bluuebunny/crossref_metadata_2025 huggingface dataset:
Calculated haemorheological profile and laboratory parameters in new diagnosed multiple myeloma patients: retrospective analysis according to survival
Authors: Carlisi Melania , Lo Presti Rosalia , Spoto Corinne , Mancuso Salvatrice , Siragusa Sergio , Caimi Gregorio
Published: November 2024

Background:

Multiple myeloma is a malignant haematological neoplasm characterised by clonal proliferation of plasma cells, with a complex clinical picture, and a significant impact on patient survival, in which the prognosis evaluation of patients is of great importance.

Objectives:

In this single-centre retrospective analysis, performed in a group of newly diagnosed multiple myeloma patients, we examined several clinical and laboratory parameters in order to evaluate their trend according to survival of patients.

Design:

We collected data from 190 newly diagnosed multiple myeloma evaluated at the Hematology Division of the ‘Paolo Giaccone’ University Hospital of Palermo from 1 January 2017 to 30 September 2022. Specifically, we performed our analysis in the entire cohort of patients and also in the specific disease isotype.

Methods:

We evaluated simple and low-cost laboratory and haemorheological parameters, the latter obtained in a calculated way. The primary endpoint was to evaluate the trend and the differences of these parameters in the study population, divided into two specific groups, deceased and survivors after a specific observation period of almost 7 years.

Results:

In the entire cohort of multiple myeloma patients, we observed a mortality rate of 40%, of whom 36.4% were men and 43.1% were women. Among the patients who died, in comparison with those who survived, it is significantly evident the increase in age, in red cell distribution width (RDW), RDW%/albumin ratio and in the RDW%/haemoglobin ratio; moreover, in the same patients subgroup, we observed a reduction in haematocrit, total serum protein, calculated whole blood viscosity (evaluated according to the de Simone formula), serum albumin, albumin/fibrinogen ratio and in haemoglobin levels.

Conclusion:

The obtained data can represent a possible starting point for subsequent targeted analyses, aimed at studying the prognostic value of each individual parameter considered, favouring an increasingly complete and immediate prognostic evaluation of patients.
Rescue immune tolerance induction with a recombinant factor Fc-fused VIII: prospective ReITIrate study of clinical, humoral and cellular immune responses
Authors: Königs Christoph , Meeks Shannon L. , Nolan Beatrice , Schmidt Anja , Löfqvist Malin , Dumont Jennifer , Leickt Lisa , Nayak Sushrusha , Lethagen Stefan
Published: November 2024

Background:

Immune tolerance induction (ITI) is the gold standard for inhibitor eradication to restore the clinical efficacy of factor replacement therapy in haemophilia. However, as ITI often requires frequent administration over extended periods, it can be considered burdensome for patients and healthcare resources. Therefore, there is a need to optimise ITI treatment, particularly in patients who failed previous ITI attempts.

Objectives:

The ReITIrate study aimed to prospectively evaluate rescue ITI with efmoroctocog alfa, an extended half-life recombinant FVIII Fc fusion protein (herein rFVIIIFc), within a limited 60-week timeframe in patients with severe haemophilia A and inhibitors who failed previous ITI attempts.

Design:

ReITIrate was a phase IV, open-label, single-arm, interventional, multicentre study.

Methods:

Primary endpoint was ITI success (negative titre, <0.6 BU/mL; incremental recovery >66%; elimination half-life ⩾7 hours) within 60 weeks. Exploratory immunophenotype analyses were performed to characterise anti-drug antibodies (ADA) and cellular immune responses.

Results:

Nine of 16 enrolled subjects completed the ITI period during ReITIrate, of which one subject attained all 3 ITI success criteria after 46 weeks with no relapse. Two subjects achieved partial success (one subject met 2/3 success criteria; one met all criteria, but not simultaneously, with inhibitor recurrence). One additional subject (ITI failure) achieved negative inhibitor titre. Across these four subjects, median (range) time to negative titre was 19 (11–60) weeks. No new safety concerns were identified. IgG4 was the major contributor to the ADA IgG response. Subjects with partial/complete ITI success had fewer IgG subclasses involved than those who failed/withdrew. Immunophenotyping indicated an increase in regulatory T-cells (CD4+CD25+CD127low), supporting the ability to perform sensitive blood sampling to identify immune tolerance markers.

Conclusion:

This study demonstrates that ITI with rFVIIIFc given within a limited timeframe has potential benefit in a difficult-to-treat inhibitor haemophilia population who failed previous ITI attempts.

Trial registration:

NCT03103542.
Redefining educational success: Analyzing the impact of closed management systems on student well-being and academic performance in Chinese technical education
Authors: Liu Jingkun , Dellova Rovena I , Yi Zhengxin
Published: November 2024

This paper investigates which open education and communication resources (OER, OECR) are used by the students of Qingdao Aviation Technology Vocational College under a system of closed management. It builds upon the theoretical backbone of Partial Least Squares (PLS) to assess some common suppositions on educational management and student learning outcomes using a robust methodological framework and observed Key Analysis. The authors posit that the findings from this study put into question prior assumptions–that anxiety of falling behind, and family/teacher support affect academic success in a closed management setting. The study instead focuses on student well-being and support structures to tell us something about academic performance. These findings are completely different from the current model of education, and highly convergent on goal number four under Sustainable Development Goals (SDG) demanding equal access to quality inclusive educational services; for all-age groups throughout humanity. Lastly, the study provides a blueprint for future educational changes that fit international education aspirations afforded by contested traditionalism.
Graduate attributes in Australian Christian higher education providers: Faith and faculty
Authors: Coetzee Narelle , Bickmore-Brand Jennie , Greentree Jacqueline
Published: November 2024

Graduate attributes are the central qualities, skills, and knowledge that Higher Education Providers aim to instill in their graduates. But how do Christian Higher Education Providers (CHEPs) embed their set of graduate attributes? In a joint Australian CHEP research project, the faculty reported that what they teach is aligned with the graduate attributes. However, when directly referencing the graduate attributes within learning material and assessments, the ‘Christian’ and/or affective attributes were challenging to implement and measure. Despite this, the institutional culture and faculty alignment were able to promote the inculcation of the graduate attributes.
Identifying Areas of High Vulnerability for Rural Veteran Food Insecurity
Authors: Bradley Sarah E. , Heuer Jacquelyn , Hahm Bridget , Pettey Kristin , Besterman-Dahan Karen
Published: November 2024

Introduction/Objectives:

Americans, including veterans, living in rural areas experience higher rates of food insecurity than the general population in the United States, but rural veteran food insecurity remains an understudied subject. Due to a lack of data on the subject, this project aimed to use geographic information systems (GIS) mapping of proxy variables for rural veteran food insecurity in order to identify areas of high vulnerability where future research could be targeted.

Methods:

Key factors which may indicate vulnerability to rural veteran food insecurity were identified in a review of the literature. These factors were mapped in ArcGIS Pro, including veteran population, community health, county rurality, and locations of food deserts.

Results:

After areas were identified that met search criteria, 3 sites were identified which serve a highly rural patient population and whose population has the highest vulnerability to rural veteran food insecurity based on search criteria.

Conclusions:

This project demonstrates how GIS mapping can be used to identify regions in the United States at high vulnerability for rural veteran food insecurity. Findings from this project will be used by the project team to develop interventions for rural veteran food insecurity which can be implemented at the local or national level.
The Power of Words: How Does Leader’s Motivating Language Affect Employees’ Organizational Commitment
Authors: Zhao Hang , Ali Mohd Helmi
Published: November 2024

The influence of leadership on organizational outcomes has long been a subject of extensive research. Our study departs from the traditional examination of broader behavioral aspects. It focuses on a specific and nuanced element within leadership styles and approaches—motivating language. Drawing on insights from the social cognitive and motivating language literature, this study provides a more nuanced understanding of how leaders can influence organizational commitment through their language choices. We conducted an online survey of 413 full-time employees across various sectors in China. The findings indicate that leaders’ motivational communication, which includes direction-giving, empathetic, and meaning-making language, positively correlates with organizational commitment. Moreover, psychological empowerment serves as a mediator in the relationship between each type of motivating language and organizational commitment. Despite the positive link between psychological empowerment and organizational commitment, relationship conflict weakens this association.
Analyzing and conceptualizing the perceived risks of working from home: A qualitative analysis following the COVID-19 pandemic
Authors: Brandt Jörn , Suess Stefan
Published: November 2024

The COVID-19 pandemic sharply increased opportunities to work from home. However, current research on working from home cannot keep up with its practical developments. In particular, studies on the risks of working from home are too undifferentiated, so most of these risks’ antecedents and effects remain unknown, along with the relationships among them. This study analyzes and conceptualizes the perceived risks of working from home following the COVID-19 pandemic. We used the Gioia methodology to analyze 22 semi-structured interviews qualitatively. Our results reveal the perceived risks of working from home, along with their antecedents and possible effects. In addition, we developed six process models to represent patterns in these perceived interrelationships between risks, antecedents, and effects. By analyzing and conceptualizing the risks of the work model, our results contribute to the literature on working from home and offer guidance for future research.
Airbnb and the COVID-19 pandemic: A geospatial analysis of Greater London
Authors: Wang Nan , Hincks Stephen
Published: November 2024

This paper examines the response of the Airbnb ‘market’ to the shock of COVID-19, exploring the spatio-temporal variations in Airbnb listings, revenues, and hosting patterns in Greater London over the pre-lockdown, lockdown, and post-lockdown periods. At an aggregate level, Airbnb listings and revenues were found to have declined during the pandemic with disruptions differentiated according to the professional or amateur status of hosts. We then disaggregate these global trends to neighbourhood level. We explore the relative importance of socio-demographic, accessibility and neighbourhood amenities to Airbnb revenue levels across the Capital over the course of the pandemic. In doing so, we expose patterns in the Airbnb market as a result of the COVID-19 shock, revealing a geography of spatial clustering in Airbnb revenue levels over time and variations and volatility based neighbourhood deprivation. While COVID-19 certainly delivered a disruptive effect on Airbnb in Greater London, the pandemic did not de-stabilise existing geographies of Airbnb, especially in Inner London, where Airbnb remains spatially entrenched and challenges around housing affordability and neighbourhood gentrification are acute.
Shortest-path tree-based method for calculating visible area with time- and memory-saving preprocessing
Authors: Tabata Shota
Published: November 2024

Visibility has extensive application in areas such as architecture, urban planning, and security. This study proposes a novel approximation method, called the shortest-path tree-based method (SPT-based method), for calculating the visible area using a random Delaunay network on a 2D plane. Various methods are available for calculating the visible area, including exact and approximation methods. However, it is difficult to calculate the visible area repeatedly in a space that has a vast number of obstacles while achieving efficient time and memory usage. The SPT-based method focuses on time- and memory-saving preprocessing. To achieve an efficient calculation of the visible area, we discretised a plane using a random Delaunay network and approximated the visible area using Dijkstra’s method. To evaluate the efficiency of the proposed method, we compared the calculation time, accuracy, and memory usage of the plane-sweep, ray-trace, brute-force, and SPT-based methods while considering the influence of the number of obstacles. This study provides valuable insights for researchers and practitioners for choosing the most suitable approach for their specific needs. Overall, the proposed method offers a time- and memory-efficient solution for calculating the visible area, making it suitable for a detailed analysis of the visual environment and providing a heuristic solution to the art gallery problem requiring repetitive calculations.
Component Restoration Models of Highway Bridges for Resilience Assessment: A Nationwide Expert-Opinion Survey Study and Application
Authors: Wang Xiaowei , Ye Aijun , Yang Dang , Wu Xueping , Zhou Lianxu , Song Kaihui , Li Jun , Peng Jun , Lou Liang , Wei Xinnong
Published: November 2024

This study performs a nationwide expert-opinion survey in Mainland China to establish component restoration models of highway bridges toward high-fidelity resilience assessment. To this end, a questionnaire based on component damage states is designed to collect expert opinions on key variables of the restoration models, including loss of functionality, traffic decision, idle time, repair strategy, and recovery time. More importantly, this study introduces the concept of repair-induced loss of functionality into the component restoration models, in addition to the traditional earthquake-induced loss of functionality. According to the survey results, both deterministic and probabilistic restoration models are developed, where the former is for practical application while the latter characterizes epistemic uncertainties in the key variables. Finally, a case study on a highway bridge with multiple types of vulnerable components is carried out to illustrate the application of the component restoration models for full bridge resilience assessment.
Expression of senescence-related CD161 promotes extranodal NK/T cell lymphoma by affecting T cell phenotype and cell cycle
Authors: Jin Chengxun , Li Xin , Zhang Chaohe
Published: November 2024

Purpose

The intention of this work is to probe the role of senescence-related gene CD161 in extranodal NK/T cell lymphoma (ENKTL).

Methods

This study used H2O2 to establish three distinct in vitro oxidative stress aging models (NKL, SNT-8, and YT). Western blotting was employed to assess the levels of two iconic aging proteins, MMP1 and P53, and flow cytometry was utilized to investigate cell cycle and the expressions of CD4, CD8, and CD161. Cell viability was evaluated via the CCK-8 assay. The transcriptome analysis assessed the differential gene expression between the control and aging group of NKL. In vivo, we established a BALB/c mice aging tumor model. After 15 days, the mice were euthanized to harvest tumors. ELISA was employed to measure aging indicators in the mouse tissues. Flow cytometry was utilized to assess the levels of CD4, CD8, and CD161 in tumor samples. Hematoxylin-eosin (HE) staining was performed to evaluate the structure and cellular morphology of the tumor tissue.

Results

In the NKL, SNT-8 and YT aging models, the levels of MMP1 and P53 proteins were significantly increased. Flow cytometry results indicated that all three cell types exhibited marked arrest in the G1 phase. Compared with the control group, the expressions of CD4 and CD161 in the aging group were significantly increased, while the expression of CD8 was decreased. Transcriptome analysis revealed 2,843 differentially expressed genes (DEGs) between the control and aging groups, with 2,060 up-regulated and 783 down-regulated genes identified. Following CD161 knockdown, cell viability of three cell types in the aging group was significantly reduced compared to the control group. The G1 phase of the cells was significantly interrupted. The expressions of CD4 and CD161 were significantly increased, and the expression of CD8 was decreased. However, in the aging + si-CD161 group, a partial alleviation of oxidative stress was observed with a reduction in CD161 expression levels. Animal experiments demonstrated that knockout of CD161 can inhibit tumor progression and partially mitigate oxidative stress.

Conclusions

CD161 may inhibit ENKTL tumor development by regulating cell cycle and T-cell phenotype.
Co-culture of human AT2 cells with fibroblasts reveals a MUC5B phenotype: insights from an organoid model
Authors: Yao Yiwen , Ritzmann Felix , Miethe Sarah , Kattler-Lackes Kathrin , Colakoglu Betül , Herr Christian , Kamyschnikow Andreas , Brand Michelle , Garn Holger , Yildiz Daniela , Langer Frank , Bals Robert , Beisswenger Christoph
Published: November 2024

Impaired interaction of fibroblasts with pneumocytes contributes to the progression of chronic lung disease such as idiopathic pulmonary fibrosis (IPF). Mucin 5B (MUC5B) is associated with IPF. Here we analyzed the interaction of primary fibroblasts and alveolar type 2 (AT2) pneumocytes in the organoid model. Single-cell analysis, histology, and qRT-PCR revealed that fibroblasts expressing high levels of fibrosis markers regulate STAT3 signaling in AT2 cells, which is accompanied by cystic organoid growth and MUC5B expression. Cystic growth and MUC5B expression were also caused by the cytokine IL-6. The PI3K-Akt signaling pathway was activated in fibroblasts. The drug dasatinib prevented the formation of MUC5B-expressing cystic organoids. MUC5B associated with AT2 cells in samples obtained from IPF patients. Our model shows that fibrotic primary fibroblasts induce impaired differentiation of AT2 cells via STAT3 signaling pathways, as observed in IPF patients. It can be used for mechanistic studies and drug development.
Mbnl1-mediated alternative splicing of circMlxipl regulates Rbbp6-involved ChREBP turnover to inhibit lipotoxicity-induced β-cell damage
Authors: Gong Yingying , Wei Meilin , Cao Xiaopei , Xu Changliu , Jin Jiewen , Pei Ling , Li Yanbing , Xiao Haipeng , Wu Liting
Published: November 2024

Background

Diabetes, a global epidemic, is the leading cause of mortality globally. The aim of this study is to get better understanding of pathophysiology of diabetes.

Methods

Palmitic acid (PA)-treated β-cells, db/db mice and high fat diet (HFD)-fed mouse model of type 2 diabetes were established. H&E was used to assess the histological changes of pancreas. IHC, FISH, western blot or qRT-PCR was employed to detect the expression of key molecules in primary islets or lipotoxic β-cells. Cell behaviors were detected by MTT, EdU incorporation assay, TUNEL assay and glucose-induced insulin secretion (GSIS). The associations among circMlxipl, Mbnl1 and Rbbp6 were validated by RIP and RNA pull-down assays, and the direct binding between Hdac3 and Mbnl1 promoter was examined by ChIP and luciferase assays. Co-IP was employed to assess the interaction between ChREBP and Rbbp6, as well as the ubiquitination of ChREBP.

Results

Hdac3 and ChREBP were upregulated, but Mbnl1 and circMlxipl were downregulated in islets from diabetic mice and lipotoxic β-cells. Mbnl1 overexpression protected against PA-induced impairments in lipotoxic β-cells through modulating back-splicing of circMlxipl and suppressing ChREBP. Hdac3 served as a transcriptional repressor of Mbnl1, and it was implicated in circMlxipl-mediated protection via regulating ChREBP expression in lipotoxic β-cells. Lack of circMlxipl inhibited Rbbp6-mediated ubiquitin-proteasomal degradation of ChREBP in lipotoxic β-cells. In vivo studies revealed that Hdac3 knockdown or Mbnl1 overexpression alleviated diabetes symptoms through circMlxipl-regulated ChREBP in diabetic mice.

Conclusion

Mbnl1-mediated alternative splicing of circMlxipl regulates Rbbp6-involved ChREBP turnover to inhibit lipotoxicity-induced β-cell damage.
PIPETS: a statistically informed, gene-annotation agnostic analysis method to study bacterial termination using 3′-end sequencing
Authors: Furumo Quinlan , Meyer Michelle M.
Published: November 2024

Background

Over the last decade the drop in short-read sequencing costs has allowed experimental techniques utilizing sequencing to address specific biological questions to proliferate, oftentimes outpacing standardized or effective analysis approaches for the data generated. There are growing amounts of bacterial 3′-end sequencing data, yet there is currently no commonly accepted analysis methodology for this datatype. Most data analysis approaches are somewhat ad hoc and, despite the presence of substantial signal within annotated genes, focus on genomic regions outside the annotated genes (e.g. 3′ or 5′ UTRs). Furthermore, the lack of consistent systematic analysis approaches, as well as the absence of genome-wide ground truth data, make it impossible to compare conclusions generated by different labs, using different organisms.

Results

We present PIPETS, (Poisson Identification of PEaks from Term-Seq data), an R package available on Bioconductor that provides a novel analysis method for 3'-end sequencing data. PIPETS is a statistically informed, gene-annotation agnostic methodology. Across two different datasets from two different organisms, PIPETS identified significant 3'-end termination signal across a wider range of annotated genomic contexts than existing analysis approaches, suggesting that existing approaches may miss biologically relevant signal. Furthermore, assessment of the previously called 3′-end positions not captured by PIPETS showed that they were uniformly very low coverage.

Conclusions

PIPETS provides a broadly applicable platform to explore and analyze 3′-end sequencing data sets from across different organisms. It requires only the 3′-end sequencing data, and is broadly accessible to non-expert users.
Moderate benefit of escape room game on learning outcome in medicine
Authors: Fedorcsak Peter
Published: November 2024

Background

Well-designed escape room games engage students with complex problems and challenge clinical and teamwork skills, but their impact on learning has been uncertain. This study aimed to estimate the effect size of escape room game on performance in a broad knowledge test.

Methods

During clinical rotation in reproductive endocrinology and infertility (REI), medical students participated in a 3-hour small-group class. For 2 semesters, groups had traditional patient visits and case discussions, and for 3 semesters, patient visits and an escape room game including debrief. The game was set up in the outpatient clinic, the puzzles were taken from clinical problems in REI, and challenges included operating an ultrasound scanner on a mannequin. Mid-semester, students completed a test of general knowledge in REI. To estimate the effect of small group class on declarative knowledge, test scores of students who had already had the class (exposed) were compared to scores of those who had not yet had the class (control).

Results

Students were highly satisfied with gamified teaching. Those who attended the small group class without the escape room game achieved similar scores on knowledge test than control students (Cohen’s d = 0.05, 95%CI -0.58 to 0.68, n = 71). Students who played the escape room game achieved marginally higher score than respective controls (Cohen’s d = 0.22, 95%CI -0.1 to 0.53, n = 182).

Conclusions

Escape room game may improve learning outcome of a traditional small group class, but the effect of a single game session on declarative knowledge is modest and is unlikely to exceed related instructional methods like simulation.
Challenges and support needs among persons with a migration background who use drugs in four European metropolitan cities
Authors: Pouille Aline , De Ruysscher Clara , van Selm Lena , van Amsterdam Jan , van den Brink Wim , Busz Machteld , Perez Gayo Roberto , Atzemis Marios , Vanderplasschen Wouter ,   the SEMID-EU consortium, Moura Joanna , Bakker Ingrid , Perez Roberto , Baghdadi Sultan , Köhlein Ralf , Leicht Astrid , Lovera Mathieu , Detrez Victor , Avril Elisabeth
Published: November 2024

Background

Persons who migrate for economic reasons, along with asylum seekers and refugees, face multiple personal experiences and societal inequalities that increase the risk of mental health problems and substance dependency, compounded by intersectional social and economic vulnerabilities. The precarious situation and limited access to care of persons with a migration background who use drugs (PMWUD) in Europe raises concern. Therefore, this qualitative study explores the challenges and support needs of a sample of PMWUD in vulnerable situations living in Amsterdam, Athens, Berlin and Paris.

Methods

This study employed a community-based participatory approach. Through semi-structured interviews with PMWUD (n = 99), we identified  (service) needs of a diversity of PMWUD in Europe. Participants were recruited through a combination of community gatekeepers, venue-based sampling, and snowball sampling. Trained community researchers conducted the interviews, which focused on participants’ living situation, substance use, physical and mental health, and employment opportunities.

Results

Despite substantial heterogeneity among the PMWUD, several common themes emerged across all groups. Participants frequently mentioned early childhood adversity, limited social networks leading to loneliness, medical, psychological, and substance use issues, histories of personal violence or poverty, homelessness, lack of necessary documents for health care, social security, and employment, and encounters with the criminal justice system. These intertwined and mutually reinforcing factors simultaneously functioned as barriers to care and support, alongside other barriers such as linguistic and cultural differences, and stigma and discrimination. Due to social exclusion, migration, and substance dependence, participants had limited reliable social networks. Therefore, they often had to rely on accessible and low-threshold services. Harm reduction services played a significant role in providing support to PMWUD. Most PMWUD indicated that basic needs for hygiene and food were met thanks to local organizations. Differences in housing opportunities and access to harm reduction services were identified in each city.

Conclusion

Structural barriers toward treatment and care, often related to administrative requirements, stand in the way of appropriate care for PMWUD. Linguistically and culturally sensitive outreach activities with limited practical requirements could break down social and treatment barriers.
The cell adhesion molecule CD44 acts as a modulator of 5-HT7 receptor functions
Authors: Borsdorf Saskia , Zeug Andre , Wu Yuxin , Mitroshina Elena , Vedunova Maria , Gaitonde Supriya A. , Bouvier Michel , Wehr Michael C. , Labus Josephine , Ponimaskin Evgeni
Published: November 2024

Background

Homo- and heteromerization of G protein-coupled receptors (GPCRs) plays an important role in the regulation of receptor functions. Recently, we demonstrated an interaction between the serotonin receptor 7 (5-HT7R), a class A GPCR, and the cell adhesion molecule CD44. However, the functional consequences of this interaction on 5-HT7R-mediated signaling remained enigmatic.

Methods

Using a quantitative FRET (Förster resonance energy transfer) approach, we determined the affinities for the formation of homo- and heteromeric complexes of 5-HT7R and CD44. The impact of heteromerization on 5-HT7R-mediated cAMP signaling was assessed using a cAMP responsive luciferase assay and a FRET-based cAMP biosensor under basal conditions as well as upon pharmacological modulation of the 5-HT7R and/or CD44 with specific ligands. We also investigated receptor-mediated G protein activation using BRET (bioluminescence resonance energy transfer)-based biosensors in both, homo- and heteromeric conditions. Finally, we analyzed expression profiles for 5-HT7R and CD44 in the brain during development.

Results

We found that homo- and heteromerization of the 5-HT7R and CD44 occur at similar extent. Functionally, heteromerization increased 5-HT7R-mediated cAMP production under basal conditions. In contrast, agonist-mediated cAMP production was decreased in the presence of CD44. Mechanistically, this might be explained by increased Gαs and decreased GαoB activation by 5-HT7R/CD44 heteromers. Unexpectedly, treatment of the heteromeric complex with the CD44 ligand hyaluronic acid boosted constitutive 5-HT7R-mediated cAMP signaling and receptor-mediated transcription, suggesting the existence of a transactivation mechanism.

Conclusions

Interaction with the hyaluronan receptor CD44 modulates both the constitutive activity of 5-HT7R as well as its agonist-mediated signaling. Heteromerization also results in the transactivation of 5-HT7R-mediated signaling via CD44 ligand.
Evidence of rustrela virus-associated feline staggering disease in Sweden since the 1970s
Authors: Thilén Emma , Rubbenstroth Dennis , Tengstrand Sofia , Pfaff Florian , Wensman Jonas Johansson , Ley Cecilia
Published: November 2024

Background

Staggering disease (SD) is a severe neurological disease that has been regularly reported in Swedish cats since the beginning of the 1970s. The aetiology of SD has been debated, but novel rustrela virus (RusV) was recently suggested as the causative agent in Swedish cases dating from 2017 onwards. However, whether RusV was associated with earlier cases of feline SD in Sweden remained unknown. Further, presence of RusV in extraneural tissues of RusV-infected cats and viral transmission routes for RusV are still unknown. Therefore, we investigated the presence of RusV in nervous tissue of historical cases of plausible feline SD in Sweden, dating back to the 1970s, as well as the presence of RusV in selected extraneural tissues.

Formalin-fixed, paraffin-embedded brain and spinal cord from 14 encephalitic cats matching the criteria for SD based on clinical and pathological records, and five non-encephalitic control cats were screened for the presence of RusV antigen and RNA using immunohistochemistry (IHC) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. Extraneural presence of RusV antigen was investigated by IHC in four known RusV-positive cats. Morphologic changes were evaluated using light microscopy. In addition, the 14 encephalitic cats were tested for Borna disease virus 1 (BoDV-1) RNA by RT-qPCR.

Results

Morphologic findings compatible with SD were confirmed in 13 of 14 encephalitic cats. All 13 cats were RusV-positive by IHC and 12 of them also by RT-qPCR. One encephalitic cat, morphologically and clinically untypical of SD, as well as all control cats tested negative for RusV RNA and showed either negative or uncertain RusV immunolabeling. There was no firm evidence of extraneural presence of RusV. All encephalitic cats were negative for BoDV-1.

Conclusions

We show that RusV has infected cats in Sweden as far back as the 1970s, whereas BoDV-1 was not detected in any of the investigated cats. This further strengthens RusV as the causative agent of feline SD. Our findings suggest that RusV is strongly neurotropic in cats and that the cat may represent a dead-end host. Further investigations into the pathogenesis of RusV-associated meningoencephalomyelitis in cats are warranted, including disease transmission, pathophysiologic responses and mechanisms of neuronal dysfunction.
Deep learning-based Emergency Department In-hospital Cardiac Arrest Score (Deep EDICAS) for early prediction of cardiac arrest and cardiopulmonary resuscitation in the emergency department
Authors: Deng Yuan-Xiang , Wang Jyun-Yi , Ko Chia-Hsin , Huang Chien-Hua , Tsai Chu-Lin , Fu Li-Chen
Published: November 2024

Background

Timely identification of deteriorating patients is crucial to prevent the progression to cardiac arrest. However, current methods predicting emergency department cardiac arrest are primarily static, rule-based with limited precision and cannot accommodate time-series data. Deep learning has the potential to continuously update data and provide more precise predictions throughout the emergency department stay.

Methods

We developed and internally validated a deep learning-based scoring system, the Deep EDICAS for early prediction of cardiac arrest and a subset of arrest, cardiopulmonary resuscitation (CPR), in the emergency department. Our proposed model effectively integrates tabular and time series data to enhance predictive accuracy. To address data imbalance and bolster early prediction capabilities, we implemented data augmentation techniques.

Results

Our system achieved an AUPRC of 0.5178 and an AUROC of 0.9388 on on data from the National Taiwan University Hospital. For early prediction, our system achieved an AUPRC of 0.2798 and an AUROC of 0.9046, demonstrating superiority over other early warning scores. Moerover, Deep EDICAS offers interpretability through feature importance analysis.

Conclusion

Our study demonstrates the effectiveness of deep learning in predicting cardiac arrest in emergency department. Despite the higher clinical value associated with detecting patients requiring CPR, there is a scarcity of literature utilizing deep learning in CPR detection tasks. Therefore, this study embarks on an initial exploration into the task of CPR detection.
Upregulation of CD244 promotes CD8+ T cell exhaustion in patients with alveolar echinococcosis and a murine model
Authors: Wang Maolin , Deng Bingqing , Jiang Tiemin , Duolikun Adilai , Li Yinshi , ainiwaer Abidan , Kang Xuejiao , Zheng Xuran , Rousu Zibigu , Yu Qian , Li Jing , Wang Hui , Zhang Chuanshan , Aji Tuerganaili , Shao Yingmei
Published: November 2024

Background

In patients with alveolar echinococcosis (AE), CD8+ T cells undergo functional exhaustion, which accelerates the malignant progression of AE. However, the role of inhibitory receptor CD244 in mediating CD8+ T cell exhaustion remains elusive.

Methods

CD244 expression on exhausted CD8+ T cells in the close liver tissue (CLT) of AE patients was analyzed using single-cell RNA sequencing data. Immunohistochemistry and immunofluorescence were employed to detect CD244 expression. Flow cytometry was used to assess the impact of CD244 on differentiation and effector function of CD8+ T cells in patients with AE, in vitro and in vivo models. Reactive oxygen species (ROS) and oxygen consumption rate (OCR) were measured to evaluate the influence of CD244 on mitochondrial function of CD8+ T cells.

Results

CD244+CD8+ T cells in the CLT of AE patients exhibit a more terminal differentiation phenotype, with reduced secretion of IFN-γ and TNF-α. In vitro studies revealed that CD8+ T cells from CD244-deficient mice produced higher levels of IFN-γ, TNF-α and Granzyme B. In vivo studies revealed that CD244 deficiency enhanced the secretion capacity of IFN-γ and TNF-α by CD8+ T cells, inhibiting the growth of metacestodes. Moreover, CD244 deficiency leads to a decrease in ROS levels in liver CD8+ T cells, while significantly increasing their adenosine triphosphate (ATP)-linked oxygen consumption rate.

Conclusions

CD244 facilitates AE disease progression by mediating immune exhaustion in CD8+ T cells.

Graphical abstract
Prognostic effects of glycaemic variability on diastolic heart failure and type 2 diabetes mellitus: insights and 1-year mortality machine learning prediction model
Authors: Yang Zhenkun , Li Yuanjie , Liu Yang , Zhong Ziyi , Ditchfield Coleen , Guo Taipu , Yang Mingjuan , Chen Yang
Published: November 2024

Background

Diastolic heart failure (DHF) and type 2 diabetes mellitus (T2DM) often coexist, causing increased mortality rates. Glycaemic variability (GV) exacerbates cardiovascular complications, but its impact on outcomes in patients with DHF and T2DM remains unclear. This study examined the relationships between GV with mortality outcomes, and developed a machine learning (ML) model for long-term mortality in these patients.

Methods

Patients with DHF and T2DM were included from the Medical Information Mart for Intensive Care IV, with admissions (2008–2019) as primary analysis cohort and admissions (2020–2022) as external validation cohort. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to evaluate the associations of GV with 90-day, 1-year, and 3-year all-cause mortality. The primary analysis cohort was split into training and internal validation cohorts, then developing ML models for predicting 1-year all-cause mortality in training cohort, which were validated using the internal and external validation cohorts.

Results

2,128 patients with DHF and T2DM were included in primary analysis cohort (meidian age 71.0years [IQR: 62.0–79.0]; 46.9% male), 498 patients with DHF and T2DM were included in the external validation cohort (meidian age 75.0years [IQR: 67.0–81.0]; 54.0% male). Multivariate Cox proportional hazards models showed that high GV tertiles were associated with higher risk of 90-day (T2: HR 1.45, 95%CI 1.09–1.93; T3: HR 1.96, 95%CI 1.48–2.60), 1-year (T2: HR 1.25, 95%CI 1.02–1.53; T3: HR 1.54, 95%CI 1.26–1.89), and 3-year (T2: HR 1.31, 95%CI: 1.10–1.56; T3: HR 1.48, 95%CI 1.23–1.77) all-cause mortality, compared with lowest GV tertile. Chronic kidney disease, creatinine, potassium, haemoglobin, and white blood cell were identified as mediators of GV and 1-year all-cause mortality. Additionally, GV and other clinical features were pre-selected to construct ML models. The random forest model performed best, with AUC (0.770) and G-mean (0.591) in internal validation, with AUC (0.753) and G-mean (0.599) in external validation.

Conclusion

GV was determined as an independent risk factor for short-term and long-term all-cause mortality in patients with DHF and T2DM, with a potential intervention threshold around 25.0%. The ML model incorporating GV demonstrated strong predictive performance for 1-year all-cause mortality, highlighting its importance in early risk stratification management of these patients.
Determinants of non-adherence to antibiotic treatment guidelines in hospitalized adults with suspected community-acquired pneumonia: a prospective study
Authors: Markussen Dagfinn Lunde , Wathne Jannicke Slettli , Ritz Christian , van Werkhoven Cornelis H. , Serigstad Sondre , Bjørneklett Rune Oskar , Ulvestad Elling , Knoop Siri Tandberg , Jenum Synne , Grewal Harleen M. S.
Published: November 2024

Background

Antimicrobial resistance (AMR) is a global health threat with millions of deaths annually attributable to bacterial resistance. Effective antimicrobial stewardship programs are crucial for optimizing antibiotic use. This study aims to identify factors contributing to deviations from antibiotic treatment guidelines in hospitalized adults with suspected community-acquired pneumonia (CAP).

Methods

We conducted a prospective study at Haukeland University Hospital's Emergency Department in Bergen, Norway, from September 2020 to April 2023. Patients were selected from two cohorts, with data on clinical and microbiologic test results collected. We analysed adherence of antibiotic therapy to guidelines for the choice of empirical treatment and therapy duration using multivariate regression models to identify predictors of non-adherence.

Results

Of the 523 patients studied, 479 (91.6%) received empirical antibiotic therapy within 48 h of admission, with 382 (79.7%) adhering to guidelines. However, among the 341 patients included in the analysis of treatment duration adherence, only 69 (20.2%) received therapy durations that were consistent with guideline recommendations. Key predictors of longer-than-recommended therapy duration included a C-reactive protein (CRP) level exceeding 100 mg/L (RR 1.37, 95% CI 1.18–1.59) and a hospital stay longer than two days (RR 1.22, 95% CI 1.04–1.43). The primary factor contributing to extended antibiotic therapy duration was planned post-discharge treatment. No significant temporal trends in adherence to treatment duration guidelines were observed following the publication of the updated guidelines.

Conclusion

While adherence to guidelines for the choice of empirical antibiotic therapy was relatively high, adherence to guidelines for therapy duration was significantly lower, largely due to extended post-discharge antibiotic treatment. Our findings suggest that publishing updated guidelines alone is insufficient to change clinical practice. Targeted stewardship interventions, particularly those addressing discharge practices, are essential. Future research should compare adherence rates across institutions to identify factors contributing to higher adherence and develop standardized benchmarks for optimal antibiotic stewardship.

Trial registration NCT04660084.
Depth use of wild Atlantic salmon post-smolts migrating through fjords
Authors: Bjerck Helge B. , Urke Henning A. , Haugen Thrond O. , Alfredsen Jo Arve , Kristensen Torstein
Published: November 2024

Juvenile Atlantic salmon (Salmo salar), known as post-smolt as they enter the sea, undergo an arduous migration from their natal rivers to their feeding grounds in the North Atlantic Ocean. It has become increasingly important to understand how post-smolts use the fjord environment as they migrate in order to properly assess the potential threats posed by large-scale salmon farming. Chief among these threats is the increased numbers of ectoparasitic salmon lice (Lepeophtheirus salmonis) inhabiting the water column, which are known to have specific depth preferences based on light, temperature, and salinity. Here, we present data on the depth use of wild Atlantic salmon post-smolts migrating through fjords. We aimed to investigate to what extent depth use varied throughout the fjord and from year to year. Using acoustic telemetry, tagged fish from four rivers in two fjords in western Norway were monitored as they migrated towards the open sea during two consecutive years. We found that post-smolts predominantly migrated in the top three meters of the water column throughout the length of both fjord systems. Among 61 successful migrants and 7013 detections, 98% of detections were in the top three meters of the water column. This corresponds well with past findings showing similar depth use in hatchery-reared smolt and in adult Atlantic salmon kelts returning to their feeding grounds after spawning. We found little evidence of a consistent diel pattern in depth use. Our results support assumptions of representative sampling when trawling the upper portion of the water column for post-smolts in order to estimate sea lice infection rates and may improve the precision of efforts to model salmon lice infection risk. The results may also be valuable in evaluating other threats to wild salmon.
Percutaneous management of chronic total occlusion of the portal vein: a retrospective analysis of technical aspects and outcomes
Authors: Dulcetta Ludovico , Marra Paolo , Muglia Riccardo , Carbone Francesco Saverio , Viganò Mauro , Di Giorgio Angelo , D’Antiga Lorenzo , Fagiuoli Stefano , Sironi Sandro
Published: November 2024

Background

Chronic total occlusion (CTO) of the portal vein is one of the main causes of portal hypertension, which may result in life-threatening complications often managed by interventional radiology (IR). The aim of this study is to report the innovative experience with percutaneous revascularization therapy in the management of portal vein CTO in paediatric and adult patients.

Materials and methods

From January 2020 to December 2023 consecutive paediatric and adult patients with severe portal hypertension resulting from portal vein CTO who underwent attempts at percutaneous recanalization were retrospectively reviewed. Technical aspects including the percutaneous approach, portal vein stenting, transjugular intrahepatic portosystemic shunt (TIPS) creation, varices embolization and clinical outcomes including adverse events and control of portal hypertension were analyzed. Technical success was defined as at least partial restoration of the portal vein patency at the final angiogram. Clinical success was defined as the improvement of clinical-laboratory signs of portal hypertension and control for variceal bleeding.

Results

Fifteen patients (median age = 21 years, range = 59 years; 10 males; 5 children) with portal vein CTO underwent a total of 25 percutaneous revascularization procedures. Nine patients (60%; 5 children, 4 adults) were liver transplant recipients. All patients except one had cavernous transformation of the extra-hepatic portal vein, involving the spleno-mesenteric confluence in 5 cases. Technical success was achieved in 13/15 (87%) patients of whom 8 had portal revascularization through the placement of an extra-hepatic stent; indeed, in six cases, a TIPS was performed to achieve sustained portal vein patency. Embolization of varices and/or cavernoma was performed in 12 patients. Adverse events occurred in 2/15 (splenic artery perforation and hemoperitoneum, one each) managed without sequelae. Technical success led to clinical success in all the 13/15 (87%) cases, with a median follow-up of 20 months (IQR 4–34 months).

Conclusion

CTO can be managed effectively by interventional radiology. Restored portal flow physiology alone is possible in most patients, while TIPS may be required in a small proportion of them, to prolong portal vein patency and control portal hypertension.
Exploring the diverse nature of business processes in organisations in Industry 4.0/5.0
Authors: Szelągowski Marek , Berniak-Woźny Justyna , Sliż Piotr , Potoczek Natalia , Napieraj Aneta , Podobińska-Staniec Marta , Senkus Piotr
Published: November 2024

The article investigates the differentiation of business processes in contemporary organisations based on their dynamics (predictability). It presents and summarises research on the nature of business processes in Industry 4.0/5.0 conducted by researchers from 7 Polish universities. The study combines a systematic literature review based on the SCOPUS database and a survey of 466 respondents with an analysis of 12,573 processes. Filling the cognitive gap in Industry 4.0/5.0 organisations, the study reveals that nearly 60% of all BPs are semi-structured processes. At the same time, it shows a strong relationship between the importance of processes for the organisation and the dynamics of their execution. This finding highlights the importance of adaptability and flexibility in organisational dynamics, reflecting the nuanced nature of most BPs. The article presents original research on a diverse sample of Polish enterprises based on the simplified Business Processes Nature Assessment Framework. The presented research results indicate the need to update the essential elements of the BPM concept, such as BPM Lifecycle, BPM implementation method, or BPM maturity assessment, to consider various assessment criteria and implementation methods depending on the nature of BPs. The study contributes to advancing both theoretical knowledge and practical applications in the field of BPM, providing valuable insights for scholars, practitioners, and policymakers alike.