most prevalent issues. Commonly cited stressors such as inspections did not score highly, due to the temporary nature of the stress being induced. This is particularly important if staff are to be encouraged into leadership roles and senior leaders are to provide support for those already occupying middle leadership positions.
‘Bullshit’ After All? Why People Consider Their Jobs Socially Useless
Authors: Walo Simon
Published: July 2023

Recent studies show that many workers consider their jobs socially useless. Thus, several explanations for this phenomenon have been proposed. David Graeber’s ‘bullshit jobs theory’, for example, claims that some jobs are in fact objectively useless, and that these are found more often in certain occupations than in others. Quantitative research on Europe, however, finds little support for Graeber’s theory and claims that alienation may be better suited to explain why people consider their jobs socially useless. This study extends previous analyses by drawing on a rich, under-utilized dataset and provides new evidence for the United States specifically. Contrary to previous studies, it thus finds robust support for Graeber’s theory on bullshit jobs. At the same time, it also confirms existing evidence on the effects of various other factors, including alienation. Work perceived as socially useless is therefore a multifaceted issue that must be addressed from different angles.
Navigating autonomous vehicles in uncertain environments with distributional reinforcement learning
Authors: Xu Shuyuan , Hao Jiachen , Chen Xuemei , Hu Yuhui
Published: July 2023

Navigation in complex urban environments is very difficult, mainly due to perceptual uncertainty caused by obstructions in the field of view. The perceptual uncertainty is mainly due to sensors obstructed by obstacles. This has a significant impact on the safety of autonomous vehicles. Existing approaches based on partially observable Markov decision processes or reinforcement learning for the uncertainty problem may lead to conservative planning and expensive computation. We propose caution-driven networks combined with distributional reinforcement learning fully parameterized quantile function, which termed Intrinsic caution module – fully parameterized quantile function (ICM-FQF). The method is also applied in the continuous action space. The method is used to evaluate two challenging scenarios, pedestrians crossing with occlusion and a unsignalized intersection with a limited field of view. The algorithm is trained and evaluated using the CARLA simulator. Compared to conventional RL algorithms, the method makes smarter decisions and reduces the rate of collisions.
Resilience in Newly Diagnosed Breast Cancer Women: The Predictive Role of Diurnal Cortisol and Social Support
Authors: Aizpurua-Perez Ibane , Arregi Amaia , Gonzalez David , Macia Patricia , Ugartemendia Gurutze , Labaka Ainitze , Zabalza Nerea , Perez-Tejada Joana
Published: July 2023

Background

Breast cancer is currently the most prevalent malignancy among women. Psychological resilience is an important factor that diminishes the stress-related emotional and psychosocial disturbances triggered when receiving the diagnosis. Furthermore, resilience appears to be associated with cortisol, the hormonal end-product of the hypothalamic-pituitary-adrenal axis; however, further studies are needed due to the mixed results reported. Thus, we aim to examine the predictive role of social support and cortisol in resilience among breast cancer patients.

Methods

A total of 132 women with primary breast cancer completed the Medical Outcomes Study-Social Support Survey (MOS-SSS) and the Resilience Scale (RS-14) and provided four salivary samples for the estimation of participants’ total daily cortisol production, for which the formula of the area under the curve with respect to the ground (AUCg) was applied. Moderation analyses were performed to study the influence of social support and AUCg on psychological resilience levels.

Results

The regression analyses showed a direct significant effect for the emotional support subscale of MOS-SSS on resilience and the interaction between emotional support and AUCg was also found to be statistically significant. Specifically, the conditional effect of emotional support on resilience was found to be significant at middle ( M = 3.08; p < .05) and low levels ( M = .59; p < .001) of AUCg.

Conclusions

Our results suggest that newly diagnosed breast cancer women with middle and low diurnal cortisol profiles may benefit more from emotional support based-interventions while women with high diurnal cortisol may need more individualized therapies.
Barriers and Facilitators to Integrating Depression Treatment Within a TB Program and Primary Care in Brazil
Authors: Sweetland Annika Claire , Gruber Mann Claudio , Fernandes Maria Jose , Silva Fatima Virginia Siqueira de Menezes , Matsuzaka Camila , Cavalcanti Maria , Fortes Sandra , Kritski Afranio , Su Austin Y. , Ambrosio Julio Cesar , Kann Bianca , Wainberg Milton L.
Published: July 2023

Tuberculosis (TB) and depression is common and is associated with poor TB outcomes. The World Health Organization End TB Strategy explicitly calls for the integration of TB and mental health services. Interpersonal Counseling (IPC) is a brief evidence-based treatment for depression that can be delivered by non-mental health specialists with expert supervision. The goal of this study was to explore potential barriers and facilitators to training non-specialist providers to deliver IPC within the TB Control Program and primary care in Itaboraí, Rio de Janeiro state. Data collection consisted of six focus groups (n = 42) with health professionals (n = 29), program coordinators (n = 7), and persons with TB (n = 6). We used open coding to analyze the data, followed by deductive coding using the Chaudoir multi-level framework for implementation outcomes. The main structural barriers identified were poverty, limited access to treatment, political instability, violence, and social stigma. Organizational barriers included an overburdened and under-resourced health system with high staff turnover. Despite high levels of stress and burnout among health professionals, several provider-level facilitators emerged including a high receptivity to, and demand for, mental health training; strong community relationships through the community health workers; and overall acceptance of IPC delivered by any type of health provider. Patients were also receptive to IPC being delivered by any type of professional. No intervention-specific barriers or facilitators were identified. Despite many challenges, integrating depression treatment into primary care in Itaboraí using IPC was perceived as acceptable, feasible, and desirable.
Are clinical registries an effective tool for hospital health services to address unwarranted clinical variation?
Authors: Bessen Taryn , O’Callaghan Gerry
Published: July 2023

Objective:

To map clinical registries within the Central Adelaide Local Health Network (CALHN); and to identify how these registries were currently used for addressing unwarranted clinical variation in care.

Method:

An online survey was sent to all Heads of Units (HoUs) within CALHN. The survey addressed participation, type of data, reporting processes and use of the clinical registries for research, quality assurance (QA), quality improvement (QI) and clinical variation in health care.

Results:

Twenty-six HoUs responded (26%); 25 contributed to a clinical registry (96%); all provided data to more than one registry, but only 34.6% had an existing financial and governance arrangement with the network. Health outcomes were the most common datapoints; 77% of all data were collected manually; and 38.5% of data analysis was risk adjusted. Access to aggregated data varied across the registries; and 65.4% of reports included benchmarks and outliers. Clinical registries were used for research in 65.4%, and QA and QI in 73.1 and 69.2%, respectively. Most used external comparators and measured clinical variation, but there was marked inconsistency in the exploring clinical variation, improving care and reporting activities.

Conclusion:

Based on this sample, clinical registries within CALHN did not currently appear to be a reliable resource to consistently address unwarranted clinical variation but were shown to be valuable resources for research and quality initiatives at a high level. Further research is required to facilitate effective integration of clinical registries with administrative and quality systems.
Does Emotion Regulation Flexibility Work? Investigating the Effectiveness of Regulatory Selection Flexibility in Managing Negative Affect
Authors: Specker Philippa , Sheppes Gal , Nickerson Angela
Published: July 2023

Regulatory selection flexibility—the ability to flexibly choose emotion regulation strategies that are appropriate to dynamic contextual demands—has been theorized as a critical component of adaptive emotional functioning. Despite this, little research has investigated whether individual differences in regulatory selection flexibility influence real-time emotional experiences. The current study aimed to test the effectiveness of regulatory selection flexibility in reducing negative affect while exposed to emotion-eliciting stimuli. Using a behavioral regulatory selection task, participants viewed negative images that differed in emotional intensity and selected between engagement cognitive change (reappraisal) or attentional disengagement (distraction) strategies to manage their emotional responses. Negative affect was rated immediately before and after the regulatory period, to index emotional experience. Greater regulatory selection flexibility was associated with greater reductions in negative affect. Our findings offer preliminary evidence for the immediate psychological benefit of regulatory selection flexibility and highlight some promising avenues for future research.
Perioperative considerations for postpneumonectomy syndrome: A case report
Authors: Yetzer Samuel , Jain Ankit , Balayan Vanshika , Bailey Caryl
Published: July 2023

Postpneumonectomy syndrome is a rare complication of a pneumonectomy. Patients may experience dyspnea, stridor, recurrent pulmonary infections, or dysphagia due to rotation and shift of the mediastinum. The current intervention of choice involves the placement of a tissue expander in the empty hemithorax to realign the mediastinum. Because this treatment can present with intraoperative anesthetic challenges and requires close monitoring, we present this case to highlight specific concerns that may need to be addressed including difficulties ventilating, complete airway collapse, hemodynamic instability, and pain control perioperatively.
Cardiac surgery risk prediction using ensemble machine learning to incorporate legacy risk scores: A benchmarking study
Authors: Dong Tim , Sinha Shubhra , Zhai Ben , Fudulu Daniel P , Chan Jeremy , Narayan Pradeep , Judge Andy , Caputo Massimo , Dimagli Arnaldo , Benedetto Umberto , Angelini Gianni D
Published: July 2023

Objective

The introduction of new clinical risk scores (e.g. European System for Cardiac Operative Risk Evaluation (EuroSCORE) II) superseding original scores (e.g. EuroSCORE I) with different variable sets typically result in disparate datasets due to high levels of missingness for new score variables prior to time of adoption. Little is known about the use of ensemble learning to incorporate disparate data from legacy scores. We tested the hypothesised that Homogenenous and Heterogeneous Machine Learning (ML) ensembles will have better performance than ensembles of Dynamic Model Averaging (DMA) for combining knowledge from EuroSCORE I legacy data with EuroSCORE II data to predict cardiac surgery risk.

Methods

Using the National Adult Cardiac Surgery Audit dataset, we trained 12 different base learner models, based on two different variable sets from either EuroSCORE I (LogES) or EuroScore II (ES II), partitioned by the time of score adoption (1996–2016 or 2012–2016) and evaluated on holdout set (2017–2019). These base learner models were ensembled using nine different combinations of six ML algorithms to produce homogeneous or heterogeneous ensembles. Performance was assessed using a consensus metric.

Results

Xgboost homogenous ensemble (HE) was the highest performing model (clinical effectiveness metric (CEM) 0.725) with area under the curve (AUC) (0.8327; 95% confidence interval (CI) 0.8323–0.8329) followed by Random Forest HE (CEM 0.723; AUC 0.8325; 95%CI 0.8320–0.8326). Across different heterogenous ensembles, significantly better performance was obtained by combining siloed datasets across time (CEM 0.720) than building ensembles of either 1996–2011 ( t-test adjusted, p = 1.67×10−6) or 2012–2019 ( t-test adjusted, p = 1.35×10−193) datasets alone.

Conclusions

Both homogenous and heterogenous ML ensembles performed significantly better than DMA ensemble of Bayesian Update models. Time-dependent ensemble combination of variables, having differing qualities according to time of score adoption, enabled previously siloed data to be combined, leading to increased power, clinical interpretability of variables and usage of data.
Positive experiences in emotional labor: Deep acting, symbolic boundaries, and labor autonomy
Authors: Mei Xiao
Published: July 2023

One important approach to studying emotional labor is to focus on its negative impact from the perspective of organizational psychology. Less attention is paid to the positive effect. This paper adopts a cultural sociology approach to study how “maternity helpers” use boundary work, such as “deep acting” and constructing symbolic boundaries, to produce positive experiences in the process of emotional labor. In deep acting, they actively distort the boundaries of the private space, introduce a family-oriented narrative, and participate in a certain amount of “philanthropic labor”. They are also engaged in constructing symbolic boundaries by promoting themselves as “childcare experts”, in order to get the upper hand when interacting and negotiating with clients. Both boundary work strategies constitute an attempt to challenge social boundaries by constructing symbolic boundaries. This paper argues that the concept of autonomy in emotional labor should adopt a relational approach, thus accounting for the ability for the laborers to autonomously choose strategies that can produce equal and meaningful social relations, rather than merely focusing on the independent self with clear boundaries or the ability to control the labor process. Nevertheless, autonomy in emotional labor is constrained by both institutional and cultural conditions.
An Intrinsic Case Study of Two-Dimensional Visual Art Appearance in Malaysia: A Checklist for Islamic Shariah View-Point
Authors: Ramli Ishak , Mokhtar Mumtaz , Masrek Mohamad Noorman , Mohd Zain Dzul Haimi , Osman Muhamad Rahimi , Ab. Gani Muhamad Abdul Aziz , Mohd Rafee Mohd Radzuan , Abdul Rahim Mohd Daud , Mohd Zamari Zarlina
Published: July 2023

Visual art is a fast-expanding field in Malaysia, especially on the development and exploration of visual appearances in visual artworks. Based on the researchers’ observation, research which are focused on producing guidelines for rules and regulations in visual art from the Islamic perspective are scarce. In all, there is only one reference that is relevant to guidelines for visual art which was produced in 1987; no improvement is implemented since then. Moreover, the guideline covers matters pertaining visual appearance in general. For this paperwork, the objective is to produce a checklist for two-dimensional visual appearance in Malaysian Visual Art. Hermeneutic intrinsic case study is the research design applied and the researchers utilize systematic review approach as well as information from interviews with experts to learn about the practices in visual appearance in the current context. Results from both types of data are analyzed using the triangulation method to produce a two-dimensional visual appearance checklist. This checklist will be used in collecting Islamic Shariah perspectives with regards to current situations in visual art.
Missed Cardiac Amyloidosis: A Potentially Treatable Disease
Authors: Vivek B.S. , Jain Ashish Kumar , Sawhney J.P.S. , Jain Rajneesh , Passey Rajiv , Mohanty Arun
Published: July 2023

Aim

To highlight the prevailing lack of suspicion of cardiac amyloidosis (CA) amongst physicians, leading to preventable delay in management of patients of heart failure (HF).

Methods

Six patients of CA diagnosed in 6 months were retrospectively analyzed. Clinical history, investigations, treatment, and follow-up data is analyzed.

Result

A speckled interventricular septum on echo favored CA. Speckle tracking showed reduced global longitudinal strain with typical left ventricular apical sparing in all patients. Bone marrow study confirmed light chain amyloidosis (AL) in all patients.

Conclusion

CA, a frequently missed diagnosis, can be detected early with the help of clinical red flag signs, echocardiogram, serum and urine immune electrophoresis and bone scan.
EASIX-1year and late mortality after allogeneic stem cell transplantation
Authors: Kordelas Lambros , Terzer Tobias , Gooley Ted , Davis Chris , Sandmaier Brenda M. , Sorror Mohamed , Penack Olaf , Schaeper Nigel D. E. , Blau Igor W. , Beelen Dietrich , Radujkovic Aleksandar , Dreger Peter , Luft Thomas
Published: July 2023

Patients with hematological malignancies who survive the first year after allogeneic stem cell transplantation (allo-SCT) without relapse have a substantial risk of nonrelapse mortality (NRM) and missing predictive markers. The Endothelial Activation and Stress Index (EASIX) predicts endothelial complications and NRM early after allo-SCT. We hypothesized that EASIX assessed 1 year after allo-SCT in survivors who were disease free may predict late NRM. Survivors who were relapse-free at 1 year after allo-SCT were retrospectively studied in 2 independent cohorts (training cohort, n = 610; merged validation cohort, n = 852). EASIX determined 1 year after allo-SCT correlated with the overall survival (OS), NRM, and relapse. Serum endothelial and inflammatory markers were measured in the training cohort and correlated with EASIX-1year, which predicted OS and NRM but not relapse risk in both the training and validation cohorts in univariable and multivariable Cox regression analyses. Brier score and c-index analyses validated the univariable EASIX effects. There was no significant interaction between EASIX-1year and incidence of chronic graft-versus-host disease (GVHD) on OS. EASIX-1year predicted the outcome irrespective of preexisting comorbidities. Principal causes of NRM in both training and validation cohorts were infections with and without GVHD as well as cardiovascular complications. EASIX-1year correlated with sCD141 and interleukin-18 but not with C-reactive protein, suppressor of tumorigenicity-2, angiopoietin-2, CXCL9, or CXCL8. To our knowledge, EASIX-1year is the first validated predictor of late overall and NRM. Patients who are high risk as defined by EASIX-1year might be considered for intensified surveillance and prophylactic measures.
The mixture assessment or allocation factor: conceptual background, estimation algorithms and a case study example
Authors: Backhaus Thomas
Published: July 2023

Current approaches for the prospective regulatory assessment of chemicals do not account sufficiently for elevated mixture risks. The Mixture Assessment Factor (MAF, better labeled a Mixture Allocation Factor) has been suggested for mixtures of industrial chemicals in the EU’s Chemicals Strategy for Sustainability, as a pragmatic tool to account for potential mixture risks already during the risk and safety assessment of individual chemicals. The MAF is to be applied in scenarios in which specific mixture risk assessments are not possible, due to a lack of data and/or the complexity of the relevant exposure scenarios. Several approaches and algorithms for calculating a MAF have been suggested in the literature. The MAFexact, which is a member of the larger MAFceiling class, is defined as the maximum fraction of the risk quotient of each chemical that is still acceptable to occur in a mixture, without the sum of risk quotients exceeding 1. This paper provides a comparative overview of the different MAF types discussed in the literature. It argues that the MAFexact is the most promising approach in the context of chemical registration and authorization under regulatory frameworks such as REACH because this approach ensures a protection level that is similar to the protection level used in the current safety assessment of individual chemicals under REACH. Other MAF approaches either disproportionally impact low-risk substances, without leading to any appreciable risk reduction, or hamper risk communication because they lead to fluctuating residual risks after the MAF application. The paper also presents a case study comparing the different MAF approaches and finally discusses the MAF concept in the wider context of chemical regulation.
The impact of supported accommodation on health and criminal justice outcomes of people released from prison: a systematic literature review
Authors: Gibbs Daisy , Stockings Emily , Larney Sarah , Bromberg Daniel J. , Shakeshaft Anthony , Farnbach Sara
Published: July 2023

Background

Supported accommodation intends to address challenges arising following release from prison; however, impact of services, and of specific service components, is unclear. We describe key characteristics of supported accommodation, including program components and outcomes/impact; and distil best-evidence components.

Methods

We conducted a systematic review, searching relevant databases in November 2022. Data were synthesised via effect direction plots according to the Synthesis Without Meta-analysis guidelines. We assessed study quality using the McGill Mixed Methods Appraisal Tool, and certainty in evidence using the GRADE framework.

Results

Twenty-eight studies were included; predominantly cross-sectional. Program components which address life skills, vocational training, AOD use, and mental health appear to positively impact criminal justice outcomes. Criminal justice outcomes were the most commonly reported, and while we identified a reduction in parole revocations and reincarceration, outcomes were otherwise mixed. Variable design, often lacking rigour, and inconsistent outcome reporting limited assessment of these outcomes, and subsequently certainty in findings was low.

Conclusion

Post-release supported accommodation may reduce parole revocations and reincarceration. Despite limitations in the literature, the findings presented herein represent current best evidence. Future studies should clearly define program components and measure their impact; use analyses which reflect the high risk of adverse outcomes, such as time-to-event analyses; and consider outcomes which reflect the range of challenges faced by people leaving prison.

Registration: PROSPERO registration CRD42020189821.
N-glycosylation acts as a switch for FGFR1 trafficking between the plasma membrane and nuclear envelope
Authors: Gregorczyk Paulina , Porębska Natalia , Żukowska Dominika , Chorążewska Aleksandra , Gędaj Aleksandra , Malinowska Agata , Otlewski Jacek , Zakrzewska Małgorzata , Opaliński Łukasz
Published: July 2023

Fibroblast growth factor receptor 1 (FGFR1) is a heavily N-glycosylated cell surface receptor tyrosine kinase that transmits signals across the plasma membrane, in response to fibroblast growth factors (FGFs). Balanced FGF/FGFR1 signaling is crucial for the development and homeostasis of the human body, and aberrant FGFR1 is frequently observed in various cancers. In addition to its predominant localization to the plasma membrane, FGFR1 has also been detected inside cells, mainly in the nuclear lumen, where it modulates gene expression. However, the exact mechanism of FGFR1 nuclear transport is still unknown. In this study, we generated a glycosylation-free mutant of FGFR1, FGFR1.GF, and demonstrated that it is localized primarily to the nuclear envelope. We show that reintroducing N-glycans into the D3 domain cannot redirect FGFR1 to the plasma membrane or exclude the receptor from the nuclear envelope. Reestablishment of D2 domain N-glycans largely inhibits FGFR1 accumulation in the nuclear envelope, but the receptor continues to accumulate inside the cell, mainly in the ER. Only the simultaneous presence of N-glycans of the D2 and D3 domains of FGFR1 promotes efficient transport of FGFR1 to the plasma membrane. We demonstrate that while disturbed FGFR1 folding results in partial FGFR1 accumulation in the ER, impaired FGFR1 secretion drives FGFR1 trafficking to the nuclear envelope. Intracellular FGFR1.GF displays a high level of autoactivation, suggesting the presence of nuclear FGFR1 signaling, which is independent of FGF. Using mass spectrometry and proximity ligation assay, we identified novel binding partners of the nuclear envelope-localized FGFR1, providing insights into its cellular functions. Collectively, our data define N-glycosylation of FGFR1 as an important regulator of FGFR1 kinase activity and, most importantly, as a switchable signal for FGFR1 trafficking between the nuclear envelope and plasma membrane, which, due to spatial restrictions, shapes FGFR1 interactome and cellular function.
Identification of pyroptosis-related genes and potential drugs in diabetic nephropathy
Authors: Yan Meng , Li Wenwen , Wei Rui , Li Shuwen , Liu Yan , Huang Yuqian , Zhang Yunye , Lu Zihao , Lu Qian
Published: July 2023

Background

Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus (DM). A growing body of research has demonstrated that the inflammatory state plays a critical role in the incidence and development of DN. Pyroptosis is a new way of programmed cell death, which has the particularity of natural immune inflammation. The inhibition of inflammatory cytokine expression and regulation of pathways related to pyroptosis may be a novel strategy for DN treatment. The aim of this study is to identify pyroptosis-related genes and potential drugs for DN.

Methods

DN differentially expressed pyroptosis-related genes were identified via bioinformatic analysis Gene Expression Omnibus (GEO) dataset GSE96804. Dataset GSE30528 and GSE142025 were downloaded to verify pyroptosis-related differentially expressed genes (DEGs). Least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a pyroptosis-related gene predictive model. A consensus clustering analysis was performed to identify pyroptosis-related DN subtypes. Subsequently, Gene Set Variation Analysis (GSVA), Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to explore the differences between DN clusters. A protein–protein interaction (PPI) network was used to select hub genes and DGIdb database was utilized to screen potential therapeutic drugs/compounds targeting hub genes.

Results

A total of 24 differentially expressed pyroptosis-related genes were identified in DN. A 16 gene predictive model was conducted via LASSO regression analysis. According to the expression level of these 16 genes, DN cases were divided into two subtypes, and the subtypes are mainly associated with inflammation, activation of immune response and cell metabolism. In addition, we identified 10 hub genes among these subtypes, and predicted 65 potential DN therapeutics that target key genes.

Conclusion

We identified two pyroptosis-related DN clusters and 65 potential therapeutical agents/compounds for DN, which might shed a light on the treatment of DN.
Screening for lysosomal diseases in a selected pediatric population: the case of Gaucher disease and acid sphingomyelinase deficiency
Authors: Di Rocco Maja , Vici Carlo Dionisi , Burlina Alberto , Venturelli Francesco , Fiumara Agata , Fecarotta Simona , Donati Maria Alice , Spada Marco , Concolino Daniela , Pession Andrea
Published: July 2023

Background

GD and ASMD are lysosomal storage disorders that enter into differential diagnosis due to the possible overlap in their clinical manifestations. The availability of safe and effective enzymatic therapies has recently led many investigators to develop and validate new screening tools, such as algorithms, for the diagnosis of LSDs where the lack of disease awareness or failure to implement newborn screening results in a delayed diagnosis.

Results

the proposed algorithm allows for the clinical and biochemical differentiation between GD and ASMD. It is based on enzyme activity assessed on dried blood spots by multiplexed tandem mass spectrometry (MS/MS) coupled to specific biomarkers as second-tier analysis.

Conclusions

we believe that this method will provide a simple, convenient and sensitive tool for the screening of a selected population that can be used by pediatricians and other specialists (such as pediatric hematologists and pediatric hepatologists) often engaged in diagnosing these disorders.