bluuebunny/crossref_metadata_2025 huggingface dataset:
Relato de uma série de casos de iatrogenias atendidas em um pronto socorro de um hospital público de ensino do oeste do Paraná decorrentes de cirurgias odontológicas ambulatoriais malsucedidas
Authors: Vidor Niviane Dorigan , Garbin Júnior Eleonor Álvaro , Griza Geraldo Luiz , Ernica Natasha Magro , Conci Ricardo Augusto
Published: March 2024

Introdução: Procedimentos clínico-cirúrgicos são frequentes nos consultórios odontológicos e devem ser realizados com cautela e responsabilidade, uma vez que hemorragias, hematomas, lesões em partes moles adjacentes, fraturas ósseas, infecções e comprometimento de estruturas anatômicas importantes podem ocorrer durante esses procedimentos. Objetivo: Analisar e relatar sete casos clínicos em que ocorreram iatrogenias e que foram atendidas no Hospital Universitário do Oeste do Paraná (HUOP). Em ambos os casos ocorreram complicações devido às falhas na execução dos procedimentos clínicos por meio dos Cirurgiões-Dentistas. Relatos de caso: Os casos abordados no presente estudos se trata de fraturas mandibulares decorrentes de exodontia de terceiro molar e remoção de protocolo inferior para higienização, hemorragia no pós-cirúrgico causada por falha na anamnese e na solicitação de exames complementares, abscessos de origem odontogênica e corpo estranho em seio maxilar após tentativa de exodontia simples. Em todos os casos foi possível observar erros, seja por falta de planejamento prévio, não execução de um bom exame clínico ou execução de técnica insuficiente. Conclusão: O profissional é o responsável por planejar adequadamente os casos e executar de maneira a garantir a segurança do paciente.
Changes in the use of continuous deep sedation in the Netherlands
Authors:   , Heijltjes Madelon Tessa
Published: March 2024

Summary
At the end of life, patients may suffer from severe symptoms. When these symptoms cannot be controlled by conventional treatment options, palliative sedation can relieve suffering. The most far reaching form of sedation is continuous deep sedation (CDS), which involves lowering the consciousness level of a dying patient deeply and continuously until the end of life. The acceptability of CDS has been highly debated in the past decades.
In the Netherlands, end-of-life practices have been studied approximately every 5 years from 1990 onwards. These studies showed that the use of CDS has increased from 8.2% to 18.3% of all deceased people between 2005 and 2015. The latest report even shows a frequency of 23%. This increase raises questions about its background and about how this increase should be valued. The aim of this thesis is to provide insight in current practices of CDS, to explore how the use of CDS has changed in the Netherlands between 2005 and 2015, and to identify reasons for the increase of the use of CDS.

In this thesis; we show results from repetitive nationwide questionnaire studies on end-of-life decision practices among physicians in the Netherlands based on a stratified sample of deaths, we present a systematic literature review, we describe data from the Dutch Care Program for the Dying that provide insight into symptoms that patients experience at the end of life, we report a questionnaire study among physicians in eight different countries about their practices and experiences with CDS, and we describe qualitative interview studies among Dutch health care professionals and Dutch patients and relatives on the use of CDS.

It can be concluded, based on the findings of this thesis that different factors may have contributed to the increase of CDS in the Netherlands. Firstly, there has been an increased awareness of the option of starting CDS among health care professionals and among the public.
Secondly, health care professionals experienced that, compared with several years before, patients, relatives, and sometimes even other health care professionals are increasingly inclined to raise the subject of CDS in cases of severe suffering.
Thirdly, there has been a broadening of the indications to start CDS. Where, previously, indications for sedation were based on symptoms of a physical origin, increasingly, in recent years, symptoms of non-physical origin, such as fear and existential suffering, more often play a role in the decision to start CDS.
Fourthly, the general opinion is that there is no need for a dying patient to suffer at the end of life, as symptoms can always be relieved, if necessary by the use of sedatives.

The increasing use of CDS demonstrates that what was originally seen as an exceptional option to relieve severe refractory suffering, has now become a more common practice in physicians end-of-life care for terminally ill patients.
HEART DISEASE PREDICTION BY EMPLOYING BEST RISK FACTORS USING MACHINE LEARNING
Authors:   Department of IT  Britts Imperial University College  Sharjah, UAE, Nellyet Annette , Ansari Salmodin ,   Nest Academy of Management Education  Dubai, UAE
Published: March 2024

Heart disease is the major global cause of death in the modern era. Heart illness might be difficult to diagnose. It requires a number of expensive diagnostic tests to be found. The scientific community is undergoing a transformation thanks to machine learning (ML), a subset of artificial intelligence. In this paper, exploratory data analysis (EDA) utilizing multivariate analysis is utilized to find correlations and outliers in the data. The study's dataset consists of 270 records with 14 variables, including age, chest pain type, blood pressure, blood glucose level, resting ECG, heart rate, and chest pain. Logistic Regression algorithm is employed on the dataset to predict heart disease on the basis of chosen risk factors that are obtained using recursive feature elimination incorporating random forest classifier method. The paper entails pre-processing methods, proposed algorithms, evaluation metrics and an accurate prediction based on the methodology.
Liver Elastography for the Detection of Methotrexate-Induced Liver Injury: A Retrospective Study
Authors: Brotherton Tim , Mahmoud Maya , Burton Sam , Qureshi Kamran
Published: March 2024

Background: Liver biopsy, the gold standard for monitoring of methotrexate-induced liver injury, is associated with significant morbidity and mortality. Transient elastography (TE) has been used as a non-invasive alternative to detect liver stiffness.

Aim: To assess the utility of TE in detecting liver fibrosis in patients with methotrexate use.

Methods: A retrospective chart review was performed for 35 patients referred to the liver clinic for evaluation of suspected methotrexate-induced liver injury. Demographic, clinical, histopathological, and elastographic data were collected and interpreted. Liver stiffness measurement (LSM) and controlled attenuation parameter were recorded from TE results.

Results: Thirty-five patients with a mean age of 58 years, including 23 females (66%), were included. The median LSM by TE was 10.8 kPa and the median controlled attenuation parameter was 303 dB/m. A total of 12 out of 35 patients (34%) had evidence of clinical and pathological advanced fibrosis. Using a cut-off elastography value of 10 kPa, the TE yielded 92% sensitivity and 93% negative predictive value for ruling out methotrexate-induced advanced liver fibrosis. Using a higher LSM cut-off point of kPa ≥15.0, specificity was calculated at 87% and positive predictive value at 80%. Area under the receiver operating characteristic curve was 0.80 (95% confidence interval).

Conclusion: FibroScan® (Echosens, Paris, France) has a high sensitivity and specificity for kPa 10 and 15, respectively, for detecting advanced liver fibrosis in patients on methotrexate.
Sparsentan, a Dual Endothelin Type A and Angiotensin II Subtype 1 Receptor Antagonist for the Treatment of Immunoglobulin A Nephropathy: Latest Trial Results, Pharmacokinetic Considerations, and Binding Profile
Authors: Roberts Eleanor
Published: March 2024

Immunoglobulin A nephropathy (IgAN) is one of the most common forms of primary glomerulonephritis. In some patients, it can progress rapidly, leading to proteinuria, kidney failure, and death. Standard of care is traditionally with an angiotensin converting enzyme inhibitor (ACEi), or an angiotensin II (Ang II) receptor blocker (ARB). More recently, drugs targeting both endothelin 1 (ET-1) and Ang II receptors have been developed, as overactivation of such is implicated in IgAN. Sparsentan is a dual ET Type A (ETAR) and Ang II subtype 1 receptor (AT1R) antagonist. The PROTECT study compared sparsentan with the ARB irbesartan, in patients with IgAN and with proteinuria of ≥1 g/day despite stable dose of ACEi/ARB for ≥90 days. Data presented at the 2023 American Society of Nephrology (ASN) Kidney Week showed that use of sparsentan led to sustained (>110 weeks) decreases in proteinuria, and a significantly greater preservation of kidney function, compared with irbesartan. The ongoing SPARTAN study is investigating the use of sparsentan in recently diagnosed, treatment-naïve patients with IgAN. Preliminary data in 12 patients showed rapid and sustained proteinuria reductions, with little change from baseline in estimated glomerular filtration rate (eGFR), body weight, or total body water mean at Week 36. In both studies, sparsentan was generally well-tolerated with, in PROTECT, a comparable safety profile to irbesartan. Data presented at the congress also showed that sparsentan consistently occupies AT1R at levels exceeding ETAR occupancy. This balance is hypothesised to contribute to sparsentan’s limited risk of fluid retention.
Artifacts Caused by Orthodontic Appliances on Magnetic Resonance Imaging: Awareness and Knowledge Level of Maxillofacial Radiologists and Orthodontists
Authors: Pamukçu Umut , Tortop Tuba , Özütürk Özge , Açık Kemaloğlu Sibel , Peker İlkay
Published: March 2024

Objective: Artifacts caused by orthodontic appliances on Magnetic Resonance Imaging (MRI) can affect the image quality and make diagnosis difficult. The debate is ongoing on whether orthodontic appliances should be removed to eliminate these problems. This study aimed to evaluate the awareness and knowledge level of dentists working in maxillofacial radiology and orthodontics about this subject through a questionnaire.

Methods: The questionnaire consisted of 20 items and four parts: A) Personal information, B) Awareness level about the artifacts and complications caused by orthodontic appliances on MRI, C) Knowledge level about the factors related to artifacts and complications caused by orthodontic appliances on MRI, and D) Preventive approaches. The questionnaire was prepared on Google Forms and sent to potential participants via e-mail. The Chi-square (χ2) test was used for the statistical analysis of the variables.

Results: Most participants were aware of the artifacts caused by orthodontic appliances on MRI (90.8%) (93.5% of maxillofacial radiologists and 88.5% of orthodontists) and thought that material type influenced the artifact formation (98.1%) (100% of maxillofacial radiologists and 96.3% of orthodontists). The percentage of participants with 1-5 years of experience who were aware of artifacts was less than those with more experience (p = .033). The percentage of orthodontists who referred patients for orthodontic appliance removal was higher than maxillofacial radiologists who requested the orthodontic appliance removal (93.5%>15%).

Conclusion: Simultaneously increasing demands for both orthodontic treatment and MRI in the society cause concerns about the MRI image quality due to artifacts on images of the head and neck region. The main output of this study is that dentists working in orthodontics and maxillofacial radiology have a high awareness and knowledge about the artifacts and complications caused by orthodontic appliances on MRI.
The Relationship Between the Mentorship Skills and Professional Attitudes of Preceptor Nurses: A Multi-Centre Study
Authors: Dikmen Meryem , Akçin Şenyuva Emine
Published: March 2024

Objective: The research was conducted to determine to evaluate the mentoring skills of the preceptor nurses, their professional attitudes and the relationship between mentorship skills and professional attitudes.

Methods: The study was conducted with all preceptor nurses who guided newly hired nurses (n: 245) that were employed at two university hospitals, two research, and training hospitals, and two private hospitals under the Turkish Ministry of Health. The data were collected between 1 August and 30 October 2017. The research was conducted with a descriptive and relationship-seeking design. The data were collected by using Nurse Information Form, the Mentorship Scale, and the Vocational Professional Attitude Inventory. Frequencies, percentages, means, standard deviations, ANOVA, t-test, Kruskal Wallis tests were used to analyze the data, while Cronbach’s alpha coefficient and Pearson analyses were used for reliability analysis.

Results: This research determined that 80.8% stated that they voluntarily worked as preceptor nurses, 58.8% said they attended training programs on the preceptor, and 84.1% expressed their relationship with the nurse they supervised as a teacher-student relationship. The participants had high mentorship skills (4.27±0.43) and high vocational professional attitudes (147.42±9.56). As the mentorship skills of the participants increased, it was observed that their vocational professional attitudes also significantly increased (p
Bortom görande
Authors: Nordlöf Charlotta
Published: March 2024

En skolas traditioner och vanor kan begränsa vilka kunskaper och syften som dominerar i teknikundervisningen. I den här texten presenteras tre kunskapskategorier som har sitt ursprung i olika kunskapstraditioner. Dessutom presenteras två begrepp - ingenjörsförmågor och medborgarförmågor – som refererar till två långsiktiga syften med teknikundervisning. Resultaten är hämtade från min avhandling som bland annat handlar om vilket teknikinnehåll tekniklärare betonar i sin undervisning. Dessa resultat, som kommer att utvecklas i texten, kan bli ett stöd för lärare när de behöver förhålla sig till tolkningsutrymmet som finns i läroplanen. Resultaten kan därmed bidra till att bredda synen på teknikämnet och dess innehåll.
Karakteristik Pelayanan Gembala Jemaat Menurut 1 Petrus 5:1-4 dan Implementasinya Bagi GPdI Zion Altar Malang
Authors: Tedjo Petter , Heryanto Doni
Published: March 2024

The characteristics of effective pastoral service, as outlined in 1 Peter 5:1-4, entail that pastors are expected to serve as role models for the congregation. Peter expresses hope that these shepherds will be good leaders for the existing flock. Rather than following behind their sheep, pastors are to lead them. The objective of this research is to enable congregation leaders at the Pentecostal Church in Indonesia Zion Altar Malang (hereafter referred to as GPdI Zion Altar Malang) to implement the service characteristics of pastoral care according to 1 Peter 5:1-4. This is prompted by the suboptimal nature of the service characteristics of pastors in their oversight of local churches. The research, conducted using qualitative methods, involved data collection from several participants, including pastors and supporting servants involved in pastoral care at GPdI Zion Altar Malang. The findings of the research revealed issues such as poorly organized financial management, suboptimal implementation of teaching programs, and exacerbated by the absence of counselling services for congregation members grappling with issues in their faith journey. Pastors acknowledge the necessity of enhancing competency to realize the characteristics of pastoral care in accordance with God’s Word, particularly as outlined in 1 Peter 5:1-4, for the spiritual growth of congregation members.
Alusi Anti-Imperial dalam Misi Universal: Elaborasi Matius 28:18-20
Authors: Prabowo Paulus Dimas
Published: March 2024

Matthew 28:18-20 is unique material from Matthew that is not found in other synoptic gospels. Considering the political situation under Roman imperialism and the initial recipients' Jewish background, it is worth asking how Matthew structured his unique material so that it was relevant to the conditions prevailing at that time. The purpose of this article is to prove that there are allusions to the Old Testament in Matthew 28:18-20 so that the intended use can be understood and fits the context. The methods used are structural analysis, style analysis, and allusion analysis. The results of the discussion prove that Matthew 28:18-20 contains allusions to Daniel 7:13-14 and Isaiah 7:14; 8:8,10 which is anti-imperial in nature so that recipients of Matthew's Gospel are given the basis and encouragement for courage in carrying out the Great Commission even in a situation of Roman imperialism.
Oral origin of the placenta microbiome in pregnant women with preeclampsia
Authors: Cooper Shontreal M. , Borgida Adam , Thacker Sejal , Hammer Erica , Hariharan Amirtha , Kuo ChiaLing , Blanck Nyle , Yuan Hanshu , Panier Hunter , Lin Qingqi , Maas Kendra , Campbell Winston , Zhou Yanjiao
Published: March 2024

Preeclampsia (PE) is a leading cause of morbidity and mortality in pregnancy with elusive etiology. Patients with PE are thought to be associated with a higher rate of periodontal diseases (PDs) and changes of oral bacteria with targeted PCR techniques. However, few studies have investigated the associations between oral microbiome dysbiosis and secondarily disseminated microbes in the placenta simultaneously in patients with PE. The association between detected microbiome in placenta and systemic inflammation in PE is also unclear. We enrolled 54 pregnant patients with and without PE and PD, and profiled the subgingival and placenta microbiome by the V4 region of 16S rRNA gene sequencing. Systemic inflammatory markers tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), lipopolysaccharide binding protein (LBP), and interleukins 6 and 8 (IL-6 and IL-8) in blood were measured by ELISA. We found that PD significantly increased the risk of PE after adjusting for age and smoking status (OR = 2.26, 95% CI = 1.14–4.48, p = 0.024). A combined group of oral-associated bacteria Veillonella, Fusobacterium, Haemophilus, Granulicatella, Streptococcus, Gemella, and Neisseria in placenta had a significantly higher prevalence in women with PE compared to women without PE (53.8% vs. 19.0%, p = 0.018), with the highest prevalence in patients with both PE and PD (58.8%). The relative abundance of Haemophilus, Veillonella, and Fusobacterium in subgingival samples was significantly higher in patients with PE than those without PE. The relative abundance of Haemophilus in subgingival samples was associated with increased risk of PE (OR = 2.11, 95% CI = 1.11–4.52, p = 0.032). Proinflammatory cytokine analysis showed that PE patients with PD had higher blood IL-8 levels than PE patients without PD (p = 0.026). CRP, LBP, and TNF-α showed no statistical difference in patients with and without PE or PD. Blood IL-6 levels were significantly higher in patients with detectable placenta microbiome compared to those without placenta microbiome (p = 0.028). Together, our data suggest a potential oral origin of the placental microbiota present in patients with PE, and the microbiota detected in placenta is associated with increased IL-6 level in the blood.
Stable knockdown of Drp1 improves retinoic acid-BDNF-induced neuronal differentiation through global transcriptomic changes and results in reduced phosphorylation of ERK1/2 independently of DUSP1 and 6
Authors: Ghani Marvi , Zohar Peleg , Ujlaki Gyula , Tóth Melinda , Amsalu Hailemariam , Póliska Szilárd , Tar Krisztina
Published: March 2024

Background: Dynamin-related protein Drp1 —a major mitochondrial fission protein— is widely distributed in the central nervous system and plays a crucial role in regulating mitochondrial dynamics, specifically mitochondrial fission and the organelle's shaping. Upregulated Drp1 function may contribute to the pathological progression of neurodegenerative diseases by dysregulating mitochondrial fission/ fusion. The study aims to investigate the effects of Drp1 on retinoic acid-BDNF-induced (RA-BDNF) neuronal differentiation and mitochondrial network reorganization in SH-SY5Y neuroblastoma cells.

Methods: We generated an SH-SY5Y cell line with stably depleted Drp1 (shDrp1). We applied RNA sequencing and analysis to study changes in gene expression upon stable Drp1 knockdown. We visualized the mitochondria by transmission electron microscopy and used high-content confocal imaging to characterize and analyze cell morphology changes and mitochondrial network reorganization during neuronal differentiation.

Results: shDrp1 cells exhibited fused mitochondrial ultrastructure with perinuclear clustering. Stable knockdown of Drp1 resulted in the upregulation of genes involved in nervous system development. High content analysis showed improved neurite outgrowth, segmentation, and extremities in differentiated shDrp1 cells. Neuronal differentiation was associated with a significant reduction in ERK1/2 phosphorylation, and ERK1/2 phosphorylation was independent of the dual specificity phosphatases DUSP1/6 in shDrp1 cells. Differentiated control underwent mitochondrial morphology remodeling, whereas differentiated shDrp1 cells retained the highly fused mitochondria and developed long, elongated structures. The shDrp1 cells responded to specific apoptotic stimuli like control in vitro, suggesting that Drp1 is not a prerequisite for apoptosis in SH-SY5Y cells. Moreover, Drp1 downregulation reduced the formation of toxic mHtt aggregates in vitro.

Discussion: Our results indicate that Drp1 silencing enhances RA-BDNF-induced neuronal differentiation by promoting transcriptional and mitochondrial network changes in undifferentiated cells. We also demonstrate that the suppression of Drp1 reduces toxic mHtt aggregate formation in vitro, suggesting protection against neurotoxicity. Thus, Drp1 may be an attractive target for further investigation in future strategies to combat neurodegenerative diseases.
Western diet-induced ultrastructural changes in mouse pancreatic acinar cells
Authors: Lipovšek Saška , Dolenšek Jurij , Dariš Barbara , Valladolid-Acebes Ismael , Vajs Tanja , Leitinger Gerd , Stožer Andraž , Skelin Klemen Maša
Published: March 2024

Mouse models of diet-induced type 2 diabetes mellitus provide powerful tools for studying the structural and physiological changes that are related to the disease progression. In this study, diabetic-like glucose dysregulation was induced in mice by feeding them a western diet, and light and transmission electron microscopy were used to study the ultrastructural changes in the pancreatic acinar cells. Acinar necrosis and vacuolization of the cytoplasm were the most prominent features. Furthermore, we observed intracellular and extracellular accumulation of lipid compounds in the form of lipid droplets, structural enlargement of the cisternae of the rough endoplasmic reticulum (RER), and altered mitochondrial morphology, with mitochondria lacking the typical organization of the inner membrane. Last, autophagic structures, i.e., autophagosomes, autolysosomes, and residual bodies, were abundant within the acinar cells of western diet-fed mice, and the autolysosomes contained lipids and material of varying electron density. While diets inducing obesity and type 2 diabetes are clearly associated with structural changes and dysfunction of the endocrine pancreas, we here demonstrate the strong effect of dietary intervention on the structure of acinar cells in the exocrine part of the organ before detectable changes in plasma amylase activity, which may help us better understand the development of non-alcoholic fatty pancreas disease and its association with endo- and exocrine dysfunction.
Public engagement and collaboration for carbon dioxide removal: lessons from a project in the Dominican Republic
Authors: Hilser Harry , Hiraldo Lia , Moreau Cheyenne , Draiby Andrea , Cox Emily , Andrews M. Grace , Winks Lewis , Walworth Nathan G.
Published: March 2024

Despite an increase in literature on public perceptions of carbon dioxide removal (CDR), there remains a paucity of evidence describing the social and developmental processes involved in the implementation of projects in-situ. This research illustrates a case study documenting a planned research project for coastal enhanced weathering—a form of ocean alkalinity enhancement—in a remote, rural area of the Northwestern Dominican Republic, a Small Island Developing State particularly at risk from climate change impacts. This paper is a collaboration between the company responsible for the project (Vesta) and researchers located in the Dominican Republic and the United Kingdom, We draw upon 2 years' worth of surveys, interviews, focus groups, group information sessions, and reflexive documentation by the Dominican Republic researchers, to present a first-hand account of local community responses to the planned research project and to coastal enhanced weathering and climate change more broadly. We discuss themes of climate vulnerability, justice, and adaptive capacity through the lens of the collaborative governance and social diffusion principles that the project was designed with. We also reflect on a program of outreach and participatory activities which was established to support community development in the areas surrounding the field trial site, as informed by exploration of community needs drawn from the research.
The “arrhythmic” presentation of peripartum cardiomyopathy: case series and critical review of the literature
Authors: Peretto Giovanni , Micaglio Emanuele , Ciconte Giuseppe , Maia Marianna , Luzzi Martina , Cariello Marianna , Bonfanti Adele Gabriella Rosa , Lazzeroni Davide , Anastasia Luigi , Cavoretto Paolo , Chieffo Alaide , Della Bella Paolo , Pappone Carlo
Published: March 2024

Peripartum Cardiomyopathy (PPCM) is a polymorphic myocardial disease occurring late during pregnancy or early after delivery. While reduced systolic function and heart failure (HF) symptoms have been widely described, there is still a lack of reports about the arrhythmic manifestations of the disease. Most importantly, a broad range of unidentified pre-existing conditions, which may be missed by general practitioners and gynecologists, must be considered in differential diagnosis. The issue is relevant since some arrhythmias are associated to sudden cardiac death occurring in young patients, and the overall risk does not cease during the early postpartum period. This is why multimodality diagnostic workup and multidisciplinary management are highly suggested for these patients. We reported a series of 16 patients diagnosed with PPCM following arrhythmic clinical presentation. Both inpatients and outpatients were identified retrospectively. We performed several tests to identify the arrhythmic phenomena, inflammation and fibrosis presence. Cardiomyopathies phenotypes were reclassified in compliance with the updated ESC guidelines recommendations. Arrhythmias were documented in all the patients during the first cardiological assessment. PVC were the most common recorder arrhythmias, followed by VF, NSVT, AF, CSD.
Prediction of ventilator weaning failure in postoperative cardiac surgery patients using vasoactive-ventilation-renal score and nomogram analysis
Authors: Zhang Zhongqi , Tang Wanchun , Ren Yankang , Zhao Yifan , You Jinjin , Wang Han , Zhao Sheng , Zuo Xiangrong
Published: March 2024

Objective

This study evaluated the predictive value of the vasoactive-ventilation-renal (VVR) score in identifying the risk of weaning failure after cardiac surgery and developing a nomogram model to help physicians improve the success rate of weaning from mechanical ventilation in adult patients undergoing postoperative cardiac surgery.

Methods

Clinical data were retrospectively collected from adult patients who underwent extracorporeal circulation cardiac surgery at the First Affiliated Hospital of Nanjing Medical University between August 2022 and April 2023 and who were subsequently transferred to the Intensive Care Unit (ICU) and treated with vasoactive drugs. Patients were divided into successful and unsuccessful weaning groups based on first-attempt weaning success. Variable selection was regularized using univariate logistic regression and Least absolute shrinkage and selection operator (LASSO) regularization. Multivariate logistic regression was performed to identify predictors and a nomogram was created to predict the risk of weaning failure.

Results

A total of 519 patients were included in the study. After selecting multiple stepwise variables, the VVR score before weaning, the modified Sequential Organ Failure Assessment (mSOFA) score on weaning day, and mechanical ventilation duration before weaning were determined as predictive indicators of weaning failure in adult patients after cardiac surgery. The optimal cut-off values for these indicators were 18.46 points, 4.33 points, and 20.50 h, respectively. The predictive model constructed using these three factors demonstrated good predictive performance.

Conclusions

The VVR score before weaning accurately predicts the probability of weaning failure in adult patients after cardiac surgery. The weaning risk-predictive nomogram model, established based on the VVR score, mSOFA score, and mechanical ventilation duration before weaning, demonstrated robust predictive ability.
A Siamese ResNeXt network for predicting carotid intimal thickness of patients with T2DM from fundus images
Authors: Gong AJuan , Fu Wanjin , Li Heng , Guo Na , Pan Tianrong
Published: March 2024

Objective

To develop and validate an artificial intelligence diagnostic model based on fundus images for predicting Carotid Intima-Media Thickness (CIMT) in individuals with Type 2 Diabetes Mellitus (T2DM).

Methods

In total, 1236 patients with T2DM who had both retinal fundus images and CIMT ultrasound records within a single hospital stay were enrolled. Data were divided into normal and thickened groups and sent to eight deep learning models: convolutional neural networks of the eight models were all based on ResNet or ResNeXt. Their encoder and decoder modes are different, including the standard mode, the Parallel learning mode, and the Siamese mode. Except for the six unimodal networks, two multimodal networks based on ResNeXt under the Parallel learning mode or the Siamese mode were embedded with ages. Performance of eight models were compared via the confusion matrix, precision, recall, specificity, F1 value, and ROC curve, and recall was regarded as the main indicator. Besides, Grad-CAM was used to visualize the decisions made by Siamese ResNeXt network, which is the best performance.

Results

Performance of various models demonstrated the following points: 1) the RexNeXt showed a notable improvement over the ResNet; 2) the structural Siamese networks, which extracted features parallelly and independently, exhibited slight performance enhancements compared to the traditional networks. Notably, the Siamese networks resulted in significant improvements; 3) the performance of classification declined if the age factor was embedded in the network. Taken together, the Siamese ResNeXt unimodal model performed best for its superior efficacy and robustness. This model achieved a recall rate of 88.0% and an AUC value of 90.88% in the validation subset. Additionally, heatmaps calculated by the Grad-CAM algorithm presented concentrated and orderly mappings around the optic disc vascular area in normal CIMT groups and dispersed, irregular patterns in thickened CIMT groups.

Conclusion

We provided a Siamese ResNeXt neural network for predicting the carotid intimal thickness of patients with T2DM from fundus images and confirmed the correlation between fundus microvascular lesions and CIMT.
Discovering single cannabidiol or synergistic antitumor effects of cannabidiol and cytokine-induced killer cells on non-small cell lung cancer cells
Authors: Li Yutao , Sharma Amit , Hoffmann Michèle J. , Skowasch Dirk , Essler Markus , Weiher Hans , Schmidt-Wolf Ingo G. H.
Published: March 2024

Introduction

A multitude of findings from cell cultures and animal studies are available to support the anti-cancer properties of cannabidiol (CBD). Since CBD acts on multiple molecular targets, its clinical adaptation, especially in combination with cancer immunotherapy regimen remains a serious concern.

Methods

Considering this, we extensively studied the effect of CBD on the cytokine-induced killer (CIK) cell immunotherapy approach using multiple non-small cell lung cancer (NSCLC) cells harboring diverse genotypes.

Results

Our analysis showed that, a) The Transient Receptor Potential Cation Channel Subfamily V Member 2 (TRPV2) channel was intracellularly expressed both in NSCLC cells and CIK cells. b) A synergistic effect of CIK combined with CBD, resulted in a significant increase in tumor lysis and Interferon gamma (IFN-g) production. c) CBD had a preference to elevate the CD25+CD69+ population and the CD62L_CD45RA+terminal effector memory (EMRA) population in NKT-CIK cells, suggesting early-stage activation and effector memory differentiation in CD3+CD56+ CIK cells. Of interest, we observed that CBD enhanced the calcium influx, which was mediated by the TRPV2 channel and elevated phosphor-Extracellular signal-Regulated Kinase (p-ERK) expression directly in CIK cells, whereas ERK selective inhibitor FR180204 inhibited the increasing cytotoxic CIK ability induced by CBD. Further examinations revealed that CBD induced DNA double-strand breaks via upregulation of histone H2AX phosphorylation in NSCLC cells and the migration and invasion ability of NSCLC cells suppressed by CBD were rescued using the TRPV2 antagonist (Tranilast) in the absence of CIK cells. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation.

Conclusions

Taken together, CBD holds a great potential for treating NSCLC with CIK cell immunotherapy. In addition, we utilized NSCLC with different driver mutations to investigate the efficacy of CBD. Our findings might provide evidence for CBD-personized treatment with NSCLC patients.
Metabolism-driven glycosylation represents therapeutic opportunities in interstitial lung diseases
Authors: Drzewicka Katarzyna , Zasłona Zbigniew
Published: March 2024

Metabolic changes are coupled with alteration in protein glycosylation. In this review, we will focus on macrophages that are pivotal in the pathogenesis of pulmonary fibrosis and sarcoidosis and thanks to their adaptable metabolism are an attractive therapeutic target. Examples presented in this review demonstrate that protein glycosylation regulates metabolism-driven immune responses in macrophages, with implications for fibrotic processes and granuloma formation. Targeting proteins that regulate glycosylation, such as fucosyltransferases, neuraminidase 1 and chitinase 1 could effectively block immunometabolic changes driving inflammation and fibrosis, providing novel avenues for therapeutic interventions.
STING agonist inflames the cervical cancer immune microenvironment and overcomes anti-PD-1 therapy resistance
Authors: Li Tianye , Zhang Weijiang , Niu Mengke , Wu Yuze , Deng Xinyue , Zhou Jianwei
Published: March 2024

Background

Cervical cancer poses a significant global threat to women’s health. However, current therapeutic interventions, such as radiotherapy, chemotherapy, surgical resection, and immune checkpoint inhibitors, face limitations in the advanced stages of the disease. Given the immunosuppressive microenvironment in cervical cancer, it is imperative to explore novel perspectives. In this regard, STING agonists have emerged as promising candidates.

Methods

The expression profiles and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Prognostic analysis of STING downstream genes (CCL5, CXCL9, CXCL10) and immune infiltration analysis were conducted using Kaplan-Meier Plotter, ESTIMATE, and deconvo_CIBERSOR. Single-cell RNA-seq (scRNA-seq) analysis was conducted to evaluate the potential of MSA-2 in cervical cancer treatment employing SingleR, chi-squared test, and Gene Set Enrichment Analysis (GSEA). Cellular interaction analysis utilized the CellChat package to assess the potentiation of cellular interaction following MSA-2 administration. Murine tumor models involving U14 and TC-1, were conducted, and the IF of tissue was subsequently conducted to assess the tumor microenvironment status after treatment.

Results

Prognosis in cervical cancer correlated with elevated expression of STING downstream genes, indicating prolonged survival and reduced recurrence. These genes positively correlated with immune infiltration, influencing stromal scores, immune scores, and estimate scores. Specific immune cell populations, including CD8+ T cells, M1-type macrophages, NK cells, and T follicular helper cells, were associated with STING downstream genes. scRNA-seq in a classic immune-excluded model revealed that MSA-2 exerts priming and activating functions on vital components within TME, and intensifies their intercellular communications. The in vivo assay ultimately demonstrated that MSA-2, either as a standalone treatment or in combination with anti-PD-1, effectively suppressed the growth of subcutaneous cervical tumors. Moreover, the combination strategy significantly augmented efficacy compared to anti-PD-1 monotherapy by eliciting a robust antitumor immune response.

Conclusion

This study highlights the pivotal role of the STING pathway and the potential of MSA-2 in reshaping the immune microenvironment in cervical cancer. Combining MSA-2 with immune checkpoint inhibitors presents a transformative approach, holding promise for improved prognosis. Further investigations are warranted to explore the broader immune landscape and potential long-term effects of MSA-2 in cervical cancer treatment.
Plasma from patients undergoing allogeneic hematopoietic stem cell transplantation promotes NETOSIS in vitro and correlates with inflammatory parameters and clinical severity
Authors: López-Andrade Bernardo , Cunill Vanesa , Andreu Valero , Bento Leyre , Segura-Guerrero Marina , Moñino Andrea , Iglesias Julio , Julià Maria Rosa , Durán Maria Antonia , Ballester Maria Carmen , Muncunill Josep , Sampol Antonia
Published: March 2024

Introduction

NETosis, the mechanism by which neutrophils release extracellular traps (NETs), is closely related to inflammation. During the allogeneic hematopoietic stem cell transplantation (allo-HSCT), different stimuli can induce NETs formation. Inflammation and endothelial injury have been associated with acute graft-versus-host disease (aGVHD) and complications after allo-HSCT. We focus on the study of NETosis and its relation with cytokines, hematological and biochemical parameters and clinical outcomes before, during and after allo-HSCT.

Methods

We evaluate the capacity of plasma samples from allo-HSCT patients to induce NETosis, in a cell culture model. Plasma samples from patients undergoing allo-HSCT had a stronger higher NETs induction capacity (NETsIC) than plasma from healthy donors throughout the transplantation process. An optimal cut-off value by ROC analysis was established to discriminate between patients whose plasma triggered NETosis (NETs+IC group) and those who did not (NETs-IC group).

Results

Prior to conditioning treatment, the capacity of plasma samples to trigger NETosis was significantly correlated with the Endothelial Activation and Stress Index (EASIX) score. At day 5 after transplant, patients with a positive NETsIC had higher interleukin (IL)-6 and C-reactive protein (CRP) levels and also a higher Modified EASIX score (M-EASIX) than patients with a negative NETsIC. EASIX and M-EASIX scores seek to determine inflammation and endothelium damage, therefore it could indicate a heightened immune response and inflammation in the group of patients with a positive NETsIC. Cytokine levels, specifically IL-8 and IL-6, significantly increased after allo-HSCT with peak levels reached on day 10 after graft infusion. Only, IL-10 and IL-6 levels were significantly higher in patients with a positive NETsIC. In our small cohort, higher IL-6 and IL-8 levels were related to early severe complications (before day 15 after transplant).

Discussion

Although early complications were not related to NETosis by itself, NETosis could predict overall non-specific but clinically significant complications during the full patient admission. In summary, NETosis can be directly induced by plasma from allo-HSCT patients and NETsIC was associated with clinical indicators of disease severity, cytokines levels and inflammatory markers.
Macrophages in acne vulgaris: mediating phagocytosis, inflammation, scar formation, and therapeutic implications
Authors: Feng Yibo , Li Jiaqi , Mo Xiaohui , Ju Qiang
Published: March 2024

Macrophages serve as a pivotal nexus in the pathogenesis of acne vulgaris, orchestrating both the elimination of Cutibacterium acnes (C. acnes) and lipid metabolic regulation while also possessing the capacity to exacerbate inflammation and induce cutaneous scarring. Additionally, recent investigations underscore the therapeutic potential inherent in macrophage modulation and challenge current anti-inflammatory strategies for acne vulgaris. This review distills contemporary advances, specifically examining the dual roles of macrophages, underlying regulatory frameworks, and emergent therapeutic avenues. Such nuanced insights hold the promise of guiding future explorations into the molecular etiology of acne and the development of more efficacious treatment modalities.
Identification and validation of hub genes expressed in ulcerative colitis with metabolic dysfunction-associated steatotic liver disease
Authors: Liu Yupei , Li Jiao , Tian Shan , Lan Qingzhi , Sun Zhiyi , Liu Chuan , Dong Weiguo
Published: March 2024

Objective

Ulcerative colitis (UC) and metabolic dysfunction-associated steatotic liver disease (MASLD) are closely intertwined; however, the precise molecular mechanisms governing their coexistence remain unclear.

Methods

We obtained UC (GSE75214) and MASLD (GSE151158) datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were acquired by the ‘edgeR’ and ‘limma’ packages of R. We then performed functional enrichment analysis of common DEGs. Hub genes were selected using the cytoHubba plugin and validated using GSE87466 for UC and GSE33814 for MASLD. Immunohistochemistry was employed to validate the hub genes’ expression in clinical samples. Immune infiltration and gene set enrichment analyses of the hub genes were performed. Finally, we estimated the Spearman’s correlation coefficients for the clinical correlation of the core genes.

Results

Within a cohort of 26 differentially regulated genes in both UC and MASLD, pathways involving cytokine-mediated signaling, cell chemotaxis, and leukocyte migration were enriched. After further validation, CXCR4, THY1, CCL20, and CD2 were identified as the hub genes. Analysis of immune infiltration patterns highlighted an association between elevated pivotal gene expression and M1 macrophage activation. Immunohistochemical staining revealed widespread expression of pivotal genes in UC- and MASLD-affected tissues. Furthermore, significant correlations were observed between the increased expression of hub genes and biochemical markers, such as albumin and prothrombin time.

Conclusion

This bioinformatics analysis highlights CXCR4, THY1, CCL20, and CD2 as crucial genes involved in the co-occurrence of UC and MASLD, providing insights into the underlying mechanisms of these two conditions.
Circulating tumor-associated antigen-specific IFNγ+4-1BB+ CD8+ T cells as peripheral biomarkers of treatment outcomes in patients with pancreatic cancer
Authors: Murakami Hirotomo , Takahama Shokichi , Akita Hirofumi , Kobayashi Shogo , Masuta Yuji , Nagatsuka Yuta , Higashiguchi Masaya , Tomokuni Akira , Yoshida Keiichi , Takahashi Hidenori , Doki Yuichiro , Eguchi Hidetoshi , Matsuura Nariaki , Yamamoto Takuya
Published: March 2024

CD8+ T cells affect the outcomes of pancreatic ductal adenocarcinoma (PDAC). Using tissue samples at pre-treatment to monitor the immune response is challenging, while blood samples are beneficial in overcoming this limitation. In this study, we measured peripheral antigen-specific CD8+ T cell responses against four different tumor-associated antigens (TAAs) in PDAC using flow cytometry and investigated their relationships with clinical features. We analyzed the optimal timing within the treatment course for effective immune checkpoint inhibition in vitro. We demonstrated that the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells was correlated with a fold reduction in CA19-9 before and after neoadjuvant therapy. Moreover, patients with TAA-specific IFNγ+4-1BB+ CD8+ T cells after surgery exhibited a significantly improved disease-free survival. Anti-PD-1 treatment in vitro increased the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells before neoadjuvant therapy in patients, suggesting the importance of the timing of anti-PD-1 inhibition during the treatment regimen. Our results indicate that peripheral immunophenotyping, combined with highly sensitive identification of TAA-specific responses in vitro as well as detailed CD8+ T cell subset profiling via ex vivo analysis, may serve as peripheral biomarkers to predict treatment outcomes and therapeutic efficacy of immunotherapy plus neoadjuvant chemotherapy.
Targeting YAP1 to improve the efficacy of immune checkpoint inhibitors in liver cancer: mechanism and strategy
Authors: Gao Yuting , Gong Yi , Lu Junlan , Hao Huiqin , Shi Xinli
Published: March 2024

Liver cancer is the third leading of tumor death, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Immune checkpoint inhibitors (ICIs) are yielding much for sufferers to hope for patients, but only some patients with advanced liver tumor respond. Recent research showed that tumor microenvironment (TME) is critical for the effectiveness of ICIs in advanced liver tumor. Meanwhile, metabolic reprogramming of liver tumor leads to immunosuppression in TME. These suggest that regulating the abnormal metabolism of liver tumor cells and firing up TME to turn “cold tumor” into “hot tumor” are potential strategies to improve the therapeutic effect of ICIs in liver tumor. Previous studies have found that YAP1 is a potential target to improve the efficacy of anti-PD-1 in HCC. Here, we review that YAP1 promotes immunosuppression of TME, mainly due to the overstimulation of cytokines in TME by YAP1. Subsequently, we studied the effects of YAP1 on metabolic reprogramming in liver tumor cells, including glycolysis, gluconeogenesis, lipid metabolism, arachidonic acid metabolism, and amino acid metabolism. Lastly, we summarized the existing drugs targeting YAP1 in the treatment of liver tumor, including some medicines from natural sources, which have the potential to improve the efficacy of ICIs in the treatment of liver tumor. This review contributed to the application of targeted YAP1 for combined therapy with ICIs in liver tumor patients.